Category: 3. Business

  • Risk prediction model for overall survival in lung cancer based on inflammatory and nutritional markers

    Risk prediction model for overall survival in lung cancer based on inflammatory and nutritional markers

    Analysis of the impact of inflammatory and nutritional markers on prognostic factors in lung cancer patients

    Univariate analysis

    This study ultimately included 500 patients with lung cancer, comprising 178 patients in the survival group and 322 patients in the deceased group. Patients in the survival group had significantly higher levels of lymphocyte count, serum albumin, hemoglobin, prognostic nutritional index (PNI), lymphocyte-to-monocyte ratio (LMR), hemoglobin-to-red cell distribution width ratio (HRR), hemoglobin-albumin-lymphocyte-platelet (HALP) score, albumin-to-globulin ratio (ALB/GLB), as well as a greater proportion of stage I cases and patients with high-to-moderate tumor differentiation. In contrast, patients in the deceased group exhibited significantly higher levels of serum globulin, age, systemic immune-inflammation index (SII Log), platelet-to-lymphocyte ratio (PLR Log), neutrophil-to-lymphocyte ratio (NLR), and a higher proportion of cases with distant metastasis, stage IV disease, Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2, and poorly differentiated tumors. Table 1.

    Table 1 Univariate analysis of clinical and laboratory indicators and poor prognostic factors in lung cancer Patients.

    LASSO regression analysis and risk prediction formula

    In this study, mortality in lung cancer patients was used as the dependent variable. Independent variables included clinical stage (coded as 1 = Stage I, 0 = Stage II/III/IV), differentiation grade (coded as 1 = low differentiation, 0 = moderate/high differentiation), ECOG PS (coded as 1 = ECOG PS 0–1, 0 = ECOG PS ≥ 2), serum albumin (measured value), LMR (measured value), HRR (measured value), ALB/GLB (measured value), and age (measured value).LASSO regression analysis identified ECOG PS 0–1, ALB/GLB, and age as independent prognostic factors for lung cancer. ECOG PS 0–1 and higher ALB/GLB levels were protective factors, while age was a significant risk factor. Specifically, the analysis indicated that each additional year of age increased the risk of mortality by approximately 7%.Table 2. The following formula was provided to calculate the mortality risk prediction score for individual patients: Exp(x) = [−0.94909] + [−0.47464 × 1(Stage I)] + [0.54761 × 1(Low differentiation)] + [−0.85073 × 1(ECOG PS 0–1)] + [−0.00427 × Serum albumin] + [−0.04974 × LMR] + [−0.28638 × HRR] + [−0.98366 × ALB/GLB] + [0.06838 × Age].The probability of mortality is calculated as: Probability = Exp(x)/[1 + Exp(x)].

    Table 2 LASSO regression analysis of prognostic risk factors in patients with lung Cancer.

    Development of a risk prediction model

    Feature selection using LASSO regression for dimensionality reduction

    In this study, LASSO regression analysis with 10-fold cross-validation was used to select the optimal log(λ) values. When log(λ) was − 2.8203 and − 3.5645, the data demonstrated stability and statistical significance. Figure 2 shows the coefficient distribution curve for different log(λ) values. Figure 3 illustrates the stepwise feature selection process, reducing 46 variables to 1. Each curve represents the trajectory of different predictor coefficients as the parameter changes.The optimal eight variables selected for constructing the lung cancer risk prediction model based on inflammation and nutrition markers were: age, Stage I, low differentiation, ECOG PS 0–1, serum albumin, LMR, HRR, and ALB/GLB.Age was identified as an independent risk factor for poor prognosis, with increasing age associated with worse outcomes. Patients with Stage I disease and ECOG PS 0–1 had better prognoses. In contrast, low differentiation, decreased serum albumin levels, and lower ALB/GLB were associated with worse outcomes. Elevated LMR and HRR were linked to improved prognosis.Table 3. Figure 2. Figure 3.

    Table 3 Multivariate analysis of prognostic factors in two independent Models.
    Fig. 2

    Cross-validation of LASSO regression analysis. Note: The vertical axis represents the cross-validation error, which serves as a metric for assessing model goodness-of-fit. A smaller value indicates better model fit. The lower horizontal axis corresponds to log(λ), where λ is the regularization parameter that controls the complexity of the model. The upper horizontal axis denotes the number of variables retained at different log(λ) values. The two vertical dashed lines indicate the optimal log(λ) value and the log(λ) value within one standard error. Specifically, the upper horizontal axis value corresponding to the left dashed line represents the number of selected variables at the optimal log(λ) value.

    Fig. 3
    figure 3

    Variable selection path in LASSO regression. Each line in a different color represents a variable. The bottom x-axis corresponds to log(λ) values, while the top x-axis indicates the number of nonzero coefficients (variables) in the model for the respective log(λ) values. The log(λ) value controls the strength of regularization in the model: smaller log(λ) values correspond to weaker regularization, allowing more variables to enter the model, whereas larger log(λ) values correspond to stronger regularization, enhancing the model’s robustness to noise but shrinking many variable coefficients to zero.As the log(λ) value increases (from smaller to larger values), the model complexity decreases, with many variable coefficients gradually shrinking to zero or becoming exactly zero. However, the coefficients of certain variables remain nonzero throughout the process. This observation suggests that the model identifies these variables as more critical features, enabling dimensionality reduction or the selection of the most important predictors.

    Near-Zero variance test of training data

    To further refine variable selection and understand their local characteristics and distribution patterns, a near-zero variance test was conducted on multiple variables. The results showed that patient age, ALB/GLB, and ECOG PS scores (≥ 2 and 0–1) were evenly distributed, suggesting their relevance to prognosis. The proportions of LMR, HRR, and ALB/GLB were 93.79%, 94.99%, and 98.20%, respectively, indicating high individual variability among these variables.Table 4.

    Table 4 Nearest neighbor variance analysis of clinical Variables.

    Collinearity test on training data (Stepwise VIF Selection)

    To improve the predictive performance of the model and address irrelevant variables, a collinearity test (VIF) was performed to further refine the feature selection. Variables such as Stage II, moderate/high differentiation, and ECOG PS ≥ 2 were stepwise excluded. The retained variables included Stage I, Stage III, Stage IV, low differentiation, ECOG PS 0–1, serum albumin (g/L), LMR, HRR, ALB/GLB, and age.The analysis identified age, clinical stage, low differentiation, ECOG PS 0–1, serum albumin levels, LMR, HRR, and ALB/GLB as independent prognostic factors.Table 5.

    Table 5 Variance inflation factors (VIF) analysis through Stepwise variable Selection.

    Recursive feature elimination

    To identify the most relevant feature variables, recursive feature elimination (RFE) was performed. The selected variables included Stage I, low differentiation, ECOG PS 0–1, serum albumin (g/L), LMR, HRR, ALB/GLB, and age.The analysis revealed that LMR had the most significant predictive performance. Serum albumin, ALB/GLB, and HRR also demonstrated strong predictive capabilities. Age, Stage I, low differentiation, and ECOG PS 0–1 showed moderate predictive value.Table 6.

    Table 6 Analysis of Cross-Validated performance metrics for all Predictors.

    Variable importance

    Finally, this study systematically evaluated the factors influencing prognosis and identified age as the most critical determinant. The factors ranked in descending order of impact were ECOG PS 0–1, ALB/GLB, poor differentiation, stage I, HRR, LMR, and serum albumin. Table 7.

    Table 7 Analysis of predictor Importance.

    Model evaluation

    ROC curve (Internal validation performed 500 Times)

    The performance of the model was evaluated using the ROC curve, with an area under the curve (AUC) of 0.7652 (95% CI: 0.7246–0.8029) and an accuracy of 0.711 (95% CI: 0.669–0.751). The model demonstrated high sensitivity (0.847) and moderate specificity (0.466), indicating good discriminatory power, making it suitable for preliminary disease screening. The positive predictive value (0.741) exceeded the negative predictive value (0.629), suggesting the model is more reliable in identifying positive cases.Internal validation was conducted using 500 bootstrap resamples. Calibration was assessed with isotonic regression fitting. The results showed an F1-score of 0.791 (range: 0–1, with higher values indicating better balance), confirming that the model achieved a good trade-off between precision and recall. These findings highlight the model’s strong predictive accuracy, good sensitivity, and reliable calibration, demonstrating its overall predictive and fitting performance.Table 8. Figure 4.

    Table 8 Analysis of performance metrics for predictive Models.
    Fig. 4
    figure 4

    Optimal cutoff point

    The ROC cut-off points, sensitivity, and specificity for eight inflammation-nutritional markers, including NLR, PLR, SII, LMR, PNI, HALP, HRR, and ALB/GLB, are presented in Supplementary Table S1. Users can select appropriate cut-off points based on their clinical context to predict future outcomes (see Supplementary_Table_S1.pdf).

    Model calibration

    The predictive performance of the model was evaluated using a visual calibration curve. The calibration curve closely aligned with the ideal curve, with a slope of 1. This indicates that the risk prediction model has good calibration performance and can provide reliable risk estimates. Figure 5.

    Fig. 5
    figure 5

    Calibration plot for the predictive model in the training dataset.

    Clinical utility of the model

    The decision curve analysis demonstrated that the predictive model (PRED.MODEL1) maintained stable performance across various risk thresholds. In the low-risk range (0.2–0.3), the model effectively identified high-risk patients requiring intervention while reducing overtreatment. In the moderate-risk range (0.3–0.6), it performed optimally, balancing treatment benefits with potential risks. Even in the high-risk range (0.6–0.8), the model retained good discriminatory ability, aiding in the identification of patients needing aggressive intervention.The model’s curve consistently remained above the reference line and was most prominent in the moderate-risk range (0.3–0.6). These findings indicate that the predictive model can effectively guide clinical decision-making. Figure 6.

    Fig. 6
    figure 6

    Decision curve analysis of PRED.MODEL1 for clinical decision-making.

    Web-Based calculator for prognostic risk prediction in patients with lung cancer

    We have developed a web-based calculator for predicting the prognostic risk of lung cancer patients. Instructions for Use: After accessing Risk Prediction Model for Overall Survival in Lung Cancer Patients, input the patient’s information as follows: Select “Yes” or “No” for “Stage I.“Select “Yes” or “No” for “Poor Differentiation.“Select “Yes” or “No” for “ECOG PS 0–1.“Enter the serum albumin level (g/L) in the designated field.Input the LMR, HRR, and ALB/GLB values in their respective fields.Enter the patient’s age in years.Once all fields are completed, click “Calculate Risk.” The probability of mortality for lung cancer patients will be automatically displayed at the bottom of the interface. For reference, see the webpage calculator interface in Fig. 7.

    Fig. 7
    figure 7

    Shows the interface of the web-based calculator.

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  • FBR Revises Customs for Medical Items Imported from China

    FBR Revises Customs for Medical Items Imported from China

    The Directorate General of Customs Valuation Karachi has revised customs values on the import of a wide range of medical items and equipment from China.

    The directorate issued Valuation Ruling 2020 of 2025 on Thursday.

    After a long period of eight years, the directorate has updated the values for the import of such equipment from China.

    According to the ruling, the directorate had previously issued Valuation Ruling No. 1202 of 2017 for medical items and equipment under Section 25A of the Customs Act. As the valuation ruling was eight years old, an exercise for the re-determination of customs values of the subject goods was initiated, based on an analysis of import data, current market trends, and the difference in market prices and customs values.

    Meetings were convened to re-evaluate the customs values of the subject goods. During these meetings, stakeholders submitted relevant documents along with their proposed values and samples, which were duly recorded.

    The customs values of the subject goods have been determined under Section 25(9), read with Section 25(7), and Customs Rule 2001.

    The rule provides that the methods of valuation employed under sub-section (9) of Section 25 of the Customs Act, 1969, may include those laid down in the sub-sections of the said section. However, reasonable flexibility in the application of such methods is in conformity with the aims and provisions of sub-section (9) of that section, it added.


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  • A randomized controlled trial on the effectiveness of low-level laser therapy versus paracetamol-caffeine for pain control during overall orthodontic treatment

    A randomized controlled trial on the effectiveness of low-level laser therapy versus paracetamol-caffeine for pain control during overall orthodontic treatment

    In the current trial, the effectiveness of a single dose of the low-level laser before each stage of the orthodontic leveling and alignment treatment and paracetamol– caffeine combination drug in reliving the orthodontic pain were evaluated.

    The current research work was a three-arm, parallel-design study. Some researchers have claimed that the split-mouth design is superior to the parallel design in the trials that evaluate patient-centered outcomes to overcome interpersonal differences such as sex, age, and psychiatric changes17. However, an inherent shortcoming of this design was the possibility of carrying the perception of pain from one side to another, resulting in difficulty in accurately determining pain by patients, especially after archwire replacement2,32. On the other hand, some studies did not find any relation between orthodontic pain perception and age or gender33.

    Adult patients with mild to moderate upper and lower crowded arches were included in the current study. Adults can express their feelings more accurately than younger people34. The applied orthodontic force depends on the position of the teeth and the crowding level, especially after orthodontic separator placement or initial archwire engagement, as the greater force may cause greater pain2,35. Many previous studies did not consider the effect of crowding degree and the selected age group in their study designs21,22,25.

    Similar to many previous studies2,4,7,18,21,22, a diode Ga-Al-As laser was used with a wavelength of 810 nm (near-infrared electromagnetic spectrum). Infrared radiation has a low absorption coefficient in hemoglobin and water; thus, more depth of penetration in the irradiated tissue, possibly reaching cortical and alveolar bone tissues4. To achieve the best results, it is important to use an appropriate amount of laser energy. In the current study, a power of 3.5 joules per point was applied, similar to the studies of Almallah et al., Owayda et al. after separators placement2,22 and studies of Qamruddin et al. and Domínguez et al. after archwires replacement4,28.

    Due to the superiority of paracetamol-caffeine (500–65 mg) over acetaminophen alone12, and a greater level of safety when compared to other locally acting NSAIDs, it was chosen in the current trial as opposed to other investigations8,9 that solely used paracetamol for orthodontic pain management. Sandue et al. demonstrated that the effectiveness of analgesics depends on the drug’s pharmacokinetics in terms of dose and timing of administration36. To maintain a healthy drug plasma level in the current study, all patients were instructed to take their prescription an hour before any replacement and to continue taking a pill every 8 h for the first couple of days. Then, as needed, in the following days. This instruction was given as the orthodontic pain peaks after 24–48 h of force application2,21.

    A small amount of spontaneous and chewing pain was perceived directly after each archwire replacement (a mean of 1 to 2 units on the NRS). The compression of the periodontal ligament fibers after orthodontic force application might be responsible for this immediate pain sensation2,23. This study showed that most patients experienced the most pain 24 to 48 h after undergoing orthodontic replacement, consistent with the results of many previous reports2,4,8,16,28. The time course of orthodontic pain may be related to biological changes after an orthodontic force is applied, specifically, the concentration of interleukin (IL) 1-beta that reaches its highest levels after 24 h37.

    Intergroup findings

    Differences less than 2 degrees on the Numeric Rating Scale (NRS) were considered not clinically significant. Understanding the minimally clinically important difference (MCID) is essential for evaluating the effectiveness of pain management modalities38.

    The spontaneous and chewing pain levels induced by orthodontic separators were significantly lower than those from the drug and control groups, just at the peak of pain after 48 h of insertion. These results were similar to Almallah and Qamruddin et al.21,22. Qamruddin et al. used 940 nm of GaAlAs laser with 200 mW for 20 s and irradiated at three points: mesial, distal, and the middle of the first molar from the buccal side only. Almallah et al. compared single versus double laser irradiation doses with 4 J/cm2 energy applied for 28 s on each of the eight selected points (4 buccal and four palatal). Neither the LLLT nor the medication could relieve the orthodontic pain induced by orthodontic separators in the other assessment times. The current results contrasted what was reported by Mirhashemi et al. who evaluated double laser irradiations with 15 J/cm2 energy applied for 11 s on each point of cervical points for mesial and distal roots of the maxillary 1 st molar20. The difference in efficacy of LLLT may be due to variations in overall laser energy, application protocol, or study methodology, as suggested by Farzan et al.17. Similarly, the above results match the outcomes of Patel et al., who used only paracetamol one hour before and after 3 and 7 h of separator placement9. In contrast, Najafi et al. suggested that preemptive paracetamol alone could be an effective option for managing orthodontic pain; however, their study lacked a control group, and the results should be viewed with care8.

    The pain levels experienced by the participants in the laser, drug, and control groups when the initial archwire (0.014 NITI) was installed were similar to those found in previous studies7,15. The 0.014 and 0.016 -NiTi-induced Pain mean scores in LLLT and paracetamol-caffeine groups were similar to those of the control group without significant differences. Conversely, Qamruddin et al. demonstrated that a single dose of Al-Ga-As laser irradiation with a power of 75 J per tooth can reduce the pain associated with the initial archwire4. The specific ability of LLLT to reduce the peak pain experienced after the separator placement, rather than after the installation of initial archwires, may be because separators induce significantly greater levels of pain than round archwires, leading to a greater concentration of inflammatory mediators, such as PGE2, IL-1β, and TNF. These mediators create a more suitable environment for laser irradiation to work effectively in reducing pain1. The study’s results indicate that the combination of paracetamol and caffeine did not provide significant relief for spontaneous and chewing pain caused by initial archwires, similar to what was observed with pain caused by separators. In a previous study by Alshammari et al., it was reported that using paracetamol or chewing gum after initial archwire installation had similar effects25. However, their study was limited by the absence of a control group, making it unclear whether the modalities used effectively controlled pain. This is particularly relevant to the current study, as pain mean scores in their study were compared to those of a control group in the current study.

    The insertion of rectangular archwires caused mild levels of pain that peaked 24 h after insertion and subsided by the end of the week in all three study groups. The laser in the current study reduced pain levels during its peak at 24 and 48 h after rectangular wire insertion, but the amount of reduction was not clinically important. These results were similar to those reported by Dominguez and Velasquez, who evaluated the effect of a low-energy GaAlAs laser with a wavelength of 830 nm and an energy of 100 J/cm2 for 22 s on the vestibular and palatal/lingual sides after 0.019*0.025 SS archwire insertion in crowded cases that were resolved without extraction28. This effect may be attributed to the cumulative effect of successive laser doses applied from the first to the final stage in this study. In the drug group, the mean values of the spontaneous and chewing pain scores after 24 and 48 h of placing the 0.016*0.022 NiTi and 0.019*0.025 NiTi archwires were the lowest among the tested groups. However, the multiple comparisons did not reveal any statistically significant differences between the drug and control groups. The medication used was not effective in alleviating mild pain levels in stages from 0.016*0.022 NITI to 19*25 SS, and this may be attributed to the fact that the pain levels induced in these stages were mild; there was no need to relieve these mild pain levels, and this psychological factor may have affected the drug’s efficacy.

    The drug intake did not significantly reduce pain levels compared to receiving no treatment, although there was some decrease. Additionally, the addition of caffeine did not appear to enhance the pain-relieving effect of paracetamol on induced pain.

    Within group findings

    Most previous studies in this area have only examined one stage, either separators2,8,21,22 or the initial archwire4,7,15,25, as the source of force. We believe that studies focusing on a single component as the source of force may draw inaccurate conclusions because the nature of pain caused by each stage may have different characteristics compared to the pain caused by other stages. Therefore, to the limit of our knowledge, this study is the first to assess all stages of leveling and alignment treatment with a fixed appliance, providing a comprehensive understanding of orthodontic pain from A to Z.

    In the current study, pain levels (spontaneous and chewing) were significantly greater in the separation and initial archwire stages compared to other stages after 24 and 48 h in the laser, drug, and control groups. However, there was no significant difference between these two stages. It is commonly believed that orthodontic pain increases proportionately to the force applied, which may explain why there was more intense pain during initial archwire alignment but decreased with the 0.016-in wire and became almost non-existent later on4. This also could be attributed to the patient’s exposure to new procedures that could increase anxiety and pain levels39. Additionally, patients may become accustomed to the fixed appliance and the pain it causes over time, although there is currently no research to support this theory.

    Specifically, the pain levels during separation were slightly greater than those induced by the 0.014 NiTi archwire. This could be interrupted by the fact that the pain caused by the separator differs from that caused by the archwire, as the separator exerts only lateral forces for teeth separation. In contrast, fixed orthodontic treatment using an archwire involves more complex movements, such as extrusion, intrusion, and uncontrolled tipping, which can contribute to a different type of pain7.

    Additionally, no significant differences were detected between the pain mean scores recorded for the initial archwire and 0.016*0.022 NiTi or 0.019*0.025 NiTi. One possible explanation is that the 0.016*0.022 NiTi archwire is the first rectangular archwire that transfers torque data, and the 0.019*0.025 NiTi wire is the largest wire that conveys the majority of torque data through the brackets40. Orthodontic pain can be a significant concern following the initial stages of orthodontic treatment, particularly after the placement of separators and the initial archwire installation. However, using buccal tubes can help avoid the need for separators.

    Limitations

    One of the limitations of the current study was that masking was not applicable due to the long-term follow-up period and patients in the control group did not receive any placebo procedure, and the placebo procedures could play an intervention role in pain studies. Additionally, the current study did not assess participants’ pain threshold before enrollment. no drop-outs were planned during sample calculation of this trial. Another limitation of the current study is that the use of medication in the drug group after the first couple of days of treatment was not tracked or analyzed through subgroup or sensitivity analysis.

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  • Gold edges down on stronger dollar, Powell's remarks in focus – Reuters

    1. Gold edges down on stronger dollar, Powell’s remarks in focus  Reuters
    2. Powell suggests rate cuts are coming — but not because Trump demanded them  CNN
    3. Gold prices drop as rate cut bets wane in anticipation of Powell speech  Investing.com
    4. Gold Price Outlook – Gold Continues to Sit Near 50 Day EMA  FXEmpire
    5. Gold prices jump as Powell says policy adjustment may be warranted  KITCO

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  • New EssentET Treatment May Address Underlying Disease

    New EssentET Treatment May Address Underlying Disease

    The monoclonal antibody INCA44989 is the first-ever treatment for essential thrombocythemia (ET) that may alter the underlying mechanism of disease for patients with mutations of calreticulin (mutCALR), according to a recent phase 1 study. The majority of patients achieved a swift and durable response.

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    The research outcomes were presented at a late-breaking session during the 2025 European Hematology Association Congress. Notably, the medication also has a very low toxicity profile.

    “The overall response rate of roughly 70% is pretty remarkable,” notes Aaron Gerds, MD, study co-author and a hematologist with Cleveland Clinic Cancer Institute. “It’s also very advantageous to have a therapy with a side effect profile like this, as it’s likely to also work well in combination with other medications.”

    Background

    ET is a myeloproliferative neoplasm with increased risk of thrombosis, hemorrhage and progression to myelofibrosis (MF) or acute myeloid leukemia. Patients with ET often suffer from extreme fatigue, night sweats, fevers, itchy skin, unintentional weight loss and/or enlarged spleen. “Controlling patients’ blood counts is very important to reduce the risk of bleeding or clotting,” explains Dr. Gerds. “However, we not only need therapies that control blood counts and improve symptoms but modify the course of disease and reduce the risk of progression to post-ET myelofibrosis or acute leukemia.”

    In recent years, researchers discovered that ET was caused by threedistinct driver mutations: JAK II, MPL and mutCALR. Roughly a quarter of patients with ET have mutCALR, which is associated with lower rates of response to treatment as well as higher risk of transformation to MF. Current treatments control blood counts and mitigate vascular complications for a certain percentage of patients, but don’t address the underlying disease and are not targeted at driver mutations.

    “All the existing treatments are non-specific in that they can’t target specific mutations, and most have considerable toxicities,” explained Dr. Gerds. “Hydroxyurea and interferons can achieve disease control in between 30-60% of patients, but they’re accompanied by hair thinning, mouth sores, and in the case of interferons, liver enzyme elevation. They’re also not appropriate for patients with auto immune disorders, as they can lead to depression and other mental health issues.”

    Study concept

    The mutCALR protein is unique in that it’s actually external to the cell so it’s susceptible to targeting. (JAK II and MPL don’t act in that manner.) Researchers sought to target mutCALR with a monoclonal antibody, which would be expected to have a minimal side effect profile.

    Several years ago, researchers conducted preclinical work in that space, deploying INCA33989 to go after mutCALR mutations. They found the therapy had a fairly remarkable response in terms of selectively targeting the mutation.

    Study design

    Building on the preclinical work, researchers at Cleveland Clinic Cancer Institute participated in a multisite, first-in-human study evaluating INCA33989 for patients with the CALR exon-9 mutation with high-risk ET or MF. Patients received INCA33989 as a monotherapy via IV every two weeks.

    Primary endpoints were dose-limiting toxicities or treatment-emergent adverse events. Secondary endpoints included symptom improvement (based on MPN-SAF TSS), treatment response using European LeukemiaNet response criteria and changes in allele burden of mutCALR.

    In the ET cohort, there were 49 patients enrolled, with a median age of 60. Initially, patients received a very low dose (24 mg) and over time titrated up to 1,500 mg.

    Study outcomes

    Sixty-six percent of patients achieved a complete response in terms of normalization of platelet count. “Even for those starting at an incredibly low dose, we were seeing transient responses,” says Dr. Gerds. Eight-nine percent of evaluable patients also had a reduction in mutCALR VAR from their baseline, with 47% achieving a reduction of 20% or more and 21% achieving a reduction of 50% or more.

    Perhaps even more importantly, the therapy seems to reduce disease burden. In the trial, a significant number of patients also achieved reductions in allele rates (a rough approximation of disease burden in ET) at a median follow-up of seven weeks. “By comparison, we don’t typically see allele burden reductions with interferons for one to two years,” says Dr. Gerds.

    Higher doses of INCA33989 correlated with improved responses. Fortunately, increasing the dose did not seem to cause many adverse events. There were no dose-limiting toxicities found, and only one patient stopped treatment due to side effects. Of the side effects observed, the most common were asymptomatic lipase, visceral venous thrombosis and diverticulitis, all of which were minimal. The medication also appears to be well tolerated by patients with ET who could not take cytoreductive therapy.

    Dr. Gerds is quick to point out that this is very preliminary study data that needs correlating with improvements in myelofibrosis-free survival, clot-free survival and overall survival. However, these early results are quite encouraging. “Given the favorable toxicity profile of INCA44989, the world is our oyster in terms of where we can take this therapy. We’re not limited by additive or combinatorial toxicities, so that broadens the possibilities for how this treatment can be developed,” Dr. Gerds says.

    What’s next

    This monoclonal antibody is just one example of how to treat somewhat rare myeloproliferative neoplasms like ET and MF. The field is rapidly evolving.

    The myelofibrosis cohort study is still enrolling, with top-line results expected around the end of the year. A parallel study outside of Cleveland Clinic is also underway investigating INCA44989 in combination with ruxolitinib. “As we bring these findings together over the next year or so, that will help identify what direction this therapy will take next,” says Dr. Gerds.

    “There is also ongoing research into bispecific antibodies as well as engineered cells like CAR T-cell therapy that may build on top of a monoclonal antibody. I expect there will be a huge wave of change in this area over the next five to ten years,” explains Dr. Gerds.

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  • Japan’s Low-Coupon Super Long Bonds Face Risk of September Slump

    Japan’s Low-Coupon Super Long Bonds Face Risk of September Slump

    Investors are avoiding Japan’s super-long bonds with lower coupons in a bearish trend that risks spreading to other tenors before they close their books at the end of next month.

    Government bonds issued years before the Bank of Japan began quantitative tightening in the summer of 2024 are underperforming as their sub 1% coupons lose out to newer debt with fixed payouts twice as high.

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  • EU speeds up plans for digital euro after US stablecoin law – Financial Times

    EU speeds up plans for digital euro after US stablecoin law – Financial Times

    1. EU speeds up plans for digital euro after US stablecoin law  Financial Times
    2. The Digital Euro Revolution and Its Blockchain Backbone  OneSafe
    3. EU exploring Ethereum, Solana for digital euro launch: FT  Cointelegraph
    4. EU Accelerates Digital Euro Plans, Considering Ethereum and Solana for Public Blockchain Implementation  Bitcoin.com News
    5. Cash is king: Why does the eurozone need a digital euro?  MSN

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  • Blockchain and Digital Assets News and Trends – August 2025

    This periodic bulletin is designed to help companies identify important legal developments governing the use and acceptance of blockchain technology, smart contracts, and digital assets.

    While the use cases for blockchain technology are vast, this bulletin focuses on uses of blockchain and smart contracts in the financial services sector. With respect to digital assets, we have organized our approach to this topic by discussing them in terms of traditional asset type or function (although the types and functions may overlap) – that is, digital assets as:

    • Securities
    • Virtual currencies
    • Commodities
    • Deposits, accounts, intangibles
    • Negotiable instruments
    • Electronic chattel paper
    • Digitized assets

    In addition to reporting on the law and regulation governing blockchain, smart contracts, and digital assets, this bulletin will discuss the legal developments supporting the infrastructure and ecosystems that enable the use and acceptance of these new technologies. 

    INSIGHT

    Second Circuit vacates NFT “insider trading” conviction, clarifies property requirement for wire fraud

    By Michael Fluhr, David Stier, Eric Forni, Eric Hall

    The US Court of Appeals for the Second Circuit has vacated the conviction of Nathaniel Chastain, a former employee of non-fungible token (NFT) marketplace OpenSea, finding that the lower court improperly instructed the jury. Chastain had been convicted of wire fraud and money laundering in connection with his trading NFTs based on non-public information about which NFT collections would be listed for sale on OpenSea.

    The decision, issued on July 31, 2025, presents key legal developments regarding the scope of “property” under the federal wire fraud statute, particularly as it applies to confidential business information. In the digital asset space, however, the decision may have broader implications for the government’s ability to police insider trading of digital assets that are not securities.

    Our alert explores the outcomes of the decision and implications for digital asset stakeholders. Read more.

    STATUTORY AND AGENCY DEVELOPMENTS

    FEDERAL DEVELOPMENTS

    White House

    • President’s Working Group publishes strategy to achieve American digital asset leadership. On January 31, the President’s Working Group on Digital Asset Markets published a comprehensive report and fact sheet identifying strategic priorities for the US to foster innovation and leadership in digital assets and blockchain technology. The report describes the exponential growth of the digital asset ecosystem, including the proliferation of cryptocurrencies, stablecoins, and decentralized finance (DeFi), and calls for clear regulatory frameworks to support responsible growth, consumer protection, and market integrity. It recommends that Congress and federal agencies clarify the legal status of digital assets, enable trading at the federal level, and ensure that banking regulations are technology-neutral and do not discriminate against lawful digital asset businesses. The report urges expeditious implementation of the Guiding and Establishing National Innovation for US Stablecoins (GENIUS) Act to establish a federal framework for stablecoins, encourages the use of US dollar-backed stablecoins to strengthen the dollar’s global role, and opposes the introduction of a central bank digital currency (CBDC) in the US. It also cites a need to modernize anti-money laundering (AML) and countering the financing of terrorism (CFT) rules for digital assets, improve tax guidance and reporting for digital asset transactions, and promote international cooperation to maintain the US’s competitive edge in digital financial technology.

    Congress

    • Bankers’ associations urge Congress to address loopholes in GENIUS Act. On August 12, the American Bankers Association and bankers’ associations in all 50 states and the District of Columbia sent a letter to US Senate leaders urging legislative action to address a perceived loophole in the GENIUS Act, which regulates payment stablecoins. The associations call for Congress to strengthen the prohibition on interest payments for payment stablecoins by extending it to brokers, dealers, exchanges, and affiliates, arguing that legislation currently allows these entities to offer yield or rewards that are effectively interest payments, which they argue undermine the law and distort market incentives. Permitting these yield or reward opportunities would, in the associations’ view, lead consumers to flee from traditional bank deposits and money market funds, resulting in a reduced supply of credit. They also request the repeal of Section 16(d) of the GENIUS Act to restore state authority over out-of-state-chartered financial institutions, citing a need for states to supervise financial entities serving their residents. Additionally, the associations advocate for closing all approval pathways that would allow nonfinancial companies, both public and private, to issue payment stablecoins, citing risks to the separation of banking and commerce and potential harm to community banks and credit access. While the associations expressed their overall support for the GENIUS Act, they asserted that closing these loopholes is necessary for protecting access to credit and promoting economic stability.

    Banking regulators

    • Federal Reserve announces end of bank cryptocurrency activities supervisory program. On August 15, the Federal Reserve Board announced it will sunset its “novel activities supervision program” and return to monitoring banks’ novel activities through the normal supervisory process, including those activities related to cryptoassets, distributed ledger technology, and partnerships with nonbanks to deliver financial services to customers. The announcement rescinded the Federal Reserve’s 2023 supervisory letter that created the program.
    • FinCEN convenes public-private partnership to promote innovation and address fraud and scam risks in the digital assets ecosystem. On August 6, the US Department of the Treasury’s Financial Crimes Enforcement Network (FinCEN) announced it brought together Treasury components, law enforcement agencies, financial institutions, regulatory technology companies, and trade groups to share insights on driving innovation in the digital assets ecosystem while protecting consumers from emerging fraud and scam threats. The FinCEN Exchange event, titled “Advancing Digital Assets Innovation While Safeguarding Consumers Against Fraud and Scam Risks,” featured comprehensive discussions on industry trends in innovation, developments in fraud and scam prevention, law enforcement’s active role in deterring financial crimes facilitated by the illicit use of digital assets, and compliance best practices in the digital assets ecosystem.
    • FinCEN warns use of crypto kiosks for scams and illegal activity. On August 4, FinCEN announced the issuance of a notice urging financial institution vigilance in identifying and reporting suspicious activity involving convertible virtual currency kiosks, notably if kiosk operators fail to meet their obligations under the Bank Secrecy Act (BSA). The notice describes how such kiosks are used to facilitate scams, fraud, and money laundering, and sets forth red flag indicators of illicit activity involving crypto kiosks.
    • FinCEN postpones and reopens AML/CFT investment adviser rule. On July 21, FinCEN announced the postponement of the effective date of the final rule establishing Anti-Money Laundering/Countering the Financing of Terrorism Program and Suspicious Activity Report Filing Requirements for Registered Investment Advisers and Exempt Reporting Advisers (IA AML Rule). The IA AML Rule was originally set to take effect on January 1, 2026, but FinCEN anticipates delaying the effective date until January 1, 2028. Additionally, FinCEN announced that it would revisit the scope of the IA AML Rule through a future rulemaking process – essentially, to tailor it “to the diverse business models and risk profiles of the investment adviser sector.”
    • Credit union trade association seeks rulemaking on custody of digital assets. On July 18, America’s Credit Unions, a national credit union trade association, wrote a letter to the Chair of the National Credit Union Administration (NCUA), requesting that the NCUA “promptly initiate rulemaking to allow credit unions to take custody of digital assets for their members.” America’s Credit Unions asserted that the recently enacted GENIUS Act provided a clear mandate to advance the ability of credit unions to be able to directly safeguard members’ digital assets, noting that banks have had a competitive advantage due to bank guidance on cryptocurrency since 2021.

    SEC

    • SEC Division of Corporation Finance issues guidance on liquid staking. On August 5, the SEC Division of Corporation Finance issued a statement addressing the regulatory treatment of liquid staking activities, which the statement refers to as a type of staking whereby owners of crypto assets deposit their assets with a third-party service provider and in return receive newly “minted” (or created) crypto assets that evidence ownership of the deposited assets and any staking rewards, like a deposit receipt. The Division takes the position that when owners of crypto assets deposit them with a third-party liquid staking provider and receive staking receipt tokens in return, these activities do not constitute securities offerings under US law, provided the arrangements remain administrative and ministerial in nature. According to the Division, the value of these receipt tokens derives from the underlying assets rather than from the managerial or entrepreneurial efforts of the provider. The statement applies the Howey test to determine that such liquid staking arrangements do not involve investment contracts or securities transactions, unless the underlying assets themselves are part of an investment contract. Accordingly, staking providers and participants do not need to register these transactions with the SEC, as long as their activities conform to the Division’s view of Liquid Staking Activities and do not extend beyond administrative functions.
    • SEC Chair reveals “Project Crypto” to modernize US digital asset regulation. On July 31, the US Securities and Exchange Commission (SEC) Chair Paul S. Atkins published remarks announcing an initiative called “Project Crypto,” which he described as “the SEC’s north star in aiding President Trump in his efforts to make America the ‘crypto capital of the world.’” Chair Atkins discussed his goal to create clear, practical rules for crypto asset distributions, custody, and trading. Under Project Crypto, the SEC will develop guidelines to distinguish between digital collectibles, commodities, stablecoins, and securities, and will facilitate the “onshoring” of crypto businesses previously driven offshore by regulatory uncertainty. The SEC plans to modernize custody requirements, enable trading of both security and non-security crypto assets on regulated platforms, and support the development of “super-apps” that offer a wide range of financial products under a single license. The initiative also seeks to accommodate decentralized finance and on-chain software systems, encourage innovation through exemptions for new business models, and ensure that regulatory frameworks do not stifle technological progress or competition in the US digital asset markets.
    • SEC announces new series of crypto roundtables in several US cities. On August 1, the SEC announced that its Crypto Task Force would be hosting a series of roundtable discussions in cities across the US, following an earlier series of roundtables held in Washington, DC. The SEC expressed particular interest in inviting crypto-related projects with ten or fewer employees that are less than two years old.
    • SEC approves in-kind creations and redemptions for crypto ETPs. On July 29, the SEC announced the approval of orders permitting in-kind creations and redemptions for crypto asset exchange-traded product (ETP) shares, including bitcoin and ether ETPs. This decision departs from previous limitations on spot bitcoin and ether ETPs, which required in-cash creations and redemptions. The change aims to make crypto ETPs more efficient and cost-effective for issuers, authorized participants, and investors. In a separately published statement, SEC Commissioner Mark Uyeda praised the orders for enabling “crypto-asset ETPs to access the tools for managing exposure more cheaply, more transparently, and with better alignment to how asset managers and investors use ETPs in other markets.” The SEC also announced approval of related proposals designed to “advance a merit-neutral approach to crypto-based products,” such as the listing and trading of mixed spot bitcoin and spot ether ETPs, options on certain spot bitcoin ETPs, Flexible Exchange options on bitcoin-based ETPs, and increased position limits for listed options on bitcoin ETPs. The SEC also announced the issuance of two scheduling orders soliciting comments on additional crypto ETP proposals. 

    CFTC

    • CFTC launches crypto sprint to advance digital asset market regulation. On August 1, the Commodity Futures Trading Commission (CFTC) announced the start of a crypto sprint to implement recommendations from the President’s Working Group on Digital Asset Markets report. Acting Chair Caroline D. Pham commented that the CFTC aims to provide regulatory clarity and foster innovation in the US digital asset markets, working closely with the SEC and other stakeholders. Since January, the CFTC has engaged with industry leaders, withdrawn outdated advisories, and issued new guidance to support crypto and digital asset entrepreneurs. The agency has also explored a digital asset markets pilot program, participated in tokenization initiatives, and completed a public comment period on 24/7 trading and perpetual derivatives, both of which are now live on CFTC-registered markets.
    • CFTC launches initiative to enable spot crypto trading on regulated US exchanges. On August 4, the CFTC announced a new initiative to facilitate the trading of spot crypto asset contracts on CFTC-registered futures exchanges, known as designated contract markets (DCMs). The initiative seeks to provide regulatory clarity for listing spot crypto assets and invites public feedback by August 18. The move is part of the CFTC’s broader strategy to implement recommendations from the President’s Working Group on Digital Asset Markets and aligns with efforts to coordinate with the SEC on digital asset regulation. The CFTC emphasizes that the Commodity Exchange Act requires retail trading of commodities involving leverage, margin, or financing to occur on a DCM, and the agency now seeks input on listing spot crypto asset contracts under its existing authority, including considerations related to securities laws and the SEC’s framework for non-security digital assets. 

    GSEs

    • Fannie Mae and Freddie Mac ordered to prepare to count cryptocurrency as an asset on mortgage applications. On June 26, William Pulte, director of the Federal Housing Finance Agency, issued an order issuing directive for the agencies to consider cryptocurrency as an asset for single-family loans delivered to Fannie Mae and Freddie Mac. The order directed each agency to “prepare a proposal for consideration of cryptocurrency as an asset for reserves in their respective single-family mortgage loan risk assessments, without conversion of said cryptocurrency to US dollars.” The agencies were to consider only cryptocurrency that can be evidenced and stored on a US-regulated centralized exchange, subject to all applicable laws. Two consumer groups, the Consumer Federation of America and the National Consumer Law Center, have written Director Pulte to abandon the directive, arguing that cryptocurrencies “are notoriously volatile and offer no meaningful indication of a borrower’s long-term financial stability or ability to pay their mortgage…, expos[ing] taxpayers to increased risk of losses [and] open the door to new forms of predatory and unsafe lending targeted at vulnerable borrowers.”

    Treasury

    • FinCEN warns financial institutions of illicit activity involving virtual currency kiosks. On August 4, the US Department of the Treasury’s Financial Crimes Enforcement Network (FinCEN) issued a notice urging US financial institutions to monitor and report suspicious activity related to convertible virtual currency (CVC) kiosks, also known as cryptocurrency ATMs, which criminals increasingly use for scams, money laundering, and drug trafficking. The notice explains that CVC kiosks allow customers to exchange cash for virtual currencies such as bitcoin, ether, and stablecoins, and that scammers often direct victims to use these kiosks to send payments under false pretenses. FinCEN reports a sharp rise in fraud and losses involving CVC kiosks, with transnational criminal organizations using them to launder drug proceeds and evade traditional financial controls. The notice states non-compliant kiosk operators frequently fail to register as money services businesses, neglect AML obligations, and facilitate structuring and other illicit practices. FinCEN provides red-flag indicators for detecting suspicious CVC kiosk activity, reminds institutions of their BSA reporting requirements, and encourages information sharing to combat the growing threat of virtual currency-related financial crime.
    • Treasury seeks comments on methods to detect illicit digital asset activity. On August 18, the US Department of the Treasury published a notice requesting public input on the use of innovative or novel methods, techniques, or strategies to detect and mitigate illicit finance risks involving digital assets. The notice fulfills a requirement of the GENIUS Act and supports the Trump Administration’s policy of supporting the responsible growth and use of digital assets, as outlined in the January 23 Executive Order 14178 on “Strengthening American Leadership in Digital Financial Technology.” Treasury seeks comment on the current or potential use of the following for such purposes: application programming interfaces, artificial intelligence (AI), digital identity verification, blockchain technology, and monitoring. Consistent with the GENIUS Act, when conducting research on these and other innovative or novel methods, techniques, or strategies, Treasury will evaluate and consider:
    • Improvements in the ability of financial institutions to detect illicit activity involving digital assets
    • Costs to regulated financial institutions
    • The amount and sensitivity of information that is collected or reviewed
    • Privacy risk associated with the information that is collected or reviewed
    • Operational challenges and efficiency considerations
    • Cybersecurity risks, and
    • Effectiveness of the methods, techniques, or strategies at mitigating illicit finance.

    Comments are due on or before October 17.

    STATE DEVELOPMENTS

    Money transmission

    • State financial regulators issue guidance on virtual currency treatment under MTMA. On June 26, the Conference of State Bank Supervisors (CSBS) announced its issuance of advisory guidance on the treatment of virtual currency when calculating a licensee’s tangible net worth under the Money Transmission Modernization Act (MTMA). State supervisors and industry experts developed the MTMA to create a consistent set of nationwide standards for tangible net worth (capital), surety bond, permissible investment (liquidity with 1-for-1 reserves), and other requirements applicable to the regulation and supervision of money transmitters. The new guidance is the first issued by the CSBS and is limited to the implementation of Sections 2.01(bb) and 10.01 regarding the tangible net worth of licensees.
    • Pennsylvania modifies money transmission law to address virtual currency. On June 27, Pennsylvania Governor Josh Shapiro signed Senate Bill 202 into law, which ensures that the transmission of virtual currency is regulated the same as fiat currency under Pennsylvania’s Money Transmitter Act (MTA). Under the new law, referred to as the Money Transmission and Virtual Currency Transmission Business Licensing Law, entities that facilitate the transfer of virtual currency for a fee will be required to meet the same licensure standards as other money transmitters. The law also modernizes key elements of the MTA, including definitions, licensing requirements, exemptions, and oversight provisions.

    ENFORCEMENT ACTIONS AND LITIGATION

    FEDERAL

    SEC

    • SEC issues cease-and-desist order against MyConstant founder for fraudulent crypto-backed lending scheme. On August 5, the SEC issued an order settling charges against Huynh Tran Quang Duy, founder and sole owner of the online lending platform MyConstant, for making material misrepresentations and misappropriating investor funds in connection with crypto-backed loans. The SEC found that from September 2020 through November 2022, Duy falsely promoted MyConstant’s loan matching service as a low-risk, crypto-collateralized investment offering returns up to 10 percent per annum. According to the order, MyConstant raised over $20 million from more than 4,000 investors, most of whom resided in the US and used investor funds to purchase at least $11.9 million of the cryptocurrency TerraUSD (UST) in personal accounts – resulting in losses of nearly $8 million when UST collapsed. Duy further diverted approximately $415,000 for personal use. The order requires Duy to cease and desist from further violations, pay over $8.3 million in disgorgement, $1.5 million in prejudgment interest, and a $750,000 civil penalty. 

    DOJ

    • Crypto influencer sentenced for defrauding cloud computing providers in cryptojacking scheme. On August 15, the US Attorney’s Office for the Eastern District of New York announced that Charles O. Parks III, also known as “CP3O,” received a sentence of one year and one day in prison for orchestrating a large-scale cryptojacking operation. Parks used fraudulent identities and false statements to obtain over $3.5 million in cloud computing services from two major providers, which he exploited to mine nearly $1 million in cryptocurrency, including Ether, Litecoin, and Monero. He laundered the proceeds through cryptocurrency exchanges, an NFT marketplace, and traditional financial channels, then converted the digital assets into cash for luxury goods. Parks promoted himself as a crypto influencer on social media, boasting about his illicit profits and offering advice based on his fraudulent activities. The court ordered him to forfeit $500,000 and a luxury car, with restitution to be determined later.
    • CEO indicted for misappropriating startup funds in cryptocurrency and online gambling scheme. On August 13, the US Attorney’s Office for the Southern District of New York announced the indictment of Richard Kim, former CEO of Zero Edge Corporation, for defrauding investors of approximately $4.3 million by falsely promising to develop a blockchain-based casino gaming app. Kim founded Zero Edge in March and represented to investors that their funds would support the development of on-chain casino games using blockchain and cryptocurrency technologies. Instead, Kim diverted about $3.8 million of the seed round funding into personal cryptocurrency accounts at multiple centralized exchanges and transferred significant amounts to another online crypto casino and other unknown wallets. Kim admitted to investors that he lost nearly all the company’s money through leveraged cryptocurrency trading and gambling and later acknowledged to the Federal Bureau of Investigation (FBI) that his actions were “completely unjustifiable.” The indictment charges Kim with securities fraud and wire fraud, each carrying a maximum sentence of 20 years in prison.
    • Estonian nationals sentenced for $577 million cryptocurrency Ponzi scheme. On August 12, the US Attorney’s Office for the Western District of Washington announced that two Estonian nationals, Sergei Potapenko and Ivan Turogin, received 16-month prison sentences for orchestrating a global cryptocurrency Ponzi scheme through their company, HashFlare. Between 2015 and 2019, HashFlare sold contracts to customers worldwide, falsely promising profits from cryptocurrency mining, while lacking the computing capacity to generate the claimed returns. Potapenko and Turogin collected over $577 million from victims and used the funds to acquire luxury vehicles, real estate, and pay out earlier investors. Authorities seized assets valued at over $450 million, including cryptocurrency, real property, and mining equipment, which will be used to compensate victims through a forthcoming remission process. The case involved significant international cooperation. Despite the sentences, DOJ had argued for longer prison terms and is considering an appeal.
    • Terraform Labs co-founder Do Kwon pleads guilty to cryptocurrency fraud. On August 12, the US Attorney’s Office for the Southern District of New York announced that Do Kwon, co-founder and former CEO of Terraform Labs, had pled guilty to multiple counts of fraud related to the collapse of the Terra blockchain ecosystem, which resulted in over $40 billion in investor losses. Kwon admitted to conspiring to commit commodities fraud, securities fraud, and wire fraud, as well as executing wire fraud, all in connection with Terraform’s suite of digital asset products, including the algorithmic stablecoin TerraUSD (UST) and the LUNA token. Prosecutors described how Kwon misrepresented the stability and functionality of Terraform’s blockchain technology, manipulated markets to artificially support UST’s $1 peg, and falsely claimed real-world adoption of the Terra blockchain for payment processing. Kwon also controlled and misused the Luna Foundation Guard’s cryptocurrency reserves and manipulated synthetic asset prices on Terra’s Mirror Protocol, despite claiming that the DeFi platform was decentralized. As part of his plea, Kwon agreed to forfeit over $19 million in proceeds and faces up to 25 years in prison, with sentencing scheduled for December 11.
    • Samourai Wallet founders plead guilty to laundering over $200 million in cryptocurrency. On August 6, the US Attorney’s Office for the Southern District of New York announced that Keonne Rodriguez and William Lonergan Hill, the CEO and CTO of Samourai Wallet, pled guilty to operating a money transmitting business that processed more than $200 million in criminal proceeds using cryptocurrency. Rodriguez and Hill developed and managed Samourai Wallet, a mobile application that provided two key services: (1) Whirlpool, a Bitcoin mixing service, and (2) Ricochet, a transaction obfuscation tool. Both were designed to conceal the origins and destinations of digital assets. The founders promoted these services to facilitate the laundering of funds from illegal activities, including dark web transactions, cyber intrusions, and fraud schemes, and actively encouraged criminals to use their platform. From 2017 to 2019, over 80,000 Bitcoin, valued at more than $2 billion at the time, passed through these services, generating over $6 million in fees for Samourai. Rodriguez and Hill each face a maximum sentence of five years in prison and agreed to forfeit more than $237 million as part of their plea agreements.
    • Cryptocurrency CEO sentenced to seven years for multi-million-dollar fraud. On July 29, the US Attorney’s Office for the Northern District of California announced that Rowland Marcus Andrade, founder and CEO of AML Bitcoin, received an 84-month federal prison sentence for wire fraud and money laundering related to a fraudulent cryptocurrency scheme. Andrade misled investors by making false claims about the development, viability, and business prospects of AML Bitcoin, including fabricating a potential agreement with the Panama Canal Authority. He raised approximately $10 million from investors, diverted over $2 million for personal use – including luxury cars and Texas real estate – and laundered funds through multiple bank accounts.
    • Arizona man pleads guilty to laundering cryptocurrency in $13 million Ponzi scheme. On July 28, DOJ announced that Vincent Anthony Mazzotta Jr. pleaded guilty to money laundering and conspiracy to obstruct justice for his role in a $13 million cryptocurrency Ponzi scheme. Mazzotta, along with co-defendant David Saffron, promised investors high-yield returns from cryptocurrency trading using automated trading robots powered by AI, operating through companies such as Mind Capital and Cloud9Capital. The conspirators created a fictitious government entity, the Federal Crypto Reserve, to further deceive victims and solicit additional funds under the pretense of investigating the disappearance of their investments. Mazzotta also worked with others to destroy evidence and falsify business records to conceal his involvement. He faces up to ten years in prison for money laundering, and up to five years for conspiracy to obstruct justice.
    • DOJ seeks forfeiture of $7.1 million in cryptocurrency linked to oil and gas investment fraud. On July 22, the US Attorney’s Office for the Western District of Washington announced a civil action to forfeit approximately $7.1 million in cryptocurrency seized during an investigation into an oil and gas storage investment fraud scheme. The scheme, which operated from at least August 2022 through August 2024, defrauded victims of about $17.9 million by convincing them to invest in purported oil tank storage opportunities, then moving the funds through various financial and cryptocurrency accounts. The perpetrators used cryptocurrencies such as Bitcoin, Tether, USD Coin, and Ether, transferring assets through at least 19 different cryptocurrency accounts, and ultimately moving much of the funds to a centralized exchange. Investigators traced the cryptocurrency to wallets and exchanges associated with Russian and Nigerian IP addresses, some of which have connections to money laundering for transnational criminal organizations. The government intends to distribute the forfeited cryptocurrency, in addition to $2.3 million previously seized from a US-based co-conspirator, to the identified victims of the fraud. 

    FINRA

    • FINRA fines firm for violations of crypto rules. On July 28, the Financial Industry Regulatory Authority (FINRA) accepted the Letter of Acceptance, Waiver, and Consent (AWC) submitted by TradeStation Securities, Inc., an online trading platform and a FINRA member. The AWC settles alleged rule violations concerning retail communications related to crypto assets. According to the AWC, the firm’s communications allegedly failed to clearly disclose that crypto assets were not offered through a registered broker-dealer, and also allegedly failed to provide a fair and balanced presentation of the benefits and risks of the crypto asset products. TradeStation Securities agreed to pay an $85,000 fine, without admission or denial of FINRA’s allegations. 

    Money transmission

    • Connecticut man admits operating illegal money transmitting business. On July 21, the US Attorney’s Office for the District of Connecticut announced that William McNeilly pleaded guilty to charges related to his operation of an unlicensed money transmitting business. McNeilly owned and operated Global Income Marketplace LLC and Global NuMedia LLC (GNM) and opened a cryptocurrency exchange account in the name of GNM – exchanging more than $1 million worth of customers’ cash, checks, and money orders for cryptocurrency. McNeilly never obtained the necessary money transmission license from the Connecticut Department of Banking. McNeilly faces a maximum prison term of 35 years on the charges. 

    FTC

    • Former CEO of Voyager Digital agrees to ban and a $2.8 million payment to resolve FTC charges. On June 27, the Federal Trade Commission (FTC) announced a proposed settlement with Stephen Ehrlich, the former CEO of crypto platform Voyager Digital, on charges that Ehrlich falsely promised that consumers’ deposits were FDIC-insured, and those deposits “would be as sage with us as at a bank.” Nonetheless, the deposits were not insured, and Voyager customers lost more than $1 billion in cryptocurrency when the company failed. The proposed settlement requires Ehrlich to pay $2.8 million and prohibits Ehrlich from marketing or selling retail products or services used to buy, sell, deposit, or trade crypto, among other activities. The FTC previously settled with Voyager in November 2023.  

    NFTs

    • NFTs can be trademarked. In Yuga Labs, Inc. v. Ryder Ripps; Jeremy Cahen (No. 24-879 DC No. 2:22-cv-04355-JFW-JEM, 9th Cir. Ct. App., July 23, 2025), the Ninth Circuit ruled that NFTs can be trademarked under the Lanham Act as they are considered “goods.” The court affirmed in part and reversed in part the district court’s judgment, and remanded the case for further proceedings, in an action under the Lanham Act and the Anticybersquatting Consumer Protection Act.

      The case concerns the popular Bored Ape Yacht Club (BAYC) NFT collection, created by plaintiff, Yuga Labs. Each BAYC NFT is associated with a unique cartoon Bored Ape. BAYC NFT owners obtain not only certain rights to the art, but also a collection of benefits and functionalities, including access to interactive digital spaces, branded merchandise, and online events. Defendants created a nearly identical NFT collection called Ryder Ripps Bored Ape Yacht Club. NFTs in defendants’ collection were associated with the exact same cartoons as BAYC NFTs.

      Yuga sued defendants in the US District Court for the Central District of California, asserting a variety of claims, including trademark infringement under the federal Lanham Act. Defendants asserted numerous defenses, including that Yuga lacks enforceable trademark rights and that use of Yuga’s marks was protected as nominative fair use and under the First Amendment. Defendants also countersued, including for violation of the Digital Millennium Copyright Act, alleging that Yuga made misrepresentations in certain takedown notices to third-party platforms.

      The district court dismissed defendants’ declaratory judgment counterclaims for lack of subject matter jurisdiction and granted summary judgment for Yuga on its two claims and on defendants’ DMCA counterclaim. The district court then held a bench trial on remedies, enjoined defendants from infringing Yuga’s marks, and awarded Yuga over $8M for disgorgement of profits, statutory damages, attorneys’ fees, and costs.

      On appeal, the Ninth Circuit reversed the district court’s grant of summary judgment for Yuga on its Lanham Act claims. The court rejected defendants’ arguments that Yuga lacked ownership in protectable marks, finding that NFTs are “goods” protected by the Lanham Act, and rejected defendants’ argument that Yuga no longer has ownership of the marks by virtue of conferring ownership of associated art to NFT holders. The court reasoned that such ownership of art did not convey a license to a trademark embodied therein, nor did holders’ use or ownership of NFTs suggest that the incorporated marks act as a source identifier for each holder.

      The court also rejected as a matter of law that defendants could show a nominative fair use, as they used the mark to refer to Yuga’s NFTs (rather than their own NFTs). The court also rejected defendants’ First Amendment argument, holding that defendants used Yuga’s marks as source identification, not protected expression.

      On the multi-factor test for likelihood of confusion, the court held triable issues of fact remained and remanded the case for further proceedings. 

    SPOTLIGHT ON INTERNATIONAL DEVELOPMENTS

    • UK HM Treasury issues cryptoassets threat assessment. On July 21, the UK HM Treasury Office of Financial Sanctions Implementation (OFSI) published a Cryptoassets Threat Assessment, addressing threats to UK financial sanctions compliance from January 2022 to May 2025. OFSI’s “key judgements” from the report include:
    • It is “almost certain” that UK cryptoasset firms “under-reported suspected breaches of financial sanctions to OFSI”
    • It is “likely” that most non-compliance by UK cryptoasset firms has occurred inadvertently due to common issues such as suspected breaches being identified after a delay in attribution, with attribution delays also contributing to failures to implement an asset freeze
    • It is “highly likely” that UK cryptoasset firms have been directly or indirectly exposed to the designated Russian exchange Garantex since its designation in 2023, resulting in breaches of UK financial sanctions
    • It is “highly likely” that UK-based cryptoasset firms are currently at risk of being targeted by DPRK-linked hackers and IT workers seeking to steal or obtain funds through illicit means
    • It is “likely” that UK cryptoasset firms are currently facilitating transfers to Iranian cryptoasset firms with suspected links to designated persons
    • Hong Kong publishes regulations for stablecoin issuers. On July 29, the Hong Kong Monetary Authority (HKMA) announced publication of documentation for the implementation of the regulatory regime for stablecoin issuers, which took effect on August 1. The documentation comprises guidance on supervision of licensed stablecoin issuers, transitional provisions for pre-existing stablecoin issuers, and compliance with AML and CFT. 

    DLA PIPER NEWS

    • The Financial Times recognizes DLA Piper as one of the Most Innovative Law Firms in North America.
    • The Legal 500 ranks DLA Piper Tier 1 in FinTech: Crypto. DLA Piper was also ranked in Tier 2 for FinTech, and Margo Tank was ranked as a “Leading Individual.”
    • Chambers FinTech Legal ranks DLA Piper in four categories including Band 2 for Blockchain and Digital Assets, and Band 3 for Payments and Lending, with Margo Tank individually recognized in Blockchain and Digital Assets and Payments and Lending.
    • DLA Piper’s Commodities, Digital Assets, and Carbon Compliance and Enforcement team draws on decades of collective experience in the commodities and securities industry to help companies navigate new and complex commodities enforcement matters, including those related to agriculture, metals, energy, digital assets, and carbon/sustainable commodities, among others.

    RECENT AND UPCOMING EVENTS

    • Era Anagnosti will moderate a panel discussion on Crypto Treasury Strategies: What You Should Know on September 18, at 12pm EST, hosted by Deal Flow Events. The panel will discuss treasury strategies regarding various types of digital assets, including objectives and key considerations, measuring performance, deal structures, capital formation, regulatory and governance considerations, microcaps and exchange-traded funds (ETFs).

    PUBLICATIONS

    • DLA Piper published its global financial services report, Financial Futures: Disruption in US and Global Financial Services, after asking nearly 800 financial services decision-makers around the world about key disruptors impacting senior leaders in financial institutions and fintechs. Access our report and read about the challenges and opportunities that AI; digitization; and environmental, social and governance (ESG) pose for the financial services industry.
    • In the book, Banking [on] Blockchain: A Legal and Regulatory Primer, published by the American Bar Association, David Stier, Emily Honsa Hicks, and Eric Hall co-authored a chapter on anti-money laundering (AML)/know your customer (KYC) requirements and the Bank Secrecy Act (BSA), as well as provided general editorial assistance on other chapters. The book is a comprehensive guide to the legal and regulatory landscape surrounding the use of blockchain technology, decentralization, and digital assets within the financial services, and offers guidance on how financial institutions may navigate the complex regulatory environment.
    • Cryptocurrency and Digital Asset Regulation, published by the American Bar Association and co-edited by Deborah Meshulam and Michael Fluhr, includes chapters by Meshulam, Fluhr, and Margo Tank.

    LISTEN

    Digital Transformation – The never-ending journey. Digital transformation is more than a trend – it’s a continuous journey. Our Tech Index 2024 looks at the rise of blockchain to the advancements in AI and the potential of quantum computing – the evolution never stops. Organizations are encouraged to adapt and lead the way in this ever-changing landscape. Mark O’Conor, Paul Allen, and Chloe Forster take a deep dive into digital transformation.

    READ

    “Fair banking” Executive Order targets politicized debanking and reputational risk

    Digital Asset Market Clarity Act: The increasing role of the CFTC in regulating crypto markets

    Digital Transformation: eSignatures and ePayments News and Trends

    Market Edge – covering SEC developments for publicly traded companies 

    Digital Digest addresses the growing challenges faced by the UK commercial and financial sector due to the increasing number of laws, regulations, and market practices affecting the digital and crypto industry.

    Contacts

    Learn more about our Blockchain and Digital Assets practice by contacting any of our editors:

    Margo Tank
    Michael Fluhr
    Liz Caires
    Eric Hall

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    Rupee declines 11 paise to 87.36 against US dollar in early trade – Deccan Herald

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    2. Indian rupee to rise at open on soft dollar, favourable momentum  Business Recorder
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    4. Rupee continues slide on looming US tariffs, posts marginal weekly loss  Reuters
    5. Indian Rupee slumps amid cautions ahead of Fed Powell’s speech  FXStreet

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  • DLA Piper secures major victory for Personal Care Product Council

    DLA Piper obtained a major victory on behalf of client Personal Care Products Council (PCPC), the largest trade association for cosmetics and personal care companies, in the US District Court for the Eastern District of California.

     

    In 2023, DLA Piper filed a complaint on behalf of PCPC challenging on First Amendment grounds the Proposition 65 warning mandate for exposure to titanium dioxide (TiO2), a commonly used ingredient in cosmetics and drugs.

     

    Last year, the Court granted a preliminary injunction, after which DLA Piper filed for summary judgment. On Tuesday, August 12, the court granted the motion for summary judgement and entered a permanent injunction.

     

    The Court held that the State could not show TiO2 caused cancer in humans, there was considerable debate about whether even high doses of TiO2 could cause cancer, and a Proposition 65 warning for TiO2 exposure would give consumers the false impression that products containing TiO2 were harmful.

     

    “The decision is a considerable victory for the cosmetics industry and all businesses challenged by Proposition 65’s onerous warning requirements for ingredients listed, without adequate evidence of harm, as carcinogens or reproductive toxins under Proposition 65,” said Partner Greg Sperla, who led the DLA Piper team that advised PCPC.

     

    In addition to Sperla, the team also included Associate Erin Heiferman (both San Francisco).

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