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Type 2 diabetes mellitus with chronic kidney disease benefits from long-term restriction of dietary protein intake: a 10-year retrospective cohort study | BMC Nutrition

Results of the T2DM with CKD cohort

Baseline data characteristics

As demonstrated in Supplementary Fig. 1, which outlines the pre-PSM screening process, 856 patients were preliminarily assessed, with 36 subsequently excluded. Exclusions were 21 cases of co-infection, 10 cases of concomitant malignant tumors, and 5 patients with thyroid disease or cirrhosis. Ultimately, 820 patients were included in the final analysis. Over an average follow-up period of 33.36 months, 277 patients reached the study endpoint (initiation of dialysis, progression to ESRD, renal transplant, serum creatinine doubling, cardiovascular and cerebrovascular diseases). These included 172 patients who progressed to ESRD, 58 patients with a 50% decline in eGFR from baseline, and 47 patients who experienced major cardiovascular or cerebrovascular events.

PSM analysis of the T2DM with CKD cohort

As shown in Supplementary Fig. 2, variables matched using propensity scores included key clinical characteristics such as sex, age, baseline SCr, and UACR. Matching was performed in a 1:1:1 ratio with a caliper value of 0.2. The balance of propensity scores across the three dietary regimen groups was evaluated using a multi-balance test.

Following 1:1:1 matching, a total of 168 patients were divided into three groups with different DPI_sUCR levels in the final analysis, as shown in Fig. 1. After an average follow-up period of 32.94 months, 53 patients reached the study endpoint. Among them, 34 progressed to end-stage renal disease, 13 experienced a 50% reduction in eGFR from baseline, and 6 had cardiovascular or cerebrovascular events. The enrollment process is detailed in Fig. 1.

In the original cohort, baseline characteristics such as gender, age, and eGFR showed significant differences among the three groups. However, after matching, these differences were balanced, as detailed in Table 1. For instance, the baseline ages of the three groups were [57.50 (50.00, 63.00) vs. 57.00 (51.75, 62.00) vs. 55.50 (50.50, 62.00) years, P = 0.672], and baseline renal function (eGFR) values were [46.89 (34.15, 73.23) vs. 55.85 (37.70, 79.26) vs. 51.98 (34.80, 90.05) ml/min/1.73 m², P = 0.548]. Other baseline characteristics also achieved balance.

Table 1 Demographic and biochemical characteristics of enrolled T2DM with CKD patients before and after propensity score matching

Baseline utilization rates of renoprotective medications were comparable across CKD stages (Table 1). Among patients with CKD stages 1–3, RAS inhibitors (RASi) were the most commonly prescribed medications, followed by SGLT2 inhibitors (SGLT2i), mineralocorticoid receptor antagonists (MRAs), and GLP-1 receptor agonists (GLP-1 analogues), both before and after PSM. In CKD stage 4, the proportions of medication use were similar. Statistical comparisons revealed no significant differences in medication use between CKD stages 1–3 and stage 4 (all p > 0.05; Chi-square tests).

Fig. 1

Flowchart of patients in the T2DM with CKD cohort after propensity score matching. Abbreviation: DPI_sUCR dietary protein intake based on sUCR equation

Real-world prognosis analysis of DPI_sUCR formula in T2DM with CKD cohort

In the matched cohort, we used the Kaplan-Meier curve to assess the relationship between three different DPI_sUCR levels and all-cause mortality. As shown in Fig. 2a, the survival curve for patients in the LPD group (DPI_sUCR <0.8 g/kg·d), calculated using the DPI_sUCR formula, was superior to that of the higher-protein diet group (DPI_sUCR >1.0 g/kg·d). Additionally, Fig. 2b illustrates that for CKD stages 3–4 patients, the survival curve for the low-protein diet group (DPI_sUCR <0.8 g/kg·d) remained better over time compared to the higher-protein group (DPI_sUCR >1.0 g/kg·d), with statistically significant results. To assess whether significant survival differences existed among patients in different dietary protein groups (based on DPI_sUCR), we performed both univariate and multivariate Cox regression analyses (Supplementary Table 1). The univariate Cox analysis revealed that, compared to patients with DPI_sUCR >1.0 g/kg·d, those with DPI_sUCR <0.8 g/kg·d had a 44% lower risk. After adjusting for age, sex, smoking history, SBP, HbA1c, Alb, UA, LDLC, and eGFR in the multivariate Cox regression analysis, the risk for patients with DPI_sUCR <0.8 g/kg·d was reduced by 54% compared to those with DPI_sUCR >1.0 g/kg·d.

After PSM, patients with DPI_sUCR <0.8 g/kg·d had a 56% lower risk of reaching the endpoint compared to those with DPI_sUCR >1.0 g/kg·d in the univariate Cox analysis. With further adjustments for age, sex, smoking history, HbA1c, eGFR, UA, and LDLC in the multivariate Cox analysis, the risk for patients with DPI_sUCR <0.8 g/kg·d was reduced by 63% compared to those with DPI_sUCR >1.0 g/kg·d.

Subgroup analysis

In this study, we explored heterogeneity by conducting subgroup analyses of both original and propensity score-matched cohorts. As illustrated in Fig. 3(a-b), subgroup analyses were stratified by gender, age, comorbidities, SBP, HbA1c, Alb, UACR, eGFR, DPI_sUCR, and other indicators, integrating results from univariable Cox analyses (Supplementary Table 1) with clinical risk factors. Before matching, subgroups with significantly lower risks (HR < 1) included: Female patients (HR 0.70, 95% CI 0.53–0.91; p = 0.009), Age ≥ 60 years (HR 0.69, 95% CI 0.51–0.92; p = 0.012) and Alb ≥ 30 g/L (HR 0.57, 95% CI 0.40–0.80; p = 0.001). Subgroups with elevated risks (HR > 1) were: UACR ≥ 300 mg/g (HR 2.79, 95% CI 1.97–3.95; p < 0.001), eGFR 30–59 ml/min/1.73 m² (HR 1.71, 95% CI 1.23–2.23; p = 0.002), eGFR < 30 ml/min/1.73 m² (HR 5.54, 95% CI 3.79–8.10; p < 0.001) and DPI_sUCR >1.0 g/kg·d (HR 1.48, 95% CI 0.91–2.41; p < 0.001). After matching, the risk associations were further refined. Protective subgroups (HR < 1) were: Female (HR 0.29, 95% CI 0.13–0.67; p = 0.004) and Alb ≥ 30 g/L (HR 0.35, 95% CI 0.15–0.82; p = 0.015). High-risk subgroups (HR > 1) were: HbA1c ≥ 7.0% (HR 2.41, 95% CI 1.09–5.31; p = 0.029), UACR ≥ 300 mg/g (HR 5.14, 95% CI 1.88–14.02; p = 0.001), eGFR < 30 ml/min/1.73 m² (HR 11.58, 95% CI 4.51–29.75; p < 0.001) and DPI_sUCR >1.0 g/kg·d (HR 3.53, 95% CI 1.54–8.09; p = 0.003). Notably, male patients and those with Alb < 30 g/L, UACR ≥ 300 mg/g, eGFR < 30 ml/min/1.73 m², and DPI_sUCR >1.0 g/kg·d consistently exhibited poorer prognosis in both cohorts (p < 0.05). The strengthened hazard ratios (e.g., eGFR < 30 subgroup increased from HR = 5.54 to 11.58) and narrower confidence intervals post-matching suggest improved estimation precision, reinforcing these factors as robust independent prognostic markers.

Fig. 2

Kaplan-Meier survival curves for the Composite Endpoint, grouped by DPI_sUCR levels. a: Kaplan-Meier curve for the Composite Endpoint within all T2DM with CKD patients. b: Kaplan-Meier curve for the Composite Endpoint within CKD 3 ~ 4 patients. Abbreviation: DPI_sUCR dietary protein intake based on sUCR equation; T2DM type 2 diabetes mellitus; CKD chronic kidney disease

Fig. 3

The subgroup analysis in T2DM CKD patients with DPI_sUCR equation. The subgroup analyses were conducted using a stratified Cox proportional-hazards re-gression model across various subgroups. a: Subgroup analyses of primary T2DM with CKD cohort. b: Subgroup analyses of T2DM with CKD cohort after PSM. Abbreviation: SBP systolic blood pressure, HGB hemoglobin, eGFR estimated glomerular filtration rate, DPI_sUCR dietary protein intake based on sUCR equation, UA uric acid, LDLC low-density lipoprotein, HbA1c, glycated hemoglobin, UACR urine albumin to creatinine ratio; T2DM type 2 diabetes mellitus; CKD chronic kidney disease; PSM propensity score matching

To balance the influence of time-related variables, we incorporated time-averaged parameters including TA-DPI_sUCR and TA-eGFR into the analysis, as shown in Fig. 4(a-b). Subgroup analyses revealed distinct prognostic patterns across cohorts. In the original unmatched cohort, female sex demonstrated protective effects (HR 0.73, 95% CI 0.56–0.94; p = 0.017), while elevated risks were observed in subgroups with TA-eGFR 30–59 ml/min/1.73 m² (HR 2.18, 95% CI 1.50–3.15; p < 0.001) and TA-eGFR < 30 ml/min/1.73 m² (HR 12.28, 95% CI 8.65–17.45; p < 0.001). Following PSM, the risk stratification intensified significantly. The protective association with female sex became more pronounced (HR 0.29, 95% CI 0.13–0.61; p = 0.001). High-risk subgroups now included both TA-DPI_sUCR and TA-eGFR categories: TA-eGFR 30–59 ml/min/1.73 m² (HR 3.09, 95% CI 1.25–7.68; p = 0.015), TA-eGFR < 30 ml/min/1.73 m² (HR 21.53, 95% CI 8.14–56.98; p < 0.001), TA-DPI_sUCR 0.8–1.0 g/kg·d (HR 2.73, 95% CI 1.35–5.53; p = 0.022) and TA-DPI_sUCR >1.0 g/kg·d (HR 3.03, 95% CI 1.17–7.83; p = 0.022). This matched analysis revealed a striking dose-response relationship between proteinuria severity (TA-DPI_sUCR) and adverse outcomes, while confirming the critical prognostic value of sex and renal dysfunction (TA-eGFR) thresholds. The results from both the original and matched cohorts indicated that the prognosis was worse in the subgroup of males with eGFR < 30 ml/min/1.73 m², and DPI_sUCR >1.0 g/kg·d.

Results of the NHANES cohort

Baseline data characteristics

The flowchart of enrolled patients is detailed in Supplementary Fig. 3 to show the inclusion process before PSM. This study initially screened 101,316 patients and excluded 99,593 patients, consisting of 43,737 patients who were younger than 18 years or older than 80 years, 3,545 patients with incomplete weight and height data, and 3,399 patients with incomplete urea nitrogen or creatinine values. Additionally, 48,392 patients were excluded due to missing 24-hour dietary review data or having two dietary protein intakes at the same level, 173 patients with an eGFR < 15 ml/min/1.73 m² or who had started dialysis at enrollment, and 347 patients who died of malignant tumors. Ultimately, 1,723 patients were included in the analysis.

Fig. 4

Time-average subgroup analysis in patients with T2DM with CKD with the DPI_sUCR equation. a: Time-average analyses of the primary T2DM with CKD cohort. b: Time-average analyses of the T2DM with CKD cohort after PSM. Abbreviation: TA-DPI_sUCR time average dietary protein intake based on sUCR equation; TA-eGFR time average esti-mated glomerular filtration rate; T2DM type 2 diabetes mellitus; CKD chronic kidney dis-ease; PSM propensity score matching

Participants were grouped based on their DPI_sUCR levels, with 694, 811 and 218 patients in three groups respectively. After an average follow-up period of 87.63 months, a total of 489 patients reached the observation endpoint (heart diseases, cerebrovascular diseases and all-cause mortality), which included 190 patients with heart disease and 29 patients with cerebrovascular disease as the cause of death.

PSM analysis of the NHANES cohort

As shown in Supplementary Fig. 4, variables matched among the three dietary regimen groups included key clinical characteristics such as sex, age and baseline SCr. The balance of these characteristics across the three groups was assessed using a multi-balance test.

After matching, a total of 390 patients were included in the final analysis. With an average follow-up period of 87.19 months, 121 patients reached the study endpoint, including 46 patients developed heart disease, 6 patients experienced cerebrovascular events, and the rest with other causes. The enrollment process is detailed in Fig. 5.

In the original cohort, significant differences in baseline characteristics such as gender, age, and eGFR were observed among the three groups. However, after matching, these differences were balanced, as detailed in Table 2. For example, the baseline ages of the three groups were [73.00 (66.00, 78.75) vs. 72.50 (65.25, 79.00) vs. 73.00 (65.00, 80.00) years, P = 0.925], and baseline renal function (eGFR) values were [52.03 (44.62, 57.23) vs. 52.17 (42.70, 57.53) vs. 51.69 (39.69, 59.18) ml/min/1.73 m², P = 0.995]. Other baseline characteristics also showed balance.

Table 2 Demographic and biochemical characteristics of enrolled NHANES participants before and after propensity score matching

Fig. 5

Flowchart of the NHANES enrolled participants after propensity score matching. Abbreviation: DPI_sUCR dietary protein intake based on sUCR equation

Real-world prognosis analysis of DPI_sUCR equation in CKD 1 ~ 4 patients

In the matched cohort, Kaplan-Meier survival analysis was applied to evaluate the relationship between different DPI_sUCR levels and all-cause mortality. As shown in Fig. 6a, patients in the restricted protein diet group (DPI_sUCR < 0.8 g/kg·d) exhibited a better survival curve compared to those in the higher protein intake group (DPI_sUCR > 1.0 g/kg·d). Specifically, in patients with CKD stage 3 (Fig. 6b), the survival curve of the restricted protein group (DPI_sUCR < 0.8 g/kg·d) was significantly better than that of the higher protein intake group (DPI_sUCR > 1.0 g/kg·d) over time. However, in CKD patients with diabetes (Fig. 6c), although the survival curve of the restricted protein group appeared better, the difference did not reach statistical significance.

To further validate the robustness of these findings, univariate Cox regression analysis was performed on the cohorts before and after matching as presented in Supplementary Table 2. Before matching, patients with DPI_sUCR < 0.8 g/kg·d had a 63% reduction in all-cause mortality compared to those with DPI_sUCR > 1.0 g/kg·d. After adjusting for confounding factors such as age, sex, smoking history, diabetes status, SBP, HbA1c, Alb, UA, CHOL and HDLC, the mortality reduction was 47% for patients with DPI_sUCR < 0.8 g/kg·d compared to those with DPI_sUCR > 1.0 g/kg·d.

In the matched cohort, after correcting for variables such as age, sex, smoking history, HbA1c, eGFR, UA, and HDLC, patients with DPI_sUCR < 0.8 g/kg·d had a 50% lower risk of all-cause mortality compared to those consuming more than 1.0 g/kg·d of dietary protein.

Fig. 6

The prognostic analysis of different DPI in CKD patients with DPI_sUCR equation. a: Kaplan-Meier curve for the Composite Endpoint within all CKD patients. b: Kaplan-Meier curve for the Composite Endpoint within CKD stage 3 patients. c: Kaplan-Meier curve for the Composite Endpoint within DKD patients. Abbreviation: DPI_sUCR dietary protein intake based on sUCR equation

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July 5, 2025
Shorter days ahead? Why Earth might spin faster on 3 days in July and August – Firstpost

Should we expect shorter days soon?

The Earth is likely to spin slightly faster in July and August, which could lead to shorter days.

Notably, the Earth completes a little more than 365 full spins on its axis each year. That is the total number of days we have in a year.

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However, it was not always like this. Some studies show that in the past, Earth took between 490 and 372 days to complete one trip around the Sun.

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So, which days in July and August might be the shortest? And what is the reason behind this change?

Let’s take a look:

Why and when Earth is predicted to spin faster

A scientist has warned that Earth’s rotation is speeding up unexpectedly, with the shortest day in history possibly just weeks away.

Graham Jones, an astrophysicist from the University of London, said the Earth’s spin may increase slightly on three specific days, July 9, July 22, and August 5, he told Daily Mail.

The difference will be very small, measured only in milliseconds.

On these days, the length of a day might drop by 1.30, 1.38, or 1.51 milliseconds, one after the other.

Experts say that even a slight change can impact satellite systems, GPS accuracy, and how we keep track of time.

The Earth is likely to spin slightly faster in July and August, which could lead to shorter days. Pixabay/Representational Image

Leonid Zotov, a researcher at Moscow State University, said: “Nobody expected this, the cause of this acceleration is not explained.”

Since 2020, scientists have observed the Earth turning slightly quicker than usual, but they are still unsure why this is happening.

Earlier, the planet had been slowing down gradually, mainly due to the moon’s pull, which over time helped shape our current 24-hour days.

Typically, the Earth takes 24 hours, or exactly 86,400 seconds, to complete one full spin, known as a solar day.

Judah Levine, a physicist at the National Institute of Standards and Technology, told Discover Magazine in 2021, “This lack of the need for leap seconds was not predicted.”

“The assumption was, in fact, that Earth would continue to slow down and leap seconds would continue to be needed. And so this effect, this result, is very surprising.”

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If the Earth keeps rotating faster, timekeepers might need to make changes to official time, which could include removing a leap second for the first time ever in 2029.

Why is Earth spinning faster?

The Earth’s rotation is not perfectly steady. It can shift by a few milliseconds now and then.

This happens because natural forces, such as earthquakes and ocean movements, can change the planet’s spin slightly.

Other reasons include melting glaciers, changes in Earth’s molten core, and weather patterns like El Nino, which can either slow down or speed up rotation by small amounts.

Scientists use atomic clocks to track these tiny changes with high precision. The recent increase in spin has caught many of them off guard.

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Is Earth’s core leaking gold and other precious metals to the surface?

According to reports, the fastest day so far was on July 5, 2024, when the Earth spun 1.66 milliseconds faster than the usual 24 hours.

Earthquakes are also known to affect the planet’s rotation. In March 2011, a magnitude 9.0 earthquake near Japan shifted the Earth’s axis and slightly shortened the length of a day.

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The Earth’s rotation is not perfectly steady. It can shift by a few milliseconds now and then. Pixabay/Representational Image

Dr Richard Gross from Nasa’s Jet Propulsion Laboratory told Popular Mechanics in 2011, “Earthquakes can change the Earth’s rotation by rearranging the Earth’s mass. This is what a spinning ice skater does to make herself spin faster. She moves her arms closer to her body, she’s moving her mass closer to the axis about which she’s rotating.”

Understanding the causes of this spin change involves looking at what’s happening inside the Earth, from moving molten layers deep in the core to powerful ocean currents and winds high in the sky.

Earth’s interior is not solid all the way through. Its centre is made of hot, liquid metal that flows and shifts. This movement can change the planet’s balance, like a skater turning faster by pulling in their arms.

Currents in the ocean and jet streams, fast air flows high up in the atmosphere, also move mass around, leading to small changes in the speed of Earth’s rotation.

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Scientists are looking at all of these, the moon’s pull, movement in the core, ocean flow, and wind, to understand what’s happening.

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July 5, 2025
Antony Gormley’s Crosby iron men over the years

Silhouetted against sunsets, half-buried in sand or standing poignantly under the moonlight – Crosby Beach’s celebrated iron men sculptures have inspired visitors for two decades.

Sir Antony Gormley’s Another Place, featuring 100 iron figures modelled on the artist’s own body, has become synonymous with the Sefton coast near Liverpool.

Marking the work’s 20th anniversary this week, Sir Antony said: “I think it’s about life and death, love and loss, and without people reacting to it, it’s nothing.”

Here are a selection of striking images of the artwork from over the years.

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July 5, 2025
OPEC+ members agree larger-than-expected oil production hike in August

The OPEC logo is displayed on a mobile phone screen in front of a computer screen displaying OPEC icons in Ankara, Turkey, on June 25, 2024.

Anadolu | Anadolu | Getty Images

Eight oil-producing nations of the OPEC+ alliance on Saturday agreed to lift their collective crude production by 548,00 barrels per day, as they continue briskly unwinding a set of voluntary supply cuts.

This subset of the alliance — comprising heavyweight producers Russia and Saudi Arabia, alongside Algeria, Iraq, Kazakhstan, Kuwait, Oman and the United Arab Emirates — met digitally earlier in the day. They had been expected to increase their output by a smaller 411,000 barrels per day.

In a statement, the OPEC Secretariat attributed the countries’ decision to raise August daily output by 548,000 barrels to “a steady global economic outlook and current healthy market fundamentals, as reflected in the low oil inventories.”

The eight producers have been implementing two sets of voluntary production cuts outside of the broader OPEC+ coalition’s formal policy.

One, totaling 1.66 million barrels per day, stays in effect until the end of next year.

Under the second strategy, the countries reduced their production by an additional 2.2 million barrels per day until the end of the first quarter.

They initially set out to boost their production by 137,000 barrels per day every month until September 2026, but only sustained that pace in April. The group then tripled the hike to 411,000 barrels per day in each of May, June and July — and are further accelerating the pace of their increases in August.

Oil prices were briefly boosted in recent weeks by the seasonal summer spike in demand and the 12-day war between Israel and Iran, which threatened both Tehran’s supplies and raised concerns over potential disruptions of supplies transported through the key Strait of Hormuz.

At the end of the Friday session, oil futures settled at $68.30 per barrel for the September-expiry Ice Brent contract and at $66.50 per barrel for front month-August Nymex WTI.

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July 5, 2025
Microsoft shuts its Pakistan office after 25 years, sparks economic concerns

Tech giant Microsoft has announced to shut down its limited operations in Pakistan as part of its global strategy to reduce workforce, which various stakeholders termed on Friday as a “troubling sign” for the country’s economy.

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Microsoft, while closing its office in Pakistan on Thursday after 25 years, cited global restructuring and a shift to a cloud-based, partner-led model.

The move came as the tech giant cut roughly 9,100 jobs worldwide (or about 4 per cent of its workforce) in its largest layoff round since 2023.

Jawwad Rehman, former founding Country Manager of Microsoft Pakistan, urged the government and IT minister to engage with the tech giants with a bold KPI (Key Performance Indicators) driven plan.

He said the exit reflected the current business climate. “Even global giants like Microsoft find it unsustainable to stay,” he posted on LinkedIn.

Former Pakistan president Arif Alvi, in a post on X, also expressed concern over Microsoft shutting down operations.

“It is a troubling sign for our economic future,” he wrote.

He claimed Microsoft once considered Pakistan for expansion, but that instability led the company to choose Vietnam instead by late 2022.

“The opportunity was lost,” he wrote.

Jawwad explained that Microsoft didn’t operate a full commercial base in Pakistan, relying instead on liaison offices focused on enterprise, education, and government clients.

Over recent years, much of that work had already shifted to local partners, while licensing and contracts were managed from its European hub in Ireland.

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July 5, 2025
Wallace Hartley sheet music part of Manchester Titanic exhibition

Rare artefacts from the Titanic shipwreck including the sheet music from the ship’s band leader Wallace Hartley who died in the sinking are to go on display in Manchester.

The RMS Titanic sank in April 1912 after it struck an iceberg on its maiden voyage from Southampton to New York killing more than 1,500 people.

The Titanic Exhibition Manchester will open from 31 July to 24 August at Manchester Central.

It will feature items such as the largest surviving fragment of the Aft Grand Staircase and the personal belongings of passengers and crew, including those from Mr Hartley, from Colne, Lancashire, who is said to have played on as the ship went down.

The Titanic vessel, which was built by Liverpool-based White Star Line and was registered in Liverpool, sank within hours of hitting an iceberg and now lies 3,800m (12,500ft) down in the Atlantic Ocean.

It remains one of the most famous shipwrecks in history that had its story turned into an Oscar-winning film.

The exhibition tells the story of the ship from its construction in Belfast, through to its maiden voyage and tragic sinking.

It examines the legacy left behind, including its impact on film and television.

Dik Barton, the first British man to dive to the Titanic, is also attending the exhibition.

He has done 22 dives to the wreck and is holding three lectures a day revealing new details about the site and what it’s like to dive 2.5 miles (4km) to the Titanic.

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July 5, 2025
Investigators compare trimodal therapy vs cystectomy in MIBC

Investigators for a recent study published in JAMA Network Open aimed to compare the value of trimodal therapy and cystectomy for muscle-invasive bladder cancer from a US health care perspective.¹ This research was spurred by a 2023 Lancet Oncology retrospective analysis that found no significant difference in metastasis-free and overall survival between the 2 treatments in specific patient cohorts.² The patients in that earlier study had solitary tumors less than 7 cm, unilateral or no hydronephrosis, adequate bladder function, and no multifocal or extensive carcinoma in situ.

For the current study, Daniel D. Joyce, MD, MS, and co-authors sought to address the remaining questions about the value of these treatments. Their findings indicated that although trimodal therapy improved the quality of life for patients with muscle-invasive bladder cancer compared with cystectomy, its significantly higher cost made it not cost-effective for society. The initial cost of trimodal therapy in their model was around $40,000.

A key aspect of their research involved sensitivity analysis to understand how varying parameters impact cost-effectiveness. They identified 2 main factors that would make trimodal therapy cost-effective: a substantial reduction in its cost to approximately $17,000, and an 11% improvement in the absolute risk reduction of metastases compared with cystectomy. This highlights current knowledge gaps regarding the comparative effectiveness of these treatments and the scarcity of long-term toxicity data for trimodal therapy, which affects both quality of life and effectiveness.

REFERENCES

1. Joyce DD, Wymer KM, Graves JA, et al. Cost-effectiveness of trimodal therapy and radical cystectomy for muscle-invasive bladder cancer. JAMA Netw Open. 2025;8(6):e2517056. doi:10.1001/jamanetworkopen.2025.17056

2. Zlotta AR, Ballas LK, Niemierko A, et al. Radical cystectomy versus trimodality therapy for muscle-invasive bladder cancer: a multi-institutional propensity score matched and weighted analysis. Lancet Oncol. 2023;24(6):669-681. doi:10.1016/S1470-2045(23)00170-5

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July 5, 2025
Muharram 9 central procession peacefully concludes in Karachi amid tight security – Pakistan

Karachi’s central mourning procession of Muharram 9 entered its destination of Hussainiya Iraniyan Imambargah in Kharadar on Saturday and peacefully concluded amid tight security, according to police.

Earlier in the week, Karachi Traffic Police issued a traffic plan for Muharram 8 to 10, outlining the procession routes as well as alternative traffic flows.

Stringent security measures are being taken across the country, such as army deployment as well as a crackdown on sectarian content and hate mongers, ahead of Ashura (Muharram 10), which will be observed tomorrow.

In Karachi, the Muharram 9 majlis started at Nishtar Park at 12:15pm, according to an alert from the police. “The number of participants is approximately 800 to 1000, and it is being led by Shahenshah Hussain Naqvi,” the alert read.

Another alert at 1:29pm said that the procession had departed the park, while another at 1:54pm read that head of the procession reached Aza Khana Zuhra, while the tail was still at Nishtar Park. A later alert at 2:16pm stated that the procession head had reached Shah Khurasan, with the tail still at the park.

The police said the procession entered its destination of Hussainiya Iraniyan Imambargah in Kharadar at 7:07pm with the tail still at Baghdadi Crossing. The procession concluded around 7:53pm.

Cellular services were also suspended in the areas adjoining the central procession’s route as well as the smaller procession’s routes across the city, according to a letter by the Sindh police chief.

According to the Karachi police chief, a total of 7,507 police personnel were deployed to monitor the main procession and its routes and passages.

“Expert police snipers have been deployed along the main procession and at the crossings and large contingent of police personnel, including senior officers of Karachi Police” is active, according to a statement from the additional inspector general of police’s office.

Traffic police personnel were also deployed to maintain traffic flow along crossings intersecting the main procession routes, as well as the alternative traffic routes arranged for Muharram 9.

Meanwhile, Sindh Home Minister Ziaul Hassan Lanjar, Karachi Mayor Murtaza Wahab, Sindh IG Ghulam Nabi Memon and Senator Waqar Mehdi reviewed security arrangements for the procession at Numaish, Nishtar Park and the Hussainiya Iraniyan Imam Bargah, a statement read.

Lanjar reviewed the security package and received a briefing from the Sindh IG and met the procession organisers.

“Peace and order in the city is our priority,” Lanjar was quoted as saying. He also directed the law enforcement agencies to take foolproof security measures, according to the press release.

Meanwhile, Wahab said, “Cleanliness arrangements have been ensured along the procession’s passageways. Proper lighting arrangements have also been made in the passageways and around them.”

On Friday, more than 5,500 police personnel were deployed across Karachi for the security of 8th Muharram processions.

Interior Minister Mohsin Naqvi said that 27,063 processions were taking place nationwide, with 7,598 majalis.

“Everything is going well,” he told reporters in Sukkur. “Sukkur has the largest procession, with approximately 1 million participants.”

The minister added that there were few blockages and praised the Sindh chief minister and other officials for taking care of the participants by arranging for special fans along procession routes, among other measures.

Punjab arrangements

Punjab Home Secretary Ahmad Javed Qazi briefed Punjab Chief Secretary Zahid Akhtar Zaman on the security situation across the province, a statement by the Public Relations Office said.

According to Qazi, more than 37,000 Muharram gatherings and 9,800 processions were being live monitored across the province. He said that Pakistan Army and Rangers personnel were also deployed to assist the police.

The chief secretary reviewed the arrangements for the Urs of Baba Farid and the Data Darbar Ghusl ceremony in Pakpattan. He also reviewed the social media monitoring process with the Cyber Patrol Cell of the Home Department.

Chief Secretary Zaman said, “All administration and police should be present in the field and follow the rules and regulations,” directing the control rooms to remain alert. He said that the main processions and gatherings are being monitored with CCTV cameras.

Meanwhile, Lahore Deputy Inspector General (DIG) Operations Faisal Kamran visited different areas of the city to review the security. He met with the organisers of the processions and instructed all officers to remain alert.

According to him, 386 gatherings were to be held and 81 mourning processions would be taken out in the city today. He said, “Over 8,000 officers and soldiers are performing security duties.”

He said that full security was being provided at all places, adding that the district administration, security agencies and other institutions were providing assistance.

“The streets on the route have been sealed with barbed wire and barriers,” he said, adding that snipers were deployed on high-rise buildings along the procession routes.

Police and community volunteers were deployed at various checkpoints, including ladies police personnel to check the mourning women, he added.

DIG Kamran advised citizens to immediately report abandoned goods, motorcycles and suspicious persons to the police.

A ‘Peace Caravan’ was launched under the supervision of DIG Kamran, which included scholars, the peace committee and police officers.

It was led by Senior Superintendent of Police (SSP) Operations Tasawur Iqbal, who, along with the superintendent of police (security(, met with leaders of different faiths.

“The aim of the peace caravan is to promote unity and solidarity in the city,” DIG Kamran said.

He said that “interfaith harmony” was a clear message to the enemies of the country, stating, “Lahore Police is taking every possible step to strengthen interfaith relations. Maintaining peace in Muharram is a shared responsibility of all of us.”

In Multan, police issued a statement outlining that 166 majalis and 80 processions were scheduled for Muharram 9.

Multan City Police Officer (CPO) Sadiq Ali Dogar said that 5,092 police personnel were deployed to protect the processions.

“We are prepared for any emergency,” Dogar was quoted as saying. “In addition to rooftop duty, police personnel in white uniforms are also present along the routes for secret surveillance. The procession routes have been sealed with barbed wire.”

The CPO added that alternative traffic routes had been provided and urged citizens to report anything suspicious to the police.

“Citizens should support the police in keeping the peace and promoting religious harmony,” Dogar said.

Earlier, Dogar, South Punjab Additional IG Kamran Khan, Counter-Terrorism Department Additional IG Waseem Sial, Multan Regional Police Officer Captain (retired) Sohail Chaudhry, Multan Commissioner Aamir Karim Khan and other officials reviewed the security package and visited the control room in the Deputy Commissioner’s office, a statement read.

The officials visited the Mumtaz Abad procession — the biggest in south Punjab — where Multan’s senior superintendent of police (operations) briefed the chief secretary and Punjab IG about the security arrangements.

The control room was also inspected, where the officials were briefed that all processions and gatherings in Multan were being monitored and controlled with the help of CCTV cameras.

Chief Secretary Zahid Akhtar Zaman and Punjab IG Dr Usman Anwar met with members of peace committees, community leaders and the organisers of mourning processions and gatherings, who appreciated the efforts of the Punjab government to maintain peace and security during Ashura and Muharram.

Peshawar

Khyber Pakhtunkhwa IG Zulfiqar Hameed visited the mourning procession in Saddar are and reviewed security arrangements.

He told Dawn.com that there were 115 processions in the city and over 10,000 security personnel are present on duty with 50,000 personnel deployed across the province.

“Fourteen districts of the province have been declared sensitive, eight as extremely sensitive. Paramilitary and army are performing security duties in the most sensitive districts. We are fighting terrorism, operations are carried out wherever necessary.”

He said the processions were proceeding as usual throughout the province.

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July 5, 2025
ICC T20 World Cup Europe Qualifier: Joe Burns tells Italy’s cricketers to ‘create a legacy’ and reach first World Cup

Joe Burns says Italy’s cricketers have the chance to “create a legacy” as he attempts to guide the European nation to their first ever World Cup.

Opening batter Burns, 35, made four centuries in 23 Tests for Australia between 2014 and 2020 but made himself available to play for Italy last year, qualifying through his grandparents.

He has since been appointed captain of Italy, who will battle it out with Guernsey, Jersey, Scotland and the Netherlands in a European regional qualifier for next year’s 2026 T20 World Cup.

The two teams who finish top of the round-robin tournament held in the Hague between 5 to 11 July will qualify for the event in India and Sri Lanka.

“We’re very confident that if we play to our best, we’ll be going to a World Cup,” Burns told BBC Sport.

“It’s not lost on us the magnitude of the impact we can have on Italian cricket. We talk a lot as a team about creating a legacy for the generations to come after us.

“To wear the Italian cap at a World Cup would make us a groundbreaking team. And we think we’ve got the team to get there.”

The first recorded game in Italy was played in Naples in 1793 by sailors from the fleet of Lord Nelson, and today there are more than 3,500 competitive players and in excess of 100 clubs.

They are currently 32nd in the International Cricket Council world rankings but do not have any proper turf pitches.

Italy’s squad have prepared for the tournament with a short training camp in Rome, some friendlies on grass in Horsham before warm-up games in the Netherlands.

Burns said there is a “huge opportunity” for cricket, and T20 in particular, to really grow in Italy and qualifying for the T20 World Cup could prove to be a major catalyst.

“I feel like Associate cricket is very much the grassroots of international cricket,” Burns added.

“But I really think that in 30, 40 or 50 years from now, Italy could be a massive player in world cricket.

“Playing Tests for Australia it was about the history that you’re honouring, and you’re carrying on in the traditions of the past, but when you play for Italy, it’s a blank canvas and you shape the future.”

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July 5, 2025
New research reveals hidden biases in AI’s moral advice

As artificial intelligence tools become more integrated into everyday life, a new study suggests that people should think twice before trusting these systems to offer moral guidance. Researchers have found that large language models—tools like ChatGPT, Claude, and Llama—consistently favor inaction over action in moral dilemmas and tend to answer “no” more often than “yes,” even when the situation is logically identical. The findings were published in the Proceedings of the National Academy of Sciences.

Large language models, or LLMs, are advanced artificial intelligence systems trained to generate human-like text. They are used in a variety of applications, including chatbots, writing assistants, and research tools. These systems learn patterns in language by analyzing massive amounts of text from the internet, books, and other sources.

Once trained, they can respond to user prompts in ways that sound natural and knowledgeable. As people increasingly rely on these tools for moral guidance—asking, for example, whether they should confront a friend or blow the whistle on wrongdoing—researchers wanted to examine how consistent and reasonable these decisions really are.

“People increasingly rely on large language models to advise on or even make moral decisions, and some researchers have even proposed using them in psychology experiments to simulate human responses. Therefore, we wanted to understand how moral decision making and advice giving of large language models compare to that of humans,” said study author Maximilian Maier of University College London.

The researchers conducted a series of four experiments comparing the responses of large language models to those of human participants when faced with moral dilemmas and collective action problems. The goal was to see whether the models reasoned about morality in the same ways that people do, and whether their responses were affected by the way questions were worded or structured.

In the first study, the researchers compared responses from four widely used language models—GPT-4-turbo, GPT-4o, Claude 3.5, and Llama 3.1-Instruct—to those of 285 participants recruited from a U.S. representative sample. Each person and model was given a set of 13 moral dilemmas and 9 collective action problems.

The dilemmas included realistic scenarios adapted from past research and history, such as whether to allow medically assisted suicide or to blow the whistle on unethical practices. The collective action problems involved conflicts between self-interest and group benefit, like deciding whether to conserve water during a drought or donate to those in greater need.

The results showed that in moral dilemmas, the language models strongly preferred inaction. They were more likely than humans to endorse doing nothing—even when taking action might help more people. This was true regardless of whether the action involved breaking a moral rule or not. For example, when the models were asked whether to legalize a practice that would benefit public health but involve a controversial decision, they were more likely to recommend maintaining the status quo.

The models also showed a bias toward answering “no,” even when the situation was logically equivalent to one where “yes” was the better answer. This “yes–no” bias meant that simply rephrasing a question could flip the model’s recommendation. Human participants did not show this same pattern. While people’s responses were somewhat influenced by how questions were worded, the models’ decisions were far more sensitive to minor differences in phrasing.

The models were also more altruistic than humans when it came to the collective action problems. When asked about situations involving cooperation or sacrifice for the greater good, the language models more frequently endorsed altruistic responses, like donating money or helping a competitor. While this might seem like a positive trait, the researchers caution that this behavior may not reflect deep moral reasoning. Instead, it could be the result of fine-tuning these models to avoid harm and promote helpfulness—values embedded during training by their developers.

To further investigate the omission and yes–no biases, the researchers conducted a second study with 474 new participants. In this experiment, the team rewrote the dilemmas in subtle ways to test whether the models would give consistent answers across logically equivalent versions. They found that the language models continued to show both biases, while human responses remained relatively stable.

The third study extended these findings to everyday moral situations by using real-life dilemmas adapted from the Reddit forum “Am I the Asshole?” These stories involved more relatable scenarios, such as helping a roommate or choosing between spending time with a partner or friends. Even in these more naturalistic contexts, the language models still showed strong omission and yes–no biases. Again, human participants did not.

These findings raise important questions about the role of language models in moral decision-making. While they may give advice that sounds thoughtful or empathetic, their responses can be inconsistent and shaped by irrelevant features of a question. In moral philosophy, consistency and logical coherence are essential for sound reasoning. The models’ sensitivity to surface-level details, like whether a question is framed as “yes” or “no,” suggests that they may lack this kind of reliable reasoning.

The researchers note that omission bias is common in humans too. People often prefer inaction over action, especially in morally complex or uncertain situations. But in the models, this bias was amplified. Unlike people, the models also exhibited a systematic yes–no bias that does not appear in human responses. These patterns were observed across different models, prompting methods, and types of moral dilemmas.

“Do not uncritically rely on advice from large language models,” Maier told PsyPost. “Even though models are good at giving answers that superficially appear compelling (for instance, another study shows that people rate the advice of large language models as slightly more moral, trustworthy, thoughtful, and correct than that of an expert ethicist), this does not mean that their advice is actually more sound. Our study shows that their advice is subject to several potentially problematic biases and inconsistencies.”

In the final study, the researchers explored where these biases might come from. They compared different versions of the Llama 3.1 model: one that was pretrained but not fine-tuned, one that was fine-tuned for general chatbot use, and another version called Centaur that was fine-tuned using data from psychology experiments. The fine-tuned chatbot version showed strong omission and yes–no biases, while the pretrained version and Centaur did not. This suggests that the process of aligning language models with expected chatbot behavior may actually introduce or amplify these biases.

“Paradoxically, we find that efforts to align the model for chatbot applications based on what the company and its users considered good behavior for a chatbot induced the biases documented in our paper,” Maier explained. “Overall, we conclude that simply using people’s judgments of how positive or negative they evaluate the responses of LLMs (a common method for aligning language models with human preferences) is insufficient to detect and avoid problematic biases. Instead, we need to use methods from cognitive psychology and other disciplines to systematically test for inconsistent responses.”

As with all research, there are some caveats to consider. The studies focused on how models respond to dilemmas. But it remains unclear how much influence these biased responses actually have on human decision-making.

“This research only showed biases in the advice LLMs give, but did not examine how human users react to the advice,” Maier said. “It is still an open question to what extent the biases in LLMs’ advice giving documented here actually sway people’s judgements in practice. This is something we are interested in studying in future work.”

The study, “Large language models show amplified cognitive biases in moral decision-making,” was authored by Vanessa Cheung, Maximilian Maier, and Falk Lieder.

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July 5, 2025