Nevin Manimala

J Neurol. 2025 Nov 2;272(11):743. doi: 10.1007/s00415-025-13491-5.

ABSTRACT

BACKGROUND: Multiple system atrophy (MSA) is a rare and progressive neurodegenerative disorder characterized by Parkinsonism, cerebellar dysfunction, and autonomic failure. Emerging evidence suggests that gut microbiota may contribute to neurodegeneration, but whether these associations are causal remains unclear.

METHODS: We conducted a two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary statistics of gut microbiota (n = 18,340) from the MiBioGen consortium and MSA (888 cases, 7,128 controls) from a recent European study. Single nucleotide polymorphisms associated with 196 bacterial taxa were selected as instrumental variables. The primary MR method was inverse-variance weighting, complemented by weighted median, MR-Egger, and MR-PRESSO. Sensitivity analyses assessed pleiotropy, heterogeneity, and robustness.

RESULTS: Six taxa showed nominal associations with MSA risk. Lentisphaeria (OR = 1.57, p = 0.035), Oscillospira (OR = 1.76, p = 0.034), Victivallales (OR = 1.57, p = 0.035), and Peptococcus (OR = 1.46, p = 0.025) were positively associated with increased risk, whereas Veillonella (OR = 0.40, p = 0.004) and Erysipelotrichaceae UCG-003 (OR = 0.60, p = 0.041) were associated with reduced risk. No evidence of pleiotropy or heterogeneity was found. None survived multiple-testing correction.

CONCLUSIONS: This MR study provides hypothesis-generating evidence suggesting potential causal relationships between gut microbiota and MSA. These taxa nominate candidate microbial targets for future mechanistic and translational studies.

PMID:41176741 | DOI:10.1007/s00415-025-13491-5

Clin Transl Oncol. 2025 Nov 2. doi: 10.1007/s12094-025-04107-5. Online ahead of print.

ABSTRACT

BACKGROUND/OBJECTIVES: Hypofractionated radiation therapy (Hypo-RT) schedules may offer radiobiological, patient convenience, and healthcare resource advantages over standard fractionated radiation therapy (S-RT) for glioblastoma (GBM). Additionally, simulated integrated boost (SIB) Hypo-RT is proven to be an effective and safe treatment. We report on our experience regarding progression-free survival (PFS), overall survival (OS), and RT-related toxicities in GBM patients treated with Hypo-RT and S-RT.

METHODS: Patients with IDH-wild-type GBM received either Hypo-RT (40.05-52.5 Gy/15 fractions) or S-RT (60-70 Gy/30 fractions). Volumetric modulated arc therapy was performed for all patients. Concomitant temozolomide (75 mg/m²/day) and adjuvant chemotherapy (TMZ 150-200 mg/m² for 5 days every 28 days) were administered. OS and PFS were estimated using the Kaplan-Meier method.

RESULTS: Ninety-five patients were treated (Hypo-RT: 52, S-RT: 43). With a median follow-up of 25 months (range 9-63), the median age was 65 and 54 years for the Hypo-RT and S-RT groups, respectively. All patients tolerated the treatment well; no significant adverse effects were observed in either group. No acute or late neurological side effects of grade ≥ 2 were reported during RT. Grade 3-4 hematologic toxicity occurred in five cases, all of which interrupted concomitant TMZ (all happening in the S-RT arm). The time to progression for the S-RT and Hypo-RT groups was 13.7 and 11.1 months, respectively (p = 0.243). Regarding OS, the S-RT group had a median OS of 28.8 months compared to 17.5 months in the Hypo-RT group (p = 0.007).

CONCLUSIONS: Although further investigations are ongoing, a statistically significant difference exists between Hypo-RT and S-RT in OS. Hypo-RT could potentially become the standard of care not only for elderly patients but also for those with poor prognosis. Further investigation with additional data is necessary to determine the most effective standard approach.

PMID:41176740 | DOI:10.1007/s12094-025-04107-5

Exp Brain Res. 2025 Nov 2;243(12):241. doi: 10.1007/s00221-025-07189-3.

ABSTRACT

Healthy adults (OA) achieve rapid isometric force production with a brief, high amplitude burst of neural excitation. In some people with Parkinson’s disease (PwPD), transient reductions in neural excitation (motor segmentation) reduce rates of force development (RFD) and prolong contractions. Segmentation has strong relationships with time and rate-based measures of slowing in rapid contractions and is reliably measured from the second derivative of force (F”(t)). We sought more information about how segmentation affects neuromuscular control in PwPD. Aim 1 was to determine the prevalence of PwPD with segmentation (PD_Seg). Aim 2 was to determine how force performance differs in PD_Seg, PwPD without segmentation (PD_NoSeg), and OA. Aim 3 was to quantify force segment durations. Fifty-seven PwPD ON medication and 22 OA performed rapid isometric finger abduction contractions to 20-60% of maximal voluntary contraction force. The median number of force segments to 90% of peak force were measured from F”(t) zero crossings. Additional outcomes included median times to peak force (tPF) and peak RFD (tRFD), and peak RFD (RFDpk). 68% of PwPD had segmentation (median segments ≥ 2, 95% CI [0.55 0.80]). PD_Seg had slower tPF, tRFD and RFDpk than PD_NoSeg and OA (all p ≤ 0.012, 0.38 ≤ r ≤ 0.85). PD_NoSeg and OA did not have statistically different tPF, tRFD, or RFDpk (p > 0.05). PD_Seg had consistent segment durations (coefficient of variation ≤ 25.5%) and shorter first segment durations compared to PD_NoSeg and OA (p < 0.001, r ≥ 0.68), indicating PD_Seg had reduced neuromuscular excitation prior to peak force. Segmentation identifies specific pathophysiology in neuromuscular control that exacerbates slowing in isometric force production.

PMID:41176739 | DOI:10.1007/s00221-025-07189-3

Cancer Med. 2025 Nov;14(21):e71350. doi: 10.1002/cam4.71350.

ABSTRACT

BACKGROUND: With treatment strategies for cancer constantly evolving, the multidisciplinary team (MDT) plays a key role in optimizing cancer care, but its real-world impact on survival remains unclear. This study aims to examine the impact of MDT on overall survival (OS) among patients with stage IV non-small cell lung cancer (NSCLC), based on real-world data including all eligible patients.

METHOD: Patients with stage IV NSCLC who were admitted for the first time to Shandong Cancer Hospital from January 1, 2021 to December 31, 2021 were divided into MDT group and non-MDT group according to MDT meeting involvement. Follow-up period extended from January 1, 2021, to May 31, 2024. Kaplan-Meier curves and log-rank tests were used to analyze survival differences, while Cox proportional hazards models were employed to identify factors associated with overall survival.

RESULT: One thousand six hundred and sixty-four patients were included. No statistical differences were found between the MDT group (n = 1238) and the Non-MDT group (n = 426) in baseline characteristics, but differences were observed in treatment modalities. The MDT group exhibited a longer median overall survival compared to the Non-MDT group (26.25 vs. 21.42 months; log-rank χ² = 4.93, p = 0.03). Furthermore, MDT was associated with a reduction in the risk of mortality (adjusted HR = 0.86; 95% CI, 0.75-0.99; p < 0.05).

CONCLUSION: MDT can effectively reduce mortality risk. Future implementation requires recognizing its potential additional benefits and developing tailored strategies.

PMID:41176729 | DOI:10.1002/cam4.71350

Cancer Med. 2025 Nov;14(21):e71341. doi: 10.1002/cam4.71341.

ABSTRACT

BACKGROUND: The low participation rate in colorectal cancer (CRC) screening may be partly attributed to the lack of consideration for the preferences of both Recipients and Providers. This study aims to explore these preferences to inform the optimization of screening design and the improvement of implementation strategies.

METHODS: A discrete choice experiment (DCE) was conducted in Shandong Province to examine CRC screening preferences of Recipients and Providers. The attributes and levels of the DCE were determined using a systematic literature review and explored qualitatively. Questionnaires were generated through a partial factor design, and used a mixed logit model to analyze the data. Relative importance scores (RIS) and marginal willingness to pay were used to quantify preferences, and probability density functions were employed to predict changes in participation rates under varying attribute levels.

RESULTS: Preference data from 570 Recipients and 532 Providers were analyzed. The DCE included five attributes: screening cost (four levels), screening interval (four levels), bowel preparation (two levels), screening accuracy (three levels), and reduction in CRC-related mortality risk (three levels). All attributes significantly influenced preferences. The RIS indicated that Recipients prioritized screening cost (42.8%), followed by interval (24.3%), mortality risk reduction (16.2%), accuracy (10.7%), and bowel preparation (6.0%), whereas Providers emphasized bowel preparation (35.4%), interval (31.7%), cost (25.1%), mortality risk reduction (6.4%), and accuracy (1.3%). Both groups showed strong support for biennial screening. Shortening the interval from 10 to 2 years increased Recipients’ willingness to pay by CNY 1052.95 and Providers’ expected charge by CNY 1370.84, which was also associated with higher predicted participation rates.

CONCLUSION: Recipients and Providers differed in the degree of preference for the five CRC screening attributes, but the directions of their preferences were consistent. Therefore, screening strategies should aim to balance the perspectives of both groups. Where feasible, a biennial screening program that includes bowel preparation, minimizes costs and mortality risk, and maximizes accuracy is recommended.

PMID:41176721 | DOI:10.1002/cam4.71341

ACS Chem Biol. 2025 Nov 2. doi: 10.1021/acschembio.5c00751. Online ahead of print.

ABSTRACT

Immunomodulatory imide drugs (IMiDs), including thalidomide, lenalidomide, and pomalidomide, can be used to induce degradation of a protein of interest that is fused to a short degron motif, which often comprises a zinc finger (ZF). These IMiDs, however, also induce the degradation of endogenous ZF-containing neosubstrates, including IKZF1, IKZF3, and SALL4. To improve degradation selectivity, we took a bump-and-hole approach to design and screen bumped IMiD analogues against 8380 ZF mutants. This yielded a bumped IMiD analogue that induces efficient degradation of a mutant ZF degron, while not affecting other cellular proteins, including IKZF1, IKZF3, and SALL4. In proof-of-concept studies, this system was applied to induce degradation of the optimum degron fused to CDK9, HPRT1, NanoLuc, or TRIM28. We anticipate that this system will be a valuable addition to the current arsenal of degron systems for use in target validation.

PMID:41176706 | DOI:10.1021/acschembio.5c00751

Ann Med. 2025 Dec;57(1):2580783. doi: 10.1080/07853890.2025.2580783. Epub 2025 Nov 2.

ABSTRACT

BACKGROUND: Although some prediction models have been developed to evaluate postpartum haemorrhage in caesarean delivery with complications, limited attention has focused on unplanned return to the operating room (UPROR), especially in twin pregnancies. On this note, this study seeks to investigate the risk factors for UPROR and Postpartum Haemorrhage (PPH) in twin pregnancies after caesarean section (CS) and develop a nomogram for predicting PPH.

OBJECTIVE: This study aimed to investigate the risk factors for UPROR and PPH in twin pregnancies after CS in China and develop a nomogram for PPH prediction.

METHODS: A multicentre retrospective cohort study was conducted. There were a total of 1198 twin pregnant women who underwent a CS at the Women’s Hospital, School of Medicine, Zhejiang University in Hangzhou, Ninghai Maternal and Child Health Hospital, Fuyang Women and Children’s Hospital in China from January 2017 to December 2021. All 1198 pregnant women were randomly divided into two groups (D for development and V for validation), one for training and one for validation by ratio 7:3. A nomogram was developed to predict PPH (blood loss ≥1000 ml) and UPROR based on the model generated by logistic regression analysis. The training cohort and the validation cohort were evaluated in PPH, and a decision curve analysis was developed.

RESULTS: 16.77% (201/1198) women experienced PPH, 142 of which (142/840, 16.90%) in the training cohort and 59 (59/358, 16.48%) in the validation cohort. Seven optimal variates were obtained as predictors of PPH in twin pregnancies, including assisted reproductive technology (ART), advanced gestational weeks, placenta previa, emergency operation, total birth weight, and the use of uterotonic and anticoagulants. The AUC for the nomogram was 0.75 (95% CI, 0.71-0.79) for the training cohort, while that was 0.83 (95% CI, 0.79-0.88) for the validation dataset. 3.67% (44/1198) of women experienced UPROR for tamponade after the CS; PPH was the cause in all cases, none of whom had a hysterectomy. Six optimal variates were obtained as predictors of UPROR in twin pregnancies, including advanced maternal age, ART, parity ≥ 1, placenta previa, total amount of amniotic fluid (ml) ≥ 1500, and twin growth discordance. The AUC for the nomogram was 0.74 (95% CI, 0.66-0.82).

CONCLUSION: The novel nomogram prediction model for UPROR in twin pregnancies via cesarean section has clinical potentials, including the prevention of PPH in twin pregnancies.

PMID:41176700 | DOI:10.1080/07853890.2025.2580783

Ann Med. 2025 Dec;57(1):2577880. doi: 10.1080/07853890.2025.2577880. Epub 2025 Nov 2.

ABSTRACT

OBJECTIVE: Phlegmasia cerulea dolens (PCD) is the most severe form of deep vein thrombosis in the lower extremities. Clinical guidelines have not systematically outlined its risk factors, diagnostic methods, or treatment strategies. In this study, the literature published over the past 30 years is reviewed to summarize the clinical features of, diagnostic approaches to, prognostic factors of, and evolving management strategies for PCD.

METHODS: A retrospective analysis was conducted on 144 PCD patients from 1990 to 2024. Demographic data, clinical features, comorbidities, diagnostic methods, treatments, and prognostic outcomes were extracted. Descriptive statistical analysis was performed, and univariate and multivariate logistic regression were used to evaluate the impact of clinical factors on prognosis.

RESULTS: The majority of PCD cases involved the left lower limb, with 93.00% of patients having thrombosis extending into the iliocaval vein. Key risk factors included venous structural abnormalities, malignant tumors, and prior venous thromboembolism, with reproductive system cancers being the most common malignancy. Endovenous debulking techniques emerged as the preferred treatment method, reducing the risk of amputation and death by 70% compared with anticoagulation or thrombectomy. Patients with bilateral limb involvement, stage III PCD, or who underwent fasciotomy had significantly greater risks of amputation and death. The overall mortality rate was 18.75%, which was due primarily to metabolic acidosis and multiple organ failure.

CONCLUSION: Multimodal imaging should be recommended for the systematic evaluation of PCD to identify underlying malignancies and venous structural abnormalities. Endovenous debulking has demonstrated advantages in improving prognosis and should be recommended as a first-line treatment for PCD.

PMID:41176699 | DOI:10.1080/07853890.2025.2577880

Recenti Prog Med. 2025 Nov;116(11):661-669. doi: 10.1701/4588.45981.

ABSTRACT

INTRODUCTION: The prognostic potential of history of allergy and atopy in glioblastoma (GBM) patients has been poorly evaluated until now. In the present work, we studied the association between history of allergy/atopy and survival length in a cohort of GBM patients. We also evaluated the association between already suggested demographic, anamnestic, clinicopathologic and molecular prognostic variables for GBM and survival.

METHODS: The study was conducted retrospectively on a cohort of 145 patients diagnosed with GBM between 2015 and 2021. Data were retrieved from clinical charts. Information on history of allergy and atopy was self-reported.

RESULTS: Median overall survival was 9.1 months (IQR 4.3-17). Patients with positive history of allergic/atopic diseases were 33 (22.8%). From univariable analysis, patients with allergies had a longer survival time than those with no allergies; however, this result was not statistically significant (HR:0.72; 95%CI 0.49-1.07). Instead, from multivariable analysis, patients aged ≥65 years resulted to have a shorter survival than the others; (HR:2.10; 95%CI 1.35-2.84), while an increased survival length is observed for patient who underwent tumor surgical resection (HR:0.46; 95%CI 0.30-0.72) and receiving adjuvant therapy (HR:0.25; 95%CI 0.17-0.38).

CONCLUSION: Although the result was not statistically significant, we found a trend of protective effect of allergies/atopies in GBM patients. In addition, the study confirmed positive effects on GBM survival of some well-known variables, such as surgical resection, adjuvant therapy, and age.

PMID:41176669 | DOI:10.1701/4588.45981

Neurol Res. 2025 Nov 2:1-8. doi: 10.1080/01616412.2025.2583441. Online ahead of print.

ABSTRACT

BACKGROUND: Intracranial hemorrhage (ICH) prevalence is increasing, yet its genetic risk factors and micronutrient associations remain unclear.

METHODS: We performed univariable and multivariable Mendelian randomization (MR) analyses using 15 micronutrients derived from genome-wide association study (GWAS) data to assess their relationship with ICH risk.

RESULTS: Univariable MR analysis suggested that genetically predicted vitamin B6 [odds ratio (OR) = 0.6 (95% CI, 0.38 to 0.96), p = 0.033] and vitamin E [OR = 0.49 (95% CI, 0.33 to 0.73), p < 0.001] were potentially associated with the risk of ICH. Other micronutrients did not exhibit statistically significant associations with ICH in this analysis. Furthermore, multivariable MR analysis revealed significant causal relationship between vitamin E and ICH [OR = 0.514 (95% CI, 0.312 to 0.845), p = 0.009].

CONCLUSION: Vitamin E levels are significantly associated with reduced ICH risk, indicating its potential as a preventative agent. Further research is needed to explore this relationship fully.

PMID:41176655 | DOI:10.1080/01616412.2025.2583441