Category: Nevin Manimala

Anal Chim Acta. 2026 Oct 22;1420:345951. doi: 10.1016/j.aca.2026.345951. Epub 2026 Jul 9.

ABSTRACT

BACKGROUND: Mesenchymal stem cells (MSCs) are often used in bone tissue engineering. However, for optimized MSC osteogenic commitment to be achieved, a deeper understanding of the cellular molecular mechanisms underlying osteodifferentiation is required. In this paper we show that this can be provided by Fourier Transform Infrared (FTIR) spectroscopy in tandem with microscopy (micro-FTIR), a methodology which may also aid the rapid early evaluation of differentiation outcomes.

RESULTS: We report a micro-FTIR time-course characterization of human adipose tissue mesenchymal stem cell (hAMSCs) osteodifferentiation (for 21 days), considering different independent experiments and biological replicates to account for cell heterogeneity, under both differentiation and proliferation (control) conditions. Despite extensive spectral variability in both groups, multivariate statistical methods revealed time-dependent spectral changes and potential spectral signatures of proliferation and osteodifferentiation extension. Under proliferation alone, spectral changes reflecting helical proteins and lipids were seen up to day 14, stabilizing thereafter. Osteodifferentiating cells exhibited higher inter- and intra-replicate variability and a distinct spectral time-course trajectory. Evidence was found of both helical and β-sheet protein structures, with a relative increase of the former from day 6, although masked by increasing sample variability. Other osteo-specific changes were noted in lipid moieties and at lower wavenumbers (1030-1115 cm^-1). The latter were found to relate to different degrees of hydroxyapatite maturity between and even within samples.

SIGNIFICANCE: Specific spectral FTIR signatures have been identified as markers of the extent of hAMSC proliferation and osteodifferentiation, potentially enabling the rapid and non-invasive evaluation of hAMSCs osteodifferentiation outcome and of inter- and intra-sample variability.

PMID:42648828 | DOI:10.1016/j.aca.2026.345951

Anal Chim Acta. 2026 Oct 22;1420:345933. doi: 10.1016/j.aca.2026.345933. Epub 2026 Jul 6.

ABSTRACT

Supercritical fluid extraction coupled on-line with supercritical fluid chromatography creates a powerful multidimensional analysis platform, but its adoption is limited by the resource-heavy process of method development. This research presents a surrogate optimization approach as a better alternative to traditional design of experiments and response surface methodology. Unlike fixed experimental designs, the surrogate model iteratively updates the response surface after each run, facilitating effective global optimization through continuous exploration and exploitation. The study adjusts both SFE- and SFC-specific variables-such as back-pressure regulation and split flow-to reduce peak FWHM and enhance extraction efficiency. Analytes, specifically reserpine, vigabatrin, hydromorphone, and hydrocodone, covering diverse physicochemical profiles, were optimized sequentially, guided by a molecular similarity metric, to broaden the design space. The surrogate model identified critical factors, including modifier concentration, chromatography pressure, dynamic extraction time, and flow rate, with adjusted coefficient of determination (R²) values reaching 0.97 as more data was collected and the model was refined. Response surface and parallel coordinate analyses showed that hydrocodone, hydromorphone, and vigabatrin favored high modifier concentrations, while reserpine had a distinct optimum more sensitive to static extraction time. Sensitivity analysis over 62.5-1000 ng mL^-1 yielded detection limits/quantification limits of 6.9/23.0 and 2.4/8.1 ng mL^-1 for hydrocodone and reserpine, respectively. Sequential optimization enhanced sensitivity by 15%, demonstrating the scalability and transferability of the surrogate optimization framework for developing SFE-SFC methods.

PMID:42648811 | DOI:10.1016/j.aca.2026.345933

BMJ Open. 2026 Aug 26;16(8):e116200. doi: 10.1136/bmjopen-2026-116200.

ABSTRACT

BACKGROUND: Health research ethics committees (HRECs) provide the administrative backbone of ethical governance by safeguarding the rights, safety and well-being of research participants and ensuring the ethical conduct of health research. Effective ethical oversight depends not only on rigorous protocol review but also on robust governance, competent personnel, adequate infrastructure, sustainable institutional support and efficient administrative systems. Despite their critical role, evidence on the administrative functionality of HRECs in Tanzania remains limited.

OBJECTIVE: To assess the administrative functionality of HRECs in mainland Tanzania, with emphasis on governance, operational procedures, human resource capacity, training, infrastructure, documentation systems and institutional support.

DESIGN: Quantitative descriptive cross-sectional study.

SETTING: All active registered HRECs in clinical, research and training institutions in mainland Tanzania.

PARTICIPANTS: 10 administrative representatives responsible for HREC secretariat functions, one from each of the 10 active registered HRECs.

METHODS: A census approach included all 10 active registered HRECs in mainland Tanzania, with one administrative representative purposively selected from each committee. Data were collected using a semi-structured questionnaire and a document review checklist adapted from the Research Ethics Committee Assessment Toolkit. The assessment covered governance, committee membership, independence, training, decision-making procedures, administrative operations, financing, documentation practices and infrastructure. Document reviews verified standard operating procedures, meeting minutes, protocol-tracking systems, approval records and archival practices. Data were analysed using descriptive statistics.

RESULTS: All 10 HRECs participated. Administrative functionality was the highest for administrative operations (94%) and decision-making procedures (93%), followed by membership standards (86%). Compliance was lower for committee independence (75%) and training (50%). Key gaps included limited structured training, inadequate institutional financing, insufficient dedicated administrative staff, weak transparency mechanisms and inconsistent administrative and digital infrastructure. Electronic protocol-tracking systems were available in 60% of HRECs.

CONCLUSIONS: Tanzanian HRECs have established a solid administrative foundation for ethical governance. However, persistent gaps in training, committee independence, financing, staffing, infrastructure and digital systems may compromise the effectiveness, transparency and sustainability of ethical oversight. Strengthening administrative standards, institutional investment, continuous professional development and digital infrastructure is essential to reinforce the administrative backbone of ethical governance and improve research ethics oversight in Tanzania and other low-income and middle-income countries.

PMID:42648778 | DOI:10.1136/bmjopen-2026-116200

BMJ Open. 2026 Aug 26;16(8):e118374. doi: 10.1136/bmjopen-2026-118374.

ABSTRACT

Postherpetic neuralgia (PHN) is the most common chronic complication of herpes zoster, characterised by persistent pain after the rash subsides with a particularly high incidence among the elderly population. Its pathological mechanism involves peripheral and central sensitisation, often leading to severe pain, sleep disturbances, emotional issues and a decline in quality of life, posing a significant burden on healthcare and society. Current clinical treatments primarily rely on pharmacological and interventional therapies yet their efficacy remains suboptimal. Stellate ganglion block (SGB), as an interventional technique targeting the sympathetic nervous system, is believed to alleviate PHN by modulating neurovascular function, inhibiting inflammatory responses and blocking pain transmission pathways. However, evidence-based data on its efficacy and safety remain insufficient and existing study results are inconsistent. Therefore, this study aims to comprehensively evaluate the effectiveness and safety of SGB in treating PHN through a systematic review and meta-analysis.

METHODS: This systematic review and meta-analysis will be conducted in strict accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search will be performed for relevant randomised controlled trials published from the inception of each database until 31 December 2025, in PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database and VIP Database. Two researchers will independently complete the literature screening, data extraction and cross-verification. The methodological quality of the included studies will be assessed using the Cochrane Risk of Bias tool. Statistical analysis will be performed using RevMan V.5.4 software: continuous variables will be analysed by calculating the mean difference and 95% CI, and dichotomous variables will be analysed by calculating the OR and 95% CI. Based on the results of heterogeneity testing (I² statistic), either a fixed-effects model or a random-effects model will be employed for data synthesis. Subgroup analyses and sensitivity analyses will be conducted to explore sources of heterogeneity, and a grading system will be used to assess the quality of the evidence.

ETHICS AND DISSEMINATION: Ethical approval is not required for this study, as it does not involve the collection of primary data from individual patients. Findings will be disseminated through peer-reviewed publication and conference presentations.

PROSPERO REGISTRATION NUMBER: CRD420251128909.

PMID:42648776 | DOI:10.1136/bmjopen-2026-118374

BMJ Open. 2026 Aug 26;16(8):e117159. doi: 10.1136/bmjopen-2026-117159.

ABSTRACT

OBJECTIVES: To investigate real-world healthcare experiences of individuals in the UK who consulted health and care professionals for nocturia. The study explored the assessments, management strategies, referrals and follow-up patterns received by patients experiencing lower urinary tract symptoms (LUTSs), as well as their level of satisfaction with those. The association of sociodemographic factors with these patterns was also analysed.

DESIGN: A cross-sectional online survey.

SETTING: Community-based, UK.

PARTICIPANTS: From 2012 completers, 453 (22.5%) reported consulting healthcare professionals for LUTS (55.0% female, 75.5% White; aged 18-65+ years; convenience sampling via online panels/networks).

INTERVENTIONS: None (observational survey study).

PRIMARY AND SECONDARY OUTCOME MEASURES: Healthcare provider consulted; assessments (eg, history, bladder diary, examinations, tests); management (eg, behavioural, pharmacological); referrals/follow-up; satisfaction; associations via χ² tests.

RESULTS: Among 453 respondents who sought professional advice for LUTS, 211 reported nocturia and 143 had nocturia confirmed through the survey’s follow-up questions. General practitioners were the most consulted providers (73.1%), but guideline-recommended tools such as bladder diaries were underutilised (13.9%). Only 12.1% were referred to specialists. Satisfaction with care was mixed: 59% were satisfied with assessment and 54% with treatment, but dissatisfaction was common around referrals, follow-up and cause explanation. Long-term conditions and disability were associated with greater unmet needs. Participants consistently called for more accessible information, clinician training and better self-management support.

CONCLUSIONS: These findings suggest that patients’ reported experiences of assessment and management varied, which may reflect differences in actual practice, recall or communication during consultations, particularly in relation to nocturia. However, because the data are cross-sectional and self-reported, these results should be interpreted cautiously. They highlight areas where patient assessment, communication and follow-up could potentially be improved.

PMID:42648773 | DOI:10.1136/bmjopen-2026-117159

BMJ Open. 2026 Aug 26;16(8):e111823. doi: 10.1136/bmjopen-2025-111823.

ABSTRACT

BACKGROUND: Approximately 96% of rifampicin resistance/multidrug-resistant tuberculosis (RR/MDR-TB) cases in Rwanda result from direct transmission rather than acquired resistance. However, the nationwide spatial distribution and transmission dynamics of RR/MDR-TB remain poorly characterised. This study aims to analyse spatial patterns of RR/MDR-TB in Rwanda and explore relationships between spatial proximity and RR/MDR-TB strains’ genetic relatedness.

METHODS: We conducted a retrospective analysis of 249 confirmed RR-TB cases across Rwanda from 2017 to 2024, using the known geolocations of patients’ residences. Spatial and space-time clustering was assessed using Kulldorff’s scan statistics. Demographic and socioeconomic determinants were evaluated using multivariable regression. For 201 cases with whole-genome sequencing data, we performed transmission analysis using a 5-SNP threshold to define recent transmission clusters and investigated spatial relationships within genetically related strains.

RESULTS: Significant spatial clustering of RR/MDR-TB was identified in 21 sectors, mainly in Nyarugenge, southern Gasabo and western Kicukiro (relative risk: 10.06; p<0.001). Our multivariable analysis showed that population density is positively associated with case notification rates. Molecular analysis revealed 88.5% of cases belonged to genotype clusters defined using a 12-SNP threshold, with 73.6% forming clusters at a strict 5-SNP threshold. Spatial K-function analysis of the six major clusters revealed heterogeneous transmission patterns, characterised by both tightly clustered outbreaks and regional transmission networks that spanned administrative boundaries. Most clusters (5/6) extended beyond Kigali, indicating that transmission networks operate across administrative divides.

CONCLUSION: RR/MDR-TB in Rwanda shows significant spatial clustering with transmission occurring through both localised and regional networks. Integrating genomic and spatial data reveals transmission patterns that extend beyond household contacts and administrative boundaries. These findings underscore the need to implement geographically targeted interventions that address community-level transmission to control RR/MDR-TB in Rwanda effectively.

PMID:42648769 | DOI:10.1136/bmjopen-2025-111823

BMJ Glob Health. 2026 Aug 26;11(8):e025404. doi: 10.1136/bmjgh-2026-025404.

ABSTRACT

INTRODUCTION: This study evaluated the operational status of Ukrainian radiotherapy (RT) centres to characterise wartime capacity following the Russian invasion and to identify priorities for improving RT delivery and resilience.

METHODS: This cross-sectional study integrated two data sources: (1) a 38-item survey conducted by Help Ukraine Group (HUG) in August 2025 across all Ukrainian RT departments, assessing patient volumes, waiting times, equipment status, cobalt-60 (Co-60) source replacement, staffing, training needs and operational challenges; and (2) International Atomic Energy Agency DIRAC datasets collected by the Grigoriev Institute (2021-2025), tracking equipment, staffing and patient volumes. Descriptive and comparative analyses were performed.

RESULTS: In December 2021, before the full-scale invasion, Ukraine operated 41 RT departments with 82 megavoltage (MV) machines (38 linear accelerators, 44 Co-60 units), 53 orthovoltage units and 36 brachytherapy afterloaders. During the first 3 months of war, four centres were occupied, most departments experienced service disruptions averaging 26 days and patient volume declined by 27.5%. Volumes recovered to baseline in 2023 and increased by 8.9% in 2024 and 9.3% in 2025 relative to 2021.In December 2025, Ukraine operated 42 RT departments with 96 MV machines (68 linear accelerators, 28 Co-60 units), 38 orthovoltage units and 34 afterloaders. However, 56% of departments still relied on Co-60 and 94.1% reported future source replacement would be unfeasible because sources were historically procured from Russia. Consequently, 78.6% of Co-60 users planned the transition to linear accelerators. Workforce shortages remain critical, with reported deficits of 41.4% for medical physicists, 33.6% for RTTs and 21.1% for radiation oncologists. Average waiting times increased from 6.4 days in 2021 to 10.3 days in 2025.

CONCLUSION: Despite ongoing war, Ukraine is actively modernising RT services, with a rapid transition from Co-60 to linear accelerators. Workforce development and targeted training are now urgently needed to convert equipment investment into sustainable clinical capacity.

PMID:42648756 | DOI:10.1136/bmjgh-2026-025404

J Immunother Cancer. 2026 Aug 26;14(8):e013527. doi: 10.1136/jitc-2025-013527.

ABSTRACT

BACKGROUND: Patients with unresectable stage III non-small cell lung cancer (NSCLC) have an unmet need for new therapies that improve survival. This phase III trial investigated the safety and efficacy of concurrent ociperlimab and tislelizumab plus concurrent chemoradiotherapy (cCRT) in treatment-naïve patients with stage III NSCLC.

METHODS: In this phase III, multicenter, randomized, multiarm, open-label trial, patients with unresectable stage III NSCLC received concurrent ociperlimab plus tislelizumab and cCRT, followed by ociperlimab plus tislelizumab (arm A), tislelizumab and cCRT, followed by tislelizumab (arm B), or cCRT, followed by durvalumab (arm C) (NCT04866017). Objectives were to compare progression-free survival (PFS), overall survival (OS), objective response rate (ORR), duration of response, disease control rate, clinical benefit rate, time to death or distant metastasis (TTDM), and safety and tolerability for arms A versus C, B versus C, and A versus B.

RESULTS: 63 patients were randomized to arms A (N=22), B (N=19), and C (N=22) prior to early trial termination. In A, B, and C, respectively, 95.5% (21/22), 84.2% (16/19), and 95.5% (21/22) were current or former smokers, and 68.2% (15/22), 73.7% (14/19), and 68.2% (15/22) had PD-L1 expression in tumor cells of ≥1%. Median PFS (95% CI) was not reached (NR) (6.3-not estimable (NE)) in A, 15.0 months (7.4 to NE) in B, and 10.4 months (5.7 to NE) in C. Median OS and TTDM were NR in any arm. ORR (95% CI) was 68.2% (45.1%-86.1%) in A, 68.4% (43.4%-87.4%) in B, and 59.1% (36.4%-79.3%) in C; all responses were partial responses. Treatment-emergent adverse events (TEAEs) occurred in all patients; in arms A, B, and C, respectively, pneumonitis occurred in 18.2% (4/22), 5.6% (1/18), and 9.1% (2/22) of patients, and interstitial lung disease occurred in 13.6% (3/22), 11.1% (2/18), and 0% of patients, of which the majority of events for each were grade 1/2. Grade ≥3 treatment-related TEAEs occurred in 68.2% (15/22), 66.7% (12/18), and 68.2% (15/22) of patients in arms A, B, and C, respectively.

CONCLUSIONS: There was a trend toward improved efficacy when adding tislelizumab with or without ociperlimab to cCRT followed by tislelizumab with or without ociperlimab compared with cCRT followed by durvalumab; however, efficacy data were for descriptive purposes only. No unexpected or new safety signals were identified.

PMID:42648750 | DOI:10.1136/jitc-2025-013527

BMJ Open Qual. 2026 Aug 26;15(3):e004387. doi: 10.1136/bmjoq-2026-004387.

ABSTRACT

BACKGROUND: Transition from paediatric to adult healthcare is particularly challenging for youth and their caregivers with complex health conditions, in part due to loss of paediatric supports and fragmentation of care, contributing to adverse outcomes. To date, transition research and policy has been largely driven by paediatric providers. Adult provider insights are critical to inform gaps in care, transition planning and enable innovative and sustainable interventions.

OBJECTIVE: To describe adult subspecialist perspectives on barriers, facilitators and opportunities to improve the transition from paediatric to adult care for youth with complex health conditions.

METHODS: An adult subspecialty advisory panel was convened as part of a quality improvement initiative, with physicians from the University of Toronto’s Department of Medicine who participated in three virtual meetings through nomination and stakeholder mapping. The first meeting focused on identifying current challenges and opportunities in transition to adult care; the second generated recommendations based on experiential knowledge and the third reviewed case studies to identify gaps and potential solutions. Discussions were recorded, transcribed and analysed using thematic qualitative analysis.

RESULTS: Adult subspecialists identified five key areas for improvement: (1) preparing patients and families for the realities of adult care; (2) bridging communication gaps between paediatric and adult systems; (3) moving beyond age-based transition toward flexible, readiness-informed care; (4) strengthening collaboration among adult providers caring for young adults; and (5) addressing structural and infrastructure barriers within adult care systems.

CONCLUSION: Adult care physicians expressed and validated that young adults have unique care needs during their transition to adult care. They highlighted the need for stronger cross-system collaboration, resources and investment to ensure effective transition. These findings highlight barriers in implementing current paediatric-led transition standards and provide a foundation for system-level, disease-agnostic approaches to improve continuity of care across the paediatric-adult divide.

PMID:42648749 | DOI:10.1136/bmjoq-2026-004387

BMJ Open Qual. 2026 Aug 26;15(3):e004321. doi: 10.1136/bmjoq-2026-004321.

ABSTRACT

Placental histopathology is central to good perinatal care, offering insight into antepartum and intrapartum events, informing neonatal management and supporting counselling for future pregnancies. Despite clear national guidance, many placentas that meet criteria are not sent for evaluation. Reasons are multifactorial, including inconsistent awareness of indications and unclear post-delivery processes. Two UK maternity units, St Thomas’ Hospital in London and the Royal Berkshire Hospital in Reading, identified local variations in practice that led to placentas not being appropriately sent. At St Thomas’ Hospital, a baseline audit performed as part of a preterm birth research study revealed only 80% of eligible deliveries had placental examination. At the Royal Berkshire Hospital, a coroner’s inquest after an unexpected neonatal death, highlighted the absence of indicated placental histology, prompting a recommendation for 48-hour retention of all placentas. A quality improvement project using Plan Do Study Act cycles was implemented at both sites. Interventions included installation of dedicated labour ward fridges for 48-hour storage with temperature monitoring, targeted education on indications for placental histology and daily cross-checking of neonatal admissions to ensure eligible placentas were sent. The primary outcome was the proportion of placentas meeting criteria sent for histopathology, focusing on deliveries <32 weeks and intrauterine deaths >18 weeks. National investigation reports at St Thomas’ Hospital were also reviewed for missing histology. Labour ward storage proved feasible and effective. At the Royal Berkshire Hospital, submission rates improved from 88% to 97% for intrauterine deaths and from 71% to 100% for very preterm births. At St Thomas’ Hospital, preterm submissions increased from 80% to 96% after education and 98% after storage, with intrauterine death remaining at 100%. Missing histology in national investigations reduced from 12% to 0%. Short-term placental storage is a low-cost, scalable intervention aligned with national maternity safety priorities.

PMID:42648748 | DOI:10.1136/bmjoq-2026-004321