Category: Nevin Manimala

Cancer Sci. 2025 Sep 22. doi: 10.1111/cas.70192. Online ahead of print.

ABSTRACT

T-cell receptor (TCR) bispecific proteins represent a pioneering therapeutic modality that harnesses the diverse target recognition capabilities inherent to TCRs while preserving the beneficial characteristics associated with protein therapeutics. However, investigations into TCR bispecific proteins, particularly within the context of lung diseases, remain limited. This study aims to elucidate their potential for the treatment of lung cancer. We employed a humanized murine model to evaluate the efficacy of TCR bispecific proteins in eradicating lung tumors in vivo. Cytotoxic activity was assessed against various lung cancer cell lines, and statistical tests were used to analyze the data. To address concerns regarding toxic side effects from systemic administration, mesenchymal stem cells (MSCs) were explored as vehicles for the targeted delivery of TCR bispecific proteins. Our findings demonstrate that TCR bispecific proteins exhibit substantial cytotoxic activity against a variety of lung cancer cell lines. MSCs, with optimal pulmonary targeting properties, were shown to persist within the lungs for over 7 days. By employing MSCs to locally secrete TCR bispecific proteins, we achieved therapeutic effects comparable to systemic administration without manifestations of immune overactivation in murine subjects. Additionally, we evaluated various cytokine combinations and discovered that the combination of IL-7, IL-21, and TCR bispecific proteins significantly augmented their capacity to eliminate antigen-negative cells in a heterogeneous tumor model. Collectively, our findings suggest that the combinatorial therapy of TCR bispecific proteins and MSCs holds considerable promise for clinical application in the treatment of lung cancer, potentially enhancing therapeutic efficacy while minimizing adverse effects.

PMID:40977380 | DOI:10.1111/cas.70192

Am J Hum Biol. 2025 Sep;37(9):e70149. doi: 10.1002/ajhb.70149.

ABSTRACT

Human biologists seek to understand how cultural, environmental, and biological forces shape observed patterns of human variation. Yet contemporary insights and approaches to observational causal inference remain underutilized in the field. We outline a structured but flexible roadmap for causal inference in human biology that begins with theory development, defines causal questions and estimands, employs directed acyclic graphs (DAGs) to clarify assumptions, and evaluates key identification criteria prior to statistical analysis. We position this framework within a spectrum of causal inference traditions, spanning from interventionist approaches rooted in well-defined, manipulable exposures to realized approaches that engage historically situated and ecologically embedded phenomena. Rather than offering a prescriptive checklist, we frame this toolkit as an opening: a step toward anthropological causal inference that integrates transparency, theoretical and methodological coherence, and the epistemological commitments of the biocultural synthesis in human biology and anthropology.

PMID:40977372 | DOI:10.1002/ajhb.70149

Aust J Prim Health. 2025 Sep;31:PY24190. doi: 10.1071/PY24190.

ABSTRACT

Research highlights a child’s environment and experiences during the first 2000days has a lasting impact on their health, development and wellbeing. In NSW, it is recommended that all children under 5years of age have free routine health and developmental checks, promoting optimal childhood development and shaping future health outcomes. There appears to be a strong indication that parents do not return for their checks. Between 2019 and 2020, a qualitative study was undertaken aiming to identify and better understand the key factors driving parents’ disengagement from child family health nursing (CFHN) services after contact in their baby’s first year. Moreover, having a greater understanding of key factors driving parents’ early service disengagement may help to reshape service delivery. During the study period, parents of infants who had received the 1-4-week health check with CFHN services were informed about the study and invited to participate. A total of 104 families gave consent to take part in phone interviews. These interviews were transcribed and analysed using straightforward thematic analysis. Qualitative data were gathered to explore families’ experiences with the CFHN services. Less than 35% of families utilised CFHN services, whereas >62% visited their general practitioners. Barriers identified included the presence of multiple services, established relationships with current health professionals, limited accessibility, convenience factors and parents’ lack of knowledge regarding CFHN services. On a positive note, half of the participants reported experiencing no barriers. This study emphasises the need for better awareness and accessibility to CFHN services. The findings are concerning, because children missing health screenings may experience delays in early identification and intervention before starting school.

PMID:40977348 | DOI:10.1071/PY24190

Brain Impair. 2025 Sep;26:IB24118. doi: 10.1071/IB24118.

ABSTRACT

Background International guidelines recommend a specialised, multidisciplinary approach to optimise outcomes post disorders of consciousness (DoC), with family education the cornerstone of management. Despite this, multidisciplinary staff report reduced confidence and skill in the management of patients with DoC, and education provision to families is inconsistent. This study aimed to evaluate the effectiveness of DoC education packages in enhancing self-perceived knowledge, confidence and skill of staff and families surrounding acute DoC management. Methods Standardised education packages were developed and delivered to: (1) neurosciences staff, and (2) families of patients with DoC. Pre and post education surveys were used to measure family and staff self-perceived knowledge, confidence and skill in management of patients with DoC. Non-parametric statistics were utilised to analyse the quantitative data, whereas thematic analysis was used to analyse open-ended responses. Results Twenty-six family members and 86 health professionals were recruited. There was a statistically significant improvement across all areas of self-perceived knowledge, confidence and skill post introduction of the education packages (all P Conclusions DoC family and staff education packages can enhance family and staff self-perceived knowledge, confidence, and skill surrounding management of patients with DoC.

PMID:40977340 | DOI:10.1071/IB24118

Lab Chip. 2025 Sep 22. doi: 10.1039/d5lc00414d. Online ahead of print.

ABSTRACT

Cumulus removal (CR), the removal of the small protective granulosa cells that surround an oocyte, is a crucial step in assisted reproductive technologies (ART). Traditional CR methods rely on vortexing or manual pipetting, which can result in inconsistencies and variability. Here, we present an open-surface platform featuring pillars that actively separates differently sized particles and removes cumulus cells from oocytes through vibration-induced flow (VIF). The platform removed 99% of small particles from the loading chamber by generating a local flow through the pillar array and separating smaller particles from larger particles. The platform was then used to remove cumulus cells from oocytes. CR under different actuation powers, time exposures, and hyaluronidase (HA) concentrations was optimized. The CR of up to 23 oocytes was accomplished simultaneously without any oocyte loss. Finally, mouse cumulus-oocyte complexes (COCs) were inseminated and CR was performed using both manual pipetting (control) and VIF. No statistical difference was observed in the fertilization and blastocyst rates, which were 90.7%, and 50.0% using manual pipetting, respectively, and 93.1% and 43.1% using VIF respectively. This platform automates CR process and reduces the technical manual labor involved in ART, paving the way for standardization and consistency within ART protocols.

PMID:40977337 | DOI:10.1039/d5lc00414d

Brain Impair. 2025 Sep;26:IB25005. doi: 10.1071/IB25005.

ABSTRACT

Background Computer-mediated communication (CMC) – using technology to engage with others via digital platforms (e.g. social media) – is an integral mode of social interaction for adolescents. Integrating CMC into rehabilitation could benefit adolescents with acquired brain injury (ABI), yet its use is under-studied. This study aimed to address this gap by co-designing a survey on CMC use among adolescents with ABI and evaluating the project team’s perceptions of engagement in the co-design process post-study. Methods The project team comprised 10 interest-holders: youth with ABI (n =2), rehabilitation professionals (n =2), researchers (n =5), and a family member (n =1). Survey co-design sessions conducted via videoconferencing were guided by the Double Diamond (DD) Framework. Mixed-methods analysis included descriptive statistics from the Patient and Public Engagement Evaluation Tool (PPEET), qualitative insights on team engagement and reflexive thematic analysis of memos, and overview of survey categories and questions. Results Five co-design sessions resulted in the Social Media Building Blocks (SMBB) survey, refined through piloting with two youth with ABI and a health literacy review. PPEET data showed strong team engagement, with 5/6 ‘strongly agreeing’ their views were heard and valued. Thematic analysis of team memos identified three themes: valuing diverse perspectives, enthusiastic engagement in co-design, and the importance of reflexivity. The final SMBB survey included four question categories: participation in online communication, accessibility, post-ABI communication experiences, and desired supports. Conclusions Project team members valued the collaborative survey design phases and engaging youth with ABI. Findings highlight co-design frameworks’ potential to enhance engagement in rehabilitation research.

PMID:40977334 | DOI:10.1071/IB25005

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2025 Sep 19. doi: 10.5507/bp.2025.025. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Intraoperative Floppy Iris Syndrome (IFIS) is a condition that can lead to a number of complications during cataract surgery that threaten final vision of patients using alpha1-adrenergic receptor antagonists (α1-ARAs). There are two recommended pharmacological approaches to preventing IFIS development: intraoperative intracameral epinephrine and application of atropine drops twice a day for one week before surgery. The primary aim of this study was to identify the incidence and grade of IFIS using these two prophylactic approaches in patients at risk of IFIS development and to determine which approach is more effective for mild and severe IFIS. The second aim was to evaluate complication rates between the two.

METHODS: The study consisted of 164 eyes of 164 men using α1-ARAs. 83 eyes were treated with atropine sulphate 1% drops (Group 1) while 81 eyes received an injection of epinephrine to the anterior chamber during cataract surgery (Group 2).

RESULTS: Even though the incidence of IFIS was lower in the epinephrine group this was not statistically significant at the 5% level (P=0.269). Apropos severity, there was a statistically significantly higher incidence of moderate and severe forms of IFIS in Group 2 (P<0.0001). There was no significant difference between groups in the development of surgical complications (P=0.165).

CONCLUSIONS: The instillation of epinephrine was more effective in preventing the overall incidence of IFIS. Nevertheless, the occurrence of IFIS in its moderate and severe forms was statistically significantly higher in this group.

TRIAL REGISTRATION: The study protocol was retrospectively registered in the Clinical Trial registry clinicaltrials.gov under ID number NCT06266962.

PMID:40977319 | DOI:10.5507/bp.2025.025

Acta Ophthalmol. 2025 Sep 22. doi: 10.1111/aos.70008. Online ahead of print.

ABSTRACT

PURPOSE: This study evaluates whether mesopic microperimetry (MMP) provides a more robust measure of retinal function compared to visual acuity (VA) in age-related macular degeneration (AMD) clinical trials, with a focus on optimal analysis strategies.

METHOD: Fellow-eyes of unilateral neovascular AMD were prospectively studied. Presenting VA was measured. The Macular Integrity Assessment Microperimeter (MAIA) was used with a 4 to 2 staircase strategy with a 10° diameter grid containing 37 loci. Three analysis strategies were calculated: the mean of 37 sensitivity thresholds (MS), the per cent reduced threshold (PRT), and the log-transformed candela mean (MS cd log). Sample size requirements were calculated for 12- and 24-month follow-ups using a paired one-sided T-test (α = 0.05, power = 0.80).

RESULTS: N = 123 were analysed (82 (65.5%) females; mean age 74.2 (7.8) years). Ranked high to low, the required sample size at 12 months was: MS (n = 51), MS cd log (n = 52), PRT (n = 139), and VA (n = 203). Similar trends were seen at 24 months, with MS requiring the smallest sample size (n = 85) and VA the largest (n = 1673).

CONCLUSION: All MMP analysis strategies outperformed VA, and MS required the least number of patients to show significant changes. This trend was consistent for both 12 and 24 months. These findings provide strong statistical arguments for the use of MMP in longitudinal within-subjects clinical trials and suggest that averaging decibels is optimal.

PMID:40977307 | DOI:10.1111/aos.70008

J Health Organ Manag. 2025 Sep 23:1-23. doi: 10.1108/JHOM-12-2024-0493. Online ahead of print.

ABSTRACT

PURPOSE: This study refines equity theory by explaining the mediating roles of job frustration and job dissatisfaction, as well as the moderating role of personal income in the relationship between discriminatory workplace favoritism and hospital employees’ intent to quit.

DESIGN/METHODOLOGY/APPROACH: The study consists of two samples. In the first sample, survey questionnaires were administered to 267 public hospital employees in Turkey. In the second sample, 1,426 university healthcare students in Turkey answered four different scenarios that narrated school favoritism as well as students’ frustration, dissatisfaction and intent to quit. Structural equation modeling and ANOVA statistical analyses were conducted.

FINDINGS: Workplace favoritism positively affected employees’ intent to quit through the mediation of job frustration and job dissatisfaction. The mediating role of job frustration between workplace favoritism and intent to quit was stronger for high-income than for low-income employees and students.

PRACTICAL IMPLICATIONS: Favoring one employee may result in voluntary organizational exit by other employees, which is costly for the organization. Favoritism may encourage employees who were not previously prone to favoritism to seek favoritism. This may create a cycle that spreads favoritism further within the organization.

ORIGINALITY/VALUE: This is the first study to investigate the role of income in the relationship between workplace favoritism and employees’ intent to quit.

PMID:40977299 | DOI:10.1108/JHOM-12-2024-0493

Breastfeed Med. 2025 Sep 22. doi: 10.1177/15568253251381804. Online ahead of print.

ABSTRACT

Objectives: Mothers of preterm infants who experience mother-infant separation frequently face increased challenges with lactation. This study aims to analyze the critical window for coming to volume (CTV) and its associated risk factors in pump-dependent mothers and to investigate the predictive value of postpartum expressed milk volume for the feeding method at discharge in preterm infants. Study Design: A prospective observational study was conducted between July 2020 and February 2021. Lactation diaries kept by mothers of preterm infants admitted to a neonatal intensive care unit in Guangzhou, China, were collected during this period. Binary multivariable Logistic regression, time-series analysis, Spearman correlation analysis, and K-Prototype cluster analysis were employed to investigate the critical window for CTV and its risk factors. The area under the receiver operating characteristic curves were used to evaluate the ability of expressed milk volume during postpartum days 8-14 to predict the feeding method at discharge for preterm infants. Results: Data from 1,232 diary days completed by 88 mothers were analyzed. 51.14% of mothers of preterm infants failed to CTV. Unscheduled pumping, a lower average pumping frequency on postpartum day 1-7, a lower average expressed breast milk volume on postpartum day 1-7, and a small intra-session bilateral volume discrepancy were identified as independent risk factors for no-CTV. During postpartum days 3-7, both pumping frequency and milk volume increased progressively. The frequency and volume of pumping between postpartum days 3 and 7 positively correlated with the milk volume on postpartum day 14. Clustering analysis based on early postpartum pumping behaviors identified two groups: High-Frequency Timed Group (HFTG) and Low-Frequency Untimed Group. The HFTG exhibited higher pumping frequency and milk volume, indicating a greater likelihood of achieving CTV. The expressed breast milk volume on postpartum day 8 significantly predicted the feeding method at discharge (Area Under the ROC Curve [AUC] [95% confidence interval]: 0.831 [0.746-0.916]), with no statistically significant difference in predictive performance compared to volumes on days 9-14 (p > 0.05). Conclusion: Postpartum days 3-7 represent the critical window for CTV among mothers of preterm infants, during which pumping behavior directly influences CTV. Postpartum day 8, as the first day following the critical window, provides an early and effective prediction of feeding outcomes at discharge.

PMID:40977274 | DOI:10.1177/15568253251381804