Nevin Manimala

J Inflamm Res. 2025 Nov 4;18:15283-15292. doi: 10.2147/JIR.S541842. eCollection 2025.

ABSTRACT

OBJECTIVE: To investigate the prognostic value of clinical and inflammatory markers predicting response to nivolumab in patients with metastatic non-small cell lung cancer (NSCLC).

MATERIALS AND METHODS: Clinical, demographic and laboratory data of stage 4 NSCLC patients who were treated between February 2021 and November 2024 were analyzed. Before nivolumab treatment, inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), prognostic nutritional index (PNI), hemoglobin-albumin-lymphocyte-platelet score (HALP), neutrophil-to-eosinophil ratio (NER) and C-reactive protein-to-albumin ratio (CAR) were calculated. Factors affecting overall survival (OS) were determined by Cox regression analysis, and ROC curve analysis was used to calculate the ideal cut-off.

RESULTS: The study included 229 NSCLC patients and the median age of the patients was 63 years. The majority were male (84.3%) and had right lung localization (56.8%). Median overall survival was calculated as 21.2 months (95% CI: 17.4-25.0). In univariate cox-regression analysis, the presence of brain metastases (HR: 2.08; p=0.004), liver metastases (HR: 1.85; p=0.014) and adrenal metastases (HR: 1.64; p=0.045) negatively affected the treatment response. Inflammatory markers such as high NLR (HR: 2.04; p<0.001), high SII (HR: 1.96; p<0.001), high CAR (HR: 1.84; p=0.001), high PLR (HR: 1.60; p=0.009) and high SIRI (HR: 1.51; p=0.021), low PNI (HR: 0.48; p<0.001), low HALP (HR: 0.49; p<0.001) and low LMR (HR: 0.65; p=0.016) were associated with poor prognosis. In multivariate analysis, the presence of brain metastasis (HR: 2.84; p<0.001), adrenal metastasis (HR: 1.64; p=0.046) and low PNI (HR: 0.44; p<0.001) together predicted poor prognosis and formed a statistical model on treatment response.

CONCLUSION: In patients with metastatic NSCLC, nivolumab treatment response is predicted by inflammatory markers and the presence of brain and adrenal metastases. It was concluded that low PNI among inflammatory markers is a strong prognostic indicator in this patient group.

PMID:41209385 | PMC:PMC12595935 | DOI:10.2147/JIR.S541842

AI Soc. 2025;40(7):5181-5194. doi: 10.1007/s00146-025-02272-3. Epub 2025 Mar 21.

ABSTRACT

The concept of alignment has undergone a remarkable rise in recent years to take center stage in the ethics of artificial intelligence. There are now numerous philosophical studies of the values that should be used in this ethical framework as well as a technical literature operationalizing these values in machine learning models. This article takes a step back to address a more basic set of critical questions: Where has the ethical imperative of alignment come from? What is the ethical logic of alignment-how, exactly, does it propose to regulate machines’ and peoples’ conduct? And what are the social and political implications of this ethics? After discussing the logical and normative implications of the term itself-in what sense alignment can have an ethical meaning-we undertake a four-part “anatomy” of alignment in contemporary large language models (LLMs): first, a relatively technical sense in sequence modeling; second, a more normative sense relating to how outputs of pre-trained models are ethically evaluated; a third sense where external values are introduced using fine-tuning techniques to manage undesired model behaviors; and fourth sense, where alignment is given extreme ethical stakes in philosophical discussions of existential risks. We find that the ethics of alignment is fundamentally concerned with the problem of control, with unintended model behaviors that arise from divergences between training objectives and the normative expectations that govern the contexts in which they are used. Alignment serves to bridge the gap between what we call an “is” normativity, of statistical patterns identified by models and an “ought” normativity where values are technically introduced in models to steer them away from undesired behaviors. By problematizing control, the ethics of alignment weakens capacities to both make more substantive ethical judgments and also political decisions about how to live with AI.

PMID:41209378 | PMC:PMC12594722 | DOI:10.1007/s00146-025-02272-3

Int J Exerc Sci. 2025 Nov 1;18(8):1175-1185. doi: 10.70252/HSMV3009. eCollection 2025.

ABSTRACT

This study explored how age affects postural stability (PS) in firefighters by focusing on two key objectives: 1) determining if age affects right-to-left anterior (ANT) reach distance asymmetry (ASYM) during the Motor Control Screen (MCS) test and 2) assessing whether the proportion of firefighters not meeting the greater than two-foot length (2FL) criterion for ANT reach differs across age groups. Data from 95 male firefighters were analyzed using the MCS ANT reach test, part of the Y-Balance Test (YBT). The key outcomes were the difference in ANT reach distances between legs (ASYM) and the proportion reaching less than or equal to 2FL. Statistical analyses used Mann-Whitney U tests for ASYM and chi-square tests for proportions. No statistical difference in ASYM was found between younger and middle-aged firefighters (U=1025, p=0.501, r=-.069). Similarly, the proportion of firefighters not meeting the greater than 2FL criterion did not significantly differ across age groups for both right and left ANT reaches (p= 0.997, ϕ=.000 for right and p= 0.547, ϕ=-.062 for left). These findings indicate that age does not significantly influence right-to-left ANT reach ASYM or the likelihood of failing to meet the greater than 2FL criterion in this firefighter population. The results suggest that PS, as measured by ANT reach ASYM and the greater than 2FL criterion, does not significantly decline with age among firefighters. This may be due to the physical demands of firefighting. Future research should explore how ANT reach measures relate to injury risk and evaluate age-specific balance training interventions.

PMID:41209371 | PMC:PMC12591606 | DOI:10.70252/HSMV3009

Int J Exerc Sci. 2025 Nov 1;18(8):1212-1227. doi: 10.70252/ERIN2946. eCollection 2025.

ABSTRACT

This study aimed to examine weekly variations and within-subject relationships between internal training intensity (ITI), perceived recovery (TQR), neuromuscular performance (CMJ), and perceived muscle soreness (PMS) during a four-week preseason period in professional soccer players. Twenty-three soccer players (age 24.8 ± 4.4 years; height 182 ± 7 cm; body mass 74.6 ± 6.7 kg) classified as Tier 3 athletes from the Croatian Second Soccer League were monitored using session rating of perceived exertion, TQR scales, countermovement jump tests, and PMS questionnaires. A significant reduction in ITI and concurrent improvement in TQR scores were observed across the preseason, with the highest intensity in week 1 and the lowest recovery in week 2. CMJ height performance declined during peak fatigue but rebounded as training intensity tapered. Repeated-measures correlations revealed negative associations between weekly ITI and TQR of the following week (r_rm = -0.72), and between ITI and CMJ (r_rm = -0.55), indicating that greater training intensities may impair both perceptual and neuromuscular recovery. The training stimulus-recovery difference index was positively associated with next-day TQR, suggesting it may serve as a sensitive marker of session-level readiness. These findings highlight the interplay between intensity, recovery, and fatigue, emphasizing the utility of low-cost subjective and objective tools for monitoring preseason responses and guiding individualized training strategies in elite soccer settings.

PMID:41209368 | PMC:PMC12591601 | DOI:10.70252/ERIN2946

J Alzheimers Dis Rep. 2025 Nov 6;9:25424823251395304. doi: 10.1177/25424823251395304. eCollection 2025 Jan-Dec.

ABSTRACT

BACKGROUND: The prevalence of Alzheimer’s disease or dementia is rising among the elderly population in the United States and globally. Sociodemographic, cancer, and neurological disorders are associated with cognitive impairment of people living in rural communities.

OBJECTIVE: This study identified the association of cognitive impairment with cancer and neurological disorders of the elderly in Cochran and Parmer Counties of rural West Texas.

METHODS: Pearson’s chi-squared, two-sample independent proportions, binary logistic regression, and multivariable logistic regression methods were utilized to analyze data.

RESULTS: Individuals aged 70 and above experiencing memory loss in Cochran and Parmer Counties had a statistically significant association with cognitive impairment (p < 0.001). In Parmer County, females diagnosed with breast cancer demonstrated a significant relationship with cognitive impairment (p < 0.05). Neurological factors, including muscle strength, cerebellar function, ability to rise from a chair, and Romberg test results, were significantly associated with an increased risk of cognitive impairments among females in both counties. After adjusting for covariates, males aged 60-69 in Parmer County, as well as memory loss among both genders, were significantly associated with cognitive impairment (p < 0.001). Additionally, females with cognitive impairment in Cochran County exhibited higher dependence on mental health services compared to males (p < 0.05).

CONCLUSIONS: Examining the association between cognitive impairment or Alzheimer’s disease and cancer and neurological disorders is important for developing interventions aimed at reducing their prevalence in underserved rural West Texas Counties.

PMID:41209366 | PMC:PMC12592674 | DOI:10.1177/25424823251395304

Resusc Plus. 2025 Oct 10;26:101127. doi: 10.1016/j.resplu.2025.101127. eCollection 2025 Nov.

ABSTRACT

BACKGROUND: In 2018 the prehospital Emergency Medical System (EMS) in Luxembourg underwent a major reorganization by the creation of a single EMS structure. We aimed to study the impact of this reorganization on outcome after out-of-hospital cardiac arrest (OHCA).

METHODS STUDY DESIGN: We conducted a before-and-after study on outcome after OHCA in Luxembourg taking advantage of the existing EuReCa studies protocols and case report forms. The first period extended from October 2017 to September 2018, and the second from September 2021 to August 2022.

SETTING: Nationwide observational database on OHCA.

PARTICIPANTS: All OHCA patients within the territory of the Grand Duchy of Luxembourg reported through an emergency call.

INTERVENTION: None.

MAIN OUTCOMES AND MEASURES: The primary outcome was the survival rate after OHCA. Secondary outcomes were rates of bystander and phone cardio-pulmonary resuscitation (CPR), return of spontaneous circulation (ROSC) rates and arrival times of EMS.

RESULTS: Over the 2 time periods, the incidence of OHCA emergency calls remained stable, whereas the confirmed OHCA increased from 236 to 375 cases per year. Bystander and phone CPR rates significantly increased, by 1.5 and 5-fold, respectively. EMS response time was significantly reduced (16:19 min vs 11:03 min, p < 0.001) and associated with significantly improved survival (OR per minute 0.83, 95 % CI 0.73-0.95). Hospital admission with ROSC increased non-significantly from 19 % to 24 % (p = 0.08) and 1-month survival increased significantly from 9 (3.8 %) to 37 survivors (9.8 %) (p = 0.006), corresponding to 28 additional lives saved within one year. No statistically significant difference could be shown on 1-month survival or ROSC rate when phone CPR or bystander CPR were performed.

CONCLUSION: Over 4 years, major structural and organizational EMS changes led to significantly shorter EMS response times and were accompanied by a significant increase of survival after OHCA. Whether other factors also have contributed to better survival remains unclear.

PMID:41209354 | PMC:PMC12593640 | DOI:10.1016/j.resplu.2025.101127

Front Netw Physiol. 2025 Oct 23;5:1664280. doi: 10.3389/fnetp.2025.1664280. eCollection 2025.

ABSTRACT

INTRODUCTION: In this work, we introduce a novel approach to one of the historically fundamental questions in neural networks: how to encode information? More particularly, we look at temporal coding in spiking networks, where the timing of a spike as opposed to the frequency, determines the information content. In contrast to previous temporal-coding schemes, which rely on the statistical properties of populations of neurons and connections, we employ a novel synaptic plasticity mechanism that allows the timing to be learnt at the single-synapse level.

METHODS: Using a formal basis from information theory, we show how a phase-coded spike train (relative to some ‘reference’ phase) can, in fact, multiplex multiple different information signals onto the same spike train, significantly improving overall information capacity. We furthermore derive limits on the channel capacity in the phase-coded spiking case, and show that the learning rule also has a continuous derivative in the input-output relation, making it potentially amenable to classical learning rules from artificial neural networks such as backpropagation.

RESULTS: Using a simple demonstration network, we show the multiplexing of different signals onto the same connection, and demonstrate that different synapses indeed can adapt using this learning rule, to specialise to different interspike intervals (i.e., phase relationships). The overall approach allows for denser encoding, and thus energy efficiency, in neural networks for complex tasks, allowing smaller and more compact networks to achieve combinations of tasks which traditionally would have required high-dimensional embeddings.

DISCUSSION: Although carried out as a study in computational spiking neural networks, the results may have insights for functional neuroscience, and suggest links to mechanisms that have been shown from neuroscientific studies to support temporal coding. To the best of our knowledge, this is the first study to solve one of the outstanding problems in spiking neural networks: to demonstrate that distinct temporal codings can be distinguished through synaptic learning.

PMID:41209333 | PMC:PMC12589081 | DOI:10.3389/fnetp.2025.1664280

Front Bioeng Biotechnol. 2025 Oct 23;13:1653208. doi: 10.3389/fbioe.2025.1653208. eCollection 2025.

ABSTRACT

BACKGROUND: Return to sports following total hip arthroplasty (THA) is important to an increasingly younger and active clientele. However, knowledge about in vivo joint forces during sports is scarce and often only estimated. As skiing is controversially debated as an activity following THA, we measured in vivo joint loads in instrumented THAs during cross-country ski simulation.

METHODS: Five untrained subjects who had previously received instrumented THAs were instructed to perform double poling and diagonal poling exercises on a ski simulator and to walk on a treadmill at 4 km/h as a reference exercise. The joint contact force, bending moment, and torsion torque on the implant were determined. Time-load patterns were generated. Loading peaks were compared intra-and inter-individually to walking. Statistical parameter mapping was used to visualise significant differences between exercises across the movement cycle.

RESULTS: Loading maxima were mostly lower or adjacent to loading maxima of walking, except for diagonal poling with foot lift. Differences in execution of double poling resulted in different time-load patterns of torsion torque. Diagonal bending moments exceeded walking bending moments slightly. Outliers were observed.

CONCLUSION: Double or diagonal poling can be safely practiced by THA patients on a ski simulator in the late postoperative period due to mostly lower or adjacent loading forces to walking. Unilateral standing phases should be minimized. Patient’s experience and bone quality affect recommendation of this sport. Limitations concern limited generalizability of small cohort and simulated environment.

PMID:41209304 | PMC:PMC12589080 | DOI:10.3389/fbioe.2025.1653208

Front Bioeng Biotechnol. 2025 Oct 24;13:1604658. doi: 10.3389/fbioe.2025.1604658. eCollection 2025.

ABSTRACT

OBJECTIVE: This study aims to compare biomechanical features during walking between children with spastic cerebral palsy (SCP) and typically developing children, providing evidence to improve walking ability and prevent falls in children with SCP.

METHODS: The study included 28 children with SCP from the paediatric physiotherapy department of the China Rehabilitation Research Centre (March 2023 to September 2024) and 28 typically developing children from a Beijing primary school as controls. Participants wore tight-fitting clothing to ensure clear visibility of reflective markers. A Vicon 3D motion capture system and AMTI force plates were used to collect data on temporal-spatial parameters, dynamic balance and kinematic parameters during gait cycles. Measurements included walking speed; step frequency, width and length; single-foot support time; peak displacements of the centre of mass (COM) and the centre of pressure; and joint angles of the pelvis, hip, knee and ankle in multiple planes.

RESULTS: Children with SCP showed significantly lower values in walking speed, stride length, step length and single-foot support time than the controls (P < 0.05). Conversely, cadence, stride time and double support time were higher in children with SCP than in the controls. Children with SCP showed greater peak COM displacement in the coronal plane but lower in the sagittal plane than the controls (P < 0.05). Significant differences were found in the range of motion of left lower extremity joints across various phases of the gait cycle (P < 0.05).

CONCLUSION: Children with SCP exhibit distinct gait patterns and dynamic balance challenges compared with their typically developing peers, underscoring the importance of personalised rehabilitation treatments to enhance their walking abilities and prevent falls.

CLINICAL TRIAL NUMBER: ChiCTR2300071226.

PMID:41209298 | PMC:PMC12592154 | DOI:10.3389/fbioe.2025.1604658

RSC Med Chem. 2025 Nov 6. doi: 10.1039/d5md00686d. Online ahead of print.

ABSTRACT

Bioisosterism, a fundamental concept in medicinal chemistry, involves the substitution of chemical groups with structural analogs that preserve similar physicochemical properties while potentially modulating potency or toxicity. To systematically investigate shifts in pChEMBL values upon such substitutions, we developed a KNIME workflow that extracts and analyzes compound pairs featuring literature-curated common bioisosteric exchanges. The workflow retrieves pChEMBL values across 88 off-targets from ChEMBL and supports decision-making through pair-level quality metrics such as the document consistency ratio and assay context consistency ratio, which assess the consistency of the source data. Our analysis revealed that ester-to-secondary-amide replacements at the muscarinic acetylcholine receptor M2 (CHMR2) result in a significant mean decrease in pChEMBL of 1.26 across 14 compound pairs (p < 0.01). In contrast, phenyl-to-furanyl substitutions at the adenosine A2A receptor (ADORA2A) led to a mean increase in pChEMBL of 0.58 across 88 compound pairs (p < 0.01). Furthermore, a second KNIME workflow was developed to assess selectivity profiles by analyzing pChEMBL shifts at secondary targets. Among 66 compound pairs active at both ADORA2A and ADORA1, the mean change at ADORA1 was only +0.14 ± 0.52, indicating a selective potency increase at ADORA2A. This exemplifies a potential case of increased potency at an off-target associated with adverse effects, while maintaining activity at a pharmacologically desirable target. Conversely, furanyl-to-phenyl replacements may selectively reduce undesired potency at ADORA2A while preserving potency at ADORA1. This framework enables systematic, data-driven evaluation of potency shifts induced by bioisosteric replacements, aiding in the identification of substitutions associated with off-target potency increases or decreases during lead optimization. The workflow offers a semi-automated, reproducible approach that integrates bioisostere generation, activity mapping, and statistical assessment in a single platform, making it readily adaptable to other compound series and target panels. In addition, it evaluates whether activity at other known targets remains unchanged, thereby providing an assessment of selectivity of the replacements. The workflow can be applied to prioritize replacement strategies that reduce off-target risks, evaluate selectivity profiles, and generate curated potency shift data to support predictive modeling efforts.

PMID:41209296 | PMC:PMC12591391 | DOI:10.1039/d5md00686d