Zubair Ahmed

Background: Amyotrophic lateral sclerosis (ALS) is a rare, neurodegenerative disease, for which there is currently no known cure. ALS primarily affects motor neurons, with rapid deterioration, meaning symptoms develop quickly, from problems with speech and muscle weakness to breathing issues and paralysis. This systematic review aimed to explore the preclinical efficacy of various genetic therapies used to target ALS using in vivo rodent models. Methods: In vivo studies of genetic therapies targeting ALS and its symptoms published between January 2015 and December 2025 were included in this review. The following databases were used: Web of Science, Scopus and PubMed. The primary outcome investigated was the total number of motor neurons, with secondary outcomes of rodent survival and muscle function by observing rotarod performance also being analysed. The SYRCLE tool was used to assess risk of bias in included studies. Results: Of the 451 studies identified by searching the databases, 53 studies were found to be eligible for this systematic review. The articles were divided into subcategories depending on the gene target of each therapy. Meta‐analysis of outcomes within appropriate studies showed significant improvements for the majority of selected outcomes ( p < 0.05), favouring genetic therapy intervention. Conclusions: Results suggest that genetic therapies in rodent models targeting ALS are effective. However, due to a high risk of bias in preclinical studies, further high‐quality studies are warranted to support this conclusion and onward translation into the clinic.

Background: Post-operative pneumonia is a commonly occurring surgical complication associated with poor patient outcomes. This study aimed to synthesise pre-operative and post-operative blood-based biomarkers associated with post-operative pneumonia. Methods: Electronic databases were searched up to April 14th, 2026. Primary studies investigating blood-based biomarkers in adults hospitalised after surgery were included. Meta-analysis was performed using the random effects model to compare pooled data for pneumonia and no-pneumonia groups using standardised mean difference. Risk of bias was assessed using the ROBINS-E tool. Results: Thirty-seven studies ( n = 15,842 patients) were included, with an overall pneumonia rate of 17.8% [15.8–20.0%]. One hundred and fifteen biomarkers were identified. Meta-analysis identified that patients who developed post-operative pneumonia had significantly lower platelet-to-neutrophil ratio ( p < 0.0001), red blood cell count ( p = 0.001), haemoglobin ( p = 0.002), albumin ( p = 0.005) and lymphocyte count ( p = 0.008) and significantly higher monocyte-to-lymphocyte ratio ( p < 0.0001), systemic immune inflammation index ( p < 0.001), systemic inflammatory response index ( p < 0.0001) and blood urea nitrogen ( p = 0.0001) at pre-operative baseline, compared to those without pneumonia. Patients who developed post-operative pneumonia were associated with significantly higher procalcitonin (PCT) at post-operative day one ( p = 0.03), two ( p = 0.0001), three ( p = 0.0004) and six ( p < 0.0001); higher C-Reactive Protein (CRP) at day two ( p = 0.02), four ( p < 0.0001) and five ( p < 0.0001); higher interleukin (IL)-6 at day three ( p = 0.001) and four ( p = 0.0002); and higher white blood cell (WBC) count at day three ( p = 0.01) and day four ( p = 0.001) post-operatively, compared to those without pneumonia. In addition, pre-operative CRP was associated with mortality within the patients who later developed post-operative pneumonia ( r = 0.70, p = 0.0009). Conclusions: The results identify blood-based biomarker signals associated with post-operative pneumonia. However, interpretation is limited by heterogeneous pneumonia definitions and inconsistent reporting of diagnosis timing across studies. The certainty of evidence is therefore limited, and thus these biomarkers cannot currently be used for prediction or diagnosis in clinical practice. Further high‑quality, prospective studies are required to establish clinically meaningful thresholds. Protocol registration: PROSPERO: CRD42024570654.

Marker-based motion analysis systems are widely used to quantify movement; however, they are expensive, time-consuming, and require specialist expertise. Consequently, markerless approaches have become increasingly popular. Although several studies have evaluated markerless methods, limited research has investigated seated functional tasks, despite their potential relevance for clinical populations. Therefore, this study evaluated the validity of two-dimensional (2D) trunk and upper-limb kinematics derived from DeepLabCut and Human Skeleton and Mesh Recovery (HSMR) against a marker-based reference system (Vicon) during seated functional tasks. Fifteen healthy participants performed four seated functional tasks. Validity of trunk (full trunk, thoracic, lumbar, and pelvic segments) and upper-limb angular displacement time-series was assessed using root mean square error (RMSE), normalised RMSE, Pearson’s correlation coefficients, and statistical parametric mapping. Agreement for discrete variables was evaluated using RMSE, Bland–Altman analysis, and intraclass correlation coefficients (ICC). Between-session reliability was assessed using ICC, standard error of measurement, and minimal detectable change. Both markerless approaches showed moderate-to-strong agreement with Vicon for full trunk, thoracic, and arm kinematics, whereas lower agreement was observed for lumbar and pelvic segments, with HSMR showing lower agreement than DeepLabCut. Between-session reliability was generally good for full trunk, thoracic, and arm segments; however, HSMR demonstrated higher reliability in the lumbar and pelvic regions. These findings support the use of low-cost single-camera markerless systems for assessing seated trunk and upper-limb kinematics, while highlighting method-specific trade-offs and the need for improved tracking of lumbar and pelvic motion.

Background: Early mobilization (EM) refers to active exercise commenced while patients are on the intensive care unit (ICU). Although the benefits of EM are well established in general ICU populations, evidence specific to the neurotrauma intensive care unit (NTICU) remains limited. This service evaluation aimed to review current EM practices in a single-center NTICU and explore the perceived barriers to EM implementation. Method: A service evaluation was conducted from 5th December 2023 to 28th March 2024, including all patients resident in the NTICU. During this period, patients underwent daily physiotherapy assessments, at which data were prospectively recorded for the suitability for EM, and barriers to EM, where this was not performed. Mobility status was quantified using the Manchester Mobility Scale (MMS), with mobilization defined as an MMS ≥ 2 (i.e., sitting on the edge of the bed or higher). Data for patient characteristics and outcomes were retrospectively collected from the electronic health record system. Results: Of 253 patients included in the service evaluation, EM (i.e., MMS ≥ 2 in the NTICU) was achieved in 149 (58.9%), with a further 76 (30.0%) mobilized on the ward after being discharged from NTICU. The most common primary barriers to EM were sedation (38.4%) and the need for acute medical care (33.9%). Logistical and process issues were the primary barrier to EM in 15.4% of assessments, most commonly insufficient staffing. Conclusion: This service evaluation is the first known report of perceived barriers to EM in a UK-based NTICU. Targeted strategies to address modifiable barriers may facilitate earlier mobilization within major trauma services. Further research is needed to evaluate the safety and impact of NTICU-specific EM protocols.

Purpose: The purpose of this paper is to synthesize current mechanistic insights and translational progress on neurocognitive aging after critical illness and to outline a framework for developing neurotherapeutic drugs for clinical application. Method: The method includes a narrative, focused review of clinical studies in patients’ neurocognitive symptoms after critical illness, such as sepsis, trauma, and burns, reported up to December 2025. Evidence was organized across domains, including acute systemic inflammation (ASI), communication channels to the central nervous system (CNS), neuroinflammation and neural integrity, autoimmunity in critically ill patients, and potential therapeutic targets and strategies. Finding: Acute illness and inflammatory states, including sepsis, trauma, and burns, can lead to accelerated neurocognitive aging, early‐onset cognitive impairment, and memory loss. In acute and critical illness, this is attributed to neuroinflammation, microvascular damage, blood–brain barrier (BBB) disruption, and microglial activation resulting from ASI and immune dysregulation. Current research suggests that it also induces cellular senescence, triggering immune dysregulation and subsequent autoimmunity and autoantibody production, contributing to the progression of neurocognitive aging amid chronic low‐grade inflammation and inflammaging. These processes affect the function and integrity of the CNS, leading to neurocognitive decline. Conclusion: This review examined the scientific basis for the development of neurocognitive aging after acute illness and how this information may be used to develop potential targets to modulate inflammatory and immune responses and treat this debilitating condition. Such interventions may reduce the burden of senescent cells, mitigate BBB breakdown, restore immune balance, and enhance the brain's neuroplasticity and resilience.

The purpose of this systematic review was to determine whether the addition of antimicrobial peptides (AMPs) to dressing materials enhances their wound healing capabilities when applied to S. aureus ‐infected wounds in rodent models. The primary objective was not to derive definitive efficacy conclusions, but to systematically assess the quality, consistency, and translational readiness of existing in vivo evidence for AMP‐based dressings in excisional wound models to inform future in vivo experimental design. The systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Two authors independently completed the literature search using three electronic databases and two databases for grey literature. Studies were included if they met pre‐established inclusion criteria. Rate of wound healing was considered as the primary outcome; the secondary outcome involved histological analyses of tissue samples of the wounds. Risk of bias was assessed using the SYRCLE risk of bias tool for animal studies and meta‐analysis was performed with pooled data from three or more studies reporting the same outcome, employing a random effects model. By the final timepoint, the meta‐analyses identified a significant increase in wound healing rate in both rats (mean difference = 2.79%, 95% CI [1.52%, 4.06%], p < 0.0001) and mice (mean difference = 32.30%, 95% CI [18.06%, 46.54%], p < 0.00001) exposed to AMP‐based dressing materials compared to AMP‐free carrier materials. The significantly improved wound healing rates provide promising evidence that these materials are suitable for promoting the wound healing of S. aureus ‐infected wounds that may be investigated further in clinical studies.

Mislocalization and aggregation of the DNA/RNA binding protein, TDP-43, is seen in most cases of amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD). Accumulating DNA damage in neurons is also a common feature of ALS-FTD. TDP-43 has several characterized roles in the regulation of the DNA damage response (DDR). This review systematically explored the relationship between TDP-43, DNA damage and the DNA damage response in various models of ALS-FTD, facilitating comparison of findings between studies using similar models. Twelve peer-reviewed papers, covering eight TDP-43 mutations out of nearly 40, were reviewed and five experimental models included: cell lines, patient-derived iPS cells, organoids, and rodent models, plus post-mortem cortex and spinal cord tissue from ALS-FTD patients. Across the studies and models, depletion of TDP-43 or ALS-linked mutations consistently increased genomic instability. Q331K-expressing cells showed a 2-3-fold reduction in DNA repair activity and a 4-6-fold increase in DDR activation, while TDP-43 -depleted cells showed a 20-fold rise in double strand breaks. TDP-43 normally binds to damaged chromatin, participates in early DDR signaling and scaffolds core DNA damage repair factors, including Ku70, XRCC4 and DNA ligase 4. This systematic review and narrative synthesis sheds light on mechanisms that explain how TDP-43 dysfunction impairs genome maintenance. When TDP-43 is mislocalized, mutated or aggregated, these interactions are disrupted, resulting in impaired DNA repair. DNA damage is also caused by increasing R-loops, dysregulation of mismatch repair gene transcription, and sequestering of repair proteins into cytoplasmic inclusions. Upstream DNA damage can further drive TDP-43 mislocalisation, creating a feed-forward loop. Given the ubiquity of TDP-43 pathology across neurodegenerative diseases, targeting the DDR mechanisms affected by TDP-43 may offer new therapeutic opportunities.

Introduction: Sport-related concussion (SRC) is a common and complex brain injury with variable recovery trajectories. The clinical assessment for SRC involves comprehensive assessment of symptoms and cognitive, visual and motor function, with tools such as the Sport Concussion Assessment Tool (SCAT) integrating these components for diagnosis and monitoring. Task-based functional magnetic resonance imaging (tb-fMRI) has emerged as a potential tool to evaluate functional brain changes post-concussion. Methods: A systematic review was conducted according to PRISMA guidelines. Five databases (Medline, Embase, PsycINFO, Scopus, Web of Science) were searched for original research studies up to July 2025 reporting tb-fMRI outcomes in SRC. Eligible studies included human participants with SRC undergoing tb-fMRI. Results: Of 1,130 records identified, plus 9 through manual searching, 15 studies met the inclusion/exclusion criteria for full text review, encompassing 273 SRC patients with an age range of 9–37 years old. A meta-analysis was not possible since numerical data was largely absent in studies. Across the studies, tb-fMRI revealed different patterns of altered brain activation, including both hypoactivation and hyperactivation during cognitive and sensorimotor tasks. Importantly, several studies showed altered activation persisted beyond symptom resolution suggesting functional recovery may lag behind clinical improvement. Conclusions: Task-based fMRI demonstrates consistent alterations in brain activity following SRC, particularly within frontoparietal networks. However, tb-fMRI findings were heterogeneous, sample sizes were small, and clinical applications such as return-to-play decisions based on functional imaging are not yet validated. To date tb-fMRI provides valuable insights into post-concussive brain function but remains an investigational tool and hence larger, standardized and longitudinal studies are needed to establish its clinical reproducibility and diagnostic utility.

Introduction: Mass casualty incidents (MCIs) present a global threat to civilians, with children often being affected and sometimes even targeted; however, there is little research regarding the preparedness exercises of healthcare professionals for such events. Methods: A systematic search of PubMed, Web of Science and Embase from inception up to July 2025, was conducted. Risk of bias was also assessed using the risk of bias in non-randomised studies of interventions exposure (ROBINS E) tool. Results: The initial search generated 223 results, and following double screening and manual citation searching, 17 observational studies were selected for narrative synthesis, since numerical data to perform meta-analysis were unavailable. The review identified a broad range of training interventions tailored for paediatric MCIs. Both brief, frequent drills and longer, mixed methods training schemes were effective, yielding gains in specific skills and a holistic sense of preparedness, including teamwork and communication. These improvements were often sustained for up to 6 months, despite a common limitation of lost to follow-up. However, the overall risk of bias in the included studies were high to very high. Discussion: MCI educational schemes appear to improve all aspects of preparedness. However, the evidence is heterogeneous, lacked standardisation in the outcome measures and contained high to very high risk of bias, suggesting that the current evidence cannot support definitive recommendations. Future research should aim to conduct high-quality studies with standardised outcome assessment tools to optimise paediatric MCI preparedness. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251084048 .