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PubMed2026

Context matters: coordinated transcriptional regulation and root plasticity under multinutrient conditions.

Plants often encounter simultaneous imbalances in multiple nutrients, but the regulatory logic coordinating their responses remains poorly understood. We aimed to uncover shared transcriptional programs and regulatory nodes underpinning multinutrient adaptation in Arabidopsis thaliana roots. We analyzed publicly available RNA-seq datasets spanning 15 nutrient and beneficial element conditions using differential expression, co-expression network (WGCNA), and gene regulatory network analysis. Selected transcription factors (TFs) were validated via root phenotyping, suberin staining, and ionomic profiling under two-nutrient stress conditions. We identified a core set of 2050 genes responsive to multiple nutrient treatments, enriched for suberin biosynthesis, and structured into modular co-expression clusters. Eight prioritized candidate TFs (ARR10, GBF3, HHO5, NAC32, NF-YA3, NF-YB2, SARD1, and WRKY33) were shown to modulate root system architecture under specific nutrient combinations. WRKY33 and NF-YB2, in particular, regulated nutrient-responsive suberin deposition and ionomic plasticity. These findings reveal suberin remodeling as a shared downstream process in multinutrient responses and suggest that plasticity is not a fixed trait but a modular, polygenic, and context-dependent outcome. Repurposed TFs with pleiotropic functions coordinate structural and physiological traits, providing regulatory entry points for improving nutrient resilience.

Plant Roots↗

PubMed2026

Ecological momentary assessment studies on food craving among healthy adults: A systematic review.

Ecological Momentary Assessment (EMA) can capture the dynamic nature of food craving in free-living conditions, addressing limitations of laboratory and retrospective reporting methods. This systematic review synthesized findings from EMA studies to characterize 1) methodological features, 2) the temporal dynamics of food craving, and 3) the relationship between craving and eating behaviors. A systematic search of PubMed and PsycINFO databases was conducted following PRISMA guidelines. The review included 23 studies that utilized EMA designs to assess food craving repeatedly in daily life among healthy adults. Most studies employed EMA protocols that prompted participants to respond at pre-specified time points and utilized single-item craving measures. Most craving measures (71%) lacked specificity regarding the type of food craved. Results revealed a consistent positive within-person association between hunger and food craving. Conversely, associations between stress/negative affect and craving were inconsistent, varying by individual traits and context. Momentary food craving appeared to predict subsequent eating outcomes. Evidence suggested food craving may be a dynamic, transient state that co-fluctuates with hunger, functioning as a proximal antecedent to food intake. However, reliance on non-specific food craving measures and EMA protocols prompting at fixed schedules limits the granular understanding of craving mechanisms. Future research requires refining food craving measurement and incorporating randomized prompting within predefined windows, or participant-initiated sampling triggered by specific events (e.g., eating occasion), to better characterize food craving dynamics in relation to eating behaviors.

Humans↗

PubMed2026

Efficacy and safety of JAK inhibitors for vitiligo: an updated systematic review and meta-analysis of randomized controlled trials.

Purpose: Janus kinase (JAK) inhibitors are a promising therapeutic option for vitiligo, but previous meta-analyses have focused mainly on topical ruxolitinib versus placebo. Newer randomized controlled trials (RCTs) evaluating oral agents and head-to-head comparisons with active treatments have not been comprehensively synthesized. Materials and methods: We searched PubMed, Embase, the Cochrane Library, and Web of Science to 11 March 2026. Eligible RCTs evaluated JAK inhibitor monotherapy versus placebo or active comparators. Two reviewers screened records, extracted data, and assessed risk of bias using RoB 2.0. The primary outcome was F-VASI75. Meta-analyses used fixed-effect or random-effects models. GRADE assessed certainty of evidence. Results: Nine RCTs (1826 patients) were included. JAK inhibitors increased F-VASI75 versus placebo (RR 4.59, 95% CI 3.20-6.59; p < 0.001). For F-VASI50, they were superior to tacrolimus (RR 1.88, 95% CI 1.02-3.45) but not significantly different from dexamethasone (RR 2.17, 95% CI 0.95-4.94). Serious adverse events were comparable between groups (RR 1.15, 95% CI 0.57-2.33). Evidence certainty was moderate. Conclusions: JAK inhibitors are effective and well tolerated for vitiligo. Topical ruxolitinib is supported as a first-line option for limited facial disease; oral agents show promise but require longer-term safety data.

Humans↗

PubMed2026

Reinforcement learning-based dynamic ensemble for missense variant effect prediction and tiered prioritization of VUS.

BACKGROUND: Accurate classification of missense variants remains a challenging task despite major advances in genomics. Numerous computational models have been developed to assist in variant classification, but often require repeated integration and benchmarking efforts. Ensemble methods have been proposed to overcome the limitations of single predictors, but mostly rely on fixed, predefined weights that constrain their ability to capture interactions among predictive signals. METHODS: We present GenixRL, a dynamic ensemble framework that reformulates model fusion as a reinforcement learning optimization problem. GenixRL uses a Q-learning agent to learn a policy that dynamically weights the probabilistic outputs of complementary predictors, including BayesDel (addAF and noAF), ClinPred, and MetaRNN. Replacing static weighting with policy learning allows GenixRL to adaptively identify optimal weightings and substantially improve classification accuracy. RESULTS: In benchmark evaluation against 25 state-of-the-art predictors, GenixRL achieved an AUROC of 0.9644 on an independent ClinVar dataset. On saturation genome editing assays for BRCA1 and BRCA2, GenixRL achieved the best performance and ranked highest on 14 of 17 clinically significant genes in a zero-shot evaluation. Applied to uncertain and conflicting ClinVar variants, GenixRL enabled tiered, evidence-based prioritization of hundreds of thousands of variants as likely pathogenic or pathogenic with high confidence, supported by orthogonal population evidence from gnomAD. CONCLUSION: GenixRL advances pathogenicity prediction for missense variants and provides an adaptive ensemble that sorts variants of uncertain significance into tiered candidates for expert curation and functional validation.

Mutation, Missense↗

PubMed2025

Autologous Fibrin Glue in Pterygium Surgery as an Alternative to Commercial Fibrin Glue.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of autologous fibrin glue in pterygium surgery, comparing it with commercial fibrin glue in terms of postoperative complications, graft stability, and recurrence rate. METHODS: A prospective, randomized, double-blind study was conducted, involving 42 patients with primary pterygium who underwent autologous conjunctival-limbal transplantation. The graft was fixed using autologous fibrin glue (Group 1, G1) or commercial fibrin glue (Group 2, G2). All patients underwent surgery performed by the same surgeon and were reevaluated on postoperative days 7, 30, 90, and 180 by an independent observer, assessing clinical parameters in the preoperative, intraoperative, and postoperative periods. RESULTS: No cases of severe adverse events were reported. Complete graft dehiscence occurred in 1 patient from G1. The G2 group had more cases of subconjunctival hemorrhage ( P = 0.0355). Pyogenic granuloma was observed in 1 patient from G2 and 2 patients from G1. There was no significant difference in recurrence rates between the groups (15% in G1 vs. 5% in G2; P = 0.2918). In both groups, graft dimensions tended to decrease slightly in the early postoperative period, followed by stabilization. CONCLUSIONS: Autologous fibrin glue demonstrated efficacy and safety comparable to commercial fibrin glue, making it a viable alternative to conjunctival graft fixation in primary pterygium surgery.

Humans↗

PubMed2026

Post-weaning social isolation increases reward-seeking behavior in mice.

Social isolation is a growing public health concern. Although isolation at any age is harmful, previous studies have shown that isolation during adolescence, correlating with critical periods of brain development, can impair cognitive function and increase the risk for psychiatric illness later in life. In this study, we utilized a mouse model of social isolation (SI) during adolescence (postnatal day 21-35) and compared performance of isolated and group-housed mice on a touchscreen-based continuous performance test (rCPT) and fixed ratio/progressive ratio (FR/PR) tasks in adulthood. SI improved performance in the rCPT and the improvement in performance was consistent across time bins within the 45-minute testing session. There were no effects of SI on reaction times or reward retrieval latencies. A possible confound for performance in the rCPT would be SI-induced changes in reward-seeking or motivation for the strawberry milk reward. We next compared the SI mice to their group-housed littermate controls on both PR and FR schedules of reinforcement and found that SI mice had higher breakpoints on a PR4 schedule and earned significantly more reinforcers on an FR1 schedule of reinforcement compared to their group-housed littermates, suggesting that high performance in the CPT may be due to increased motivation for food rewards. These data indicate that SI during adolescence has significant effects on reward-seeking behavior in adult mice and may provide a useful behavioral model for studying the link between SI and risk for neuropsychiatric disorders.

Animals↗

PubMed2026

Sacral Neuromodulation in the Management of Refractory Pediatric Lower Urinary Tract Dysfunction.

INTRODUCTION: Sacral neuromodulation is currently used in the pediatric patient population for refractory lower urinary tract dysfunction (LUTD). Evidence, however, is currently limited for institutional experiences of long-term outcomes for sacral neuromodulation in the pediatric patient population. OBJECTIVE: The objective of this study is to perform a retrospective review of a large multi-institutional cohort of pediatric patients that underwent sacral neuromodulation (SNM) for refractory LUTD, focused on rates of symptom improvement, quality of life, and bowel-bladder dysfunction measures following device implantation. Secondary objectives included assessing device complication rates and device removals due to failure or successful resolution of symptoms. METHODS: We performed a retrospective cohort study of pediatric patients at three children's hospitals that underwent SNM device implantation for refractory LUTD. Patients 4-18 years of age who were diagnosed with refractory LUTD and managed at a participating institution with follow-up were included. Outcomes were evaluated at baseline and post-operatively after two-stage device implantation at initial follow-up and annually until device removal or final follow-up. RESULTS: From 2010 to 2022, a total of 205 children underwent SNM procedures at three pediatric hospital centers. 204 patients completed the two-stage procedure for permanent device implantation with a median follow-up of 3.4 years (1.3, 4.9). One hundred seventy-eight patients reported partial (25%) or complete (54%) device response/symptom improvement by final follow-up. Comparison of patient-reported validated questionnaires completed at baseline and by final follow-up visit revealed significant improvement in median Pediatric Quality of Life Inventory (PedsQL) (p = 0.004) and Vancouver Nonneurogenic Lower Urinary Tract Dysfunction/Dysfunctional Elimination Syndrome bowel-bladder dysfunction (BBD) scores (p < 0.001). Of those with any device complication (n = 43;21%), 19 patients required device revision, and 20 required complete device removal. Separately, twenty-eight patients (13%) underwent device removal due to resolution of symptoms or treatment success at a median period of 5 years (4,7). CONCLUSION: SNM use demonstrated a majority of patients reporting at least partial subjective symptom improvement following device implantation across multiple institutions by final follow-up. SNM is a viable treatment option for refractory LUTD in the pediatric patient if willing to undergo an invasive procedure and in which thorough counseling of risks and benefits has occurred.

Humans↗

PubMed2026

Optimizing focal vibration therapy for balance and gait: A systematic review.

OBJECTIVE: This systematic review evaluated the efficacy of focal (localized) vibration therapy (FVT) applied to muscles/tendons on balance, gait, and mobility, with a specific focus on defining optimal vibration protocols (frequency, amplitude, dosing) and muscle-targeting strategies to maximize sensorimotor recovery. METHODS: A systematic review was conducted across six databases (CINHAL, Embase, Medline, Web of Science, Scopus, CENTRAL) from January 2000 to May 2025. Studies were included if they involved human participants, applied FVT therapeutically, and reported balance, gait, or mobility outcomes. Data extraction included study characteristics, intervention protocols, and outcomes. Methodological quality was assessed using the PEDro scale. RESULTS: Sixty-two studies (n = 2090 participants) were included. Methodological quality assessment (PEDro scale) indicated 44% of studies met high-quality standards. Biomechanical analysis identified the quadriceps, gastrocnemius/soleus, and plantar muscles as the most effective vibration sites, given their critical roles in gait propulsion and postural stability. The synthesis of protocol data indicated a promising therapeutic window characterized by a vibration frequency of 80-120 Hz (primarily fixed sinusoidal waveforms at a single frequency) and an amplitude of 0.2-0.5 mm (reported only in 12 studies; amplitude was not reported in 23 studies), applied bilaterally for a minimum of 3 sessions per week over 4-12 weeks, which could lead to improved balance and gait performance with benefits sustained for up to 5 months. CONCLUSION: FVT shows potential to improve gait and balance, particularly when targeting lower-extremity muscles with optimized vibration parameters. To advance the field, future research must prioritize the development of standardized protocols and investigate neurophysiological mechanisms to refine FVT as a precision bioengineering solution for mobility deficits.

Humans↗

PubMed2026

Fundamentals of pacemakers ECG interpretation - part 2.

BACKGROUND: Modern pacemakers incorporate arrhythmia-response algorithms, ventricular pacing minimization protocols, and safety mechanisms that generate ECG patterns indistinguishable from pathological AV block, sensing malfunction, or device-mediated tachycardia. Failure to recognize these algorithm-driven signatures leads to unnecessary interventions, misdiagnosis, and inappropriate device reprogramming. This manuscript is the second in a two-part series on pacemaker ECG interpretation. METHODS: We conducted a narrative review of peer-reviewed literature and device-specific documentation on algorithm-driven ECG behavior, synthesizing evidence across arrhythmia recognition, upper rate physiology, ventricular pacing minimization, mode switching, safety mechanisms, and hysteresis algorithms. RESULTS: Pacemaker-mediated tachycardia produces regular paced wide-complex tachycardia locked at the upper tracking rate, initiated by any event with retrograde VA conduction. Ventricular tachycardia is identified by QRS morphology diverging from the known paced pattern, absent pacing spikes, and AV dissociation. Upper rate Wenckebach behavior mimics Mobitz type I AV block; 2:1 upper rate response mimics second-degree AV block. Ventricular pacing minimization algorithms produce isolated nonconducted P waves and prolonged AV intervals that simulate pathological conduction disease. Mode switching causes abrupt rate drops misidentified as output failure. Ventricular safety pacing generates a conspicuously short, fixed AV interval. Three discrete pacing artifacts reflect AV-sequential cardiac resynchronization therapy (CRT), ventricular safety pacing in CRT, or His-bundle pacing with backup RV output. Rate and AV hysteresis produce pauses and wandering AV intervals mimicking oversensing or Wenckebach periodicity. CONCLUSIONS: Recognizing algorithm-driven ECG patterns requires knowledge of device timing intervals and refractory periods, which lets clinicians distinguish programmed behavior from true malfunction or cardiac arrhythmia.

Humans↗

PubMed2026

Genomic and Molecular Interaction Analysis of NodD1 in a Novel Bradyrhizobium yuanmingense sp. B64 Isolate for Nodulation and Symbiosis of Legume Plants.

Rhizobial bacteria are known for their ability to fix nitrogen for leguminous plants and their essential function for sustainable agriculture. This study characterizes the taxonomic status and functional potential of the Bradyrhizobium B64 isolate using integrated genomic and molecular approaches. The whole genome of the B64 isolate was sequenced via Illumina paired-end technology. Species delimitation was performed using average nucleotide identity (ANI) and digital DNA-DNA Hybridization (dDDH). The NodD1 protein structure was modeled using AlphaFold3 and validated by Ramachandran plot analysis. Molecular docking was then conducted to evaluate interactions between NodD1 and four signaling flavonoids: Apigenin, Daidzein, Genistein, and Naringenin. Genomic analysis revealed a maximum ANI of 94.4% and dDDH values between 51.4 and 62.4%. Since these values fall below the standard prokaryotic thresholds (ANI < 95%; dDDH < 70%), the B64 isolate is identified as a novel species. Physiological assays confirmed nitrogen fixation (1.97 ppm), IAA production (3.67 ppm), and phosphate solubilization (26.10 ppm). Structural validation showed 100% of NodD1 residues in allowed regions, ensuring high model reliability. Docking simulations demonstrated strong binding affinities across all flavonoids, with binding free energies ranging from - 8.8 to - 9.0 kcal/mol. Daidzein exhibited the highest thermodynamic stability (- 9.0 kcal/mol), whereas apigenin showed the most extensive residue interaction network. The B64 isolate is a novel Bradyrhizobium species with a high symbiotic capacity. The stable NodD1-flavonoid interactions provide a molecular basis for efficient nodulation, positioning B64 as a promising candidate for developing lipo-chitooligosaccharide (LCO)-based biofertilizers.

Bradyrhizobium↗

PubMed2026

Does co-administration of cannabidiol (CBD) influence the plasma availability of delta-9-tetrahydrocannabinol (THC) and its active metabolite in humans? A systematic review and meta-analysis.

BACKGROUND: Research on the pharmacokinetic influence of cannabidiol (CBD) on delta-9-tetrahydrocannabinol (THC) has produced equivocal results. METHODS: We conducted a systematic search following PRISMA guidelines (last search: 24th November 2025, PROSPERO: CRD42023480695). Included studies were acute dosing trials that administered a) a single, fixed dose of THC and b) a matched dose of THC co-administered with CBD. Our objective was to investigate between-group differences in the Cmax, AUCt and AUCinf of circulating THC and its active metabolite, 11-hydroxy-THC (11-OH-THC). Hedges' g and ratio of means (RoM) were pooled from random-effects meta-analyses. The dose-effects of CBD and THC on Hedges' g were explored using meta-regression. Risk of bias was assessed using the Cochrane Collaboration tool RoB 2. RESULTS: 14 studies were included (12 crossover, two parallel group; seven oral administration, five inhalation, one IV, one mixed IV and oral; total participants: 341). In meta-analyses, average AUCt of THC was significantly higher in CBD co-administration study arms versus THC-only (Hedges' g= 0.526, 95%CI= 0.222-0.830), with very low certainty evidence. Both Cmax and AUCt of 11-OH-THC were significantly higher in CBD co-administration study arms (Cmax: g= 0.428, 0.115-0.741; AUCt: g= 0.692, 0.284-1.099), both with medium certainty evidence. In meta-regression analyses, CBD demonstrated dose effects on the Hedges' g of the Cmax and AUCt of 11-OH-THC (P < 0.05), but not THC levels. CONCLUSIONS: Cannabis users and prescribers of cannabinoid-based products should be made aware of the potential for drug-drug pharmacokinetic interactions between CBD and THC.

Humans↗

PubMed2026

Feasibility and Efficacy of Lorlatinib in Japanese Patients With Relapsed/Refractory ALK-Aberrant Neuroblastoma.

Lorlatinib, a third-generation ALK inhibitor, was administered off-label to five heavily pretreated patients with relapsed or refractory ALK-aberrant neuroblastoma. ALK alterations included F1174L, R1275Q, BEND5::ALK fusion, and ALK amplification; three patients had MYCN amplification. Best responses were three partial responses and two disease progressions. The longest progression-free survival (6.7 months) occurred in a patient with F1174L and non-amplified MYCN, whereas rapid progression was observed in two MYCN-amplified cases. Lorlatinib was generally well tolerated with manageable adverse events. These findings suggest that lorlatinib is a feasible therapeutic option in ALK-aberrant neuroblastoma and that clinical heterogeneity in treatment response warrants further investigation.

Humans↗

PubMed2026

Comparative Bioavailability of Trimodal (CTx-1301) Versus Bimodal Dexmethylphenidate Modified-Release Formulations in Adults with Attention-Deficit/Hyperactivity Disorder: A Randomized, Single-Dose, Crossover Study.

BACKGROUND AND OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder that often requires sustained symptom control throughout the day. Although bimodal extended-release dexmethylphenidate (d-MPH XR) formulations provide initial and intermediate drug release, they may not consistently maintain therapeutic exposure into the late afternoon and evening. Trimodal formulations with an additional delayed release component may extend drug exposure later in the day, although this remains to be established. To explore differences in pharmacokinetic (PK) profiles between trimodal (CTx-1301) and bimodal delivery of d-MPH XR, a comparative bioavailability study was conducted at the highest and lowest doses for both formulations. METHODS: In this randomized, 4-period, crossover study, adults with ADHD received single doses of CTx-1301 (50 mg and 6.25 mg) and d-MPH XR (40 mg and 5 mg). Comparative bioavailability was assessed through adjusted geometric mean ratios for exposure parameters (maximum observed plasma concentration [Cmax], area under plasma concentration-time curve to last measurable concentration [AUClast] and extrapolated to infinity [AUC0-inf]), with a prespecified bioequivalence range of 0.80 to 1.25. Secondary endpoints included partial AUCs and safety assessments. RESULTS: The study population (N = 45) was predominantly male (88.9%) and White (55.6%), with mean age of 29.6 ± 8.01 years. Adjusted geometric mean ratios comparing the primary exposure parameters (Cmax, AUClast, and AUC0-inf) for CTx-1301 versus d-MPH XR were within the bioequivalence range (0.80-1.25) at both the high and low doses. The CTx-1301-to-d-MPH XR partial AUC ratios were within the bioequivalence range from 0 to 9 hours post-dose. At later intervals (AUC9-12 and AUC12-16), adjusted geometric mean ratios exceeded the upper bioequivalence threshold, consistent with the expected contribution of the third medication release component. Dose proportionality was observed between the two CTx-1301 doses and two d-MPH XR formulations. CTx-1301 was generally well tolerated. The most commonly reported adverse events included tachycardia, insomnia, headache, nausea, and euphoric mood. The incidence of treatment-emergent adverse events was numerically lower with CTx-1301 than with d-MPH XR; however, no statistical analysis was performed. CONCLUSIONS: Key exposure parameters including Cmax, AUClast, and AUC0-inf for trimodal CTx-1301 were statistically bioequivalent to bimodal d-MPH XR. Interval‑specific PK analyses demonstrated higher exposure with CTx‑1301 during later post-dose intervals (9-16 h), consistent with the formulation's third release component. However, the clinical relevance of these PK differences requires further evaluation. CTx-1301 demonstrated dose proportionality and was well tolerated at high and low doses. REGISTRATION: ClinicalTrials.gov, NCT04138498; 19 September 2019.

Humans↗

PubMed2026

Effect of Smoking in Oropharyngeal Cancer Treated With TORS: Systematic Review and Meta-Analysis.

OBJECTIVE: While smoking has been implicated as a risk factor for recurrence in HPV-associated oropharyngeal squamous cell cancer (OPSCC) treated with definitive chemoradiation, its prognostic impact on surgically treated OPSCC is less clear. DATA SOURCES: MEDLINE, Embase, CENTRAL, and Scopus. REVIEW METHODS: Articles describing patients with HPV-associated OPSCC treated with transoral robotic surgery (TORS), which reported oncologic outcomes by smoking history, were included. RESULTS: 2079 patients were included across 12 studies. Median age was 58.5 years, and 1808 (87.0%) were male. HPV-associated disease was reported in 1681 (80.9%) patients. T stage was most commonly T2 in 831 (40.0%) and T1 in 764 (36.7%). N stage was N2 in 854 (41.1%), N1 in 544 (26.2%), and N0 in 307 (14.8%). 931 (44.8%) were considered individuals with a smoking history, while 1045 (50.3%) were considered without a smoking history. Median follow up was 33.7 months. Meta-analysis using a fixed effects model demonstrated an overall hazard ratio of 1.4 (95% confidence interval 1.0-2.0) for disease recurrence, 2.7 (95% confidence interval 1.5-4.8) for overall survival, and 1.4 (95% confidence interval 0.4-4.6) for disease specific survival. CONCLUSIONS: In this population of predominantly HPV-associated OPSCC treated with TORS, meta-analysis demonstrated no significant difference in recurrence-free survival or disease-specific survival between individuals with and without a smoking history. Individuals with a smoking history appeared to have worse overall survival, although only five studies reported on this outcome. Further research is required to clarify the prognostic influence of smoking on OPSCC treated with TORS.

Humans↗

PubMed2026

Theta-range SEEG stimulation for intracranial mapping: extending conventional 1-Hz and 50-Hz protocols.

OBJECTIVE: Electrical brain stimulations (EBS) are central to epileptic network identification and functional mapping during stereo-electroencephalography, yet stimulation frequencies remain empirical, and standardized across patients and brain regions, producing false negatives and false positives, and potentially compromising surgical outcome. We prospectively investigated theta-range EBS (7 Hz) in the temporal lobe, a prominent physiological frequency band in this region, and compared it with conventional 1-Hz and 50-Hz protocols. METHODS: We analyzed 1,408 temporal EBS in 25 drug-resistant epileptic patients. Epileptic responses (afterdischarges, seizures) and clinical signs were assessed across the epileptic network and temporal structures (amygdala, hippocampus, neocortex, parahippocampal gyrus, white matter), and confronted to stimulation parameters (frequency, intensity, duration, total charge). RESULTS: At matched intensity and duration, 7-Hz EBS were associated with a higher occurrence of afterdischarges and clinical signs than 1-Hz EBS in several temporal structures. Effects on usual seizure induction were less consistent. Comparisons with 50 Hz showed no systematic significant differences, with responses observed at one or both frequencies depending on structure and outcome. When controlling for total charge, frequency-related differences were attenuated. Some effects were sporadically observed at both intermediate frequency and charge quantity. CONCLUSIONS: EBS responses emerge from the interaction between all electrical parameters and anatomical location and local excitability, and can hardly be disentangled. However, 7-Hz EBS can provide complementary clinical information during temporal-lobe mapping, with a targeted approach. SIGNIFICANCE: These findings support targeted evaluation of broader stimulation parameter spaces, including intermediate frequencies, rather than routine reliance on fixed low- and high-frequency protocols alone.

Humans↗

PubMed2026

Tranexamic acid in spontaneous intracerebral hemorrhage: an updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Tranexamic acid (TXA) is a well-established antifibrinolytic medication in the general population. However, its efficacy and safety for patients with spontaneous intracerebral hemorrhage (ICH) remain inconclusive. Consequently, we conducted a systematic review and meta-analysis to assess the effectiveness and safety of TXA for spontaneous ICH. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) following established methodological standards. Our search encompassed eight electronic databases from inception to April 25, 2024. The primary outcome was a reduction in all-cause mortality. The secondary outcomes included improvements in functional independence, neurological impairment, activities of daily living, and reduction in hematoma expansion (HE). Fixed-effects or random-effects model were performed for pooled data where eligible. RESULTS: A total of 9 RCTs that initially enrolled 3,124 patients were included. There were no significant differences observed concerning all-cause mortality (RR, 1.03; 95% CI [0.89-1.18]), hematoma expansion (RR, 0.90; 95% CI [0.80-1.00]), improvement of functional independence (RR, 1.02; 95% CI [0.92-1.12], neurological impairment (MD, -0.88 [95% CI, -2.22-0.45]), or activities in daily living (MD, -0.83 [95% CI, -29.25-12.59]). The pooled data indicated that TXA for ICH was associated with a decrease in hematoma volume from baseline (MD, -1.74; 95% CI [-2.47 to -1.02]). No significant difference in adverse events was observed between the TXA group and the control group. CONCLUSIONS: In summary, TXA does not affect all-cause mortality, functional outcomes, or neurological impairment, nor does it reduce HE, despite reducing hematoma volulume. TXA use for ICH requires careful clinical consideration.

Humans↗

PubMed2026

Proteomic insights into the immunomodulatory effects of Ca/Sr co-doped sol-gel coatings for titanium implants.

Ionic functionalization of biomaterial coatings has emerged as a powerful strategy to regulate early host responses at the implant interface. However, how combined Ca/Sr incorporation governs the adsorbed proteome and downstream immune signaling remains poorly understood. This study analyses, employing in vitro tests and proteomics, the effect of adding Sr and Ca to Si-based coatings designed to bioactivate Ti implants. Hybrid Si-based coatings were synthesized by the sol-gel route with a fixed Ca content (0.5 wt%) and increasing Sr contents (0.5, 1.0, 1.5 wt%), and their physicochemical properties, ion release kinetics, and hydrolytic stability were characterized. The coatings remained highly crosslinked despite Ca/Sr incorporation, whereas the highest Sr content increased hydrolytic degradation to around 70% after 56 days. Proteomic analysis identified 183 adsorbed proteins, of which 56 were differentially adsorbed on Ca/Sr-coatings, mainly associated with immune and coagulation pathways. In vitro, RAW 264.7 showed increased gene expression of TNF-α and TGF-β; with an enhanced TNF-α secretion by the addition of Ca and Sr. In parallel, MC3T3-E1 indicated that Ca/Sr-coatings were not cytotoxic and did not impair cell proliferation. However, ALP activity was reduced in the co-doped groups, indicating that the immunomodulatory effects induced by Ca/Sr incorporation were not accompanied by enhanced early osteogenic differentiation. The Ca/Sr combination induced alterations in the adsorption of immune-related proteins, which correlated with the in vitro findings. The deeper insight into how Ca/Sr mixtures modulate protein adsorption on biomaterial surfaces may be key to understanding the immunomodulatory capacity of these bioactive cations.

Animals↗

PubMed2026

Playing with Fire, Losing the Drive: Bidirectional Links Between Problematic Smartphone Use and Grit Dimensions.

This study examined bidirectional longitudinal associations between grit dimensions (consistency of interest [CI] and perseverance of effort [PE]) and problematic smartphone use (PSU) and tested cognitive flexibility as a mediating mechanism. A sample of 1,641 Chinese university students (55.2 percent female; Mage = 20.1 years) completed measures at two time points 6 months apart. A four-variable cross-lagged panel model revealed that CI and PSU negatively predicted each other over time, whereas PSU unidirectionally predicted decreased PE. Cognitive flexibility partially mediated the PSU-to-PE pathway (indirect effect = -0.004, 95 percent bootstrap CI [-0.010, -0.0001]). Competing models analysis confirmed this directionality: the forward mediation (PSU → cognitive flexibility → PE) was significant, whereas the reverse was not. These findings demonstrate that grit dimensions exhibit distinct longitudinal patterns with PSU and identify cognitive flexibility as a cognitive mechanism through which PSU specifically undermines effort persistence. Implications for dimensional approaches to grit and targeted interventions are discussed.

Humans↗