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Does Timing Matter? Age of First Mobile Phone Acquisition and Psychological Outcomes in Middle and Late Adolescence.

The age at which adolescents acquire their first smartphone has decreased markedly in recent years; however, evidence on its long-term effects on psychosocial adjustment remains limited. This study investigated whether age at first mobile phone acquisition is associated with psychosocial functioning in middle and late adolescence, including social integration and competence, emotion regulation difficulties, disordered eating behaviors and problematic social media use (PSMU). The sample comprised 1179 adolescents aged 15-17 years (53.8% female). Linear regression and generalized additive mixed models were used to examine both linear and nonlinear associations, adjusting for age, gender and school clustering. Earlier smartphone acquisition was linearly but weakly associated with greater emotion regulation difficulties, disordered eating and PSMU, even after adjustment for covariates. In contrast, associations with social integration and competence were nonlinear: acquiring a first smartphone between ages 6 and 10 or after age 13 was associated with lower social integration in adolescence, whereas acquisition between ages 11 and 13 was linked to higher social functioning. These findings suggest that the developmental timing of first smartphone access shows a modest association with subsequent psychosocial functioning during middle and late adolescence. Focusing on the timing of access, alongside other demographic and contextual factors, may contribute to a better understanding of digital influences on adolescent well-being.

Humans

Signal recognition particle 14 binds to importin α in Plasmodium falciparum.

BACKGROUND: The eukaryotic signal recognition particle (SRP) consists of six proteins and one SRP RNA. This ribonucleoprotein complex assembles inside the nucleus. Nucleocytoplasmic transport is an essential process for the biogenesis of signal recognition particles (SRPs) as well as for the survival of a cell. There are studies on cells that indicate the import receptor is responsible for import of SRP proteins into nucleus, but there is a lack of evidence that SRP proteins directly bind with import receptors. METHODS AND RESULTS: Coding sequences of SRP 14 and importin α were amplified from synthesized cDNA and genomic DNA, respectively, of Plasmodium falciparum cultivated in vitro culture. The amplified products were cloned and expressed in E. coli, followed by purification. A binding study was conducted on glutathione-agarose as well as in a 96-well plate format at different concentrations of SRP 14 with immobilized importin α. CONCLUSION: This is the first report of direct binding between importin α and a eukaryotic signal recognition particle 14 (SRP 14). A cost-effective 96-well plate-based assay has also been developed to study the binding of cargoes of importin α.

Plasmodium falciparum

Long-term outcomes after a randomized phase II trial of nerve growth factor eye drops for optic pathway gliomas: four-year follow-up findings in children.

PURPOSE: A previous double-blind, randomized, placebo-controlled, phase II clinical trial reported beneficial effects of a short-term treatment (10 days) with murine nerve growth factor (mNGF) eye drops on visual function in children with optic pathway gliomas (OPG). The present study aimed to evaluate long-term changes in clinical and neuroradiological parameters in the cohort of OPG patients who had previously participated in the phase II mNGF trial. METHODS: Fifteen of the 18 patients originally enrolled in the phase II mNGF trial agreed to undergo clinical and neuroradiological monitoring over a 48-month follow-up period. Of these, 9 had originally been randomized to mNGF and 6 to placebo; no additional treatment (mNGF, chemotherapy, or radiotherapy) was administered during the extended follow-up. Every 6 months, patients underwent general clinical and neuro-ophthalmological examination, visual evoked potentials (VEP), and photopic negative response of the electroretinogram (PhNR). Brain MRI was performed every 12 months. RESULTS: Comparison of initial and final follow-up median values revealed no statistically significant changes in visual acuity, VEP amplitude, PhNR amplitude, or visual field radius. No significant differences were observed in any parameter relative to baseline values of the mNGF trial. Brain MRI demonstrated stable disease in all patients throughout the observation period. CONCLUSION: These findings, obtained in an observational extension of the original randomized cohort, indicate favorable long-term safety and tolerability of a short-term course of topical mNGF in children with OPG, with sustained visual and neuroradiological stability over four years, rather than evidence of persistent treatment efficacy. Further prospective, adequately powered and randomized clinical studies are needed to confirm both the short- and long-term clinical efficacy of NGF treatment in preventing OPG-induced visual loss.

Humans

Improving Community-Based Care for Adolescents with ADHD: a Randomized Controlled Trial of Artificial Intelligence-Assisted Fidelity Supports.

Cognitive-behavioral treatments (CBTs) for adolescents with ADHD demonstrate promise of long-term effects on outcome. However, their implementation in routine care community clinics faces barriers that impact quantity, efficiency, and quality of delivery, as well as client outcomes. This study is a randomized controlled trial designed to evaluate the impact of an AI-assisted service delivery model on therapist implementation of Supporting Teens' Autonomy Daily (STAND), a CBT blended with Motivational Interviewing (MI) for adolescents with ADHD. Adolescents with ADHD (N = 51), who were clients at three community mental health agencies, received treatment from 23 therapists. There was randomization of adolescents and therapists to AI-assisted or standard implementation supports. In addition to standard supports (i.e., training, standard facilitation resources, technical assistance, case supervision), AI-assisted support package included digitized facilitation resources housed in a clinical dashboard (Care4), feedback on content fidelity, and AI-generated feedback on MI implementation quality. The AI-assisted group was associated with more efficient treatment delivery and lower number of appointments attended by the adolescent. There was also a significant decrement in MI quality over time in the AI-assisted group compared to the standard support group. Feedback in focus groups indicated that therapists perceived a task-oriented mindset to be associated with receipt of the AI-assisted support package, leading therapists to prioritize efficiency over relational aspects of therapy. Following the results of this trial, a future, larger RCT should examine the impact of the AI-assisted implementation model on mental health outcomes and cost savings to organizations, third party payers, and clients. Trial registration number: NCT05135065; https://www.clinicaltrials.gov ; Registered September 2021.

Humans

An updated systematic review of buffalo nutritional requirements (2000-2024).

Buffaloes (Bubalus bubalis) are large ruminants with a superior ability to digest and utilize low-quality forages, producing milk and meat of higher quality compared to cattle. Despite their importance in animal production, buffaloes remain the focus of relatively few studies aimed at defining their nutritional requirements, which often results in inadequate diet formulation and management. There, this study aimed to conduct a systematic review of the literature on buffalo nutritional requirements, considering only open-access papers published in English and in indexed journals. A total of 58 studies met the inclusion criteria. Most of them focused on dairy buffaloes, particularly on the evaluation of crude protein, energy levels, and fiber content in the diet. Mineral nutrition was addressed in eight studies; however, in general the evaluated levels showed no significant effects. In contrast, very few or no studies were found concerning beef buffaloes, growing animals, reproduction, or other production stages. These findings highlight a critical gap in the literature and reinforce the urgent need to direct more research efforts and resources toward establishing species-specific nutritional requirements, particularly for beef buffaloes.

Animals

PGPR inoculation and growth enhancement of crops cultivated in hydroponic systems.

Plant growth-promoting rhizobacteria (PGPR) are ubiquitous rhizosphere microorganisms that promote plant health through various mechanisms. Although the study of PGPR inoculants in soil has been done for ages, their application in hydroponic systems has received relatively limited attention. This review identifies PGPR inoculants that are commonly used in hydroponics, methods of application, and their effects on plant growth and nutrient use efficiency. Literature shows that PGPR inoculants improve plant performance in controlled hydroponic systems through the production of growth-stimulating substances, nitrogen fixation, and improved nutrient acquisition. However, the plant growth responses are highly variable depending on the composition of nutrient solutions, environmental factors, crop and microbe species, and the type of hydroponic system. The review identifies various challenges of PGPR inoculation in hydroponic systems and future research directions to address the current gaps. Generally, the productivity of hydroponic systems can be enhanced through advanced inoculation strategies and the development of suitable carrier materials to improve inoculant survival, viability, and functions. Emphasis should also be placed on designing system-specific microbial consortia and Synthetic communities that are tailored to the unique ecological conditions of hydroponic systems.

Hydroponics

Robotic-assisted transbronchial biopsy versus computed tomography-guided transthoracic needle biopsy for peripheral pulmonary lesions: a systematic review and meta-analysis of direct comparative studies.

Robotic-assisted bronchoscopy (RAB) and computed tomography-guided transthoracic biopsy (CTTB) are competing strategies for sampling peripheral pulmonary lesions (PPLs). Whether they differ in yield or safety is uncertain. To our knowledge, this is the first systematic review restricted to direct comparisons. We searched MEDLINE, Europe PMC, Scopus, Web of Science and ClinicalTrials.gov from inception to 7 July 2026 for studies directly comparing RAB with CTTB in adults with PPLs. The primary outcome was strict 2024 American Thoracic Society/American College of Chest Physicians diagnostic yield. Risk of bias was assessed with ROBINS-I and certainty with GRADE. A cohort-genealogy step identified, per outcome, the largest set of cohorts sharing no patients; only that set was pooled, with Hartung-Knapp and Mantel-Haenszel sensitivity analyses. Five retrospective studies from one US health system were eligible. Four share patients; at most three cohorts are mutually independent. Across those three, diagnostic yield was comparable (risk ratio [RR] 0.99, 95% confidence interval [CI] 0.93-1.06; I²=24%; Hartung-Knapp 0.87-1.13), with an identical relative effect under strict and intermediate definitions although absolute yields fell from 88% to 74-84% under strict criteria. Pneumothorax requiring a chest tube and/or admission was about three-quarters less frequent with RAB across all three cohorts (RR 0.25, 95% CI 0.14-0.46; I²=0%; Hartung-Knapp 0.07-0.96). Strict yield (RR 0.99) and any pneumothorax (RR 0.06) were reported by two cohorts each and neither survives the few-studies correction. RAB took about 50 min longer than CTTB where same-session staging endobronchial ultrasound was counted in the robotic time, but only about 8 min longer than CTTB where it was not. Only one cohort reported yield by lesion size category and none reported yield by bronchus sign or lung zone, so lesion-level subgroups could not be pooled. Certainty was low for pleural complications and very low elsewhere. Low-certainty evidence indicates that RAB is associated with fewer pleural complications, with no statistically detectable difference in diagnostic yield; equivalence was not formally established. Because all evidence is retrospective, confined to one health system, and almost never stratified by lesion size or accessibility, these findings are hypothesis-generating and require a multicenter randomized trial.

Humans

Interhospital transfer and outcomes after robotic emergency general surgery: a national analysis.

The outcomes of patients transferred to receiving centers who subsequently undergo robotic EGS remain uncharacterized at a national level. We aimed to quantify the association between transfer and outcomes among adults undergoing robotic EGS. We performed a retrospective cohort study of the Nationwide Readmissions Database (2016-2019) including adult nonelective admissions undergoing robotic EGS. Interhospital transfer versus direct admission was the exposure. Survey-weighted logistic regression estimated adjusted odds ratios (aOR) for clinical outcomes; generalized linear models with gamma family and log link estimated adjusted mean ratios (aMR) for length of stay (LOS) and cost. Average marginal effects provided adjusted risks/means and absolute differences. Among 26,869 unweighted robotic EGS admissions, representing an estimated 46,517 admissions nationally, 246 unweighted admissions were interhospital transfers, representing an estimated 444 transfers (1.0%) nationally. Transfers were older, more comorbid, and more severely ill and were treated predominantly at large, teaching hospitals. After adjustment, transfer was associated with a higher risk of postprocedural complications (8.0% vs. 3.5%; aRR 2.26, 95% CI 1.25-3.27), non-home discharge (31.2% vs. 18.9%; aRR 1.65, 95% CI 1.38-1.92), longer LOS (11.49 vs. 5.53 days; AMR 2.08, 95% CI 1.78-2.42), and higher cost ($43,340 vs. $21,821; AMR 1.99, 95% CI 1.68-2.35). The association with postprocedural complications was attenuated after additional adjustment for APR-DRG Severity of Illness, whereas associations with non-home discharge, LOS, and cost persisted. Among patients undergoing robotic EGS, interhospital transfer is independently associated with higher complication burden and greater resource use. Transferred patients represent a small but distinctly high-risk subgroup whose worse outcomes may reflect drivers that extend beyond the choice of surgical approach.

Humans

Beyond da Vinci: a systematic review of next-generation multiport robotic platforms in pediatric surgery.

As robotic surgery expands beyond the da Vinci platform, the relevance of new-generation systems to pediatric patients remains uncertain. This review examined the technical characteristics, applications, and perioperative outcomes of alternative multiport robotic platforms in children. PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane Library were searched through 28 February 2026 in accordance with PRISMA 2020. Owing to clinical heterogeneity, findings were synthesized narratively, with Wilson 95% confidence intervals for key binary outcomes. Six studies reported 166 patients across 27 procedure types. Senhance accounted for 164 patients, while Hugo RAS and Hinotori were each represented by one patient. Ages ranged from 15 days to 17 years and weights from 3.8 to more than 100 kg. Senhance was the only platform used with 3-mm robotic instruments. Conversion or planned escalation occurred in 19 patients (11.4%; 95% CI, 7.5-17.2%). Four intraoperative complications were reported (2.4%; 95% CI, 0.9-6.0%). Across all reports, 20 patients experienced postoperative complications (12.0%; 95% CI, 7.9-17.9%). In the largest cohort, seven patients required reintervention (4.6%; 95% CI, 2.2-9.2%) and seven were readmitted (4.6%; 95% CI, 2.2-9.2%). No deaths or comparative pediatric studies were reported. Published experience remains sparse and is almost entirely limited to Senhance. Current evidence describes early clinical use without establishing comparative safety, effectiveness, or platform superiority. Prospective multicenter studies with standardized reporting are needed.

Humans

Applications of artificial intelligence in robot-assisted surgery: a systematic review.

To characterize applications of artificial intelligence (AI) in robot-assisted surgery, summarize technical and clinical performance, and assess the quality of the available evidence. PubMed, Web of Science Core Collection, and Scopus were searched for English-language journal articles published from 1 January 2020 through 31 October 2025. Randomized, observational, model-development, validation, and feasibility studies evaluating AI in robot-assisted surgery or closely related image-guided minimally invasive workflows were eligible. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment. Owing to heterogeneity in surgical procedures, AI tasks, analytical units, validation strategies, and outcomes, findings were synthesized descriptively without statistical pooling. The review was registered in the International Prospective Register of Systematic Reviews (CRD420251175699). Seventeen studies were included: seven clinical prediction or decision-support studies, eight intraoperative recognition, segmentation, or image-guided studies, and two training or workflow studies. Five prediction studies reported area-under-the-curve values of 0.74-0.95. Technical studies reported F1 or Dice scores of 0.525-0.995 and task-specific accuracies of 0.840-0.998. Two randomized studies suggested benefits for personalized suturing feedback and automated camera control, but neither established improved patient outcomes. Only one study had low overall risk of bias; the remaining studies were at high or unclear risk or raised some concerns. AI applications in robot-assisted surgery show promise for prediction, intraoperative perception, training, and workflow support. Evidence primarily demonstrates technical feasibility rather than established clinical effectiveness. Independent multicenter validation and prospective evaluation of patient, educational, and workflow outcomes are required before widespread implementation.

Robotic Surgical Procedures

Robot-assisted versus manual percutaneous vascular interventions across vascular territories: a systematic review and meta-analysis.

Robot-assisted percutaneous vascular intervention (R-PVI) has expanded beyond coronary procedures, but previous reviews were largely coronary-focused and observational. Recent randomized controlled trials (RCTs) warrant broader reassessment of R-PVI versus manual percutaneous vascular intervention (M-PVI) across vascular territories. PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from database inception to January 31, 2026, following PRISMA guidelines. RCTs and observational studies including &#x2265;10 adult patients in total were eligible. Comparative studies informed primary analyses, while single-arm studies provided supportive evidence. Primary outcomes were clinical success rate and major adverse cardiovascular/cerebrovascular events (MACE) rate. Secondary outcomes included mortality rate, technical success rate, procedural time metrics, contrast volume, and radiation exposure. Random-effects models were used. Forty studies were included: 3 RCTs, 10 comparative observational studies, and 27 single-arm observational studies, comprising 3,870 patients undergoing R-PVI and 1,142 undergoing M-PVI. Comparative analyses showed similar clinical success rates (RR 1.00, P = 0.46), MACE rates (RR 0.72, P = 0.43), and mortality. Single-arm pooled estimates for clinical and technical success were 98.76% and 96.09%, respectively. R-PVI prolonged total procedure time overall (MD 15.92&#xa0;min, P = 0.01), with consistent increases in the neurovascular, RCT, and non-RCT subgroups. Fluoroscopy time was also longer (MD 1.91&#xa0;min, P = 0.04), mainly in the RCT subgroup (MD 2.83&#xa0;min, P = 0.001). In contrast, intravascular intervention time was unchanged overall and in RCTs, but was prolonged in non-RCTs (MD 8.72&#xa0;min, P = 0.006). Operator radiation exposure was markedly reduced (MD -33.97 &#x3bc;Sv, P < 0.001), whereas patient radiation exposure and contrast volume were similar. R-PVI appears feasible and safe across selected vascular procedures. Its clearest benefit is reduced operator radiation exposure, whereas lower whole-procedure efficiency remains its main limitation.

Humans

Sutureless versus renorrhaphy in robot-assisted off-clamp partial nephrectomy: a systematic review and meta-analysis.

BACKGROUND: The necessity of routine parenchymal renorrhaphy during off-clamp robot-assisted partial nephrectomy (RAPN) remains uncertain. This study aimed to compare perioperative, functional, safety, and oncological outcomes between sutureless and conventional renorrhaphy. METHODS: We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. Comparative studies evaluating sutureless versus conventional renorrhaphy during purely off-clamp RAPN were included. Trifecta achievement was the primary outcome. Random-effects models were used for pooled analyses, with subgroup analysis according to study design. RESULTS: Four studies involving 787 patients, including one randomized controlled trial (RCT) and three propensity score-matched (PSM) studies, were included. The overall pooled estimate showed no statistically significant difference in Trifecta achievement (RR 1.17, 95% CI 0.97-1.41), with substantial heterogeneity (I&#xb2; = 86.5%). The PSM studies favored the sutureless approach (RR 1.26, 95% CI 1.05-1.52), whereas the RCT yielded an RR of 0.97 (95% CI 0.92-1.04) and met the prespecified noninferiority criterion without demonstrating superiority. The sutureless approach was associated with a smaller perioperative eGFR decline (MD&#x2009;-&#x2009;3.89, 95% CI&#x2009;-&#x2009;6.16 to -&#x2009;1.62), while no significant difference was observed in eGFR at 3 months. No statistically significant differences were identified in major complications, blood transfusion, or positive surgical margins; urinary and vascular complications were sparsely reported. CONCLUSIONS: In selected patients undergoing purely off-clamp RAPN, randomized evidence supports the noninferiority of a strategy that omits routine parenchymal renorrhaphy while permitting clinically necessary selective repair, but does not demonstrate superiority. Favorable estimates from PSM studies remain vulnerable to intraoperative treatment-selection bias. Current evidence is insufficient to determine whether omission of renorrhaphy affects urinary complications, long-term renal function, or oncological outcomes. REGISTRATION: This systematic review was registered prospectively in PROSPERO (CRD420261435995).

Humans

Robot-assisted versus freehand cannulated-screw fixation for femoral neck fractures: a systematic review of technical, clinical and adoption outcomes.

Robot-assisted guidance may improve the technical precision of percutaneous cannulated-screw fixation for femoral neck fractures. Whether these procedural advantages translate into better clinical outcomes remains uncertain. We compared robot-assisted and conventional freehand fixation in adults with femoral neck fractures. MEDLINE, Embase and CINAHL were searched from inception to 15 July 2026 without language restrictions. Google Scholar was used only as a supplementary search source, together with forward and backward citation searching. Comparative studies of robot-assisted versus freehand fluoroscopy-guided cannulated-screw fixation were included. Risk of bias was assessed using RoB 2 and ROBINS-I, with the Newcastle-Ottawa Scale used as a complementary appraisal of non-randomised studies. Random-effects meta-analyses included prediction intervals and prespecified sensitivity analyses. The protocol was registered prospectively (PROSPERO CRD420261465038). Sixteen comparative studies involving 1,293 participants were included. Of these, 597 underwent robot-assisted fixation and 696 underwent freehand fixation. Two studies reporting random allocation and 14 non-randomised studies were included in the study. Robot-assisted fixation was associated with fewer guide-wire manipulations, greater screw-placement accuracy and 13.9 fewer fluoroscopic acquisitions per procedure (95% confidence interval [CI] -20.3 to -7.5). Earlier radiographic healing and modestly higher final Harris Hip Scores were also observed. Pooled estimates suggested lower risks of union failure, avascular necrosis and composite complications. Fluoroscopy duration, overall operative time and reoperation did not differ significantly. Heterogeneity was substantial for several continuous outcomes, with prediction intervals crossing the null for several estimates, indicating that the magnitude of benefit varied considerably between studies. Some clinical associations were also sensitive to eligibility-restricted analyses. Robot-assisted cannulated-screw fixation improves technical execution compared with freehand fixation. Patient-important clinical superiority and economic value have not been established, and evidence concerning learning curves, operator acceptability and system reliability remains insufficient. Current evidence does not support routine widespread adoption; adequately powered multicentre randomised trials incorporating economic and implementation evaluation are required.

Humans

Robot-assisted bladder diverticulectomy in adults: a systematic review and pooled analysis of perioperative and functional outcomes.

Robot-assisted bladder diverticulectomy (RABD) is used for symptomatic acquired bladder diverticula, but evidence is dispersed across small single-centre series and the only dedicated systematic review dates from 2010. We reviewed contemporary perioperative and functional outcomes of RABD. Following a protocol registered on the Open Science Framework ( https://doi.org/10.17605/OSF.IO/54CFT ), PubMed, Embase, the Cochrane Library, Scopus and Web of Science were searched from inception to 30 August 2026 (initial search June 2026, re-run and broadened for this version), following PRISMA 2020. Eligible studies were original series of five or more adults undergoing robot-assisted bladder diverticulectomy reporting extractable outcomes. Two reviewers independently screened, extracted data and appraised risk of bias with the Joanna Briggs Institute checklist for case series, with third-reviewer adjudication. Binary outcomes were pooled as proportions with Wilson 95% confidence intervals (CI); continuous outcomes were summarised as patient-number-weighted descriptive values, because mixed median/mean reporting and clinical heterogeneity precluded a formal pooled-effect meta-analysis. Twelve studies (146 patients) were included and all outcomes were extracted from the full-text reports. A transperitoneal route was used throughout. There were no conversions to open surgery (0/129; 95% CI 0-2.9%). Major complications (Clavien-Dindo&#x2009;&#x2265;&#x2009;III) occurred in 3.0% (4/135; 95% CI 1.2-7.4%). Patient-number-weighted descriptive values (combining study-level medians and means, and therefore not a pooled mean) were: operative time 163 min, blood loss 99 mL, length of stay 3.6 days and catheter duration 7.7 days. Symptom scores and post-void residual improved in every reporting series, significantly in five. The single non-randomised comparison with open surgery reported fewer major complications after RABD (5% [1/20] vs. 50% [3/6], p&#x2009;=&#x2009;0.007), but the open arm comprised only six patients and this finding should not be regarded as comparative evidence. Across these series, RABD was feasible with low reported short-term morbidity in selected patients: no conversions to open surgery were recorded in the studies reporting conversion status, the major-complication rate was low, and symptom scores and post-void residual improved in every series that measured them. A minority of patients had an incidentally detected intradiverticular tumour; oncological outcomes were not an endpoint of this review. Evidence remains limited by small, heterogeneous, mostly retrospective series, so these findings should be read as descriptive; prospective comparative data are warranted.

Humans

Artificial Intelligence for Diagnosis, Risk Stratification, and Prognosis of Neuroblastoma - A Systematic Review and Meta-Analysis.

PURPOSE: To synthesizes evidence on artificial intelligence (AI) performance in neuroblastoma (NB) diagnosis, risk stratification, prognosis, and genomic characterization. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted following PRISMA 2020 guidelines (PROSPERO: CRD42024539475) across five databases. Meta-analyses used random-effects models with logit-transformed Area Under the Curve (AUCs) and cluster-robust standard errors. AI models were classified as Machine Learning Models (MLM) or Hybrid Nomograms (HN) based on their construction methodology. RESULTS: Of 3,742 articles identified, 53 were included. MLMs demonstrated higher point estimates than radiologists in differential diagnosis (AUC: 0.87 vs. 0.83), though this difference was not statistically significant and carried substantial uncertainty. HNs achieved stronger performance in risk stratification (AUC: 0.87). AI-derived nomograms (AUC: 0.9) and gene signatures (AUC: 0.8) outperformed conventional prognostic markers descriptively. Chemotherapy response prediction remained below clinical utility thresholds across all model types. Only 33.9% of models reported calibration and 24.5% underwent external validation. CONCLUSIONS: AI demonstrates proof-of-concept across multiple NB clinical domains. However, clinical adoption remains premature given persistent gaps in external validation, calibration, dataset size, and pediatric-specific model development. Future studies should test these models prospectively in multicenter pediatric cohorts, ideally through COG or SIOPEN, using shared definitions for diagnosis, risk group, treatment response, and survival outcomes.

Humans

Harnessing Endogenous Plasticity Rather than Reprogramming of Mature Cells Will Advance Regenerative Medicine, Cancer Treatment and Rejuvenation.

The successful culture of human embryonic stem (hES) cells from inner cell mass cells of blastocyst stage 'spare' embryos in 1998, followed by induced pluripotent stem (iPS) cells in 2006, which allowed somatic cells to be reprogrammed to pluripotency using the Yamanaka factors, transformed regenerative biology and inspired extensive global efforts towards developing pluripotent stem cell-based applications. However, hES and iPS cells, as well as organoids generated from them, largely retain fetal-like characteristics, which limits their relevance for clinical translation. Concurrently, the prevailing assumption published in leading journals that adult tissues lack endogenous stem cells has led to the belief that mature cells dedifferentiate and reprogram during in vivo regeneration upon chronic injury, and that the appearance of embryonic/fetal markers in diabetes, heart failure, cancer, and many other chronic disease states reflects dedifferentiation of mature cells. We suggest that the prevailing concepts of dedifferentiation and reprogramming, both in vitro and in vivo, require careful re-evaluation. Adult somatic cells possibly do not truly dedifferentiate, neither in vitro nor in vivo. Instead, tissue-resident, pluripotent, very small embryonic-like stem cells (VSELs) in multiple organs account for the observed biology. In vitro "reprogramming" responses to Yamanaka factors likely reflect selective activation and expansion of VSELs/early progenitors rather than the dedifferentiation/ reprogramming of mature adult somatic cells. Likewise, the embryonic/fetal-like signatures reported in multiple disease states including cancer reflect expansion of immature tissue-specific progenitors that arise from VSELs but fail to differentiate normally due to a damaged microenvironment in vivo. Therapeutic strategies involving transplantation of MSCs, MUSE cells, or their secreted exosomes improve disease outcomes, possibly by restoring the damaged niche that supports functional tissue repair by VSELs. Although direct evidence to support this is lacking at present, recognising the central role of VSELs/progenitors and their niche in maintaining tissue homeostasis in vivo could resolve existing roadblocks and guide more effective endogenous regenerative therapies for diseased tissues and age-related dysfunctions.

Humans

Targeting Gasdermins for Therapeutic Interventions in Central Nervous System Injury.

Central nervous system (CNS) injuries are the leading cause of permanent disability and premature death in adults worldwide, with their incidence continuing to rise amid social development. These injuries not only severely impair the quality of life but also impose a heavy burden on the global public health system. Current clinical interventions, such as decompression and thrombolysis, can alleviate primary injury but fail to effectively reverse the secondary neuroinflammatory damage. Traditional anti-inflammatory therapies, which cannot block the upstream source of the inflammatory cascade, have led to repeated failures in global clinical translation research over the past decades. Gasdermins were first characterized in studies of systemic inflammatory diseases. These proteins form transmembrane pores to drive the release of proinflammatory factors and inflammatory cell death, serving as key mediators of host innate immunity. Recent studies have revealed that gasdermins play critical roles in regulating the initiation and amplification of neuroinflammation following CNS injury. To clarify the therapeutic potential of gasdermins as targets for injury repair, this review systematically summarizes the structure and function of gasdermins, as well as their cell-specific activation and regulatory mechanisms. We further elaborate on their pathological roles in these injuries and the corresponding therapeutic strategies, aiming to provide a theoretical reference for basic research and clinical translation in this field.

Humans

Oral semaglutide for weight loss and liver fibrosis in overweight and obesity: A randomized controlled trial.

BACKGROUND AND OBJECTIVES: Obesity is a leading risk factor for fatty liver disease and weight loss has been shown to improve liver parameters. This study evaluates the efficacy of oral semaglutide for weight loss in individuals with overweight or obesity, excluding those with diabetes mellitus. METHODS: A randomized, open-label, controlled trial was conducted at the Asian Institute of Gastroenterology, Hyderabad, from June 2022 to December 2023. Adults (&#x2265;&#x2009;18&#xa0;years) with a body mass index (BMI)&#x2009;&#x2265;&#x2009;30 or&#x2009;&#x2265;&#x2009;27 with comorbidities (pre-diabetes, hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease) were randomized into two groups. Both groups received counselling on a reduced-calorie diet and increased physical activity. Group 1 also received oral semaglutide, starting at 3&#xa0;mg/day and titrated to 14&#xa0;mg/day over two to four&#xa0;weeks. The objectives were to assess the effects of semaglutide on weight loss, non-invasive markers of liver fibrosis and cardiometabolic parameters. (ClinicalTrials.gov ID: NCT05442450). RESULTS: Total 116 participants (58 per group) completed the study. At 28&#xa0;weeks, the mean percentage weight reduction was -10.47% (SD 5.3) in the Semaglutide group vs. -2.4% (SD 4.5) in the control group (p&#x2009;<&#x2009;0.001). Semaglutide treatment significantly improved alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) levels, along with reductions in the aspartate aminotransferase to platelet ratio index (APRI) score, liver fat content and liver stiffness. However, NFS (NAFLD fibrosis score) and FIB-4 (fibrosis-4 index) did not show significant reductions. Improvements in BMI, waist circumference, HbA1c, fasting insulin and C-reactive protein (CRP) were significantly greater with semaglutide (p&#x2009;<&#x2009;0.001). Total fat mass decreased by 7.3&#xa0;kg vs. 1.74&#xa0;kg (p&#x2009;<&#x2009;0.0001) in controls, while visceral fat ratings dropped by 3.67 vs. 0.6 (p&#x2009;<&#x2009;0.0001). CONCLUSIONS: In adults with overweight or obesity without diabetes, oral semaglutide, combined with dietary and lifestyle modifications, led to significant and clinically meaningful weight loss and metabolic improvements compared to lifestyle modifications alone.

Adult