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The Impact of Video Game Experience on Surgical Performance: A Systematic Review.

OBJECTIVE: To assess whether video gaming experience is associated with improved surgical performance in the surgeon population across laparoscopic, robotic, and other surgical modalities, and evaluate its implications on surgical training and education. METHODS: A structured literature search was conducted across five databases on 29th November 2024 in adherence to PRISMA guidelines. Comparative studies evaluating surgical performance outcome data between surgeons with differing video game experience were eligible for inclusion. Outcomes evaluated were time to complete task, error rate, accuracy, economy of motion, and overall score. Included studies were assessed for risk of bias using ROBINS-I and RoB 2. RESULTS: 15 studies involving 641 participants were included, comprising one randomized controlled trial and 14 nonrandomized studies. All nonrandomized studies were judged to be at moderate or serious risk of bias, and the single randomized controlled trial was judged to be at serious risk of bias. Differences in study design and outcome measures meant that quantitative synthesis could not be performed. Across laparoscopic studies, video gaming experience was associated with improved overall score and time to task completion predominantly in the period prior to structured training interventions, with accuracy findings consistently favoring gamers in the two studies reporting this outcome. Error rate and economy of motion findings were inconsistent or predominantly nonsignificant. No meaningful association was identified across nonlaparoscopic modalities. CONCLUSIONS: Video gaming may be associated with improved surgical performance in surgeons, though this appears restricted to laparoscopic tasks and the pretraining intervention period. As a low-cost and accessible activity, video gaming may represent a practical informal adjunct to formal surgical training to help ease the transition into structured technical training. Surgical program directors need not alter existing selection criteria or training modules based on the available literature.

Video Games

Biologic-biologic and biologic-JAK inhibitor combination therapy in refractory systemic autoinflammatory diseases.

OBJECTIVES: Systemic autoinflammatory diseases (SAIDs) arise from genetic defects in innate immunity, leading to dysregulated activation of inflammatory pathways, including interleukin (IL)-1, IL-6, TNF, and JAK/STAT. Clinical manifestations range from recurrent fever to severe complications such as encephalitis and AA amyloidosis. Management aims to control inflammation using immunosuppressive agents and targeted monotherapies (biologics or JAK inhibitors). Advanced combination therapy (ACT), defined as the use of biologics and/or JAK inhibitors in combination, has emerged as a strategy for refractory disease. METHODS: In this observational retrospective longitudinal cohort study, patients with SAIDs treated with ACT were included. Demographic, clinical, treatment, and safety data were collected. Treatment response was assessed using a composite outcome incorporating corticosteroid dose, C-reactive protein (CRP), and clinical improvement and categorized as non-response, partial response, or complete response. RESULTS: Thirty-eight patients (median age 30 years [range 4-76]) were included. The most common indications for ACT were pyogenic arthritis, pyoderma gangrenosum and acne (PAPA), mevalonate kinase deficiency (MKD), and undifferentiated SAIDs. Most patients had disease-related complications and were dependent on glucocorticoids and/or opioids to control inflammation and pain, respectively. Following multiple ACT trials, complete response was observed in 21 patients (55.3%), partial response in 12 (31.6%), and no response in 5 (13.1%). Overall, 65 ACT regimens were administered, most commonly combining IL-1 and TNF inhibitors. Thirty-nine regimens were discontinued because of lack of efficacy, secondary loss of response, or adverse events. At the final follow-up, 26 patients (68%) remained on ACT, with a median treatment duration of 60 months (range, 11-186). CONCLUSIONS: ACT offers significant clinical benefits for patients with difficult-to-treat SAIDs, though challenges such as secondary loss of efficacy and infection risks remain.

Humans

Variability in β-human chorionic gonadotropin concentrations following evacuation of a hydatidiform mole pregnancy: A retrospective cohort study from Vietnam.

BackgroundGestational trophoblastic disease refers to a group of tumors defined by abnormal trophoblastic proliferation. This disease produces a distinct tumor marker, beta-human chorionic gonadotropin, which can be useful for diagnosis and follow-up. The objective of this study was to investigate the variations in serum beta-human chorionic gonadotropin levels after uterine evacuation as well and the progression of gestational trophoblastic neoplasia.Materials and methodsThis retrospective cohort study was conducted at Tu Du Hospital, Vietnam, between January 2019 and December 2020. All patients diagnosed with molar pregnancy were analyzed retrospectively based on serial serum beta-human chorionic gonadotropin levels following uterine evacuation. Post-evacuation outcomes, including relapsed molar pregnancy and gestational trophoblastic neoplasia, were also monitored.ResultsWe enrolled 560 patients with molar pregnancy, including 298 with complete hydatidiform mole and 262 with partial hydatidiform mole. Severe symptoms were more common in those with complete hydatidiform mole. Over the follow-up period, 97 cases of gestational trophoblastic neoplasia were noted. The data show that the median time to gestational trophoblastic neoplasia diagnosis was 8.75&#x2009;&#xb1;&#x2009;4.41 (4-26) weeks. In terms of variations in the serum beta-human chorionic gonadotropin levels, the generalized estimating equation model showed a faster decline in the complete hydatidiform mole group than in the partial hydatidiform mole group. Similarly, regression in serum beta-human chorionic gonadotropin levels was significantly more rapid in patients who progressed to gestational trophoblastic neoplasia than in those with relapsed molar pregnancy (-11,593 vs. -20,651.22 and -12,946.26 vs. -46,329.23 mUI/mL, p&#x2009;<&#x2009;0.001).ConclusionsSurveillance of serum beta-human chorionic gonadotropin levels remains essential for gestational trophoblastic neoplasia monitoring in patients with molar pregnancy following surgical evacuation. The post-evacuation serum beta-human chorionic gonadotropin level regression curve helps distinguish gestational trophoblastic neoplasia from hydatidiform moles. Further evidence is required to strengthen these findings.

Humans

Effects of acute hypoxia followed by reoxygenation on intestinal histomorphology, oxidative stress and hypoxia signaling biomarkers, and microbiota in pikeperch (Sander lucioperca).

In aquatic environments, natural and anthropogenic factors commonly reduce dissolved oxygen (DO) and trigger hypoxia, which threatens the health and survival of aquatic organisms. As an important economic fish species in China, pikeperch (Sander lucioperca) is extremely sensitive to hypoxia. However, there are relatively few reports on how hypoxia and reoxygenation affect its intestinal physiology and microbial community. Three treatment groups were set for pikeperch: normoxia (DO&#xa0;=&#xa0;8.5&#xa0;&#xb1;&#xa0;0.5&#xa0;mg/L), 48&#xa0;h hypoxia (DO&#xa0;=&#xa0;2.5&#xa0;&#xb1;&#xa0;0.1&#xa0;mg/L), and reoxygenation (48&#xa0;h hypoxia followed by 6&#xa0;h reoxygenation at normal DO), to evaluate alterations in intestinal histopathology, tight junction gene expression, oxidative stress, hypoxia signaling molecules and intestinal microbiota composition. The results showed that hypoxia significantly decreased muscularis thickness by approximately 32.5% and reduced the expression of tight junction genes (Occludin, Claudin2, and ZO-2). Moreover, hypoxia significantly increased oxidative stress index levels (GSH-Px, CAT, and MDA), markedly upregulated the expression of Bax, Caspase3, and HIF-1&#x3b1;, while significantly downregulating the expression of Bcl-2, Egln1, and Egln2. Notably, reoxygenation elicited partial compensatory effects against these hypoxia-induced changes. 16S rRNA sequencing analysis revealed that hypoxic stress altered the intestinal microbial community composition of pikeperch and increased its diversity. In the hypoxia group, the abundance of the phylum Bacillota, along with the genera Halomonas and Acinetobacter, was significantly elevated, whereas in the reoxygenation group, the genus Lactobacillus increased approximately 180-fold. The results indicated that hypoxia caused intestinal oxidative damage, cell apoptosis, and intestinal microbiota dysbiosis in pikeperch, while short-term reoxygenation achieved partial recovery from these hypoxia-triggered intestinal injuries. The present research provides valuable references for in-depth exploration of the molecular mechanisms behind the response of pikeperch to acute hypoxia and reoxygenation stress, while also offering a novel perspective to understand the mechanism by which hypoxia impacts intestinal health in fish.

Animals

A systematic review of sleep hygiene interventions in physically and operationally demanding occupations.

Workers in physically and operationally demanding (POD) occupations (e.g. military personnel, emergency responders, law enforcement) experience disrupted sleep due to irregular schedules and high-stress work environments. Given the importance of sleep for physical and cognitive performance, interventions to improve sleep in POD occupations are crucial yet remain under-researched. To investigate the effectiveness of sleep hygiene interventions in improving sleep quality and quantity outcomes for POD occupations, a systematic review was conducted across five databases (PubMed, CINAHL, SPORTDiscus, PsycINFO, Web of Science) in September 2024. Eligible studies involved workers in POD occupations where a sleep hygiene intervention was compared against a waitlist or passive control. Ten studies were included, eight randomised controlled trials (RCTs) and two non-randomised controlled trials (NRCTs). Narrative synthesis identified Structured Training Programs (n&#x202f;=&#x202f;7), Phone Assistance Programs (n&#x202f;=&#x202f;2), and Single Lecture Interventions (n&#x202f;=&#x202f;1). Evidence certainty ranged from Very Low to Moderate, converging towards Low quality due to imprecision, risk of bias, and indirectness. Structured Training Programs showed moderate improvements in sleep quality and small-to-moderate effects on sleep duration. Phone Assistance Programs had minimal effects, and Single Lecture Interventions had negligible impact. Higher-quality research is urgently needed to assess sleep hygiene interventions in POD occupations.

Humans

Artificial Intelligence in Diagnosing Depression Through Behavioural Cues: A Diagnostic Accuracy Systematic Review and Meta-Analysis.

AIM: To synthesise existing evidence concerning the application of AI methods in detecting depression through behavioural cues among adults in healthcare and community settings. DESIGN: This is a diagnostic accuracy systematic review. METHODS: This review included studies examining different AI methods in detecting depression among adults. Two independent reviewers screened, appraised and extracted data. Data were analysed by meta-analysis, narrative synthesis and subgroup analysis. DATA SOURCES: Published studies and grey literature were sought in 11 electronic databases. Hand search was conducted on reference lists and two journals. RESULTS: In total, 30 studies were included in this review. Twenty of which demonstrated that AI models had the potential to detect depression. Speech and facial expression showed better sensitivity, reflecting the ability to detect people with depression. Text and movement had better specificity, indicating the ability to rule out non-depressed individuals. Heterogeneity was initially high. Less heterogeneity was observed within each modality subgroup. CONCLUSIONS: This is the first systematic review examining AI models in detecting depression using all four behavioural cues: speech, texts, movement and facial expressions. IMPLICATIONS: A collaborative effort among healthcare professionals can be initiated to develop an AI-assisted depression detection system in general healthcare or community settings. IMPACT: It is challenging for general healthcare professionals to detect depressive symptoms among people in non-psychiatric settings. Our findings suggested the need for objective screening tools, such as an AI-assisted system, for screening depression. Therefore, people could receive accurate diagnosis and proper treatments for depression. REPORTING METHOD: This review followed the PRISMA checklist. PATIENTS OR PUBLIC CONTRIBUTION: No patients or public contribution.

Humans

Integrated photoelectrocatalytic reduction and oxidation processes to achieve efficient degradation of fluoxetine in pharmaceutical wastewater.

Fluorinated organic compounds have been frequently detected in aquatic environments, with the widespread use of fluorinated drugs. The existing processes of urban sewage treatment plants are difficult to completely remove these pollutants containing the persistent C-F bonds. In this work, an integrated system of UV-activated sulfite and UV-assisted electrochemical oxidation was innovatively constructed for efficient degradation of fluoxetine. For the UV-activated sulfite unit system, when the sulfite dosage was 0.5 mmol/L and the initial pH was about 10, the defluorination efficiency of 5 mg/L fluoxetine wastewater under nitrogen atmosphere was about 98 %. Subsequently, the UV-assisted electrochemical oxidation unit system was employed to treat the reduced wastewater mentioned above. When the sodium chloride dosage was 25 mmol/L, the initial pH was about 5, and the current density was 30 mA/cm2, the total organic carbon (TOC) removal of the wastewater arrived at 65 %. Active species capture experiments and ESR tests confirmed that hydrated electrons, hydroxyl, and chlorine radicals were the main components for the efficient degradation of fluoxetine. According to the analysis of Fukui function and HPLC-MS, the degradation pathway of pollutants was proposed including defluorination and mineralization. Meanwhile, the toxicity of intermediates was predicted using the ECOSAR program. In addition, the verification test of actual wastewater treatment indicated that the defluorination and TOC removal efficiency of fluorouracil by the integrated system were similar to those for fluoxetine. This work provided a new approach for the efficient degradation of fluorinated organic pollutants in pharmaceutical wastewater.

Fluoxetine

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&#x2009;=&#x2009;0.004) and Vancouver Nonneurogenic Lower Urinary Tract Dysfunction/Dysfunctional Elimination Syndrome bowel-bladder dysfunction (BBD) scores (p&#x2009;<&#x2009;0.001). Of those with any device complication (n&#x2009;=&#x2009;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

Obinutuzumab or Tacrolimus in Primary Membranous Nephropathy.

BACKGROUND: Studies of obinutuzumab, a type II anti-CD20 antibody, have shown efficacy in the treatment of hematologic cancers and autoimmune diseases. An evaluation of the efficacy and safety of obinutuzumab in patients with primary membranous nephropathy is needed. METHODS: In a phase 3 trial, we randomly assigned adults with primary membranous nephropathy in a 1:1 ratio to receive intravenous obinutuzumab or oral tacrolimus. The primary end point was complete remission (defined as a urinary protein-to-creatinine ratio of 0.3 or lower and a stable estimated glomerular filtration rate [eGFR]) at week 104. Key secondary end points were complete or partial remission at week 104, complete remission at week 76, a sustained reduction in the eGFR of at least 30%, duration of complete remission, and change in the Patient-Reported Outcomes Measurement Information System Fatigue T score from baseline to week 104. Fixed-sequence hierarchical testing was performed. Safety was assessed. RESULTS: A total of 142 patients underwent randomization. At week 104, complete remission was observed in 26 of 71 patients in the obinutuzumab group and in 4 of 70 patients in the tacrolimus group (37% vs. 6% with multiple imputation for missing data; adjusted difference, 31 percentage points; 95% CI, 18 to 44; P<0.001). The analyses of complete or partial remission at week 104 and complete remission at week 76 also showed a significant treatment effect. The analysis of a sustained eGFR reduction did not show a significant treatment effect; thus, subsequent end points in the hierarchy were not formally tested for significance. Adverse events of grade 3 or higher were reported in 16 patients (22%) in the obinutuzumab group and in 13 patients (19%) in the tacrolimus group; serious adverse events occurred in 12 (17%) and 10 (14%), respectively. There were 61 and 57 infections per 100 patient-years in the obinutuzumab and tacrolimus groups, respectively; 3 and 4 serious infections per 100 patient-years; and 11 and 14 serious adverse events per 100 patient-years. Adverse drug reactions with obinutuzumab included infusion-related reactions, respiratory tract infections, and neutropenia. One patient in each group died during escape therapy. CONCLUSIONS: Obinutuzumab was superior to tacrolimus in inducing complete remission in patients with primary membranous nephropathy. (Funded by F. Hoffmann-La Roche; MAJESTY ClinicalTrials.gov number, NCT04629248.).

Adult

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

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&#xa0;=&#xa0;45) was predominantly male (88.9%) and White (55.6%), with mean age of 29.6&#xa0;&#xb1;&#xa0;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&#x2011;specific PK analyses demonstrated higher exposure with CTx&#x2011;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

Molecular Landscape and Advanced Diagnostic Technologies for BRAF Mutations in Cancer: From Quantitative PCR and ddPCR to CRISPR-Based Platforms.

BRAF mutations are key oncogenic alterations across multiple malignancies, including melanoma, thyroid carcinoma, colorectal cancer, non-small cell lung cancer, glioma, and hairy cell leukemia. The most prevalent variant, BRAF-V600E, induces constitutive activation of the MAPK signaling pathway, promoting tumor progression and influencing therapeutic responsiveness. Accurate detection of BRAF alterations is therefore essential for molecular classification, prognostic assessment, treatment selection, and resistance surveillance. This review summarizes the molecular heterogeneity of BRAF mutations and critically evaluates current diagnostic methodologies. Conventional approaches such as allele-specific PCR and Sanger sequencing are compared with advanced quantitative platforms, including high-resolution melting analysis, droplet digital PCR, and next-generation sequencing, with emphasis on analytical sensitivity, mutation coverage, and clinical applicability. Emerging technologies such as CRISPR-based assays, rolling circle amplification systems, and nanoparticle-based biosensors and point-of-care diagnostic platforms are also discussed for their potential to enhance ultra-sensitive detection, particularly in liquid biopsy settings. These emerging tools are highlighted for their potential to enable ultra-sensitive, rapid, and decentralized mutation detection, particularly in liquid biopsy settings. Key challenges, including intratumoral heterogeneity, low allele-frequency variants, FFPE-associated artifacts, and clonal evolution under therapeutic pressure, are examined within a translational framework. In addition, we examine critical barriers to clinical implementation, including standardization, cost, and global accessibility of molecular diagnostics, and outline potential solutions through scalable technologies and decentralized testing strategies. We propose that optimal BRAF testing requires a mutation subclass-informed and clinically integrated strategy combining comprehensive baseline profiling with longitudinal molecular monitoring. Future diagnostic paradigms will likely integrate multi-omics data and artificial intelligence (AI)-assisted interpretation to refine precision oncology implementation. Looking forward, we propose that optimal BRAF testing will require integration of multi-omics profiling with AI-assisted interpretation, enabling automated variant classification, real-time clinical decision support, and improved prediction of therapeutic response and resistance.

Humans

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 &#x2192; cognitive flexibility &#x2192; 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

Effectiveness of a blended care intervention in physiotherapy with exercise and education for patients with hip or knee osteoarthritis (SmArt-E): A multicentre pragmatic randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of a twelve-month smartphone-assisted physiotherapy (SmArt-E) intervention versus usual care in hip and/or knee osteoarthritis (OA), and to assess usability and patient satisfaction with the digital support. METHOD: We conducted a multicentre, pragmatic, parallel-group randomized controlled trial in 27 physiotherapy practices in Germany. Patients with physician-diagnosed hip and/or knee OA aged &#x2265;50 (hip) or &#x2265;38 years (knee) were randomly allocated to SmArt-E (IG; n=166) or usual care (CG; n=164). The twelve-month intervention combined supervised and smartphone-assisted training and education (blended care). Primary outcomes were pain (NRS, 0-10) and physical function (HOOS/KOOS-ADL, 0-100) at twelve months. Secondary outcomes followed OARSI domains; usability and patient satisfaction were also assessed. RESULTS: Among 330 participants (mean age 64&#xb1;8 years), baseline NRS was 3.2&#xb1;2.3 in the CG and 3.5&#xb1;2.4 in the IG; HOOS/KOOS-ADL was 71.6&#xb1;17.7 and 69.4&#xb1;17.5, respectively. No significant between-group differences were found for pain (-0.36; 95% CI: -0.84 to 0.12; p=0.14) or physical function (2.66; 95% CI: -0.46 to 5.77; p=0.09). Among 13 secondary outcomes, significant differences favouring the IG emerged at three and twelve months for several domains; however, effect sizes were small and unlikely to be clinically meaningful. CONCLUSION: SmArt-E did not demonstrate superior effectiveness over usual care in mild hip and/or knee OA. Both groups improved over time, with slightly more favourable but clinically inconclusive outcomes in the IG. Findings highlight the need to refine the intervention, better identify eligible patients, and optimize digital and in-person components.

Humans

Systematic evaluation of one-dimensional-to-two-dimensional near-infrared spectroscopy transformations with deep learning for quantifying coconut sap adulteration.

Near-infrared (NIR) spectroscopy have limitations when combined with deep learning (DL) algorithms because they rely on low-dimensional datasets. Therefore, we investigated the potential of transforming one-dimensional (1D) NIR spectra into two-dimensional (2D) spectrograms using synchronous and asynchronous techniques and the continuous wavelet transform (CWT) and their effectiveness by integrating with DL for detecting adulteration in coconut sap. NIR spectra (12,500-4000&#xa0;cm-1) were collected from binary mixtures (0%-100%;w/w). The performance of all DL (convolutional neural networks-CNN, AlexNet and ResNet) models was compared with that of partial least squares (PLS). The models were ranked in the mentioned order based on their performances: 2D-CWT&#xa0;>&#xa0;2D-asynchronous > 2D-synchronous > 1D/2D-PLS. The important features of the best model can be explained and visualized using gradient-weighted-class-activation-mapping. The findings highlight that the 1D-to-2D NIR data transformation combined with DL is a highly robust approach because it addresses the feature representation gap in NIR data and effectively captures the spatial-spectral correlations.

Spectroscopy, Near-Infrared

DNM1L depletion leads to accelerated heteroplasmy shifting of m.10191C allele through ATG7-dependent pathways.

Nucleotide composition bias in mitochondrial DNA (mtDNA) makes the heavy strand prone to form a DNA secondary structure called a guanine quadruplex (G4). This secondary structure has been shown to inhibit polymerase processivity in vitro. We previously identified pathogenic mtDNA variants that lead to increased G4-forming propensity, including a T to C mutation at m.10191 (m.10191&#xa0;T&#xa0;>&#xa0;C) that causes Leigh syndrome. Cells treated with G4 binding agent (G4BA) berberine show a reduction in m.10191C pathogenic heteroplasmy levels. To help better understand the underlying mechanism behind berberine-induced heteroplasmy shift, we examined the relationship between mitochondrial fission and berberine-mediated shift. Here we show that knockdown of the fission factor DNM1L leads to an accelerated heteroplasmy shift towards the healthy mtDNA allele, lowering m.10191C by 10% in 3&#xa0;weeks, compared to the 5&#xa0;weeks required for berberine alone. The specific mechanism involves ATG7, as knockdown of ATG7 is able to partially delay this accelerated heteroplasmy shift. Taken together, we show that DNM1L knockdown is able to accelerate berberine-induced m.10191C heteroplasmy shifting through an autophagy-related mechanism.

Humans

A transcription factor-focused CRISPR screen identifies SKI as a BCL11A-independent repressor of &#x3b6;-globin.

The regulation of &#x3b1;-like globin genes, particularly the embryonic &#x3b6;-globin gene (HBZ), remains incompletely understood. To identify transcriptional regulators of HBZ, we establish a GFP reporter system based on the HBZ-P2A-GFP allele in erythroid cell lines and conduct a CRISPR/Cas9 screen targeting 1639 transcription factors. This screen identifies SKI as a potent HBZ repressor. Functional validation shows that SKI loss increases HBZ expression without impairing erythropoiesis, whereas SKI overexpression suppresses HBZ. Tet-on-inducible SKI overexpression and auxin-inducible SKI degradation indicate that SKI rapidly represses HBZ transcription. Transcriptome profiling further reveals that SKI deletion activates HBZ while minimally affecting other erythroid genes. Mechanistically, genome-wide occupancy analyses show that SKI binds the distal enhancers HS-10 and HS-40, with partial co-occupancy by BCL11A. Despite this overlap, dual knockout of SKI and BCL11A synergistically increases HBZ expression, as does base editing of the SKI-binding site within HS-10. We also identify a naturally occurring variant (chr16:193207G>A) within this enhancer in &#x3b1;-thalassemia patients with elevated &#x3b6;-globin levels. Together, these findings establish SKI as a direct, BCL11A-independent transcriptional repressor of &#x3b6;-globin. This work advances our understanding of globin gene regulation and suggests targeted &#x3b6;-globin reactivation as a potential therapeutic strategy for &#x3b1;-thalassemia.

Enhancer

AI-driven snapshot hyperspectral imaging for on-line sorting systems in food industry: From real-time sensing to intelligent decision-making.

High-throughput food sorting requires rapid, non-destructive detection of external defects, foreign materials, and internal quality attributes in heterogeneous food matrices. Conventional scanning hyperspectral imaging may suffer from motion-induced spatial-spectral mismatches, whereas snapshot hyperspectral imaging (S-HSI) captures spectral images within a single integration time. However, its advantage is limited by trade-offs in resolution, signal-to-noise ratio (SNR), reconstruction uncertainty, and calibration stability, which are further amplified by variable tissue structure, surface reflection, moisture, and fat distribution in foods. This review critically examines artificial intelligence (AI)-driven S-HSI for on-line food sorting within a sensing-representation-decision-execution framework. Compact architectures are compared according to their physical constraints, food-sorting suitability, and ability to support mapping between spectral responses and physicochemical quality attributes. AI strategies are reviewed for spectral reconstruction, image restoration, spatial-spectral representation, band selection, uncertainty-aware decision-making, and edge implementation. AI can partially compensate for snapshot-specific limitations, but current evidence remains largely limited to laboratory or prototype studies. Future work should link system performance to food safety and quality outcomes by reporting throughput, decision latency, calibration drift, missed-detection risk, false-rejection cost, and closed-loop sorting success.

Hyperspectral Imaging