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Spasmodic dysphonia is characterized by involuntary spasms of the laryngeal muscles occurring during vocal fold adduction or abduction; the underlying cause remains unknown. Management of spasmodic dysphonia ranges from surgical interventions and voice therapy to pharmacological injections into the laryngeal musculature; however, no currently available treatment provides a permanent cure. In routine practice, these patients often initially consult a voice or speech-language pathologist. Voice pathologists therefore require evidence-based research findings regarding the potential utility of initiating therapy alone versus early referral to a laryngologist, as well as identifying which types and severities of spasmodic dysphonia may benefit from standalone voice therapy. To systematically evaluate the available evidence regarding standalone voice therapy as a treatment approach for individuals with spasmodic dysphonia and identify existing evidence gaps. Systematic review. Studies involving children or adults diagnosed with all subtypes of spasmodic dysphonia (adductor, abductor, and mixed forms) through clinical and/or instrumental assessment were considered eligible for the study. Studies involving participants with an unconfirmed SD diagnosis, muscle tension dysphonia without SD, or structural/organic voice disorders unrelated to SD were excluded. Eligible study designs included randomized controlled trials, nonrandomized studies, cohort studies, before-and-after studies, and case series involving at least three participants. Studies involving patients undergoing standalone voice therapy, including behavioral voice therapy, resonant voice therapy, vocal function exercises, respiratory-phonatory coordination training, relaxation-based approaches, and compensatory voice strategies of any duration or frequency, were considered eligible. Risk of bias was planned using RoB 2 (randomized studies) and ROBINS-I (nonrandomized studies). This assessment was not performed due to the absence of included studies. A narrative synthesis was planned. Meta-analysis was not feasible due to the absence of eligible studies. A total of 29 records were identified through database searching and supplementary sources. All records were imported into Rayyan for screening. No duplicate records were removed. During title and abstract screening, 22 records were excluded as they did not meet the eligibility criteria. Seven articles were retrieved for full-text assessment. Following full-text review, all seven articles were excluded due to the inclusion of botulinum toxin as part of the intervention, absence of standalone voice therapy outcomes, or non-interventional study designs. Therefore, no studies met the inclusion criteria for qualitative or quantitative synthesis INTERPRETATION: This systematic review identified a critical evidence gap regarding standalone voice therapy for spasmodic dysphonia. The absence of eligible studies prevents conclusions regarding effectiveness, but highlights the need for rigorous prospective studies evaluating patient selection, intervention protocols, and clinically meaningful outcomes.

Albashaireh ZS, Altallaq MK. Assessment of patient satisfaction and esthetic outcomes following treatment of post-orthodontic white spot lesions using a bioactive adhesive and resin infiltrant: a randomized split-mouth clinical trial. Journal of Dentistry. 2026;167:106565. Split-mouth randomized clinical trial of 20 orthodontically treated patients (13 female, 7 male) involving 120 teeth with anterior white spot lesions (WSLs). Each participant received ICON resin infiltration or Hi-Bond Universal in contralateral quadrants. Esthetic changes were assessed by the patients and by two independent clinicians using a 100-point visual analogue scale (VAS) at one-month recall. Participants aged 16-30 years and who had completed fixed orthodontic treatment at least one month before enrollment were included. Eligible participants presented with at least one visible WSL on the labial surfaces of the anterior teeth or premolars on contralateral quadrants. All participants were required to have good oral hygiene, clinically healthy gingival tissues, and no evidence of active periodontal disease. Categorical outcome data were presented using descriptive summary measures including frequencies and percentages. The proportion of satisfactory vs. unsatisfactory outcomes (paired binary data) was compared between the Hi-Bond Universal and ICON treatments using the McNemar test. Overall patient satisfaction was equally high (80%) for both treatments, and there were no significant differences between patient or clinician ratings. Inter-assessor agreement was deemed "fair" for both groups (Cohen's kappa 0.318-0.340). Thus, both ICON and Hi-Bond Universal effectively masked WSLs, as deemed by subjective esthetic evaluation. Both bioactive adhesives and resin infiltration achieve satisfactory esthetic outcomes in masking demineralized enamel, at least in the short-term. Further longitudinal studies comparing the outcomes of these materials would be beneficial to determine whether these effects are sustained over time.

The emission of volatile organic compounds (VOCs) during the loading and unloading of organic liquids in chemical-industrial parks has yet to receive widespread scholarly attention, despite its pronounced impact on front-line operators. This study presents a comparative field investigation of VOC emissions from loading/unloading operations at six chemical enterprises in an East China industrial park, using photochemical assessment monitoring stations (PAMS) and TO-15 methods for species-resolved quantification. Subsequently, a quantitative analysis was conducted to assess ozone formation potential (OFP), toxification, and an on-site health risk evaluation, encompassing six representative companies. This research builds upon previous studies by expanding both the number of facilities investigated and the diversity of species detected. The findings reveal that halohydrocarbons, alkenes, and aromatics, which together account for 96 % of total emissions, are the primary contributors to VOC emissions in these companies. Of these, alkenes contribute the most significantly to OFP, a result that aligns with similar studies. Furthermore, compounds such as 1,3-butadiene and benzene emerge as substantial contributors to long-term health risks, with aromatics serving as major agents for both carcinogenic and non-carcinogenic effects. These findings provide crucial insights for the development of VOCs control strategies for process flows involving the loading and unloading of organic liquids in chemical industrial parks.

Chronic pain represents a complex debilitating condition that extends beyond the protective function of physiological pain, often persisting as an independent disease entity. Chronic primary and secondary pain syndromes reflect a multifaceted continuum involving nociceptive, neuropathic and nociplastic mechanisms. The maladaptive plasticity of the peripheral and central nervous system (encompassing the ascending and descending pain pathways) sustains hypersensitivity and correlates with comorbid alterations in mood, cognition, sleep and fatigue, underpinned by functional reorganization of brain networks. In this scenario, traditional analgesics frequently demonstrate limited efficacy, while current guidelines recommend antiepileptic agents and antidepressants, particularly gabapentinoids and duloxetine, as first line pharmacological options. This review explores the mechanistic rationale and clinical evidence supporting the combined use of gabapentinoids and duloxetine in chronic pain management. These agents act on distinct yet complementary targets: gabapentinoids reduce excitatory neurotransmission via modulation of calcium channel activity, whereas duloxetine restores descending noradrenergic inhibition and alleviates comorbid symptoms. Clinical trial and meta-analyses highlight their individual efficacy in diabetic peripheral neuropathy, postherpetic neuralgia and fibromyalgia. Among gabapentinoids, pregabalin exhibits a favourable pharmacokinetic profile that allows rapid titration and demonstrates effectiveness against anxiety-related sleep disorders. Importantly, emerging evidence suggests that their combination may offer additional benefit, particularly in patients with residual pain despite monotherapy, though evidence remains limited to small, short-term studies. This review provides proof of concept by bridging theoretical knowledge and real-life clinical settings aiming to develop treatment protocols based on predominant pain mechanisms that can effectively control hypersensitivity and improve quality of life.

Cardiac dysfunction is increasingly recognized in children with severe malaria and may result from recurrent ischemia-reperfusion injury, endothelial dysfunction, and severe anaemia. However, the burden of cardiac abnormalities remains poorly characterized in many malaria-endemic countries, including Nigeria. This study evaluated cardiac function in children with severe malaria using echocardiography. A cross-sectional study involving 100 children with severe malaria and 100 age- and sex-matched controls was conducted in Enugu, Nigeria. All participants underwent transthoracic echocardiography to assess right and left ventricular systolic and diastolic function using parameters including tricuspid annular plane systolic excursion (TAPSE), tricuspid regurgitant velocity (TRV), mitral inflow velocity (MV E/A), left ventricular ejection fraction (LVEF), and mitral annular plane systolic excursion (MAPSE). Children with severe malaria had significantly higher TRV (1.3&#x2009;&#xb1;&#x2009;0.8 vs 0.9&#x2009;&#xb1;&#x2009;0.4&#xa0;m/s; p&#x2009;=&#x2009;0.001) and lower LVEF (65.5&#x2009;&#xb1;&#x2009;23.2 vs 69&#x2009;&#xb1;&#x2009;9.8; p&#x2009;=&#x2009;0.04) than controls. Abnormal TAPSE occurred in 4% of subjects compared with none of the controls (p&#x2009;=&#x2009;0.04). The prevalence of abnormal MRV was greater in subjects than controls (16% vs 6%; p&#x2009;=&#x2009;0.04), while abnormal LVEF occurred in 7% versus 1% respectively (p&#x2009;=&#x2009;0.03). Left ventricular diastolic dysfunction assessed by abnormal MAPSE was more common in subjects (32% vs 13%; p&#x2009;=&#x2009;0.03). TAPSE positively correlated with age (r&#x2009;=&#x2009;0.5, p&#x2009;<&#x2009;0.001). &#xa0;Children with severe malaria demonstrate significant systolic and diastolic cardiac dysfunction, particularly those with severe malarial anaemia. Early echocardiographic evaluation may improve detection and management of cardiovascular complications in severe malaria. &#x2022; Severe malaria remains a major cause of childhood morbidity and mortality, particularly in sub-Saharan Africa. Cardiovascular involvement is increasingly recognized as an important complication resulting from microvascular sequestration, endothelial dysfunction, haemolysis, inflammation, and severe anaemia. Previous studies have reported abnormalities in right and left ventricular function among children with severe malaria. Echocardiography is a useful non-invasive tool for assessing cardiac function and pulmonary hemodynamics. However, evidence on malaria-associated cardiac dysfunction remains limited, especially in African populations where malaria burden is highest. &#x2022; This study evaluated cardiac function in children with severe malaria using echocardiographic parameters including TAPSE, TRV, tricuspid inflow E/A ratio, LVEF, and fractional shortening. It demonstrated significant systolic and diastolic abnormalities affecting both right and left ventricular function, particularly among children with severe malarial anaemia. The findings provide important region-specific data from Nigeria and help address the limited evidence regarding cardiovascular complications of severe malaria in African children. The study supports early echocardiographic assessment for detecting subclinical cardiac dysfunction, improving risk stratification, and enhancing clinical management in severe malaria.

Cognitive flexibility-the ability to adapt behavior when contingencies change-is impaired in psychiatric disorders involving prefrontal dysfunction. The medial prefrontal cortex (mPFC) relies on noradrenergic input from the locus coeruleus (LC), yet the molecular mechanisms enabling this neuromodulatory control remain unclear. Here we show that GluN2A-containing NMDA receptors are required for LC-mPFC regulation of network dynamics and reversal learning in male mice. Optogenetic activation of LC&#x2192;mPFC projections enhanced reversal learning in wild-type and heterozygous mice but not in global Grin2a knockouts, whereas LC inhibition impaired performance only in wild-type animals. In slices, norepinephrine and LC stimulation induced gamma and high-frequency oscillations in wild-type mPFC that were blocked by &#x3b1;2-adrenergic antagonism, but these oscillatory responses were undetectable in Grin2a mutants. Grin2a mutants also exhibited increased LC axonal density and elevated norepinephrine transporter expression in prelimbic cortex, consistent with enhanced noradrenergic clearance capacity. Together, these findings identify GluN2A as a key determinant of LC-prefrontal circuit function supporting cognitive flexibility. They suggest that functional deficits in these mutants should be interpreted within the context of compensatory structural hyperinnervation resulting from global GluN2A deficiency, which may reflect a developmental adaptation rather than acute signaling loss. Furthermore, these results promote &#x3b1;2-adrenergic pathways as potential entry points for restoring prefrontal network coordination.Significance statement Cognitive flexibility is often impaired in psychiatric disorders, yet how norepinephrine engages prefrontal network dynamics remains unclear. We investigate how global GluN2A deficiency affects LC-mPFC dynamics while accounting for potential systemic and developmental contributions. These findings show that global GluN2A deficiency disrupts noradrenergic induction of synchronized oscillatory activity and highlight &#x3b1;2-adrenergic pathways as a candidate therapeutic entry point for improving prefrontal network function. Importantly, our results suggest that functional deficits in global knockout models must be interpreted within the context of compensatory structural changes in circuit architecture, such as hyperinnervation.

Deficient DNA mismatch repair/microsatellite instability-high (dMMR/MSI-H) cancers are very sensitive to immune checkpoint inhibitors (ICIs), yet their use is frequently complicated by immune-related adverse events (irAEs). Our study analyzed the impact of grade &#x2265;3 irAEs (immune-related severe adverse events (irSAEs)) on survival in patients with dMMR/MSI-H digestive cancers treated with ICIs. We conducted an international, multicenter, ambispective study involving 1,175 patients from 34 centers. The primary endpoint was the correlation between the occurrence of irSAEs and progression-free survival (PFS). Secondary endpoints included factors associated with irSAEs, correlation between irSAEs and overall response rate (ORR) and overall survival (OS). Prespecified landmark and time-dependent survival models were used to account for the time to irSAE occurrence. Among 1,175 patients treated with ICIs for digestive cancers, 49.1% were female, median age was 66.9 years (IQR 53.7-77.3) and 82.9% had colorectal cancer. Overall, 382 patients (32.5%) had an irAE, including 117 (10.0%) irSAEs. Median time to irSAEs occurrence was 3.78 months (IQR 1.97-7.62). The most frequent irSAEs were gastrointestinal (3.4%), hepatic (1.8%) and dermatologic (1.0%). The only factor associated with irSAEs was the use of an ICI combination versus monotherapy (20.0% vs 11.4%, p=0.03). Among patients with irSAEs, 71.5% received oral and 29.8% intravenous corticosteroids, and 15.7% immunosuppressive agents. Overall, in 26.9% of patients, ICIs were resumed following irSAEs, with an irAE recurrence rate of 57.1%. irSAE was associated with a better ORR (48.6% vs 34.6%, p<0.0001). The multivariable Cox model revealed that irSAE as a time-dependent variable was not associated with better PFS (HR=1.280 (95% CI 0.898 to 1.824), p=0.172) or OS (HR=1.043 (95% CI 0.712 to 1.528), p=0.828). Likewise, landmark analysis at 3 months and 6 months also showed that irSAEs were not associated with better PFS or OS. The occurrence of irSAE was not independently associated with better survival in patients with dMMR/MSI-H digestive cancers treated with ICIs.

Rapid-acting antidepressants like ketamine and serotonergic psychedelics show promise for treatment-resistant depression (TRD), but the molecular mechanisms that contribute to their therapeutic effects remain unclear. Induced pluripotent stem cells (iPSCs) offer a platform to model human cortical neurons and investigate drug effects in a human-relevant system. Here, iPSCs from individuals with TRD and healthy volunteers (HVs) were differentiated into mature cortical-like neurons and treated for six and 24&#x2009;h with agents being investigated as rapid-acting antidepressants, including (2&#x2009;R,6&#x2009;R)-hydroxynorketamine (HNK), psilocybin, lysergic acid diethylamide (LSD), and 2,5-Dimethoxy-4-iodoamphetamine (DOI). Bulk and single-cell RNA sequencing assessed global and cell-type-specific transcriptomic responses. Synaptic proteins were evaluated via Western blotting and immunocytochemistry. To validate translational relevance, transcriptomic results were compared to CSF proteomics from ketamine-treated HVs. Despite differing initial pharmacological targets, overall gene expression across all compounds was highly correlated at matched timepoints compared to vehicle control, suggesting shared downstream effects. Both glutamatergic and serotonergic drugs converged on pathways involving inflammation, mTORC1 signaling, and cellular growth. At the single-cell level, (2&#x2009;R,6&#x2009;R)-HNK showed distinct cell-type specific alterations: upregulation in excitatory neurons and concomitant downregulation of inhibitory neuron populations. Differentially expressed genes from (2&#x2009;R,6&#x2009;R)-HNK-treated neurons also overlapped with CSF proteomic signatures from ketamine-treated individuals, supporting the model's translational relevance. This study is the first to assess multiple putative rapid-acting antidepressants in parallel using an iPSC-derived neuron model. Both convergent and drug-specific changes in gene expression and pathway enrichment were observed across diverse compounds, supporting the use of human iPSC-derived neurons in antidepressant drug discovery. Clinical Trial Registry: www.clinical trials.gov, NCT02484456.

Rule-based field triage protocols used by Emergency Medicine Service (EMS) personnel for assessment and prioritization of trauma patients achieve suboptimal field triage performance. An On Scene Injury Severity Prediction (OSISP) model was previously developed on Swedish trauma data with indications to improve field triage performance. This study aims to apply OSISP on external Norwegian data to assess its performance and clinical impact on unseen data. Adult trauma incidents involving EMS resources at the scene of incident were included. An eXtreme Gradient Boosting OSISP model was developed on Swedish trauma registry (SweTrau) data for 2013-2020 and trained to predict severely injured patients defined as new injury severity score (NISS)&#x2009;>&#x2009;15. OSISP was evaluated on Norwegian trauma registry (NTR) data for 2017-2022. The model performance on NTR data was evaluated using overall performance measures for discrimination and calibration (receiver operating characteristic curve, precision-recall curve, area under these curves, Brier score, calibration curve, calibration slope, calibration in the large). OSISP's clinical impact was assessed by evaluating its under- and overtriage rates and comparing to current clinical outcome and mortality. The raw data from SweTrau and NTR had 75,602 and 76,529 registrations, with 47,357 and 29,709 remaining after applying eligibility criteria. In the included data, there were 16.9% and 25.2% patients with NISS&#x2009;>&#x2009;15 in SweTrau and NTR, respectively. The OSISP predictors represented age, sex, details of the patient's condition, incident and injury details, vital signs, and administrative details. OSISP applied on NTR data yielded an overall performance of AUCROC=0.83, AUCPR=0.64, Brier score&#x2009;=&#x2009;0.14, calibration slope&#x2009;=&#x2009;0.79, and calibration in the large=-0.09. On its own, OSISP reduced undertriage to 5.0% but increased overtriage to 61.0%, while the complementary use (NTR's triage outcomes combined with OSISP's predictions) reduced undertriage to 2.7%, overtriage to 19.7% (compare to current clinical practice with an undertriage&#x2009;=&#x2009;56.0% and overtriage&#x2009;=&#x2009;30.6%), and mortality from 4.1% to 3.4-3.5%. OSISP's overall performance was successfully validated and a potential capability to improve triage and decrease mortality was observed, also for elderly and patients from the northern region, groups often missed with current triage tools. Not applicable. Not applicable.

Passion fruit (Passiflora edulis) leaves displaying yellow spot symptoms were collected in La R&#xe9;union. Whilst viral indexing suggested single infections with potyviruses, high-throughput sequencing revealed both single and mixed infections involving cowpea aphid-borne mosaic virus (CABMV; species Potyvirus vignae) and a previously undescribed potyvirus, for which the name passion fruit yellow spot virus (PaYSV; tentative species Potyvirus passifloraflavamaculae) is proposed. Complete genome sequences (9,626 nucleotides) of two PaYSV isolates were obtained from these samples, using RNA sequencing after ribodepletion. The two isolates were highly similar (>&#x2009;99.3% nucleotide identity) and shared the highest nucleotide (63.6%) and amino acid (71.7%) identities at the polyprotein level with passion fruit woodiness virus (PWV; Potyvirus passiflorae), values that are below the species demarcation thresholds. Our results provide compelling molecular and phylogenetic evidence for the presence of a novel potyvirus species infecting passion fruit in La R&#xe9;union.

Endoscopic treatment of small lesions involving the appendiceal orifice remains technically challenging. Although endoscopic submucosal dissection (ESD) enables en bloc resection, it may represent overtreatment for such lesions. In contrast, forceps-assisted polypectomy; strip biopsy may serve as an effective therapeutic option. The aim of this study was to propose a practical, real-world treatment strategy and to evaluate the clinical usefulness of strip biopsy. This retrospective single-center study included patients who underwent endoscopic treatment for appendiceal orifice lesions between May 2017 and September 2025. Patients were classified into strip biopsy or ESD group. Procedural outcomes and adverse events were compared. Twenty-two appendiceal orifice lesions were included, with 14 treated by strip biopsy and 8 by ESD. Baseline characteristics were comparable. Procedure time was significantly shorter in the strip biopsy group (6.6&#x2009;&#xb1;&#x2009;2.9 vs. 45.9&#x2009;&#xb1;&#x2009;31.3&#xa0;min, p&#x2009;<&#x2009;0.05). En bloc resection rates were 93 and 100%, respectively. No perforation occurred, and delayed bleeding was observed in one ESD case only. Positive or unclear horizontal margins were more frequent in the strip biopsy group than in the ESD group (50 vs. 13%, p&#x2009;=&#x2009;0.16). Among patients who completed 1-year surveillance colonoscopy, no local recurrence was observed. Strip biopsy may be a feasible and rapid treatment option for carefully selected small appendiceal orifice lesions without endoscopic features suggestive of malignancy. However, because of the retrospective design, small sample size, and limited follow-up data, further prospective studies with larger cohorts and longer follow-up are warranted.

The discovery of clathrin was a foundational event in membrane traffic research. Its identification as the major protein component of the coat that surrounds endocytic vesicles kickstarted the biochemical and molecular characterization of endocytosis. During this explosive period of cell biology, there was a parallel storyline involving clathrin which developed more slowly. It emerged that clathrin has an alternative function during mitosis, and that this function is unrelated to its membrane trafficking role. Clathrin forms part of a multiprotein complex that stabilizes microtubules of the mitotic spindle during the chromosome segregation events that occur during cell division. Due to this dual functionality, clathrin is sometimes referred to as a "moonlighting" protein. In this Perspective, we will take a look at this secret life of clathrin and examine how it carries out its mitotic function.

Acute myeloid leukaemia (AML) is a highly heterogeneous haematologic malignancy in which transfusion support represents an essential component of comprehensive patient care. This review aims to provide an updated synthesis of recent progress in the development and clinical application of machine learning models based on multimodal big data for precision transfusion management in AML, addressing the persistent limitations of conventional, empirically guided transfusion practices. We systematically reviewed the literature on multimodal data integration-including electronic health records, genomic, proteomic and other high-dimensional datasets-in the context of AML transfusion management. The applications of machine learning algorithms such as decision trees, random forests and neural networks were analysed in the contexts of transfusion demand prediction and transfusion reaction risk assessment, with reference to representative clinical case studies demonstrating their practical utility. Multimodal big data demonstrates substantial value in optimising transfusion strategies for AML patients. Machine learning models have shown promising performance in predicting transfusion demand and assessing transfusion reaction risks, with clinical case studies supporting their practical utility. However, major challenges persist, including data privacy protection, data standardisation across platforms and model interpretability for clinical adoption. The integration of multimodal big data with advanced machine learning methodologies holds substantial promise for enabling precision, individualised transfusion management in AML. Future directions involving federated learning and explainable artificial intelligence are anticipated to address current limitations, ultimately contributing to improved transfusion safety and clinical outcomes in AML patients.

Resilience is a dynamic process of adapting to stress. Identifying modifiable resilience factors (RFs) remains challenging due to the difficulty of studying individuals before, during, and after a stressor in real time. We addressed this by investigating modifiable protective factors in the context of university exams, a predictable and impactful stressor, and focused on medical students to examine RFs in a vulnerable cohort under standardized conditions. In this exploratory study, we used data from the three-wave 'RESIST' Study involving 451 medical students from the UK. Our investigation covered three timepoints with differing levels of stress (1) a non-exam period, (2) an exam period, and (3) post-exams at the end of the term. We examined the distinct impact of 13 modifiable RFs at individual, family, and community levels. Specifically, we investigated their relative importance and their cumulative impact with regard to self-reported mental health symptoms at three timepoints. We found the highest relative importance rankings for self-esteem, brooding, and distress tolerance. While most individual resilience factors had negligible-to-small effects, the sum of all 13 effects was similar to the effects of self-reported mental health symptoms at the previous timepoint on themselves. Our findings shed light on the role of RFs, and their cumulative and timing effects, and their associations with exam-related self-reported mental health problems among medical students.

Participation in online communities centered around self-harming and suicidal behavior is a complex phenomenon characterized by potentially harmful social dynamics, though it may also involve support. While previous studies have explored peer support within these communities, less is known about how engagement may influence personal recovery and the functions these communities serve. Therefore, this study explored experiences of personal recovery in the context of participating in unmoderated online communities centered around self-harming and suicidal behavior. This qualitative deductive-inductive secondary analysis re-examined interview data originally collected to explore peer support exchanges within online communities centered around self-harm and suicidal behavior, using reflexive thematic analysis informed by the CHIME-D (Connectedness, Hope, Identity, Meaning, Empowerment, and Difficulties) framework to examine personal recovery in this context. The dataset consisted of semi-structured interviews with twelve women and one non-binary participant (aged 21-49 years) from all five Danish regions, all with lived experience of psychiatric disorders and previous psychiatric admissions. Participants described how engagement supported personal recovery through mutual recognition, reciprocity, and shared experience. They also described tensions between their own experiences of these communities as meaningful recovery spaces and professionals' predominantly risk-oriented interpretations, contributing to stigma and concealment. Recovery was experienced as complex and ambivalent, involving not only support but also ongoing attachment, emotional burden, and difficulty disengaging. Participants also described challenges related to moral responsibility towards others, exposure to distressing content, and balancing recovery with ongoing participation. Examining recovery in digital self-harm networks highlights important nuances in understanding the roles and functions these networks may serve. Applying the CHIME-D framework provided a nuanced understanding of how online communities centered around self-harming and suicidal behavior may contribute to personal recovery, advancing our understanding of the functions they serve and what motivates participation. The findings highlight recovery as a non-linear process shaped by both supportive and challenging dimensions of online engagement and underscore the importance of recognizing these communities as meaningful, though double-edged, contexts for recovery.

Peripheral nerve ultrasound in the pain medicine clinic remains largely non-standardized. The purpose of this technical note is to propose a structured point-of-care ultrasound protocol for systematic peripheral nerve evaluation in the interventional pain medicine setting. The Peripheral Nerve Assessment Protocol (PNAP) was developed based on the existing peripheral nerve ultrasound literature, established point-of-care ultrasound models, and clinical experience in interventional pain medicine. The protocol targets 10 nerves across four anatomical regions using a four-step assessment sequence: static survey, dynamic provocation, Doppler interrogation, and contralateral comparison. Sonographic diagnostic criteria and a three-tier clinical decision framework are presented to guide same-visit treatment planning. The protocol integrates diagnostic assessment with procedural decision-making within a single clinical encounter. The PNAP provides a reproducible methodology for peripheral nerve assessment in the interventional pain medicine clinic that may serve as a foundation for future validation studies.

This article outlines a practical approach for general practitioners to evaluate and diagnose orthopedic conditions in small animals. Thorough history-taking for cases of lameness is reviewed, and the determination of onset, duration, severity, progression, and response to treatment is emphasized. Gait evaluation is described, which can identify the affected limb, lameness severity, and suspected neurologic involvement. Standing orthopedic examination techniques help assess symmetry and joint effusion. The recumbent exam is used to determine the source of the lameness through the assessment of pain, instability, and the application of targeted examination techniques and maneuvers such as the cranial drawer test.

Gallbladder cancer (GBC), the most common malignancy of the biliary tract, exhibits a high propensity for lymphatic system invasion. However, the mechanisms underlying lymphatic metastasis in GBC remain poorly understood. Here, we demonstrate that C-C motif chemokine ligand 21 (CCL21) is significantly upregulated in GBC and positively correlates with lymphatic vessel density and lymph node metastasis. Both in vivo and in vitro experiments confirm that CCL21/CCR7 axis promotes lymphangiogenesis and lymphatic metastasis in GBC. Mechanistically, CCL21/CCR7 modulates Vascular Endothelial Growth Factor-D (VEGF-D) mRNA N6-Methyladenosine (m6A) modification in an AlkB homolog 5 (ALKBH5)-dependent manner, thereby regulating VEGF-D protein expression. Site-directed mutagenesis experiments reveal that m6A modification sites in the coding sequence (CDS) region of VEGF-D mRNA are critical for VEGF-D protein regulation. Collectively, our findings highlight that CCL21/CCR7 regulates VEGF-D expression via m6A modification, driving lymphatic metastasis in GBC.

Highly multiplexed immunofluorescence imaging visualizes and quantifies protein levels at single-cell resolution in intact tissues at low cost and high scalability. Analysis of these data involves multiple steps with many method and parameter choices that must be adapted to the data and analytical objectives. There is an unmet need for a toolbox that offers flexible end-to-end coverage of the workflow. Here we present 'spatialproteomics', a Python package that addresses these challenges. Spatialproteomics enables the processing and analysis of large imaging data, including steps such as segmentation, image processing and cell-type classification, while synchronizing shared coordinates across data modalities. We demonstrate spatialproteomics on images of reactive lymph nodes and B cell non-Hodgkin lymphomas from 132 patients. We showcase an end-to-end analysis from raw images to statistical characterization of how cell type composition and spatial distribution vary across indolent and aggressive lymphomas. Furthermore, we show how spatialproteomics can process Gigapixel whole-slide images.