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461 papers

Initiation of High-Potency Benzodiazepine Prescriptions Among Survivors of Severe Trauma.

Oldner A et al. · Jul 1, 2026

Background Trauma is a major public health concern that often leads to long-term psychological distress and chronic pain. Benzodiazepines (BZDs) are sometimes prescribed for anxiety, insomnia, or acute stress-related symptoms, but long-term use is associated with dependence and adverse outcomes. The extent to which BZDs are initiated after trauma, and their implications for long-term health, remain poorly understood. This study aimed to assess the association between trauma exposure and initiation of high-potency BZDs, identify risk factors within the trauma cohort and examine the association between new BZD use and long-term mortality. Methods We conducted a population-based cohort study using data from a regional trauma registry linked to Swedish national health registers. New initiation of BZD prescriptions was defined as filling at least one prescription within 6 months after trauma. Multivariable logistic regression was used to assess associations between trauma exposure and BZD initiation and to identify risk factors within the trauma cohort. Cox proportional hazards regression evaluated the association between new BZD use and 6-18-month mortality. Results The study included 12,206 BZD-naive trauma patients and 66,801 matched controls. Trauma exposure was independently associated with new high-potency BZD use. Within the trauma cohort, risk factors included older age, psychiatric comorbidity, substance abuse, pre-traumatic opioid or sedative-hypnotic drug use, penetrating trauma, and higher injury severity. New BZD use was associated with markedly elevated 6-18-month mortality (adjusted HR 2.9, 95% CI 2.0-4.2, p Conclusions Trauma exposure independently predicted initiation of high-potency BZDs among previously BZD-naive patients. Psychiatric comorbidity, substance use, and greater injury severity were important risk factors. The association between new BZD use and increased long-term mortality underscores the need for cautious prescribing and structured follow-up after trauma. Editorial comment This study examines initiation of high-potency benzodiazepines among previously naive survivors of severe trauma using linked registry data. It shows that trauma exposure is strongly associated with new benzodiazepine use, particularly in older, comorbid, and vulnerable patients. Initiation is also associated with higher subsequent mortality, likely reflecting underlying clinical and psychosocial risk rather than a causal drug effect.

Psychology

Lessons from the field: implementing an electronic clinical decision support app for acute febrile illness in rural Cambodia.

Mishra A et al. · Jul 1, 2026

To improve the management of acute febrile illness in rural low- and middle-income country (LMIC) primary care settings, we developed the Electronic clinical Decision support for Acute fever Management (EDAM) app and evaluated it through a cluster-randomised trial in rural Cambodian primary health centres (PHCs). In parallel, we conducted structured, mixed methods observations at a subset of participating PHCs to document key challenges in screening, enrolling and managing patients. A key lesson was the critical importance of user-centred design to align digital tools with health worker workflows and capabilities. The lessons from these observations may help guide researchers and policymakers developing novel digital health solutions for low- and semi-skilled health workers in rural LMIC settings. Our experiences could offer valuable insights, as there are few documented digital health interventions designed for these contexts. Furthermore, navigating the challenges of implementation and subsequent evaluation remains a significant hurdle for the field.

Health Professions

'It's Primarily Around Their Viral Load': Public Health Decision-Making and HIV Risk Assemblages in Ontario, Canada.

Daroya E et al. · Jul 1, 2026

In Ontario, Canada, public health authorities can issue and enforce orders to people living with HIV (PLWH). However, how public health practitioners determine when someone's behaviours constitute 'significant' risk remains underexplored. We drew on assemblage theory to examine how HIV risk is co-constituted through the interplay among biomedical technologies, institutional practices, legal frameworks and social discourses. We conducted 18 semi-structured interviews with public health personnel and used reflexive thematic analysis. Five interrelated themes emerged. First, high viral load was considered a potential risk indicator when associated with high-risk activities. Second, discontinuity in HIV care may flag individuals for intervention. Third, co-infection with sexually transmissible and blood-borne infections (STBBI) triggered a viral load review to assess HIV exposure potential. Fourth, noncompliance with public health directives positioned PLWH as needing management. Fifth, Undetectable = Untransmittable (U = U) discourses have reconfigured and neutralised risk, functioning as a technology of reflexive governance. However, uptake of U = U was described as uneven across Ontario's public health units, leading to variable, and sometimes coercive, approaches. By conceptualising HIV risk as emergent, this study challenges individualised notions of responsibility and highlights the relational production of risk. Adoption of U = U and equity-based public health practices is needed to ensure nonpunitive HIV responses.

Social Sciences

Antibiotics in Veterinary Ophthalmology: Resistance, Stewardship, and Emerging Antibiotic-Sparing Strategies.

Sebbag L et al. · Jul 1, 2026

Antimicrobial resistance (AMR) is a growing challenge in veterinary ophthalmology, particularly in cases of bacterial keratitis, where progressive stromal infection can threaten vision and globe integrity within hours to days. This review synthesizes current evidence on pathogen distribution, antimicrobial susceptibility profiles, multidrug resistance (MDR) prevalence, and determinants of nonsusceptibility in veterinary patients, highlighting the emerging role of antibiotic-sparing alternatives. Across contemporary studies, Staphylococcus pseudintermedius, β-hemolytic streptococci, and Pseudomonas aeruginosa are consistently among the most frequently isolated pathogens. The highest MDR burdens are reported in referral populations and among methicillin-resistant staphylococci worldwide. Feline data remain comparatively limited but show regional variability in resistance patterns, while equine studies reveal temporal shifts in isolate distribution and a rising prevalence of methicillin-resistant organisms in tertiary settings. Recent topical antimicrobial exposure is the most consistently identified predictor of reduced culture positivity and elevated resistance rates in subsequent ocular isolates, highlighting the importance of early microbiologic sampling and judicious antibiotic use. Interpreting antimicrobial susceptibility testing (AST) in ophthalmology remains challenging because clinical breakpoints are generally derived from systemic dosing regimens, despite substantially higher, albeit transient, drug concentrations being achieved at the ocular surface following topical administration. Moreover, the ocular surface microenvironment, including tear proteins, inflammation, biofilm formation, and concurrent serum therapy, may substantially influence antimicrobial activity and therapeutic response. The review concludes with practical ophthalmology-specific stewardship recommendations, a One Health perspective on resistant ocular pathogens, and a forward-looking discussion of antibiotic-sparing adjuncts within a broader multimodal strategy to preserve antimicrobial effectiveness.

Medicine

Targeting the Lipid Metabolism Proteins FASN and GPAM in Alveolar Type II Cells Decreases Lung Metastasis.

Liu XZ et al. · Jul 1, 2026

Cancer cells that seed in the lung require lipids often produced by alveolar type II (AT2) cells. However, whether overt metastases depend on AT2 cell-derived lipids and whether AT2 cells can be targeted to reduce metastasis growth remains unknown. We discovered that breast cancer-derived lung metastases stimulate the proliferation of AT2 cells in their vicinity and reprogram them into lipid feeder cells in mice and patients using spatial analysis. Mechanistically, the metastasis secretome activates the transcription factor sterol regulatory element-binding transcription factor 1 (SREBP-1) in AT2 cells, enhancing the expression of key de novo lipid synthesis genes, including fatty acid synthase (FASN) and glycerol-3-phosphate acyltransferase 1 (GPAM). Deleting Fasn selectively in AT2 cells or targeting FASN and GPAM systemically significantly impairs lung metastasis growth in mice. In summary, we discovered that overt metastases reprogram AT2 cells and that targeting the lipid metabolism of AT2 cells impairs metastasis growth. Significance Current therapies in oncology targeting the cancer or immune cell compartment of tumors show limited efficacy against breast cancer-derived metastases. We discovered that decreasing the lipid metabolism of lung resident AT2 cells is sufficient to impair lung metastasis growth in mice without apparent adverse effects.

Biochemistry, Genetics and Molecular Biology

Diffusion-weighted Imaging Distortion in Prostate MRI: A Cross-sectional Study Comparing Supine and Prone Positioning.

Lee KL et al. · Jul 1, 2026

Objectives Diffusion weighted imaging (DWI) is a key component of multiparametric (mp) prostate MRI. DWI using echo-planar techniques is susceptible to distortion at the recto-prostatic air-tissue interface. This study was to determine whether prone patient positioning reduces adjacent rectal air and DW image distortion when compared with standard-of-care supine positioning. Materials and methods This prospective study included consecutive patients undergoing mpMRI for suspected PCa between 2023 and 2024. Prostate segmentation was performed on DW and contrast-enhanced images. DWI distortion was measured quantitatively. Qualitative image quality of DWI and T2-weighted imaging (T2WI) was evaluated using PI-QUAL version 2; a separate 5-point clinically based Likert scale was employed to evaluate the volume of rectal air adjacent to the prostate. Results Fifty-two patients were enrolled. In total, 58% of patients expressed a preference for supine imaging versus 20% for prone imaging. Qualitative DWI image quality improved significantly in the prone position [median: 4 (3 to 4)] versus supine [3 (1 to 4)]; P 4 cm 3 of supine rectal air (n = 19), distortion was significantly reduced by prone imaging [3.49 mm (2.84 to 4.03)] compared with supine [4.60 mm (3.17 to 5.95)]; P = 0.02. The mean additional scanning time for the necessary prone imaging was 8 minutes 18 seconds. Conclusions Prone positioning significantly reduces DWI distortion artefact when rectal air is present, but consistently results in degraded T2WI quality.

Medicine

Clinical and research applications of fibroblast activation protein-α inhibitor tracers: a review.

Desaulniers M et al. · Jul 1, 2026

In the last decade, fibroblast activation protein-α inhibitors (FAPIs), which target the cancer-associated fibroblasts of the tumour microenvironment, have become a topic of great interest. In oncology, FAPI PET/CT imaging has repeatedly demonstrated a higher lesion detection rate than other conventional imaging modalities such as CT or 18F-FDG PET/CT for several tumours. In some cases, the initial staging and therapeutic management may even change. Some FAPI radioligands may also be labelled with therapeutic radionuclides for theranostic applications. It is thus possible to treat certain metastatic cancers with FAPI radioligand therapy (FAPI-RLT), which is generally well tolerated with little toxicity. Recently, new FAPIs have been developed with the particularity of having a higher binding affinity for the target, which further improves the lesion detection rate on PET/CT and clinical outcomes following FAPI-RLT. This review provides recent updates in the clinical use of FAPI PET/CT and FAPI-RLT and discusses potential emergent applications, including in inflammation imaging.

Medicine

The Human Dorsolateral Prefrontal Cortex in Pain and Pain Modulation: A Review and Activation-Likelihood Estimation Approach.

Crawford LS et al. · Jul 1, 2026

Background The dorsolateral prefrontal cortex (dlPFC) has become a cornerstone of pain neuroscience, believed critically involved in processing acute and chronic pain, as well as in pain modulation. The dlPFC is thought to balance sensory perception with the cognitive appraisal of noxious stimuli. In humans however, the dlPFC spans several cortical nodes, and little attention has been given to precisely which subareas are tethered to these delineable processes. The primary goal of this review and co-ordinate based meta-analysis was to precisely map dlPFC areas engaged under varied effects on overall pain perception. Methods Here, we combined a stringent meta-analytic approach of neuroimaging studies reporting dlPFC activation as a core finding (i.e., within title, abstract, or keywords of each manuscript), with activation likelihood estimation to determine dlPFC engagement across experimental acute pain (combined n = 814), chronic pain (combined n = 2467), and the pain modulatory phenomenon of placebo analgesia (combined n = 791), conditioned pain modulation (combined n = 184), and offset analgesia (combined n = 47). Through activation likelihood estimate and foci analysis, we produced schema of the similar and disparate locations of dlPFC activity within and between pain perceptual and modulatory effects. Results During both acute and chronic pain and in placebo analgesia, we identified remarkably similar activation patterns predominantly within Brodmann areas 8, 9, and 46-with no clear laterality effect and the left and right cortical hemispheres engaged regardless of the site of experimentally applied or conditionally-present pain. Offset analgesia and conditioned pain modulation appeared to preferentially engage Brodmann areas 8 and 45, and 9 and 46, respectively. Conclusions Despite the dlPFC large cortical surface area, these findings suggest that both the percept and inhibition of pain by placebo engage a similar focussed area of this region. Better understanding of exactly which cortical components of the extensive cortical pain system are involved in pain perception and modulation is critical for refining novel treatments such as non-invasive brain stimulation which seek to target and modulate specific sites of cortical processing to alleviate pain. Significance statement This meta-analysis precisely maps the dorsolateral prefrontal cortex (dlPFC) subregions engaged across acute pain, chronic pain and major endogenous pain-modulation paradigms. By integrating data from more than 4000 participants, it provides the most anatomically resolved evidence to date that dlPFC engagement is a shared feature of pain perception and modulation. These findings refine the cortical targets most relevant for therapeutic neuromodulation and strengthen the rationale for dlPFC-focused interventions in pain treatment.

Neuroscience

Clinical Remission of an Unresectable Presumptive Haemangiosarcoma in a Dog Treated With Toceranib, Piroxicam, and Propranolol: A Case Report.

Park WD. · Jul 1, 2026

Haemangiosarcoma (HSA) is a highly aggressive vascular tumour in dogs, characterised by rapid growth, early metastasis, and poor prognosis despite conventional treatment with surgery and doxorubicin-based chemotherapy. A 14-year-old spayed female Maltese (4.14 kg) was presented with progressive abdominal distension and anorexia. Imaging revealed a large retroperitoneal mass, and computed tomography identified a 12.1 × 8.0 × 8.5 cm heterogeneous tumour. Exploratory laparotomy confirmed the lesion was unresectable, and biopsy findings were most consistent with presumptive haemangiosarcoma (HSA) due to the small, cautery-affected specimen. Medical therapy was initiated with toceranib phosphate (10 mg every other day), followed one week later by propranolol (0.3 mg/kg twice daily) and piroxicam (0.3 mg/kg once daily). The patient was monitored every 2-4 weeks with physical examination and serial haematology and serum biochemistry. Two months after initiating therapy, the abdominal ultrasonography demonstrated tumour reduction to 4.9 × 2.7 cm, and after 7 months the mass was no longer detectable on radiographic follow-up imaging (radiography and ultrasonography). Throughout treatment, haematologic and biochemical values remained within reference intervals, no clinically significant adverse effects were observed, and the owner reported resolution of abdominal distension with improved activity. This case demonstrates that combined therapy with toceranib, propranolol, and piroxicam achieved radiographic and clinically sustained remission of unresectable canine presumptive HSA while preserving quality of life. These findings suggest that multimodal therapy targeting angiogenesis and tumour growth pathways may represent a promising alternative strategy for managing this malignancy and warrant further clinical evaluation.

Medicine

Explainable machine learning for patient-specific quality assurance in intensity-modulated radiotherapy based on anatomical structures.

Zhang X et al. · Jul 1, 2026

Background Patient-specific quality assurance (PSQA) plays a pivotal role in intensity-modulated radiotherapy (IMRT) to ensure accurate dose delivery. However, conventional measurement-based PSQA approaches are labor-intensive and provide limited insight into the underlying factors contributing to variations in gamma passing rates (GPRs). Anatomical characteristics of the planning target volume (PTV) and organs at risk (OARs) may contain predictive information relevant to GPR performance, yet their potential has not been fully explored within interpretable machine learning frameworks. Purpose This study aimed to develop an interpretable machine learning (ML) framework for predicting GPRs in IMRT based on anatomical features extracted from the PTV and OARs. Methods A retrospective cohort of 243 clinical chest IMRT plans was analyzed. Radiomic and dosimetric features were extracted for each anatomical structure. Two ML regression models-Random Forest (RF) and eXtreme Gradient Boosting (XGBoost)-were developed to predict GPRs for the PTV and OARs under four gamma criteria (3%/3 mm, 3%/2 mm, 2%/3 mm, and 2%/2 mm). The GPR obtained by comparing the dose distribution reconstructed using the independent Monte Carlo (MC) dose calculation software ArcherQA (Wisdom Technology Company Limited, Hefei, China)-based on linear accelerator delivery log files-with the original planned dose distribution was used as the reference standard, and calculated using global gamma analysis with a 10% dose threshold. Model performance was evaluated using the mean absolute error (MAE), root mean square error (RMSE), and Spearman's rank correlation coefficient. Shapley Additive Explanations (SHAP) were applied to interpret feature contributions in the best-performing model. Results Both models demonstrated robust predictive performance across different anatomical structures and gamma criteria. As the gamma criteria became less stringent, prediction errors decreased accordingly. Prediction accuracy was relatively high for OARs; for example, under the 3%/3 mm criterion, the test-set MAE was 0.06% ± 0.01% for the heart and 0.26% ± 0.04% for the whole lung. In contrast, the prediction error was relatively larger for the PTV, with a test-set MAE of 1.98% ± 0.31% under the same criterion. SHAP analysis revealed that texture-related radiomic features contributed most substantially to model predictions. Moreover, feature importance patterns varied according to organ type and gamma-criterion stringency. Conclusions Multi-omics descriptors derived from anatomical structures can reliably predict GPRs in IMRT. The proposed interpretable ML framework not only achieves accurate prediction but also enhances mechanistic understanding through SHAP-based explanations. These findings provide valuable insights into dose verification variability and offer a practical, transparent tool for IMRT patient-specific quality assurance.

Physics and Astronomy