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Patagonian toothfish (Dissostichus eleginoides) is a highly prized resource in markets due to the quality of its meat. The Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR) implemented controls and regulations in response to the sharp rise in the illegal fishing of D. eleginoides in the 1990s. Today, four fisheries in waters close to the southern tip of South America are managed in accordance with stringent sustainability standards. Even though they are separate management units, both abundance assessments and annual catch allocations are conducted using different criteria regarding stock considerations across the region, leaving one of the fundamental premises of fisheries management unclear. This study examines historical data and recent research to explore the potential differentiation between Patagonian toothfish populations in South American waters, which is crucial for the management of diverse fisheries. Genetic studies, otolith microchemistry, morphometry, parasitic fauna, tagging programs, reproductive characteristics, and the impact of ocean circulation on dispersal and recruitment were analyzed. Tagging studies in the southern hemisphere oceans confirm the species’ affinity to specific habitats, suggesting minimal fish exchange between South American fishing grounds. From a fisheries perspective, this review suggests the existence of distinct stocks of the species structured along the shelf and slope of the southern cone of America based on reproduction areas along the continental shelves and slope, the diverse parasitic fauna, the variability in stable isotopes and trace elements of otoliths, and the little significant exchange of fish between current fishing grounds. All of this could lead to considering the D. eleginoides fishery as independent exploitation units.

Abstract Background Reference values for lung volumes are necessary to identify and diagnose restrictive lung diseases and hyperinflation, but the values have to be validated in the relevant population. Our aim was to investigate the Global Lung Function Initiative (GLI) reference equations in a representative healthy Austrian population and create population-derived reference equations if poor fit was observed. Methods We analysed spirometry and body plethysmography data from 5371 respiratory healthy subjects (6–80 years) from the Austrian LEAD Study. Fit with the GLI equations was examined using z-scores and distributions within the limits of normality. LEAD reference equations were then created using the LMS method and the generalized additive model of location shape and scale package according to GLI models. Results Good fit, defined as mean z-scores between + 0.5 and -0.5,was not observed for the GLI static lung volume equations, with mean z-scores > 0.5 for residual volume (RV), RV/TLC (total lung capacity) and TLC in both sexes, and for expiratory reserve volume (ERV) and inspiratory capacity in females. Distribution within the limits of normality were shifted to the upper limit except for ERV. Population-derived reference equations from the LEAD cohort showed superior fit for lung volumes and provided reproducible results. Conclusion GLI lung volume reference equations demonstrated a poor fit for our cohort, especially in females. Therefore a new set of Austrian reference equations for static lung volumes was developed, that can be applied to both children and adults (6–80 years of age).

A groundbreaking remote sensing approach that uses three Bastnäsite Indices (BI) to detect rare earth elements (REEs) was initially developed using ore samples from the Sulfide Queen mine in California and later applied to various well-studied ground-based, drone-based, airborne, and spaceborne imaging spectrometers across a wide range of scales, from micrometers to tens of meters. In this work, those same innovative techniques have revealed the existence of a potential site for extracting REEs. Data from AVIRIS-NG, AVIRIS-Classic, HISUI, DESIS, EnMAP, EO-1 Hyperion, PRISMA, and EMIT were utilized to map Ivanpah Dry Lake, which is located fourteen kilometers northeast of the Sulfide Queen mine. Although this area was not previously associated with REE deposits, BI maps have indicated the presence of a site that has remained enriched in REEs for decades, suggesting an opportunity for further exploration and mining. Historically, a pipeline transported wastewater from facilities at the Sulfide Queen mine to evaporation ponds on or near Ivanpah Dry Lake, where wastewater may have contained concentrated REEs. This research highlights imaging spectroscopy not only as a valuable tool for rapidly identifying and efficiently extracting REEs, but also as a means of recovering REEs from supposed waste.

Summary: Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition. Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors. Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job. Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors. Funding: Wellcome Trust.

Recent developments in biomimetic hydrogel research have expanded the scope of biomedical technologies that can be used to model, diagnose, and treat a wide range of medical conditions. Cancer presents one of the most intractable challenges in this arena due to the surreptitious mechanisms that it employs to evade detection and treatment. In order to address these challenges, biomimetic design principles can be adapted to beat cancer at its own game. Biomimetic design strategies are inspired by natural biological systems and offer promising opportunities for developing life-changing methods to model, detect, diagnose, treat, and cure various types of static and metastatic cancers. In particular, focusing on the cellular and subcellular phenomena that serve as fundamental drivers for the peculiar behavioral traits of cancer can provide rich insights into eradicating cancer in all of its manifestations. This review highlights promising developments in biomimetic nanocomposite hydrogels that contribute to cancer therapies via enhanced drug delivery strategies and modeling cancer mechanobiology phenomena in relation to metastasis and synergistic sensing systems. Creative efforts to amplify biomimetic design research to advance the development of more effective cancer therapies will be discussed in alignment with international collaborative goals to cure cancer.

Rationale: Preserved ratio impaired spirometry (PRISm) is a recently recognized spirometric pattern defined by a ratio of forced expiratory volume in 1 second to forced vital capacity of at least 0.70 and a forced expiratory volume in 1 second  <80% of reference. For unclear reasons, PRISm is associated with increased cardiovascular (CV) morbidity and mortality. Arterial stiffness is a major mechanism of CV disease, which can be measured by carotid-femoral pulse-wave velocity (cfPWV). Objectives: We explored the hypothesis that cfPWV would be increased in individuals with PRISm and airflow limitation (AL). Methods: We measured forced spirometry, lung volumes by body plethysmography, and cfPWV in 9,466 subjects recruited from the general population in the Austrian cross-sectional LEAD (Lung, Heart, Social, Body) study and tested the association of arterial stiffness with PRISm and AL by multivariable linear regression analysis. Individuals younger than 18 years were excluded from the study. Results: Individuals with PRISm (n = 431; 4.6%) were of similar age to those with normal spirometry (n = 8,136; 85.9%) and significantly younger than those with AL (n = 899; 9.5%). Arterial hypertension, diabetes mellitus, coronary artery disease, heart failure, and peripheral arterial occlusive disease were significantly more common in individuals with PRISm than in those with normal lung function and similar to those with AL. There was a significant association between PRISm and arterial stiffness on bivariate linear regression analysis (crude model, β = 0.038; 95% confidence interval [CI], 0.016–0.058), which persisted after robust adjustment for clinical confounders upon multivariable analysis (final model, β = 0.017; 95% CI, 0.001–0.032). cfPWV was significantly higher in individuals with PRISm irrespective of the presence of established CV disease or pulmonary restriction. AL also showed a significant association with arterial stiffness on multivariable linear regression analysis (final model, β = 0.025; 95% CI, 0.009–0.042). Conclusions: Arterial stiffness measured by cfPWV is increased in individuals with PRISm independent of CV disease and risk factors. The pathobiological mechanisms underlying this association deserve further research. [ABSTRACT FROM AUTHOR]

Recent developments in biomimetic hydrogel research have expanded the scope of biomedical technologies that can be used to model, diagnose, and treat a wide range of medical conditions. Cancer presents one of the most intractable challenges in this arena due to the surreptitious mechanisms that it employs to evade detection and treatment. In order to address these challenges, biomimetic design principles can be adapted to beat cancer at its own game. Biomimetic design strategies are inspired by natural biological systems and offer promising opportunities for developing life-changing methods to model, detect, diagnose, treat, and cure various types of static and metastatic cancers. In particular, focusing on the cellular and subcellular phenomena that serve as fundamental drivers for the peculiar behavioral traits of cancer can provide rich insights into eradicating cancer in all of its manifestations. This review highlights promising developments in biomimetic nanocomposite hydrogels that contribute to cancer therapies via enhanced drug delivery strategies and modeling cancer mechanobiology phenomena in relation to metastasis and synergistic sensing systems. Creative efforts to amplify biomimetic design research to advance the development of more effective cancer therapies will be discussed in alignment with international collaborative goals to cure cancer. [ABSTRACT FROM AUTHOR]

The study of brain gyrification may provide useful information on the cytoarchitecture and connectivity of the brain. One of the methods that have been developed to estimate brain gyrification, known as surface ratio (SR), has not yet been studied in schizophrenia. Here we aimed to assess whether SR could provide new insights on the brain structure of schizophrenia patients and the severity of symptoms. We also computed a more established brain gyrification measure, namely absolute mean curvature (AMC). We analyzed 63 magnetic resonance images, 25 from schizophrenia patients with treatment-resistant auditory verbal hallucinations (SCH-H), 18 from schizophrenia patients without hallucinations (SCH-NH), and 20 from healthy controls (HC). The SR measure revealed that SCH-H patients had a more folded orbitofrontal cortex than SCH-NH patients and HC. Gyrification in this region was also negatively associated with positive symptoms, specifically with the delusions and conceptual disorganization items, only in the SCH-H group. Regarding the AMC measure, we identified two areas where HC showed more gyrification than SCH-H patients, but no relationships arose with symptoms. The hypergyrification of the orbitofrontal cortex displayed by SCH-H patients, as captured by the SR measure, suggests aberrant and/or excessive wiring in these patients, which in turn could give rise to auditory verbal hallucinations. Alternatively, we comment on potential compensatory mechanisms that may better explain the negative association between orbitofrontal gyrification and positive symptomatology. The SR measure captured the most relevant differences and associations, making it a promising biomarker in schizophrenia., Competing Interests: Conflicts of interest Dr. Roldán has served as advisor or speaker for the companies Otsuka, Rovi and Angelini (unrelated to the present work). The rest of the authors have nothing to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Mucosal healing is critical to maintain and restore intestinal homeostasis in inflammation. Previous data provide evidence that glial cell line-derived neurotrophic factor (GDNF) restores epithelial integrity by largely undefined mechanisms. Here, we assessed the role of GDNF for mucosal healing. In dextran sodium sulphate (DSS)-induced colitis in mice application of GDNF enhanced recovery as revealed by reduced disease activity index and histological inflammation scores. In biopsy-based wounding experiments GDNF application in mice improved healing of the intestinal mucosa. GDNF-induced epithelial recovery was also evident in wound assays from intestinal organoids and Caco2 cells. These observations were accompanied by an increased number of Ki67-positive cells in vivo after GDNF treatment, which were present along elongated proliferative areas within the crypts. In addition, the intestinal stem cell marker and R-spondin receptor LGR5 was significantly upregulated following GDNF treatment in all experimental models. The effects of GDNF on cell proliferation, LGR5 and Ki67 upregulation were blocked using the RET-specific inhibitor BLU-667. Downstream of RET-phosphorylation, activation of Src kinase was involved to mediate GDNF effects. GDNF promotes intestinal wound healing by promoting cell proliferation. This is mediated by RET-dependent activation of Src kinase with consecutive LGR5 upregulation, indicating activation of the stem cell niche., (© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Background and Objectives: Attack prevention is crucial in managing neuromyelitis optica spectrum disorders (NMOSDs). Eculizumab (ECU), an inhibitor of the terminal complement cascade, was highly effective in preventing attacks in a phase III trial of aquaporin-4 (AQP4)-IgG seropositive(+) NMOSDs. In this article, we evaluated effectiveness and safety of ECU in routine clinical care., Methods: We retrospectively evaluated patients with AQP4-IgG+ NMOSD treated with ECU between December 2014 and April 2022 at 20 German and 1 Austrian university center(s) of the Neuromyelitis Optica Study Group (NEMOS) by chart review. Primary outcomes were effectiveness (assessed using annualized attack rate [AAR], MRI activity, and disability changes [Expanded Disability Status Scale {EDSS}]) and safety (including adverse events, mortality, and attacks after meningococcal vaccinations), analyzed by descriptive statistics., Results: Fifty-two patients (87% female, age 55.0 ± 16.3 years) received ECU for 16.2 (interquartile range [IQR] 9.6 - 21.7) months. Forty-five patients (87%) received meningococcal vaccination before starting ECU, 9 with concomitant oral prednisone and 36 without. Seven of the latter (19%) experienced attacks shortly after vaccination (median: 9 days, IQR 6-10 days). No postvaccinal attack occurred in the 9 patients vaccinated while on oral prednisone before starting ECU and in 25 (re-)vaccinated while on ECU. During ECU therapy, 88% of patients were attack-free. The median AAR decreased from 1.0 (range 0-4) in the 2 years preceding ECU to 0 (range 0-0.8; p < 0.001). The EDSS score from start to the last follow-up was stable (median 6.0), and the proportion of patients with new T2-enhancing or gadolinium-enhancing MRI lesions in the brain and spinal cord decreased. Seven patients (13%) experienced serious infections. Five patients (10%; median age 53.7 years) died on ECU treatment (1 from myocardial infarction, 1 from ileus with secondary sepsis, and 3 from systemic infection, including 1 meningococcal sepsis), 4 were older than 60 years and severely disabled at ECU treatment start (EDSS score ≥ 7). The overall discontinuation rate was 19%., Discussion: Eculizumab proved to be effective in preventing NMOSD attacks. An increased risk of attacks after meningococcal vaccination before ECU start and potentially fatal systemic infections during ECU-particularly in patients with comorbidities-must be considered. Further research is necessary to explore optimal timing for meningococcal vaccinations., Classification of Evidence: This study provides Class IV evidence that eculizumab reduces annualized attack rates and new MRI lesions in AQP4-IgG+ patients with NMOSD.

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Jason Zucker reports support from the National Institutes of Health and receipt of honoraria from academic medical centers or educational centers for educational lectures. Shauna H. Gunaratne reports receipt of honoraria from the International Antiviral Society-USA for an invited review and from the New York State Department of Health AIDS Institute for work on guidelines. John G. Zampella reports receipt of honoraria from the Vaseline Healing Project and compensated participation on advisory boards (Merck, Ferndale Pharma Group, Janssen, and Dermavant), service as deputy chair of the American Academy of Dermatology State Society Relationship Committee, and co-chair of the American Academy of Dermatology LGBTQ Expert Research Group. No other potential conflicts of interest were disclosed.

Background: Chemotherapy-induced cognitive impairment (CICI) is a well-recognized side effect of breast cancer treatment. However, prospective long-term evaluations of CICI using standardized neuropsychological tests are scarce., Patients and Methods: This prospective longitudinal cohort study investigated cognitive dysfunction and its impact on quality of life and everyday functioning in patients with breast cancer receiving first-line chemotherapy compared to patients with breast cancer without chemotherapy. Assessment occurred prior to chemotherapy, postchemotherapy (median 6 months), and 2-3 years later. We used standardized neuropsychological tests, questionnaires, and scales to assess patients' quality of life and functioning. Additionally, serum analysis for neurodegenerative markers and autoantibodies was conducted., Results: We included n = 53 patients. Overall cognitive function declined statistically significantly (P = .046) postchemotherapy compared to control patients, mostly driven by a reduced figural memory (P = .011). Patients who received chemotherapy showed a greater reduction in quality of life (increased fatigue symptoms, P = .023; reduced Karnofsky index, P < .001); however, without a statistically significant effect on cognitive decline. The neurodegenerative markers Neurofilament light chain (NfL) and phosphorylated Neurofilament heavy chain (pNfH) increased statistically significantly (P < .001) postchemotherapy and pNfH correlated with overall cognitive function. After 2-3 years, both cognitive performance and quality of life were comparable between chemotherapy-treated and control patients., Conclusion: Our findings suggest that chemotherapy statistically significantly contributes to overall cognitive dysfunction in patients with breast cancer, which disappears after 2-3 years, indicating a recovery in both objectively measurable cognitive function and subjective quality of life. Future research should examine larger sample sizes and explore screening indicators, particularly pNfH., (© The Author(s) 2024. Published by Oxford University Press.)

Objective: We aimed to characterize calcium-containing crystals present in synovial fluid from patients with knee osteoarthritis (OA) using Raman spectroscopy, and specifically investigate the biological effects of calcite crystals., Design: Thirty-two synovial fluid samples were collected pre-operatively from knee OA patients undergoing total joint arthroplasty. An integrated Raman polarized light microscope was used for identification of crystals in synovial fluid. Human peripheral blood mononuclear cells (PBMC's), human OA articular chondrocytes (HACs) and fibroblast-like synoviocytes (FLSs) were exposed to calcite crystals. Expression of relevant cytokines and inflammatory genes were measured using enzyme-linked immuno sorbent assay (ELISA) and real-time polymerase chain reaction (PCR)., Results: Various calcium-containing crystals were identified, including calcium pyrophosphate (37.5 %) and basic calcium phosphate (21.8 %), but they were never found simultaneously in the same OA synovial fluid sample. For the first time, we discovered the presence of calcite crystals in 93.8 % of the samples, while dolomite was detected in 25 % of the cases. Characterization of the cellular response to calcite crystal exposure revealed increased production of innate immune-derived cytokines by PBMC's, when co-stimulated with lipopolysaccharide (LPS). Additionally, calcite crystal stimulation of HACs and FLSs resulted in enhanced secretion of pro-inflammatory molecules and alterations in the expression of extracellular matrix remodeling enzymes., Conclusions: This study highlights the unique role of Raman spectroscopy in OA crystal research and identified calcite as a novel pro-inflammatory crystal type in OA synovial fluid. Understanding the role of specific crystal species in the OA joint may open new avenues for pharmacological interventions and personalized approaches to treating OA., Competing Interests: Declaration of Competing Interest Cees Otto: Shareholder of Hybriscan Technologies B.V., a company which produces and sells Raman spectrometer devices, including H-iRPolM which was used for this study. Matthijs Janssen, Tim L Jansen: Shareholders of Crystalytics B.V., a company interested in development of tools used for clinical identification of synovial crystals. Tim Welting: Shareholder of Chondropeptix, Inventor of: WO2017/178251, WO2017/178253, WO2023/280615. Guus van den Akker: Inventor of WO2023/280615. All other authors have no potential conflicts of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Comprehensive characterization of the metabolome in cerebrospinal fluid (CSF) and serum by Nuclear Magnetic Resonance (NMR) spectroscopy may identify biomarkers and contribute to the understanding of the pathophysiology of neurological diseases., Methods: Metabolites were determined by NMR spectroscopy in stored CSF/serum samples of 20 patients with Parkinson's disease, 25 patients with other neuro-degenerative diseases, 22 patients with cerebral ischemia, 48 patients with multiple sclerosis, and 58 control patients with normal CSF findings. The data set was analysed using descriptive and multivariate statistics, as well as machine learning models., Results: CSF glucose and lactic acid measured by NMR spectroscopy and routine clinical chemistry showed a strong correlation between both methods (glucose, R 2  = 0.87, n = 173; lactic acid, R 2  = 0.74, n = 173). NMR spectroscopy detected a total of 99 metabolites; 51 in both, CSF and serum, 16 in CSF only, and 32 in serum only. CSF concentrations of some metabolites increased with age and/or decreasing blood-brain-barrier function. Metabolite detection rates were overall similar among the different disease groups. However, in two-group comparisons, absolute metabolite levels in CSF and serum discriminated between multiple sclerosis and neurodegenerative diseases (area under the curve (AUC) = 0.96), multiple sclerosis and Parkinson's disease (AUC = 0.89), and Parkinson's disease and control patients (AUC = 0.91), as demonstrated by random forest statistical models. Orthogonal partial least square discriminant analysis using absolute metabolite levels in CSF and serum furthermore permitted separation of Parkinson's disease and neurodegenerative diseases. CSF propionic acid levels were about fourfold lower in Parkinson's disease as compared to neurodegenerative diseases., Conclusions: These findings outline the landscape of the CSF and serum metabolome in different categories of neurological diseases and identify age and blood-brain-barrier function as relevant co-factors for CSF levels of certain metabolites. Metabolome profiles as determined by NMR spectroscopy may potentially aid in differentiating groups of patients with different neurological diseases, including clinically meaningful differentiations, such as Parkinson's disease from other neurodegenerative diseases., (© 2024. The Author(s).)

Objective: Raman spectroscopy is proposed as a next-generation method for the identification of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluid. As the interpretation of Raman spectra requires specific expertise, the method is not directly applicable for clinicians. We developed an approach to demonstrate that the identification process can be automated with the use of machine learning techniques. The developed system is tested in a point-of-care-setting at our outpatient rheumatology department., Methods: We collected synovial fluid samples from 446 patients with various rheumatic diseases from three centra. We analyzed all samples with our Raman spectroscope and used 246 samples for training and 200 samples for validation. Trained observers classified every Raman spectrum as MSU, CPP or else. We designed two one-against-all classifiers, one for MSU and one for CPP. These classifiers consisted of a principal component analysis model followed by a support vector machine., Results: The accuracy for classification of CPP using the 2023 ACR/EULAR CPPD classification criteria was 96.0% (95% CI 92.3-98.3), while the accuracy for classification of MSU with using the 2015 ACR/EULAR gout classification criteria was 92.5% (95% CI 87.9-95.7). Overall, the accuracy for classification of pathological crystals was 88.0% (95% CI 82.7-92.2). The model was able to discriminate between pathologic crystals, artifacts, and other particles such as microplastics., Conclusion: We here demonstrate that potentially complex Raman spectra from clinical patient samples can be successfully classified by a machine learning approach, resulting in an objective diagnosis independent of the opinion of the medical examiner., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: The proportion of intense tropical cyclones is expected to increase in a changing climate. However, there is currently no consistent and comprehensive assessment of infectious disease risk following tropical cyclone exposure across countries and over decades. We aimed to explore the tropical cyclone-associated hospitalisation risks and burden for cause-specific infectious diseases on a multi-country scale., Methods: Hospitalisation records for infectious diseases were collected from six countries and territories (Canada, South Korea, New Zealand, Taiwan, Thailand, and Viet Nam) during various periods between 2000 and 2019. The days with tropical cyclone-associated maximum sustained windspeeds of 34 knots or higher derived from a parametric wind field model were considered as tropical cyclone exposure days. The association of monthly infectious diseases hospitalisations and tropical cyclone exposure days was first examined at location level using a distributed lag non-linear quasi-Poisson regression model, and then pooled using a random-effects meta-analysis. The tropical cyclone-attributable number and fraction of infectious disease hospitalisations were also calculated., Findings: Overall, 2·2 million people who were hospitalised for infectious diseases in 179 locations that had at least one tropical cyclone exposure day in the six countries and territories were included in the analysis. The elevated hospitalisation risks for infectious diseases associated with tropical cyclones tended to dissipate 2 months after the tropical cyclone exposure. Overall, each additional tropical cyclone day was associated with a 9% (cumulative relative risk 1·09 [95% CI 1·05-1·14]) increase in hospitalisations for all-cause infectious diseases, 13% (1·13 [1·05-1·21]) for intestinal infectious diseases, 14% (1·14 [1·05-1·23]) for sepsis, and 22% (1·22 [1·03-1·46]) for dengue during the 2 months after a tropical cyclone. Associations of tropical cyclones with hospitalisations for tuberculosis and malaria were not significant. In total, 0·72% (95% CI 0·40-1·01) of the hospitalisations for all-cause infectious diseases, 0·33% (0·15-0·49) for intestinal infectious diseases, 1·31% (0·57-1·95) for sepsis, and 0·63% (0·10-1·04) for dengue were attributable to tropical cyclone exposures. The attributable burdens were higher among young populations (aged ≤19 years) and male individuals compared with their counterparts, especially for intestinal infectious diseases. The heterogeneous spatiotemporal pattern was further revealed at the country and territory level-tropical cyclone-attributable fractions showed a decreasing trend in South Korea during the study period but an increasing trend in Viet Nam, Taiwan, and New Zealand., Interpretation: Tropical cyclones were associated with persistent elevated hospitalisation risks of infectious diseases (particularly sepsis and intestinal infectious diseases). Targeted interventions should be formulated for different populations, regions, and causes of infectious diseases based on evidence on tropical cyclone epidemiology to respond to the increasing risk and burden., Funding: Australian Research Council, Australian National Health, and Medical Research Council., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: We studied the performance of integrated Raman polarized light microscopy (iRPolM) for the identification of calcium pyrophosphate (CPP)-associated arthritis (CPPD)., Methods: This is a diagnostic accuracy study including 400 consecutive synovial fluid samples from a single hospital in the Netherlands. Accuracy measures were calculated against polarized light microscopy (PLM) and the 2023 American College of Rheumatology (ACR)/EULAR criteria set for CPPD., Results: The interrater reliability between iRPolM and the 2023 ACR/EULAR criteria set for CPPD was strong (κ = 0.88). The diagnostic performance of iRPolM compared to the 2023 ACR/EULAR criteria set was sensitivity 86.0% (95% confidence interval [CI] 73.3-94.2), specificity 99.1% (95% CI 97.5-99.8), positive likelihood ratio 100.33 (95% CI 32.3-311.3), negative likelihood ratio 0.14 (95% CI 0.07-0.28), positive predictive value 93.5% (95% CI 82.2-97.8), negative predictive value 98.0% (95% CI 82.2-97.8), and accuracy 97.5% (95% CI 95.5-98.8). We allowed rheumatologists to rate the certainty of their microscopic identification of CPP and found a large correspondence between iRPolM and a certain identification (κ = 0.87), whereas only 10% of the uncertain CPP identifications could be confirmed with iRPolM. We identified several novel particle types in synovial fluid analysis, including calcium carbonate crystals, deposited carotenoids, microplastics, and three types of Maltese cross birefringent objects., Conclusion: iRPolM can easily identify CPP crystals with a strong diagnostic performance. PLM alone is not specific enough to reliably resolve complicated cases, and the implementation of Raman spectroscopy in rheumatology practice can be of benefit to patients with suspected CPPD., (© 2024 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

We show that redox active iron can induce a regulated form of non-apoptotic cell death and tissue damage called ferroptosis that can contribute to secondary damage and functional loss in the acute and chronic periods after spinal cord injury (SCI) in young, adult, female mice. Phagocytosis of red blood cells at sites of hemorrhage is the main source of iron derived from hemoglobin after SCI. Expression of hemeoxygenase-1 that induces release of iron from heme, is increased in spinal cord macrophages 7 days after injury. While iron is stored safely in ferritin in the injured spinal cord, it can, however, be released by NCOA4-mediated shuttling of ferritin to autophagosomes for degradation (ferritinophagy). This leads to the release of redox active iron that can cause free radical damage. Expression of NCOA4 is increased after SCI, mainly in macrophages. Increase in the ratio of redox active ferrous (Fe 2+ ) to ferric iron (Fe 3+ ) is also detected after SCI by capillary electrophoresis inductively coupled mass spectrometry. These changes are accompanied by other hallmarks of ferroptosis, i.e., deficiency in various elements of the antioxidant glutathione (GSH) pathway. We also detect increases in enzymes that repair membrane lipids (ACSL4 and LPCAT3) and thus promote on-going ferroptosis. These changes are associated with increased levels of 4-hydroxynonenal (4-HNE), a toxic lipid peroxidation product. Mice with mild SCI (30 kdyne force) treated with the ferroptosis inhibitor (UAMC-3203-HCL) either early or delayed times after injury showed improvement in locomotor recovery and secondary damage. Cerebrospinal fluid and serum samples from human SCI cases show evidence of increased iron storage (ferritin), and other iron related molecules, and reduction in GSH. Collectively, these data suggest that ferroptosis contributes to secondary damage after SCI and highlights the possible use of ferroptosis inhibitors to treat SCI., (© 2024. The Author(s).)

Leukemia comprises a diverse group of bone marrow tumors marked by cell proliferation. Current diagnosis involves identifying leukemia subtypes through visual assessment of blood and bone marrow smears, a subjective and time-consuming method. Our study introduces the characterization of different leukemia subtypes using a global clustering approach of Raman hyperspectral maps of cells. We analyzed bone marrow samples from 19 patients, each presenting one of nine distinct leukemia subtypes, by conducting high spatial resolution Raman imaging on 319 cells, generating over 1.3 million spectra in total. An automated preprocessing pipeline followed by a single-step global clustering approach performed over the entire data set identified relevant cellular components (cytoplasm, nucleus, carotenoids, myeloperoxidase (MPO), and hemoglobin (HB)) enabling the unsupervised creation of high-quality pseudostained images at the single-cell level. Furthermore, this approach provided a semiquantitative analysis of cellular component distribution, and multivariate analysis of clustering results revealed the potential of Raman imaging in leukemia research, highlighting both advantages and challenges associated with global clustering.

Progression to psychosis has been associated with increased cortical thinning in the frontal, temporal and parietal lobes in individuals at clinical high risk for the disorder (CHR-P). The timing and spatial extent of these changes are thought to be influenced by age. However, most evidence so far stems from adult samples. Longitudinal studies are essential to understanding the neuroanatomical changes associated to transition to psychosis during adolescence, and their relationship with age. We conducted a longitudinal, multisite study including adolescents at CHR-P and healthy controls (HC), aged 10-17 years. Structural images were acquired at baseline and at 18-month follow-up. Images were processed with the longitudinal pipeline in FreeSurfer. We used a longitudinal two-stage model to compute the regional cortical thickness (CT) change, and analyze between-group differences controlling for age, sex and scan, and corrected for multiple comparisons. Linear regression was used to study the effect of age at baseline. A total of 103 individuals (49 CHR-P and 54 HC) were included in the analysis. During follow-up, the 13 CHR-P participants who transitioned to psychosis exhibited greater CT decrease over time in the right parietal cortex compared to those who did not transition to psychosis and to HC. Age at baseline correlated with longitudinal changes in CT, with younger individuals showing greater cortical thinning in this region. The emergence of psychosis during early adolescence may have an impact on typical neuromaturational processes. This study provides new insights on the cortical changes taking place prior to illness onset., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Extracellular vesicles (EVs) released from cells attract interest for their possible role in health and diseases. The detection and characterization of EVs is challenging due to the lack of specialized methodologies. Raman spectroscopy, however, has been suggested as a novel approach for biochemical analysis of EVs. To extract information from the spectra, a novel deep learning architecture is explored as a versatile variant of autoencoders. The proposed architecture considers the frequency range separately from the intensity of the spectra. This enables the model to adapt to the frequency range, rather than requiring that all spectra be pre-processed to the same frequency range as it was trained on. It is demonstrated that the proposed architecture accepts Raman spectra of EVs and lipoproteins from 13 biological sources and from two laboratories. High reconstruction accuracy is maintained despite large variances in frequency range and noise level. It is also shown that the architecture is able to cluster the biological nanoparticles by their Raman spectra and differentiate them by their origin without pre-processing of the spectra or supervision during learning. The model performs label-free differentiation, including separating EVs from activated vs. non-activated blood platelets and EVs/lipoproteins from prostate cancer patients versus non-cancer controls. The differentiation is evaluated by creating a neural network classifier that observes the features extracted by the model to classify the spectra according to their sample origin. The classification reveals a test sensitivity of 92.2 % and selectivity of 92.3 % over 769 measurements from two labs that have different measurement configurations., (© 2024. The Author(s).)

Background: Pleural effusion and chylothorax are common complications in the treatment of congenital diaphragmatic hernia (CDH). We set out to identify risk factors for chylothorax development in patients with CDH and to investigate the association of pleural effusion and chylothorax with neonatal morbidity and mortality. Methods: In this retrospective cohort study, we included 396 neonates with CDH treated at our institution between January 2013 and June 2019. Preoperative and postoperative chest radiographs and clinical data were evaluated and correlated with morbidity, complications and mortality. Results: Laboratory-confirmed chylothorax occurred in 58 (18.6%) of all CDH cases. Pleural effusion was frequently observed as a postoperative complication but also occurred as a pre-existing condition. Neonates with large defects of size C and D, patch repair, the need for presurgical and/or postsurgical ECMO support, pulmonary hypertension, liver-up phenomenon and lower relative fetal lung volume were associated with higher occurrences of chylothorax. After stepwise logistic regression, larger CDH defects ( p < 0.0001) and the need for postsurgical ECMO ( p = 0.0158) remained significant risk factors for CTX to occur (AUC 0.71). The same potential risk factors were used to assess their association with both presurgical and postsurgical pleural effusion. After stepwise logistic regression, only the need for presurgical ECMO remained significantly associated with presurgical PE ( p < 0.01, AUC 0.65) and patch repair as the therapeutic intervention remained significantly associated with the occurrence of postsurgical PE ( p < 0.0001, AUC 0.80). Patients with CTX had longer durations of both MV ( p < 0.0001) and subsequent ventilatory assistance with spontaneous breathing ( p = 0.0004), increased total lengths of hospitalization ( p < 0.0001), increased durations of ECMO ( p < 0.01) and increased incidences of CLD ( p < 0.0001) compared to patients without CTX. No significant difference could be found for survival in both groups ( p = 0.12). Conclusions: Our data suggest that the incidence of chylothorax is associated with large diaphragmatic defects, the need for postsurgical ECMO and the development of chronic lung disease, but not with survival.

Inappropriate ordering practices, either under or over ordering of diagnostic tests, are recognized problems with possible negative downstream consequences. As the menu of clinical tests, especially molecular tests grows, it is becoming increasingly important to provide guidance to providers on the appropriate utilization. Diagnostic stewardship programs have been established at many institutions to help direct the appropriate utilization of laboratory testing to ultimately guide patient management and treatment decisions. Many molecular tests have now received Clinical Laboratory Improvement Amendments (CLIA)-waived status for use in a point-of-care (POC) setting; however, parallel diagnostic stewardship programs have not been established to help guide providers on how best to use these tests. In this article, we will discuss the available molecular POC tests and opportunities and challenges for establishing diagnostic stewardship programs for molecular testing performed in the POC setting., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: More intense tropical cyclones (TCs) are expected in the future under a warming climate scenario, but little is known about their mortality effect pattern across countries and over decades. We aim to evaluate the TC-specific mortality risks, periods of concern (POC) and characterize the spatiotemporal pattern and exposure-response (ER) relationships on a multicountry scale., Methods and Findings: Daily all-cause, cardiovascular, and respiratory mortality among the general population were collected from 494 locations in 18 countries or territories during 1980 to 2019. Daily TC exposures were defined when the maximum sustained windspeed associated with a TC was ≥34 knots using a parametric wind field model at a 0.5° × 0.5° resolution. We first estimated the TC-specific mortality risks and POC using an advanced flexible statistical framework of mixed Poisson model, accounting for the population changes, natural variation, seasonal and day of the week effects. Then, a mixed meta-regression model was used to pool the TC-specific mortality risks to estimate the overall and country-specific ER relationships of TC characteristics (windspeed, rainfall, and year) with mortality. Overall, 47.7 million all-cause, 15.5 million cardiovascular, and 4.9 million respiratory deaths and 382 TCs were included in our analyses. An overall average POC of around 20 days was observed for TC-related all-cause and cardiopulmonary mortality, with relatively longer POC for the United States of America, Brazil, and Taiwan (>30 days). The TC-specific relative risks (RR) varied substantially, ranging from 1.04 to 1.42, 1.07 to 1.77, and 1.12 to 1.92 among the top 100 TCs with highest RRs for all-cause, cardiovascular, and respiratory mortality, respectively. At country level, relatively higher TC-related mortality risks were observed in Guatemala, Brazil, and New Zealand for all-cause, cardiovascular, and respiratory mortality, respectively. We found an overall monotonically increasing and approximately linear ER curve of TC-related maximum sustained windspeed and cumulative rainfall with mortality, with heterogeneous patterns across countries and regions. The TC-related mortality risks were generally decreasing from 1980 to 2019, especially for the Philippines, Taiwan, and the USA, whereas potentially increasing trends in TC-related all-cause and cardiovascular mortality risks were observed for Japan., Conclusions: The TC mortality risks and POC varied greatly across TC events, locations, and countries. To minimize the TC-related health burdens, targeted strategies are particularly needed for different countries and regions, integrating epidemiological evidence on region-specific POC and ER curves that consider across-TC variability., Competing Interests: YG is a member of the Editorial Board of PLOS Medicine. All other authors declare no competing interests., (Copyright: © 2024 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition., Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors., Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job., Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors., Funding: Wellcome Trust., Competing Interests: Fatima Rodrigues declares grants and personal fees from A. Menarini, Boehringer Ingelheim, Teva Pharma, Novartis, GlaxoSmithKline, AstraZeneca, VitalAire and Nippon Gases outside the submitted work. Wan C. Tan received grants from the Canadian Institute of Heath Research (CIHR/Rx&D Collaborative Research Program Operating Grants- 93,326) with industry partners Astra Zeneca Canada Ltd., Boehringer-Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, Novartis Pharma Canada Inc., Nycomed Canada Inc., Pfizer Canada Ltd. for conducting the longitudinal population-based Canadian Cohort of Obstructive Lung Disease (CanCOLD) study on COPD. David Mannino is a consultant to GSK, AstraZeneca, Regeneron, Genentech, COPD Foundation, and expert witness on behalf of people suing Tobacco Industry (Schlesinger Law Firm). Sonia Buist is Chair of the Data Safety & Monitoring Board for the RELIANCE Clinical Trial. Frits Franssen declares personal fees from AstraZeneca, Chiesi, GlaxoSmithKline, MSD, Pieris, and Verona Pharma. Robab Breyer-Kohansal declares consulting fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Menarini, Novartis Pharma, and Sanofi, and participation on advisory boards for AstraZeneca, Menarini, and Sanofi. Thorarinn Gislason received a grant from the Icelandic Research Fund. Kevin Mortimer declares participation on advisory boards for AstraZeneca and GlaxoSmithKline. Sylvia Hartl declares grants from GSK, Chiesi Farma, Menarini Pharma, and AstraZeneca, and participation on advisory boards for Menarini Pharma and GSK. AFSA declares a grant from the COLT Foundation (CF/01/21)., (© 2024 The Author(s).)

Transcutaneous spinal cord stimulation (tSCS) provides a promising therapy option for individuals with injured spinal cords and multiple sclerosis patients with spasticity and gait deficits. Before the therapy, the examiner determines a suitable electrode position and stimulation current for a controlled application. For that, amplitude characteristics of posterior root muscle (PRM) responses in the electromyography (EMG) of the legs to double pulses are examined. This laborious procedure holds potential for simplification due to time-consuming skin preparation, sensor placement, and required expert knowledge. Here, we investigate mechanomyography (MMG) that employs accelerometers instead of EMGs to assess muscle activity. A supervised machine-learning classification approach was implemented to classify the acceleration data into no activity and muscular/reflex responses, considering the EMG responses as ground truth. The acceleration-based calibration procedure achieved a mean accuracy of up to 87% relative to the classical EMG approach as ground truth on a combined cohort of 11 healthy subjects and 11 patients. Based on this classification, the identified current amplitude for the tSCS therapy was in 85%, comparable to the EMG-based ground truth. In healthy subjects, where both therapy current and position have been identified, 91% of the outcome matched well with the EMG approach. We conclude that MMG has the potential to make the tuning of tSCS feasible in clinical practice and even in home use.

Working dogs perform complex tasks that require both physical and behavioral soundness. Two case studies demonstrate how fitness training moderated arousal levels, facilitated training, and improved performance measures in different situations. Fitness training can be beneficial when integrated as part of a working dog's training regimen because it can have a significant influence on their overall health, behavior, and ability to perform their working role effectively., (Copyright © 2023 Elsevier Inc. All rights reserved.)