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Laparoscopic bariatric surgery versus any non-surgical intervention for adolescents or adults with obesity: protocol for a systematic review with meta-analysis and trial sequential analysis of randomised clinical trials
Get PDFIntroduction: The number of people living with obesity is increasing rapidly worldwide, and the WHO estimates approximately 5 million deaths yearly from non-communicable diseases related to elevated body mass index (BMI). The most effective treatment for weight loss is bariatric surgery, but due to the associated risks and the need for lifelong care, this is not a viable treatment for every patient. With the advent of gut-hormone-based medications to treat obesity, the effectiveness of non-surgical treatment is approaching that of surgical interventions. We therefore aim to investigate the beneficial and harmful effects of laparoscopic bariatric surgery versus any non-surgical treatment. Methods and analysis: We will conduct a systematic review with meta-analysis applying our eight-step procedure to assess thresholds for clinical significance and trial sequential analysis to mitigate the risk of random errors. To identify relevant trials, we will search for both published and unpublished trials, without any language restriction, in major medical databases (CENTRAL, MEDLINE, EMBASE, LILACS, SCI-EXPANDED and CPCI-S) and trial registries. The date range covered by the search is from database inception until final search date—within 3 months prior to submission of final results manuscript. Two review authors will independently screen references, extract data and perform risk-of-bias assessment using the Cochrane Risk of Bias Tool 2 and the Grading of Recommendations, Assessment, Development and Evaluations. We will include randomised clinical trials comparing laparoscopic surgery currently in use with any non-surgical comparator in adults or adolescents with BMI >30 kg/m2. Quasi-randomised studies or non-randomised studies will not be included. Our critical outcomes are all-cause mortality, serious adverse events and quality of life, and our important outcomes are major cardiovascular events, weight at follow-up, physical function and glycaemic control. In addition, we have two explorative outcomes: metabolic syndrome or Z-score and reported incident of alcohol abuse or other addictive disorder or self-inflicted harm. Ethics and dissemination: This review will collect and perform secondary analysis of data from publicly available sources and ethical approval is therefore not required. The findings will be published in peer-reviewed journals and presented at relevant scientific conferences. We will strive to publish with open access. Awareness will be made through social media platforms. This review aims to help clinicians in identifying best practices in the wide-spanning field of obesity treatment. PROSPERO registration number: CRD420251135341
Biochemical profiling provides a low-cost and globally accessible method to detect falsified vaccines and insulin
Get PDFFor many decades, there have been numerous reported cases of falsified liquid medical products, including vaccine and insulin preparations worldwide, but to date, there has been a lack of affordable and accessible analytical methods for biological medicines and vaccine authenticity testing. A conventional clinical chemistry analyser (Abbott Architect c16000) was used to determine the concentrations of analytes in genuine liquid biological products (vaccines and insulin) and falsified vaccine surrogates. Eight analytes were measured for each sample: sodium, potassium, chloride, calcium, magnesium, phosphate, glucose and protein. Each genuine liquid product had unique concentrations of analytes when tested using the eight methods applied, allowing clear differentiation from the falsified surrogates. In a blinded study, reproducibility was significantly high when the samples were run intra- and inter-batch up to 9 times over 9 different days, and it was possible to identify most of the samples by analyte presence alone. Imprecision was < 1.0 CV% for ion-selective electrode methods and typically < 5 CV% for spectrophotometric methods. A decision tree was created which was able to identify all samples. We demonstrate for the first time that a conventional clinical chemistry analyser provides a low-cost method to accurately differentiate genuine products from falsified surrogate liquid medicines and vaccines. This novel method has the potential to be used globally due to widespread use of clinical chemistry analysers in hospitals across the world, including in low- and middle-income countries where many cases of falsified medicines have been identified
Interpretable rheumatoid arthritis scoring via anatomy-aware multiple instance learning
Get PDFThe Sharp/van der Heijde (SvdH) score has been widely used in clinical trials to quantify radiographic damage in Rheumatoid Arthritis (RA), but its complexity has limited its adoption in routine clinical practice. To address the inefficiency of manual scoring, this work proposes a two-stage pipeline for interpretable image-level SvdH score prediction using dual-hand radiographs. Our approach extracts disease-relevant image regions and integrates them using attention-based multiple instance learning to generate image-level features for prediction. We propose two region extraction schemes: 1) sampling image tiles most likely to contain abnormalities, and 2) cropping patches containing disease-relevant joints. With Scheme 2, our best individual score prediction model achieved a Pearson’s correlation coefficient (PCC) of 0.943 and a root mean squared error (RMSE) of 15.73. Ensemble learning further boosted prediction accuracy, yielding a PCC of 0.945 and RMSE of 15.57, achieving state-of-the-art performance that is comparable to that of experienced radiologists (PCC = 0.97, RMSE = 18.75). Finally, our pipeline effectively identified and made decisions based on anatomical structures which clinicians consider relevant to RA progression
Emerging semantic segmentation from positive and negative coarse label learning
Get PDFLarge annotated datasets are vital for training segmentation models, but pixel-level labeling is time-consuming, error-prone, and often requires scarce expert annotators, especially in medical imaging. In contrast, coarse annotations are quicker, cheaper, and easier to produce, even by non-experts. In this paper, we propose to use coarse drawings from both positive (target) and negative (background) classes in the image, even with noisy pixels, to train a convolutional neural network (CNN) for semantic segmentation. We present a method for learning the true segmentation label distributions from purely noisy coarse annotations using two coupled CNNs. The separation of the two CNNs is achieved by high fidelity with the characters of the noisy training annotations. We propose to add a complementary label learning that encourages estimating negative label distribution. To illustrate the properties of our method, we first use a toy segmentation dataset based on MNIST. We then present the quantitative results of experiments using publicly available datasets: Cityscapes dataset for multi-class segmentation, and retinal images for medical applications. In all experiments, our method outperforms state-of-the-art methods, particularly in the cases where the ratio of coarse annotations is small compared to the given dense annotations
Tectonics of continental convergence in Central and West Asia
Get PDFThis thesis presents three case studies of tectonically converging mountain ranges across West and Central Asia, examining how and whether this convergence is accommodated by earthquakes. In northern Tajikistan, where the Pamir and Tian Shan have fully converged, I use calibrated earthquake relocations and analysis of tectonic geomorphology to find that the 1949 Mw 7.6 Khait Earthquake occurred not on the geomorphically well expressed boundary fault, but within a previously unmapped structure in the Tian Shan basement. I show vertical axis rotations within the Tian Shan accommodate up to half the convergence rate between the Pamir and Tian Shan, demonstrating the greatest seismic hazard can lie on cryptic faults. In the Kura Basin of Azerbaijan, I use time series InSAR to reveal that the convergence between the Turkish Iranian Plateau and Greater Caucasus is accommodated by rapid creep on faults in the sedimentary cover, and hypothesise gravitational collapse of basin sediments into the South Caspian Basin as an additional driving force of this creep. Finally, I use calibrated earthquake relocation to demonstrate that the 1985 Mw 6.9 Wuqia Earthquake occurred beneath the sedimentary cover of the Tarim Basin, northwest China. I find that the earthquake occurred on a buried, slow moving transpressive strike slip fault formed during more rapid strike-slip motion between the Pamir and Tarim Basin. Overall this thesis extends our knowledge of how converging zones in continental interiors behave, and demonstrates that the greatest seismic hazard in a region is not necessarily on the most geomorphically well-expressed faults
Search for the lepton number violating process * * This work is supported in part by National Key R&D Program of China under Contracts Nos. 2023YFA1606000, 2023YFA1606704; National Natural Science Foundation of China (NSFC) under Contracts Nos. 12035009, 11635010, 11935015, 11935016, 11935018, 12025502, 12035013, 12061131003, 12192260, 12192261, 12192262, 12192263, 12192264, 12192265, 12221005, 12225509, 12235017, 12361141819; the Chinese Academy of Sciences (CAS) Large-Scale Scientific Facility Program; CAS under Contract No. YSBR-101; 100 Talents Program of CAS; The Institute of Nuclear and Particle Physics (INPAC) and Shanghai Key Laboratory for Particle Physics and Cosmology; German Research Foundation DFG under Contract No. FOR5327; Istituto Nazionale di Fisica Nucleare, Italy; Knut and Alice Wallenberg Foundation under Contracts Nos. 2021.0174, 2021.0299; Ministry of Development of Turkey under Contract No. DPT2006K-120470; National Research Foundation of Korea under Contract No. NRF-2022R1A2C1092335; National Science and Technology fund of Mongolia; National Science Research and Innovation Fund (NSRF) via the Program Management Unit for Human Resources & Institutional Development, Research and Innovation of Thailand under Contract No. B50G670107; Polish National Science Centre under Contract No. 2024/53/B/ST2/00975; Swedish Research Council under Contract No. 2019.04595; U. S. Department of Energy under Contract No. DE-FG02-05ER41374
No full textBased on events collected with the BESIII detector, we search for the lepton number violating decay for the first time. The upper limit on the branching fraction of this decay is set to at the 90% confidence level with a frequentist method. This is the first search for decays with a lepton number change by two, offering valuable insights into the underlying physical processes
Topographical Variation of Iron‐Rimmed Lesions in the Multiple Sclerosis Brain and Spinal Cord: A Neuropathological Study
Get PDFParamagnetic‐rim lesions are a novel diagnostic marker in multiple sclerosis (MS) and are associated with poor prognosis due to their link with chronic inflammation and disease progression. Analyzing 46 postmortem MS cases, researchers found no iron rims in 67 white matter and 85 grey matter spinal cord lesions, despite most being active. In contrast, iron rims appeared in 20.9% of cortical and 80% of subcortical brain lesions, especially in deeper myelin‐rich cortical layers. These findings highlight the regional variability of iron accumulation and have important implications for interpreting iron‐rims in MS diagnosis, monitoring, and prognostication. ANN NEUROL 202
Nicotinamide N-Methyl Transferase (NNMT) Sustains Innate Sensitivity to NAMPT Inhibition in YAP-dependent Stem-like/Mesenchymal Prostate Cancer
Get PDFEmbryo secretome regulation of the endometrial epithelial transcriptome: development of a model to test for embryo viability
Get PDFThe aim of this study was to develop an advanced in vitro model of human endometrium using single-cell-derived endometrial epithelial organoids, enabling the study of embryo secretome–endometrial crosstalk at the maternal–fetal interface. Single-cell-derived organoids generated from endometrial tissue of a parous 39-year-old woman recapitulated hormone-responsive decidualization, as demonstrated by expression of SPP1 and acetyl-α-tubulin. When cultured in embryo culture media, organoid viability was maintained with no cytotoxicity, but proliferation was suppressed, likely due to the lower concentrations of the required factors in organoid growth media. Organoids were stimulated with culture supernatants from morphologically good-quality embryos with known pregnancy outcomes (live birth (n = 4) vs no pregnancy (n = 4)). Transcriptomic profiling (RNA-sequencing) revealed that 32 genes were differentially expressed (DEGs) in organoids exposed to the culture supernatants from live-birth embryos versus non-pregnant outcomes: 24 upregulated and 8 downregulated. These DEGs were enriched for biological processes related to cell motility and cytoskeletal dynamics. In conclusion, soluble factors secreted by human blastocysts achieving live birth selectively modulate the endometrial epithelial transcriptome, enhancing pathways involved in cytoskeletal remodeling and immune modulation. This embryo-directed remodeling likely facilitates endometrial receptivity for successful implantation to occur. Our organoid model provides a robust platform for further investigating implantation failure
