Abstract Background In neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), neutrophils are found in CNS lesions. We previously demonstrated that NMOSD neutrophils show functional deficiencies. Thus, we hypothesized that neutrophil accumulation in the CNS may be facilitated by impairments affecting mechanisms of neutrophil death. Objective To evaluate cell death in blood neutrophils from aquaporin-4 (AQP4)-IgG-seropositive NMOSD and MOGAD patients as well as matched healthy controls (HC) using in vitro assays....

Abstract Background Metastatic breast carcinoma is commonly considered during differential diagnosis when metastatic disease is detected in females. In addition to the tumor morphology and documented clinical history, sensitive and specific immunohistochemical (IHC) markers such as GCDFP-15, mammaglobin, and GATA3 are helpful for determining breast origin. However, these markers are reported to show lower sensitivity in certain subtypes, such as triple-negative breast cancer (TNBC). Materials and methods Using bioinformatics analyses, we identified a potential diagnostic...

Abstract Background Triptans are migraine-specific acute treatments. A well-accepted definition of triptan failure is needed in clinical practice and for research. The primary aim of the present Consensus was to provide a definition of triptan failure. To develop this definition, we deemed necessary to develop as first a consensus definition of effective treatment of an acute migraine attack and of triptan-responder. Main body The Consensus process included a preliminary literature review, a Delphi round and...

ObjectivesIn adult aortic arch surgery, moderate hypothermic circulatory arrest (HCA) with selective antegrade cerebral perfusion (SACP) (MoHACP) is widely used, but the application of mild HCA with SACP (MiHACP) is still controversial. This meta-analysis aimed to compare clinical outcomes using MiHACP or MoHACP.MethodsStudies comparing outcomes of MiHACP or MoHACP in adult aortic arch surgery were searched from four databases from inception through April 2022. Primary outcomes were postoperative permanent neurological deficit (PND), temporary neurological deficit...

Abstract Aneuploidy, chromosomal instability, somatic copy-number alterations, and whole-genome doubling (WGD) play key roles in cancer evolution and provide information for the complex task of phylogenetic inference. We present MEDICC2, a method for inferring evolutionary trees and WGD using haplotype-specific somatic copy-number alterations from single-cell or bulk data. MEDICC2 eschews simplifications such as the infinite sites assumption, allowing multiple mutations and parallel evolution, and does not treat adjacent loci as independent, allowing overlapping copy-number events....

Abstract Object Scarlet fever is an acute respiratory infectious disease that endangers public health and imposes a huge economic burden. In this paper, we systematically studied its spatial and temporal evolution and explore its potential ecological drivers. The goal of this research is to provide a reference for analysis based on surveillance data of scarlet fever and other acute respiratory infectious illnesses, and offer suggestions for prevention and control. Method This research is based on...

Photochromic sapphires show an optically controllable orange coloration under ambient temperature, which strongly affects the color appearance and market value of gemstone sapphires. An in-situ absorption spectroscopy combined with a tunable excitation light source has been developed to investigate the wavelength- and time dependence of sapphire’s photochromism. An excitation of ≤370 nm and ≥410 nm introduces and removes the orange coloration, respectively, accompanied by a stable absorption band at 470 nm. Both the color enhancement...

Abstract Background The expression changes of some proteins are associated with cancer progression, and can be used as biomarkers in cancer diagnosis. Automated systems have been frequently applied in the large-scale detection of protein biomarkers and have provided a valuable complement for wet-laboratory experiments. For example, our previous work used an immunohistochemical image-based machine learning classifier of protein subcellular locations to screen biomarker proteins that change locations in colon cancer tissues. The tool could recognize...

Abstract Background Chronic health conditions have a big impact on disability, morbidity, and mortality worldwide. Smartphone health applications (apps) can improve the health of patients with chronic conditions and enhance the quality and efficiency of healthcare. The number of randomized controlled trials (RCTs) of smartphone health apps is increasing, but a collection of the available evidence into a single database is still missing. The purpose of this study is to describe Smartphone-RCCT, which is an...

For novel molecularly targeted agents and immunotherapies, the objective of dose-finding is often to identify the optimal biological dose, rather than the maximum tolerated dose. However, optimal biological doses may not be the same for different indications, challenging the traditional dose-finding framework. Therefore, we proposed a Bayesian phase I/II basket trial design, named “shotgun-2,” to identify indication-specific optimal biological doses. A dose-escalation part is conducted in stage I to identify the maximum tolerated dose and...

Abstract Background Leaf size affects crop canopy morphology and photosynthetic efficiency, which can influence forage yield and quality. It is of great significance to mine the key genes controlling leaf development for breeding new alfalfa varieties. In this study, we mapped leaf length (LL), leaf width (LW), and leaf area (LA) in an F1 mapping population derived from a cultivar named ZhongmuNo.1 with larger leaf area and a landrace named Cangzhou with smaller leaf area....

BackgroundMuscle ultrasound represents a promising approach to aid diagnoses of neuromuscular diseases in critically ill patients. Unfortunately, standardization of ultrasound measurements in clinical research is lacking, making direct comparisons between studies difficult. Protocols are required to assess qualitative muscle changes during an ICU stay in patients at high risk for the development of neuromuscular acquired weakness (ICUAW).MethodsWe conducted a retrospective, observational analysis comprised of three prospective observational studies with the aim of diagnosing muscle changes...

Introduction:Immune checkpoint inhibitors (ICIs) have demonstrated promising efficacy as monotherapy in patients with pulmonary sarcomatoid carcinoma (PSC). We performed the current multi-institutional, real-world study to assess the efficacy of ICIs plus chemotherapy in patients with PSC.Methods:All consecutive patients with locally advanced or metastatic PSC from three centers treated with ICIs between January 2018 and July 2021 were enrolled. Programmed death ligand 1 (PD-L1) expression was stained and evaluated using immunohistochemical with 22C3. Single-cell RNA sequencing...

Photochromic sapphires show an optically controllable orange coloration under ambient temperature, which strongly affects the color appearance and market value of gemstone sapphires. An in-situ absorption spectroscopy combined with a tunable excitation light source has been developed to investigate the wavelength- and time dependence of sapphire’s photochromism. An excitation of ≤370 nm and ≥410 nm introduces and removes the orange coloration, respectively, accompanied by a stable absorption band at 470 nm. Both the color enhancement...

Abstract Background Associated with increased morbidity and mortality, postoperative pulmonary complications (PPCs) often occur after major abdominal surgery. Diaphragmatic dysfunction is suggested to play an important role in the development of PPCs and diaphragm echodensity can be used as an indicator of diaphragm function. This study aimed to determine whether diaphragm echodensity could predict the occurrence of PPCs in patients after major abdominal surgery. Methods Diaphragm ultrasound images of patients after major abdominal surgery were...

Abstract Background People with spinal cord injury (SCI) frequently develop neuropathic pain (NP) that worsens disability and diminishes rehabilitation efficacy. Chronic NP is presently incurable due to poor understanding of underlying mechanisms. We hypothesized that multilocus neuroinflammation (NIF) might be a driver of SCI NP, and tested it by investigating whether NP coexisted with central NIF, neurotransmission (NTM), neuromodulation (NML) and neuroplasticity (NPL) changes post-SCI. Methods Female Sprague–Dawley rats (230–250 g) with T10 compression or...

Abstract Background Inappropriate use of antibiotics in children is common in many countries. The purpose of the study was to explore patterns of antibiotic prescribing in children’s outpatient clinics in primary care institutions in a province of southwest China. Methods We obtained electronic prescription data from 75 primary care institutions in Guizhou province in 2020. The classification of incorrect spectrum of antibiotics, unnecessary use and combined use of antibiotics was based on the Guiding Principle...

Abstract Background Structured and harmonized implementation of molecular tumor boards (MTB) for the clinical interpretation of molecular data presents a current challenge for precision oncology. Heterogeneity in the interpretation of molecular data was shown for patients even with a limited number of molecular alterations. Integration of high-dimensional molecular data, including RNA- (RNA-Seq) and whole-exome sequencing (WES), is expected to further complicate clinical application. To analyze challenges for MTB harmonization based on complex molecular datasets, we...

Abstract Chimeric fusion transcription factors are oncogenic hallmarks of several devastating cancer entities including pediatric sarcomas, such as Ewing sarcoma (EwS) and alveolar rhabdomyosarcoma (ARMS). Despite their exquisite specificity, these driver oncogenes have been considered largely undruggable due to their lack of enzymatic activity. Here, we show in the EwS model that – capitalizing on neomorphic DNA-binding preferences – the addiction to the respective fusion transcription factor EWSR1-FLI1 can be leveraged to express therapeutic genes....

Abstract Background and aim The role of dietary protein and glycemic index on insulin resistance (based on TyG index) within a nutritional program for weight loss and weight maintenance was examined. Methods This study analyzed 744 adults with overweight/obesity within the DIOGenes project. Patients who lost at least 8% of their initial weight (0–8 weeks) after a low-calorie diet (LCD) were randomly assigned to one of five ad libitum diets designed for weight maintenance (8–34...

Abstract Background Entrustable professional activities (EPAs) have been defined to promote the workplace participation of undergraduate medical students, generally in the context of high-income countries with a focus on the secondary and tertiary health care sectors. These EPAs have limited applicability to training and health care contexts in low- to middle-income countries that have a focus on primary health care, for instance, the context of community medicine. The purpose of this article is to report...

Abstract Introduction Severe COVID-19 leads to important changes in circulating immune-related proteins. To date it has been difficult to understand their temporal relationship and identify cytokines that are drivers of severe COVID-19 outcomes and underlie differences in outcomes between sexes. Here, we measured 147 immune-related proteins during acute COVID-19 to investigate these questions. Methods We measured circulating protein abundances using the SOMAscan nucleic acid aptamer panel in two large independent hospital-based COVID-19 cohorts in Canada...

For novel molecularly targeted agents and immunotherapies, the objective of dose-finding is often to identify the optimal biological dose, rather than the maximum tolerated dose. However, optimal biological doses may not be the same for different indications, challenging the traditional dose-finding framework. Therefore, we proposed a Bayesian phase I/II basket trial design, named “shotgun-2,” to identify indication-specific optimal biological doses. A dose-escalation part is conducted in stage I to identify the maximum tolerated dose and...

Abstract Background Gastric cancer is often comorbid with hypertension and diabetes mellitus and increases the mortality risk. Materials and methods We conducted this prospective cohort study to investigate antidiabetics and antihypertensives’ impact on gastric cancer survival. 3012 patients with gastric carcinoma undergoing radical gastrectomy were enrolled since January 2000 and followed up until July 2020. Results Hypertension and diabetes patients had worse survival than patients without hypertension and diabetes [median survival time (MST): 48 versus...

Abstract Background Gastric cancer is often comorbid with hypertension and diabetes mellitus and increases the mortality risk. Materials and methods We conducted this prospective cohort study to investigate antidiabetics and antihypertensives’ impact on gastric cancer survival. 3012 patients with gastric carcinoma undergoing radical gastrectomy were enrolled since January 2000 and followed up until July 2020. Results Hypertension and diabetes patients had worse survival than patients without hypertension and diabetes [median survival time (MST): 48 versus...