Browse Articles

A multidimensional approach to quantum state tomography of photoelectron wavepackets

A survey of obstetric ultrasound uses and priorities for artificial intelligence-assisted obstetric ultrasound in low- and middle-income countries

Abstract Obstetric ultrasound (OBUS) is recommended as part of antenatal care for pregnant individuals worldwide. To better understand current uses of OBUS in low- and middle-income countries and perceptions regarding potential use of artificial intelligence (AI)-assisted OBUS, we conducted an anonymous online global survey. A total of 176 respondents representing 34 countries participated, including 41% physicians, 49% nurses or midwives, and 6% ultrasound technicians. Most had received OBUS training (72%), reported expertise (60%) and confidence (77%) in OBUS use, and had access to ultrasound (85%). Assessment of gestational age, fetal viability, fetal presentation, and multiple gestation were both the most common OBUS uses and among the most highly prioritized for AI-assisted OBUS development. Most respondents noted ultrasound access was important (84%) and agreed that OBUS improves quality of care (98%) and patient outcomes (97%). Of the 34% expressing reservations associated with using AI-assisted OBUS, healthcare providers not understanding the technology (71%), misdiagnosis (62%), and cost (59%) were the most common. Better understanding the OBUS user, the pregnant individual, and the context, and taking care to ensure responsible, sustainable, and inclusive development and use of AI-assisted OBUS will be critical to successful integration and implementation and to increasing access to OBUS.

Enhancing cybersecurity via attribute reduction with deep learning model for false data injection attack recognition

Identification of novel genetic variants associated with feline cardiomyopathy using targeted next-generation sequencing

Abstract Cardiomyopathies are the most common heritable heart diseases in cats and humans. This study aimed to identify novel genetic variants in cats with hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM) using a targeted panel of genes associated with human cardiomyopathy. Cats were phenotyped for HCM/RCM by echocardiography ± necropsy. DNA was extracted from residual blood, and targeted next-generation sequencing was performed on two separate feline cohorts: an across-breed cohort (23 healthy cats and 21 HCM-affected pedigree or Domestic Shorthair cats), and a within-breed cohort of Birman pedigree cats (14 healthy, 8 HCM-affected, and 6 RCM-affected). Genome Analysis Toolkit was used for variant discovery. Genomic association analyses, including the covariates breed, age, and sex, were conducted to identify genetic variants of interest. We identified genetic variants associated with both HCM and RCM susceptibility in the sarcomeric genes ACTC1 , ACTN2 , MYH7 , TNNT2 and the non-sarcomeric gene CSRP3 in the Birman pedigree cats. These findings suggest that, as proposed in humans, there is at least partial overlap in the genetic background between the HCM and RCM phenotypes in cats. These findings offer potential insights for comparative cardiac research and translational medicine.

Identification of therapeutic targets for Alzheimer’s Disease Treatment using bioinformatics and machine learning

TRα1 mutant suppresses KLF9 to cause endometrial metaplasia with ectopic IL-33 expression leading to uterine fibrosis and infertility

Abstract Thyroid hormone receptors (TRs) mediate the genomic actions of thyroid hormone. Mutations of THRA gene cause a human disease known as resistance to thyroid hormone (RTHα). We created a mouse model expressing a dominant negative mutated TRα1 (Thra1PV/+ mice) that exhibits growth retardation, bone abnormalities, constipation, and anemia, as found in RTHα patients. In addition, female Thra1PV/+ mice exhibit decreased fertility. In the present study, we aimed to characterize the molecular events leading to infertility. Histologically, there was progressive uterine atrophy in Thra1PV/+ mutant mice, characterized by squamous metaplasia of the endometrial mucosa and endometrial fibrosis. RNA-seq analysis of laser-captured micro-dissected endometrium and spatial transcriptomics revealed a key role for Krüppel-like factor (Klf9), a directly-regulated TR target gene, in normal endometrial differentiation. Klf9 was suppressed in the endometrium of mice harboring mutated TRα1 and pathway analysis revealed that deficient Klf9 signaling was associated with squamous differentiation, consistent with the endometrial metaplasia observed histologically. Further, we showed that this metaplastic endometrial mucosa was the source of ectopic IL-33, which was associated with increased T-cell infiltrates, destruction of glands, and endometrial fibrosis. Our studies provide new insights to understand uterine epithelial morphogenesis and how thyroid dysfunction could lead to female infertility.

Geometric morphometrics approach for classifying children’s nutritional status on out of sample data

Prognostic impact of moderate to severe anemia associated with renal dysfunction in patients with heart failure

Dimethyl fumarate effects on paraquat-induced hepatotoxicity in mice via anti-oxidative, anti-inflammatory, and anti-apoptotic activities

The computerized algorithm for renal assessment improves diagnostic accuracy of renal impairment in hospitalized patients

Abstract In hospitalized patients, acute kidney injury (AKI) is an important adverse event associated with high mortality and medical costs. Accurate diagnosis and timely management of AKI are essential for improving the outcomes of in-hospital AKI, and delayed diagnosis or misdiagnosis hinders advancements in AKI care. To ameliorate this problem, several electronic AKI alert systems have been proposed but have shown inconsistent effects on AKI outcomes. Before electronic systems can improve AKI outcomes, it is important to confirm their diagnostic accuracy. The purposes of the present study were to establish an easy-to-construct computerized algorithm for the diagnosis of renal impairment and to test its accuracy. The present study retrospectively included 1551 patients hospitalized in Wanfang Hospital with serum creatinine (SCr) levels > 1.3 mg/dL. A computerized algorithm was constructed to identify AKI events and chronic kidney disease (CKD) in these patients. Previous SCr tests were reviewed to define baseline SCr levels. A SCr level increased > 1.5 times from baseline was defined as AKI. An estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m 2 for > 90 days was defined as CKD. Discharge diagnoses made by the attending physicians were defined as “clinician’s diagnoses.” The researcher’s diagnoses, made by experienced nephrologists according to the same criteria, were the gold standard to which the computerized algorithms and the clinician’s diagnoses were compared. The diagnoses made by the computerized algorithm and clinician were compared with the researcher’s diagnoses to define their accuracy. Among the included patients, the mean age was 73.0 years; in-hospital mortality was 14.8%, and AKI was present in 28.6% of patients. Regarding the diagnostic accuracy for AKI, the computerized algorithm achieved a sensitivity of 85.6% and a specificity of 98.8%. The main cause of false-negative (FN) AKI diagnosis was AKI occurring prior to the outpatient visit, before the indexed hospitalization. Regarding the diagnostic accuracy for CKD, the computerized algorithm achieved a sensitivity of 94.7% and specificity of 100%. The main cause of FN CKD diagnosis was the lack of previous eGFR records. The computerized algorithm exhibited significantly superior accuracy compared to the clinician’s diagnoses for both AKI (95.0% vs. 57.0%) and CKD (96.5% vs. 73.6%). We developed a simple and easy-to-construct computerized algorithm for the diagnosis of renal impairment that demonstrated significantly improved diagnostic accuracy for AKI and CKD compared to that of clinicians. In the future, an algorithmic approach for the differential diagnosis of AKI and a decision guide should be incorporated into this system.

Kinematic characteristics in patients with subcortical vascular cognitive impairment: a quantitative analysis of digitized spiral drawing metrics

GATFELPA integrates graph attention networks and enhanced label propagation for robust community detection

Ground-state flavin-dependent enzymes catalyzed enantioselective radical trifluoromethylation

De novo design of protein minibinder agonists of TLR3

Abstract Toll-like Receptor 3 (TLR3) is a pattern recognition receptor that initiates antiviral immune responses upon binding double-stranded RNA (dsRNA). Several nucleic acid-based TLR3 agonists have been explored clinically as vaccine adjuvants in cancer and infectious disease, but present substantial manufacturing and formulation challenges. Here, we use computational protein design to create novel miniproteins that bind to human TLR3 with nanomolar affinities. Cryo-EM structures of two minibinders in complex with TLR3 reveal that they bind the target as designed, although one partially unfolds due to steric competition with a nearby N-linked glycan. Multivalent forms of both minibinders induce NF-κB signaling in TLR3-expressing cell lines, demonstrating that they may have therapeutically relevant biological activity. Our work provides a foundation for the development of specific, stable, and easy-to-formulate protein-based agonists of TLRs and other pattern recognition receptors.

Machine learning-enhanced high-resolution exposure assessment of ultrafine particles

Construction of functional covalent organic framework films by modulator and solvent induced polymerization

Versatile nitrate-respiring heterotrophs are previously concealed contributors to sulfur cycle

Abstract Heterotrophic denitrifiers play crucial roles in global carbon and nitrogen cycling. However, their inability to oxidize sulfide renders them vulnerable to this toxic molecule, which inhibits the key enzymatic reaction responsible for reducing nitrous oxide (N2O), thereby raising greenhouse gas emissions. Here, we applied microcosm incubations, community-isotope-corrected DNA stable-isotope probing, and metagenomics to characterize a cohort of heterotrophic denitrifiers in estuarine sediments that thrive by coupling sulfur oxidation with denitrification through chemolithoheterotrophic metabolism. Remarkably, ecophysiology experiments from enrichments demonstrate that such heterotrophs expedite denitrification with sulfur acting as alternative electron sources and substantially curtail N2O emissions in both organic-rich and organic-limited environments. Their flexible, non-sulfur-dependent physiology may confer competitive advantages over conventional heterotrophic denitrifiers in detoxifying sulfide, adapting to organic matter fluctuations, and mitigating greenhouse gas emissions. Our study provides insights into the ecological role of heterotrophic denitrifiers in microbial communities with implications for sulfur cycling and climate change.

Measuring mean radiant temperature for indoor comfort assessment using low-resolution optical sensors

Degeneracy-breaking and long-lived multimode microwave electromechanical systems enabled by cubic silicon-carbide membrane crystals

NSm is a critical determinant for bunyavirus transmission between vertebrate and mosquito hosts

Abstract Bunyavirales is a very large order including viruses infecting a variety of taxonomic groups such as arthropods, vertebrates, plants, and protozoa. Some bunyaviruses are transmitted between vertebrate hosts by blood-sucking arthropods and cause major diseases in humans and animals. It is not understood why only some bunyaviruses have evolved the capacity to be transmitted by arthropod vectors. Here we show that only vector-borne bunyaviruses express a non-structural protein, NSm, whose function has so far remained largely elusive. Using as experimental system Bunyamwera virus (BUNV) and its invertebrate host, Aedes aegypti, we show that NSm is dispensable for viral replication in mosquito cells in vitro but is absolutely required for successful infection in the female mosquito following a blood meal. More specifically, NSm is required for cell-to-cell spread and egress from the mosquito midgut, a known barrier to viral infection. Notably, the requirement for NSm is specific to the midgut; bypassing this barrier by experimental intrathoracic infection of the mosquito eliminates the necessity of NSm for virus spread in other tissues, including the salivary glands. Overall, we unveiled a key evolutionary process that allows the transmission of vector-borne bunyaviruses between arthropod and vertebrate hosts.