A genome-wide atlas of human cell morphology.

A key challenge of the modern genomics era is developing empirical data-driven representations of gene function. Here we present the first unbiased morphology-based genome-wide perturbation atlas in human cells, containing three genome-wide genotype-phenotype maps comprising CRISPR-Cas9-based knockouts of >20,000 genes in >30 million cells. Our optical pooled cell profiling platform (PERISCOPE) combines a destainable high-dimensional phenotyping panel (based on Cell Painting) with optical sequencing of molecular barcodes and a scalable open-source analysis pipeline to facilitate massively parallel screening of pooled perturbation libraries.

Early childhood growth and nutritional status in India: trends in five National Family Health Surveys spanning 1992 and 2021.

Background/objective: To evaluate the weight and height status of under-five children between 1992 and 2021 in relation to nutritional context.

Subjects/methods: The study is based on the lengths/heights and weights of children <5 years in five national surveys (n = 505,026). After evaluating normality of the distributions, heights, and weights were expressed as z-scores relative to the WHO reference.

Pulsed laser deposition assisted epitaxial growth of cesium telluride photocathodes for high brightness electron sources.

The development of high-brightness electron sources is critical to state-of-the-art electron accelerator applications like X-ray free electron laser (XFEL) and ultra-fast electron microscopy. Cesium telluride is chosen as the electron source material for multiple cutting-edge XFEL facilities worldwide. This manuscript presents the first demonstration of the growth of highly crystalized and epitaxial cesium telluride thin films on 4H-SiC and graphene/4H-SiC substrates with ultrasmooth film surfaces.

Electrophysiological characterization of human KCNT1 channel modulators and the therapeutic potential of hydroquinine and tipepidine in KCNT1 mutation-associated epilepsy mouse model.

Patients suffering epilepsy caused by the gain-of-function mutants of the hKCNT1 potassium channels are drug refractory. In this study, we cloned a novel human KCNT1B channel isoform using the brain cDNA library and conducted patch-clamp and molecular docking analyses to characterize the pharmacological properties of the hKCNT1B channel using thirteen drugs. Among cinchona alkaloids, we found that hydroquinine exerted the strongest blocking effect on the hKCNT1B channel, especially the F313L mutant.

Black-vs-white racial disparities in 30-day outcomes following primary and revisional metabolic and bariatric surgery: a MBSAQIP database analysis.

Background: Previous studies have demonstrated Black-vs-White disparities in postoperative outcomes following primary metabolic and bariatric surgery (MBS). With the rising prevalence of MBS, it is important to examine racial disparities using quality indicators in primary and revisional procedures. This study explores Black-vs-White disparities in postoperative outcomes following primary and revisional MBS.

Short-term outcomes of mesh-suture repair in the treatment of ventral hernias: a single-center study.

Background: Defect closure with mesh suture is a novel technique for hernia repair. Originally described as the construction of lightweight macroporous polypropylene mesh strips as a suture material, it is now available as an FDA-approved product. Mesh suture better distributes tensile forces and reduces fascial tearing compared to traditional suture but requires less implanted material and tissue dissection compared to planar mesh.

A systematic review of portable technologies for the early assessment of motor development in infants.

Early screening and evaluation of infant motor development are crucial for detecting motor deficits and enabling timely interventions. Traditional clinical assessments are often subjective, without fully capturing infants' "real-world" behavior. This has sparked interest in portable, low-cost technologies to objectively and precisely measure infant motion at home, with a goal of enhancing ecological validity.

Long-term liver outcomes after metabolic surgery in compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis.

No therapy has been shown to reduce the risk of major adverse liver outcomes (MALO) in patients with cirrhosis due to metabolic dysfunction-associated steatohepatitis (MASH). The Surgical Procedures Eliminate Compensated Cirrhosis In Advancing Long-term (SPECCIAL) observational study compared the effects of metabolic surgery and nonsurgical treatment in patients with obesity and compensated histologically proven MASH-related cirrhosis. Using a doubly robust estimation methodology to balance key baseline characteristics between groups, the time-to-incident MALO was compared between 62 patients (68% female) who underwent metabolic surgery and 106 nonsurgical controls (71% female), with a mean follow-up of 10.

Age-related p53 SUMOylation accelerates senescence and tau pathology in Alzheimer's disease.

Aging is a major risk factor for Alzheimer's disease (AD). With the prevalence of AD increased, a mechanistic linkage between aging and the pathogenesis of AD needs to be further addressed. Here, we report that a small ubiquitin-related modifier (SUMO) modification of p53 is implicated in the process which remarkably increased in AD patient's brain.

RECQL4 requires PARP1 for recruitment to DNA damage, and PARG dePARylation facilitates its associated role in end joining.

RecQ helicases, highly conserved proteins with pivotal roles in DNA replication, DNA repair and homologous recombination, are crucial for maintaining genomic integrity. Mutations in RECQL4 have been associated with various human diseases, including Rothmund-Thomson syndrome. RECQL4 is involved in regulating major DNA repair pathways, such as homologous recombination and nonhomologous end joining (NHEJ).

Evaluating AI performance in nephrology triage and subspecialty referrals.

Artificial intelligence (AI) has shown promise in revolutionizing medical triage, particularly in the context of the rising prevalence of kidney-related conditions with the aging global population. This study evaluates the utility of ChatGPT, a large language model, in triaging nephrology cases through simulated real-world scenarios. Two nephrologists created 100 patient cases that encompassed various aspects of nephrology.

Comparison of aesthetic perception and acceptability of silver diamine fluoride staining between Spanish and Italian parents.

Assessing parental aesthetic acceptability of Silver Diamine Fluoride (SDF) staining is crucial for its potential implementation in paediatric dentistry in different regions. This study aimed to compare aesthetic perceptions and acceptance of SDF staining between Spanish and Italian parents, and assess weather acceptability is influenced by location, child's cooperation, or demographic background. A cross-sectional comparative study was conducted among Spanish and Italian parents at three university dental clinics, using a validated Italian version of the questionnaire "Parental perceptions of Silver Diamine Fluoride Dental Color Changes".

Social epidemiology of early adolescent nutrition.

Background: This study aimed to investigate associations between sociodemographic factors and dietary intake among a diverse population of early adolescents ages 10-13 years in the United States.

Methods: We examined data from the Adolescent Brain Cognitive Development (ABCD) Study in Year 2 (2018-2020, ages 10-13 years, N = 10,280). Multivariable linear regression models were conducted to estimate the adjusted associations between sociodemographic factors (age, sex, race and ethnicity, household income, parental education) and dietary intake of various food groups, measured by the Block Kids Food Screener.

Long-term burden of body mass index since childhood and impaired physical performance in midlife.

Background: The impact of long-term burden of body mass index (BMI) since childhood on physical performance in midlife remains unclear. We aimed to investigate the association between cumulative exposure to BMI since childhood and midlife physical performance by using data from the Bogalusa Heart Study (BHS).

Methods: This longitudinal study consisted of 749 participants (aged 37.

International myeloma working group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma.

T-cell redirecting therapy (TCRT), specifically chimeric antigen receptor T-cell therapy (CAR T-cells) and bispecific T-cell engagers (TCEs) represent a remarkable advance in the treatment of multiple myeloma (MM). There are several products available around the world and several more in development targeting primarily B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GRPC5D). The relatively rapid availability of multiple immunotherapies brings the necessity to understand how a certain agent may affect the safety and efficacy of a subsequent immunotherapy so MM physicians and patients can aim at optimal sequential use of these therapies.

Implications of frequent hitter E3 ligases in targeted protein degradation screens.

Targeted protein degradation (TPD) offers a promising approach for chemical probe and drug discovery that uses small molecules or biologics to direct proteins to the cellular machinery for destruction. Among the >600 human E3 ligases, CRBN and VHL have served as workhorses for ubiquitin-proteasome system-dependent TPD. Identification of additional E3 ligases capable of supporting TPD would unlock the full potential of this mechanism for both research and pharmaceutical applications.

The interplay of uncertainty, relevance and learning influences auditory categorization.

Auditory perception requires categorizing sound sequences, such as speech or music, into classes, such as syllables or notes. Auditory categorization depends not only on the acoustic waveform, but also on variability and uncertainty in how the listener perceives the sound - including sensory and stimulus uncertainty, the listener's estimated relevance of the particular sound to the task, and their ability to learn the past statistics of the acoustic environment. Whereas these factors have been studied in isolation, whether and how these factors interact to shape categorization remains unknown.

Cytoplasmic mRNA decay and quality control machineries in eukaryotes.

mRNA degradation pathways have key regulatory roles in gene expression. The intrinsic stability of mRNAs in the cytoplasm of eukaryotic cells varies widely in a gene- and isoform-dependent manner and can be regulated by cellular cues, such as kinase signalling, to control mRNA levels and spatiotemporal dynamics of gene expression. Moreover, specialized quality control pathways exist to rid cells of non-functional mRNAs produced by errors in mRNA processing or mRNA damage that negatively impact translation.