Nevin Manimala

Nature. 2023 Aug 17. doi: 10.1038/s41586-023-06536-0. Online ahead of print.

ABSTRACT

The integer quantum anomalous Hall (QAH) effect is a lattice analog of the quantum Hall effect at zero magnetic field^1-3. This striking phenomenon occurs in systems with topologically nontrivial bands and spontaneous time-reversal symmetry breaking. Discovery of its fractional counterpart in the presence of strong electron correlations, i.e., the fractional quantum anomalous Hall (FQAH) effect^4-7, would open a new chapter in condensed matter physics. Here, we report direct observation of both integer and fractional QAH effects in electrical measurements on twisted bilayer MoTe₂. At zero magnetic field, near filling factor [Formula: see text] (one hole per moiré unit cell) we see an integer QAH plateau in the Hall resistance R_xy quantized to [Formula: see text] while longitudinal resistance R_xx vanishes. Remarkably, at [Formula: see text] and [Formula: see text] we see plateau features in R_xy at [Formula: see text] and [Formula: see text], respectively, while R_xx remains small. All features shift linearly versus applied magnetic field with slopes matching the corresponding Chern numbers [Formula: see text], [Formula: see text], and [Formula: see text], precisely as expected for integer and fractional QAH states. Additionally, at zero magnetic field, R_xy is approximately 2[Formula: see text] near half filling ([Formula: see text]) and varies linearly as [Formula: see text] is tuned. This behavior resembles that of the composite Fermi liquid in the half-filled lowest Landau level of a two-dimensional electron gas at high magnetic field^8-14. Direct observation of the FQAH and associated effects paves the way for researching charge fractionalization and anyonic statistics at zero magnetic field.

PMID:37591304 | DOI:10.1038/s41586-023-06536-0

Lancet. 2023 Aug 14:S0140-6736(23)01554-4. doi: 10.1016/S0140-6736(23)01554-4. Online ahead of print.

ABSTRACT

BACKGROUND: IgA nephropathy is a chronic immune-mediated kidney disease and a major cause of kidney failure worldwide. The gut mucosal immune system is implicated in its pathogenesis, and Nefecon is a novel, oral, targeted-release formulation of budesonide designed to act at the gut mucosal level. We present findings from the 2-year, phase 3 NefIgArd trial of Nefecon in patients with IgA nephropathy.

METHODS: In this phase 3, multicentre, randomised, double-blind, placebo-controlled trial, adult patients (aged ≥18 years) with primary IgA nephropathy, estimated glomerular filtration rate (eGFR) 35-90 mL/min per 1·73 m², and persistent proteinuria (urine protein-creatinine ratio ≥0·8 g/g or proteinuria ≥1 g/24 h) despite optimised renin-angiotensin system blockade were enrolled at 132 hospital-based clinical sites in 20 countries worldwide. Patients were randomly assigned (1:1) to receive 16 mg/day oral capsules of Nefecon or matching placebo for 9 months, followed by a 15-month observational follow-up period off study drug. Randomisation via an interactive response technology system was stratified according to baseline proteinuria (<2 or ≥2 g/24 h), baseline eGFR (<60 or ≥60 mL/min per 1·73 m²), and region (Asia-Pacific, Europe, North America, or South America). Patients, investigators, and site staff were masked to treatment assignment throughout the 2-year trial. Optimised supportive care was also continued throughout the trial. The primary efficacy endpoint was time-weighted average of eGFR over 2 years. Efficacy and safety analyses were done in the full analysis set (ie, all randomly assigned patients). The trial was registered on ClinicalTrials.gov, NCT03643965, and is completed.

FINDINGS: Patients were recruited to the NefIgArd trial between Sept 5, 2018, and Jan 20, 2021, with 364 patients (182 per treatment group) randomly assigned in the full analysis set. 240 (66%) patients were men and 124 (34%) were women, and 275 (76%) identified as White. The time-weighted average of eGFR over 2 years showed a statistically significant treatment benefit with Nefecon versus placebo (difference 5·05 mL/min per 1·73 m² [95% CI 3·24 to 7·38], p<0·0001), with a time-weighted average change of -2·47 mL/min per 1·73 m² (95% CI -3·88 to -1·02) reported with Nefecon and -7·52 mL/min per 1·73 m² (-8·83 to -6·18) reported with placebo. The most commonly reported treatment-emergent adverse events during treatment with Nefecon were peripheral oedema (31 [17%] patients, vs placebo, seven [4%] patients), hypertension (22 [12%] vs six [3%]), muscle spasms (22 [12%] vs seven [4%]), acne (20 [11%] vs two [1%]), and headache (19 [10%] vs 14 [8%]). No treatment-related deaths were reported.

INTERPRETATION: A 9-month treatment period with Nefecon provided a clinically relevant reduction in eGFR decline and a durable reduction in proteinuria versus placebo, providing support for a disease-modifying effect in patients with IgA nephropathy. Nefecon was also well tolerated, with a safety profile as expected for a locally acting oral budesonide product.

FUNDING: Calliditas Therapeutics.

PMID:37591292 | DOI:10.1016/S0140-6736(23)01554-4

Dev Cell. 2023 Aug 14:S1534-5807(23)00366-0. doi: 10.1016/j.devcel.2023.07.019. Online ahead of print.

ABSTRACT

Basic helix-loop-helix genes, particularly proneural genes, are well-described triggers of cell differentiation, yet information on their dynamics is limited, notably in human development. Here, we focus on Neurogenin 3 (NEUROG3), which is crucial for pancreatic endocrine lineage initiation. By monitoring both NEUROG3 gene expression and protein in single cells using a knockin dual reporter in 2D and 3D models of human pancreas development, we show an approximately 2-fold slower expression of human NEUROG3 than that of the mouse. We observe heterogeneous peak levels of NEUROG3 expression and reveal through long-term live imaging that both low and high NEUROG3 peak levels can trigger differentiation into hormone-expressing cells. Based on fluorescence intensity, we statistically integrate single-cell transcriptome with dynamic behaviors of live cells and propose a data-mapping methodology applicable to other contexts. Using this methodology, we identify a role for KLK12 in motility at the onset of NEUROG3 expression.

PMID:37591246 | DOI:10.1016/j.devcel.2023.07.019

Am J Nephrol. 2023 Aug 17. doi: 10.1159/000533257. Online ahead of print.

ABSTRACT

INTRODUCTION: The current prevalence of chronic kidney disease (CKD) is substantial, and CKD individuals face a heightened risk of mortality, encompassing both all-cause and cause-specific outcomes. The current study aims to investigate the potential impact of adhering to Life Essential 8 (LE8) on reducing mortality among CKD individuals.

METHODS: Using the National Health and Nutrition Survey (NHANES) data from 2005 to 2018, we analyzed 22,420 United States adults (≥20 years old). CKD is defined by urinary albumin-to-creatinine ratio (≥30 mg/g or 3 mg/mmol) and estimated glomerular filtration rate (<60 ml/min/1.73m2). The components of LE8, including diet, physical activity (PA), nicotine exposure, sleep, Body Mass Index, blood lipids, blood glucose, and blood pressure (BP) were measured and given a score of 0-100. The total LE8 score was the unweighted average of all components and was divided into low cardiovascular health (CVH) (0-49), moderate CVH (50-79), and high CVH (80-100). Cox proportional hazards regression model was used to explore the associations of LE8 with all-cause, cardiovascular disease (CVD), and cancer mortality, which were followed prospectively by the National Center for Health Statistics until December 31, 2019.

RESULTS: In the overall population, individuals with moderate CVH had a 47% lower risk of CKD, while high CVH was linked to a 55% lower risk compared to low CVH. During a median follow-up of 7.58 years, CKD individuals had a 93% higher all-cause mortality rate and a 149% higher CVD mortality rate compared to those without CKD. Among the CKD individuals, every 10-point increase in LE8 score was associated with reduced risks of 17% for all-cause mortality (especially PA, nicotine exposure, blood glucose, and BP), 18% for CVD mortality (especially PA), and 12% for cancer mortality (especially PA and sleep health). In additional and sensitivity analysis, the results remained significant after further consideration of potential confounding of renal function. Additionally, LE8 demonstrated superior risk stratification for CVD mortality among CKD patients compared with LS7. Interaction was observed between LE8 and age, education level, marital status, and drinking status.

CONCLUSIONS: The current study demonstrates that adherence to higher LE8 levels within CKD individuals is associated with a reduced risk of both all-cause and cause-specific mortality.

PMID:37591229 | DOI:10.1159/000533257

Int J Med Inform. 2023 Aug 11;178:105177. doi: 10.1016/j.ijmedinf.2023.105177. Online ahead of print.

ABSTRACT

OBJECTIVE: To develop a machine-learning (ML) model using administrative data to estimate risk of adverse outcomes within 30-days of a benzodiazepine (BZRA) dispensation in older adults for use by health departments/regulators.

DESIGN, SETTING AND PARTICIPANTS: This study was conducted in Alberta, Canada during 2018-2019 in Albertans 65 years of age and older. Those with any history of malignancy or palliative care were excluded.

EXPOSURE: Each BZRA dispensation from a community pharmacy served as the unit of analysis.

MAIN OUTCOMES AND MEASURES: ML algorithms were developed on 2018 administrative data to predict risk of any-cause hospitalization, emergency department visit or death within 30-days of a BZRA dispensation. Validation on 2019 administrative data was done using XGBoost to evaluate discrimination, calibration and other relevant metrics on ranked predictions. Daily and quarterly predictions were simulated on 2019 data.

RESULTS: 65,063 study participants were included which represented 633,333 BZRA dispensation during 2018-2019. The validation set had 314,615 dispensations linked to 55,928 all-cause outcomes representing a pre-test probability of 17.8%. C-statistic for the XGBoost model was 0.75. Measuring risk at the end of 2019, the top 0.1 percentile of predicted risk had a LR + of 40.31 translating to a post-test probability of 90%. Daily and quarterly classification simulations resulted in uninformative predictions with positive likelihood ratios less than 10 in all risk prediction categories. Previous history of admissions was ranked highest in variable importance.

CONCLUSION: Developing ML models using only administrative health data may not provide health regulators with sufficient informative predictions to use as decision aids for potential interventions, especially if considering daily or quarterly classifications of BZRA risks in older adults. ML models may be informative for this context if yearly classifications are preferred. Health regulators should have access to other types of data to improve ML prediction.

PMID:37591010 | DOI:10.1016/j.ijmedinf.2023.105177

J Forensic Nurs. 2023 Jul-Sep 01;19(3):E24-E29. doi: 10.1097/JFN.0000000000000443. Epub 2023 Jun 14.

ABSTRACT

BACKGROUND: Appropriate clinical decision making (CDM) is very important for emergency nurses when working with forensic patients with violence-related injuries and can improve patient outcomes. Therefore, it is essential for emergency nurses to have the basic skills to make the right clinical decisions when working with forensic patients.

AIM: The aim of this study was to evaluate the CDM of emergency nurses when caring for forensic patients.

METHODS: This study was conducted using a cross-sectional design. Nurses working in the seven emergency departments of Rasht hospitals, Guilan Province, Iran, were recruited to take part in the study. Data collection was performed via census sampling from September to November 2019. Data were collected via a two-part questionnaire developed by the researcher(s) that addressed (a) demographic characteristics and (b) simulated scenarios that assessed their CDM in caring for forensic patients.

FINDINGS: One hundred ninety-two emergency nurses participated in this study. The mean score of CDM in forensic nursing was moderate (56.46; 95% CI [54.49, 58.43]). Of the participants, 60.42% of the emergency nurses had moderate CDM knowledge related to forensic nursing, whereas only 2.8% had desirable knowledge of CDM. There was a statistically significant relationship between CDM in forensic nursing and the history of encountering forensic patients ( p = 0.008).

CONCLUSION: CDM scores regarding emergency nurses’ knowledge of forensic nursing were moderate. Knowledge of and CDM in forensic nursing is very important and provides high-quality safe care for forensic patients.

IMPLICATIONS FOR CLINICAL FORENSIC NURSING PRACTICE: This study highlights the importance of additional education and professional development in forensic nursing, for emergency nurses, and should be considered further by nursing administrators and nursing educators.

PMID:37590945 | DOI:10.1097/JFN.0000000000000443

JCO Oncol Pract. 2023 Aug 17:OP2200851. doi: 10.1200/OP.22.00851. Online ahead of print.

ABSTRACT

PURPOSE: There is strong evidence that hospital volume is associated with improved outcomes for patients undergoing cancer surgery. Lack of access to high-volume hospitals (HVHs) may contribute to rural-urban disparities in cancer outcomes. Yet, methods used to classify hospitals as high-volume vary, making interpretation of evidence on hospital volume complex. This study examines urban-rural differences in receipt of cancer surgery at HVHs and sensitivity to volume thresholds used.

MATERIALS AND METHODS: Using 2017-2020 statewide Pennsylvania Health Care Cost Containment Council inpatient data, we implemented logistic regression models to examine the association between rural residence and cancer surgery at a HVH using different volume thresholds that are commonly used in the literature: top 10%, 20%, 25%, and 30%.

RESULTS: The relationship between rural residence and treatment in a HVH varied by cancer type, and for some cancers, varied in direction, magnitude, or statistical significance, depending on the volume threshold used. Rural patients with cancers of pancreas or esophagus were consistently more likely to receive surgery at HVHs across all four thresholds. For rectum, colon, bladder, lung, and breast cancers, rural patients were consistently less likely to receive surgery at HVHs. For prostate, brain, and stomach cancers, there was less consistency in the relationship between rural residence and treatment.

CONCLUSION: For many cancers, patients residing in rural areas are less likely to receive care at HVHs. Findings highlight the complexity of examining patterns of cancer care at HVHs and can inform efforts to direct patients to HVHs.

PMID:37590899 | DOI:10.1200/OP.22.00851

J Glob Health. 2023 Aug 18;13:04086. doi: 10.7189/jogh.13.04086.

ABSTRACT

BACKGROUND: Approximately 4.4 million children die peripartum annually, primarily in low- and middle-income countries. Accurate mortality tracking is essential to prioritising prevention efforts but is undermined by misclassification between stillbirths (SBs) and early neonatal deaths (ENNDs) in household surveys, which serve as key data sources. We explored and quantified associations between peripartum provider-mother interactions and misclassification of SBs and ENNDs in Guinea-Bissau.

METHODS: Using a case-control design, we followed up on women who had reported a SB or ENND in a retrospective household survey nested in the Bandim Health Project’s Health and Demographic Surveillance Systems (HDSS). Using prospective HDSS registration as the reference standard, we linked the survey-reported deaths to the corresponding HDSS records and cross-tabulated SB/ENND classification to identify cases (discordant classification between survey and HDSS) and controls (concordant classification). We further interviewed cases and controls on peripartum provider-mother interactions and analysed data using descriptive statistics and logistic regressions.

RESULTS: We interviewed 278 women (cases: 63 (23%); controls: 215 (77%)). Most cases were SBs misclassified as ENNDs (n/N = 49/63 (78%)). Three-fourths of the interviewed women reported having received no updates on the progress of labour and baby’s health intrapartum, and less than one-fourth inquired about this information. In comparison with births where women did inquire for information, misclassification was less likely when women did not inquire and recalled no doubts about progress of labour (odds ratio (OR) = 0.51; 95% confidence interval (CI) = 0.28-0.91), or baby’s health (OR = 0.54; 95% CI = 0.30-0.97). Most women reported that service providers’ death notifications lasted <5 minutes (cases: 23/27 (85%); controls: 61/71 (86%)), and most often encompassed neither events leading to the death (cases: 19/27 (70%); controls: 55/71 (77%)) nor causes of death (cases: 20/27 (74%); controls: 54/71 (76%)). Misclassification was more likely if communication lasted <1 compared to 1-4 minutes (OR = 1.83; 95% CI = 1.10-3.06) and if a formal service provider had informed the mother of the death compared to a family member (OR = 1.57; 95% CI = 1.04-2.36).

CONCLUSIONS: Peripartum provider-mother interactions are limited in Guinea-Bissau and associated with birth outcome misclassifications in retrospective household surveys. In our study population, misclassification led to overestimated neonatal mortality.

PMID:37590896 | DOI:10.7189/jogh.13.04086

Metab Syndr Relat Disord. 2023 Aug;21(6):306-313. doi: 10.1089/met.2022.0100.

ABSTRACT

Objectives: Various diseases are associated with obesity and metabolism. We sought to investigate the risk of cardiovascular disease (CVD) in diverse metabolic obesity phenotypes. Methods and Results: A prospective observational study of 1517 participants ≥25 years of age without CVD at baseline was conducted. Participants were categorized into four groups based on the condition of central obesity and metabolic health status: metabolically healthy normal weight, metabolically healthy obesity (MHO), metabolically unhealthy normal weight, and metabolically unhealthy obese (MUO). A multivariate Cox regression analysis was used to analyze the relationship between different obesity phenotypes and CVD. During 14830.49 person-years of follow-up, there were 244 incident cases of CVD. Of the 1517 participants, 72 (4.75%) and 812 (53.53%) were classified as having MHO and MUO, respectively. MHO and MUO had a tendency toward a higher risk of CVD [adjusted hazard ratios (HRs) = 1.49, 95% confidence interval (CI): 1.11-2.02 and HR = 1.25, 95% CI: 1.00-1.55, respectively] based on the waist circumference criterion. Conclusion: MHO and MUO can increase the risk of CVD.

PMID:37590875 | DOI:10.1089/met.2022.0100

Otol Neurotol. 2023 Aug 15. doi: 10.1097/MAO.0000000000003984. Online ahead of print.

ABSTRACT

OBJECTIVE: To identify key risk factors for the development of bilateral Ménière’s disease.

STUDY DESIGNS: Observational study.

SETTING: Four NHS Trusts and four independent hospitals or clinics, within three distinct urban and rural regions within the United Kingdom (Norfolk, Leicestershire, and London).

METHODS: Patients with Ménière’s disease were identified at ENT or audiovestibular medicine secondary/tertiary care and specialist private clinics. A range of patient-reported data, questionnaire data, and clinical data (audiometric, radiological, and specialist balance testing data) was inputted into a bespoke database. A logistic regression model was used to identify potential risk factors for bilateral Ménière’s disease compared with unilateral Ménière’s disease.

RESULTS: A total of 411 participants were recruited into this study, 263 from NHS Trusts and 148 from independent hospitals or clinics. In our cohort of patients, 22% of individuals were identified as having bilateral Ménière’s disease. Two statistically significant independent variables were identified as risk factors for the development of bilateral Ménière’s disease: the presence of psoriasis and a history of ear infections.

CONCLUSIONS: Psoriasis and a history of ear infection have been identified as key risk factors for the development of bilateral Ménière’s disease. It is anticipated that further work based on this finding will allow a better understanding of the underlying pathophysiological mechanisms that predispose to the development of Ménière’s disease symptoms.

PMID:37590874 | DOI:10.1097/MAO.0000000000003984