Miracle-dz/UniFAR-FTUs huggingface dataset:
Forward Modeling of Galaxy Populations for Cosmological Redshift Distribution Inference

We present a forward-modeling framework for estimating galaxy redshift distributions from photometric surveys. Our forward model is composed of: a detailed population model describing the intrinsic distribution of the physical characteristics of galaxies, encoding galaxy evolution physics; a stellar population synthesis model connecting the physical properties of galaxies to their photometry; a data model characterizing the observation and calibration processes for a given survey; and explicit treatment of selection cuts, both into the main analysis sample and for the subsequent sorting into tomographic redshift bins. This approach has the appeal that it does not rely on spectroscopic calibration data, provides explicit control over modeling assumptions and builds a direct bridge between photo-z inference and galaxy evolution physics. In addition to redshift distributions, forward modeling provides a framework for drawing robust inferences about the statistical properties of the galaxy population more generally. We demonstrate the utility of forward modeling by estimating the redshift distributions for the Galaxy And Mass Assembly (GAMA) survey and the Vimos VLT Deep Survey (VVDS), validating against their spectroscopic redshifts. Our baseline model is able to predict tomographic redshift distributions for GAMA and VVDS with respective biases of Δz ≲ 0.003 and Δz ≃ 0.01 on the mean redshift—comfortably accurate enough for Stage III cosmological surveys—without any hyperparameter tuning (i.e., prior to doing any fitting to those data). We anticipate that with additional hyperparameter fitting and modeling improvements, forward modeling will provide a path to accurate redshift distribution inference for Stage IV surveys.
Impact of germ cell ablation on the activation of the brain–pituitary–gonadal axis in precocious Atlantic salmon (Salmo salar L.) males

The germ cells are essential for sexual reproduction by giving rise to the gametes, but the importance of germ cells for gonadal somatic functions varies among vertebrates. The RNA‐binding dead end (Dnd) protein is necessary for the specification and migration of primordial germ cells to the future reproductive organs. Here, we ablated the gametes in Atlantic salmon males and females by microinjecting dnd antisense gapmer oligonucleotides at the zygotic stage. Precocious maturation was induced in above 50% of both germ cell‐depleted and intact fertile males, but not in females, by exposure to an off‐season photoperiod regime. Sterile and fertile males showed similar body growth, but maturing fish tended to be heavier than their immature counterparts. Pituitary fshβ messenger RNA levels strongly increased in maturing sterile and fertile males concomitant with the upregulated expression of Sertoli and Leydig cell markers. Plasma concentrations of 11‐ketotestosterone and testosterone in maturing sterile males were significantly higher than the basal levels in immature fish, but lower than those in maturing fertile males. The study demonstrates that germ cells are not a prerequisite for the activation of the brain–pituitary–gonad axis and sex steroidogenesis in Atlantic salmon males, but may be important for the maintenance of gonadal somatic functions.
Protective effect of Rhein against vancomycin‐induced nephrotoxicity through regulating renal transporters and Nrf2 pathway

Vancomycin (VCM)'s nephrotoxicity limits its application and therapeutic efficiency. The aim of this study was to determine the protective effect of rhein against VCM‐induced nephrotoxicity (VIN). VIN models were established in rats and NRK‐52E cells. Rhein up‐regulated the expressions of renal organic anion transporter (Oat) 1, Oat3, organic cation transporter 2 (Oct2), multidrug resistance‐associated protein 2 (Mrp2), mammal multidrug and toxin extrusion proteins 1 (Mate 1) and P‐glycoprotein (P‐gp) to facilitate the efflux of plasma creatinine, blood urea nitrogen (BUN), and plasma indoxyl sulfate. Rhein increased the expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) to regulate the expression of Mrp2, P‐gp, and Mate 1. The increased level of superoxide dismutase (SOD), decreased level of malondialdehyde (MDA) and reduced number of apoptosis cells were observed after treatment of rhein. Rhein decreased the number of apoptosis cells as well as increased the expression of B‐cell lymphoma‐2 (Bcl‐2) and decreased expressions of Bcl‐2‐like protein 4 (Bax). ML385, as a typical inhibitor of Nrf2, reversed the protective effects of rhein in cells. Rhein oriented itself in the site of Keap1, inhibiting the Keap1–Nrf2 interaction. Rhein ameliorated VIN mainly through regulating the expressions of renal transporters and acting on Nrf2 pathway.
Morbidity and long-term outcome of surgery for renal hyperparathyroidism: results from a prospective cohort

Abstract Purposes Surgery remains an important treatment option for renal hyperparathyroidism (rHPT). The number of long-term outcome studies of parathyroidectomy is limited. Methods All consecutive patients with a parathyroidectomy for rHPT between 09/2009 and 04/2021 in a Belgian tertiary referral hospital were prospectively enrolled. The main outcomes were (long-term) cured proportion and postoperative morbidity (hypocalcemia, recurrent laryngeal nerve (RLN) palsy, re-intervention for bleeding, and wound morbidity). Results Sixty patients with a median age of 57 years were analyzed, including 23 patients before kidney transplantation, 23 patients without kidney transplantation, and 14 patients after kidney transplantation. Median time to transplant was 15 (6–24) months after parathyroidectomy. Morbidity was low with only two non-urgent returns to theatre (wound infection and non-compressive hematoma), two temporary RLN paralyses, and no 30-day mortality. Length of hospital stay was longer in patients with parathyroidectomy before kidney transplant, due to a more severe and prolonged need for calcium supplementation. After a median follow-up of 63 months, 37 patients (62%) were still alive, and 11 patients (18%) developed a recurrence. Conclusions This single-surgeon, single-center cohort with long-term follow-up confirms the safety and excellent ‘cure’ proportions of surgery for rHPT but stretches the importance of long-term follow-up.
E-cigarette vaping associated acute lung injury (EVALI): state of science and future research needs

Abstract “E-Cigarette (e-cig) Vaping-Associated Acute Lung Injury” (EVALI) has been linked to vitamin-E-acetate (VEA) and Δ-9-tetrahydrocannabinol (THC), due to their presence in patients’ e-cigs and biological samples. Lacking standardized methodologies for patients’ data collection and comprehensive physicochemical/toxicological studies using real-world-vapor exposures, very little data are available, thus the underlying pathophysiological mechanism of EVALI is still unknown. This review aims to provide a comprehensive and critical appraisal of existing literature on clinical/epidemiological features and physicochemical-toxicological characterization of vaping emissions associated with EVALI. The literature review of 161 medical case reports revealed that the predominant demographic pattern was healthy white male, adolescent, or young adult, vaping illicit/informal THC-containing e-cigs. The main histopathologic pattern consisted of diffuse alveolar damage with bilateral ground-glass-opacities at chest radiograph/CT, and increased number of macrophages or neutrophils and foamy-macrophages in the bronchoalveolar lavage. The chemical analysis of THC/VEA e-cig vapors showed a chemical difference between THC/VEA and the single THC or VEA. The chemical characterization of vapors from counterfeit THC-based e-cigs or in-house-prepared e-liquids using either cannabidiol (CBD), VEA, or medium-chain triglycerides (MCT), identified many toxicants, such as carbonyls, volatile organic compounds, terpenes, silicon compounds, hydrocarbons, heavy metals, pesticides and various industrial/manufacturing/automotive-related chemicals. There is very scarce published toxicological data on emissions from THC/VEA e-liquids. However, CBD, MCT, and VEA emissions exert varying degrees of cytotoxicity, inflammation, and lung damage, depending on puffing topography and cell line. Major knowledge gaps were identified, including the need for more systematic-standardized epidemiological surveys, comprehensive physicochemical characterization of real-world e-cig emissions, and mechanistic studies linking emission properties to specific toxicological outcomes.
Pathways of atopic disease and neurodevelopmental impairment: assessing the evidence for infant antibiotics

ABSTRACT Introduction Epidemiologic studies are starting to report associations between antibiotic use in early life and neurodevelopmental disorders. Through mechanisms within the gut microbiota-brain axis, indeed, it is plausible that infant antibiotic treatment plays a role in the development of atopic disease and neurodevelopmental disorders. Areas covered This narrative review summarizes and interprets published evidence on infant antibiotic use in future outcomes of atopic disease, and neurodevelopmental delay and disorders, including attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). To this end, we critically assess study bias from two main confounding factors, maternal/infant infection and infant feeding status. We also discuss common mechanisms that link atopy and neurodevelopment, and propose hypotheses related to immune activation and the gut microbiome. Expert opinion Atopic disease and neurodevelopmental disorders share many risk factors and biological pathways. Infant antibiotic use has been linked to both disorders and is likely a marker for prenatal or infant infection. The mediating role of breastfeeding can also not be discounted. The exploration of causal pathways along the gut-brain axis leading toward neurodevelopmental impairment is evolving and of future interest.
Dose-Response Association of Low and Normal Ankle Brachial Index With the Risk of Cardiovascular Disease Morbidity and Mortality

We quantitatively evaluated the dose-response association of low and normal ankle brachial index (ABI) with the risk of morbidity and mortality from cardiovascular diseases (CVDs). PubMed, Embase, and Web of Science were systematically searched for cohort studies. Random effects or fixed effects models were used to estimate the pooled relative risks (RRs) and 95% confidence intervals (95% CIs). Generalized least squares regression was used to assess study-specific dose-response associations per 0.1 ABI decrease. Restricted cubic splines were used to evaluate linear or nonlinear trends. Twelve cohort studies (57 031 participants) were included in this meta-analysis. For low vs normal ABI levels, the pooled RRs were 2.03 (95% CI, 1.72–2.41; I 2 = 52.9%; pheterogeneity=0.030) and 2.29 (95% CI, 1.98–2.64; I 2 = 39.5%; pheterogeneity =0.158) for CVD morbidity and CVD mortality, respectively. For per 0.1 ABI decrease from 1.40 the risk for CVD morbidity and CVD mortality increased by 8% (1.08, 95% CI 1.04–1.11) and 11% (1.11, 95% CI 1.07–1.15), respectively. Restricted cubic splines showed inverse linear associations for CVD morbidity and CVD mortality. As a non-invasive index, lower ABI was significantly associated with the increased risk of morbidity and mortality from CVDs in an inverse linear manner.
Identifying non-communicable disease multimorbidity patterns and associated factors: a latent class analysis approach

Objective In the absence of adequate nationally-representative empirical evidence on multimorbidity, the existing healthcare delivery system is not adequately oriented to cater to the growing needs of the older adult population. Therefore, the present study identifies frequently occurring multimorbidity patterns among older adults in India. Further, the study examines the linkages between the identified patterns and socioeconomic, demographic, lifestyle and anthropometric correlates. Design The present findings rest on a large nationally-representative sample from a cross-sectional study. Setting and participants The study used data on 58 975 older adults (45 years and older) from the Longitudinal Ageing Study in India, 2017–2018. Primary and secondary outcome measures The study incorporated a list of 16 non-communicable diseases to identify commonly occurring patterns using latent class analysis. The study employed multinomial logistic regression models to assess the association between identified disease patterns with unit-level socioeconomic, demographic, lifestyle and anthropometric characteristics. Results The present study demonstrates that older adults in the country can be segmented into six patterns: ‘relatively healthy’, ‘hypertension’, ‘gastrointestinal disorders–hypertension–musculoskeletal disorders’, ‘musculoskeletal disorders–hypertension–asthma’, ‘metabolic disorders’ and ‘complex cardiometabolic disorders’. Additionally, socioeconomic, demographic, lifestyle and anthropometric factors are significantly associated with one or more identified disease patterns. Conclusions The identified classes ‘hypertension’, ‘metabolic disorders’ and ‘complex cardiometabolic disorders’ reflect three stages of cardiometabolic morbidity with hypertension as the first and ‘complex cardiometabolic disorders’ as the last stage of disease progression. This underscores the need for effective prevention strategies for high-risk hypertension group. Also, targeted interventions are essential to reduce the burden on the high-risk population and provide equitable health services at the community level.
Chemotherapy-induced peripheral neuropathy onset is associated with early risk of depression and anxiety in breast cancer survivors.

OBJECTIVE The objective was to assess for an association between chemotherapy-induced peripheral neuropathy (CIPN) onset and development of depression and anxiety in breast cancer (BrCa) survivors. METHODS A retrospective observational cohort was used and identified from Optum's De-identified Clinformatics® Data Mart Database years 2012-2015. Three groups of women were derived based on BrCa and CIPN status: BrCa+/CIPN+ (n = 244), BrCa+/CIPN- (n = 8870), and BrCa-/CIPN- (n = 1,125,711). The ratio of the prevalence ratios (RPR) determined if the change in risk of depression and anxiety from the 12-month preindex period to postindex period I (0-6 months) and II (7-12 months) was different for BrCa+/CIPN+ compared to BrCa+/CIPN- and BrCa-/CIPN-. RESULTS The adjusted RPR for depression was significantly elevated for BrCa+/CIPN+ compared to BrCa+/CIPN- and BrCa-/CIPN- for postindex periods I (RPR = 1.35 [1.10,1.65] and 1.33 [1.08,1.63], respectively) and II (RPR = 1.53 [1.21,1.94] and 1.50 [1.17,1.93], respectively). The RPR for anxiety was significantly elevated for BrCa+/CIPN+ compared to BrCa+/CIPN- and BrCa-/CIPN- for postindex periods I (RPR = 1.37 [1.12,1.67] and 1.31 [1.06,1.61], respectively) and II (RPR = 1.41 [1.13,1.76] and 1.28 [1.02,1.62], respectively). CONCLUSIONS Among BrCa survivors, CIPN onset is associated with a subsequent increased 12-month risk of depression and anxiety. Depression and anxiety screening should be considered in BrCa+/CIPN+ survivors, particularly given their known impact on fall risk. The observed association between CIPN and an increased risk of depression and anxiety should be further studied in prospective studies.
Bereavement in the Time of COVID-19: Learning from Experiences of those Bereaved as a Result of Deaths in an Acute Hospital Setting in 2020

The COVID-19 pandemic has resulted in many people experiencing bereavement in challenging circumstances. In April 2020 at a large London Trust, a “Bereavement Welfare Hub” was established to offer support and advice by telephone to relatives and carers of all adults who died as inpatients. Data from BWH call records regarding 809 adults who died at the Trust in March, April and May 2020 were collated. A random selection of 149 call records were examined using thematic analysis. Six themes which influenced the bereavement experiences and grief status of call recipients were identified. These included family and community support, care up to the point of death, communication, care after death and death rituals and customs. Several factors positively and negatively influenced the experiences of people bereaved during the first wave of COVID-19. From these findings, recommendations have been made which have the potential to improve the bereavement experience, particularly during the pandemic era.
IPMK modulates hepatic glucose production and insulin signaling

Hepatic glucose production (HGP) is crucial for the maintenance of normal glucose homeostasis. Although hepatic insulin resistance contributes to excessive glucose production, its mechanism is not well understood. Here, we show that inositol polyphosphate multikinase (IPMK), a key enzyme in inositol polyphosphate biosynthesis, plays a role in regulating hepatic insulin signaling and gluconeogenesis both in vitro and in vivo. IPMK‐deficient hepatocytes exhibit decreased insulin‐induced activation of Akt‐FoxO1 signaling. The expression of messenger RNA levels of phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose 6‐phosphatase (G6pc), key enzymes mediating gluconeogenesis, are increased in IPMK‐deficient hepatocytes compared to wild type hepatocytes. Importantly, re‐expressing IPMK restores insulin sensitivity and alleviates glucose production in IPMK‐deficient hepatocytes. Moreover, hepatocyte‐specific IPMK deletion exacerbates hyperglycemia and insulin sensitivity in mice fed a high‐fat diet, accompanied by an increase in HGP during pyruvate tolerance test and reduction in Akt phosphorylation in IPMK deficient liver. Our results demonstrate that IPMK mediates insulin signaling and gluconeogenesis and may be potentially targeted for treatment of diabetes.
Is one annotation enough? A data-centric image classification benchmark for noisy and ambiguous label estimation

High-quality data is necessary for modern machine learning. However, the acquisition of such data is difficult due to noisy and ambiguous annotations of humans. The aggregation of such annotations to determine the label of an image leads to a lower data quality. We propose a data-centric image classification benchmark with ten real-world datasets and multiple annotations per image to allow researchers to investigate and quantify the impact of such data quality issues. With the benchmark we can study the impact of annotation costs and (semi-)supervised methods on the data quality for image classification by applying a novel methodology to a range of different algorithms and diverse datasets. Our benchmark uses a two-phase approach via a data label improvement method in the first phase and a fixed evaluation model in the second phase. Thereby, we give a measure for the relation between the input labeling effort and the performance of (semi-)supervised algorithms to enable a deeper insight into how labels should be created for effective model training. Across thousands of experiments, we show that one annotation is not enough and that the inclusion of multiple annotations allows for a better approximation of the real underlying class distribution. We identify that hard labels can not capture the ambiguity of the data and this might lead to the common issue of overconfident models. Based on the presented datasets, benchmarked methods, and analysis, we create multiple research opportunities for the future directed at the improvement of label noise estimation approaches, data annotation schemes, realistic (semi-)supervised learning, or more reliable image collection.
Probing the Robustness of Independent Mechanism Analysis for Representation Learning

One aim of representation learning is to recover the original latent code that generated the data, a task which requires additional information or inductive biases. A recently proposed approach termed Independent Mechanism Analysis (IMA) postulates that each latent source should influence the observed mixtures independently, complementing standard nonlinear independent component analysis, and taking inspiration from the principle of independent causal mechanisms. While it was shown in theory and experiments that IMA helps recovering the true latents, the method's performance was so far only characterized when the modeling assumptions are exactly satisfied. Here, we test the method's robustness to violations of the underlying assumptions. We find that the benefits of IMA-based regularization for recovering the true sources extend to mixing functions with various degrees of violation of the IMA principle, while standard regularizers do not provide the same merits. Moreover, we show that unregularized maximum likelihood recovers mixing functions which systematically deviate from the IMA principle, and provide an argument elucidating the benefits of IMA-based regularization.
Global and Local Bounds on the Fundamental Ratio of Triangles and Quadrilaterals

We present a new, computer-assisted, proof that for all triangles in the plane, the equilateral triangle uniquely maximizes the ratio of the first two Dirichlet-Laplacian eigenvalues. This proves an independent proof the triangular Ashbaugh-Benguria-Payne-Polya-Weinberger conjecture first proved in arXiv:0707.3631 [math.SP] and arXiv:2009.00927 [math.SP]. Inspired by arXiv:1109.4117 [math.SP], the primary method is to use a perturbative estimate to determine a local optimum, and to then use a continuity estimate for the fundamental ratio to perform a rigorous computational search of parameter space. We repeat a portion of this proof to show that the square is a strict local optimizer of the fundamental ratio among quadrilaterals in the plane
Are Non-animal Systemic Safety Assessments Protective? A Toolbox and Workflow

Abstract An important question in toxicological risk assessment is whether non-animal new approach methodologies (NAMs) can be used to make safety decisions that are protective of human health, without being overly conservative. In this work, we propose a core NAM toolbox and workflow for conducting systemic safety assessments for adult consumers. We also present an approach for evaluating how protective and useful the toolbox and workflow are by benchmarking against historical safety decisions. The toolbox includes physiologically based kinetic (PBK) models to estimate systemic Cmax levels in humans, and 3 bioactivity platforms, comprising high-throughput transcriptomics, a cell stress panel, and in vitro pharmacological profiling, from which points of departure are estimated. A Bayesian model was developed to quantify the uncertainty in the Cmax estimates depending on how the PBK models were parameterized. The feasibility of the evaluation approach was tested using 24 exposure scenarios from 10 chemicals, some of which would be considered high risk from a consumer goods perspective (eg, drugs that are systemically bioactive) and some low risk (eg, existing food or cosmetic ingredients). Using novel protectiveness and utility metrics, it was shown that up to 69% (9/13) of the low risk scenarios could be identified as such using the toolbox, whilst being protective against all (5/5) the high-risk ones. The results demonstrated how robust safety decisions could be made without using animal data. This work will enable a full evaluation to assess how protective and useful the toolbox and workflow are across a broader range of chemical-exposure scenarios.