bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimal adjustment sets for causal query estimation in partially observed biomolecular networks
Authors: Mohammad-Taheri Sara , Tewari Vartika , Kapre Rohan , Rahiminasab Ehsan , Sachs Karen , Tapley Hoyt Charles , Zucker Jeremy , Vitek Olga 
Published: June 2023

Abstract
Causal query estimation in biomolecular networks commonly selects a ‘valid adjustment set’, i.e. a subset of network variables that eliminates the bias of the estimator. A same query may have multiple valid adjustment sets, each with a different variance. When networks are partially observed, current methods use graph-based criteria to find an adjustment set that minimizes asymptotic variance. Unfortunately, many models that share the same graph topology, and therefore same functional dependencies, may differ in the processes that generate the observational data. In these cases, the topology-based criteria fail to distinguish the variances of the adjustment sets. This deficiency can lead to sub-optimal adjustment sets, and to miss-characterization of the effect of the intervention. We propose an approach for deriving ‘optimal adjustment sets’ that takes into account the nature of the data, bias and finite-sample variance of the estimator, and cost. It empirically learns the data generating processes from historical experimental data, and characterizes the properties of the estimators by simulation. We demonstrate the utility of the proposed approach in four biomolecular Case studies with different topologies and different data generation processes. The implementation and reproducible Case studies are at https://github.com/srtaheri/OptimalAdjustmentSet.
An intrinsically interpretable neural network architecture for sequence-to-function learning
Authors: Balcı Ali Tuğrul , Ebeid Mark Maher , Benos Panayiotis V , Kostka Dennis , Chikina Maria 
Published: June 2023

Abstract

Motivation
Sequence-based deep learning approaches have been shown to predict a multitude of functional genomic readouts, including regions of open chromatin and RNA expression of genes. However, a major limitation of current methods is that model interpretation relies on computationally demanding post hoc analyses, and even then, one can often not explain the internal mechanics of highly parameterized models. Here, we introduce a deep learning architecture called totally interpretable sequence-to-function model (tiSFM). tiSFM improves upon the performance of standard multilayer convolutional models while using fewer parameters. Additionally, while tiSFM is itself technically a multilayer neural network, internal model parameters are intrinsically interpretable in terms of relevant sequence motifs.

Results
We analyze published open chromatin measurements across hematopoietic lineage cell-types and demonstrate that tiSFM outperforms a state-of-the-art convolutional neural network model custom-tailored to this dataset. We also show that it correctly identifies context-specific activities of transcription factors with known roles in hematopoietic differentiation, including Pax5 and Ebf1 for B-cells, and Rorc for innate lymphoid cells. tiSFM’s model parameters have biologically meaningful interpretations, and we show the utility of our approach on a complex task of predicting the change in epigenetic state as a function of developmental transition.

Availability and implementation
The source code, including scripts for the analysis of key findings, can be found at https://github.com/boooooogey/ATAConv, implemented in Python.
Chromothripsis detection with multiple myeloma patients based on deep graph learning
Authors: Yu Jixiang , Chen Nanjun , Zheng Zetian , Gao Ming , Liang Ning , Wong Ka-Chun 
Published: June 2023

Abstract

Motivation
Chromothripsis, associated with poor clinical outcomes, is prognostically vital in multiple myeloma. The catastrophic event is reported to be detectable prior to the progression of multiple myeloma. As a result, chromothripsis detection can contribute to risk estimation and early treatment guidelines for multiple myeloma patients. However, manual diagnosis remains the gold standard approach to detect chromothripsis events with the whole-genome sequencing technology to retrieve both copy number variation (CNV) and structural variation data. Meanwhile, CNV data are much easier to obtain than structural variation data. Hence, in order to reduce the reliance on human experts’ efforts and structural variation data extraction, it is necessary to establish a reliable and accurate chromothripsis detection method based on CNV data.

Results
To address those issues, we propose a method to detect chromothripsis solely based on CNV data. With the help of structure learning, the intrinsic relationship-directed acyclic graph of CNV features is inferred to derive a CNV embedding graph (i.e. CNV-DAG). Subsequently, a neural network based on Graph Transformer, local feature extraction, and non-linear feature interaction, is proposed with the embedding graph as the input to distinguish whether the chromothripsis event occurs. Ablation experiments, clustering, and feature importance analysis are also conducted to enable the proposed model to be explained by capturing mechanistic insights.

Availability and implementation
The source code and data are freely available at https://github.com/luvyfdawnYu/CNV_chromothripsis.
Floral morphology and development of Epimedium pubescens and Plagiorhegma dubium (Berberidaceae) and their systematic significance
Authors: Zhang Yu , Gong Jing-Zhi , Gui Chao-Xia , Xie Si-Yu , Yang Zhao-Ping , Luo Min-Rong , Ning Sui-Xia , Chang Zhao-Yang , Kang Bing , Zhao Liang , De Craene Louis Ronse 
Published: June 2023

Abstract
Epimedium and Plagiorhegma are the representatives of two early-diverging clades in Podophylloideae of Berberidaceae. Flowers are dimerous and trimerous respectively, but their floral development is little known. Here, we used scanning electron microscopy to clarify the structure and development of flower and inflorescence in Epimedium pubescens and Plagiorhegma dubium and compared these with other Berberidaceae to better understand floral evolution within the family. Our results show that the two genera share some significant features. The petal and stamen primordia emerge independently. The carpel is ascidiate from the earliest stages of development. The ovule is anatropous and bitegmic. However, E. pubescens has a paniculate inflorescence, while a lateral floral bud is initiated but aborted in P. dubium. In E. pubescens, both inner sepals and petals are delayed compared with other organs (vs. delay in petal development only for P. dubium). Petals of E. pubescens have a nectariferous spur (vs. no nectariferous tissue for P. dubium). The style of E. pubescens is long with a flat stigma (vs. short with trumpet-shaped stigma for P. dubium). These differences suggest that Epimedium and Plagiorhegma may not be closely related and support placing them separately in two clades of Podophylloideae, complementing results from molecular studies.
A mobile APP-based, customizable automated device for self-administered olfactory testing and an implementation of smell identification test
Authors: Lan Zhihao , Yang Qing X , Lyu Zhi-hong , Feng Cailing , Wang Liansheng , Ji Baowei , Yu Xuefei , Xin Sherman Xuegang 
Published: June 2023

Abstract
Olfactory tests are used for the evaluation of ability to detect and identify common odors in humans psychophysically. Olfactory tests are currently administered by professionals with a set of given odorants. Manual administration of such tests can be labor and cost intensive and data collected as such are confounded with experimental variables, which adds personnel costs and introduces potential errors and data variability. For large-scale and longitudinal studies, manually recorded data must be collected and compiled from multiple sites. It is difficult to standardize the way data are collected and recorded. There is a need for a computerized smell test system for psychophysical and clinical applications. A mobile digital olfactory testing system (DOTS) was developed, consisting of an odor delivery system (DOTS-ODD) and a mobile application program (DOTS-APP) connected wirelessly. The University of Pennsylvania Smell Identification Test was implemented in DOTS and compared to its commercial product on a cohort of 80 normosmic subjects and a clinical cohort of 12 Parkinson’s disease patients. A test–retest was conducted on 29 subjects of the normal cohort. The smell identification scores obtained from the DOTS and standard UPSIT commercial test are highly correlated (r = 0.714, P &lt; 0.001), and test–retest reliability coefficient was 0.807 (r = 0.807, P &lt; 0.001). The DOTS is customizable and mobile compatible, which allows for the implementation of standardized olfactory tests and the customization of investigators’ experimental paradigms. The DOTS-APP on mobile devices offers capabilities for a broad range of on-site, online, or remote clinical and scientific chemosensory applications.
Active Surveillance and Contact Precautions for Preventing Methicillin-Resistant Staphylococcus aureus Healthcare-Associated Infections During the COVID-19 Pandemic
Authors: Evans Martin E , Simbartl Loretta A , McCauley Brian P , Flarida Linda K , Jones Makoto M , Harris Anthony D , Perencevich Eli N , Rubin Michael A , Hicks Natalie R , Kralovic Stephen M , Roselle Gary A 
Published: June 2023

Abstract

Background
Statistically significant decreases in methicillin-resistant Staphylococcus aureus (MRSA) healthcare-associated infections (HAIs) occurred in Veterans Affairs (VA) hospitals from 2007 to 2019 using a national policy of active surveillance (AS) for facility admissions and contact precautions for MRSA colonized (CPC) or infected (CPI) patients, but the impact of suspending these measures to free up laboratory resources for testing and conserve personal protective equipment for coronavirus disease 2019 (COVID-19) on MRSA HAI rates is not known.

Methods
From July 2020 to June 2022 all 123 acute care VA hospitals nationwide were given the rolling option to suspend (or re-initiate) any combination of AS, CPC, or CPI each month, and MRSA HAIs in intensive care units (ICUs) and non-ICUs were tracked.

Results
There were 917 591 admissions, 5 225 174 patient-days, and 568 MRSA HAIs. The MRSA HAI rate/1000 patient-days in ICUs was 0.20 (95% confidence interval [CI], .15–.26) for facilities practicing “AS + CPC + CPI” compared to 0.65 (95% CI, .41–.98; P &lt; .001) for those not practicing any of these strategies, and in non-ICUs was 0.07 (95% CI, .05–.08) and 0.12 (95% CI, .08–.19; P = .01) for the respective policies. Accounting for monthly COVID-19 facility admissions using a negative binomial regression model did not change the relationships between facility policy and MRSA HAI rates. There was no significant difference in monthly facility urinary catheter-associated infection rates, a non-equivalent dependent variable, in the policy categories in either ICUs or non-ICUs.

Conclusions
Facility removal of MRSA prevention practices was associated with higher rates of MRSA HAIs in ICUs and non-ICUs.
Opportunities to improve the management of anemia in peritoneal dialysis patients: lessons from a national study in routine clinical practice
Authors: Portoles Jose , Serrano Salazar Maria Luisa , González Peña Olga , Gallego Domínguez Sandra , Vera Rivera Manel , Caro Espada Jara , Herreros García Alba , Munar Vila Maria Antonia , José Espigares Huete Maria , Sosa Barrios Haridian , Paraíso Vicente , Mariscal de Gante Loreto , Bajo Maria Auxiliadora , Mijaylova Antonia Gueorguieva , Pascual Pajares Elena , Areste Fosalba Nuria , Espinel Laura , Tornero Molina Fernando , Pizarro Sánchez Soledad , Ortega Díaz Mayra , Cases Aleix , Quiroga Borja 
Published: June 2023

ABSTRACT

Background
Current guidelines establish the same hemoglobin (Hb) and iron biomarkers targets for hemodialysis (HD) and peritoneal dialysis (PD) in patients receiving erythropoiesis-stimulating agents (ESAs) even though patients having PD are usually younger, more active and less comorbid. Unfortunately, specific renal anemia [anemia in chronic kidney disease (aCKD)] trials or observational studies on PD are scanty. The aims of this study were to describe current aCKD management, goals and adherence to clinical guidelines, identifying opportunities for healthcare improvement in PD patients.

Methods
This was a retrospective, nationwide, multicentre study including patients from 19 PD units. The nephrologists collected baseline data, demographics, comorbidities and data related to anemia management (laboratory values, previously prescribed treatments and subsequent adjustments) from electronic medical records. The European adaptation of KDIGO guidelines was the reference for definitions, drug prescriptions and targets.

Results
A total of 343 patients (mean age 62.9 years, 61.2% male) were included; 72.9% were receiving ESAs and 33.2% iron therapy [20.7% intravenously (IV)]. Eighty-two patients were receiving ESA without iron therapy, despite 53 of them having an indication according to the European Renal Best Practice guidelines. After laboratory results, iron therapy was only started in 15% of patients. Among ESA-treated patients, 51.9% had an optimal control [hemoglobin (Hb) 10–12 g/dL] and 28.3% between 12–12.9 g/dL. Seventeen patients achieved Hb &gt;13 g/dL, and 12 of them remained on ESA after overshooting. Only three patients had Hb &lt;10 g/dL without ESAs. Seven patients (2%) met criteria for ESA resistance (epoetin dose &gt;300 IU/kg/week). The highest tertile of erythropoietin resistance index (&gt;6.3 UI/kg/week/g/dL) was associated with iron deficiency and low albumin corrected by renal replacement therapy vintage and hospital admissions in the previous 3 months.

Conclusion
Iron therapy continues to be underused (especially IV). Low albumin, iron deficiency and prior events explain most of the ESA hyporesponsiveness. Hb targets are titrated to/above the upper limits. Thus, several missed opportunities for adequate prescriptions and adherence to guidelines were identified.
Inferior vena cava ultrasound and other techniques for assessment of intravascular and extravascular volume: an update
Authors: Kaptein Elaine M , Kaptein Matthew J 
Published: June 2023

ABSTRACTGoals of volume management are to accurately assess intravascular and extravascular volume and predict response to volume administration, vasopressor support or volume removal.Data are reviewed that support the following:(i) Dynamic parameters reliably guide volume administration and may improve clinical outcomes compared with static parameters, but some are invasive or only validated with mechanical ventilation without spontaneous breathing.(ii) Ultrasound visualization of inferior vena cava (IVC) diameter variations with respiration reliably assesses intravascular volume and predicts volume responsiveness.(iii) Although physiology of IVC respiratory variations differs with mechanical ventilation and spontaneous breathing, the IVC collapsibility index (CI) and distensibility index are interconvertible.(iv) Prediction of volume responsiveness by IVC CI is comparable for mechanical ventilation and spontaneous breathing patients.(v) Respiratory variations of subclavian/proximal axillary and internal jugular veins by ultrasound are alternative sites, with comparable reliability.(vi) Data support clinical applicability of IVC CI to predict hypotension with anesthesia, guide ultrafiltration goals, predict dry weight, predict intra-dialytic hypotension and assess acute decompensated heart failure.(vii) IVC ultrasound may complement ultrasound of heart and lungs, and abdominal organs for venous congestion, for assessing and managing volume overload and deresuscitation, renal failure and shock.(viii) IVC ultrasound has limitations including inadequate visualization.Ultrasound data should always be interpreted in clinical context. Additional studies are required to further assess and validate the role of bedside ultrasonography in clinical care.
Pathogenesis and management of abdominal aortic aneurysm
Authors: Golledge Jonathan , Thanigaimani Shivshankar , Powell Janet T , Tsao Phil S 
Published: June 2023

Abstract
Abdominal aortic aneurysm (AAA) causes ∼170 000 deaths annually worldwide. Most guidelines recommend asymptomatic small AAAs (30 to &lt;50 mm in women; 30 to &lt;55 mm in men) are monitored by imaging and large asymptomatic, symptomatic, and ruptured AAAs are considered for surgical repair. Advances in AAA repair techniques have occurred, but a remaining priority is therapies to limit AAA growth and rupture. This review outlines research on AAA pathogenesis and therapies to limit AAA growth. Genome-wide association studies have identified novel drug targets, e.g. interleukin-6 blockade. Mendelian randomization analyses suggest that treatments to reduce low-density lipoprotein cholesterol such as proprotein convertase subtilisin/kexin type 9 inhibitors and smoking reduction or cessation are also treatment targets. Thirteen placebo-controlled randomized trials have tested whether a range of antibiotics, blood pressure–lowering drugs, a mast cell stabilizer, an anti-platelet drug, or fenofibrate slow AAA growth. None of these trials have shown convincing evidence of drug efficacy and have been limited by small sample sizes, limited drug adherence, poor participant retention, and over-optimistic AAA growth reduction targets. Data from some large observational cohorts suggest that blood pressure reduction, particularly by angiotensin-converting enzyme inhibitors, could limit aneurysm rupture, but this has not been evaluated in randomized trials. Some observational studies suggest metformin may limit AAA growth, and this is currently being tested in randomized trials. In conclusion, no drug therapy has been shown to convincingly limit AAA growth in randomized controlled trials. Further large prospective studies on other targets are needed.
Mechanisms of fever-induced QT prolongation and torsades de pointes in patients with KCNH2 mutation
Authors: Usuda Keisuke , Hayashi Kenshi , Nakajima Tadashi , Kurata Yasutaka , Cui Shihe , Kusayama Takashi , Tsuda Toyonobu , Tada Hayato , Kato Takeshi , Sakata Kenji , Usui Soichiro , Fujino Noboru , Tanaka Yoshihiro , Kaneko Yoshiaki , Kurabayashi Masahiko , Tange Shoichi , Saito Takekatsu , Ohta Kunio , Yamagishi Masakazu , Takamura Masayuki 
Published: June 2023

Abstract

Aims
Patients with particular mutations of type-2 long QT syndrome (LQT2) are at an increased risk for malignant arrhythmia during fever. This study aimed to determine the mechanism by which KCNH2 mutations cause fever-induced QT prolongation and torsades de pointes (TdP).

Methods and results
We evaluated three KCNH2 mutations, G584S, D609G, and T613M, in the Kv11.1 S5-pore region, identified in patients with marked QT prolongation and TdP during fever. We also evaluated KCNH2 M124T and R269W, which are not associated with fever-induced QT prolongation. We characterized the temperature-dependent changes in the electrophysiological properties of the mutant Kv11.1 channels by patch-clamp recording and computer simulation. The average tail current densities (TCDs) at 35°C for G584S, WT+D609G, and WT+T613M were significantly smaller and less increased with rising temperature from 35°C to 40°C than those for WT, M124T, and R269W. The ratios of the TCDs at 40°C to 35°C for G584S, WT+D609G, and WT+T613M were significantly smaller than for WT, M124T, and R269W. The voltage dependence of the steady-state inactivation curve for WT, M124T, and R269W showed a significant positive shift with increasing temperature; however, that for G584S, WT+D609G, and WT+T613M showed no significant change. Computer simulation demonstrated that G584S, WT+D609G, and WT+T613M caused prolonged action potential durations and early afterdepolarization formation at 40°C.

Conclusion
These findings indicate that KCNH2 G584S, D609G, and T613M in the S5-pore region reduce the temperature-dependent increase in TCDs through an enhanced inactivation, resulting in QT prolongation and TdP at a febrile state in patients with LQT2.
Trans-Acting Genotypes Associated with mRNA Expression Affect Metabolic and Thermal Tolerance Traits
Authors: Drown Melissa K , Oleksiak Marjorie F , Crawford Douglas L 
Published: June 2023

AbstractEvolutionary processes driving physiological trait variation depend on the underlying genomic mechanisms. Evolution of these mechanisms depends on the genetic complexity (involving many genes) and how gene expression impacting the traits is converted to phenotype. Yet, genomic mechanisms that impact physiological traits are diverse and context dependent (e.g., vary by environment and tissues), making them difficult to discern. We examine the relationships between genotype, mRNA expression, and physiological traits to discern the genetic complexity and whether the gene expression affecting the physiological traits is primarily cis- or trans-acting. We use low-coverage whole genome sequencing and heart- or brain-specific mRNA expression to identify polymorphisms directly associated with physiological traits and expressed quantitative trait loci (eQTL) indirectly associated with variation in six temperature specific physiological traits (standard metabolic rate, thermal tolerance, and four substrate specific cardiac metabolic rates). Focusing on a select set of mRNAs belonging to co-expression modules that explain up to 82% of temperature specific traits, we identified hundreds of significant eQTL for mRNA whose expression affects physiological traits. Surprisingly, most eQTL (97.4% for heart and 96.7% for brain) were trans-acting. This could be due to higher effect size of trans- versus cis-acting eQTL for mRNAs that are central to co-expression modules. That is, we may have enhanced the identification of trans-acting factors by looking for single nucleotide polymorphisms associated with mRNAs in co-expression modules that broadly influence gene expression patterns. Overall, these data indicate that the genomic mechanism driving physiological variation across environments is driven by trans-acting heart- or brain-specific mRNA expression.