bluuebunny/crossref_metadata_2025_split huggingface dataset:
The potential of artificial intelligence-based applications in kidney pathology
Authors: Büllow Roman D. , Marsh Jon N. , Swamidass S. Joshua , Gaut Joseph P. , Boor Peter 
Published: February 2022

Purpose of review
The field of pathology is currently undergoing a significant transformation from traditional glass slides to a digital format dependent on whole slide imaging. Transitioning from glass to digital has opened the field to development and application of image analysis technology, commonly deep learning methods (artificial intelligence [AI]) to assist pathologists with tissue examination. Nephropathology is poised to leverage this technology to improve precision, accuracy, and efficiency in clinical practice.

Recent findings
Through a multidisciplinary approach, nephropathologists, and computer scientists have made significant recent advances in developing AI technology to identify histological structures within whole slide images (segmentation), quantification of histologic structures, prediction of clinical outcomes, and classifying disease. Virtual staining of tissue and automation of electron microscopy imaging are emerging applications with particular significance for nephropathology.

Summary
AI applied to image analysis in nephropathology has potential to transform the field by improving diagnostic accuracy and reproducibility, efficiency, and prognostic power. Reimbursement, demonstration of clinical utility, and seamless workflow integration are essential to widespread adoption.
Bacterial diarrhoea
Authors: Kotloff Karen L. 
Published: February 2022

Purpose of review
This review describes recent findings about the burden of bacterial diarrhoea and its potential complications, newer diagnostics, the emerging threat of multidrug resistance, and the promise of vaccines in development.

Recent findings
Introduction of rotavirus vaccines in over 110 countries has changed the landscape of diarrheal pathogens. In upper middle and high-income countries, the incidence of rotavirus-specific and all-cause gastroenteritis has declined substantially, and norovirus has become the major pathogen in many settings. Bacterial pathogens cause approximately 10–15% of episodes, most often Shigella, nontyphoidal Salmonella (NTS) Campylobacter and Shiga toxin-producing Escherichia coli (STEC). In lower income countries, bacterial pathogens remain a major cause of medically attended diarrhoea with Shigella, Campylobacter and enterotoxigenic Escherichia coli (ETEC) predominating. Multidrug-resistant strains of Shigella, NTS and, Campylobacter have emerged globally requiring judicious use of antibiotics according to current guidance.

Summary
Management of bacterial diarrhoea includes standard fluid and electrolyte therapy, vigilance for potential complications, and use of antibiotics for children who have moderate-severe illness due to pathogens for which efficacy has been demonstrated, or for those at high risk for severe disease. The threat of multiply resistant strains provides impetus for preventive strategies such as development of vaccines.
Surgical management of complex neonatal airway abnormalities
Authors: Tuliszewski Robert M. , Brigger Matthew T. 
Published: February 2022

Purpose of review
The neonatal airway is subject to a variety of developmental abnormalities with a wide range of complexity. Symptomatic pathologies present in a spectrum ranging from simple noisy breathing or poor feeding to frank respiratory distress. Diagnosis requires a high index of suspicion, characterization of noisy breathing, and identification of obstructive symptoms such as increased work of breathing, retractions, and difficulty feeding. Surgical management is directed by the pathology.

Recent findings
The past several years have seen an expansion of surgical innovation as endoscopic and open techniques have evolved. We reviewed articles related to neonatal and infant airway diagnoses since 2020 with the goal of providing a current review and update of developing techniques. Specifically, we discuss some of the exciting trends in surgical management of vocal fold paralysis, laryngeal clefts, subglottic stenosis, tracheobronchomalacia as well as the role of ex utero intrapartum therapy (EXIT procedures).

Summary
An underlying theme in evolving surgical management is the exciting advancements in technology, including 3-D printing, and expansion of minimally invasive endoscopic techniques. Though some of these developments are in the initial stages of utilization, they may be potential sources to transform surgical management in the future.
Transplant in acute alcoholic hepatitis: a relative contraindication
Authors: Jakhete Neha , Abutaleb Ameer , Shetty Kirti 
Published: February 2022

Purpose of review
The aim of this review is to provide a critical analysis of liver transplantation for alcoholic hepatitis, with an emphasis on barriers to long-term success in current implementation strategies across the United States.

Recent findings
Alcohol-associated liver disease is the most rapidly increasing indication for liver transplantation in the USA. Its most severe form, acute alcoholic hepatitis, has a rising incidence particularly in the young, and is associated with a high mortality risk. Although excellent outcomes following liver transplantation for alcoholic hepatitis can be achieved, several barriers limit its routine use. These constraints include risk of allograft dysfunction, the recognition of alcohol use disorder as a multisystem disease and ethical considerations.

Summary
Although liver transplantation is an important option in a carefully selected group of candidates, it should not be considered the standard of care in this condition. Consistency, transparency and consensus are necessary to formulate and implement policy changes at the national level. Following liver transplantation, wraparound services are important for relapse prevention, and to ensure long-term success and survival in this challenging group of patients.
Interleukin-17A is associated with flow-mediated dilation and interleukin-4 with carotid plaque in persons with HIV
Authors: Wanjalla Celestine N. , Temu Tecla M. , Mashayekhi Mona , Warren Christian M. , Shepherd Bryan E. , Gangula Rama , Fuseini Hubaida , Bailin Samuel , Gabriel Curtis L. , Gangula Pandu , Madhur Meena S. , Kalams Spyros , Mallal Simon A. , Harrison David G. , Beckman Joshua A. , Koethe John R. 
Published: February 2022

Objective:
Chronic inflammation contributes to the high burden of cardiovascular disease (CVD) in persons with HIV (PWH). HIV has broad effects on innate and adaptive immune cells, including innate lymphoid cells (ILCs) and CD4+ T-helper cells. At present, the relationship between CVD and plasma cytokines reflecting ILC/T-helper responses in PWH is not well defined. We investigated relationships between plasma cytokines and subclinical atherosclerosis.

Design:
A cross-sectional study.

Methods:
We recruited 70 PWH on a single antiretroviral regimen (efavirenz, teno- fovir, and emtricitabine) with at least 12 months of suppressed viremia and 30 HIVnegative controls. We quantified plasma cytokines and chemokines, including inter- feron-g, interleukin (IL)-4, IL-13, and IL-17A, markers of macrophage activation, and markers of endothelial activation using multiplex assays and ELISA. Cytokines were grouped using Ward's hierarchical clustering. Brachial artery flow-mediated dilation (FMD) and carotid plaque burden were determined using ultrasound. Multivariable linear regression and negative binomial regression analyses were used to assess the relationships of plasma biomarkers and endpoints adjusted for CVD risk factors.

Results:
We identified three distinct clusters in PWH, one containing Th1/Th2/ILC1/ ILC2 type cytokines, one with Th17/ILC3/macrophage-related cytokines, and a less specific third cluster. Lower FMD was associated with higher plasma IL-17A and macrophage inflammatory protein-1 a. In contrast, IL-4, a Th2/ILC2 type cytokine, was associated with carotid plaque. When HIV-negative controls were added to the models clustering was more diffuse, and these associations were attenuated or absent.

Conclusion:
Th17/ILC3 and Th2/ILC2-mediated immune mechanisms may have distinct roles in endothelial dysfunction and atherosclerotic plaque formation, respectively, in PWH.
Perioperative Renin–Angiotensin System Inhibitors Improve Major Outcomes of Heart Failure Patients Undergoing Cardiac Surgery
Authors: Zhang Yan-Qing , Liu Xiao-Gang , Ding Qian , Berguson Mark , Morris Rohinton J. , Liu Hong , Goldhammer Jordan E. 
Published: February 2022

Objective:
The aim of this study was to study the association of perioperative administration of renin angiotensin system inhibitors (RASi) and clinical outcomes of patients with heart failure (HF) undergoing cardiac surgery.

Summary Background Data:
It is controversial whether the perioperative RASi should be administered in HF patients undergoing cardiac surgery.

Methods:
A total of 2338 patients with HF and undergoing CABG and/or valve surgeries at multiple hospitals from 2001 to 2015 were identified from STS database. After adjustment using propensity score and instrumental variable, logistic regression was conducted to analyze the influence of preoperative continuation of RASi (PreRASi) on short-term in-hospital outcomes. Independent risk factors of 30-day mortality, major adverse cardiovascular events (MACE), and renal failure were analyzed by use of stepwise logistic regression. The effects of pre- and postoperative use of RASi (PostRASi) on long-term mortality were analyzed using survival analyses. Stepwise Cox regression was conducted to analyze the independent risk factors of 6-year mortality. The relationships of HF status and surgery type with perioperative RASi, as well as PreRASi-PostRASi, were also evaluated by subgroup analyses.

Results:
PreRASi was associated with lower incidences of 30-day mortality [P < 0.0001, odds ratio (OR): 0.556, 95% confidence interval (CI) 0.405−0.763], stroke (P =0.035, OR: 0.585, 95% CI: 0.355−0.962), renal failure (P =0.007, OR: 0.663, 95% CI: 0.493–0.894). Both PreRASi (P =0.0137) and PostRASi (P =0.007) reduced 6-year mortality compared with the No-RASi groups.

Conclusions:
Pre- and postoperative use of RASi was associated with better outcomes for the patients who have HF and undergo CABG and/or valve surgeries. Preoperative continuation and postoperative restoration are warranted in these patients.
A Nationwide Prospective Clinical Trial on Active Surveillance in Patients With Non-intraabdominal Desmoid-type Fibromatosis
Authors: Schut Anne-Rose W. , Timbergen Milea J. M. , van Broekhoven Danique L. M. , van Dalen Thijs , van Houdt Winan J. , Bonenkamp Johannes J. , Sleijfer Stefan , Grunhagen Dirk J. , Verhoef Cornelis 
Published: February 2022

Objective:
To assess tumor behavior and the efficacy of active surveillance (AS) in patients with desmoid-type fibromatosis (DTF).

Summary of Background Data:
AS is recommended as initial management for DTF patients. Prospective data regarding the results of AS are lacking.

Methods:
In this multicenter prospective cohort study (NTR4714), adult patients with non-intraabdominal DTF were followed during an initial AS approach for 3 years. Tumor behavior was evaluated according to Response Evaluation Criteria in Solid Tumors. Cumulative incidence of the start of an active treatment and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Factors predictive for start of active treatment were assessed by Cox regression analyses.

Results:
A total of 105 patients started with AS. Median tumor size at baseline was 4.1cm (interquartile range 3.0–6.6). Fifty-seven patients had a T41A CTNNB1 mutation; 14 patients a S45F CTNNB1 mutation. At 3 years, cumulative incidence of the start of active treatment was 30% (95% confidence interval [CI] 21–39) and PFS was 58% (95% CI 49–69). Median time to start active treatment and PFS were not reached at a median follow-up of 33.7 months. During AS, 32% of patients had stable disease, 28% regressed, and 40% demonstrated initial progression. Larger tumor size (≥5 cm; hazard ratio = 2.38 [95% CI 1.15–4.90]) and S45F mutation (hazard ratio = 6.24 [95% CI 1.92–20.30]) were associated with the start of active treatment.

Conclusions:
The majority DTF patients undergoing AS do not need an active treatment and experience stable or regressive disease, even after initial progression. Knowledge about the natural behavior of DTF will help to tailor the follow-up schedule to the individual patient.
Sabulibacter ruber gen. nov., sp. nov., a novel bacterium in the family Hymenobacteraceae, isolated from desert soil
Authors: Lian Wen-Hui , Li Shuai , Lin Zhi-Liang , Han Jia-Rui , Mohamad Osama Abdalla Abdelshafy , Li Li , Lin Ying , Hozzein Wael N. , Dong Lei , Li Wen-Jun 
Published: February 2022

A novel Gram-stain-negative, aerobic, oxidase-positive, catalase-positive, non-motile, short rod-shaped, red-pigmented strain, designated as SYSU D00434T, was isolated from a dry sandy soil sample collected from the Gurbantunggut desert in Xinjiang, north-west PR China. Strain SYSU D00434T was found to grow at 4–37 °C (optimum, 28–30 °C), pH 6.0–8.0 (optimum, pH 7.0) and with 0–1.5 % (w/v) NaCl (optimum, 0–0.5 %). The predominant respiratory quinone was MK-7 and the major fatty acids (>10 %) were C16 : 1
ω5c, iso-C15 : 0, summed feature 3 (C16 : 1
ω6c and/or C16 : 1
ω7c) and summed feature 4 (anteiso-C17 : 1 B and/or iso-C17 : 1 I). The polar lipids consisted of phosphatidylethanolamine, two unidentified polar lipids, two unidentified aminolipids, two unidentified phospholipids and two unidentified glycolipids. The genomic DNA G+C content of strain SYSU D00434T was 50.6 mol%. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain SYSU D00434T belonged to the family

Hymenobacteraceae

, and shared a sequence similarity of less than 94.6 % to all validly named taxa. Based on the phenotypic, phylogenetic and chemotaxonomic properties, strain D00434T is proposed to represent a new species of a new genus, named Sabulibacter ruber gen. nov., sp. nov., within the family

Hymenobacteraceae

. The type strain is SYSU D00434T (=CGMCC 1.18624T=KCTC 82276T=MCCC 1K04975T).
A Novel de novo TP63 Mutation in Whole Exome Sequencing of a Syrian Family with Oral Cleft and Ectrodactyly
Authors: Simpson Claire L. , Kimble Danielle C. , Chandrasekharappa Settara C. ,   NISC Comparative Sequencing Program, Alqosayer Khalid , Holzinger Emily , Carrington Blake , McElderry John , Sood Raman , Al-Souqi Ghaith , Albacha-Hejazi Hasan , Bailey-Wilson Joan E. 
Published: February 2022

Oral clefts and ectrodactyly are common, heterogeneous birth defects. We performed whole exome sequencing (WES) analysis in a Syrian family. The proband presented with both orofacial clefting and ectrodactyly. A paternal side second-degree relative with only an oral cleft was deceased and unavailable for analysis. Variant annotation, Mendelian inconsistencies, and novel variants in known cleft genes were examined. Candidate variants were validated using Sanger sequencing. Twentyeight candidate de novo events were identified, one of which is in a known oral cleft and ectrodactyly gene, TP63 (c.956G>T, p.Arg319Leu), and confirmed by Sanger sequencing. A triallelic SNV was also found in HLA-DRB5, which is similar to and overlaps the known oral cleft gene HLA-DRB1.TP63 mutations are associated with multiple autosomal dominant orofacial clefting and limb malformation disorders. The p.Arg319Leu mutation seen in this patient is de novo but also novel. A known mutation 1bp upstream (rs121908839, c.955C>T, p.Arg319Cys) causes ectrodactyly, providing evidence that mutating this codon is deleterious. It is unclear whether this patient’s mutation is responsible for the entire phenotype. Generation and characterization of tp63 knockout zebrafish showed necrosis and rupture of the head at 3 days postfertilization. The embryonic phenotype could not be rescued by injection of zebrafish or human mRNA. Further functional analysis is needed to determine what proportion of the phenotype is due to this mutation.
Direct and indirect mortality impacts of the COVID-19 pandemic in the US, March 2020-April 2021
Authors: Lee Wha-Eum , Park Sang Woo , Weinberger Daniel M , Olson Donald , Simonsen Lone , Grenfell Bryan T. , Viboud Cécile 
Published: February 2022

AbstractExcess mortality studies provide crucial information regarding the health burden of pandemics and other large-scale events. Here, we used time series approaches to separate the direct contribution of SARS-CoV-2 infections on mortality from the indirect consequences of pandemic interventions and behavior changes in the United States. We estimated deaths occurring in excess of seasonal baselines stratified by state, age, week and cause (all causes, COVID-19 and respiratory diseases, Alzheimer’s disease, cancer, cerebrovascular disease, diabetes, heart disease, and external causes, including suicides, opioids, accidents) from March 1, 2020 to April 30, 2021. Our estimates of COVID-19 excess deaths were highly correlated with SARS-CoV-2 serology, lending support to our approach. Over the study period, we estimate an excess of 666,000 (95% Confidence Interval (CI) 556000, 774000) all-cause deaths, of which 90% could be attributed to the direct impact of SARS-CoV-2 infection, and 78% were reflected in official COVID-19 statistics. Mortality from all disease conditions rose during the pandemic, except for cancer. The largest direct impacts of the pandemic were seen in mortality from diabetes, Alzheimer’s, and heart diseases, and in age groups over 65 years. In contrast, the largest indirect consequences of the pandemic were seen in deaths from external causes, which increased by 45,300 (95% CI 30,800, 59,500) and were statistically linked to the intensity of non-pharmaceutical interventions. Within this category, increases were most pronounced in mortality from accidents and injuries, drug overdoses, and assaults and homicides, while the rate of death from suicides remained stable. Younger age groups suffered the brunt of these indirect effects. Overall, on a national scale, the largest consequences of the COVID-19 pandemic are attributable to the direct impact of SARS-CoV-2 infections; yet, the secondary impacts dominate among younger age groups, in periods of stricter interventions, and in mortality from external causes. Further research on the drivers of indirect mortality is warranted to optimize interventions in future pandemics.
Quantifying the economic impact of Peristenus relictus establishment on host Lygus hesperus populations in California organic strawberry
Authors: Nieto Diego J. , Bick Emily , Pickett Charles H. 
Published: February 2022

AbstractLygus hesperus is a key pest in California-grown strawberries, in part because it lacks specialized natural enemies. In response, the specialist European nymphal parasitoid Peristenus relictus was released, and subsequently established, along the California Central Coast. A simulation model, based on field-collected L. hesperus immigration rates and 16 years of parasitism data, compared simulated pest populations with and without parasitism by P. relictus. After 10 years, L. hesperus population reductions exceeded 95% in weeds and alfalfa, and 70% in strawberry. These simulated results were in agreement with field-based P. relictus longitudinal studies. The averted value loss associated with L. hesperus, due to the establishment of P. relictus, is estimated at $1,901 per acre in organic strawberry.
Development of methylation-based biomarkers for breast cancer detection by model training and validation in synthetic cell-free DNA
Authors: de Procé Sophie Marion , Adamowicz Martyna , Dutta Prasun , Warlow Sophie J. , Moss Joshua , Shemer Ruth , Dor Yuval , Robert Christelle , Aitman Timothy J. 
Published: February 2022

AbstractCirculating tumour-derived DNA (ctDNA) carries the genetic and epigenetic characteristics of the tumour from which it is derived and can give information about the biology and tissue origins of the underlying tumour. DNA methylation is an epigenetic mark that is specific to individual tissues and, as methylation profiles are disrupted in tumours, they can indicate the tissue of origin and cancer type of ctDNA. We have developed a set of methylation biomarkers for detecting breast cancer in plasma cell-free DNA (cfDNA). First, we mined publicly available methylation datasets to create synthetic methylation profiles that were modelled to reflect cfDNA from healthy subjects and cancer patients. These profiles were restricted to the most differentially methylated CpGs between breast tumour samples and haematopoietic cells. Regularised logistic regression models were trained using 10-fold cross-validation on synthetic cfDNA datasets with distinct fractions of breast tumour DNA spiked in silico into healthy cfDNA with the addition of 10% of a mix of different tissues. Initial validation with synthetic cfDNA permitted detection of breast cancer-derived DNA with as little as 0.25% tumour DNA spiked in silico into healthy subject cfDNA with an area under ROC curve (AUC) of 0.63. Performances of classifiers increased with increased fractions of spike-in tumour DNA (AUCs 0.77 and 0.93 at tumour DNA fractions 0.5% and 1% respectively). We then combined the most discriminative CpG markers from our models with methylation markers of breast cancer that had already been published to obtain a single marker set. In vitro testing of MCF-7 breast cancer cell line DNA spiked into leukocyte DNA showed highly significant correlation for individual markers between laboratory-measured and published methylation data for MCF-7 and leukocytes (R > 0.89, P < 2.2 × 10−16). These preliminary data indicate promising results for detection of breast cancer cell line DNA using this methylation marker set, which now require testing in cfDNA from breast cancer patients and healthy controls.
A novel consensus-based computational pipeline for rapid screening of antibody therapeutics for efficacy against SARS-CoV-2 variants of concern including omicron variant
Authors: Kumar Naveen , Kaushik Rahul , Zhang Kam Y. J. , Uversky Vladimir N. , Srivastava Pratiksha , Sahu Upasana , Sood Richa , Bhatia Sandeep 
Published: February 2022

AbstractMultiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to evolve carrying flexible amino acid substitutions in the spike protein’s receptor binding domain (RBD). These substitutions modify the binding of the SARS-CoV-2 to human angiotensin-converting enzyme 2 (hACE2) receptor and have been implicated in altered host fitness, transmissibility and efficacy against antibody therapeutics and vaccines. Reliably predicting the binding strength of SARS-CoV-2 variants RBD to hACE2 receptor and neutralizing antibodies (NAbs) can help assessing their fitness, and rapid deployment of effective antibody therapeutics, respectively. Here, we introduced a two-step computational framework with three-fold validation that first identified dissociation constant as a reliable predictor of binding affinity in hetero-dimeric and –trimeric protein complexes. The second step implements dissociation constant as descriptor of the binding strengths of SARS-CoV-2 variants RBD to hACE2 and NAbs. Then, we examined several variants of concern (VOCs) such as Alpha, Beta, Gamma, Delta, and Omicron and demonstrated that these VOCs RBD bind to the hACE2 with enhanced affinity. Furthermore, the binding affinity of Omicron variant’s RBD was reduced with majority of the RBD-directed NAbs, which is highly consistent with the experimental neutralization data. By studying the atomic contacts between RBD and NAbs, we revealed the molecular footprints of four NAbs (GH-12, P2B-1A1, Asarnow_3D11, and C118) — that may likely neutralize the recently emerged omicron variant — facilitating enhanced binding affinity. Finally, our findings suggest a computational pathway that could aid researchers identify a range of current NAbs that may be effective against emerging SARS-CoV-2 variants.