bluuebunny/crossref_metadata_2025 huggingface dataset:
Anemia, Weight Status, and Fatigue Among Farmworkers in California
Authors: Olivares Leslie V. , Engle-Stone Reina , Arnold Charles D. , Langer Chelsea E. , Schenker Marc B.
Published: June 2022

Objective

This study aimed to determine the prevalence of anemia and overweight/obesity and assess the relationships between hematocrit (Hct) and body mass index (BMI), and between fatigue and Hct, among a sample of farmworkers in California.

Methods

We estimated the prevalence of anemia (using Hct), overweight/obesity (BMI ≥25 kg/m2), and self-reported fatigue in 587 farmworkers. Multivariable linear and logistic regression models were used to examine the associations between Hct and BMI, and between fatigue and Hct.

Results

Anemia prevalence was 3.1%, overweight/obesity prevalence was 80.7%, and 78% of workers reported fatigue at work. There was no association between Hct and BMI or between Hct and reported fatigue. Women were more likely than men to have lower Hct and higher BMI.

Conclusions

A majority of farmworkers in this sample were overweight/obese, but anemia was uncommon. Anemia among more vulnerable subgroups of farmworkers should be explored.
Papillary renal cell carcinoma: current and controversial issues
Authors: Angori Silvia , Lobo João , Moch Holger
Published: June 2022

Purpose of the review

Papillary renal cell carcinoma (pRCC) is the second most frequent renal cancer subtype and represents 15–20% of all RCC. Classification of pRCC is changing because novel tumour entities have been discovered in the last years. In this review, we summarise recent studies relevant for the understanding of the molecular complexity and the broader differential diagnosis of pRCC.

Recent findings

It has been 25 years ago, that pRCC was morphologically subdivided into type 1 and type 2. Recently described tumour entities in the 2022 WHO classification challenged this concept and allow a new view on the molecular background in pRCC. Biphasic hyalinizing psammomatous RCC and papillary renal neoplasm with reversed polarity are emerging tumour entities derived from the new concept of molecularly defined RCC subtypes. Immune checkpoint inhibition and tyrosine kinase inhibitors have been introduced as the new backbone in the first-line treatment of advanced pRCCs. To identify novel targeted treatments for patients with pRCC it is crucial to investigate the specific molecular background of pRCC considering emerging pRCC subtypes.

In the future, a deeper understanding of the correlation between molecular aberrations and new pRCC subtypes may improve the classification of pRCC patients and could reveal potential predictive biomarkers for each subgroup.
Advances in ureteral stent technology
Authors: Mawhorter Michael , Streeper Necole M.
Published: June 2022

Purpose of review

Ureteral stents are an invaluable tool for urologists but suffer from several drawbacks, including: limited durability due to stent encrustation, significant morbidity from bothersome urinary symptoms, pain and infection, risk of the forgotten stent and costly removal. This review highlights key advances in ureteral stent technology that seek to address these issues.

Recent findings

Over the past 2 years clinical trials have brought ureteral stent technology aimed to reduce stent-associated morbidity closer to clinical application. Stent material and changes to stent design show promise in improving patient tolerability without increasing complications. Low-tech innovations such as magnetic and catheter snare removal may quickly reduce costs. Radical advances such as biodegradable stent materials remain in preclinical models but show promise for eliminating the need for stent removal.

The ideal ureteral stent does not currently exist in clinical practice. This review highlights key studies that have advanced ureteral stent technology in the past 2 years.
Management of Gastroesophageal Reflux Disease in Esophageal Atresia Patients: A Cross-Sectional Survey amongst International Clinicians
Authors: van Lennep Marinde , Gottrand Frederic , Faure Christophe , Omari Taher I. , Benninga Marc A. , van Wijk Michiel P. , Krishnan Usha
Published: June 2022

Objectives:

After surgical repair, up to 70% of esophageal atresia (EA) patients suffer from gastroesophageal reflux disease (GERD). The ESPGHAN/NASPGHAN guidelines on management of gastrointestinal complications in EA patients were published in 2016. Yet, the implementation of recommendations on GERD management remains poor.

We aimed to assess GERD management in EA patients in more detail, to identify management inconsistencies, gaps in current knowledge, and future directions for research.

Methods:

A digital questionnaire on GERD management in EA patients was sent to all members of the ESPGHAN EA working group and members of the International network of esophageal atresia (INoEA).

Results:

Forty responses were received. Thirty-five (87.5%) clinicians routinely prescribed acid suppressive therapy for 1–24 (median 12) months. A fundoplication was considered by 90.0% of clinicians in case of refractory GERD with persistent symptoms despite maximal acid suppressive therapy and in 92.5% of clinicians in case of GERD with presence of esophagitis on EGD. Half of clinicians referred patients with recurrent strictures or dependence on transpyloric feeds. Up to 25.0% of clinicians also referred all long-gap EA patients for fundoplication, those with long-term need of acid suppressants, recurrent chest infections and feedings difficulties.

Conclusions:

Respondents’ opinions on the optimal duration for routine acid suppressive therapy and indications for fundoplication in EA patients varied widely. To improve evidence-based care for EA patients, future prospective multicenter outcome studies should compare different diagnostic and treatment regimes for GERD in patients with EA. Complications of therapy should be one of the main outcome measures in such trials.
Systematic Review and Guidelines for Perioperative Management of Pediatric Patients Undergoing Major Plastic Surgery Procedures, with a Focus on Free Tissue Transfer
Authors: Mountziaris Paschalia M. , Rudolph Christina M. , Fournier Craig T. , Haykal Siba , Ricci Joseph A. , Rezak Kristen M. , Patel Ashit
Published: June 2022

Background:

Microsurgical free tissue transfer has been successfully implemented for various reconstructive applications in children. The goal of this study was to identify the best available evidence on perioperative management of pediatric patients undergoing free tissue transfer and to use it to develop evidence-based care guidelines.

Methods:

A systematic review was conducted in the PubMed, Embase, Scopus, and Cochrane Library databases. Because a preliminary search of the pediatric microsurgical literature yielded scant data with a low level of evidence, pediatric anesthesia guidelines for healthy children undergoing major operations were also included. Exclusion criteria included vague descriptions of perioperative care, case reports, and studies of syndromic or chronically ill children.

Results:

Two hundred four articles were identified, and 53 met inclusion criteria. Management approaches specific to the pediatric population were used to formulate recommendations. High-quality data were found for anesthesia, analgesia, fluid administration/blood transfusion, and anticoagulation (Level I Evidence). Lower quality evidence was identified for patient temperature (Level III Evidence) and vasodilator use (Level IV Evidence). Key recommendations include administering sevoflurane for general anesthesia, implementing a multimodal analgesia strategy, limiting preoperative fasting, restricting blood transfusions until hemoglobin level is less than 7 g/dl unless the patient is symptomatic, and reserving chemical venous thromboembolism prophylaxis for high-risk patients.

Conclusions:

Pediatric-specific guidelines are important, as they acknowledge physiologic differences in children, which may be overlooked when extrapolating from adult studies. These evidence-based recommendations are a key first step toward standardization of perioperative care of pediatric patients undergoing plastic surgical procedures, including free tissue transfer, to improve outcomes and minimize complications.
Real-Time Assessment of Free Flap Capillary Circulation Using Videocapillaroscopy
Authors: Matsui Chihiro , Lao William W. , Tanaka Takakuni , Tsuji Nao , Matsui Yuki , Orgun Doruk , Sugawara Yasushi , Mizuno Hiroshi
Published: June 2022

Background:

Free tissue transfer is a common method of reconstruction for various surgical defects. Many clinical assessment methods, including flap color monitoring and capillary refill time measurements, are commonly used to assess the microcirculation of the flap, yet there is no objective tool available that can clear real-time visualization of the flap microcirculation. The purpose of this study was to use a novel videocapillaroscope to evaluate the circulation changes on free flap skin surfaces while purposely clamping pedicle vessels.

Methods:

Ten patients who underwent free flap transfer for head and neck cancer from November of 2019 to June of 2020 were included in the study. Videocapillaroscopic observation was performed after flap elevation, and changes in the flap skin capillary circulation with artery-controlled and vein-controlled clamping were recorded.

Results:

Average total surgery time was 517.91 minutes (SD, 73.3 minutes), average flap elevation time was 102.9 minutes (SD, 18.3 minutes). When the pedicle artery or vein was purposely clamped, the movement of red blood cells in blood vessels stopped; when clamps were removed after 60 seconds, the restoration of red blood cell movements was rapidly observed. When the pedicle artery was clamped, the number of visualizable blood vessels decreased and flap color became relatively white. When the pedicle vein was clamped, the number of visualizable blood vessels increased, and flap color tone had a tendency toward red.

Conclusion:

Novel videocapillaroscopy can be utilized for objective real-time flap monitoring by directly visualizing flap skin capillary microcirculation.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Is calcitonin gene-related peptide a reliable biochemical marker of migraine?
Authors: Tesfay Betel , Karlsson William Kristian , Moreno Rogelio Dominguez , Hay Debbie L. , Hougaard Anders
Published: June 2022

Purpose of review

The aim of this study was to provide an overview of clinical studies on calcitonin gene-related peptide (CGRP) measurements in body fluids of migraine patients and to discuss the validity of CGRP measurement as a clinical biomarker of migraine.

Recent findings

Several studies have reported increased CGRP levels in venous blood, saliva and tear fluid of migraine patients compared with healthy controls and in migraine patients during attacks compared with the interictal state, suggesting that CGRP may be a feasible biomarker of migraine. However, the findings of studies investigating CGRP levels in migraine patients are generally conflicting and measurements of CGRP levels are challenged by several methodological issues. Reported differences in CGRP levels between patients with chronic migraine relative to episodic migraine have also been inconsistent. There is also a well documented involvement of CGRP in several nonmigraine pain disorders, including cluster headache and common pain conditions such as osteoarthritis.

Current evidence does not justify the usage of CGRP levels as a biomarker for diagnosing migraine or for determining the severity of the disease in individual patients. However, CGRP measurements could prove useful in the future as clinically relevant biomarkers for predicting the response to therapy, including anti-CGRP migraine drugs.
From basic mechanisms to therapeutic perspectives in cluster headache
Authors: Moreno-Ajona David , Hoffmann Jan
Published: June 2022

Purpose of review

The pathophysiological understanding of cluster headache has evolved significantly over the past years. Although it is now well known that the trigeminovascular system, the parasympathetic system and the hypothalamus play important roles in its pathomechanism, we increasingly understand the functional role several neurotransmitters and hormones play in the communication between these structures.

Recent findings

This work will give an overview of the current understanding of the role of calcitonin gene-related peptide, vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, melatonin and orexins in cluster headache. On the basis of recent evidence, this study will also review the relevance of the monoclonal calcitonin gene-related peptide antibody galcanezumab as well as the sleep-regulating hormone melatonin in the treatment of cluster headache.

Herein, we aim to review the basic mechanisms implicated in the pathophysiology of cluster headache and how the increased mechanistic understanding may lead to the discovery of novel therapeutic targets.
The longest mitochondrial protein in metazoans is encoded by the male-transmitted mitogenome of the bivalve
Scrobicularia plana
Authors: Tassé Mélanie , Choquette Thierry , Angers Annie , Stewart Donald T. , Pante Eric , Breton Sophie
Published: June 2022

Cytochrome c oxidase subunit II (COX2) is one of the three mitochondrially encoded proteins of the complex IV of the respiratory chain that catalyses the reduction of oxygen to water. The
cox2
gene spans about 690 base pairs in most animal species and produces a protein composed of approximately 230 amino acids. We discovered an extreme departure from this pattern in the male-transmitted mitogenome of the bivalve
Scrobicularia plana
with doubly uniparental inheritance (DUI) of mitochondrial DNA (mtDNA), which possesses an important in-frame insertion of approximately 4.8 kb in its
cox2
gene. This feature—an enlarged male
cox2
gene—is found in many species with DUI; the COX2 protein can be up to 420 amino acids long. Through RT-PCRs, immunoassays and comparative genetics, the evolution and functionality of this insertion in
S. plana
were characterized. The in-frame insertion is conserved among individuals from different populations and bears the signature of purifying selection seemingly indicating maintenance of functionality. Its transcription and translation were confirmed: this gene produces a polypeptide of 1892 amino acids, making it the largest metazoan COX2 protein known to date. We hypothesize that these extreme modifications in the COX2 protein affect the metabolism of mitochondria containing the male-transmitted mtDNA in
Scrobicularia plana
.
Computational lung modelling in respiratory medicine
Authors: Neelakantan Sunder , Xin Yi , Gaver Donald P. , Cereda Maurizio , Rizi Rahim , Smith Bradford J. , Avazmohammadi Reza
Published: June 2022

Computational modelling of the lungs is an active field of study that integrates computational advances with lung biophysics, biomechanics, physiology and medical imaging to promote individualized diagnosis, prognosis and therapy evaluation in lung diseases. The complex and hierarchical architecture of the lung offers a rich, but also challenging, research area demanding a cross-scale understanding of lung mechanics and advanced computational tools to effectively model lung biomechanics in both health and disease. Various approaches have been proposed to study different aspects of respiration, ranging from compartmental to discrete micromechanical and continuum representations of the lungs. This article reviews several developments in computational lung modelling and how they are integrated with preclinical and clinical data. We begin with a description of lung anatomy and how different tissue components across multiple length scales affect lung mechanics at the organ level. We then review common physiological and imaging data acquisition methods used to inform modelling efforts. Building on these reviews, we next present a selection of model-based paradigms that integrate data acquisitions with modelling to understand, simulate and predict lung dynamics in health and disease. Finally, we highlight possible future directions where computational modelling can improve our understanding of the structure–function relationship in the lung.
Modelling the impact of birth control policies on China’s population and age: effects of delayed births and minimum birth age constraints
Authors: Wang Yue , Dessalles Renaud , Chou Tom
Published: June 2022

We consider age-structured models with an imposed refractory period between births. These models can be used to formulate alternative population control strategies to China’s one-child policy. By allowing any number of births, but with an imposed delay between births, we show how the total population can be decreased and how a relatively older age distribution can be generated. This delay represents a more ‘continuous’ form of population management for which the strict one-child policy is a limiting case. Such a policy approach could be more easily accepted by society. Our analyses provide an initial framework for studying demographics and how social constraints influence population structure.
Captive Asian short-clawed otters (
Aonyx cinereus
) learn to exploit unfamiliar natural prey
Authors: Saliveros Alexander M. , Bowden-Parry Madison , McAusland Fraser , Boogert Neeltje J.
Published: June 2022

Foraging plays a vital role in animal life histories, and learning whether unfamiliar food items are palatable is a key part of this process. Animals that engage in extractive foraging must also learn how to overcome the protective measures of their prey. While otters (subfamily Lutrinae) are a taxon known for their extractive foraging behaviour, how they learn about prey palatability and acquire extractive foraging techniques remains poorly understood. Here we investigated (i) how captive Asian short-clawed otters (
Aonyx cinereus
) learned to interact with, and extract meat from, unfamiliar natural prey and (ii) how their exploitation of such prey compared to their ability to overcome artificial foraging tasks containing familiar food rewards. Network-based diffusion analysis showed that otters learned to interact with unfamiliar natural prey by observing their group mates. However, once interacting with the prey, they learned to extract the meat mainly asocially. In addition, otters took longer to overcome the protective measures of unfamiliar natural prey than those of extractive food puzzles. Asian short-clawed otter populations are declining in the wild. Increasing our understanding of how they learn to overcome novel foraging challenges could help develop pre-release training procedures as part of reintroduction programmes for otter conservation.
Synthesis and photochromism of catechol-containing symmetrical azobenzene compounds
Authors: Fan Suju , Lam Yintung , He Liang , Xin John H.
Published: June 2022

Symmetrical azobenzene derivatives with two catechol groups, 1d–4d, were synthesized as kinds of novel compounds, and the structures were confirmed using mass spectrometry and nuclear magnetic resonance spectroscopy. These compounds could attain photostationary state rapidly in solution upon UV irradiation, and their photochromism had good reversibility. Substituents and their positions on azobenzene chromophore had obvious influence on the maximum absorption and photochromic performances of these as-synthesized compounds. Electron-donating group on
ortho
positions could contribute to the redshift π–π* band. The sulfonamide group that is bonded to dopamine molecules and azobenzene rings caused a negligible n–π* transition of
cis
isomer, resulting in photobleaching upon UV irradiation. Among the four compounds, 4d had the strongest electron-donating
ortho
-methoxy substituents and lower planarity; thus its absorption could decrease more significantly upon UV irradiation of the same intensity, and its
cis
-to-
trans
conversion could be up to 63%. Furthermore, owing to the presence of catechol groups, 4d showed an effective affinity and adhesion to substrate, and on the surface of substrate, a weak colour change could be observed upon UV irradiation, but the reversibility was poorer than that in solution.
The virtues and vices of protein citrullination
Authors: Christophorou Maria A.
Published: June 2022

The post-translational modification of proteins expands the regulatory scope of the proteome far beyond what is achievable through genome regulation. The field of protein citrullination has seen significant progress in the last two decades. The small family of peptidylarginine deiminase (PADI or PAD) enzymes, which catalyse citrullination, have been implicated in virtually all facets of molecular and cell biology, from gene transcription and epigenetics to cell signalling and metabolism. We have learned about their association with a remarkable array of disease states and we are beginning to understand how they mediate normal physiological functions. However, while the biochemistry of PADI activation has been worked out in exquisite detail
in vitro
, we still lack a clear mechanistic understanding of the processes that regulate PADIs within cells, under physiological and pathophysiological conditions. This review summarizes and discusses the current knowledge, highlights some of the unanswered questions of immediate importance and gives a perspective on the outlook of the citrullination field.
Calculating bond dissociation energies of X−H (X=C, N, O, S) bonds of aromatic systems via density functional theory: a detailed comparison of methods
Authors: Trung Nguyen Quang , Mechler Adam , Hoa Nguyen Thi , Vo Quan V.
Published: June 2022

In this study, the performance of 17 different density functional theory functionals was compared for the calculation of the bond dissociation energy (BDE) values of X−H (X=C, N, O, S) bonds of aromatic compounds. The effect of the size of the basis set (expansions of 6-31(G)) was also assessed for the initial geometry and zero-point energy calculations, followed by the single-point BDE calculations with different model chemistries with the 6-311 + (3df,2p) basis set. It was found that the size of the basis set for geometry optimization has a much smaller effect on the accuracy of BDE than the choice of functional for the following single-point calculations. The M06-2X, M05-2X and M08−HX functionals yielded highly accurate BDE values compared to experimental data (with the average mean unsigned error MUE = 1.2–1.5 kcal mol
−1
), performing better than any of the other functionals. The results suggest that geometry optimization may be performed with B3LYP functional and a small basis set, whereas the M06-2X, M05-2X and M08-HX density functionals with a suitably large basis set offer the best method for calculating BDEs of ArX−H (X=C, N, O, S) bonds.
Isolation of Clostridioides difficile PCR Ribotype 027 from single-use hospital gown ties
Authors: Waterfield Shannon , Ahmed Humaira , Jones Imogen Anne , Burky Robert , Joshi Lovleen Tina
Published: June 2022

Background.

Clostridioides difficile

is a spore-forming pathogen responsible for antibiotic-associated diarrhoea. In the USA high incidence of

C. difficile

infection (CDI) in clinical environments has led to interest in

C. difficile

spore transmission.

Hypothesis. Single use hospital surgical gown ties act as a reservoir for

C. difficile

spores.

Aim. This study sought to examine whether single-use hospital surgical gown ties used in surgery, from an acute healthcare facility, harboured

C. difficile

spores.

Methodology. Used surgical gowns ties worn by clinicians in the healthcare facility were examined for

C. difficile

spore presence via spread plate and anaerobic culture. The colonies isolated from each gown tie were subcultured on

C. difficile

selective agar for phenotypic confirmation. Presumptive

C. difficile

colonies were examined using

C. difficile

Quik Check Complete, 16–23S PCR Ribotyping and MALDI-TOF analysis.

Results. In total 17 suspected

C. difficile

colonies were isolated from 15 gown ties via culture.

C. difficile

Quik Check Complete found two isolates as possible

C. difficile

. MALDI-TOF and PCR Ribotyping confirmed one isolate as

C. difficile

PCR ribotype 027 associated with clinical outbreaks.

Discussion. Our study revealed the presence of hypervirulent

C. difficile

ribotype 027 spores on single-use gown ties. This highlights the potential of gown ties as a vector of spore transmission across clinical environments, especially when gowns are not worn appropriately.

Conclusions. Appropriate compliance to infection control procedures by healthcare workers is essential to prevent spore dissemination across clinical facilities and reduce CDI rates.
Curation of the AMRFinderPlus databases: applications, functionality and impact
Authors: Feldgarden Michael , Brover Vyacheslav , Fedorov Boris , Haft Daniel H. , Prasad Arjun B. , Klimke William
Published: June 2022

Antimicrobial resistance (AMR) is a significant public health threat. Low-cost whole-genome sequencing, which is often used in surveillance programmes, provides an opportunity to assess AMR gene content in these genomes using in silico approaches. A variety of bioinformatic tools have been developed to identify these genomic elements. Most of those tools rely on reference databases of nucleotide or protein sequences and collections of models and rules for analysis. While the tools are critical for the identification of AMR genes, the databases themselves also provide significant utility for researchers, for applications ranging from sequence analysis to information about AMR phenotypes. Additionally, these databases can be evaluated by domain experts and others to ensure their accuracy. Here we describe how we curate the genes, point mutations and blast rules, and hidden Markov models used in NCBI’s AMRFinderPlus, along with the quality-control steps we take to ensure database quality. We also describe the web interfaces that display the full structure of the database and their newly developed cross-browser relationships. Then, using the Reference Gene Catalog as an example, we detail how the databases, rules and models are made publicly available, as well as how to access the software. In addition, as part of the Pathogen Detection system, we have analysed over 1 million publicly available genomes using AMRFinderPlus and its databases. We discuss how the computed analyses generated by those tools can be accessed through a web interface. Finally, we conclude with NCBI’s plans to make these databases accessible over the long-term.
Bone Marrow Adiposity, Bone Mineral Density and Wnt/β-catenin Pathway Inhibitors Levels in Hemodialysis Patients
Authors: Wang Yue-Pei , Khelifi Nada , Halleux Cyrille de , Ung Roth-Visal , Samson France , Gagnon Claudia , Mac-Way Fabrice
Published: June 2022

Background: Marrow adipose tissue (MAT) is known to accumulate in patients with chronic kidney disease. This pilot study aimed to evaluate bone mineral density (BMD), MAT, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) using computed tomography (CT) scans and to explore correlations between bone parameters, circulating Wnt/β-catenin pathway inhibitor levels, and adipose tissue parameters.Methods: Single-center cross-sectional pilot study conducted in hemodialysis patients at the Centre Universitaire de Québec, Hôtel-Dieu de Québec hospital, Canada. CT-scan slices were acquired at the levels of the hip, L3 vertebra, and tibia. Volumetric and areal BMD, tibia cortical thickness, VAT and SAT area, and fat marrow index (FMI) were analyzed using the Mindways QCT Pro software. Blood levels of sclerostin, dickkopf-related protein 1 (DKK1), fibroblast growth factor 23, and α-Klotho were assessed. Spearman’s rho test was used to evaluate correlations.Results: Fifteen hemodialysis patients (median age, 75 [66–82] years; 80% male; dialysis vintage, 39.3 [27.4–71.0] months) were included. While inverse correlations were obtained between L3 FMI and BMD, positive correlations were found between proximal tibial FMI and vertebral and tibial BMD, as well as with tibial (proximal and distal) cortical thickness. VAT had a positive correlation with α-Klotho levels, whereas L3 FMI had a negative correlation with DKK1 levels.Conclusions: CT-scan allows simultaneous evaluation of bone and marrow adiposity in dialysis patients. Correlations between MAT and BMD vary depending on the bone site evaluated. DKK1 and α-Klotho levels correlate with adipose tissue accumulation in dialysis patients.
Parathyroid Crisis as Presentation of Atypical Parathyroid Adenoma: Two Diagnostically Challenging Cases
Authors: Landeta Galo Andrés Salvador , Montes Alexis Trejo , Jimenéz Tania Islem Gamboa , Guadalupe Vargas-Ortega , Baldomero González-Virla , Lourdes Balcázar-Hernández
Published: June 2022

Atypical parathyroid adenoma (APA) is a rare cause of primary hyperparathyroidism (PHPT) and represents a diagnostic challenge since it is an intermediate form of parathyroid neoplasm of uncertain malignant potential with atypical histological features that require differential diagnosis of parathyroid carcinoma (PC). We present 2 cases of parathyroid crisis as a presentation of APA. The first case was that of a 56-year-old man with parathyroid crisis, constitutional syndrome, and anemia, with evidence of APA after en bloc resection, evolving with hungry bone syndrome after surgery and curation criteria at 6 months after parathyroidectomy (PTX). The second case was a 64-year-old woman with acute chronic kidney disease and parathyroid crisis, with evidence of APA after selective PTX and >50% reduction in parathyroid hormone levels after surgery; however, persistent PHPT at 6 months post-surgery was observed. These cases represented a diagnostic challenge due to their rare clinical presentation (parathyroid crisis), with a heterogeneous spectrum of target organ damage and infrequent symptoms (constitutional syndrome and acute chronic renal disease), in turn caused by a rare pathology (APA). The presentation of these patients may be indicative of PC; however, histopathological diagnosis is a key to the diagnosis of APA. The differential diagnosis of APA vs. PC in clinical practice is indispensable.
Solid fuel use status in the household and the risk of elevated blood pressure: findings from the 2017/18 Bangladesh Demographic and Health Survey
Authors: Paul Diba , Chowdhury Dia , Ali Hazrat , Islam Md. Syful , Ali Khan Md Mostaured , Khan Md. Nuruzzaman
Published: June 2022

Introduction

Prevalence of hypertension is now increasing rapidly in Bangladesh, particularly among the socio-economically disadvantaged population. This could be linked to their higher use of solid fuel; however, related evidence is scarce in Bangladesh. We aimed to determine the associations of household solid fuel use and its exposure level with systolic blood pressure, diastolic blood pressure and hypertension.

Methods

Total of 7,320 women’s data extracted from the 2017/18 Bangladesh Demographic and Health Survey were analysed. We considered three outcome variables: (i) systolic blood pressure (continuous response), (ii) diastolic blood pressure (continuous response) and (iii) hypertension status (yes, no). Cooking fuel use (clean fuel vs solid fuel) and levels of exposure to household air pollution (HAP) through solid fuel use (unexposed, moderately exposed, highly exposed) were our primary exposure of interest. A multilevel mixed-effects Poisson regression model with robust variance was used to determine the association between exposure and outcome variable adjusting for confounders.

Results

Around 82% of the total respondents analysed used solid fuel for cooking. The overall age-standardised prevalence of hypertension was 28%. The likelihood of becoming hypertension was found 1.44 times (95% CI, 1.04-1.89) higher among respondents who used solid fuel as compared to the respondents who used clean fuel. The likelihood of hypertension was found to be increased with the increased exposure to HAP through the solid fuel used; 1.61 times (95% CI, 1.07-2.20) higher among the moderate exposure group and 1.80 times (95% CI, 1.27-2.32) higher among higher exposure group as compared to the women who used clean fuel. Similar associations were reported for systolic blood pressure and diastolic blood pressure.

Conclusion

Solid fuel use elevate systolic blood pressure, diastolic blood pressure and increases the likelihood of becoming hypertensive. Policies and programs are important to increase awareness about the adverse effects of solid fuel use on health, including hypertension. Focus should also be given to reducing solid fuel use and ensuring proper ventilation at the solid fuel use place.
A Deep Learning Enhanced Compartmental Model and its Application in Modeling Omicron Dynamics and Development in China
Authors: Deng Qi
Published: June 2022

The mainstream compartmental models require stochastic parameterization to estimate the transmission parameters between compartments, which depends upon detailed statistics on epidemiological characteristics that are economically and resource-wide expensive to collect. As an alternative, deep learning techniques are effective in estimating these stochastic parameters with greatly reduced dependency on data particularity. We apply deep learning to estimate transmission parameters of a customized compartmental model, then feed the estimated transmission parameters to the compartmental model to predict the development of the Omicron epidemics in China for 28 days. The average levels of predication accuracy of the model are 98% and 92% for number of infections and deaths, respectively.
Invariant categorical color regions across illuminant change coincide with focal colors
Authors: Morimoto Takuma , Yamauchi Yasuki , Uchikawa Keiji
Published: June 2022

Are there regions in a color space where color categories are invariant across illuminant changes? If so, what characteristics make them more stable than other regions? To address these questions, we asked observers to give a color name to 424 colored surfaces, presented one at a time, under various chromatic illuminants. Results showed a high degree of categorical color constancy, especially under illuminants that occur in the natural environment. It was also shown that surfaces selected as a focal color (the best example of a color category) are more resistant to illuminant change than non-focal color samples. This might imply that categorically invariant regions might have become focal colors to facilitate object identification and communication with others under a variety of lighting environments. We additionally ran an asymmetric color matching experiment to quantify the shift of color appearance induced by illuminant changes using surfaces that were all named gray, thereby disentangling the appearance-based color constancy from the categorical color constancy (which are often confounded). Results suggested that the appearance of color samples largely shifted due to illuminant changes even though all samples were named gray; showing that the constancy of a color category is substantially more robust than the constancy of color appearance.
Workplace infection control measures and perceived organizational support during the COVID-19 pandemic in Japan: a prospective cohort study
Authors: Mori Takahiro , Nagata Tomohisa , Ando Hajime , Hino Ayako , Tateishi Seiichiro , Tsuji Mayumi , Matsugaki Ryutaro , Fujino Yoshihisa , Mori Koji ,   the CORoNaWork project
Published: June 2022

Objective

We investigated whether workplace infection control measures during the COVID-19 pandemic could increase perceived organizational support (POS).

Methods

This prospective cohort study was conducted in Japan from December 2020 to December 2021 using a questionnaire survey. There were 18,560 respondents at follow-up; we investigated 4,971 who rated low POS at baseline. The participants were asked a single question about POS and nine about workplace infection control measures. We determined the odds ratios (ORs) of high POS at follow-up using multilevel logistic regression analysis.

Results

The groups of 5–6 (OR=1.29; 95% confidence interval [CI], 1.05–1.57; P=0.014) and 7–9 workplace infection control measures (OR=1.54; 95% CI, 1.28–1.85; P<0.001) had significantly higher ORs than the group with 0–2 measures.

Conclusions

Health support for employees through workplace infection control measures can increase POS.
Machine Learning Applications and Advancements in Alcohol Use Disorder: A Systematic Review
Authors: Hurtado Myrna , Siefkas Anna , Attwood Misty M , Iqbal Zohora , Hoffman Jana
Published: June 2022

Background

Alcohol use disorder (AUD) is a chronic mental disorder that leads to harmful, compulsive drinking patterns that can have serious consequences. Advancements are needed to overcome current barriers in diagnosis and treatment of AUD.

Objectives

This comprehensive review analyzes research efforts that apply machine learning (ML) methods for AUD prediction, diagnosis, treatment and health outcomes.

Methods

A systematic literature review was conducted. A search performed on 12/02/2020 for published articles indexed in Embase and PubMed Central with AUD and ML-related terms retrieved 1,628 articles. We identified those that used ML-based techniques to diagnose AUD or make predictions concerning AUD or AUD-related outcomes. Studies were excluded if they were animal research, did not diagnose or make predictions for AUD or AUD-related outcomes, were published in a non-English language, only used conventional statistical methods, or were not a research article.

Results

After full screening, 70 articles were included in our review. Algorithms developed for AUD predictions utilize a wide variety of different data sources including electronic health records, genetic information, neuroimaging, social media, and psychometric data. Sixty-six of the included studies displayed a high or moderate risk of bias, largely due to a lack of external validation in algorithm development and missing data.

Conclusions

There is strong evidence that ML-based methods have the potential for accurate predictions for AUD, due to the ability to model relationships between variables and reveal trends in data. The application of ML may help address current underdiagnosis of AUD and support those in recovery for AUD.
GlycoEnzOnto: A GlycoEnzyme Pathway and Molecular Function Ontology
Authors: Groth Theodore , Gunawan Rudiyanto , Diehl Alexander D. , Neelamegham Sriram
Published: June 2022

The ‘glycoEnzymes’ include a set of proteins having related enzymatic, metabolic, transport, structural and cofactor functions. Current there is no established ontology to describe glycoEnzyme properties and to relate them to glycan biosynthesis pathways. We present GlycoEnzOnto, an ontology describing 386 human glycoEnzymes curated along 135 glycosylation pathways, 134 molecular functions and 22 cellular compartments. The pathways described regulate nucleotide-sugar metabolism, glycosyl-substrate/donor transport, glycan biosynthesis, and degradation. The role of each enzyme in the glycosylation initiation, elongation/branching, and capping/termination phases is described. IUPAC linear strings present systematic human/machine readable descriptions of individual reaction steps and enable automated knowledge-based curation of biochemical networks. All GlycoEnzOnto knowledge is integrated with the Gene Ontology (GO) biological processes. GlycoEnzOnto enables improved transcript overrepresentation analyses and glycosylation pathway identification compared to other available schema, e.g. KEGG and Reactome. Overall, GlycoEnzOnto represents a holistic glycoinformatics resource for systems-level analyses.

Availability

https://github.com/neel-lab/GlycoEnzOnto
Gene amplification acts as a molecular foothold to facilitate cross-species adaptation and evasion of multiple antiviral pathways
Authors: Banerjee Shefali , Smith Cathy , Geballe Adam , Rothenburg Stefan , Kitzman Jacob O. , Brennan Greg
Published: June 2022

Cross-species spillover events are responsible for many of the pandemics in human history including COVID-19; however, the evolutionary mechanisms that enable these events are poorly understood. We have previously modeled this process using a chimeric vaccinia virus expressing the rhesus cytomegalovirus-derived PKR antagonist RhTRS1 in place of its native PKR antagonists; E3L and K3L (VACVΔEΔK+RhTRS1). Using this virus, we demonstrated that gene amplification of rhtrs1 occurred early during experimental evolution and was sufficient to fully rescue virus replication in partially resistant African green monkey (AGM) fibroblasts. Notably, this rapid gene amplification also allowed limited virus replication in otherwise completely non-permissive human fibroblasts, suggesting that gene amplification may act as a “molecular foothold” to facilitate viral adaptation to multiple species. In this study, we demonstrate that there are multiple barriers to VACVΔEΔK+RhTRS1 replication in human cells, mediated by both PKR and RNase L. We experimentally evolved three AGM-adapted virus populations in human fibroblasts. Each population adapted to human cells bimodally, via an initial 10-fold increase in replication after only two passages followed by a second 10-fold increase in replication by passage nine. Using our Illumina-based pipeline, we found that some SNPs which had evolved during the prior AGM adaptation were rapidly lost, while 13 singlebase substitutions and short indels increased over time, including two SNPs unique to HFF adapted populations. Many of these changes were associated with components of the viral RNA polymerase, although no variant was shared between all three populations. Taken together, our results demonstrate that rhtrs1 amplification was sufficient to increase viral tropism after passage in an “intermediate species” and subsequently enabled the virus to adopt different, species-specific adaptive mechanisms to overcome distinct barriers to viral replication in AGM and human cells.
Amygdalar and ERC Rostral Atrophy and Tau Pathology Reconstruction in Preclinical Alzheimer’s Disease
Authors: Stouffer Kaitlin M. , Chen Claire , Kulason Sue , Xu Eileen , Witter Menno P. , Ceritoglu Can , Albert Marilyn S. , Mori Susumu , Troncoso Juan , Tward Daniel J. , Miller Michael I.
Published: June 2022

Previous research has emphasized the unique impact of Alzheimer’s Disease (AD) pathology on the medial temporal lobe (MTL), a reflection that tau pathology is particularly striking in the entorhinal and transentorhinal cortex (ERC, TEC) early in the course of disease. However, other brain regions are affected by AD pathology during its early phases. Here, we use longitudinal diffeomorphometry to measure the atrophy rate from MRI of the amygdala compared with that in the ERC and TEC in controls, individuals who progressed from normal cognition to mild cognitive impairment (MCI), and individuals with MCI who progressed to AD dementia, using a dataset from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Our results show significantly higher atrophy rates of the amygdala in both preclinical and MCI ‘converters’ compared to controls, with rates of volume loss comparable to rates of thickness loss in the ERC and TEC. Using our recently developed method, referred to as Projective LDDMM, we map measures of neurofibrillary tau tangles (NFTs) from digital pathology to MRI atlases and reconstruct, for the first time, dense 3D spatial distributions of NFT density within regions of the MTL. The distribution of NFTs is consistent with the MR atrophy rates, revealing high densities not only in ERC, but in the amygdala and rostral third of the MTL. The similarity of the location of NFTs and shape changes in a well-defined clinical population suggests that amygdalar atrophy rate, as measured through MRI may be a viable biomarker for AD.

PACS

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2000 MSC

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Highlights

Amygdala atrophy rate estimated from MRIs in preclinical Alzheimer’s disease (AD)

3D distributions of neurofibrillary tau tangles (NFTs) reconstructed from 2D histology

NFTs highest in the rostral medial temporal lobe, including amygdala and ERC

Amygdala atrophy rate is comparable to ERC atrophy rate in preclinical AD

Amygdala and ERC atrophy rates as potential biomarkers rooted in NFT pathology
Hepatocyte PPARγ contributes to the progression of non-alcoholic steatohepatitis in male and female obese mice
Authors: Lee Samuel M. , Muratalla Jose , Karimi Saman , Diaz-Ruiz Alberto , Frutos Maria Dolores , Guzman Grace , Ramos-Molina Bruno , Cordoba-Chacon Jose
Published: June 2022

Background & Aims

Non-alcoholic steatohepatitis (NASH) is associated with obesity and increased expression of hepatic peroxisome proliferator-activated receptor γ (PPARγ) in humans. Although we previously showed that the expression of PPARγ in hepatocytes contributes to the development NASH in lean mice, the relevance of hepatocyte PPARγ in the development of NASH associated with obesity is still poorly understood.

Methods

Hepatocyte PPARγ was knocked out (PpargΔHep) after the development of high-fat diet-induced obesity in male and female mice and before NASH was induced with a high fat, cholesterol and fructose (HFCF) diet. We assessed the effect of the diets and PpargΔHep on body composition and glucose homeostasis, as well as on the liver pathology, gene expression, and metabolome. In addition, liver biopsies from a cohort of 102 bariatric surgery patients were assessed for liver histology and gene expression.

Results

PPARγ expression, specifically PPARγ2, is mostly derived from hepatocytes and increased by high fat diets. PpargΔHep reduced HFCF-induced NASH progression without altering steatosis. Interestingly, PpargΔHep reduced the expression of key genes involved in hepatic fibrosis in HFCF-fed male and female mice, and collagen- stained fibrotic area in the liver of HFCF-fed male mice. In addition, transcriptomic and metabolomic data suggested that HFCF-diet regulated hepatic amino acid metabolism in a hepatocyte PPARγ-dependent manner. Specifically, PpargΔHep increased betaine-homocysteine methyltransferase expression and reduced homocysteine levels in HFCF- fed male mice. In a cohort of 102 bariatric surgery patients, 16 cases of NASH were associated with increased insulin resistance and hepatic PPARγ expression.

Conclusions

Hepatocyte PPARγ expression associated with obesity could regulate methionine metabolism and the progression of fibrosis in NASH.
Nirmatrelvir Resistant SARS-CoV-2 Variants with High Fitness in Vitro
Authors: Zhou Yuyong , Gammeltoft Karen Anbro , Ryberg Line Abildgaard , Pham Long V. , Fahnøe Ulrik , Binderup Alekxander , Hernandez Carlos Rene Duarte , Offersgaard Anna , Fernandez-Antunez Carlota , Peters Günther Herbert Johannes , Ramirez Santseharay , Bukh Jens , Gottwein Judith Margarete
Published: June 2022

The oral protease inhibitor nirmatrelvir is expected to play a pivotal role for prevention of severe cases of coronavirus disease 2019 (COVID-19). To facilitate monitoring of potentially emerging resistance, we studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) escape from nirmatrelvir. Resistant variants selected in cell culture harbored different combinations of substitutions in the SARS-CoV-2 main protease (Mpro). Reverse genetic studies in a homologous infectious cell culture system revealed up to 80-fold resistance conferred by the combination of substitutions L50F and E166V. Resistant variants had high fitness increasing the likelihood of occurrence and spread of resistance. Molecular dynamics simulations revealed that E166V and L50F+E166V weakened nirmatrelvir-Mpro binding. The SARS-CoV-2 polymerase inhibitor remdesivir retained activity against nirmatrelvir resistant variants and combination of remdesivir and nirmatrelvir enhanced treatment efficacy compared to individual compounds. These findings have implications for monitoring and ensuring treatment programs with high efficacy against SARS-CoV-2 and potentially emerging coronaviruses.