bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytotoxic response of phagocytes in patients newly infected with pulmonary
Mycobacterium tuberculosis
determined using plasma tumor necrosis factor-alpha, malondialdehyde, and superoxide dismutase: an observational study
Authors: Olaniyan Mathew Folaranmi , Ojediran Tolulope Busayo , Monsuru Sunday Mutiu
Published: January 2021

Objective:

Pulmonary
Mycobacterium tuberculosis
infection can trigger cellular and humoral innate immune responses, which may cause death of the pathogen and or host cells/tissue. We aimed to determine the cytotoxic response of phagocytes in patients with pulmonary
Mycobacterium tuberculosis
infection based on plasma tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), and superoxide dismutase (SOD) levels.

Methods:

In this observational study, patients newly infected with pulmonary
Mycobacterium tuberculosis
(
n
=31; age 37-62 years) and age-matched uninfected volunteers (
n
=50) were recruited as test and control volunteers, respectively in Owo, Nigeria. The study protocol was reviewed and approved by the Research and Ethics Committee of the Department of Medical Laboratory Science, Achievers University, Owo, Nigeria (AUO/MLS/VII/2009/212). Anti-hepatitis C virus, human immunodeficiency virus antigen/antibody, hepatitis B virus surface antigen, and plasma TNF-α were determined by enzyme-linked immunosorbent assay, SOD, and MDA were determined by colorimetry,
Plasmodium
by Giemsa thick blood film staining, and acid-fast bacilli in sputum were detected by Ziehl-Neelsen staining.

Results:

All participants had normal blood glucose levels and tested negative for human immunodeficiency virus antigen/antibody, anti-hepatitis C virus, hepatitis B virus surface antigen, and
Plasmodium
spp., and had no medical history of cancer. Infected patients had significantly higher plasma MDA and TNF-α levels and significantly lower SOD levels compared with control subjects (all
P
<0.05).

Conclusion:

Mycobacterium tuberculosis
infection elicited a cytotoxic response by phagocytes, evidenced by significant increases in MDA and TNF-α and a significant decrease in SOD levels.
Case Series Comparing Physical Therapy International Clinical Education Experiences in a Developed and Developing Country and Measuring Against Professional Standards and Guidelines
Authors: Erdman Ellen , Black Jill
Published: January 2021

Background.

With a growing vision for globalization and internationalization in higher education, a number of Commission on the Accreditation of Physical Therapy Education (CAPTE)–accredited physical therapist education programs across the United States have begun to routinely place their students at international sites for one of their full-time clinical education experiences in both developed and developing countries. The purpose of this article is to compare and contrast the physical therapy international clinical education experience in both the developed and developing country and compare the experiences to professional standards and guidelines.

Case Description.

This case series describes the experience of 9 physical therapy students in an 8- to 10-week, full-time, international, clinical education experience. Four were placed in the developed country of Italy, and 5 were placed in the developing country of Belize. All students participated in preclinical preparation and experienced cultural immersion for the 8–10 weeks that they participated in the full-time clinical education experience.

Outcomes.

Evaluative materials consisted of a student weekly questionnaire, an electronic student journal, a Clinical Site Evaluation Form, and comments/ratings from the student's self-assessment on the American Physical Therapy Association's Clinical Performance Instrument. Analysis of the data demonstrated that the participants were experiencing a depth and breadth of clinical experiences commensurate with CAPTE criteria in both the developed and developing settings. Both settings afforded learning experiences in cross-cultural communication and cultural considerations with the developing country posing more cross-cultural practice challenges than the developed country.

Discussion and Conclusions.

Comparison of the data with a proposed model and guidelines for optimizing international clinical education experiences demonstrated alignment in both the developed and developing country experiences. Both international clinical education experiences met CAPTE standards and other professional standards and proved to be a broadening experience for the participants.
Nausea and Vomiting in 2021
Authors: Heckroth Matthew , Luckett Robert T. , Moser Chris , Parajuli Dipendra , Abell Thomas L.
Published: January 2021

Goal:

A comprehensive review of treatments for nausea and vomiting (N/V).

Background:

N/V are common symptoms encountered in medicine. While most cases of acute N/V related to a specific cause can be straightforward to manage, other cases of acute N/V such as chemotherapy-induced N/V and especially chronic unexplained N/V can be difficult to control, leading to a significant decline in the patient’s quality of life and increased cost of medical care from repeated hospitalizations.

Study:

Traditional management has relied on pharmacotherapy which may be inadequate in a certain proportion of these patients. Many of the medications used in the management of N/V have significant side effect profiles making the need for new and improved interventions of great importance.

Results:

This review covers a broad review of the pathophysiology of N/V, pharmacotherapy, including safety concerns and controversies with established pharmaceuticals, newer immunotherapies, bioelectrical neuromodulation (including gastric electrical stimulation), behavioral and surgical therapies, and complementary medicine.

Conclusion:

On the basis of emerging understandings of the pathophysiology of N/V, improved therapies are becoming available.
Specialized Emergency Department Assessment and Multidisciplinary Intervention After Discharge Improve Management of Patients With Inflammatory Bowel Diseases
Authors: Goren Idan , Barkan Revital , Biron Irit A. , Leibovitzh Haim , Golan Maya A. , Eran Hagar B. , Snir Yifat , Broitman Yelena , Konikoff Tom , Amir-Barak Hadar , Yafee Hadar , Adani Edna , Shiber Shachaf , Steiner Hadas , Drescher Michael J. , Dotan Iris , Yanai Henit
Published: January 2021

Goal:

The aim was to assess proactive specialized inflammatory bowel diseases (IBD) emergency department (ED) consultation and multidisciplinary IBD team (IBD-MDT) intervention on IBD-related patient outcomes after discharge.

Background:

Despite advances in patient care, IBD-related ED visits have increased and substantially contribute to the IBD burden.

Methods:

Consecutive patients with IBD (below 50 y) who visited the ED during November 2017 to April 2018 (intervention group) were compared with patients with IBD that visited the same ED during 2014 to 2017 (standard-care group). The primary outcomes were hospitalization and ED revisits at 30, 90, and 180 days.

Results:

The intervention group (45 patients, mean age 32.43±8.6 y, 57.8% male) and the standard-care group (237 patients) had comparable baseline characteristics, including age, sex, and IBD type, and similar rates of hospital admissions from the ED (46.7% vs. 38.8%, P=0.32). The intervention group more frequently underwent computed tomography (40% vs. 8%, P<0.001) and surgical interventions (13.3% vs. 0.8%, P<0.001) within the same hospital admission, compared with the standard-care group. In the intervention group, 24 patients were discharged from the ED, of whom 17 patients visited the IBD clinic (median 5 d postdischarge) and the majority were referred to ambulatory IBD-MDT services (dietitian: 46.7%, psychologist: 6.7%, advanced endoscopist: 8.9%, and proctology services: 6.7%). The intervention group had significantly fewer ED revisits than the standard-care group (30 d: 4.4% vs. 19.8%, P=0.013; 90 d: 4.4% vs. 35.9%, P<0.001; 180 d: 6.7% vs. 43%, P<0.001).

Conclusion:

Proactive specialized ED assessments and IBD-MDT interventions after a hospital discharge were preferable; they significantly reduced the ED revisit rate for at least 6 months.
Effectiveness of Water Jelly Ingestion for Both Rehabilitation and Prevention of Aspiration Pneumonia in Elderly Patients With Moderate to Severe Dysphagia
Authors: Morita Atsushi , Horiuchi Akira , Horiuchi Ichitaro , Takada Hidetoshi
Published: January 2021

Background and Aims:

We evaluated the effectiveness of water jelly ingestion for both rehabilitation and the prevention of aspiration pneumonia in a retrospective analysis of elderly patients with moderate to severe dysphagia.

Patients and Methods:

Study 1: consecutive patients with borderline ingestion in an endoscopic swallowing evaluation were enrolled (n=36, 18 men and 18 women: mean age 82±9 y) and categorized into a group with water jelly (50 to 100 mL) ingestion training 3×/day or an untrained control group. Their food intake levels were then compared using a Food Intake Level Scale. Study 2: consecutive patients who were hospitalized because of aspiration pneumonia were enrolled (n=64, 35 men and 29 women: mean age 81±9 y) and categorized into a group with cyclic ingestion of water jelly immediately after each meal or a control group. The incidence of aspiration pneumonia that was newly developed during hospitalization was compared between the groups.

Results:

In study 1, 36 patients with a Hyodo-Komagane score of 8 were enrolled. Three of the 12 (25%) patients who underwent water jelly ingestion training were able to eat a pureed diet (level 5, 2 patients; level 6, 1 patient) while none of the 24 patients (0%) who did not undergo this training were able to eat any form of diet (levels 5 and 6, no patients) (P=0.011). In study 2, 64 patients were enrolled. No newly developed aspiration pneumonia was observed in the 34 patients (0%) who received cyclic water jelly ingestion, whereas 17% (5/30) of patients not receiving water jelly after meals newly developed aspiration pneumonia during hospitalization (P=0.031).

Conclusions:

Water jelly ingestion was effective for both rehabilitation and the prevention of aspiration pneumonia in elderly patients with moderate to severe dysphagia.
Digital Navigation Improves No-Show Rates and Bowel Preparation Quality for Patients Undergoing Colonoscopy
Authors: Solonowicz Olga , Stier Matthew , Kim Karen , Kupfer Sonia , Tapper Elliot , Sengupta Neil
Published: January 2021

Objectives:

Because of high historical no-show rates and poor bowel preparation quality in our unit, we sought to evaluate whether text message navigation for patients scheduled for colonoscopy would reduce no-show rates and improve bowel preparation quality compared with usual care.

Methods:

We performed a randomized controlled quality improvement study from April to August 2019 in an urban academic endoscopy unit. All patients scheduled for colonoscopy were randomly assigned to a control group that received usual care (paper instructions/nursing precalls) or to the intervention group that received usual care plus the text message program [short message service (SMS)]. The program provided timed-release instructions on dietary modifications and bowel preparation before colonoscopy. The primary outcome was no-shows. Secondary outcomes were no-show/same-day cancellations, no-show/cancellations within 7 days of the procedure, and bowel preparation quality.

Results:

A total of 1625 patients were randomized (SMS=833, control=792). No-show rates were significantly lower in the SMS group compared with the control group (8% vs. 14%; P<0.0001). Similar results were found for no-show/same-day cancellations (10% vs. 16%; P=0.0003), and no-show/cancellations within 7 days (18% vs. 26%; P=0.0008). There was no difference in adequate bowel preparation for all colonoscopies between the groups (89% vs. 87%; P=0.47). However, rates of adequate bowel preparation for screening/surveillance colonoscopies were significantly higher in SMS versus control groups (93% vs. 88%; P=0.04).

Conclusions:

Text message navigation for patients scheduled for colonoscopy improved the quality of colorectal cancer screening by decreasing no-show rates and increasing adequate bowel preparation rates in patients undergoing screening colonoscopy compared with usual care.
Feasibility and preliminary reliability and validity of remote sitting balance assessments among wheelchair users
Authors: Abou Libak , Rice Laura A. , Frechette Mikaela L. , Sosnoff Jacob J.
Published: January 2021

The aim of this study was to investigate the feasibility and preliminary validity and reliability of remote sitting balance assessment. Seven wheelchair users (mean age: 42.7 ± 19.74 years) participated in an in-person and remote sitting balance assessment. The assessments were compared to investigate the concurrent validity of the remote assessment. Reliability of remote assessment was evaluated using intraclass coefficient correlation (ICC) and the Bland-Altman. No significant differences were observed between the mean scores of in-person and remote administrations of the clinical tests (P’s > 0.05). High to very high agreement was found between in-person and remote assessments (ICC = 0.88–0.982, P < 0.05). The agreement was confirmed by Bland-Altman graph analysis. Preliminary results indicate remote sitting balance assessment is feasible to perform, valid, and reliable.
Psychosocial Problems in Relation to Spiritual Orientation and Religious Coping Among Oncology Muslim Patients
Authors: Harbali Sevil Masat , Koç Zeliha
Published: January 2021

Background

Patients generally turn to religion and spirituality when coping with the diagnosis and treatment of chronic diseases.

Objective

The aim of this study was to assess psychosocial problems in relation to spiritual orientation and religious coping among Muslim oncology patients.

Methods

This cross-sectional, correlational study enrolled 406 oncology inpatient participants. Participants completed the Distress Thermometer, the Religious Coping Styles Scale, the Spiritual Orientation Scale, and the The Functional Assessment of Cancer Therapy - General Quality of Life Scale.

Results

As the spiritual orientation levels of the participants increased, use of a positive religious coping strategy also increased and distress levels decreased. In addition, general perceived quality of health increased as spiritual orientation levels and positive religious coping strategy use increased. Participants reported using prayer, daily prayer attendance, offerings, and consulting religious experts to seek healing.

Conclusions

Oncology patients in Turkey experience increased spiritual orientation levels while coping with illness-related psychosocial problems and use positive religious coping methods.

Implications for Practice

The religious beliefs and spiritual orientations of Turkish oncology patients affect their cancer experience, their care, and their quality of life. Determining the religious and spiritual coping methods used by patients to cope with illness-related psychosocial problems may make it easier for nurses to plan patient-specific nursing care.
Ian Jackson's Sphincter Pharyngoplasty
Authors: Mittermiller Paul A. , Staffenberg David A.
Published: January 2021

Velopharyngeal insufficiency (VPI) after cleft palate repair remains an intriguing problem for the cleft surgeon. While other options for the treatment of VPI, in many ways the sphincter pharyngoplasty has become a reliable and satisfying operation. When the applied to the properly selected patient, it rearranges the palatopharyngeus muscles to provide dynamic closure of the newly created central velopharngeal port. The dynamic action is particularly satisfying to the surgeon. The surgery evolved in part because of the dedication and creativity of Dr Ian Jackson who's description is closest to the design used today. In his memory we felt it fitting to review Dr Jackson's involvement with the surgery over the decades as well as include our own thoughts on the advantages of the procedure.
Impacted Lower Third Molar Under Inferior Alveolar Canal: Technical Strategy for Minimally Invasive Extraoral Surgical Approach
Authors: Laino Luigi , Mariani Pierluigi , Laino Gregorio , Cervino Gabriele , Cicciù Marco
Published: January 2021

Ectopic lower third molar is an uncommon condition, and its etiology remains unclear. The main approach used for its surgical removal is the intraoral one, but there are cases in which this may not be the best option. When the lower third molar is located below the lower alveolar canal or when it is close to the lower edge of the jaw, the most recommended approach is the extraoral one. The critical issues related to the extraoral approach are the possibility of damaging anatomical structures such as marginal mandibular branch of the facial nerve (craniofacial nerve VII), facial artery and vein, and submental artery. This complication can occur during incision and dissection of the superficial layers or during osteotomy with rotating instruments.

This paper reports a case of extraction of ectopic lower third molar using a minimally invasive extraoral approach combined with piezoelectric surgery in order to prevent intraoperative injury of anatomical structures.
Supra-Temporalis Approach for Treating Zygomaticomaxillary Complex Fracture
Authors: Xing Zhankui , Ren Rong , Xia Xin , Yang Lan
Published: January 2021

Purpose:

There are multiple approaches described to access the zygomaticomaxillary complex (ZMC) fractures: lateral eyebrow, upper blepharoplasty, coronal, subciliary, subtarsal, infraorbital, transconjunctival, and transoral. All these approaches have their advantages, disadvantages, and indications according to location of fracture, degree of displacement, and surgeon's experience with a specific technique. However, there is not a good approach for treating the zygomatic arch or body fracture. In this paper, the authors described a supra-temporalis approach to treat the zygomatic arch or body fracture.

Patients and Methods:

Eight patients with traumatically ZMC fractures who received open reduction and internal stable fixation with supra-temporalis approach were retrospectively reviewed. A minimized supra-temporalis incision and trans-temporalis fascia access was used. Blunt dissection was performed perpendicularly to the fractured zygomatic arch and body. The open reduction and internal fixation of ZMC fractures were performed. After confirming that the fracture was fixed rigidly, the incision was closed layer by layer.

Results:

Using this approach, the zygomatic arch, body, frontozygomatic suture, and fracture stumps were exposed perpendicularly. No extensive incision was needed and minimal invasion was realized. Postoperative CT scan showed that the fractures been repositioned and fixed in the normal position. Facial asymmetry was reconstructed and keep in the follow-up.

Conclusions:

Supra-temporalis approach gave an optimal view of the bony field, which allowed surgeons to work perpendicularly to the fracture, and facilitated the reduction of the displaced fractured stumps. It was regarded as an ideal and valuable alternative in this potentially complicated procedure.
Simultaneous Condylar Reconstruction by Free Ramus Osteotomy Graft After Complete Condylectomy for Osteochondroma
Authors: Hoang Tuan-Anh , Lee Kevin C. , Chuang Sung-Kiang
Published: January 2021

Mandibular condyle osteochondromas cause morphologic and functional disturbances. Multiple options exist for reconstructing the condylar segment following complete condylectomy. In this series, we describe 3 cases of mandibular condyle osteochondroma treated with complete condylectomy, orthognathic surgery, and a novel free ramus osteotomy graft. This is the first report to reconstruct the temporomandibular joint using a free ramus graft. Through this single-staged approach we were able to avoid recurrence, preserve function, and restore facial balance without a separate donor site or an alloplastic implant.
SAINT: automatic taxonomy embedding and categorization by Siamese triplet network
Authors: Lu Yang Young , Wang Yiwen , Zhang Fang , Bai Jiaxing , Wang Ying
Published: January 2021

Motivation

Understanding the phylogenetic relationship among organisms is the key in contemporary evolutionary study and sequence analysis is the workhorse towards this goal. Conventional approaches to sequence analysis are based on sequence alignment, which is neither scalable to large-scale datasets due to computational inefficiency nor adaptive to next-generation sequencing (NGS) data. Alignment-free approaches are typically used as computationally effective alternatives yet still suffering the high demand of memory consumption. One desirable sequence comparison method at large-scale requires succinctly-organized sequence data management, as well as prompt sequence retrieval given a never-before-seen sequence as query.

Results

In this paper, we proposed a novel approach, referred to as SAINT, for efficient and accurate alignment-free sequence comparison. Compared to existing alignment-free sequence comparison methods, SAINT offers advantages in two aspects: (1) SAINT is a weakly-supervised learning method where the embedding function is learned automatically from the easily-acquired data; (2) SAINT utilizes the non-linear deep learning-based model which potentially better captures the complicated relationship among genome sequences. We have applied SAINT to real-world datasets to demonstrate its empirical utility, both qualitatively and quantitatively. Considering the extensive applicability of alignment-free sequence comparison methods, we expect SAINT to motivate a more extensive set of applications in sequence comparison at large scale.

Availability

The open source, Apache licensed, python-implemented code will be available upon acceptance.

Supplementary information

Supplementary data are available atBioinformaticsonline.
Design of Specific Primer Sets for the Detection of SARS-CoV-2 Variants of Concern B.1.1.7, B.1.351, P.1, B.1.617.2 using Artificial Intelligence
Authors: Perez-Romero Carmina A. , Tonda Alberto , Mendoza-Maldonado Lucero , Coz Etienne , Tabeling Patrick , Vanhomwegen Jessica , Claassen Eric , Garssen Johan , Kraneveld Aletta D. , Lopez-Rincon Alejandro
Published: January 2021

As the COVID-19 pandemic continues, new SARS-CoV-2 variants with potentially dangerous features have been identified by the scientific community. Variant B.1.1.7 lineage clade GR from Global Initiative on Sharing All Influenza Data (GISAID) was first detected in the UK, and it appears to possess an increased transmissibility. At the same time, South African authorities reported variant B.1.351, that shares several mutations with B.1.1.7, and might also present high transmissibility. Earlier this year, a variant labelled P.1 with 17 non-synonymous mutations was detected in Brazil. Recently the World Health Organization has raised concern for the variants B.1.617.2 mainly detected in India but now exported worldwide. It is paramount to rapidly develop specific molecular tests to uniquely identify new variants. Using a completely automated pipeline built around deep learning and evolutionary algorithms techniques, we designed primer sets specific to variants B.1.1.7, B.1.351, P.1 and respectively. Starting from sequences openly available in the GISAID repository, our pipeline was able to deliver the primer sets for each variant. In-silico tests show that the sequences in the primer sets present high accuracy and are based on 2 mutations or more. In addition, we present an analysis of key mutations for SARS-CoV-2 variants. Finally, we tested the designed primers for B.1.1.7 using RT-PCR. The presented methodology can be exploited to swiftly obtain primer sets for each new variant, that can later be a part of a multiplexed approach for the initial diagnosis of COVID-19 patients.
A method for detection of permeation events in Molecular Dynamics simulations of lipid bilayers
Authors: Camilo Carlos R. S. , Ruggiero J. Roberto , de Araujo Alexandre S.
Published: January 2021

The cell membrane is one of the most important structures of life. Understanding its functioning is essential for several human knowledge areas, mainly how it controls the efflux of substances between the cytoplasm and the environment. Being a complex structure, composed of several classes of compounds such as lipids, proteins, sugars, etc., a convenient way to mimic it is through a phospholipid bilayer. The Molecular Dynamics simulation of lipid bilayers in solution is the main computational approach to model the cell membrane. In this work, we present a method to detect permeation events of molecules through the lipid bilayer, characterizing its crossing time and trajectory. By splitting the simulation box into well-defined regions, the method distinguishes the passage of molecules through the bilayer from artifacts produced by crossing molecules through the simulation box edges when using periodic boundary conditions. We apply the method to study the spontaneous permeation of water molecules through bilayers with different lipid compositions and modeled with different force fields. Our method successfully characterizes the permeation events, and the results obtained show that the frequency and time of permeation are independent of the force field used to model the phospholipids. Besides, it is observed that the increase in the concentration of cholesterol molecules in lipid bilayers induces the reduction of permeation events due to its compacting action on the bilayer, making it denser and, therefore, hindering the diffusion of water molecules inside it. The computational tool to perform the method discussed here is available on https://github.com/crobertocamilo/MD-permeation.
Optimising expression quantitative trait locus mapping workflows for single-cell studies
Authors: Cuomo Anna S.E. , Alvari Giordano , Azodi Christina B. ,   single-cell eQTLGen consortium, McCarthy Davis J. , Bonder Marc Jan
Published: January 2021

Single-cell RNA-sequencing (scRNA-seq) has enabled the unbiased, high-throughput quantification of gene expression specific to cell types and states. With the cost of scRNA-seq decreasing and techniques for sample multiplexing improving, population-scale scRNA-seq, and thus single-cell expression quantitative trait locus (sc-eQTL) mapping, is increasingly feasible. Mapping of sc-eQTL provides additional resolution to study the regulatory role of common genetic variants on gene expression across a plethora of cell types and states, and promises to improve our understanding of genetic regulation across tissues in both health and disease. While previously established methods for bulk eQTL mapping can, in principle, be applied to sc-eQTL mapping, there are a number of open questions about how best to process scRNA-seq data and adapt bulk methods to optimise sc-eQTL mapping. Here, we evaluate the role of different normalisation and aggregation strategies, covariate adjustment techniques, and multiple testing correction methods to establish best practice guidelines. We use both real and simulated datasets across single-cell technologies to systematically assess the impact of these different statistical approaches and provide recommendations for future single-cell eQTL studies that can yield up to twice as many eQTL discoveries as default approaches ported from bulk studies.
Shape Recovery of Deformed Biomolecular Droplets: Dependence on Condensate Viscoelasticity
Authors: Zhou Huan-Xiang
Published: January 2021

A theoretical study on the shape dynamics of phase-separated biomolecular droplets is presented, highlighting the importance of condensate viscoelasticity. Previous studies on shape dynamics have modeled biomolecular condensates as purely viscous, but recent data have shown them to be viscoelastic. Here we present an exact analytical solution for the shape recovery dynamics of deformed biomolecular droplets. The shape recovery of viscous droplets has an exponential time dependence, with the time constant given by the “viscocapillary” ratio, i.e., viscosity over interfacial tension. In contrast, the shape recovery dynamics of viscoelastic droplets is multi-exponential, with shear relaxation yielding additional time constants. During shape recovery, viscoelastic droplets exhibit shear thickening (increase in apparent viscosity) at fast shear relaxation rates but shear thinning (decrease in apparent viscosity) at slow shear relaxation rates. These results highlight the importance of viscoelasticity and expand our understanding of how material properties affect condensate dynamics in general, including aging.
Automated annotation of rare-cell types from single-cell RNA-sequencing data through synthetic oversampling
Authors: Bej Saptarshi , Galow Anne-Marie , David Robert , Wolfien Markus , Wolkenhauer Olaf
Published: January 2021

The research landscape of single-cell and single-nuclei RNA sequencing is evolving rapidly, and one area that is enabled by this technology, is the detection of rare cells. An automated, unbiased and accurate annotation of rare subpopulations is challenging. Once rare cells are identified in one dataset, it will usually be necessary to generate other datasets to enrich the analysis (e.g., with samples from other tissues). From a machine learning perspective, the challenge arises from the fact that rare cell subpopulations constitute an imbalanced classification problem.

We here introduce a Machine Learning (ML)-based oversampling method that uses gene expression counts of already identified rare cells as an input to generate synthetic cells to then identify similar (rare) cells in other publicly available experiments. We utilize single-cell synthetic oversampling (sc-SynO), which is based on the Localized Random Affine Shadowsampling (LoRAS) algorithm. The algorithm corrects for the overall imbalance ratio of the minority and majority class.

We demonstrate the effectiveness of the method for two independent use cases, each consisting of two published datasets. The first use case identifies cardiac glial cells in snRNA-Seq data (17 nuclei out of 8,635). This use case was designed to take a larger imbalance ratio (∼1 to 500) into account and only uses single-nuclei data. The second use case was designed to jointly use snRNA-Seq data and scRNA-Seq on a lower imbalance ratio (∼1 to 26) for the training step to likewise investigate the potential of the algorithm to consider both single cell capture procedures and the impact of “less” rare-cell types. For validation purposes, all datasets have also been analyzed in a traditional manner using common data analysis approaches, such as the Seurat3 workflow.

Our algorithm identifies rare-cell populations with a high accuracy and low false positive detection rate. A striking benefit of our algorithm is that it can be readily implemented in other and existing workflows. The code basis is publicly available at FairdomHub (https://fairdomhub.org/assays/1368) and can easily be transferred to train other customized approaches.
The Generalizability of Clinical Prediction Models for Patients with Acute Coronary Syndromes: Results from Independent External Validations
Authors: Wessler Benjamin S. , Nelson Jason , Park Jinny G. , McGinnes Hannah , Upshaw Jenica , Van Calster Ben , van Klaveren David , Steyerberg Ewout , Kent David M.
Published: January 2021

Purpose

It is increasingly recognized that clinical prediction models (CPMs) often do not perform as expected when they are tested on new databases. Independent external validations of CPMs are recommended but often not performed. Here we conduct independent external validations of acute coronary syndrome (ACS) CPMs.

Methods

A systematic review identified CPMs predicting outcomes for patients with ACS. Independent external validations were performed by evaluating model performance using individual patient data from 5 large clinical trials. CPM performance with and without various recalibration techniques was evaluated with a focus on CPM discrimination (c-statistic, % relative change in c-statistic) as well as calibration (Harrell’s Eavg, E90, Net Benefit).

Results

Of 269 ACS CPMs screened, 23 (8.5%) were compatible with at least one of the trials and 28 clinically appropriate external validations were performed. The median c statistic of the CPMs in the derivation cohorts was 0.76 (IQR, 0.74 to 0.78). The median c-statistic in these external validations was 0.70 (IQR, 0.66 to 0.71) reflecting a 24% decrement in discrimination. However, this decrement in discrimination was due mostly to narrower case-mix in the validation cohorts compared to derivation cohorts, as reflected in the median model based c-statistic [0.71 (IQR 0.66 to 0.75). The median calibration slope in external validations was 0.84 (IQR, 0.72 to 0.98) and the median Eavg (standardized by the outcome rate) was 0.4 (IQR, 0.3 to 0.8). Net benefit indicates that most CPMs had a high risk of causing net harm when not recalibrated, particularly for decision thresholds not near the overall outcome rate.

Conclusion

Independent external validations of published ACS CPMs demonstrate that models tested in our sample had relatively well-preserved discrimination but poor calibration when externally validated. Applying ‘off-the-shelf’ CPMs often risks net harm unless models are recalibrated to the populations on which they are used.
Excess mortality associated with the COVID-19 pandemic among Californians 18–65 years of age, by occupational sector and occupation: March through October 2020
Authors: Chen Yea-Hung , Glymour Maria , Riley Alicia , Balmes John , Duchowny Kate , Harrison Robert , Matthay Ellicott , Bibbins-Domingo Kirsten
Published: January 2021

Background

Though SARS-CoV-2 outbreaks have been documented in occupational settings and though there is speculation that essential workers face heightened risks for COVID-19, occupational differences in excess mortality have, to date, not been examined. Such information could point to opportunities for intervention, such as workplace modifications and prioritization of vaccine distribution.

Methods and findings

Using death records from the California Department of Public Health, we estimated excess mortality among Californians 18–65 years of age by occupational sector and occupation, with additional stratification of the sector analysis by race/ethnicity. During the COVID-19 pandemic, working age adults experienced a 22% increase in mortality compared to historical periods. Relative excess mortality was highest in food/agriculture workers (39% increase), transportation/logistics workers (28% increase), facilities (27%) and manufacturing workers (23% increase). Latino Californians experienced a 36% increase in mortality, with a 59% increase among Latino food/agriculture workers. Black Californians experienced a 28% increase in mortality, with a 36% increase for Black retail workers. Asian Californians experienced an 18% increase, with a 40% increase among Asian healthcare workers. Excess mortality among White working-age Californians increased by 6%, with a 16% increase among White food/agriculture workers.

Conclusions

Certain occupational sectors have been associated with high excess mortality during the pandemic, particularly among racial and ethnic groups also disproportionately affected by COVID-19. In-person essential work is a likely venue of transmission of coronavirus infection and must be addressed through strict enforcement of health orders in workplace settings and protection of in-person workers. Vaccine distribution prioritizing in-person essential workers will be important for reducing excess COVID mortality.
Getting Blood from a Stone: Improving Neural Inferences without Additional Neural Data
Authors: Halpern David J. , Gureckis Todd M.
Published: January 2021

In recent years, the cognitive neuroscience literature has come under criticism for containing many low-powered studies, limiting the ability to make reliable statistical inferences. Typically, the suggestion for increasing power is to collect more data with neural signals. However, many studies in cognitive neuroscience use parameters estimated from behavioral data in order to make inferences about neural signals (such as fMRI BOLD signal). In this paper, we explore how cognitive neuroscientists can learn more about their neuroimaging signal by collecting data onbehavior alone. We demonstrate through simulation that knowing more about the marginal distribution of behavioral parameters can improve inferences about the mapping between cognitive processes and neural data. In realistic settings of the correlation between cognitive and neural parameters, additional behavioral data can lead to the same improvement in the precision of inferences more cheaply and easily than collecting additional data from subjects in a neuroimaging study. This means that when conducting an neuroimaging study, researchers now have two knobs to turn in a design analysis: the number of subjects collected in the scanner and the number of behavioral subjects collected outside the scanner (in the lab or online).
Piezo1 and BKCachannels in human atrial fibroblasts: interplay and remodelling in atrial fibrillation
Authors: Jakob Dorothee , Klesen Alexander , Allegrini Benoit , Darkow Elisa , Aria Diana , Emig Ramona , Chica Ana Simon , Rog-Zielinska Eva A. , Guth Tim , Beyersdorf Friedhelm , Kari Fabian A. , Proksch Susanne , Hatem Stéphane N. , Karck Matthias , Künzel Stephan R , Guizouarn Hélène , Schmidt Constanze , Kohl Peter , Ravens Ursula , Peyronnet Rémi
Published: January 2021

Aims

Atrial Fibrillation (AF) is an arrhythmia of increasing prevalence in the aging population of developed countries. One of the important indicators of AF is sustained atrial dilatation, highlighting the importance of mechanical overload in the pathophysiology of AF. The mechanisms by which atrial cells, including fibroblasts, sense and react to changing mechanical forces, are not fully elucidated. Here, we characterise stretch-activated ion channels (SAC) in human atrial fibroblasts and changes in SAC-presence and -activity associated with AF.

Methods and Results

Using primary cultures of human atrial fibroblasts, isolated from patients in sinus rhythm or sustained AF, we combine electrophysiological, molecular and pharmacological tools to identify SAC. Two electrophysiological SAC-signatures were detected, indicative of cation-nonselective and potassium-selective channels. Using siRNA-mediated knockdown, we identified the nonselective SAC as Piezo1. Biophysical properties of the potassium-selective channel, its sensitivity to calcium, paxilline and iberiotoxin (blockers), and NS11021 (activator), indicated presence of calcium-dependent ‘big potassium channels’, BKCa. In cells from AF patients, Piezo1 activity and mRNA expression levels were higher than in cells from sinus rhythm patients, while BKCaactivity (but not expression) was downregulated. Both Piezo1-knockdown and removal of extracellular calcium from the patch pipette resulted in a significant reduction of BKCacurrent during stretch. No co-immunoprecipitation of Piezo1 and BKCawas detected.

Conclusions

Human atrial fibroblasts contain at least two types of ion channels that are activated during stretch: Piezo1 and BKCa. While Piezo1 is directly stretch-activated, the increase in BKCaactivity during mechanical stimulation appears to be mainly secondary to calcium influxviaSAC such as Piezo1. During sustained AF, Piezo1 is increased, while BKCaactivity is reduced, highlighting differential regulation of both channels. Our data support the presence and interplay of Piezo1 and BKCain human atrial fibroblasts in the absence of physical interactions between the two channel proteins.
Adipocyte lipolysis abrogates skin fibrosis in a Wnt/DPP4-dependent manner
Authors: Jussila A. , Caves E. , Zhang B. , Kirti S. , Steele M. , Lei V. , Hamburg-Shields E. , Lydon J. , Ying Y. , Lafyatis R , Rajagopalan S. , Horsley V. , Atit R.P.
Published: January 2021

Tissue fibrosis in many organs results from altered and excessive extracellular matrix (ECM) protein deposition1. Concomitant with ECM expansion, resident lipid-filled cells including mature adipocytes are lost in human and mouse fibrosis2-5, yet the mechanisms that drive mature adipocyte lipid loss and their contribution to tissue fibrosis are unknown. Here, we identify an early, fibro-protective role of mature adipocyte lipolysis driven by Wnt signaling during fibrosis onset. Using chemical and genetic mouse models of skin fibrosis, we show that fibrotic stimuli induce and maintain lipolysis in mature dermal adipocytes. Loss of the lipolytic rate-limiting enzyme adipocyte triglyceride lipase (ATGL)6,7in murine dermal adipocytes exacerbates bleomycin-induced fibrosis development. Adipocyte lipolysis is stimulated in the early stages of Wnt signaling-induced skin fibrosis and by Wnt agonistsin vitro. Furthermore, deletion or inhibition of the Wnt target gene, CD26/Dipeptidyl peptidase 4 (DPP4) prevented Wnt-induced lipolysis and skin fibrosis in mice. Notably, DPP4 expression correlates with skin fibrosis severity in human patients. Thus, we propose that adipocyte-derived fatty acids and the Wnt-DPP4 axis act as essential regulators of ECM homeostasis within tissues and provide a therapeutic avenue to manipulate fibrosis.
Current strategic limitations of phylogenetic tools badly impact the inference of an evolutionary tree
Authors: Nasika Shamantha , Runthala Ashish
Published: January 2021

For drawing an evolutionary relationship among several protein sequences, the phylogenetic tree is usually constructed through maximum likelihood-based algorithms. To improve the accuracy of these methodologies, many parameters like bootstrap methods, correlation coefficient and residue-substitution models are presumably over-ranked to derive biologically credible relationships. Although the accuracy of protein sequence alignment and the substitution matrix are preliminary constraints to define the biological accuracy of the overlapped sequences/residues, the alignment is not iteratively optimized through the statistical testing of residue-substitution models. The study majorly highlights the potential pitfalls that significantly affect the accuracy of an evolutionary protocol. It emphasizes the need for a more accurate scrutiny of the entire phylogenetic methodology. The need of iterative optimizations is illustrated to construct a biologically credible and not mathematically optimal tree for a sequence dataset.
Elimination of glutamatergic transmission from Hb9 interneurons does not impact treadmill locomotion
Authors: Koronfel Lina M. , Kanning Kevin C. , Alcos Angelita , Henderson Christopher E. , Brownstone Robert M.
Published: January 2021

The spinal cord contains neural circuits that can produce the rhythm and pattern of locomotor activity. It has previously been postulated that a rhythmogenic population of glutamatergic neurons, termed Hb9 interneurons, contributes to this rhythmogenesis. The homeobox gene, Hb9, is expressed in these interneurons as well as motor neurons. We developed a mouse line in which cre recombinase activity is inducible in neurons expressing Hb9. We then used this line to eliminate vesicular glutamate transporter 2 from Hb9 interneurons, and found that there were no deficits in treadmill locomotion. We conclude that glutamatergic neurotransmission by Hb9 interneurons is not required for locomotor rhythmogenesis. The role of these neurons in neural circuits remains elusive.
Taxonomic, ecological and morphological diversity of Ponto-Caspian gammaridean amphipods: a review
Authors: Copilaș-Ciocianu Denis , Sidorov Dmitry
Published: January 2021

Thanks to its dynamic geological history the Ponto-Caspian region harbors a unique and unusually adaptable fauna, notorious for its invasive species. Gammarid amphipods attained considerable diversity, becoming the world’s second most speciose ancient-lake amphipod radiation. Nonetheless, apart from a few invasive species, this group remains poorly studied. Herein, we review and quantify the taxonomic, morphological and ecological diversity, as well as phylogenetic context of Ponto-Caspian gammarids within the adaptive radiation framework. Published molecular phylogenies indicate that this radiation has a monophyletic mid-Miocene Paratethyan origin, and is nested within the morphologically-conserved Atlanto-Mediterranean genusEchinogammarus. We find extensive disparity in body shape, size, ornamentation and appendage length, along a broad ecological gradient from mountain springs to depths exceeding 500 m, on virtually all substrate types (including symbiosis). We propose four putative ecomorphs that appear convergent with distantly related oceanic and Baikal Lake taxa. Thus, the identified patterns support the adaptive radiation model, although extensive further research is needed. A checklist and provisional key to all known endemic species are provided to facilitate taxonomic research. Ponto-Caspian gammarids could be a potentially powerful model for studying adaptive radiations and invasive species evolution.
Effect of Highly Loaded Nanohydroxyapatite Composite Scaffolds Prepared via Melt Extrusion Additive Manufacturing on the Osteogenic Differentiation of Human Mesenchymal Stromal Cells
Authors: Cámara-Torres María , Sinha Ravi , Sanchez Alberto , Habibovic Pamela , Patelli Alessandro , Mota Carlos , Moroni Lorenzo
Published: January 2021

The field of bone tissue engineering seeks to mimic the bone extracellular matrix composition, balancing the organic and inorganic components. In this regard, additive manufacturing (AM) of highly loaded polymer-calcium phosphate (CaP) composites holds great promise towards the design of bioactive scaffolds. Yet, the biological performance of such scaffolds is still poorly characterized. In this study, melt extrusion AM (ME-AM) was used to fabricate poly(ethylene oxide terephthalate)/poly(butylene terephthalate) (PEOT/PBT)-nanohydroxyapatite (nHA) scaffolds with up to 45 wt% nHA, which presented significantly enhanced compressive mechanical properties, to evaluate theirin vitroosteogenic potential as a function of nHA content. While osteogenic gene upregulation and matrix mineralization were observed on all scaffold types when cultured in osteogenic media, human mesenchymal stromal cells did not present an explicitly clear osteogenic phenotype, within the evaluated timeframe, in basic media cultures (i.e. without osteogenic factors). Yet, due to the adsorption of calcium and inorganic phosphate ions from cell culture media and simulated body fluid, the formation of a CaP layer was observed on PEOT/PBT-nHA 45 wt% scaffolds, which is hypothesized to account for their osteoinductivity in the long termin vitro,and osteoconductivityin vivo.
Synaptic inhibition in the lateral habenula shapes reward anticipation
Authors: Lalive Arnaud L. , Congiu Mauro , Clerke Joseph A. , Tchenio Anna , Ge Yuan , Mameli Manuel
Published: January 2021

The nervous system can associate neutral cues with rewards to promote appetitive adaptive behaviors. The lateral habenula (LHb) contributes to such behaviors as rewards and reward-predictive cues inhibit this structure and engage LHb-to-dopamine circuits. However, the mechanistic understanding of reward encoding within the LHb remains unknown. We report that, in mice, acquisition of anticipatory licking in a reward-conditioning task potentiates postsynaptic GABAergic transmission, leaving excitatory synapses unaffected. Conversely, LHb-targeted manipulations of postsynaptic GABAergic function via pharmacological blockade or impairment of GABAAreceptor trafficking decrease anticipatory licking. Hence, inhibitory signaling within LHb enables the expression of appetitive behaviors.