bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Properties of a Purified Reconstituted Bilayer Matrix Design Support Natural Wound Healing Activities
Authors: Armstrong David G. , Orgill Dennis P. , Galiano Robert D. , Glat Paul , Kaufman Jarrod , Mehr Marco , Zelen Charles M.
Published: May 2021

Background:

Biomaterial engineering has produced numerous matrices for use in tissue repair, utilizing various materials and processing methods, which can impact the ability of the products to encourage wound healing. Recently, we observed favorable clinical outcomes, using a novel purified reconstituted bilayer matrix (PRBM; Geistlich Derma-Gide) to treat chronic diabetic foot ulcers.

Methods:

Evaluations of the structural and functional characteristics of PRBM in vitro were performed to assess how this biomaterial may affect the favorable clinical results observed by influencing the wound environment and key physiologic mechanisms necessary for the healing process. Investigations included scanning electron microscopy, cell culture analyses, gene expression assays, matrix metalloproteinase activity assessment, and pH measurement.

Results:

Cross-sectional scanning electron microscopy demonstrated a distinct bilayer structure with porous and compact layers. The PRBM structure allowed cell types involved in wound healing to bind and proliferate. Expression analysis of growth factor-responsive genes demonstrated binding and preservation of bioactive growth factors TGF-β1, bFGF, and VEGF by PRBM. Boyden chamber migration assays revealed increased cellular migration compared with controls. In the presence of PRBM, the activity of MMP-1, MMP-2, and MMP-9 was significantly lower compared with control samples. pH of the PRBM in solution was slightly acidic.

Conclusions:

Based on in vitro evaluations, it appears that the PRBM processing without deleterious chemical crosslinking results in a suitable ECM possessing characteristics to aid natural wound healing, including cell attachment, migration, proliferation, differentiation, and angiogenesis. These in vitro data support the promising healing rate observed clinically when chronic DFUs are treated with PRBM.
Diagnosing Common Deadly Infections in the Era of COVID-19
Authors: Zyablitskaya Mariya , Suarez Maria J. , Gupta Aanchal , Samaroo-Campbell Jevon , Nakeshbandi Mohamed , Chapnick Edward K. , Ghitan Monica
Published: May 2021

The COVID-19 pandemic has challenged clinicians to recognize COVID-19 as one of the diagnostic explanation for common presentations, including fever, cough, and shortness of breath. Latent tuberculosis is responsible for 80% of active tuberculosis cases in the United States, and presentation can vary from asymptomatic to disseminated disease. This potential diagnosis should be thoroughly investigated in foreign-born patients in US hospitals, regardless of travel history and presenting symptoms. We report a patient diagnosed with postpartum disseminated tuberculosis with hematogenous spread to the fetus.
Seasonal variation of peptic ulcer disease, peptic ulcer bleeding, and acute pancreatitis
Authors: Yoon Jin Young , Cha Jae Myung , Kim Ha Il , Kwak Min Seob
Published: May 2021

Although gastrointestinal diseases are reported at various times throughout the year, some particular seasons are associated with a higher incidence of these diseases. This study aimed to identify the seasonal variations of peptic ulcer (PU), peptic ulcer bleeding (PUB), and acute pancreatitis (AP) in South Korea.

We conducted a retrospective, observational cohort study of all subjects aged >18 years between 2012 and 2016 using the Health Insurance Review and Assessment-National Patient Samples database, previously converted to the standardized Observational Medical Outcomes Partnership-Common Data Model. We assessed the overall seasonal variations of PU, PUB, and AP and further analyzed seasonal variations according to age and sex subgroups.

In total, 14,626 patients with PU, 3575 with PUB, and 9023 with AP were analyzed for 5 years. A clear seasonal variation was noted in PU, with the highest incidence rate during winter, the second highest during spring, the third highest during summer, and the lowest incidence during autumn for 5 years (P < .001). PUB also showed significant seasonal fluctuations, with winter peak for 4 years, except 1 year, which had a spring peak (P < .001). However, AP showed no clear seasonal variations (P = .090). No significant differences in the seasonal variation of PU, PUB, and AP were observed according to sex and age subgroups (<60 years vs ≥60 years).

Seasonal variation of PU and PUB should be considered when determining allocation of available health care resources.
Effect of golimumab on health-related quality of life, other patient-reported outcomes and healthcare resource utilization in patients with moderate-to-severe ulcerative colitis: a real-world multicenter, noninterventional, observational study in Greece
Authors: Gatopoulou Anthia , Christodoulou Dimitrios K. , Katsanos Konstantinos H. , Bakos Dimitrios , Mouzas Ioannis , Tzouvala Maria , Theodoropoulou Angeliki , Paspatis Gregorios , Theocharis George , Thomopoulos Konstantinos , Giouleme Olga , Kourikou Anastasia , Manolakopoulos Spilios , Zampeli Evanthia , Michopoulos Spyros , Karatzas Pantelis , Katsaros Marios , Moschovis Dimitris , Orfanoudaki Eleni , Livieratos Achilleas , Petrikkou Evangelia , Mantzaris Gerassimos J.
Published: May 2021

Background and aims

This real-world study assessed the impact of golimumab on health-related quality of life (HRQoL) and other patient-reported outcomes (PROs) in patients with ulcerative colitis over 12 months in Greece.

Methods

GO-LIFE was a noninterventional, prospective, multicenter, 12-month study. Patients who had moderately-to-severely active ulcerative colitis were naïve to antitumor necrosis factor (anti-TNFα) therapy and had failed previous conventional therapy. Patients received golimumab as per label. The primary endpoint was patients achieving inflammatory bowel disease questionnaire 32-item (IBDQ-32) remission at 12 months. Secondary endpoints, at 6 and 12 months, included patients achieving IBDQ-32 response; the mean change in the treatment satisfaction questionnaire for medication (TSQM) and the work productivity and activity impairment in ulcerative colitis (WPAI:UC) questionnaires; changes in healthcare utilization; patients achieving clinical response and remission; adherence rates and the percentage of patients who discontinued golimumab.

Results

IBDQ-32 remission was achieved by 76.9% of patients at 12 months. Mean changes in all TSQM and WPAI:UC domain scores at 12 months were statistically significant. Clinical remission was achieved by 49.4 and 50.6% of patients at 6 and 12 months, and clinical response by 59.3 and 56.8%, respectively. All patients but one (80/81) had high adherence (≥80%) to golimumab treatment over 12 months. Ulcerative colitis-related health care resource utilization was reduced during the follow-up period.

Conclusions

In real-world settings, treatment with golimumab resulted in meaningful improvements in HRQoL and other PROs, and in disease activity at 6 and 12 months in patients with moderately-to-severely active ulcerative colitis who were naïve to anti-TNFa therapy.
Polyethylene glycol combined with linaclotide is an effective and well-tolerated bowel preparation regimen for colonoscopy: an endoscopist-blinded, randomized, controlled trial
Authors: Zhang Menghan , Zou Wenlu , Xu Changqin , Jia Ruzhen , Liu Keke , Xu Qianqian , Xu Hongwei
Published: May 2021

Background and Aim

Bowel preparation is an important determinant of the quality of colonoscopy. The traditional split-dose regimen of 4 L polyethylene glycol (PEG) solutions for bowel preparation is effective but poorly tolerated. The aim of this was to study the efficacy and tolerability of using linaclotide as an adjunctive agent with low-volume PEG for bowel preparation.

Methods

This was an endoscopist-blinded, randomized, controlled trial of 432 patients randomly assigned to three groups: 2 L PEG, 4 L PEG and 2 L PEG + 290 µg linaclotide (2 L PEG + L group). The primary outcome measure was efficacy of bowel preparation according to the Boston Bowel Preparation Scale (BBPS), with secondary outcomes of patients’ tolerance, defecating frequency, complications, sleeping quality, cecal intubation rate, preparation-to-colonoscopy interval, withdrawal time, cecal intubation time, and adenoma and polyp detection rates.

Results

The percentage of adequate bowel preparation in the 2 L PEG + L group was higher than that of the 2 L PEG group (87.9% vs. 77.0%; P = 0.017), but not the 4 L PEG group (87.9% vs. 91.4%; P = 0.339). In terms of the mean (SD) BBPS score for the total and segmental colons, the bowel cleansing efficacy of 2 L PEG + L was superior to that of 2 L PEG and similar to that of 4 L PEG. Patient’s tolerance (including complications, willingness to repeat and sleeping quality) were compatible between the 2 L and 2 L + L group, and the 4 L group was the worst among these three groups.

Conclusion

Two liters of PEG combined with 290 µg linaclotide was an effective and well-tolerated bowel preparation regimen.
Efficacy and safety of a simple home-based resistance exercise program for older adults with low muscle mass: a prospective longitudinal clinical trial
Authors: Kuptniratsaikul Vilai , Thanakiatpinyo Thanitta , Pongratanakul Rinlada , Chinsawangwattanakul Pornsiri , Srisomnuek Ananya , Inthibal Suwicha
Published: May 2021

Low muscle mass is a common condition among older adults that adversely affects strength, physical performance and quality of life. This study aimed to investigate the efficacy and safety of a simple home-based resistance exercise program for older adults with low muscle mass, which was defined as appendicular skeletal mass (ASM) measured by bioimpedance analysis lower than 5.7 kg/m2 in females, and lower than 7.0 kg/m2 in males. This home-based resistance exercise program targets 10 muscles with a frequency of 3–5 days/week for 24 weeks. ASM, grip strength, gait speed and functional reach were measured at baseline, 3 and 6 months. The same four outcomes were then remeasured at 9 months to assess long-term effects. A total of 112 participants (average age: 70 years) were recruited. The mean difference between baseline and 6 months was statistically significant for all outcomes, including ASM [0.12 kg/m2: 95% confidence interval (CI), 0.05–0.18; P = 0.001], gait speed (0.19 meter/s: 95% CI, 0.14–0.25; P < 0.001), grip strength (2.06 kg: 95% CI, 1.32–2.80; P < 0.001), and functional reach distance (4.18 cm: 95% CI, 3.18–5.18; P < 0.001). Change over time for all main outcomes from baseline to 9 months also showed statistically significant improvement. The most commonly reported adverse events were muscle pain, joint pain and fatigue. The majority of participants (90–93%) had good exercise compliance, even at the end of the study. In conclusion, this 24-week simple home-based resistance exercise program significantly improved all main outcomes with low adverse events, and most participants continued the program after the end of the intervention.
Peer Review
Authors: Tornwall Joni , McGaughy Melinda , Schubert Carolyn
Published: May 2021

Background:

Students who value peer feedback processes are more likely to provide supportive feedback to peers.

Purpose:

The purpose of this study was to explore the factors that motivate and demotivate students to provide supportive feedback to peers.

Method:

A secondary analysis of qualitative data collected from 148 graduate nursing students in 7 master's-level courses was conducted to identify the themes related to motivating and demotivating factors in peer review and how they related to students' sense of value for providing supportive peer feedback.

Results:

Common themes included perceived potential for supportive peer feedback to improve self, peer, and team performance, and quality of patient care. Themes related to demotivation included lack of time and fear of negative impact on peers.

Conclusion:

Faculty should emphasize to students the positive impact of supportive peer feedback on nursing care. Assignments can be structured to promote a fair exchange of supportive feedback between peers.
Using Facial Recognition Tools for Health Assessment
Authors: Boczar Daniel , Avila Francisco R. , Carter Rickey E. , Moore Pamela A. , Giardi Davide , Guliyeva Gunel , Bruce Charles J. , McLeod Christopher J. , Forte Antonio Jorge
Published: May 2021

The number of applications for facial recognition technology is increasing due to the improvement in image quality, artificial intelligence, and computer processing power that has occurred during the last decades. Algorithms can be used to convert facial anthropometric landmarks into a computer representation, which can be used to help identify nonverbal information about an individual's health status. This article discusses the potential ways a facial recognition tool can perform a health assessment. Because facial attributes may be considered biometric data, clinicians should be informed about the clinical, ethical, and legal issues associated with its use.
Providing Optimal Rejuvenation to the Jawline and Perioral Area Using Neuromodulators and Hyaluronic Acid Dermal Fillers
Authors: Varga Rachel
Published: May 2021

Including the jawline in aesthetic assessment has become increasingly popular when using both surgical and nonsurgical techniques. Facial aging processes include bone resorption, fat pad atrophy, and a breakdown of the quality of collagen and elastin in the skin. To provide optimal treatment of the jawline using nonsurgical techniques, it is important to consider all of these aspects before planning treatment. Men and women have different facial aging processes and ideal facial ratios that must be respected. The objective of this article is to discuss the use of botulinum toxin A and hyaluronic acid filler injectable treatments, deoxycholic acid injectable treatments, and cryolipolysis treatments and explain how these treatments can be utilized for optimal rejuvenation of the jawline and perioral area.
Prevalence and outcomes of pregnancies in women with HIV over a 20-year period
Authors: Kowalska Justyna D. , Pelchen-Matthews Annegret , Ryom Lene , Losso Marcelo H. , Trofimova Tatiana , Mitsura Viktar M. , Khromova Irina , Paduta Dzmitry , Stephan Christoph , Domingo Pere , Bakowska Elzbieta , Monforte Antonella d’Arminio , Oestergaard Lars , Jablonowska Elzbieta , Kuznetsova Anastasiia , Moreno Santiago , Vasylyev Marta , Pradier Christian , Battegay Manuel , Vandekerckhove Linos , Castagna Antonella , Raben Dorthe , Mocroft Amanda
Published: May 2021

Objective:

To evaluate time trends in pregnancies and pregnancy outcomes among women with HIV in Europe.

Design:

European multicentre prospective cohort study.

Methods:

EuroSIDA has collected annual cross-sectional audits of pregnancies between 1996 and 2015. Pregnancy data were extracted and described. Odds of pregnancy were modelled, adjusting for potential confounders using logistic regression with generalized estimating equations.

Results:

Of 5535 women aged 16 to <50 years, 4217 (76.2%) had pregnancy information available, and 912 (21.6%) reported 1315 pregnancies. The proportions with at least one pregnancy were 28.1% (321/1143) in East, 24.5% (146/596) in North, 19.8% (140/706) in West/Central, 19.3% (110/569) in Central East and 16.2% (195/1203) in South Europe. Overall 319 pregnancies (24.3%) occurred in 1996–2002, 576 (43.8%) in 2003–2009 and 420 (31.9%) in 2010–2015. After adjustment, the odds of pregnancy were lower in 1996–2002, in South, Central East and East compared to West/Central Europe, in older women, those with low CD4+ cell count or with prior AIDS, and higher in those with a previous pregnancy or who were hepatitis C virus positive.

Outcomes were reported for 999 pregnancies in 1996–2014, with 690 live births (69.1%), seven stillbirths (0.7%), 103 spontaneous (10.3%) and 199 medical abortions (19.9%).

Conclusions:

Around 20% of women in EuroSIDA reported a pregnancy, with most pregnancies after 2002, when more effective antiretroviral therapy became available. Substantial differences were seen between European regions. Further surveillance of pregnancies and outcomes among women living with HIV is warranted to ensure equal access to care.
Incidental Detection of Sinonasal Inverted Papilloma With 68Ga-FAPI PET/CT in a Patient With Esophageal Cancer
Authors: Liu Huipan , Yang Xiao , Liu Lin , Lei Lei , Chen Yue
Published: May 2021

A 68-year-old man with newly diagnosed esophageal cancer was included in a clinical trial of 68Ga-FAPI PET/CT study in tumors (ChiCTR2100044131). Increased tracer uptake was noted in esophageal cancer. In addition, sinonasal inverted papilloma also revealed increased FAPI activity.
Low-field thoracic magnetic stimulation increases peripheral oxygen saturation levels in coronavirus disease (COVID-19) patients: a single-blind, sham-controlled, crossover study
Authors: Dominguez-Nicolas Saul M , Manjarrez Elias
Published: May 2021

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may cause low oxygen saturation (SpO2) and respiratory failure in coronavirus disease (COVID-19) patients. Hence the increase of SpO2 levels could be crucial for the quality of life and recovery of these patients. Here we introduce an electromagnetic device termed low-field thoracic magnetic stimulation (LF-ThMS) system. This device was designed to non-invasively deliver a pulsed magnetic field from 100 to 118 Hz and 10.5 to 13.1 mT (i.e., 105 to 131 Gauss) to the dorsal thorax. We show that these frequencies and magnetic flux densities are safe for the patients. We also present a proof-of-concept that a single session of LF-ThMS applied for 30 minutes to the dorsal thorax of 17 COVID-19 patients significantly increases their SpO2 levels. We designed a single-blind, sham-controlled, crossover study on 5 COVID-19 patients who underwent two sessions of the study (real and sham LF-ThMS) and 12 COVID-19 patients who underwent only the real LF-ThMS. We found a statistically significant correlation between magnetic flux density, frequency, or temperature associated with the real LF-ThMS and SpO2 levels in all COVID-19 patients. However, the five patients of the sham-controlled study did not exhibit a significant change in their SpO2 levels during sham stimulation. All the patients did not present adverse events after the LF-ThMS intervention.

Trial registration

ClinicalTrials.gov

Identifier

NCT04895267
Ivermectin for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials
Authors: Roman Yuani M. , Burela Paula Alejandra , Pasupuleti Vinay , Piscoya Alejandro , Vidal Jose E. , Hernandez Adrian V.
Published: May 2021

Background

We systematically assessed benefits and harms of the use of ivermectin (IVM) in COVID-19 patients.

Methods

Published and preprint randomized controlled trials (RCTs) assessing IVM effects on COVID-19 adult patients were searched until March 15, 2021 in five engines. Primary outcomes were all-cause mortality, length of stay (LOS), and adverse events (AE). Secondary outcomes included viral clearance and severe AEs. We evaluated risk of bias (RoB) using the Cochrane RoB 2·0 tool. Inverse variance random effect meta-analyses were performed with quality of evidence (QoE) evaluated using GRADE methodology. Subgroup analyses by severity of disease and RoB, and sensitivity analyses by time of follow-up were conducted.

Results

Ten RCTs (n=1173) were included. Controls were standard of care [SOC] in five RCTs and placebo in five RCTs. RCTs sample size ranged from 24 to 398 patients, mean age from 26 to 56 years-old, and severity of COVID-19 disease was mild in 8 RCTs, moderate in one RCT, and mild and moderate in one RCT. IVM did not reduce all-cause mortality vs. controls (RR 0.37, 95%CI 0.12 to 1.13, very low QoE). IVM did not reduce LOS vs. controls (MD 0.72 days, 95%CI -0.86 to 2.29, very low QoE). AEs, severe AE and viral clearance were similar between IVM and controls (low QoE for these three outcomes). Subgroups by severity of COVID-19 or RoB were mostly consistent with main analyses; all-cause mortality in three RCTs at high RoB was reduced with IVM. Sensitivity analyses excluding RCTs with follow up <21 days showed no difference in all-cause mortality.

Conclusions

In comparison to SOC or placebo, IVM did not reduce all-cause mortality, length of stay or viral clearance in RCTs in COVID-19 patients with mostly mild disease. IVM did not have effect on AEs or SAEs. IVM is not a viable option to treat COVID-19 patients.
Infection control, occupational and public health measures including mRNA-based vaccination against SARS-CoV-2 infections to protect healthcare workers from variants of concern: a 14-month observational study using surveillance data
Authors: Yassi Annalee , Grant Jennifer M. , Lockhart Karen , Barker Stephen , Sprague Stacy , Okpani Arnold I. , Wong Titus , Daly Patricia , Henderson William , Lubin Stan , Sing Chad Kim
Published: May 2021

Background

We evaluated measures to protect healthcare workers (HCWs) in Vancouver, Canada, where variants of concern (VOC) went from <1% in February 2021 to >92% in mid-May. Canada has amongst the longest periods between vaccine doses worldwide, despite Vancouver having the highest P.1 variant rate outside Brazil.

Methods

With surveillance data since the pandemic began, we tracked laboratory-confirmed SARS-CoV-2 infections, positivity rates, and vaccine uptake in all 25,558 HCWs in Vancouver Coastal Health, by occupation and subsector, and compared to the general population. We employed Cox regression modelling adjusted for age and calendar-time to calculate vaccine effectiveness (VE) against SARS-CoV-2 in fully vaccinated (≥ 7 days post-second dose), partially vaccinated (14 days post vaccine) and unvaccinated HCWs; we also compared with unvaccinated community members of the same age-range.

Findings

Only 3.3% of our HCWs became infected, mirroring community rates, with peak positivity of 9.1%, compared to 11.8% in the community. As vaccine coverage increased, SARS-CoV-2 infections declined significantly in HCWs, despite a surge with predominantly VOC; unvaccinated HCWs had an infection rate of 1.3/10,000 person-days compared to 0.89 for HCWs post first dose, and 0.30 for fully vaccinated HCWs. VE compared to unvaccinated HCWs was 37.2% (95% CI: 16.6-52.7%) 14 days post-first dose, 79.2% (CI: 64.6-87.8%) 7 days post-second dose; one dose provided significant protection against infection until at least day 42. Compared with community infection rates, VE after one dose was 54.7% (CI: 44.8-62.9%); and 84.8% (CI: 75.2-90.7%) when fully vaccinated.

Interpretation

Predominantly droplet-contact precautions, with N95s required for aerosol generating medical procedures and available as needed according to point-of-care risk assessment, has been a highly effective approach to preventing occupational infection in HCWs, with one dose of mRNA vaccination further reducing infection risk despite VOC and transmissibility concerns. Delaying second doses to allow more widespread vaccination against severe disease, with strict public health, occupational health and infection control measures, has been effective in protecting the healthcare workforce.
Atlas of functional connectivity relationships across rare and common genetic variants, traits, and psychiatric conditions
Authors: Moreau Clara A. , Kumar Kuldeep , Harvey Annabelle , Huguet Guillaume , Urchs Sebastian , Douard Elise A. , Schultz Laura M. , Sharmarke Hanad , Jizi Khadije , Martin Charles-Olivier , Younis Nadine , Tamer Petra , Rolland Thomas , Martineau Jean-Louis , Orban Pierre , Shin David , Silva Ana Isabel , Hall Jeremy , van den Bree Marianne B.M. , Owen Michael J. , Linden David E. J. , Labbe Aurelie , Maillard Anne M. , Nowakowski Tomasz J. , Lippé Sarah , Bearden Carrie E. , Almasy Laura , Glahn David C. , Thompson Paul M. , Bourgeron Thomas , Bellec Pierre , Jacquemont Sebastien
Published: May 2021

Polygenicity and pleiotropy are key properties of the genomic architecture of psychiatric disorders. An optimistic interpretation of polygenicity is that genomic variants converge on a limited set of mechanisms at some level from genes to behavior. Alternatively, convergence may be minimal or absent.

We took advantage of brain connectivity, measured by resting-state functional MRI (rs- fMRI), as well as rare and common genomic variants to understand the effects of polygenicity and pleiotropy on large-scale brain networks, a distal step from genes to behavior. We processed ten rs-fMRI datasets including 32,988 individuals, to examine connectome-wide effects of 16 copy number variants (CNVs), 10 polygenic scores, 6 cognitive and brain morphometry traits, and 4 idiopathic psychiatric conditions.

Although effect sizes of CNVs on connectivity were correlated to cognition and number of genes, increasing polygenicity was associated with decreasing effect sizes on connectivity. Accordingly, the effect sizes of polygenic scores on connectivity were 6-fold lower compared to CNVs. Despite this heterogeneity of connectivity profiles, multivariate analysis identified convergence of genetic risks and psychiatric disorders on the thalamus and the somatomotor network. Based on spatial correlations with transcriptomic data, we hypothesize that excitatory thalamic neurons may be primary contributors to brain alteration profiles shared across genetic risks and conditions. Finally, pleiotropy measured by genetic and transcriptomic correlations between 38 pairs of conditions/traits showed significant concordance with connectomic correlations, suggesting a substantial causal genetic component for shared connectivity.

Such findings open avenues to delineate general mechanisms - amenable to intervention - across conditions and genetic risks.

One sentence summary

Effects of rare and common genomic variants on brain functional connectivity shed light on the impact of polygenicity and pleiotropy in psychiatry.
A statistical model of COVID-19 testing in populations: effects of sampling bias and testing errors
Authors: Böttcher Lucas , D’Orsogna Maria R. , Chou Tom
Published: May 2021

We develop a statistical model for the testing of disease prevalence in a population. The model assumes a binary test result, positive or negative, but allows for biases in sample selection and both type I (false positive) and type II (false negative) testing errors. Our model also incorporates multiple test types and is able to distinguish between retesting and exclusion after testing. Our quantitative framework allows us to directly interpret testing results as a function of errors and biases. By applying our testing model to COVID-19 testing data and actual case data from specific jurisdictions, we are able to estimate and provide uncertainty quantification of indices that are crucial in a pandemic, such as disease prevalence and fatality ratios.
Homeostasis Equation: An Approach to Theoretical Medicine
Authors: Jang Ryoungwoo , Ji Sunghwan
Published: May 2021

Homeostasis is kind of force that makes living organism to live. In this study, we suggest an integral equation that models homeostasis in living organism. We also showed that various situations can be modeled by homeostasis, and give mathematical interpretation of mechanism of living organism. With our proposed integral equation, one can handle homeostasis quantitatively, and this approach is expected to unveil various hidden properties of living organism.
A random forest model for forecasting regional COVID-19 cases utilizing reproduction number estimates and demographic data
Authors: Galasso Joseph , Cao Duy M. , Hochberg Robert
Published: May 2021

Abstract

During the COVID-19 pandemic, predicting case spikes at the local level is important for a precise, targeted public health response and is generally done with compartmental models. The performance of compartmental models is highly dependent on the accuracy of their assumptions about disease dynamics within a population; thus, such models are susceptible to human error, unexpected events, or unknown characteristics of a novel infectious agent like COVID-19. We present a relatively non-parametric random forest model that forecasts the number of COVID-19 cases at the U.S. county level. Its most prioritized training features are derived from easily accessible, standard epidemiological data (i.e., regional test positivity rate) and the effective reproduction number (Rt) from compartmental models. A novel input training feature is case projections generated by aligning estimated effective reproduction number (pre-computed by COVIDActNow.org) with real time testing data until maximally correlated, helping our model fit better to the epidemic’s trajectory as ascertained by traditional models. Poor reliability of Rt is partially mitigated with dynamic population mobility and prevalence and mortality of non-COVID-19 diseases to gauge population disease susceptibility. The model was used to generate forecasts for 1, 2, 3, and 4 weeks into the future for each reference week within 11/01/2020 - 01/10/2021 for 3068 counties. Over this time period, it maintained a mean absolute error (MAE) of less than 300 weekly cases/100,000 and consistently outperformed or performed comparably with gold-standard compartmental models. Furthermore, it holds great potential in ensemble modeling due to its potential for a more expansive training feature set while maintaining good performance and limited resource utilization.
ABO blood group is involved in the quality of the specific immune response
Authors: Gil-Manso Sergio , Blanco Iria Miguens , Motyka Bruce , Halpin Anne , Lopez-Esteban Rocio , Perez-Fernandez Veronica A. , Carbonell Diego , López-Fernández Luis Andrés , West Lori , Correa-Rocha Rafael , Pion Marjorie
Published: May 2021

Since December 2019, the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread throughout the world. To eradicate it, it is crucial to acquire a strong and long-lasting anti-SARS-CoV-2 immunity, by either natural infection or vaccination. We collected blood samples 12–305 days after positive polymerase chain reactions (PCRs) from 35 recovered individuals infected by SARS-CoV-2. Peripheral blood mononuclear cells were stimulated with SARS-CoV-2-derived peptide pools, such as the Spike (S), Nucleocapsid (N), and Membrane (M) proteins, and we quantified anti-S immunoglobulins in plasma. After 10 months post-infection, we observed a sustained SARS-CoV-2-specific CD4+ T-cell response directed against M-protein, but responses against S- or N-proteins were lost over time. Besides, we demonstrated that A-group individuals presented significantly higher frequencies of specific CD4+ T-cell responses against Pep-M than O-group individuals. The A-group subjects also needed longer to clear the virus and they lost cellular immune responses over time, compared to the O-group individuals, who showed a persistent specific immune response against SARS-CoV-2. Therefore, the S-specific immune response was lost over time, and individual factors determine the sustainability of the body’s defences, which must be considered in the future design of vaccines to achieve continuous anti-SARS-CoV-2 immunity.

This work describes that cellular responses against SARS-CoV-2 M-protein can be detected after 10 months but were lost against S- and N-proteins. Moreover, the individual factors; ABO-group and age influence the sustainability of the specific humoral and cellular immunity against SARS-CoV-2.
Dimerization of SARS-CoV-2 nucleocapsid protein affects sensitivity of ELISA based diagnostics of COVID-19
Authors: Khan Wajihul Hasan , Khan Nida , Mishra Avinash , Gupta Surbhi , Bansode Vikrant , Mehta Deepa , Bhambure Rahul , Rathore Anurag S.
Published: May 2021

Diagnostics has played a significant role in effective management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nucleocapsid protein (N protein) is the primary antigen of the virus for development of sensitive diagnostic assays. Thus far, limited knowledge exists about the antigenic properties of the N protein. In this paper, we demonstrate the significant impact of dimerization of SARS-CoV-2 nucleocapsid protein on sensitivity of enzyme-linked immunosorbent assay (ELISA) based diagnostics of COVID-19. The expressed purified protein from E.coli consists of two forms, dimeric and monomeric forms, which have been further characterized by biophysical and immunological means. Indirect ELISA indicated elevated susceptibility of the dimeric form of the nucleocapsid protein for identification of protein-specific monoclonal antibody as compared to the monomeric form of the protein. These findings have also been confirmed with the modelled structure of monomeric and dimeric nucleocapsid protein via HHPred software and its solvent accessible surface area, which indicates higher stability and antigenicity of the dimeric type as compared to the monomeric form. It is evident that use of the dimeric form will increase the sensitivity of the current nucleocapsid dependent ELISA for rapid COVID-19 diagnostic. Further, the results indicate that monitoring and maintaining of the monomerdimer composition is critical for accurate and robust diagnostics.

Graphical abstract
Epigenomic signature of the progeroid Cockayne syndrome exposes distinct and common features with physiological ageing
Authors: Crochemore Clément , Chica Claudia , Garagnani Paolo , Lattanzi Giovanna , Horvath Steve , Sarasin Alain , Franceschi Claudio , Bacalini Maria Giulia , Ricchetti Miria
Published: May 2021

Cockayne syndrome (CS) and UV-sensitivity syndrome (UVSS) are rare genetic disorders caused by mutation of the DNA repair and chromatin remodelling proteins CSA or CSB, but only CS patients display a progeroid and neurodegenerative phenotype. As epigenetic modifications constitute a well-established hallmark of ageing, we characterized genome-wide DNA methylation (DNAm) of fibroblasts from CS versus UVSS patients and healthy donors. The analysis of differentially methylated positions and regions revealed a CS-specific epigenetic signature, enriched in developmental transcription factors, transmembrane transporters, and cell adhesion factors. The CS-specific signature compared to DNAm changes in other progeroid diseases and regular ageing, identifyied commonalities and differences in epigenetic remodelling. CS shares DNAm changes with normal ageing more than other progeroid diseases do, and according to the methylation clock CS samples show up to 13-fold accelerated ageing. Thus, CS is characterized by a specific epigenomic signature that partially overlaps with and exacerbates DNAm changes occurring in physiological aging. Our results unveil new genes and pathways that are potentially relevant for the progeroid/degenerative CS phenotype.
Genome-wide identification and prediction of SARS-CoV-2 mutations show an abundance of variants: Integrated study of bioinformatics and deep neural learning
Authors: Hossain Md. Shahadat , Pathan A. Q. M. Sala Uddin , Islam Md. Nur , Tonmoy Mahafujul Islam Quadery , Rakib Mahmudul Islam , Munim Md. Adnan , Saha Otun , Fariha Atqiya , Al Reza Hasan , Roy Maitreyee , Bahadur Newaz Mohammed , Rahaman Md. Mizanur
Published: May 2021

Genomic data analysis is a fundamental system for monitoring pathogen evolution and the outbreak of infectious diseases. Based on bioinformatics and deep learning, this study was designed to identify the genomic variability of SARS-CoV-2 worldwide and predict the impending mutation rate. Analysis of 259044 SARS-CoV-2 isolates identify 3334545 mutations (14.01 mutations per isolate), suggesting a high mutation rate. Strains from India showed the highest no. of mutations (48) followed by Scotland, USA, Netherlands, Norway, and France having up to 36 mutations. Besides the most prominently occurring mutations (D416G, F106F, P314L, and UTR:C241T), we identify L93L, A222V, A199A, V30L, and A220V mutations which are in the top 10 most frequent mutations. Multi-nucleotide mutations GGG>AAC, CC>TT, TG>CA, and AT>TA have come up in our analysis which are in the top 20 mutational cohort. Future mutation rate analysis predicts a 17%, 7%, and 3% increment of C>T, A>G, and A>T, respectively in the future. Conversely, 7%, 7%, and 6% decrement is estimated for T>C, G>A, and G>T mutations, respectively. T>G\A, C>G\A, and A>T\C are not anticipated in the future. Since SARS-CoV-2 is evolving continuously, our findings will facilitate the tracking of mutations and help to map the progression of the COVID-19 intensity worldwide.
DLPacker: Deep Learning for Prediction of Amino Acid Side Chain Conformations in Proteins
Authors: Misiura Mikita , Shroff Raghav , Thyer Ross , Kolomeisky Anatoly B.
Published: May 2021

Abstract

Prediction of side chain conformations of amino acids in proteins (also termed ‘packing’) is an important and challenging part of protein structure prediction with many interesting applications in protein design. A variety of methods for packing have been developed but more accurate ones are still needed. Machine learning (ML) methods have recently become a powerful tool for solving various problems in diverse areas of science, including structural biology. In this work we evaluate the potential of Deep Neural Networks (DNNs) for prediction of amino acid side chain conformations. We formulate the problem as image-to-image transformation and train a U-net style DNN to solve the problem. We show that our method outperforms other physics-based methods by a significant margin: reconstruction RMSDs for most amino acids are about 20% smaller compared to SCWRL4 and Rosetta Packer with RMSDs for bulky hydrophobic amino acids Phe, Tyr and Trp being up to 50% smaller.
CZON-cutter: a CRISPR-Cas9 system with multiplexed organelle imaging in a simple unicellular alga
Authors: Tanaka Naoto , Mogi Yuko , Fujiwara Takayuki , Yabe Kannosuke , Toyama Yukiho , Higashiyama Tetsuya , Yoshida Yamato
Published: May 2021

The simple cellular structure of the unicellular alga Cyanidioschyzon merolae consists of one nucleus, one mitochondrion, one chloroplast, and one peroxisome per cell and offers unique advantages to investigate mechanisms of organellar proliferation and the cell cycle. Here, we describe an engineered clustered, regularly interspaced, short palindromic repeats (CRISPR)-associated protein 9 (Cas9) system, CZON-cutter, for simultaneous genome editing and organellar visualization. We engineered a C. merolae strain expressing a nuclear-localized Cas9-Venus nuclease to target editing at a locus defined by a single-guide RNA (sgRNA). We then successfully edited the algal genome and visualized the mitochondrion and peroxisome in transformants by fluorescent protein reporters with different excitation wavelengths. Fluorescent protein labeling of organelles in living transformants allows validation of phenotypes associated with organellar proliferation and the cell cycle, even when the edited gene is essential. Combined with the exceptional biological features of C. merolae, CZON-cutter will be instrumental for investigating cellular and organellar division in a high-throughput manner.

An engineered CRISPR-Cas9 system, named CZON-cutter, for simultaneous genome editing and fluorescent protein labeling of organelles in Cyanidioschyzon merolae can be used to validate intracellular function of a particular gene, even if it is essential.
Monitoring of SARS-CoV-2 B.1.1.7 variant early-phase spreading in South-Moravian Region in the Czech Republic and evaluation of its pathogenicity
Authors: Diabelko Daniel , Dvorackova Milada , Heroldova Monika Dvorakova , Forte Giancarlo , Cundrle Ivan , Ruzicka Filip , Vrbsky Jan
Published: May 2021

SARS-CoV-2 emerged in Wuhan, China, in December 2019. Starting in January 2020, over a period of several months, the initial virus (Wuhan-Hu-1/2019; Wu et al. 2020) diverged in a descendant strain carrying D614G amino acid mutation in spike protein. By summer 2020 this novel coronavirus (nCoV) became the most dominant form of the virus circulating worldwide and raised serious international concern. Currently (April 2021), there are 3598 subsequent PANGO branched lineages recognized that carry numerous mutations. To date, the most emerging lineages of SARS-CoV-2 worldwide include B.1.1.7 lineage with a frequency of 48% followed by several dozens of others with frequencies 7.5% or less, such as B.1.351, B.1.1.28, B.1.2, B.1.1.519, P.1, R.1, etc. (www.nextrain.org, Centers for Disease Control and Prevention; CDC 2020 www.cdc.gov).

In this study, we monitored the spreading of B.1.1.7 lineage from the early phase of its appearance until it became predominant in the South-Moravian region of the Czech Republic. We measured significantly associated clinical marker (Ct; cycle threshold) correlating with viral load in B.1.1.7 lineage. Interestingly, we found that the spreading of B.1.1.7 strain was associated with a shift in patients average age, as compared to the former predominant lineage. Finally, we calculated the impact of the B.1.1.7 lineage on hospitalization and case fatality of the patients on the intensive care unit in the central South-Moravian faculty hospital.
Visualizing the Role of Lipid Dynamics during Infrared Neural Stimulation with Hyperspectral Stimulated Raman Scattering Microscopy
Authors: Adams Wilson R , Gautam Rekha , Locke Andrea , Borrachero-Conejo Ana I. , Dollinger Bryan , Throckmorton Graham A. , Duvall Craig , Jansen E Duco , Mahadevan-Jansen Anita
Published: May 2021

Infrared neural stimulation, or INS, is a method of using pulsed infrared light to yield label-free neural stimulation with broad experimental and translational utility. Despite its robust demonstration, the mechanistic and biophysical underpinnings of INS have been the subject of debate for more than a decade. The role of lipid membrane thermodynamics appears to play an important role in how fast IR-mediated heating nonspecifically drives action potential generation. Direct observation of lipid membrane dynamics during INS remains to be shown in a live neural model system. To directly test the involvement of lipid dynamics in INS, we used hyperspectral stimulated Raman scattering (hsSRS) microscopy to study biochemical signatures of high-speed vibrational dynamics underlying INS in a live neural cell culture model. Findings suggest that lipid bilayer structural changes are occurring during INSin vitroin NG108-15 neuroglioma cells. Lipid-specific signatures of cell SRS spectra were found to vary with stimulation energy and radiant exposure. Spectroscopic observations were verified against high-speed ratiometric fluorescence imaging of a conventional lipophilic membrane structure reporter, di-4-ANNEPS. Overall, the presented data supports the hypothesis that INS causes changes in the lipid membrane of neural cells by changing lipid membrane packing order – which coincides with likelihood of cell stimulation. Furthermore, this work highlights the potential of hsSRS as a method to study biophysical and biochemical dynamics safely in live cells.
Distinct movement patterns generate stages of spider web-building
Authors: Corver Abel , Wilkerson Nicholas , Miller Jeremiah , Gordus Andrew
Published: May 2021

The geometric complexity and stereotypy of spider webs have long generated interest in their algorithmic origin. Like other examples of animal architecture, web construction is the result of several assembly phases that are driven by distinct behavioral stages coordinated to build a successful structure. Manual observations have revealed a range of sensory cues and movement patterns used during web construction, but methods to systematically quantify the dynamics of these sensorimotor patterns are lacking. Here, we apply an analytical pipeline to quantify web-making behavior of the orb-weaverUloborus diversus. Position tracking revealed stereotyped stages of construction that could occur in typical or atypical progressions across individuals. Using an unsupervised clustering approach, we identified general and stage-specific leg movements. A Hierarchical Hidden Markov Model revealed that stages of web-building are characterized by stereotyped sequences of actions largely shared across individuals, regardless of whether these stages progress in a typical or atypical fashion. Web stages could be predicted based on action-sequences alone, revealing that web-stages are a physical manifestation of underlying behavioral phases.

Highlights

Spider centroid trajectories indicate stereotyped progression of web-building stages.

Unsupervised movement clustering reveals a shared set of movements which correspond to previously defined behaviors that define web-making across individuals.

Stages of web-building use both stage-specific and non-specific behaviors.

Stereotyped and distinct action sequences are predictive of stages of web-building.
BaySiCle: A Bayesian Inference joint kNN method for imputation of single-cell RNA-sequencing data making use of local effect
Authors: Singh Abhishek Narain
Published: May 2021

There is a marked technical variability and a high amount of missing observations in the single-cell data that we obtain from experiments. Apart from that clearly each of the batch of experiments have a batch effect on every cell in the batch. This batch effect can be taken into advantage for dealing with imputation, given that all the cells in a given batch belong to the same tissue. Here we introduce ‘BaySiCle’, a novel Bayesian inference based method combined with k-nearest neighbors algorithm for the imputation of missing data in scRNA-seq counts. The priors are found out based on expression value across cells for all the single cells of the same batch. We demonstrate using sample scRNA-seq datasets and simulated expression data that BaySiCle allows robust imputation of missing values generating realistic transcript distributions that match single molecule fluorescence in situ hybridization measurements. By using priors as obtained by the dataset structures in the not just the experimental set-up batch, but also the same group of cells, BaySiCle improves accuracy of imputation to be that much closer to its similar alternatives.

Availability and implementation

The Python Jupyter notebook ‘BaySiCle’ is published on GitHub GitHub - abinarain/BaySiCel: Single Cell Data Imputation using Bayesian statistics and kNN
Hydrodynamics of gliding penguin flipper suggests the adjustment of sweepback with swimming speeds
Authors: Maeda Masateru , Harada Natsuki , Tanaka Hiroto
Published: May 2021

Hydrodynamic performance of a gliding penguin flipper (wing) considering the backward sweep was estimated with computational fluid dynamics (CFD) simulation. A flipper of a gentoo penguin (Pygoscelis papua) was 3D scanned, smoothed, and a numerical fluid mesh was generated. For accurate yet resource-saving computation, an embedded large-eddy simulation (ELES) methods was employed, where the flow near the flipper was solved with large-eddy simulation (LES) and flow far away from the flipper was solved with Reynolds-averaged Navier-Stokes (RANS). The relative flow speed was fixed at 2 m s−1, close to the typical foraging speed for the penguin species. The sweep angle was set to be 0°, 30°, and 60°, while the angle of attack was varied between −40° and 40°, both are within the realistic ranges in the wing kinematics measurement of penguins in an aquarium. It was revealed that a higher sweep angle reduces the lift slope, but the lift coefficient is unchanged at a high angle of attack. Drag coefficient was reduced across the angles of attack with increasing the sweep angles. The drag polars suggest the sweep angle may be adjusted with the change in swimming speed and anhedral (negative dihedral) angle to minimise drag while maintaining the vertical force balance to counteract the positive buoyancy. This will effectively expand the swimming envelope of the gliding penguin, similar to a flying counterpart such as swift.