bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactation and gestation controls on calcium isotopic compositions in a mammalian model
Authors: Hassler Auguste , Martin Jeremy E , Ferchaud Stéphane , Grivault Doryan , Le Goff Samuel , Albalat Emmanuelle , Hernandez Jean-Alexis , Tacail Théo , Balter Vincent
Published: April 2021

Lactation and gestation are among the physiological events that trigger the most intense changes in body calcium (Ca) fluxes. Along with the composition of the animal 2021 diet, these events are suspected to impact the Ca isotopic composition of Ca body reservoirs but their dynamics are poorly understood. In this study, we monitored a group of domestic sows across a full reproduction cycle. We collected tissues and fluids (blood, urine, milk, colostrum, umbilical blood, adult and piglet bones) at different steps of gestation and lactation, and analyzed their Ca isotopic compositions (i.e. δ44/42Ca) by means of multi-collector inductively coupled plasma mass spectrometry. Among other results, we report the first observations of Ca isotopic fractionation between maternal and umbilical blood (Δ44/42Caumbilical blood-sow blood = −0.18 ± 0.11‰, n = 3). Our data also highlight that gestation and lactation periods are characterized by small diet-bone Ca isotopic offsets (Δ44/42Cabone-diet = −0.28 ± 0.11‰, n = 3), with 44Ca-enriched blood compositions during nursing (Δ44/42Canursing blood-gestation blood = $+ 0.42{\rm{\,\,}}_{ - 0.12}^{ + 0.11}$‰, n = 3). Under the light of an up-to-date mammalian box model, we explored different scenarios of gestation and lactation Ca fluxes experienced by a sow-like animal. These simulations suggest that gestation changes on body δ44/42Ca values may result from the intensification of Ca absorption by the animal, whereas the production of 44Ca-depleted milk is the main driver for the 44Ca enrichment in blood during lactation. In addition, our results also support that bone mineralization could be associated with a more restricted Ca isotopic fractionation than previously envisioned. Together, these results refine the framework of Ca isotope applications, notably regarding the monitoring of human bone balance and the study of species and ecosystems from the present and the past.
Chemistry and biology of ferritin
Authors: Plays Marina , Müller Sebastian , Rodriguez Raphaël
Published: April 2021

Iron is an essential element required by cells and has been described as a key player in ferroptosis. Ferritin operates as a fundamental iron storage protein in cells forming multimeric assemblies with crystalline iron cores. We discuss the latest findings on ferritin structure and activity and its link to cell metabolism and ferroptosis. The chemistry of iron, including its oxidation states, is important for its biological functions, its reactivity, and the biology of ferritin. Ferritin can be localized in different cellular compartments and secreted by cells with a variety of functions depending on its spatial context. Here, we discuss how cellular ferritin localization is tightly linked to its function in a tissue-specific manner, and how impairment of iron homeostasis is implicated in diseases, including cancer and coronavirus disease 2019. Ferritin is a potential biomarker and we discuss latest research where it has been employed for imaging purposes and drug delivery.
Proteo3Dnet: a web server for the integration of structural information with interactomics data
Authors: Postic Guillaume , Andreani Jessica , Marcoux Julien , Reys Victor , Guerois Raphaël , Rey Julien , Mouton-Barbosa Emmanuelle , Vandenbrouck Yves , Cianferani Sarah , Burlet-Schiltz Odile , Labesse Gilles , Tufféry Pierre
Published: April 2021

Proteo3Dnet is a web server dedicated to the analysis of mass spectrometry interactomics experiments. Given a flat list of proteins, its aim is to organize it in terms of structural interactions to provide a clearer overview of the data. This is achieved using three means: (i) the search for interologs with resolved structure available in the protein data bank, including cross-species remote homology search, (ii) the search for possibly weaker interactions mediated through Short Linear Motifs as predicted by ELM—a unique feature of Proteo3Dnet, (iii) the search for protein–protein interactions physically validated in the BioGRID database. The server then compiles this information and returns a graph of the identified interactions and details about the different searches. The graph can be interactively explored to understand the way the core complexes identified could interact. It can also suggest undetected partners to the experimentalists, or specific cases of conditionally exclusive binding. The interest of Proteo3Dnet, previously demonstrated for the difficult cases of the proteasome and pragmin complexes data is, here, illustrated in the context of yeast precursors to the small ribosomal subunits and the smaller interactome of 14–3–3zeta frequent interactors. The Proteo3Dnet web server is accessible at http://bioserv.rpbs.univ-paris-diderot.fr/services/Proteo3Dnet/.
antiSMASH 6.0: improving cluster detection and comparison capabilities
Authors: Blin Kai , Shaw Simon , Kloosterman Alexander M , Charlop-Powers Zach , van Wezel Gilles P , Medema Marnix H , Weber Tilmann
Published: April 2021

Many microorganisms produce natural products that form the basis of antimicrobials, antivirals, and other drugs. Genome mining is routinely used to complement screening-based workflows to discover novel natural products. Since 2011, the "antibiotics and secondary metabolite analysis shell—antiSMASH" (https://antismash.secondarymetabolites.org/) has supported researchers in their microbial genome mining tasks, both as a free-to-use web server and as a standalone tool under an OSI-approved open-source license. It is currently the most widely used tool for detecting and characterising biosynthetic gene clusters (BGCs) in bacteria and fungi. Here, we present the updated version 6 of antiSMASH. antiSMASH 6 increases the number of supported cluster types from 58 to 71, displays the modular structure of multi-modular BGCs, adds a new BGC comparison algorithm, allows for the integration of results from other prediction tools, and more effectively detects tailoring enzymes in RiPP clusters.
Safety and efficacy of the combination of nivolumab plus ipilimumab in patients with melanoma and asymptomatic or symptomatic brain metastases (CheckMate 204)
Authors: Tawbi Hussein A , Forsyth Peter A , Hodi F Stephen , Lao Christopher D , Moschos Stergios J , Hamid Omid , Atkins Michael B , Lewis Karl , Thomas Reena P , Glaspy John A , Jang Sekwon , Algazi Alain P , Khushalani Nikhil I , Postow Michael A , Pavlick Anna C , Ernstoff Marc S , Reardon David A , Puzanov Igor , Kudchadkar Ragini R , Tarhini Ahmad A , Sumbul Anne , Rizzo Jasmine I , Margolin Kim A
Published: April 2021

Background

In patients with melanoma and asymptomatic brain metastases (MBM), nivolumab plus ipilimumab provided an intracranial response rate of 55%. Here, we present the first report for patients who were symptomatic and/or required corticosteroids and updated data for asymptomatic patients.

Methods

Patients with measurable MBM, 0.5-3.0 cm, were enrolled into Cohort A (asymptomatic) or Cohort B (stable neurologic symptoms and/or receiving corticosteroids). Nivolumab, 1 mg/kg, and ipilimumab, 3 mg/kg, were given intravenously every 3 weeks ×4, followed by nivolumab, 3 mg/kg, every 2 weeks until progression, unacceptable toxicity, or 24 months. The primary endpoint was intracranial clinical benefit rate (CBR; complete response [CR], partial response [PR], or stable disease ≥6 months).

Results

Symptomatic patients (N = 18) received a median of one nivolumab and ipilimumab combination dose and had an intracranial CBR of 22.2%. Two of 12 patients on corticosteroids had CR; 2 responded among the 6 not on corticosteroids. Median intracranial progression-free survival (PFS) and overall survival (OS) were 1.2 and 8.7 months, respectively. In contrast, with 20.6 months of follow-up, we confirmed an intracranial CBR of 58.4% in asymptomatic patients (N = 101); median duration of response, PFS, and OS were not reached. No new safety signals were observed.

Conclusions

Nivolumab plus ipilimumab provides durable clinical benefit for asymptomatic patients with MBM and should be considered for first-line therapy. This regimen has limited activity in MBM patients with neurologic symptoms and/or requiring corticosteroids, supporting the need for alternative approaches and methods to reduce the dependency on corticosteroids.

Clinical trial registration. ClinicalTrials.gov, NCT02320058.
Impact of Upper Extremity Impairment and Trunk Control on Self-Care Independence in Children With Upper Motor Neuron Lesions
Authors: Keller Jeffrey W , Fahr Annina , Lieber Jan , Balzer Julia , van Hedel Hubertus J A
Published: April 2021

Objective

The purpose of this study was to evaluate the relative importance of different approaches to measure upper extremity selective voluntary motor control (SVMC), spasticity, strength, and trunk control for explaining self-care independence in children affected by upper motor neuron lesions.

Methods

Thirty-one patients (mean [SD] age = 12.5 [3.2] years) with mild to moderate arm function impairments participated in this observational study. Self-care independence was evaluated with the Functional Independence Measure for children (WeeFIM). Upper extremity SVMC was quantified with the Selective Control of the Upper Extremity Scale (SCUES), a similarity index (SISCUES) calculated from simultaneously recorded surface electromyography muscle activity patterns, and an accuracy and involuntary movement score derived from an inertial-measurement-unit–based assessgame. The Trunk Control Measurement Scale was applied and upper extremity spasticity (Modified Ashworth Scale) and strength (dynamometry) were assessed. To determine the relative importance of these factors for self-care independence, 3 regression models were created: 1 included only upper extremity SVMC measures, 1 included upper extremity and trunk SVMC measures (overall SVMC model), and 1 included all measures (final self-care model).

Results

In the upper extremity SVMC model (total variance explained 52.5%), the assessgame (30.7%) and SCUES (16.5%) were more important than the SISCUES (4.5%). In the overall SVMC model (75.0%), trunk SVMC (39.0%) was followed by the assessgame (21.1%), SCUES (11.0%), and SISCUES (4.5%). In the final self-care model (82.1%), trunk control explained 43.2%, upper extremity SVMC explained 23.1%, spasticity explained 12.3%, and strength explained 2.3%.

Conclusion

Although upper extremity SVMC explains a substantial portion of self-care independence, overall trunk control was even more important. Whether training trunk control and SVMC can translate to improved self-care independence should be the subject of future research.

Impact

This study highlights the importance of trunk control and selective voluntary motor control for self-care independence in children with upper motor neuron lesions.
The Independent Effects of Psychosocial Stressors on Subclinical Psychosis: Findings From the Multinational EU-GEI Study
Authors: Pignon Baptiste , Lajnef Mohamed , Kirkbride James B , Peyre Hugo , Ferchiou Aziz , Richard Jean-Romain , Baudin Grégoire , Tosato Sarah , Jongsma Hannah , de Haan Lieuwe , Tarricone Ilaria , Bernardo Miguel , Velthorst Eva , Braca Mauro , Arango Celso , Arrojo Manuel , Bobes Julio , Del-Ben Cristina Marta , Di Forti Marta , Gayer-Anderson Charlotte , Jones Peter B , La Cascia Caterina , Lasalvia Antonio , Menezes Paulo Rossi , Quattrone Diego , Sanjuán Julio , Selten Jean-Paul , Tortelli Andrea , Llorca Pierre-Michel , van Os Jim , Rutten Bart P F , Murray Robin M , Morgan Craig , Leboyer Marion , Szöke Andrei , Schürhoff Franck
Published: April 2021

The influence of psychosocial stressors on psychosis risk has usually been studied in isolation and after the onset of the disorder, potentially ignoring important confounding relationships or the fact that some stressors that may be the consequence of the disorder rather than preexisting. The study of subclinical psychosis could help to address some of these issues. In this study, we investigated whether there was (i) an association between dimensions of subclinical psychosis and several psychosocial stressors including: childhood trauma, self-reported discrimination experiences, low social capital, and stressful life experiences, and (ii) any evidence of environment–environment (ExE) interactions between these factors. Data were drawn from the EUGEI study, in which healthy controls (N = 1497) and siblings of subjects with a psychotic disorder (N = 265) were included in six countries. The association between psychosocial stressors and subclinical psychosis dimensions (positive, negative and depressive dimension as measured by the Community Assessment of Psychic Experiences (CAPE) scale) and possible ExE interactions were assessed using linear regression models. After adjusting for sex, age, ethnicity, country, and control/sibling status, childhood trauma (β for positive dimension: 0.13, negative: 0.49, depressive: 0.26) and stressful life events (positive: 0.08, negative: 0.16, depressive: 0.17) were associated with the three dimensions. Lower social capital was associated with the negative and depression dimensions (negative: 0.26, depressive: 0.13), and self-reported discrimination experiences with the positive dimension (0.06). Our findings are in favor of independent, cumulative and non-specific influences of social adversities in subclinical psychosis in non-clinical populations, without arguments for E × E interactions.
Gluteal Soft-Tissue Repositioning Using Polydioxane Threads
Authors: Lee Won , Jung Young-Choon , Yang Eun-Jung
Published: April 2021

BACKGROUND

Buttock reshaping has recently gained popularity. Gluteal soft-tissue repositioning can be performed using polydioxane threads, followed by anthropometric measurements.

OBJECTIVE

To evaluate the effectiveness of polydioxane threads for noninvasive gluteal soft-tissue repositioning.

MATERIALS AND METHODS

From February 2018 to August 2019, 27 women (mean age, 38.9 years; range, 26–65 years) underwent thread lifting. Multiple polydioxane threads (total, 24–30 threads for each buttock side) were used for gluteal soft-tissue repositioning. The treatment outcomes were based on comparisons of the preoperative and postoperative findings.

RESULTS

The mean ratio of the upper and lower vertical proportions of the buttocks changed from 63:37 preoperatively to 55:45 postoperatively. The mean projection angle of the upper portion decreased from 60.1° preoperatively to 54.3° postoperatively. Twenty-four patients (86%) were satisfied with the results up to 8 months postoperatively. One patient developed persistent pain (>1 month), and 4 patients showed skin dimpling, which resolved within 2 weeks after minimal massages. No hematomas, foreign body sensation, or thread protrusions were noted.

CONCLUSION

Polydioxane threads could be an alternative, minimally invasive tool for buttock lifting. Our novel technique of repositioning the buttock soft tissue improved lifting and augmentation and provided a better buttock shape.
#15 Versus #15c Scalpel Blades for Skin Incisions: Accuracy With and Without Magnification
Authors: Iwanaga Joe , Kato Tomotaka , Dumont Aaron S. , Tubbs R. Shane
Published: April 2021

BACKGROUND

Use of a #15 blade is the most popular way for making skin incisions in dermatology. For finer and more accurate incisions, a #15c blade can be used. However, there is no evidence that demonstrates the superiority of the #15c blade over the #15 blade.

OBJECTIVE

This study aimed to compare the skin incisions made with a #15 blade and #15c blade using varied magnifications.

METHODS AND MATERIALS

Twenty fresh chicken thighs with intact skin were used in this study. Incisions were made on the skin using #15 and #15c blades with ×1.0, ×2.5, and ×5.0 magnification. The accuracy of the incision (length and depth) made by the different scalpel blades and magnifications was analyzed using the 2 × 3 chi-squared test. Logistic regression analysis was applied to determine factors of the incision depth and length.

RESULTS

No statistically significant differences were found in the evaluations of length or depth using the 2 × 3 chi-squared test. However, the multiple logistic regression analyses showed that the incision length and depth were associated with use of the #15c scalpel blade.

CONCLUSION

Use of a #15c scalpel blade with ×5.0 magnification is recommended for making incisions when less than 1- to 2-mm accuracy is required.
Comparison of Outcomes of Glaucoma Drainage Implant Surgery With or Without Prior Failed Trabeculectomy
Authors: Dawson Emily F. , Rosenberg Nicole C. , Meyer Alissa M. , Culpepper Brady E. , Bolch Charlotte A. , Wilson Mary K. , Nguyen Phuong T. , Rodgers Cooper D. , Smith Ryan J. , Blake Charles R. , Sherwood Mark B.
Published: April 2021

Precis:

A comparison of 186 glaucoma patients with mixed diagnoses who underwent nonvalved glaucoma drainage device (GDD) implant surgery showed similar long-term intraocular pressure (IOP), medication, and visual acuity (VA) outcomes between those with prior failed trabeculectomy surgery versus those without.

Purpose:

The purpose of this study was to evaluate whether prior failed trabeculectomy adversely affects the outcome of glaucoma tube surgery.

Patients and Methods:

A total of 186 eyes of 186 patients who underwent a nonvalved GDD implant surgery by a single surgeon between 1996 and 2015 at a University practice were included. Patients were of mixed diagnoses and over 18 years old. Before the GDD surgery, 65 had a previous failed glaucoma filtering surgery and 121 had no prior glaucoma surgery. Demographic information, preoperative and postoperative IOP, medication, VA, and complications were collected from chart review.

Results:

No significant difference was noted in mean IOP and mean medication use (13.0 and 12.6 mm Hg on 2.0 and 1.7 medication classes at 5 y postoperatively, respectively), mean VA and change in VA from baseline, or numbers of complications (P>0.05), between eyes that had a prior failed filtration surgery and those that had not. Kaplan-Meier plots for failure over 5 years using a lower limit of <5 mm Hg and an upper limit of ≥18, ≥15, or ≥12 mm Hg did not show a significant difference between groups. Subanalyses were performed to examine only primary glaucoma eyes and results were similar. Further group subanalyses comparing those with baseline IOP ≥25 or <25 mm Hg, age 65 and above or below 65 years and those specifically with Baerveldt 350 mm2 implants also did not show significant differences.

Conclusion:

Prior failed filtration surgery does not appear to affect the outcome of future GDD surgery.
Increased rebleeding and mortality in patients with gastrointestinal bleeding treated with anticoagulant drugs compared to antiplatelet drugs
Authors: Hosni Mohammad , Rahal Mahmoud , Tamim Hani , Daniel Fady , Al Hashash Jana , Sharara Ala I. , Soweid Assaad , Shaib Yasser H. , Mourad Fadi H. , Wehbeh Antonios N. , Rockey Don C. , Barada Kassem
Published: April 2021

Background/Aim

We determined the effect of antiplatelet and anticoagulant agents on rebleeding and mortality in patients with gastrointestinal bleeding.

Methods

This was a prospective study of patients admitted with gastrointestinal bleeding between 2013 and 2018. Outcomes were compared among patients on antiplatelet agents only, anticoagulant drugs only, combination therapy, and none. The association between mortality, rebleeding, and type of antithrombotic medication on admission and discharge was determined using multivariate analysis.

Results

A total of 509 patients were followed up for a median of 19 months. End of follow-up rebleeding and mortality rates were 19.4% and 23.0%, respectively. Independent predictors of mortality were age [hazard ratio (HR) = 1.025 per year increase, P = 0.002], higher Charlson Comorbidity Index (HR = 1.4, P < 0.0001), severe bleeding (HR = 2.1, P < 0.0001), and being on anticoagulants (HR = 2.3, P = 0.002). Being on antiplatelets was protective against rebleeding (HR = 0.6, P = 0.047). Those on anticoagulants were more likely to die (HR = 2.5, P < 0.0001) and to rebleed (HR = 2.1, P = 0.01) than those on antiplatelets. Antithrombotic drug discontinuation upon discharge was associated with increased mortality in patients with cardiovascular disease.

Conclusion

In gastrointestinal bleeding, rebleeding and mortality were associated with being on anticoagulant drugs, while being on antiplatelet agents was protective against rebleeding. Discontinuation of antithrombotics upon discharge increased the risk of death. The findings inform risk stratification and decisions regarding continuation or discontinuation of antithrombotics.
A population-based US study of hepatitis C diagnosis rate
Authors: Yeo Yee Hui , Kam Leslie Y. , Le Michael H. , Jeong Donghak , Dang Nolan , Henry Linda , Cheung Ramsey , Nguyen Mindie H.
Published: April 2021

Background

Underdiagnosis of HCV infection may hinder the obtainment of 2030 elimination goal.

Objective

To estimate the pre-DAA HCV diagnosis rate to inform future public health effort.

Methods

Data were obtained from three nationwide databases (Truven Health MarketScan Research Database 2007–2014, US Census Bureau 2012–2016 and NHANES 2007–2014). HCV diagnosis was defined with either one inpatient or two outpatient HCV International Classification of Disease 9 codes, providing the number of patients with diagnosed HCV (Truven). US Census Bureau data were used for age- and sex-standardization. We derived the total (diagnosed and undiagnosed) HCV infection using the NHANES database. To determine the rate and number of undiagnosed HCV, we subtracted diagnosed HCV burden (Truven) from the total HCV burden (NHANES).

Results

Of the 198 073 302 privately insured Americans, 1.49% (2 951 490 persons) had HCV infection. However, only 362 672 (12.29%) persons were diagnosed with HCV, leaving 2 588 818 (87.71%) undiagnosed. About two-third (68.04%) and one-third (33.04%) of diagnosed HCV patients had HCV RNA or genotype tests overall, with even lower rates for the ≥65 age group, respectively.

Conclusion

In the pre-DAA era, only 12% of insured Americans with HCV were diagnosed. While this grim statistic is expected to rise, much more effort is needed to enhance the HCV care cascade.
Perspectives of using photodynamic therapy as antimicrobial therapy in endodontics
Authors: Piątek Dominika , Gerasymchuk Yuriy , Korona-Głowniak Izabela , Bachanek Teresa , Malm Anna , Łukowiak Anna
Published: April 2021

In times of multidrug resistance of bacteria, photodynamic therapy (PDT) seems to be promising in many fields of medicine, including endodontics, especially in the case of previous failures of root canal treatment and periapical lesions formation. PDT is based on the use of a light source and photosensitizers (PSs). Irradiation caused by the appropriately selected wavelength of light initiates the formation of singlet oxygen and/or free radicals, which provides the antimicrobial activity responsible for effective disinfection. In this manuscript, we compare the findings from all available papers of authors who perform their research in vivo. Despite the fact that they conducted their research in various ways, the results obtained in the course of these studies indicated an effective antibacterial effect of PDT in endodontic treatment. The second part of our work focuses on the perspectives of finding the best PSs that are used in PDT method with great expectations for materials based on graphene oxide as those which are not only carriers but also factors influencing the increase in the efficiency of the particles attached to them.
Application of machine-learning techniques in classification of HIV medical care status for people living with HIV in South Carolina
Authors: Olatosi Bankole , Sun Xiaowen , Chen Shujie , Zhang Jiajia , Liang Chen , Weissman Sharon , Li Xiaoming
Published: April 2021

Objectives:

Ending the HIV epidemic requires innovative use of data for intelligent decision-making from surveillance through treatment. This study sought to examine the usefulness of using linked integrated PLWH health data to predict PLWH's future HIV care status and compare the performance of machine-learning methods for predicting future HIV care status for SC PLWH.

Design:

We employed supervised machine learning for its ability to predict PLWH's future care status by synthesizing and learning from PLWH's existing health data. This method is appropriate for the nature of integrated PLWH data because of its high volume and dimensionality.

Methods:

A data set of 8888 distinct PLWH's health records were retrieved from an integrated PLWH data repository. We experimented and scored seven representative machine-learning models including Bayesian Network, Automated Neural Network, Support Vector Machine, Logistic Regression, LASSO, Decision Trees and Random Forest to best predict PLWH's care status. We further identified principal factors that can predict the retention-in-care based on the champion model.

Results:

Bayesian Network (F = 0.87, AUC = 0.94, precision = 0.87, recall = 0.86) was the best predictive model, followed by Random Forest (F = 0.78, AUC = 0.81, precision = 0.72, recall = 0.85), Decision Tree (F = 0.76, AUC = 0.75, precision = 0.70, recall = 0.82) and Neural Network (cluster) (F = 0.75, AUC = 0.71, precision = 0.69, recall = 0.81).

Conclusion:

These algorithmic applications of Bayesian Networks and other machine-learning algorithms hold promise for predicting future HIV care status at the individual level. Prediction of future care patterns for SC PLWH can help optimize health service resources for effective interventions. Predictions can also help improve retention across the HIV continuum.
Estimating the influence of Twitter on pre-exposure prophylaxis use and HIV testing as a function of rates of men who have sex with men in the United States
Authors: Chan Man-pui Sally , Morales Alex , Zlotorzynska Maria , Sullivan Patrick , Sanchez Travis , Zhai Chengxiang , Albarracín Dolores
Published: April 2021

Objective(s):

Acceptance of pre-exposure prophylaxis (PrEP) and testing for HIV is likely to vary as a function of the norms and communications within a geographic area. This study examined associations involving county tweets, in person communications, and HIV prevention and testing in regions with higher (vs. lower) estimated rates of men who have sex with men (MSM).

Design and Methods:

Ecological analyses examined (a) tweets about HIV (i.e. tweet rates per 100 000 county population and topic probabilities in 1959 US counties); (b) individual-level survey data about HIV prevention and testing and communications about PrEP and HIV (N = 30 675 participants); and (c) estimated county-level MSM rates (per 1 000 adult men).

Results:

In counties with higher rates of MSM, tweet rates were directly associated with PrEP use and HIV testing (rs = .06, BF10 > 10). Topics correlated with PrEP use (rs = −0.06 to 0.07, BF10 > 10) and HIV testing (rs = −0.05 to 0.05, BF10 > 10). Mediation analyses showed that hearing about and discussing PrEP mediated the relations between tweet rates and PrEP use (b

i

∗ = 0.01–0.05, BF10 > 100) and between topics and PrEP use (b

i

∗ = −0.04– 0.05, BF10 > 10). Moreover, hearing about PrEP was associated with PrEP use, which was in turn associated with tweet rates (b

i

∗ = 0.01, BF10 > 100) and topics (b

i

∗ = −0.03 – 0.01, BF10 > 10).

Conclusions:

Rates of MSM appear to lead to HIV tweets in a region, in person communications about PrEP, and, ultimately, actual PrEP use. Also, as more men hear about PrEP, they may use PrEP more and may tweet about HIV.
Power of Big Data in ending HIV
Authors: Olatosi Bankole , Vermund Sten H. , Li Xiaoming
Published: April 2021

The articles in this special issue of AIDS focus on the application of the so-called Big Data science (BDS) as applied to a variety of HIV-applied research questions in the sphere of health services and epidemiology. Recent advances in technology means that a critical mass of HIV-related health data with actionable intelligence is available for optimizing health outcomes, improving and informing surveillance. Data science will play a key but complementary role in supporting current efforts in prevention, diagnosis, treatment, and response needed to end the HIV epidemic. This collection provides a glimpse of the promise inherent in leveraging the digital age and improved methods in Big Data science to reimagine HIV treatment and prevention in a digital age.
Testicular microvascular flow is altered in Klinefelter syndrome and predicts circulating testosterone
Authors: Carlomagno Francesco , Pozza Carlotta , Tenuta Marta , Pofi Riccardo , Tarani Luigi , Sesti Franz , Minnetti Marianna , Gianfrilli Daniele , Isidori Andrea M.
Published: April 2021

Context

Experimental studies on Klinefelter syndrome (KS) reported increased intratesticular testosterone (T) levels coexisting with reduced circulating levels. Abnormalities in testicular microcirculation have been claimed; however, no studies investigated in vivo testicular blood flow dynamics in humans with KS.

Objective

To analyze the testicular microcirculation in KS by contrast-enhanced ultrasonography (CEUS) and correlate vascular parameters with endocrine function.

Design and Setting

Prospective study. University Settings.

Patients

51 testicular scans, 17 testes from 10 T-naïve subjects with KS and 34 testes from age-matched eugonadal men (CNT) who underwent CEUS for incidental nonpalpable testicular lesions.

Main Outcomes

CEUS kinetic parameters.

Results

CEUS revealed slower testicular perfusion kinetics in subjects with KS than in age-matched CNT. Specifically, the wash-in time (Tin, p = 0.008), mean transit time (MTT, p = 0.008), time to peak (TTP, p < 0.001), and washout time (Tout 50%, p = 0.008) were all prolonged. Faster testicular blood flow was associated with higher total T levels. Principal component analysis and multiple linear regression analyses confirmed the findings, and supported a role for reduced venous blood flow as independent predictor of total T levels.

Conclusions

Testicular venous blood flow is altered in KS and independently predicts T peripheral release.
The effect of population mobility restrictive measures on the incidence of SARS-CoV-2 infection in the early phase of the pandemic
Authors: Modelli de Andrade Luis Gustavo , Ferreira Gustavo Fernandes , Tedesco-Silva Helio
Published: April 2021

Background

This analysis aims to assess the association between population restrictive measures and the cumulative number of confirmed COVID-19 cases in the early phase of pandemic.

Methods

We compared mobility data extracted from the Mobility Reports provided by Google with the cumulative number of confirmed cases of COVID-19 of 15 countries provided by John Hopkins University. We compered the number of confirmed COVID-19 cases before and after the peak effect (PE) of population mobility restrictions in each country, defined as the highest percent reduction in mobility measurements.

Results

Time to PE of population mobility restrictions ranged between 16 and 45 days after the report of the index COVID-19 confirmed case in each country. The most frequent reductions in activities were retail & recreation, parks, and transit & stations, ranging from 30% to 90%. Despite this variability in PE among the countries, the predicted smooth effect after the PE of population mobility restrictions was observed in almost all countries.

Conclusions

These data suggest that the reduction in mobility was associated with a decrease in the cumulative total number of COVI-19 cases in each country, underscoring that the use of widely available real-time surveillance data might be a valuable resource during this pandemic.
Effect of remedial teaching on academic performance of poorly performing students in Pharmacology
Authors: Modi Sophia B , Bindulatha Nair R , Libu GK
Published: April 2021

Purpose

Significant learning difficulties requiring remediation has been observed to be experienced by many medical trainees. Research with regard to individualized remedial teaching based on pedagogical diagnosis is a strong need of the time. The objectives of this study were to assess the effect of remedial teaching in improving academic performance among poorly performing students in Pharmacology and to assess factors that could affect academic performance.

Method

The study was conducted in 2019. Academically poor performing students (< 50 % marks in Pharmacology first sessional exam) were selected after getting informed consent. After obtaining baseline information andStudy skills self-assessment inventoryinformation from all students, academically poor performing students (53 students) were identified and they were randomized into two groups. One group (26 students) received academic support alone. The second group (27 students) received academic support, sessions on study skills, stress-coping strategies and counselling regarding their academic and non-academic problems.

Results

The improvement in test scores among all participants of remedial sessions was statistically significant. Mean pre-test marks 5.27 ± 3.6 post test 14.63 ± 1.24 and the difference is statistically significant. Though apparently high 10.02 ± 3.25 Vs. 8.59 ± 3.55, the post intervention gain in scores is not statistically significant between Academic support + special package group Vs. Academic support alone group (P value 0.16)

Conclusion

Tailored or individualised remediation measures can greatly enhance the academic performance of undergraduate medical students and help them make satisfactory progress on the course.
Ultra-fast, high throughput and inexpensive detection of SARS-CoV-2 seroconversion
Authors: Conzentino Marcelo S. , Santos Tatielle P. C. , Selim Khaled A. , Wagner Berenike , Alford Janette T. , Deobald Nelli , Paula Nigela. M. , Rego Fabiane G. M. , Zanette Dalila L. , Aoki Mateus N. , Nardin Jeanine M. , Huergo Maria C.C. , Reis Rodrigo A. , Huergo Luciano F.
Published: April 2021

A technique allowing high throughput, fast and low-cost quantitative analysis of human IgG antibodies reacting to SARS-CoV-2 antigens will be required to understand the levels of protecting antibodies in the population raised in response to infections and/or to immunization. We described previously a fast, simple, and inexpensive Ni2+magnetic bead immunoassay which allowed detection of human antibodies reacting against the SARS-CoV-2 nucleocapsid protein using a minimal amount of serum or blood. A major drawback of the previously described system was that it only processed 12 samples simultaneously. Here we describe a manually operating inexpensive 96 well plate magnetic extraction / homogenization process which allows high throughput analysis delivering results of 96 samples in chromogenic format in 12 minutes or in fluorescent ultrafast format which takes only 7 minutes. We also show that His tag antigen purification can be performed on the fly while loading antigens to the Ni2+magnetic beads in a process which takes only 12 min reducing the pre analytical time and cost. Finally, we show that the magnetic bead immunoassay is antigen flexible and can be performed using either Nucleocapsid, Spike or Spike RBD. The method performed with low inter and intra assay variability using different antigens and detection modes and was able to deliver >99.5% specificity and >95% sensitivity for a cohort of 203 pre pandemic and 63 COVID-19 positive samples.
SARS-CoV-2 transmission dynamics in Belarus revealed by genomic and incidence data analysis
Authors: Nemira Alina , Adeniyi Ayotomiwa Ezekiel , Gasich Elena L. , Bulda Kirill Y. , Valentovich Leonid N. , Krasko Anatoly G. , Glebova Olga , Kirpich Alexander , Skums Pavel
Published: April 2021

Since the emergence of COVID-19, a series of non-pharmaceutical interventions (NPIs) has been implemented by governments and public health authorities world-wide to control and curb the ongoing pandemic spread. From that perspective, Belarus is one of a few countries with a relatively modern healthcare system, where much narrower NPIs have been put in place. Given the uniqueness of this Belarusian experience, the understanding its COVID-19 epidemiological dynamics is essential not only for the local assessment, but also for a better insight into the impact of different NPI strategies globally. In this work, we integrate genomic epidemiology and surveillance methods to investigate the emergence and spread of SARS-CoV-2 in the country. The observed Belarusian SARS-CoV-2 genetic diversity originated from at least eighteen separate introductions, at least five of which resulted in on-going domestic transmissions. The introduction sources represent a wide variety of regions, although the proportion of regional virus introductions and exports from/to geographical neighbors appears to be higher than for other European countries. Phylodynamic analysis indicates a moderate reduction in the effective reproductive number ℛe after the introduction of limited NPIs, with the reduction magnitude generally being lower than for countries with large-scale NPIs. On the other hand, the estimate of the Belarusian ℛe at the early epidemic stage is comparable with this number for the neighboring ex-USSR country of Ukraine, where much broader NPIs have been implemented. The actual number of cases by the end of May, 2020 was predicted to be 2-9 times higher than the detected number of cases.
Expanding access to SARS-CoV-2 IgG and IgM serologic testing using fingerstick whole blood, plasma, and rapid lateral flow assays
Authors: Anderson Mark , Holzmayer Vera , Vallari Ana , Taylor Russell , Moy James , Cloherty Gavin
Published: April 2021

Serologic testing for SARS-CoV-2 antibodies can be used to confirm diagnosis, estimate seroprevalence, screen convalescent plasma donors, and assess vaccine efficacy. Several logistical and infrastructure challenges limit access to SARS-CoV-2 serologic testing. Dried blood spot (DBS) samples have been used for serology testing of various diseases in resource-limited settings. We examined the use of DBS samples and capillary blood (fingerstick) plasma collected in Microtainer tubes for SARS-CoV-2 testing with the automated Abbott ARCHITECT™ SARS-CoV-2 IgG (List 6R86) and IgM assays and use of venous whole blood with a prototype PANBIO™ rapid point-of-care lateral flow SARS-CoV-2 IgG assay. The ARCHITECT™ SARS-CoV-2 IgG assay was initially optimized for use with DBS, venous and capillary plasma, and venous whole blood collected from patients with symptoms and PCR-confirmed COVID-19 and negative asymptomatic controls. Assay linearity and reproducibility was confirmed with 3 contrived DBS samples, with sample stability and signal recovery after 14 days at room temperature. ARCHITECT™ SARS-CoV-2 IgG and IgM assay results showed high concordance between fingerstick DBS and venous DBS samples, and between fingerstick DBS and venous whole blood samples (n=61). Discordant results were seen in 3 participants (2 IgG, 1 IgM) who were in the process of seroreversion at the time of sample collection and had results near the assay cutoff. Use of fingerstick plasma collected in Microtainer tubes (n=109) showed 100% concordant results (R2=0.997) with matched patient venous plasma on the ARCHITECT™ SARS-CoV-2 IgG assay. High concordance of assay results (92.9% positive, 100% negative) was also observed for the PANBIO™ SARS-CoV-2 IgG assay compared to the ARCHITECT™ SARS-CoV-2 IgG assay run with matched venous plasma (n=61). Fingerstick DBS and plasma samples are easy and inexpensive to collect and, along with the use of rapid point-of-care testing platforms, will expand access to SARS-CoV-2 serology testing, particularly in resource-limited areas.
Cross-Species Analysis Defines the Conservation of Anatomically-Segregated VMH Neuron Populations
Authors: Affinati Alison H. , Sabatini Paul V. , True Cadence , Tomlinson Abigail J. , Kirigiti Melissa , Lindsley Sarah R. , Li Chien , Olson David P. , Kievit Paul , Myers Martin G. , Rupp Alan C.
Published: April 2021

The ventromedial hypothalamic nucleus (VMH) controls diverse behaviors and physiologic functions, suggesting the existence of multiple VMH neural subtypes with distinct functions. Combing Translating Ribosome Affinity Purification with RNA sequencing (TRAP-seq) data with snRNA-seq data, we identified 24 mouse VMH neuron clusters. Further analysis, including snRNA-seq data from macaque tissue, defined a more tractable VMH parceling scheme consisting of 6 major genetically- and anatomically-differentiated VMH neuron classes with good cross-species conservation. In addition to two major ventrolateral classes, we identified three distinct classes of dorsomedial VMH neurons. Consistent with previously-suggested unique roles for leptin receptor (Lepr)-expressing VMH neurons,Leprexpression marked a single dorsomedial class. We also identified a class of glutamatergic VMH neurons that resides in the tuberal region, anterolateral to the neuroanatomical core of the VMH. This atlas of conserved VMH neuron populations provides an unbiased starting point for the analysis of VMH circuitry and function.
Coupled exoskeleton assistance simplifies control and maintains metabolic benefits: a simulation study
Authors: Bianco Nicholas A. , Franks Patrick W. , Hicks Jennifer L. , Delp Scott L.
Published: April 2021

Assistive exoskeletons can reduce the metabolic cost of walking, and recent advances in exoskeleton device design and control have resulted in large metabolic savings. Most exoskeleton devices provide assistance at either the ankle or hip. Exoskeletons that assist multiple joints have the potential to provide greater metabolic savings, but can require many actuators and complicated controllers, making it difficult to design effective assistance. Coupled assistance, when two or more joints are assisted using one actuator or control signal, could reduce control dimensionality while retaining metabolic benefits. However, it is unknown which combinations of assisted joints are most promising and if there are negative consequences associated with coupled assistance. Since designing assistance with human experiments is expensive and time-consuming, we used musculoskeletal simulation to evaluate metabolic savings from multi-joint assistance and identify promising joint combinations. We generated 2D muscle-driven simulations of walking while simultaneously optimizing control strategies for simulated lower-limb exoskeleton assistive devices to minimize metabolic cost. Each device provided assistance either at a single joint or at multiple joints using massless, ideal actuators. To assess if control could be simplified for multi-joint exoskeletons, we simulated different control strategies in which the torque provided at each joint was either controlled independently or coupled between joints. We compared the predicted optimal torque profiles and changes in muscle and whole-body metabolic power consumption across the single joint and multi-joint assistance strategies. We found multi-joint devices–whether independent or coupled–provided 50% greater metabolic savings than single joint devices. The coupled multi-joint devices were able to achieve most of the metabolic savings produced by independently-controlled multi-joint devices. Our results indicate that device designers could simplify multi-joint exoskeleton designs by reducing the number of torque control parameters through coupling, while still maintaining large reductions in metabolic cost.
The view of microbes as energy converters illustrates the trade-off between growth rate and yield
Authors: Wilken St. Elmo , Frazão Victor Vera , Saadat Nima P. , Ebenhöh Oliver
Published: April 2021

The application of thermodynamics to microbial growth has a long tradition that originated in the middle of the 20thcentury. This approach reflects the view that self-replication is a thermodynamic process that is not fundamentally different from mechanical thermodynamics. The key distinction is that a free energy gradient is not converted into mechanical (or any other form of) energy, but rather into new biomass. As such, microbes can be viewed as energy converters that convert a part of the energy contained in environmental nutrients into chemical energy that drives self-replication. Before the advent of high-throughput sequencing technologies, only the most central metabolic pathways were known. However, precise measurement techniques allowed for the quantification of exchanged extracellular nutrients and heat of growing microbes with their environment. These data, together with the absence of knowledge of metabolic details, drove the development of so-called black box models, which only consider the observable interactions of a cell with its environment and neglect all details of how exactly inputs are converted into outputs. Now, genome sequencing and genome-scale metabolic models provide us with unprecedented detail about metabolic processes inside the cell. However, the derived modelling approaches make surprisingly little use of thermodynamic concepts. Here, we review classical black box models and modern approaches that integrate thermodynamics into genome-scale metabolic models. We also illustrate how the description of microbial growth as an energy converter can help to understand and quantify the trade-off between microbial growth rate and yield.

Perspective

Microbial growth is the foundation of many biotechnological applications. The key to optimizing microbial growth lies in thermodynamics, similar to how classical thermodynamics helped optimize steam engines in the 19thcentury.

Genome-scale metabolic models have become widely available, and are used to predict microbial growth. These predictions often fail because these models do not distinguish between growth rate and yield.

Classical black box models present a sound thermodynamic theory, by viewing microbes as energy converters. Incorporating such concepts into genome-scale metabolic models has the promise to advance our fundamental understanding of microbial growth, and thus to improve the predictive power of these models.
Polygenic adaptation from standing genetic variation allows rapid ecotype formation
Authors: Fuhrmann Nico , Prakash Celine , Kaiser Tobias S.
Published: April 2021

Adaptive ecotype formation is the first step to speciation, but the genetic underpinnings of this process are poorly understood. Marine midges of the genusClunio(Diptera) have recolonized Northern European shore areas after the last glaciation. In response to local tide conditions they have formed different ecotypes with respect to timing of adult emergence, oviposition behavior and larval habitat. Genomic analysis confirms the recent establishment of these ecotypes, reflected in massive haplotype sharing between ecotypes, irrespective of whether there is ongoing gene flow or geographic isolation. QTL mapping and genome screens reveal patterns of polygenic adaptation from standing genetic variation. Ecotype-associated loci prominently include circadian clock genes, as well as genes affecting sensory perception and nervous system development, hinting to a central role of these processes in ecotype formation. Our data show that adaptive ecotype formation can occur rapidly, with ongoing gene flow and largely based on a re-assortment of existing alleles.