bluuebunny/crossref_metadata_2025 huggingface dataset:
Splint Padding Thickness: Temperature Effects and X-ray Visualization
Authors: Everson Peter J. , Sura Tej , Udawatta Thiran , Nicolaou Daemeon , Watson John Tracy
Published: January 2021

Objectives:

The purpose of this study was to determine if the thickness of splint padding could be determined on X-rays, and whether increasing layers of splint padding have an effect on temperature at the skin after placement.

Methods:

Both in vitro and in vivo testing was performed. Ten cadaveric lower extremities were used. A thermocouple was placed on the posterior calf for temperature determination. Cadavers were used with short leg posterior splints with sidebars placed using various thicknesses of padding: (1) 2 layers of Webril, (2) 4 layers of Webril, (3) 2 × 2 padding (Webril followed by kerlix, then repeated), and (4) bulky cotton padding. A splint with no padding was used as a control. Lateral X-rays of the ankle were obtained. The padding thickness was measured. The change in temperature at the level of the skin was measured throughout the process. The test was then repeated in vivo to correlate the cadaver findings with a live subject.

Results:

The mean thickness of the 5 padding types could be reliably determined on X-ray. Our cadaver temperature data shows that all padding thickness tested decreased temperature change after plaster curing, with no significant difference between wraps. Live subject testing showed similarities between the 2-layer Webril and 2 × 2 padding, and between the 4-layer Webril and bulky padding.

Conclusions:

Padding thickness can be consistently determined on X-ray. We determined that at least 2 layers of Webril significantly decrease temperature change at the level of the skin caused by plaster curing. Two layers of Webril can be identified on X-ray by measuring at least 1 mm of padding.
Opioid Use After Intensive Care: A Nationwide Cohort Study
Authors: von Oelreich Erik , Eriksson Mikael , Sjölund Karl-Fredrik , Discacciati Andrea , Larsson Emma , Oldner Anders
Published: January 2021

OBJECTIVE:

To describe opioid use after ICU admission, identify factors associated with chronic opioid use after critical care, and determine if chronic opioid use is associated with an increased risk of death.

DESIGN:

Retrospective cohort study.

SETTING:

Sweden including all registered ICU admissions between 2010 and 2018.

PATIENTS:

Adults surviving the first two quarters after ICU admission were eligible for inclusion. A total of 265,496 patients were screened and 61,094 were ineligible.

INTERVENTIONS:

Admission to intensive care.

MEASUREMENTS AND MAIN RESULTS:

Among 204,402 individuals included in the cohort, 22,138 developed chronic opioid use following critical care. Mean opioid consumption peaked after admission followed by a continuous decline without returning to baseline during follow-up of 24 months. Factors associated with chronic opioid use included high age, female sex, presence of comorbidities, preadmission opioid use, and ICU length of stay greater than 2 days. Adjusted hazard ratio for death 6–18 months after admission for chronic opioid users was 1.7 (95% CI, 1.6–1.7; p < 0.001). In the subset of patients not using opioids prior to admission, similar findings were noted.

CONCLUSIONS:

Mean opioid consumption is increased 24 months after ICU admission despite the lack of evidence for long-term opioid treatment. Given the high number of ICU entries and risk of excess mortality for chronic users, preventing opioid misuse is important when improving long-term outcomes after critical care.
Branched Multipeptide-combined Adjuvants Potentially Improve the Antitumor Effects on Glioblastoma
Authors: Tran Thi-Anh-Thuy , Kim Young-Hee , Jung Shin , Kim In-Young , Moon Kyung-Sub , Jang Woo-Youl , Lee Hyun-Ju , Lee Je-Jung , Jung Tae-Young
Published: January 2021

The promising immunotherapy effects of a multiple antigenic peptide on glioblastoma (GBM) in a previous study encourage the use of adjuvants to enhance its therapeutic efficacy. Among adjuvants, pan HLA-DR-binding epitope (PADRE) and anti-programmed cell death protein 1 (anti-PD1) have potentially been tested for cancer immunotherapy. Therefore, here we evaluated the ability of PADRE and anti-PD1 to enhance the function of the branched multipeptide against GBM. The potential utility of tumor-associated antigens (ErbB-2 and WT-1) targeting GBM with HLA-A24 was confirmed and a branched multipeptide was constructed from these antigens. The effects of the branched multipeptide and PADRE on immunophenotyping and polarized Th cytokine production in dendritic cells were clarified. The expression of PD1 on T cells and PDL1 on GBM cells was also investigated. The interferon-γ enzyme-linked immunospot and lactate dehydrogenase release assays were performed to determine the function of GBM peptide antigen-specific cytotoxic T cells against GBM cells. Overall, this study showed that both ErbB-2 and WT-1 are potential candidates for branched multipeptide construction. The branched multipeptide and PADRE enhanced the expression of major histocompatibility complex and co-stimulatory molecules and the production of polarized Th1 cytokines in dendritic cells. The increase in the number of interferon-γ+ effector T cells was consistent with the increase in the percentage specific lysis of GBM target cells by GBM peptide antigen-specific cytotoxic T cells in the presence of the branched multipeptide, PADRE, and anti-PD1. Our study suggests the combination of branched multipeptide and adjuvants such as PADRE and anti-PD1 can potentially enhance the effects of immunotherapy for GBM treatment.
SENIOR–LØKEN SYNDROME
Authors: Yahalom Claudia , Volovelsky Oded , Macarov Michal , Altalbishi Alaa , Alsweiti Yahya , Schneider Nina , Hanany Mor , Khan Muhammad Imran , Cremers Frans P.M. , Anteby Irene , Banin Eyal , Sharon Dror , Khateb Samer
Published: January 2021

Purpose:

To report genetic and clinical findings in a case series of 10 patients from eight unrelated families diagnosed with Senior–Løken syndrome.

Methods:

A retrospective study of patients with Senior–Løken syndrome. Data collected included clinical findings electroretinography and ocular imaging. Genetic analysis was based on molecular inversion probes, whole-exome sequencing (WES), and Sanger sequencing.

Results:

All patients who underwent electrophysiology (8/10) had widespread photoreceptor degeneration. Genetic analysis revealed two mutations in NPHP1, two mutations in NPHP4, and two mutations in IQCB1 (NPHP5). Five of the six mutations identified in the current study were found in a single family each in our cohort. The IQCB1-p.R461* mutation has been identified in 3 families. Patients harboring mutations in IQCB1 were diagnosed with Leber congenital amaurosis, while patients with NPHP4 and NPHP1 mutations showed early and sector retinitis pigmentosa, respectively. Full-field electroretinography was extinct for 6 of 10 patients, moderately decreased for two, and unavailable for another 2 subjects. Renal involvement was evident in 7/10 patients at the time of diagnosis. Kidney function was normal (based on serum creatinine) in patients younger than 10 years. Mutations in IQCB1 were associated with high hypermetropia, whereas mutations in NPHP4 were associated with high myopia.

Conclusion:

Patients presenting with infantile inherited retinal degeneration are not universally screened for renal dysfunction. Modern genetic tests can provide molecular diagnosis at an early age and therefore facilitate early diagnosis of renal disease with recommended periodic screening beyond childhood and family planning.
Xanthogranulomatous pancreatitis combined with multifocal necrosis: A case report and literature review
Authors: Tang Xuemei , Lu Wenming
Published: January 2021

Xanthogranulomatous inflammation is rare and occurs in several viscera in the body, such as the kidney, gallbladder, bone, and stomach. The pathogenesis of Xanthogranulomatous pancreatitis (XGP) is not well understood, and the disease is characterized by lipid-laden histiocytes deposited at various sites in the organs. XGP associated with multifocal necrosis is extremely rare. In this report, we described a case of XGP associated with multifocal necrosis and included a review of the literature.
Evaluating Nonresponse Weighting Adjustment for the Population-Based HIV Impact Assessment Surveys on Incorporating Survey Outcomes
Authors: Lin Tien-Huan , Cervantes Flores Ismael , Saito Suzue , Bain Rommel
Published: January 2021

Background:

The nonresponse weighting adjustment of the Population-based HIV Impact Assessment (PHIA) surveys uses the weighting class method in combination with a tree analysis to identify predictors significant to response propensity. Variable selection for this type of nonresponse adjustment identifies auxiliary variables correlated with response propensity alone and produces 1 set of weights applicable for all analyses of the survey data. An alternative approach identifies auxiliary variables correlated to both the response probability and selected key outcome variables. This approach may identify a different set of variables for the nonresponse adjustments and may produce more efficient estimates for the key outcome variables.

Setting:

The PHIA surveys from 2016 to 2017.

Methods:

Weighting class, joint-classification, and two-step modeling.

Results:

There was little difference among estimates produced by the alternative weighting methods and the PHIA estimates. The joint-classification method produced more efficient estimates (ie, smaller design effects) compared with the PHIA method, while the two-step method was inconclusive.

Conclusions:

The efficiency of the estimates produced by the PHIA weighting method closely resembles those specifically targeted at key survey outcomes and serves well as a multipurpose weight.
Changes in Sexual Behavior, PrEP Adherence, and Access to Sexual Health Services Because of the COVID-19 Pandemic Among a Cohort of PrEP-Using MSM in the South
Authors: Pampati Sanjana , Emrick Kayla , Siegler Aaron J. , Jones Jeb
Published: January 2021

Background:

The coronavirus disease 2019 (COVID-19) pandemic has had unforeseen consequences on the delivery of HIV and sexually transmitted disease (STD) prevention services. However, little is known about how the pandemic has impacted pre-exposure prophylaxis (PrEP)-using men who have sex with men (MSM).

Methods:

Data come from an online cohort of PrEP-using MSM in the Southern United States from October 2019 to July 2020. Participants were administered 10 surveys in total, including 1 ad hoc survey specifically on COVID-19. We conducted a cross-sectional analysis of this ad hoc survey (n = 56) and present changes in sexual behaviors and utilization of and access to sexual health services. Using linear mixed-effect regression models, we also analyzed data from the larger cohort and document how sexual behaviors and PrEP use varied longitudinally across several months.

Results:

A fifth of participants discontinued or changed how often they take PrEP because of COVID-19. A quarter of the cohort documented challenges when attempting to access PrEP, HIV testing, or STD testing. For all sexual behaviors examined longitudinally—number of male sexual partners, anal sex acts, condomless anal sex, and oral sex (all measured in the past 2 weeks)—there was a decrease from February to April followed by an increase from April to June.

Discussion:

Our findings suggest reduced access to and utilization of STD and HIV services coupled with a continuation of behaviors which confer STD/HIV risk. Ensuring appropriate delivery of STD/HIV prevention services during this pandemic is imperative.
Primary Cutaneous Natural Killer/T-Cell Lymphoma
Authors: Lu Xia , Kan Ying , Wang Wei , Yang Jigang
Published: January 2021

A 24-year-old man with a history of hemophagocytic lymphohistiocytosis (HLH) presented with swelling of the left foot and skin ulcer. The patient received bone marrow transplantation for HLH 3 years ago for his HLH. Biopsy of left foot skin demonstrated primary cutaneous natural killer/T-cell lymphoma: a posttransplant lymphoproliferative disorder. FDG PET/CT images demonstrated multiple foci of abnormal accumulation in the body, especially in the skin. Follow-up PET/CT after chemotherapy demonstrated that most abnormal activities disappeared except for the lesion in the left foot.
Intramedullary Metacarpal Screw Fracture Fixation
Authors: Geada Luis R. , Cochrane Shannon , Schroeder Carol , Luscia Chris , Mir Haaris , Daniali Lily , Pulikkottil Benson J.
Published: January 2021

Intramedullary metacarpal screw fixation has shown promising results and quick functional recovery with the proper postoperative rehabilitation. The rehabilitative process after this procedure has not been compared across literature. A retrospective review of literature was used to recommend a therapy timeline, activity and recommendations to allow for proper postoperative rehabilitation for optimal results. An illustrative case report is presented to explain technique and outcomes.
Sporofaciens musculi gen. nov., sp. nov., a novel bacterium isolated from the caecum of an obese mouse
Authors: Rasmussen Torben Sølbeck , Streidl Theresa , Hitch Thomas C. A. , Wortmann Esther , Deptula Paulina , Kofoed Michael V. W. , Riedel Thomas , Neumann-Schaal Meina , Hansen Michael , Nielsen Dennis Sandris , Clavel Thomas , Vogensen Finn Kvist
Published: January 2021

A bacterial strain, designated WCA-9-b2T, was isolated from the caecal content of an 18-week-old obese C57BL/6NTac male mouse. According to phenotypic analyses, the isolate was rod-shaped, strictly anaerobic, spore-forming, non-motile and Gram-stain-positive, under the conditions tested. Colonies were irregular and non-pigmented. Analysis of the 16S rRNA gene sequence indicated that the isolate belonged to the orderClostridialeswithDorea longicatenaATCC 27755T(94.9 % sequence identity),Ruminococcus gnavusATCC 29149T(94.8%) andClostridium scindensATCC 35704T(94.3%) being the closest relatives. Whole genome sequencing showed an average nucleotide identity <74.23 %, average amino acid identity <64.52–74.67 % and percentage of conserved proteins values <50 % against the nine closest relatives (D. longicatena,Ruminococcus gnavus,C. scindens,Dorea formicigenerans,Ruminococcus lactaris,Clostridium hylemonae,Merdimonas faecis,Faecalicatena contortaandFaecalicatena fissicatena). The genome-based G+C content of genomic DNA was 44.4 mol%. The major cellular fatty acids were C16 : 0(24.5%), C18 : 1cis9 (19.8 %), C16 : 0DMA (11.7%), C18 : 0(8.4%) and C14 : 0(6.6%). Respiratory quinones were not detected. The predominant metabolic end products of glucose fermentation were acetate and succinate. Production of CO2and H2were detected. Based on these data, we propose that strain WCA-9-b2Trepresents a novel species within a novel genus, for which the nameSporofaciens musculigen. nov., sp. nov. is proposed. The type strain is WCA-9-b2T(=DSM 106039T=CECT 30156T).
SARS-CoV-2 seropositivity and subsequent infection risk in healthy young adults: a prospective cohort study
Authors: Letizia Andrew G. , Ge Yongchao , Vangeti Sindhu , Goforth Carl , Weir Dawn L , Kuzmina Natalia A. , Chen Hua Wei , Ewing Dan , Soares-Schanoski Alessandra , George Mary-Catherine , Graham William D. , Jones Franca , Bharaj Preeti , Lizewski Rhonda A. , Lizewski Stephen A. , Marayag Jan , Marjanovic Nada , Miller Clare , Mofsowitz Sagie , Nair Venugopalan D. , Nunez Edgar , Parent Danielle M. , Porter Chad K. , Ana Ernesto Santa , Schilling Megan , Stadlbauer Daniel , Sugiharto Victor , Termini Michael , Sun Peifang , Tracy Russell. P. , Krammer Florian , Bukreyev Alexander , Ramos Irene , Sealfon Stuart C.
Published: January 2021

Background

The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subsequent infection among seropositive young adults was studied prospectively.

Methods

The study population comprised 3,249 predominantly male, 18-20-year-old Marine recruits. Upon arrival at a Marine-supervised two-week quarantine, participants were assessed for baseline SARS-CoV-2 IgG seropositivity, defined as a 1:150 dilution or greater on receptor binding domain and full-length spike protein enzyme-linked immunosorbent (ELISA) assays. SARS-CoV-2 infection was assessed by PCR at initiation, middle and end of the quarantine. After appropriate exclusions, including participants with a positive PCR during quarantine, we performed three biweekly PCR tests in both seropositive and in seronegative groups once recruits left quarantine and entered basic training and baseline neutralizing antibody titers on all subsequently infected seropositive and selected seropositive uninfected participants.

Findings

Among 189 seropositive participants, 19 (10.1%) had at least one positive PCR test for SARS-CoV-2 during the six-week follow-up (1.1 cases per person-year). In contrast, 1,079 (48.0%) of the 2,247 seronegative participants tested positive (6.2 cases per person-year). The incidence rate ratio was 0.18 (95% CI 0.11-0.28, p<0.00001). Among seropositive recruits, infection was associated with lower baseline full-length spike protein IgG titers (p<0.0001). Compared with seronegative recruits, seropositive recruits had about 10-fold lower viral loads (ORF1ab gene, p<0.005), and trended towards shorter duration of PCR positivity (p=0.18) and more frequent asymptomatic infections (p=0.13). Among seropositive participants, baseline neutralizing titers were detected in 45 of 54 (83.3%) uninfected and in 6 of 19 (31.6%) infected participants during the 6 weeks of observation (ID50 difference p<.0001).

Interpretation

Seropositive young adults had about one-fifth the risk of subsequent infection compared with seronegative individuals. Although antibodies induced by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralization activity or immunity against subsequent infection. These findings may be relevant for optimization of mass vaccination strategies.

Funding

Defense Health Agency and Defense Advanced Research Projects Agency
The E484K mutation in the SARS-CoV-2 spike protein reduces but does not abolish neutralizing activity of human convalescent and post-vaccination sera
Authors: Jangra Sonia , Ye Chengjin , Rathnasinghe Raveen , Stadlbauer Daniel ,   PVI study group, Krammer Florian , Simon Viviana , Martinez-Sobrido Luis , García-Sastre Adolfo , Schotsaert Michael
Published: January 2021

One year in the coronavirus disease 2019 (COVID-19) pandemic, the first vaccines are being rolled out under emergency use authorizations. It is of great concern that newly emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can escape antibody-mediated protection induced by previous infection or vaccination through mutations in the spike protein. The glutamate (E) to Lysine (K) substitution at position 484 (E484K) in the receptor binding domain (RBD) of the spike protein is present in the rapidly spreading variants of concern belonging to the B.1.351 and P.1 lineages. We performed in vitro microneutralization assays with both the USA-WA1/2020 virus and a recombinant (r)SARS-CoV-2 virus that is identical to USA-WA1/2020 except for the E484K mutation introduced in the spike RBD. We selected 34 sera from study participants based on their SARS-CoV-2 spike ELISA antibody titer (negative [N=4] versus weak [N=8], moderate [N=11] or strong positive [N=11]). In addition, we included sera from five individuals who received two doses of the Pfizer SARS-CoV-2 vaccine BNT162b2. Serum neutralization efficiency was lower against the E484K rSARS-CoV-2 (vaccination samples: 3.4 fold; convalescent low IgG: 2.4 fold, moderate IgG: 4.2 fold and high IgG: 2.6 fold) compared to USA-WA1/2020. For some of the convalescent donor sera with low or moderate IgG against the SARS-CoV-2 spike, the drop in neutralization efficiency resulted in neutralization ID50 values similar to negative control samples, with low or even absence of neutralization of the E484K rSARS-CoV-2. However, human sera with high neutralization titers against the USA-WA1/2020 strain were still able to neutralize the E484K rSARS-CoV-2. Therefore, it is important to aim for the highest titers possible induced by vaccination to enhance protection against newly emerging SARS-CoV-2 variants. Two vaccine doses may be needed for induction of high antibody titers against SARS-CoV-2. Postponing the second vaccination is suggested by some public health authorities in order to provide more individuals with a primer vaccination. Our data suggests that this may leave vaccinees less protected against newly emerging variants.
Depression Symptoms During the COVID-19 Pandemic among Well-educated, Employed Adults with Low Infection Risks
Authors: Thomas Duncan , Brown Tyson , Taylor Donald H. , Lawton Ralph , Lee Victoria K. , Mburi Menna , Wong Michelle , Kranton Rachel
Published: January 2021

Levels and distributions of depression symptoms 8-10 months after the onset of the COVID-19 pandemic are reported in a population of faculty, staff, and students at Duke University who faced minimal infection and economic disruption due to the pandemic. Almost 5,000 respondents age 18-81 years who completed the 20-item Center for Epidemiological Studies-Depression (CES-D) battery reported high rates of depression symptoms with more than 40% reporting levels that indicate risk of moderate depression and 25% indicating risk of severe depression. There is a very steep age gradient with the highest levels reported by the youngest respondents of whom over 40% are at risk of severe depression. Symptoms are worse among those who report the demands of work often interfere with family responsibilities but these pressures neither explain the high reported rates nor the steep age gradient. Severe depression risks are highest among students. High levels of depression symptoms during the pandemic appear to be persistent and not confined to those at greatest risk of infection or economic insecurity.
SARS-CoV-2 antigenemia/viremia masks seroconversion in a COVID-19 patient
Authors: Belogiannis Konstantinos , Florou Venetia A. , Fragkou Paraskevi C. , Ferous Stefanos , Chatzis Loukas , Polyzou Aikaterini , Lagopati Nefeli , Touliatou Aikaterini , Vassilakos Demetrios , Kittas Christos , Tzioufas Athanasios G. , Tsiodras Sotiris , Gorgoulis Vassilis
Published: January 2021

Immune responses against SARS-CoV-2 have been vigorously analyzed. It has been proposed that a subset of mild or asymptomatic cases with undetectable antibodies may clear the virus in a T-cell cytotoxic-dependent manner, albeit recent data revealed the importance of B-cells in that regard. We hypothesized that underdiagnosed antigenemia/viremia may conceal humoral response possibly through immunocomplex formation. We report the first case of late-onset seroconversion detected following decline in antigenemia/viremia levels. Consequently, classification of at least a subset of COVID-19 cases as non-responders might not represent a true immunobiological phenomenon, rather reflect antibody masking due to prolonged antigenemia/viremia.
First detection and report of SARS-CoV-2 Spike protein N501Y mutations in Oklahoma USA
Authors: Narayanan Sai , Patil Girish , More Sunil , Saliki Jeremiah , Kaul Anil , Ramachandran Akhilesh
Published: January 2021

We describe the detection of SARS-CoV-2 (VOC)B.1.1.7 lineage in Oklahoma, USA. Various mutations in the S gene and ORF8 with similarity to the genome of B.1.1.7 lineage were detected in 4 of the 6 genomes sequenced and reported here. The sequences have been made available in GISAID. Presence of novel lineages indicate the need for frequent whole genome sequencing to better understand pathogen dynamics in different geographical locations.
Evaluation of spike protein antigens for SARS-CoV-2 serology
Authors: Jagtap Suraj , Ratnasri K , Valloly Priyanka , Sharma Rakhi , Maurya Satyaghosh , Gaigore Anushree , Ardhya Chitra , Biligi Dayananda S. , Desiraju Bapu Koundinya , Mouli Natchu Uma Chandra , Kumar Saini Deepak , Roy Rahul
Published: January 2021

Background

Spike protein domains are being used in various serology-based assays to detect prior exposure to SARS-CoV-2 virus. However, there has been limited comparison of human antibody titers against various spike protein antigens among COVID-19 infected patients.

Methods

We compared four spike proteins (RBD, S1, S2 and a stabilized spike trimer (ST)) representing commonly used antigens for their reactivity to human IgG antibodies using indirect ELISA in serum from COVID-19 patients and pre-2020 samples. ST ELISA was also compared against the EUROIMMUN IgG ELISA test. Further, we estimated time appropriate IgG and IgA seropositivity rates in COVID-19 patients using a panel of sera samples collected longitudinally from the day ofonset of symptoms (DOS).

Results

Among the four spike antigens tested, the ST demonstrated the highest sensitivity (86.2%; 95% CI: 77.8-91.7%), while all four antigens showed high specificity to COVID-19 sera (94.7-96.8%). 13.8% (13/94) of the samples did not show seroconversion in any of the four antigen-based assays. In a double-blinded head-to-head comparison, ST based IgG ELISA displayed a better sensitivity (87.5%, 95%CI: 76.4-93.8%) than the EUROIMMUN IgG ELISA (67.9%, 95% CI: 54.8-78.6%). Further, in ST-based assays, we found 48% and 50% seroconversion in the first six days (from DOS) for IgG and IgA antibodies, respectively, which increased to 84% (IgG) and 85% (IgA) for samples collected ≥22 days DOS.

Conclusions

Comparison of spike antigens demonstrates that spike trimer protein is a superior option as an ELISA antigen for COVID-19 serology.

Highlights

Spike trimer displays the highest antibody titer in SARS-CoV-2 infections among spike protein antigens.

Spike trimer IgG ELISA displays a sensitivity of 50% within six days and 86.2% after 14 days from onset of symptoms.

IgA and IgG responses to spike trimer antigen were comparable and concomitant in time after infection.

16% (IgG) and 15% (IgA) of COVID-19 RT-PCR positive patients did not seroconvert even after 21 days from onset of symptoms.
Self-Reported Mask Wearing Greatly Exceeds Directly Observed Use: Urgent Need for Policy Intervention in Kenya
Authors: Jakubowski Aleksandra , Egger Dennis , Nekesa Carolyne , Lowe Layna , Walker Michael , Miguel Edward
Published: January 2021

Background

Many countries in sub-Saharan Africa have so far avoided large outbreaks of COVID-19, perhaps due to the strict lockdown measures that were imposed early in the pandemic. Yet the harsh socio-economic consequences of the lockdowns have led many governments to ease the restrictions in favor of less stringent mitigation strategies. In the absence of concrete plans for widespread vaccination, masks remain one of the few tools available to low-income populations to avoid the spread of SARS-CoV-2 for the foreseeable future.

Methods

We compare mask use data collected through self-reports from phone surveys and direct observations in public spaces from population-representative samples in Ugunja subcounty, a rural setting in Western Kenya. We examine mask use in different situations and compare mask use by gender, age, location, and the riskiness of the activity

Findings

We assess mask use data from 1,960 phone survey respondents and 9,549 direct observations. While only 12% of people admitted in phone interviews to not wearing a mask in public, 90% of people we observed did not have a mask visible (77.7% difference, 95% CI 0.742, 0.802). Self-reported mask use was significantly higher than observed mask use in all scenarios (i.e. in the village, in the market, on public transportation).

Interpretation

We find limited compliance with the national government mask mandate in Kenya using directly observed data, but high rates of self-reported mask use. This vast gap suggests that people are aware that mask use is socially desirable, but in practice they do not adopt this behavior.

Focusing public policy efforts on improving adoption of mask use via education and behavioral interventions may be needed to improve compliance.

Funding

Weiss Family Foundation, International Growth Centre
Association of COVID-19 incidence with objectively and subjectively measured mental health proxies in the Austrian Football League: an epidemiological study
Authors: van der Zee-Neuen Antje , Seymer Alexander , Schaffler-Schaden Dagmar , Herfert Juergen , O Brien James , Johansson Tim , Kutschar Patrick , Ludwig Stephan , Stoeggl Thomas , Keeley David , Flamm Maria , Osterbrink Juergen
Published: January 2021

Objective
We aimed to explore the association of COVID-19 incidence with mental health in 225 team and staff members of five professional Austrian Football clubs captured by objective (location variance) or subjective (self-reported sleep quality, level of recovery, perceived risk of infection) mental health proxies.
Methods
Data collected during the implementation of a novel monitoring concept to enable safe continuation of professional Football during the COVID-19 pandemic were matched with Austrian COVID-19 incidence data and smartphone collected location data (time-period June 17th to July 31st, 2020). Multivariable linear regression models explored the association of COVID-19 incidence, defined as daily novel or active cases of COVID-19, with the objective and subjective health proxies while adjusting for the occurrence of one COVID-19 case in a staff member in one of the clubs, team status (i.e. player vs staff) and game days.
Results
Data from 115 participants were analysed. An increasing number of novel COVID-19 cases was significantly associated with deteriorating sleep quality (B 0.48, 95% CI 0.05; 1.00) but with none of the other mental health proxies. An increasing number of active COVID-19 cases was significantly associated with an increase in perceived infection risk (B 0.04, 95% CI 0.00; 0.07) and location variance (B 0.28, 95% CI 0.06; 0.49).
Conclusion
The adverse association of an increasing COVID-19 incidence with mental health in professional Footballers and staff members became obvious particularly in subjectively measured mental health. During the ongoing pandemic, targeted mental care should be included in the daily routines of this population.
RNA sequencing of a large number of psoriatic patients identifies 131 novel miRNAs and 11 miRNAs associated with disease severity
Authors: Solvin Å.Ø. , Chawla K. , Olsen L.C. , Danielsen K. , Jenssen M. , Furberg A.S. , Saunes M. , Hveem K. , Sætrom P. , Løset M.
Published: January 2021

Background

MicroRNAs are small regulatory molecules that are dysregulated in psoriasis. Despite previous efforts, much is unknown about the regulatory mechanisms of psoriasis genetics and their contributions to disease development and activity.

Objectives

To globally characterize the miRNAome of psoriatic skin in a large sample of psoriatic cases and controls for increased understanding of psoriasis pathophysiology.

Methods

Skin biopsies from psoriatic cases (n=75) and non-psoriatic controls (n=57) were RNA sequenced. Count data was meta-analyzed with a previously published dataset (cases, n=24, controls, n=20), increasing the number of psoriatic cases four-fold from previously published studies. Differential expression analyses were performed comparing lesional psoriatic (PP), non-lesional psoriatic (PN) and control (NN) skin. Further, functional enrichment and cell specific analyses were performed.

Results

We identified 439 significantly differentially expressed miRNAs (DEMs), of which 131 were novel and 11 were related to disease severity. Meta-analyses identified 20 DEMs between PN and NN, suggesting an inherent change in all psoriatic skin. By integrating the miRNA transcriptome with mRNA target interactions, we identified several functionally enriched terms, including ‘thyroid hormone signaling’, ‘insulin resistance’ and various infectious diseases. Cell specific expression analyses revealed that the upregulated DEMs were enriched in epithelial and immune cells.

Conclusions

We have provided the most comprehensive overview of the miRNome in psoriatic skin to date and identified a miRNA signature related to psoriasis severity. Our results may represent molecular links between psoriasis and related comorbidities and have outlined potential directions for future functional studies to identify biomarkers and treatment targets.
Genetic and structural basis for recognition of SARS-CoV-2 spike protein by a two-antibody cocktail
Authors: Dong Jinhui , Zost Seth J. , Greaney Allison J. , Starr Tyler N. , Dingens Adam S. , Chen Elaine C. , Chen Rita E. , Case James Brett , Sutton Rachel E. , Gilchuk Pavlo , Rodriguez Jessica , Armstrong Erica , Gainza Christopher , Nargi Rachel S. , Binshtein Elad , Xie Xuping , Zhang Xianwen , Shi Pei-Yong , Logue James , Weston Stuart , McGrath Marisa E. , Frieman Matthew B. , Brady Tyler , Tuffy Kevin , Bright Helen , Loo Yueh-Ming , McTamney Patrick , Esser Mark , Carnahan Robert H. , Diamond Michael S. , Bloom Jesse D. , Crowe James E.
Published: January 2021

The SARS-CoV-2 pandemic has led to an urgent need to understand the molecular basis for immune recognition of SARS-CoV-2 spike (S) glycoprotein antigenic sites. To define the genetic and structural basis for SARS-CoV-2 neutralization, we determined the structures of two human monoclonal antibodies COV2-2196 and COV2-21301, which form the basis of the investigational antibody cocktail AZD7442, in complex with the receptor binding domain (RBD) of SARS-CoV-2. COV2-2196 forms an “aromatic cage” at the heavy/light chain interface using germline-encoded residues in complementarity determining regions (CDRs) 2 and 3 of the heavy chain and CDRs 1 and 3 of the light chain. These structural features explain why highly similar antibodies (public clonotypes) have been isolated from multiple individuals1–4. The structure of COV2-2130 reveals that an unusually long LCDR1 and HCDR3 make interactions with the opposite face of the RBD from that of COV2-2196. Using deep mutational scanning and neutralization escape selection experiments, we comprehensively mapped the critical residues of both antibodies and identified positions of concern for possible viral escape. Nonetheless, both COV2-2196 and COV2-2130 showed strong neutralizing activity against SARS-CoV-2 strain with recent variations of concern including E484K, N501Y, and D614G substitutions. These studies reveal germline-encoded antibody features enabling recognition of the RBD and demonstrate the activity of a cocktail like AZD7442 in preventing escape from emerging variant viruses.
Linking objective measures of physical activity and capability with brain structure in healthy community dwelling older adults
Authors: Sanders Anne-Marthe , Richard Geneviève , Kolskår Knut , Ulrichsen Kristine M. , Kaufmann Tobias , Alnæs Dag , Beck Dani , Dørum Erlend S. , de Lange Ann-Marie G. , Nordvik Jan Egil , Westlye Lars T.
Published: January 2021

Maintaining high levels of daily activity and physical capability have been proposed as important constituents to promote healthy brain and cognitive aging. Studies investigating the associations between brain health and physical activity in late life have, however, mainly been based on self-reported data or measures designed for clinical populations. In the current study, we examined cross-sectional associations between physical activity, recorded by an ankle-positioned accelerometer for seven days, physical capability (grip strength, postural control, and walking speed), and neuroimaging based surrogate markers of brain health in 122 healthy older adults aged 65-88 years. We used a multimodal brain imaging approach offering two complementary structural MRI based indicators of brain health: white matter diffusivity and coherence based on diffusion tensor imaging and subcortical and global brain age based on brain morphology inferred from T1-weighted MRI data. The analyses revealed a significant association between global white matter fractional anisotropy (FA) and walking speed, indicating higher white matter coherence in people with higher pace. We also found a significant interaction between sex and brain age on number of daily steps, indicating younger-appearing brains in more physically active women, with no significant associations among men. These results provide insight into the intricate associations between different measures of brain and physical health in old age, and corroborate established public health advice promoting physical activity.
Pre-existing cell subpopulations in primary prostate cancers display surface fingerprint of docetaxel-resistant cells
Authors: Drápela Stanislav , Kvokačková Barbora , Fedr Radek , Kurfürstová Daniela , Morong Martin , Študent Vladimír , van Weerden Wytske M. , Puhr Martin , Culig Zoran , Bouchal Jan , Souček Karel
Published: January 2021

Background

Docetaxel resistance represents a leading obstacle in the therapy of prostate cancer (PCa), resulting in lethal disease. Intratumoral heterogeneity, which is frequently driven by epithelial-mesenchymal plasticity significantly contributes to the limited treatment response, chemoresistance, and subsequent poor prognosis of patients with lethal PCa.

Methods

We employed a high-throughput flow cytometry screening to identify cell surface fingerprint that associates with docetaxel resistance in PCa cells. Using patient-derived xenografts, we validated protein expression of the most robustly changed antigensin vivoand further assessed this 6-molecule surface fingerprint in primary PCa tumors.

Results

We revealed the overexpression of SSEA-4 antigen in bothin vitroandin vivodocetaxel-resistant models and confirmed the SSEA-4 enrichment in a subpopulation of freshly isolated primary PCa tumors. The level of ST3GAL2, an enzyme that is critically involved in the SSEA-4 synthesis, correlated with increased expression of CD44, CD59, and CD95 and reduced expression of EpCAM and CD9. SSEA-4 was further directly linked to the antimicrotubule agent resistance and poor prognosis in PCa patients.

Conclusions

We propose that the 6-molecule surface fingerprint associates with docetaxel resistance and pre-exists in a cell subpopulation of primary PCa tumors even before docetaxel treatment.
Emergence of a smooth interface from growth of a dendritic network against a mechanosensitive contractile material
Authors: Sharma Medha , Jiang Tao , Jiang Zi Chen , Moguel-Lehmer Carlos E. , Harris Tony J. C.
Published: January 2021

Structures and machines require smoothening of raw materials. Self-organized smoothening guides cell and tissue morphogenesis, and is relevant to advanced manufacturing. Across the syncytial Drosophila embryo surface, smooth interfaces form between expanding Arp2/3-based actin caps and surrounding actomyosin networks, demarcating the circumferences of nascent dome-like compartments used for pseudo-cleavage. We found that smoothening of the actomyosin interfaces requires Arp2/3 in vivo. To dissect the physical basis of this requirement, we reconstituted the interacting networks using node-based models. When actomyosin networks were simulated with clearances instead of Arp2/3 networks, rough boundaries persisted with low levels of myosin contractility. With addition of expanding Arp2/3 networks, network-network interfaces failed to smoothen, but accumulated myosin nodes and tension. After incorporating actomyosin mechanosensitivity, Arp2/3 network growth induced local contractility and smoothening of the interfaces, effects also evident in vivo. In this way, a smooth structure can emerge from the lateral interaction of irregular starting materials.
mTOR repression in response to amino acid starvation promotes ECM degradation through MT1-MMP endocytosis arrest
Authors: Colombero Cecilia , Remy David , Antoine Sandra , Macé Anne-Sophie , Monteiro Pedro , ElKhatib Nadia , Fournier Margot , Dahmani Ahmed , Montaudon Elodie , Montagnac Guillaume , Marangoni Elisabetta , Chavrier Philippe
Published: January 2021

Under conditions of starvation, normal and tumor epithelial cells can rewire their metabolism towards the consumption of extracellular matrix-derived components as nutrient sources. The mechanism of pericellular matrix degradation by starved cells has been largely overlooked. Here we show that matrix degradation by breast and pancreatic tumor cells and patient-derived xenograft explants increases by one order of magnitude upon amino acid and growth factor deprivation. In addition, we found that collagenolysis requires the invadopodia components, TKS5 and the transmembrane metalloproteinase, MT1-MMP, which are key to the tumor invasion program. Increased collagenolysis is controlled by mTOR repression upon nutrient depletion or pharmacological inhibition by rapamycin. Our results reveal that starvation hampers clathrin-mediated endocytosis, resulting in MT1-MMP accumulation in arrested clathrin-coated pits. Our study uncovers a new mechanism whereby mTOR repression in starved cells leads to the repurposing of abundant plasma membrane clathrin-coated pits into robust ECM-degradative assemblies.
The SARS-CoV-2 Y453F mink variant displays a striking increase in ACE-2 affinity but does not challenge antibody neutralization
Authors: Bayarri-Olmos Rafael , Rosbjerg Anne , Johnsen Laust Bruun , Helgstrand Charlotte , Bak-Thomsen Theresa , Garred Peter , Skjoedt Mikkel-Ole
Published: January 2021

SARS-CoV-2 transmission from humans to animals has been reported for many domesticated species, including cats, dogs and minks. Identification of novel spike gene mutations appearing in minks has raised major concerns about potential immune evasion and challenges for the global vaccine strategy. The genetic variant, known as “cluster-five”, arose among farmed minks in Denmark and resulted in a complete shutdown of the world’s largest mink production. However, the functional properties of this new variant are not established. Here we present functional data on the Y453F cluster-five receptor-binding domain (RBD) and show that it does not decrease established humoral immunity or affect the neutralizing response in a vaccine model based on wild-type RBD or spike. However, it binds the human ACE-2 receptor with a four-fold higher affinity suggesting an enhanced transmission capacity and a possible challenge for viral control.
Orc4 spatiotemporally stabilizes centromeric chromatin
Authors: Sreekumar Lakshmi , Kumari Kiran , Guin Krishnendu , Bakshi Asif , Varshney Neha , Thimmappa Bhagya C. , Narlikar Leelavati , Padinhateeri Ranjith , Siddharthan Rahul , Sanyal Kaustuv
Published: January 2021

The establishment of centromeric chromatin and its propagation by the centromere-specific histone CENPA is mediated by epigenetic mechanisms in most eukaryotes. DNA replication origins, origin binding proteins, and replication timing of centromere DNA are important determinants of centromere function. The epigenetically regulated regional centromeres in the budding yeast Candida albicans have unique DNA sequences that replicate earliest in every chromosome and are clustered throughout the cell cycle. In this study, the genome-wide occupancy of the replication initiation protein Orc4 reveals its abundance at all centromeres in C. albicans. Orc4 is associated with four different DNA sequence motifs, one of which coincides with tRNA genes (tDNA) that replicate early and cluster together in space. Hi-C combined with genome-wide replication timing analyses identify that early replicating Orc4-bound regions interact with themselves stronger than with late replicating Orc4-bound regions. We simulate a polymer model of chromosomes of C. albicans and propose that the early replicating and highly enriched Orc4-bound sites preferentially localize around the clustered kinetochores. We also observe that Orc4 is constitutively localized to centromeres, and both Orc4 and the helicase Mcm2 are essential for cell viability and CENPA stability in C. albicans. Finally, we show that new molecules of CENPA are recruited to centromeres during late anaphase/telophase, which coincides with the stage at which the CENPA-specific chaperone Scm3 localizes to the kinetochore. We propose that the spatiotemporal localization of Orc4 within the nucleus, in collaboration with Mcm2 and Scm3, maintains centromeric chromatin stability and CENPA recruitment in C. albicans.
Facilitated crystal handling using a simple device for evaporation reduction in microtiter plates
Authors: Barthel Tatjana , Huschmann Franziska U. , Wallacher Dirk , Feiler Christian G. , Klebe Gerhard , Weiss Manfred S. , Wollenhaupt Jan
Published: January 2021

In the past two decades, most of the steps in a macromolecular crystallography experiment have undergone tremendous development with respect to speed, feasibility and increase of throughput. The part of the experimental workflow that is still a bottleneck, despite significant efforts, involves the manipulation and harvesting of the crystals for the diffraction experiment. Here, a novel low-cost device is presented that functions as a cover for 96-well crystallization plates. This device enables access to the individual experiments one at a time by its movable parts, while minimizing evaporation of all other experiments of the plate. In initial tests, drops of many typically used crystallization cocktails could be successfully protected for up to 6 h. Therefore, the manipulation and harvesting of crystals is straightforward for the experimenter, enabling significantly higher throughput. This is useful for many macromolecular crystallography experiments, especially multi-crystal screening campaigns.
2,5-Dimethylbufotenine and 2,5-dimethylbufotenidine: novel derivatives of natural tryptamines found in Bufo alvarius toads
Authors: Pham Duyen N. K. , Chadeayne Andrew R. , Golen James A. , Manke David R.
Published: January 2021

The solid-state structure of the bufotenine derivative bis(5-methoxy-2,N,N-trimethyltryptammonium) (5-MeO-2-Me-DMT) fumarate (systematic name: bis{[2-(5-methoxy-2-methyl-1H-indol-3-yl)ethyl]dimethylazanium} (2E)-but-2-enedioate), 2C14H21N2O+·C4H2O4
2−, the bufotenidine derivative 5-methoxy-2,N,N,N-tetramethyltryptammonium (5-MeO-2-Me-TMT) iodide {systematic name: [2-(5-methoxy-2-methyl-1H-indol-3-yl)ethyl]trimethylazanium iodide}, C15H23N2O+·I−, and the hydrate of the same {systematic name: [2-(5-methoxy-2-methyl-1H-indol-3-yl)ethyl]trimethylazanium iodide monohydrate}, C15H23N2O+·I−·H2O, are reported. The structure of 5-MeO-2-Me-DMT fumarate possesses one tryptammonium cation and a half of a fumarate dianion in the asymmetric unit, linked together by N—H...O hydrogen bonds in infinite two-dimensional networks parallel to the (101) plane. The structure of 5-MeO-2-Me-TMT iodide possesses one tryptammonium cation and one iodide anion in the asymmetric unit. The ions are linked via N—H...I hydrogen bonds, and indoles are coupled in dimers through π–π interactions. The hydrate of 5-MeO-2-Me-TMT iodide possesses one tryptammonium cation, one iodide anion and one water molecule in the asymmetric unit. It shows N—H...I and O—H...I hydrogen bonds that couple the tryptammonium cations into dimers.
1-[5-(3,5-Dimethoxyphenyl)-3-(2-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl]ethanone
Authors: Yoo Miri , Koh Dongsoo
Published: January 2021

In the title compound, C20H22N2O4, two benzene rings bearing methoxy substituents are connected by a central acetylpyrazoline ring: the dihedral angle between the benzene rings is 83.7 (1)°. In the crystal, pairwise C—H...O hydrogen bonds generate inversion dimers and additional weak C—H...O interactions link the dimers into chains propagating along the c-axis direction.