bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Earplugs and Eye Masks on Sleep Quality in Surgical ICU Patients at Risk for Frequent Awakenings
Authors: Obanor Osamudiamen O. , McBroom Mandy M. , Elia Jennifer M. , Ahmed Farzin , Sasaki Jun D. , Murphy Kelly M. , Chalk Shannon , Menard Gloria A. , Pratt Nadia V. , Venkatachalam Aardhra M. , Romito Bryan T.
Published: April 2021

OBJECTIVES:

Sleep disturbances may contribute to the development of delirium, prolonged ICU stay, and increased mortality. There is conflicting data on the effectiveness of earplugs and eye masks for sleep promotion in the ICU. This study evaluates the impact of earplugs and eye masks on sleep quality in postoperative surgical ICU patients at risk for frequent awakenings.

DESIGN:

Prospective randomized controlled trial.

SETTING:

Surgical ICU within the University of Texas Southwestern Medical Center.

PATIENTS:

Adult, female patients admitted to the surgical ICU requiring hourly postoperative assessments following breast free flap surgery between February 2018 and October 2019.

INTERVENTIONS:

Patients were randomized into an intervention group or a control group. The intervention group received earplugs and eye masks in addition to standard postoperative care, whereas the control group received standard postoperative care.

MEASUREMENTS AND MAIN RESULTS:

The primary outcome was overall sleep quality assessed via the Richards-Campbell Sleep Questionnaire. Secondary outcomes of patient satisfaction and rates of ICU delirium were assessed with a modified version of the Family Satisfaction in the ICU survey and the Confusion Assessment Method for the ICU. After a planned interim analysis, the study was stopped early because prespecified criteria for significance were attained. Compared with the control group’s average Richards-Campbell Sleep Questionnaire total score of 47.3 (95% CI, 40.8–53.8), the intervention group’s average Richards-Campbell Sleep Questionnaire total score was significantly higher at 64.5 (95% CI, 58.3–70.7; p = 0.0007). There were no significant between-group differences for Confusion Assessment Method for the ICU scores or modified Family Satisfaction in the ICU survey scores.

CONCLUSIONS:

These results suggest that earplugs and eye masks are effective in improving sleep quality in ICU patients undergoing frequent assessments. The results strengthen the evidence for nonpharmacologic sleep-promoting adjuncts in the ICU.
Mitochondria-Rich Fraction Isolated From Mesenchymal Stromal Cells Reduces Lung and Distal Organ Injury in Experimental Sepsis*
Authors: de Carvalho Luiza Rachel Pinheiro , Abreu Soraia Carvalho , de Castro Ligia Lins , Andrade da Silva Luísa Helena , Silva Paula Matos , Vieira Juliana Borges , Santos Renata Trabach , Cabral Marianna Ribeiro , Khoury Maroun , Weiss Daniel J. , Lopes-Pacheco Miquéias , Silva Pedro Leme , Cruz Fernanda Ferreira , Rocco Patricia Rieken Macedo
Published: April 2021

OBJECTIVES:

To ascertain whether systemic administration of mitochondria-rich fraction isolated from mesenchymal stromal cells would reduce lung, kidney, and liver injury in experimental sepsis.

DESIGN:

Animal study.

SETTING:

Laboratory investigation.

SUBJECTS:

Sixty C57BL/6 male mice.

INTERVENTIONS:

Sepsis was induced by cecal ligation and puncture; sham-operated animals were used as control. At 24 hours after surgery, cecal ligation and puncture and Sham animals were further randomized to receive saline or mitochondria-rich fraction isolated from mesenchymal stromal cells (3 × 106) IV. At 48 hours, survival, peritoneal bacterial load, lung, kidney, and liver injury were analyzed. Furthermore, the effects of mitochondria on oxygen consumption rate and reactive oxygen species production of lung epithelial and endothelial cells were evaluated in vitro.

MEASUREMENTS AND MAIN RESULTS:

In vitro exposure of lung epithelial and endothelial cells from cecal ligation and puncture animals to mitochondria-rich fraction isolated from mesenchymal stromal cells restored oxygen consumption rate and reduced total reactive oxygen species production. Infusion of exogenous mitochondria-rich fraction from mesenchymal stromal cells (mitotherapy) reduced peritoneal bacterial load, improved lung mechanics and histology, and decreased the expression of interleukin-1β, keratinocyte chemoattractant, indoleamine 2,3-dioxygenase-2, and programmed cell death protein 1 in lung tissue, while increasing keratinocyte growth factor expression and survival rate in cecal ligation and puncture-induced sepsis. Mitotherapy also reduced kidney and liver injury, plasma creatinine levels, and messenger RNA expressions of interleukin-18 in kidney, interleukin-6, indoleamine 2,3-dioxygenase-2, and programmed cell death protein 1 in liver, while increasing nuclear factor erythroid 2-related factor-2 and superoxide dismutase-2 in kidney and interleukin-10 in liver.

CONCLUSIONS:

Mitotherapy decreased lung, liver, and kidney injury and increased survival rate in cecal ligation and puncture-induced sepsis.
In-hospital Bleeding Outcomes of Oral Anticoagulant and Dual Antiplatelet Therapy During Percutaneous Coronary Intervention: An Analysis From the Japanese Nationwide Registry
Authors: Yashima Fumiaki , Inohara Taku , Nishida Hiroaki , Shimoji Kenichiro , Ueno Koji , Noma Shigetaka , Yamaji Kyohei , Ishii Hideki , Tanaka Nobuhiro , Kohsaka Shun , Amano Tetsuya , Ikari Yuji
Published: April 2021

The type of periprocedural antithrombotic regimen that is the safest and most effective in percutaneous coronary intervention (PCI) patients on oral anticoagulant (OAC) therapy has not been fully investigated. We aimed to retrospectively investigate the in-hospital bleeding outcomes of patients receiving OAC and antiplatelet therapies during PCI using Japanese nationwide multicenter registry data. A total of 26,938 patients who underwent PCI with OAC and antiplatelet therapies between 2016 and 2017 were included. We investigated in-hospital bleeding requiring blood transfusion, mortality, and stent thrombosis according to the antithrombotic regimens used at the time of PCI: OAC + single antiplatelet therapy (double therapy) and OAC + dual antiplatelet therapy (triple therapy). The antiplatelet agents included aspirin, clopidogrel, and prasugrel. The OAC agents included warfarin and direct OACs. Adjusting the dose of OAC or intermitting OAC before PCI was at each operator's discretion. In the study population [mean age (SD), 73.5 (9.5) years; women, 21.5%], the double therapy and triple therapy groups comprised 5546 (20.6%) and 21,392 (79.4%) patients, respectively. Bleeding requiring transfusion was not significantly different between the groups [adjusted odds ratio (aOR), 0.700; 95% confidence interval (CI), 0.420–1.160; P = 0.165] (triple therapy as a reference). Mortality was not significantly different (aOR, 1.370; 95% CI, 0.790–2.360; P = 0.258). Stent thrombosis was significantly different between the groups (aOR, 3.310; 95% CI, 1.040–10.500; P = 0.042) (triple therapy as a reference). In conclusion, for patients on OAC therapy who underwent PCI, periprocedural triple therapy may be safe with respect to in-hospital bleeding risks. However, further investigations are warranted to establish the safety and efficacy of periprocedural triple therapy.
Effect of Inhibition of the JAK2/STAT3 Signaling Pathway on the Th17/IL-17 Axis in Acute Cellular Rejection After Heart Transplantation in Mice
Authors: Zhang Ming , Xu Ming , Wang Kaijie , Li Long , Zhao Jinping
Published: April 2021

Acute immune rejection is one of the most serious complications of heart transplantation, and its mechanism has always been a hot spot. Th17 cells and cytokine interleukin-17 (IL-17) have been proved to be involved in acute immune rejection, and the signaling pathway mechanism has attracted our interest. It has been confirmed that the Janus kinase 2-signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway is involved in the differentiation of CD4+ T cells, so we focus on whether the JAK2/STAT3 signaling pathway is involved in the occurrence of acute immune rejection by regulating the Th17/IL-17 axis. In this study, we used Bagg’s Albino c mice and C57BL/6 mice to construct heterotopic heart transplantation models, which were divided into the acute rejection group and AG490-treated group (n = 5), and donor tissue and serum were collected in 3 experimental days from the recipient mice for H&E staining analysis of paraffin sections and ELISA, Western blot, flow cytometry, and real time-polymerase chain reaction. The results showed that the acute rejection rating of the heart decreased, and the expression of related factors decreased significantly after using the inhibitor AG490, suggesting that the JAK2/STAT3 signaling pathway regulates expression of the Th17/IL-17 axis in cardiac allograft rejection.
Systematic Review and Meta-analysis: The Effects of Prophylactic Proton Pump Inhibitor Treatment in Patients With Coronary Heart Disease Receiving Dual Antiplatelet Therapy
Authors: Li Yang , Ren Xingshu , Fang Zhenfei
Published: April 2021

Dual antiplatelet therapy (DAPT) and proton pump inhibitors (PPIs) are widely used in clinical treatment. However, the pharmacokinetic interaction between PPIs and DAPT is still unclear in patients with cardiovascular disease. This systematic review and meta-analysis aimed to evaluate the risks and benefits of the combination of PPI and DAPT in patients with coronary heart disease. The PubMed, EMBASE, Cochrane, and Web of Science databases were systematically searched from inception to April 1, 2020, for eligible studies. The outcomes investigated in this study included major adverse cardiovascular events, myocardial infarction, all-cause death, gastrointestinal complications, and platelet function testing. Studies were excluded from the review if other gastrointestinal medication or aspirin or P2Y12 receptor inhibitor monotherapy was administered. The review included 52 studies, and data from 40 studies were extracted for meta-analysis. No association was found between the risk of adverse clinical outcomes and the combination of PPI and DAPT based on the randomized controlled trial data (risk ratio: 0.98; 95% confidence interval: 0.87–1.09; P = 0.877; I2 = 0%). However, an increased risk of adverse clinical outcomes due to the use of PPIs was observed in patients treated with DAPT based on the data from observational studies (risk ratio: 1.259; 95% confidence interval: 1.079–1.468; P = 0.003; I2 = 67.8%), although the heterogeneity of these studies was high. In conclusion, this systematic review and meta-analysis demonstrated that pharmacokinetic interactions between PPI and DAPT do not lead to adverse clinical outcomes.
Contribution of WNT2B Genetic Variants to Ischemic Stroke Occurrence in a Chinese Han Population
Authors: Yuan Haozheng , Fan Pei , Yao Li , Lv Yuying , Wei Haidong , Zheng Juan , Han Xinsheng
Published: April 2021

Wnt signaling pathway–related WNT2B gene was upregulated in ischemic brain damage. We aimed to assess the contribution of WNT2B genetic variant to ischemic stroke (IS) susceptibility in the Chinese Han population. Five polymorphisms including rs3790606, rs351364, rs3790608, rs12037987, and rs10776752 in WNT2B were genotyped using Agena MassARRAY platform in 476 healthy controls and 501 patients with IS. Odds ratio (OR) and 95% confidence interval (CI) adjusted for age and gender were estimated by logistic regression analysis. Analysis of variance was used to evaluate the association between genotypes of WNT2B variants and blood lipid parameters. Rs12037987 (OR = 1.82, 95% CI: 1.18–2.82, P = 0.007) and rs10776752 (OR = 1.74, 95% CI: 1.13–2.68, P = 0.012) were related to the increased IS susceptibility. Interestingly, rs12037987 (OR = 2.01, P = 0.028) and rs10776752 (OR = 2.02, P = 0.028) had the higher IS risk in the subjects younger than or equal to 65 years. Rs12037987 (OR = 2.70, P = 0.013), rs10776752 (OR = 2.71, P = 0.012), and rs3790606 (OR = 1.89, P = 0.036) manifested an increasing-risk association with IS occurrence in women. Moreover, rs3790606 genotype was related to serum levels of triglyceride (P = 0.008) and total cholesterol (P = 0.001). Our study reported that rs12037987 and rs10776752 were associated with the increased risk for IS in the Chinese Han population. Our findings may be useful for insight into the contribution of WNT2B variants to the complex pathogenesis of IS.
CircJARID2 Regulates Hypoxia-Induced Injury in H9c2 Cells by Affecting miR-9-5p–Mediated BNIP3
Authors: Cai Xinyong , Li Bin , Wang Yunxia , Zhu Hongmin , Zhang Ping , Jiang Panpan , Yang Xu , Sun Jianhua , Hong Lang , Shao Liang
Published: April 2021

Myocardial infarction (MI) is a common cardiovascular disease, and many circular RNAs (circRNAs) have been found to participate in the pathological process. This study was to research circRNA jumonji and AT-rich interaction domain containing 2 (circJARID2) in MI. MI cell model was established by hypoxia treatment in H9c2 cells. CircJARID2 and microRNA-9-5p (miR-9-5p) levels were examined using real-time polymerase chain reaction. Cell viability detection was performed by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (Edu) assays. Cell apoptosis was evaluated by flow cytometry and caspase-3 activity assay. Apoptotic markers and B-cell lymphoma-2 (Bcl-2) interacting protein 3 (BNIP3) were quantified by western blot. Inflammatory cytokines were determined via enzyme-linked immunosorbent assay. The genic interaction was analyzed through dual-luciferase reporter and RNA immunoprecipitation assays. Hypoxia induced the upregulation of circJARID2 expression in H9c2 cells. The hypoxia-induced cell viability inhibition, apoptosis promotion, and inflammatory response were all counterbalanced by knockdown of circJARID2. CircJARID2 interacted with miR-9-5p, and its function in regulating the hypoxia-induced cell injury was also dependent on targeting miR-9-5p. BNIP3 acted as a target gene of miR-9-5p, and circJARID2 had positive effect on BNIP3 expression by binding to miR-9-5p. MiR-9-5p played a protective role for H9c2 cells against the hypoxia-induced injury via targeting BNIP3. CircJARID2 overexpression contributed to the hypoxia-induced H9c2 cell injury by sponging miR-9-5p to upregulate BNIP3 expression, showing a novel molecular network of MI pathomechanism.
Multisystem Inflammatory Syndrome in Infants <12 months of Age, United States, May 2020–January 2021
Authors: Godfred-Cato Shana , Tsang Clarisse A. , Giovanni Jennifer , Abrams Joseph , Oster Matthew E. , Lee Ellen H. , Lash Maura K. , Le Marchand Chloe , Liu Caterina Y. , Newhouse Caitlin N. , Richardson Gillian , Murray Meghan T. , Lim Sarah , Haupt Thomas E. , Hartley Amanda , Sosa Lynn E. , Ngamsnga Kompan , Garcia Ali , Datta Deblina , Belay Ermias D.
Published: April 2021

Background:

Multisystem inflammatory syndrome in children (MIS-C), temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been identified in infants <12 months old. Clinical characteristics and follow-up data of MIS-C in infants have not been well described. We sought to describe the clinical course, laboratory findings, therapeutics and outcomes among infants diagnosed with MIS-C.

Methods:

Infants of age <12 months with MIS-C were identified by reports to the CDC’s MIS-C national surveillance system. Data were obtained on clinical signs and symptoms, complications, treatment, laboratory and imaging findings, and diagnostic SARS-CoV-2 testing. Jurisdictions that reported 2 or more infants were approached to participate in evaluation of outcomes of MIS-C.

Results:

Eighty-five infants with MIS-C were identified and 83 (97.6%) tested positive for SARS-CoV-2 infection; median age was 7.7 months. Rash (62.4%), diarrhea (55.3%) and vomiting (55.3%) were the most common signs and symptoms reported. Other clinical findings included hypotension (21.2%), pneumonia (21.2%) and coronary artery dilatation or aneurysm (13.9%). Laboratory abnormalities included elevated C-reactive protein, ferritin, d-dimer and fibrinogen. Twenty-three infants had follow-up data; 3 of the 14 patients who received a follow-up echocardiogram had cardiac abnormalities during or after hospitalization. Nine infants had elevated inflammatory markers up to 98 days postdischarge. One infant (1.2%) died after experiencing multisystem organ failure secondary to MIS-C.

Conclusions:

Infants appear to have a milder course of MIS-C than older children with resolution of their illness after hospital discharge. The full clinical picture of MIS-C across the pediatric age spectrum is evolving.
Well tolerability and highly effective treatment response for hepatitis C virus-human immunodeficiency virus–coinfected patients treated by all-oral direct-acting antivirals
Authors: Su Pin-Shuo , Su Chien-Wei , Wu Sih-Hsien , Wei Tien-Hsin , Chu Chi-Jen , Lin Chung-Chi , Lee Shou-Dong , Wang Yuan-Jen , Lee Fa-Yauh , Huang Yi-Hsiang , Hou Ming-Chih
Published: April 2021

Background:

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection is common because the two pathogens share their transmission route. Studies have suggested that coinfection is associated with accelerated hepatic fibrosis, increased hepatic decompensation, and hepatocellular carcinoma development. Historically, the sustained virological response (SVR) rates for patients undergoing pegylated interferon (PEG-IFN)-based therapy are poor owing to advanced liver disease, immune dysfunction, and poor medical adherence. This study aimed to investigate the efficacy and safety of oral direct-acting antivirals (DAAs) in HCV-HIV–coinfected patients.

Methods:

Between January 2017 and February 2020, 52 consecutive HCV-HIV–coinfected patients treated with oral DAAs (paritaprevir/ritonavir, ombitasvir, and dasabuvir: 7; daclatasvir and asunaprevir: 1; glecaprevir and pibrentasvir: 15; and sofosbuvir-based drugs: 29) were enrolled. The DAA regimen was selected based on the genotype/subtypes, patient characteristics, potential drug-drug interaction profiles, and health insurance reimbursement criteria. SVR12 was defined as undetectable HCV RNA (<15 IU/mL) at the end of therapy and 12 weeks after therapy completion.

Results:

The mean age of the enrolled patients was 42 ± 10.2 years; 92.3% of the patients were male and 32.7% had advanced fibrosis or cirrhosis. Nine (17.3%) patients had failed previous IFN therapy. The genotype distribution was as follows: 1a: 8; 1b: 23; 2: 14; 3: 1; and 6: 6. The baseline HCV RNA level before DAA administration was 6.56 ± 0.9 log10 IU/mL, and 67.3% of patients had baseline HCV RNA >2 000 000 IU/mL. After posttreatment follow-up, all 52 patients (100%) achieved SVR12. Subjective and laboratory adverse events during therapy were generally mild, and none of the patients terminated therapy early.

Conclusion:

A highly effective treatment response and good tolerability were achieved using the oral DAAs for the HCV-HIV–coinfected patient population, which has been considered difficult to treat using IFN-based therapy in the past with urgent unmet medical needs.
Evaluation of the relationship between central serous chorioretinopathy and liver cirrhosis: A nationwide, population-based study
Authors: Hsu Chia-Chen , Chen Yi-Hao , Huang Ke-Hao , Chen JiannTorng , Chung Chi-Hsiang , Liang Chang-Min , Chien Wu-Chien , Chen Ching-Long
Published: April 2021

Background:

Central serous chorioretinopathy (CSCR) and liver cirrhosis share numerous risk factors and may have possible connections. We aimed to investigate whether patients with liver cirrhosis and the severity of cirrhosis have an increased incidence of CSCR.

Methods:

This population-based retrospective cohort study was conducted by collecting data from the Taiwan National Health Insurance Research Database from January 1, 2000, to December 31, 2015. We included patients who were newly diagnosed with cirrhosis and selected an equal number of sex- and age-matched control subjects. The effect of cirrhosis on the risk of CSCR was examined via a Cox proportional hazard regression analysis. The cumulative incidence of CSCR was assessed with the Kaplan-Meier method and the log-rank test.

Results:

Both groups in this study comprised a total of 25 925 individuals. The cirrhotic patients had a significantly higher cumulative risk of developing CSCR in following years than patients without cirrhosis (log-rank test < 0.001). Furthermore, compared with noncirrhotic patients, the risk of CSCR was increased 3.59-fold (95% confidence interval [CI], 2.31-5.28) in cirrhotic patients with complications, and 2.34-fold (95% CI, 1.27-3.24) in cirrhotic patients without complications. Additionally, male sex, springtime, diabetes mellitus, hepatitis B virus, and hepatitis C virus statistical significantly increased the incidence of CSCR.

Conclusion:

Cirrhosis is an independent indicator of CSCR. Among the cirrhotic population, patients with ascites and other complications have a higher incidence of CSCR than those with uncomplicated cirrhosis. Physicians should be observant when managing cirrhotic patients with visual disturbances.
Health‐Related Quality of Life and Distress of Parents of Children With Avoidant Restrictive Food Intake Disorder
Authors: Krom Hilde , van Oers Hedy A. , van der Sluijs Veer Liesbeth , van Zundert Suzanne M.C. , Otten Marie‐Anne G.M. , Haverman Lotte , Benninga Marc A. , Kindermann Angelika
Published: April 2021

Objectives:

Health‐related quality of life (HRQOL) of children with avoidant restrictive food intake disorder (ARFID) is impaired.

Aim:

To measure HRQOL and distress of parents of children with ARFID.

Methods:

Cross‐sectional cohort study. Parents of children with ARFID, visiting our multidisciplinary feeding team, completed questionnaires on the online Quality of Life in Clinical Practice portal; the Questionnaire for Adult's Health Related Quality of Life to assess parental HRQOL and the Distress Thermometer for Parents. Reference groups of parents of healthy (HC) and chronically ill children (CIC) were used.

Results:

Eighty‐five mothers and 62 fathers of 89 children with ARFID (58% female, median age 1.9 years) were included (response rate 68%). No differences were found regarding HRQOL in 11 of 12 domains between parents of children with ARFID and HC. Mothers of children with ARFID reported significantly higher HRQOL regarding pain and fathers a significantly lower HRQOL on depressive emotions compared to HC. No differences were found in overall and clinical distress scores between parents of children with ARFID and HC/CIC. Mothers of children with ARFID had significantly higher distress scores regarding cognitive problems compared to HC and parenting problems in children <2 years compared to HC/CIC. Significantly higher distress scores on parenting problems in children <2 years were found in fathers of children with ARFID compared to HC/CIC.

Conclusion:

Most HRQOL and distress scores of parents of children with ARFID were comparable to reference groups. Since parents of children with ARFID perceive a lack of understanding and support from the environment, professionals should suggest peer support through patient's organizations. Furthermore, it is important to offer professional support since parents indicated that they would like to talk to a professional about their situation.
Immunomodulation in Children: The Role of the Diet
Authors: Verduci Elvira , Köglmeier Jutta
Published: April 2021

Immune maturation and response to inflammation depend on good nutritional status. Protein and amino acid deficiencies can compromise innate and adaptive immune functions, particularly following injury or during illness. Dietary omega-3 long-chain fatty acids, prebiotics and micronutrients are beneficial to the immune system. A complex interplay exists between diet, microbiome, and epigenetic factors. The effect of single nutrients on immune function may hence be difficult to study. Well-designed intervention studies, investigating the effects of whole dietary pattern on the immune system, are needed.
An Exploration of Sedentary Behavior Patterns in Community-Dwelling People With Stroke: A Cluster-Based Analysis
Authors: Hendrickx Wendy , Riveros Carlos , Askim Torunn , Bussmann Johannes B. J. , Callisaya Michele L. , Chastin Sebastien F. M. , Dean Catherine , Ezeugwu Victor , Jones Taryn M. , Kuys Suzanne S. , Mahendran Niruthikha , Manns Patricia J. , Mead Gillian , Moore Sarah A. , Paul Lorna , Pisters Martijn F. , Saunders David H. , Simpson Dawn B. , Tieges Zoë , Verschuren Olaf , English Coralie
Published: April 2021

Background and Purpose:

Long periods of daily sedentary time, particularly accumulated in long uninterrupted bouts, are a risk factor for cardiovascular disease. People with stroke are at high risk of recurrent events and prolonged sedentary time may increase this risk. We aimed to explore how people with stroke distribute their periods of sedentary behavior, which factors influence this distribution, and whether sedentary behavior clusters can be distinguished?

Methods:

This was a secondary analysis of original accelerometry data from adults with stroke living in the community. We conducted data-driven clustering analyses to identify unique accumulation patterns of sedentary time across participants, followed by multinomial logistical regression to determine the association between the clusters, and the total amount of sedentary time, age, gender, body mass index (BMI), walking speed, and wake time.

Results:

Participants in the highest quartile of total sedentary time accumulated a significantly higher proportion of their sedentary time in prolonged bouts (P < 0.001). Six unique accumulation patterns were identified, all of which were characterized by high sedentary time. Total sedentary time, age, gender, BMI, and walking speed were significantly associated with the probability of a person being in a specific accumulation pattern cluster, P < 0.001 – P = 0.002.

Discussion and Conclusions:

Although unique accumulation patterns were identified, there is not just one accumulation pattern for high sedentary time. This suggests that interventions to reduce sedentary time must be individually tailored.

Video Abstract available for more insight from the authors (see the Video Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A343).
Changes in Sexual Behavior Related to the COVID-19 Stay-at-Home Orders Among Young Black Men Who Have Sex With Women in New Orleans, LA
Authors: Craig-Kuhn Megan Clare , Schmidt Norine , Scott Glenis , Gomes Gérard , TatahMentan Mom , Enaholo Ososese , Guzman Stephanie , Tannis Ayzsa , Hall Jacob , Triggs Daniel R. , Kissinger Patricia J.
Published: April 2021

Background

COVID-19 stay-at-home orders enacted in New Orleans, LA on March 16, 2020, may have caused changes in the way young men interacted with sex partners.

Methods

An online substudy was conducted (May 21, 2020 to June 9, 2020) among Black men who have sex with women, 18 years and older, and who had previously enrolled in the parent study Check It (May 17, 2017 to March 6, 2020) to assess changes in sexual behavior during the stay-at-home orders.

Results

Among 111 participants, from enrollment in Check It to during stay-at-home orders, recent vaginal sex declined from 96.4% to 47.8% (P < 0.0001), reports of multiple female sex partners declined from 45.0% to 14.4% (P < 0.0001), and sexual abstinence increased from 3.6% to 38.7% (P < 0.0001). Among those who did have vaginal sex, condomless sex rates did not change between enrollment in Check It and the substudy (64.5% vs 67.9%, P = 0.68). During stay-at-home orders oral sex, virtual sex, and pornography viewing were 40.5%, 42.3%, and 76.6%, respectively. Some (17.1%) acquired a new sex partner during stay-at-home orders, and 44.1% left their home to meet a partner for sex. Only 27.9% had seen information about safe sex during the pandemic. Income was diminished for 62.2% and 23.4% moved away from New Orleans when stay-at-home orders were enacted.

Conclusions

Although there was an overall reduction in physical sex, half of participants reported physical sex, with many leaving their home to have sex during stay-at-home orders and many not using condoms. Others adopted sexual abstinence, increased virtual sex, and/or pornography viewing, which may have protected them from both sexually transmitted infections and COVID-19.
Three-Dimensional Facial Anthropometric Analysis With and Without Landmark Labelling: Is There a Real Difference?
Authors: Gibelli Daniele , Cappella Annalisa , Bertozzi Filippo , Sala Davide , Sitta Sara , Tasso Damiano Rosario , Tomasi Francesca , Dolci Claudia , Sforza Chiarella
Published: April 2021

Introduction:

The actual role of landmarks labeling before three-dimensional (3D) facial acquisition is still debated. In this study, several measurements were compared among textured labeled (TL), unlabeled (NL), and untextured (NTL) 3D facial models.

Materials and Methods:

The face of 50 subjects was acquired through stereophotogrammetry. Landmark coordinates were extracted from TL, NL, and NTL facial models, and 33 linear and angular measurements were calculated, together with surface area and volume. Accuracy of measurements among TL, NL, and NTL models was assessed through calculation of relative technical error of measurement (rTEM). The intra- and inter-observer errors for each type of facial model were calculated.

Results:

Intra- and inter-observer error of measurements increased passing from textured to NTL and NL 3D models. Average rTEMs between TL models, and NTL and NL models were 4.5 ± 2.6% and 4.7 ± 2.8%, respectively, almost all measurements being classified as “very good” or “good.” Only for orbital height and its inclination, mandibular ramus length, nasal convexity, alar slope angle, and facial divergence, rTEM was classified as “moderate” or “poor.”

Conclusions:

Accuracy and precision of measurements decrease when landmarks are not previously labeled; attention must be taken when measurements have a low magnitude or involve landmarks requiring palpation.
Functional Improvement of Tacrolimus-Induced Parkinsonism With Amantadine After Liver Transplantation: A Case Report
Authors: Diaz-Segarra Nicole , Edmond Arline , Yonclas Peter
Published: April 2021

Drug-induced parkinsonism is the most common type of drug-induced movement disorder, whose symptoms can decrease patient quality of life and reduce medication compliance. Tacrolimus is a routinely used immunosuppressant agent after liver transplantation, with a well-known neurotoxic profile. There have been rare reports of tacrolimus-induced parkinsonism, but its pharmacologic management and functional impact remain poorly characterized in the literature. We present a case of tacrolimus-induced parkinsonism in a 62-year-old man after a liver transplant, resulting in significant neurologic impairments and multiple barriers to hospital discharge. His tremor, rigidity, bradykinesia, gait dysfunction, dysphonia, and dysphagia significantly improved after starting low-dose amantadine, with increased functional independence that allowed for a safe discharge. This is the first case in the literature detailing tacrolimus-induced parkinsonism's functional impairments improving with amantadine monotherapy.
Sertraline-Induced Amotivationel Syndrome in a 12-Year-Old Girl: A Case Report
Authors: Yildiz Bayindir Busra , Karayagmurlu Ali
Published: April 2021

Sertraline is a safe and effective agent frequently used in the treatment of childhood depression and obsessive compulsive disorder. Amotivational syndrome is also an important clinical manifestation characterized by decreased capacity to make and carry out long-term plans and lack of motivation. This report describes the development of amotivational syndrome in a 12-year-old girl receiving sertraline monotherapy and successful management of this side effect with discontinuation of sertraline and initiation of fluoxetine therapy. This case is presented because, to the best of our knowledge, there have been very few case reports regarding the development of sertraline-related amotivational syndrome and, more importantly, because of the very low number of case reports in which amotivational syndrome was managed by switching to a different selective serotonin reuptake inhibitor.
The Cost-Effectiveness of Tocilizumab (Actemra) Therapy in Giant Cell Arteritis
Authors: Jogimahanti Arjun V. , Kini Ashwini T. , Irwin Lauren E. , Lee Andrew G.
Published: April 2021

Background:

Tocilizumab (Actemra) is a humanized anti–interleukin-6 receptor antibody that has been used as a steroid-sparing agent in giant cell arteritis (GCA). Although the clinical effects are well described in GCA, the cost-effectiveness of the use of tocilizumab in GCA is ill defined. The purpose of this study was to determine the cost-effectiveness of tocilizumab in GCA compared with prednisone alone.

Methods:

A retrospective study of 32 patients with biopsy-proven GCA comparing prednisone alone (16 patients) and prednisone with tocilizumab (16 patients) was performed. The cost for tocilizumab therapy for 26 weeks with mild and severe side effects (Groups 1 and 2, respectively) and for 52 weeks with mild and severe side effects (Group 3 and 4, respectively) was compared with estimated costs of mild and severe steroid-induced side effects (Groups 5 and 6, respectively). Statistical analysis between groups was conducted using independent sample t tests.

Results:

Three out of the 4 group combinations of tocilizumab with prednisone demonstrated a statistically significant (P < 0.05) difference in cost compared with prednisone alone for GCA. Group 2 (26-week tocilizumab therapy with severe steroid-induced side effects), with no statically significant difference in price when compared with steroid therapy alone and far fewer side effects, demonstrated the potential use of tocilizumab in GCA therapy. As expected, longer treatment duration with tocilizumab was associated with greater cost. With respect to side effect severity, the number of side effects of steroid therapy was inversely associated with difference in cost between tocilizumab therapy and steroid side effect treatment.

Conclusion:

This study demonstrates that combination therapy of tocilizumab and prednisone is significantly more expensive than steroids alone with or without accounting for the cost of steroid-induced side effects in treated GCA. The difference in cost between the 2 therapy types is directly related to tocilizumab therapy duration and inversely related to the number or severity of steroid side effects. Patients with GCA who require a shorter duration of steroid therapy and are at risk for a high number of side effects from steroid use may be potential candidates for tocilizumab therapy, from an economic perspective.
Shear Relaxation Governs Dynamic Processes of Biomolecular Condensates
Authors: Ghosh Archishman , Kota Divya , Zhou Huan-Xiang
Published: April 2021

Phase-separated biomolecular condensates must respond agilely to biochemical and environmental cues in performing their wide-ranging cellular functions, but our understanding of condensate dynamics is lagging. Ample evidence now indicates biomolecular condensates as viscoelastic fluids, where shear stress relaxes at a finite rate, not instantaneously as in viscous liquids. Yet the fusion dynamics of condensate droplets has only been modeled based on viscous liquids, with fusion time given by the viscocapillary ratio (viscosity over interfacial tension). Here we used optically trapped polystyrene beads to measure the viscous and elastic moduli and the interfacial tensions of four types of droplets. Our results challenge the viscocapillary model, and reveal that the relaxation of shear stress governs fusion and other dynamic processes of condensates.
Visualization of subcortical structures in non-human primates in vivo by Quantitative Susceptibility Mapping at 3T MRI
Authors: Yoshida Atsushi , Ye Frank Q , Yu David K , Leopold David A , Hikosaka Okihide
Published: April 2021

Magnetic resonance imaging (MRI) is now an essential tool in the field of neuroscience involving non-human primates (NHP). Structural MRI scanning using T1-weighted (T1w) or T2-weighted (T2w) images provides anatomical information, particularly for experiments involving deep structures such as the basal ganglia and cerebellum. However, for certain subcortical structures, T1w and T2w images fail to reveal important anatomical details. To better visualize such structures in the macaque brain, we applied a relatively new method called quantitative susceptibility mapping (QSM), which enhances tissue contrast based on the local tissue magnetic susceptibility. To evaluate the visualization of important structures, we quantified the the contrast-to-noise ratios (CNRs) of the ventral pallidum (VP), globus pallidus external and internal segments (GPe and GPi), substantia nigra (SN), subthalamic nucleus (STN) in the basal ganglia and the dentate nucleus (DN) in the cerebellum. For these structures, the QSM method significantly increased the CNR, and thus the visibility, beyond that in either the T1w or T2w images. In addition, QSM values of some structures were correlated to the age of the macaque subjects. These results indicate that the QSM method can enable the clear identification of certain subcortical structures that are invisible in more traditional scanning sequences.

Highlights

NHP subcortical structures are challenging to see in conventional T1w and T2w images

We applied quantitative susceptibility mapping (QSM) to identify them easily

QSM clearly visualized basal ganglia and cerebellar nucleus of high brain iron content

CNRs of some subcortical nucleus were significantly higher in QSM

QSM values of several subcortical nucleus increased with age
Identification of a signature of evolutionarily conserved stress-induced mutagenesis in cancer
Authors: Cisneros Luis H. , Vaske Charles , Bussey Kimberly J.
Published: April 2021

The clustering of mutations observed in cancer cells is reminiscent of the stress-induced mutagenesis (SIM) response in bacteria. SIM employs error-prone polymerases resulting in mutations concentrated around DNA double-strand breaks with an abundance that decays with genomic distance. We performed a quantitative study on single nucleotide variant calls for whole-genome sequencing data from 1,950 tumors and non-inherited mutations from 129 normal samples. We introduce statistical methods to identify mutational clusters and quantify their distribution patterns. Our results show that mutations in both normal and cancer samples are indeed clustered and have shapes indicative of SIM. We also found that clusters of mutations colocalize more prevalently in normal samples than in cancer, suggesting loss of regulation leading to increased randomness in the mutational process during carcinogenesis.
RegVar: Tissue-specific Prioritization of Noncoding Regulatory Variants
Authors: Lu Hao , Ma Luyu , Quan Cheng , Li Lei , Lu Yiming , Zhou Gangqiao , Zhang Chenggang
Published: April 2021

Noncoding genomic variants constitute the majority of trait-associated genome variations; however, identification of functional noncoding variants is still a challenge in human genetics, and a method systematically assessing the impact of regulatory variants on gene expression and linking them to potential target genes is still lacking. Here we introduce a deep neural network (DNN)-based computational framework, RegVar, that can accurately predict the tissue-specific impact of noncoding regulatory variants on target genes. We show that, by robustly learning the genomic characteristics of massive variant-gene expression associations in a variety of human tissues, RegVar vastly surpasses all current noncoding variants prioritization methods in predicting regulatory variants under different circumstances. The unique features of RegVar make it an excellent framework for assessing the regulatory impact of any variant on its putative target genes in a variety of tissues. RegVar is available as a webserver athttp://regvar.cbportal.org/.
The DNA-to-cytoplasm ratio broadly activates zygotic gene expression in Xenopus
Authors: Jukam David , Kapoor Rishabh R , Straight Aaron F , Skotheim Jan M.
Published: April 2021

In multicellular animals, the first major event after fertilization is the switch from maternal to zygotic control of development. During this transition, zygotic gene transcription is broadly activated in an otherwise quiescent genome in a process known as zygotic genome activation (ZGA). In fast developing embryos, ZGA often overlaps with the slowing of initially synchronous cell divisions at the mid-blastula transition (MBT). Initial studies of the MBT led to the nuclear-to-cytoplasmic ratio model where MBT timing is regulated by the exponentially increasing amounts of some nuclear component ‘N’ titrated against a fixed cytoplasmic component ‘C’. However, more recent experiments have been interpreted to suggest that ZGA is independent of the N/C ratio. To determine the role of the N/C ratio in ZGA, we generatedXenopusfrog embryos with ∼3-fold differences in genomic DNA (i.e., “N”) by usingX. tropicalissperm to fertilizeX. laeviseggs with or without their maternal genome. Resulting embryos have otherwise identicalX. tropicalisgenome template amounts, embryo sizes, andX. laevismaternal environments. We used theX. tropicalispaternally derived mRNA to identify a high confidence set of exclusively zygotic transcripts. Both ZGA and the increase in cell cycle duration are delayed in embryos with ∼3-fold less DNA per cell. Thus, DNA is an important component of the N/C ratio, which is indeed a critical regulator of zygotic genome activation inXenopusembryos.
Alterations in protein translation and carboxylic acid catabolic processes in diabetic kidney disease
Authors: Collins Kimberly S. , Eadon Michael T. , Cheng Ying-Hua , Barwinska Daria , Ferreira Ricardo Melo , McCarthy Thomas W. , Janosevic Danielle , Syed Farooq , Maier Bernhard , El-Achkar Tarek M. , Kelly Katherine J. , Phillips Carrie L. , Hato Takashi , Sutton Timothy A. , Dagher Pierre C.
Published: April 2021

Diabetic kidney disease (DKD) remains the leading cause of end stage kidney disease despite decades of study. Alterations in the glomerulus and kidney tubules both contribute to the pathogenesis of DKD although the majority of investigative efforts have focused on the glomerulus. We sought to examine the differential expression signature of human DKD in the glomerulus and proximal tubule and corroborate our findings in the db/db mouse model of diabetes. A transcriptogram network analysis of RNAseq data from laser microdissected (LMD) human glomerulus and proximal tubule of DKD and reference nephrectomy samples revealed enriched pathways including rhodopsin-like receptors, olfactory signaling, and ribosome (protein translation) in the proximal tubule of human DKD biopsy samples. The translation pathway was also enriched in the glomerulus. Increased translation in diabetic kidneys was validated using polyribosomal profiling in the db/db mouse model of diabetes. Using single nuclear RNA sequencing (snRNAseq) of kidneys from db/db mice, we prioritized additional pathways identified in human DKD. The top overlapping pathway identified in the murine snRNAseq proximal tubule clusters and the human LMD proximal tubule compartment was carboxylic acid catabolism. Using ultra-performance liquid chromatography-mass spectrometry, the fatty acid catabolism pathway was also found to be dysregulated in the db/db mouse model. The Acetyl-CoA metabolite was down-regulated in db/db mice, aligning with the human differential expression of the genes ACOX1 and ACACB. In summary, our findings demonstrate that proximal tubular alterations in protein translation and carboxylic acid catabolism are key features in both human and murine DKD.
Inferring the stabilization effects of SARS-CoV-2 variants on the binding with ACE2 receptor
Authors: Miotto Mattia , Di Rienzo Lorenzo , Gosti Giorgio , Bo’ Leonardo , Parisi Giacomo , Piacentini Roberta , Boffi Alberto , Ruocco Giancarlo , Milanetti Edoardo
Published: April 2021

With the progression of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, several variants of the virus are emerging with mutations distributed all over the viral sequence. While most of them are expected to have little to no effects at the phenotype level, some of these variants presenting specific mutations on the Spike protein are rapidly spreading, making urgent the need of characterizing their effects on phenotype features like contagiousness and antigenicity. With this aim, we performed extensive molecular dynamics simulations on a selected set of possible Spike variants in order to assess the stabilizing effect of particular amino acid substitutions, with a special focus on the mutations that are both characteristic of the top three most worrying variants at the moment, i.e the English, South African and Amazonian ones, and that occur at the molecular interface between SARS-CoV-2 Spike protein and its human ACE2 receptor. We characterize these variants’ effect in terms of (i) residues mobility, (ii) compactness, studying the network of interactions at the interface, and (iii) variation of shape complementarity via expanding the molecular surfaces in the Zernike basis. Overall, our analyses highlighted greater stability of the three variant complexes with respect to both the wild type and two negative control systems, especially for the English and Amazonian variants. In addition, in the three variants, we investigate the effects a not-yet observed mutation in position 501 could provoke on complex stability. We found that a phenylalanine mutation behaves similarly to the English variant and may cooperate in further increasing the stability of the South African one, hinting at the need for careful surveillance for the emergence of such kind of mutations in the population. Ultimately, we show that the observables we propose describe key features for the stability of the ACE2-spike complex and can help to monitor further possible spike variants.
A biosensor to gauge protein homeostasis resilience differences in the nucleus compared to cytosol of mammalian cells
Authors: Raeburn Candice B. , Ormsby Angelique , Moily Nagaraj S. , Cox Dezerae , Ebbinghaus Simon , Dickson Alex , McColl Gawain , Hatters Danny M.
Published: April 2021

An extensive network of chaperones and other proteins maintain protein homeostasis and guard against inappropriate protein aggregation that is a hallmark of neurodegenerative diseases. Using a fluorescence resonance energy-based biosensor that simultaneously reports on intact cellular chaperone holdase activity and detrimental aggregation propensity, we investigated the buffering capacity of the systems managing protein homeostasis in the nucleus of the human cell line HEK293 compared to the cytosol. We found that the nucleus showed lower net holdase activity and reduced capacity to suppress protein aggregation, suggesting that the nuclear quality control resources are less effective compared to those in the cytosol. Aggregation of mutant huntingtin exon 1 protein (Httex1) in the cytosol appeared to deplete cytosolic chaperone supply by depleting holdase activity. Unexpectedly, the same stress increased holdase activity in the nucleus suggesting that proteostasis stress can trigger a rebalance of chaperone supply in different subcellular compartments. Collectively the findings suggest the cytosol has more capacity to manage imbalances in proteome foldedness than the nucleus, but chaperone supply can be redirected into the nucleus under conditions of proteostasis stress caused by cytosolic protein aggregation.