bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing Serum Levels of Vitamin D and Zinc in Novel Coronavirus–Infected Patients and Healthy Individuals in Northeastern Iran, 2020
Authors: Hosseini Seyed Javad , Moradi Bagher , Marhemati Mahmood , Firouzian Ali Asghar , Ildarabadi Eshagh , Abedi Ali , Firooz Mahbobeh
Published: August 2021

Background

COVID-19 infection has recently become a pandemic disease around the world, and its risk factors have not fully evaluated. This study aimed to compare the serum vitamin D (Vit D) and zinc levels in patients infected with novel coronavirus and healthy volunteers (HVs).

Methods

This was a single-center, cross-sectional study conducted on 56 patients (32 severe cases and 24 nonsevere) admitted to the COVID-19 ward and 46 HVs living in Esfarayen City, North Khorasan Province of Iran. Serum levels of Vit D and zinc in admitted patients to the COVID-19 ward and HVs were measured.

Results

The average levels of serum Vit D in severe cases, nonsevere cases, and HVs were 31.03 ± 15.49, 37.25 ± 18.49, and 39.33 ± 14.83, respectively (P = 0.05). Moreover, the average concentrations of serum zinc in severe cases, nonsevere cases, and HVs were 31.03 ± 15.49, 37.25 ± 18.49, and 39.33 ± 14.83, respectively (P = 0.01). Mortality rate, reinfection (for 5 months), and length of hospital stay in severe cases were higher than in nonsevere cases (P > 0.05).

Conclusions

Results showed that severe cases had lower levels of Vit D than did other groups and were marginally significant. Also, severe cases had a significantly low level of zinc when compared with nonsevere cases and HVs. Levels of Vit D and zinc can affect the incidence of COVID-19 infection.
Primary Subcutaneous Phaeohyphomycosis Caused by Cladosporium cladosporioides
Authors: Viola Kelly Scapin , Ricci Giannina , D'Elia Maria Paula Barbieri , Pott-Junior Henrique
Published: August 2021

Here, we report a rare case of a 48-year-old female immunocompetent patient who presented with a subcutaneous phaeohyphomycosis caused by Cladosporium cladosporioides. Diagnostic confirmation was established by molecular analysis of the biopsy sample, and the patient was successfully treated with itraconazole monotherapy. This case should raise the clinician's awareness of such condition and point to molecular analysis as an important diagnostic tool.
Neurobiological antecedents of multisite pain in children
Authors: Kaplan Chelsea M. , Schrepf Andrew , Mawla Ishtiaq , Ichesco Eric , Boehnke Kevin F. , Beltz Adriene , Foxen-Craft Emily , Puglia Michael P. , Tsodikov Alexandre , Williams David A. , Hassett Afton L. , Clauw Daniel J. , Harte Steven E. , Harris Richard E.
Published: August 2021

Altered brain structure and function is evident in adults with multisite chronic pain. Although many such adults trace their pain back to childhood, it has been difficult to disentangle whether central nervous system alterations precede or are consequences of chronic pain. If the former is true, aberrant brain activity may identify children vulnerable to developing chronic pain later in life. We examined structural and functional brain magnetic resonance imaging metrics in a subset of children from the first 2 assessments of the Adolescent Brain and Cognitive Development Study. Children (aged 9-10) who were pain free at baseline and then developed multisite pain 1 year later (n = 115) were matched to control children who were pain free at both timepoints (n = 230). We analyzed brain structure (cortical thickness and gray matter volume) and function (spontaneous neural activity and functional connectivity). Results were deemed significant at the cluster level P < 0.05 false discovery rate corrected for multiple comparisons. At baseline, children who subsequently developed multisite pain had increased neural activity in superior parietal /primary somatosensory and motor cortices and decreased activity in the medial prefrontal cortex. They also exhibited stronger functional connectivity between the salience network, somatosensory, and default mode network regions. No significant differences in the brain structure were observed. Increased neural activity and functional connectivity between brain regions, consistent to that seen in adults with chronic pain, exist in children before developing multisite pain. These findings may represent a neural vulnerability to developing future chronic pain.
Correlations between bladder wall thickness and clinical manifestations in female patients with detrusor underactivity and detrusor overactivity–with–detrusor underactivity
Authors: Yu Ping-Hsuan , Lin Chih-Chieh , Fan Yu-Hua , Lin Alex T. L. , Huang William J. S.
Published: August 2021

Background:

Among female patients with lower urinary tract symptoms, detrusor underactivity (DU), and detrusor overactivity–with–detrusor underactivity (DO-DU) are two common diagnoses. Here, we investigated the correlations between bladder wall thickness (BWT) and clinical manifestations of the two diagnoses.

Methods:

From 2011 to 2016, female patients with DU or DO-DU, diagnosed at our institute, were recruited. We analyzed their urodynamic parameters and collected three questionnaires (IPSS, UDI-6, OABSS). Using transabdominal sonography, the BWT was recorded. DU was defined as follows: maximum free flow rate (Q
max) ≤ 15 cc/s; detrusor pressure at maximum flow (P
detQmax) ≤ 20 cmH2O; bladder capacity > 150 cc. DO-DU was defined as follows: Q
max ≤ 15 cc/s; P
detQmax ≤ 20 cmH2O; bladder capacity ≤ 150 cc. The BWTs of the two groups were compared using the Mann–Whitney U test; the correlations among the BWTs and the results of three questionnaires were analyzed using Spearman’s rank correlation coefficient.

Results:

Forty-eight female patients with DU and 13 with DO-DU were recruited. Demographic data revealed no differences between the two groups. The mean BWT of the DO-DU patients was significantly larger than that of the DU patients (4.11 vs 3.42 mm; p = 0.001). In the DO-DU group, a high correlation existed between the BWT and some of the UDI-6 items (urgency incontinence: r = 0.831, p = 0.006; incontinence related to activity: r = 0.884, p = 0.002; small amounts of leakage: r = 0.809, p = 0.008). The BWT of the DO-DU patients also exhibited a moderate correlation with the urgency incontinence from the OABSS questionnaire (r = 0.679; p = 0.044). No correlations existed between the BWT of the DU patients and any of the data from the three questionnaires.

Conclusion:

The BWT in the DO-DU patients was significantly thicker than that in the DU patients. The DO-DU patients with thicker bladder walls also had higher UDI-6 scores for both urgency and urgency incontinence.
Adaptive Challenges, Adaptive Work, and Adaptive Leadership Among Women Living With HIV in the Southern United States: Findings From a Qualitative Study
Authors: Bailey Donald E. , Caiola Courtney , Adimora Adaora A. , Ramirez Catalina , Holt Lauren , Johnson Ragan , Koch Amie , McGee Kara , McMillian-Bohler Jacquelyn M. , Randolph Schenita D. , Ritchwood Tiarney D. , Relf Michael V.
Published: August 2021

Women living with HIV have a higher burden of non-AIDS comorbidities and prevalence of chronic conditions. The Adaptive Leadership Framework for Chronic Illness clarifies living with complex health challenges by delineating the technical work of health care providers as well as the adaptive work and leadership behaviors of patients and their providers. We conducted a descriptive, qualitative study of women residing in the Southern United States who were participating in the Women's Interagency HIV Study in North Carolina. Twenty-two participants (mean age = 52.2 years; 90.9% self-identifying as Black or African American) completed semi-structured qualitative interviews. We identified adaptive challenges (e.g., affective and disclosure challenges) and adaptive work and leadership behaviors. Women learned skills to care for their health and support their families and to work with their providers to manage their care. Findings support the importance of identifying leadership behaviors for the purpose of developing person-centered interventions.
Developing Clinical Reasoning in a Physician Assistant Curriculum: The University of Sheffield approach
Authors: Gray James , Darling-Pomranz Claire , Jackson Ben
Published: August 2021

Clinical reasoning remains a key area for development amongst clinical students across the world. Physician assistant (PA) roles (physician associate in the United Kingdom) are rapidly expanding, and there is a need to ensure that this core skill is reflected in course curricula. This article presents how the University of Sheffield has integrated clinical reasoning into the curriculum for its PA course. This includes recognizing the need to consider different approaches to reasoning and how they are taught, the assessment of reasoning across Miller's pyramid, and other considerations that contribute to embedding reasoning within the course. We discuss the implications of our approach and comment on issues that we may need to consider in the future.
Efficacy of Platelet-Rich Plasma Versus Placebo in the Treatment of Tendinopathy: A Meta-analysis of Randomized Controlled Trials
Authors: Dai Wenli , Yan Wenqiang , Leng Xi , Wang Jian , Hu Xiaoqing , Cheng Jin , Ao Yingfang
Published: August 2021

Objective:

To evaluate the efficacy of platelet-rich plasma (PRP) injections versus placebo in the treatment of tendinopathy.

Data Sources:

We performed a systematic literature search in MEDLINE, Embase, Scopus, CINAHL, Cochrane Library, and ClinicalTrials.gov through November 2020 to identify randomized controlled trials (RCTs) that evaluated the clinical efficacy of PRP versus placebo for the treatment of tendinopathy. Outcomes were analyzed on an intention-to-treat basis with random-effects models.

Main Results:

A total of 13 RCTs were included in this meta-analysis. The pooled analysis showed no significant difference in pain relief at 4 to 6 weeks (standard mean difference [SMD]: −0.18, 95% confidence intervals [CI]: −0.62 to 0.26), 12 weeks (SMD: −0.14, 95% CI: −0.55 to 0.26), and ≥24 weeks (SMD: −0.56, 95% CI: −1.16 to 0.05) or function improvement at 4 to 6 weeks (SMD: 0.11, 95% CI: −0.13 to 0.35), 12 weeks (SMD: 0.18, 95% CI: −0.13 to 0.49), and ≥24 weeks (SMD: 0.26, 95% CI: −0.14 to 0.66) for PRP compared with placebo in the treatment of tendinopathy. The sensitivity analysis indicated no significant difference in pain relief or function improvement at 12 weeks between PRP and placebo for different types of tendinopathies, treatment regimens, leukocyte concentrations, or cointerventions.

Conclusions:

Platelet-rich plasma injection was not found to be superior to placebo in the treatment of tendinopathy, as measured by pain relief and functional improvement at 4 to 6, 12, and ≥24 weeks.
Individualized Prediction of Acute Pancreatitis Recurrence Using a Nomogram
Authors: Hu Xuehai , Yang Bo , Li Jie , Bai Xuesong , Li Shilin , Liu Honglan , Zhang Hongyu , Zeng Fanxin
Published: August 2021

Objectives

The objective of this study was to develop and validate a model, based on the blood biochemical (BBC) indexes, to predict the recurrence of acute pancreatitis patients.

Methods

We retrospectively enrolled 923 acute pancreatitis patients (586 in the primary cohort and 337 in the validation cohort) from January 2014 to December 2016. Aiming for an extreme imbalance between recurrent acute pancreatitis (RAP) and non-RAP patients (about 1:4), we designed BBC index selection using least absolute shrinkage and selection operator regression, along with an ensemble-learning strategy to obtain a BBC signature. Multivariable logistic regression was used to build the RAP predictive model.

Results

The BBC signature, consisting of 35 selected BBC indexes, was significantly higher in patients with RAP (P < 0.001). The area under the curve of the receiver operating characteristic curve of BBC signature model was 0.6534 in the primary cohort and 0.7173 in the validation cohort. The RAP predictive nomogram incorporating the BBC signature, age, hypertension, and diabetes showed better discrimination, with an area under the curve of 0.6538 in the primary cohort and 0.7212 in the validation cohort.

Conclusions

Our study developed a RAP predictive nomogram with good performance, which could be conveniently and efficiently used to optimize individualized prediction of RAP.
Impact of Postoperative Glycemic Control on Postoperative Morbidity in Patients Undergoing Open Pancreaticoduodenectomy
Authors: Yun Regina , Javed Ammar A. , Jarrell Andrew S. , Crow Jessica , Wright Michael J. , Burkhart Richard A. , Rybny Joseph , Wolfgang Christopher L. , Kruer Rachel M.
Published: August 2021

Objective

To evaluate the impact of postoperative glycemic control on postoperative morbidity in patients undergoing a pancreaticoduodenectomy.

Methods

A retrospective study was performed on patients at The Johns Hopkins Hospital between April 2015 and April 2016. Data were collected on postoperative insulin regimens, blood glucose, rates of hyperglycemia and hypoglycemia, and postoperative complications and were evaluated.

Results

Out of 244 patients, 114 (46.7%) experienced at least 1 hyperglycemic (>180 mg/dL) episode and 16 (6.6%) experienced at least 1 hypoglycemic episode (<70 mg/dL) during the first postoperative 24 hours. Early postoperative hyperglycemia (>180 mg/dL) was associated with a significantly higher rate of surgical site infections (15.7% vs 7%; P = 0.031). Late postoperative hyperglycemia (>180 mg/dL) was associated with a significantly higher rate of fistulas (4.3% vs 14.6%; P = 0.021).

Conclusions

Early hyperglycemia (>180 mg/dL) is associated with a higher risk of surgical site infections while late hyperglycemia is associated with a higher risk of fistulas. Intensive glucose control (<150 mg/dL) was not demonstrated to decrease the risk of postoperative complications. Similar to other critically ill populations, targeting a glucose goal of <180 mg/dL may be an appropriate target to reduce morbidity without increasing the risk of hypoglycemia.
Endoscopic Versus Laparoscopic Treatment for Pancreatic Pseudocysts
Authors: Hao Wenzhen , Chen Yunli , Jiang Yu , Yang Aiming
Published: August 2021

Objective

The aim of the study was to evaluate the efficacy and safety of endoscopic treatment for pancreatic pseudocysts (PPCs) compared with laparoscopic treatment.

Methods

The Embase, Medline, Cochrane Library, Web of Science databases, China National Knowledge Infrastructure Chinese citation database, and WANFANG database were systematically searched to identify all comparative trials investigating endoscopic versus laparoscopic treatment for PPC. The main outcome measures included treatment success rate, adverse events, recurrence rate, operation time, intraoperative blood loss, and hospital stay.

Results

Six studies with 301 participants were included. The results suggested that there was no difference in rates of treatment success (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.40–2.01; P = 0.79), adverse events (OR, 0.80, 95% CI, 0.38–1.70; P = 0.57), or recurrence (OR, 0.55, 95% CI, 0.22−1.40; P = 0.21) between endoscopic and laparoscopic treatments. However, the endoscopic group exhibited reduced operation time (weighted mean difference [WMD], −67.11; 95% CI, −77.27 to −56.96; P < 0.001), intraoperative blood loss (WMD, −65.23; 95% CI, −103.38 to −27.08; P < 0.001), and hospital stay (WMD, −2.45; 95% CI, −4.74 to −0.16; P = 0.04).

Conclusions

Endoscopic treatment might be suitable for PPC patients.
North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper on the Diagnosis and Management of Pediatric Acute Liver Failure
Authors: Squires James E. , Alonso Estella M. , Ibrahim Samar H. , Kasper Vania , Kehar Mohit , Martinez Mercedes , Squires Robert H.
Published: August 2021

Pediatric acute liver failure (PALF) is a rare, rapidly progressive clinical syndrome with significant morbidity and mortality. The phenotype of PALF manifests as abrupt onset liver dysfunction, which can be brought via disparate etiology. Management is reliant upon intensive clinical care and support, often provided by the collaborative efforts of hepatologists, critical care specialists, and liver transplant surgeons. The construction of an age‐based diagnostic approach, the identification of a potential underlying cause, and the prompt implementation of appropriate therapy can be lifesaving; however, the dynamic and rapidly progressive nature of PALF also demands that diagnostic inquiries be paired with monitoring strategies for the recognition and treatment of common complications of PALF. Although liver transplantation can provide a potential life‐saving therapeutic option, the ability to confidently determine the certainness that liver transplant is needed for an individual child has been hampered by a lack of adequately tested clinical decision support tools and accurate predictive models. Given the accelerated progress in understanding PALF, we will provide clinical guidance to pediatric gastroenterologists and other pediatric providers caring for children with PALF by presenting the most recent advances in diagnosis, management, pathophysiology, and associated outcomes.
Use of Job Classifications, Career Ladders, and the Applied Epidemiology Competencies to Support Recruitment, Retention, and Practice of State Health Department Epidemiologists
Authors: Daly Elizabeth R. , Arrazola Jessica , Umble Karl
Published: August 2021

Context:

State health departments report that recruitment and retention of qualified epidemiologists is a significant challenge to ensuring epidemiology capacity to support essential public health services.

Objective:

To collect information on the use of epidemiology job classifications, career ladders, and professional competencies in state health departments to inform workforce development activities that improve epidemiology capacity.

Design:

Electronic survey of the designated state epidemiologist.

Setting:

Fifty state health departments and the District of Columbia.

Participants:

State epidemiologists working in state health departments.

Main Outcome Measures:

Use and perceived benefit of epidemiology job classifications, career ladders, and professional competencies.

Results:

All 50 states and the District of Columbia responded to the survey. Most state health departments reported having epidemiology-specific job classifications (n = 44, 90%) and career ladders (n = 36, 71%) in place. State epidemiologists strongly agreed or agreed that having an epidemiology-specific classification positively contributed to recruitment (n = 37, 84%) and retention (n = 29, 66%) of epidemiologists in their agency. State epidemiologists strongly agreed or agreed that having an epidemiology-specific career ladder positively contributed to recruitment (n = 24, 69%) and retention (n = 23, 66%) of epidemiologists in their agency. Only 10 (29%) state epidemiologists reported using the applied epidemiology competencies to develop or revise their jurisdiction's epidemiology career ladder.

Conclusions:

State health departments should implement well-maintained epidemiology-specific job classifications and career ladders that are based on current epidemiology competencies. Career ladders should be supported with opportunities for competency-based training to support career progression.
Patient Safety Strategies in Psychiatry and How They Construct the Notion of Preventable Harm: A Scoping Review
Authors: Svensson Jakob
Published: August 2021

Objectives

The literature on patient safety in psychiatry has not been explored systematically in terms of what interventions are used, how they are used, and what type of (preventable) harm is targeted. The aims of this scoping review are to explore patient safety strategies used in psychiatry and determine how they construct the notion of preventable harm.

Method

A scoping review of literature on patient safety in psychiatry published in English between 2000 and 2019 was conducted using Scopus, MEDLINE, PsycInfo, and CINAHL. Keywords of patient safety strategies and possible outcomes were coded from the results, discussion, or conclusion. Patient safety strategies were inductively categorized into themes according to the focus of the strategy.

Results

The review introduces 7 focus areas of patient safety strategies identified within the psychiatric literature: “risk management,” “healthcare practitioners,” “patient observation,” “patient involvement,” “computerized methods,” “admission and discharge,” and “security.” The result shows that patient safety strategies mainly aim to reduce suicide, self-harm, violence, and falls and present a large diversity of measures, often aimed at reducing variability while increasing standardization.

Conclusions

The strategies that are supported in the literature to achieve safer psychiatry mainly arise from linear cause-effect models and rely on staff performance, competence, and compliance. Contemporary safety science acknowledges the performance variability of everyday normal work and sees risk as the dynamic migration of these daily activities. The field of psychiatry has not yet included this view of safety in the strategic actions to reduce preventable harm.
Utility and Clinical Implications of Appendicular Skeleton Magnetic Resonance Imaging in Multiple Myeloma: A Single-Institutional 15-Year Experience
Authors: Shieh Alice C. , Faraji Navid , Smith Daniel , Parikh Keval , Ramaiya Nikhil H.
Published: August 2021

Objective

The aim of this study was to evaluate the utility of appendicular skeleton magnetic resonance imaging (MRI) in the management of multiple myeloma over 15 years.

Methods

A total of 107 appendicular MRIs were obtained from 67 patients. Variables including age, sex, diagnosis, stage, indication, transplant status, MRI result, and treatment course were analyzed.

Results

The most common indication was pain (76.6%). The most commonly affected bone groups were the proximal lower (54.3%) and upper extremity (47.6%). Most (83%) positive examinations demonstrated focal disease. Advanced Durie-Salmon stage was associated with increase in appendicular disease (P = 0.0056). Increasing age and prior negative positron emission tomography/computed tomography were associated with a decrease in appendicular disease (P = 0.0036 and 0.0011). When neoplasm was seen, 58.5% underwent management alteration. Advanced stage and history of relapse were associated with treatment alterations (P = 0.0096 and 0.0031).

Conclusion

Appendicular MRIs comprised 9.6% of MRIs ordered. Appendicular MRI elucidates both neoplastic and nonneoplastic causes of pain. Most examinations with MRI positive for myeloma had subsequent skeletal disease and resulted in altered management.
Management of Tessier Type 3 Cleft With a Novel Reverse Palatal Expander
Authors: Kim Erinn N. , Moss Whitney D. , Yamashiro Duane K. , Tuncer Fatma B. , Siddiqi Faizi A.
Published: August 2021

The purpose of this clinical report is to present the novel management of a type Tessier 3 cleft which was treated using a palatal expander in reverse fashion to reapproximate the craniofacial skeleton allowing for closure of the palate and soft tissue of the cleft. Reapproximation of the bony component of the cleft was achieved without osteotomies and allowed for easier and earlier realignment of the bony and soft tissue components of the cleft. To our knowledge, this is the first use of reverse palatal expansion in the treatment of type 3 Tessier cleft. Reverse palatal expansion made management of this cleft more straightforward and should be considered as a useful adjunct in the management of wide facial clefts.
Forehead Flap Templates for Nasal Reconstruction Digitally Developed From 2D and 3D Images
Authors: Fishman Zachary , Whyne Cari M. , Fialkov Jeffery A.
Published: August 2021

The forehead flap is the gold standard procedure for nasal reconstruction to address a partial or complete rhinectomy. Traditionally, the three-dimensional (3D) nasal defect is manually templated intraoperatively to design the two-dimensional (2D) flap shape on intact morphology. In this clinical study, digital preoperative planning is used to template with computer-assisted design and manufacturing. Preoperative digital templates were implemented for 3 representative patients (1 in Supplementary Digital Content, http://links.lww.com/SCS/D60). This includes designs for a hemi-rhinectomy case from 3D mirroring, a partial total rhinectomy case generated from a 3D scan, and a total rhinectomy case generated from a 3D morphable model based on a prepathology 2D photo. Digital unwrapping flattened the patient's 3D nasal geometry designs to 2D skin flap shapes. Finally, the 2D designs were printed as traceable intraoperative templates at a 1:1 scale. This clinical study demonstrates the application of digital 3D preoperative templating to improve workflow for nasal reconstruction.
Adverse events following COVID-19 virus vaccination in Japanese young population: The first cross-sectional study conducted by a questionnaire survey after the first-time-injection
Authors: Suehiro Marie , Okubo Shinya , Nakajima Kensuke , Kanda Kosuke , Hayakawa Masanobu , Oiso Shigeru , Kabashima Tsutomu , Fujita Hideaki , Ando Yukio , Muro Takahiro
Published: August 2021

A cross-sectional study was conducted to clarify the adverse events of COVID-19 vaccines in Japanese young population.

The proportion of participants with adverse events at the vaccination site (immediately or within 30 minutes after vaccination) was 0.5%, and anaphylaxis occurred in one female student (0.03%).

We analyzed 1,877 data obtained from a questionnaire survey of 1,993 vaccinated individuals. Eighty-two percent of participants complained of local adverse events. Injection site pain was the most common local adverse event (71%). Systemic adverse events occurred in 48% of participants. The most common adverse event was myalgia (34%).

A multivariable logistic regression model was used to determine risk factors.

Local adverse events were associated with sex (female) and allergy history, with odds ratios (ORs) (95% confidence interval [CI]) of 2.15 (1.69-2.73) and 1.73 (1.10-2.74), respectively. Systemic adverse events were associated with sex (female), age (<20 years old), allergy history, and history of adverse events with previous medications, with ORs (95% CI) of 2.49 (2.03-3.06), 1.80 (1.44-2.24), 1.39 (1.03-1.89), and 1.53 (1.02-2.29).

The results of this study clarified for the first time that age less than 20 years is a risk factor for systemic adverse events from the COVID-19 Vaccine Moderna Intramuscular Injection. This information will give impacts on considering adverse events and its mechanisms in mRNA vaccination.
Cytocapsular Tube-Based Precise Cancer Diagnosis in Colon Cancers
Authors: Yi Tingfang , Wagner Gerhard , Ganshirt Stephen
Published: August 2021

Colorectal (colon) cancer ranks second in terms of cancer lethality worldwide. It is estimated that approximately 1.93 million new colorectal (colon) cancer cases and approximate one million colorectal cancer deaths occur worldwide in 2020 alone. Cancer metastasis is a major source of cancer lethality. Mechanisms underlying colorectal cancer metastases are long-term obscure. Recently, a new organelle associated with aggressive cancer cells, dubbed cytocapsular tube, was recognized to conduct cancer cell metastases in tissues in vivo. Here, we investigated the roles of cytocapsular tubes in colon cancer metastasis in 9 subtypes of colon cancers with original clinical colon cancer tissues, paracancer tissues of colon cancer, and metastatic colon cancers in multiple other tissues and organs. We found that colon cancer metastasized via cytocapsular tubes and their networks in clinical tissues in vivo. Furthermore, we applied the cytocapsular tube analyses in precise cancer diagnosis in clinical colon cancers and obtained better outcomes in clinical colon cancer management.
Systemic and mucosal IgA responses are variably induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection against subsequent infection
Authors: Sheikh-Mohamed Salma , Isho Baweleta , Chao Gary Y.C. , Zuo Michelle , Cohen Carmit , Lustig Yaniv , Nahass George R. , Salomon-Shulman Rachel E. , Blacker Grace , Fazel-Zarandi Mahya , Rathod Bhavisha , Colwill Karen , Jamal Alainna , Li Zhijie , de Launay Keelia Quin , Takaoka Alyson , Garnham-Takaoka Julia , Patel Anjali , Fahim Christine , Paterson Aimee , Li Angel Xinliu , Haq Nazrana , Barati Shiva , Gilbert Lois , Green Karen , Mozafarihashjin Mohammad , Samaan Philip , Budylowski Patrick , Siqueira Walter L. , Mubareka Samira , Ostrowski Mario , Rini James M. , Rojas Olga L. , Weissman Irving L. , Tal Michal Caspi , McGeer Allison , Regev-Yochay Gili , Straus Sharon , Gingras Anne-Claude , Gommerman Jennifer L.
Published: August 2021

Although SARS-CoV-2 infects the upper respiratory tract, we know little about the amount, type, and kinetics of antibodies (Ab) generated at this site in response to intramuscular COVID-19 vaccination, and whether these Ab protect against subsequent “breakthrough” infections. We collected longitudinal serum and saliva samples from participants receiving two doses of mRNA COVID-19 vaccines over a 6-month period and measured the relative level of anti-Spike and anti-Receptor Binding Domain (RBD) Ab. We detected anti-Spike/RBD IgG and IgA and associated secretory component in the saliva of most participants receiving 1 dose of mRNA vaccine. Administration of a second dose of mRNA boosted the IgG but not the IgA response, with only 30% of participants remaining positive for IgA at this timepoint. At 6 months post-dose 2, these participants exhibited greatly diminished anti-Spike/RBD IgG and IgA levels concomitant with a reduction in neutralizing activity in the saliva, although the level of secretory component associated anti-Spike was less susceptible to decay. Examining two prospective cohorts of subjects that were monitored for infections post-vaccination, we found that participants who were subsequently infected with SARS-CoV-2 had lower levels of vaccine-induced serum anti-Spike/RBD IgA at 2-4 weeks post-dose 2 compared to participants who did not experience an infection, whereas IgG levels were comparable between groups. These data emphasize the importance of developing COVID-19 vaccines that elicit a durable IgA response.

One-Sentence Summary

Our study delves into whether intra-muscular mRNA vaccination regimes confer a local IgA response in the oral cavity and whether the IgA response is associated with protection against breakthrough infection.
Aspergillosis and Mucormycosis in COVID-19 Patients; a Systematic Review and Meta-analysis
Authors: Afzal Saira , Nasir Mehreen
Published: August 2021

Fungal infections have increased in number since the onset of this lethal pandemic. The aim of this study is to assess risk factors and case fatality in COVID-19 cases with aspergillosis or mucormycosis. Systematic review and meta-analysis was done according to PRISMA guidelines. Data bases used were Google scholar, Pakmedinet, PUBMED and MEDLINE. 21 case reports and case series of mucormycosis in COVID-19 patients were identified and mean age was 56.3 years (36 males and 12 females). The most common comorbidity was diabetes and site was Rhino orbital mucormycosis. Case fatality of 48 combined cases was calculated to be 52%. 19 articles of aspergillosis were included. Diabetes was the most common comorbidity in cases. The number of male cases were more than females. Incidence of aspergillosis in critically sick COVID-19 patients was calculated to be 9.3%. Case fatality was calculated to be 51.2%. Screening can be a beneficial tool for decreasing the morbidity and mortality.
SARS-CoV-2-specific Humoral and Cell-mediated Immune Responses after Immunization with Inactivated COVID-19 Vaccine in Kidney Transplant Recipients (CVIM 1 Study)
Authors: Bruminhent Jackrapong , Sethaudom Chavachol , Chaumdee Pongsathon , Boongird Sarinya , Kiertiburanakul Sasisopin , Malathum Kumthorn , Nongnuch Arkom , Phuphuakrat Angsana , Jirasiritham Sopon , Janphram Chitimaporn , Thotsiri Sansanee , Upama Supparat , Assanatham Montira ,   Ramathibodi Transplant Infectious Diseases (RTID) Study Group
Published: August 2021

Immunogenicity following inactivated SARS-CoV-2 vaccination among solid organ transplant recipients has not been assessed. Seventy-five patients (37 kidney transplant [KT] recipients and 38 non-transplant controls) received two doses, at 4-week intervals, of an inactivated whole-virus SARS-CoV-2 vaccine. SARS-CoV-2-specific humoral (HMI) and cell-mediated immunity (CMI) were measured before, 4 weeks post-first dose, and 2 weeks post-second dose. The median age of KT recipients was 50 years (IQR, 42–54) and 89% were receiving calcineurin inhibitors/mycophenolate/corticosteroid regimens. The median time since transplant was 4.5 years (IQR, 2–9.5). Among 35 KT patients, anti-RBD IgG titer after vaccination was not significantly different to baseline, but was significantly lower than in controls (7.8 [95%CI 0.2–15.5] vs 2,691 [95%CI 1,581–3,802], p<0.001) as well as the percentage of surrogate virus neutralizing antibody inhibition (2 [95% CI −1-6] vs 71 [95%CI 61–81], p<0.001). However, the mean of SARS-CoV-2 mixed peptides-specific T-cell responses measured by enzyme-linked immunospot assays was significantly increased compared with baseline (66 [95%CI 36–99] vs. 34 [95%CI 19–50] T-cells/106PBMCs, p=0.02) and comparable to that in controls. Our findings revealed weak HMI and marginal CMI responses in fully vaccinated KT recipients receiving inactivated SARS-CoV-2 vaccine. (Thai Clinical Trials Registry, TCTR20210226002).
Tear antibodies to SARS-CoV-2: implications for transmission
Authors: Selva Kevin J. , Davis Samantha K. , Haycroft Ebene R. , Lee Wen Shi , Lopez Ester , Reynaldi Arnold , Davenport Miles P. , Kent Helen E. , Juno Jennifer A. , Chung Amy W. , Kent Stephen J.
Published: August 2021

Objectives

SARS-CoV-2 can be transmitted by aerosols and the ocular surface may be an important route of transmission. Little is known about protective antibody responses to SARS-CoV-2 in tears after infection or vaccination. We analysed SARS-CoV-2 specific IgG and IgA responses in human tears after either COVID-19 infection or vaccination.

Methods

We recruited 16 subjects with COVID-19 infection an average of 7 months previously and 15 subjects before and 2 weeks after Comirnaty (Pfizer-BioNtech) vaccination. Plasma, saliva and basal tears were collected. Pre-pandemic plasma, saliva and basal tears from 11 individuals were included as healthy controls. Antibody responses to 5 SARS-CoV-2 antigens were measured via multiplex.

Results

IgG antibodies to Spike and Nucleoprotein were detected in tears, saliva and plasma from subjects with prior SARS-CoV-2 infection in comparison to uninfected controls. While RBD-specific antibodies were detected in plasma, minimal RBD-specific antibodies were detected in tears and saliva. In contrast, high levels of IgG antibodies to Spike and RBD, but not Nucleoprotein, were induced in tears, saliva and plasma of subjects receiving 2 doses of the Comirnaty vaccine. Increased levels of IgA1 and IgA2 antibodies to SARS-CoV-2 antigens were detected in plasma following infection or vaccination, but were unchanged in tears and saliva.

Conclusion

Both infection and vaccination induce SARS-CoV-2-specific IgG antibodies in tears. RBD-specific IgG antibodies in tears were induced by vaccination but were not present 7 months post-infection. This suggests neutralising antibodies may be low in the tears late following infection.
Exploring polygenic-environment and residual-environment interactions for depressive symptoms within the UK Biobank
Authors: Gillett Alexandra C. , Jermy Bradley S. , Lee S. Hong , Pain Oliver , Howard David M. , Hagenaars Saskia P. , Hanscombe Ken B. , Coleman Jonathan R. I. , Lewis Cathryn M.
Published: August 2021

Substantial advances have been made in identifying genetic contributions to depression, but little is known about how the effect of genes can be modulated by the environment, creating a gene-environment interaction. Using multivariate reaction norm models (MRNMs) within the UK Biobank (N=61294-91644), we investigate whether the polygenic and residual variation of depressive symptoms are modulated by 25 a-priori selected covariate traits: 12 environmental variables, 5 biomarkers and polygenic risk scores for 8 mental health disorders. MRNMs provide unbiased polygenic-covariate interaction estimates for a quantitative trait by controlling for outcome-covariate correlations and residual-covariate interactions. Of the 25 selected covariates, 11 significantly modulate depressive symptoms, but no single interaction explains a large proportion of phenotypic variation. Results are dominated by residual-covariate interactions, suggesting that covariate traits (including neuroticism, childhood trauma and BMI) typically interact with unmodelled variables, rather than a genome-wide polygenic score, to influence depressive symptoms. Only average sleep duration has a polygenic-covariate interaction explaining a demonstrably non-zero proportion of the variability in depressive symptoms. This effect is small, accounting for only 1.22% (95% CI [0.54,1.89]) of variation. The presence of an interaction highlights a specific focus for intervention, but the negative results here indicate a limited contribution from polygenic-environment interactions.
SARS-CoV-2 viral load monitoring by extraction-free testing of saliva
Authors: Qiu Yue , Lu Ling , Gao Dexiang , McGrath Patrick , Han Chann , Kogut Igor , Blomquist Bob , Yao Xin , Zevallos Jose P. , Harry Brian L. , Lu Shi-Long
Published: August 2021

Real-time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) remains the foundation of SARS-CoV-2 testing due to its accessibility, scalability, and superior assay performance. Variability in specimens and methods prevent standardization of RT-qPCR assays and reliable quantitative reporting to assess viral load. We developed an extraction-free RT-qPCR assay for detection of SARS-CoV-2 in saliva and monitored viral load until convalescence in COVID-19 patients. Comparison of 231 matched anterior nares swab and saliva specimens demonstrated that extraction-free testing of saliva has equivalent analytical and clinical assay performance compared to testing of RNA extracts from either anterior nares or saliva specimens. Analysis of specimen pairs revealed higher viral loads in the nasal cavity compared to the oral cavity, although this difference did not impact clinical sensitivity for COVID-19. Extraction-free testing of a combination specimen consisting of both nasal swab and saliva is also demonstrated. Assessment of viral load by RT-qPCR and parallel digital droplet PCR (ddPCR) revealed that cycle threshold (Ct) values less than approximately 30 correlated well with viral load, whereas Ct values greater than 30 correspond to low viral loads <10 copies/µL. Therefore, extraction-free saliva testing maximizes testing efficiency without compromising assay performance and approximates viral loads >10 copies/µL. This technology can facilitate high-throughput laboratory testing for SARS-CoV-2, monitor viral load in individual patients, and assess efficacy of therapies for COVID-19.
Reactivation of transposable elements following hybridization in fission yeast
Authors: Tusso Sergio , Suo Fang , Liang Yue , Du Li-Lin , Wolf Jochen B.W.
Published: August 2021

Hybridization is thought to reactivate transposable elements (TEs) that were efficiently suppressed in the genomes of the parental hosts. Here, we provide evidence for this ‘genomic shock hypothesis’ in the fission yeast Schizosaccharomyces pombe. In this species, two divergent lineages (Sp and Sk) have experienced recent, likely human induced, hybridization. We used long-read sequencing data to assemble genomes of 37 samples derived from 31 S. pombe strains spanning a wide range of ancestral admixture proportions. A comprehensive TE inventory revealed exclusive presence of long terminal repeat (LTR) retrotransposons. Sequence analysis of active full-length elements, as well as solo-LTRs, revealed a complex history of homologous recombination. Population genetic analyses of syntenic sequences placed insertion of many solo-LTRs prior to the split of the Sp and Sk lineages. Most full-length elements were inserted more recently after hybridization. With the exception of a single full-length element with signs of positive selection, both solo-LTRs, and in particular, full-length elements carried signatures of purifying selection indicating effective removal by the host. Consistent with reactivation upon hybridization, the number of full-length LTR retrotransposons, varying extensively from zero to 87 among strains, significantly increased with the degree of genomic admixture. This study gives a detailed account of global TE diversity in S. pombe, documents complex recombination histories within TE elements and provides evidence for the ‘genomic shock hypothesis’.
pamlr: a toolbox for analysing animal behaviour using pressure, acceleration, temperature, magnetic and light data in R
Authors: Dhanjal-Adams Kiran L. , Willener Astrid S. T. , Liechti Felix
Published: August 2021

Light-level geolocators have revolutionised the study of animal behaviour. However, lacking precision, they cannot be used to infer behaviour beyond large-scale movements. Recent technological developments have allowed the integration of barometers, magnetometers, accelerometers and thermometers into geolocator tags, offering new insights into the behaviour of species which were previously impossible to tag.

Here, we introduce an R toolbox for identifying behavioural patterns from multisensor geolocator tags, with functions specifically designed for data visualisation, calibration, classification and error estimation. Some functions are also tailored for identifying specific behavioural patterns in birds (most common geolocators-tagged species), but are flexible for other applications.

Finally, we highlight opportunities for applying this toolbox to other species beyond birds, the behaviours they might identify and their potential applications beyond behavioural analyses.

Data archiving

Currently, the package is on github and will be submitted to CRAN after review. The supporting code (package manual) for this paper is also on https://kiranlda.github.io/PAMLrManual/index.html, but will later be hosted by the Swiss Ornithological Institute.

pamlr: a toolbox for analysing animal behaviour using pressure, acceleration, temperature, magnetic and light data in R
Multitask group Lasso for Genome Wide association Studies in diverse populations
Authors: Nouira Asma , Azencott Chloé-Agathe
Published: August 2021

Genome-Wide Association Studies, or GWAS, aim at finding Single Nucleotide Polymorphisms (SNPs) that are associated with a phenotype of interest. GWAS are known to suffer from the large dimensionality of the data with respect to the number of available samples. Other limiting factors include the dependency between SNPs, due to linkage disequilibrium (LD), and the need to account for population structure, that is to say, confounding due to genetic ancestry.

We propose an efficient approach for the multivariate analysis of multi-population GWAS data based on a multitask group Lasso formulation. Each task corresponds to a subpopulation of the data, and each group to an LD-block. This formulation alleviates the curse of dimensionality, and makes it possible to identify disease LD-blocks shared across populations/tasks, as well as some that are specific to one population/task. In addition, we use stability selection to increase the robustness of our approach. Finally, gap safe screening rules speed up computations enough that our method can run at a genome-wide scale.

To our knowledge, this is the first framework for GWAS on diverse populations combining feature selection at the LD-groups level, a multitask approach to address population structure, stability selection, and safe screening rules. We show that our approach outperforms state-of-the-art methods on both a simulated and a real-world cancer datasets.
Regulus infers signed regulatory networks in few samples from regions and genes activities
Authors: Louarn Marine , Collet Guillaume , Barré Ève , Fest Thierry , Dameron Olivier , Siegel Anne , Chatonnet Fabrice
Published: August 2021

Motivation

Transcriptional regulation is performed by transcription factors (TF) binding to DNA in context-dependent regulatory regions and determines the activation or inhibition of gene expression. Current methods of transcriptional regulatory networks inference, based on one or all of TF, regions and genes activity measurements require a large number of samples for ranking the candidate TF-gene regulation relations and rarely predict whether they are activations or inhibitions. We hypothesize that transcriptional regulatory networks can be inferred from fewer samples by (1) fully integrating information on TF binding, gene expression and regulatory regions accessibility, (2) reducing data complexity and (3) using biology-based logical constraints to determine the global consistency of the candidate TF-gene relations and qualify them as activations or inhibitions.

Results

We introduce Regulus, a method which computes TF-gene relations from gene expressions, regulatory region activities and TF binding sites data, together with the genomic locations of all entities. After aggregating gene expressions and region activities into patterns, data are integrated into a RDF endpoint. A dedicated SPARQL query retrieves all potential relations between expressed TF and genes involving active regulatory regions. These TF-region-gene relations are then filtered using a logical consistency check translated from biological knowledge, also allowing to qualify them as activation or inhibition. Regulus compares favorably to the closest network inference method, provides signed relations consistent with public databases and, when applied to biological data, identifies both known and potential new regulators. Altogether, Regulus is devoted to transcriptional network inference in settings where samples are scarce and cell populations are closely related. Regulus is available at https://gitlab.com/teamDyliss/regulus
Reproducibility and reusability limitations in Regulatory Circuits: analysis and solutions
Authors: Louarn Marine , Siegel Anne , Fest Thierry , Dameron Olivier , Chatonnet Fabrice
Published: August 2021

The Regulatory Circuits project is among the most recent and the most complete attempts to identify cell-type specific regulatory networks in Human. It is one of the largest efforts of public genomics data integration, based on data from the major consortia FANTOM5, ENCODE and Roadmap Epigenomics. This project is a main provider of biological data, cited more than 224 times (Google Scholar) and its resulting networks were used in at least 42 other articles.

For such a general resource, reproducibility of both the outputs (regulation networks) and methods (data integration pipeline) is a major issue, since biological data are updated regularly. In addition, users may want to introduce new data into the Regulatory Circuits framework to provide networks about previously uncharacterized cell types or to add information about specific regulators, which require to re-execute the whole pipeline on the new data.

In this article, we analyze the various factors limiting reproducibility of the Regulatory Circuits data and methods. Starting from a factual description of our understanding of the methods used in Regulatory Circuits, our contribution is two-fold: we propose (1) a characterization of the different levels of reusability, reproducibility and conceptual issues in the original workflow and (2) a new implementation of the workflow ensuring its consistency with the published description and allowing for an easier reuse and reproduction of the published outputs. Both are applicable beyond the case of Regulatory Circuits.