bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of acquired tracheoesophageal fistula after tracheostomy decannulation by videofluoroscopic swallowing study
Authors: Yoo Dong Ho , Choi Min Soo , Lee Byeong Ju , Shin Yong Beom , Yoon Jin A , Kim Sang Hun
Published: March 2021

Rationale:

Videofluoroscopic swallowing study (VFSS) is a noninvasive radiographic procedure that examines the oral, pharyngeal, and cervical esophageal stages of swallowing. Tracheoesophageal fistula (TEF) is difficult to diagnose depending on its size and location. However, how VFSS can be of benefit in the diagnosis of TEF has not been reported yet.

Patient concerns:

A 64-year-old man who had been tracheostomized post spinal tumor resection surgery at the cervical level 1 to 2, had his tracheostomy tube removed approximately 25 years ago. After decannulation, he reported coughing while swallowing food, foreign sensation in the neck and repeated bouts of pneumonia ever since.

Diagnosis:

VFSS revealed, for the first time, acquired TEF after tracheostomy decannulation as the cause of repetitive aspiration pneumonia.

Intervention:

VFSS was performed in this case.

Outcomes:

In the background of suspected TEF based on VFSS results, the patient underwent a computed tomography scan of the chest and airway in the prone position, followed by bronchoscopy, which confirmed the existence of a TEF. He then underwent primary closure of the fistula. The patient had an uneventful recovery and is currently symptom-free 10 months after the surgery.

Lessons:

This case alerts clinicians to the possibility of TEF as a diagnosis when the aspirate leaks from the upper esophagus and through the posterior wall of trachea in the esophageal phase of VFSS.
Predictive value of inflammatory factors on coronary restenosis after percutaneous coronary intervention in patients with coronary heart disease
Authors: Chu Xin , Wang Ruzhu , Song Guixian , Jiang Xiaohan
Published: March 2021

Background

Evidence reveals that inflammatory factors can predict coronary restenosis in patients suffering from coronary heart disease (CHD) after percutaneous coronary intervention (PCI). Perhaps, inflammatory factors are promising biomarkers for the diagnosis of coronary restenosis after PCI. However, the accuracy of inflammatory factors has not been systematically evaluated. Therefore, it is necessary to perform a meta-analysis to certify the diagnostic values of inflammatory factors on coronary restenosis after PCI.

Methods

China National Knowledge Infrastructure (CNKI), Wanfang, VIP, China Biology Medicine disc (CBM), PubMed, EMBASE, Cochrane Library and Web of Science were searched for relevant studies to explore the potential diagnostic values of inflammatory factors on coronary restenosis after PCI from inception to January 2021. All data were extracted by 2 experienced researchers independently. The risk of bias about the meta-analysis was confirmed by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The data extracted were synthesized and heterogeneity was investigated as well. All of the above statistical analyses were carried out with Stata 16.0.

Results

The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.

Conclusion

This study clarified confusions about the specificity and sensitivity of inflammatory factors on coronary restenosis after PCI, thus further guiding their promotion and application.

Ethics and dissemination

Ethical approval will not be necessary since this systematic review and meta-analysis will not contain any private information of participants or violate their human rights.

Trial Registration Number:

DOI 10.17605/OSF.IO/N28JX.
Systematic review shows no strong evidence regarding the use of elastic taping for pain improvement in patients with primary knee osteoarthritis
Authors: Heddon Stephan , Saulnier Nicole , Mercado Jorge , Shalmiyev Michelle , Berteau Jean-Philippe
Published: March 2021

Background:

A recent trend in the field of primary knee osteoarthritis suggests that elastic tape (e.g., K-tape) relieves pressure on the joint by increasing tension on fascia. Elastic tape (ET) is expected to decrease pain and help patients to recover faster.

Objective:

This systematic review aims to analyze the efficacy of this method on pain in patients with knee osteoarthritis by using The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score.

Data sources:

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard for reporting systematic reviews of qualitative and quantitative evidence, we used 3 electronic databases, PubMed, Cochrane, and EBSCO, and grey literature was included.

Study eligibility criteria:

Articles were screened for duplicates, screened for inclusion and exclusion criteria, and critically appraised.

Participants and Intervention:

People older than 45 years old with primary osteoarthritis (OA) and application of ET.

Study appraisal and synthesis methods:

2005 Oxford standard.

Results:

Amongst all the papers found, 6 Randomized Control Trials (RCT) for a total of 392 participants met the criteria and were included in our review. Three papers out of the 6 RCT had low risks of bias. When the ET was compared to sham taping, the results show no to moderate decreases of WOMAC scores in patients with primary knee osteoarthritis.

Limitations:

We focused on a single index test (WOMAC) and could not perform meta-analyses.

Conclusion and implications of key findings:

Although ET does not provide strong adverse outcomes, our data do not support the use of ET as a treatment alone because of too slight reductions of the WOMAC score for reaching clinical efficiency. Thus, our systematic review shows no strong evidence regarding the use of elastic taping for pain improvement in patients with primary knee osteoarthritis.
Frequency of pre-treatment may not increase the immune-related adverse events of RCC patients treated with nivolumab
Authors: Mizutani Kosuke , Ito Toshiki , Takahara Kiyoshi , Ando Ryosuke , Ishihara Takuma , Yasui Takahiro , Shiroki Ryoichi , Miyake Hideaki , Koie Takuya
Published: March 2021

Nivolumab has shown good prognosis in renal cell carcinoma (RCC) patients previously treated with targeted therapy. We aimed to study irAE (immune-related adverse event) due to nivolumab and numbers of previous treatment lines in RCC patients. Between October 2016 and November 2019, 114 patients were treated with nivolumab as second- and later-line therapy. Among them, 110 patients with complete data were evaluated in this retrospective observational study. The primary endpoint was the relation between irAE and numbers of previous targeted therapies. Secondary endpoints were the relation of irAE with the duration of nivolumab treatment and with best overall response. For the primary analysis, proportional odds logistic regression was used to assess the effect of the number of prior therapies on the grade of any irAE as the ordinal variable. For the secondary analysis, binomial logistic regression models adjusted for the covariates were prepared to confirm the association between the incidence of irAE and the number of courses, number of nivolumab treatments and best overall response. Overall, 69, 66, 33, 13, 9 and 9 patients were treated with sunitinib, axitinib, pazopanib, sorafenib, temsirolimus and everolimus, respectively, prior to nivolumab. In total, 60 adverse events (Grade 1, 21; Grade 2, 21; Grade 3, 14; Grade 4, 2; not evaluated, 2) were identified in the patients treated with nivolumab. Ordered logistic regression analysis showed that the adjusted odds ratios of numbers of prior treatment for grade of irAE were 1.12 (numbers of prior treatment: 2 to 1) and 1.31 (3 to 1). Odds ratios of the numbers of nivolumab treatments and best overall response for the incidence of irAE were not significant. No statistically significant relations were found between grade of irAE and numbers of treatments prior to nivolumab. Patients treated with nivolumab should be closely monitored for irAE regardless number of previous therapies.
Autoimmune manifestations associated with myelodysplastic syndrome predict a poor prognosis
Authors: Arinobu Yojiro , Kashiwado Yusuke , Miyawaki Kohta , Ayano Masahiro , Kimoto Yasutaka , Mitoma Hiroki , Akahoshi Mitsuteru , Miyamoto Toshihiro , Horiuchi Takahiko , Akashi Koichi , Niiro Hiroaki
Published: March 2021

We evaluated the clinical characteristics of autoimmune manifestations (AIMs) associated with myelodysplastic syndrome (MDS) to elucidate whether AIMs impacted MDS outcomes in Japan.

This retrospective study including 61 patients who received a new diagnosis of MDS between January 2008 and December 2015 was conducted by the review of electronic medical records for the presence of AIMs within a 1-year period prior to or following the diagnosis of MDS.

AIMs were identified in 12 of the 61 (20.0%) patients with MDS. The neutrophil counts and C-reactive protein levels in peripheral blood were significantly elevated in patients with AIMs, and the survival was shorter in those with AIMs compared to those without AIMs. Multivariate analysis demonstrated that the presence of AIMs and higher-risk disease according to the International Prognositic Scoring System (IPSS) were independent risk factors for increased mortality (hazard ratio, 4.76 and 4.79, respectively).

This retrospective study revealed that the prognosis was poor in patients with MDS-associated AIMs. The treatment of MDS using the current algorithms is based on prognostic scoring systems such as IPSS. Treatment strategies for patients with MDS-associated AIMs should be reconsidered, even in those with low-risk MDS according to the IPSS.
Cell cycle regulation in human hair follicle dermal papilla cells using nonthermal atmospheric pressure plasma-activated medium
Authors: Lee Jin-Woo , Kim Kyungsook , Jung Minhyung , Kim Youngsun
Published: March 2021

Nonthermal atmospheric pressure (NAP) plasmas have recently been developed and have been used for wound healing, blood coagulation, and cancer therapy. NAP plasmas can induce either cell proliferation or cell death, depending on the dose. Due to their efficacy and application easily, plasma activated mediums (PAMs) have been used in human cells recently.

In atmosphere, NAP plasmas react with molecular content of air such as N2, O2, H2O vapor, etc, and generate a variety of reactive oxygen and nitrogen species. High reactive oxygen species (ROS) levels promote damage of cellular DNA, proteins, and lipids. Such damage can lead to cell-cycle arrest, and cellular death. However, low levels of ROS have been caused an increase in cell cycle progression.

Human skin is arranged in 3 layers, including (from top to bottom) the epidermis (and its appendages), the dermis, and the hypodermis. Human dermal papilla cells (DPCs) are located in the middle or even deep part of the dermis. DPCs play a key role in hair regeneration, and a lot of effort have been made to promote DPC hair formation ability. DPC is increased proliferation, delayed senescence, and enhanced hair by depending on the amount of ROS through the NAP-PAM treatment.

In this study, we used NAP plasmas to the human hair follicle DPCs exposed from 0 to 20 minutes, so we were investigated the effects of PAM on cell proliferation and cell cycle progression. After NAP-PAM treatment for 24 hours, cell cycle was arrested in the G0/G1 phase. The NAP-PAM-treated human hair follicle DPCs recovered gradually after 48 hours of the treatment compared to the untreated cells.

Therefore, this approach offers promising results for further application of NAP-PAM in clinical dermatology. In future, it can be applied clinically in the form of active water that can delay the progression of baldness and alopecia areata.
Fecal neopterin level determination: can be a useful screening test for colorectal polyps?
Authors: Kilciler Ayse Guldem , Kutluana Ufuk , Mizrak Soycan
Published: March 2021

Background

Colorectal cancer (CRC) is a leading cause of cancer death worldwide. The main precursor lesion leading to CRC is the adenomatous colorectal polyp (CP). Nowadays, there is no recognized perfect screening test of CP and CRC. Neopterin is an important marker of cellular inflammation. In this study, we aimed to evaluate comparatively immunochromatographic fecal occult blood test (iFOBT) and fecal neopterin levels (FNLs) in patients with CP and controls.

Methods

One hundred eleven patients diagnosed with CP and 68 individuals with negative colonoscopy were included in the study. iFOBT and FNLs were assessed in patients and controls.

Results

FNLs and iFOBT positivity were significantly higher in patients with CP than in controls (17.15 ± 3.55 µmol/L/g vs. 12.25 ± 2.19 µmol/L/g, P = 0.00 and 46.8% vs. 14.8%, P = 0.00, respectively). FNLs were significantly higher in cases with adenomatous polyps than in hyperplastic polyps (P = 0.002). FNL ≥14.00 µmol/L/g was the best cutoff value to differentiate between patients with CP from controls (P = 0.000). A multiple logistic regression analysis showed that high FNL was positively correlated with presence, number, diameter of CPs, and presence of adenoma (P < 0.005). The sensitivity of high FNL for CP was 81.1%, which was superior to iFOBT positivity (47.7%, P < 0.001).

Discussion

FNL level is significantly increased in CPs. The FNL exhibited increased sensitivity for identifying CP and adenomatous lesions compared with iFOBT. FNL determination could have as a new screening and diagnostic test for CP.
Gastrointestinal manifestations of COVID-19: results from a European centre
Authors: Leal Tiago , Costa Emanuel , Arroja Bruno , Gonçalves Raquel , Alves Joana
Published: March 2021

Background

Infection due to severe acute respiratory syndrome coronavirus 2 is typically associated with a respiratory syndrome, but gastrointestinal symptoms have been described in early reports from China. However, data from European centres are scarce.

Objectives

We aimed to characterise the gastrointestinal manifestations of patients with coronavirus disease 2019 (COVID-19) and their disease course.

Methods

Patients admitted at our centre between March and April 2020 with diagnosis of COVID-19 were included. Asymptomatic patients or those without symptom information were excluded. Clinical features, laboratory data and disease severity (mechanical ventilation, intensive care admission or death) were analysed.

Results

Two-hundred one patients were included (median age 71 years; 56.2% male). Digestive symptoms were reported by 60 (29.9%) patients during the disease course, being part of the disease presentation in 34 (16.9%). The most frequent were diarrhoea in 36 patients (17.9%). Patients with gastrointestinal symptoms were younger (P = 0.032), had higher haemoglobin levels (P = 0.002) and lower C-reactive protein (P = 0.045) and potassium levels (P = 0.004). Patients with digestive symptoms had less severe disease (28.3 vs. 44.0%; P = 0.038). Regarding liver damage, aspartate aminotransferase (AST) was elevated in 65.2% of patients and alanine aminotransferase (ALT) in 62.7%, but these patients did not present a more severe disease (elevated AST P = 0.062; elevated ALT P = 0.276).

Conclusion

A significant portion of COVID-19 patients have digestive symptoms, mostly at presentation. This should be taken into account in order to keep a high level of suspicion to reach an early diagnosis and setup infection control measures to control the transmission rate. This subgroup of patients appears to have a less severe disease course.
Clinical course and outcome among patients with acute pancreatitis and COVID-19
Authors: Kumar Vivek , Barkoudah Ebrahim , Souza Daniel A.T. , Jin David X. , McNabb-Baltar Julia
Published: March 2021

Background

The data on clinical course and outcome of acute pancreatitis among patients with coronavirus disease 2019 (COVID-19) are sparse. In this study, we analyzed the clinical profiles of patients with COVID 19 and acute pancreatitis.

Methods

This retrospective study was conducted on Research Patient Data Registry data which was pooled from five Mass General Brigham Healthcare Network hospitals. We extracted data on demographics, symptoms, ICU transfer, mechanical ventilation, laboratories’ profiles, imaging findings, and patient outcomes.

Result

Of 985 screened adult patients, 17 were eligible for the study, 9 (52.9%) were admitted primarily for respiratory failure and developed acute pancreatitis after a median of 22.5 days (13–76 days) from the onset of COVID-19 symptoms. On contrary, eight patients presented with typical symptoms and were diagnosed with acute pancreatitis, the majority with mild severity (62.5%) on admission. Patients who were admitted primarily with severe COVID-19 illness were younger (median age 57 vs. 63 years), females (55.6 vs. 25%), of Hispanic ethnicity (55.6 vs. 25%), and obese (88.9 vs. 37.5%). The median peak lipase, C reactive protein, ferritin, lactate dehydrogenase, D-dimer were higher among patients who developed acute pancreatitis later during hospitalization. Patients who developed acute pancreatitis later also experienced higher episodes of necrotizing pancreatitis (11.1% vs. 0), thromboembolic complications (55.6 vs. 12.5%), and higher mortality (37.5 vs. 12.5%).

Conclusion

Acute pancreatitis is not common among patients with COVID-19. Patients with COVID-19 who had acute pancreatitis on admission had more benign course and overall better outcome as compared to the patients who developed acute pancreatitis during hospitalization.
Implementation and Evaluation of a Cloud-Based, Evidence-Based Nurse Mentor Training Program
Authors: Hancock Lynne M.
Published: March 2021

As part of an ongoing commitment to professional development, this American Nurses Credentialing Center Magnet-designated pediatric academic medical center provided a 1.5-hour self-paced vendor mentor training e-course to nurse mentors. A pretest–posttest design demonstrated that mentor training significantly improved mentor knowledge, skills, confidence, beliefs, and overall score, but not values. The results support that nurses benefit from mentor training, and a self-paced asynchronous e-course is a cost-effective educational strategy to increase the adoption of mentoring behaviors.
Financing Preventive Medicine Graduate Medical Education
Authors: Jung Paul , Lushniak Boris D.
Published: March 2021

Financing US preventive medicine residency programs has been a persistently difficult issue. The unique nature of preventive medicine renders training more burdensome and costly than other specialties. This article describes the numerous and varied federal sources of Graduate Medical Education funding to outline available residency financing options for the specialty of preventive medicine. This information could be utilized by various preventive medicine organizations in their efforts to strengthen the specialty.
The Association Between Risk Behaviors and Vaping Among Youth in New Mexico
Authors: Fatemi Nasrin N. , Cruz Theresa H. , Kesler Denece O. , Schiff Melissa A.
Published: March 2021

Context:

Electronic-cigarette use, or vaping, among youth has increased substantially in recent years. Tobacco smoking shows a strong association with other risk behaviors, but the association between vaping and other risk behaviors has rarely been explored. We examine the relationship between youth vaping and substance use, risky driving behaviors, and lack of bicycle helmet use.

Program:

Data from the 2015 and 2017 New Mexico Youth Risk and Resiliency Survey were analyzed to evaluate the association between the use of e-cigarettes and other youth risk behaviors. Study participants were high school students, grades 9 to 12. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI).

Evaluation:

A majority of students reported ever using e-cigarettes (54%). In 2015, e-cigarette users were more likely than nonusers to be Hispanic (65% vs 54%, P ≤ .001) and 16 years of age or older (58% vs 42%, P = .018). We found strong, statistically significant associations between e-cigarette use and not wearing a bicycle helmet (OR = 2.62, 95% CI: 1.95-3.51), texting while driving (OR = 2.18, 95% CI: 1.79-2.66), driving after drinking (OR = 2.95, 95% CI: 1.61-5.40), current marijuana use (OR = 6.38, 95% CI: 4.65-8.76), current painkiller use (OR = 2.47, 95% CI: 1.63-3.77), and current heroin use (OR = 0.15, 95% CI: 0.06-0.33). Driving after drinking was not significantly associated with e-cigarette use in 2017.

Discussion:

E-cigarette use is associated with multiple other risk behaviors among youth. Further research should focus on environmental and policy efforts to reduce access to e-cigarettes by youth as well as interventions that address the underlying causes of the constellation of risk behaviors.
Availability of Naloxone in 2 Underserved Urban Communities in Georgia
Authors: Saraiya Parth , Hutchins Sonja S. , Crump Sherry , Morgan Jay , Wilkinson Tramaine , Walker Carla Durham , Taylor Beverly
Published: March 2021

In 2016, unintentional injuries became the third leading cause of death in the United States. In 2018, 54% of 103 672 unintentional injury deaths were due to drug overdoses among adults 19 to 64 years of age. In Georgia, opioid overdose deaths continued to increase, despite a 2014 state law for naloxone use to prevent deaths, and a 2017 amendment for more widespread community use without a prescription. Given these policies, naloxone availability in pharmacies in underserved communities remains unclear. Our objective is to explore naloxone availability in such communities. Three Public Health and Preventive Medicine residents during a social-cultural-behavioral longitudinal rotation conducted interviews of 9 community pharmacists. Several themes emerged: more education was needed, and naloxone was available only by prescription in certain pharmacies or in limited amounts. Additional assessments among community members and sectors can examine the extent to which policies to expand naloxone availability and accessibility are implemented, including reduced naloxone costs.
Evaluation of Communication and Safety Behaviors During Hospital-Wide Code Response Simulation
Authors: Ren Dennis M. , Abrams Anna , Banigan Maureen , Batabyal Rachael , Chamberlain James M. , Garrow Amanda , Izem Rima , Nicholson Laura , Ottolini Mary , Patterson Mary , Sarnacki Rachel , Walsh Heather A. , Zaveri Pavan
Published: March 2021

Introduction

To understand the baseline quality of team communication behaviors at our organization, we implemented institution-wide simulation training and measured the performance of safety behaviors of ad hoc teams in emergent situations.

Methods

Clinicians participated in 2 interprofessional video-recorded simulation scenarios, each followed by debriefing. Using a standardized evaluation instrument, 2 reviewers independently evaluated the presence or absence of desired team safety behaviors, including escalating care, sharing a mental model, establishing leadership, thinking out loud, and identifying roles and responsibilities. We also scored the quality of sharing the mental model, closed-loop communication, and overall team performance on a 7-point scale. Discordant reviews were resolved with scoring by an additional reviewer.

Results

A total of 1404 clinicians participated in 398 simulation scenarios, resulting in 257 usable videos. Overall, teams exhibited desired behaviors at the following frequencies: escalating care, 85%; sharing mental models, 66%; verbally establishing leadership, 6%; thinking out loud, 87%; and identifying roles and responsibilities, 27%. Across all reviews, the quality of the graded behaviors (of 7 points) was 2.8 for shared mental models, 3.3 for closed-loop communication, and 3.2 for overall team performance.

Conclusions

In a simulation setting with ad hoc teams, there was variable performance on completing safety behaviors and only a fair quality of graded communication behaviors. These results establish a baseline assessment of communication and teamwork behaviors and will guide future quality improvement interventions.
Role of high-dose exposure in transmission hot zones as a driver of SARS-CoV-2 dynamics
Authors: Wodarz Dominik , Komarova Natalia L. , Schang Luis M.
Published: March 2021

Epidemiological data about SARS-CoV-2 spread indicate that the virus is not transmitted uniformly in the population. The transmission tends to be more effective in select settings that involve exposure to relatively high viral dose, such as in crowded indoor settings, assisted living facilities, prisons or food processing plants. To explore the effect on infection dynamics, we describe a new mathematical model where transmission can occur (i) in the community at large, characterized by low-dose exposure and mostly mild disease, and (ii) in so-called transmission hot zones, characterized by high-dose exposure that can be associated with more severe disease. The model yields different types of epidemiological dynamics, depending on the relative importance of hot zone and community transmission. Interesting dynamics occur if the rate of virus release/deposition from severely infected people is larger than that of mildly infected individuals. Under this assumption, we find that successful infection spread can hinge upon high-dose hot zone transmission, yet the majority of infections are predicted to occur in the community at large with mild disease. In this regime, residual hot zone transmission can account for continued virus spread during community lockdowns, and the suppression of hot zones after community interventions are relaxed can cause a prolonged lack of infection resurgence following the reopening of society. This gives rise to the notion that targeted interventions specifically reducing virus transmission in the hot zones have the potential to suppress overall infection spread, including in the community at large. Epidemiological trends in the USA and Europe are interpreted in light of this model.
A statistical method for identifying different rules of interaction between individuals in moving animal groups
Authors: Schaerf T. M. , Herbert-Read J. E. , Ward A. J. W.
Published: March 2021

The emergent patterns of collective motion are thought to arise from application of individual-level rules that govern how individuals adjust their velocity as a function of the relative position and behaviours of their neighbours. Empirical studies have sought to determine such rules of interaction applied by ‘average’ individuals by aggregating data from multiple individuals across multiple trajectory sets. In reality, some individuals within a group may interact differently from others, and such individual differences can have an effect on overall group movement. However, comparisons of rules of interaction used by individuals in different contexts have been largely qualitative. Here we introduce a set of randomization methods designed to determine statistical differences in the rules of interaction between individuals. We apply these methods to a case study of leaders and followers in pairs of freely exploring eastern mosquitofish (
Gambusia holbrooki
). We find that each of the randomization methods is reliable in terms of: repeatability of
p
-values, consistency in identification of significant differences and similarity between distributions of randomization-based test statistics. We observe convergence of the distributions of randomization-based test statistics across repeat calculations, and resolution of any ambiguities regarding significant differences as the number of randomization iterations increases.
Nonverbal category knowledge limits the amount of information encoded in object representations: EEG evidence from 12-month-old infants
Authors: Pomiechowska Barbara , Gliga Teodora
Published: March 2021

To what extent does language shape how we think about the world? Studies suggest that linguistic symbols expressing conceptual categories (‘apple’, ‘squirrel’) make us focus on categorical information (e.g. that you saw a squirrel) and disregard individual information (e.g. whether that squirrel had a long or short tail). Across two experiments with preverbal infants, we demonstrated that it is not language but nonverbal category knowledge that determines what information is packed into object representations. Twelve-month-olds (N= 48) participated in an electroencephalography (EEG) change-detection task involving objects undergoing a brief occlusion. When viewing objects from unfamiliar categories, infants detected both across- and within-category changes, as evidenced by their negative central wave (Nc) event-related potential. Conversely, when viewing objects from familiar categories, they did not respond to within-category changes, which indicates that nonverbal category knowledge interfered with the representation of individual surface features necessary to detect such changes. Furthermore, distinct patterns of γ and α oscillations between familiar and unfamiliar categories were evident before and during occlusion, suggesting that categorization had an influence on the format of recruited object representations. Thus, we show that nonverbal category knowledge has rapid and enduring effects on object representation and discuss their functional significance for generic knowledge acquisition in the absence of language.
Investigations into the synthesis of a nucleotide dimer via mechanochemical phosphoramidite chemistry
Authors: Johnston C. , Hardacre C. , Migaud M. E.
Published: March 2021

Liquid-assisted mechanochemistry as a versatile approach for the coupling of a nucleoside phosphoramidite with a 5′-OH partially protected nucleoside has been investigated. Noted advantages over reported methods were a simplified reaction protocol, a drastic reduction in the use of toxic solvents, the facilitation of mechanochemical reactions through the improved mixing of solid reagents, and low hydrolytic product formation.
Microarthropod contributions to fitness variation in the common moss
Ceratodon purpureus
Authors: Shortlidge Erin E. , Carey Sarah B. , Payton Adam C. , McDaniel Stuart F. , Rosenstiel Todd N. , Eppley Sarah M.
Published: March 2021

The evolution of sustained plant–animal interactions depends critically upon genetic variation in the fitness benefits from the interaction. Genetic analyses of such interactions are limited to a few model systems, in part because genetic variation may be absent or the interacting species may be experimentally intractable. Here, we examine the role of sperm-dispersing microarthropods in shaping reproduction and genetic variation in mosses. We established experimental mesocosms with known moss genotypes and inferred the parents of progeny from mesocosms with and without microarthropods, using a pooled sequencing approach. Moss reproductive rates increased fivefold in the presence of microarthropods, relative to control mesocosms. Furthermore, the presence of microarthropods increased the total number of reproducing moss genotypes, and changed the rank-order of fitness of male and female moss genotypes. Interestingly, the genotypes that reproduced most frequently did not produce sporophytes with the most spores, highlighting the challenge of defining fitness in mosses. These results demonstrate that microarthropods provide a fitness benefit for mosses, and highlight the potential for biotic dispersal agents to alter fitness among moss genotypes.
Genetic associations with severe COVID-19
Authors: Murphy Nicholas M. , Dite Gillian S. , Allman Richard
Published: March 2021

Identification of host genetic factors that predispose individuals to severe COVID-19 is important, not only for understanding the disease and guiding the development of treatments, but also for risk prediction when combined to form a polygenic risk score (PRS). Using population controls, Pairo-Castineira et al. identified 12 SNPs (a panel of 8 SNPs and a panel of 6 SNPs, with two SNPs in both panels) associated with severe COVID-19. Using controls with asymptomatic or mild COVID-19, we were able to replicate the association with severe COVID-19 for only three of their SNPs and found marginal evidence for an association for one other. When combined as an 8-SNP PRS and a 6-SNP PRS, we found no evidence of association with severe COVID-19. The difference in our results and the results of Pairo-Castineira et al. might be the choice of controls: population controls vs controls with asymptomatic or mild COVID-19.
Prevalence of anti-SARS-CoV-2 antibodies in Poznań, Poland, after the first wave of the COVID-19 pandemic
Authors: Lorent Dagny , Nowak Rafal , Roxo Carolina , Lenartowicz Elzbieta , Makarewicz Aleksandra , Zaremba Bartosz , Nowak Szymon , Kuszel Lukasz , Stefaniak Jerzy , Kierzek Ryszard , Zmora Pawel
Published: March 2021

In comparison to other European countries, during the first months of COVID-19 pandemic, Poland reported relatively low number of confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. To estimate the scale of pandemic in Poland, a serosurvey of antibodies against SARS-CoV-2 was performed after the first wave of COVID-19 in Europe (March – May 2020). Within this study, we collected samples from July 28 to September 24, 2020 and based on the ELISA results, we found that 1.67% (25/1500, 95%CI 1.13 - 2.45) of the Poznan (Poland) metropolitan area’s population had antibodies against SARS-CoV-2 after the first wave of COVID-19. However, the presence of anti-SARS-CoV-2 IgG antibodies was confirmed with immunoblot in 56% (14/25) samples, what finally resulted in decrease of seroprevalence, i.e. 0.93% (14/1500, 95%CI 0.56 - 1.56). The positive anti-SARS-CoV-2 IgG results were associated with age, occupation related to constant contact with people, travelling abroad, non-compliance with epidemiological recommendations and direct contact with the novel coronavirus. Our findings confirm the low SARS-CoV-2 incidence in Poland and imply that the population had little herd immunity heading into the second and third wave of the pandemic, and therefore herd immunity contributed little to prevent the high numbers of SARS-CoV-2 infections and COVID-19 related deaths in Poland during these subsequent waves.
Improved performance of saliva for the detection of the B.1.351 variant in South Africa
Authors: Chu Chun Yat , Marais Gert , Opperman Christoffel , Doolabh Deelan , Iranzadeh Arash , Marais Carisa , Cox Helen , Williamson Carolyn , Hardie Diana , Brink Adrian
Published: March 2021

Assessment of the unknown performance of saliva for the detection of the novel SARS-CoV-2 variant of concern (VOC) B.1.351 (501Y.V2) lineage is essential as saliva has been shown to be an equivalent, less invasive and a less costly alternative to nasopharyngeal swabs for the molecular detection of SARS-CoV-2 infection in pre-variant studies. Between 1st August 2020 and 16th January 2021, we enrolled 410 eligible ambulatory participants who presented to Groote Schuur Hospital (GSH) in Cape Town, South Africa for SARS-CoV-2 testing. Of these, 300 were enrolled prior to, and 110 after, the initial detection and replacement of wild-type by the B.1.351 variant. All participants provided a supervised self-collected mid-turbinate (MT) and saliva (SA) swab, in addition to the standard HCW collected NP swab which were all tested by RT-PCR in an accredited diagnostic laboratory. Positive percent agreement to NP swab for SA swabs pre- and post-variant were 51.5% and 72.5% respectively while these values for MT swabs were 75.8% and 77.5%. The negative percent agreement for all swab types during all periods was >98%. The basis for this marked improvement of SA swabs as a diagnostic sample for B.1.351 virus is still being investigated.
Clustering of patient comorbidities within electronic medical records enables high-precision COVID-19 mortality prediction
Authors: Lannou Erwann Le , Post Benjamin , Haar Shlomi , Brett Stephen J. , Kadirvelu Balasundaram , Faisal A. Aldo
Published: March 2021

We present an explainable AI framework to predict mortality after a positive COVID-19 diagnosis based solely on data routinely collected in electronic healthcare records (EHRs) obtained prior to diagnosis. We grounded our analysis on the ½ Million people UK Biobank and linked NHS COVID-19 records. We developed a method to capture the complexities and large variety of clinical codes present in EHRs, and we show that these have a larger impact on risk than all other patient data but age. We use a form of clustering for natural language processing of the clinical codes, specifically, topic modelling by Latent Dirichlet Allocation (LDA), to generate a succinct digital fingerprint of a patient’s full secondary care clinical history, i.e. their comorbidities and past interventions. These digital comorbidity fingerprints offer immediately interpretable clinical descriptions that are meaningful, e.g. grouping cardiovascular disorders with common risk factors but also novel groupings that are not obvious. The comorbidity fingerprints differ in both their breadth and depth from existing observational disease associations in the COVID-19 literature. Taking this data-driven approach allows us to avoid human-induction bias and confirmation bias during selection of what are important potential predictors of COVID-19 mortality. Together with age, these digital fingerprints are the single most important factor in our predictor. This holds the potential for improving individual risk profiling for clinical decisions and the identification of groups for public health interventions such as vaccine programmes. Combining our digital precondition fingerprints with demographic characteristics allow us to match or exceed the performance of existing state-of-the-art COVID-19 mortality predictors (EHCF) which have been developed through expert consensus. Our precondition fingerprinting and entire mortality prediction analytics pipeline are designed so as to be rapidly redeployable, e.g. for COVID-19 variants or other pre-existing diseases.
Assessing the impact of multiple comorbidities on fatal outcome in young COVID-19
Authors: Monroy-Castillero Paulino , Friedman Eitan , Revuelta-Herrera Arturo , Yochelis Arik
Published: March 2021

A Bayesian analysis with the use of a rank-biserial correlation algorithm was applied to identify the impact of multiple comorbid conditions on fatal COVID-19 outcome in young adult cases (40-50 years). The demonstration was conducted for a publicly available database provided by the Mexican authority, in the absence of other alternative free-access repositories with information per patient. The methodology here proposed showed that even in the face of small sample sizes, it is possible to highlight deleterious synergistic comorbid conditions.

Young adult cases with COVID-19 and co-existing diabetes, obesity, hypertension, CRF, or COPD were found more likely to have a fatal outcome compared with having no co-morbidities (X2-6 times). With the methodology proposed, we show that having diabetes or hypertension in addition to CRF increased risk for mortality more than what is expected from independent effect (adverse synergistic effect), whereas in patients with obesity, the additional presence of diabetes or hypertension do not increase markedly the death risk due to COVID-19. Quantitative analysis of having two comorbidities highlights the combinations of morbid conditions that are more likely to be associated with fatal outcomes in younger adults COVID-19 cases in a clinically applicable manner.

The clinical implication of this method needs to be prospectively assessed.
Diagnostic Value of Symptoms for Pediatric SARS-CoV-2 Infection in a Primary Care Setting
Authors: Weng Chien-Hsiang , Butt Wesley Wing Wah , Brooks Meredith B. , Clarke Claudia , Jenkins Helen E. , Holland Sabina D. , Chiang Silvia S.
Published: March 2021

Purpose

To evaluate the diagnostic value of symptoms used in the screening approaches by daycares and schools for identifying children and adolescents with possible SARS-CoV-2 infection, we designed a large observational study utilizing the data from primary care settings.

Methods

This cohort study included children and adolescents evaluated in a network of clinics in Rhode Island. Participants were age-stratified: 0-4, 5-11, and 12-17 years. We estimated the sensitivity, specificity, and area under the receiver operating curve (AUC) of individual symptoms and three symptom combinations: a probable case definition published by the Rhode Island Department of Health (RIDOH), and two novel combinations generated by different statistical approaches to maximize sensitivity and AUC. We evaluated the test characteristics of symptom combinations both with and without consideration of COVID-19 exposure.

Results

Two-hundred seventeen (39.1%) of 555 participants were SARS-CoV-2-infected. Fever was more common among 0-4 years-olds (p=0.002); older children more frequently reported fatigue (p=0.02) and anosmia or ageusia (p=0.047). In children >5 years old, anosmia or ageusia had 94-98% specificity. In all age groups, exposure history most accurately predicted infection. In combination with COVID-19 exposure history, various symptom combinations had sensitivity >95% but specificity <30%. No individual symptom or symptom combination had AUC ≥0.70.

Conclusions

Anosmia or ageusia in children ≥5 years old and dyspnea in children 5-11 years old should raise providers’ index of suspicion for COVID-19. However, our overall findings underscore the limited diagnostic value of symptoms and the critical need for widely available, efficient testing.
Modeling High-grade serous ovarian carcinoma using a combination ofin vivoelectroporation and CRISPR/Cas9 mediated genome editing
Authors: Teng Katie , Ford Mathew , Harwalkar Keerthana , Li YuQi , Farnell David , Yamanaka Nobuko , Tuyet Nhung Ton Nu , Huntsman David , Arseneau Jocelyne , Yamanaka Yojiro
Published: March 2021

Ovarian cancer remains the most lethal gynecological cancer today. High-grade serous ovarian carcinoma (HGSC) is the most common and lethal type of ovarian cancer and is most frequently diagnosed at advanced stages. Here, we developed a novel strategy to generate somatic ovarian cancer mouse models using a combination ofin vivoelectroporation and CRISPR/Cas9 mediated genome editing. We mutated tumor suppressor genes associated with HGSC in two different combinations;Brca1, Tp53, Ptenwith/withoutLkb1and successfully generated HGSC, however, with different latencies and pathophysiology. By utilizing Cre lineage tracing in our system, we visualized peritoneal micrometastases in an immune-competent environment. Because our strategy is flexible in selecting mutation combinations and targeting areas, it would be useful for generating ovarian cancer mouse models.

Significance Statement

High grade serous ovarian cancer (HGSC) is the most common ovarian malignancy but our knowledge of early tumorigenesis is still quite limited due to late diagnosis of patients. We developed a new strategy of generating mouse ovarian cancer models using a combination of in vivo electroporation and CRISPR-mediated genome editing. We demonstrated that a combination of three tumor suppressor gene mutations (Brca1, Tp53 and Pten) is sufficient to develop HGSCs. Interesting, an additional mutation inLkb1drastically changed tumor latency, penetrance and pathophysiology through changing its cell-of-origin. Our strategy is highly flexible in selection of mutation combinations and targeting areas in immune competent mice and useful to study early tumorigenesis of ovarian cancer.
Taxonomic scale dependency of Bergmann’s patterns: A cross-scale comparison of hawkmoths and birds along a tropical elevational gradient
Authors: Mungee Mansi , Pandit Rohan , Athreya Ramana
Published: March 2021

Bergmann’s rule predicts a larger body size for endothermic organisms in colder environments. The multiplicity of patterns and processes is expected because body size and temperature are two most fundamental factors on which many physiological, ecological and evolutionary processes depend, affecting all levels of biological organization, from individuals to communities. The confounding results from previous studies may be due to the differences in taxonomic (intraspecific, interspecific and community) and spatial (latitudinal vs elevational) scales. We compared Bergmann’s patterns for endotherms (Aves) and ectotherms (Lepidoptera:Sphingidae) along a same 2.6 km elevational transect in the eastern Himalayas. Using a large data spanning 3,302 hawkmoths (76 morpho-species) and 15,746 birds (245 species), we compared the patterns at the intraspecific (hawkmoths only), interspecific and community scales. At the interspecific scale, we account for phylogenetic non-independence in body mass by using a heirarchical linear mixed effects model for hawkmoths, and a phylogenetic generalised least squares model for birds. We assess the importance of using abundance-weighted metrics at the community scales, after accounting for spatial auto-correlation in communities. Hawkmoths exhibited positive Bergmann’s pattern at the intraspecific and abundance-weighted community scale. Intraspecific variation accounted for a substantial 33% variation at the community level. Contrary to this, birds exhibited a strong converse-Bergmann’s pattern at interspecific and community scales, both with- and without-abundance. Overall, all metrics which incorporate local traits and/or species abundances show stronger correlations than when this information is lacking. The multiplicity of patterns at a single location provides the opportunity to disentangle the relative contribution of individual- and species-level processes by integrating data across multiple nested taxonomic scales for the same taxa. We suggest that future studies of Bergmann’s patterns should explicitly address taxonomic- and spatial-scale dependency, with species relative abundance and intraspecific trait variation as essential ingredients especially at short elevational scales.
Whole-genome-basedHelicobacter pylorigeographic surveillance: a visualized and expandable webtool
Authors: Jiang Xiaosen , Xu Zheng , Zhang Tongda , Li Yuan , Li Wei , Tan Hongdong
Published: March 2021

Helicobacter pyloriexhibits specific geographic distributions that related to the clinical outcomes. Despite the high infection rate ofH. pylorithroughout the world, the genetic epidemiology surveillance ofH. pyloristill needs to be improved. Here, we used single nucleotide polymorphisms (SNPs) profiling approach based on whole genome sequencing (WGS) that facilitates genomic population analyses ofH. pyloriand encourages the dissemination of microbial genotyping strategies worldwide. A total number of 1,211 publicH. pylorigenomes were downloaded and used to construct the typing tool, named as HPTT (H. pyloriTyping Tool). Combined with the metadata, we developed two levels of genomic typing, including a continent scale and a country scale that nested in the continent scale. Results showed that Asia was the largest isolates source in our dataset, while isolates from Europe and Oceania were comparatively more widespread. More specifically, Switzerland and Australia are the main source of widespread isolates in their corresponding continents. To integrate all the typing information and enable researchers to compare their own dataset against the existing global database in an easy and rapid way, a user-friendly website (https://db.cngb.org/HPTT/) was developed with both genomic typing tool and visualization tool. To further confirm the validity of the website, ten newly assembled genomes were downloaded and tested precisely located on the branch as we expected. In summary,H. pylorityping tool (HPTT) is a novel genomic epidemiological tool that can achieve high resolution analysis of genomic typing and visualizing simultaneously, providing insights into the genetic population structure analysis, evolution analysis and epidemiological surveillance ofH. pylori.