bluuebunny/crossref_metadata_2025 huggingface dataset:
A National Profile of Children Receiving Pediatric Concurrent Hospice Care, 2011 to 2013
Authors: Lindley Lisa C. , Cozad Melanie J. , Svynarenko Radion , Keim-Malpass Jessica , Mack Jennifer W.
Published: March 2021

When the 2010 Patient Protection and Affordable Care Act (ACA) was passed, it fundamentally changed end-of-life care for children. Concurrent Care for Children (ACA, section 2302) enables Medicaid/Children's Health Insurance Program children with a prognosis of 6 months to live to use hospice care while continuing treatment for their terminal illness. Although ACA, section 2302, was enacted a decade ago, little is known about these children. The purpose of this study was to generate the first-ever national profile of children enrolled in concurrent hospice care. Using data from multiple sources, including US Medicaid data files from 2011 to 2013, a descriptive analysis of the demographic, community, hospice, and clinical characteristics of children receiving concurrent hospice care was conducted. The analysis revealed that the national sample was extremely medically complex, even for children at end of life. They received care within a complicated system involving primary care providers, hospices, and hospitals. These findings have clinical and care coordination implications for hospice nurses.
Best Practices for Using Telehealth in Hospice and Palliative Care
Authors: Webb Michelle , Hurley Susan Lysaght , Gentry Jennifer , Brown Melanie , Ayoub Cynthia
Published: March 2021

Hospice and palliative care providers throughout the United States have continued to provide compassionate patient- and family-centered care during the COVID-19 (coronavirus disease 2019) pandemic while adapting to the need for scrupulous infection control measures and the accelerated use of telehealth. Prior to the pandemic, hospice and palliative care adopted telehealth slowly compared with other specialties, but its rapidly increasing utilization during the COVID-19 pandemic has long-term implications for access to primary and specialty palliative care, particularly for patients in rural communities and populations experiencing inequitable access to services. Telehealth also shows great promise for leveraging technology to provide care more effectively and efficiently. As more provider organizations become equipped with telehealth infrastructure, and as advocacy for broader reimbursement of these services grows, telehealth services for hospice and palliative care are expected to continue. This article highlights the work of expert clinicians from multiple hospice and palliative care organizations to develop best practices for conducting telehealth visits in inpatient and community settings. The authors propose that best practices be compiled and considered to ensure quality-driven, evidence-based clinical practice guidelines with interprofessional applicability.
Religious Involvement, Depressive Symptoms, and Burden in Caregivers of Terminally Ill Patients
Authors: Asano Reiko , Kellogg Anela , Sulmasy Dan , Anderson Kelley M. , Nolan Marie T.
Published: March 2021

Caring for terminally ill patients can be emotionally burdensome. Previous research has demonstrated that caregiving is associated with anxiety and depression. Research on caregivers of terminally ill patients is limited by retrospective studies with small samples. This study aimed to (1) describe religiosity, religious coping, and depressive symptoms in caregivers of persons with amyotrophic lateral sclerosis or advanced cancer; (2) examine the relationship between religiosity and depressive symptoms in caregivers of persons with amyotrophic lateral sclerosis or advanced cancer; (3) examine the relationship between religious coping and depressive symptoms in caregivers of persons with amyotrophic lateral sclerosis or advanced cancer. A descriptive exploratory design was used to analyze data from a larger 5-year National Institutes of Health–funded multisite randomized controlled trial (the TAILORED study). Nearly half of the caregivers screened positive for depressive symptoms, and negative religious coping was associated with higher depressive symptoms (P < .001). Spouse caregivers reported higher depressive symptoms than nonspouse caregivers. Many caregivers experienced depression, which was mitigated by positive religious coping.
Does Exercise Increase Vestibular and Ocular Motor Symptom Detection After Sport-Related Concussion?
Authors: Popovich Michael , Almeida Andrea , Lorincz Matthew , Eckner James T. , Freeman Jeremiah , Streicher Nicholas , Alsalaheen Bara
Published: March 2021

Background and Purpose:

Postconcussive vestibular and ocular motor symptoms are common and contribute to longer recovery. The Vestibular/Ocular Motor Screening (VOMS) is used to detect such symptoms, but a VOMS performed at rest may miss symptoms that are only provoked by exertion. Supervised exercise challenges (SECs) have been shown to detect concussion-related symptoms provoked by physical exertion. The purpose of this study was to determine whether athletes undergoing an SEC will exhibit greater symptom provocation with the VOMS compared to a VOMS performed at rest prior to an SEC.

Methods:

Thirty-six athletes (58.3% male) between ages 10 and 18 years and within 30 days of concussion were included. All participants completed VOMS assessments at rest and immediately after an SEC. VOMS total symptom score increases were calculated for both pre- and post-SEC assessments compared using Wilcoxon ranked sum tests. The frequencies of positive assessments for each VOMS item were compared using McNemar's test.

Results:

There were significant increases in post-SEC symptom provocation scores compared with pre-SEC scores for all VOMS items. The post-SEC VOMS identified 29 participants (80.6%) as positive in at least 1 VOMS item compared with 21 participants (58.3%) identified as positive pre-SEC (P = 0.008). For all VOMS items, the post-SEC VOMS identified participants who were previously negative on a pre-SEC VOMS but became positive after the SEC.

Discussion and Conclusions:

An SEC performed prior to a VOMS assessment may increase the detection of vestibular and ocular motor symptoms that may be missed if the VOMS was performed only at rest.

Video Abstract available for more insight from the authors (see the Video Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A342).
Improved Gonorrhea and Chlamydia Testing Among Men Who Have Sex With Men Living With HIV Through Implementation of Self-Collected Tests
Authors: Park Ina U. , Reminick Dominique , Schapiro Jeffrey M. , Hurley Leo B. , Hare Charles Brad , Slome Sally , Flamm Jason A. , Anderson Alexandra , Silverberg Michael J. , Allerton Michael W.
Published: March 2021

We implemented self-collected gonorrhea/chlamydia testing in 17 medical centers in California serving men who have sex with men living with HIV. From 2012 to 2018, gonorrhea/chlamydia testing increased from 45.2% to 63.4%. Among those tested, rectal testing increased from 42.0% to 77.3%; pharyngeal testing increased from 31.0% to 79.9% (all, P
trend < 0.0001).
“Empowering Our People”: Impact of a Culturally Adapted Evidence-Based Intervention on Sexually Transmitted Infection Risks Among Native Americans With Binge Substance Use
Authors: Tingey Lauren , Chambers Rachel , Littlepage Shea , Lee Angelita , Slimp Anna , Melgar Laura , Cwik Mary , Gaydos Charlotte , Rompalo Anne , Rosenstock Summer
Published: March 2021

Background

The objective of this study was to evaluate a culturally adapted evidence-based intervention called EMPWR (Educate, Motivate, Protect, Wellness and Respect) for impacts on sexually transmitted infection (STI) screening and sexual health risk behaviors.

Methods

We enrolled Native American adults with recent binge substance use from a rural, reservation community in the Southwest into a 1:1 randomized controlled trial conducted on July 2015 to June 2019. All participants were offered non–clinic-based self-administered STI screening. Data were collected via self-report at baseline, 3 months, and 6 months after the intervention. Baseline and end line data are presented.

Results

Three hundred one participants were enrolled and had a mean age of 33.8 years; 46.5% of the sample were female, and 9.1% were employed at baseline. EMPWR participants were more likely to complete STI self-screening than control participants (38.2% vs. 23.8%, P = 0.0275). EMPWR participants reported fewer unprotected sex acts in the past 3 months (9.3 vs. 16.0, P = 0.001) and were more likely to refuse sex if their partner was not tested (23.6% vs. 12.4%, P = 0.049). The between-group difference in STI positivity 1 year after study completion was nearing statistical significance (intervention: 39.5% vs. control: 59.6%, P = 0.0575).

Conclusions

The culturally adapted evidence-based intervention, EMPWR, increased uptake of STI screening and refusal of sex if partner was not STI tested and decreased the frequency of unprotected sex acts among Native American adults with recent binge substance use living on a rural reservation. Future research is needed to examine EMPWR impacts among other Native American subgroups and its potential for advancing sexual health equity in this high-priority population.
Return of Positive Test Results to Participants in Sexually Transmitted Infection Prevalence Studies: Research Ethics and Responsibilities
Authors: Grubbs Joshua C. , Millum Joseph , Rietmeijer Cornelis A. , Kilmarx Peter H.
Published: March 2021

Background

In prevalence studies of sexually transmitted infections (STIs), investigators often provide syndromic management for symptomatic participants but may not provide specific treatment for asymptomatic individuals with positive laboratory test results because of the delays between sample collection and availability of results as well as logistical constraints in recontacting study participants.

Methods

To characterize the extent of this issue, 80 prevalence studies from the World Health Organization's Report on Global Sexually Transmitted Infection Surveillance, 2018, were reviewed. Studies were classified as to whether clinically relevant positive results were returned or if this was not specified.

Results

More than half (56%) of the cited studies did not specify if participants were notified of clinically relevant positive STI test results. The percentages were similar for low- and middle-income country populations (57%) and high-income country populations (53%).

Conclusions

The absence of documentation of the provision of test results raises the possibility that in some instances, results may not have been communicated, with potential negative effects for participants, their sexual partners, and newborns. From an ethical perspective, clinically relevant results should be returned to study participants and treating clinicians in a timely fashion to ensure appropriate management of identified infections. Study authors should document if they returned test results to study participants and report on numbers lost to follow-up.
Milk Phospholipid Profiling Among Japanese Women with Differing Docosahexaenoic Acid Levels
Authors: Ueno Hiroshi M. , MacKenzie Andrew , Scott Dawn , Higurashi Satoshi , Toba Yasuhiro , Kobayashi Toshiya
Published: March 2021

Objectives:

To characterize the milk phospholipids (PLs) profile using phosphorus-31 nuclear magnetic resonance (31P-NMR) and to investigate the effect of elevated milk docosahexaenoic acid (DHA) levels on PLs profiles in Japanese mothers.

Methods:

Milk samples from eligible patients with high and low DHA from a former cross-sectional study (n = 20; n = 10 for each group) were included. Fifteen milk PLs were analyzed using 31P-NMR, and the profiles were compared group-wise using Mann–Whitney U-test. The P value of <0.05 was considered statistically significant.

Results:

The median DHA content in milk was 1.13% and 0.29% for the high and low milk DHA groups, respectively. Twelve PLs, excluding lysophosphatidylserine, cardiolipin, and phosphatidylglycerol, were detected in all participants with 100% positive results. The median concentrations and proportions of total PLs, sphingophospholipids, and glycerophospholipids were comparable between groups. The proportions of choline-containing glycerophospholipid were significantly higher in the high milk DHA group than that in the low milk DHA group (24.09% [median, interquartile range: 23.08%–26.38%] and 21.41% [20.74%–22.84%], P = 0.019). Although the proportions of phosphatidylinositol were significantly lower in the high milk DHA group than that in the low milk DHA group (6.62% [5.75%–6.72%] versus 7.63% [7.11%–8.16%], P = 0.002), while that of phosphatidylcholine (21.90% [18.51%–23.22%] versus 19.78% [18.17%–20.26%], P = 0.059) and alkyl-acyl phosphatidylcholine (0.60% [0.40%–0.74%] versus 0.33% [0.14%–0.51%], P = 0.059) were higher in the former than that in the latter.

Conclusions:

Our results were comparable to that of the previous literature. Large variations in the milk DHA might affect the composition of choline-containing glycerophospholipids in Japanese mothers. However, possible confounders were not excluded in the study populations.
A Low-FODMAP Diet in the Management of Children With Functional Abdominal Pain Disorders: A Protocol of a Systematic Review
Authors: Stróżyk Agata , Horvath Andrea , Szajewska Hania
Published: March 2021

Objectives:

The available interventions for the management of children with functional abdominal pain disorders (FAPD) are limited. A diet low in fermentable oligosaccharides, disaccharides monosaccharides, and polyols (FODMAPs) is widely used in adults and children with FAPD, despite limited available evidence. We aim to systematically review evidence on the efficacy and safety of using a low-FODMAP diet for the management of children with FAPD.

Methods:

The Cochrane Library, EMBASE, and MEDLINE databases will be searched for randomized controlled trials (RCTs) that compare the use a low-FODMAP diet (preferably a 3-step low-FODMAP diet but also only a strict low-FODMAP diet or restriction of individual FODMAPs) with any comparator (i.e., standardized [i.e., average national] or other diet or no intervention) in children with FAPD (regardless of the definition). Each FAPD and each low-FODMAP diet or individual FODMAP restriction will be assessed separately. The Cochrane Collaboration’s tool for assessing the risk of bias will be used. The primary outcome will be the abdominal pain intensity. The secondary outcomes will be abdominal pain frequency, stool consistency, other gastrointestinal symptoms, school performance, and psychological functioning associated with FAPD, parent’s work absenteeism associated with FAPD of a child, health-related quality of life, compliance, growth, and adverse events. The findings will be published in a peer-reviewed journal and submitted to relevant conferences.

Conclusion:

This systematic review of rigorous methodological design will update current evidence on the efficacy and safety of using a low-FODMAP diet. However, it may be limited by the quality of the included studies.
The Immune Checkpoint Inhibitor LAG-3 and Its Ligand GAL-3 in Vulvar Squamous Neoplasia
Authors: Cocks Margaret M. , Mills Anne M.
Published: March 2021

Vulvar squamous cell carcinoma (vSCC), although rare, carries significant morbidity and a high rate of recurrence. Treatment options beyond surgical excision remain limited. Lymphocyte activation gene-3 (LAG-3) and its binding partner galectin-3 (GAL-3) are an immuno-inhibitory checkpoint pair that represent potential immunotherapy targets for the treatment of vSCC. This study examined the expression of LAG-3 and GAL-3 alongside programmed cell death ligand-1 expression in invasive SCC and vulvar intraepithelial neoplasia (VIN) by immunohistochemical analysis of formalin-fixed paraffin-embedded tissue. A total of 35 cases were selected for evaluation: 13 VIN3 [human papillomavirus (HPV)-associated VIN/usual-type VIN], 2 differentiated VIN (dVIN), 16 HPV-associated vSCC, and 4 dVIN-associated vSCC. LAG-3+ tumor-infiltrating lymphocytes were identified in 91% (32/35) of cases of vulvar squamous neoplasia. Tumor cells were positive for GAL-3 in 71% of the vulvar neoplasia cases. HPV-associated vSCC was more likely to demonstrate GAL-3 tumoral positivity when compared with dVIN-associated vSCC (24/29 vs. 1/6, P=0.004). We observed co-expression of all 3 immunomarkers in 40% (14/35) of cases evaluated. In light of these findings, use of immunomodulatory drugs that target the LAG-3/GAL-3 pathway may be potentially beneficial in vSCC and efficacy may be increased when combined with anti-programmed cell death ligand-1 therapy.
Unusual Presentation of Herpes Zoster Infection Mimicking Soft Tissue Metastases of Breast Cancer on 18F-FDG PET/CT Imaging
Authors: Soydas Turan Basak , Bozkurt M. Fani
Published: March 2021

Herpes zoster infection caused by reactivation of dormant varicella zoster virus results in painful vesicular rash in corresponding dermatome. We report a case of a 56-year-old woman with breast cancer who was referred to PET/CT scan for adjuvant chemotherapy response assessment. Her scan showed multiple FDG-avid skin lesions. Blinded to the patient’s clinical information, these skin lesions initially looked suspicious for soft tissue metastases. However, the patient history revealed that she had been experiencing herpes zoster infection during the scan, and these lesions with FDG uptake were eventually confirmed to be caused by herpes zoster infection by physical examination.
Elevated 99mTcO4 − Activity in Adenocarcinoma of the Lung
Authors: Ming Hui , Chen Yuanhao , Yu Hui
Published: March 2021

A 73-year-old man experienced chest tightness and shortness of breath for 9 months. Chest CT revealed a large right upper lobe mass. Pathology from CT-guided biopsy demonstrated poorly differentiated adenocarcinoma of the lung. Whole-body bone scan was acquired to evaluate possible bone metastasis. However, he was injected with 99mTcO4
− erroneously instead of 99mTc-MDP. The images showed a focus of elevated activity of 99mTcO4
− in the known lung lesion.
Spatiotemporal Evolution of Radiation Myositis on 18F-FDG PET/CT Following Hypofractionated Radiotherapy of Intramuscular Melanoma Metastases
Authors: Spaas Mathieu , Van den Broeck Bliede , Creytens David , Kruse Vibeke , Ost Piet
Published: March 2021

Radiation myositis is an infrequent late adverse effect of radiotherapy (RT), more commonly seen after hypofractionated regimens. We present the case of a 52-year-old woman with oligorecurrent metastatic melanoma who, several months after receiving local hypofractionated RT, developed a painful swelling at the irradiated site. As an integral part of routine oncologic follow-up, 18F-FDG PET/CT allowed accurate visualization of the affected region and when matched with RT treatment plans clearly illustrated their apparent overlap. This case demonstrates the utility of 18F-FDG PET/CT in the early detection and monitoring of radiation myositis and highlights the importance of a multidisciplinary approach in melanoma care.
18F-FDG and 68Ga-FAPI PET/CT in the Evaluation of Ground-Glass Opacity Nodule
Authors: Chen Haojun , Pang Yizhen , Meng Tinghua , Yu Xiuyi , Sun Long
Published: March 2021

A 50-year-old woman with a newly detected pulmonary ground-glass opacity (GGO) nodule underwent PET/CT to determine the likelihood of malignancy. This patient was enrolled in the prospective study (NCT04588064) to determine the effectiveness of 18F-FDG and 68Ga-FAPI PET/CT for characterization of the GGO nodule. On PET/CT images, minimal 18F-FDG uptake but intense 68Ga-FAPI uptake was observed in this GGO nodule. This patient subsequently underwent video-assisted thoracoscopic surgery, and postoperative pathological examination confirmed the diagnosis of invasive adenocarcinoma. This case presented an example where 68Ga-FAPI PET/CT showed higher tracer uptake than 18F-FDG in the malignant GGO nodule.
Use of 68Ga-FAPI PET/CT for Evaluation of Peritoneal Carcinomatosis Before and After Cytoreductive Surgery
Authors: Zhao Liang , Pang Yizhen , Wei Jihong , Hao Bing , Chen Haojun
Published: March 2021

A 55-year-old woman underwent 18F-FDG and 68Ga-FAPI PET/CT for tumor detection and staging under the prospective study NCT04416165. Both scans showed a mass lesion with increased tracer uptake in the pancreas. Moreover, 68Ga-FAPI PET/CT showed a greater number of abnormal foci in the mesentery and omentum than that shown with 18F-FDG. These abnormal foci were suspected to be metastases from pancreatic cancer. The patient subsequently underwent a cytoreductive surgery, and postoperative histopathology confirmed the diagnosis of acinar cell carcinoma of pancreas. Follow-up 68Ga-FAPI PET/CT (3 months after surgery) showed an excellent response with decreasing 68Ga-FAPI activity in the whole abdomen.
Unexpected 99mTcO4 − Uptake by Lung Adenocarcinoma
Authors: Knappe Luisa , Muoio Barbara , Migliora Paola , Paone Gaetano , Giovanella Luca
Published: March 2021

A 76-year-old woman underwent 99mTcO4
− thyroid scintigraphy to clarify thyrotoxicosis. In addition to suppressed thyroid uptake, an atypical tracer accumulation appeared on already know pulmonary adenocarcinoma in the left lung upper lobe. Surgical pathology was reviewed confirming the diagnosis of lung adenocarcinoma with focal mucins production and excluding a misdiagnosed differentiated thyroid carcinoma metastasis.
How Clean Are You Really? A Simulation Study of Droplet Splash Using an Acrylic Box During Cardiopulmonary Resuscitation
Authors: Lumlertgul Suthaporn , Inboriboon Pholaphat Charles
Published: March 2021

Summary Statement

In light of the COVID-19 pandemic, protocols to reduce risk of exposure to healthcare teams have been implemented. The use of an acrylic box during intubation and cardiopulmonary resuscitation has been adopted worldwide. A study was conducted to assess the effectiveness of an acrylic box in limiting contamination. The findings indicate that healthcare workers are still vulnerable to exposure despite the use of personal protective equipment (PPE) and an acrylic box. The causes of contamination were related to improper PPE donning and doffing and incomplete coverage by the acrylic box. Institutions should focus on ensuring proper donning and doffing of PPE and incorporating high-fidelity simulation training to prepare teams to resuscitate COVID-19 patients.
Using a Systems-Focused Simulation to Rapidly Prepare for Large Volume COVID-19 Vaccination
Authors: Stone Kimberly , Enriquez Brianna , Keilman Ashley , German Kylene , Straight Ami , Demmert Karen Rancich , York Tammy , Reid Jennifer
Published: March 2021

Summary Statement

The goal of vaccinating large numbers of staff and nonstaff against COVID-19 with a novel vaccine necessitated rapid modifications to an existing workforce vaccination program. We performed a series of 3 iterative systems-focused simulations and debriefings in the span of 1 week to evaluate existing vaccination clinic space, trial a new physical space for the COVID-19 vaccine clinic, identify existing process gaps, and determine necessary changes for maximum efficiency and safety. By using iterative systems-focused simulations, we were able to perform a gap analysis on the existing program, develop and stabilize new processes, and focus on emergency preparedness.
Factors preventing SARS-CoV-2 transmission during unintentional exposure in a GP practice: a cohort study of patient contacts; Germany, 2020
Authors: Boender T. Sonia , Bender Jennifer K. , Krüger Angelika , Michaelis Kai , Buchholz Udo
Published: March 2021

Two general practitioners (GPs) a with SARS-CoV-2 infection provided in-person patient care to patients of their joint medical practice before and after symptom onset, up until SARS-CoV-2 laboratory confirmation. In a retrospective cohort study of patient contacts, we assessed the risk (frequency and determinants) of SARS-CoV-2 transmission from the GPs to their patients. Our findings support the use of facemasks for GPs, and short consultation time, to minimize the risk of transmission.

Two general practitioners (GPs) with SARS-CoV-2 infection provided in-person patient care to patients of their joint medical practice before and after symptom onset, up until SARS-CoV-2 laboratory confirmation. Through active contact tracing, the local public health authorities recruited the cohort of patients that had contact with either GP in their putative infectious period. In this cohort of patient contacts, we assess the frequency and determinants of SARS-CoV-2-transmission from GPs to patients. We calculated incidence rate ratios (IRR) to explore the type of contact as explanatory variable for COVID-19 cases. Among the cohort of 83 patient contacts, we identified 22 (27%) COVID-19 cases including 17 (21%) possible, 3 (4%) probable, and 2 (2%) confirmed cases. All 22 cases had contact with a GP when the GP did not wear a mask, and/or when contact was ≥10 minutes. Importantly, patients who had contact <10 minutes with a GP wearing a facemask were at reduced risk (IRR 0.21; 95%CI 0.01-0.99) of COVID-19. This outbreak investigation adds to the body of evidence in supporting current guidelines on measures at preventing transmission of SARS-CoV-2 in an outpatient setting.
A synthetic receptor platform enables rapid and portable monitoring of liver dysfunction via engineered bacteria
Authors: Chang Hung-Ju , Zuniga Ana , Conejero Ismael , Voyvodic Peter L. , Gracy Jerome , Fajardo-Ruiz Elena , Cohen-Gonsaud Martin , Cambray Guillaume , Pageaux Georges-Philippe , Meszaros Magdalena , Meunier Lucy , Bonnet Jerome
Published: March 2021

Bacterial biosensors, or bactosensors, are promising field-deployable agents for medical and environmental diagnostics. However, the lack of scalable frameworks to systematically program ligand detection limits their applications. Here we present a synthetic receptor platform, termed EMeRALD (Engineered Modularized Receptors Activated via Ligand-induced Dimerization) which supports the modular assembly of sensing modules onto a high-performance, generic signaling scaffold controlling gene expression in E. coli. We applied EMeRALD to detect bile salts, a biomarker of liver dysfunction, by repurposing sensing modules from enteropathogenic Vibrio species. We improved the sensitivity and lowered the limit-of-detection of the sensing module by directed evolution. We then engineered a colorimetric bactosensor detecting pathological bile salt levels in serum from patients having undergone liver transplant, providing an output detectable by the naked-eye. The EMeRALD technology enables functional exploration of natural sensing modules and rapid engineering of synthetic receptors for diagnostics, environmental monitoring, and control of therapeutic microbes.
Symptoms and risk factors for hospitalization of COVID-19 presented in primary care
Authors: Rabady S , Hoffmann K , Brose M , Lammel O , Poggenburg S , Redlberger-Fritz M , Stiasny K , Wendler M , Weseslindtner L , Zehetmayer S , Kamenski G
Published: March 2021

Objective

To extend knowledge of early symptoms as a precondition of early identification, and to gain understanding of associations between early symptoms and the development of a severe course of the disease.

Design

Retrospective observational study

Setting

Austrian GP practices in the year 2020, patients above 18 years were included.

Participants

We recruited 22 practices who included altogether 295 participants with a positive SARS-CoV-2 test.

Main outcome measures

Data collection comprised basic demographic data, risk factors and the recording of symptoms at several points in time in the course of the illness. Descriptive analyses for possible associations between demographics and symptoms were conducted by means of cross table. Group differences (hospitalized yes/no) were assessed using Fisher’s exact test. The significance level was set to 0.05; due to the observational character of the study, no adjustment for multiplicity was performed.

Results

Little more than one third of patients report symptoms generally understood to be typical for Covid-19. Most patients present with a variety of unspecific complaints. We found symptoms indicating complicated disease, depending on when they appear. The number of symptoms is likely to be a predictor for the need of hospital care. More than 50% of patients still experience symptoms 14 days after onset.

Conclusions

Underrating unspecific symptoms as possible indicators for SARS-CoV-2 infection harbours the danger of overlooking early disease. Monitoring patients during their illness using the indicators for severe disease we identified may help to identify patients who are likely to profit from early intervention.

Data availability statement

All data referred to in the manuscript are available from: Department of General Medicine and Family Practice, Karl Landsteiner Privatuniversitaet, Krems, Austria

Article Summary

Strengths and limitations

This study investigates data on the course of COVID-19 collected exclusively from patients in primary care and explores a wide range of symptoms.

GPs were free to make their own testing decision according to their clinical judgement, and they followed each patient individually from day 1 to day 10 or 14.

Limitations of our study concern the limited number of patients, due to the increased workload under difficult working conditions during the pandemic as well as the effort not being remunerated. However, the number of cases needed to identify group differences was calculated in advance, and this number has been reached. Our overall results are in accordance with our preliminary result analyses.
Using Google Health Trends to investigate COVID-19 incidence in Africa
Authors: Fulk Alexander , Romero-Alvarez Daniel , Abu-Saymeh Qays , Saint Onge Jarron M. , Peterson A. Townsend , Agusto Folashade B.
Published: March 2021

The COVID-19 pandemic has caused over 350 million cases and over five million deaths globally. From these numbers, over 10 million cases and over 200 thousand deaths have occurred on the African continent as of 22 January 2022. Prevention and surveillance remain the cornerstone of interventions to halt the further spread of COVID-19. Google Health Trends (GHT), a free Internet tool, may be valuable to help anticipate outbreaks, identify disease hotspots, or understand the patterns of disease surveillance.

We collected COVID-19 case and death incidence for 54 African countries and obtained averages for four, five-month study periods in 2020-2021. Average case and death incidences were calculated during these four time periods to measure disease severity. We used GHT to characterize COVID-19 incidence across Africa, collecting numbers of searches from GHT related to COVID-19 using four terms: ‘coronavirus’, ‘coronavirus symptoms’, ‘COVID19’, and ‘pandemic’. The terms were related to weekly COVID-19 case incidences for the entire study period via multiple linear regression analysis and weighted linear regression analysis. We also assembled 72 predictors assessing Internet accessibility, demographics, economics, health, and others, for each country, to summarize potential mechanisms linking GHT searches and COVID-19 incidence.

COVID-19 burden in Africa increased steadily during the study period as in the rest of the world. Important increases for COVID-19 death incidence were observed for Seychelles and Tunisia over the study period. Our study demonstrated a weak correlation between GHT and COVID-19 incidence for most African countries. Several predictors were useful in explaining the pattern of GHT statistics and their relationship to COVID-19 including: log of average weekly cases, log of cumulative total deaths, and log of fixed total number of broadband subscriptions in a country. Apparently, GHT may best be used for surveillance of diseases that are diagnosed more consistently.

GHT-based surveillance for an ongoing epidemic might be useful in specific situations, such as when countries have significant levels of infection with low variability. Overall, GHT-based surveillance showed little applicability in the studied countries. Future studies might assess the algorithm in different epidemic contexts.
SARS-CoV-2 infection risk among unvaccinated is negatively associated with community-level vaccination rates
Authors: Milman Oren , Yelin Idan , Aharony Noga , Katz Rachel , Herzel Esma , Ben-Tov Amir , Kuint Jacob , Gazit Sivan , Chodick Gabriel , Patalon Tal , Kishony Roy
Published: March 2021

Mass vaccination has the potential to curb the current COVID-19 pandemic by protecting vaccinees from the disease and possibly lowering the chance of transmission to unvaccinated individuals. The high effectiveness of the widely-administered BNT162b vaccine in preventing not only the disease but also infection suggests a potential for a population-level effect, critical for disease eradication. However, this putative effect is difficult to observe, especially in light of highly fluctuating spatio-temporal epidemic dynamics. Here, analyzing vaccination records and test results collected during a rapid vaccine rollout for a large population from 223 geographically defined communities, we find that the rates of vaccination in each community are highly correlated with a later decline in infections among a cohort of under 16 years old which are unvaccinated. These results provide observational evidence that vaccination not only protects individual vaccinees but also provides cross-protection to unvaccinated individuals in the community.
Proteasome autophagy is specifically regulated and requires factors dispensible for general autophagy
Authors: Waite Kenrick A. , Burris Alicia , Vontz Gabrielle , Lang Angelica , Roelofs Jeroen
Published: March 2021

Changing physiological conditions can increase the need for protein degradative capacity in eukaryotic cells. Both the ubiquitin-proteasome system and autophagy contribute to protein degradation. However, proteasomes are also an autophagy substrate. Thus, these processes must be differentially regulated depending on the physiological conditions presented. The signals and molecular mechanisms that govern proteasome autophagy are only partly elucidated. Our data indicate that chemical inhibition of TORC1 with rapamycin induces a bi-phasic response where proteasome levels are upregulated followed by an autophagy-dependent reduction. Surprisingly, several conditions that result in inhibited TORC1 exclusively induce proteasome autophagy (i.e. without any proteasome upregulation), suggesting a convergence of signals upstream of proteasome autophagy under different physiological conditions. Indeed, several conditions that activate general autophagy did not induce proteasome autophagy further distinguishing between proteasome autophagy and general autophagy. Consistent with this, we found that Atg11, the receptor for selective autophagy, and the map kinases Mpk1, Mkk1, and Mkk2, all play a role in autophagy of proteasomes, while they are dispensible for general autophagy. In all, our data provide new insights into the molecular regulation of proteasome autophagy by demonstrating that these complexes are specifically regulated under different autophagy inducing conditions.
NTRK oncogenic fusions are exclusively associated with the serrated neoplasia pathway in the colorectum and begin to occur in sessile serrated lesions
Authors: Kim Jung Ho , Hong Jeong Hoon , Choi Yoon-La , Lee Ji Ae , Seo Mi-kyoung , Lee Mi-Sook , An Sung Bin , Sung Min Jung , Cho Nam-Yun , Kim Sung-Su , Shin Young Kee , Kim Sangwoo , Kang Gyeong Hoon
Published: March 2021

Background

NTRK fusions are emerging tissue-agnostic drug targets in malignancies including colorectal cancers (CRCs), but their detailed landscape in the context of various colorectal carcinogenesis pathways remains to be investigated.

Methods

Pan-TRK expression was assessed by immunohistochemistry in retrospectively collected colorectal epithelial tumor tissues, including 441 CRCs (133 microsatellite instability-high (MSI-high) and 308 microsatellite stable (MSS)) and 565 premalignant colorectal lesions (300 serrated lesions and 265 conventional adenomas). TRK-positive cases were subjected to next-generation sequencing and/or fluorescence in situ hybridization to confirm NTRK rearrangements.

Results

TRK positivity was not observed in any of the MSS CRCs, conventional adenomas, traditional serrated adenomas, or hyperplastic polyps, whereas TRK positivity was observed in 11 of 58 (19%) sporadic MSI-high CRCs, 4 of 23 (17%) sessile serrated lesions with dysplasia (SSLDs), and 5 of 132 (4%) SSLs. The 11 TRK-positive MSI-high CRCs commonly harbored CpG island methylator phenotype-high (CIMP-high), MLH1 methylation, KRAS/BRAF wild-type, and NTRK1 or NTRK3 fusion (TPM3-NTRK1, TPR-NTRK1, LMNA-NTRK1, SFPQ-NTRK1, ETV6-NTRK3, or EML4-NTRK3). Both NTRK1 or NTRK3 rearrangement and KRAS/BRAF wild-type were detected in all nine TRK-positive SSL(D)s, seven of which demonstrated MSS and/or CIMP-low. TRK overexpression and early dysplastic changes are occasionally co-localized in the crypt base area of SSLs. Age-related occurrence patterns suggest that the progression interval from NTRK-rearranged SSLs to CRCs may be shorter than from BRAF-mutated SSLs to CRCs.

Conclusion

NTRK-rearranged colorectal tumors develop exclusively through the serrated neoplasia pathway and can be initiated from non-dysplastic SSLs without KRAS/BRAF mutations prior to full occurrence of MSI-high/CIMP-high.
Six-month pulmonary impairment after severe COVID-19: a prospective, multicenter follow-up study
Authors: Faverio Paola , Luppi Fabrizio , Rebora Paola , Busnelli Sara , Stainer Anna , Catalano Martina , Parachini Luca , Monzani Anna , Galimberti Stefania , Bini Francesco , Bodini Bruno Dino , Betti Monia , Giacomi Federica De , Scarpazza Paolo , Oggionni Elisa , Scartabellati Alessandro , Bilucaglia Luca , Ceruti Paolo , Modina Denise , Harari Sergio , Caminati Antonella , Valsecchi Maria Grazia , Bellani Giacomo , Foti Giuseppe , Pesci Alberto
Published: March 2021

Background and objective

Long-term pulmonary sequelae following SARS-CoV-2 pneumonia are not yet confirmed, however preliminary observations suggests a possible relevant clinical, functional and radiological impairment. The aim of this study was to identify and characterise pulmonary sequelae caused by SARS-CoV-2 pneumonia at 6-month follow-up.

Methods

In this multicenter, prospective, observational cohort study, patients hospitalised for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support (“oxygen only”, “continuous positive airway pressure (CPAP)” and “invasive mechanical ventilation (IMV)”) and followed up at 6 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6 minutes walking test, chest X-ray, physical exam and modified Medical Research Council (mMRC) dyspnoea score were collected.

Results

Between March and June 2020, 312 patients were enrolled (83, 27% women; median [IQR] age 61.1 [53.4,69.3] years). The parameters that showed the highest rate of impairment were DLCO and chest-X-ray, in 46% and 25% of patients, respectively. However, only a minority of patients reported dyspnoea (31%), defined as mMRC ≥ 1, or showed a restrictive ventilatory defects (9%). In the logistic regression model, having asthma as comorbidity was associated with DLCO impairment at follow-up, while prophylactic heparin administration during hospitalisation appeared as a protective factor. Need for invasive ventilatory support during hospitalisation was associated with chest imaging abnormalities.

Conclusion

DLCO and radiological assessment appear to be the most sensitive tools to monitor patients with COVID-19 during follow-up. Future studies with longer follow-up are warranted to better understand pulmonary sequelae.

Summary at a glance

DLCO and radiological assessment are the most sensitive tools to monitor COVID-19 patients at 6-month follow-up. Invasive ventilatory support is a risk factor for detection of radiological abnormalities, but not for DLCO impairment, at follow-up. Whileuse of prophylactic heparin acts as a protective factor on the development of DLCOimpairment.
Development and validation of the RCOS prognostic index: a bedside multivariable logistic regression model to predict hypoxaemia or death in patients with SARS-CoV-2 infection
Authors: Alvarez-Uria Gerardo , Gandra Sumanth , Gurram Venkata R , Reddy Raghu P , Midde Manoranjan , Kumar Praveen , Arce Ketty E
Published: March 2021

Previous COVID-19 prognostic models have been developed in hospital settings, and are not applicable to COVID-19 cases in the general population. There is an urgent need for prognostic scores aimed to identify patients at high risk of complications at the time of COVID-19 diagnosis. The RDT COVID-19 Observational Study (RCOS) collected clinical data from patients with COVID-19 admitted regardless of the severity of their symptoms in a general hospital in India. We aimed to develop and validate a simple bedside prognostic score to predict the risk of hypoxaemia or death.

4035 patients were included in the development cohort and 2046 in the validation cohort. The primary outcome occurred in 961 (23.8%) and 548 (26.8%) patients in the development and validation cohorts, respectively. The final model included 12 variables: age, systolic blood pressure, heart rate, respiratory rate, aspartate transaminase, lactate dehydrogenase, urea, C-reactive protein, sodium, lymphocyte count, neutrophil count and neutrophil/lymphocyte ratio. In the validation cohort, the area under the receiver operating characteristic curve (AUROCC) was 0.907 (95% CI, 0.892-0.922) and the Brier Score was 0.098. The decision curve analysis showed good clinical utility in hypothetical scenarios where admission of patients was decided according to the prognostic index. When the prognostic index was used to predict mortality in the validation cohort, the AUROCC was 0.947 (95% CI, 0.925-0.97) and the Brier score was 0.0188.

If our results are validated in other settings, the RCOS prognostic index could help improve the decision making in the current COVID-19 pandemic, especially in resource limited-settings.
Benchmarking small-variant genotyping in polyploids
Authors: Cooke Daniel P , Wedge David C , Lunter Gerton
Published: March 2021

Genotyping from sequencing is the basis of emerging strategies in the molecular breeding of polyploid plants. However, compared with the situation for diploids, where genotyping accuracies are confidently determined with comprehensive benchmarks, polyploids have been neglected; there are no benchmarks measuring genotyping error rates for small variants using real sequencing reads. We previously introduced a variant calling method – Octopus – that accurately calls germline variants in diploids and somatic mutations in tumors. Here, we evaluate Octopus and other popular tools on whole-genome tetraploid and hexaploid datasets created using in silico mixtures of diploid Genome In a Bottle samples. We find that genotyping errors are abundant for typical sequencing depths, but that Octopus makes 25% fewer errors than other methods on average. We supplement our benchmarks with concordance analysis in real autotriploid banana datasets.
Identification of candidate genes for self-compatibility in perennial ryegrass (Lolium perenneL.)
Authors: Cropano Claudio , Manzanares Chloé , Yates Steven , Copetti Dario , Do Canto Javier , Lübberstedt Thomas , Koch Michael , Studer Bruno
Published: March 2021

Self-incompatibility (SI) is a genetic mechanism preventing self-pollination in approximately 40% of plant species. Two multiallelic loci, calledSandZ, control the gametophytic SI system of the grass family (Poaceae), which contains all major forage grasses. Loci independent fromSandZhave been reported to disrupt SI and lead to self-compatibility (SC). A locus causing SC in perennial ryegrass (Lolium perenneL.) was previously mapped on linkage group (LG) 5 in a F2population segregating for SC. Using a subset of the same population (n=68), we first performed low-resolution quantitative trait locus (QTL) mapping to exclude the presence of additional, previously undetected contributors to SC. The previously reported QTL on LG 5 explained 38.4% of the phenotypic variation, and no significant contribution from other genomic regions was found. This was verified by the presence of significantly distorted markers in the region overlapping with the QTL. Second, we fine mapped the QTL to 0.26 cM using additional 2,056 plants and 23 novel sequence-based markers. Using an Italian ryegrass (Lolium multiflorumLam.) genome assembly as reference, the markers flanking SC were estimated to span a ~3 Mb region encoding for 57 predicted genes. Among these, seven genes were proposed as relevant candidate genes based on their annotation and function described in previous studies. Our work is a step forward to identify SC genes in forage grasses and provides diagnostic markers for marker-assisted introgression of SC into elite germplasm.

Key message

A previously reported QTL conferring self-compatibility to perennial ryegrass was fine mapped to a 0.26 cM locus, corresponding to an estimated ~ 3 Mb physical region containing 57 predicted protein-encoding genes.
Evolutionary trade-offs at the ArabidopsisWRR4Aresistance locus underpin alternateAlbugocandida recognition specificities
Authors: Castel Baptiste , Fairhead Sebastian , Furzer Oliver J. , Redkar Amey , Wang Shanshan , Cevik Volkan , Holub Eric B. , Jones Jonathan D. G.
Published: March 2021

The oomyceteAlbugo candidacauses white rust of Brassicaceae, including vegetable and oilseed crops, and wild relatives such asArabidopsis thaliana. NovelWhite Rust Resistance(WRR)-genes from Arabidopsis enable new insights into plant/parasite co-evolution.WRR4Afrom Arabidopsis accession Col-0 provides resistance to many but not all white rust races, and encodes a nucleotide-binding (NB), leucine-rich repeat (LRR) (NLR) immune receptor protein. Col-0WRR4Aresistance is broken by a Col-0-virulent isolate ofA. candidarace 4 (AcEx1). We identified an allele ofWRR4Ain Arabidopsis accession Oy-0 and other accessions that confers full resistance to AcEx1.WRR4AOy-0carries a C-terminal extension required for recognition of AcEx1, but reduces recognition of several effectors recognized by theWRR4ACol-0allele.WRR4AOy-0confers full resistance to AcEx1 when expressed as a transgene in the oilseed cropCamelina sativa.

Significance

A C-terminal extension in an allele of the Arabidopsis resistance-protein WRR4A changes effector recognition specificity, enabling theWRR4AOy-0allele to confer immunity toAlbugo candidaraces that overcome theWRR4ACol-0allele. This resistance can be transferred to the oil-producing cropCamelina sativa.

Graphical abstract
Shared and unique properties of place cells in anterior cingulate cortex and hippocampus
Authors: Bota Ayaka , Goto Akihiro , Tsukamoto Suzune , Schmidt Alexander , Wolf Fred , Luchetti Alessandro , Nakai Junichi , Hirase Hajime , Hayashi Yasunori
Published: March 2021

In the brain, spatial information is represented by neurons that fire when an animal is at specific locations, including place cells in hippocampus and grid cells in entorhinal cortex. But how this information is processed in downstream brain regions still remains elusive. Using chronic Ca2+imaging, we examined the activity of neurons in anterior cingulate cortex (ACC), a brain region implicated in memory consolidation, and found neurons that fire in a manner consistent with the properties of place cells. While the ACC place cells showed stability, location and context specificity similar to the hippocampal counterparts, they also have unique properties. Unlike hippocampal place cells that immediately formed upon exposure to a novel environment, ACC place cells increased over days. Also, ACC place cells tend to have additional place fields whereas typical hippocampal place cells have only one. Hippocampal activity is required for the formation of ACC place cells, but once they are established, hippocampal inactivation did not have any impact on ACC place cell firing. We thus identified features of ACC place cells that carry spatial information in a unique fashion.