bluuebunny/crossref_metadata_2025 huggingface dataset:
Deteriorating Patient Training Using Nonimmersive Virtual Reality
Authors: Singleton Heidi , James Janet , Penfold Simone , Falconer Liz , Priego-Hernandez Jacqueline , Holley Debbie , Burden David
Published: July 2021

Recent nurse education pedagogical strategies are starting to embrace the use of virtual patient simulations in higher education settings. This study evaluated student, simulation technician, and lecturer perspectives on student performance after virtual training for care of a deteriorating diabetic patient. Second year nursing students learned using a virtual patient simulation, which was a follow-up of a randomized controlled trial that took place during the academic year 2017–2018. Group and individual interviews were conducted comprising the 21 staff and students involved in the virtual reality simulation in four individual lecture sessions. Five themes emerged from this study: engagement, immersion, confidence, knowledge, and challenges. Student participants found that the virtual reality exercise aided their understanding of the complex concepts associated with hypoglycemia, provided immediate feedback about their clinical decisions, could be completed multiple times, and provided more opportunities for safe practice, complimenting their ward and clinical skills experiences. Simulation technicians and lecturing staff also recognized these benefits but identified challenges, including time and cost constraints. We recommend further research into potential benefits and challenges, including likely consequences of increased use of virtual reality technologies for nurse education curriculum design.
Chemical Peels as Field Therapy for Actinic Keratoses: A Systematic Review
Authors: Jiang Angela J. , Soon Seaver L. , Rullan Peter , Brody Harold J. , Monheit Gary D. , Lee Kachiu C.
Published: July 2021

BACKGROUND

Actinic keratoses (AKs) are a common premalignant cutaneous neoplasm and can progress to squamous cell carcinoma. A variety of treatment options are available for field therapy of diffuse AKs.

OBJECTIVE

This review systematically analyzes the use of chemical peels for treatment of AKs.

MATERIALS AND METHODS

A systematic review of PubMed was performed searching from 1946 to March 2020 to identify the literature on chemical peels for AKs.

RESULTS

Of the 151 articles identified, 5 met inclusion criteria for review. Four of the reviewed articles demonstrated the efficacy of chemical peels in reducing AK count and minimal adverse effects. In some studies, chemical peels exhibited potential to prevent additional AK formation and development of keratinocyte carcinomas.

CONCLUSION

Chemical peels are an efficacious and affordable treatment option for field treatment of AKs. With improved patient tolerance and adherence, chemical peels are an attractive option for field therapy of AKs for both dermatologists and patients.
The Contribution of Thoracic Radiation Dose Volumes to Subsequent Development of Cardiovascular Disease in Cancer Survivors
Authors: Reilly Carolyn Miller , Higgins Melinda , Butler Javed , Esiashvili Natia , Fei Baowei , Flynn Tommy , Dormer James D. , Schreibmann Eduard
Published: July 2021

Background

Although radiation therapy (RT) has been recognized for contributing to cardiovascular disease (CVD), it is unknown whether specific doses received by cardiovascular tissues influence development.

Objective

In this pilot study, we examined the contribution of RT dose distribution on the development of CVD events in patients with cancer within 5 years of RT.

Methods

A retrospective case-controlled design was used matching 28 cases receiving thoracic RT who subsequently developed an adverse CVD event with 28 controls based upon age, gender, and cancer type. Dose volume histograms of nongated computed tomography scans received during RT characterized the dose delivered to the heart. Heart chambers were segmented using an atlas approach, and radiomics features for the segmentation as well as planning dose in each chamber were tabulated for analysis.

Result

No significant differences were observed in the RT dose statistics between groups, preexisting CVD, nor significant differences of RT doses delivered to distinct chambers of the heart. Cases were found to have greater CVD risk factors at the time of cancer diagnosis. Morphological significant differences for perimeter on border (P = .043), equivalent spherical radius (P = .050), and elongation (P = .038) were observed, with preexisting CVD having the highest values (ie, larger hearts).

Conclusion

Traditional CVD risk factors were more prevalent in the cases who developed CVD. No differences were observed in doses of RT. Of note, we observed significant differences in heart morphology and mass in known diseased hearts on the pretreatment scans. These new metrics may have implications for the measurement and quantification of CVD.
The Predictive Ability of the Full and Short Versions of the Orebro Questionnaire for Absenteeism and Presenteeism Over the Subsequent 12 Months, in a Cohort of Young Community-Based Adult Workers
Authors: Beales Darren , Larsson Maria EH , O'Sullivan Peter , Straker Leon , Linton Steven J. , Smith Anne
Published: July 2021

Objective:

The primary purpose of this study was to investigate the predictive ability of the Örebro Musculoskeletal Pain Screening Questionnaire (ÖMPSQ) in regard to work productivity (absenteeism and presenteeism) in early adulthood.

Methods:

A prospective study was performed using data from the Raine Study Generation 2 (Gen2) 22-year follow-up. The ÖMPSQ was completed at baseline, and absenteeism and presenteeism assessed at four intervals over the following 12 months.

Results:

In early adulthood, the full and short versions of the ÖMPSQ showed some predictive ability for work absenteeism but the Receiver Operator Characteristic demonstrated poor discrimination. There was no evidence of predictive ability for presenteeism.

Conclusion:

Further work is required to increase the fidelity of screening for risk of reduced work productivity at the population level.
Latinx Teens' Perspectives on Exposure to Intimate Partner Violence
Authors: Montalvo-Liendo Nora , Grogan-Kaylor Andrew , Nava Angeles , Chilton Jenifer , Pepper Catherine , Alvarado Eliza D.
Published: July 2021

Introduction

Intimate partner violence is a significant public health issue facing communities across the country and worldwide, and we know that many children are witness or exposed to the violence. Substantial research related to exposure of children to family violence exists; however, research specific to adolescents exposed to intimate partner violence remains minimally explored.

Methods

This mixed-methods study sought to understand the experiences and perspectives of Latinx teens with histories of exposure to intimate partner violence. The study combined focus groups with (n = 25) Latinx teens and pretests and posttests using the Strengths and Difficulties Questionnaire and Attitudes and Beliefs about Violence.

Results

Twenty-five Latinx teens participated in the groups. The participants were 13–17 years old, with a mean age of 14.3 years. Participants provided several perspectives in which teens deal with exposure to intimate partner violence. Teens stated that “safety” was identified as “protecting themselves” or “protecting their siblings.” Findings suggest a need for teens to discuss intimate partner violence issues and develop positive and effective coping strategies.

Discussions

This study sought to understand Latinx teens' experiences of their exposure to intimate partner violence. Study limitations included a small high-risk sample from a nonprofit agency located in south Texas adjacent to the U.S.–Mexico border offering services to domestic violence and sexual assault victims and their children. This study shows promise for developing an evidence-based program that is developmentally and culturally appropriate for teens exposed to family violence.
Treatment Outcome of the Bony Obliteration Tympanoplasty Versus Nonobliterative Techniques in Cholesteatoma Surgery: A Retrospective Analysis
Authors: van der Toom Hylke F. E. , van der Schroeff Marc P. , Metselaar Mick , van Linge Anne , Vroegop Jantien L. , Pauw Robert J.
Published: July 2021

Objective:

In cholesteatoma surgery, obliteration of the mastoid and epitympanic space (bony obliteration tympanoplasty, BOT) is an increasingly used technique with low recurrent and residual cholesteatoma rates. While factors as the postoperative hearing level and infection rate are important for the patient as well, these outcome parameters are not frequently reported on in current literature. The objective of this study is to evaluate the recurrent and residual cholesteatoma rates of the BOT technique and nonobliterative canal wall up (CWU) and canal wall down (CWD) mastoidectomy in a large patient cohort. Secondary objectives were to evaluate the infection rate and hearing outcome for all three techniques.

Design:

Retrospective cohort study.

Setting:

Single-center study.

Patients:

All 337 adult patients (≥18 yrs) who underwent primary or revision cholesteatoma surgery between January 2013 and March 2019 were included.

Main Outcome and Measures:

Recurrent cholesteatoma rates, residual cholesteatoma rates, postoperative infections and other complications, hearing outcome.

Results:

The estimated combined rate of recurrent and residual cholesteatoma at 5 years follow-up was 7.6% in the BOT group, 34.9% in the CWU group, and 17.9% in the CWD group. The postoperative infection rate in the different groups ranged from 4.3% to 4.9%. The median gain in AC threshold level varied from 0.0 dB in the BOT and CWD group to 3.8 dB in the CWU group.

Conclusions:

We show that cholesteatoma recurrence rates after the BOT technique in our clinic are significantly lower compared to CWU surgery. There were no differences in infection rate and no clinically relevant differences in postoperative hearing between the BOT, CWU, and CWD technique.
Higher Readmission Rates After Hip Fracture Among Patients With Vestibular Disorders
Authors: Curry Steven D. , Carotenuto Alessandro , DeLuna Devin A. , Maar Dennis J. , Huang Ye , Samson Kaeli K. , Siebler Justin C. , Hatch Jonathan L.
Published: July 2021

Objective:

Falls in older adults are associated with high morbidity and mortality. Patients with vestibular disorders may have an increased risk. The purpose of this study was to examine the outcomes among patients with underlying vestibular disorders who have hip fractures and identify predictors of increased morbidity and mortality.

Study design:

Retrospective cohort study.

Setting:

Tertiary care academic medical center.

Patients:

Two hundred one adults diagnosed with a vestibular disorder and hip fracture due to a ground-level fall were compared to 327 age- and sex-matched controls with fractures due to ground-level falls without vestibular diagnoses. Patients were treated between 2013 and 2019.

Main outcome measures:

Length of hospital stay, 30-day readmission rate, and 30-day mortality rate.

Results:

Thirty-day readmission rate after hip fracture was significantly increased in patients with vestibular disorders compared to matched controls (p < 0.001), odds ratio 3.12 (95% confidence interval 1.84–5.39). Reasons for readmission in the vestibular patient group included higher rates of repeat falls, infections, and recurrent vestibular symptoms. Use of medication classes associated with falls or hip fractures was not significantly different between groups, except for lower rates of antihypertensive use in the vestibular group (54.0% vs. 67.7%, p = 0.002). No significant difference was found for length of hospital stay (7.34 ± 4.95 vs. 8.14 ± 20.50 days, p = 0.51) or 30-day mortality rate (5.0% vs. 4.6%, p = 0.99). No significant differences were found between groups for age, sex, race, rate of surgical treatment for hip fracture, or disposition at discharge.

Conclusions:

Patients with vestibular disorders are at a significantly higher risk of hospital readmission within 30 days after discharge for treatment for hip fracture.
Cerebral Venous Sinus Thrombosis Caused by Neuro-Behçet Disease Accidentally Detected by 68Ga-FAPI PET/CT
Authors: Lin Meiyan , Xue Qianqian , You Xin , Yao Shaobo , Miao Weibing
Published: July 2021

A 26-year-old man presented with recurrent oral ulcer, temporal headache, and blurred vision for 4 months. The giant cell arteritis was suspected, and 18F-FDG and 68Ga-FAPI PET/CT were done. There was no hypermetabolic lesion in 18F-FDG PET/CT. However, 68Ga-FAPI PET/CT showed multiple increased FAPI uptake lesions in the cerebral venous sinus. High-resolution MR venography revealed multiple chronic cerebral venous sinus thrombosis. Neuro-Behçet disease was diagnosed finally. This case showed 68Ga-FAPI PET/CT may play some role in the management of neuro-Behçet disease.
A Systematic Review of Breast Reconstruction Options After Mastectomy in Massive Weight Loss Patients
Authors: Sinik Lauren , Egan Katie G. , Patel Krishna , Nazir Niaman , Butterworth James A.
Published: July 2021

Given global trends in obesity and bariatric surgeries, there are an increasing number of women presenting for breast reconstruction after massive weight loss. There is a paucity of literature about breast reconstruction after mastectomy in patients with a history of massive weight loss. A literature review revealed 10 articles that discussed outcomes of different reconstruction techniques in patients with massive weight loss. Autologous reconstruction techniques and implant-based reconstruction techniques were assessed to evaluate the advantages, disadvantages, and indications of each approach specific to this unique patient population. This article provides a summary of expected outcomes, including complication profiles. Ultimately, consideration should be given for breast reconstruction of mastectomy defects in patients with a history of massive weight loss, as satisfactory results are demonstrated to be possible. Both autologous reconstruction and implant-based reconstruction present feasible options, although reconstruction in this patient population may be associated with increased need for revisions and a higher complication rate compared with patients without a history of massive weight loss. For this reason, it is imperative to appropriately manage preoperative expectations in patients with a history of massive weight loss.
Age- and Sex-Related Measurements of Total Craniofacial Soft Tissue Thickness and Fat in a Central Chinese Population
Authors: He Renke , Yang Wenxiu , Wu Di , Wang Haining
Published: July 2021

In this study, data related to the total soft tissue thickness and fat layer thickness of 41 anatomical landmarks were extracted from the craniofacial computerized tomography data of 280 Chinese individuals (160 males and 120 females). The measurements were assessed according to the following factors: a. sex, b. age, and c. sex × age. Descriptive statistics and a differential analysis were carried out in each group to analyze both the total soft tissue thickness and fat layer thickness. The results showed the following. 1. The results showed that the greater the total thickness of the soft tissue, the thicker the fat layer. 2. The thicknesses of the head and face soft tissues are strongly affected by sex. The total thickness of all landmark points in the men, except for the zygomatic points, was on average greater than that in the women. In contrast to the total thickness, the fat layer, except for the point of rhinion, in the women was larger than that in the men. 3. In the comparison of the 4 age groups, most feature points did not show an evident increasing or decreasing trend with age in the total thickness of the soft tissue. However, regarding the thickness of fat, the thickness at the other points, except for the feature infraorbital fossa point, decreased with age. 4. In the analysis of the sex × age group, no statistically significant differences were found at any landmark points. This paper is significant for facial reconstruction and cosmetic surgery in the Chinese population.
Endoscopic Endonasal Approach for Clipping Anterior Communicating Artery Aneurysms From Cadaver Studies and Three-Dimensional Printed Models to a Clinical Case
Authors: Qin Kun , Guo Wenlong , Zheng Jiantao , Tian Ge , Jiang Hui , Tang Kai , Shu Hang , Zhou Dong , Chen Guangzhong
Published: July 2021

Objectives:

Anterior communicating artery (ACoA) aneurysm is one of the most common intracranial aneurysms, and it is also the aneurysm with the highest rupture rate. With the improvement of endoscopic techniques, it is possible to use an endoscopic endonasal approach (EEA) to clip ACoA aneurysms. For further analysis of the EEA for clipping ACoA aneurysms, we used cadaver heads and three-dimensional (3D)-printed models to finish the anatomical study, and we finally selected 1 clinical case to complete the clipping through the EEA.

Materials and Methods:

We first collected 3 cadaver heads to simulate the EEA. Then, the imaging data of 29 real cases of ACoA aneurysm were collected, and the model of an aneurysm was prepared by 3D printing technology; then, the EEA was used to simulate the clipping of the aneurysm model. Finally, a clinical case with 2 ACoA aneurysms was selected to adopt the EEA for clipping.

Results:

Both the cadaver head and 3D-printed aneurysm model could simulate aneurysm clipping with the EEA. The clinical case of the selected ACoA aneurysm can successfully complete the clipping through the EEA.

Conclusions:

3D-printed models are a good method to study the anatomical characteristics of a surgical approach. For specially selected ACoA aneurysms, the EEA is relatively simple method that can be used to clip the aneurysm successfully. The EEA for clipping ACoA aneurysms is a useful complement to the current traditional craniotomy approaches and endovascular embolization.
Giant Deep Orbital Dermoid Cyst Presenting in Infancy
Authors: Park Kathryn S. , Ting Michelle , Dallalzadeh Liane O. , Movaghar Mansoor , Korn Bobby S. , Kikkawa Don O. , Liu Catherine Y.
Published: July 2021

Orbital dermoid cysts are benign choristomas that are very common in children and occur most often as a lateral or medial mass associated with the frontozygomatic or frontoethmoidal suture line. The authors present an unusual case of an occult giant deep orbital dermoid cyst in infancy that initially presented with a small, benign appearance and central upper eyelid location on clinical exam. Orbitotomy with complete excision prevented further ocular sequelae in this 11-month-old.
Dataset for Pathology Reporting of Colorectal Cancer
Authors: Loughrey Maurice B. , Webster Fleur , Arends Mark J. , Brown Ian , Burgart Lawrence J. , Cunningham Chris , Flejou Jean-Francois , Kakar Sanjay , Kirsch Richard , Kojima Motohiro , Lugli Alessandro , Rosty Christophe , Sheahan Kieran , West Nicholas P. , Wilson Richard H. , Nagtegaal Iris D.
Published: July 2021

Objective:

The aim of this study to describe a new international dataset for pathology reporting of colorectal cancer surgical specimens, produced under the auspices of the International Collaboration on Cancer Reporting (ICCR).

Background:

Quality of pathology reporting and mutual understanding between colorectal surgeon, pathologist and oncologist are vital to patient management. Some pathology parameters are prone to variable interpretation, resulting in differing positions adopted by existing national datasets.

Methods:

The ICCR, a global alliance of major pathology institutions with links to international cancer organizations, has developed and ratified a rigorous and efficient process for the development of evidence-based, structured datasets for pathology reporting of common cancers. Here we describe the production of a dataset for colorectal cancer resection specimens by a multidisciplinary panel of internationally recognized experts.

Results:

The agreed dataset comprises eighteen core (essential) and seven non-core (recommended) elements identified from a review of current evidence. Areas of contention are addressed, some highly relevant to surgical practice, with the aim of standardizing multidisciplinary discussion. The summation of all core elements is considered to be the minimum reporting standard for individual cases. Commentary is provided, explaining each element's clinical relevance, definitions to be applied where appropriate for the agreed list of value options and the rationale for considering the element as core or non-core.

Conclusions:

This first internationally agreed dataset for colorectal cancer pathology reporting promotes standardization of pathology reporting and enhanced clinicopathological communication. Widespread adoption will facilitate international comparisons, multinational clinical trials and help to improve the management of colorectal cancer globally.
Beyond the RCT: When are Randomized Trials Unnecessary for New Therapeutic Devices, and What Should We Do Instead?
Authors: Páez Arsenio , Rovers Maroeska , Hutchison Katrina , Rogers Wendy , Vasey Baptiste , McCulloch Peter
Published: July 2021

Objective:

The aim of this study was to develop an evidence-based framework for evaluation of therapeutic devices, based on ethical principles and clinical evidence considerations

Summary Background Data:

Nearly all medical products which do not work solely through chemical action are regulated as medical devices. Their huge range of purposes, mechanisms of action and risks pose challenges for regulation. High-profile implantable device failures have fuelled concerns about the level of clinical evidence needed for market approval. Calls for more rigorous evaluation lack clarity about what kind of evaluation is appropriate, and are commonly interpreted as meaning more randomized controlled trials (RCTs). These are valuable where devices are genuinely new and claim to offer measurable therapeutic benefits. Where this is not the case, RCTs may be inappropriate and wasteful.

Methods:

Starting with a set of ethical principles and basic precepts of clinical epidemiology, we developed a sequential decision-making algorithm for identifying when an RCT should be performed to evaluate new therapeutic devices, and when other methods, such as observational study designs and registry-based approaches, are acceptable.

Results:

The algorithm clearly defines a group of devices where an RCT is deemed necessary, and the associated framework indicates that an IDEAL 2b study should be the default clinical evaluation method where it is not.

Conclusions:

The algorithm and recommendations are based on the principles of the IDEAL-D framework for medical device evaluation and appear eminently practicable. Their use would create a safer system for monitoring innovation, and facilitate more rapid detection of potential hazards to patients and the public.
Is tactical combat casualty care in terrorist attacks suitable for civilian first responders?
Authors: Borgers Felix , Van Boxstael Sam , Sabbe Marc
Published: July 2021

INTRODUCTION

Prehospital management of intentional mass casualty incidents is a unique challenge to Emergency Medical Services. Tactical Combat Casualty Care (TCCC) and the use of tourniquets for extremity hemorrhage have already proven to reduce mortality on the battlefield. This literature review aims to determine the place of these military concepts in a civilian high-threat prehospital setting.

METHODS

The PubMed database was searched for articles published between January 1, 2000, and December 1, 2019, containing descriptions, discussions, or experiences of the application of tourniquets or other TCCC-based interventions in the civilian prehospital setting. Data extraction focused on identifying important common themes in the articles.

RESULTS

Of the 286 identified articles, 30 were selected for inclusion. According to the Oxford Centre for Evidence-based Medicine Levels of Evidence, overall level of evidence was low. Most articles were observational, retrospective cohort studies without a nontourniquet control group. Outcome measures and variables were variably reported. Two articles specifically analyzed tourniquet use during high-threat situations, and three described their application by law enforcement personnel. Overall, tourniquets were found to be effective in stopping major limb bleeding. Reported mortality was low and related complications appeared to be infrequent. Only four articles mentioned the application of other TCCC-based maneuvers, such as airway and respiratory management.

CONCLUSION

This literature review shows that tourniquets appear to be safe tools associated with few complications and might be effective in controlling major bleeding in civilian limb trauma. For example, during mass casualty incidents, their use could be justified. Training and equipping ambulance and police services to deal with massive bleeding could likewise improve interoperability and victim survival in a civilian high-threat prehospital setting. More qualitative research is needed to further evaluate the effects of hemorrhage control training for first responders on patient outcomes. Literature describing the application of other TCCC-based principles is limited, which makes it difficult to draw conclusions regarding their use in a civilian setting.

LEVEL OF EVIDENCE

Systematic review, level III.
Paracentral Acute Middle Maculopathy in Pregnancy
Authors: Scott Rachel A. , Bhat Nita , Bindiganavile Shruthi H. , Li Helen K. , Lee Andrew G.
Published: July 2021

A 31-year-old previously healthy, pregnant woman presented with acute, unilateral, painless paracentral vision loss in the left eye. The results of neuroimaging studies were normal. Hypercoagulable workup was negative, and fundus examination showed no retinal emboli and no retinal vascular abnormalities. The patient had well-controlled blood pressure and did not have eclampsia/preeclampsia. Although a presumptive referral diagnosis of “optic neuritis” was made, optical coherence tomography (OCT) of the macula showed a hyperreflective band involving the inner nuclear layer, consistent with paracentral acute middle maculopathy (PAMM). Furthermore, OCT angiography (OCT-A) showed flow attenuation of the outer retinal capillary plexus, further supporting a diagnosis of PAMM in pregnancy. Clinicians should be aware of the benefit of OCT-A as a complement to macular OCT in the evaluation of acute monocular vision loss mimicking retrobulbar optic neuropathy, particularly when signs and findings of other retinal vasculopathy are absent. PAMM should be considered in pregnant patients with acute visual changes.
Rapid typing of carbapenem-resistant Acinetobacter baumannii and Acinetobacter nosocomialis by multiplex Pan- and OXA-PCR assays
Authors: Chen Hsing-Yu , Chuang Chuan-Chung , Chou Yu-Ching , Hsu Wei-Jane , Lin I-Chieh ,   ACTION study group, Sun Jun-Ren
Published: July 2021

Introduction. Outbreaks of carbapenem-resistant

A. baumannii

and

A. nosocomialis

have occurred worldwide in healthcare settings. Rapid and reliable molecular typing of bacterial isolates is vital for the effective surveillance of institutional outbreaks. The Pan-PCR and OXA-PCR assays are two multiplex PCR-based assays for the molecular typing of

Acinetobacter

species.

Gap statement. However, few studies have investigated the discriminatory power of two multiplex PCR assays in in the genotyping of

Acinetobacter

species.

Aim. We aimed to evaluate the efficacies of the Pan-PCR and OXA-PCR assays for molecular typing of

A. baumannii

and

A. nosocomialis

.

Methodology. A total of 105 carbapenem-resistant

A. baumannii

isolates (CRABs) and 93 carbapenem-resistant

A. nosocomialis

isolates (CRANs) obtained from blood cultures were used for molecular typing by the Pan-PCR and OXA-PCR assays and two multilocus sequence typing (MLST) schemes.

Results. The isolates were individually divided into 12 and 21 different sequence types via the Pasteur and Oxford MLST schemes, respectively. Additionally, these isolates were distinguished into 18 different types by the Pan-PCR and OXA-PCR assays. The results of the Pan-PCR and OXA-PCR assays distinguished CRABs and CRANs with a sensitivity of 98.13 % and a specificity of 100 %.

Conclusion. The Pan-PCR and OXA-PCR assays are promising alternative methods for rapid molecular typing of CRABs and CRANs in a routine laboratory setting.
Is photosynthetic enhancement sustained through three years of elevated CO2exposure in 175-year oldQuercus robur?
Authors: Gardner A , Ellsworth DS , Crous KY , Pritchard J , MacKenzie AR
Published: July 2021

Current carbon cycle models attribute rising atmospheric CO2as the major driver of the increased terrestrial carbon sink, but with substantial uncertainties. The photosynthetic response of trees to elevated atmospheric CO2is a necessary step, but not the only one, for sustaining the terrestrial carbon uptake, but can vary diurnally, seasonally and with duration of CO2exposure. Hence we sought to quantify the photosynthetic response of the canopy-dominant species,Quercus robur, in a mature deciduous forest to elevated CO2(eCO2) (+150 μmol mol-1CO2) over the first three years of a long-term free air CO2enrichment facility at the Birmingham Institute of Forest Research in central England (BIFoR FACE). Over three thousand measurements of leaf gas exchange and related biochemical parameters were conducted in the upper canopy to assess the diurnal and seasonal responses of photosynthesis during the 2ndand 3rdyear of eCO2exposure. Measurements of photosynthetic capacity via biochemical parameters, derived from CO2response curves, (VcmaxandJmax) together with leaf nitrogen concentrations from the pre-treatment year to the 3rdyear of eCO2exposure, were examined. We hypothesized an initial enhancement in light-saturated net photosynthetic rates (Asat) with CO2enrichment of ≈37% based on theory but also expected photosynthetic capacity would fall over the duration of the study. Over the three-year period, Asatof upper-canopy leaves was 33 ± 8 % higher (mean and standard error) in trees grown in eCO2compared with ambient CO2(aCO2), and photosynthetic enhancement decreased with decreasing light. There were no significant effects of CO2treatment onVcmaxorJmax, nor leaf nitrogen. Our results suggest that matureQ. roburmay exhibit a sustained, positive response to eCO2without photosynthetic downregulation, suggesting that, with adequate nutrients, there will be sustained enhancement in C assimilated by these mature trees. Further research will be required to understand the location and role of the additionally assimilated carbon.
Early initiation of corticosteroids in patients hospitalized with COVID-19 not requiring intensive respiratory support: cohort study
Authors: Crothers Kristina , DeFaccio Rian , Tate Janet , Alba Patrick R. , Goetz Matthew , Jones Barbara , King Joseph T. , Marconi Vincent , Ohl Michael E. , Rentsch Christopher T. , Rodriguez-Barradas Maria C. , Shahrir Shahida , Justice Amy C. , Akgün Kathleen M. ,   Veterans Aging Cohort Study Clinical COVID-19 Working Group
Published: July 2021

Objectives

To determine whether early oral or parenteral corticosteroids compared to no corticosteroids are associated with decreased mortality in patients hospitalized with coronavirus disease 2019 (COVID-19) who are not on intensive respiratory support (IRS) within 48 hours of admission.

Design

Observational cohort study

Setting

Nationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated US national healthcare system

Participants

9,058 patients admitted to a Veterans Affairs Medical Center between June 7, 2020-December 5, 2020 within 14-days after SARS-CoV-2 positive test; exclusion criteria include less than a 48 hour stay, receipt of prior systemic corticosteroids, and no indication of acute medical care for COVID-19.

Main outcome measure

90-day all-cause mortality

Results

Of 9,058 total patients (95% men, median age 71 years, 27% black), 6,825 (75%) were not on IRS within 48 hours. Among the 3,025 patients on no oxygen, 598 (20%) received corticosteroids and 283 (9%) died; of 3,800 patients on low-flow nasal cannula oxygen (NC), 2,808 (74%) received corticosteroids and 514 (13%) died. In stratified, inverse probability weighted Cox proportional hazards models comparing those who did and did not receive corticosteroids, patients on no oxygen experienced an 89% increased risk for 90-day mortality (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.33 to 2.68); there was weak evidence of increased mortality among patients on NC (HR 1.21, 95% CI 0.94 to 1.57). Results were robust in subgroup analyses including restricting corticosteroids to dexamethasone, and in sensitivity analyses employing different modeling approaches.

Conclusions

In patients hospitalized with COVID-19, we found no evidence of a mortality benefit associated with early initiation of corticosteroids among those on no oxygen or NC in the first 48 hours, though there was evidence of potential harm. These real-world findings support that clinicians should consider withholding corticosteroids in these populations and further clinical trials may be warranted.
Single Cell Transcriptomics Reveals Cell Type Specific Diversification in Human Heart Failure
Authors: Koenig Andrew L. , Shchukina Irina , Andhey Prabhakar S , Zaitsev Konstantin , Lai Lulu , Amrute Junedh , Bajpai Geetika , Bredemeyer Andrea , Smith Gabriella , Jones Cameran , Terrebonne Emily , Rentschler Stacey L. , Artyomov Maxim N. , Lavine Kory J.
Published: July 2021

Heart failure represents a major cause of morbidity and mortality worldwide. Single cell transcriptomics have revolutionized our understanding of cell composition and associated gene expression across human tissues. Through integrated analysis of single cell and single nucleus RNA sequencing data generated from 45 individuals, we define the cell composition of the healthy and failing human heart. We identify cell specific transcriptional signatures of heart failure and reveal the emergence of disease associated cell states. Intriguingly, cardiomyocytes converge towards a common disease associated cell state, while fibroblasts and myeloid cells undergo dramatic diversification. Endothelial cells and pericytes display global transcriptional shifts without changes in cell complexity. Collectively, our findings provide a comprehensive analysis of the cellular and transcriptomic landscape of human heart failure, identify cell type specific transcriptional programs and states associated with disease, and establish a valuable resource for the investigation of human heart failure.
Neural Fragility of the Intracranial EEG Network Decreases after Surgical Resection of the Epileptogenic Zone
Authors: Li Adam , Myers Patrick , Warsi Nebras , Gunnarsdottir Kristin M. , Kim Sarah , Jirsa Viktor , Ochi Ayako , Otusbo Hiroshi , Ibrahim George M. , Sarma Sridevi V.
Published: July 2021

Over 15 million patients with epilepsy worldwide do not respond to medical therapy and may benefit from surgical treatment. In focal epilepsy, surgical treatment requires complete removal or disconnection of the epileptogenic zone (EZ). However, despite detailed multimodal pre-operative assessment, surgical success rates vary and may be as low as 30% in the most challenging cases. Here we demonstrate that neural fragility, a dynamical networked-system biomarker of epileptogenicity, decreases following successful surgical resection. Moreover, neural fragility increases or remains constant when seizure-freedom is not achieved. We demonstrate this retrospectively in a virtual patient with epilepsy using the Virtual Brain neuroinformatics platform, and subsequently on six children with epilepsy with pre- and post-resection intra-operative recordings. Finally, we compare neural fragility as a putative biomarker of epileptogenicity against established spectral metrics, such as high frequency oscillations and find that neural fragility is a superior biomarker of epileptogenicity.
Androgen receptor pathway activity assay for sepsis diagnosis and prediction of favorable prognosis
Authors: Bouwman Wilbert , Verhaegh Wim , van de Stolpe Anja
Published: July 2021

Introduction

Sepsis is a life-threatening complication of a bacterial infection. It is hard to predict which patients with a bacterial infection will develop sepsis, and accurate and timely diagnosis, as well as assessment of prognosis, is difficult. Aside from antibiotics-based treatment of the causative infection and circulation-supportive measures, treatment options remain limited. Better understanding of the immuno-pathophysiology of sepsis may lead to improved diagnostic and therapeutic solutions.

Functional activity of the innate (inflammatory) and adaptive immune response is controlled by a dedicated set of cellular signal transduction pathways in the various immune cell types. To develop an immune response-based diagnostic assay for sepsis and provide novel therapeutic targets, signal transduction pathway activities were analyzed in whole blood samples from patients with sepsis.

Methods

A validated and previously published set of signal transduction pathway (STP) assays, determining immune cell function, was used to analyze public Affymetrix expression microarray data from clinical studies containing data from pediatric and adult patients with sepsis. STP assays enable quantitative measurement of STP activity on individual patient sample data, and were used to calculate activity of androgen receptor (AR), estrogen receptor (ER), JAK-STAT1/2, JAK-STAT3, Notch, Hedgehog, TGFβ, FOXO-PI3K, MAPK-AP1, and NFκB signal transduction pathways.

Results

Activity of AR and TGFβ pathways was increased in children and adults with sepsis. Using the mean plus two standard deviations of normal pathway activity (in healthy individuals) as threshold, diagnostic assay parameters were determined. For diagnosis of pediatric sepsis, the AR pathway assay showed high sensitivity (77%) and specificity (97%), with a PPV of 99% and NPV of 50%. For prediction of favorable prognosis (survival), PPV was 95%, NPV was 21%. The TGFβ pathway activity assay performed slightly less for diagnosing sepsis, with a sensitivity of 64% and specificity of 98% (PPV 99%, NPV 39%).

Conclusion

The AR and TGFβ pathways have an immunosuppressive role, suggesting a causal relation between increased pathway activity and sepsis immunopathology. STP assays have been converted to qPCR assays for further evaluation of clinical utility for sepsis diagnosis and prediction of prognosis, as well as for prediction of risk at developing sepsis in patients with a bacterial infection. STPs may present novel therapeutic targets in sepsis.
Screening power of STIR muscle MRI in Critical illness myo-neuropathy and GBS in the ICU
Authors: Maramattom Boby Varkey
Published: July 2021

Introduction

Critical illness myo-neuropathy [CIMN] or ICU acquired weakness [CIMN] is a common cause of weakness in ICU patients. It is diagnosed by clinical features, nerve conduction studies and muscle/nerve biopsies.

Methods

The MRI muscle STIR images of 7 patients with suspected CIMN and 7 GBS patients were reviewed.

Results

All 7 patients with CIMN showed diffuse muscle edema, predominating in the lower limbs. Only one patient with GBS showed abnormal MRI changes (14%) and MRI was normal in 86%. The sensitivity of MRI to detect CIMN was 100%, whereas the specificity was 85.7%. Thus, the positive predictive value of MRI in this situation was 87.5% and the negative predictive value was 100%.

Conclusions

Muscle STIR imaging may help to differentiate between CIMN and GBS and can modify the diagnostic algorithm of CIMN.
Image and structured data analysis for prognostication of health outcomes in patients presenting to the Emergency Department during the COVID-19 pandemic
Authors: Butler Liam , Karabayir Ibrahim , Tootooni Mohammad Samie , Afshar Majid , Goldberg Ari , Akbilgic Oguz
Published: July 2021

Background

Patients admitted to the emergency department (ED) with COVID-19 symptoms are routinely required to have chest radiographs and computed tomography (CT) scans. COVID-19 infection has been directly related to development of acute respiratory distress syndrome (ARDS) and severe infections lead to admission to intensive care and can also lead to death. The use of clinical data in machine learning models available at time of admission to ED can be used to assess possible risk of ARDS, need for intensive care unit (ICU) admission as well as risk of mortality. In addition, chest radiographs can be inputted into a deep learning model to further assess these risks.

Purpose

This research aimed to develop machine and deep learning models using both structured clinical data and image data from the electronic health record (EHR) to adverse outcomes following ED admission.

Materials and Methods

Light Gradient Boosting Machines (LightGBM) was used as the main machine learning algorithm using all clinical data including 42 variables. Compact models were also developed using 15 the most important variables to increase applicability of the models in clinical settings. To predict risk of the aforementioned health outcome events, transfer learning from the CheXNet model was implemented on our data as well. This research utilized clinical data and chest radiographs of 3571 patients 18 years and older admitted to the emergency department between 9th March 2020 and 29th October 2020 at Loyola University Medical Center.

Main Findings

Our research results show that we can detect COVID-19 infection (AUC = 0.790 (0.746-0.835)) and predict the risk of developing ARDS (AUC = 0.781 (0.690-0.872), ICU admission (AUC = 0.675 (0.620-0.713)), and mortality (AUC = 0.759 (0.678-0.840)) at moderate accuracy from both chest X-ray images and clinical data.

Principal Conclusions

The results can help in clinical decision making, especially when addressing ARDS and mortality, during the assessment of patients admitted to the ED with or without COVID-19 symptoms.
Anxiety and depression symptoms after COVID-19 infection: results from the COVID Symptom Study app
Authors: Klaser Kerstin , Thompson Ellen J. , Nguyen Long H. , Sudre Carole H. , Antonelli Michela , Murray Benjamin , Canas Liane S. , Molteni Erika , Graham Mark S. , Kerfoot Eric , Chen Liyuan , Deng Jie , May Anna , Hu Christina , Guest Andy , Selvachandran Somesh , Drew David A , Modat Marc , Chan Andrew T. , Wolf Jonathan , Spector Tim D. , Hammers Alexander , Duncan Emma L. , Ourselin Sebastien , Steves Claire J.
Published: July 2021

Background

Mental health issues have been reported after SARS-CoV-2 infection. However, comparison to prevalence in uninfected individuals and contribution from common risk factors (e.g., obesity, comorbidities) have not been examined. We identified how COVID-19 relates to mental health in the large community-based COVID Symptom Study.

Methods

We assessed anxiety and depression symptoms using two validated questionnaires in 413,148 individuals between February and April 2021; 26,998 had tested positive for SARS-CoV-2. We adjusted for physical and mental pre-pandemic comorbidities, BMI, age, and sex.

Findings

Overall, 26.4% of participants met screening criteria for general anxiety and depression. Anxiety and depression were slightly more prevalent in previously SARS-CoV-2 positive (30.4%) vs. negative (26.1%) individuals. This association was small compared to the effect of an unhealthy BMI and the presence of other comorbidities, and not evident in younger participants (≤40 years). Findings were robust to multiple sensitivity analyses. Association between SARS-CoV-2 infection and anxiety and depression was stronger in individuals with recent (<30 days) vs. more distant (>120 days) infection, suggesting a short-term effect.

Interpretation

A small association was identified between SARS-CoV-2 infection and anxiety and depression symptoms. The proportion meeting criteria for self-reported anxiety and depression disorders is only slightly higher than pre-pandemic.

Funding

Zoe Limited, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, Medical Research Council UK
‘The Thousand Polish Genomes Project’ - a national database of Polish variant allele frequencies
Authors: Kaja Elżbieta , Lejman Adrian , Sielski Dawid , Sypniewski Mateusz , Gambin Tomasz , Suchocki Tomasz , Dawidziuk Mateusz , Golik Paweł , Wojtaszewska Marzena , Stępień Maria , Szyda Joanna , Lisiak-Teodorczyk Karolina , Wolbach Filip , Kołodziejska Daria , Ferdyn Katarzyna , Woźna Alicja , Żytkiewicz Marcin , Bodora-Troińska Anna , Elikowski Waldemar , Król Zbigniew , Zaczyński Artur , Pawlak Agnieszka , Gil Robert , Wierzba Waldemar , Dobosz Paula , Zawadzka Katarzyna , Zawadzki Paweł , Sztromwasser Paweł
Published: July 2021

Although Slavic populations account for over 3.5% of world inhabitants, no centralized, open source reference database of genetic variation of any Slavic population exists to date. Such data are crucial for either biomedical research and genetic counseling and are essential for archeological and historical studies. Polish population, homogenous and sedentary in its nature but influenced by many migrations of the past, is unique and could serve as a good genetic reference for middle European Slavic nations.

The aim of the present study was to describe first results of analyses of a newly created national database of Polish genomic variant allele frequencies. Never before has any study on the whole genomes of Polish population been conducted on such a large number of individuals (1,079).

A wide spectrum of genomic variation was identified and genotyped, such as small and structural variants, runs of homozygosity, mitochondrial haplogroups and Mendelian inconsistencies. The allele frequencies were calculated for 943 unrelated individuals and released publicly as The Thousand Polish Genomes database. A precise detection and characterisation of rare variants enriched in the Polish population allowed to confirm the allele frequencies for known pathogenic variants in diseases, such as Smith-Lemli-Opitz syndrome (SLOS) or Nijmegen breakage syndrome (NBS). Additionally, the analysis of OMIM AR genes led to the identification of 22 genes with significantly different cumulative allele frequencies in the Polish (POL) vs European NFE population. We hope that The Thousand Polish Genomes database will contribute to the worldwide genomic data resources for researchers and clinicians.
Holistic Characterization of Tumor Monocyte-to-Macrophage Differentiation Integrates Distinct Immune Phenotypes in Kidney Cancer
Authors: Mujal Adriana M. , Combes Alexis J. , Rao Arjun R. , Binnewies Mikhail , Samad Bushra , Tsui Jessica , Boissonnas Alexandre , Pollack Joshua L. , Argüello Rafael J. , Ruhland Megan K. , Barry Kevin C. , Chan Vincent , Krummel Matthew F.
Published: July 2021

The tumor immune microenvironment (TIME) is commonly infiltrated by diverse collections of myeloid cells. Yet, the complexity of myeloid cell identity and plasticity has challenged efforts to define bona fide populations and determine their connections to T cell function and their relation to patient outcome. Here we leverage single-cell RNA-sequencing (scRNA-seq) analysis of several mouse and human tumors and find that monocyte-macrophage diversity is characterized by a combination of conserved lineage states as well as transcriptional programs accessed along the differentiation trajectory. Using mouse models, we also find that tumor monocyte-to-macrophage progression is profoundly tied to regulatory T cell (Treg) abundance. Importantly, in human kidney cancer, heterogeneity in macrophage accumulation and myeloid composition corresponded to variance in, not only Treg density, but also the quality of infiltrating CD8+ T cells. In this way, holistic analysis of monocyte-to-macrophage differentiation creates a framework for critically different immune states in kidney tumors.