bluuebunny/crossref_metadata_2025_split huggingface dataset:
H4K20me3 and H3K79me3 epigenetic changes in Endometriosis and endometrial tissues (LB844)
Authors: Rodriguez‐Deliz Carla , Monteiro Janice , Cruz‐Cosme Ruth , Flores Idhaliz 
Published: June 2021

The significance of epigenetic changes in the etiology and pathogenesis of endometriosis is being progressively recognized. However, the function of lysine‐histone epigenetic modifications and furthermore, their role in the pathology of this disease remains unclear. We lead a study aimed to identify specific epigenetic profiles and evaluate possible associations with gene expression to provide insights about the pathological processes occurring in endometriosis. Objective: Identify the methylation pattern of lysine‐histones H4K20me3 and H3K79me3 and chromatin modulation by gene activation in endometrial tissues. Methods: We used endometrial tissues from 9 women, with and without endometriosis. Macro‐dissection was achieved by following pathology protocols. Tissues were homogenized and disaggregated using a bullet blender. Total histone extraction was carried out using an Epiquick Kit (Epigentek) and then, western blots (WB) were performed. Both, the H4K20me3 and H3K79me3 were detected in all endometrial tissues by WB. Chromatin immuno‐precipitation (ChIP) assay was performed using an Epiquick Kit. The promoter gene region between ‐27024569‐ 27025759, 100027589 ‐ 100028694 and ‐41275101 ‐ 4127670 of the ARID1A (220 pb), LOX‐4 (176 pb) and CTNNB1 (241 pb) genes were amplified with the correspondent primers, designed using ENCODE at UCSC Genome Browser program. PCR products were electrophoresed, stained with SYBR™ Green, and visualized. Results: There were higher levels of methylation of both 17kDa H4K20me3 and H3K79me3 in the endometrial tissue from women with endometriosis when compared to women without endometriosis (p < 0.05). ChIP assay demonstrated that ARID1A was expressed with H4K20me3, whereas with H3K79me3, it was silenced. However, Lox‐4 was silenced by both histones. Conclusion: Our results show that histone H4K20me3 and H3K79me3 modifications may be useful as a biomarker for detection and treatment of endometrial lesions.Grant Funding Source: NIH‐NICHD Grant # R01‐050559, NIGMS S06‐GM 08239 (IF) ARRA supplement to R01‐050559 (IF), RCMI G12‐MD007579, PRCTRC U54‐MD007587, NIH NIGMS R25GM096955 to UPR‐Ponce.
Lymph transport in rat mesenteric lymphatics experiencing edemagenic stress (LB851)
Authors: Rahbar Elaheh , Akl Tony , Cote Gerard , Moore James , Zawieja David 
Published: June 2021

Objective: To assess lymphatic adaptations to edema, we evaluated lymph transport function in rat mesenteric lymphatics under normal and increased fluid volume (edemagenic) conditions in situ.Methods: Twelve rats were infused with saline (venous infusion, 0.2 ml/min/100g body weight) to induce edema. We intravitally measured mesenteric lymphatic diameter and contraction frequency, as well as immune cell velocity and density before, during and after infusion.Results: A 10‐ and 6‐fold increase in lymph velocity (0.1‐1 mm/s) and flow rate (0.1‐0.6 µL/min), were observed post‐infusion, respectively (p<0.05). There were also increases in contraction frequency and fractional pump flow 1‐minute post‐infusion (p<0.05). Time‐averaged wall shear stress increased 10 times post‐infusion to nearly 1.5 dynes/cm2 (p<0.05). Similarly, maximum shear stress rose from 5 dynes/cm2 to 40 dynes/cm2.Conclusions: Lymphatic vessels adapted to edemagenic stress by increasing lymph transport. Specifically, increases in lymphatic contraction frequency, lymph velocity, and shear stress were statistically significant. Although the changes in lymphatic diameter were not statistically significant, lymph pumping increased post‐infusion. These results suggest that edemagenic conditions stimulate lymph transport via increases in lymphatic contraction frequency, lymph velocity and flow. These changes, consequently, resulted in large increases in wall shear stress, which will activate nitric oxide pathways and modulate lymphatic transport function.Grant Funding Source: NIH Grant No. R01 HL094269, NSF Graduate Research Fellowship
Virtual Team Rounding: A Cross-Specialty Inpatient Care Staffing Program to Manage COVID-19 Surges
Authors: Becker Nora V. , Bakshi Salina , Martin Kate L. , Bougrine Amina , Andrade Jonathan , Massey Paul R. , Hirner Jesse P. , Eccleston Julie , Choudhry Niteesh K. , Britton Kathryn A. , Landman Adam B. , Licurse Adam M. , Carlile Narath , Mendu Mallika L. 
Published: June 2021

Problem
The SARS-CoV-2 (COVID-19) pandemic presented numerous challenges to inpatient care, including overtaxed inpatient medicine services, surges in patient censuses, disrupted patient care and educational activities for trainees, underused providers in certain specialties, and personal protective equipment shortages and new requirements for physical distancing. In March 2020, as the COVID-19 surge began, an interdisciplinary group of administrators, providers, and trainees at Brigham and Women’s Hospital created an inpatient virtual staffing model called the Virtual Team Rounding Program (VTRP).

Approach
The conceptual framework guiding VTRP development was rapid-cycle innovation. The VTRP was designed iteratively using feedback from residents, physician assistants, attendings, and administrators from March to June 2020. The VTRP trained and deployed a diverse set of providers across specialties as “virtual rounders” to support inpatient teams by joining and participating in rounds via videoconference and completing documentation tasks during and after rounds. The program was rapidly scaled up from March to June 2020.

Outcomes
In a survey of inpatient providers at the end of the pilot phase, 10/10 (100%) respondents reported they were getting either “a lot” or “a little” benefit from the VTRP and did not find the addition of the virtual rounder burdensome. During the scaling phase, the program grew to support 24 teams. In a survey at the end of the contraction phase, 117/187 (62.6%) inpatient providers who worked with a virtual rounder felt the rounder saved them time. VTRP leadership collaboratively and iteratively developed best practices for challenges encountered during implementation.

Next Steps
Virtual rounding provides a valuable extension of inpatient teams to manage COVID-19 surges. Future work will quantitatively and qualitatively assess the impact of the VTRP on inpatient provider satisfaction and well-being, virtual rounders’ experiences, and patient care outcomes.
Is Academic Attainment or Situational Judgment Test Performance in Medical School Associated With the Likelihood of Disciplinary Action? A National Retrospective Cohort Study
Authors: Sam Amir H. , Bala Laksha , Westacott Rachel J. , Brown Celia 
Published: June 2021

PurposeDisciplinary action imposed on physicians indicates their fitness to practice medicine is impaired and patient safety is potentially at risk. This national retrospective cohort study sought to examine whether there was an association between academic attainment or performance on a situational judgment test (SJT) in medical school and the risk of receiving disciplinary action within the first 5 years of professional practice in the United Kingdom.MethodThe authors included data from the UK Medical Education Database for 34,865 physicians from 33 U.K. medical schools that started the UK Foundation Programme (similar to internship) between 2014 and 2018. They analyzed data from 2 undergraduate medical assessments used in the United Kingdom: the Educational Performance Measure (EPM), which is based on academic attainment, and SJT, which is an assessment of professional attributes. The authors calculated hazard ratios (HRs) for EPM and SJT scores.ResultsThe overall rate of disciplinary action was low (65/34,865, 0.19%) and the mean time to discipline was 810 days (standard deviation [SD] = 440). None of the physicians with fitness to practice concerns identified as students went on to receive disciplinary action after they qualified as physicians. The multivariate survival analysis demonstrated that a score increase of 1 SD (approximately 7.6 percentage points) on the EPM reduced the hazard of disciplinary action by approximately 50% (HR = 0.51; 95% confidence interval [CI]: 0.38, 0.69;P< .001). There was not a statistically significant association between the SJT score and the hazard of disciplinary action (HR = 0.84; 95% CI: 0.62, 1.13;P= .24).ConclusionsAn increase in EPM score was significantly associated with a reduced hazard of disciplinary action, whereas performance on the SJT was not. Early identification of increased risk of disciplinary action may provide an opportunity for remediation and avoidance of patient harm.
Individual mortality risk predictive system of patients with acute-on-chronic liver failure based on a random survival forest model
Authors: Zhang Zhi-Qiao , He Gang , Luo Zhao-Wen , Cheng Can-Chang , Wang Peng , Li Jing , Zhu Ming-Gu , Ming Lang , He Ting-Shan , Ouyang Yan-Ling , Huang Yi-Yan , Wu Xing-Liu , Ye Yi-Nong 
Published: June 2021

Abstract

Background:
The basis of individualized treatment should be individualized mortality risk predictive information. The present study aimed to develop an online individual mortality risk predictive tool for acute-on-chronic liver failure (ACLF) patients based on a random survival forest (RSF) algorithm.

Methods:
The current study retrospectively enrolled ACLF patients from the Department of Infectious Diseases of The First People's Hospital of Foshan, Shunde Hospital of Southern Medical University, and Jiangmen Central Hospital. Two hundred seventy-six consecutive ACLF patients were included in the present study as a model cohort (n = 276). Then the current study constructed a validation cohort by drawing patients from the model dataset based on the resampling method (n = 276). The RSF algorithm was used to develop an individual prognostic model for ACLF patients. The Brier score was used to evaluate the diagnostic accuracy of prognostic models. The weighted mean rank estimation method was used to compare the differences between the areas under the time-dependent ROC curves (AUROCs) of prognostic models.

Results:
Multivariate Cox regression identified hepatic encephalopathy (HE), age, serum sodium level, acute kidney injury (AKI), red cell distribution width (RDW), and international normalization index (INR) as independent risk factors for ACLF patients. A simplified RSF model was developed based on these previous risk factors. The AUROCs for predicting 3-, 6-, and 12-month mortality were 0.916, 0.916, and 0.905 for the RSF model and 0.872, 0.866, and 0.848 for the Cox model in the model cohort, respectively. The Brier scores were 0.119, 0.119, and 0.128 for the RSF model and 0.138, 0.146, and 0.156 for the Cox model, respectively. The nonparametric comparison suggested that the RSF model was superior to the Cox model for predicting the prognosis of ACLF patients.

Conclusions:
The current study developed a novel online individual mortality risk predictive tool that could predict individual mortality risk predictive curves for individual patients. Additionally, the current online individual mortality risk predictive tool could further provide predicted mortality percentages and 95% confidence intervals at user-defined time points.
Current and future drug combination strategies based on programmed death-1/programmed death-ligand 1 inhibitors in non-small cell lung cancer
Authors: Cheng Ying , Li Hui , Zhang Liang , Liu Jing-Jing , Yang Chang-Liang , Zhang Shuang 
Published: June 2021

Abstract
In recent years, immune checkpoint inhibitors (ICIs) have made breakthroughs in the field of lung cancer and have become a focal point for research. Programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor monotherapy was the first to break the treatment pattern for non-small cell lung cancer (NSCLC). However, owing to the limited benefit of ICI monotherapy at the population level and its hyper-progressive phenomenon, it may not meet clinical needs. To expand the beneficial range of immunotherapy and improve its efficacy, several research strategies have adopted the use of combination immunotherapy. At present, multiple strategies, such as PD-1/PD-L1 inhibitors combined with chemotherapy, anti-angiogenic therapy, cytotoxic T-lymphocyte-associated protein 4 inhibitors, and radiotherapy, as well as combined treatment with new target drugs, have been evaluated for clinical practice. To further understand the current status and future development direction of immunotherapy, herein, we review the recent progress of ICI combination therapies for NSCLC.
Stem cell therapy for chronic obstructive pulmonary disease
Authors: Chen Yun-Tian , Miao Kang , Zhou Linfu , Xiong Wei-Ning 
Published: June 2021

Abstract
Chronic obstructive pulmonary disease (COPD), characterized by persistent and not fully reversible airflow restrictions, is currently one of the most widespread chronic lung diseases in the world. The most common symptoms of COPD are cough, expectoration, and exertional dyspnea. Although various strategies have been developed during the last few decades, current medical treatment for COPD only focuses on the relief of symptoms, and the reversal of lung function deterioration and improvement in patient's quality of life are very limited. Consequently, development of novel effective therapeutic strategies for COPD is urgently needed. Stem cells were known to differentiate into a variety of cell types and used to regenerate lung parenchyma and airway structures. Stem cell therapy is a promising therapeutic strategy that has the potential to restore the lung function and improve the quality of life in patients with COPD. This review summarizes the current state of knowledge regarding the clinical research on the treatment of COPD with mesenchymal stem cells (MSCs) and aims to update the understanding of the role of MSCs in COPD treatment, which may be helpful for developing effective therapeutic strategies in clinical settings.
Identification of Hard Ticks in the United States: A Practical Guide for Clinicians and Pathologists
Authors: Laga Alvaro C. , Mather Thomas N. , Duhaime Roland J. , Granter Scott R. 
Published: June 2021

Abstract:
According to guidelines published by the Infectious Disease Society of America, Lyme disease prophylaxis is possible if a tick can be identified as Ixodes scapularis (nymphal or adult) within 72 hours of tick removal. However, a recent survey of medical practitioners indicates generally poor proficiency in tick identification. In this study, we provide a simple, practical guide to aid medical practitioners in identifying the most commonly encountered human biting ticks of North America.
Freeze-Dried Versus Cryopreserved Amniotic Membranes in Corneal Ulcers Treated by Overlay Transplantation: A Case–Control Study
Authors: Memmi Benjamin , Leveziel Loïc , Knoeri Juliette , Leclère Amélie , Ribes Olivier , Despiaux Marie-Claire , Bouheraoua Nacim , Nordmann Jean-Philippe , Baudouin Christophe , Borderie Vincent 
Published: June 2021

Purpose:
The purpose of this study was to assess cryopreserved amniotic membrane (C-AM) versus chorion-free freeze-dried amniotic membrane (FD-AM) overlay transplantation for corneal ulcers in a French tertiary ophthalmology hospital.

Methods:
Between March and July 2020, when C-AMs were not available because of the COVID-19 pandemic, 28 corneal ulcers underwent FD-AM overlay transplantation and were retrospectively compared with 22 corneal ulcers treated with C-AM during the same period in 2018. All patients had at least 3 months of follow-up, and those who underwent combined surgeries were excluded. Ulcers were assessed at baseline and then at 72 hours, 1 month, and 3 months. Population demographics, follow-up time, ulcer etiologies, epithelial defect size, ulcer depth, and complications were also recorded.

Results:
Baseline characteristics and clinical features of both groups were comparable. There was no statistically significant difference in the number of overlay AM transplantations (P = 0.52) or early detachments (P = 0.57). At 3 months, the corneal healing rate was almost the same in both groups (89% and 91% for FD-AM and C-AM, respectively; P = 0.87). Complications were equally uncommon (11% and 9%, respectively; P = 0.92). In logistic regression, the type of the membrane did not influence corneal healing at 1 month (P = 0.42) or 3 months (P = 0.99), regardless of the depth of the ulcer. However, whatever the type of AM used, the deeper the ulcer was, the less likely it was to heal at 3 months (P = 0.02).

Conclusions:
This is the first study that provides positive insight into the effectiveness of FD-AM compared with C-AM when used as overlay transplantation for treating corneal ulcers.
Intraobserver Repeatability of Tomographic, Pachymetric, and Anatomical Measurements in Healthy Eyes Using a New Swept-Source Optical Coherence Topographer
Authors: Escolano Serrano Jaime , Tarazona Jaimes Claudia Patricia , Monera Lucas Carlos Enrique , Romero Valero Daniel , Moya Martínez Alejandro , Martínez Toldos José Juan 
Published: June 2021

Purpose:
The purpose of this study was to evaluate the intraobserver repeatability of several corneal parameters in healthy eyes using a new swept-source optical coherence topographer.

Methods:
Fifty right eyes of 50 subjects were enrolled in this study. A single examiner performed 3 consecutive measurements using the Anterion swept-source optical coherence tomography. The following corneal parameters were evaluated: average keratometry (K), steep K, flat K, astigmatism, best fit sphere, and maximum keratometry on the anterior and posterior surfaces at 3 mm, average K, steep K, flat K, and astigmatism in the total corneal power map at 3 mm, central corneal thickness and thinnest point thickness in the pachymetric map, and corneal diameter. To assess the repeatability of the measurements, we calculated the following indexes: intrasubject SD (Sw), coefficient of variation, coefficient of repeatability, and intraclass correlation coefficient (ICC).

Results:
High repeatability was reported for all the evaluated corneal parameters, with Sw values lower than 0.027, coefficient of variation values lower than 0.066%, and coefficient of repeatability values lower than 0.187. ICC values showed a high correlation between measurements in all cases, being the lowest value for the astigmatism of the anterior surface (ICC = 0.92); for the rest, ICC values were larger than 0.98. Finally, we have not found statistically significant differences between repeated measurements (P > 0.05).

Conclusions:
The anterior segment measurements provided by the Anterion swept-source optical coherence tomography device show high intraobserver repeatability in healthy eyes.
Factors predicting the risk of biochemical incomplete response in well-differentiated thyroid cancer after total thyroidectomy
Authors: Ora Manish , Nazar Aftab Hasan , Mishra Prabhakar , Barai Sukanta , Arya Amitabh , Pradhan Prasanta Kumar , Gambhir Sanjay 
Published: June 2021

Background
Differentiated thyroid cancer (DTC) is the most common endocrine carcinoma with an overall good prognosis. However, persistent or recurrent disease (P/R disease) and incomplete biochemical response (BIR) are causes of morbidity. Histopathology and TNM stage may not predict P/R disease and BIR in all patients. Various clinical parameters, histopathological features and preablative-stimulated thyroglobulin (presTg) have been proposed to predicts P/R disease. However, there is uncertainty for presTg cutoff and diagnostic accuracy. The study’s objective was to predict the BIR before radioiodine ablation from available clinical, histopathological and biochemical parameters.

Methods
A retrospective, single-center study, including DTC patients, was done. Demography and factors predicting BIR evaluated.

Result
In comparison to the patients in remission, patients with BIR were older (P = 0.042), had higher presTg (P < 0.001), and lymph nodes (LN) metastases [central or lateral compartment (P < 0.001)]. Visualization of LN on whole-body scan (P = 0.014), higher TNM stage (P = 0.001) and distance metastasis (P < 0.001) were also associated with BIR. On multivariate analysis, high presTg (P < 0.001) and LN metastases (LNscan and histopathologically proven LN involvement, P < 0.001) were associated with BIR. A presTg level ≥12.30 ng/ml has high sensitivity (90.6%) and specificity (80.6%) to predict the BIR (odds ratio 39.90).

Conclusions
The presTg and LN involvement are robust markers that predict BIR. A raised presTg level with LN metastases and nonvisualization of the LN on the whole-body scan is a worrying feature for the future BIR. We propose the inclusion of high presTg as a high-risk factor in DTC.
Scapulothoracic Articulation Disorders on 99mTc-MDP Bone Scintigraphy
Authors: Crowley Connor , Rieter William J. 
Published: June 2021

Abstract
Disorders of the scapulothoracic articulation can cause significant pain, as well as an audible “snapping” or crepitus in advanced cases. Although radiography, CT, and MRI are used in the diagnosis of these conditions, little is known about their manifestations on nuclear imaging. We present a case of symmetric uptake at the inferior scapulothoracic articulations mimicking metastatic disease on a staging bone scan. Recognition of this pattern of activity is not only important to accurately exclude malignancy, but also to aid referring providers in addressing potential causes of patient morbidity.
Metrics to relate COVID-19 wastewater data to clinical testing dynamics
Authors: Xiao Amy , Wu Fuqing , Bushman Mary , Zhang Jianbo , Imakaev Maxim , Chai Peter R , Duvallet Claire , Endo Noriko , Erickson Timothy B , Armas Federica , Arnold Brian , Chen Hongjie , Chandra Franciscus , Ghaeli Newsha , Gu Xiaoqiong , Hanage William P , Lee Wei Lin , Matus Mariana , McElroy Kyle A , Moniz Katya , Rhode Steven F , Thompson Janelle , Alm Eric J 
Published: June 2021

AbstractWastewater surveillance has emerged as a useful tool in the public health response to the COVID-19 pandemic. While wastewater surveillance has been applied at various scales to monitor population-level COVID-19 dynamics, there is a need for quantitative metrics to interpret wastewater data in the context of public health trends. We collected 24-hour composite wastewater samples from March 2020 through May 2021 from a Massachusetts wastewater treatment plant and measured SARS-CoV-2 RNA concentrations using RT-qPCR. We show that the relationship between wastewater viral titers and COVID-19 clinical cases and deaths varies over time. We demonstrate the utility of three new metrics to monitor changes in COVID-19 epidemiology: (1) the ratio between wastewater viral titers and clinical cases (WC ratio), (2) the time lag between wastewater and clinical reporting, and (3) a transfer function between the wastewater and clinical case curves. We find that the WC ratio increases after key events, providing insight into the balance between disease spread and public health response. We also find that wastewater data preceded clinically reported cases in the first wave of the pandemic but did not serve as a leading indicator in the second wave, likely due to increased testing capacity. These three metrics could complement a framework for integrating wastewater surveillance into the public health response to the COVID-19 pandemic and future pandemics.