bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional repression of TaNOX10 by TaWRKY19 compromises ROS generation and enhances wheat susceptibility to stripe rust
Authors: Wang Ning , Fan Xin , He Mengying , Hu Zeyu , Tang Chunlei , Zhang Shan , Lin Dexing , Gan Pengfei , Wang Jianfeng , Huang Xueling , Gao Caixia , Kang Zhensheng , Wang Xiaojie 
Published: January 2022

Abstract
Reactive oxygen species (ROS) are vital for plant immunity and regulation of their production is crucial for plant health. While the mechanisms that elicit ROS production have been relatively well studied, those that repress ROS generation are less well understood. Here, via screening Brachypodium distachyon RNA interference mutants, we identified BdWRKY19 as a negative regulator of ROS generation whose knockdown confers elevated resistance to the rust fungus Puccinia brachypodii. The three wheat paralogous genes TaWRKY19 are induced during infection by virulent P. striiformis f. sp. tritici (Pst) and have partially redundant roles in resistance. The stable overexpression of TaWRKY19 in wheat increased susceptibility to an avirulent Pst race, while mutations in all three TaWRKY19 copies conferred strong resistance to Pst by enhancing host plant ROS accumulation. We show that TaWRKY19 is a transcriptional repressor that binds to a W-box element in the promoter of TaNOX10, which encodes an NADPH oxidase and is required for ROS generation and host resistance to Pst. Collectively, our findings reveal that TaWRKY19 compromises wheat resistance to the fungal pathogen and suggest TaWRKY19 as a potential target to improve wheat resistance to the commercially important wheat stripe rust fungus.
Developing a Parental Leave Policy in Undergraduate Medical Education: A Successful Student–Administration Collaboration
Authors: Gaghan Lindsey , Parker Bao-Tran 
Published: January 2022

Problem
Most medical schools lack parental leave policies, leaving medical students vulnerable to discrimination, diminished educational opportunities, delays in graduation or matching, and breaches of privacy. This report outlines the steps taken by student-leaders to advocate for such a policy and the lessons learned along the way.

Approach
In September 2018, leaders of the Family Support Initiative, a medical student interest group at the University of North Carolina School of Medicine, initiated the process of advocating for a clear, official parental leave policy. Certain elements proved essential in bringing about institutional change, including active involvement of a faculty advocate; well-documented student testimonials; commitment from top administrative leaders; involvement of the Title IX office and legal counsel; creating space for authentic collaboration; building clear, flexible mechanisms for making up missed time; and consideration of preclinical training and regional campuses.

Outcomes
The Education Committee unanimously approved the New Child Adjustment Policy in June 2019. The policy was published online; shared broadly in various formats with students, faculty, and members of the university health system; and announced at class meetings and new student orientations. Faculty advisors were trained on its content and procedures. Administrators and students report that the policy has informed their discussions around family planning and made these conversations easier to navigate.

Next Steps
The process model outlined here is intended to serve as a roadmap for other institutions. While student input should inform the development of parental leave policies, institutions are morally and ethically responsible for providing parental leave policies that address the key components outlined here. The authors will further study the impact of this policy on student satisfaction and academic performance. The authors urge the Liaison Committee on Medical Education and Commission on Osteopathic College Accreditation to make clear, inclusive, student-centered parental leave policies a requirement for accreditation.
ICU Resource Limitations During Peak Seasonal Influenza: Results of a 2018 National Feasibility Study
Authors: Lane Christianne Joy , Bhatnagar Manas , Lutrick Karen , Maves Ryan C. , Weiner Debra , Rios Olvera Daisy , Uyeki Timothy M. , Cobb J. Perren , Brown Joan C. ,   for the Discovery Program Resilience and Emergency Preparedness (Discovery PREP)
Published: January 2022

OBJECTIVES:
Demonstrate the feasibility of weekly data collection and analysis of public health emergency (PHE) data. Assess fluctuations in, and challenges of, resource matching and potential effect on patient care for influenza in ICUs.

DESIGN:
Multicenter prospective noninterventional study testing effectiveness of leveraging the Discovery Critical Care Research Network Program for Resilience and Emergency Preparedness (Discovery-PREP) in performing PHE research. A 20-question internet survey was developed to prospectively assess ICU influenza-related resource stress. An informatics tool was designed to track responses; data were analyzed within 24 hours of weekly survey completion by the team biostatistician for timely reporting.

PARTICIPANTS:
Critical care and Emergency Medicine Discovery-PREP network investigators self-selected to participate in the voluntary query.

SETTING:
ICUs of 13 hospitals throughout the United States, 12 academic, and one community.

INTERVENTIONS:
ICU physicians were electronically surveyed weekly over 17 weeks during the influenza season (January 2018–April 2018). Responses were collected for 48 hours after each email query.

MEASUREMENTS AND MAIN RESULTS:
The average weekly response among the sites was 79% (range, 65–100%). Significant stress, defined as alterations in ICU staffing and/or resource allocation, occurred in up to 41% of sites during the national peak of influenza activity. These alterations included changes in staffing, not accepting external patient transfers, and canceling elective surgery. During this same period, up to 17% of the sites indicated that these changes might not have been sufficient to prevent potentially avoidable patient harm.

CONCLUSIONS:
This novel approach to querying ICU operational stress indicated that almost half of participating sites experienced critical care resource limitations during peak influenza season and required process and/or staffing changes to better balance resources with patient care demands. This weekly national reporting infrastructure could be adapted and expanded to better inform providers, hospital emergency management teams, and government leaders during PHEs.
A Prospective Observational Study Comparing Clinical Sepsis Criteria to Protein Biomarkers Reveals a Role for Vascular Dysfunction in Burn Sepsis
Authors: Burmeister David M. , Heard Tiffany C. , Chao Tony , Alcover Karl , Wagner Amanda , Chung Kevin K. , Akers Kevin S. 
Published: January 2022

OBJECTIVES:
To compare the diagnostic value of clinical sepsis criteria to novel protein biomarkers in the burn patient.

DESIGN:
Prospective observational study.

SETTING:
American Burn Association verified Burn Center ICU.

PATIENTS:
Burn patients (n = 24) and healthy volunteers (n = 10).

INTERVENTIONS:
Enrolled burn patients (n = 24) were stratified based on whether or not they met a clinical definition of sepsis. Four separate clinical criteria for sepsis were analyzed for their diagnostic sensitivity and specificity, which were compared to a panel of protein biomarkers. The most significant protein biomarkers were further analyzed via the area under the receiver operating characteristic curves (AUROCs).

MEASUREMENTS AND MAIN RESULTS:
Of the clinical criteria, SEPSIS-2 criteria led to the highest AUROC (0.781; p < 0.001), followed by the quick Sequential Organ Failure Assessment score (AUROC = 0.670; p = 0.022). Multiplexing revealed a number of inflammatory proteins (complement C5) and matrix metalloproteinases (MMP1, MMP7) that were significantly elevated in septic samples compared with both healthy controls and nonseptic burn samples. Furthermore, three proteins associated with endothelial dysfunction and glycocalyx shedding revealed diagnostic potential. Specifically, syndecan-1, p-selectin, and galectin-1 were all significantly elevated in sepsis, and all resulted in an AUROC greater than 0.7; analyzing the sum of these three markers led to an AUROC of 0.808.

CONCLUSIONS:
These data reveal several potential biomarkers that may help with sepsis diagnosis in the burn patient. Furthermore, the role of endotheliopathy as a mechanistic etiology for sepsis after burns warrants further investigation.
Resuscitation fluids as drugs: targeting the endothelial glycocalyx
Authors: Wang Guangjian , Zhang Hongmin , Liu Dawei , Wang Xiaoting 
Published: January 2022

Abstract
Fluid resuscitation is an essential intervention in critically ill patients, and its ultimate goal is to restore tissue perfusion. Critical illnesses are often accompanied by glycocalyx degradation caused by inflammatory reactions, hypoperfusion, shock, and so forth, leading to disturbed microcirculatory perfusion and organ dysfunction. Therefore, maintaining or even restoring the glycocalyx integrity may be of high priority in the therapeutic strategy. Like drugs, however, different resuscitation fluids may have beneficial or harmful effects on the integrity of the glycocalyx. The purpose of this article is to review the effects of different resuscitation fluids on the glycocalyx. Many animal studies have shown that normal saline might be associated with glycocalyx degradation, but clinical studies have not confirmed this finding. Hydroxyethyl starch (HES), rather than other synthetic colloids, may restore the glycocalyx. However, the use of HES also leads to serious adverse events such as acute kidney injury and bleeding tendencies. Some studies have suggested that albumin may restore the glycocalyx, whereas others have suggested that balanced crystalloids might aggravate glycocalyx degradation. Notably, most studies did not correct the effects of the infusion rate or fluid volume; therefore, the results of using balanced crystalloids remain unclear. Moreover, mainly animal studies have suggested that plasma may protect and restore glycocalyx integrity, and this still requires confirmation by high-quality clinical studies.
Update on classification, diagnosis, and management of immunoglobulin G4-related disease
Authors: Chen Yu , Cai Shaozhe , Dong Lingli , Umehara Hisanori 
Published: January 2022

Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized chronic fibro-inflammatory autoimmune disease, and its recognition has been constantly increasing worldwide over the last few years. A correct and timely recognition, as well as appropriate intervention, is crucial for the treatment of IgG4-RD. For certain subtypes of IgG4-RD, organ-specific criteria are formulated to make the diagnosis more accurate. New biomarkers have emerged in the recent years to aid the disease diagnosis, its prognosis prediction, as well as therapy response monitoring. Although recurrence is very common in IgG4-RD, glucocorticoid is still the first-line treatment for the majority of patients. The factors that affect the likelihood of disease relapse are multifaceted. The selection strategy of various steroid-sparing agents is still being explored. Besides, when patients have special sites involvement leading to severe clinical conditions, surgical operation or interventional therapy should also be considered. An update on classification, diagnosis, and management of IgG4-RD is provided in the current study to fully elucidate the recommended clinical practice of this mysterious disease.
Chemotherapy-Induced Arrhythmias
Authors: Essa Hani , Dobson Rebecca , Lip Gregory Y. H. 
Published: January 2022

Abstract:
Cardio-oncology is a subspeciality within cardiology that has developed primarily as a consequence of the cardiovascular implications of cancer and its therapeutics. Arrhythmias are increasingly recognized as an adverse feature of many chemotherapeutic agents. This relationship is poorly defined and studied in the literature compared with other side effects of chemotherapy. In this review, we appraise the published literature on arrhythmogenic consequences of chemotherapeutic agents and summarize the available evidence. Atrial fibrillation (AF) and other supraventricular tachycardias are frequently observed in patients receiving chemotherapy. High rates of AF are seen with certain agents such as tyrosine kinase inhibitors eg, ibrutinib and the mechanism for this is poorly defined but likely related to off-target effects. The management of AF in cardio-oncology is similar to that of the noncancer patient with certain nuances. Mainly that bleeding and stroke risk stratification tools are not validated in the cancer population. In this patient cohort, treatment decisions are usually led by anecdotal evidence rather than an evidence base. This leads to treatment heterogeneity between clinicians. Furthermore, various drug interactions can limit the choice of therapy, particularly with respect to anticoagulant drugs. Many chemotherapeutic agents have been implicated in QT interval (A Measurement calculated from the start of the Q wave to the end of the T wave on the electrocardiogram approximating the time taken for ventricular relaxation.) of these, arsenic trioxide and several tyrosine kinase inhibitors are classic culprits. In patients receiving these agents, it is advisable to perform a baseline electrocardiogram and monitor the QT interval. If the (QT interval corrected for heart rate) increases by 60 milliseconds from baseline or is greater than 500 milliseconds, it is advisable to suspend treatment temporarily. Moving forward, further trials are required in the field of cardio-oncology to better understand the relationship between chemotherapeutic agents and arrhythmia.
OBJECTIVE AND QUANTITATIVE ESTIMATION OF THE OPTIMAL TIMING FOR EPIRETINAL MEMBRANE SURGERY ON THE BASIS OF METAMORPHOPSIA
Authors: Kanzaki Yuki , Doi Shinichiro , Matoba Ryo , Kanzaki Sayumi , Kimura Shuhei , Hosokawa Mio M. , Shiode Yusuke , Takasu Ippei , Morizane Yuki 
Published: January 2022

Purpose:
To establish an objective and quantitative biomarker of metamorphopsia in epiretinal membranes (ERMs) and determine the optimal timing for ERM surgery.

Methods:
Retrospectively, 172 eyes with ERM were reviewed. Retinal folds because of tangential traction by ERM were visualized by en-face optical coherence tomography. The maximum depth of retinal folds (MDRF) within the parafovea was quantified. Metamorphopsia was quantified by M-CHARTS. The change in the distance between the retinal vessels after ERM surgery and the preoperative total depth of retinal folds between the vessels were quantified using en-face optical coherence tomography and optical coherence tomography angiography.

Results:
Significant correlations were observed between preoperative MDRF and M-CHARTS scores before and at 6 months after surgery (r = 0.617 and 0.460, respectively; P < 0.001) and change in the distance between the retinal vessels after ERM surgery and preoperative total depth of retinal folds between the vessels (r = 0.471; P = 0.013). The preoperative MDRF values at which M-CHARTS scores were 0.5 before and 6 months after the surgery were 69 µm and 118 µm, respectively.

Conclusion:
The MDRF is an objective and quantitative biomarker of metamorphopsia in ERM. To maintain patients' quality of vision, ERM surgery may be performed when the preoperative MDRF ranges between 69 µm and 118 µm.
CYP2C19 Genotyping Plus Therapeutic Drug Monitoring Dependent Voriconazole Treatment for Invasive Pulmonary Aspergillosis in a Patient with Liver Failure
Authors: Shen Chuan , Zhao Qian , Li Ziyue , Wang Wei , Zhao Yalin , Kong Lingya , Xie Jing , Zhao Caiyan 
Published: January 2022

Abstract
Invasive pulmonary aspergillosis (IPA) is a lethal infectious disease with high mortality in patients with liver failure. Early recognition of the risk factors prompting earlier diagnosis and treatment may improve the outcomes. Voriconazole is recommended as the first-line drug for IPA, but hepatotoxicity limits its use in the context of liver diseases. We report a case of a 63-year-old female who was admitted to the Third Affiliated Hospital of Hebei Medical University due to IPA after glucocorticoid therapy for liver failure. The polymorphism of cytochrome P450 (CYP) isoenzymes showed CYP2C19∗1/∗2 genotype associated with intermediate metabolism of voriconazole. However, the patient developed side effects such as skin rash, vomiting, hyperbilirubinemia, and alteration of consciousness, even if she received half of the recommended dosage for voriconazole. Therapeutic drug monitoring (TDM) was applied to guide the dosage adjustment of voriconazole in this patient, and consequently, the patient presented a favorable outcome. In conclusion, genotyping screening plus TDM dependent individualized treatment of voriconazole may improve the survival of liver failure patient with IPA.
Skin Cancer Back to Basics
Authors: Bai Heidi , Brickley Sylvana 
Published: January 2022

ABSTRACT
Amelanotic melanoma is a rare subtype of cutaneous melanoma. Sun exposure is a known primary risk factor; however, the mechanism for amelanosis is poorly understood. Amelanotic melanoma is challenging to recognize clinically because of absence of pigment and its resemblance to a variety of benign and malignant neoplasms. Detection often occurs at late or metastatic stages, leading to poorer outcomes. Surgical excision is the current standard of care, with adjuvant therapies under investigation. This article discusses the clinical assessment and management of AM to improve early recognition and patient outcomes.
A decade of rising alcoholic liver disease hospital admissions and deaths in Irish hospitals, 2007–2016: a retrospective cross-sectional analysis
Authors: Armstrong Paul R. , Ring Éabha , MacNicholas Ross 
Published: January 2022

Background
Alcoholic liver disease (ALD) is a major cause of both liver cirrhosis and hepatocellular carcinoma (HCC) in Ireland.

Aims
The aim of the study was to identify the epidemiological profile, temporal trends, development of complications and mortality arising from inpatient care episodes linked to ALD in Ireland from 2007 to 2016.

Methods
This was a national retrospective study that analysed data on patient discharges from hospitals across Ireland. The Hospital Inpatient Enquiry System was used to gather this data. The main outcome measures were the number of hospital discharges for patients with ALD or HCC, also expressed per 100 000 population, the mortality rate associated with ALD and the prevalence of complications associated with ALD.

Results
A total of 33 794 hospital discharges were examined. There was a 38% increase in hospital discharges and 300% increase in HCC coding for patients with ALD between 2006 and 2016. There were 73 hospital discharges with ALD per 100 000 population in 2016. That year, 40 482 bed days were required for inpatient management equating to 120 beds per day. Deaths from ALD rose by 29% over the 10-year period. Cirrhosis was diagnosed in 57% and 24% had ascites. Mortality was 9.8% rising to 16% with variceal bleeding and 42% with acute kidney injury. Only 31% were under the care of a gastroenterologist or hepatologist.

Conclusion
Ireland is seeing a rise in ALD-related hospital admissions and deaths, including HCC which increased three-fold. ALD is a preventable disease, and public health interventions are of proven benefit and required to reverse this trend.
The evolution of partner specificity in mutualisms
Authors: Carlson Christopher , Akçay Erol , Morsky Bryce 
Published: January 2022

AbstractMutualistic species vary in their level of partner specificity, which has important evolutionary, ecological, and management implications. Yet, the evolutionary mechanisms which underpin partner specificity are not fully understood. Most work on specialization focuses on the trade-off between generalism and specialism, where specialists receive more benefits from preferred partners at the expense of benefits from non-preferred partners, while generalists receive similar benefits from all partners. Because all mutualisms involve some degree of both cooperation and conflict between partners, we highlight that specialization to a mutualistic partner can be cooperative, increasing benefit to a focal species and a partner, or antagonistic, increasing resource extraction by a focal species from a partner. We devise an evolutionary game theoretic model to assess the evolutionary dynamics of cooperative specialization, antagonistic specialization, and generalism. Our model shows that cooperative specialization leads to bistability: stable equilibria with a specialist host and its preferred partner excluding all others. We also show that under cooperative specialization with spatial effects, generalists can thrive at the boundaries between differing specialist patches. Under antagonistic specialization, generalism is evolutionarily stable. We provide predictions for how a cooperation-antagonism continuum may determine the patterns of partner specificity that develop within mutualistic relationships.
Effect of vitamin D on infection and inflammation in patients with cystic fibrosis: a systematic review and meta-analysis
Authors: Begum Nelufa , Tarique Abdullah Al , Blake Tamara , Vilcins Dwan , Islam Mohammad Zahirul , Islam Nazrul , Ware Robert S , Sly Peter 
Published: January 2022

ABSTRACTBackgroundCystic fibrosis (CF) is a genetic disorder in which the respiratory system gets clogged with mucus leads to progressive lung damage. There is no known cure for CF but several treatments to manage symptoms and reduce complications. Vitamin D deficiency is common in CF associated with increased infection and inflammation. This systematic review and meta-analysis will evaluate the effectiveness of vitamin D treatment in reducing respiratory tract infection and inflammation in patients with CF.MethodsRandomized and quasi-randomised studies in CF patients with control groups will be identified. The antibacterial activity of vitamin D supplementation will help in reducing respiratory tract infection and inflammation in CF. Overall effects of vitamin D in terms of infection and inflammatory markers such as C-reactive protein, inflammatory cytokine interleukin (IL)-6, IL-8, IL-17, IL-23, antimicrobial peptide (LL-37), lung function defined by forced expiratory volume in 1 second (FEV1) %, other assessed respiratory parameters will be calculated using random-effect models. Study quality will be assessed using RoB 2 – A revised Cochrane Risk of Bias tool for randomised trials. The overall quality of evidence for each outcome will be summarised according to the Grading of Recommendations Assessment, Development, and Evaluations (GRADE) framework.