bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hereditary systemic autoinflammatory diseases and Schnitzler’s syndrome
Authors: Kacar Mark , Pathak Shelly , Savic Sinisa 
Published: September 2019

Abstract
The systemic autoinflammatory diseases are disorders of the innate immune system distinguished by severe inflammation resulting from dysregulation of the innate immune system. Hereditary fever syndromes, such as FMF, TNF receptor-associated periodic syndrome, cryopyrin-associated periodic syndromes and mevalonate kinase deficiency, were the first group of systemic autoinflammatory diseases for which a genetic basis was established, between 1999 and 2001. Currently according to the latest report of the international union of immunological societies, 37 separate monogenic disorders were classified as autoinflammatory. In addition to the abovementioned monogenic conditions, we describe Schnitzler’s syndrome, a well-defined, acquired autoinflammatory condition without a clear genetic basis. For the purposes of this review, we discuss several conditions defined by the latest consensus process as systemic autoinflammatory diseases. We focus on those disorders where recent studies have contributed to further phenotypic characterization or had an impact on clinical management.
Novel motif is capable of determining CCR and CCR-like proteins based on the divergence of CCRs in plants
Authors: Chao Nan , Jiang Wen-Ting , Wang Xue-Chun , Jiang Xiang-Ning , Gai Ying 
Published: September 2019

Abstract
Cinnamoyl-coenzyme A reductases (CCRs) have been reported as key enzymes involved in monolignol biosynthesis. In this study, a motif-aware workflow based on a new signature motif effectively distinguished CCRs from CCR-like proteins. The divergence of CCRs and CCR-like sequences in Populus tomentosa Carr, Panicum virgatum L, Oryza sativa L and Selaginella moellendorffii Hieron suggests that NWYCY is not efficient for CCR recognition. The novel motif H202(X)2K205 (CCR-SBM or CCR substrate binding motif) was introduced to distinguish between CCRs and CCR-like proteins. The site-directed mutant R205K in Os(I)CCR-like and H202 in PtoCCR7 resulted in the rescue and loss of activity, respectively, further validating the fact that CCR-SBM is critical for maintaining CCR activity. The molecular docking using feruloyl-cinnamoyl-coenzyme A (CoA) as the ligand and binary PhCCR-NADP structures as receptors indicated an interaction between H202 and K205 with CoA moiety. The genuine CCRs and CCR-like proteins from several angiosperms and gymnosperms were screened using a motif-aware workflow and were validated using a biochemical assay. Our results suggest that the motif-aware workflow is efficient and effective for the identification of CCRs and CCR-like proteins in land plants and can be used as a more accurate way of identifying genuine CCRs among land plants.
Choosing Words Wisely: Residents’ Use of Rhetorical Appeals in Conversations About Unnecessary Tests
Authors: Tseng Eric K. , Mukerji Geetha , Weinerman Adina , Fuller Jonathan , McLeod Anne , Wong Brian M. , Kuper Ayelet , Stroud Lynfa S. 
Published: September 2019

Purpose
To characterize how residents employ rhetorical appeals (i.e., the strategic use of communication to achieve specifiable goals) when discussing unnecessary diagnostic tests with patients.

Method
In 2015, senior hematology residents from 10 Canadian universities participating in a national formative objective structured clinical examination (OSCE) completed a resource stewardship communication station. In this communication scenario, a standardized patient (SP) portrayed a patient requesting unnecessary thrombophilia testing following early pregnancy loss. The authors performed a thematic analysis of audio transcripts using a qualitative description approach to identify residents’ rhetorical appeals to logic (rational appeals), credibility, and emotion.

Results
For persuasive communication, residents (n = 27) relied primarily on rational appeals that fit into 3 categories (with themes) focused on medical evidence (poor utility, professional guidelines and recommendations), avoidance of harm (insurance implications, unnecessary or potentially harmful interventions, patient anxiety), and reassurance to patient (normalizing, clinical pretest probability, criteria for reconsidering testing). Appeals to credibility and emotion were rarely used.

Conclusions
In an OSCE setting, residents relied predominantly on rational appeals when engaging SPs in conversations about unnecessary tests. These observations yield insights into how recent emphasis within residency education on appropriate test utilization may manifest when residents put recommendations into practice in conversations with patients. This study’s framework of rational appeals may be helpful in designing communication curricula about unnecessary testing. Future studies should explore rhetoric about unnecessary testing in the clinical environment, strategies to teach and coach residents leading these conversations, and patients’ preferences and responses to different appeals.
Taking Students as They Should Be: Restoring Trust in Undergraduate Medical Education
Authors: Slavin Stuart , Smith Gregory 
Published: September 2019

A recently published editorial focused on trust in the relationship between teacher and learner; in this Invited Commentary, the authors examine trust between administrators, course directors, curriculum committees, and medical students, exploring the ways that a lack of trust may be manifest, how this impacts students, and how trust can be built in undergraduate medical education (UME).
The hierarchical and paternalistic culture in medical education can skew curricular and policy decisions in the direction of distrust of students, leading to overscheduling and overprogramming of students through much of UME and to inflexible policies and procedures. Students may feel unheard or disrespected by some administrators and course directors when asking for changes, particularly when advocating for reductions in workload or increased flexibility. The collective impact of this lack of trust appears substantial, leaving many students with feelings of frustration, resentment, and cynicism.
Trust can be built, and efforts to do so have little associated cost. Administrators and course directors need to demonstrate respect, compassion, flexibility, and trust in students. Trust is built on relationships, and administrators should avoid isolation and engage meaningfully with students. Efforts should be made to reduce overscheduling of students so that they have more opportunity to pursue activities in which they can find meaning. Flexibility in scheduling of mandatory sessions and exams should be introduced wherever possible. If we take these collective steps, students will be more likely to find a path to becoming the doctors they are capable of becoming.
Clinical Practice Guidelines and Consensus Statements About Pain Management in Critically Ill End-of-Life Patients: A Systematic Review
Authors: Durán-Crane Alejandro , Laserna Andrés , López-Olivo María A. , Cuenca John A. , Díaz Diana Paola , Cardenas Yenny Rocío , Urso Catherine , O’Connell Keara , Azimpoor Kian , Fowler Clara , Price Kristen J. , Sprung Charles L. , Nates Joseph L. 
Published: September 2019

Objectives:
To identify and synthesize available recommendations from scientific societies and experts on pain management at the end-of-life in the ICU.

Data Sources:
We conducted a systematic review of PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and Biblioteca Virtual en Salud from their inception until March 28, 2019.

Study Selection:
We included all clinical practice guidelines, consensus statements, and benchmarks for quality.

Data Extraction:
Study selection, methodological quality, and data extraction were performed independently by two investigators. A quality assessment was performed by four investigators using the Appraisal of Guidelines for Research and Evaluation II instrument. The recommendations were then synthesized and categorized.

Data Synthesis:
Ten publications were included. The Appraisal of Guidelines for Research and Evaluation II statement showed low scores in various quality domains, especially in the applicability and rigor of development. Most documents were in agreement on five topics: 1) using a quantitative tool for pain assessment; 2) administering narcotics for pain relief and benzodiazepines for anxiety relief; 3) against prescribing neuromuscular blockers during withdrawal of life support to assess pain; 4) endorsing the use of high doses of opioids and sedatives for pain control, regardless of the risk that they will hasten death; and 5) using quality indicators to improve pain management during end-of-life in the ICU.

Conclusions:
In spite of the lack of high-quality evidence, recommendations for pain management at the end-of-life in the ICU are homogeneous and are justified by ethical principles and agreement among experts. Considering the growing demand for the involvement of palliative care teams in the management of the dying patients in the ICU, there is a need to clearly define their early involvement and to further develop comprehensive evidence-based pain management strategies. Based on the study findings, we propose a management algorithm to improve the overall care of dying critically ill patients.
Fluid intake and clinicopathological characteristics of bladder cancer: the West Midlands Bladder Cancer Prognosis Programme
Authors: van Hensbergen Mitch , van Osch Frits H.M. , Jochems Sylvia , James Nicholas D. , Wallace D. Michael A. , Wesselius Anke , Cheng K.K. , Bryan Richard T. , Zeegers M.P. 
Published: September 2019

Objective
Between 10 and 20% of bladder cancer patients who are diagnosed with nonmuscle-invasive bladder cancer will progress to muscle-invasive disease. Risk of progression depends on several factors at diagnosis including age, tumour stage, grade, size and number, and the presence or absence of carcinoma in situ. Fluid intake may be related to these factors.

Methods
Data of 1123 participants from the West Midlands Bladder Cancer Prognosis Programme were used. Data collection was via a semistructured questionnaire, and case report forms were used to collect clinicopathological data. Fluid intake was measured for six main categories: alcoholic fluids, hot fluids, fruit fluids, milk, fizzy drinks, and water, and converted into quintile variables. Multilevel mixed-effects linear regression was performed for every beverage category per clinicopathological variable and corrected for age, gender, and smoking status.

Results
Age at diagnosis was distributed differently amongst those in different total fluid intake quintiles (predicted means 71.5, 70.9, 71.5, 69.9, and 67.4, respectively) and showed a significant inverse linear trend in alcohol (P < 0.01), hot fluids (P < 0.01), and total fluids intake (P < 0.01), in nonmuscle-invasive bladder cancer patients.

Conclusion
Our results suggest an inverse association for alcohol intake and total fluid intake with age at diagnosis. These results should be confirmed by future studies, alongside a possible (biological) mechanism that could influence tumour growth, and the effect of micturition frequency.
Noninvasive Hemodynamic Monitoring of Cocaine-Induced Changes in Cardiac Output and Systemic Vascular Resistance in Subjects With Chronic Cocaine Use Disorder
Authors: Van Tassell Benjamin W. , Westman Peter , Trankle Cory , Johns Sade , Kadariya Dinesh , Buckley Leo , Carbone Salvatore , Abbate Antonio , Moeller Frederick Gerard 
Published: September 2019

Background:
Cocaine use disorder (CUD) is a common problem in the United States and worldwide. The mechanisms by which cocaine induces acute cardiovascular toxicity are various. When systemically absorbed through inhaled or intravenous routes, cocaine induces an acute rise in the heart rate (HR) and blood pressure (BP) leading to a significant increase in the cardiac output (CO) and myocardial oxygen demand. Subjects with chronic CUD represent a special population that has experienced long-term cocaine exposure, often without showing signs of cardiovascular disease. We herein present prospectively collected data on the acute hemodynamic effects of intravenous cocaine in a cohort of nontreatment-seeking individuals with CUD without cardiovascular disease.

Methods and Results:
Baseline physiologic data were collected while participants underwent infusion of escalating doses of cocaine (10, 20, and 40 mg administered over 2 minutes) at baseline and after receiving single-blind placebo treatment. Continuous noninvasive hemodynamic monitoring was performed throughout the infusion sessions using the ccNexfin finger cuffs (Edwards Lifesciences Corp, Irvine, CA). The recorded arterial BP tracings allowed for the measurement of beat-to-beat changes in HR, BP, stroke volume, CO, and systemic vascular resistance (SVR). None of the subjects experienced a treatment-related serious adverse event. Cocaine produced significant dose-dependent increases in median HR, BP, CO, and +dP/dt (a measure of cardiac contractility) and a significant dose-dependent reduction in median SVR.

Conclusions:
Intravenous cocaine in a cohort of otherwise healthy subjects with CUD produced dose-dependent increases in CO, largely explained by an increase in HR, accompanied by a dose-dependent decrease in SVR.
Demodex-Mite Infestation in Cilia and its Association With Ocular Surface Parameters in Japanese Volunteers
Authors: Mizuno Miki , Kawashima Motoko , Uchino Miki , Suzuki Natsume , Mitamura Hiroto , Uchino Yuichi , Yokoi Norihiko , Tsubota Kazuo 
Published: September 2019

Objectives:
To investigate the presence of Demodex mites on the eyelashes of a Japanese population and to explore its associations with subjective ocular symptoms and clinical ocular surface signs, including lid margin findings and fluorescein breakup time (FBUT).

Methods:
Sixty-three Japanese Tokyo-based volunteers were examined (24 men and 39 women; mean±SD of age, 50.6±15.8 years). Eyelash sampling was performed by epilating three lashes from the center of the right upper eyelid. Eyelashes were tested for Demodex mites with a light microscope. The subjects completed questionnaires to assess subjective symptoms and risk factors for dry eye disease (DED) and underwent general examinations for DED, including FBUT and cornea-conjunctival staining with fluorescein. Meibomian gland function was also investigated in lid margin findings, vascularity and mucocutaneous junction movement, lid irregularity, plugging, pouting, and meibum secretion grade scores.

Results:

Demodex mites were found in 20.6% (13/63) of the volunteers. Lid margin vascularity and meibum grades in the upper eyelid margins were significantly associated with the presence of Demodex mites. However, there were no significant differences in the diagnosis of meibomian gland dysfunction, FBUT, or ocular surface discomfort between the subjects with or without Demodex mites.

Conclusions:

Demodex mites are not rare in the cilia of a Japanese population. Lid margin vascularity and lower meibum quality may be associated with the presence of Demodex mites.
Association Between Dyslipidemia and Dry Eye Syndrome Among the Korean Middle-Aged Population
Authors: Choi Hye Rin , Lee Jung Hyun , Lee Hyung Keun , Song Jong Suk , Kim Hyeon Chang 
Published: September 2019

Purpose:
Dry eye syndrome (DES) is a common eye disease caused by tear deficiency or excessive tear evaporation. Because the tear film layers play a major role in the pathogenesis of the evaporative dry eye, some previous articles have suggested the possible mechanism of dyslipidemia and DES. However, the previous results were inconsistent and few studies were conducted to find the independent relationship between dyslipidemia and DES. Therefore, we investigated the association of dyslipidemia with DES in middle-aged Korean adults.

Methods:
This study was conducted on 2272 participants (854 men and 1418 women) enrolled in the Study Group for Environmental Eye Disease (2013–2017) after excluding people who have taken lipid-lowering medication. Participants with total cholesterol ≥240 mg/dL or high-density lipoprotein cholesterol <40 mg/dL or low-density lipoprotein cholesterol ≥160 mg/dL or triglycerides ≥200 mg/dL are defined as having dyslipidemia. Using the ocular surface disease index, we measured the DES severity and defined DES as an ocular surface disease index score ≥13.

Results:
Men with dyslipidemia had an odds ratio of 1.29 (95% confidence interval, 0.97–1.71) for DES in an unadjusted model compared with those without DES. After adjusting for age, body mass index, hypertension, diabetes, occupations, smoking and drinking status, exercise, contact lens use, computer use, study cohorts, and calendar year of examinations, the adjusted odds ratio for DES was 1.40 (1.03–1.90) in men. However, there was no significant association between dyslipidemia and DES in women, even after stratifying by menopausal status.

Conclusions:
Our findings suggest that dyslipidemia may be associated with the prevalence of DES in Korean men, but not in women.
Expression of Lubricin in the Human Amniotic Membrane
Authors: Wang Jingyi , Chen Di , Sullivan David A. , Xie Huatao , Li Ying , Liu Yang 
Published: September 2019

Purpose:
Lubricin, a boundary lubricant, is the body's unique antiadhesive, antifibrotic, antifriction, and antiinflammatory glycoprotein. This amphiphile is produced by numerous tissues and acts to regulate a number of processes, such as homeostasis, shear stress, tissue development, innate immunity, inflammation, and wound healing. We hypothesize that lubricin is also synthesized and expressed by the amniotic membrane (AM), which also possesses antiadhesive, antifibrotic, and antiinflammatory properties. We also hypothesize that lubricin, at least in part, mediates these AM capabilities. Our goal was to test our hypothesis.

Methods:
We obtained multiple samples of fresh, cryopreserved (CP), and freeze-dried (FD) human AMs, as well as fresh placental tissue as positive controls, and processed them for light microscopy, immunofluorescence, and western blot analyses. We also evaluated the ability of recombinant human lubricin to associate with FD-AMs.

Results:
Our results demonstrate that all fresh placental, fresh AM, and CP-AM samples contained lubricin. Lubricin was expressed in placental chorionic villi, AM epithelial and stromal cells, and CP-AM epithelia. No lubricin could be detected in FD-AMs but could be restored in FD-AMs after overnight incubation with recombinant human lubricin.

Conclusions:
This study supports our hypothesis that lubricin is expressed in human AMs. In addition, our data show that preservation methods influence the extent of this expression. Indeed, the disappearance of lubricin in FD-AMs may explain why dried AM reportedly loses its antiinflammatory and antiscarring abilities. It is possible that lubricin may mediate, at least in part, many of the biological properties of AMs.
Intraocular Degradation of XEN45 Gel Stent 3 Years After its Implantation
Authors: Widder Randolf A. , Kühnrich Pia , Hild Matthias , Rennings Corinna , Szumniak Alexander , Rössler Gernot F. 
Published: September 2019

Introduction:
We report a case of XEN45 Gel Stent removal 3 years after its implantation. The stent had degraded with a closed lumen, so a new stent was implanted.

Case Report:
A 63-year-old woman was scheduled for XEN45 Gel Stent implantation. Three years after the primary surgery and 2 years after a surgical revision, second revision surgery was required. The conjunctiva was opened, and the implanted XEN Gel Stent was stripped of the adhesive scar tissues. No aqueous humor flow was seen through the stent, and therefore, the stent was removed. The intrascleral and intracameral parts had degraded. The surface of the stent was irregular and cobbled. A part of the lumen in the middle of the stent had closed.

Discussion:
We detected changes in the stent after its removal during the surgical revision with conjunctival opening, which is our standard approach for failed XEN Gel Stents. Most surgeons advise needling of the stent in cases of failure. However, in cases of needling, changes in the stent might not have been detected. Thus, the number of patients with similar changes as this report might be higher than the publications suggest. No unique characteristics distinguished this patient from those who had a functional XEN Gel Stent. The stent, in this case, might have been of inferior quality as an exception, or all stents might degrade over time. Therefore, gonioscopy should be performed carefully to detect any changes in the stent. In cases of suspected stent degradation, we recommend a revision surgery with conjunctival opening and removal of the stent in cases of degradation.
Evaluation of treatment results and prognostic factors of uterine sarcoma: A single-center experience
Authors: Momtahan Mozhdeh , Emami Fatemeh , Sari Aslani Fatemeh , Akbarzadeh-Jahromi Mojgan 
Published: September 2019

Background:
Uterine sarcomas (US) constitute a rare heterogeneous group of gynecological malignancies with aggressive characteristics and poor prognosis. Identifying the histopathological factors that determine the prognosis of the tumor and efficacy of various treatment modalities provides a reliable source for efficient treatment of affected patients. This study presents our 11-year experience with US in the south of Iran.

Methods:
Medical records of 42 patients (2001-2012) with endometrial stromal sarcoma (ESS), leiomyosarcoma (LMS), and malignant mixed Müllerian tumor (MMMT) were investigated. Hazard ratio (HR) and 2- and 5-year survival of patients were analyzed based on the patients’ age, histopathological characteristics (tumor type, stage, necrosis, and mitotic index), and treatment modalities.

Results:
Twenty-four patients survived with median follow-up of 42.5 months; 18 died within 17 months, and 52.4% had recurrence, of whom 12 died. Two- and five-year survival rate was 78.6% and 61.9%, respectively, longest for ESS and shortest for MMMT. Higher age, tumor stage, necrosis, and mitotic index increased the HR of mortality. Radiotherapy resulted in a better survival, compared with chemotherapy alone or combined with radiotherapy.

Conclusion:
Although ESS had the best prognosis, MMMT was the most aggressive tumor with the shortest survival time. Histological type of the tumor, staging, tumor necrosis, and mitotic index had prognostic roles. Adjuvant radiotherapy resulted in a better survival, compared with surgery alone in early stage.