bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disrupting the MYC-TFEB Circuit Impairs Amino Acid Homeostasis and Provokes Metabolic Anergy
Authors: Fernandez Mario R. , Schaub Franz X. , Yang Chunying , Li Weimin , Yun Seongseok , Schaub Stephanie K. , Dorsey Frank C. , Liu Min , Steeves Meredith A. , Ballabio Andrea , Tzankov Alexandar , Chen Zhihua , Koomen John M. , Berglund Anders E. , Cleveland John L. 
Published: February 2022

Abstract

MYC family oncoproteins are regulators of metabolic reprogramming that sustains cancer cell anabolism. Normal cells adapt to nutrient-limiting conditions by activating autophagy, which is required for amino acid (AA) homeostasis. Here we report that the autophagy pathway is suppressed by Myc in normal B cells, in premalignant and neoplastic B cells of Eμ-Myc transgenic mice, and in human MYC-driven Burkitt lymphoma. Myc suppresses autophagy by antagonizing the expression and function of transcription factor EB (TFEB), a master regulator of autophagy. Mechanisms that sustained AA pools in MYC-expressing B cells include coordinated induction of the proteasome and increases in AA transport. Reactivation of the autophagy-lysosomal pathway by TFEB disabled the malignant state by disrupting mitochondrial functions, proteasome activity, AA transport, and AA and nucleotide metabolism, leading to metabolic anergy, growth arrest, and apoptosis. This phenotype provides therapeutic opportunities to disable MYC-driven malignancies, including AA restriction and treatment with proteasome inhibitors.

Significance:
MYC suppresses TFEB and autophagy and controls amino acid homeostasis by upregulating amino acid transport and the proteasome, and reactivation of TFEB disables the metabolism of MYC-driven tumors.
Ischemic Stroke Severity and Mortality in Patients With and Without Atrial Fibrillation
Authors: Vinding Naja E. , Kristensen Søren L. , Rørth Rasmus , Butt Jawad H. , Østergaard Lauge , Olesen Jonas B. , Torp‐Pedersen Christian , Gislason Gunnar H. , Køber Lars , Kruuse Christina , Johnsen Søren P. , Fosbøl Emil L. 
Published: February 2022

Background
Our objective was to investigate stroke severity and subsequent rate of mortality among patients with and without atrial fibrillation (AF). Contemporary data on stroke severity and prognosis in patients with AF are lacking.

Methods and Results

First‐time ischemic stroke patients from the Danish Stroke Registry (January 2005–December 2016) were included in an observational study. Patients with AF were matched 1:1 by sex, age, calendar year, and CHA
2
DS
2
‐VASc score with patients without AF. Stroke severity was determined by the Scandinavian Stroke Scale (0–58 points). The rate of death was estimated by Kaplan‐Meier plots and multivariable Cox regression. Among 86 458 identified patients with stroke, 17 205 had AF. After matching, 14 662 patients with AF and 14 662 patients without AF were included (51.8% women; median age, 79.6 years [25th–75th percentile, 71.8–86.0]). More patients with AF had very severe stroke (0–14 points) than patients without AF (13.7% versus 7.9%,
P
<0.01). The absolute rates of 30‐day and 1‐year mortality were significantly higher for patients with AF (12.1% and 28.4%, respectively) versus patients without AF (8.7% and 21.8%, respectively). This held true in adjusted models for 30‐day mortality (hazard ratio [HR], 1.40 [95% CI, 1.30–1.51]). However, this association became nonsignificant when additionally adjusting for stroke severity (HR, 1.10 [95% CI, 1.00–1.23]). AF was associated with a higher rate of 1‐year mortality (HR, 1.39 [95% CI, 1.32–1.46]), although it was mediated by stroke severity (HR, 1.15 [95% CI, 1.09–1.23], model including stroke severity).

Conclusions
In a contemporary nationwide cohort of patients with ischemic stroke, patients with AF had more severe strokes and higher mortality than patients without AF. The difference in mortality was mainly driven by stroke severity.
Inverse Association Between Bystander Use of Audiovisual Feedback From an Automated External Defibrillator and Return of Spontaneous Circulation
Authors: Obling Laust , Hassager Christian , Blomberg Stig Nikolaj , Folke Fredrik 
Published: February 2022

Background
Treatment with an automated external defibrillator (AED) improves outcome in out‐of‐hospital cardiac arrest (OHCA). Audiovisual feedback from an AED may assist bystanders achieve higher quality cardiopulmonary resuscitation. However, the association between audiovisual feedback and clinical outcomes is not well assessed in real‐life OHCA. The aim of this study was to assess the association between audiovisual feedback from an AED used in bystander resuscitation with rates of return of spontaneous circulation (ROSC) and 30‐day survival in a real‐life cohort of patients with OHCA.

Methods and Results

We included 325 patients treated with bystander AED use before arrival of emergency medical services during 2016 to 2019 from the Capital Region of Denmark. Patients were divided into a “feedback” and a “nonfeedback” group, depending on presence of audiovisual feedback from the AED. Audiovisual feedback was defined as voice prompts with continuous feedback to ongoing resuscitation. Rates of ROSC upon hospital admission and 30‐day survival were assessed, and univariate and multivariable models were applied to decide the association to audiovisual feedback. Multivariable models were adjusted for sex, age, primary heart rhythm, and location of OHCA. A total of 155 (48%) patients had a bystander AED applied with audiovisual feedback and 170 (52%) without audiovisual feedback. A lower rate of ROSC was found in the feedback group compared with the nonfeedback group (33% [n=51] versus 45% [n=76];
P
=0.03). No association was observed between AV feedback and 30‐day survival (feedback=27% [n=42] and nonfeedback=31% [n=53];
P
=0.49). In the unadjusted logistic regression model, audiovisual feedback was associated with a decreased chance of ROSC (odds ratio, 0.61; 95% CI, 0.38–0.95;
P
=0.03), which remained significant after adjusted analysis (odds ratio, 0.53; 95% CI, 0.29–0.97;
P
=0.04), whereas we found no significant association between audiovisual feedback and 30‐day survival in the unadjusted and adjusted analyses.

Conclusions
Audiovisual feedback from an AED used by bystanders was associated with a lower chance of ROSC at hospital admission, but we found no significant difference in 30‐day survival. Focus on early and correct bystander cardiopulmonary resuscitation and AED use remain key for OHCA survival.
Large‐Conductance Calcium‐Activated Potassium Channel Opener, NS1619, Protects Against Mesenteric Artery Remodeling Induced by Agonistic Autoantibodies Against the Angiotensin II Type 1 Receptor
Authors: Wang Meili , Yin Xiaochen , Li Shuanglei , Zhang Xi , Yi Ming , He Chunyu , Li Xiaoyue , Wang Wei , Zhang Suli , Liu Huirong 
Published: February 2022

Background
Agonistic autoantibodies against the angiotensin II type 1 receptor (AT1‐AAs) extensively exist in patients with hypertensive diseases and have been demonstrated to play crucial roles in the pathophysiological process of vascular remodeling. However, the treatment options are limited. The large‐conductance calcium‐activated potassium (BK) channel is a critical regulator and potential therapeutic target of vascular tone and architecture. We have previously observed that AT1‐AAs have an inhibitory effect on BK channels. However, whether BK channel dysfunction is involved in AT1‐AAs‐induced vascular remodeling and the therapeutic effect of BK channel opener is unclear.

Methods and Results

In our study, mesenteric arteries from AT1‐AAs‐positive rats exhibited increased wall thickness, narrowing of the arteriolar lumen, and increased collagen accumulation. Patch clamp test results showed that the voltage sensitivity of BK channel declined in mesenteric arteriolar smooth muscle cells from AT1‐AAs‐positive rats. Experiments with freshly isolated mesenteric arteriolar smooth muscle cells showed that AT1‐AAs reduced the opening probability, open levels, open dwell time, and calcium sensitivity of BK channel. Experiments with HEK293T cells transfected with GFP‐ZERO‐BK α‐subunit plasmids suggested a BK channel α‐subunit‐dependent mechanism. BK channel α‐subunit deficient, namely
KCNMA1
−/−
rats showed a phenotype of mesenteric artery remodeling. The administration of NS1619, a specific BK channel opener targeting the α‐subunit, reversed the phenotypic transition and migration induced by AT1‐AAs in cultured mesenteric arteriolar smooth muscle cells. Finally, perfusion of NS1619 significantly relieved the pathological effects induced by AT1‐AAs in vivo.

Conclusions
In summary, we provide compelling evidence that BK channel α‐subunit dysfunction mediates AT1‐AAs‐induced mesenteric artery remodeling. Preservation of BK channel activity may serve as a potential strategy for the treatment of AT1‐AAs‐induced maladaptive resistance artery remodeling.
Health‐Related Quality of Life in Older Patients With Advanced Heart Failure: Findings From the SUSTAIN‐IT Study
Authors: Grady Kathleen L. , Andrei Adin‐Cristian , Elenbaas Christian , Warzecha Anna , Baldridge Abigail , Kao Andrew , Spertus John A. , Pham Duc‐Thinh , Dew Mary Amanda , Hsich Eileen , Cotts William , Hartupee Justin , Pamboukian Salpy V. , Pagani Francis D. , Petty Michael , Lampert Brent , Johnson Maryl , Murray Margaret , Takeda Koji , Yuzefpolskaya Melana , Silvestry Scott , Kirklin James K. , Yancy Clyde 
Published: February 2022

Background
There is a paucity of research describing health‐related quality of life (HRQOL) in older adults considered for advanced heart failure surgical therapies. Using data from our SUSTAIN‐IT (Sustaining Quality of Life of the Aged: Heart Transplant or Mechanical Support) study, we aimed to compare HRQOL among 3 groups of older (60–80 years) patients with heart failure before heart transplantation (HT) or long‐term mechanical circulatory support (MCS) and identify factors associated with HRQOL: (1) HT candidates with MCS, (2) HT candidates without MCS, or (3) candidates ineligible for HT and scheduled for long‐term MCS.

Methods and Results

Patients from 13 US sites completed assessments, including self‐reported measures of HRQOL (EuroQol‐5 Dimension Questionnaire, Kansas City Cardiomyopathy Questionnaire–12), depressive symptoms (Personal Health Questionnaire–8), anxiety (State‐Trait Anxiety Inventory–state form), cognitive status (Montreal Cognitive Assessment), and performance‐based measures (6‐minute walk test and 5‐m gait speed). Analyses included ANOVA, χ
2
tests, Fisher’s exact tests, and linear regression. The sample included 393 patients; the majority of patients were White men and married. Long‐term MCS candidates (n=154) were significantly older and had more comorbidities and a higher New York Heart Association class than HT candidates with MCS (n=118) and HT candidates without MCS (n=121). Long‐term MCS candidates had worse HRQOL than HT candidates with and without MCS (EQ‐5D visual analog scale scores, 46±23 versus 68±18 versus 54±23 [
P
<0.001] and Kansas City Cardiomyopathy Questionnaire–12 overall summary scores, 35±21 versus 60±21 versus 49±22 [
P
<0.001], respectively). In multivariable analyses, lower 6‐minute walk distance, higher New York Heart Association class, depressive symptoms, and not being an HT candidate with MCS were significantly associated with worse overall HRQOL.

Conclusions
Our findings demonstrate important differences in overall and domain‐specific HRQOL of older patients with heart failure before HT or long‐term MCS. Understanding HRQOL differences may guide decisions toward more appropriate and personalized advanced heart failure therapies.
Vengeful Promises: The Agency of Love Oaths as Materially Hybrid Texts in Late Seventeenth-Century Japan
Authors: Leca Radu 
Published: February 2022

Abstract
This article focuses on the historical use and meanings of early modern oaths (Jp. kishōmon 起請文). These materially hybrid texts were initially stamped (on one side) and then inscribed by hand in ink (on the other side), often even in blood. Since they are an inextricable combination of print and handwriting, they complicate such dichotomies and open up a series of issues central to the understanding of scribal practices in early modern Japan. This article moves beyond their content analysis to address issues of materiality and agency along with the relationship between orality, writing and bodily practices.
Thyroid Cartilage Compression Causing Bow Hunter’s Syndrome
Authors: Hong Xinyuan , D’heygere Emmanuel , Prisman Eitan 
Published: February 2022

Objectives and Methods: We report a unique case of Bow Hunter’s syndrome with a dominant aberrantly coursing right vertebral artery (VA), presenting with persistent dizziness and syncope despite previous decompressive surgery at vertebral levels C5-C6. Results: Re-evaluation with computed tomography-scan during provocation of dizziness by neck rotation revealed compression of the right VA at level C6 from against the ipsilateral posterior border and superior cornu of the thyroid cartilage. Laryngoplasty resulted in complete resolution of symptoms. Conclusion: This extremely rare cause of Bow’s Hunter’s syndrome should be considered, especially in refractory cases after neurosurgical decompression, and surgical management is straightforward and successful.
Otolaryngology Program Director, House-Staff, and Student Opinions: Step 1 Pass/Fail Score Reporting
Authors: Kay Hannah G. , Makhoul Alan T. , Ganesh Kumar Nishant , Pontell Matthew E. , Drolet Brian C. , Whigham Amy S. 
Published: February 2022

Objective(s): To compare otolaryngology program director, house-staff, and medical student perspectives on the score reporting change of USMLE Step 1 to pass/fail. Methods: Separate electronic surveys were sent to program directors of ACGME-accredited otolaryngology programs (Cronbach’s alpha = .87), otolaryngology house-staff (Cronbach’s alpha = .91), and medical students interested in otolaryngology (Cronbach’s alpha = .76). Results: Among the 51 otolaryngology program directors that completed the survey (response rate of 46.8%), 17.6% favored reporting USMLE Step 1 as pass/fail. A majority believed the reporting change would make it more difficult to screen (74.5%) and objectively compare applicants (82.4%). Step 2 CK scores will be more important to most program directors due to the reporting change (83.7%). Of the 93 house-staff that completed surveys, most did not favor the reporting change (61.3%). Over half (54.0%) of the 87 medical students that completed surveys did not support the scoring change, and most (65.5%) did not feel that it would decrease anxiety around residency applications (65.5%). Most house-staff and medical students felt that the scoring change would put non-U.S. MD students at a disadvantage (65.6% of house-staff, 69.8% of medical students). Conclusion: Most survey respondents do not agree with the decision to report Step 1 as pass/fail. Despite its intended goals, most do not believe pass/fail Step 1 reporting will improve medical student well-being and believe it will put certain student populations at a greater disadvantage.
Study Mullins effect of polyurethane reinforcement with halloysite nanotube by molecular dynamics simulation
Authors: Heidari Pebdani Mohammadreza 
Published: February 2022

Molecular dynamics simulation was applied to study the irreversible strain through loading and unloading cyclic tests of polyurethane (PU) reinforced with halloysite nanotube (HNT). The influences of the stretching cycle rate, different temperatures, the volume of halloysite nanotube and the density rate of the hard and soft domain of PU were studied on the permanent set. The results illustrate that the residual strain was increasing when the stretching loading is increasing, for example, with increasing strain load to 250% the residual strain increased to 55%. In contrast, the increasing volume fraction of HNT and hard part content of PU lead to lower residual strain. The recovery of the permanent set is achievable by increasing temperature from 1 K to 200 K residual strain is decreased to 52%. An Ogden constitutive and the theory of pseudo-elasticity were adopted to simulate this composite in the ABAQUS software. This model has proposed a reasonable prediction of plastic deformation.
Barriers and facilitators for parents in end-of-life decision-making for neonates at the Neonatal Intensive Care Unit: A qualitative study
Authors: Piette Veerle , Dombrecht Laure , Deliens Luc , Cools Filip , Chambaere Kenneth , Goossens Linde , Naulaers Gunnar , Laroche Sabine , Cornette Luc , Bekaert Eline , Decoster Pauline , Beernaert Kim , Cohen Joachim 
Published: February 2022

Background: Mortality and end-of-life decision-making can occur in newborns, especially within the Neonatal Intensive Care Unit. For parents, participating in end-of-life decision-making is taxing. Knowledge is lacking on what support is helpful to parents during decision-making. Aim: To identify barriers and facilitators experienced by parents in making an end-of-life decision for their infant. Design: Qualitative study using face-to-face semi-structured interviews. Setting/participants: We interviewed 23 parents with a child that died after an end-of-life decision at a Neonatal Intensive Care Unit between April and September 2018. Results: Parents stated barriers and facilitators within 4 themes: 1. Clinical knowledge and prognosis; 2. Quality of information provision; 3. Emotion regulation; and 4. Psychosocial environment. Facilitators include knowing whether the prognosis includes long-term negative quality of life, knowing all treatment options, receiving information according to health literacy level, being able to process intense emotions, having experienced counseling and practical help. Barriers include a lack of general medical knowledge, being unprepared for a poor prognosis, having an uninformed psychologist. Conclusions: We found that clinical information and psychosocial support aid parents in decision-making. Information is best tailored to health literacy. Psychosocial support can be provided by experienced, informed counselors, social services and sibling support, distinguishing between verbal and non-verbal coping preferences, and calm, familiar architecture. Intense emotions may hinder absorption of clinical information, therefore interventions to aid emotion regulation and reduce cognitive load may be looked at in further research. Adjustment of the Situations, Opinions and Options, Parents, Information, Emotions framework based on our results can be evaluated.
Transperitoneal laparoscopic simple nephrectomy for giant hydronephrosis: Tips and tricks to make it easier
Authors: Ali Ahmed Issam , Abdel-Karim Aly M , Abdelghani Mostafa M , Eldakhakhny Amr , Fawzy Ahmed M , Hassan Ali , Rohiem Mahmoud F , Galal Ehab M 
Published: February 2022

Purpose: We report our experience with transperitoneal laparoscopic nephrectomy (LN) for giant hydronephrosis (GH) and compare the outcome data with open nephrectomy (ON). Patients and methods: The retrospective data of 88 patients (52 males and 36 females) who underwent LN or ON for treatment of GH in the period between October 2015 and December 2019 were investigated. LN was performed in 38 patients, while 50 patients underwent ON. We compared the two groups for success, operative time, and intraoperative and postoperative complications. Results: The mean age of the patients in the LN group was 45.8 ± 11.4 years, and it was 44.7 ± 10.8 years in the ON group. The mean operative time in the LN group was statistically significantly longer when compared with the ON group195 ± 18 min versus 127 ± 22 min ( p = 0.01).The estimated blood loss was significantly greater in the ON group ( p = 0.01). However, no patients required blood transfusions in either group. The visual analog pain (VAP) scores were significantly higher on both day 1 and day 2 in the ON group 3.6 ± 0.9 and 2 ± 0.7 versus 2.7 ± 0.6 and 1.4 ± 0.5 in LN group, ( p = 0.01). Conclusion: LN for GH is feasible, safe, and efficacious. Compared to open surgery, the laparoscopic approach resulted in significantly shorter hospital stays, decreased morbidity, and quicker recovery. Some tips and tricks could help to do it in an easier way and reduce the operative time.
Childhood Experiences of Companion Animal Abuse and its Co-Occurrence with Domestic Abuse: Evidence from a National Youth Survey in Norway
Authors: Muri Karianne , Augusti Else-Marie , Bjørnholt Margunn , Hafstad Gertrud Sofie 
Published: February 2022

It is increasingly acknowledged that companion animal abuse often occurs in the same contexts as other types of abuse, particularly domestic abuse. However, the co-occurrence and strengths of these associations in the general population have not been well established in research. With data from a large representative sample of Norwegian adolescents, we aimed to determine 1) the extent to which Norwegian children are exposed to companion animal abuse in the family, 2) whether and how companion animal abuse is linked to other forms of domestic abuse that children experience, and 3) background factors associated with companion animal abuse. A total of 9240 adolescents aged 12–16 years ( Mage 14.7) participated in the digital school-based survey. Four percent ( n = 380) reported that they had ever witnessed a parent being violent towards a family companion animal, whereas 1% ( n = 125) had experienced that an adult in the household had threatened to harm a companion animal. There was a substantial overlap between companion animal abuse and child abuse, and it most frequently co-occurred with psychological abuse and less severe forms of physical child abuse. This resonates with conceptualizations of domestic abuse as an ongoing pattern of psychological abuse and coercive control. The risk factors identified for companion animal abuse in this representative sample of adolescents were similar to known risk factors for domestic abuse. Low socioeconomic status and parents’ substance abuse, parents’ psychiatric illness, and parents’ history of incarceration entailed a greater risk of experiencing companion animal abuse. We conclude that companion animal abuse co-occurs with other forms of domestic abuse and that it may be considered a part of the repertoire of domestic abuse that impacts children.
Antenatal dexamethasone retarded fetal long bones growth and development by down-regulating of insulin-like growth factor 1 signaling in fetal rats
Authors: Qiu Junlan , Fan Xiaorong , Ding Hongmei , Zhao Meng , Xu Ting , Lei Jiahui , Ji Bingyu , Zhuang Zhixiang , Gao Qinqin 
Published: February 2022

Objective Dexamethasone (DEX), a synthetic glucocorticoid, has been widely used as a medication for premature delivery. However, the side effects of antenatal DEX treatment on fetal bone development, as well as the underlying mechanisms still remain to be elucidated. Here, we aimed to explore the effects and the related mechanisms of antenatal DEX exposure during late pregnancy on fetal bone growth and development. Methods Pregnant Sprague–Dawley rats were randomly divided into DEX group and vehicle group from gestational day 14 (GD14). Pregnant rats in DEX group were intraperitoneally injected once with DEX (200 µg/kg body weight) on GD14, 16, 18, and 20. The vehicle group rats were administered the same amount of normal saline at the same time. Pregnant rats were anesthetized at GD21 to harvest fetal femurs for analysis. Results Antenatal DEX treatment delayed fetal skeletal growth via inhibiting extracellular matrix (ECM) synthesis and downregulating insulin-like growth factor 1 (IGF1) signaling. Several components of IGF1 signaling pathway, including IGF1 receptor, insulin receptor substrate, as well as serine–threonine protein kinase, were down-regulated in fetal growth plate chondrocytes following DEX treatment. Conclusion This study indicated that antenatal DEX treatment-retarded fetal skeletal growth was associated with the down-regulation of IGF1 signaling in growth plate chondrocytes, providing important information about the impact of antenatal DEX application four courses on premature infant.