bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ulnar Nerve Strain in Functional Elbow and Shoulder Motions
Authors: Vinitpairot Chaiyos , Jianmongkol Surut , Thammaroj Tala , Wattanakamolchai Settapon 
Published: August 2019

Background: Shoulder and elbow motions can affect ulnar nerve strain. However, there is no evidence that links this kind of strain to specific activities. The purpose of this study was to examine ulnar nerve strain at the elbow resulting from normal daily activities. Methods: This study was conducted using thirty fresh frozen cadaveric elbows from subjects who had no deformities or history of previous upper extremity surgery. Strain was calculated based on nerve elongation. Ulnar nerve strain at the elbow from motion related to common daily activities was measured in both normal nerves and nerves in which gliding motion was restricted. The results of these measurement were then compared. Results: Activities related to extreme elbow and shoulder motions, such as cellular phone use, yielded an average strain of 6.3%. In addition, we found that nerve strain increased significantly in conditions in which gliding motion was restricted. Nerve strain due to motion associated with cellular phone use, for example, rose by 69.1%. Conclusions: Elbow flexion and shoulder abduction in daily activities are associated with increases in ulnar nerve strain, but this may not cause permanent damage to the nerve. After nerve gliding motion had been restricted, nerves that normally exhibited less strain often had even increased higher levels of strain than those nerves that normally exhibited high strain.
Absence of gravin-mediated signaling inhibits development of high-fat diet-induced hyperlipidemia and atherosclerosis
Authors: Fan Qiying , Yin Xing , Rababa’h Abeer , Diaz Diaz Andrea , Wijaya Cori S. , Singh Sonal , Suryavanshi Santosh V. , Vo Henry Hiep , Saeed Moawiz , Zhang Yang , McConnell Bradley K. 
Published: August 2019

Gravin, an A-kinase anchoring protein, is known to play a role in regulating key processes that lead to inflammation and atherosclerosis development, namely, cell migration, proliferation, and apoptosis. We investigated the role of gravin in the development of high-fat diet (HFD)-induced atherosclerosis and hyperlipidemia. Five-week-old male wild-type (WT) and gravin-t/t mice were fed a normal diet or an HFD for 16 wk. Gravin-t/t mice showed significantly lower liver-to-body-weight ratio, cholesterol, triglyceride, and very low-density lipoprotein levels in serum as compared with WT mice on HFD. Furthermore, there was less aortic plaque formation coupled with decreased lipid accumulation and liver damage, as the gravin-t/t mice had lower levels of serum alanine aminotransferase and aspartate aminotransferase. Additionally, gravin-t/t HFD-fed mice had decreased expression of liver 3-hydroxy-3-methyl-glutaryl-CoA reductase, an essential enzyme for cholesterol synthesis and lower fatty acid synthase expression. Gravin-t/t HFD-fed mice also exhibited inhibition of sterol regulatory element binding protein-2 (SREBP-2) expression, a liver transcription factor associated with the regulation of lipid transportation. In response to platelet-derived growth factor receptor treatment, gravin-t/t vascular smooth muscle cells exhibited lower intracellular calcium transients and decreased protein kinase A- and protein kinase C-dependent substrate phosphorylation, notably involving the Erk1/2 signaling pathway. Collectively, these results suggest the involvement of gravin-dependent regulation of lipid metabolism via the reduction of SREBP-2 expression. The absence of gravin-mediated signaling lowers blood pressure, reduces plaque formation in the aorta, and decreases lipid accumulation and damage in the liver of HFD mice. Through these processes, the absence of gravin-mediated signaling complex delays the HFD-induced hyperlipidemia and atherosclerosis.NEW & NOTEWORTHY The gravin scaffolding protein plays a key role in the multiple enzymatic pathways of lipid metabolism. We have shown for the first time the novel role of gravin in regulating the pathways related to the initiation and progression of atherosclerosis. Specifically, an absence of gravin-mediated signaling decreases the lipid levels (cholesterol, triglyceride, and VLDL) that are associated with sterol regulatory element binding protein-2 downregulation.
ZBTB7A Mediates the Transcriptional Repression Activity of the Androgen Receptor in Prostate Cancer
Authors: Han Dong , Chen Sujun , Han Wanting , Gao Shuai , Owiredu Jude N. , Li Muqing , Balk Steven P. , He Housheng Hansen , Cai Changmeng 
Published: August 2019

Abstract

Loss of expression of context-specific tumor suppressors is a critical event that facilitates the development of prostate cancer. Zinc finger and BTB domain containing transcriptional repressors, such as ZBTB7A and ZBTB16, have been recently identified as tumor suppressors that play important roles in preventing prostate cancer progression. In this study, we used combined ChIP-seq and RNA-seq analyses of prostate cancer cells to identify direct ZBTB7A-repressed genes, which are enriched for transcriptional targets of E2F, and identified that the androgen receptor (AR) played a critical role in the transcriptional suppression of these E2F targets. AR recruitment of the retinoblastoma protein (Rb) was required to strengthen the E2F–Rb transcriptional repression complex. In addition, ZBTB7A was rapidly recruited to the E2F–Rb binding sites by AR and negatively regulated the transcriptional activity of E2F1 on DNA replication genes. Finally, ZBTB7A suppressed the growth of castration-resistant prostate cancer (CRPC) in vitro and in vivo, and overexpression of ZBTB7A acted in synergy with high-dose testosterone treatment to effectively prevent the recurrence of CRPC. Overall, this study provides novel molecular insights of the role of ZBTB7A in CRPC cells and demonstrates globally its critical role in mediating the transcriptional repression activity of AR.

Significance:
ZBTB7A is recruited to the E2F–Rb binding sites by AR and negatively regulates the transcriptional activity of E2F1 on DNA replication genes.
GPR56 Drives Colorectal Tumor Growth and Promotes Drug Resistance through Upregulation of MDR1 Expression via a RhoA-Mediated Mechanism
Authors: Zhang Sheng , Chatterjee Treena , Godoy Carla , Wu Ling , Liu Qingyun J. , Carmon Kendra S. 
Published: August 2019

Abstract

Drug resistance continues to be a major obstacle of effective therapy for colorectal cancer, leading to tumor relapse or treatment failure. Cancer stem cells (CSC) or tumor-initiating cells are a subpopulation of tumor cells which retain the capacity for self-renewal and are suggested to be implicated in drug resistance. LGR5 is highly expressed in colorectal cancer and marks CSCs that drive tumor growth and metastasis. LGR5(+) CSCs cells were shown to interconvert with more drug-resistant LGR5(−) cancer cells, and treatment with LGR5-targeted antibody–drug conjugates (ADC) eliminated LGR5(+) tumors, yet a fraction of LGR5(−) tumors eventually recurred. Therefore, it is important to identify mechanisms associated with CSC plasticity and drug resistance in order to develop curative therapies. Here, we show that loss of LGR5 in colon cancer cells enhanced resistance to irinotecan and 5-fluorouracil and increased expression of adhesion G-protein–coupled receptor, GPR56. GPR56 expression was significantly higher in primary colon tumors versus matched normal tissues and correlated with poor survival outcome. GPR56 enhanced drug resistance through upregulation of MDR1 levels via a RhoA-mediated signaling mechanism. Loss of GPR56 led to suppression of tumor growth and increased sensitivity of cancer cells to chemotherapy and monomethyl auristatin E–linked anti–LGR5 ADCs, by reducing MDR1 levels. These findings suggest that upregulation of GPR56 may be a mechanism associated with CSC plasticity by which LGR5(−) cancer cells acquire a more drug-resistant phenotype.

Implications:
Our findings suggest that targeting GPR56 may provide a new strategy for the treatment of colorectal cancer and combatting drug resistance.
Thermally Processed Oil Exaggerates Colonic Inflammation and Colitis-Associated Colon Tumorigenesis in Mice
Authors: Zhang Jianan , Chen Xijing , Yang Ran , Ma Qin , Qi Weipeng , Sanidad Katherine Z. , Park Yeonhwa , Kim Daeyoung , Decker Eric A. , Zhang Guodong 
Published: August 2019

Abstract
Frying in vegetable oil is a popular cooking and food processing method worldwide; as a result, the oils used for frying are widely consumed by the general public and it is of practical importance to better understand their health impacts. To date, the effects of frying oil consumption on human health are inconclusive, making it difficult to establish dietary recommendations or guidelines. Here we show that dietary administration of frying oil, which was prepared under the conditions of good commercial practice, exaggerated dextran sodium sulfate (DSS)-induced colitis and azoxymethane (AOM)/DSS-induced colon tumorigenesis in mice. In addition, dietary administration of frying oil impaired intestinal barrier function, enhanced translocation of lipopolysaccharide (LPS) and bacteria from the gut into the systemic circulation, and increased tissue inflammation. Finally, to explore the potential compounds involved in the actions of the frying oil, we isolated polar compounds from the frying oil and found that administration of the polar compounds exacerbated DSS-induced colitis in mice. Together, our results showed that dietary administration of frying oil exaggerated development of inflammatory bowel disease (IBD) and IBD-associated colon tumorigenesis in mice, and these effects could be mediated by the polar compounds in the frying oil.
Association of Diabetes Mellitus With Health Status Outcomes in Young Women and Men After Acute Myocardial Infarction: Results From the VIRGO Study
Authors: Ding Qinglan , Funk Marjorie , Spatz Erica S. , Whittemore Robin , Lin Haiqun , Lipska Kasia J. , Dreyer Rachel P. , Spertus John A. , Krumholz Harlan M. 
Published: August 2019

Background

Diabetes mellitus increases the risk of mortality after acute myocardial infarction (
AMI
). However, little is known about the association of diabetes mellitus with post‐
AMI
health status outcomes (symptoms, functioning, and quality of life) in younger adults.

Methods and Results

We investigated the association between diabetes mellitus and health status during the first 12 months after
AMI
, using data from 3501 adults with
AMI
(42.6% with diabetes mellitus) aged 18 to 55 years enrolled in the
VIRGO
(Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study. Health status was measured with Seattle Angina Questionnaire (
SAQ
), 12‐item Short‐Form Health Survey, and EuroQol‐Visual Analogue Scale at baseline hospitalization, 1‐month, and 12‐months post‐
AMI
. At baseline, patients with diabetes mellitus had significantly worse
SAQ
‐angina frequency (81±22 versus 86±19),
SAQ
‐physical limitations (77±28 versus 85±23),
SAQ
‐quality of life (55±25 versus 57±23), 12‐item Short‐Form Health Survey mental (44±13 versus 46±12)/physical functioning (41±12 versus 46±12), and EuroQol‐Visual Analogue Scale (61±22 versus 66±21) than those without diabetes mellitus. Over time, both groups (with and without diabetes mellitus) improved considerably and the differences in health status scores progressively narrowed (except for 12‐item Short‐Form Health Survey physical functioning). In the linear‐mixed effects models, adjusted for sociodemographics, cardiovascular risk factors, comorbidities, clinical characteristics, psychosocial factors, healthcare use, and
AMI
treatment, diabetes mellitus was associated with worse health status at baseline but not after discharge, and the association did not vary by sex.

Conclusions

At baseline, young adults with diabetes mellitus had poorer health status than those without diabetes mellitus. After
AMI
, however, they experienced significant improvements and diabetes mellitus was not associated with worse angina,
SAQ
‐physical limitations, mental functioning, and quality of life, after adjustment for baseline covariates.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov/
. Unique identifier:
NCT
00597922.
A Century of Progress in Severe Convective Storm Research and Forecasting
Authors: Brooks Harold E. , Doswell III Charles A. , Zhang Xiaoling , Chernokulsky A. M. Alexander , Tochimoto Eigo , Hanstrum Barry , de Lima Nascimento Ernani , Sills David M. L. , Antonescu Bogdan , Barrett Brad 
Published: August 2019

AbstractsThe history of severe thunderstorm research and forecasting over the past century has been a remarkable story involving interactions between technological development of observational and modeling capabilities, research into physical processes, and the forecasting of phenomena with the goal of reducing loss of life and property. Perhaps more so than any other field of meteorology, the relationship between researchers and forecasters has been particularly close in the severe thunderstorm domain, with both groups depending on improved observational capabilities.The advances that have been made have depended on observing systems that did not exist 100 years ago, particularly radar and upper-air systems. They have allowed scientists to observe storm behavior and structure and the environmental setting in which storms occur. This has led to improved understanding of processes, which in turn has allowed forecasters to use those same observational systems to improve forecasts. Because of the relatively rare and small-scale nature of many severe thunderstorm events, severe thunderstorm researchers have developed mobile instrumentation capabilities that have allowed them to collect high-quality observations in the vicinity of storms.Since much of the world is subject to severe thunderstorm hazards, research has taken place around the world, with the local emphasis dependent on what threats are perceived in that area, subject to the availability of resources to study the threat. Frequently, the topics of interest depend upon a single event, or a small number of events, of a particular kind that aroused public or economic interests in that area. International cooperation has been an important contributor to collecting and disseminating knowledge.As the AMS turns 100, the range of research relating to severe thunderstorms is expanding. The time scale of forecasting or projecting is increasing, with work going on to study forecasts on the seasonal to subseasonal time scales, as well as addressing how climate change may influence severe thunderstorms. With its roots in studying weather that impacts the public, severe thunderstorm research now includes significant work from the social science community, some as standalone research and some in active collaborative efforts with physical scientists.In addition, the traditional emphases of the field continue to grow. Improved radar and numerical modeling capabilities allow meteorologists to see and model details that were unobservable and not understood a half century ago. The long tradition of collecting observations in the field has led to improved quality and quantity of observations, as well as the capability to collect them in locations that were previously inaccessible. Much of that work has been driven by the gaps in understanding identified by theoretical and operational practice.
The Relationship between Overshooting Tops in a Tornadic Supercell and Its Radar-Observed Evolution
Authors: Bluestein Howard B. , Lindsey Daniel T. , Bikos Daniel , Reif Dylan W. , Wienhoff Zachary B. 
Published: August 2019

Abstract
This is a study of a tornadic supercell in Kansas on 14 May 2018 in which data of relatively high spatiotemporal resolution from a mobile, polarimetric, X-band, Doppler radar were integrated with GOES-16 geosynchronous satellite imagery, and with fixed-site, surveillance, S-band polarimetric Doppler radar data. The data-collection period spanned the early life of the storm from when it was just a series of ordinary cells, with relatively low cloud tops, through its evolution into a supercell with much higher cloud tops, continuing through the formation and dissipation of a brief tornado, and ending after the supercell came to a stop and reversed direction, produced another tornado, and collided with a quasi-linear convective system. The main goal of this study was to examine the relationship between the overshooting tops and radar observed features prior to and during tornadogenesis. The highest radar echo top was displaced about 10 km, mainly to the north or northeast of the main updraft and cloud top, from the supercell phase through the first tornado phase of the supercell phase, after which the updraft and the cloud top became more closely located and then jumped ahead; this behavior is consistent with what would be expected during cyclic mesocyclogenesis. The change in direction of the supercell later on occurred while the nocturnal low-level jet was intensifying. No relationship was apparent between changes in the highest cloud-top height and tornadogenesis, but changes in cloud-top heights (rapid increases and rapid decreases) were related to two phases in multicell evolution and to supercell formation.
Range of Normal and Abnormal Syndesmotic Measurements Using Weightbearing CT
Authors: Hagemeijer Noortje Catharina , Chang Song Ho , Abdelaziz Mohamed Elghazy , Casey Jack Christopher , Waryasz Gregory Richard , Guss Daniel , DiGiovanni Christopher William 
Published: August 2019

Background: Early recognition of syndesmotic instability is critical for optimizing clinical outcome. Injuries causing a more subtle instability, however, can be difficult to diagnose. The purpose of this study was to evaluate both distal tibiofibular articulations using weightbearing computed tomography (CT) in patients with known syndesmotic instability, thereafter comparing findings between the injured and uninjured sides. We also aimed to define the range of normal measurement variation among patients without syndesmotic injury. Methods: Patients with unilateral syndesmotic instability requiring operative fixation ( n = 12) underwent preoperative bilateral ankle weightbearing CT. A separate cohort of patients without ankle injury who also underwent bilateral ankle weightbearing CT were included as comparative controls ( n = 24). For each weightbearing CT, a series of 7 axial plane tibiofibular joint measurements, including 1 angular measurement, were utilized to evaluate parameters of the syndesmotic anatomy at a level 1 cm above the tibial plafond. Values were recorded by 2 independent observers to assess for interobserver reliability. Results: Among those with unilateral syndesmotic instability, values differed between the injured and uninjured sides in 4 of the 7 measurements performed including the syndesmotic area: direct anterior, middle, and posterior differences, and sagittal translation ( P < .001, < .001, < .001, and < .001, respectively). In the control population without ankle injury, no differences were identified between any of the bilateral measurements ( P value range, .172-.961). Conclusion: This study highlights the ability of weightbearing CT to effectively differentiate syndesmotic diastasis among patients with surgically confirmed syndesmotic instability from those without syndesmotic instability. It underscores the substantial utility and importance of using the contralateral, uninjured side as a valid internal control whenever the need for confirming potential syndesmotic instability arises. Prospective studies are necessary to fully understand the accuracy of weightbearing CT in diagnosing occult syndesmotic instability among patients for whom the diagnosis remains in question. Level of Evidence: Level III, comparative diagnostic study.
Functional Outcome and Quality of Life After Nonoperative Treatment of Posterior Process Fractures of the Talus
Authors: Wijers Olivier , Engelmann Esmee W.M. , Posthuma Jelle J. , Halm Jens A. , Schepers Tim 
Published: August 2019

Background: Fractures of the posterior process of the talus are frequently overlooked, possibly leading to nonunion, arthritis, and chronic pain. Given the rare occurrence, previous case series have been small and without functional outcome scores. Therefore, we aimed to provide evidence on outcomes after nonoperative and operative management of posterior process fractures of the talus. Methods: All patients treated at a level 1 trauma center between 2012 and 2018 were retrospectively evaluated. Patient, fracture, and treatment characteristics were collected, and functional outcome as well as quality of life were assessed. Twenty-nine patients with posterior process fractures of the talus were identified in our database. Results: The most frequently seen mechanism of trauma was fall from height in 13 patients (44.8%). Twenty-two patients underwent primary arthrodesis or operative reduction and fixation of the fracture (75.9%). Eighty-two percent of the patients returned the questionnaires with a mean follow-up of 6 years. The 2 patients with primary arthrodesis were excluded from outcome analysis. The mean Foot Function Index score was 1.8 (range 0.0-10). The mean American Orthopaedic Foot & Ankle Society (AOFAS) score was 78.7 points (range 0-100). The mean quality of life EuroQol-5D (EQ-5D) index score was 0.78 (range −0.26 to 1). The mean visual analog scale (VAS) on overall patient satisfaction was 8.2 (range 1-10). Conclusion: Operative management of extended posterior talar fractures was found to provide good functional outcome, quality of life, and patient satisfaction. Although the patients treated nonoperatively were found to have less severe injuries, they demonstrated worse overall outcome, which is supportive of surgical management. Nonoperative treatment is therefore only justified in selected patients. Level of Evidence: Level IV, retrospective case series.
Practical management of riociguat in patients with pulmonary arterial hypertension
Authors: Halank Michael , Tausche Kristin , Grünig Ekkehard , Ewert Ralf , Preston Ioana R. 
Published: August 2019

Riociguat is one of several approved therapies available for patients with pulmonary arterial hypertension (PAH). Treatment should be initiated and monitored at an expert center by a physician experienced in treating PAH, and the dose adjusted in the absence of signs and symptoms of hypotension. In certain populations, including patients with hepatic or renal impairment, the elderly, and smokers, riociguat exposure may differ, and dose adjustments should therefore be made with caution according to the established scheme. Common adverse events are often easily managed, particularly if they are discussed before starting therapy. Combination therapy with riociguat and other PAH-targeted agents is feasible and generally well tolerated, although the coadministration of phosphodiesterase type 5 inhibitors (PDE5i) and riociguat is contraindicated. An open-label, randomized study is currently ongoing to assess whether patients who do not achieve treatment goals while receiving PDE5i may benefit from switching to riociguat. In this review, we provide a clinical view on the practical management of patients with PAH receiving riociguat, with a focus on the opinions and personal experience of the authors. The reviews of this paper are available via the supplemental material section.