bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac ankyrin repeat protein contributes to dilated cardiomyopathy and heart failure
Authors: Zhang Na , Ye Feiming , Zhou Yu , Zhu Wei , Xie Cuiping , Zheng Haiqiong , Chen Han , Chen Jinghai , Xie Xiaojie 
Published: March 2021

AbstractCardiac ankyrin repeat protein (CARP) is a cardiac‐specific stress‐response protein which exerts diverse effects to modulate cardiac remodeling in response to pathological stimuli. We examined the role of CARP in postnatal cardiac development and function under basal conditions in mice. Transgenic mice that selectively overexpressed CARP in heart (CARP Tg) exhibited dilated cardiac chambers, impaired heart function, and cardiac fibrosis as assessed by echocardiography and histological staining. Furthermore, the mice had a shorter lifespan and reduced survival rate in response to ischemic acute myocardial infarction. Immunofluorescence demonstrated the overexpressed CARP protein was predominantly accumulated in the nuclei of cardiomyocytes. Microarray analysis revealed that the nuclear localization of CARP was associated with the suppression of calcium‐handling proteins. In vitro experiments revealed that CARP overexpression resulted in decreased cell contraction and calcium transient. In post‐mortem cardiac specimens from patients with dilated cardiomyopathy and end‐stage heart failure, CARP was significantly increased. Taken together, our data identified CARP as a crucial contributor in dilated cardiomyopathy and heart failure which was associated with its regulation of calcium‐handling proteins.
SMURF2‐mediated ubiquitin signaling plays an essential role in the regulation of PARP1 PARylating activity, molecular interactions, and functions in mammalian cells
Authors: Ilić Nataša , Tao Yulei , Boutros‐Suleiman Sandy , Kadali Venkata Narasimha , Emanuelli Andrea , Levy‐Cohen Gal , Blank Michael 
Published: March 2021

AbstractPoly(ADP‐ribose) polymerase 1 (PARP1) is a key molecular stress sensor and response mediator implicated in multiple cellular functions in health and diseases. Despite its importance and intrinsic involvement in pivotal molecular and cellular processes, including DNA repair, transcription regulation, chromatin organization, and cell death, the regulatory mechanisms of PARP1 are poorly understood. In this study, we show that SMURF2, a HECT‐type E3 ubiquitin ligase and suggested tumor suppressor, physically interacts with PARP1 in different cellular settings, directly ubiquitinates it in vitro and stimulates its PARylation activity in cells, the phenomenon that required SMURF2 E3 ubiquitin ligase function. Intriguingly, in the cellular environment SMURF2 was found to regulate the dynamic exchange of ubiquitin moieties on PARP1, mostly decreasing its monoubiquitination. Through the set of systematic mass spectrometry analyses conducted on SMURF2‐modified cells, we identified on PARP1 18 lysine residues (out of 126 present in PARP1) as sites which ubiquitination was considerably affected by SMURF2. Subsequent site‐directed mutagenesis coupled with in cellula ubiquitination and PARylation assays unveiled K222 as a critical site enabling a cross talk between SMURF2‐modulated monoubiquitination of PARP1 and its activity, and pointed to K498, S507, and a KTR triad (K498/K521/K524) as the main auto‐PARylation sites affected by SMURF2. The results also uncovered that SMURF2 controls PARP1 interactome, influencing its functions and expression in a context‐dependent manner. Taken together, these findings suggest that SMURF2‐mediated ubiquitin signaling plays an essential role in PARP1 regulation, beyond the regulation of its protein expression.
Some dystrophy phenotypes of dystrophin‐deficient mdx mice are exacerbated by mild, repetitive daily stress
Authors: Lindsay Angus , Holm John , Razzoli Maria , Bartolomucci Alessandro , Ervasti James M. , Lowe Dawn A. 
Published: March 2021

AbstractPsychosocial stressors can cause physical inactivity, cardiac damage, and hypotension‐induced death in the mdx mouse model of Duchenne muscular dystrophy (DMD). Because repeated exposure to mild stress can lead to habituation in wild‐type mice, we investigated the response of mdx mice to a mild, daily stress to determine whether habituation occurred. Male mdx mice were exposed to a 30‐sec scruff restraint daily for 12 weeks. Scruff restraint induced immediate physical inactivity that persisted for at least 60 minutes, and this inactivity response was just as robust after 12 weeks as it was after one day. Physical inactivity in the mdx mice was not associated with acute skeletal muscle contractile dysfunction. However, skeletal muscle of mdx mice that were repeatedly stressed had slow‐twitch and tetanic relaxation times and trended toward high passive stiffness, possibly due to a small but significant increase in muscle fibrosis. Elevated urinary corticosterone secretion, adrenal hypertrophy, and a larger adrenal cortex indicating chronic activation of the hypothalamic‐pituitary‐adrenal (HPA) axis were measured in 12‐week stressed mdx mice relative to those unstressed. However, pharmacological inhibition of the HPA axis did not affect scruff‐induced physical inactivity and acute corticosterone injection did not recapitulate the scruff‐induced phenotype, suggesting the HPA axis is not the driver of physical inactivity. Our results indicate that the response of mdx mice to an acute mild stress is non‐habituating and that when that stressor is repeated daily for weeks, it is sufficient to exacerbate some phenotypes associated with dystrophinopathy in mdx mice.
Mistaken Identity: Frequency and Effects of Gender-Based Professional Misidentification of Resident Physicians
Authors: Berwick Shana , Calev Hila , Matthews Andrew , Mukhopadhyay Amrita , Poole Brian , Talan Jordan , Hayes Margaret M. , Smith C. Christopher 
Published: March 2021

Purpose
Evaluation of the medical profession at all levels has exposed episodes of gender-based role misidentification whereby women physicians are disproportionately misidentified as nonphysicians. The authors of this study investigate this phenomenon and its repercussions, quantifying the frequency with which resident physicians experience role misidentification and the effect this has on their experience and behavior.

Method
In 2018, the authors conducted a cross-sectional survey study of internal medicine, surgical, and emergency medicine residents at a single, large, urban, tertiary academic medical center. The survey tool captured both the self-reported frequency and effect of professional misidentification. The authors used a t test and linear multivariate regression to analyze the results.

Results
Of the 260 residents who received the survey, 186 (72%) responded, and the authors analyzed the responses of 182. All 85 of the women respondents (100%) reported being misidentified as nonphysicians at least once in their professional experience by patients or staff members, compared with 49% of the 97 men respondents. Of those 182 residents, 35% of women were misidentified more than 8 times per month by patients compared with 1% of men. Of the 85 women physicians responding to the survey, 38% felt angry and 36% felt less satisfied with their jobs as a result of misidentification compared with, respectively, 7% and 9% of men. In response to role misidentification, 51% of women changed their manner of attire and 81% changed their manner of introduction, compared with, respectively, 7% and 37% of men.

Conclusions
These survey results demonstrate that women physicians are more likely than men physicians to be misidentified as nonphysicians and that role misidentification provokes gender-polarized psychological and behavioral responses that have potentially important professional ramifications.
Diclofenac Is Superior to Paracetamol in Postoperative Pain Scores and Analgesic Consumption in Supratentorial Craniotomy With No Difference in Platelet and Clot Function: A Prospective Randomized Controlled Trial
Authors: Rajkiran Ragula , Soni Shiv Lal , Jangra Kiran , Bhagat Hemant , Singh Ajay , Singh Apinderpreet , Panda Nidhi B. , Kaloria Narender 
Published: March 2021

Background:
The use of nonsteroidal anti-inflammatory drugs in neurosurgery remains controversial because of potential risk of hematoma formation secondary to platelet dysfunction. This study aimed to investigate the efficacy and safety of diclofenac compared with paracetamol for the management of postcraniotomy pain.

Methods:
In all, 110 adult patients undergoing craniotomy for supratentorial tumors were randomized to receive either intravenous paracetamol (15 mg/kg) or intravenous diclofenac sodium (1.5 mg/kg) 30 minutes before the end of surgery and postoperatively at 12-hour intervals up to 48 hours. The analgesic efficacy of diclofenac and paracetamol was assessed using the Numerical Rating Scale (NRS) score at 12, 24, and 48 hours after surgery. We also examined the need for rescue analgesia, coagulation profiles using a Sonoclot analyzer, and incidence of intracranial hematoma formation.

Results:
At 24 hours postsurgery, NRS scores were lower in group D than in group P; median (interquartile range) and mean rank NRS score in group D was 3.00 (1.0), 43.71, respectively, compared with 3.00 (1.0), 59.29 in group P (P=0.004). Patients in group P received more rescue analgesia than those in group D. Coagulation profiles were similar between groups at 24 hours. Activated clotting time was longer in group D (128.76±12.61 s) than in group P (123.84±09.77 s; P=0.03) at 48 hours, although remained within normal limits in both groups; clot rate and platelet function were similar at 48 hours. There was no difference in the incidence of postoperative tumor bed hematoma.

Conclusion:
Compared with paracetamol, diclofenac sodium provided more effective postoperative analgesia at 24 hours with no evidence of adverse effects on coagulation profiles in patients undergoing craniotomy for supratentorial tumors.
What Can a Child Do With One Normal-Hearing Ear? Speech Perception and Word Learning in Children With Unilateral and Bilateral Hearing Losses Relative to Peers With Normal Hearing
Authors: Pittman Andrea L. , de Diego-Lázaro Beatriz 
Published: March 2021

Objectives:
To examine the effects of unilateral hearing loss on children’s ability to perceive familiar words and to learn and retain new words. Because children with unilateral hearing loss receive full auditory input in one ear, their performance was expected to be consistent with that of children with normal hearing rather than that of children with moderate bilateral hearing loss.

Design:
Participants were 36 school-age children with normal hearing bilaterally, 11 children with moderate bilateral hearing loss, and 11 children with mild-to-profound unilateral hearing loss (six right and five left). Half of the normally hearing children and two-thirds of the children with unilateral hearing loss were from bilingual Spanish/English-speaking homes. One of the 11 children with bilateral hearing loss was from a bilingual Spanish/English-speaking home. All children completed a word recognition test in English and in Spanish, a word-learning task comprised of nonsense words constructed using the phonotactic rules of English, Spanish, and Arabic, and a next-day word-retention test.

Results:
Word recognition did not differ across groups in English or Spanish. Learning and retention of nonsense words was highest for the children with normal hearing in all three languages. The children with unilateral and bilateral losses learned and recalled the English nonsense words as well as their normally hearing peers, but performance for the Spanish and Arabic nonsense words was significantly and similarly reduced by hearing loss in either ear.

Conclusions:
Failure to learn and retain new words given a full auditory representation in one ear suggests that children with unilateral and bilateral hearing losses may share a unifying feature of impairment at the level of the central auditory system.
A novel universal medial approach for difficult posteromedial tibial plateau fractures: a prospective case series
Authors: Fathy Ayman , Michael Fady 
Published: March 2021

Background:
Tibial plateau fractures are considered to be one of the most common fractures with an increasing incidence of motor vehicle accidents. Posteromedial fracture, in particular, is considered a more challenging case. Combination of posteromedial fragment fracture with central articular depression or medial condyle fracture make it much more difficult to reduce and adequately fix the fractured fragments. The aims of this study were to describe a new extensile medial approach for the management of different types of tibial plateau fractures with posteromedial fragments and to evaluate results using this approach.

Methods:
Between January 2015 and January 2017, 15 patients with Schatzker IV, V, or VI fractures, in combination with a posteromedial fragment, were operated for open reduction of the fracture with restoration of the articular surface alignment. Fixation was done by double plate osteosynthesis. Complete healing time and knee-function scores were recorded in the follow-up period.

Results:
The average age of patients was 41.8 yr; the mean follow-up period was 30 mo. One patient had superficial wound dehiscence and was treated conservatively. No patients with knee instability or loss of reduction were reported.

Conclusions:
The posteromedial approach offers a very good access to view, reduce, and fix difficult posteromedial fractures together with comminuted tibial plateau fractures without the need for dissection of the neurovascular bundle in the fossa or soft-tissue injury.

Level of Evidence:
Level IV.
Management trends of clavicular fractures at a level 1 trauma center: a retrospective chart review
Authors: Taylor Aaron , Simske Natasha M. , Wilson Eleanor S. , Jasty Naveen , Vallier Heather A. 
Published: March 2021

Background:
Controversy remains regarding optimal treatment of clavicular fractures, despite evidence touting lower nonunion rates for operative interventions. Given increasing evidence supporting operative treatment, the goal of this study was to observe trends in operative versus nonoperative treatment over a 15-year period.

Methods:
One thousand and eighty nine patients with any clavicular fracture (AO Foundation/Orthopaedic Trauma Association 15A to 15AC) between 2004 and 2018 were identified. Patient records were queried for demographic information, injuries to the head or chest, and treatment modality (operative vs. nonoperative). Independent sample t-tests, Fisher exact, or chi-square tests were used for analysis, with P less than 0.05 representing significance.

Results:
Of the 1089 qualified patients, the average age was 47.5 yr and 70.7% were men. Two hundred forty-two patients (20.2%) were managed operatively. Two hundred seventy-one patients (24.8%) had isolated injuries. Operative clavicle management increased from 6.4% of patients in 2004 and 2005 to 31.5% in 2018 (P<0.001). During this time, both patient age and chest-injury rates increased (both P<0.01). Patients with head injuries had a fixation rate of 4.8%, compared with 45.5% in patients with chest injuries. Those fixation rates differed from the rate for isolated clavicular fractures (30.9%) and those polytraumatized patients who had both chest and head injuries (18.8%) (P=0.026).

Conclusions:
Our data indicated that from 2004 to 2018, there was a five-fold increase in the rate of operative management of clavicular fractures. This rise in fixation rates may substantially influence the rate of complications, secondary surgeries, and cost of additional healthcare utilization. It is important to counsel patients individually to limit unnecessary surgery.

Level of Evidence:
Level IV.
Role of machine learning in management of degenerative spondylolisthesis: a systematic review
Authors: El-Daw Sherif , El-Tantawy Ahmad , Aly Tarek , Ramadan Mohamed 
Published: March 2021

Background:
Machine learning is a field of artificial intelligence that allows a computer system to learn through repetitive processes and improve with experience. Precise study of medical data benefits early disease recognition, patient care, and community services.

Methods:
The purpose of this systematic review was to assess the evidence for effectiveness of machine learning and artificial intelligence in the management of spondylolisthesis. A literature search of published and unpublished articles resulted in the retrieval of more than 1000 potential studies on the subject area. Eight were reviewed according to inclusion criteria.

Results:
Expert medical doctors examined the pelvis and lumbar spine shape and orientation to diagnose spondylolisthesis. However, some shape and orientation parameters were misleading and unclear. Therefore, automatic diagnosis methods (classification methods) have been proposed to help medical doctors. The most important parameter of classification was found to be the grade of spondylolisthesis.

Conclusions:
Although the proposed results may be misleading, the studies provided evidence to suggest that two-thirds of the patients with grade I spondylolisthesis were stable enough to tolerate decompression without fusion, but that one-third of the patients appeared to develop instability over time. This instability often led to reoperation for spinal fusion at the level of listhesis. It is possible to create a predictive machine learning algorithm that is calibrated and accurate to predict discharge placement.

Level of Evidence:
Level I.
Anterior Controllable Antedisplacement and Fusion (ACAF) Technique for the Treatment of Multilevel Cervical Spondylotic Myelopathy With Spinal Stenosis (MCSMSS)
Authors: Luo Xi , Wang Shunmin , Sun Kaiqiang , Sun Jingchuan , Wang Yuan , Jiang Jialin , Zhao Feng , Guo Yongfei , Shi Jiangang 
Published: March 2021

Study Design:
Retrospective study.

Objective:
To investigate the clinical effect of anterior controllable antedisplacement and fusion (ACAF) technique for the treatment of multilevel cervical spondylotic myelopathy with spinal stenosis (MCSMSS), compared with hybrid decompression fixation (HDF).

Summary of Background Data:
A retrospective analysis of 94 cases with MCSMSS was carried out. Fifty-four patients were treated with ACAF, whereas 40 patients were treated with HDF.

Methods:
The operation time, intraoperative blood loss, postoperative complications, Japanese Orthopedic Association score, Neck Disability Index score, parameters at axial computed tomography, cervical curvature and the Kang grade were compared between 2 groups.

Results:
The patients were followed up for 12–17 (15.6±1.6) months. Compared with HDF, ACAF group achieved better decompression according to computed tomography measurement and Kang grade (P<0.05), and recovered to a greater cervical Cobb angle (P<0.05). However, Japanese Orthopedic Association score and Neck Disability Index showed no significant difference 1 year after surgery (P>0.05). In addition, ACAF presented longer operation time (P<0.05) and similar intraoperative blood loss (P>0.05), compared with HDF. In terms of complications, ACAF produced less incidences of cerebrospinal fluid leakage, implant complication, epidural hematoma, and C5 palsy compared with HDF.

Conclusions:
ACAF is an effective method for the treatment of MCSMSS. In comparison to HDF, ACAF has the advantages of more sufficient decompression, more satisfactory cervical curvature, and lower incidence rates of complications.
A risk score system for stratifying the risk of relapse in B cell acute lymphocytic leukemia patients after allogenic stem cell transplantation
Authors: Cao Le-Qing , Zhou Yang , Liu Yan-Rong , Xu Lan-Ping , Zhang Xiao-Hui , Wang Yu , Chen Huan , Chen Yu-Hong , Wang Feng-Rong , Han Wei , Sun Yu-Qian , Yan Chen-Hua , Tang Fei-Fei , Mo Xiao-Dong , Liu Kai-Yan , Fan Qiao-Zhen , Chang Ying-Jun , Huang Xiao-Jun 
Published: March 2021

Abstract

Background
For patients with B cell acute lymphocytic leukemia (B-ALL) who underwent allogeneic stem cell transplantation (allo-SCT), many variables have been demonstrated to be associated with leukemia relapse. In this study, we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT.

Methods
A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People's Hospital from December 2010 to December 2015 were enrolled in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT, and establish a risk score to identify patients with different probabilities of relapse. The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables.

Results
All patients achieved neutrophil engraftment, and 95.4% of patients achieved platelet engraftment. The 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality were 20.7%, 70.4%, 65.6%, and 13.9%, respectively. Multivariate analysis showed that patients with positive post-transplantation minimal residual disease (MRD), transplanted beyond the first complete remission (≥CR2), and without chronic graft-versus-host disease (cGVHD) had higher CIR (P
< 0.001, P = 0.004, and P
< 0.001, respectively) and worse LFS (P
< 0.001, P = 0.017, and P
< 0.001, respectively), and OS (P
< 0.001, P = 0.009, and P
< 0.001, respectively) than patients without MRD after transplantation, transplanted in CR1, and with cGVHD. A risk score for predicting relapse was formulated with the three above variables. The 5-year relapse rates were 6.3%, 16.6%, 55.9%, and 81.8% for patients with scores of 0, 1, 2, and 3 (P
< 0.001), respectively, while the 5-year LFS and OS values decreased with increasing risk score.

Conclusion
This new risk score system might stratify patients with different risks of relapse, which could guide treatment.
Exercise Protocol With Limited Shoulder Range of Motion for 15 or 30 Days After Conservative Surgery for Breast Cancer With Oncoplastic Technique
Authors: Rizzi Samantha K.L.A. , Haddad Cinira A.S. , Giron Patrícia S. , Figueira Patrícia V.G. , Estevão Amanda , Elias Simone , Nazário Afonso C.P. , Facina Gil 
Published: March 2021

Objective:
The objective is to evaluate the effect of limiting shoulder range of motion (ROM) for 15 or 30 days on surgical complications and on shoulder ROM, pain, and upper limb function of breast cancer patients following conservative oncoplastic surgery.

Materials and Methods:
A randomized clinical trial was conducted with 60 women with breast cancer who underwent conservative oncoplastic surgery. The day after surgery, all patients started an exercise protocol with shoulder exercises limited to 90 degrees. Two weeks after surgery they were randomized into Free ROM Group (n=30) or Limited ROM Group (n=30). The Free ROM Group was allowed to perform shoulder exercises with unlimited ROM; the Limited ROM Group continued with shoulder movement restricted at 90 degrees until 30 days after surgery, at which time they were also allowed free ROM. The primary outcome was the incidence of postoperative complications (dehiscence, seroma, infection, and necrosis) and secondary outcomes were shoulder ROM, pain, and upper limb function.

Results:
No difference in the incidence of postoperative scar complications between groups was noted. There was no difference between the groups in shoulder joint amplitude, pain, or upper limb function.

Conclusions:
The free ROM exercise protocol 15 days post surgery was safe concerning cicatricial complications.