bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and Landscape of Actionable Genomic Alterations in Renal Cell Carcinoma
Authors: Attalla Kyrollis , DiNatale Renzo G. , Rappold Phillip M. , Fong Christopher J. , Sanchez-Vega Francisco , Silagy Andrew W. , Weng Stanley , Coleman Jonathan , Lee Chung-Han , Carlo Maria I. , Durack Jeremy C. , Solomon Stephen B. , Reuter Victor E. , Russo Paul , Chan Timothy A. , Motzer Robert J. , Schultz Nikolaus D. , Reznik Ed , Voss Martin H. , Hakimi A. Ari 
Published: July 2021

Abstract

Purpose:
We report our experience with next-generation sequencing to characterize the landscape of actionable genomic alterations in renal cell carcinoma (RCC).

Experimental Design:
A query of our institutional clinical sequencing database (MSK-IMPACT) was performed that included tumor samples from 38,468 individuals across all cancer types. Somatic variations were annotated using a precision knowledge database (OncoKB) and the available clinical data stratified by level of evidence. Alterations associated with response to immune-checkpoint blockade (ICB) were analyzed separately; these included DNA mismatch repair (MMR) gene alterations, tumor mutational burden (TMB), and microsatellite instability (MSI). Data from The Cancer Genome Atlas (TCGA) consortium as well as public data from several clinical trials in metastatic RCC were used for validation purposes. Multiregional sequencing data from the TRAcking Cancer Evolution through Therapy (TRACERx) RENAL cohort were used to assess the clonality of somatic mutations.

Results:
Of the 753 individuals with RCC identified in the MSK-IMPACT cohort, 115 showed evidence of targetable alterations, which represented a prevalence of 15.3% [95% confidence interval (CI), 12.7%–17.8%). When stratified by levels of evidence, the alterations identified corresponded to levels 2 (11.3%), 3A (5.2%), and 3B (83.5%). A low prevalence was recapitulated in the TCGA cohort at 9.1% (95% CI, 6.9%–11.2%). Copy-number variations predominated in papillary RCC tumors, largely due to amplifications in the MET gene. Notably, higher rates of actionability were found in individuals with metastatic disease (stage IV) compared with those with localized disease (OR, 2.50; 95% CI, 1.16–6.16; Fisher's P = 0.01). On the other hand, the prevalence of alterations associated with response to ICB therapy was found to be approximately 5% in both the MSK-IMPACT and TCGA cohorts and no associations with disease stage were identified (OR, 1.35; 95% CI, 0.46–5.40; P = 0.8). Finally, multiregional sequencing revealed that the vast majority of actionable mutations occurred later during tumor evolution and were only present subclonally in RCC tumors.

Conclusions:
RCC harbors a low prevalence of clinically actionable alterations compared with other tumors and the evidence supporting their clinical use is limited. These aberrations were found to be more common in advanced disease and seem to occur later during tumor evolution. Our study provides new insights on the role of targeted therapies for RCC and highlights the need for additional research to improve treatment selection using genomic profiling.
Maternal Heart Failure
Authors: Bright Rachel A. , Lima Fabio V. , Avila Cecilia , Butler Javed , Stergiopoulos Kathleen 
Published: July 2021

Abstract
Heart failure (HF) remains the most common major cardiovascular complication arising in pregnancy and the postpartum period. Mothers who develop HF have been shown to experience an increased risk of death as well as a variety of adverse cardiac and obstetric outcomes. Recent studies have demonstrated that the risk to neonates is significant, with increased risks in perinatal morbidity and mortality, low Apgar scores, and prolonged neonatal intensive care unit stays. Information on the causal factors of HF can be used to predict risk and understand timing of onset, mortality, and morbidity. A variety of modifiable, nonmodifiable, and obstetric risk factors as well as comorbidities are known to increase a patient's likelihood of developing HF, and there are additional elements that are known to portend a poorer prognosis beyond the HF diagnosis. Multidisciplinary cardio‐obstetric teams are becoming more prominent, and their existence will both benefit patients through direct care and increased awareness and educate clinicians and trainees on this patient population. Detection, access to care, insurance barriers to extended postpartum follow‐up, and timely patient counseling are all areas where care for these women can be improved. Further data on maternal and fetal outcomes are necessary, with the formation of State Maternal Perinatal Quality Collaboratives paving the way for such advances.
Reconciling Seemingly Contradictory Results from the Oregon Health Insurance Experiment and the Massachusetts Health Reform
Authors: Kowalski Amanda E. 
Published: July 2021

Abstract
A headline result from the Oregon Health Insurance Experiment is that emergency room (ER) utilization increased. A seemingly contradictory result from the Massachusetts health reform is that ER utilization decreased. I reconcile both results by identifying treatment effect heterogeneity within the Oregon experiment and extrapolating it to Massachusetts. Even though Oregon compliers increased their ER utilization, they were adversely selected relative to Oregon never takers, who would have decreased their ER utilization. Massachusetts expanded coverage from a higher level to healthier compliers. Therefore, Massachusetts compliers are comparable to a subset of Oregon never takers, which can reconcile the results.
Impacts of Multi-Timescale Circulations on Meridional Moisture Transport
Authors: Liu Qiao , Li Tim , Zhou Weican 
Published: July 2021

AbstractRelative impacts of the climatological annual mean, the climatological annual variation, the synoptic, the intra-seasonal and the inter-annual flows on meridional moisture transport were investigated based on reanalysis data. Due to an in-phase relationship between the poleward wind and specific humidity, the synoptic and intra-seasonal motions contribute about 50% and 30% of the maximum zonal and annual mean poleward moisture transport in the middle latitudes, respectively. The preferred latitudinal location (40°N or S) of the maximum zonal mean moisture transport by the synoptic motion is attributed to the combined effect of the maximum wind variability poleward of 40°N or S in association with atmospheric baroclinic instability and the maximum moisture variability equatorward of 40°N or S in association with the anomalous advection of the mean moisture. While the MJO and ENSO have a small contribution to the long-term mean transport, they may strongly affect regional moisture transport through interaction with the mean moisture and through the modulation to higher-frequency modes. A statistical relationship between tropical cyclone (TC) moisture and intensity was constructed based on a large number of high-resolution Weather Research and Forecasting (WRF) model simulations, and the so-derived relationship was further applied to estimate TC moisture transport. It is found that TC transport accounts for about 30% (53%) of the climatological seasonal mean total moisture transport over key northern (southern) hemispheric TC track regions in the northern (southern) hemispheric TC season.
Tropical and subtropical forcing of future southern hemisphere stationary wave changes
Authors: Patterson Matthew , Woollings Tim , Bracegirdle Thomas J. 
Published: July 2021

AbstractStationary wave changes play a significant role in the regional climate change response in Southern Hemisphere (SH) winter. In particular, almost all CMIP5 models feature a substantial strengthening of the westerlies to the south of Australia and enhancement of the subtropical jet over the eastern Pacific in winter. In this study we investigate the mechanisms behind these changes, finding that the stationary wave response can largely be explained via reductions in the magnitude of the upper level Rossby wave source over the tropical / subtropical East Pacific. The Rossby wave source changes in this region are robust across the model ensemble and are strongly correlated with changes to low latitude circulation patterns, in particular, the projected southward migration of the Hadley cell and weakening of the Walker circulation. To confirm our mechanism of future changes, we employ a series of barotropic model experiments in which the barotropic model is given a background state identical to a particular CMIP5 model and an anomalous Rossby wave source is imposed. This simple approach is able to capture the primary features of the ensemble mean change, including the cyclonic anomaly south of Australia, and is also able to capture many of the inter-model differences. These findings will help to advance our understanding of the mechanisms underpinning SH extratropical circulation changes under climate change.
Discrimination experienced by Aboriginal and Torres Strait Islander males in Australia: Associations with suicidal thoughts and depressive symptoms
Authors: Haregu Tilahun , Jorm Anthony F , Paradies Yin , Leckning Bernard , Young Jesse T , Armstrong Gregory 
Published: July 2021

Introduction: Globally, Indigenous populations have higher rates of suicidal behavior and psychological distress compared to non-Indigenous populations. Indigenous populations also report high rates of exposure to discrimination, which could potentially contribute to poor mental health outcomes. The objectives of this paper were to estimate the prevalence of discrimination among Aboriginal and Torres Strait Islander males in Australia and to examine the role of discrimination in the association between Aboriginal and Torres Strait Islander status and suicidal thoughts and depressive symptoms. Methods: We used cross-sectional data on 13,697 males aged 18–55 years from the Australian Longitudinal Study on Male Health. We undertook a Poisson regression with robust standard error analyses to examine Aboriginal and Torres Strait Islander status and self-perceived exposure to discrimination in the past 2 years as correlates of recent suicidal ideation. We used zero-inflated negative binomial regression to assess Aboriginal and Torres Strait Islander status and self-perceived exposure to discrimination as correlates of recent depressive symptoms. Results: Aboriginal and Torres Strait Islander males have a twofold higher prevalence of self-perceived discrimination (39.2% vs 19.3%, p < 0.001), suicidal ideation (21.8% vs 9.4%, p < 0.001) and moderate or worse depressive symptoms (24.0% vs 12.2%, p < 0.001) as compared to their non-Indigenous counterparts. After adjusting for sociodemographics and substance use, Aboriginal and Torres Strait Islander status was significantly associated with suicidal thoughts (odds ratio = 1.49, p = 0.019) and depressive symptoms (prevalence rate ratio = 1.19, p = 0.018). About 15.3% and 28.7% of the association between Aboriginal and Torres Strait Islander status and suicidal thoughts and depressive symptoms, respectively, was explained by discrimination. Conclusion: Our analyses add to evidence that discrimination is a contributor to mental health disparities between Aboriginal and Torres Strait Islander and non-Indigenous populations in Australia. Reducing discrimination ought to be considered as part of strategies to improve the social and emotional well-being of Aboriginal and Torres Strait Islander people.
Targeting reactive nitroxidative species in preclinical models of migraine
Authors: Akerman Simon , Salvemini Daniela , Romero-Reyes Marcela 
Published: July 2021

Background Reactive nitroxidative species, such as nitric oxide but particularly peroxynitrite, have been strongly implicated in pain mechanisms. Targeting peroxynitrite is anti-nociceptive in pain models, but little is known about its role in migraine mechanisms. Given the need to validate novel targets for migraine headache, our objective was to study the potential of reactive nitroxidative species, particularly peroxynitrite, as novel targets for drug discovery and their role in migraine mechanisms. Methods We recorded neuronal activity in rats with extracellular electrodes and examined the effects of targeting nitric oxide or peroxynitrite on ongoing and cranial-evoked firing rates of central trigeminocervical neurons. We injected calcitonin gene-related peptide (which produces migraine-like headache in migraineurs) and characterized neuronal responses to cranial stimulation and on behavioral responses to nociceptive periorbital stimulation and determined the effects of targeting reactive nitroxidative species on the mediated changes. Results L-NAME (nitric oxide synthase inhibitor) and Fe(III)5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato chloride (FeTPPS; peroxynitrite decomposition catalyst) inhibited ongoing and dural-evoked responses of trigeminocervical neurons, without affecting normal facial-cutaneous responses. Calcitonin gene-related peptide caused activation and sensitization of dural-responsive trigeminovascular neurons with hypersensitivity to intracranial and extracranial stimulation, and reduction of periorbital withdrawal thresholds. Only the peroxynitrite decomposition catalyst prevented these neuronal and behavioral nociceptive responses. Discussion The data support that calcitonin gene-related peptide mediates the underlying neurobiological mechanisms related to the development of migraine-like headache. They also confirm the role of nitric oxide and implicate peroxynitrite production along the trigeminovascular migraine pathway in these mechanisms. The data also support peroxynitrite as a novel and potentially effective target for migraine treatment. The current drug development focus on peroxynitrite decomposition catalysts for chronic pain disorders should therefore extend to migraine.
Bowel ultrasound enhances predictive value based on clinical indicators: a scoring system for moderate-to-severe endoscopic activities in patients with ulcerative colitis
Authors: Zhang Mengmeng , Zhang Huimin , Zhu Qingli , Bai Xiaoyin , Zhou Qingyang , Ruan Gechong , Li Wenbo , Ma Li , Xiao Mengsu , Yang Hong , Qian Jiaming 
Published: July 2021

Background and Aim: The aim was to assess non-invasive factors among clinical features, laboratory, and bowel ultrasound (BUS) characteristics and to develop a scoring system to predict endoscopic activities for ulcerative colitis (UC) patients. Methods: We performed a retrospective study collecting UC patients between January 2015 to September 2020. Logistic regression was performed to predict moderate-to-severe endoscopic activities, defined as endoscopic Mayo score ⩾2. Model performance was described with discrimination and calibration ability and validated by internal and external methods. Results: A total of 103 and 29 patients were enrolled in the modeling and validation groups, respectively. Stool frequency ⩾5 times/day, hematochezia, erythrocyte sedimentation rate (ESR), and colonic wall flow in BUS were included into two predictive models for endoscopic activities, both with good discrimination ability [Area under curve (AUC) 0.879 and 0.882, p  < 0.001] and a sensitivity of 76.7% and specificity of 92.3%, which showed an adequate calibration ability by using the Hosmer–Lemeshow test ( p = 0.14 and 0.07). The external validation displayed consistent results with the above mentioned. Nomograms were also established for these models. Conclusion: We developed predictive models for endoscopic disease activities by using noninvasive factors based on stool frequency, hematochezia, ESR, and colonic wall blood flow in BUS. These models performed well in the internal and external validation.
ARTHROSCOPIC TREATMENT OF POSTERIOR ANKLE IMPINGEMENT IN PEDIATRIC ATHLETES AND ITS OUTCOMES - A PROSPECTIVE STUDY
Authors: Kushare Indranil , Ghanta Ramesh , Allahabadi Sachin , Kastan Kristen , Stone Tracie , Gomez Jorge , McKay Scott 
Published: July 2021

Background: Posterior ankle impingement (PAI) is a known cause of posterior ankle pain in athletes performing repetitive plantarflexion motions, such as in soccer. Even though it is well-described in adults, literature on PAI in pediatric patients is scarce. Purpose: The purpose was to describe prospective outcomes after arthroscopic management of posterior ankle impingement in pediatric and adolescent patients. Methods: An IRB-approved prospective study was performed at a tertiary children’s hospital from 2016-2020. Patients <18 years of age who were diagnosed with posterior ankle impingement and underwent posterior ankle arthroscopy with minimum 3-month post-operative follow-up were included. Data collected included pre-operative demographics and sporting activities, clinical and radiologic findings. Visual Analogue Scale (VAS) scores, and American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores were collected at the initial and follow-up visits. Results: A total of 50 patients (65 ankles; 28 females), were included with mean age 13.3 years. Football and soccer were the most commonly implicated sports. All patients underwent initial conservative management including relative rest, immobilization and/or physical therapy for an average period of 44 weeks. The indication for surgery was failure of conservative management to improve symptoms. All patients underwent posterior ankle arthroscopy with arthroscopic confirmation of impingement pathology followed by debridement. The pathology was predominantly bony (Os trigonum, Stieda process) in 54%, and predominantly soft tissue (low flexor hallucis longus belly, ganglion cyst in the ankle, hypertrophied posterior ankle ligaments) in 46%. All 50 patients (100%) returned to sports at an average 8.5 ± 4.1 weeks. 51 ankles had radiographs done at 1 years post-operatively which did not show recurrence or any new osseous abnormalities. At mean follow up of 26 months, there was a statistically significant improvement in VAS scores (7.0 to 0.53, p<0.05) and AOFAS scores (63.9 to 95.6, p<0.05) from pre- to post-operative final follow-up. Complications included numbness over lateral part of the heel (sural nerve distribution) in 1 patient. Conclusion: The first prospective study on pediatric PAI demonstrates that arthroscopic treatment, after failed conservative management, allowed patients to return to prior level of activity and sports, and resulted in improved pain relief and higher functional parameters. Complications associated with this procedure were minimal.
DOES BRAIN ACTIVATION DURING FUNCTIONAL MOVEMENT TASKS DIFFERENTIATE BETWEEN GOOD AND BAD MOVERS? AN INTEGRATED NEUROIMAGING ASSESSMENT OF MOTOR CONTROL IN YOUNG ATHLETES
Authors: Anand Manish , Diekfuss Jed A. , Grooms Dustin R. , Slutsky-Ganesh Alexis B. , Bonnette Scott , Riehm Christopher , Foss Kim D. Barber , DiCesare Christopher A. , Myer Gregory D. 
Published: July 2021

Background: Aberrant frontal and sagittal plane knee motor control biomechanics contribute to increased anterior cruciate ligament (ACL) injury risk. Emergent data further indicates alterations in brain function may underlie ACL injury high risk biomechanics and primary injury. However, technical limitations have limited our ability to assess direct linkages between maladaptive biomechanics and brain function. Hypothesis/Purpose: (1) Increased frontal plane knee range of motion would associate with altered brain activity in regions important for sensorimotor control and (2) increased sagittal plane knee motor control timing error would associate with altered activity in sensorimotor control brain regions. Methods: Eighteen female high-school basketball and volleyball players (14.7 ± 1.4 years, 169.5 ± 7 cm, 65.8 ± 20.5 kg) underwent brain functional magnetic resonance imaging (fMRI) while performing a bilateral, combined hip, knee, and ankle flexion/extension movements against resistance (i.e., leg press) Figure 1(a). The participants completed this task to a reference beat of 1.2 Hz during four movement blocks of 30 seconds each interleaved in between 5 rest blocks of 30 seconds each. Concurrent frontal and sagittal plane range of motion (ROM) kinematics were measured using an MRI-compatible single camera motion capture system. Results: Increased frontal plane ROM was associated with increased brain activity in one cluster extending over the occipital fusiform gyrus and lingual gyrus ( p = .003, z > 3.1). Increased sagittal plane motor control timing error was associated with increased brain activity in multiple clusters extending over the occipital cortex (lingual gyrus), frontal cortex, and anterior cingulate cortex ( p < .001, z > 3.1); see Figure 1 (b). Conclusion: The associations of increased knee frontal plane ROM and sagittal plane timing error with increased activity in regions that integrate visuospatial information may be indicative of an increased propensity for knee injury biomechanics that are, in part, driven by reduced spatial awareness and an inability to adequately control knee abduction motion. Increased activation in these regions during movement tasks may underlie an impaired ability to control movements (i.e., less neural efficiency), leading to compromised knee positions during more complex sports scenarios. Increased activity in regions important for cognition/attention associating with motor control timing error further indicates a neurologically inefficient motor control strategy. [Figure: see text]
THE CLINICAL UTILITY OF THE VESTIBULAR AND OCULAR MOTOR SCREENING FOR PROTRACTED RECOVERY IN PEDIATRIC CONCUSSION PATIENTS
Authors: Caze Todd J. ,   August Price PsyD, Knell Gregory , Ellis Christine , Abt John , Burkhart Scott 
Published: July 2021

Background: Sports-related concussions (SRCs) are a concern for youth athletes and their subsequent healthy development into adulthood. Protracted recovery (>28 days) from a SRC may lead to long-term complications resultant of persistent symptoms. There is a current lack in understanding of the factors contributing to protracted recovery from SRC in children, and in particular no tools exist to identify those SRC patients that may be more likely have a protracted recovery in an acute clinical setting. Hypothesis/Purpose: To examine the relationship between initial Vestibular and Ocular Motor Screening (VOMS) and protracted recovery from concussion in youth. Methods: Children aged 8-12 years old, who were diagnosed with a SRC and seen in a concussion specialty clinic within 7-days of injury were included in the analysis. VOMS was administered during the initial visit. A positive VOMS score was defined as any 2-point increase from baseline in patient reported symptom severity on dizziness, fogginess, headache, and nausea, or any convergence measure greater than 6 centimeters. Recovery time (days) was the interval between date of injury and date of medical clearance. Multivariable logistic regressions were used to determine the odds of protracted recovery based on an initial positive VOMS. Results: A total of 108 males (mean age=10.8, sd=1.3) and 66 females (mean age=10.8, sd=1.4), took a median (IQR) 20.0 (15.0-28.5) and 22.0 (15.0-34.0) days to recover, respectively. After controlling for age and days since injury, those with a positive VOMS were 3.92 (95% CI = 1.58-9.71, p=0.003) times more likely to have a protracted recovery compared to those with a negative VOMS. When stratified by sex, observed effects were more amplified among males (OR=5.92, 95% CI=1.59-21.96, p=0.008), than among females (OR=2.44, 95% CI=0.61-9.71, p=0.21). Conclusion: There is a need to determine the relationship between SRC assessment measures and recovery time to improve clinical management and outcomes. In this sample of pediatric concussion patients aged 8-12 years, the VOMS displayed potential as a tool to screen for delayed recovery among males. Future studies should confirm these findings in other, larger samples, while taking into consideration other factors that may influence recovery time.