bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNA TROJAN promotes proliferation and resistance to CDK4/6 inhibitor via CDK2 transcriptional activation in ER+ breast cancer
Authors: Jin Xi , Ge Li-Ping , Li Da-Qiang , Shao Zhi-Ming , Di Gen-Hong , Xu Xiao-En , Jiang Yi-Zhou 
Published: May 2020

AbstractBackgroundEstrogen receptor-positive (ER+) breast cancers represent approximately two-thirds of all breast cancers and have a sustained risk of late disease recurrence. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have shown significant efficacy in ER+ breast cancer. However, their effects are still limited by drug resistance. In this study, we aim to explore the role of long noncoding RNA TROJAN in ER+ breast cancer.MethodsThe expression level of TROJAN in breast cancer tissue and cell lines was determined by quantitative real-time PCR. In vitro and in vivo assays as well as patient derived organoid were preformed to explore the phenotype of TROJAN in ER+ breast cancer. The TROJAN-NKRF-CDK2 axis were screened and validated by RNA pull-down, mass spectrometry, RNA immunoprecipitation, microarray, dual-luciferase reporter and chromatin immunoprecipitation assays.ResultsHerein, we showed that TROJAN was highly expressed in ER+ breast cancer. TROJAN promoted cell proliferation and resistance to a CDK4/6 inhibitor and was associated with poor survival in ER+ breast cancer. TROJAN can bind to NKRF and inhibit its interaction with RELA, upregulating the expression of CDK2. The inhibition of TROJAN abolished the activity of CDK2, reversing the resistance to CDK4/6 inhibitor. A TROJAN antisense oligonucleotide sensitized breast cancer cells and organoid to the CDK4/6 inhibitor palbociclib both in vitro and in vivo.ConclusionsTROJAN promotes ER+ breast cancer proliferation and is a potential target for reversing CDK4/6 inhibitor resistance.
Validity and reliability of wearable inertial sensors in healthy adult walking: a systematic review and meta-analysis
Authors: Kobsar Dylan , Charlton Jesse M. , Tse Calvin T.F. , Esculier Jean-Francois , Graffos Angelo , Krowchuk Natasha M. , Thatcher Daniel , Hunt Michael A. 
Published: May 2020

Abstract
Background
Inertial measurement units (IMUs) offer the ability to measure walking gait through a variety of biomechanical outcomes (e.g., spatiotemporal, kinematics, other). Although many studies have assessed their validity and reliability, there remains no quantitive summary of this vast body of literature. Therefore, we aimed to conduct a systematic review and meta-analysis to determine the i) concurrent validity and ii) test-retest reliability of IMUs for measuring biomechanical gait outcomes during level walking in healthy adults.

Methods
Five electronic databases were searched for journal articles assessing the validity or reliability of IMUs during healthy adult walking. Two reviewers screened titles, abstracts, and full texts for studies to be included, before two reviewers examined the methodological quality of all included studies. When sufficient data were present for a given biomechanical outcome, data were meta-analyzed on Pearson correlation coefficients (r) or intraclass correlation coefficients (ICC) for validity and reliability, respectively. Alternatively, qualitative summaries of outcomes were conducted on those that could not be meta-analyzed.

Results
A total of 82 articles, assessing the validity or reliability of over 100 outcomes, were included in this review. Seventeen biomechanical outcomes, primarily spatiotemporal parameters, were meta-analyzed. The validity and reliability of step and stride times were found to be excellent. Similarly, the validity and reliability of step and stride length, as well as swing and stance time, were found to be good to excellent. Alternatively, spatiotemporal parameter variability and symmetry displayed poor to moderate validity and reliability. IMUs were also found to display moderate reliability for the assessment of local dynamic stability during walking. The remaining biomechanical outcomes were qualitatively summarized to provide a variety of recommendations for future IMU research.

Conclusions
The findings of this review demonstrate the excellent validity and reliability of IMUs for mean spatiotemporal parameters during walking, but caution the use of spatiotemporal variability and symmetry metrics without strict protocol. Further, this work tentatively supports the use of IMUs for joint angle measurement and other biomechanical outcomes such as stability, regularity, and segmental accelerations. Unfortunately, the strength of these recommendations are limited based on the lack of high-quality studies for each outcome, with underpowered and/or unjustified sample sizes (sample size median 12; range: 2–95) being the primary limitation.
Dry needling for spine related disorders: a scoping review
Authors: Funk Matthew F. , Frisina-Deyo Aric J. 
Published: May 2020

AbstractIntroduction/BackgroundThe depth and breadth of research on dry needling (DN) has not been evaluated specifically for symptomatic spine related disorders (SRD) from myofascial trigger points (TrP), disc, nerve and articular structures not due to serious pathologies. Current literature appears to support DN for treatment of TrP. Goals of this review include identifying research published on DN treatment for SRD, sites of treatment and outcomes studied.MethodsA scoping review was conducted following Levac et al.’s five part methodological framework to determine the current state of the literature regarding DN for patients with SRD.ResultsInitial and secondary search strategies yielded 55 studies in the cervical (C) region (71.43%) and 22 in the thoracolumbar-pelvic (TLP) region (28.57%). Most were randomized controlled trials (60% in C, 45.45% in TLP) and clinical trials (18.18% in C, 22.78% in TLP). The most commonly treated condition was TrP for both the C and TLP regions. In the C region, DN was provided to 23 different muscles, with the trapezius as treatment site in 41.88% of studies. DN was applied to 31 different structures in the TLP region. In the C region, there was one treatment session in 23 studies (41.82%) and 2–6 treatments in 25 (45.45%%). For the TLP region, one DN treatment was provided in 8 of the 22 total studies (36.36%) and 2–6 in 9 (40.9%). The majority of experimental designs had DN as the sole intervention. For both C and TLP regions, visual analogue scale, pressure pain threshold and range of motion were the most common outcomes.ConclusionFor SRD, DN was primarily applied to myofascial structures for pain or TrP diagnoses. Many outcomes were improved regardless of diagnosis or treatment parameters. Most studies applied just one treatment which may not reflect common clinical practice. Further research is warranted to determine optimal treatment duration and frequency. Most studies looked at DN as the sole intervention. It is unclear whether DN alone or in addition to other treatment procedures would provide superior outcomes. Functional outcome tools best suited to tracking the outcomes of DN for SRD should be explored.
The Manchurian candidate: chiropractors as propagators of neoliberalism in health care
Authors: Gliedt Jordan A. , Holmes Benjamin D. , Nelson David A. 
Published: May 2020

AbstractThe rise of neoliberalism has influenced the health care sector, including the chiropractic profession. The neoliberal infiltration of market justice behavior is in direct conflict with the fiduciary agreement to serve the public good before self-interests and has compromised the chiropractor, who now may act as an agent of neoliberalism in health care. The purpose of this paper is to present an overview of the impact of neoliberalism on the chiropractic profession and provide recommendations for a professional philosophical shift from a market justice model to a communal and social justice model.
Four-color fluorescence in-situ hybridization is useful to assist to distinguish early stage acral and cutaneous melanomas from dysplastic junctional or compound nevus
Authors: Lai Yumei , Wu Yan , Liu Ruping , Lu Aiping , Zhou Lixin , Jia Lin , Diao Xinting , Li Zhongwu 
Published: May 2020

Abstract
Background/objective
Acral and cutaneous melanomas are usually difficult to accurately diagnose in the early stage, owing to the similarity in clinical manifestations and morphology with those of dysplastic nevus (DN). In this study, we aimed to evaluate the diagnostic value of four-color fluorescence in-situ hybridization (FISH) probes specific to the RREB1,CCND1,and MYB genes, and centromere of chromosome 6, in distinguishing DN and melanoma.

Methods
Fifty one DN and 58 melanoma cases were collected and tested with four-color FISH. Histological features were reviewed and concordant morphologic diagnosis by three pathologists was considered the golden criterion.

Results
Fifty DN and 59 melanoma cases, with 37 melanomas in situ and 22 melanomas in Clark level 2, were confirmed finally; among them, 42 (71.2%) cases were acral. A comparison of clinicopathological features between the two entities showed that several features were considerably more frequently observed in the melanoma group, including more mitotic figures, stratum corneum pigmentation, lymphocyte infiltration, cell atypia, successive or pagetoid melanocyte growth pattern in the epidermis, larger tumor size, and older age at diagnosis. FISH was positive in 3 (6.0%) DN and 56 (94.9%) melanoma cases according to Gerami’s criteria. In distinguishing the two groups, the sensitivity of the four-color FISH was 94.9% and specificity was 94.0%.We found that CCND1 gain was the most sensitive, either in Gerami’s or Gaiser’s criteria. Further analysis showed that CCND1gain was more obvious in the acral group of melanoma.

Conclusions
We conclude that the four-color FISH test was highly sensitive and specific in distinguishing early-stage acral and cutaneous melanomas from dysplastic nevus in Chinese population, and the most sensitive criterion was the gain of CCND1.
Grading variation in 2,934 patients with ductal carcinoma in situ of the breast: the effect of laboratory- and pathologist-specific feedback reports
Authors: van Dooijeweert Carmen , van Diest Paul J. , Baas Inge O. , van der Wall Elsken , Deckers Ivette A. G. 
Published: May 2020

Abstract
Background
Histologic grade of ductal carcinoma in situ of the breast (DCIS) may become the single biomarker that decides whether patients will be treated. Yet, evidence shows that grading variation in daily practice is substantial. To facilitate quality improvement, feedback reports, in which laboratory-specific case-mix adjusted proportions per grade were benchmarked against other laboratories, were sent to the individual laboratories by March 1, 2018. One year later, the effect of these feedback reports on inter-laboratory variation was studied.

Methods
Synoptic pathology reports of all pure DCIS resection specimens between March 1, 2017 and March 1, 2019 were retrieved from PALGA (the nationwide Dutch pathology registry). Laboratory-specific proportions per grade were compared to the overall proportion in the year before and after feedback. The absolute deviation for all three grades at once, represented by the overall deviation score (ODS), was calculated as the sum of deviations from the grade-specific overall proportions. Case-mix adjusted, laboratory-specific odds ratios (ORs) for high- (grade III) versus low-grade (grade I-II) DCIS were obtained by multivariable logistic regression.

Results
Overall, 2954 DCIS reports from 31 laboratories were included. After feedback, the range between laboratories decreased by 22 and 6.5% for grades II and III, while an increase of 6.2% was observed for grade I. Both the mean ODS (27.2 to 24.1%) and maximum ODS (87.7 to 59.6%) decreased considerably. However, the range of case-mix adjusted ORs remained fairly stable and substantial (0.39 (95% CI: 0.18–0.86) to 3.69 (95% CI: 1.30–10.51)).

Conclusion
A promising decrease in grading variation was observed after laboratory-specific feedback for DCIS grades II-III, while this was not observed for DCIS grade I. Overall, grading variation remained substantial which needs to be addressed considering its clinical implications. Nationwide consensus on a classification, and training of (expert breast) pathologists, for example by e-learning, may help to further improve grading standardization.
Knowledge-based repositioning of the anti-HCV direct antiviral agent Sofosbuvir as SARS-CoV-2 treatment
Authors: Buonaguro Luigi , Buonaguro Franco M. 
Published: May 2020

AbstractThe new human coronavirus named SARS-CoV-2 is a positive-sense RNA virus for which no specific drugs are currently available. A knowledge-based analysis strongly suggests a possible repositioning of the anti-HCV direct antiviral agent (DAA) Sofosbuvir as treatment for SARS-CoV-2. Indeed, the RNA-dependent RNA-polymerases (RdRp) of the two viruses show high sequence and structural homology, supporting the likelihood of binding the Sofosbuvir molecule with similar efficiency. Such a repositioning would allow the containment of the SARS-CoV-2 pandemic and limit the progression of disease to potentially deadly COVID19.
Radiographic findings have an association with weight bearing and locomotion in English bulldogs
Authors: Mölsä Sari Helena , Hyytiäinen Heli Katariina , Morelius Kaj Mikael , Palmu Maria Katariina , Pesonen Tommi Sakari , Lappalainen Anu Katriina 
Published: May 2020

AbstractBackgroundEnglish bulldogs are known to be prone to skeletal problems, but knowledge is lacking of the effect of these problems on locomotion and function. This study was undertaken to report the conformational, orthopaedic and radiographic findings in a cohort of English bulldogs in Finland and to evaluate how these findings affect weight bearing and locomotion of the dogs. Twenty-eight English bulldogs were prospectively recruited to this cross-sectional study. An orthopaedic examination, measurements of conformation, static and dynamic weight bearing, and radiographic examinations of elbow, hip, stifle joints and spine were done.ResultsThe English bulldogs carried a mean of 67.3% and 62.1% of their body weight in front limbs while standing and trotting, respectively. Front and hind limb lameness was seen in 20.8% (5/24) and 12.5% (3/24) of dogs, respectively. At orthopaedic examination, abnormal palpation findings (i.e. pain response, crepitation, swelling or subjectively decreased range of motion) were observed in a median of one joint (range 0–5) in each dog. Medial patellar luxation was diagnosed in 33.0% (8/24) of the evaluated dogs. At radiographic examination, elbow dysplasia was diagnosed in 48.2% (27/56) of elbow joints and severe hip dysplasia in 55.4% (31/56) of hip joints. The grade of elbow dysplasia was negatively associated with the ratio of static weight bearing between the front and hind limbs (slope estimate − 1.46, 95% CI − 2.75 to − 0.16, P = 0.03) and in dynamic weight bearing the ratio of total pressure index between the front and hind limbs (slope estimate − 0.088, 95% CI − 0.164 to 0.025, P = 0.03). The severity of hip dysplasia or hip osteoarthritis was not associated with the amount of static or dynamic weight bearing, but all except one dog were diagnosed with Fédération Cynologique Internationale grade C, D or E hips (dysplastic). In the spine, 78.6% (22/28) of the dogs had at least one malformed vertebra.ConclusionsOrthopaedic diseases and abnormal radiographic findings were common in the English bulldogs studied. The static weight bearing of the dogs was heavily distributed to the front limbs. With increasing severity of elbow dysplasia, the static and dynamic weight bearing shifted from dysplastic elbows to hind limbs.
Reactive cutaneous capillary endothelial proliferation in advanced hepatocellular carcinoma patients treated with camrelizumab: data derived from a multicenter phase 2 trial
Authors: Wang Feng , Qin Shukui , Sun Xinchen , Ren Zhenggang , Meng Zhiqiang , Chen Zhendong , Chai Xiaoli , Xiong Jianping , Bai Yuxian , Yang Lin , Zhu Hong , Fang Weijia , Lin Xiaoyan , Chen Xiaoming , Li Enxiao , Wang Linna , Yan Ping , Zou Jianjun 
Published: May 2020

Abstract
Background
Association of immune-related adverse events with tumor response has been reported. Reactive cutaneous capillary endothelial proliferation (RCCEP) is the most common adverse event related to camrelizumab, an immune checkpoint inhibitor, but lack of comprehensive analyses. In this study, we conducted comprehensive analyses on RCCEP in advanced hepatocellular carcinoma (HCC) patients treated with camrelizumab monotherapy.

Methods
Data were derived from a Chinese nationwide, multicenter phase 2 trial of camrelizumab in pre-treated advanced HCC. The occurrence, clinicopathological characteristics, and prognostic value of RCCEP were analyzed.

Results
With a median follow-up of 12.5 months, 145 of the 217 camrelizumab-treated patients (66.8%) experienced RCCEP (all grade 1 or 2). RCCEP occurred on the skin surface, mainly on the skin surface of head, face, and trunk. RCCEP could be divided into 5 types including “red-nevus-like,” “pearl-like,” “mulberry-like,” “patch-like,” and “tumor-like,” according to the morphological features. RCCEP biopsy and pathology showed capillary endothelial hyperplasia and capillary hyperplasia in dermis. Significant association between RCCEP occurrence with higher objective response rate was observed (19.3% vs. 5.6%; one-sided p = 0.0044). Compared with those without RCCEP, patients with RCCEP had prolonged progression-free survival (median PFS; 3.2 months vs. 1.9 months; one-sided p < 0.0001) and overall survival (median OS; 17.0 months vs. 5.8 months; one-sided p < 0.0001). In multivariable analyses, the development of RCCEP was significantly associated with prolonged PFS and OS after adjusting for baseline covariates. In addition, the landmark analyses of PFS and OS were consistent with the unadjusted analysis.

Conclusions
RCCEP occurred on the skin surface and was an immune response of skin capillary endothelial cells. RCCEP occurrence positively associated with outcomes of camrelizumab in advanced HCC.
Pulmonary complications associated with veno-arterial extra-corporeal membrane oxygenation: a comprehensive review
Authors: Roumy Aurélien , Liaudet Lucas , Rusca Marco , Marcucci Carlo , Kirsch Matthias 
Published: May 2020

AbstractVeno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a life-saving technology that provides transient respiratory and circulatory support for patients with profound cardiogenic shock or refractory cardiac arrest. Among its potential complications, VA-ECMO may adversely affect lung function through various pathophysiological mechanisms. The interaction of blood components with the biomaterials of the extracorporeal membrane elicits a systemic inflammatory response which may increase pulmonary vascular permeability and promote the sequestration of polymorphonuclear neutrophils within the lung parenchyma. Also, VA-ECMO increases the afterload of the left ventricle (LV) through reverse flow within the thoracic aorta, resulting in increased LV filling pressure and pulmonary congestion. Furthermore, VA-ECMO may result in long-standing pulmonary hypoxia, due to partial shunting of the pulmonary circulation and to reduced pulsatile blood flow within the bronchial circulation. Ultimately, these different abnormalities may result in a state of persisting lung inflammation and fibrotic changes with concomitant functional impairment, which may compromise weaning from VA-ECMO and could possibly result in long-term lung dysfunction. This review presents the mechanisms of lung damage and dysfunction under VA-ECMO and discusses potential strategies to prevent and treat such alterations.
Functional evaluation of five BRCA2 unclassified variants identified in a Sri Lankan cohort with inherited cancer syndromes using a mouse embryonic stem cell-based assay
Authors: Sirisena Nirmala , Biswas Kajal , Sullivan Teresa , Stauffer Stacey , Cleveland Linda , Southon Eileen , Dissanayake Vajira H. W. , Sharan Shyam K. 
Published: May 2020

AbstractNext-generation sequencing of Sri Lankan families with inherited cancer syndromes resulted in the identification of five BRCA2 variants of unknown clinical significance. Interpreting such variants poses significant challenges for both clinicians and patients. Using a mouse embryonic stem cell-based functional assay, we found I785V, N830D, and K2077N to be functionally indistinguishable from wild-type BRCA2. Specific but mild sensitivity to olaparib and reduction in homologous recombination (HR) efficiency suggest partial loss of function of the A262T variant. This variant is located in the N-terminal DNA binding domain of BRCA2 that can facilitate HR by binding to dsDNA/ssDNA junctions. P3039P is clearly pathogenic because of premature protein truncation caused by exon 23 skipping. These findings highlight the value of mouse embryonic stem cell-based assays for determining the functional significance of variants of unknown clinical significance and provide valuable information regarding risk estimation and genetic counseling of families carrying these BRCA2 variants.
Insulin resistance contributes to racial disparities in breast cancer prognosis in US women
Authors: Gallagher Emily J. , Fei Kezhen , Feldman Sheldon M. , Port Elisa , Friedman Neil B. , Boolbol Susan K. , Killelea Brigid , Pilewskie Melissa , Choi Lydia , King Tari , Nayak Anupma , Franco Rebeca , Cruz Daliz , Antoniou Irini M. , LeRoith Derek , Bickell Nina A. 
Published: May 2020

Abstract
Background
Racial disparities in breast cancer survival between Black and White women persist across all stages of breast cancer. The metabolic syndrome (MetS) of insulin resistance disproportionately affects more Black than White women. It has not been discerned if insulin resistance mediates the link between race and poor prognosis in breast cancer. We aimed to determine whether insulin resistance mediates in part the association between race and breast cancer prognosis, and if insulin receptor (IR) and insulin-like growth factor receptor (IGF-1R) expression differs between tumors from Black and White women.

Methods
We conducted a cross-sectional, multi-center study across ten hospitals. Self-identified Black women and White women with newly diagnosed invasive breast cancer were recruited. The primary outcome was to determine if insulin resistance, which was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR), mediated the effect of race on prognosis using the multivariate linear mediation model. Demographic data, anthropometric measurements, and fasting blood were collected. Poor prognosis was defined as a Nottingham Prognostic Index (NPI) > 4.4. Breast cancer pathology specimens were evaluated for IR and IGF-1R expression by immunohistochemistry (IHC).

Results
Five hundred fifteen women were recruited (83% White, 17% Black). The MetS was more prevalent in Black women than in White women (40% vs 20%, p < 0.0001). HOMA-IR was higher in Black women than in White women (1.9 ± 1.2 vs 1.3 ± 1.4, p = 0.0005). Poor breast cancer prognosis was more prevalent in Black women than in White women (28% vs 15%. p = 0.004). HOMA-IR was positively associated with NPI score (r = 0.1, p = 0.02). The mediation model, adjusted for age, revealed that HOMA-IR significantly mediated the association between Black race and poor prognosis (β = 0.04, 95% CI 0.005–0.009, p = 0.002). IR expression was higher in tumors from Black women than in those from White women (79% vs 52%, p = 0.004), and greater IR/IGF-1R ratio was also associated with higher NPI score (IR/IGF-1R >  1: 4.2 ± 0.8 vs IR/IGF-1R = 1: 3.9 ± 0.8 vs IR/IGF-1R < 1: 3.5 ± 1.0, p < 0.0001).

Conclusions
In this multi-center, cross-sectional study of US women with newly diagnosed invasive breast cancer, insulin resistance is one factor mediating part of the association between race and poor prognosis in breast cancer.