bluuebunny/crossref_metadata_2025_split huggingface dataset:
'You’re the best liar in the world’: a grounded theory study of rowing athletes’ experience of low back pain
Authors: Wilson Fiona , Ng Leo , O'Sullivan Kieran , Caneiro J P , O'Sullivan Peter PB , Horgan Alex , Thornton Jane S , Wilkie Kellie , Timonen Virpi 
Published: October 2020

ObjectivesLow back pain (LBP) is common in rowers and leads to considerable disability and even retirement. The athlete voice can help clinicians to better understand sport-related pain disorders. We aimed to capture the lived experience of LBP in rowers.MethodsCross-sectional qualitative study using a grounded theory approach. Adult competitive rowers with a rowing-related LBP history were recruited in Australia and Ireland. Data were collected through interviews that explored: context around the time of onset of their LBP and their subsequent journey, experiences of management/treatment, perspectives around present beliefs, fears, barriers and expectations for the future.ResultsThe 25 rowers (12 women/13 men) who participated were aged 18–50 years; they had a mean 12.1 years of rowing experience. They discussed a culture of concealment of pain from coaches and teammates, and fear of being judged as ‘weak’ because of the limitations caused by LBP. They reported fear and isolation as a result of their pain. They felt that the culture within rowing supported this. They reported inconsistent messages regarding management from medical staff. Some rowers reported being in a system where openness was encouraged—they regarded this a leading to better outcomes and influencing their LBP experience.ConclusionsRowers’ lived experience of LBP was influenced by a pervasive culture of secrecy around symptoms. Rowers and support staff should be educated regarding the benefits of early disclosure and rowers should be supported to do so without judgement.
Impact of COVID-19 on the diagnosis, assessment and management of children with inflammatory bowel disease in the UK: implications for practice
Authors: Maclean Abbie , Ashton James J , Garrick Vikki , Beattie R Mark , Hansen Richard 
Published: October 2020

The assessment and management of patients with known, or suspected, paediatric inflammatory bowel disease (PIBD) has been hugely impacted by the COVID-19 pandemic. Although current evidence of the impact of COVID-19 infection in children with PIBD has provided a degree of reassurance, there continues to be the potential for significant secondary harm caused by the changes to normal working practices and reorganisation of services.Disruption to the normal running of diagnostic and assessment procedures, such as endoscopy, has resulted in the potential for secondary harm to patients including delayed diagnosis and delay in treatment. Difficult management decisions have been made in order to minimise COVID-19 risk for this patient group while avoiding harm. Initiating and continuing immunosuppressive and biological therapies in the absence of normal surveillance and diagnostic procedures have posed many challenges.Despite this, changes to working practices, including virtual clinic appointments, home faecal calprotectin testing kits and continued intensive support from clinical nurse specialists and other members of the multidisciplinary team, have resulted in patients still receiving a high standard of care, with those who require face-to-face intervention being highlighted.These changes have the potential to revolutionise the way in which patients receive routine care in the future, with the inclusion of telemedicine increasingly attractive for stable patients. There is also the need to use lessons learnt from this pandemic to plan for a possible second wave, or future pandemics as well as implementing some permanent changes to normal working practices.In this review, we describe the diagnosis, management and direct impact of COVID-19 in paediatric patients with IBD. We summarise the guidance and describe the implemented changes, evolving evidence and the implications of this virus on paediatric patients with IBD and working practices.
Mortality in biopsy-confirmed nonalcoholic fatty liver disease: results from a nationwide cohort
Authors: Simon Tracey G , Roelstraete Bjorn , Khalili Hamed , Hagström Hannes , Ludvigsson Jonas F 
Published: October 2020

ObjectivePopulation-based data are lacking regarding the risk of overall and cause-specific mortality across the complete histological spectrum of non-alcoholic fatty liver disease (NAFLD).DesignThis nationwide, matched cohort study included all individuals in Sweden with biopsy-confirmed NAFLD (1966 to 2017; n=10 568). NAFLD was confirmed histologically from all liver biopsies submitted to Sweden’s 28 pathology departments, after excluding other etiologies of liver disease, and further categorised as, simple steatosis, non-fibrotic steatohepatitis (NASH), non-cirrhotic fibrosis and cirrhosis. NAFLD cases were matched to ≤5 general population comparators by age, sex, calendar year and county (n=49 925). Using Cox regression, we estimated multivariable-adjusted HRs (aHRs) and 95% CIs.ResultsOver a median of 14.2 years, 4,338 NAFLD patients died. Compared with controls, NAFLD patients had significantly increased overall mortality (16.9 vs 28.6/1000 PY; difference=11.7/1000 PY; aHR=1.93, 95% CI=1.86 to 2.00). Compared with controls, significant excess mortality risk was observed with simple steatosis (8.3/1000 PY, aHR=1.71, 95% CI=1.64 to 1.79), non-fibrotic NASH (13.4/1000 PY, aHR=2.14, 95% CI=1.93 to 2.38), non-cirrhotic fibrosis (18.4/1000 PY, aHR=2.44, 95% CI=2.22 to 2.69) and cirrhosis (53.6/1000 PY, aHR=3.79, 95% CI=3.34 to 4.30)(ptrend<0.01). This dose-dependent gradient was similar when simple steatosis was the reference (ptrend<0.01). The excess mortality associated with NAFLD was primarily from extrahepatic cancer (4.5/1000 PY, aHR=2.16, 95% CI=2.03 to 2.30), followed by cirrhosis (2.7/1000 PY, aHR=18.15, 95% CI=14.78 to 22.30), cardiovascular disease (1.4/1000 PY, aHR=1.35, 95% CI=1.26 to 1.44) and hepatocellular carcinoma (HCC) (1.2/1000 PY, aHR=11.12, 95% CI=8.65 to 14.30).ConclusionAll NAFLD histological stages were associated with significantly increased overall mortality, and this risk increased progressively with worsening NAFLD histology. Most of this excess mortality was from extrahepatic cancer and cirrhosis, while in contrast, the contributions of cardiovascular disease and HCC were modest.
Pulmonary complications in trauma patients with obstructive sleep apnea undergoing pelvic or lower limb operation
Authors: Fiorentino Michele , Hwang Franchesca , Pentakota Sri Ram , Livingston David H , Mosenthal Anne C 
Published: October 2020

BackgroundObstructive sleep apnea (OSA) is increasingly prevalent in the range of 2% to 24% in the US population. OSA is a well-described predictor of pulmonary complications after elective operation. Yet, data are lacking on its effect after operations for trauma. We hypothesized that OSA is an independent predictor of pulmonary complications in patients undergoing operations for traumatic pelvic/lower limb injuries (PLLI).MethodsNationwide Inpatient Sample (2009–2013) was queried for International Classification of Diseases, Ninth Revision, Clinical Modification codes for PLLI requiring operation. Elective admissions and those with concurrent traumatic brain injury with moderate to prolonged loss of consciousness were excluded. Outcome measures were pulmonary complications including ventilatory support, ventilator-associated pneumonia, pulmonary embolism (PE), acute respiratory distress syndrome (ARDS), and respiratory failure. Multivariable logistic regression analysis was used, adjusting for OSA, age, sex, race/ethnicity, and specific comorbidities (obesity, chronic lung disease, and pulmonary circulatory disease). P<0.01 was considered statistically significant.ResultsAmong the 337 333 patients undergoing PLLI operation 3.0% had diagnosed OSA. Patients with OSA had more comorbidities and were more frequently discharged to facilities. Median length of stay was longer in the OSA group (5 vs 4 days, p<0.001). Pulmonary complications were more frequent in those with OSA. Multivariable logistic regression showed that OSA was an independent predictor of ventilatory support (adjusted odds ratio (aOR), 1.37; 95% CI,1.24 to 1.51), PE (aOR 1.40; 95% CI, 1.15 to 1.70), ARDS (aOR 1.36; 95% CI,1.23 to 1.52), and respiratory failure (aOR 1.90; 95% CI, 1.74 to 2.06).ConclusionOSA is an independent and underappreciated predictor of pulmonary complications in those undergoing emergency surgery for PLLI. More aggressive screening and identification of OSA in trauma patients undergoing operation are necessary to provide closer perioperative monitoring and interventions to reduce pulmonary complications and improve outcomes.Level of evidencePrognostic Level IV.
The Amino-Terminal Oligomerization Domain of Angiopoietin-2 Affects Vascular Remodeling, Mammary Gland Tumor Growth, and Lung Metastasis in Mice
Authors: Kapiainen Emmi , Kihlström Minna K. , Pietilä Riikka , Kaakinen Mika , Ronkainen Veli-Pekka , Tu Hongmin , Heikkinen Anne , Devarajan Raman , Miinalainen Ilkka , Laitakari Anna , Ansarizadeh Mohammadhassan , Zhang Qin , Wei Gong-Hong , Ruddock Lloyd , Pihlajaniemi Taina , Elamaa Harri , Eklund Lauri 
Published: October 2020

Abstract

Angiopoietin-2 (ANGPT2) is a context-dependent TIE2 agonistic or antagonistic ligand that induces diverse responses in cancer. Blocking ANGPT2 provides a promising strategy for inhibiting tumor growth and metastasis, yet variable effects of targeting ANGPT2 have complicated drug development. ANGPT2443 is a naturally occurring, lower oligomeric protein isoform whose expression is increased in cancer. Here, we use a knock-in mouse line (mice expressing Angpt2443), a genetic model for breast cancer and metastasis (MMTV-PyMT), a syngeneic melanoma lung colonization model (B16F10), and orthotopic injection of E0771 breast cancer cells to show that alternative forms increase the diversity of Angpt2 function. In a mouse retina model of angiogenesis, expression of Angpt2443 caused impaired venous development, suggesting enhanced function as a competitive antagonist for Tie2. In mammary gland tumor models, Angpt2443 differentially affected primary tumor growth and vascularization; these varying effects were associated with Angpt2 protein localization in the endothelium or in the stromal extracellular matrix as well as the frequency of Tie2-positive tumor blood vessels. In the presence of metastatic cells, Angpt2443 promoted destabilization of pulmonary vasculature and lung metastasis. In vitro, ANGPT2443 was susceptible to proteolytical cleavage, resulting in a monomeric ligand (ANGPT2DAP) that inhibited ANGPT1- or ANGPT4-induced TIE2 activation but did not bind to alternative ANGPT2 receptor α5β1 integrin. Collectively, these data reveal novel roles for the ANGPT2 N-terminal domain in blood vessel remodeling, tumor growth, metastasis, integrin binding, and proteolytic regulation.

Significance:
This study identifies the role of the N-terminal oligomerization domain of angiopoietin-2 in vascular remodeling and lung metastasis and provides new insights into mechanisms underlying the versatile functions of angiopoietin-2 in cancer.
See related commentary by Kamiyama and Augustin, p. 35
Comparative Genomics Reveals Distinct Immune-oncologic Pathways in African American Men with Prostate Cancer
Authors: Awasthi Shivanshu , Berglund Anders , Abraham-Miranda Julieta , Rounbehler Robert J. , Kensler Kevin , Serna Amparo , Vidal Adriana , You Sungyong , Freeman Michael R. , Davicioni Elai , Liu Yang , Karnes R. Jeffrey , Klein Eric A. , Den Robert B. , Trock Bruce J. , Campbell Joshua D. , Einstein David J. , Gupta Raavi , Balk Steven , Lal Priti , Park Jong Y. , Cleveland John L. , Rebbeck Timothy R. , Freedland Stephen J. , Yamoah Kosj 
Published: October 2020

Abstract

Purpose:
The role of immune-oncologic mechanisms of racial disparities in prostate cancer remains understudied. Limited research exists to evaluate the molecular underpinnings of immune differences in African American men (AAM) and European American men (EAM) prostate tumor microenvironment (TME).

Experimental Design:
A total of 1,173 radiation-naïve radical prostatectomy samples with whole transcriptome data from the Decipher GRID registry were used. Transcriptomic expressions of 1,260 immune-specific genes were selected to assess immune-oncologic differences between AAM and EAM prostate tumors. Race-specific differential expression of genes was assessed using a rank test, and intergene correlational matrix and gene set enrichment was used for pathway analysis.

Results:
AAM prostate tumors have significant enrichment of major immune-oncologic pathways, including proinflammatory cytokines, IFNα, IFNγ, TNFα signaling, ILs, and epithelial–mesenchymal transition. AAM TME has higher total immune content score (ICSHIGH) compared with 0 (37.8% vs. 21.9%, P = 0.003). AAM tumors also have lower DNA damage repair and are genomically radiosensitive as compared with EAM. IFITM3 (IFN-inducible transmembrane protein 3) was one of the major proinflammatory genes overexpressed in AAM that predicted increased risk of biochemical recurrence selectively for AAM in both discovery [HRAAM = 2.30; 95% confidence interval (CI), 1.21–4.34; P = 0.01] and validation (HRAAM = 2.42; 95% CI, 1.52–3.86; P = 0.0001) but not in EAM.

Conclusions:
Prostate tumors of AAM manifest a unique immune repertoire and have significant enrichment of proinflammatory immune pathways that are associated with poorer outcomes. Observed immune-oncologic differences can aid in a genomically adaptive approach to treating prostate cancer in AAM.
Heat Shock Protein-90 Inhibition Alters Activation of Pancreatic Stellate Cells and Enhances the Efficacy of PD-1 Blockade in Pancreatic Cancer
Authors: Zhang Yuchen , Ware Michael B. , Zaidi Mohammad Y. , Ruggieri Amanda N. , Olson Brian M. , Komar Hannah , Farren Matthew R. , Nagaraju Ganji Purnachandra , Zhang Chao , Chen Zhengjia , Sarmiento Juan M. , Ahmed Rafi , Maithel Shishir K. , El-Rayes Bassel F. , Lesinski Gregory B. 
Published: October 2020

Abstract
Pancreatic ductal adenocarcinoma (PDAC) has a prominent fibrotic stroma, which is a result of interactions between tumor, immune and pancreatic stellate cells (PSC), or cancer-associated fibroblasts (CAF). Targeting inflammatory pathways present within the stroma may improve access of effector immune cells to PDAC and response to immunotherapy. Heat shock protein-90 (Hsp90) is a chaperone protein and a versatile target in pancreatic cancer. Hsp90 regulates a diverse array of cellular processes of relevance to both the tumor and the immune system. However, to date the role of Hsp90 in PSC/CAF has not been explored in detail. We hypothesized that Hsp90 inhibition would limit inflammatory signals, thereby reprogramming the PDAC tumor microenvironment to enhance sensitivity to PD-1 blockade. Treatment of immortalized and primary patient PSC/CAF with the Hsp90 inhibitor XL888 decreased IL6, a key cytokine that orchestrates immune changes in PDAC at the transcript and protein level in vitro. XL888 directly limited PSC/CAF growth and reduced Jak/STAT and MAPK signaling intermediates and alpha-SMA expression as determined via immunoblot. Combined therapy with XL888 and anti–PD-1 was efficacious in C57BL/6 mice bearing syngeneic subcutaneous (Panc02) or orthotopic (KPC-Luc) tumors. Tumors from mice treated with both XL888 and anti–PD-1 had a significantly increased CD8+ and CD4+ T-cell infiltrate and a unique transcriptional profile characterized by upregulation of genes associated with immune response and chemotaxis. These data demonstrate that Hsp90 inhibition directly affects PSC/CAF in vitro and enhances the efficacy of anti–PD-1 blockade in vivo.
Targeting Dormant Ovarian Cancer CellsIn Vitroand in anIn VivoMouse Model of Platinum Resistance
Authors: Huang Zhiqing , Kondoh Eiji , Visco Zachary R. , Baba Tsukasa , Matsumura Noriomi , Dolan Emma , Whitaker Regina S. , Konishi Ikuo , Fujii Shingo , Berchuck Andrew , Murphy Susan K. 
Published: October 2020

AbstractSpheroids exhibit drug resistance and slow proliferation, suggesting involvement in cancer recurrence. The protein kinase C inhibitor UCN-01 (7-hydroxystaurosporine) has shown higher efficacy against slow proliferating and/or quiescent ovarian cancer cells. In this study, tumorigenic potential was assessed using anchorage-independent growth assays and spheroid-forming capacity, which was determined with ovarian cancer cell lines as well as primary ovarian cancers. Of 12 cell lines with increased anchorage-independent growth, 8 formed spheroids under serum-free culture conditions. Spheroids showed reduced proliferation (P &lt; 0.0001) and Ki-67 immunostaining (8% vs. 87%) relative to monolayer cells. Spheroid formation was associated with increased expression of mitochondrial pathway genes (P ≤ 0.001) from Affymetrix HT U133A gene expression data. UCN-01, a kinase inhibitor/mitochondrial uncoupler that has been shown to lead to Puma-induced mitochondrial apoptosis as well as ATP synthase inhibitor oligomycin, demonstrated effectiveness against spheroids, whereas spheroids were refractory to cisplatin and paclitaxel. By live in vivo imaging, ovarian cancer xenograft tumors were reduced after primary treatment with carboplatin. Continued treatment with carboplatin was accompanied by an increase in tumor signal, whereas there was little or no increase in tumor signal observed with subsequent treatment with UCN-01 or oltipraz. Taken together, our findings suggest that genes involved in mitochondrial function in spheroids may be an important therapeutic target in preventing disease recurrence.
Informal Caregivers’ Administration of Hospice Prescribed Lorazepam to Homecare Patients With Anxiety
Authors: Ropri Fatima , Weisse Carol S. 
Published: October 2020

Background: A growing number of informal caregivers (IFCs) manage hospice patients’ anxiety by administering lorazepam (Ativan), yet little is known about prescribing practices in home care or the extent to which IFCs carry out regimens. Design and Methods: Data on hospice prescribed lorazepam was determined through a retrospective review of medication records from 216 deceased patients. The dose of lorazepam and type of regimen (i.e., scheduled, PRN, combination) as well as frequency with which it was administered by IFCs was calculated upon admission to a residential care home and on patients’ day of death. Results: The majority (63.1%) of patients were prescribed lorazepam on admission to the home, and more (79.5%) were prescribed lorazepam on the day of death. While higher doses of lorazepam were prescribed and administered on the day of death, the percentage of medication consumed was low on admission (17%) and day of death (27%). Nearly all (92.8%) prescribed lorazepam on the day of death were allowed PRN medication. For PRN only regimens, less than a quarter (24.4%) of patients were given lorazepam on admission with less than half (40.4%) given it while dying. Highest lorazepam administration rates (91.2%) occurred on the day of death when lorazepam was prescribed under a combined regimen. Conclusion: The high frequency of PRN regimens reveal that IFCs are frequently tasked with making decisions about if and when to administer lorazepam. Low overall lorazepam administration suggests a closer monitoring of lorazepam use and enhanced support of IFCs may be needed.
Satisfaction, functional outcomes and predictors in hip arthroscopy: a cohort study
Authors: van der Valk Mara R , Wolterbeek Nienke , van Assen Tijmen , Veen M Remmelt 
Published: October 2020

Introduction: Hip arthroscopy is not always successful, leading to high rates of total hip arthroplasty (THA) after arthroscopy. The aim of this study was to identify risk factors for THA, revision arthroscopy and low patient satisfaction and to compare outcomes of the different procedures of primary hip arthroscopy. Methods: A total of 91 primary hip arthroscopy procedures in 90 patients (66% female) were analysed. Data were gathered from patient files and a questionnaire was sent to patients including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), modified Harris Hip Score (mHHS), the EuroQol 5-dimension and questions about return to sports, satisfaction and pain before and after surgery. Using regression analyses, predictive factors for the outcomes were identified. Results: After a mean of 1.6 years, 4 patients (4%) underwent revision arthroscopy and 10 (11%) a THA. Of the responders (62%), 66% of the patients was satisfied to very satisfied about the surgery. Mean mHHS score was 75.3 (SE 1.9) and the mean WOMAC score was 81.0 (SE 2.8). Return to sports rate was 58%. A higher age was a significant predictor for lower satisfaction ( p = 0.008) and a longer duration of symptoms was a significant predictor for worse mHHS outcome scores ( p = 0.005). Conclusion: A higher age is a predictor for a lower satisfaction and a longer duration of symptoms before surgery has a negative influence on functional outcome. No risk factors for THA or revision arthroscopy were found and there were no significant differences in outcome measurements between the performed surgeries.
Environmental enrichment alleviates the deleterious effects of stress in experimental autoimmune encephalomyelitis
Authors: Fournier Antoine Philippe , Baudron Erwan , Wagnon Isabelle , Aubert Philippe , Vivien Denis , Neunlist Michel , Bardou Isabelle , Docagne Fabian 
Published: October 2020

Background Clinical observations support the hypothesis that stressful events increase relapse occurrence in multiple sclerosis patients, while stress-reduction strategies can modulate this effect. However, a direct cause-effect relationship between stress level and relapse cannot be firmly established from these data. Objectives The purpose of this work was to address whether modulation of stress could interfere with symptom relapse in an animal model of multiple sclerosis with relapsing-remitting course. Methods Mice bred in standard or enriched environment were subjected to repeated acute stress during the remission phase of relapsing-remitting PLP-induced experimental autoimmune encephalomyelitis. Results We report that repeated acute stress induced a twofold increase in relapse incidence in experimental autoimmune encephalomyelitis. On the other hand, environmental enrichment reduced relapse incidence and severity, and reversed the effects of repeated acute stress. Conclusion These data provide the platform for further studies on the biological processes that link stress and multiple sclerosis relapses in a suitable animal model.