bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profiling Human Androgen Receptor Mutations Reveals Treatment Effects in a Mouse Model of Prostate Cancer
Authors: O'Mahony Orla A. , Steinkamp Mara P. , Albertelli Megan A. , Brogley Michele , Rehman Haniya , Robins Diane M. 
Published: December 2020

Abstract
Gain-of-function mutations in the androgen receptor (AR) are found in prostate cancer and are implicated in the failure of hormone therapy. Most studies have emphasized the ligand-binding domain (LBD) where mutations can create promiscuous receptors, but mutations in the NH2-terminal transactivation domain have also been found. To assess AR alteration as a mechanism of treatment resistance, a mouse model (h/mAR-TRAMP) was used in which the murine AR coding region is replaced by human sequence and prostate cancer initiated by a transgenic oncogene. Mice received either no treatment, androgen depletion by castration, or treatment with antiandrogens, and 20 AR transcripts were sequenced per end-stage tumor. All tumors expressed several mutant alleles, although most mutations were low frequency. Some mutations that occurred multiple times within the population were differentially located dependent on treatment. Mutations in castrated or antiandrogen-treated mice were widely dispersed but with a prominent cluster in the LBD (amino acids 736-771), whereas changes in intact mice centered near the NH2-terminal polymorphic glutamine tract. Functional characterization of selected LBD mutant alleles showed diverse effects on AR activity, with about half of the mutations reducing transactivation in vitro. One receptor, AR-R753Q, behaved in a cell- and promoter-dependent manner, although as a germ-line mutation it causes androgen insensitivity syndrome. This suggests that alleles that are loss of function during development may still activate a subset of AR targets to become gain of function in tumorigenesis. Mutant ARs may thus use multiple mechanisms to evade cancer treatment. (Mol Cancer Res 2008;6(11):1691–701)
УЛЬТРАСТРУКТУРНИЙ СТАН СІТКІВКИ ТА ЗОРОВОГО НЕРВА В ЕКСПЕРИМЕНТІ НЕІНФЕКЦІЙНОГО ПЕРЕДНЬОГО ТА СЕРЕДНЬОГО УВЕЇТУ НА КРОЛЯХ БЕЗ ЛІКУВАННЯ ТА ПРИ ВИКОРИСТАННІ НЕЙРОПРОТЕКТОРА
Authors: Zborovska O. V. , Molchanyuk N. I. , Dorokhova O. E. , Horyanova I. S. 
Published: December 2020

В літературі відсутні відомості про нейродегенеративні процеси в сітківці і зоровому нерві при передніх і середніх увеїтах. Мета – провести порівняльне ультраструктурне дослідження зорових нервів, сітчастої і судинної оболонок ока при неінфекційному передньому і середньому увеїтах в експерименті. Матеріал і методи. Експеримент проведений на 4 кролях: 1 група – 2 кролі (без лікування), 2 група – 2 кролі (використовувався нейропротектор). Вивчали ультраструктуру хоріокапілярів (ХК), сітківки і зорових нервів (ЗН) кролів через 10 діб. Результати. В 1 групі в ЗН виявили глибокі деструктивні процеси в нервових волокнах, мієліновій оболонці, в гліальних клітинах із руйнуванням їх плазмолем, а також вогнищевий міжклітинний набряк. У судинній і сітчастій оболонках виявили гідропічну дегенерацію ендотеліальних клітин ХК і клітин сітківки, особливо ПЕС, а також міжклітинний набряк в ділянці ФК. У 2 групі в ЗН деформація мієлінових облонок, набряк в аксоплазмі трапляються в меншій мірі і в меншій кількості НВ. В аксоплазмі більшості НВ мітохондрії та інші органели мали нормальну ультраструктуру. Найбільш збереженими виявилися НВ дрібного калібру. В шарі ХК переважали ЄК з ознаками компенсаційно-відновних процесів. Поряд з цим частина ЄК ХК залишалися в стані набряку. Висновки. Передній і середній неінфекційний увеїт, який моделювали за допомогою кінської сироватки, викликає нейродегенеративні зміни в сітчастій оболонці і ЗН, а при використанні нейропротектора (протягом 10 днів) явища нейродегенерації були виражені в меншій мірі.
Визначення значень показників стрес-факторів у цієнтів Львівської обласної клінічної лікарні з дистрофічно-запальними захворюваннями тканин пародонта в крові та ротовій рідині
Authors: Shevchuk M. М. , Pupin Т. I. , Bandrivska N. N. 
Published: December 2020

Резюме. З метою вивчення стресогенних факторів у крові й ротовій рідині осіб із дистрофічно-запальними захворюваннями тканин пародонта, які перебували на лікуванні в різних відділеннях Львівської обласної клінічної лікарні (ЛОКЛ), визначали активність ɑ-амілази, вмісту глюкози та кортизолу.
Мета дослідження – вивчити значення показників стрес-факторів у пацієнтів ЛОКЛ із дистрофічно-запальними захворюваннями тканин пародонта.
Матеріали і методи. Активність ɑ-амілази та концентрацію глюкози у крові та ротовій рідині людей з’ясовували ензиматичним колометричним методом. Обчислення концентрації кортизолу в крові та ротовій рідині хворих здійснювали за допомогою твердофазного імуноферментного аналізу на апаратіStatFax-303 з використанням тест набору «Стероид ИФА-кортизол» фірми «Алкор-Био». Забір крові у хворих виконувався вранці, натще, після 12-годинної перерви в їжі, з ліктьової вени, ротову рідину для досліджень збирали ранком натще, шляхом спльовування у мірні пробірки, без стимуляції. Для оцінки ступеня вірогідності отриманих результатів дослідження використовували варіаційно-статистичний метод аналізу за допомогою Microsoft Excel. Статистичне обчислення результатів клінічних і лабораторних досліджень здійснювали за загальноприйнятими методами.
Результати досліджень та їх обговорення. Активність ɑ-амілази в середньому у хворих із ДЗЗТП була вище, порівняно з контролем: у крові – у 1,5 раза, р<0,01 та у ротовій рідині – у 2,0 рази, р<0,05. Вміст глюкози у середньому в пацієнтів із дистрофічно-запальними захворюваннями тканин пародонта (ДЗЗТП) при різних загальносоматичних захворюваннях був вище, порівняно з відповідними даними у контрольній групі: в крові – у 1,3 раза, р<0,05 та в ротовій рідині – у 1,8 раза, р<0,01. Вміст кортизолу в середньому у хворих із ДЗЗТП був вище, порівняно з даними осіб контрольної групи: у крові – 1,5 раза та в ротовій рідині – у 1,8 раза, р<0,05.
Висновки. Збільшення активності ɑ-амілази, концентрацій глюкози та кортизолу в пацієнтів із захворюваннями тканин пародонта у крові та ротовій рідині можуть свідчити про зниження стресо­стійкості організму і бути об’єктивними маркерами стресогенного впливу на організм, зумовленого взаємообтяжуючим впливом соматичних і пародонтологічних захворювань.
Le fāʾ al-sababiyya vu par Raḍī l-Dīn al-Astarābāḏī : logique et pragmatique
Authors: Larcher Pierre 
Published: December 2020

Résumé
Pour le grammairien Raḍī l-Dīn al-Astarābāḏī (m. après 688/1289), le fāʾ al-sababiyya (« causal ») constitue une intersection entre deux des trois fāʾ distingués par la grammaire arabe : le fāʾ d’apodose (fāʾ al-ǧawāb ou al-ǧazāʾ), apparaissant entre protase et apodose d’un système conditionnel (in p fa-q) et systèmes assimilés, c’est-à-dire circonstancielles et relatives ayant une valeur conditionnelle, et le fāʾ coordonnant deux phrases (p fa-q). Dans les deux cas, fa- présente q comme la conséquence de p, qui en est la cause. La relation de cause à conséquence est à entendre ici au sens large de la logique naturelle et non au sens strict de l’implication logique, q pouvant ne pas être une affirmation. Mais Raḍī l-Dīn al-Astarābāḏī neutralise aussitôt le sens du fa- « causal », en observant qu’on peut convertir (ʿaks) p fa-q (p donc q) en q fa-p (q car p). Et il va plus loin dans le même sens, en reliant le fāʾ dit explétif au fāʾ causal. Ce fāʾ est ainsi appelé parce qu’il peut apparaître ou non, soit après une subordonnée circonstancielle, sans valeur conditionnelle, ou un simple complément circonstanciel, soit entre le thème et le propos d’une phrase nominale, le thème pouvant être une relative non conditionnelle ou un simple syntagme nominal. Pour Raḍī l-Dīn al-Astarābāḏī, ce fāʾ signale que ce qui le suit est aussi « inséparable » (luzūm) de ce qui le précède que l’apodose de la protase et, ce, bien que ce qui le précède n’ait pas de valeur conditionnelle. Sous un habillage logique, il reconnaît en fait que les trois fāʾ n’en font qu’un, ayant une même distribution/fonction (mawqiʿ). Celle-ci est facilement reformulable dans les termes de la « théorie de l’énonciation » du linguiste suisse Charles Bally (1865-1947) : fa- est un segmentateur, délimitant le thème (phrase, proposition ou syntagme) du propos de l’énoncé.
Anastomotic Leak is Increased With Clostridium difficile Infection After Colectomy: Machine Learning-Augmented Propensity Score Modified Analysis of 46 735 Patients
Authors: Baker Sarah E. , Monlezun Dominique J. , Ambroze Wayne L. , Margolin David A. 
Published: December 2020

Background Clostridium difficile infection (CDI) is now the most common cause of healthcare-associated infections, with increasing prevalence, severity, and mortality of nosocomial and community-acquired CDI which makes up approximately one third of all CDI. There are also increased rates of asymptomatic colonization particularly in high-risk patients. C difficile is a known collagenase-producing bacteria which may contribute to anastomotic leak (AL). Methods Machine learning-augmented multivariable regression and propensity score (PS)–modified analysis was performed in this nationally representative case-control study of CDI and anastomotic leak, mortality, and length of stay for colectomy patients using the ACS-NSQIP database. Results Among 46 735 colectomy patients meeting study criteria, mean age was 61.7 years (SD 14.38), 52.2% were woman, 72.5% were Caucasian, 1.5% developed CDI, 3.1% developed anastomotic leak, and 1.6% died. In machine learning (backward propagation neural network)-augmented multivariable regression, CDI significantly increases anastomotic leak (OR 2.39, 95% CI 1.70-3.36; P < .001), which is similar to the neural network results. Having CDI increased the independent likelihood of anastomotic leak by 3.8% to 6.8% overall, and in dose-dependent fashion with increasing ASA class to 4.3%, 5.7%, 7.6%, and 10.0%, respectively, for ASA class I to IV. In doubly robust augmented inverse probability weighted PS analysis, CDI significantly increases the likelihood of AL by 4.58% (95% CI 2.10-7.06; P < .001). Conclusions This is the first known nationally representative study on CDI and AL, mortality, and length of stay among colectomy patients. Using advanced machine learning and PS analysis, we provide evidence that suggests CDI increases AL in a dose-dependent manner with increasing ASA Class.
Hospital Presentations of Acute Diverticulitis During COVID-19 Pandemic may be More Likely to Require Surgery due to Increased Severity: A Single-Centre Experience
Authors: Hossain Naveed , Naidu Vishnu , Hosny Shady , Khalifa Mohamed , Mathur Pawan , Al Whouhayb Maitham 
Published: December 2020

Background The novel coronavirus disease 2019 (COVID-19) pandemic has resulted in fewer emergency presentations of many acute medical and surgical conditions. The purpose of this study was to assess the severity of disease at presentation and quantify the change in number of presentations during this period. Methods This retrospective study includes all patients diagnosed with acute diverticulitis on abdominopelvic computerised tomography (CT) between March 1, 2020 and June 30, 2020, compared to the same period in 2019. Follow up scans on the index admission were excluded. Hinchey grade was assessed for all CT scans. Inflammatory markers were analysed, along with outcome measures including length of stay and mortality. Results Acute diverticulitis was diagnosed in 52 CT scans in the acute pandemic period – a decrease of 51.4%. Average age at presentation was unchanged (63.3 ± 14.3 vs. 62.8 ± 13.8, P = .848). The number of Hinchey II, III and IV presentations were significantly higher in the acute pandemic period (28.8% vs. 11.2%, P = .005) and significantly more emergency operations were carried out (7.69% vs. .93%, P = .04). Mortality was not significantly increased, nor were serum levels of C-reactive protein, white cell count and lactate. Discussion During the COVID-19 pandemic, fewer patients presented and were diagnosed with acute diverticulitis. A significantly greater proportion presented at a more advanced stage and required emergency surgery, suggesting late presentation. Our findings support the need for maintaining acute surgical services and the provision of early radiological and surgical input in patients presenting with signs and symptoms of acute diverticulitis in future pandemics.
Impact of Chemoprophylaxis on Thromboembolism Following Operative Fixation of Pelvic Fractures
Authors: Berning Bennett J. , Magnotti Louis J. , Lewis Richard H. , Corley Catherine E. , Lim Garrett H. , Doty John B. , Fabian Timothy C. , Croce Martin A. , Sharpe John P. 
Published: December 2020

Background Venous thromboembolism (VTE) is a common cause of serious morbidity and mortality. While chemoprophylaxis decreases VTE, there is the theoretical risk of increased hemorrhagic complications. The purpose of this study was to evaluate the impact of preoperative anticoagulation on VTE and bleeding complications in patients with blunt pelvic fractures requiring operative fixation. Methods Patients with blunt pelvic fractures requiring operative fixation over 10.5 years were identified. Patients were stratified by age, severity of shock, operative management, and timing and duration of anticoagulation. Outcomes were evaluated to determine risk factors for bleeding complications and VTE. Results 310 patients were identified: 212 patients received at least one dose of preoperative anticoagulation and 98 received no preoperative anticoagulation. 68% were male with a mean injury severity score and Glasgow Coma Scale of 26 and 13, respectively. Bleeding complications occurred in 24 patients and 21 patients suffered VTE. Patients with VTE had a greater initial severity of shock (resuscitation transfusions, 4 vs. 2 units, P = .02). Despite longer time to mobilization (4 vs. 3 days, P = .001), patients who received their scheduled preoperative doses within 48 hours of arrival had no significant differences in the number of deep vein thrombosis events (5.2% vs. 5.7%, P = .99), but fewer episodes of pulmonary embolism (PE) (1.5% vs. 6.8%, P = .03) with no difference in bleeding complications (7.5% vs. 8%, P = .87) compared to either patients who had their doses held until after 48 hours of arrival or received no preoperative anticoagulation. Discussion Preoperative anticoagulation prior to pelvic fixation reduced the risk of PE without increasing bleeding complications. Preoperative anticoagulation is safe and beneficial in this group of patients.
Xerostomia and Taste Alterations in COVID-19
Authors: Belchior Fontenele Maria Natally , Pedrosa Marlus da Silva 
Published: December 2020

A recent letter published in the Ear, Nose & Throat Journal called attention to the hypothesis that the xerostomia reported in patients with the Coronavirus Disease 2019 (COVID-19) occurs due to the neuroinvasive and neurotropism potential of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In fact, angiotensin-converting enzyme 2 (ACE-2), the main site of entry of SARS-CoV-2 into the cell, was found to be present in the ductal elements of salivary gland and several other tissues. However, some points are worth to be addressed.
Housing adaptations and housing accessibility problems among older adults with long-standing spinal cord injury
Authors: Norin Lizette , Slaug Björn , Haak Maria , Iwarsson Susanne 
Published: December 2020

Introduction Adults with spinal cord injuries are living longer than previously, and a majority are living in ordinary housing in the community. Housing accessibility is important for maintaining independent occupational performance for this population, but knowledge in this area is insufficient. We investigated housing adaptations and current accessibility problems among older adults with long-standing (>10 years) spinal cord injuries. Method Data from home visits among 122 older adults with spinal cord injuries in Sweden were used. Housing adaptations and environmental barriers were descriptively analysed. Findings Kitchens, entrances, and hygiene areas were common locations for housing adaptations and environmental barriers that generated accessibility problems. The most common adaptations were ramps, wheelchair-accessible stovetops, and ceiling-lifts. Wall-mounted cupboards and high shelves (kitchen), inaccessible storage areas (outside the dwelling), and a lack of grab bars (hygiene area) generated the most accessibility problems. Conclusion Despite housing adaptations, there are considerable accessibility problems in the dwellings of older adults with long-standing spinal cord injuries in Sweden, indicating that long-term follow-up of the housing situation of this population is necessary. Focusing on accessible housing as a prerequisite for occupational performance is at the core of occupational therapy, deserving attention on the individual as well as the societal level.
Approaches to Defining Healthy Diets: A Background Paper for the International Expert Consultation on Sustainable Healthy Diets
Authors: Kumanyika Shiriki , Afshin Ashkan , Arimond Mary , Lawrence Mark , McNaughton Sarah A. , Nishida Chizuru 
Published: December 2020

Background: Healthy diets promote optimal growth and development and prevent malnutrition in all its forms, including undernutrition, obesity, and diet-related noncommunicable diseases (NCDs). Objective: This background paper for the International Expert Consultation on Sustainable Healthy Diets characterizes healthy diets and their implications for food system sustainability. Methods: Three complementary approaches to defining healthy diets are compared: World Health Organization (WHO) guidelines or recommendations developed between 1996 and 2019; 2017 Global Burden of Disease (GBD) risk factor study estimates of diet-related risk–outcome associations; and analyses associating indices of whole dietary patterns with health outcomes in population studies and clinical trials. Results: World Health Organization dietary recommendations are global reference points for preventing undernutrition and reducing NCD risks; they emphasize increasing intakes of fruits, vegetables (excepting starchy root vegetables), legumes, nuts, and whole grains; limiting energy intake from free sugars and total fats; consuming unsaturated rather than saturated or trans fats; and limiting salt intake. Global Burden of Disease findings align well with WHO recommendations but include some additional risk factors such as high consumption of processed meat; this approach quantifies contributions of diet-related risks to the NCD burden. Evidence on whole dietary patterns supports WHO and GBD findings and raises concerns about potential adverse health effects of foods with high levels of industrial processing. Conclusions: Implied shifts toward plant foods and away from animal foods (excepting fish and seafood), and for changes in food production systems have direct relevance to the sustainability agenda.
Changing the Care Paradigm for Patients: Advanced Illness Beds Care Model
Authors: Rimar Alexander , Friedman M. Isabel , Quinteros Maria G. , Gooch Rebecca A. , Masick Kevin D. , DaCosta Nicholas , Spooner Rachael L. 
Published: December 2020

Background: Over 90 million Americans suffer from advanced illness (AI) and spend their last days of life in critical care units receiving costly, unwanted, aggressive medical care. Objective: Evaluate the impact of a specialized care model in medical/surgical units for hospitalized geriatric patients and patients with complex care requirements where designated AI beds align care with patient’s wishes/goals, minimize aggressive interventions, and influence efficient resource utilization. Design: US based multi-facility retrospective, longitudinal descriptive study of screened positive AI patients in AI Beds (N = 1,237) from 3 facilities from 2015 to 2017. Results: Patient outcomes included 60% referrals to AI beds from ICU, a decrease of 39-49% in average ICU LOS, a 23% reduction of AI bed patient expirations, 9.0% referrals to hospice, and projected cost savings of $4,361.66/patient, US dollars. Conclusion: Allocating AI beds to deliver care to AI patients resulted in a decreased cost of care by reducing overall hospital LOS, mortality, and efficient use of both critical care and hospital resources.
Targeting BRAF-Mutant Biliary Tract Cancer: Recent Advances and Future Challenges
Authors: Rizzo Alessandro , Federico Alessandro Di , Ricci Angela Dalia , Frega Giorgio , Palloni Andrea , Pagani Rachele , Tavolari Simona , Marco Mariacristina Di , Brandi Giovanni 
Published: December 2020

Background: Biliary tract cancers (BTCs) represent a heterogeneous group of aggressive solid tumors with limited therapeutic options, and include gallbladder cancer (GBC), ampulla of Vater cancer (AVC), intrahepatic cholangiocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (eCCA). Methods & Results: In the current review, we will discuss recent results of clinical trials testing targeted therapies in BRAF-mutant BTCs, with a particular focus on the recently published Phase II ROAR trial and ongoing active and recruiting clinical trials. Conclusions: Although the extended use of molecular profiling has paved the way toward a new era in BTC management, targeted therapies are limited to iCCA so far, and the prognosis of patients with metastatic disease has substantially not changed in the last decade. In this discouraging scenario, BRAF inhibition is currently emerging as a novel treatment option in patients harboring BRAF mutations.
Evaluation of 2 Commercially Systems for Detection of Serum Squamous Cell Carcinoma Antigen in Pan Squamous Cell Carcinoma
Authors: Chen Hao , Tian Liru , Chen Jiahong , Sun Peng , Han Runkun , Wu Xingping , Dai Shuqin 
Published: December 2020

Background: This study compared the analytical performance of the Elecsys 602 (Roche Diagnostics) system with the I2000 (Abbott laboratories) system for the quantitative measurement of squamous cell carcinoma antigen (SCCA) to assess its role as an indicator in pan squamous cell carcinoma. Methods: 435 serum samples included pan squamous cell cancer group (n = 318) and healthy subjects (n = 52) and non-squamous cell group (n = 41) and benign diseases group (n = 24) were measured by 2 systems and compared. Results: The within-run precision coefficient of variation (CV) for Abbott and Roche systems were 3.34-4.88% and 0.95 -1.96%, and the total precision CV were 2.89-9.48% and 3.97-5.38%, respectively. Good correlation was showed in Abbott and Roche systems (slopes = 0.749, r = 0.9658). Serum SCCA in the groups of nasopharyngeal carcinomas, lung squamous cell carcinoma, esophageal squamous cell carcinoma, bladder cancer and cervical squamous cell carcinoma under the curve area (AUC) was more than 0.5, while the AUC in the non- nasopharyngeal carcinomas head and neck squamous cell carcinoma was less than 0.5. The AUC of 2 systems was statistically different in lung squamous cell carcinoma and nasopharyngeal carcinomas (P < 0.05). The levels of SCCA of 2 systems were similarities in esophageal squamous cell carcinoma(stage IV vs. stage 0a-II)and bladder cancer(stage I vs. stage Oa)and cervical squamous cell carcinoma(stage IIB-III vs. stage I-IIA), which advanced stage had higher level of SCCA than early stage. But the SCCA levels of 2 systems were inconsistent in bladder cancer (stage II-IV vs. stage Oa in Abbott), head and neck squamous cell carcinoma (stage IV vs. stage Oa-I in the Roche) and lung squamous cell carcinoma (stage III vs. stage I-II in the Roche). (P < 0.05) Conclusions: 2 systems correlated well in SCCA detection of squamous cell carcinoma, but there were individual differences. Serum SCCA may also contribute to the diagnosis of bladder cancer.