bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic hypothermia initiated within 6 hours of birth is associated with reduced brain injury on MR biomarkers in mild hypoxic-ischaemic encephalopathy: a non-randomised cohort study
Authors: Montaldo Paolo , Lally Peter J , Oliveira Vânia , Swamy Ravi , Mendoza Josephine , Atreja Gaurav , Kariholu Ujwal , Shivamurthappa Vijayakumar , Liow Natasha , Teiserskas Justinas , Pryce Russell , Soe Aung , Shankaran Seetha , Thayyil Sudhin 
Published: November 2018

ObjectiveTo examine the effect of therapeutic hypothermia on MR biomarkers and neurodevelopmental outcomes in babies with mild hypoxic-ischaemic encephalopathy (HIE).DesignNon-randomised cohort study.SettingEight tertiary neonatal units in the UK and the USA.Patients47 babies with mild HIE on NICHD neurological examination performed within 6 hours after birth.InterventionsWhole-body cooling for 72 hours (n=32) or usual care (n=15; of these 5 were cooled for <12 hours).Main outcome measuresMRI and MR spectroscopy (MRS) within 2 weeks after birth, and a neurodevelopmental outcome assessment at 2 years.ResultsThe baseline characteristics in both groups were similar except for lower 10 min Apgar scores (p=0.02) in the cooled babies. Despite this, the mean (SD) thalamic NAA/Cr (1.4 (0.1) vs 1.6 (0.2); p<0.001) and NAA/Cho (0.67 (0.08) vs 0.89 (0.11); p<0.001) ratios from MRS were significantly higher in the cooled group. Cooled babies had lower white matter injury scores than non-cooled babies (p=0.02). Four (27%) non-cooled babies with mild HIE developed seizures after 6 hours of age, while none of the cooled babies developed seizures (p=0.008). Neurodevelopmental outcomes at 2 years were available in 40 (85%) of the babies. Adverse outcomes were seen in 2 (14.3%) non-cooled babies, and none of the cooled babies (p=0.09).ConclusionsTherapeutic hypothermia may have a neuroprotective effect in babies with mild HIE, as demonstrated by improved MRS biomarkers and reduced white matter injury on MRI. This may warrant further evaluation in adequately powered randomised controlled trials.
Distribution of diabetes, hypertension and non-communicable disease risk factors among adults in rural Bangladesh: a cross-sectional survey
Authors: Fottrell Edward , Ahmed Naveed , Shaha Sanjit Kumer , Jennings Hannah , Kuddus Abdul , Morrison Joanna , Akter Kohenour , Nahar Badrun , Nahar Tasmin , Haghparast-Bidgoli Hassan , Khan A K Azad , Costello Anthony , Azad Kishwar 
Published: November 2018

BackgroundNon-communicable diseases (NCDs) are increasing in low-income settings. We conducted a survey of risk factors, blood pressure and blood glucose in rural Bangladesh and assessed variations by age, sex and wealth.MethodsWe surveyed a random sample of 12 280 adults aged>30 years in 96 villages in rural Bangladesh. Fieldworkers measured blood glucose and conducted an glucose tolerance test with a repeat blood test 120 min post glucose ingestion. Blood pressure, anthropometric, socioeconomic, lifestyle and behavioural risk factors data were also collected. Data were analysed to describe the prevalence of diabetes, intermediate hyperglycaemia, hypertension and NCD risk factors by age, sex and wealth.ResultsWomen had higher levels of overweight or obesity and lower levels of physical activity and fruit and vegetable consumption than men; 63% of men used tobacco compared with 41.3% of women. Overweight or obesity and abdominal obesity (waist to hip ratio) increased with socioeconomic status (least poor vs most poor: OR (95% CI) 3.21 (2.51 to 4.11) for men and 2.83 (2.28 to 3.52) for women). Tobacco use, passive smoke exposure and salt consumption fell with increasing socioeconomic status in both sexes. Clustering of risk factors showed more than 70% of men and women reported at least three risk factors. Women in the least poor group were 33% more likely to have three or more risk factors compared with women in the most poor group (1.33 (95% CI 1.17 to 1.58)). The combined prevalence of impaired fasting glucose, impaired glucose tolerance and diabetes was 26.1% among men and 34.9% among women, and increased with age. The prevalence of prehypertension and hypertension was 30.7% and 15.9% among men and 27.2% and 22.5% among women, with similar rising prevalence with age.ConclusionNCD risk factors, hyperglycaemia and raised blood pressure are an immediate health threat in rural Bangladesh. Initiatives to improve detection, treatment and prevention strategies are needed.
Community palliative medicine out-of-hours needs and the 7-day week: a service evaluation
Authors: Doré Matthew , Willis Derek 
Published: November 2018

BackgroundEvidence regarding out-of-hours (OOH) community palliative care provision is required to inform the need for a 7-day work.AimThis paper seeks to provide evidence for this discussion by defining general practitioners’ (GPs) OOH workload and patients’ demographics, symptomology and interventions. By quantifying the challenges faced, we can understand current practice and focus on what provision is required.DesignUsing Shropshire Doctors Co-operative’s recorded data, the authors have collated a representative picture of the OOH GP palliative care practice over a year from 161 OOH GP–patient interactions.SettingPrimary care.ResultsPalliative care makes up 11.4% of the total OOH GP home visits (HV). Overall 56% of OOH GP HVs are for patients who are expected to die within 48 hours, with 80% of the symptoms being agitation, secretions and pain. Overall 5.7% of OOH GP palliative HVs resulted in hospital admission; however, this decreased to 0.6% adjusting for the last 48-hour prognosis.ConclusionOOH Shropshire GPs deal with a wide variety of scenarios in a heterogeneous population. The greatest demand is from 17:00 to 00:00 (65% of the total shift) on weekdays, and from 09:00 to 00:00 on weekends (82% of the shift). These data begin to quantify the role being performed by OOH GPs, have implications for service provision and support 7-day work.
Virtual patient educational intervention for the development of shared decision-making skills: a pilot study
Authors: Jacklin Simon , Chapman Stephen , Maskrey Neal 
Published: November 2018

BackgroundShared decision-making (SDM) involves a healthcare professional and a patient forming a congruent partnership, within which information is shared and decisions are made which align with the patient’s values. SDM does not occur to the extent it ought to; SDM requires practice. Virtual reality could help facilitate this practice.ObjectiveTo pilot an interactive, high-fidelity virtual patient (VP) who simulates SDM within a primary care consultation.MethodAcademic pharmacists and doctors were recruited from the Keele University. Participants completed prequestionnaires and postquestionnaires.Results18 participants (14 pharmacists and 4 medical doctors) completed the study. 89% (n=16) suggested the VP was ‘enjoyable’ or ‘highly enjoyable’ to use and 72% (n=13) suggested it was ‘very accessible’. There were diverse views about the way in which the user made their reply to the VP with ratings ranging from ‘very poor’ (n=2) to ‘very good’ (n=5); the modal rating was indifference (n=7). It seemed the multiple choice system caused the participants to feel restricted but it was unclear why those who liked the system did so.ConclusionsThe VP was found to be enjoyable and thought-provoking. The data suggest that this type of intervention could be useful at many different stages of a professional’s career although the multiple-choice conversation style may be too restrictive for more experienced consulters.
Use of ultrasonography to identify a periocular plant foreign body in a dog
Authors: Wait Courtney , Meekins Jessica Marie , Tucker‐Mohl Katherine , Biller David 
Published: November 2018

A one‐year‐old female spayed miniature schnauzer was referred to the Kansas State University Veterinary Health Center Ophthalmology Service for evaluation of chronic purulent discharge and conjunctival hyperaemia of the right eye. Two months before presentation, the dog was treated by its primary veterinarian for grass awn foreign bodies in the periocular area. Three visible grass awns were removed, and an associated superficial corneal ulcer healed without complication. However, ocular discharge and conjunctival hyperaemia persisted. Due to the patient’s history and the focal pattern of conjunctival hyperaemia, diagnostic imaging (ultrasound) was recommended to screen for retained plant foreign material. The dog was anaesthetised, and a hyperechoic linear structure was identified in the dorsolateral periocular space on ultrasound examination. The plant material was successfully extracted during a brief conjunctival exploration, and the previously reported clinical signs subsequently resolved over the course of one week.
Comparative digestibility of energy and nutrients in four fibrous ingredients fed to barrows at three different initial body weights
Authors: Xie F. , Li Y.K. , Zhao J.B. , Li Z.C. , Liu L. , Cao Y.H. , Zhang S. 
Published: November 2018

This study was conducted to determine the digestible energy (DE) and metabolizable energy (ME) values and apparent total tract digestibility (ATTD) of nutrients in four fibrous ingredients [corn distillers’ dried grains with solubles (DDGS), soybean hull, wheat bran, and corn bran] fed to barrows at three different growth stages. Thirty growing barrows, 30 finishing barrows, and 30 fattening barrows (initial body weights of 29.04, 58.57, and 105.65 kg, respectively) were individually housed in metabolism crates and allotted to one of four test diets or a basal corn–soybean meal diet in a 3 × 5 factorial design. Fecal and urine samples were collected for 5 d after a 12 d adaption period. The DE and ME values and ATTD of gross energy (GE), organic matter (OM), crude protein, and acid detergent fiber (ADF) in wheat bran, as well as the ATTD of GE, OM, neutral detergent fiber (NDF), and ADF in corn DDGS, and ATTD of NDF and ADF in soybean hull, were greater (P < 0.05) in pigs at stage 3 compared with those at stages 1 and 2. In conclusion, both body weight and fibrous ingredients have effects on energy values and nutrient digestibility in barrows.
Aberrant Activation of β-Catenin Signaling Drives Glioma Tumorigenesis via USP1-Mediated Stabilization of EZH2
Authors: Ma Li , Lin Kangyu , Chang Guoqiang , Chen Yiwen , Yue Chen , Guo Qing , Zhang Sicong , Jia Zhiliang , Huang Tony T. , Zhou Aidong , Huang Suyun 
Published: November 2018

Abstract

Aberrant activation of β-catenin signaling is a critical driver for tumorigenesis, but the mechanism underlying this activation is not completely understood. In this study, we demonstrate a critical role of β-catenin signaling in stabilization of enhancer of zeste homolog 2 (EZH2) and control of EZH2-mediated gene repression in oncogenesis. β-Catenin/TCF4 activated the transcription of the deubiquitinase USP1, which then interacted with and deubiquitinated EZH2 directly. USP1-mediated stabilization of EZH2 promoted its recruitment to the promoters of CDKN1B, RUNX3, and HOXA5, resulting in enhanced enrichment of histone H3K27me3 and repression of target gene expression. In human glioma specimens, expression levels of nuclear β-catenin, USP1, and EZH2 correlated with one another. Depletion of β-catenin/USP1/EZH2 repressed glioma cell proliferation in vitro and tumor formation in vivo. Our findings indicate that a β-catenin–USP1-EZH2 axis orchestrates the interplay between dysregulated β-catenin signaling and EZH2-mediated gene epigenetic silencing during glioma tumorigenesis.

Significance:
These findings identify the β-catenin-USP1-EZH2 signaling axis as a critical mechanism for glioma tumorigenesis that may serve as a new therapeutic target in glioblastoma.
Rare, Pathogenic Germline Variants in Fanconi Anemia Genes Increase Risk for Squamous Lung Cancer
Authors: Esai Selvan Myvizhi , Klein Robert J. , Gümüş Zeynep H. 
Published: November 2018

Abstract

Purpose:
Lung cancer is the leading cause of cancer deaths worldwide, with substantially better prognosis in early-stage as opposed to late-stage disease. Identifying genetic factors for lung squamous cell carcinoma (SqCC) risk will enable their use in risk stratification, and personalized intensive surveillance, early detection, and prevention strategies for high-risk individuals.

Experimental Design:
We analyzed whole-exome sequencing datasets of 318 cases and 814 controls (discovery cohort) and then validated our findings in an independent cohort of 444 patients and 3,479 controls (validation cohort), all of European descent. We also combined all the samples from both cohorts, which, after principal component analysis (PCA) and population stratification, included 765 cases and 4,344 controls (combined cohort). We focused on rare, pathogenic variants found in the ClinVar database and used penalized logistic regression to identify genes in which such variants are enriched in cases. All statistical tests were two-sided.

Results:
We observed an overall enrichment of rare, deleterious germline variants in Fanconi anemia genes in cases with SqCC [joint analysis odds ratio (OR) = 3.08; P = 1.4e−09; 95% confidence interval (CI), 2.2–4.3]. Consistent with previous studies, BRCA2 in particular exhibited an increased overall burden of rare, deleterious variants (joint OR = 3.2; P = 8.7e−08; 95% CI, 2.1–4.7). More importantly, rare, deleterious germline variants were enriched in Fanconi anemia genes even without the BRCA2 rs11571833 variant that is strongly enriched in lung SqCC cases (joint OR = 2.76; P = 7.0e−04; 95% CI, 1.6–4.7).

Conclusions:
These findings can be used toward the development of a genetic diagnostic test in the clinic to identify SqCC high-risk individuals, who can benefit from personalized programs, improving prognosis.
MTORC1/2 Inhibition as a Therapeutic Strategy forPIK3CAMutant Cancers
Authors: Fricke Stephanie L. , Payne Susan N. , Favreau Peter F. , Kratz Jeremy D. , Pasch Cheri A. , Foley Tyler M. , Yueh Alexander E. , Van De Hey Dana R. , Depke Mitchell G. , Korkos Demetra P. , Sha Gioia Chengcheng , DeStefanis Rebecca A. , Clipson Linda , Burkard Mark E. , Lemmon Kayla K. , Parsons Benjamin M. , Kenny Paraic A. , Matkowskyj Kristina A. , Newton Michael A. , Skala Melissa C. , Deming Dustin A. 
Published: November 2018

AbstractPIK3CA mutations are common in clinical molecular profiling, yet an effective means to target these cancers has yet to be developed. MTORC1 inhibitors are often used off-label for patients with PIK3CA mutant cancers with only limited data to support this approach. Here we describe a cohort of patients treated with cancers possessing mutations activating the PI3K signaling cascade with minimal benefit to treatment with the MTORC1 inhibitor everolimus. Previously, we demonstrated that dual PI3K/mTOR inhibition could decrease proliferation, induce differentiation, and result in a treatment response in APC and PIK3CA mutant colorectal cancer. However, reactivation of AKT was identified, indicating that the majority of the benefit may be secondary to MTORC1/2 inhibition. TAK-228, an MTORC1/2 inhibitor, was compared with dual PI3K/mTOR inhibition using BEZ235 in murine colorectal cancer spheroids. A reduction in spheroid size was observed with TAK-228 and BEZ235 (−13% and −14%, respectively) compared with an increase of &gt;200% in control (P &lt; 0.001). These spheroids were resistant to MTORC1 inhibition. In transgenic mice possessing Pik3ca and Apc mutations, BEZ235 and TAK-228 resulted in a median reduction in colon tumor size of 19% and 20%, respectively, with control tumors having a median increase of 18% (P = 0.02 and 0.004, respectively). This response correlated with a decrease in the phosphorylation of 4EBP1 and RPS6. MTORC1/2 inhibition is sufficient to overcome resistance to everolimus and induce a treatment response in PIK3CA mutant colorectal cancers and deserves investigation in clinical trials and in future combination regimens.
BRCA Reversion Mutations in Circulating Tumor DNA Predict Primary and Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma
Authors: Lin Kevin K. , Harrell Maria I. , Oza Amit M. , Oaknin Ana , Ray-Coquard Isabelle , Tinker Anna V. , Helman Elena , Radke Marc R. , Say Carmen , Vo Lan-Thanh , Mann Elaina , Isaacson Jeffrey D. , Maloney Lara , O'Malley David M. , Chambers Setsuko K. , Kaufmann Scott H. , Scott Clare L. , Konecny Gottfried E. , Coleman Robert L. , Sun James X. , Giordano Heidi , Brenton James D. , Harding Thomas C. , McNeish Iain A. , Swisher Elizabeth M. 
Published: November 2018

Abstract

A key resistance mechanism to platinum-based chemotherapies and PARP inhibitors in BRCA-mutant cancers is the acquisition of BRCA reversion mutations that restore protein function. To estimate the prevalence of BRCA reversion mutations in high-grade ovarian carcinoma (HGOC), we performed targeted next-generation sequencing of circulating cell-free DNA (cfDNA) extracted from pretreatment and postprogression plasma in patients with deleterious germline or somatic BRCA mutations treated with the PARP inhibitor rucaparib. BRCA reversion mutations were identified in pretreatment cfDNA from 18% (2/11) of platinum-refractory and 13% (5/38) of platinum-resistant cancers, compared with 2% (1/48) of platinum-sensitive cancers (P = 0.049). Patients without BRCA reversion mutations detected in pretreatment cfDNA had significantly longer rucaparib progression-free survival than those with reversion mutations (median, 9.0 vs. 1.8 months; HR, 0.12; P &lt; 0.0001). To study acquired resistance, we sequenced 78 postprogression cfDNA, identifying eight additional patients with BRCA reversion mutations not found in pretreatment cfDNA.

Significance:
BRCA reversion mutations are detected in cfDNA from platinum-resistant or platinum-refractory HGOC and are associated with decreased clinical benefit from rucaparib treatment. Sequencing of cfDNA can detect multiple BRCA reversion mutations, highlighting the ability to capture multiclonal heterogeneity.
This article is highlighted in the In This Issue feature, p. 151
ТРУДНОСТИ ДИФФЕРЕНЦИАЛЬНОЙ ДИАГНОСТИКИ СКЛЕРОДЕРМОПОДОБНОГО ПАРАНЕОПЛАСТИЧЕСКОГО СИНДРОМА И СИСТЕМНОЙ СКЛЕРОДЕРМИИ КАК ФАКТОРА ОНКОЛОГИЧЕСКОГО РИСКА
Authors: Holovach I. Yu. , Yehudina Ye. D. 
Published: November 2018

Системная склеродермия (ССД) – аутоиммунное заболевание соединительной ткани, характеризующееся прогрессирующим фиброзом кожи и внутренних органов. Характерные клинические признаки ССД могут маскировать онкологические заболевания, а паранеопластический процесс, в свою очередь, маскируется симптомами ССД.
Цель исследования – показать необходимость дифференциальной диагностики склеродермоподобного паранеопластического синдрома и ССД как фактора онкологического риска.
Материалы и методы. Проведен обзор и анализ данных научно-медицинской литературы.
Результаты исследований и их обсуждения. Иммунные реакции, участвующие в патогенезе ССД, могут способствовать развитию онкологической патологии; поэтому пациенты с факторами риска развития заболевания требуют наблюдения за возможным развитием неопластического процесса. Пациенты с ССД и аутоантителами к РНК-полимеразе III имеют значительный риск развития рака. Риск канцерогенеза наиболее высокий в первый год после постановки диагноза ССД. С другой стороны, симптомы ССД могут быть маской различных видов рака. Паранеопластический склеродермоподобный синдром, непосредственно не связан с первичной опухолью и ее метастазами, а обусловлен сложными вторичными воспалительно-дегенеративными изменениями системного, локального либо дистантного характера, зачастую протекающими в виде проявлений “перекреста” (overlap) ревматического и опухолевого заболеваний. Предполагается, что раковые клетки могут индуцировать синтез вещества, инициирующего фиброз кожи и внутренних органов. Дифференциация между идиопатической формой ССД, склеродермоподобным паранеопластическим синдромом и развитием рака на фоне ССД вызывает множество трудностей. В статье представлен анализ дифференциально-диагностических мероприятий, предлагается схема скрининга для ведения пациентов с диагнозом ССД, находящихся в группе риска развития малигнизации.
Выводы. Результаты анализа источников литературы доказывают актуальность углубленного изучения пациента с впервые выявленным склеродермоподобным синдромом, особенно в пожилом возрасте.
АКТИВНІСТЬ ПРОЦЕСІВ ПЕРОКСИДАЦІЇ ЛІПІДІВ У ХВОРИХ НА ХРОНІЧНИЙ ГЕНЕРАЛІЗОВАНИЙ ПАРОДОНТИТ І ЦУКРОВИЙ ДІАБЕТ 2 ТИПУ
Authors: Balitska O. Yu. , Bondarenko Yu. I. , Habor G. G. 
Published: November 2018

З патогенетичної точки зору, діабет асоціюється із порушенням захисних систем організму, включаючи імунний та антиоксидантний захист, а також із розвитком оксидативного стресу.
Мета дослідження – встановити особливості процесів пероксидації ліпідів у плазмі крові хворих на хронічний генералізований пародонтит у поєднанні з цукровим діабетом 2 типу.
Матеріали і методи. Проведено обстеження 20 практично здорових осіб (контрольна група), 36 хворих із клінічно встановленим діагнозом цукрового діабету 2 типу (ЦД) (друга група), 32 пацієнтів із підтвердженим діагнозом хронічного генералізованого пародонтиту (ХГП) (третя група) і 32 хворих із поєднанням ЦД і ХГП (четверта група).
Результати досліджень та їх обговорення. Встановлено підвищений вміст ТБК-АП у плазмі крові пацієнтів четвертої групи з ХГП на тлі ЦД 2 типу, які перевищували на 23,4 % результати другої і на 53,7 % − третьої груп (р<0,05). Рівень активних форм оксигену, показників дієнових і трієнових кон’югатів також був найвищим у хворих на ЦД 2 типу з поєднаною патологію тканин пародонта. Отримані дані вказують на надмірну активацію вільнорадикальних процесів за рахунок гіперпродукції АФК в усіх дослідних групах, що зумовлювало розвиток досліджуваних патологій.
Висновки. У пацієнтів із хронічним генералізованим пародонтитом встановлено інтенсифікацію процесів вільнорадикального окиснення, що характеризувалася зростанням АФК та концентрації дієнових, трієнових кон’югатів та ТБК-активних продуктів.
The Sensitivity of Land–Atmosphere Coupling to Modern Agriculture in the Northern Midlatitudes
Authors: McDermid Sonali Shukla , Montes Carlo , Cook Benjamin I. , Puma Michael J. , Kiang Nancy Y. , Aleinov Igor 
Published: November 2018

AbstractModern agricultural land cover and management are important as regional climate forcings. Previous work has shown that land cover change can significantly impact key climate variables, including turbulent fluxes, precipitation, and surface temperature. However, fewer studies have investigated how intensive crop management can impact background climate conditions, such as the strength of land–atmosphere coupling and evaporative regime. We conduct sensitivity experiments using a state-of-the-art climate model with modified vegetation characteristics to represent modern crop cover and management, using observed crop-specific leaf area indexes and calendars. We quantify changes in land–atmosphere interactions and climate over intensively cultivated regions situated at transitions between moisture- and energy-limited conditions. Results show that modern intensive agriculture has significant and geographically varying impacts on regional evaporative regimes and background climate conditions. Over the northern Great Plains, modern crop intensity increases the model simulated precipitation and soil moisture, weakening hydrologic coupling by increasing surface water availability and reducing moisture limits on evapotranspiration. In the U.S. Midwest, higher growing season evapotranspiration, coupled with winter and spring rainfall declines, reduces regional soil moisture, while crop albedo changes also reduce net surface radiation. This results overall in reduced dependency of regional surface temperature on latent heat fluxes. In central Asia, a combination of reduced net surface energy and enhanced pre–growing season precipitation amplify the energy-limited evaporative regime. These results highlight the need for improved representations of agriculture in global climate models to better account for regional climate impacts and interactions with other anthropogenic forcings.