bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temperature stability of oxytocin ampoules labelled for storage at 2°C–8°C and below 25°C: an observational assessment under controlled accelerated and temperature cycling conditions
Authors: Nguyen Tri-Hung , Lambert Peter , Minhas Rajpreet Singh , McEvoy Claire , Deadman Kim , Wright Philip , Prankerd Richard J , Mogatle Seloi , McIntosh Michelle P 
Published: July 2019

IntroductionOxytocin, administered via injection, is recommended by WHO for the prevention and treatment of postpartum haemorrhage. However, the susceptibility of oxytocin injection to thermal degradation has led WHO and UNICEF to recommend cold-chain storage of all oxytocin products. Nevertheless, some oxytocin products supplied to the global market are labelled for storage at ≤25°C, often with a shorter shelf-life relative to products labelled for refrigeration. Differences in labelled storage requirements can lead to uncertainties among stakeholders around the relative stability of oxytocin products and specifically whether ≤25°C products are more resistant to degradation. Such confusion can potentially influence policies associated with procurement, distribution, storage and the use of oxytocin in resource-poor settings.ObjectivesTo compare the stability of oxytocin injection ampoules formulated for storage at ≤25°C with those labelled for refrigerated storage.DesignAccelerated and temperature cycling stability studies were performed with oxytocin ampoules procured by the United Nations Population Fund (UNFPA) from four manufacturers.MethodUsing oxytocin ampoules procured by UNFPA, accelerated stability (up to 120 days) and temperature cycling (up to 135 days between elevated and refrigerated temperatures) studies were performed at 30°C, 40°C and 50°C. Oxytocin content was quantified using a validated HPLC-UV method.ResultsAll ampoules evaluated exhibited similar stability profiles under accelerated degradation conditions with the exception of one product formulated for ≤25°C storage, where the rate of degradation increased at 50°C relative to other formulations. Similar degradation trends at elevated temperatures were observed during temperature cycling, while no significant degradation was observed during refrigerated periods of the study.ConclusionOxytocin ampoules formulated for non-refrigerated storage demonstrated comparable stability to those labelled for refrigerated storage and should not be interpreted by stakeholders as offering a more stable alternative. Furthermore, these products should not be procured for use in territories with high ambient temperatures, where all oxytocin injection products should be supplied and stored under refrigerated conditions.
A multicentre randomised feasibility STUdy evaluating the impact of a prognostic model for Management of BLunt chest wall trauma patients: STUMBL Trial
Authors: Battle Ceri , Hutchings Hayley A , Driscoll Timothy , O’Neill Claire , Groves Sam , Watkins Alan , Lecky Fiona Elizabeth , Jones Sally , Gagg James , Body Richard , Abbott Zoe , Evans Phillip A 
Published: July 2019

ObjectiveA new prognostic model has been developed and externally validated, the aim of which is to assist in the management of the blunt chest wall trauma patient in the emergency department (ED). The aim of this trial is to assess the feasibility and acceptability of a definitive impact trial investigating the clinical and cost-effectiveness of a new prognostic model for the management of patients with blunt chest wall trauma in the ED.DesignStepped wedge feasibility trial.SettingFour EDs in England and Wales.ParticipantsAdult blunt chest wall trauma patients presenting to the ED with no concurrent, life-threatening injuries.InterventionA prognostic model (the STUMBL score) to guide clinical decision-making.Outcome measuresPrimary: participant recruitment rate and clinicians’ use of the STUMBL score. Secondary: composite outcome measure (mortality, pulmonary complications, delayed upgrade in care, unplanned representations to the ED), physical and mental components of quality of life, clinician feedback and health economic data gathering methodology for healthcare resource utilisation.ResultsQuantitative data were analysed using the intention-to-treat principle. 176 patients were recruited; recruitment targets were achieved at all sites. Clinicians used the model in 96% of intervention cases. All feasibility criteria were fully or partially met. After adjusting for predefined covariates, there were no statistically significant differences between the control and intervention periods. Qualitative analysis highlighted that STUMBL was well-received and clinicians would support a definitive trial. Collecting data on intervention costs, health-related quality of life and healthcare resource use was feasible.DiscussionWe have demonstrated that a fully powered randomised clinical trial of the STUMBL score is feasible and desirable to clinicians. Minor methodological modifications will be made for the full trial.Trial registration numberISRCTN95571506; Post-results.
Health status of care home residents: practicality and construct validity of data collection by staff at scale
Authors: Benson Tim , Bowman Clive 
Published: July 2019

BackgroundMedical diagnoses and assessed need for care are the prerequisites for planning and delivery of care to residents of care homes. Assessing the effectiveness of care is difficult. The aim of this study was to test the practicality and construct validity of thehowRuhealth status measure using secondary analysis of a large data set.MethodThe data came from a Bupa Care Homes Census in 2012, which covered 24 506 residents in 395 homes internationally (UK, Australia and New Zealand). Staff completed optical mark readable forms about each resident using a short generic health status measure,howRu. Response rates were used to assess practicality and expected relationships between health status and independent variables were used to assess the construct validity.Results and discussion19,438 forms were returned (79.3%) in 360 care homes (91.1%); complete health status data were recorded for 18 617 residents (95.8% of those returned). Missing values for any health status items mostly came from a small number of homes. The relationships betweenhowRuand independent variables support construct validity. Factor analysis suggests three latent variables (discomfort, distress and disability/dependence).ConclusionsHowRuproved easy to use and practical at scale. ThehowRuhealth status measure shows good construct validity.
Transradial access for neurointerventions: management of access challenges and complications
Authors: Brunet Marie-Christine , Chen Stephanie H , Peterson Eric C 
Published: July 2019

BackgroundNumerous large randomized trials have shown a significant morbidity and mortality benefit with the transradial approach (TRA) over the transfemoral approach (TFA) for endovascular procedures. However, this technique is routinely avoided or aborted due to unfamiliarity with the technique and the associated anatomical difficulties that may be faced in this approach. The objective of this review is to identify both the common and uncommon challenges that may be encountered during a transradial approach for cerebrovascular catheterization and to provide tips and tricks to overcome the transradial learning curve.MethodA careful review of the literature and of all our transradial cases was carried out to identify the common challenges and complications that are encountered when using TRA for diagnostic cerebral angiography and neurointerventions.ResultsA stepwise approach is provided to prevent and manage common challenges including radial artery access failure, radial artery spasm, radial artery anomalies and tortuosity, radial artery occlusion, radial artery perforation and hematoma, subclavian tortuosity and anomalies, and catheter knots and kinks.ConclusionThe ability to recognize and navigate anatomical variations and complications unique to TRA will accelerate learning, decrease unnecessary morbidity and mortality, and further advance the neurovascular field.
Thrombectomy for acute ischemic stroke in nonagenarians compared with octogenarians
Authors: Sussman Eric S , Martin Blake , Mlynash Michael , Marks Michael P , Marcellus David , Albers Gregory , Lansberg Maarten , Dodd Robert , Do Huy M , Heit Jeremy J 
Published: July 2019

IntroductionMultiple randomized trials have shown that endovascular thrombectomy (EVT) leads to improved outcomes in acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Elderly patients were poorly represented in these trials, and the efficacy of EVT in nonagenarian patients remains uncertain.MethodsWe performed a retrospective cohort study at a single center. Inclusion criteria were: age 80–99, LVO, core infarct <70 mL, and salvageable penumbra. Patients were stratified into octogenarian (80–89) and nonagenarian (90–99) cohorts. The primary outcome was the ordinal score on the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included dichotomized functional outcome (mRS ≤2 vs mRS ≥3), successful revascularization, symptomatic intracranial hemorrhage (ICH), and mortality.Results108 patients met the inclusion criteria, including 79 octogenarians (73%) and 29 nonagenarians (27%). Nonagenarians were more likely to be female (86% vs 58%; p<0.01); there were no other differences between groups in terms of demographics, medical comorbidities, or treatment characteristics. Successful revascularization (TICI 2b–3) was achieved in 79% in both cohorts. Median mRS at 90 days was 5 in octogenarians and 6 in nonagenarians (p=0.09). Functional independence (mRS ≤2) at 90 days was achieved in 12.5% and 19.7% of nonagenarians and octogenarians, respectively (p=0.54). Symptomatic ICH occurred in 21.4% and 6.4% (p=0.03), and 90-day mortality rate was 63% and 40.9% (p=0.07) in nonagenarians and octogenarians, respectively.ConclusionsNonagenarians may be at higher risk of symptomatic ICH than octogenarians, despite similar stroke- and treatment-related factors. While there was a trend towards higher mortality and worse functional outcomes in nonagenarians, the difference was not statistically significant in this relatively small retrospective study.
No longer beeting around the bush: a review of potential sex differences with dietary nitrate supplementation
Authors: Wickham Kate A. , Spriet Lawrence L. 
Published: July 2019

Over the last decade there has been substantial interest in the health and athletic performance benefits associated with acute and chronic dietary nitrate (NO3–) supplementation. Dietary NO3–, commonly found in leafy green and root vegetables, undergoes sequential reduction to nitrite and nitric oxide (NO) via the enterosalivary circulation. Importantly, NO has been shown to elicit a number of biological effects ranging from blood pressure reduction to improved exercise economy and athletic performance. However, a common absence within biological research is the lack of female participants, which is often attributed to the added complexity of hormonal fluctuations throughout the menstrual cycle. Despite mounting evidence supporting significant anthropometric, metabolic, and physiological differences between the sexes, this problem extends to the field of dietary NO3–supplementation where women are underrepresented as research participants. This review examines the existing dietary NO3–supplementation research with regards to dietary NO3–pharmacokinetics, resting blood pressure, exercise economy and performance, and mechanisms of action. It also provides evidence and rationale for potential sex differences in response to dietary NO3–supplementation and future directions for this field of research.Novelty Dietary NO3–supplementation has been shown to have positive impacts on health and athletic performance in generally male populations. However, women are underrepresented in dietary NO3–supplementation research. The present evidence suggests that sex differences exist in response to dietary NO3–supplementation and this review highlights avenues for future research.
Chromosomal Instability in Tumor Initiation and Development
Authors: Bach Duc-Hiep , Zhang Wei , Sood Anil K. 
Published: July 2019

AbstractChromosomal instability (CIN) is one of the major forms of genomic instability in various human cancers and is recognized as a common hallmark of tumorigenesis and heterogeneity. However, some malignant tumors show a paucity of chromosomal alterations, suggesting that tumor progression and evolution can occur in the absence of CIN. It is unclear whether CIN is stable between precursor lesions, primary tumor, and metastases or if it evolves during these steps. In this review, we describe the influence of CIN on the various steps in tumor initiation and development. Given the recognized significant effects of CIN in cancer, CIN-targeted therapeutics could have a major impact on improving clinical outcomes.
The Epidemiology of Gastric Cancers in the Era of Helicobacter pylori Eradication: A Nationwide Cancer Registry-Based Study in Taiwan
Authors: Chang Jeffrey S. , Kuo Sung-Hsin , Chu Pei-Yi , Shan Yan-Shen , Tsai Chia-Rung , Tsai Hui-Jen , Chen Li-Tzong 
Published: July 2019

Abstract

Background:
Helicobacter pylori eradication has been shown to decrease gastric adenocarcinoma risk. The epidemiology of gastric lymphoma, which is also associated with H. pylori, and other rare subtypes of gastric cancer is less clear. This study comprehensively evaluated the incidence trend and the survival of gastric cancer in Taiwan by histologic subtype.

Methods:
The incidence trends of gastric cancer in Taiwan from 1996 and 2013 were evaluated using data from the Taiwan Cancer Registry. The life-table method and the Cox proportional hazards analysis were used to evaluate the survival of gastric cancer.

Results:
The incidence of all gastric cancers in Taiwan decreased from 15.97 per 100,000 in 1996 to 11.57 per 100,000 in 2013. The most frequent histologic subtype of gastric cancer in Taiwan was adenocarcinoma, followed by lymphoma and sarcoma (mainly gastrointestinal stromal tumor). The best survival was in patients with sarcoma, followed by lymphoma, neuroendocrine tumor, and adenocarcinoma. Generally, women had a better survival than men. The incidence of adenocarcinoma significantly decreased from 13.56 per 100,000 in 1996 to 9.82 per 100,000 in 2013 (P &lt; 0.0001). In contrast, the incidences of mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma did not decrease.

Conclusions:
The incidence of adenocarcinoma and lymphoma, both of which are associated with H. pylori, showed diverging trends. The survival of gastric cancer differed by histologic subtype and sex.

Impact:
The disparity in the incidence trends between gastric lymphoma and adenocarcinoma, both associated with H. pylori, warranted the need to search for additional risk factors of gastric lymphoma.
Enhanced Activity of Variant DNA Polymerase β (D160G) Contributes to Cisplatin Therapy by Impeding the Efficiency of NER
Authors: Wang Meina , Li Enjie , Lin Lin , Kumar Alagamuthu Karthick , Pan Feiyan , He Lingfeng , Zhang Jing , Hu Zhigang , Guo Zhigang 
Published: July 2019

Abstract

Cisplatin, commonly used in a variety of cancer treatments, induces apoptosis in cancer cells by causing lethal DNA damage. Several DNA repair pathways participate in regulation of cisplatin treatment, leading to cisplatin sensitivity or resistance in cancer cells. DNA polymerase β (pol β), a key protein involved in base excision repair, confers a response to cisplatin therapy that is dependent on polymerase activity. Pol β D160G mutation with enhanced polymerase activity, previously identified in clear cell renal cell carcinoma, enhances the sensitivity of human cancer cells and mouse xenografts to cisplatin by limiting the efficiency of nucleotide excision repair (NER). Notably, the D160G mutation impedes the recruitment of XPA to cisplatin-induced sites of DNA damage, leading to unrepaired damage and further inducing cell death. Molecular architecture analysis indicated that the D160G mutation alters protein–DNA interactions and the surface electrostatic properties of the DNA-binding regions, resulting in greater DNA affinity and polymerase activity compared with wild-type pol β. Collectively, these results indicate that enhancing pol β activity impedes the efficiency of NER and provide a promising adjuvant therapeutic strategy for cisplatin chemotherapy.

Implications:
Our studies demonstrate that polβ D160G mutation with enhanced polymerase activity impedes NER efficiency during the repair of cisplatin-induced DNA damage, leading to increased cisplatin sensitivity in cancer cells.
An LKB1–SIK Axis Suppresses Lung Tumor Growth and Controls Differentiation
Authors: Murray Christopher W. , Brady Jennifer J. , Tsai Min K. , Li Chuan , Winters Ian P. , Tang Rui , Andrejka Laura , Ma Rosanna K. , Kunder Christian A. , Chu Pauline , Winslow Monte M. 
Published: July 2019

Abstract

The kinase LKB1 is a critical tumor suppressor in sporadic and familial human cancers, yet the mechanisms by which it suppresses tumor growth remain poorly understood. To investigate the tumor-suppressive capacity of four canonical families of LKB1 substrates in vivo, we used CRISPR/Cas9-mediated combinatorial genome editing in a mouse model of oncogenic KRAS-driven lung adenocarcinoma. We demonstrate that members of the SIK family are critical for constraining tumor development. Histologic and gene-expression similarities between LKB1- and SIK-deficient tumors suggest that SIKs and LKB1 operate within the same axis. Furthermore, a gene-expression signature reflecting SIK deficiency is enriched in LKB1-mutant human lung adenocarcinomas and is regulated by LKB1 in human cancer cell lines. Together, these findings reveal a key LKB1–SIK tumor-suppressive axis and underscore the need to redirect efforts to elucidate the mechanisms through which LKB1 mediates tumor suppression.

Significance:
Uncovering the effectors of frequently altered tumor suppressor genes is critical for understanding the fundamental driving forces of cancer growth. Our identification of the SIK family of kinases as effectors of LKB1-mediated tumor suppression will refocus future mechanistic studies and may lead to new avenues for genotype-specific therapeutic interventions.
This article is highlighted in the In This Issue feature, p. 1469
«Ленин» Владимира Маяковского
Authors: Niero Alessandro 
Published: July 2019

Темой статьи является перевод поэмы Владимирa Маяковскoго «Ленин», выполненный профессором, переводчиком, поэтом, литературоведом и специалистом по русской литературе ХХ века Анджело Марией Рипеллино по поручению Туринского издательства Эйнауди в 1967 году (через пятьдесят лет после Октябрьской революции!). Перевод Рипеллино – наглядный пример работы, которая проводится не по личному выбору переводчика, а по приглашению издателя (своего рода «социальный заказ»). При подобных обстоятельствах, можно предполагать, что между переводчиком и переведенным существует относительно низкая степень конгениальности. Это подтверждается не только в «Предисловии» Рипеллино к переводу, а также в письме Рипеллино к Гвидо Давико Бонино, редактору издательства, написанном в период работы над «Лениным». Несмотря на это, перевод, сделанный Рипеллино чрезвычайно интересен. В его подходе к стихотворному переводу, есть разительное отличие от его же переводов Б.Пастернака (1957) и А.Блока (1960), и в последствии В.Хлебникова (1968). Для «Ленина» Рипеллино употребляет как можно больше рифм, ассонансов, консонансов и т.д. – словом он настолько заботится о формальных особенностях поэмы, что (идеологическое) содержание ее частично отходит на задний план. По всей вероятности, Рипеллино таким образом хочет привлечь внимание читателя скорее к Маяковскому, как к «революционному поэту», чем к Маяковскому, как к «поэту Революции».
Extended distribution record of two bellflower species of Codonopsis (Campanulaceae) from the Indian state of Arunachal Pradesh
Authors: Kanwal Khilendra Singh , Tiwari Umeshkumar Lalchand , Yama Lod , Lodhi Mahendra Singh 
Published: July 2019

Codonopsis foetens Hook.f. and C. thalictrifolia Wall., two high altitude plants occurring at an elevation of 3300–4800 m, are recorded from Arunachal Pradesh State in India for the first time. These species were collected from Nagula Wetland complex of Tawang District of the state. Detailed description, occurrence, distribution, flowering and fruiting season, and picture pale of the species are provided in this paper for their easy identification in the field.
Diurnal Serianthes nelsonii Merr. leaflet paraheliotropism reduces leaflet temperature, relieves photoinhibition, and alters nyctinastic behavior
Authors: Marler Thomas Edward 
Published: July 2019

The diel cycle of Serianthes nelsonii leaflet movements was characterized under four levels of shade from full sun to 22% sunlight transmission to determine the photoprotective components of diurnal leaflet movements and the relationship to patterns of nocturnal leaflet movements. Treatments also included negating paraheliotropism by re-orienting plants every 15min throughout the photoperiod such that the plants never experienced a predictable solar vector. The timing of leaflet closure to avoid high light, the shape of the diurnal curve depicting leaflet angle, and the maximum extent of leaflet closure were influenced by the shade treatments. Protection of leaf function by paraheliotropism was also influenced by shade treatment, with the full sun plants exhibiting the greatest level of protection. Leaflet heat gain was reduced 50% by leaflet movement as determined by direct measurements of leaf-to-air temperature differences. Midday quantum efficiency of photosystem II was increased 120% by leaflet movement as determined by direct measurements of pulse modulated chlorophyll fluorescence. The extent of nyctinastic leaflet closure was greatest in the high light plants that moved the most midday and least in the shaded plants that moved the least midday, indicating the extent of diurnal paraheliotropism controlled the amplitude of nocturnal leaflet movement. Serianthes nelsonii is highly skilled at using movement to reduce leaflet exposure to the solar vector, providing instantaneous behavioral control over heat gain and photoinhibition. This case study of an endemic tree species in Micronesia has added to the nascent field of conservation physiology, and indicated that heliotropism of S. nelsonii leaves may provide the species with the ability to minimize high light damage during increased temperatures associated with climate change.