bluuebunny/crossref_metadata_2025_split huggingface dataset:
A nationwide causal mediation analysis of survival following ST-elevation myocardial infarction
Authors: Dondo Tatendashe Bernadette , Hall Marlous , Munyombwe Theresa , Wilkinson Chris , Yadegarfar Mohammad E , Timmis Adam , Batin Philip D , Jernberg Tomas , Fox Keith AA , Gale Chris P 
Published: April 2020

ObjectiveInternational studies report a decline in mortality following ST-elevation myocardial infarction (STEMI). The extent to which the observed improvements in STEMI survival are explained by temporal changes in patient characteristics and utilisation of treatments is unknown.MethodsCohort study using national registry data from the Myocardial Ischaemia National Audit Project between first January 2004 and 30th June 2013. 232 353 survivors of hospitalisation with STEMI as recorded in 247 hospitals in England and Wales. Flexible parametric survival modelling and causal mediation analysis were used to estimate the relative contribution of temporal changes in treatments and patient characteristics on improved STEMI survival.ResultsOver the study period, unadjusted survival at 6 months and 1 year improved by 0.9% and 1.0% on average per year (HR: 0.991, 95% CI: 0.988 to 0.994 and HR: 0.990, 95% CI: 0.987 to 0.993, respectively). The uptake of primary percutaneous coronary intervention (PCI) (HR: 1.025, 95% CI: 1.021 to 1.028) and increased prescription of P2Y12inhibitors (HR: 1.035, 95% CI: 1.031 to 1.039) were significantly associated with improvements in 1-year survival. Primary PCI explained 16.8% (95% CI: 10.8% to 31.6%) and 13.2% (9.2% to 21.9%) of the temporal survival improvements at 6 months and 1 year, respectively, whereas P2Y12inhibitor prescription explained 5.3% (3.6% to 8.8%) of the temporal improvements at 6 months but not at 1 year.ConclusionsFor STEMI in England and Wales, improvements in survival between 2004 and 2013 were significantly explained by the uptake of primary PCI and increased use of P2Y12inhibitors at 6 months and primary PCI only at 1 year.Trial registration numberNCT03749694
Resistance to carbapenems and other antibiotics in Klebsiella pneumoniae found in seals indicates anthropogenic pollution
Authors: Duff James Paul , AbuOun Manal , Bexton Steve , Rogers Jon , Turton Jane , Woodford Neil , Irvine Richard , Anjum Muna , Teale Christopher 
Published: April 2020

BackgroundThe beta‐lactamase enzyme OXA‐48 has spread widely in recent years in Enterobacteriaceae associated with man, disseminated primarily on incompatibility group L/M plasmids. OXA‐48 confers resistance to carbapenems, important antimicrobials for treating highly resistant bacterial infections in humans. This enzyme has rarely been detected in bacteria from animals. Furthermore, the use of carbapenem compounds is not permitted in food‐producing animals in Europe and to our knowledge has not been reported in food‐producing animals globally.MethodsBacterial isolates from lesions in stranded, free‐living, juvenile common seals (Phoca vitulina) were identified. Antimicrobial susceptibility testing and whole genome sequencing analysis were used to characterise antimicrobial resistance genes carried by the bacteria.ResultsHere, we report the detection of Klebsiella pneumoniae subspecies pneumoniae carrying the bla
OXA‐48 gene on an incompatibility group L/M plasmid from an infection in a common seal.ConclusionEvidence is accruing that marine mammals may be infected with bacteria originating from anthropogenic sources, such as human sewage, contaminating the environment.
Stable three generation standard-like model from a tachyonic ten dimensional heterotic-string vacuum
Authors: Faraggi Alon E. , Matyas Viktor G. , Percival Benjamin 
Published: April 2020

AbstractRecently it was proposed that the ten dimensional tachyonic superstring vacua may serve as good starting points for the construction of viable phenomenological models. Such phenomenologically viable models enlarge the space of possible string solutions, and may offer novel insight into some of the outstanding problems in string phenomenology. In this paper we present a three generation standard-like model that may be regarded as a compactification of a ten dimensional tachyonic vacuum. We discuss the features of the model as compared to a similar model that may be regarded as compactification of the ten dimensional $$SO(16)\times SO(16)$$SO(16)×SO(16) heterotic-string. We further argue that in the four dimensional model all the geometrical moduli are fixed perturbatively, whereas the dilaton may be fixed by hidden sector non-perturbative effects.
Stromal Platelet–Derived Growth Factor Receptor-β Signaling Promotes Breast Cancer Metastasis in the Brain
Authors: Thies Katie A. , Hammer Anisha M. , Hildreth Blake E. , Steck Sarah A. , Spehar Jonathan M. , Kladney Raleigh D. , Geisler Jennifer A. , Das Manjusri , Russell Luke O. , Bey Jerome F. , Bolyard Chelsea M. , Pilarski Robert , Trimboli Anthony J. , Cuitiño Maria C. , Koivisto Christopher S. , Stover Daniel G. , Schoenfield Lynn , Otero Jose , Godbout Jonathan P. , Chakravarti Arnab , Ringel Matthew D. , Ramaswamy Bhuvaneswari , Li Zaibo , Kaur Balveen , Leone Gustavo , Ostrowski Michael C. , Sizemore Steven T. , Sizemore Gina M. 
Published: April 2020

Abstract

Platelet-derived growth factor receptor-beta (PDGFRβ) is a receptor tyrosine kinase found in cells of mesenchymal origin such as fibroblasts and pericytes. Activation of this receptor is dependent on paracrine ligand induction, and its preferred ligand PDGFB is released by neighboring epithelial and endothelial cells. While expression of both PDGFRβ and PDGFB has been noted in patient breast tumors for decades, how PDGFB-to-PDGFRβ tumor–stroma signaling mediates breast cancer initiation, progression, and metastasis remains unclear. Here we demonstrate this paracrine signaling pathway that mediates both primary tumor growth and metastasis, specifically, metastasis to the brain. Elevated levels of PDGFB accelerated orthotopic tumor growth and intracranial growth of mammary tumor cells, while mesenchymal-specific expression of an activating mutant PDGFRβ (PDGFRβD849V) exerted proproliferative signals on adjacent mammary tumor cells. Stromal expression of PDGFRβD849V also promoted brain metastases of mammary tumor cells expressing high PDGFB when injected intravenously. In the brain, expression of PDGFRβD849V was observed within a subset of astrocytes, and aged mice expressing PDGFRβD849V exhibited reactive gliosis. Importantly, the PDGFR-specific inhibitor crenolanib significantly reduced intracranial growth of mammary tumor cells. In a tissue microarray comprised of 363 primary human breast tumors, high PDGFB protein expression was prognostic for brain metastases, but not metastases to other sites. Our results advocate the use of mice expressing PDGFRβD849V in their stromal cells as a preclinical model of breast cancer–associated brain metastases and support continued investigation into the clinical prognostic and therapeutic use of PDGFB-to-PDGFRβ signaling in women with breast cancer.

Significance:
These studies reveal a previously unknown role for PDGFB-to-PDGFRβ paracrine signaling in the promotion of breast cancer brain metastases and support the prognostic and therapeutic clinical utility of this pathway for patients.
See related article by Wyss and colleagues, p. 594
УДОСКОНАЛЕННЯ СКЛАДУ І РОЗРОБКА ЕКСТЕМПОРАЛЬНОЇ ТЕХНОЛОГІЇ ПЕСАРІЇВ ІЗ ДОКСИЦИКЛІНОМ ХІКЛАТОМ НА ОСНОВІ МАСЛА КАКАО
Authors: Chushenko V. M. , Yarnykh T. G. , Rukhmakova O. A. , Yuryeva G. B. 
Published: April 2020

Мета роботи. Удосконалення складу і розробка екстемпоральної технології песаріїв із доксицикліном хіклатом на основі масла какао.
Матеріали і методи. Встановлено, що рецептурні прописи для лікування вагінальних інфекцій досить часто представлені песаріями із доксицикліну хіклатом на поліетиленоксидній основі. З метою їх удосконалення до складу лікарського засобу, окрім доксицикліну хіклату, введено лінімент синтоміцину, димексид і ментол. Як супозиторну основу використано суміш масла какао із воском бджолиним. Приготування песаріїв здійснено методом виливання з урахуванням вимог ДФУ 2.0 і Настанови МОЗУ «Вимоги до виготовлення нестерильних лікарських засобів в умовах аптек». Для визначення фармакотехнологічних показників модельних зразків лікарського засобу вивчено їх опис (однорідність), температуру плавлення і стійкість до руйнування.
Результати й обговорення. З метою визначення оптимального співвідношення масла какао і воску бджолиного у складі супозиторної основи досліджено фармакотехнологічні показники їх модельних зразків. Для подальших досліджень обрано співвідношення компонентів 92,5:7,5 і 95,0:5,0. При вивченні впливу емульгаторів (емульгатор Т-2, лецитин) на деякі показники якості песаріїв встановлено, що лише зразки лікарського засобу на обраній супозиторній основі у співвідношенні 95,0:5,0 із вмістом лецитину в кількості 2–3 % відповідають вимогам ДФУ за показниками «Опис» і «Температура плавлення». Експериментально доведено, що доксицикліну хіклат легко змішується з лініментом синтоміцину, що сприяє його рівномірному розподілу в супозиторній основі. Такий спосіб введення антибіотика значно покращує якість отриманих песаріїв (відсутній ефект осідання).
При розробці екстемпоральної технології лікарського засобу методом виливання визначено зворотний коефіцієнт заміщення доксицикліну хіклату на маслі какао, який становить 0,81. Зразки песаріїв, виготовлені за запропонованою технологією, проаналізовано за показниками якості відповідно до вимог ДФУ 2.0, чинних наказів, інструкцій і настанов МОЗ України.
Висновки. Проведено експериментальні дослідження з удосконалення складу екстемпоральних песаріїв із доксицикліном хіклатом для лікування інфекційного вагініту. До складу лікарського засобу, окрім доксицикліну хіклату, введено лінімент синтоміцину, димексид і ментол. Як супозиторну основу використано суміш масла какао і воску бджолиного у співвідношенні 95,0:5,0. Розроблено екстемпоральну технологію песаріїв методом виливання. Показано, що отримані зразки песаріїв повністю відповідають вимогам ДФУ до даної лікарської форми.
МАРКЕТИНГОВІ ДОСЛІДЖЕННЯ АСОРТИМЕНТУ КОНТРАСТНИХ ЛІКАРСЬКИХ ЗАСОБІВ, РЕПРЕЗЕНТОВАНИХ НА ФАРМАЦЕВТИЧНОМУ РИНКУ УКРАЇНИ
Authors: Palchevska T. A. , Baula O. P. , Saliy O. O. , Bessarabov V. I. , Tarasenko H. V. , Kuryshko H. H. 
Published: April 2020

Мета роботи. Провести аналіз вітчизняного фармацевтичного ринку контрастних лікарських засобів (КЛЗ); встановити обсяг асортиментних позицій вітчизняних виробників та визначити домінуючий сегмент за якісним складом досліджуваних ЛЗ.
Матеріали і методи. Аналіз проводили на основі даних Державного реєстру лікарських засобів України, електронних баз даних, інформаційно-пошукової програми «Моріон» станом на 2019 рік. Отримані дані досліджень опрацьовували методами узагальнення, систематизації, графічного, порівняльного та структурного аналізу.
Результати й обговорення. Встановлено, що до групи зареєстрованих КЛЗ відноситься 36 найменуваннь, з них 31 ЛЗ належать до йодовмісних КЛЗ (5 ЛЗ – йонні, 26 ЛЗ – нейонні), 5 препаратів складають контрастні засоби на основі гадолінію та барію.
Лідером імпортних препаратів є фірма-виробник і заявник Юнік Фармасьютикал Лабораторіз, Індія, частка якої складає 27,8 %. Обсяг вітчизняного асортиментного сегмента знаходиться на рівні 33,4 %, провідне місце серед вітчизняних виробників посідає фармацевтичне підприємство ПАТ «Фармак».
Вивчено структуру асортименту дослiджуваної групи за торговельними назвами (ТН) та країнами-виробниками: загальна кількість ТН становить 17 найменувань КЛЗ, із них 5 ТН – лікарські засоби вітчизняних фармацевтичних підприємств. До основного складу досліджених контрастних ЛЗ входить 10 активних фармацевтичних інгредієнтів (АФІ), а також такі допоміжні речовини, як трометамол і/або трометамін та меглюмін, що сприяють зменшенню негативної реакції на організм людини та покращують загальні властивості КЛЗ.
Висновки. Встановлено, що український ринок КЛЗ формується, в основному, за рахунок iмпортних ЛЗ, їх питома вага складає 66,6 %. Встановлено відсутність вітчизняного виробництва нейонних йодовмісних КЛЗ: йопромід, йодиксанол.
Geoffrey Hill’s Poetic Incarnational Theology
Authors: Russell Jesse 
Published: April 2020

Abstract
Geoffrey Hill’s poems are saturated with the cluttered bleakness of the nihilistic view of the natural world, but in Hill’s own Christian incarnational theology it is precisely this filthy world into which Christ was incarnated in order to redeem humans from Original Sin. Fortified with but also rattled by the Incarnation and the doctrine of Original Sin, in his poems Hill is faced with the profound, agonizing existential choice to embrace Christ or reject Christianity as a farce, and it is this perilous pose that serves as the theological grounding of the oeuvre the man who now, sadly, was the greatest contemporary Christian poet.
Wuthering Heights
Authors: Stuchiner Judith 
Published: April 2020

Abstract
This essay views Lockwood’s first dream in Brontë’s Wuthering Heights, in which “the famous Jabes Branderham preach[es] from the text,” as a “slice” of Methodist history. Enlisting E.P. Thompson’s suggestion that Jabes Branderham is modeled after Methodist Jabez Bunting, I argue that Brontë’s presentation of Methodism in the dream contains valuable socio-economic information. As an aspiring member of the gentry, Lockwood fears the subversive potential of Methodism and resents Branderham’s preaching of it and Joseph’s observance of it. I argue further that Brontë uses Methodism as a tool in her characterization of Lockwood and Joseph.
Perception of Peace Actors on the Nexus between Criminal Gangs and Violent Extremism in the Coast of Kenya
Authors: Shauri Halimu Suleiman , Mutubwa Hassan Mohamed , Mwaka Musa Timothy 
Published: April 2020

Abstract
A growing body of scholarly literature suggests convergence or linkage between Criminal Gangs (CGs) and Violent Extremism (VE) in various parts of the world (Hubschle, 2011). However, the connection between CG and VE remains unclear and contrast substantially, based on area, context and perspective of criminal gangs and VE groups. While studies have been done in other parts of the world, no such studies have been done in the Coastal Region of Kenya to link CGs and VE groups. This is despite the widespread operation of VE groups such as the Somali based Al-Shabaab and many criminal gangs in the region to mention a few the Kapenguria six, Wajukuu wa Babu, Wakali Wao, Wakali Kwanza, Wajukuu wa Bibi, Wajukuu wa Mtume among others. Accordingly, this study provides the perception of peace actors, community, government and civil society personnel, on the Coast of Kenya on the nexus between criminal gangs and VE. The findings are based on a survey study involving sixty (60) peace actors who responded to a questionnaire study that was distributed in May and June 2019 in Mombasa, Kenya.
<p><strong><em>Alternaria telliensis sp. nov</em>., a new species isolated from <em>Solanaceae</em> in Algeria</strong></p>
Authors: BESSADAT NABAHAT , HAMON BRUNO , BATAILLE-SIMONEAU NELLY , MABROUK KIHAL , SIMONEAU PHILIPPE 
Published: April 2020

During a biodiversity survey of Alternaria associated with leaf spot and blight of Solanaceae, a large collection of strains was obtained from samples collected in north-western regions of Algeria in 2013–2018 growing seasons. Amongst these strains, three isolates recovered from tomato and potato had morphological traits different from that usually observed for Alternaria species previously reported on Solanaceae. Based on analysis of a sequence dataset corresponding to portions of the glyceraldehyde-3-phosphate dehydrogenase (gpd), translation elongation factor 1-alpha (tef1) and RNA polymerase second largest subunit (rpb2) genes along with morphological observations, isolates were identified as a new species in the section Japonicae. This novel species, described here as Alternaria telliensis, is phylogenetically and morphologically distinct from A. japonica and A. nepalensis in this section. Pathogenicity tests were performed and isolates were found to be weakly pathogenic to tomato and potato (Solanaceae) while highly aggressive on radish, cabbage and turnip (Brassicaceae) plants.
A Hybrid Precipitation Index Inspired by the SPI, PDSI, and MCDI. Part I: Development of the Index
Authors: Chelton Dudley B. , Risien Craig M. 
Published: April 2020

AbstractThe filtering properties of the standardized precipitation index (SPI), the Palmer drought severity index (PDSI), and the model calibrated drought index (MCDI) are investigated to determine their relations to past, present, and future precipitation anomalies in regions with a wide diversity of precipitation characteristics. All three indices can be closely approximated by weighted averages of precipitation, but with different weighting. The SPI is well represented by one-sided, uniformly weighted averages; the MCDI is well represented by one-sided, exponentially weighted averages; and the PDSI is well represented by two-sided, exponentially weighted averages with much higher weighting of past and present precipitation than future precipitation. Detailed analyses identify interpretational complications and other undesirable features in the SPI and PDSI. In addition, the PDSI and MCDI are each restricted to single regionally specific “intrinsic” time scales that can significantly differ between the two indices. Inspired by the strengths of the SPI, PDSI, and MCDI, a hybrid index is developed that consists of exponentially weighted averages of past and present precipitation that are implicit in the PDSI and MCDI. The explicit specification of the exponential weighting allows users to control the time scale of the hybrid index to investigate precipitation variability on any time scale of interest. This advantage over the PDSI and MCDI is analogous to the controllability of the time scale of the SPI, but the exponentially fading memory is more physical than the uniform weighting of past and present precipitation in the SPI.
Evaluation of neoadjuvant gonadotropin administration with downregulation by testosterone prior to second time microsurgical testicular sperm extraction: A prospective case–control study
Authors: Amer Medhat Kamel , Ahmed Hossam ElDin Hosni , GamalEl Din Sameh Fayek , Fawzy Megawer Ahmed , Ahmed Ahmed Ragab 
Published: April 2020

Purpose: The aim of this prospective study was to determine whether there is a beneficial role of combining gonadotropin administration with testosterone downregulation in non-obstructive azoospermia patients prior to a second time microsurgical testicular sperm extraction after a negative one. Methods: A total of 40 non-obstructive azoospermia men were recruited from a specialized IVF center from 2014 to 2016. Participants were divided equally into two groups: Group A was subjected to testosterone downregulation alone for 1 month and then combined with gonadotropin administration for 3 months prior to second time testicular sperm extraction; Group B (controls) underwent second time microsurgical testicular sperm extraction without prior hormonal therapy. Results: Mean baseline follicle-stimulating hormone levels of the controls and the cases were 26.9 ± 11.8 and 25.4 ± 8.7, respectively. One month after testosterone downregulation, follicle-stimulating hormone level of the cases was normalized and became 2.4 ± 1.2. There was no statistically significant difference between baseline follicle-stimulating hormone levels of the controls and cases (p = 0.946). Remarkably, two cases were positive after downregulation (10%) and no controls were positive at second testicular sperm extraction (0%). There was no statistically significant difference between sperm retrieval after the second microsurgical testicular sperm extraction in the controls and the cases (p = 0.072). Conclusion: Patients who underwent first time testicular sperm extraction with unfavorable outcome due to different techniques may benefit from testosterone downregulation combined with neoadjuvant gonadotropin administration as it had shown positive sperms retrieval in 2 out of the 20 cases, especially those with hypergonadotropic azoospermia.
Pediatric Palliative Care During End of Life: A Privilege of a Few in a Tertiary Referral Hospital From Colombia
Authors: Cuervo-Suarez Maria Isabel , Claros-Hulbert Angélica , Manzano-Nunez Ramiro , Muñoz Mauricio , García Ximena 
Published: April 2020

Background: We aim to describe the access to palliative care (PC) in hospitalized children during end-of-life care and compare the circumstances surrounding the deaths of hospitalized children as a basis for implementing a pediatric PC program at our institution. Methods: We performed a retrospective chart review of deceased pediatric patients at a tertiary referral hospital in Colombia. The study group was selected by randomly drawing a sample of 100 observations from the 737 deceased children from 2013 to 2016. A 1:1 propensity score (PS) matching was performed to compare the characteristics and outcomes between PC and non-PC treated patients. Results: We included 87 patients. After PS matching, we found that patients under the care of non-PC physicians were more likely to die in the pediatric intensive care unit (non-PC: 6/10 vs PC: 1/10; P = .02), to be on vasopressor agents and mechanical ventilation (non-PC: 7/10 vs PC: 1/10; P = .02), and to receive cardiopulmonary resuscitation at the end of life (non-PC: 5/10 vs PC: 0/10; P = .03). In contrast, a significantly higher proportion of patients under the care of the pediatric PC team died with comfort measures (non-PC: 2/10 vs 8/10; P = .02) and nonescalation of care in physician orders (non-PC: 5/10 vs PC: 10/10; 0.03). Conclusion: In this study, only 10 of 87 patients were treated by the pediatric PC team at the end of life. The latter finding is concerning and is a call to action to improve access to pediatric PC at our institution.
Impact of Automated Targeted Medication Review Electronic Alerts to Reduce Potentially Inappropriate Medication Prescribing Among Medicare Enrolled Patients With Dementia
Authors: Silva-Almodóvar Armando , Malfara Andrea , Nahata Milap C. 
Published: April 2020

Background: Background:Finding ways to reduce prescribing of potentially inappropriate medications (PIMs) among patients with dementia is necessary. Objectives: To evaluate an automated targeted medication review (TMR) service to reduce PIM prescribing among patients with dementia. Methods: This was a retrospective observational analysis of patients in a Medication Therapy Management (MTM) program for year 2017. Patients included if Medicare enrolled, MTM eligible, had dementia, and with PIM prescribing. Descriptive statistics described reduced PIM prescribing. Odds ratios (ORs) assessed prescriber relationship with PIM prescribing. Regression evaluated relationship between patient characteristics and discontinued PIMs. Results: A total of 33 696 TMRs were triggered for 17 933 patients. Four months later, 11 608 TMRs led to a discontinued PIM among 8002 patients. Medications with the largest discontinuations were antihistamines (56%), muscle relaxants (53%), antiemetics (53%), and typical antipsychotics (40%). Physician primary care providers (PCPs) were more likely than nonphysician PCPs (OR = 4.54; 95% CI = 4.15-4.97; P < 0.001), psychiatrists (OR = 1.64; 95%CI = 1.44-1.86; P < 0.001), and neurologists (OR = 4.48; 95% CI = 4.07-4.93; P < 0.001) to prescribe medications to treat dementia and PIMs. Regression showed that younger age, female gender, higher poverty level, and a greater number of pharmacies, medications, and prescribers were associated with discontinued PIMs. Conclusions and Relevance: TMRs were effective in reducing PIM prescribing. Younger patients, individuals living in higher poverty levels, and patients with multiple prescribers or pharmacies may benefit most from this service. TMRs in primary care offices may reduce PIM prescribing.