bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of Immunosuppression Withdrawal in Pediatric Liver Transplant Recipients: Moving Toward Personalized Management
Authors: Feng Sandy , Bucuvalas John C. , Mazariegos George V. , Magee John C. , Sanchez‐Fueyo Alberto , Spain Katharine M. , Lesniak Andrew , Kanaparthi Sai , Perito Emily , Venkat Veena L. , Burrell Bryna E. , Alonso Estella M. , Bridges Nancy D. , Doo Edward , Gupta Nitika A. , Himes Ryan W. , Ikle David , Jackson Annette M. , Lobritto Steven J. , Jose Lozano Juan , Martinez Mercedes , Ng Vicky L. , Rand Elizabeth B. , Sherker Averell H. , Sundaram Shikha S. , Turmelle Yumirle P. , Wood‐Trageser Michele , Demetris Anthony J. 
Published: August 2020

Background and Aims
Tolerance is transplantation’s holy grail, as it denotes allograft health without immunosuppression and its toxicities. Our aim was to determine, among stable long‐term pediatric liver transplant recipients, the efficacy and safety of immunosuppression withdrawal to identify operational tolerance.

Approach and Results
We conducted a multicenter, single‐arm trial of immunosuppression withdrawal over 36‐48 weeks. Liver tests were monitored biweekly (year 1), monthly (year 2), and bimonthly (years 3‐4). For‐cause biopsies were done at investigators’ discretion but mandated when alanine aminotransferase or gamma glutamyltransferase exceeded 100 U/L. All subjects underwent final liver biopsy at trial end. The primary efficacy endpoint was operational tolerance, defined by strict biochemical and histological criteria 1 year after stopping immunosuppression. Among 88 subjects (median age 11 years; 39 boys; 57 deceased donor grafts), 33 (37.5%; 95% confidence interval [CI] 27.4%, 48.5%) were operationally tolerant, 16 were nontolerant by histology (met biochemical but failed histological criteria), and 39 were nontolerant by rejection. Rejection, predicted by subtle liver inflammation in trial entry biopsies, typically (n = 32) occurred at ≤32% of the trial‐entry immunosuppression dose and was treated with corticosteroids (n = 32) and/or tacrolimus (n = 38) with resolution (liver tests within 1.5 times the baseline) for all but 1 subject. No death, graft loss, or chronic, severe, or refractory rejection occurred. Neither fibrosis stage nor the expression level of a rejection gene set increased over 4 years for either tolerant or nontolerant subjects.

Conclusions
Immunosuppression withdrawal showed that 37.5% of selected pediatric liver‐transplant recipients were operationally tolerant. Allograft histology did not deteriorate for either tolerant or nontolerant subjects. The timing and reversibility of failed withdrawal justifies future trials exploring the efficacy, safety, and potential benefits of immunosuppression minimization.
Low‐dose pembrolizumab and nivolumab were efficacious and safe in relapsed and refractory classical Hodgkin lymphoma: Experience in a resource‐constrained setting
Authors: Chan Thomas S. Y. , Hwang Yu‐Yan , Khong Pek‐Lan , Leung Anskar Y. H. , Chim Chor‐Sang , Tse Eric W. C. , Kwong Yok‐Lam 
Published: August 2020

AbstractThe efficacy and safety of low‐dose anti‐PD1 antibodies in relapsed/refractory classical Hodgkin lymphoma (cHL) require confirmation. Pembrolizumab (100 mg every 3 weeks, Q3W) or nivolumab (40 mg Q2W) were administered to patients with relapsed/refractory cHL. In the pembrolizumab cohort (N = 11), who had failed a median of three (1–6) therapies (brentuximab vedotin [BV]: 91%; autologous hematopoietic stem cell transplantation [auto‐HSCT]: 18%), the overall response rate (ORR) by positron emission tomography–computed tomography was 100% (metabolic complete response [mCR]: 73%; partial response [PR]: 27%). Median cumulative dose for achieving best response was 400 (300–800) mg. Median progression‐free survival (PFS) was 35 months. Median overall survival (OS) was not reached. Adverse events (AEs) of grade 1–2 were observed in three patients. In the nivolumab cohort (N = 6), who had failed a median of three (2–6) therapies (BV: 50%; auto‐HSCT: 17%; allogeneic HSCT: 34%), the ORR was 100% (mCR: 67%; PR: 17%; indeterminate response: 17%). Median cumulative dose for achieving best response was 160 (160–360) mg. Median PFS was 33 months. Median OS was not reached. AEs of grade 1–2 were observed in four patients, two of whom had pre‐existing autoimmune conditions. Five patients with Epstein–Barr virus (EBV) positive Reed–Sternberg cells underwent monitoring of plasma EBV DNA, which became negative in four mCR patients but remained positive in one PR patient who died ultimately from refractory lymphoma. Low‐dose pembrolizumab and nivolumab were highly efficacious and safe in relapsed/refractory cHL. These observations have significant financial implications in resource‐constrained settings.
Rural communities in Africa should not be forgotten in responses to COVID‐19
Authors: Ogunkola Isaac Olushola , Adebisi Yusuff Adebayo , Imo Uchenna Frank , Odey Goodness Ogeyi , Esu Ekpereonne , Lucero‐Prisno Don Eliseo 
Published: August 2020

SummaryRural areas in Africa make up a large proportion of the continent. Since the emergence of COVID‐19 on the continent, major attention and responses have been placed on urban areas. Rural areas are typified by certain challenges which may serve as limitations to the provision of resources and tools for COVID‐19 responses in these areas. These major challenges include limited access to these areas due to poor road networks which may hamper the possibility of conveying resources and manpower. Shortage of healthcare workforce in these areas, poor health facilities/structures and limited access to COVID‐19 diagnostics services may also make containment challenging. It is therefore important that investment should be made in these areas towards providing the necessary tools, resources, and manpower to ensure effective containment of COVID‐19 and to alleviate the plight caused by the pandemic in rural Africa. Rural communities in Africa should not be left behind in COVID‐19 responses.
On the controls of preferential flow in soils of different hillslope position and lithological origin
Authors: Tang Qicheng , Duncan Jonathan M. , Guo Li , Lin Henry , Xiao Dacheng , Eissenstat David M. 
Published: August 2020

AbstractSoils derived from different lithologies and their controls on preferential flow remain underexplored in forested landscapes. In the same lithology, the propensity for preferential flow occurrence at different hillslope positions also remains largely elusive. By utilizing a soil moisture response time method, we compared preferential flow occurrence between a shale site (Shale Hills, silt loam soils) and a sandstone site (Garner Run, sandy loam soils) at four hillslope positions: ridge‐top, North‐ and South‐facing mid‐slopes and toe slope, for over 2 years. The catchments are neighbouring and covered by temperate forest. For the four hillslope positions, Shale Hills had higher preferential flow frequencies compared to Garner Run. Between these two catchments, the South‐facing mid‐slope sites showed the highest contrasts in preferential flow frequency (33.5% of events at Shale Hills vs. 8.8% at Garner Run) while the ridge‐top sites showed the lowest contrasts (18.7 vs. 13.2%). Additionally, over the unfrozen period, for seven out of eight monitoring sites, drier antecedent conditions tended to be more favourable for preferential flows to occur, with significant (p < .01) relationships at two sites. Except for the South‐facing mid‐slope sites, both Shale Hills and Garner Run had two preferential flow pathways. The characteristic preferential flow pathways at Shale Hills were the Bwand C horizons, and for Garner Run, preferential flow moved from the E/AE horizon to the Bwhorizon. This study shows that shale‐derived soils tended to have higher preferential flow occurrence than sandstone soils, but hillslope positions exhibit different levels of contrasts. More effort should be paid to study the impact of lithology on preferential flows in the context of land surface modelling and biogeochemical reactions to improve ecosystem services of headwater catchments.
Dynamics of selecting Islamic home financing
Authors: Khan Muhammad Y. , Ud Din Shahab , Khan Majid J. , Javeed Anam 
Published: August 2020

AbstractIslamic financing products are modes of finance based on principles of profit and loss sharing, no interest and no remunerative betting or speculation. Islamic home financing is one such mode of financing which is based on ownership sharing or deferred payment arrangement with the bank, hence avoiding chances of interest and speculation. This study examines the factors that affect customers' decision in selecting Islamic home financing services. A quantitative research methodology was adopted to study the dynamics of Islamic home financing by determining the level of key factors in Pakistani consumer market. Using stratified random sampling technique, data was collected from 250 bank customers through five‐point Likert scale questionnaires. Various tests were applied to check the reliability, sampling adequacy and correlation. Multiple regression analysis was applied for hypothesis testing. The findings of the study reveal that the level of knowledge, media advertisement, bank reputation, product choices and Shariah compliance are the key factors for the Pakistani bank customers who selected Islamic home financing. More importantly, we find no significant impact of price and bank services on selection of Islamic home financing. The results of the study enable the Islamic banking professionals and managers to identify the factors that are most valuable to customers for the selection of Islamic home financing over conventional home financing modes. They are suggested to develop strategies and plans to educate people more about Islamic home finance and develop their product portfolio to provide people with more Shariah compliant choices. This study contributes to the Islamic banking literature by extending and identifying the factors of Islamic home financing.
The profitability of Ichimoku Kinkohyo based trading rules in stock markets and FX markets
Authors: Deng Shangkun , Yu Haoran , Wei Chenyang , Yang Tianxiang , Tatsuro Shimada 
Published: August 2020

AbstractThis paper examines the profitability of trading rules based on a Japanese technical analysis method called Ichimoku Kinkohyo. First, the trading strategies based on several entry and exit strategies of Ichimoku Kinkohyo charting were designed. Then, we investigated their profitability on four stock indices of the world's famous stock exchanges over 1995 to 2018, and on four important currency pairs over 2003 to 2018. By using the default parameter setting (9, 26, 52) of Ichimoku Kinkohyo, we found that although several profitable trading strategies were obtained for stock index trading and currency trading during the Subperiod 1, experimental results in the Subperiod 2 revealed that they failed to create values consistently. Finally, evidence from parameter sweep showed that several Ichimoku trading strategies may well prove to be profitable on stock index trading, but none was found for currency trading.
Automatic breast cancer detection based on optimized neural network using whale optimization algorithm
Authors: Fang Hong , Fan Hongyu , Lin Shan , Qing Zhang , Sheykhahmad Fatima Rashid 
Published: August 2020

AbstractBreast cancer is the second deadliest type of cancer. Early detection of breast cancer can considerably improve the effectiveness of treatment. A significant early sign of breast cancer is the mass. However, separating the cancerous masses from the normal portions of the breast tissue is usually a challenge for radiologists. Recently, because of the availability of high‐accuracy computing, computer‐aided detection systems based on image processing have become capable of accurately diagnosing the various types of cancers. The main purpose of this study is to utilize a powerful image segmentation method for the diagnosis of cancerous regions through mammography, based on a new configuration of the multilayer perceptron (MLP) neural network. The most popular method for minimizing the errors in an MLP neural network is backpropagation. However, this method has certain drawbacks, such as a low convergence speed and becoming trapped at the local minimum. In this study, a new training algorithm based on the whale optimization algorithm is proposed for the MLP network. This algorithm is capable of solving various problems toward the current algorithms for the analyzed systems. The proposed method is validated on the Mammographic Image Analysis Society database, which contains 322 digitized mammography images, and the Digital Database for Screening Mammography, which contains approximately 2500 digitized mammography images. To assess the detection performance of the proposed system, the correct detection rate, percentage of identification with false acceptance, and percentage of identification with false rejection were evaluated and compared using various methods. The results indicate that the proposed method is highly efficient and yields significantly better accuracy compared with other methods.
“To be or not to be in the ward”: The impact of COVID‐19 on the role of hospital‐based clinical pharmacists—A qualitative study
Authors: Cheong Mark W. L. 
Published: August 2020

AbstractIntroductionThe coronavirus disease 2019 (COVID‐19) pandemic has significantly affected health care systems around the world. In many hospitals and health care facilities, services and health care workers have been reorganized and restructured to meet the demands of the pandemic. The impact of the pandemic on hospital‐based clinical pharmacists and their ability to deliver pharmaceutical care is currently unknown.ObjectiveThis study aimed to explore the impact of the COVID‐19 pandemic on hospital‐based clinical pharmacists working in Malaysia and the implications on how clinical pharmacy is perceived as a health care service.MethodsA qualitative study was designed to meet the research objectives. Nineteen hospital‐based clinical pharmacists consented and participated in one‐on‐one, semi‐structured interviews. The interviews were transcribed and analyzed using an iterative thematic analysis approach.ResultsThe experiences and views of the participants were reported. Three main themes were developed: “Reassignment and other changes in clinical pharmacist roles,” “Adapting clinical pharmacy services to COVID‐19,” and “The need for clinical pharmacists in the ward.” The findings indicate that in many cases, clinical pharmacy services were fully or partially withdrawn from the ward to reduce the risk of infection and to conserve the usage of personal protective equipment. Despite this, clinical pharmacists continued to support patient care in hospitals through the use of technology. The withdrawal of clinical pharmacy services, however, raises concern that the role of clinical pharmacists is still poorly recognized.ConclusionClinical pharmacists in hospitals continue to support patient care despite the disruption caused by the COVID‐19 pandemic. Greater support and recognition of their role is required in order to empower and enhance their ability to deliver pharmaceutical care.
Rethinking the Drug Distribution and Medication Management Model: How a New York City Hospital Pharmacy Department Responded to COVID‐19
Authors: Dzierba Amy L. , Pedone Trisha , Patel Mona K. , Ciolek Alana , Mehta Monica , Berger Karen , Ramos Liz G. , Patel Viha D. , Littlefield Audrey , Chuich Taylor , May Hetal B. , Muir Justin , Verkerk Brittany S. , Poon Teresa , Der‐Nigoghossian Caroline , Nikolos Peter , Gunther Michelle , Shah Jenny , Witenko Corey J. 
Published: August 2020

AbstractBeginning in March 2020, New York City began the fight against coronavirus disease 2019. Health care workers were faced with a disease that led to significant morbidity and mortality with no proven therapies. As hospitals became inundated with patients and underwent rapid expansion of capacity, resources such as drugs, protective and medical equipment, and hospital staff became limited. Pharmacists played a critical role in the management of clinical care and drug delivery during the pandemic. As members of the department of pharmacy within NewYork‐Presbyterian Hospital, we describe our experiences and processes to overcome challenges faced during the pandemic. Strict inventory management through the use of daily usage reports, frequent communication, and minimization of waste was critical for the management of drug shortages. The creation of guidelines, protocols, and restrictions were not only used to mitigate drug shortages, but also helped educate health care providers and guided medication use. Managing technology through setting up new automatic dispensing cabinets to address hospital expansions and modifying the electronic order entry system to include new protocols and drug shortage information were also vital. Additional key pharmacist functions included provision of investigational drug service support and training of pharmacists, prescribers, nurses, and respiratory therapists to educate and standardize medication use. Through implementation of operational and clinical processes, pharmacists managed critical drug inventory and guided patient treatment. As the pandemic continues, pharmacists will remain vital members of the multidisciplinary team dedicated to the fight against the virus.
miRNA Mechanisms Underlying the Association of Beta Blocker Use and Bone Mineral Density
Authors: Nevola Kathleen T , Kiel Douglas P , Zullo Andrew R , Weiss Stefan , Homuth Georg , Foessl Ines , Obermayer-Pietsch Barbara , Motyl Katherine J , Lary Christine W 
Published: August 2020

ABSTRACT
Osteoporosis is a debilitating and costly disease that causes fractures in 33% of women and 20% of men over the age of 50 years. Recent studies have shown that beta blocker (BB) users have higher bone mineral density (BMD) and decreased risk of fracture compared with non-users. The mechanism underlying this association is thought to be due to suppression of adrenergic signaling in osteoblasts, which leads to increased BMD in rodent models; however, the mechanism in humans is unknown. Also, several miRNAs are associated with adrenergic signaling and BMD in separate studies. To investigate potential miRNA mechanisms, we performed a cross-sectional analysis using clinical data, dual-energy X-ray absorptiometry (DXA) scans, and miRNA and mRNA profiling of whole blood from the Framingham Study's Offspring Cohort. We found nine miRNAs associated with BB use and increased BMD. In parallel network analyses, we discovered a subnetwork associated with BMD and BB use containing two of these nine miRNAs, miR-19a-3p and miR-186-5p. To strengthen this finding, we showed that these two miRNAs had significantly higher expression in individuals without incident fracture compared with those with fracture in an external data set. We also noted a similar trend in association between these miRNA and Z-score as calculated from heel ultrasound measures in two external cohorts (SOS-Hip and SHIP-TREND). Because miR-19a directly targets the ADRB1 mRNA transcript, we propose BB use may downregulate ADRB1 expression in osteoblasts through increased miR-19a-3p expression. We used enrichment analysis of miRNA targets to find potential indirect effects through insulin and parathyroid hormone signaling. This analysis provides a starting point for delineating the role of miRNA on the association between BB use and BMD. © 2020 American Society for Bone and Mineral Research (ASBMR).
Abstract
Current studies show adrenergic signaling through ADRB2 in mice causes increased RANKL signaling, leading to osteoclast differentiation, increased bone resorption, and decreased bone mass. Beta blockers block this signaling, restoring balanced bone remodeling. Our study shows that beta blocker users have increased miR-19a-3p and miR-186-5p expression and that these miRNA are positively associated with hip and spine bone mineral density. We propose that miR-19a-3p targets ADRB1 mRNA for degradation, decreasing the receptors available for signaling. These miRNA may also affect bone mineral density through insulin signaling, PTH signaling, estrogen signaling, and TGF-beta signaling.
Effects of Combination Denosumab and High-Dose Teriparatide Administration on Bone Microarchitecture and Estimated Strength: The DATA-HD HR-pQCT Study
Authors: Ramchand Sabashini K , David Natalie L , Lee Hang , Bruce Michael , Bouxsein Mary L , Leder Benjamin Z , Tsai Joy N 
Published: August 2020

ABSTRACT
In postmenopausal women at high risk of fracture, we previously reported that combined denosumab and high-dose (HD; 40 μg) teriparatide increased spine and hip bone mineral density (BMD) more than combination with standard-dose teriparatide (SD; 20 μg). To assess the effects of these combinations on bone microarchitecture and estimated bone strength, we performed high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia in these women, who were randomized to receive either teriparatide 20 μg (n = 39) or 40 μg (n = 37) during months 0 to 9 overlapped with denosumab 60 mg s.c. given at months 3 and 9, for a 15-month study duration. The 69 women who completed at least one study visit after baseline are included in this analysis. Over 15 months, increases in total BMD were higher in the HD-group than the SD-group at the distal tibia (5.3% versus 3.4%, p = 0.01) with a similar trend at the distal radius (2.6% versus 1.0%, p = 0.06). At 15 months, cortical porosity remained similar to baseline, with absolute differences of −0.1% and −0.7% at the distal tibia and −0.4% and −0.1% at the distal radius in the HD-group and SD-group, respectively; p = NS for all comparisons. Tibial cortical tissue mineral density increased similarly in both treatment groups (1.3% [p &lt; 0.0001 versus baseline] and 1.5% [p &lt; 0.0001 versus baseline] in the HD-group and SD-group, respectively; p = 0.75 for overall group difference). Improvements in trabecular microarchitecture at the distal tibia and estimated strength by micro-finite element analysis at both sites were numerically greater in the HD-group compared with SD-group but not significantly so. Together, these findings suggest that short-term treatment combining denosumab with either high- or standard-dose teriparatide improves HR-pQCT measures of bone density, microstructure, and estimated strength, with greater gains in total bone density observed in the HD-group, which may be of benefit in postmenopausal women with severe osteoporosis. © 2020 American Society for Bone and Mineral Research (ASBMR).