bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactobacillus Fermentum ZS40 prevents secondary osteoporosis in Wistar Rat
Authors: Liu Xinhong , Fan Jian‐Bo , Hu Jing , Li Fang , Yi Ruokun , Tan Fang , Zhao Xin
Published: August 2020

Using retinoic acid to inducer, we successfully established a rat model of secondary osteoporosis and verified the preventive effect of Lactobacillus fermentum ZS40 (ZS40) on secondary osteoporosis. Serum biochemical indicators showed that ZS40 can effectively slow down bone resorption caused by retinoic acid, increase blood content of calcium, phosphorus, bone alkaline phosphatase, bone gla protein, and insulin‐like growth factor 1, and decrease blood content of tartrate‐resistant acid phosphatase (TRAP) 5b. qRT‐PCR results showed that ZS40 could upregulate mRNA expressions of β‐catenin, Wnt10b, Lrp5, Lrp6, Runx2, ALP, RANKL, and OPG, and downregulate mRNA expression of DKK1, RANK, TRACP, and CTSK in the rats’ spinal cord. Results following TRAP staining showed that ZS40 could slow down retinoic acid‐induced formation of osteoclasts. Micro‐CT results showed that ZS40 could reduce Tb.Sp, increase BV/TV, Tb.N, Tb.Th, and ultimately increase bone mineral density of rats in vivo. These findings indicate that ZS40 might have a potential role in preventing retinoic acid‐induced secondary osteoporosis in vivo.
Surface site‐formation processes in northern Tierra del Fuego (Argentina): A case study of the Amalia 4 Site
Authors: Oría Jimena , Salemme Mónica , Vázquez Martín , Bártoli Valeria , López Ramiro
Published: August 2020

Surface site studies in Fuegian archaeology have mainly been undertaken with distributional or spatial approaches. However, issues related to integrity, resolution, and/or other aspects of site‐formation processes still require attention. In this study, the study of these processes is proposed as an initial step to enhancing the comprehension of human use‐of‐space and circulation in the Fuegian steppe. The Amalia 4 Site serves as an ideal case study to analyze the potential movement that was likely involved in the distribution of archaeological materials recorded on the surface. Different lines of evidence were evaluated: (a) Topographic aspects were related to the dimensions and weight of lithic artifacts and bone remains; (b) test pits and subsurface collections were carried out with the purpose of recording flakes and debris of less than 10 mm (microdebris) or other buried materials; (c) some retouched artifacts were observed at higher magnifications to evaluate differential alterations among exposure times; (d) an exhaustive task of refitting lithic artifacts was conducted; (e) a taphonomic study of the skeletal remains was carried out. The aim of all these studies was to contribute to the understanding of the postdepositional dynamics and to come up with alternative hypotheses in relation to site‐formation processes.
Apatite at Niutoushan U–Pb–Zn deposit in Xiangshan ore field: A tracer for hydrothermal fluid
Authors: Wang Cuiyun , Li Xiaofeng , Wei Xingling
Published: August 2020

The volcanic‐hosted Xiangshan uranium ore field is the largest uranium deposit in Jiangxi Province, South China. In this ore field, Pb–Zn mineralization has been discovered beneath the uranium orebodies at Niutoushan‐Heyuanbei area. Apatite is a ubiquitous accessory mineral in the volcanic rocks, as well as the U and Pb–Zn alteration–mineralization zones. Six main types of apatite, which show the evolution of volcanic magma and hydrothermal fluids, have been observed on the basis of textures, associated mineral assemblages, chemical compositions (halogen, MnO, FeO, and SO3, etc.), and mineral inclusions. For magmatic primary apatite, porphyritic lava‐hosted P‐Apa and P‐Apb have higher F/Cl ratios and lower contents of MnO and FeO than rhyodacite‐hosted R‐Ap. For hydrothermal apatite, U‐Ap1‐a, U‐Ap1‐b, and S‐Ap1 are recognized as hydrothermal‐affected apatite, while U‐Ap2 and S‐Ap2 as apatite precipitating from hydrothermal fluid. U‐Ap1‐a and U‐Ap1‐b, hosted in the green‐stained alteration zone, are characterized by highly heterogeneous BSE imaging and contain monazite and ThSiO4 inclusions. Such apatites record the remobilization and reprecipitation of rare earth elements (REEs), Th and U by a relatively high‐temperature, F‐ and CO2‐enriched but Na‐depleted fluid at the early REE‐phase stage. U‐Ap2 occurring in pitchblende–fluorite dominated ore sample, is featured with negligible Cl, variable F and relatively higher Ti contents. It records a new hydrothermal pulse of relatively low temperature, oxidized, highly Ca‐, Ti‐, and F‐enriched but Cl‐depleted which probably conduces to leaching and transporting significant amounts of uranium. S‐Ap1 and S‐Ap2 hosted within the sericite–quartz–carbonate alteration halo on both sides of Pb–Zn–Fe sulphide veinlets, have relatively high Cl and variable F content. This apatite records reduced, Cl‐, Ca‐enriched, magmatic‐derived fluid events. Combined with previous researches, the apatite data suggest that U and Pb–Zn mineralization may form from two spatially and temporally distinct hydrothermal systems. Thus, apatite can fingerprint multi‐stage hydrothermal fluids and be treated as a useful tool for mineral exploration.
Reservoir variations and heterogeneities under valley‐monadnock palaeo‐geomorphology in hinterland area of the Junggar Basin, northwestern China: Sedimentary characteristics and diagenetic alterations
Authors: Gao Chonglong , Ren Ying , Liu Bo , Ji Youliang , Wang Jian , Sun Yonghe , Zhang Yue , Zhang Xiaohai , He Songlin
Published: August 2020

Palaeo‐geomorphology can exert significant effects on reservoir quality via controlling the distribution of depositional facies and diagenetic alterations. However, little attention has been paid to the studies of the reservoir variations and heterogeneities under distinctive valley‐monadnock palaeo‐geomorphology. Taking the Lower Cretaceous Qingshuihe Formation (K1q) in the Junggar Basin as an example, this study improves the current understanding of reservoir potential within topography of this kind by examining the link between depositional facies, diagenesis and their impact on reservoir quality. In total, nine types of lithofacies can be identified in the K1q reservoirs, which can be further grouped into lowstand systems tract (LST) gravelly braided river and debris flow deposits and transgressive systems tract (TST) sandy braided river delta deposits. These reservoirs are rich in rock fragments and characterized by moderate porosity and moderate to low permeability with development of intergranular and dissolution pores. Generally, detrital composition has a greater impact on reservoir quality of the LST conglomerates than on that of the TST sandstones. However, texture maturity only shows positive correlation with physical properties of the sandstone reservoirs. The mechanical compaction was responsible for the major destruction of the initial porosity. However, the large heterogeneities in calcite cements account for the extremely heterogeneous reservoir quality. Calcite cements formed during eodiagenesis usually show poikilotopic fabric and preferentially concentrated inthe basal coarser units/facies within inidividual fining‐upward successions. Consequently, the upper finer units/facies became more favourable for the secondary dissolution and oil charging processes during mesodiagenesis. In contrast, the amounts of authigenic quartz and clay minerals are relatively low. Nevertheless, the contents of different authigenic clay minerals show a variety of relationships with the reservoir quality. The valley‐monadnock topography spatially controls the scales of the LST and TST reservoirs. The simultaneously evolutionary processes between the back‐filling of the valleys and weathering of the monadnocks resulted in the prolonged residence time and large area of depositional water contacting with the weathering crust. This may give rise to the formation of alkaline pore fluids and facilitate the nucleation and growth of eogenetic carbonate cements and grain‐coating chlorite. Furthermore, the reservoir quality generally displays an increasing trend from the monadnock to the valley thalweg due to the increase of hydrodynamic strength and the less influence of mélange debris flow deposits.
Hardening subnational budget constraints via administrative subordination: The Italian experience of recovery plans in regional health services
Authors: Bordignon Massimo , Coretti Silvia , Piacenza Massimiliano , Turati Gilberto
Published: August 2020

Since 2007, Italian regions running large deficits underwent recovery plans (Piani di Rientro) imposed by the central government. The goal was twofold: regions were asked (i) to restore a balanced budget and (ii) to continue supply the set of services defined by the constitution. We investigate whether recovery plans have reached their objectives. Our evidence suggests that recovery plans have proved to be an effective mechanism to eliminate subnational governments deficits. We also do not find any significant effects on health care utilization and on citizens' health. Overall, spending efficiency has likely improved.
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

The 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

Rural 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

Soils 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

Islamic 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

This 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

Breast 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

Introduction

The 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.

Objective

This 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.

Methods

A 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.

Results

The 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.

Conclusion

Clinical 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

Beginning 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

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

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 < 0.0001 versus baseline] and 1.5% [p < 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).
Identification of mitochondrial function‐associated lncRNAs in septic mice myocardium
Authors: Shi Yingzhou , Zheng Xiaohe , Zheng Mingzhi , Wang Linlin , Chen Yingying , Shen Yueliang
Published: August 2020

The present study aimed to analyze long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression profiles in septic mice heart and to identify potential lncRNAs and mRNAs that be responsible for cardiac mitochondrial dysfunction during sepsis. Mice were treated with 10 mg/kg of lipopolysaccharides to induce sepsis. LncRNAs and mRNAs expression were evaluated by using lncRNA and mRNA microarray or real‐time polymerase chain reaction technique. LncRNA‐mRNA coexpression network assay, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed. The results showed that 1275 lncRNAs were differentially expressed in septic myocardium compared with those in the control group. A total of 2769 mRNAs were dysregulated in septic mice heart, most of which are mainly related to the process of inflammation, mitochondrial metabolism, oxidative stress, and apoptosis. Coexpression network analysis showed that 14 lncRNAs were highly correlated with 11 mitochondria‐related differentially expressed mRNA. Among all lncRNAs and their cis‐acting mRNAs, 41 lncRNAs‐mRNA pairs (such as NONMMUG004378 and Apaf1 gene) were enriched in GO terms and KEGG pathways. In summary, we gained some specific lncRNAs and their potential target mRNAs that might be involved in mitochondrial dysfunction in septic myocardium. These findings provide a panoramic view of lncRNA and might allow developing new treatment strategies for sepsis.
Long noncoding RNA LEF1‐AS1 acts as a microRNA‐10a‐5p regulator to enhance MSI1 expression and promote chemoresistance in hepatocellular carcinoma cells through activating AKT signaling pathway
Authors: Gao Jun , Dai Chao , Yu Xin , Yin Xiang‐Bao , Zhou Fan
Published: August 2020

Long noncoding RNAs (lncRNAs) contribute to the development of hepatocellular carcinoma (HCC), which could regulate various HCC biological characteristics. Here, the study seeks to investigate the role of lncRNA LEF1‐AS1 in HCC cell chemoresistance by regulating microRNA (miR)‐10a‐5p and Musashi1 (MSI1). The microarray‐based analysis was employed to identify the HCC‐related lncRNA‐miRNA‐gene regulatory network. Expression patterns of LEF1‐AS1, miR‐10a‐5p, and MSI1 in the HCC cell lines, tissues were accessed by means of reverse transcription‐quantitative polymerase chain reaction. Next, the interaction among LEF1‐AS1, miR‐10a‐5p, and MSI1 in HCC was accessed by bioinformatics and dual‐luciferase reporter gene assay. Then, the cell line resistant to cisplatin was established, which was then treated with sh/oe‐lncRNA LEF1‐AS1, miR‐10a‐5p‐mimic, and oe/sh‐MSI1 vectors alone or in combination. Afterward, the effect of LEF1‐AS1, miR‐10a‐5p, and MSI1 on HCC cell chemoresistance, proliferation, and apoptosis was assessed. At last, in vivo experiments confirmed the role of MSI1 in tumor growth and chemoresistance in HCC. LEF1‐AS1 might potentially affect the growth and chemoresistance of HCC cells by regulating miR‐10a‐5p and MSI1. LEF1‐AS1 and MSI1 expression patterns were elevated, while miR‐10a‐5p was repressed in HCC tissues and cell lines. LEF1‐AS1 combined to miR‐10a‐5p and regulated MSI1, thereby activating the protein kinase B (AKT) signaling pathway. Knockdown of LEF1‐AS1 and MSI1 or elevation of miR‐10a‐5p compromised the proliferation of Huh7 cell line resistant to DDP and promoted its chemosensitivity and apoptosis. At last, these in vitro findings were also confirmed in vivo. Our results unraveled LEF1‐AS1 acts as a miR‐10a‐5p modulator to promote chemoresistance of HCC cells by stimulating MSI1 and activating the AKT signaling pathway, which might provide a novel therapeutic target for HCC.
Cancer metastasis‐associated protein 1 localizes to the nucleolus and regulates pre‐rRNA synthesis in cancer cells
Authors: Liu Jian , Li Chunxiao , Xue Hongsheng , Li Lina , Liu Qun , Wang Haijuan , Wen Tao , Qian Haili
Published: August 2020

Metastasis‐associated protein 1 (MTA1) is a critical component of the nucleosome remodeling and histone deacetylase (NuRD) complex. MTA1 has several biological functions, and it is closely associated with the malignant properties of human cancers; however, the mechanisms and subcellular localization of MTA1 in cells remain unclear. Some initial studies indicated that MTA1 was absent from the nucleolus; however, several NuRD components were recently found to be present in the nucleolus, where they regulate preribosomal RNA (pre‐rRNA) transcription. In this study, we demonstrated that MTA1 is definitely localized to the nucleolus and regulates pre‐rRNA transcription, which is consistent with the recent reports on NuRD. To determine if MTA1 was present in the nucleolus, we utilized the following complementary molecular approaches: immunofluorescence, GFP‐tag tracking, immunoelectron microscopy, and immunoprecipitation (IP). To examine the role of MTA1 in rRNA synthesis, we performed quantitative polymerase chain reaction analysis. We revealed that both endogenous and exogenous MTA1 showed apparent granule‐like nucleolar subcellular localization. MTA1 interacts with two major resident nucleolar proteins, nucleolin and nucleophosmin. Immunofluorescent colocalization analyses showed that MTA1 localizes to the fibrillarin‐deficient regions of the nucleolus, and Co‐IP experiments indicated that there was no interaction between MTA1 and fibrillarin; further, fibrillarin was not identified in the MTA1 interactome. Loss‐ and gain‐of‐function studies indicated that MTA1 promotes pre‐rRNA transcription in cancer cells. Collectively, our data identify MTA1 as a novel nucleolar protein, and activation of pre‐rRNA transcription in cancer cells may be an alternative mechanism by which MTA1 promotes malignancies.
A longitudinal study of the impact of school delinquency on self‐worth development among Black American adolescents
Authors: Tomek Sara , Moore Heather , Hooper Lisa M. , Bolland Anneliese C. , Robinson Cecil D. , Bolland John M.
Published: August 2020

Previous research found adolescents with low self‐worth often utilize delinquency as a method of “self‐enhancing” as proposed by Kaplan, which suggests the effects of delinquency can be both enhancing and damaging to adolescents' later reports of self‐worth. We tested Kaplan's self‐enhancing thesis to determine the extent to which different levels of self‐worth in early adolescents foretell long‐term levels of self‐worth associated with delinquency among adolescents placed at‐risk. Data from a sample of 982 primarily Black American (95%) adolescents living in high‐poverty neighborhoods were analyzed using global and behavioral self‐worth measures collected annually between the ages of 12–17, with school delinquency as the self‐enhancing mechanism. Gender (45% female, 55% male) and baseline self‐worth measures were included in the model. We found empirical support for the positive effects of school delinquency consistent with self‐enhancing theories, although with younger female participants only. Specifically, engaging in delinquent behaviors at age 12 had a positive effect on a females' behavioral self‐worth. There were, however, differential effects for males. Although delinquency increased self‐worth among females in the short‐term, long‐term effects were negative, as greater school delinquency resulted in lower self‐worth at age 17. Additional gender results and implications for findings are discussed.
Placement of chronically homeless into different types of permanent supportive housing before and after a coordinated entry system: The influence of severe mental illness, substance use disorder, and dual diagnosis on housing configuration and intensity of services
Authors: Dickson‐Gomez Julia , Quinn Katherine , McAuliffe Timothy , Bendixen Arturo , Ohlrich Jessica
Published: August 2020

Aims

Permanent supportive housing (PSH) is designed to house people who experience chronic homelessness with one or more of the following: serious mental illness (SMI), substance use disorders (SUD) or human immunodeficiency virus. The Department of Housing and Urban Development has required major metropolitan areas to develop a coordinated entry system (CES) to prioritize access to PSH to those who need it the most. The aim of this paper is to determine whether PSH residents with SMI, SUD, or dual diagnosis were more likely to be housed after implementation of CES and were more likely to be housed in housing models with more intensive services provided.

Methods

A cross‐sectional survey with 855 residents of different PSH models.

Results

Those with SMI, SUD, or dual diagnosis were not more likely to be housed using the CES but were more likely to be housed in higher intensity service programs.

Conclusions

Those with SMI are more likely to be housed in PSH with high‐intensity services.
Monotonic torsional resistance and fatigue resistance of novel SCOPE RS instruments
Authors: Orhan Ekim Onur , Ertuğrul İhsan Furkan , Tosun Samet
Published: August 2020

To evaluate monotonic torsional resistance and fatigue resistance of novel SCOPE RS instruments and to compare ROTATE, Hyflex CM, OneCurve, and ProTaper Next instruments as a counterpart. The instrument groups were as follows: SCOPE RS; ROTATE; HyflexCM; OneCurve; ProTaperNext. The cyclic fatigue resistance of unused instruments was tested at both room and body temperatures (n = 10). The time to fracture, the mean number of cycles until failure, and the length of the fractured fragments were analyzed. The monotonic torsional resistance of new instruments was measured in accordingly American National Standards/American Dental Association No. 28 and International Organization for Standardization 3630–1:2008 specifications (n = 10). The maximum torque and angular deflection at break were recorded. The fractographic examination was performed by scanning electron microscope. Energy‐dispersive X‐ray spectroscopy was used to investigate the microstructure of NiTi instruments. One‐way ANOVA with Games‐Howell Post Hoc multiple comparisons tests were used (p < .05). The ROTATE had superior cyclic fatigue resistance than other groups in both temperature conditions (p < .01). However, it exhibited lower torsional resistance than SCOPE RS (p < .01). SCOPE RS had superior torsional resistance than other groups (p < .01). Micrographs revealed typical features of fatigue behaviors in all groups. Weight percentages of the Ni and Ti revealed similarity for all instruments. The novel SCOPE RS instruments presented superior monotonic torsional resistance but failed to show any improvement in the cyclic fatigue resistance compared with its counterparts, ROTATE, HyflexCM, and OneCurve.
Skeletal and muscular pelvic morphology of hillstream loaches (Cypriniformes: Balitoridae)
Authors: Crawford Callie H. , Randall Zachary S. , Hart Pamela B. , Page Lawrence M. , Chakrabarty Prosanta , Suvarnaraksha Apinun , Flammang Brooke E.
Published: August 2020

The rheophilic hillstream loaches (Balitoridae) of South and Southeast Asia possess a range of pelvic girdle morphologies, which may be attributed to adaptations for locomotion against rapidly flowing water. Specifically, the connectivity of the pelvic plate (basipterygium) to the vertebral column via a sacral rib, and the relative size and shape of the sacral rib, fall within a spectrum of three discrete morphotypes: long, narrow rib that meets the basipterygium; thicker, slightly curved rib meeting the basipterygium; and robust crested rib interlocking with the basipterygium. Species in this third category with more robust sacral rib connections between the basipterygium and vertebral column are capable of walking out of water with a tetrapod‐like lateral‐sequence, diagonal‐couplet gait. This behavior has not been observed in species lacking direct skeletal connection between the vertebrae and the pelvis. The phylogenetic positions of the morphotypes were visualized by matching the morphological features onto a novel hypothesis of relationships for the family Balitoridae. The morphotypes determined through skeletal morphology were correlated with patterns observed in the pelvic muscle morphology of these fishes. Transitions towards increasingly robust pelvic girdle attachment were coincident with a more anterior origin on the basipterygium and more lateral insertion of the muscles on the fin rays, along with a reduction of the superficial abductors and adductors with more posterior insertions. These modifications are expected to provide a mechanical advantage for generating force against the ground. Inclusion of the enigmatic cave‐adapted balitorid Cryptotora thamicola into the most data‐rich balitorid phylogeny reveals its closest relatives, providing insight into the origin of the skeletal connection between the axial skeleton and basipterygium.
Dynamical downscaling simulation of the East Asian summer monsoon in a regional Climate‐Weather Research and Forecasting model
Authors: Li Qingquan , Wang Tao , Wang Fang , Liang Xin‐Zhong , Zhao Chongbo , Dong Lili , Zhao Chunyu , Xie Bing
Published: August 2020

A regional Climate‐Weather Research and Forecasting (CWRF) model with a 30‐km horizontal resolution was applied to simulate the East Asian summer monsoon (EASM) and climate in China from 1980 to 2016. As compared with observations and reanalysis data, the model can reasonably reproduce the spatial distributions of the climatological mean atmospheric circulation and water vapour transport in East Asia, as well as the seasonal advance and retreat of EASM and rain bands. The correlation coefficient between the EASM circulation index in the simulation and reanalysis is .97. The model can well represent the geographic distributions of summer mean temperature and precipitation over most of China. However, model biases still exist, in particular the skill in the Yangtze–Huaihe River basin is relatively low. The simulated climatological mean temperature and precipitation deviations from observations may be related to the model's systematic circulation biases, with a thicker lower troposphere (i.e., higher temperature between 500 and 1,000 hPa) over most of China (except for the south and southwest) and a thinner one over the coastal oceans in summertime. Compared with the reanalysis, the model overestimates the land‐ocean thermal contrast, which causes the South Asian High shifted to the north and east, as well as the subtropical high and tropical convective activity located further north and persisted longer. Consequently, more water vapour transports northward, leading to more precipitation over North China–Northeast China and less precipitation over the Yangtze and Huaihe River basin. Therefore, the enhanced land‐ocean thermal contrast may be a major factor for the stronger EASM in the model, and corresponding precipitation and temperature biases in China. This analysis provides important information for further improving model performance in EASM simulation.
Appropriate Phosphorus Intake by Parenteral Nutrition Prevents Metabolic Bone Disease of Prematurity in Extremely Low‐Birth‐Weight Infants
Authors: Motokura Kouji , Tomotaki Seiichi , Hanaoka Shintaro , Yamauchi Takeru , Tomotaki Hiroko , Iwanaga Kougoro , Niwa Fusako , Takita Junko , Kawai Masahiko
Published: August 2020

Background

Metabolic bone disease (MBD) is a common disorder in extremely low‐birth‐weight (ELBW) infants. However, no studies have investigated whether high‐dose calcium (Ca) and phosphorus (P) supplementation by parenteral nutrition (PN) prevents MBD in ELBW infants. This study aimed to identify the effect of PN on MBD in ELBW infants.

Methods

We retrospectively analyzed ELBW infants who were admitted between April 2011 and March 2017. ELBW infants were divided into the low‐P group (n = 22) and the high‐P group (n = 26) according to the dose of parenteral P supply. Biochemical and radiological markers of MBD and treatments were analyzed.

Results

Mean daily parenteral intake of Ca and P in the first week was significantly higher in the high‐P group than in the low‐P group (both P ≤ .001). Serum alkaline phosphatase (ALP) levels were significantly higher in the low‐P group than in the high‐P group in the first month. ELBW infants in the low‐P group received alfacalcidol much more frequently than those in the high‐P group. There was a trend of a higher rate of x‐ray changes in the low‐P group than in the high‐P group. No infants developed bone fractures.

Conclusion

Appropriate P intake by PN is required to ensure high Ca intake, reduce ALP levels in the first month, and prevent MBD from hyperparathyroidism and does not worsen x‐ray findings in ELBW infants.