bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular vesicles produced by bone marrow mesenchymal stem cells attenuate renal fibrosis, in part by inhibiting the RhoA/ROCK pathway, in a UUO rat model
Authors: Shi Zhengzhou , Wang Qi , Zhang Youbo , Jiang Dapeng 
Published: June 2020

Abstract
Background
Extracellular vesicles produced by bone marrow mesenchymal stem cells (BMSC-EVs) can play important roles in the repair of injured tissues. Though numerous studies have reported the effect of EVs on renal fibrosis, the underlying mechanisms remain unclear. We hypothesized that BMSC-EVs containing milk fat globule–epidermal growth factor–factor 8 (MFG-E8) could attenuate renal fibrosis by inhibiting the RhoA/ROCK pathway.

Methods
We investigated whether BMSC-EVs have anti-fibrotic effects in a rat model of renal fibrosis, in which rats were subjected to unilateral ureteral obstruction (UUO), as well as in cultured HK2 cells. Extracellular vesicles from BMSCs were collected and co-cultured with HK2 cells during transforming growth factor-β1 (TGF-β1) treatment. HK2 cells co-cultured with TGF-β1 were also treated with the ROCK inhibitor, Y-27632.

Results
Compared with the Sham group, UUO rats displayed fibrotic abnormalities, accompanied by an increased expression of α-smooth muscle actin and Fibronectin and reduced expression of E-cadherin. These molecular and pathological changes suggested increased inflammation in damaged kidneys. Oxidative stress, as evidenced by an increased level of MDA and decreased levels of SOD1 and Catalase, was also observed in UUO kidneys. Additionally, activation of cleaved caspase-3 and PARP1 and increased apoptosis in the proximal tubules confirmed tubular cell apoptosis in the UUO group. All of these phenotypes exhibited by UUO rats were suppressed by treatment with BMSC-EVs. However, the protective effect of BMSC-EVs was completely abolished by the inhibition of MFG-E8. Consistent with the in vivo results, treatment with BMSC-EVs reduced inflammation, oxidative stress, apoptosis, and fibrosis in HK-2 cells stimulated with TGF-β1 in vitro. Interestingly, treatment with Y-27632 protected HK-2 cells against inflammation and fibrosis, although oxidative stress and apoptosis were unchanged.

Conclusions
Our results show that BMSC-EVs containing MFG-E8 attenuate renal fibrosis in a rat model of renal fibrosis, partly through RhoA/ROCK pathway inhibition.
Translational strategy using multiple nuclear imaging biomarkers to evaluate target engagement and early therapeutic efficacy of SAR439859, a novel selective estrogen receptor degrader
Authors: Besret Laurent , d’Heilly Sébastien , Aubert Cathy , Bluet Guillaume , Gruss-Leleu Florence , Le-Gall Françoise , Caron Anne , Andrieu Laurent , Vincent Sylvie , Shomali Maysoun , Bouaboula Monsif , Voland Carole , Ming Jeffrey , Roy Sébastien , Rao Srinivas , Carrez Chantal , Jouannot Erwan 
Published: June 2020

Abstract
Purpose
Preclinical in vivo nuclear imaging of mice offers an enabling perspective to evaluate drug efficacy at optimal dose and schedule. In this study, we interrogated sufficient estrogen receptor occupancy and degradation for the selective estrogen receptor degrader (SERD) compound SAR439859 using molecular imaging and histological techniques.

Material and methods
[18F]FluoroEstradiol positron emission tomography (FES-PET), [18F]FluoroDeoxyGlucose (FDG) PET, and [18F]FluoroThymidine (FLT) PET were investigated as early pharmacodynamic, tumor metabolism, and tumor proliferation imaging biomarkers, respectively, in mice bearing subcutaneous MCF7-Y537S mutant ERα+ breast cancer model treated with the SERD agent SAR439859. ER expression and proliferation index Ki-67 were assessed by immunohistochemistry (IHC). The combination of palbociclib CDK 4/6 inhibitor with SAR439859 was tested for its potential synergistic effect on anti-tumor activity.

Results
After repeated SAR439859 oral administration over 4 days, FES tumoral uptake (SUVmean) decreases compared to baseline by 35, 57, and 55% for the 25 mg/kg qd, 12.5 mg/kg bid and 5 mg/kg bid treatment groups, respectively. FES tumor uptake following SAR439859 treatment at different doses correlates with immunohistochemical scoring for ERα expression. No significant difference in FDG uptake is observed after SAR439859 treatments over 3 days. FLT accumulation in tumor is significantly decreased when palbociclib is combined to SAR439859 (− 64%) but not different from the group dosed with palbociclib alone (− 46%). The impact on proliferation is corroborated by Ki-67 IHC data for both groups of treatment.

Conclusions
In our preclinical studies, dose-dependent inhibition of FES tumoral uptake confirmed target engagement of SAR439859 to ERα. FES-PET thus appears as a relevant imaging biomarker for measuring non-invasively the impact of SAR439859 on tumor estrogen receptor occupancy. This study further validates the use of FLT-PET to directly visualize the anti-proliferative tumor effect of the palbociclib CDK 4/6 inhibitor alone and in combination with SAR439859.
Radii problems for some classes of analytic functions associated with Legendre polynomials of odd degree
Authors: Ebadian Ali , Cho Nak Eun , Analouei Adegani Ebrahim , Bulut Serap , Bulboacă Teodor 
Published: June 2020

AbstractThe aim of the present paper is to study radii problems for two general classes including various known subclasses of analytic functions associated with the normalized form of Legendre polynomials of odd degree. We also obtain some special cases of the main results presented here with some useful examples.
Approximation of functions in generalized Zygmund class by double Hausdorff matrix
Authors: Nigam H. K. , Mursaleen M. , Rani Supriya 
Published: June 2020

AbstractIn the present work, we emphasize, for the first time, the error estimation of a two-variable function $g(y,z)$
g
(
y
,
z
)
in the generalized Zygmund class $Y_{r}^{(\xi )}$

Y
r

(
ξ
)

($r\geq 1$
r
≥
1
) using the double Hausdorff matrix means of its double Fourier series. In fact, in this work, we establish two theorems on error estimation of a two-variable function of g in the generalized Zygmund class.
A new approach to interval-valued inequalities
Authors: Younus Awais , Asif Muhammad , Alzabut Jehad , Ghaffar Abdul , Nisar Kottakkaran Sooppy 
Published: June 2020

AbstractThe objective of this work is to advance and simplify the notion of Gronwall’s inequality. By using an efficient partial order and concept of gH-differentiability on interval-valued functions, we investigate some new variants of Gronwall type inequalities on time scales.
Commentary on substance use disorders and risk of suicide in a general US population: a case control study by Lynch et al.
Authors: Little Virna , James Mary Crawford 
Published: June 2020

AbstractIn response to the findings of the Lynch et al. study on the association of suicide mortality and substance use disorder, this commentary addresses the need for increased suicide assessment and screening for patients who identify with substance use disorders in health settings such as primary care practices and emergency departments. Lynch et al. found that all categories of substance use disorders were associated with increased risk of suicide. We present the Suicide Safer Care project as one model to address this need. The Suicide Safer Care project contains a training model that provides education on basic principles of suicide prevention and skills for integration into practice. Data collected from pre- and post-training surveys of participants demonstrates the success of the training in increasing knowledge and confidence in identification and treatment of patients at risk of suicide. Utilizing training techniques such as Suicide Safer Care and combining it with the findings from Lynch et al. providers in primary care settings and emergency departments can optimize the number of patients they identify with suicide risk, impacting the number of patients who receive treatment and the number of potential lives saved.
Choosing internet-based treatment for problematic alcohol use—why, when and how? Users’ experiences of treatment online
Authors: Ekström Veronica , Johansson Magnus 
Published: June 2020

Abstract
Background
Internet-based treatment has emerged as a cost-effective option for reaching people who for different reasons are not reached by traditional treatment. Internet-based treatment for problematic alcohol use, specifically, has been found to show results on par with other forms of treatment. However, in-depth knowledge of users’ experiences is required to understand what works, and what needs further development. The aim of this study is to investigate the help-seeking motives among users of an internet-based service for problematic alcohol use, as well as the users’ experiences of the support available through the service.

Method
The study consists of a thematic analysis of interviews with 38 former users of the internet-based intervention Alkoholhjälpen.

Results
The analysis shows that health and relationship factors, as well as feelings of shame, were important motives for the users’ decisions to reduce their drinking. Availability and anonymity seem to have been important reasons for choosing internet-based support. The different treatment components, i.e. ICBT program, therapist support and discussion forum, were each perceived as helpful by some users but not by others. Treatment components were described as more useful when users were able to personally identify with the content, and when it helped them reflect on their own alcohol consumption.

Conclusions
There are several aspects that are relevant, beyond the comparison between components, if we want to understand what works and for whom in internet-based treatment. Internet-based treatment services should be generous in terms of options for the users.
Growth of micro and small scale enterprises and its driving factors: empirical evidence from entrepreneurs in emerging region of Ethiopia
Authors: Meressa Hayelom Abrha 
Published: June 2020

Abstract
Purpose
The purpose of this study was to examine micro and small scale enterprises’ growth determinants operating in Benishangul-Gumuz Regional State of Ethiopia as emerging region.

Design/methodology/approach
The study adopted an explanatory research design with arrangement of primary data collection via a cross-sectional survey questionnaire followed by mixed research approach. The sample of this study was 220 enterprises determined by Yamane’s formula and selected using proportional stratified random sampling technique.

Findings
The result of regression analysis revealed that initial investment, access to land, access to finance, location, sectoral engagement, market linkage, and business experience are significant in explaining growth in one hand. On the other side, however, gender, education, ownership, formal recording, and financial management practice are found to be insignificant variables in determining enterprises’ growth.

Research limitations/implications
More evidence is needed on micro and small scale enterprises’ growth determinants before any generalization of the results can be made. In addition, the empirical tests were conducted only on 220 entrepreneurs since 2018. Therefore, the results of the study cannot be assumed to extend beyond this group of entrepreneurs to different study periods.

Practical implications
The study might help the entrepreneurs in addressing the factors affecting growth to take actions toward developing their performance and in turn contribute to employment, export participation, poverty alleviation, and women empowerment.

Originality/value
This paper adds to the literature on the determinants of micro- and small-scale enterprises’ growth. In particular, it tests the impact of initial investment, access to land, access to finance, location, sectoral engagement, market linkage, business experience, education, ownership structure, and financial management practice on growth of enterprises.
Reservoirs of antimicrobial resistance genes in retail raw milk
Authors: Liu Jinxin , Zhu Yuanting , Jay-Russell Michele , Lemay Danielle G. , Mills David A. 
Published: June 2020

Abstract
Background
It has been estimated that at least 3% of the USA population consumes unpasteurized (raw) milk from animal sources, and the demand to legalize raw milk sales continues to increase. However, consumption of raw milk can cause foodborne illness and be a source of bacteria containing transferrable antimicrobial resistance genes (ARGs). To obtain a comprehensive understanding of the microbiome and antibiotic resistome in both raw and processed milk, we systematically analyzed 2034 retail milk samples including unpasteurized milk and pasteurized milk via vat pasteurization, high-temperature-short-time pasteurization, and ultra-pasteurization from the United States using complementary culture-based, 16S rRNA gene, and metagenomic sequencing techniques.

Results
Raw milk samples had the highest prevalence of viable bacteria which were measured as all aerobic bacteria, coliform, and Escherichia coli counts, and their microbiota was distinct from other types of milk. 16S rRNA gene sequencing revealed that Pseudomonadaceae dominated raw milk with limited levels of lactic acid bacteria. Among all milk samples, the microbiota remained stable with constant bacterial populations when stored at 4 °C. In contrast, storage at room temperature dramatically enriched the bacterial populations present in raw milk samples and, in parallel, significantly increased the richness and abundance of ARGs. Metagenomic sequencing indicated raw milk possessed dramatically more ARGs than pasteurized milk, and a conjugation assay documented the active transfer of blaCMY-2, one ceftazidime resistance gene present in raw milk-borne E. coli, across bacterial species. The room temperature-enriched resistome differed in raw milk from distinct geographic locations, a difference likely associated with regionally distinct milk microbiota.

Conclusion
Despite advertised “probiotic” effects, our results indicate that raw milk microbiota has minimal lactic acid bacteria. In addition, retail raw milk serves as a reservoir of ARGs, populations of which are readily amplified by spontaneous fermentation. There is an increased need to understand potential food safety risks from improper transportation and storage of raw milk with regard to ARGs.
Treatment of coronavirus disease 2019 in Shandong, China: a cost and affordability analysis
Authors: Li Xue-Zheng , Jin Feng , Zhang Jian-Guo , Deng Yun-Feng , Shu Wei , Qin Jing-Min , Ma Xin , Pang Yu 
Published: June 2020

Abstract
Background
Coronavirus disease 2019 (COVID-19) is now a global public threat. Given the pandemic of COVID-19, the economic impact of COVID-19 is essential to add value to the policy-making process. We retrospectively conducted a cost and affordability analysis to determine the medical costs of COVID-19 patients in China, and also assess the factors affecting their costs.

Methods
This analysis was retrospectively conducted in Shandong Provincial Chest Hospital between 24 January and 16 March 2020. The total direct medical expenditures were analyzed by cost factors. We also assessed affordability by comparing the simulated out-of-pocket expenditure of COVID-19 cases relative to the per capita disposable income. Differences between groups were tested by student t test and Mann-Whitney test when appropriate. A multiple logistic regression model was built to determine the risk factors associated with high cost.

Results
A total of 70 COVID-19 patients were included in the analysis. The overall mean cost was USD 6827 per treated episode. The highest mean cost was observed in drug acquisition, accounting for 45.1% of the overall cost. Total mean cost was significantly higher in patients with pre-existing diseases compared to those without pre-existing diseases. Pre-existing diseases and the advanced disease severity were strongly associated with higher cost. Around USD 0.49 billion were expected for clinical manage of COVID-19 in China. Among rural households, the proportions of health insurance coverage should be increased to 70% for severe cases, and 80% for critically ill cases to avoid catastrophic health expenditure.

Conclusions
Our data demonstrate that clinical management of COVID-19 patients incurs a great financial burden to national health insurance. The cost for drug acquisition is the major contributor to the medical cost, whereas the risk factors for higher cost are pre-existing diseases and severity of COVID-19. Improvement of insurance coverage will need to address the barriers of rural patients to avoid the occurrence of catastrophic health expenditure.
RBM45 associates with nuclear stress bodies and forms nuclear inclusions during chronic cellular stress and in neurodegenerative diseases
Authors: Collins Mahlon , Li Yang , Bowser Robert 
Published: June 2020

AbstractThe RNA binding protein (RBP) RBM45 forms nuclear and cytoplasmic inclusions in neurons and glia in amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP), and Alzheimer’s disease (AD). The normal functions of RBM45 are poorly understood, as are the mechanisms by which it forms inclusions in disease. To better understand the normal and pathological functions of RBM45, we evaluated whether the protein functions via association with several membraneless organelles and whether such an association could promote the formation of nuclear RBM45 inclusions. Under basal conditions, RBM45 is diffusely distributed throughout the nucleus and does not localize to membraneless organelles, including nuclear speckles, Cajal bodies, or nuclear gems. During cellular stress, however, nuclear RBM45 undergoes a reversible, RNA-binding dependent incorporation into nuclear stress bodies (NSBs). Chronic stress leads to the persistent association of RBM45 with NSBs and the irreversible accumulation of nuclear RBM45 inclusions. We also quantified the cell type- and disease-specific patterns of RBM45 pathology in ALS, FTLD-TDP, and AD. RBM45 nuclear and cytoplasmic inclusions are found in both neurons and glia in ALS, FTLD-TDP, and AD but are absent in non-neurologic disease controls. Across neurodegenerative diseases, RBM45 nuclear inclusion pathology occurs more frequently than cytoplasmic RBM45 inclusion pathology and exhibits cell type-specific variation. Collectively, our results define new stress-associated functions of RBM45, a mechanism for nuclear RBM45 inclusion formation, a role for NSBs in the pathogenesis of ALS, FTLD-TDP, and AD, and further underscore the importance of protein self-association to both the normal and pathological functions of RBPs in these diseases.
Ongoing 5-year+ survival after multiple metastasectomies, followed by CAPOX plus bevacizumab, for metastatic colorectal cancer
Authors: Matsuishi Kozue , Miyamoto Yuji , Hiyoshi Yukiharu , Tokunaga Ryuma , Imai Katsunori , Hayashi Hiromitsu , Yamashita Yoichi , Yoshida Naoya , Baba Hideo 
Published: June 2020

Abstract
Background
Advancements in chemotherapy for metastatic colorectal cancer (mCRC) have improved long-term outcomes, and median survival currently exceeds 30 months. The recommended treatment for mCRC is multidisciplinary, including a combination of surgical resection and chemotherapy. In this study, we report the case of a patient who has survived for more than 5 years after an initial diagnosis of mCRC while undergoing first-line chemotherapy and six repeat metastasectomies.

Case presentation
A 55-year-old man was diagnosed at our hospital with sigmoid colon cancer and hepatic metastasis. We performed laparoscopic sigmoidectomy and hepatic segmentectomy (segment 5 [S5] and S8). After resecting the primary tumor and liver metastasis, other metastases were found. Together with perioperative chemotherapy (CAPOX + bevacizumab), we performed repeated metastasectomies for liver metastasis (S4 and S7), pulmonary S1 metastasis, aortic lymph node metastasis, and right adrenal metastasis. With six metastasectomies, the patient has survived for more than 5.5 years.

Conclusions
Multidisciplinary treatment extends survival and improves the quality of life in patients with mCRC. Planned surveillance after metastasectomy may also be necessary to promote the early detection of recurrence in these patients.
A case of small cell neuroendocrine carcinoma of the ampulla of Vater
Authors: Ito Hiroharu , Wada Yoshiyuki , Takami Yuko , Ryu Tomoki , Ureshino Hiroki , Imamura Hajime , Sasaki Shin , Ohno Akihisa , Hijioka Masayuki , Kaku Toyoma , Kawabe Ken , Kawauchi Shigeto , Saitsu Hideki 
Published: June 2020

Abstract
Background
Gastroenteric neuroendocrine carcinomas (NECs) account for 6.2% of gastroenteric neuroendocrine tumors (NETs), and only 1% or less of gastroenteric NETs occur in the ampulla of Vater (AoV). Clinical features of NEC of the AoV remain obscure.

Case presentation
A 65-year-old man visited a general practitioner because of jaundice, and an abdominal contrast-enhanced computed tomography scan revealed a tumor of 11 mm in diameter, which was enhanced in the arterial phase at the duodenal papilla, with dilation of the upstream bile duct. Gastrointestinal scope revealed an unexposed tumor of the AoV. Based on a biopsy of the site, a moderately differentiated tubular adenocarcinoma was suspected, and pancreatoduodenectomy was performed. Histopathological examination revealed dysplasia and highly proliferative small tumor cells, with solid and nodular formation at the AoV. Histological analysis showed a high mitotic count, and immunohistochemical staining revealed a Ki-67 index of 40–50% and cells positive for synaptophysin, chromogranin A, and p53. Small cell-type NEC was finally diagnosed. Four months post pancreatoduodenectomy, multiple liver metastases developed, and systemic chemotherapy was administered. Salvage liver resection for liver metastases was performed 14 months after the pancreatoduodenectomy. Unfortunately, multiple liver metastases developed 2 months after liver resection, and the patient died 18 months after the pancreatoduodenectomy.

Conclusions
Neuroendocrine carcinoma originating from the bile duct is very rare; therefore, in this article, we provide a review of the literature and a case report.
Nondegenerated cystic neuroendocrine tumor of the pancreas: a case report
Authors: Noda Keisuke , Kuroki Tamotsu , Yamashita Mampei , Hirayama Takanori , Natsuda Koji , Kobayashi Shinichiro , Tokunaga Takayuki , Yamanouchi Kosho , Takeshita Hiroaki , Miura Shiro , Maeda Shigeto 
Published: June 2020

Abstract
Background
Pancreatic neuroendocrine tumors (PNETs) are typically solid neoplasms but, in very rare cases, present as cystic lesions. We describe a case of a cystic neuroendocrine tumor that developed as a small cystic lesion.

Case presentation
In 2011, a 66-year-old Japanese woman underwent computed tomography (CT) that revealed a cystic lesion in the tail of the pancreas measuring 9 mm. She did not have any symptoms. She underwent a CT scan every year thereafter. The cystic lesion gradually increased and was 40 mm in 2019; endoscopic retrograde pancreatography (ERP) was then performed. Cytological examination demonstrated class IIIb adenocarcinoma, and we conducted laparoscopic distal pancreatectomy. Pathological examination showed PNET.

Conclusion
Although cystic change of PNET is generally caused by ischemia or necrosis inside the tumor, in our case, PNET occurred as a small cyst that increased without changing form.