bluuebunny/crossref_metadata_2025_split huggingface dataset:
What fragile factors hinder the pace of China’s alleviation efforts of the poverty-stricken population? A study from the perspective of impoverishment caused by medical expenses
Authors: Wang Jiahui , Qi Xinye , Shan Linghan , Wang Kexin , Tan Xiao , Kang Zheng , Ning Ning , Liang Libo , Gao Lijun , Jiao Mingli , Cui Yu , Hao Yanhua , Wu Qunhong , Li Ye 
Published: July 2022

Abstract
Objective
China has made remarkable achievements in poverty alleviation. However, with the change in economic development and age structure, the population stricken by poverty due to medical expenses and disability accounted for 42.3 and 14.4% of the total poverty-stricken population, respectively. Accordingly, it is crucial to accurately pinpoint the characteristics of people who are about to become poor due to illness. In this study, we analyzed the incidence of impoverishment by medical expense at the provincial, family, and different medical insurance scheme levels to identify the precise groups that are vulnerable to medical-related poverty.

Method
Data were extracted from the Fifth National Health Service Survey in China in 2013 through a multi-stage, stratified, and random sampling method, leaving 93,570 households (273,626 people) for the final sample. The method recommended by World Health Organization (WHO) was adopted to calculate impoverishment by medical expense, and logistic regression was adopted to evaluate its determinants.

Results
The poverty and impoverishment rate in China were 16.2 and 6.3% respectively. The poverty rate in western region was much higher than that of central and eastern regions. The rate of impoverishment by medical expense (IME) was higher in the western region (7.2%) than that in the central (6.5%) and eastern (5.1%) regions. The New Cooperative Medical Scheme (NCMS) was associated with the highest rate (9.1%) of IME cases. The top three diseases associated with IME were malignant tumor, congenital heart disease, and mental disease. Households with non-communicable disease members or hospitalized members had a higher risk on IME. NCMS-enrolled, poorer households were more likely to suffer from IME.

Conclusion
The joint roles of economic development, health service utilization, and welfare policies result in medical impoverishment for different regions. Poverty and health service utilization are indicative of households with high incidence of medical impoverishment. Chronic diseases lead to medical impoverishment. The inequity existing in different medical insurance schemes leads to different degrees of risk of IME. A combined strategy to precise target multiple vulnerabilities of poor population would be more effective.
Adherence challenges and opportunities for optimizing care through enhanced adherence counseling for adolescents with suspected HIV treatment failure in Kenya
Authors: Gill Michelle M. , Ndimbii James N. , Otieno-Masaba Rose , Ouma Millicent , Jabuto Stella , Ochanda Boniface 
Published: July 2022

Abstract
Background
Adolescents living with HIV (ALHIV) experience higher mortality and are more likely to have poor antiretroviral therapy (ART) adherence and unsuppressed viral load (VL) compared to adults. Enhanced adherence counseling (EAC) is a client-centered counseling strategy that aims to identify and address barriers to optimal ART use and can be tailored to the unique needs of adolescents. This study aimed to better understand adherence barriers among ALHIV with suspected treatment failure and their experience with EAC to inform future programming.

Methods
A qualitative study was conducted in Homa Bay and Turkana counties, Kenya in 2019 with adolescents and caregivers of children and adolescents living with HIV with suspected treatment failure after ≥6 months on ART and who had received ≥1 EAC sessions. Sixteen focus group discussions (FGDs) were conducted; five FGDs each were held with adolescents 12–14 years (n = 48) and 15–19 years (n = 36). Caregivers (n = 52) participated in six FGDs. Additionally, 17 healthcare workers providing pediatric/adolescent HIV services participated in in-depth interviews. Audio recordings were transcribed and translated from Kiswahili or Dholuo into English and coded using MAXQDA software. Data were thematically analyzed by participant group.

Results
Participants identified adolescents’ fear of being stigmatized due to their HIV status and their relationship with and level of support provided by caregivers. This underpinned and often undermined adolescents’ ART-taking behavior and progress towards more independent medication management. Adolescents were generally satisfied with EAC and perceived it to be important in improving adherence and reducing VL. However, problems were noted with facility-based, individual EAC counseling, including judgmental attitudes of providers and difficulties traveling to and keeping EAC clinic appointments. Participant-suggested improvements to EAC included peer support groups in addition to individual counseling, allowing for greater flexibility in the timing and location of sessions and greater caregiver involvement.

Conclusions
The findings provide opportunities to better tailor EAC interventions to promote improved ALHIV adherence and caregiver-supported disease management. Multi-prong EAC interventions that include peer-led and community approaches and target adolescent and caregiver treatment literacy may improve EAC delivery, address issues contributing to poor adherence, and position adolescents to achieve viral suppression.

Trial registration
ClinicalTrials.gov: NCT04915469.
A CCR5 antagonist, maraviroc, alleviates neural circuit dysfunction and behavioral disorders induced by prenatal valproate exposure
Authors: Ishihara Yasuhiro , Honda Tatsuya , Ishihara Nami , Namba Kaede , Taketoshi Makiko , Tominaga Yoko , Tsuji Mayumi , Vogel Christoph F. A. , Yamazaki Takeshi , Itoh Kouichi , Tominaga Takashi 
Published: July 2022

Abstract
Background
Valproic acid (VPA) is a clinically used antiepileptic drug, but it is associated with a significant risk of a low verbal intelligence quotient (IQ) score, attention-deficit hyperactivity disorder and autism spectrum disorder in children when it is administered during pregnancy. Prenatal VPA exposure has been reported to affect neurogenesis and neuronal migration and differentiation. In addition, growing evidence has shown that microglia and brain immune cells are activated by VPA treatment. However, the role of VPA-activated microglia remains unclear.

Methods
Pregnant female mice received sodium valproate on E11.5. A microglial activation inhibitor, minocycline or a CCR5 antagonist, maraviroc was dissolved in drinking water and administered to dams from P1 to P21. Measurement of microglial activity, evaluation of neural circuit function and expression analysis were performed on P10. Behavioral tests were performed in the order of open field test, Y-maze test, social affiliation test and marble burying test from the age of 6 weeks.

Results
Prenatal exposure of mice to VPA induced microglial activation and neural circuit dysfunction in the CA1 region of the hippocampus during the early postnatal periods and post-developmental defects in working memory and social interaction and repetitive behaviors. Minocycline, a microglial activation inhibitor, clearly suppressed the above effects, suggesting that microglia elicit neural dysfunction and behavioral disorders. Next-generation sequencing analysis revealed that the expression of a chemokine, C–C motif chemokine ligand 3 (CCL3), was upregulated in the hippocampi of VPA-treated mice. CCL3 expression increased in microglia during the early postnatal periods via an epigenetic mechanism. The CCR5 antagonist maraviroc significantly suppressed neural circuit dysfunction and post-developmental behavioral disorders induced by prenatal VPA exposure.

Conclusion
These findings suggest that microglial CCL3 might act during development to contribute to VPA-induced post-developmental behavioral abnormalities. CCR5-targeting compounds such as maraviroc might alleviate behavioral disorders when administered early.
Evaluating the productivity of ancient Pu’er tea trees (Camellia sinensis var. assamica): a multivariate modeling approach
Authors: Zhang Shuqiao , Liu Wendou , Cheng Xinmeng , Wang Zizhi , Yuan Fengjun , Wu Wengui , Liao Shengxi 
Published: July 2022

AbstractBackgroundThe demand for productive economic plant resources is increasing with the continued growth of the human population. Ancient Pu’er tea trees [Camellia sinensisvar.assamica(J. W. Mast.) Kitam.] are an important ecological resource with high economic value and large interests. The study intends to explore and evaluate critical drivers affecting the species’ productivity, then builds formulas and indexes to make predicting the productivity of such valuable plant resources possible and applicable.ResultsOur analysis identified the ideal values of the seven most important environmental variables and their relative contribution (shown in parentheses) to the distribution of ancient Pu’er tea trees: annual precipitation, ca. 1245 mm (28.73%); min temperature of coldest month, ca. 4.2 °C (18.25%); precipitation of driest quarter, ca. 47.5 mm (14.45%); isothermality, 49.9% to 50.4% (14.11%); precipitation seasonality, ca. 89.2 (6.77%); temperature seasonality, ca. 391 (4.46%); and solar radiation, 12,250 to 13,250 kJ m−2 day−1(3.28%). Productivity was indicated by the total value (viz. fresh leaf harvested multiplied by unit price) of each tree. Environmental suitability, tree growth, and management positively affected productivity; regression weights were 0.325, 0.982, and 0.075, respectively. The degree of productivity was classified as follows: > 0.8, “highly productive”; 0.5–0.8, “productive”; 0.3–0.5, “poorly productive”; and < 0.3, “unproductive”. Overall, 53% of the samples were categorized as “poorly productive” or “unproductive”; thus, the management of these regions require attention.ConclusionsThis model improves the accuracy of the predictions of ancient Pu’er tea tree productivity and will aid future analyses of distribution shifts under climate change, as well as the identification of areas suitable for Pu’er tea tree plantations. Our modeling framework provides insights that facilitate the interpretation of abstract concepts and could be applied to other economically valuable plant resources.
Granulomatosis with polyangiitis in a patient with polydipsia, facial nerve paralysis, and severe otologic complaints: a case report and review of the literature
Authors: Koenen Lukas , Elbelt Ulf , Olze Heidi , Zappe Sören , Dommerich Steffen 
Published: July 2022

Abstract
Background
Granulomatosis with polyangiitis, formerly known as Wegener granulomatosis, is a necrotizing vasculitis with granulomatous inflammation that belongs to the class of antineutrophil cytoplasmic antibodies-positive diseases. It occurs in a localized and a systemic form and may present with a variety of symptoms. Involvement of the upper respiratory tract is very common, while neurologic, endocrinological, and nephrological dysfunction may occur.

Case presentation
We describe the case of a 29-year-old Central European male patient presenting with severe bilateral sensorineural hearing loss, otorrhea, and one-sided facial nerve paralysis. The patient was unsuccessfully treated with i.v. antibiotics at another hospital in Berlin, and tympanic tubes were inserted. After presentation to our emergency room, he was hospitalized and further diagnostics started. Increased fluid intake and 12 kg weight gain over the last months were reported. The patient was diagnosed with granulomatosis with polyangiitis and diabetes insipidus. The patient’s condition improved after treatment with rituximab.

Discussion
A comprehensive PubMed search of all articles with granulomatosis with polyangiitis and diabetes insipidus was conducted to assess which combination of symptoms occurs simultaneously and whether other parts of the pituitary are commonly involved. The 39 selected articles, describing 61 patients, showed that ear–nose–throat involvement occurred most commonly, in 71% of cases. Of patients, 59% had involvement of the anterior pituitary gland, while true panhypopituitarism occurred in 13% of cases. Only one case report featured the same set of symptoms as described herein.

Conclusion
Granulomatosis with polyangiitis is a highly variable disease, commonly involving the upper airways, but that may present with symptoms solely related to the pituitary gland. Clinicians should have a low threshold to investigate for granulomatosis with polyangiitis in patients with therapy-resistant otorrhea. Patients may present with a complex set of symptoms, and integrating different specialists when additional symptoms occur may lead to faster diagnosis.
Melatonin in cryopreservation media improves transplantation efficiency of frozen–thawed spermatogonial stem cells into testes of azoospermic mice
Authors: Kazemzadeh Shokoofeh , Mohammadpour Shahram , Madadi Soheila , Babakhani Azar , Shabani Maryam , Khanehzad Maryam 
Published: July 2022

Abstract
Background
Cryostorage of spermatogonial stem cells (SSCs) is an appropriate procedure for long-term storage of SSCs for fertility preservation. However, it causes damage to cellular structures through overproduction of ROS and oxidative stress. In this study, we examined the protective effect of melatonin as a potent antioxidant in the basic freezing medium to establish an optimal cryopreservation method for SSCs.

Methods
SSCs were obtained from the testes of neonatal male mice aged 3–6 days. Then, 100 μM melatonin was added to the basic freezing medium containing DMSO for cryopreservation of SSCs. Viability, apoptosis-related markers (BAX and BCL2), and intracellular ROS generation level were measured in frozen–thawed SSCs before transplantation using the MTT assay, immunocytochemistry, and flow cytometry, respectively. In addition, Western blotting and immunofluorescence were used to evaluate the expression of proliferation (PLZF and GFRα1) and differentiation (Stra8 and SCP3) proteins in frozen–thawed SSCs after transplantation into recipient testes.

Results
The data showed that adding melatonin to the cryopreservation medium markedly increased the viability and reduced intracellular ROS generation and apoptosis (by decreasing BAX and increasing BCL2) in the frozen–thawed SSCs (p < 0.05). The expression levels of proliferation (PLZF and GFRα1) and differentiation (Stra8 and SCP3) proteins and resumption of spermatogenesis from frozen–thawed SSCs followed the same pattern after transplantation.

Conclusions
The results of this study revealed that adding melatonin as an antioxidant to the cryopreservation medium containing DMSO could be a promising strategy for cryopreservation of SSCs to maintain fertility in prepubertal male children who suffer from cancer.
Mesenchymal stem cells improve liver fibrosis and protect hepatocytes by promoting microRNA-148a-5p-mediated inhibition of Notch signaling pathway
Authors: Zhou Qing , Rong Chao , Gu Tengfei , Li Hongda , Wu Lei , Zhuansun Xuemei , Zhao Xin , Xiao Zuorun , Kuang Yuting , Xu Sanrong , Wang Shouli 
Published: July 2022

Abstract
Background
Mesenchymal stem cells (MSCs) are considered to be a potential therapeutic tool for liver fibrosis. Inhibiting the activation of hepatic stellate cells (HSCs) and protecting hepatocytes are important mechanisms for the anti-fibrotic effect of MSCs. However, how MSCs inhibit liver fibrosis by regulating the expression of microRNAs (miRNAs) has not been fully clarified.

Methods
Transforming growth factor-β1 (TGF-β1)-activated HSCs LX-2 were single cultured or co-cultured with human umbilical cord mesenchymal stem cells (HUC-MSCs). High-throughput sequencing was used to evaluate the differentially expressed microRNAs (DEMs) between the two groups. Quantitative real-time PCR (qRT-PCR), Western blot, and transfection experiments were used to investigate and screen the most significantly up-regulated DEM. Bioinformatics analysis was used to predict the target mRNAs and the potential functions of the DEM. The possible mechanism of HUC-MSCs against liver fibrosis was analyzed by co-culture experiment of HUC-MSCs with LX-2 cells, and HUC-MSCs treatment of Bile duct ligation (BDL)-induced liver fibrosis in mice. Finally, the mechanism of the DEM regulating liver fibrosis was confirmed in human liver fibrosis specimens.

Results
MicroRNA-148a-5p (miR-148a-5p) was the most significantly up-regulated DEM in activated LX-2 cells co-cultured with HUC-MSCs compared with LX-2 cells single cultured. Up-regulation of the expression of miR-148a-5p in activated LX-2 cells could significantly inhibit the expression of hepatic fibrosis markers α-SMA and Col1α1. Notch2 was one target gene of miR-148a-5p. Co-cultured with HUC-MSCs could inhibit the activation of LX-2 cells by inhibiting the expression of the Notch2 and the Notch signaling pathway. In addition, HUC-MSCs treatment could up-regulate the expression of miR-148a-5p in liver tissue and hepatocytes, promote the proliferation and avoid the apoptosis of hepatocytes, and reduce the degree of fibrosis by inhibiting expression of the Notch2 and the Notch signaling pathway in BDL-induced liver fibrosis mice. Moreover, miR-148a-5p was down-regulated and Notch2 was up-regulated in fibrotic human liver tissues compared with the normal livers.

Conclusions
HUC-MSCs treatment could inhibit HSCs activation, protect hepatocytes, and alleviate BDL-induced liver fibrosis in mice by up-regulating the expression of miR-148-5p and inhibiting the Notch signaling pathway. The down-regulation of miR-148-5p and up-regulation of Notch2 could be used as biomarkers to monitor the progression of liver fibrosis.
Drug-free in vitro activation combined with 3D-bioprinted adipose-derived stem cells restores ovarian function of rats with premature ovarian insufficiency
Authors: Li Qian , Zheng Jiahua , Li Zhongkang , Xiao Yanlai , Zhang Mingle , Shi Wenxin , Gao He , Huang Xianghua , Zhang Jingkun 
Published: July 2022

Abstract
Background
Emerging drug-free in vitro activation (IVA) technique enables patients with premature ovarian insufficiency (POI) to restore ovarian function and conceive their own genetic offspring. However, various issues have greatly restricted its clinical application. Transplantation of adipose-derived stem cells (ADSCs) has promising roles in restoring ovarian function of rats with POI, but insufficient retention has greatly hampered their efficiency. Here, we designed a 3D-bioprinted engineering ovary composed of drug-free IVA and ADSCs, which may prolong the retention of ADSCs and construct an early vascular microenvironment, thus compensating for the disadvantages of drug-free IVA to some extent and ameliorating impaired ovarian function in the POI rats.

Methods
After intraperitoneal injection of cyclophosphamide, the POI model rats were randomized into 5 groups: (1) POI group; (2) ovarian fragments group; (3) 3D scaffold combined with ovarian fragments group; (4) ovarian fragments combined with ADSCs group; (5) 3D scaffold with ADSCs combined with ovarian fragments as 3D-bioprinted engineering ovary group. Normal rats were identified as the control group. The localization of CM-Dil-labeled ADSCs and co-localization with CD31 were observed to examine the distribution and underlying mechanism of differentiation. Histomorphological and immunohistochemical analyses were performed to calculate follicle number and assess proliferation and apoptosis of granulosa cells (GCs). Immunofluorescence staining was used to evaluate angiogenesis. Hormone levels were measured to evaluate the restoration of endocrine axis. Western blot analysis and RT-PCR were conducted to explore the potential mechanism.

Results
CM-Dil-labeled ADSCs were distributed in the interstitium of ovaries and had significantly higher retention in the 3D-bioprinted engineering ovary group. Several regions of the co-staining for CM-Dil and CD31 were in the area of vascular endothelial cells. Meanwhile, the follicle counts, GCs proliferation, neoangiogenesis, and hormone levels were significantly improved in the 3D-bioprinted engineering ovary group, as compared with other groups. Furthermore, the ovarian function was ameliorated and angiogenesis was promoted through regulating the PI3K/AKT pathway.

Conclusion
Our results suggested that 3D-bioprinted engineering ovary had great potential for restoring impaired ovarian function of rats with POI, which could compensate for the disadvantages of drug-free IVA to some extent.
Podocytes derived from human induced pluripotent stem cells: characterization, comparison, and modeling of diabetic kidney disease
Authors: Bejoy Julie , Farry Justin M. , Peek Jennifer L. , Cabatu Mariana C. , Williams Felisha M. , Welch Richard C. , Qian Eddie S. , Woodard Lauren E. 
Published: July 2022

AbstractBackgroundIn diabetic kidney disease, high glucose damages specialized cells called podocytes that filter blood in the glomerulus. In vitro culture of podocytes is crucial for modeling of diabetic nephropathy and genetic podocytopathies and to complement animal studies. Recently, several methods have been published to derive podocytes from human-induced pluripotent stem cells (iPSCs) by directed differentiation. However, these methods have major variations in media composition and have not been compared.MethodsWe characterized our accelerated protocol by guiding the cells through differentiation with four different medias into MIXL1+ primitive streak cells with Activin A and CHIR for Wnt activation, intermediate mesoderm PAX8+ cells via increasing the CHIR concentration, nephron progenitors with FGF9 and Heparin for stabilization, and finally into differentiated podocytes with Activin A, BMP-7, VEGF, reduced CHIR, and retinoic acid. The podocyte morphology was characterized by scanning and transmission electron microscopy and by flow cytometry analysis for podocyte markers. To confirm cellular identity and niche localization, we performed cell recombination assays combining iPSC-podocytes with dissociated mouse embryonic kidney cells. Finally, to test iPSC-derived podocytes for the modeling of diabetic kidney disease, human podocytes were exposed to high glucose.ResultsPodocyte markers were expressed at similar or higher levels for our accelerated protocol as compared to previously published protocols that require longer periods of tissue culture. We confirmed that the human podocytes derived from induced pluripotent stem cells in twelve days integrated into murine glomerular structures formed following seven days of culture of cellular recombinations. We found that the high glucose-treated human podocytes displayed actin rearrangement, increased cytotoxicity, and decreased viability.ConclusionsWe found that our accelerated 12-day method for the differentiation of podocytes from human-induced pluripotent stem cells yields podocytes with comparable marker expression to longer podocytes. We also demonstrated that podocytes created with this protocol have typical morphology by electron microscopy. The podocytes have utility for diabetes modeling as evidenced by lower viability and increased cytotoxicity when treated with high glucose. We found that multiple, diverse methods may be utilized to create iPSC-podocytes, but closely mimicking developmental cues shortened the time frame required for differentiation.