bluuebunny/crossref_metadata_2025 huggingface dataset:
The spatiotemporal regulations of epicatechin biosynthesis under normal flowering and the continuous inflorescence removal treatment in Fagopyrum dibotrys
Authors: Guo Xinwei , Luo Zuliang , Zhang Min , Huang Linfang , Wang Hui , Li Yuting , Qiao Xu , Li Ailian , Wu Bin
Published: July 2022

Background

Flowering is a critical physiological change that interferes with not only biomass yield but also secondary metabolism, such as the biosynthesis of flavonoids, in rhizome/root plants. The continuous inflorescence removal (CIR) treatment is frequently conducted to weaken this effect. Fagopyrum dibotrys (D.Don) H.Hara (Golden buckwheat) is a kind of rhizome medicinal plant rich in flavonoids and is widely used for the treatment of lung diseases. The CIR treatment is usually conducted in F. dibotrys because of its excessive reproductive growth. To uncover the molecular mechanisms, comprehensive analysis was performed using metabolome and transcriptome data obtained from normally bloomed and the CIR treated plants.

Results

Metabolome results demonstrated that in the rhizomes of F. dibotrys, its bioactive compound called epicatechin has higher amount than most of the detected precursors. Compared with the normally bloomed plants, the level of epicatechin in the rhizomes of the CIR group increased by 25% at the withering stage. Based on 96 samples of the control and the CIR groups at 4 flowering stages for 4 tissues, RNA-Seq results revealed a 3 ~ 5 times upregulations of all the key enzyme genes involved in the biosynthesis of epicatechin in both time (from the bud stage to the withering stage) and spatial dimensions (from the top of branch to rhizome) under the CIR treatment compared to normal flowering. Integrated analysis of LC–MS/MS and transcriptome revealed the key roles of several key enzyme genes besides anthocyanidin reductase (ANR). A total of 93 transcription factors were identified to co-expressed with the genes in epicatechin biosynthetic pathway. The flowering activator SQUAMOSA promoter-binding protein like (SPLs) exhibited opposite spatiotemporal expression patterns to that of the epicatechin pathway genes; SPL3 could significantly co-express with all the key enzyme genes rather than the flowering repressor DELLA. Weighted gene co-expression network analysis (WGCNA) further confirmed the correlations among chalcone synthases (CHSs), chalcone isomerases (CHIs), ANRs, SPLs and other transcription factors.

Conclusions

SPL3 might dominantly mediate the effect of normal flowering and the CIR treatment on the biosynthesis of epicatechin in rhizomes mainly through the negative regulations of its key enzyme genes including CHS, CHI and ANR.
Impact of direct-acting antiviral treatment of hepatitis C on the quality of life of adults in Ukraine
Authors: Benade M. , Rosen S. , Antoniak S. , Chasela C. , Stopolianska Y. , Barnard T. , Gandhi M. M. , Ivanchuk I. , Tretiakov V. , Dible J. , Minior T. , Chew K. W. , van der Horst C. , Tsenilova Z. , Sanne I.
Published: July 2022

Background

Direct-acting antivirals (DAAs) are highly effective in achieving sustained virologic response among those with chronic hepatitis C virus (HCV) infection. Quality of life (QOL) benefits for an HCV-infected population with high numbers of people who inject drugs and people living with HIV (PLHIV) in Eastern Europe have not been explored. We estimated such benefits for Ukraine.

Methods

Using data from a demonstration study of 12-week DAA conducted in Kyiv, we compared self-reported QOL as captured with the MOS-SF20 at study entry and 12 weeks after treatment completion (week 24). We calculated domain scores for health perception, physical, role and social functioning, mental health and pain to at entry and week 24, stratified by HIV status.

Results

Among the 857 patients included in the final analysis, health perception was the domain that showed the largest change, with an improvement of 85.7% between entry and week 24. The improvement was larger among those who were HIV negative (104.4%) than among those living with HIV (69.9%). Other domains that showed significant and meaningful improvements were physical functioning, which improved from 80.5 (95% CI 78.9–82.1) at study entry to 89.4 (88.1–90.7) at 24 weeks, role functioning (64.5 [62.3–66.8] to 86.5 [84.9–88.2]), social functioning (74.2 [72.1–76.2] to 84.8 [83.2–86.5]) and bodily pain (70.1 [68.2–72.0] to 89.8 [88.5–91.1]). Across all domains, QOL improvements among PLHIV were more modest than among HIV-negative participants.

Conclusion

QOL improved substantially across all domains between study entry and week 24. Changes over the study period were smaller among PLHIV.
Arterioureteral fistula after radical cystectomy and ureterocutaneostomy: two case reports and a systematic literature review
Authors: Jiang Zhiwen , Wang Jian , Cui Jianfeng , Chen Shouzhen , Qu Sifeng , Wang Wenfu , Guo Hu , Shi Benkang , Zhu Yaofeng
Published: July 2022

Background

Arterioureteral fistula (AUF) is a rare, life-threatening condition wherein communication occurs between a ureter and the common, internal, or external iliac artery. The sensitivity of common clinical imaging examination for AUF is low, which leads to a delayed diagnosis and increased mortality. In addition, the increased use of ureteral stents contributes to the growing frequency of AUF.

Case presentation

Our two patients were 74 and 65 years old males respectively. They both had a medical history of bladder cancer and underwent radical cystectomy with ureterocutaneostomy. The patients underwent routine catheter exchange during over 1 year postradical cystectomy and subsequently experienced intermittent gross pulsatile haematuria. After a series of imaging examinations failed to identify the cause, the patients were ultimately diagnosed with AUF and treated with interventional radiotherapy, followed by broad-spectrum antibiotics. Positive effects were found.

Conclusions

The incidence of AUF is increased with the prolongation of survival in patients with related risk factors. This case report aims to highlight early diagnosis and management of AUF to lower the mortality.
Factors associated with delay in seeking care for breast symptoms
Authors: Soh Jien Yen , Yahya Maya Mazuwin , Bachok Norsa’adah , Wan Zain Wan Zainira , Wong Michael Pak-Kai , Zakaria Zaidi , Hashim Isa Merican Siti Rahmah , Md Hashim Mohd Nizam , Wan Mokhter Wan Mokhzani , Ramely Rosnelifaizur , Zakaria Andee Dzulkarnaen , Mohamad Ikhwan Sani
Published: July 2022

Background

Breast cancer is the most common cancer in women worldwide. Early detection and intervention are associated with better prognosis and survival. The study aim was to investigate the factors associated with delayed presentation among women with breast symptoms.

Methods

After ethics approval, a cross-sectional study was conducted from January to October 2020 in women with new breast cancer symptoms at their first visit to our clinic. The “Delayed Presentation” questionnaires in the Malay language were used and distributed among the participants. Demographic data and presentation time were recorded. Presentation time was defined as the duration of symptoms prior to visiting any health care facilities. Respondents with presentation times > 90 days comprised the delayed group. The potential factors associated with the delayed presentation were analyzed using cross-tabulation and multiple logistic regression.

Results

There were 106 respondents to the questionnaire, with a mean age of 34.0 (SD: 11.2) years, and 73.6% (n = 78) were < 39 years old. A total of 35.8% (n = 38) visited the local government clinic first and only 28.3% (n = 30) came to the BestARi clinic directly. The reasons for presentation were a palpable breast lump on breast self-examination (75.5%, n = 80), mastalgia (15.1%, n = 16), nipple discharge (5.7%, n = 6), skin changes (0.9%, n = 1), and others (2.8%, n = 3). Among the respondents, 10.4% (n = 11) had alternative treatments prior to presentation to a hospital. The mean presentation time was 98.9 (SD: 323.7) days. Most of the participants (61.3%, n = 65) presented to us within 1 month. The delayed presentation group accounted for 19.8% (n = 21) of the respondents. The factor that was significantly associated with delayed presentation was the participants’ perception of symptoms as not dangerous (adjusted OR 3.05, 95% CI 1.11, 8.38).

Conclusions

The percentage of delayed presentations among our patients was lower than the percentage reported in a previous study. Interpretation of a symptom as harmless by the respondent was the only factor significantly associated with delayed presentation.
Peer evaluation and feedback for invasive medical procedures: a systematic review
Authors: Thai Theresa , Louden Diana K. N. , Adamson Rosemary , Dominitz Jason A. , Doll Jacob A.
Published: July 2022

Background

There is significant variability in the performance and outcomes of invasive medical procedures such as percutaneous coronary intervention, endoscopy, and bronchoscopy. Peer evaluation is a common mechanism for assessment of clinician performance and care quality, and may be ideally suited for the evaluation of medical procedures. We therefore sought to perform a systematic review to identify and characterize peer evaluation tools for practicing clinicians, assess evidence supporting the validity of peer evaluation, and describe best practices of peer evaluation programs across multiple invasive medical procedures.

Methods

A systematic search of Medline and Embase (through September 7, 2021) was conducted to identify studies of peer evaluation and feedback relating to procedures in the field of internal medicine and related subspecialties. The methodological quality of the studies was assessed. Data were extracted on peer evaluation methods, feedback structures, and the validity and reproducibility of peer evaluations, including inter-observer agreement and associations with other quality measures when available.

Results

Of 2,135 retrieved references, 32 studies met inclusion criteria. Of these, 21 were from the field of gastroenterology, 5 from cardiology, 3 from pulmonology, and 3 from interventional radiology. Overall, 22 studies described the development or testing of peer scoring systems and 18 reported inter-observer agreement, which was good or excellent in all but 2 studies. Only 4 studies, all from gastroenterology, tested the association of scoring systems with other quality measures, and no studies tested the impact of peer evaluation on patient outcomes. Best practices included standardized scoring systems, prospective criteria for case selection, and collaborative and non-judgmental review.

Conclusions

Peer evaluation of invasive medical procedures is feasible and generally demonstrates good or excellent inter-observer agreement when performed with structured tools. Our review identifies common elements of successful interventions across specialties. However, there is limited evidence that peer-evaluated performance is linked to other quality measures or that feedback to clinicians improves patient care or outcomes. Additional research is needed to develop and test peer evaluation and feedback interventions.
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

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

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

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

Background

The 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.

Results

Our 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.

Conclusions

This 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

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

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

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

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

Background

In 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.

Methods

We 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.

Results

Podocyte 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.

Conclusions

We 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.
Medical science students’ experiences of test anxiety: a phenomenological study
Authors: Badrian Majid , Bazrafkan Leila , Shakour Mahsa
Published: July 2022

Introduction

The studies show test anxiety is a common disorder in students that causes academic failure. There are not enough studies and specific theoretical background about test anxiety and ways to deal with it, so the purpose of this study was to do a qualitative study to fully understand the ways to deal with test anxiety in medical Sciences students.

Materials and methods

This is a qualitative study. The participants are the students of the last 2 years of pharmacy, medicine and dentistry at Isfahan University of Medical Sciences. Ten students were selected by purposeful sampling, and interviews continued until the data saturation stage and the lack of access to new data. The data were analyzed by seven-level Colaizzi method.

Findings

After analyzing data, about 50 codes were extracted. These codes divided into 16 subclasses, and among them, ultimately five main themes are extracted: “Prayer and Dialogue with God”, “Interaction and communication with friends and relatives”, “studying strategies”, “Finding ways to relax and self-care” and “Negative strategies” were extracted.

Conclusions

The result of this study showed that students often use positive strategies to overcome the test anxiety and try to use positive strategies, but some students are advised of undesirable strategies such as misuse of authorized drugs and writing cheating that that lead to a lot of complex problems. The educational system should do its utmost effort to empower students to manage the anxiety by learning the best strategies.
The impact of working capital management on credit rating
Authors: Abuhommous Ala’a Adden , Alsaraireh Ahmad Salim , Alqaralleh Huthaifa
Published: July 2022

This study investigates the possible nonlinear relationship between working capital and credit rating. Furthermore, it examines the relationship between the three components of working capital (inventory, accounts receivable, and accounts payable) and a firm’s credit rating. Employing data for U.S listed firms for the period between 1985 and 2017, the results of our ordered probit model show a nonlinear relationship between working capital and its components and credit rating. Finally, we find that the deviation from the optimal working capital adversely affects the credit rating. The results of this study are of significant importance for policy makers, managers, decision makers, and credit-rating agencies, as they help highlight the importance of working capital management for a firm’s credit rating.
Simulation translation differences between craft groups
Authors: Gard Jye , Duong Chi , Murtagh Kirsty , Gill Jessica , Lambe Katherine , Summers Ian
Published: July 2022

Background

Many simulation-based clinical education events (SBCEE) aim to prepare healthcare professionals with the knowledge, skills, and features of professionalism needed to deliver quality patient care. However, how these SBCEE learnings are translated into broader workplace practices by learners from different craft groups has not been described.

Objectives

To understand how learners from different craft groups (doctors and nurses) anticipate simulation-based learnings will translate to their workplaces and the process by which translation occurs.

Design

Qualitative descriptive study design using pre- and post-SBCEE questionnaires.

Settings

A large tertiary Australian hospital-based simulation centre that facilitates SBCEE for multi-professional graduate and undergraduate clinicians from 16 hospitals.

Methods

Participants who attended SBCEEs between May and October 2021 completed questionnaires at two touchpoints, on the day of attending a SBCEE and 6 weeks after. Based on a phenomenological approach, the study examined clinicians’ experiences in relation to simulation education, intended simulation learning use in the workplace, and perceived success in subsequently using these learnings to improve clinical outcomes. Qualitative inductive thematic data analysis was used to develop narratives for different learner cohorts.

Results

Three overarching themes were identified regarding simulation participants’ perceptions of the success of translating simulation learnings into the workplace. These were: scenario-workplace mirroring, self-assessment, and successful confidence. Doctor participants found it difficult to map SBCEE learnings to their workplace environments if they did not mirror those used in simulation. Nurses sought peer evaluation to analyse the effectiveness of their workplace translations, whereas doctors relied on self-assessment. Learners from both craft groups highly prized ‘confidence-building’ as a key indicator of improved workplace performance achieved through SBCEE learning.

Conclusion

A diverse range of factors influences healthcare workers’ experiences in translating simulation learnings to their workplace. To equip simulation learners to translate learnings from a SBCEE into their clinical practices, we suggest the following areas of focus: co-development of translation plans with learners during the delivery of an SBCEE including the indicators of success, above table discussions on the generalisability of learnings to different environments and contexts, smart investment in simulation outputs, and cautious championing of confidence-building.
The Economic Effects of Mafia: Firm Level Evidence
Authors: Mirenda Litterio , Mocetti Sauro , Rizzica Lucia
Published: July 2022

We analyze the effects of Mafia infiltration in the legal economy. Combining information from investigative records with panel data on firms’ governance and balance sheets, we build an indicator of infiltration in firms located in an area with no tradition of Mafia. We show that Mafia targets young and less efficient firms and that infiltration generates a significant rise in firms’ revenues, with no proportionate growth in production inputs and a deterioration of the firm’s financial situation leading to market exit. These findings are consistent with a story of predatory behavior in which infiltration is used for money laundering or rent extraction. (JEL D22, G32, G34, K42, L25)
Centralized Admissions, Affirmative Action, and Access of Low-Income Students to Higher Education
Authors: Mello Ursula
Published: July 2022

I analyze how two reforms, introduced to expand college access in Brazil, impacted enrollments of low-SES students. The first policy centralized applications in a nationwide platform (SISU), and the second expanded affirmative action quotas (AA) to a uniform share of 50 percent of vacancies offered by degree. Results show that SISU changes enrollment decisions of high-SES students, crowding out low-SES groups from the least competitive degrees disproportionately. In contrast, AA increases enrollments of low-SES individuals not only mechanically but also through behavioral responses. Finally, their interaction creates a complementary effect, protecting the low-SES groups from the crowding-out of centralization. (JEL I23, I24, I28, O15)
Adaptation and Adverse Selection in Markets for Natural Disaster Insurance
Authors: Wagner Katherine R. H.
Published: July 2022

This paper quantifies frictions in uptake, tests for adverse selection, and analyzes welfare effects of proposed reforms in natural disaster insurance markets. I find that willingness to pay is remarkably low. In high-risk flood zones, fewer than 60 percent of homeowners purchase flood insurance even though premiums are only two-thirds of own costs. Estimating flood insurance demand and cost elasticities using house-level variation in premiums from recent US congressional reforms reveals that these homeowners select into insurance based on observable differences in adaptation but not private information about risk. These findings change the sign of predicted welfare effects of proposed policies. (JEL D82, G22, Q54)
EMOTIONAL CLOSENESS WITH THE FATHER AND THE IMAGE OF THE FUTURE SPOUSE OF GIRLS
Authors: NARTIKOEVA Z.K. , ILCHENKO V.V.
Published: July 2022

The article presents an empirical study of the peculiarities of the relationship to the father and the image of the future spouse in girls. The level of emotional intimacy with the father and the image of the future marriage partner were revealed. Correlation links between the level of emotional intimacy with the father and the image of the future marriage partner are determined.
Healthcare Management and Marketing
Authors: Kosova A. A. , Blagodareva M. S. , Chertopolokhova S. B. , Shestakova A. A. , Shastin A. S.
Published: July 2022

Данный электронно-образовательный ресурс предназначен для студентов шестого курса медико-профилактического факультета, однако может применяться и для обучения студентов медиков других специальностей с целью формирования знаний, умений и навыков, необходимых специалисту для управленческой работы на предприятиях здравоохранения и в Федеральной службе по надзору в сфере защиты прав потребителей. Программа составлена с учетом передового отечественного и зарубежного опыта, направлена на развитие навыка использования теоретических знаний в практической деятельности ЭОР состоит из 14 разделов, содержащих теоретический материал, и тестовые контроли. Теоретическая часть представлена лекционным материалом в виде аудиолекций и презентаций. В контрольном блоке обучающемуся предлагается ответить на тестовые контроли, задача которых проверить уровень усвоения теоретического материала.
Digital Touchpoints Effectiveness and its Impact on Consumer Brand Engagement in Biotechnology Start-Up
Authors: Hustima Sahara Shifa , Armelia Windasari Nila
Published: July 2022

Start-ups are currently in the spotlight in all countries, especially in developed countries, where they are seen as a critical driver of economic growth and a source of long-term jobs. In addition, consumers are increasingly interested in using digital touchpoints to fulfil their daily needs. Marketers of biotechnology start-ups realize that in this competitive era of commercial initiatives, it is difficult to find the point of engagement between consumer and brand to be more pleasant and smooth. This study aims to understand the effectiveness of digital touchpoints in influencing consumer brand engagement at biotechnology start-up. The methodology used factor analysis and regression analysis from an online survey. The respondents were selected by giving questionnaires to consumers who had bought one or more products from biotechnology start-up. The main finding showed digital touchpoints affected consumer brand engagement at biotechnology start-up (0.000, p < 0.01). However, the results with moderator variable of hedonic value (0.4235) and utilitarian value (0.5147)does not moderated digital touchpoints effectiveness on consumer brand engagement (p > 0.05). This study provide a new perspective on measurement items of digital touchpoints effectiveness and provides information for marketers to pay attention to important aspects for increase the engagement of several digital touchpoints.
Customer Profiling in the Ambit of Gaming: portraying lifestyles
Authors: Machado Dutra Matheus José
Published: July 2022

Customer profiling is a tool for lifestyle visualization that combines creative imagination techniques with storytelling and statistical methods to fabricate easily interpretable representations of the consumer’s everyday life. This paper suggests employing the data-driven method allied with the storytelling approach for modeling engaging gamer profiles. Developing a profile is a sensible process that utilizes data and statistics to produce credible results. Therefore, the methodology principally involved the exploratory factor analysis for uncovering latent variables that influence the gaming lifestyle and the non-hierarchical cluster analysis to separate data cases with different characteristics and group members with similar attributes. The analyzed dataset gathered 1.588 participants from 80 countries. The results support the customer profiling methodology as a valid instrument for consumer behavior analysis and lifestyle visualization
Forming Student Teams to Incorporate Soft Skills and Commonality of Schedule
Authors: Bowers Andrew , Bowers Melissa R. , Bryan Nana , Letizia Paolo , Murphy Spencer
Published: July 2022

It is widely recognized that students’ learning can be enhanced and facilitated when students have the opportunity to work together in teams. As a consequence, the pursuit of a methodology to form optimal student teams continues to challenge academics. Based on a review of related literature, we propose a model that includes new approaches to two team criteria. The first is a discrete optimization approach to commonality of schedule. To facilitate team meetings, we offer an exact formulation to ensure students on a given team share a minimum number of common time slots during which they are available. The second team criterion is sufficient soft skills. Using a unique text analysis approach, we ensure that each team includes students with adequate soft skills, such as leadership and interpersonal skills. Our analytic approach enhances the students’ learning experience and class performance and simplifies the faculty task of forming teams.

History: This paper was refereed.