bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pneumocystis jirovecii colonization and its association with pulmonary diseases: a multicenter study based on a modified loop-mediated isothermal amplification assay
Authors: Xue Ting , Ma Zhuang , Liu Fan , Du Weiqin , He Li , Wang Jinyan , An Chunli 
Published: March 2020

Abstract
Background
Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungal pathogen and the role of its colonization in pulmonary diseases has become a popular focus in recent years. The aim of this study was to develop a modified loop-mediated isothermal amplification (LAMP) assay for detection of Pneumocystis jirovecii (P. jirovecii) DNA amongst non-HIV patients with various pulmonary diseases and use it to examine the prevalence and assess the association of P. jirovecii colonization with clinical characteristics of these diseases.

Methods
We modified the previously reported LAMP assay for P. jirovecii by adding real-time detection. This method was used to detect P. jirovecii colonization in pulmonary samples collected from 403 non-HIV patients with various pulmonary diseases enrolled from 5 hospitals in China. We determined the prevalence of P. jirovecii colonization in 7 types of pulmonary diseases and assessed the association of P. jirovecii colonization with clinical characteristics of these diseases.

Results
The modified LAMP assay showed no cross-reactivity with other common pulmonary microbes and was 1000 times more sensitive than that of conventional PCR. Using the modified LAMP assay, we detected P. jirovecii colonization in 281 (69.7%) of the 403 patients enrolled. P. jirovecii colonization was more common in interstitial lung diseases than in chronic obstructive pulmonary disease (COPD) (84.6% vs 64.5%, P < 0.05). Patients with acute exacerbation of COPD had a higher prevalence of P. jirovecii colonization compared to patients with stabilized COPD (67.4% vs 43.3%, P < 0.05). P. jirovecii colonization was associated with decreased pulmonary function, increased levels of 1,3-β-D-glucan and C-reactive protein, and decreased levels of CD4+ T-cell counts (P < 0.05 for each). Approximately 70% of P. jirovecii colonized patients had confections with other fungi or bacteria.

Conclusions
We developed a modified LAMP assay for detecting P. jirovecii. Our multi-center study of 403 patients supports that P. jirovecii colonization is a risk factor for the development of pulmonary diseases and highlights the need to further study the pathogenesis and transmission of P. jirovecii colonization in pulmonary diseases.
Side effect concerns and their impact on women’s uptake of modern family planning methods in rural Ghana: a mixed methods study
Authors: Schrumpf Leah A. , Stephens Maya J. , Nsarko Nathaniel E. , Akosah Eric , Baumgartner Joy Noel , Ohemeng-Dapaah Seth , Watt Melissa H. 
Published: March 2020

Abstract
Background
Despite availability of modern contraceptive methods and documented unmet need for family planning in Ghana, many women still report forgoing modern contraceptive use due to anticipated side effects. The goal of this study was to examine the use of modern family planning, in particular hormonal methods, in one district in rural Ghana, and to understand the role that side effects play in women’s decisions to start or continue use.

Methods
This exploratory mixed-methods study included 281 surveys and 33 in-depth interviews of women 18–49 years old in the Amansie West District of Ghana between May and July 2018. The survey assessed contraceptive use and potential predictors of use. In-depth interviews examined the context around uptake and continuation of contraceptive use, with a particular focus on the role of perceived and experienced side effects.

Results
The prevalence of unmet need for modern family planning among sexually active women who wanted to avoid pregnancy (n = 135) was 68.9%. No factors were found to be significantly different in comparing those with a met need and unmet for modern family planning. Qualitative interviews revealed significant concerns about side effects stemming from previous method experiences and/or rumors regarding short-term impacts and perceived long-term consequences of family planning use. Side effects mentioned include menstrual changes (heavier bleeding, amenorrhea or oligomenorrhea), infertility and childbirth complications.

Conclusion
As programs have improved women’s ability to access modern family planning, it is paramount to address patient-level barriers to uptake, in particular information about side effects and misconceptions about long-term use. Unintended pregnancies can be reduced through comprehensive counseling about contraceptive options including accurate information about side effects, and the development of new contraceptive technologies that meet women’s needs in low-income countries.
Role of limonin in anticancer effects of Evodia rutaecarpa on ovarian cancer cells
Authors: Bae Jae Ryul , Park Wook Ha , Suh Dong Hoon , No Jae Hong , Kim Yong Beom , Kim Kidong 
Published: March 2020

Abstract
Background
Ovarian cancer therapy generally involves systemic chemotherapy with anticancer drugs; however, chemotherapy with a platinum-based drug has often been shown to cause adverse reactions and drug resistance in ovarian cancer patients. Evodia rutaecarpa (ER) reportedly shows anticancer activity against various types of cancer cells. However, the effects of ER have not yet been fully uncovered in ovarian cancer.

Methods
In the present study, we investigated the anticancer effects of an ER extract and its components against the ovarian cancer cell lines SKOV-33, A2780, RMUG-S and a cisplatin-resistant SKOV-3 cell line (CisR SKOV-3). Cell viability and colony formation assays along with subcellular fractionation analysis, immunoblotting, and immunofluorescence staining were performed.

Results
ER treatment led to a significant reduction in the viability of SKOV-3 cells. Moreover, limonin, a compound found in ER, reduced the viability of both serous-type (SKOV-3 and A2780) and mucinous-type (RMUG-S) ovarian cancer cells by inducing apoptosis via activation of the p53 signaling pathway. Furthermore, limonin reversed the drug resistance through activation of apoptosis in CisR SKOV-3.

Conclusion
Taken together, our findings suggest that limonin contributes to the anti-ovarian cancer effects of ER by inducing apoptosis via activation of the p53 signaling pathway.
Perceptions and attitudes towards dementia among university students in Malaysia
Authors: Griffiths Alys Wyn , Cheong Wing Loong , Saw Pui San , Parveen Sahdia 
Published: March 2020

Abstract
Background
One of the major challenges worldwide is the stigma associated with dementia. There is limited dementia awareness within Malaysian communities, including levels of confusion regarding the differences between dementia and the usual ageing progress, which can lead to delays in support seeking. The need for additional training and education for healthcare professionals has been highlighted. The present study aimed to evaluate the benefits of a one-hour dementia education session (Dementia Detectives workshop) for pharmacy and medicine undergraduate students at a Malaysian university.

Methods
Participants attended the workshop and completed pre- (Time 1) and post-workshop (Time 2) questionnaires consisting of validated measures exploring attitudes towards dementia and older people more broadly.

Results
A total of 97 students were recruited. Attitudes towards people with dementia showed significant positive changes between Time 1 and Time 2, whereas no differences were found for attitudes towards older people.

Conclusions
As medical and pharmacy students develop theoretical knowledge, practical skills and professional attitudes during their undergraduate studies, it is important for students to also learn about the humanistic side of diseases and conditions through workshops such as the one presented here. Further research should now be conducted to consider how Dementia Detectives can be delivered to non-healthcare students and what the barriers and facilitators to wider delivery are.
The contribution of electronic health records to risk management through accreditation of residential aged care homes in Australia
Authors: Yu Ping , Jiang Tao , Hailey David , Ma Jun , Qian Siyu 
Published: March 2020

Abstract
Background
The Australian government has implemented a compulsory aged care accreditation system to guide and monitor the risk management approach in registered residential aged care (RAC) homes. This research assessed the contribution of electronic health records (EHR) to risk management in RAC homes in relation to the extent that aged care accreditation fulfils its role.

Methods
A convenience sample of 5560 aged care accreditation reports published from 2011 to 2018 was manually downloaded from the Accreditation Agency web site. A mixed-method approach of text data mining and manual content analysis was used to identify any significant differences in failure to meet accreditation outcomes among the RAC homes. This took account of whether EHR or paper records were used, year of accreditation, and size and location of the homes.

Results
It appears that aged care accreditation was focused on structure and process, with limited attention to outcome. There was a big variation between homes in their use of measurement indicators to assess accreditation outcomes. No difference was found in outcomes between RAC homes using EHR and those using paper records. Only 3% of the RAC homes were found to have failed some accreditation outcomes. Failure in monitoring mechanism was the key factor for failing many accreditation outcomes. The top five failed outcomes were Human Resource Management, Clinical Care, Information Systems, Medication Management and Behavioural Management.

Conclusions
Sub-optimal outcomes have limited the effectiveness of accreditation in driving and monitoring risk management for care recipient safety in RAC homes. Although EHR is an important structure and process component for RAC services, it made a limited contribution to risk management for accreditation in Australian RAC homes. Either EHR was not effective, or the accreditation process was not robust enough to recognize its influence. Aged care accreditation in Australia needs to develop further outcome-based measures that are supported by robust data infrastructure and clear guidance.
Analyzing the situation of older family caregivers with a focus on health-related quality of life and pain: a cross-sectional cohort study
Authors: Fagerström Cecilia , Elmståhl Sölve , Wranker Lena Sandin 
Published: March 2020

Abstract
Background
For a significant proportion of the older population, increasing age is associated with health problems and worsening health. Older family caregivers are largely responsible for care of next-of-kin living at home, which impacts their own physical and mental health both positively and negatively. However, evidence is insufficient regarding the health situation of older caregivers. The aim of this study was to investigate health-related quality of life (HRQoL) and pain, and their associations, among caregivers aged ≥60 years.

Methods
The participants (n = 3444) were recruited from the Swedish National Study on Aging and Care-Blekinge and Good Aging in Skåne during 2001–2004. Participants aged ≥60 years were selected randomly and underwent cognitive tests, with demographic information obtained through questionnaires. The response rate was 60%. A predefined research protocol was used. HRQoL was measured with the Short-Form Health Survey, dimension mental health. Logistic regression models were used to investigate the associations between HRQoL and pain as well as control factors.

Results
Family caregiving was reported by 395 (11.5%) of the participants, and 56.7% of the caregivers reported pain. Family caregivers reported lower pain intensity on the Visual Analogue Scale and were younger, on median, than non-caregivers. Irrespective of caregiver status, pain was associated with mental HRQoL. Concerns about personal health and financial status had the strongest associations with mental HRQOL in both groups, but the levels were higher among caregivers.

Conclusion
Pain was one factor associated with low HRQoL regardless of family caregiver status and remained important when controlling for factors related to advanced age. This finding remained among family caregivers, though they reported lower pain intensity. Factors other than pain were shown to be important to mental HRQoL and should also be taken into consideration when discussing actions for family caregivers to maintain and improve health and HRQoL.

Trial registration number
Not applicable.
Runt-related transcription factor 1 promotes apoptosis and inhibits neuroblastoma progression in vitro and in vivo
Authors: Hong Mei , He Jing , Li Duo , Chu Yuanyuan , Pu Jiarui , Tong Qiangsong , Joshi Harish C. , Tang Shaotao , Li Shiwang 
Published: March 2020

Abstract
Background
Runt-related transcription factor 1 (RUNX1) is a heterodimeric transcription factor that binds to the core element of many enhancers and promoters and can accelerate apoptosis in various tumors. However, the regulatory mechanisms underlying RUNX1 expression in neuroblastoma (NB), a highly malignant tumor in childhood, remain largely unclear. In this study, we aimed to assess the role of RUNX1 in NB and to reveal the underlying mechanisms that may contribute to finding a potential therapeutics strategy against NB.

Methods
Growth, invasion, metastasis and angiogenesis were assessed using Cell Counting Kit-8 (CCK-8) immunocytochemistry, and studies involving soft agar, cell invasion, tube formation and whole animals. The levels of expression were measured using real-time quantitative PCR for RNA, Western blot and immunostaining analyses for proteins. Luciferase reporter and chromatin immunoprecipitation assays indicated that RUNX1 directly binds within the BIRC5, CSF2RB and NFKBIA promoter regions to facilitate transcription. The level of apoptosis was assessed by determining mitochondrial membrane potential and flow cytometry.

Results
RUNX1 was highly expressed in ganglioneuroma (GN) and well-differentiated (WD) tissues relative to the poorly differentiated (PD) and undifferentiated (UD) ones. Moreover, RUNX1 effectively reduced cell viability, invasion, metastasis, angiogenesis, and promoted apoptosis in vitro and in vivo. RUNX1 reduced BIRC5 transcription and increased CSF2RB and NFKBIA transcription by directly binding BIRC5, CSF2RB and NFKBIA promoters. In addition, cytotoxic drugs, especially cisplatin, significantly increased RUNX1 expression in NB cells and promoted apoptosis.

Conclusions
These data show that RUNX1 is an independent surrogate marker for the progression of NB and it can be used for monitoring NB prognosis during therapy.
Monocytic HLA-DR expression kinetics in septic shock patients with different pathogens, sites of infection and adverse outcomes
Authors: Leijte Guus P. , Rimmelé Thomas , Kox Matthijs , Bruse Niklas , Monard Céline , Gossez Morgane , Monneret Guillaume , Pickkers Peter , Venet Fabienne 
Published: March 2020

Abstract
Background
Decreased monocytic (m)HLA-DR expression is the most studied biomarker of sepsis-induced immunosuppression. To date, little is known about the relationship between sepsis characteristics, such as the site of infection, causative pathogen, or severity of disease, and mHLA-DR expression kinetics.

Methods
We evaluated mHLA-DR expression kinetics in 241 septic shock patients with different primary sites of infection and pathogens. Furthermore, we used unsupervised clustering analysis to identify mHLA-DR trajectories and evaluated their association with outcome parameters.

Results
No differences in mHLA-DR expression kinetics were found between groups of patients with different sites of infection (abdominal vs. respiratory, p = 0.13; abdominal vs. urinary tract, p = 0.53) and between pathogen categories (Gram-positive vs. Gram-negative, p = 0.54; Gram-positive vs. negative cultures, p = 0.84). The mHLA-DR expression kinetics differed between survivors and non-survivors (p < 0.001), with an increase over time in survivors only. Furthermore, we identified three mHLA-DR trajectories (‘early improvers’, ‘delayed or non-improvers’ and ‘decliners’). The probability for adverse outcome (secondary infection or death) was higher in the delayed or non-improvers and decliners vs. the early improvers (delayed or non-improvers log-rank p = 0.03, adjusted hazard ratio 2.0 [95% CI 1.0–4.0], p = 0.057 and decliners log-rank p = 0.01, adjusted hazard ratio 2.8 [95% CI 1.1–7.1], p = 0.03).

Conclusion
Sites of primary infection or causative pathogens are not associated with mHLA-DR expression kinetics in septic shock patients. However, patients showing delayed or no improvement in or a declining mHLA-DR expression have a higher risk for adverse outcome compared with patients exhibiting a swift increase in mHLA-DR expression. Our study signifies that changes in mHLA-DR expression over time, and not absolute values or static measurements, are of clinical importance in septic shock patients.
Generation of functional salivary gland tissue from human submandibular gland stem/progenitor cells
Authors: Sui Yi , Zhang Siqi , Li Yongliang , Zhang Xin , Hu Waner , Feng Yanrui , Xiong Jingwei , Zhang Yuanyuan , Wei Shicheng 
Published: March 2020

Abstract
Background
Organ replacement regenerative therapy based on human adult stem cells may be effective for salivary gland hypofunction. However, the generated tissues are immature because the signaling factors that induce the differentiation of human salivary gland stem cells into salivary glands are unknown.

Methods
Isolated human submandibular gland stem/progenitor cells (hSMGepiS/PCs) were characterized and three-dimensionally (3D) cultured to generate organoids and further induced by fibroblast growth factor 10 (FGF10) in vitro. The induced spheres alone or in combination with embryonic day 12.5 (E12.5) mouse salivary gland mesenchyme were transplanted into the renal capsules of nude mice to assess their development in vivo. Immunofluorescence, quantitative reverse transcriptase-polymerase chain reaction, calcium release analysis, western blotting, hematoxylin–eosin staining, Alcian blue–periodic acid-Schiff staining, and Masson’s trichrome staining were performed to assess the structure and function of generated tissues in vitro and in vivo.

Results
The isolated hSMGepiS/PCs could be long-term cultured with a stable genome. The organoids treated with FGF10 [FGF10 (+) group] exhibited higher expression of salivary gland–specific markers; showed spatial arrangement of AQP5+, K19+, and SMA+ cells; and were more sensitive to the stimulation by neurotransmitters than untreated organoids [FGF10 (−) group]. After heterotopic transplantation, the induced cell spheres combined with mouse embryonic salivary gland mesenchyme showed characteristics of mature salivary glands, including a natural morphology and saliva secretion.

Conclusion
FGF10 promoted the development of the hSMGepiS/PC-derived salivary gland organoids by the expression of differentiation markers, structure formation, and response to neurotransmitters in vitro. Moreover, the hSMGepiS/PCs responded to the niche in mouse embryonic mesenchyme and further differentiated into salivary gland tissues with mature characteristics. Our study provides a foundation for the regenerative therapy of salivary gland diseases.
High cholesterol induces apoptosis and autophagy through the ROS-activated AKT/FOXO1 pathway in tendon-derived stem cells
Authors: Li Kaiqun , Deng Ye , Deng Ganming , Chen Pengyu , Wang Yutian , Wu Hangtian , Ji Zhiguo , Yao Zilong , Zhang Xianrong , Yu Bin , Zhang Kairui 
Published: March 2020

Abstract
Background
Hypercholesterolemia increases the risk of tendon pain and tendon rupture. Tendon-derived stem cells (TDSCs) play a vital role in the development of tendinopathy. Our previous research found that high cholesterol inhibits tendon-related gene expression in TDSCs. Whether high cholesterol has other biological effects on TDSCs remains unknown.

Methods
TDSCs isolated from female SD rats were exposed to 10 mg/dL cholesterol for 24 h. Then, cell apoptosis was assessed using flow cytometry and fluorescence microscope. RFP-GFP-LC3 adenovirus transfection was used for measuring autophagy. Signaling transduction was measured by immunofluorescence and immunoblotting. In addition, Achilles tendons from ApoE −/− mice fed with a high-fat diet were histologically assessed using HE staining and immunohistochemistry.

Results
In this work, we verified that 10 mg/dL cholesterol suppressed cell proliferation and migration and induced G0/G1 phase arrest. Additionally, cholesterol induced apoptosis and autophagy simultaneously in TDSCs. Apoptosis induction was related to increased expression of cleaved caspase-3 and BAX and decreased expression of Bcl-xL. The occurrence of autophagic flux and accumulation of LC3-II demonstrated the induction of autophagy by cholesterol. Compared with the effects of cholesterol treatment alone, the autophagy inhibitor 3-methyladenine (3-MA) enhanced apoptosis, while the apoptosis inhibitor Z-VAD-FMK diminished cholesterol-induced autophagy. Moreover, cholesterol triggered reactive oxygen species (ROS) generation and activated the AKT/FOXO1 pathway, while the ROS scavenger NAC blocked cholesterol-induced activation of the AKT/FOXO1 pathway. NAC and the FOXO1 inhibitor AS1842856 rescued the apoptosis and autophagy induced by cholesterol. Finally, high cholesterol elevated the expression of cleaved caspase-3, Bax, LC3-II, and FOXO1 in vivo.

Conclusion
The present study indicated that high cholesterol induced apoptosis and autophagy through ROS-activated AKT/FOXO1 signaling in TDSCs, providing new insights into the mechanism of hypercholesterolemia-induced tendinopathy.

Graphical abstract
High cholesterol induces apoptosis and autophagy through the ROS-activated AKT/FOXO1 pathway in tendon-derived stem cells.
Therapeutic efficacy of catalpol against apoptosis in cardiomyocytes derived from human induced pluripotent stem cells
Authors: Yang Lingchao , Feng Xiangfei , Li Yigang , Zhang Song , Ying Yu 
Published: March 2020

AbstractCardiac arrhythmia is an irregular heart rhythm that can lead to serious heart conditions and various organ disorders, and may cause sudden cardiac death. Catalpol belongs to the iridoid glycoside family and is highly abundant in Rehmannia glutinosa Libosch. The study included five groups such as group I (normal control), group II (treatment control), group III (low-dose treatment), group IV (medium-dose treatment) and group V (high-dose treatment). We investigated the therapeutic effects of catalpol on cardiac arrhythmia in human-induced pluripotent stem cells (iPSCs). Cell viability, lactate dehydrogenase (LDH) levels, lipid peroxidation, antioxidant activity, and caspase-3 and caspase-9 activities and protein levels were measured in normal control, treatment control, and treated (1, 10, and 100 µM) iPSC groups. Compared with the treatment control group, catalpol supplementation (1, 10, and 100 µM) increased iPSC cell viability by 7.5, 27.3, and 65.8%, respectively; reduced the LDH levels by 10.4, 31.3, and 75.2%, respectively; and reduced the lipid peroxidation levels by 7.7, 33.0, and 62.6%, respectively. The antioxidant levels were significantly higher in the treatment control group than in the normal control group. Catalpol (100 µM) reduced the caspase-3 and caspase-9 activities by more than 30% and increased expression of the corresponding proteins by more than 50%. These findings suggest that the naturally occurring iridoid glycoside catalpol is effective against aconitine-induced cardiac arrhythmia in iPSCs.