bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modaline sulfate promotes Oct4 expression and maintains self-renewal and pluripotency of stem cells through JAK/STAT3 and Wnt signaling pathways
Authors: Mei Xianglin , Zhao Hanhan , Ai Huihan , Wang Shuyue , Song Zhenbo , Zheng Lihua , Wang Guannan , Sun Ying , Bao Yongli 
Published: August 2021

Abstract
Background
Stem cells have been extensively explored for a variety of regenerative medical applications and they play an important role in clinical treatment of many diseases. However, the limited amount of stem cells and their tendency to undergo spontaneous differentiation upon extended propagation in vitro restrict their practical application. Octamer-binding transcription factor-4 (Oct4), a transcription factor belongs to the POU transcription factor family Class V, is fundamental for maintaining self-renewal ability and pluripotency of stem cells.

Methods
In the present study, we used the previously constructed luciferase reporters driven by the promoter and 3’-UTR of Oct4 respectively to screen potential activators of Oct4. Colony formation assay, sphere-forming ability assay, alkaline phosphatase (AP) activity assay and teratoma-formation assay were used to assess the role of modaline sulfate (MDLS) in promoting self-renewal and reinforcing pluripotency of P19 cells. Immunofluorescence, RT-PCR, and western blotting were used to measure expression changes of stem-related genes and activation of related signaling pathways.

Results
We screened 480 commercially available small-molecule compounds and discovered that MDLS greatly promoted the expression of Oct4 at both mRNA and protein levels. Moreover, MDLS significantly promoted the self-renewal capacity of P19 cells. Also, we observed that the expression of pluripotency markers and alkaline phosphatase (AP) increased significantly in MDLS-treated colonies. Furthermore, MDLS could promote teratoma formation and enhanced differentiation potential of P19 cells in vivo. In addition, we found that in the presence of LIF, MDLS could replace feeder cells to maintain the undifferentiated state of OG2-mES cells (Oct4-GFP reporter gene mouse embryonic stem cell line), and the MDLS-expanded OG2-mES cells showed an elevated expression levels of pluripotency markers in vitro. Finally, we found that MDLS promoted Oct4 expression by activating JAK/STAT3 and classic Wnt signaling pathways, and these effects were reversed by treatment with inhibitors of corresponding signaling pathways.

Conclusions
These findings demonstrated, for the first time, that MDLS could maintain self-renewal and pluripotency of stem cells.
FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2
Authors: Chen Yang , Liang Weilian , Liu Ke , Shang Zhengjun 
Published: August 2021

Abstract
Background
Epithelial-mesenchymal transition (EMT) and cell stemness are implicated in the initiation and progression of oral squamous cell carcinoma (OSCC). Revealing the intrinsic regulatory mechanism may provide effective therapeutic targets for OSCC.

Results
In this study, we found that Forkhead box D1 (FOXD1) was upregulated in OSCC compared with normal samples. Patients with a higher FOXD1 expression had a poorer overall survival and disease-free survival. Immunohistochemical staining results showed that FOXD1 expression was related to the clinical stage and relapse status of OSCC patients. When FOXD1 expression was knocked down in CAL27 and SCC25 cells, the migration, invasion, colony formation, sphere formation, and proliferation abilities decreased. Moreover, EMT and stemness-related markers changed remarkably, which indicated that the EMT process and cell stemness were inhibited. Conversely, overexpression of FOXD1 promoted EMT and cell stemness. Further study demonstrated that FOXD1 could bind to the promoter region and activate the transcription of SNAI2. In turn, the elevated SNAI2 affected EMT and cell stemness. An in vivo study showed that FOXD1-overexpressing CAL27 cells possessed a stronger tumorigenic ability.

Conclusions
Our findings revealed a novel mechanism in regulating EMT and cell stemness and proposed FOXD1 as a potential marker for the diagnosis and treatment of OSCC.
Management of proximal femur fractures in the elderly: current concepts and treatment options
Authors: Fischer H. , Maleitzke T. , Eder C. , Ahmad S. , Stöckle U. , Braun K. F. 
Published: August 2021

AbstractAs one of the leading causes of elderly patients’ hospitalisation, proximal femur fractures (PFFs) will present an increasing socioeconomic problem in the near future. This is a result of the demographic change that is expressed by the increasing proportion of elderly people in society. Peri-operative management must be handled attentively to avoid complications and decrease mortality rates. To deal with the exceptional needs of the elderly, the development of orthogeriatric centres to support orthogeriatric co-management is mandatory. Adequate pain medication, balanced fluid management, delirium prevention and the operative treatment choice based on comorbidities, individual demands and biological rather than chronological age, all deserve particular attention to improve patients’ outcomes. The operative management of intertrochanteric and subtrochanteric fractures favours intramedullary nailing. For femoral neck fractures, the Garden classification is used to differentiate between non-displaced and displaced fractures. Osteosynthesis is suitable for biologically young patients with non-dislocated fractures, whereas total hip arthroplasty and hemiarthroplasty are the main options for biologically old patients and displaced fractures. In bedridden patients, osteosynthesis might be an option to establish transferability from bed to chair and the restroom. Postoperatively, the patients benefit from early mobilisation and early geriatric care. During the COVID-19 pandemic, prolonged time until surgery and thus an increased rate of complications took a toll on frail patients with PFFs. This review aims to offer surgical guidelines for the treatment of PFFs in the elderly with a focus on pitfalls and challenges particularly relevant to frail patients.
The Swedish RAND-36: psychometric characteristics and reference data from the Mid-Swed Health Survey
Authors: Ohlsson-Nevo Emma , Hiyoshi Ayako , Norén Paulina , Möller Margareta , Karlsson Jan 
Published: August 2021

Abstract
Background
This study aims to evaluate data quality, scaling properties, and reliability of the Swedish RAND-36 in a general population sample and to present reference data for the Swedish population.

Methods
Testing of data quality, scaling assumptions and reliability followed methods recommended for the International Quality of Life Assessment Project, previously used for psychometric testing of SF-36 and RAND-36. Data were collected via regular mail for a random stratified sample of the general population in a Swedish county. Weighted means for RAND-36 scores were used and differences by sex, age, education, and occupational groups were tested.

Results
The response rate was 42%, and the sample comprised 3432 persons (45% men, 55% women) with a median age of 56.9 years. The internal consistency reliability was satisfactory, with Cronbach’s alphas > 0.80 for all eight scales. The percentage of missing items was low, ranging between 1.3% and 3.2%. No floor effects (≥15%) were noted, while ceiling effects were observed for physical functioning, role-functioning/physical, pain, role-functioning/emotional, and social functioning. Item–scale correlations were satisfactory (r ≥ 0.40). Correlations among the physical health scales were strong (range 0.58–0.68) as were the correlations among the mental health scales (range 0.58–0.73). Men reported significantly better health-related quality of life (HRQoL) on all scales, although the gender differences were small. Comparisons among age groups showed approximately equal scores among those 20–29, 30–39, and 40–49 years, while significant decreases in physical health were observed in the older age groups. Substantially worse physical health scores were observed in the oldest age group (80+). Significant differences among age groups were noted also for the mental health scales; however, better energy/fatigue and emotional well-being scores were seen in the older age groups, except for the oldest (80+). Those with university education reported significantly better scores on all scales compared to those with mandatory education.

Conclusions
The study suggests that the Swedish version of RAND-36 is an acceptable and reliable instrument for measuring HRQoL in the general population. The study provides reference data that can be used for norm-based comparisons.
Whistleblowing on photovoltaic operations in Nigeria: panacea for sustainable development
Authors: Okoro Ugochukwu K. , Chineke Theo Chidiezie 
Published: August 2021

Abstract
Background
There is no gainsaying about the importance of energy to the growth, development and socioeconomic well-being of any society. Photovoltaics (PV) have been identified not only as a means of meeting the energy needs of the Nigerian population but also as a tool in its national development. In this study, we reviewed the policy efforts of Nigeria in improving the renewable energy spread and the PV operations and utilization across the country.

Results
The technical audit of PV operations in Nigeria is evaluated using questionnaires administered in the 27 Local Government Areas in Imo State, as a case study. The component items in the latent variable scales of the audit have been tested for internal consistency using the Cronbach’s alpha. The good variable scale “Appropriateness for energy need” indicated a dissenting perception, whereas the acceptable variable scales “Adequacy in energy efficiency” and “Sustainability of PV project” indicated significant confidence in their perceptions. The perception in the energy need, which is associated with the limitations in PV utilization, is perceived as wrongdoings.

Conclusions
The whistleblowing policy is advocated as a germane measure to reduce or stop these wrongdoings and improve PV utilization and spread in Nigeria.
Effect of tourniquet application on cement penetration in primary total knee arthroplasty: a meta-analysis
Authors: Yao Shuxin , Zhang Weijie , Ma Jianbing , Wang Jianpeng 
Published: August 2021

AbstractBackgroundTourniquet application is expected to improve surgery exposure and cementation process in total knee arthroplasty (TKA) but its effectiveness remains controversial and needs to be further explored. The aim of this meta-analysis was to assess the effect of tourniquet in primary TKA. The hypothesis is that the tourniquet application affects the cement penetration in TKA.MethodsA search was conducted in PubMed, Embase, and the Cochrane Library for the potentially eligible articles. Two independent researchers reviewed the articles retrieved against the pre-designed inclusion and exclusion criteria. In primary TKA, cement penetration was assessed, and the data between the tourniquet-assisted and non-tourniquet-assisted TKAs were compared. Statistical significance was set atP < 0.05.ResultsA total of 4 randomized controlled trials and 3 non-randomized controlled trials (involving 675 patients) were included. There was no significant difference between the tourniquet-assisted and non-tourniquet-assisted TKAs in terms of cement penetration (P > 0.05). There were no significant differences in the total surgical time, blood loss, blood transfusion, the Knee Society Score, and the visual analogue scale (VAS) between the two kinds of procedures (P > 0.05).ConclusionsTourniquet application may not affect cement penetration in primary TKA and may not help reduce blood loss, ease knee pain or improve the knee function. A surgeon may choose to use a tourniquet or not according to his or her own preference.Level of EvidenceLevel Ib, meta-analysis.
From spectral broadening to recompression: dynamics of incoherent optical waves propagating in the fiber
Authors: Ye Jun , Ma Xiaoya , Zhang Yang , Xu Jiangming , Zhang Hanwei , Yao Tianfu , Leng Jinyong , Zhou Pu 
Published: August 2021

AbstractInterplay between dispersion and nonlinearity in optical fibers is a fundamental research topic of nonlinear fiber optics. Here we numerically and experimentally investigate an incoherent continuous-wave (CW) optical field propagating in the fiber with normal dispersion, and introduce a distinctive spectral evolution that differs from the previous reports with coherent mode-locked fiber lasers and partially coherent Raman fiber lasers [Nat. Photonics 9, 608 (2015).]. We further reveal that the underlying physical mechanism is attributed to a novel interplay between group-velocity dispersion (GVD), self-phase modulation (SPM) and inverse four-wave mixing (IFWM), in which SPM and GVD are responsible for the first spectral broadening, while the following spectral recompression is due to the GVD-assisted IFWM, and the eventual stationary spectrum is owing to the dominant contribution of GVD effect. We believe this work can not only expand the light propagation in the fiber to a more general case and help advance the physical understanding of light propagation with different statistical properties, but also benefit the applications in sensing, telecommunications and fiber lasers.
Prenatal Androgen Exposure Alters KNDy Neurons and Their Afferent Network in a Model of Polycystic Ovarian Syndrome
Authors: Moore Aleisha M , Lohr Dayanara B , Coolen Lique M , Lehman Michael N 
Published: August 2021

Abstract
Polycystic ovarian syndrome (PCOS), the most common endocrinopathy affecting women worldwide, is characterized by elevated luteinizing hormone (LH) pulse frequency due to the impaired suppression of gonadotrophin-releasing hormone (GnRH) release by steroid hormone negative feedback. Although neurons that co-express kisspeptin, neurokinin B, and dynorphin (KNDy cells) were recently defined as the GnRH/LH pulse generator, little is understood about their role in the pathogenesis of PCOS. We used a prenatal androgen-treated (PNA) mouse model of PCOS to determine whether changes in KNDy neurons or their afferent network underlie altered negative feedback. First, we identified elevated androgen receptor gene expression in KNDy cells of PNA mice, whereas progesterone receptor and dynorphin gene expression was significantly reduced, suggesting elevated androgens in PCOS disrupt progesterone negative feedback via direct actions upon KNDy cells. Second, we discovered GABAergic and glutamatergic synaptic input to KNDy neurons was reduced in PNA mice. Retrograde monosynaptic tract-tracing revealed a dramatic reduction in input originates from sexually dimorphic afferents in the preoptic area, anteroventral periventricular nucleus, anterior hypothalamic area and lateral hypothalamus. These results reveal 2 sites of neuronal alterations potentially responsible for defects in negative feedback in PCOS: changes in gene expression within KNDy neurons, and changes in synaptic inputs from steroid hormone-responsive hypothalamic regions. How each of these changes contribute to the neuroendocrine phenotype seen in in PCOS, and the role of specific sets of upstream KNDy afferents in the process, remains to be determined.
Phosphorylated cingulin localises GEF-H1 at tight junctions to protect vascular barriers in blood endothelial cells
Authors: Holzner Silvio , Bromberger Sophie , Wenzina Judith , Neumüller Karin , Holper Tina-Maria , Petzelbauer Peter , Bauer Wolfgang , Weber Benedikt , Schossleitner Klaudia 
Published: August 2021

ABSTRACT
Dysfunction of vascular barriers is a critical step in inflammatory diseases. Endothelial tight junctions (TJs) control barrier function, and the cytoplasmic adaptor protein cingulin connects TJs to signalling pathways. However, local events at TJs during inflammation are largely unknown. In this study, we investigate the local response of TJ adaptor protein cingulin and its interaction with Rho guanine nucleotide exchange factor H1 (GEF-H1, also known as ARHGEF2) upon vascular barrier disruption to find a new approach to counteract vascular leak. Based on transendothelial-electrical-resistance (TEER) measurements, cingulin strengthened barrier integrity upon stimulation with histamine, thrombin and VEGF. Cingulin also attenuated myosin light chain 2 (MLC2; also known as MYL2) phosphorylation by localising GEF-H1 to cell junctions. By using cingulin phosphomutants, we verified that the phosphorylation of the cingulin head domain is required for its protective effect. Increased colocalisation of GEF-H1 and cingulin was observed in the vessels of vasculitis patients compared to those in healthy skin. Our findings demonstrate that cingulin can counteract vascular leak at TJs, suggesting the existence of a novel mechanism in blood endothelial cells that protects barrier function during disease.
High-risk human-caused pathogen exposure events from 1975-2016
Authors: Manheim David , Lewis Gregory 
Published: August 2021

Biological agents and infectious pathogens have the potential to cause very significant harm, as the natural occurrence of disease and pandemics makes clear. As a way to better understand the risk of Global Catastrophic Biological Risks due to human activities, rather than natural sources, this paper reports on a dataset of 71 incidents involving either accidental or purposeful exposure to, or infection by, a highly infectious pathogenic agent. There has been significant effort put into both reducing the risk of purposeful spread of biological weapons, and biosafety intended to prevent the exposure to, or release of, dangerous pathogens in the course of research. Despite these efforts, there are incidents of various types that could potentially be controlled or eliminated by different lab and/or bioweapon research choices and safety procedures. The dataset of events presented here was compiled during a project conducted in 2019 to better understand biological risks from anthropic sources. The events which are listed are unrelated to clinical treatment of naturally occurring outbreaks, and are instead entirely the result of human decisions and mistakes. While the events cover a wide range of cases, the criteria used covers a variety of events previously scattered across academic, policy, and other unpublished or not generally available sources.
Reverse transcription PCR to detect low density malaria infections
Authors: Christensen Peter , Bozdech Zbynek , Watthanaworawit Wanitda , Rénia Laurent , Malleret Benoît , Ling Clare , Nosten François 
Published: August 2021

Background: Targeted malaria elimination strategies require highly sensitive tests to detect low density malaria infections (LDMI). Commonly used methods for malaria diagnosis such as light microscopy and antigen-based rapid diagnostic tests (RDTs) are not sensitive enough for reliable identification of infections with parasitaemia below 200 parasites per milliliter of blood. While targeted malaria elimination efforts on the Thailand-Myanmar border have successfully used high sample volume ultrasensitive quantitative PCR (uPCR) to determine malaria prevalence, the necessity for venous collection and processing of large quantities of patient blood limits the widespread tractability of this method. Methods: Here we evaluated a real-time reverse transcription PCR (RT-qPCR) method that reduces the required sample volume compared to uPCR. To do this, 304 samples collected from an active case detection program in Kayin state, Myanmar were compared using uPCR and RT-qPCR. Results: Plasmodium spp. RT-qPCR confirmed 18 of 21 uPCR Plasmodium falciparum positives, while P. falciparum specific RT-qPCR confirmed 17 of the 21 uPCR P. falciparum positives. Combining both RT-qPCR results increased the sensitivity to 100% and specificity was 95.1%. Conclusion: Malaria detection in areas of low transmission and LDMI can benefit from the increased sensitivity of ribosomal RNA detection by RT-PCR, especially where sample volume is limited. Isolation of high quality RNA also allows for downstream analysis of malaria transcripts.
Association of abnormal fetal echocardiography with some obstetric records
Authors: Najafian Mahin , Barati Mojgan , Aberumand Sareh , Nasehi Nahal , Emami-moghaddam Abdolrahman 
Published: August 2021

Background To evaluate the history of some obstetrical records of pregnant women who were referred for fetal echocardiography for any reason. Methods This was a retrospective study on 1772 documents of referred pregnant women, which was conducted in Narges diagnostic clinic staff (Ahvaz city, Iran) from 2017-2020. In this study, all document data of pregnant women who referred for fetal echocardiography for any reason have been reviewed. Results Our study showed that there is a significant relationship between abnormal fetal echocardiography with history of miscarriage, stillbirth and a previous child with Down syndrome. Conclusion Although our study showed that abnormal fetal echocardiography was associated with stillbirth, miscarriage, and a history of having a previous child with Down syndrome, but many cases had abnormal echocardiography didn't have a history of having a previous child with CHD, increased NT and high-risk aneuploidy screening test.
Changing the tide: influencing factors for midwives on vaginal breech birth skill acquisition
Authors: Furtado Vairi , Kitson-Reynolds Ellen 
Published: August 2021

BackgroundBreech presentation at term occurs in 3%–5% of pregnancies. Many midwives are not skilled in vaginal breech births which affects the safety of vaginal breech birth. This research study begins to explore the influencing factors for skill attainment and potential areas for change to enhance education and competence.MethodThis was a small exploratory qualitative study that used a focus group with four participants for data collection.FindingsThe influence of internal and external factors in midwives' competence are represented by a ‘continuum of change’ and by moving from a place of fear to one of educational enlightenment. This encompasses three themes: ‘not a good place’, ‘changing the tide’ and ‘new normal’.ConclusionEducation of student midwives and registered midwives is key in creating a safe space for vaginal breech births. Introducing normal physiology early in curriculums can impact the initial framing of vaginal breech birth. The uptake of specialised physiological breech birth training by registered midwives and other birth practitioners is upskilling all practitioners.