bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and Antitumor Activity Evaluation in Vitro of Novel 5-cyano-6-phenyl-2,4-Disubstituted Pyrimidine Derivatives
Authors: Si Xiaojie , Gao Chao , Chi Lingling , Wang Hao , Zhang Yutong , Dai Honglin , Liu Limin , Wang Zhangjie , Zheng Jiaxin , Ke Yu , Liu Hongmin , Zhang Qiurong 
Published: June 2022

Abstract
In order to search for new antitumor drugs with high efficiency, a series of novel 5-cyano-6phenyl-2,4-disubstituted pyrimidine derivatives were designed, synthesized and evaluated for antiproliferative activity against four human cancer cell lines (MGC-803, PC-3, A549 and H1975) using MTT assay in vitro. Among them, compound N-(3-chloro-4-fluorophenyl)-2-((5-cyano-4phenyl-6-(pyrimidin-2-ylthio) pyrimidin-2-yl) thio) acetamide (15n) showed good anti-tumor proliferation activity against four tested cancer cell lines, with IC50 values of 1.86±0.27μM to PC-3 cell. The antitumor activity was significantly better than that of the positive control 5-Fluorouracil. Further mechanism studies showed that compound (15n) inhibited the clonal formation and migration of PC-3 cells in a concentration dependent manner, and induced PC-3 cell cycle arrest in G0/G1 phase, thereby inhibiting the proliferation of PC-3 cells. At the same time, compound (15n) induced PC-3 cell apoptosis in a concentration dependent and time-dependent manner. When the concentration of compound (15n) is 4 μM, the proportion of apoptotic cells was 66.13%. And compound (15n) promoted the accumulation of reactive oxygen species in PC-3 cells in a concentration dependent manner.
An important tool in lymphedema management: validation of turkish version of the gynecologic cancer lymphedema questionnaire
Authors: abakay hanife , abdulrezzak ümmühan , akbayrak türkan 
Published: June 2022

Abstract
Backround: The aim of this study was to research the reliability and validity of the Turkish version of the Gynecologic Cancer Lymphedema Questionnaire (GCLQ) for individuals with gynecologic cancer.Materials and Method: The study included 60 patients who underwent gynecologic cancer surgery with lower limb lymphedema (LLLE) in the lymphedema group (LE) and 30 who underwent gynecologic cancer surgery without LLLE in the non-LE group. The Turkish adaptation of the GCLQ was completed by considering the cultural adaptation process. For the evaluation of lymphedema, circumference measurement, skin layer thickness and lymphoscintigraphy assessments were performed. The intraclass correlation (ICC) coefficient was calculated for GCLQ test-retest reliability, the Cronbach alpha was calculated for internal consistency reliability and the criteria validity method was used for survey validity.Results: The symptom subsections and total score of the GCLQ, the ICC values for test-retest points were 0.780, 0.968, 0.695, 0.945, 0.896, 0.945, and 0.947. The Cronbach 𝛼 values for internal consistency were 0.928, 0.824, 0.656, 0.429, 0.923 and 0.948 for the subsections. Criteria validity was used for the validity analysis and statistically significant (p<0.05) positive correlations were determined between skin fold thickness measurements and total points on the scale in the LE group for values at the midpoint of the right and left tibial shaft (r=0.336, r=0.284).Conclusion: The GCLQ was determined to be a reliable and valid scale to differentiate patients with LLLE from those without LLLE in a Turkish female population.
Maternity protection for female non-standard workers in South Africa: the case of domestic workers
Authors: Pereira-Kotze Catherine , Doherty Tanya , Faber Mieke 
Published: June 2022

Abstract
Background
Many women work in positions of non-standard employment, with limited legal and social protection. Access to comprehensive maternity protection for all working could ensure that all women and children can access health and social protection. This study aimed to describe the maternity protection benefits available to women in positions of non-standard employment in South Africa, using domestic workers as a case study.
Methods
A qualitative descriptive study design was used. National policy documents containing provisions on maternity protection were identified and analysed. Interviews were conducted with purposively selected key informants. Data extracted from published policy documents and information obtained from interviews were triangulated. A thematic analysis approach was used for evaluation of policy content and analysis of the interviews.
Results
Twenty-nine policy and legislative documents were identified that contain provisions on maternity protection relevant to non-standard workers. These documents together with three key informant interviews and two media releases are used to describe availability and accessibility of maternity protection benefits for non-standard workers in South Africa, using domestic workers as a case study. Maternity protection is available in South Africa for some non-standard workers. However, the components of maternity protection are dispersed through many policy documents and there is weak alignment within government on maternity protection. Implementation, monitoring, and enforcement of existing maternity protection policy is inadequate. It is difficult for non-standard workers in South Africa to access maternity protection benefits, particularly cash benefits. Some non-standard workers in South Africa have unique challenges in accessing maternity protection, for example domestic workers whose place of work is a private household and therefore difficult to monitor.
Conclusion
The heterogeneity of non-standard employment makes it challenging for many women to access maternity protection entitlements. There are policy amendments that could be made and improvements to policy implementation that would improve non-standard workers’ access to maternity protection. Potential long-term benefits to women and children’s health and development could come from making comprehensive maternity protection available and accessible to all women.
A new approach to fixed point methodologies for cyclic contraction mappings in C*-algebra-valued b-metric spaces
Authors: Rashwan Rashwan A. , Omran Saleh , Hammad Hasanen A. , Gamal Mohamed 
Published: June 2022

Abstract
In this manuscript, we focused our attention on extracting some fixed point results for cyclic contraction mappings under a new contractive condition in the context of C*-algebra. These results are considered a generalization and extension of some results in the literature such as the results of Banach, Kannan and Chatterjea in the setting of C*-algebra valued b-metric space (shortly C*-algebra Vb − MS). We present some new definitions and nontrivial examples to support our main results.Mathematics Subject Classification: 47H10, 46L07.
COVID-19 vaccination acceptance in underserved urban areas of Islamabad and Rawalpindi: Results from a cross-sectional survey
Authors: Kazmi Twangar , Khan Adnan Ahmad , Abdullah Mujahid , Safdar Rana Muhammad , Afzal Sabeen , Khan Ayesha 
Published: June 2022

Abstract
Background:
Urban slums are home to a significant number of marginalized individuals and are often excluded from public services. This study explores the determinants of willingness and uptake of COVID-19 vaccines in urban slums in Pakistan.
Methods:
The study is a cross-sectional survey of 1760 individuals from five urban slums in Rawalpindi and Islamabad. The survey was conducted between June 16 and 26, 2021 to ask about the experience of COVID-19 infection, willingness and registrations to receive, and actual vaccinations.
Results:
A prior experience of COVID-19 infection was uncommon in any locality in that only 2–17% had encountered the infection themselves or by a family member. Willingness to receive vaccination and uptake correlated with increasing age, education, employment, prior infection in the family (but not self), family vaccination, and knowing of and living close to a vaccination center. Both willingness and vaccination were the lowest in the two informal settlements that are the furthest from public facilities.
Conclusions:
We found low lived experience with COVID-19 infection in urban slums, which was associated with moderate willingness and low vaccination rates. Interventions that seek to vaccinate individuals against COVID-19 must account for urban poor settlement populations and overcome structural barriers such as distance from vaccination services, perhaps by bringing such services to these communities.
Improved Delivery of Mcl-1 and survivin siRNA combination in breast cancer cells with additive siRNA complexes
Authors: Santadkha Tinnabhop , Skolpap Wanwisa , K.C. Remant , Ansari Aysha , Kucharski Cezary , Uludağ Hasan 
Published: June 2022

Abstract
This study aimed at investigating the influence of commercial transfection reagents (Prime-Fect, Leu-Fect A, and Leu-Fect C) complexed with different siRNAs (CDC20, HSP90, Mcl-1 and Survivin) in MDA-MB-436 breast cancer cells and the impact of incorporating an anionic additive, Trans-Booster, for improving in vitro gene silencing and delivery efficiency. Gene silencing was quantitatively analyzed by real-time RT-PCR while cell proliferation and siRNA uptake were evaluated by the MTT assay and flow cytometry, respectively. Amongst the investigated siRNAs and transfection reagents, Mcl-1/Prime-Fect complexes showed the highest inhibition of cell viability and most effective siRNA delivery. The effect of various formulations on transfection efficiency showed that a anionic additive with 1:1 ratio with siRNA was optimal achieving the lowest cell viability compared to untreated cells and negative control siRNA treatment (p<0.05). Furthermore, the combination of Mcl-1 and survivin siRNA suppressed the growth of MDA-MB-436 cells more effectively than treatment with the single siRNAs and resulted in a cell viability as low as ~20% (vs. non-treated cells). This aligned well with the induction of apoptosis as analyzed by flow cytometry, which revealed higher apoptotic cells with the combination treatment group. We conclude that commercial transfection reagents formulated with Mcl-1/Survivin siRNA combination could serve as a potent anti-proliferation agent in treatment of breast cancers.
Changes in plasma fatty acids profile in hyperketonemic ewes during early lactation revealed by gas chromatography (GC) technique
Authors: Lisuzzo Anastasia , Fiore Filippo , Harvatine Kevin , Mazzotta Elisa , Berlanda Michele , Spissu Nicoletta , Badon Tamara , Contiero Barbara , Moscati Livia , Fiore Enrico 
Published: June 2022

Abstract
The transition from late pregnancy to early lactation is characterized by marked changes in energy balance of dairy ruminants. The mobilization of adipose tissue led to an increase in plasma non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHB). The aim of this study was to analyze the total plasma fatty acids of healthy and hyperketonemic dairy ewes in early lactation through gas chromatography (GC) to evaluate metabolic alterations. An observational study was used with a cross-sectional experimental design. Forty-six Sarda dairy ewes were enrolled in the immediate post-partum (7±3 days in milk) and divided into two groups according to serum BHB concentration: non-hyperketonemic group (n=28; BHB<0.86 mmol/L) and hyperketonemic group (n=18; BHB≥0.86 mmol/L). A two-way ANOVA included the effect of group and parity was used to evaluate differences in fatty acids concentrations. A total of 34 plasma fatty acids was assessed using GC. Among them, twelve fatty acids were significant and three tended to significance. Only NEFA concentration and stearic acid were influenced by parity. The study revealed relationships with lipid metabolism, inflammatory and immune responses. In conclusion, GC represents a useful tool in the study of hyperketonemia and primiparous dairy ewes might show a greater risk to develop this disease.
Public Engagement in Micro-Hydro Technology in Central Java, Indonesia
Authors: Pradheksa Pratama Yudha , Arimbi Putri Cahya 
Published: June 2022

Abstract
* Indonesia's abundance of rivers and waterfalls boosted the potential for micro-hydro in remote areas.* Public engagement in micro-hydro is important to Indonesia's decarbonization targets.* The engagement has been driven mostly by social and economic concerns, as well as environmental ones.* Micro-hydro development requires equitable engagement between local stakeholders and credential experts, supported by decentralized regulations.
The faunal Ponto-Caspianization of European waterways
Authors: Soto Ismael , Cuthbert Ross N. , Ricciardi Anthony , Ahmed Danish A. , Altermatt Florian , Archambaud-Suard Gaït , Bonada Núria , Cañedo-Argüelles Miguel , Csabai Zoltan , Datry Thibault , Dick Jaimie T. A. , Floury Mathieu , Forio Marie Anne Eurie , Forcellini Maxence , Fruget Jean-François , Gallardo Belinda , Goethals Peter , Haase Peter , Hudgins Emma J. , Jones J. Iwan , Kouba Antonín , Leitner Patrick , Lizée Marie-Helène , Maire Anthony , Murphy John F. , Ozolins Davis , Rasmussen Jes Jessen , Schäfer Ralf , Schmidt-Kloiber Astrid , Skuja Agnija , Stubbington Rachel , Lee Gea H. Van der , Vannevel Rudy , Várbíró Gábor , Verdonschot Ralf C. M. , Welti Ellen A.R. , Wiberg-Larsen Peter , Haubrock Phillip J. , Briski Elizabeta 
Published: June 2022

Abstract
As alien invasive species are a key driver of biodiversity loss, understanding patterns of rapidly changing global species compositions depends upon knowledge of biological invasion dynamics and trends. The Ponto-Caspian region is among the most notable donor regions for aquatic invasive species in Europe. Using macroinvertebrate time series collected over 52 years (1968–2020) at 265 sites across 11 European countries, we examined the occurrences, invasion rates and interspecific interactions of freshwater Ponto-Caspian fauna, as well as biotic homogenization trends in European waterways. According to our data, Ponto-Caspian macroinvertebrates increased from two species in 1972 to 29 species in 2012 and we found a greater richness of invading Ponto-Caspian macroinvertebrates in datasets collected closer to the source region. This may reflect dispersal lag times, indicating that more distant sites will be increasingly invaded in the future. The pioneering Ponto-Caspian species that arrived first were often bivalves (46.5% of cases), particularly Dreissena polymorpha, followed secondarily by amphipods (83.8%; primarily Chelicorophium curvispinum and Dikerogammarus villosus). With increasing invasions, the time between consecutively-appearing invaders decreased six-fold, indicating potential facilitations that improved invasion success of subsequent taxa. We detected a negative relationship between the abundance trends of the first and second Ponto-Caspian macroinvertebrate species, suggesting that interactions between these species are asymmetrical, with the initial invader facilitating the subsequent invader at the potential cost of its own population growth rate. Lastly, we found that macroinvertebrate communities became increasingly similar over time. European invasion rates from the Ponto-Caspian region suggest a high potential for future invasions from this region, with more hotspots and donor regions likely emerging.
Mullerian adenosarcoma: clinicopathologic and molecular characterization highlighting recurrent BAP1 loss and distinctive features of high-grade tumors
Authors: Boroujeni Amir Momeni , Kertowidjojo Elizabeth , Wu Xinyu , Soslow Robert , Chiang Sarah , Silva Edaise da , Weigelt Britta , Chui M. Herman 
Published: June 2022

Abstract
Mullerian adenosarcoma is an uncommon mesenchymal tumor of the gynecologic tract, usually of uterine origin. Tumors are generally low-grade and associated with good prognosis, whereas high-grade adenosarcomas are rare and less well studied. Herein, we sought to characterize the molecular features of 27 adenosarcomas (primary uterine, n = 19, cervical, n = 3, ovarian, n = 4, peritoneal, n = 1), enriched for high-grade tumors (n = 17) subjected to targeted panel sequencing. Recurrent genetic alterations in adenosarcomas included TP53 mutations (n = 4, 15%), restricted to high-grade cases, BAP1 homozygous deletions (n = 4, 15%), DICER1 mutations (n = 4, 15%), ARID1A mutations (n = 3), TERT promoter mutations (n = 2) and amplification (n = 1), ATRX frameshift mutation/homozygous deletions (n = 3), MDM2 (n = 2), CDK4 (n = 2) and CCNE1 (n = 2) amplifications, as well as alterations involving members of the PI3K (PTEN, n = 3; PIK3CA, n = 4; AKT1, n = 2) and MAPK (KRAS, n = 4, BRAF, n = 2) signaling pathways. One tumor harbored an ESR1-NCOA3 fusion and another had an MLH1 homozygous deletion, associated with loss of MLH1 and PMS2 protein expression. The fraction of genome altered was significantly higher in high-grade compared to low-grade adenosarcomas (P = 0.001). Somatic ATRX frameshift mutations were found in two patients with low-grade adenosarcoma with high-grade recurrences and one case of high-grade adenosarcoma with an adjacent low-grade component. Immunohistochemical analysis for BAP1 revealed loss of nuclear expression in 6/24 (25%) cases, including all 4 tumors with BAP1 deletions. Notably, out of 196 mesenchymal neoplasms of gynecologic origin, BAP1 homozygous deletion was only found in adenosarcomas (4/27,15% adenosarcomas vs 0/169, 0% other mesenchymal neoplasms, P = 0.0003). This study demonstrates that high-grade adenosarcomas are heterogeneous at the molecular level and are characterized by genomic instability and TP53 mutations; ATRX loss may be involved in high-grade transformation of low-grade adenosarcoma; and BAP1 inactivation appears to be a specific pathogenic driver in a subset of adenosarcomas.
A feasibility study on Plantago psyllium L. seed gum electrospinnability: The effect of sonication and gelatin as an auxiliary polymer
Authors: Mohajeri Parisa , Sourki Abdollah Hematian , Nikoo Alireza Mehregan , Gholamhosseinpour Aliakbar , Dalvi-Isfahan Mohsen 
Published: June 2022

Abstract
The authors have requested that this preprint be removed from Research Square.
Sex Differences in Students’ Performance in VR-based Learning of Gross Anatomical Education
Authors: Wang Chao-Ying , Yin Ti , Ma Kuo-Hsing , Shyu Jia-Fwu , Cheng Chia-Pi , Huang Yun-Ling , Chiang Ming-Hsien 
Published: June 2022

Abstract
Background: Studying anatomy has always challenged medical students. The coronavirus disease 2019 pandemic has transformed medical education worldwide, and virtual reality (VR) has recently emerged as a useful learning tool to promote memorization through understanding and visualization. With a remarkable rise in the use of remote learning methods during the pandemic, more schools are adopting distance learning through VR for anatomy. However, scholars have yet to explore the potential sex differences among students who use VR-based anatomical learning. Thus, we investigated the effects of teaching strategies on learners’ experiences with and performance in an anatomy course using VR-based learning. Method: Fifty first-year medical students enrolled in a human anatomy course were provided with VR devices for anatomical learning. They received a questionnaire comprising four determinants of experience: demographic background, discomfort symptoms, satisfaction levels, and opinions about the VR-based learning experience after their final examination. Student performance was then compared to previous performances over three-semester years when traditional teaching methods were used. A three-way mixed-model ANOVA was used to test the effects of sex, examination, and teaching methods on the examination scores. Results: VR-based learning resulted in better exam scores when compared to the traditional learning method. Female students experienced significantly higher disorientation symptoms compared with male students, and male students showed significant improvement in laboratory examination performance. Results showed that VR-based teaching can facilitate gross anatomical learning among first-year medical students and improve the laboratory performance of male students. Conclusion: Medical schools can use VR to teach anatomy effectively; however, faculty should be prepared to support inexperienced users when learning to use a VR system. Future research should further explore sex differences for reliability.
Chemical Inhibition of Mitochondrial Fission Improves Mitochondrial Function and Subdues Hyperglycemia Induced Stress in Placental Trophoblast Cells
Authors: KOLAÇ Umut Kerem , Yalcin Gizem Donmez , Yalcin Abdullah 
Published: June 2022

Abstract
Gestational diabetes mellitus (GDM) is a metabolic complication that affects millions of pregnant women in the world. Placental tissue function is endangered by hyperglycemia during GDM, which is correlated to increased incidences of pregnancy complications. Recently we showed that due to a significant decrease in mitochondrial fusion, mitochondrial dynamics equilibrium is altered in placental tissues from GDM patients. It is not known whether the decrease in mitochondrial fusion causes a decrease in mitochondrial function in placental cells. Here we show that chemical inhibition of mitochondrial fission in cultured placental trophoblast cells leads to an increase in mitochondrial fusion and improves the physiological state of these cells and hence, their capacity to cope in a hyperglycemic environment. Specifically, mitochondrial fission inhibition led to a reduction in reactive oxygen species (ROS) generation, mitochondrial unfolded protein marker expressions, and mitochondrial depolarization. It supported the increase in mitochondrial antioxidant enzyme expressions as well. Mitochondrial fission inhibition also increases the placental cell insulin sensitivity during hyperglycemia. Our results suggest that mitochondrial fusion/fission equilibrium is critical for placental cell function and signify the therapeutic potential of small molecule inhibitors of fission during GDM.
Efficacy and safety of Anlotinib plus PD-1 blockade for the treatment of advanced non-small cell lung cancer: A Retrospective study
Authors: Pan Xiaoting , Dai Anwei 
Published: June 2022

Abstract
Purpose: Both anlotinib and programmed cell death protein 1(PD-1) have been demonstrated anti-tumor efficacy in non-small cell lung cancer (NSCLC) in clinical. However, the number of prospective research of this combination therapy is limited in the literature. In this retrospective study, we aim to evaluate the efficacy and safety of anlotinib plus PD-1 blockade for the treatment of advanced NSCLC patients. Methods: 40 advanced NSCLC patients who received combination treatment at traditional Chinese medicine hospital of Kunshan were selected between January 1, 2020 and December 31, 2021 and 31 eligible patients were screened for further study. Progression free survival (PFS) and overall survival (OS) were the primary end points. The safety of the combination treatment was assessed by the incidence of adverse events. Results: The combined therapeutic regimen of anlotinib and PD-1 blockade in 31 advanced NSCLC patients gained a median PFS of 6.4 months (95% CI 5.4-7.4 months) and the median overall survival(mOS) was 15.4 months (95% CI 13.4-17.4 months). Of all the eligible patients, 4 patients achieved partial respone(PR) and none of these patients achieved complete response(CR). The overall response rate(ORR) and the disease control rate(DCR) were 12.9% and 54.8% respectively. The common adverse events were fatigue, loss of appetite, nausea, hypertension and hand-foot syndrome during the treatment.Conclusion: The combination of anlotinib and PD-1 blockade has promising efficacy for the advanced NSCLC patients and the toxicity is tolerable.