bluuebunny/crossref_metadata_2025_split huggingface dataset:
GnRH antagonist weakens endometrial stromal cells growth ability by decreasing c-kit receptor expression
Authors: Xu Ding-Fei , Liu Pei-Pei , Fan Lu , Xie Qi , Zhang Zhi-Qin , Wang Li-Qun , Wu Qiong-Fang , Tan Jun 
Published: February 2022

Abstract
Background
Several surveys have reported that patients treated with gonadotropin-releasing hormone antagonist (GnRH-ant) protocol showed a significantly lower rate of implantation and clinical pregnancy compared to GnRH agonist (GnRH-a) protocol during in vitro fertilization-fresh embryo transfer. Subsequent studies imputed this poor outcome to the negative effects of GnRH-ant on endometrial receptive. However, the mechanisms were not fully understood.

Methods
The clinical data of 2815 patients undergoing fresh embryo transfer in our center were analyzed. Human endometrial stromal cells (ESCs) from healthy women undergoing elective pregnancy termination of a normal pregnancy at 8–10 weeks gestation were treated with GnRH-analogs or imatinib (c-kit receptor inhibitor). CCK8 and Flow cytometry were used to investigated the growth ability of ESCs. Immunofluorescence staining and western blot was used to detected the target proteins.

Results
The clinical data showed that the endometrial thickness on HCG Day were significantly lower in GnRH-ant group. Although no difference of embryo quality in these two groups, GnRH-ant group showed remarkably decreased rate of HCG positive, embryo implantation and pregnancy. Moreover, GnRH-ant significantly reduced the proliferation and induced the apoptosis of ESCs. Furthermore, the expression and activation of c-kit receptor, which played pivotal roles during embryo implantation, were observably decreased by GnRH-ant. Inhibiting the activation of c-kit by imatinib remarkably suppressed the proliferation and promoted the apoptosis of ESCs. Additionally, the phosphorylation of AKT and expression of Cyclin D1, which were closely related with cellular growth, were distinctly lessened after treating with imatinib.

Conclusions
In summary, our study showed that GnRH-ant weakened the activization of c-kit receptor by decreasing its expression, causing the impaired growth ability of ESCs. Our findings provided a new insight into the effects of GnRH-ant on endometrium.
Building global capacity for COVID-19 vaccination through interactive virtual learning
Authors: Goldin Shoshanna , Hood Nancy , Pascutto Alexandre , Bennett Celine , Barbosa de Lima Ana Carolina , Devereaux Nicole , Caric Aleksandra , Rai Karan , Desai Shalini , Lindstrand Ann , Struminger Bruce 
Published: February 2022

Abstract
Background
To support the introduction of the COVID-19 vaccine, the World Health Organization and its partners developed an interactive virtual learning initiative through which vaccination stakeholders could receive the latest guidance, ask questions, and share their experiences. This initiative, implemented between 9 February 2021 and 15 June 2021, included virtual engagement between technical experts and participants during a 15-session interactive webinar series as well as web and text-messaging discussions in English and French.

Methods
This article uses a mixed-methods approach to analyze survey data collected following each webinar and a post-series survey conducted after the series had concluded. Participant data were tracked for each session, and feedback surveys were conducted after each session to gauge experience quality and content usability. Chi-square tests were used to compare results across professions (health workers, public health practitioners, and others).

Results
The COVID-19 Vaccination: Building Global Capacity webinar series reached participants in 179 countries or 93% of the WHO Member States; 75% of participants were from low- and middle-income countries. More than 60% of participants reported using the resources provided during the sessions, and 47% reported sharing these resources with colleagues. More than 79% of participants stated that this initiative significantly improved their confidence in preparing for and rolling out COVID-19 vaccinations; an additional 20% stated that the initiative “somewhat” improved their confidence. In the post-series survey, 70% of participants reported that they will “definitely use” the knowledge derived from this learning series in their work; an additional 20% will “probably use” and 9% would “possibly use” this knowledge in their work.

Conclusion
The COVID-19 Vaccination: Building Global Capacity learning initiative used a digital model of dynamic, interactive learning at scale. The initiative enhanced WHO’s ability to disseminate knowledge, provide normative guidance, and share best practices to COVID-19 vaccination stakeholders in real time. This approach allowed WHO to hear the information needs of stakeholders and respond by developing guidance, tools, and training to support COVID-19 vaccine introduction. WHO and its partners can learn from this capacity-building experience and apply best practices for digital interactive learning to other health programs moving forward.
The effect of Ebola virus disease on maternal health service utilisation and perinatal outcomes in West Africa: a systematic review
Authors: Kassa Zemenu Yohannes , Scarf Vanessa , Fox Deborah 
Published: February 2022

Abstract
Background
Ebola outbreaks pose a major threat to global public health, especially in Sub-Saharan Africa. These outbreaks disrupt the already fragile maternal health services in West Africa. The aims of this study is to assess the effect of Ebola virus disease (EVD) on maternal health service utilisation and perinatal outcomes.

Methods
This systematic review was conducted in West Africa, and the databases used were Medline, PubMed, CINAHL, Scopus, EMBASE and African journals online. Studies that reported the effect of the Ebola outbreak on maternal health services in West Africa were eligible for this systematic review. The search was limited to articles written in the English language only and published between 2013 and 2020. Three authors independently appraised the articles, and the data were extracted using a standardised data extraction format. The findings were synthesised using a narrative summary, tables, and figures.

Results
Twelve studies met the inclusion criteria and were used for this systematic review synthesis. The results showed that antenatal care significantly decreased during Ebola virus disease and strove to recover post-Ebola virus disease. Women were less likely to have institutional childbirth during Ebola virus disease and struggled to recover post-Ebola virus disease. In addition, this review revealed a substantially higher rate of maternal mortality post EVD than those observed before or during the outbreak.

Conclusion
Based on our findings, antenatal care, institutional childbirth, and postnatal care are attempting to recover post-Ebola virus disease. We recommended that responsible bodies and stakeholders need to prepare locally tailored interventions to increase the number of women attending ANC, institutional childbirth, and PNC services post-EVD and future outbreaks including COVID-19. In order to build trust, creating community networks between health care providers and trusted community leaders may increase the number of women attending antenatal care (ANC), institutional childbirth and postnatal care (PNC) post-EVD and during future outbreaks. Further studies are needed to examine health centre and hospital availability and accessibility, and capacity to deliver maternal health services post-Ebola virus disease and future outbreaks.
How can we consider variable RBE and LETd prediction during clinical practice? A pediatric case report at the Normandy Proton Therapy Centre using an independent dose engine
Authors: Mein Stewart , Kopp Benedikt , Vela Anthony , Dutheil Pauline , Lesueur Paul , Stefan Dinu , Debus Jürgen , Haberer Thomas , Abdollahi Amir , Mairani Andrea , Tessonnier Thomas 
Published: February 2022

Abstract
Background
To develop an auxiliary GPU-accelerated proton therapy (PT) dose and LETd engine for the IBA Proteus®ONE PT system. A pediatric low-grade glioma case study is reported using FRoG during clinical practice, highlighting potential treatment planning insights using variable RBE dose (DvRBE) and LETd as indicators for clinical decision making in PT.

Methods
The physics engine for FRoG has been modified for compatibility with Proteus®ONE PT centers. Subsequently, FRoG was installed and commissioned at NPTC. Dosimetric validation was performed against measurements and the clinical TPS, RayStation (RS-MC). A head patient cohort previously treated at NPTC was collected and FRoG forward calculations were compared against RS-MC for evaluation of 3D-Γ analysis and dose volume histogram (DVH) results. Currently, treatment design at NPTC is supported with fast variable RBE and LETd calculation and is reported in a representative case for pediatric low-grade glioma.

Results
Simple dosimetric tests against measurements of iso-energy layers and spread-out Bragg Peaks in water verified accuracy of FRoG and RS-MC. Among the patient cohort, average 3D-Γ applying 2%/2 mm, 3%/1.5 mm and 5%/1 mm were > 97%. DVH metrics for targets and OARs between FRoG and RayStation were in good agreement, with ∆D50,CTV and ∆D2,OAR both ⪅1%. The pediatric case report demonstrated implications of different beam arrangements on DvRBE and LETd distributions. From initial planning in RayStation sharing identical optimization constraints, FRoG analysis led to plan selection of the most conservative approach, i.e., minimized DvRBE,max and LETd,max in OARs, to avoid optical system toxicity effects (i.e., vision loss).

Conclusion
An auxiliary dose calculation system was successfully integrated into the clinical workflow at a Proteus®ONE IBA facility, in excellent agreement with measurements and RS-MC. FRoG may lead to further insight on DvRBE and LETd implications to help clinical decision making, better understand unexpected toxicities and establish novel clinical procedures with metrics currently absent from the standard clinical TPS.
Similarities and differences between rat and mouse chondrocyte gene expression induced by IL-1β
Authors: Ding Dao-Fang , Xue Yan , Zhang Jun-Peng , Zhang Zeng-Qiao , Li Wen-Yao , Cao Yue-Long , Xu Jian-Guang 
Published: February 2022

Abstract
Background
Osteoarthritis (OA) is the most prevalent degenerative joint disease. In vitro experiments are an intuitive method used to investigate its early pathogenesis. Chondrocyte inflammation models in rats and mice are often used as in vitro models of OA. However, similarities and differences between them in the early stages of inflammation have not been reported.

Objective
This paper seeks to compare the chondrocyte phenotype of rats and mice in the early inflammatory state and identify chondrocytes suitable for the study of early OA.

Methods
Under similar conditions, chondrocytes from rats and mice were stimulated using the same IL-1β concentration for a short period of time. The phenotypic changes of chondrocytes were observed under a microscope. The treated chondrocytes were subjected to RNA-seq to identify similarities and differences in gene expression. Chondrocytes were labelled with EdU for proliferation analysis. Cell proliferation-associated proteins, including minichromosome maintenance 2 (MCM2), minichromosome maintenance 5 (MCM5), Lamin B1, proliferating cell nuclear antigen (PCNA), and Cyclin D1, were analysed by immunocytochemical staining, cell immunofluorescence, and Western blots to verify the RNA-seq results.

Results
RNA-seq revealed that the expression patterns of cytokines, chemokines, matrix metalloproteinases, and collagen were similar between the rat and mouse chondrocyte inflammation models. Nonetheless, the expression of proliferation-related genes showed the opposite pattern. The RNA-seq results were further verified by subsequent experiments. The expression levels of MCM2, MCM5, Lamin B1, PCNA, and Cyclin D1 were significantly upregulated in rat chondrocytes (P < 0.05) and mouse chondrocytes (P < 0.05).

Conclusions
Based on the findings, the rat chondrocyte inflammation model may help in the study of the early pathological mechanism of OA.
Caregivers’ experience of sleep management in Smith–Magenis syndrome: a mixed-methods study
Authors: Agar Georgie , Bissell Stacey , Wilde Lucy , Over Nigel , Williams Caitlin , Richards Caroline , Oliver Chris 
Published: February 2022

Abstract
Background
Smith–Magenis syndrome (SMS) is a rare genetic syndrome associated with a unique profile of early morning waking and daytime sleepiness. Children with SMS evidence high rates of self-injury and aggression and have a preference for adult over peer attention, with strong motivation to interact with a particular caregiver. In addition, people with SMS have lower adaptive functioning skills relative to cognitive abilities and demonstrate high levels of impulsivity. Taken together, these factors may result in individuals being awake overnight requiring vigilant caregiver supervision. Despite these complexities, no study has described the strategies caregivers take to keep their children with SMS safe overnight or considered the impact of these experiences on caregivers or the wider family.

Methods
The current study used a mixed-methods approach to consider sleep management strategies and challenges for caregivers of people with SMS at different ages. Caregivers completed an international online survey about sleep management and related difficulties, use of interventions and access to services and support. Semi-structured interviews were conducted with 14 caregivers in the UK to increase understanding of caregiver experiences and priorities for change in the UK context. Interviews were transcribed verbatim and coded using thematic analysis.

Results
Evidence from the online survey (n = 40) revealed wide-ranging impacts of poor sleep on the person with SMS and the wider family. Only 5% of caregivers reported that the sleep problems had no impact on their child, and 76% reported a moderately or extremely significant impact on themselves. For some individual caregivers, sleep management difficulties improved over time whereas for others no change was reported. Weekly respite emerged as the ideal provision for 49% of caregivers, although only 14% had access to this. The majority of caregivers (54%) received no respite. Thematic analysis of qualitative interviews revealed interactions between aspects of the behavioural phenotype of SMS which may contribute to complex and unusual presentations in relation to sleep management and safety.

Conclusions
Caregivers’ priorities for sleep management and support were delineated, with key implications for services in terms of the use of SMS-sensitive strategies and respite provision.
CXCR4-targeted nanotoxins induce GSDME-dependent pyroptosis in head and neck squamous cell carcinoma
Authors: Rioja-Blanco Elisa , Arroyo-Solera Irene , Álamo Patricia , Casanova Isolda , Gallardo Alberto , Unzueta Ugutz , Serna Naroa , Sánchez-García Laura , Quer Miquel , Villaverde Antonio , Vázquez Esther , León Xavier , Alba-Castellón Lorena , Mangues Ramon 
Published: February 2022

AbstractBackgroundTherapy resistance, which leads to the development of loco-regional relapses and distant metastases after treatment, constitutes one of the major problems that head and neck squamous cell carcinoma (HNSCC) patients currently face. Thus, novel therapeutic strategies are urgently needed. Targeted drug delivery to the chemokine receptor 4 (CXCR4) represents a promising approach for HNSCC management. In this context, we have developed the self-assembling protein nanotoxins T22-PE24-H6 and T22-DITOX-H6, which incorporate the de-immunized catalytic domain ofPseudomonas aeruginosa(PE24) exotoxin A and the diphtheria exotoxin (DITOX) domain, respectively. Both nanotoxins contain the T22 peptide ligand to specifically target CXCR4-overexpressing HNSCC cells. In this study, we evaluate the potential use of T22-PE24-H6 and T22-DITOX-H6 nanotoxins for the treatment of HNSCC.MethodsT22-PE24-H6 and T22-DITOX-H6 CXCR4-dependent cytotoxic effect was evaluated in vitro in two different HNSCC cell lines. Both nanotoxins cell death mechanisms were assessed in HNSCC cell lines by phase-contrast microscopy, AnnexinV/ propidium iodide (PI) staining, lactate dehydrogenase (LDH) release assays, and western blotting. Nanotoxins antitumor effect in vivo was studied in a CXCR4+HNSCC subcutaneous mouse model. Immunohistochemistry, histopathology, and toxicity analyses were used to evaluate both nanotoxins antitumor effect and possible treatment toxicity. GSMDE and CXCR4 expression in HNSCC patient tumor samples was also assessed by immunohistochemical staining.ResultsFirst, we found that both nanotoxins exhibit a potent CXCR4-dependent cytotoxic effect in vitro. Importantly, nanotoxin treatment triggered caspase-3/Gasdermin E (GSDME)-mediated pyroptosis. The activation of this alternative cell death pathway that differs from traditional apoptosis, becomes a promising strategy to bypass therapy resistance. In addition, T22-PE24-H6 and T22-DITOX-H6 displayed a potent antitumor effect in the absence of systemic toxicity in a CXCR4+subcutaneous HNSCC mouse model. Lastly, GSDME was found to be overexpressed in tumor tissue from HNSCC patients, highlighting the relevance of this strategy.ConclusionsAltogether, our results show that T22-PE24-H6 and T22-DITOX-H6 represent a promising therapy for HNSCC patients. Remarkably, this is the first study showing that both nanotoxins are capable of activating caspase-3/GSDME-dependent pyroptosis, opening a novel avenue for HNSCC treatment.
Effect of Nigella sativa supplementation on kidney function, glycemic control, oxidative stress, inflammation, quality of life, and depression in diabetic hemodialysis patients: study protocol for a double-blind, randomized controlled trial
Authors: Rahmani Alireza , Maleki Vahid , Niknafs Bahram , Tavakoli-Rouzbehani Omid Mohammad , Tarighat-Esfanjani Ali 
Published: February 2022

Abstract
Background and objectives
The kidney is probably the most crucial target of microvascular damage in diabetes, which can ultimately eventuate end-stage renal disease (ESRD). Hemodialysis is the most usual way of renal replacement therapy in ESRD. Patients receiving hemodialysis are susceptible to many complications like hyperglycemia, inflammation, depression, anxiety, and poor quality of life. So, they are constrained to consume many drugs. Medicinal herbs are used in different cultures as a reliable source of natural remedies. This study aims to determine the efficacy of Nigella sativa (NS) oil supplementation on blood glucose, kidney function tests, inflammation, oxidative stress, quality of life, and depression in hemodialysis patients.

Methods and analysis
This double-blind, randomized controlled trial will enroll 46 patients with diabetes mellitus who give hemodialysis thrice a week. Patients who have an inflammatory or infectious disease and who are receiving nonsteroidal anti-inflammatory drugs will be excluded. Patients will be randomized to the treatment and control group, which will be recommended using two soft gels of NS and paraffin oil, respectively. Laboratory tests will be assessed at baseline and end of the study, including fasting blood sugar, glycated albumin, insulin, creatinine, blood urea nitrogen, urea, uric acid, superoxide dismutase, malondialdehyde, total antioxidant capacity, high sensitive C reactive protein, and 24-h urine volume. Also, the kidney disease and quality of life and hospital anxiety and depression scale questionnaires will be evaluated.

Discussion
Previous studies have reported a positive effect of Nigella sativa supplementation in chronic kidney disease, but there is no evidence that this plant is safe in hemodialysis patients. The results of this study can be helpful in better control of blood sugar and kidney function and reduce complications in diabetic hemodialysis patients.

Trial registration
Iranian Registry of Clinical Trials . Registered on 31 May 2020
DNA-based quantification and counting of transmission stages provides different but complementary parasite load estimates: an example from rodent coccidia (Eimeria)
Authors: Jarquín-Díaz Víctor Hugo , Balard Alice , Ferreira Susana Carolina Martins , Mittné Vivian , Murata Julia Mari , Heitlinger Emanuel 
Published: February 2022

AbstractBackgroundCounting parasite transmission stages in faeces is the classical measurement to quantify “parasite load”. DNA-based quantifications of parasite intensities from faecal samples are relatively novel and often validated against such counts. When microscopic and molecular quantifications do not correlate, it is unclear whether oocyst counts or DNA-based intensity better reflects biologically meaningful concepts. Here, we investigate this issue using the example ofEimeria ferrisi(Coccidia), an intracellular parasite of house mice (Mus musculus).MethodsWe performed an infection experiment of house mice withE. ferrisi, in which the intensity of infection correlates with increased health impact on the host, measured as temporary weight loss during infection. We recorded the number of parasite transmissive stages (oocysts) per gram of faeces (OPG) and, as a DNA-based measurement, the number ofEimeriagenome copies per gram of faeces for 10 days post-infection (dpi). We assessed weight loss relative to the day of experimental infection as a proxy of host health and evaluated whether DNA or oocyst counts are better predictors of host health.ResultsAbsolute quantification ofEimeriaDNA and oocyst counts showed similar but slightly diverging temporal patterns during 10 dpi. We detectedEimeriaDNA earlier than the first appearance of oocysts in faeces. Additionally,EimeriaOPGs within each dpi did not explain parasite DNA intensity. Early dpi were characterized by high DNA intensity with low oocyst counts, while late infections showed the opposite pattern. The intensity ofEimeriaDNA was consistently a stronger predictor of either maximal weight loss (1 value per animal during the infection course) or weight loss on each day during the experiment when controlling for between-dpi and between-individual variance.ConclusionsEimeria ferrisioocyst counts correlate weakly with parasite intensity assessed through DNA quantification. DNA is likely partially derived from life-cycle stages other than transmissive oocysts. DNA-based intensities predict health outcomes of infection for the host more robustly than counts of transmissive stages. We conclude that DNA-based quantifications should not necessarily require validation against counts of transmissive stages. Instead, DNA-based load estimates should be evaluated as complementary sources of information with potential specific biological relevance for each host-parasite system.Graphical Abstract