bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contested notions of challenges affecting Community Health Workers in low- and middle-income countries informed by the Silences Framework
Authors: Musoke David , Nyashanu Mathew , Bugembe Henry , Lubega Grace Biyinzika , O’Donovan James , Halage Abdullah Ali , Gibson Linda 
Published: January 2022

AbstractDespite increasing evidence of the challenges affecting Community Health Workers (CHWs) such as those related to training, supportive supervision and remuneration, there is a need to explore concerns and challenges from the perspective of CHWs themselves. This commentary highlights some of the contested and unexplored notions of challenges affecting CHWs in low- and middle-income countries (LMICs) informed by the Silences Framework. This framework defines experiences that are under-explored, misunderstood or difficult to share because of the often invisible power relations within communities, but also in setting the research agenda. These challenges include the heavy workload imposed by several stakeholders, dealing with religious and cultural practices, and gendered barriers of care. The workload of CHWs is a major source of stress and anxiety as they have to balance both government and other stakeholders’ agendas to deliver interventions with their own need to provide for their families for those whose work is unpaid. The tensions of CHWs carrying out their work among members of the community whose religious or cultural beliefs are different from theirs also needs to be considered. Gender issues are an impediment to the work of CHWs, particularly with community members of the opposite sex around sensitive health issues. Lastly, CHWs have found themselves victims of domestic suspicion while fulfilling their duties in communities, such as when seen having conversations with spouses of other individuals in the community. Solutions to these challenges need to be co-produced with CHWs to both to strengthen their relationship with the communities they serve and shape more sustainable interventions for delivery of healthcare in LMICs.
Estimating the impact of donor programs on child mortality in low- and middle-income countries: a synthetic control analysis of child health programs funded by the United States Agency for International Development
Authors: Weiss William , Piya Bhumika , Andrus Althea , Ahsan Karar Zunaid , Cohen Robert 
Published: January 2022

Abstract
Background
Significant levels of funding have been provided to low- and middle-income countries for development assistance for health, with most funds coming through direct bilateral investment led by the USA and the UK. Direct attribution of impact to large-scale programs funded by donors remains elusive due the difficulty of knowing what would have happened without those programs, and the lack of detailed contextual information to support causal interpretation of changes.

Methods
This study uses the synthetic control analysis method to estimate the impact of one donor’s funding (United States Agency for International Development, USAID) on under-five mortality across several low- and middle-income countries that received above average levels of USAID funding for maternal and child health programs between 2000 and 2016.

Results
In the study period (2000–16), countries with above average USAID funding had an under-five mortality rate lower than the synthetic control by an average of 29 deaths per 1000 live births (year-to-year range of − 2 to − 38). This finding was consistent with several sensitivity analyses.

Conclusions
The synthetic control method is a valuable addition to the range of approaches for quantifying the impact of large-scale health programs in low- and middle-income countries. The findings suggest that adequately funded donor programs (in this case USAID) help countries to reduce child mortality to significantly lower rates than would have occurred without those investments.
CTPS1 promotes malignant progression of triple-negative breast cancer with transcriptional activation by YBX1
Authors: Lin Yuxiang , Zhang Jie , Li Yan , Guo Wenhui , Chen Lili , Chen Minyan , Chen Xiaobin , Zhang Wenzhe , Jin Xuan , Jiang Meichen , Xiao Han , Wang Chuan , Song Chuangui , Fu Fangmeng 
Published: January 2022

Abstract
Background
Cytidine nucleotide triphosphate synthase 1 (CTPS1) is a CTP synthase which play critical roles in DNA synthesis. However, its biological regulation and mechanism in triple-negative breast cancer (TNBC) has not been reported yet.

Methods
The expression of CTPS1 in TNBC tissues was determined by GEO, TCGA databases and immunohistochemistry (IHC). The effect of CTPS1 on TNBC cell proliferation, migration, invasion, apoptosis and tumorigenesis were explored in vivo and in vitro. In addition, the transcription factor Y-box binding protein 1 (YBX1) was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. Pearson correlation analysis was utilized to assess the association between YBX1 and CTPS1 expression.

Results
CTPS1 expression was significantly upregulated in TNBC tissues and cell lines. Higher CTPS1 expression was correlated with a poorer disease-free survival (DFS) and overall survival (OS) in TNBC patients. Silencing of CTPS1 dramatically inhibited the proliferation, migration, invasion ability and induced apoptosis of MDA-MB-231 and HCC1937 cells. Xenograft tumor model also indicated that CTPS1 knockdown remarkably reduced tumor growth in mice. Mechanically, YBX1 could bind to the promoter of CTPS1 to promote its transcription. Furthermore, the expression of YBX1 was positively correlated with CTPS1 in TNBC tissues. Rescue experiments confirmed that the enhanced cell proliferation and invasion ability induced by YBX1 overexpression could be reversed by CTPS1 knockdown.

Conclusion
Our data demonstrate that YBX1/CTPS1 axis plays an important role in the progression of TNBC. CTPS1 might be a promising prognosis biomarker and potential therapeutic target for patients with triple-negative breast cancer.
Identification of COPA as a potential prognostic biomarker and pharmacological intervention target of cervical cancer by quantitative proteomics and experimental verification
Authors: Bao Huiqiong , Li Xiaobin , Cao Zhixing , Huang Zhihong , Chen Li , Wang Mingbing , Hu Jiali , Li Wenting , Sun Hongwei , Jiang Xue , Mei Ping , Li Huawen , Lu Ligong , Zhan Meixiao 
Published: January 2022

AbstractBackgroundCervical cancer is the most fatal gynecological carcinoma in the world. It is urgent to explore novel prognostic biomarkers and intervention targets for cervical cancer.MethodsThrough integrated quantitative proteomic strategy,we investigated the protein expression profiles of cervical cancer; 28 fresh frozen tissue samples (11 adenocarcinoma (AC), 12 squamous cell carcinoma (SCC) and 5 normal cervixes (HC)) were included in discover cohort; 45 fresh frozen tissue samples (19 AC, 18 SCC and 8 HC) were included in verification cohort; 140 paraffin-embedded tissues samples of cervical cancer (85 AC and 55 SCC) were used for immunohistochemical evaluation (IHC) of coatomer protein subunit alpha (COPA) as a prognostic biomarker for cervical cancer; how deficiency of COPA affects cell viability and tumorigenic ability of cervical cancer cells (SiHa cells and HeLa cells) were evaluated by cell counting kit-8 and clone formation in vitro.ResultsWe identified COPA is a potential prognostic biomarker for cervical cancer in quantitative proteomics analysis. By retrospective IHC analysis, we additionally verified the proteomics results and demonstrated moderate or strong IHC staining for COPA is an unfavourable independent prognostic factor for cervical cancer. We also identified COPA is a potential pharmacological intervention target of cervical cancer by a series of in vitro experiments.ConclusionThis study is the first to demonstrate that COPA may contribute to progression of cervical cancer. It can serve as a potential prognostic biomarker and promising intervention target for cervical cancer.
FOXA1 can be modulated by HDAC3 in the progression of epithelial ovarian carcinoma
Authors: Lou Tong , Liu Chongdong , Qu Hong , Zhang Zhiqiang , Wang Shuzhen , Zhuang Huiyu 
Published: January 2022

AbstractFOXA1 is associated with malignant tumors, but the function of FOXA1 in EOC is unclear. HDAC3 can influence the proliferation, migration and invasion ability of EOC. In this study, we wanted to explore the function of FOXA1 in ovarian cancer and the relationship between HDAC3 and FOXA1.The expression of HDAC3 and FOXA1 was detected by immunohistochemical staining of primary lesions from 127 epithelial ovarian carcinoma patients. A proliferation assay, a Transwell assay, an apoptosis assay and animal experiments were used to assess the proliferation, invasion and apoptosis abilities of ovarian cancer cells before and after transfection with FOXA1. The relevance of the in vitro findings was confirmed in xenografts. The H-scores for FOXA1 and HDAC3 staining in FIGO stage III-IV were noticeably higher and predicted adverse clinical outcomes in patients with ovarian cancer. The expression level of HDAC3 was significantly correlated with the expression level of FOXA1. Invasion, proliferation and apoptosis capacity and tumor formation were decreased in the FOXA1-knockdown cells. Experiments in xenografts confirmed that HDAC3 mediated tumor formation. In conclusion, FOXA1 can be modulated by HDAC3 through the Wnt/β-catenin signaling pathway, and FOXA1 plays essential roles in the proliferation, apoptosis and invasion of EOC cell lines and xenograft experiments.
Management skin manifestation of multisystem inflammatory syndrome associated with SARS-CoV-2
Authors: Bayram Yeter Eylul , Yildiz-Sevgi Dilek , Yavuz Ayse , Cancetin Merve , Gurler Mehmet Yavuz 
Published: January 2022

Abstract
Background
Multisystem inflammatory syndrome (MIS), which develops after a past covid-19 infection. MIS can be described in different tissue inflammation, including the heart, lung, kidney, brain, skin, eye, and or gastrointestinal organs at the presence of COVID-19. Initially, MIS was described in Europe in children infected with SARS-CoV-2, then it was recently seen in the USA in 2020. MIS is a rare but serious disease condition associated with COVID-19 that can affect children (MIS-C) and adults (MIS-A).

Case presentation
A 44-year-old male who showed MIS-A in 59-day after his first covid-19 contact history. The patient presented to our emergency department with complaints of high fever, nausea, weakness, redness of the eyes, headache, and joint pain. On the second day of his hospitalization, a maculopapular skin lesion was seen in most of the skin. His fever could not be controlled even given paracetamol and broad effective antibiotics. His clinical, radiological, and laboratory findings showed that he had MIS-A. The patient was given intravenous pulse methylprednisolone and intravenous immunoglobulin (IVIG). These treatments, then, resulted in improvement of his clinical conditions, including fever and skin lesions, on the second day of the treatment. The patient was discharged in 14 days after the treatment.

Conclusion
This report indicated that diagnosis and treatment of MIS-A could result in reducing patient morbidity and mortality.
Progress on the roles of MEF2C in neuropsychiatric diseases
Authors: Zhang Zhikun , Zhao Yongxiang 
Published: January 2022

AbstractMyocyte Enhancer Factor 2 C (MEF2C), one of the transcription factors of the MADS-BOX family, is involved in embryonic brain development, neuronal formation and differentiation, as well as in the growth and pruning of axons and dendrites. MEF2C is also involved in the development of various neuropsychiatric disorders, such as autism spectrum disorders (ASD), epilepsy, schizophrenia and Alzheimer’s disease (AD). Here, we review the relationship between MEF2C and neuropsychiatric disorders, and provide further insights into the mechanism of these diseases.
AHSA1 is a promising therapeutic target for cellular proliferation and proteasome inhibitor resistance in multiple myeloma
Authors: Gu Chunyan , Wang Yajun , Zhang Lulin , Qiao Li , Sun Shanliang , Shao Miaomiao , Tang Xiaozhu , Ding Pinggang , Tang Chao , Cao Yuhao , Zhou Yanyan , Guo Mengjie , Wei Rongfang , Li Nianguang , Xiao Yibei , Duan Jinao , Yang Ye 
Published: January 2022

Abstract
Background
Currently, multiple myeloma (MM) is still an incurable plasma cell malignancy in urgent need of novel therapeutic targets and drugs.

Methods
Bufalin was known as a highly toxic but effective anti-cancer compound. We used Bufalin as a probe to screen its potential targets by proteome microarray, in which AHSA1 was the unique target of Bufalin. The effects of AHSA1 on cellular proliferation and drug resistance were determined by MTT, western blot, flow cytometry, immunohistochemistry staining and xenograft model in vivo. The potential mechanisms of Bufalin and KU-177 in AHSA1/HSP90 were verified by co-immunoprecipitation, mass spectrometry, site mutation and microscale thermophoresis assay.

Results
AHSA1 expression was increased in MM samples compared to normal controls, which was significantly associated with MM relapse and poor outcomes. Furthermore, AHSA1 promoted MM cell proliferation and proteasome inhibitor (PI) resistance in vitro and in vivo. Mechanism exploration indicated that AHSA1 acted as a co-chaperone of HSP90A to activate CDK6 and PSMD2, which were key regulators of MM proliferation and PI resistance respectively. Additionally, we identified AHSA1-K137 as the specific binding site of Bufalin on AHSA1, mutation of which decreased the interaction of AHSA1 with HSP90A and suppressed the function of AHSA1 on mediating CDK6 and PSMD2. Intriguingly, we discovered KU-177, an AHSA1 selective inhibitor, and found KU-177 targeting the same site as Bufalin. Bufalin and KU-177 treatments hampered the proliferation of flow MRD-positive cells in both primary MM and recurrent MM patient samples. Moreover, KU-177 abrogated the cellular proliferation and PI resistance induced by elevated AHSA1, and decreased the expression of CDK6 and PSMD2.

Conclusions
We demonstrate that AHSA1 may serve as a promising therapeutic target for cellular proliferation and proteasome inhibitor resistance in multiple myeloma.
M1-like tumor-associated macrophages cascade a mesenchymal/stem-like phenotype of oral squamous cell carcinoma via the IL6/Stat3/THBS1 feedback loop
Authors: You Yuanhe , Tian Zhuowei , Du Zhong , Wu Kailiu , Xu Guisong , Dai Meilu , Wang Yan’an , Xiao Meng 
Published: January 2022

Abstract
Background
Tumor-associated macrophages (TAMs) have a leading position in the tumor microenvironment. Previously, we have demonstrated that M1-like TAMs activated by exosome-transferred THBS1 promote malignant migration in oral squamous cell carcinoma (OSCC). However, the functional roles and associated molecular mechanisms of the activated M1-like TAMs need to be further clarified in OSCC.

Methods
Conditioned Media (CM) were harvested from the exosome activated M1-like TAMs. We measured the malignant behaviors of OSCC under the treatment of CM from M1-like TAMs by performing colony forming assays, invasion assays, wound-healing assays, spheroid forming assays and in vivo xenograft experiments. The underlying mechanisms were investigated by RNA-seq, cytokines analysis, intracellular signaling pathway analysis, ChIP assays, bioinformatics analysis and validation.

Results
M1-like TAMs significantly promoted the epithelial-mesenchymal transition (EMT) process, and induced the cancer-stem like cells (CSCs) by upregulating the expression of MME and MMP14 in OSCC cells. Cytokine analysis revealed a shark increase of IL6 secretion from M1-like TAMs. Blocking IL6 in the CM from M1-like TAMs could significantly weaken its effects on the colony forming, invasion, migration, microsphere forming and xenograft forming abilities of OSCC cells. Cellular signaling assays indicated the activation of Jak/Stat3 pathway in the OSCC cells treated by the CM from M1-like TAMs. Blocking the activation of the Jak/Stat3 pathway could significantly weaken the effects of M1-like TAMs on the colony forming, invasion, migration, microsphere forming and xenograft forming abilities of OSCC cells. Further RNA-seq analysis and bioinformatics analysis revealed an increased expression of THBS1 in the OSCC cells treated by M1-like TAMs. Bioinformatics prediction and ChIP assays revealed the activation of Stat3 by CM from M1-like TAMs could directly promote the transcription of THBS1 in OSCC cells.

Conclusions
We proposed that M1-like TAMs could cascade a mesenchymal/stem-like phenotype of OSCC via the IL6/Stat3/THBS1 feedback loop. A better understanding on the functional roles and associated molecular mechanisms of M1-like TAMs might facilitate the development of novel therapies for supplementing the current treatment strategies for OSCC patients.
Comparison of the kinematics, repeatability, and reproducibility of five different multi‐segment foot models
Authors: Yoo Hyo Jeong , Park Hye Sun , Lee Dong‐Oh , Kim Seong Hyun , Park Gil Young , Cho Tae‐Joon , Lee Dong Yeon 
Published: January 2022

AbstractBackgroundMulti‐segment foot models (MFMs) for assessing three‐dimensional segmental foot motions are calculated via various analytical methods. Although validation studies have already been conducted, we cannot compare their results because the experimental environments in previous studies were different from each other. This study aims to compare the kinematics, repeatability, and reproducibility of five MFMs in the same experimental conditions.MethodsEleven healthy males with a mean age of 26.5 years participated in this study. We created a merged 29‐marker set including five MFMs: Oxford (OFM), modified Rizzoli (mRFM), DuPont (DFM), Milwaukee (MiFM), and modified Shriners Hospital for Children Greenville (mSHCG). Two operators applied the merged model to participants twice, and then we analysed two relative angles of three segments: shank‐hindfoot (HF) and hindfoot‐forefoot (FF). Coefficients of multiple correlation (CMC) and mean standard errors were used to assess repeatability and reproducibility, and statistical parametric mapping (SPM) of the t‐value was employed to compare kinematics.ResultsHF varus/valgus of the MiFM and mSHCG models, which rotated the segment according to radiographic or goniometric measurements during the reference frame construction, were significantly more repeatable and reproducible, compared to other models. They showed significantly more dorsiflexed HF and plantarflexed FF due to their static offset angles. DFM and mSHCG showed a greater range of motion (ROM), and some models had significantly different FF points of peak angle.ConclusionsUnder the same conditions, rotating the segment according to the appropriate offset angle obtained from radiographic or goniometric measurement increased reliability, but all MFMs had clinically acceptable reliability compared to previous studies. Moreover, in some models, especially HF varus/valgus, there were differences in ROM and points of peak angle even with no statistical difference in SPM curves. Therefore, based on the results of this study, clinicians and researchers involved in the evaluation of foot and ankle dysfunction need an understanding of the specific features of each MFM to make accurate decisions.
Modulatory effects of R10 fraction of garlic (Allium sativum L.) on hormonal levels, T cell polarization, and fertility-related genes in mice model of polycystic ovarian syndrome
Authors: Falahatian Somaye , Haddad Raheem , Pakravan Nafiseh 
Published: January 2022

AbstractPolycystic ovary syndrome (PCOS) is an inflammatory endocrine-metabolic disorder related to reproductive system characterized by polycystic ovarian morphology, androgen excess, and chronic anovulation. Current treatments haven’t been very successful in PCOS treatment and the problem still remains as a challenge. Therefore, new approaches should be applied to overcome the disease. Previous studies demonstrated immunomodulatory effects of R10 fraction of garlic in the treatment of inflammatory conditions such as cancer. Considering previous studies suggesting immunomodulatory therapy for PCOS, therapeutic effects of R10 fraction was evaluated in a mouse model of PCOS. To do so, PCOS was developed by intramuscular injection of estradiol valerate. Treatment with R10 fraction, isolated from garlic, was performed and the alterations in hormonal levels (estradiol, progesterone, and testosterone), T cell polarization markers (IFN-γ, IL-4, and IL-17), and expression of fertility-related genes (Gpx3 and Ptx3) were evaluated. The results showed that hormonal levels were elevated in PCOS model comparing to normal animals but were markedly modulated after treatment with R10 fraction. Moreover, a severe disturbance in T cell polarization with a significant reduction of fertility-related genes expression were detected in PCOS-induced ovaries. Treatment with R10 fraction also represented modulatory effects on T cell polarization by increasing IL-4 and decreasing IL-17 and IFN-γ levels. Accordingly, fertility-related genes were also modulated following treatment with R10 fraction in PCOS. Our study elucidated that R10 fraction of garlic possess immunomodulatory effects alleviating PCOS symptoms. This approach could be adjusted to give rise the optimum therapeutic results and considered as a candidate therapeutic approach for PCOS.
Prevalence of COVID-19 in children affected by allergic rhinoconjunctivitis and asthma: results from the second “SIAIP rhinosinusitis and conjunctivitis committee” survey
Authors: Brindisi Giulia , Zicari Anna Maria , Parisi Giuseppe Fabio , Diaferio Lucia , Indolfi Cristiana , Marchese Giuseppe , Ghiglioni Daniele Giovanni , Umano Giuseppina Rosaria , Klain Angela , Marseglia Gian Luigi , Del Giudice Michele Miraglia 
Published: January 2022

Abstract
Background
The role of allergic sensitization seems to be protective against SARS CoV2 infection. The aim of this study was to evaluate, using online surveys, the impact of COVID-19 on Italian allergic children, comparing the prevalence of AR and asthma symptoms between the first and second pandemic wave.

Methods
Both surveys were emailed to Italian pediatricians in April 2020 (first survey) and in March 2021 (second survey). The first one was related to the impact of COVID-19 and the most frequently reported symptoms. The second one was superimposed on the previous one, taking into account some additional aspects in the management of disease.

Results
A total of 99 pediatricians participated in the first survey and 267 in the second one. The first survey showed that, asthma and allergic rhinoconjunctivitis prevalence was mostly between 0 and 20% throughout the country. The second survey showed a lower prevalence of both diseases nationwide in comparison to the first one. Comparing the two surveys, statistically significant differences were reported only in the distribution of asthma prevalence in Southern Italy while no differences were highlighted in the North and in the Center. Finally regarding allergic rhinoconjunctivitis prevalence, no differences were noticed nationwide.

Conclusions
Allergic rhinoconjunctivitis and asthma, if under control, did not represent risk factors for the susceptibility to SARS CoV2. Therefore, it is strongly recommended to continue therapies during COVID-19 outbreak, according to the international guidelines. However, being COVID-19 a new disease, actual knowledge will undergo continuous improvements over time.