bluuebunny/crossref_metadata_2025_split huggingface dataset:
A qualitative study on professionals’ attitudes and views towards the introduction of patient reported measures into public maternity care pathway
Authors: Chen An , Väyrynen Kirsi , Leskelä Riikka-Leena , Heinonen Seppo , Lillrank Paul , Tekay Aydin , Torkki Paulus 
Published: July 2021

Abstract
Background
The importance and potential benefits of introducing patient reported measures (PRMs) into health care service have been widely acknowledged, yet the experience regarding their implementation into practice is limited. There is a considerable paucity of research in adopting PRMs in maternity care routine. This study, which utilizes the PRMs included in Pregnancy and Childbirth (PCB) outcome set developed by International Consortium for Health Outcomes Measurement (ICHOM) as sample measures, aims to elicit Finnish professionals’ views on PRMs and to explore the applicability of PRMs in Finnish public maternity care.

Methods
This qualitative study, applying semi-structured interviews, described the local professionals’ views towards the application of PRMs in Finnish public maternity care. Professionals were asked to assess the PRMs defined in ICHOM PCB set and provide their expectations and concerns on the implementation of PRMs in Finnish public maternity service.

Results
Twenty professionals participated in the interviews. Participants agreed on the importance and relevance of the PRMs questions included in ICHOM PCB set for delivering and developing maternity care in Finland. However, they criticized the number and length of questions as well as the recommended time points of data collection. In addition, for a successful implementation, various steps like developing suitable questions, redesigning service pathway and protocols, and motivating women to respond to PRMs questions were considered to be important. Also, some potential obstacles, difficulties and risks associated with the implementation were underlined.

Conclusion
This study indicates that the implementation of PRMs into Finnish public maternity service is possible, highly relevant and important. However, the adoption of PRMs into routine practice may be challenging and will require a series of efforts. This study shows viewpoints from Finnish professionals who have not participated in developing the ICHOM PCB standard set and provides important insights on the development and implementation of PRMs.
Early response of methanogenic archaea to H2 as evaluated by metagenomics and metatranscriptomics
Authors: Kakuk Balázs , Wirth Roland , Maróti Gergely , Szuhaj Márk , Rakhely Gábor , Laczi Krisztián , Kovács Kornél L. , Bagi Zoltán 
Published: July 2021

Abstract
Background
The molecular machinery of the complex microbiological cell factory of biomethane production is not fully understood. One of the process control elements is the regulatory role of hydrogen (H2). Reduction of carbon dioxide (CO2) by H2 is rate limiting factor in methanogenesis, but the community intends to keep H2 concentration low in order to maintain the redox balance of the overall system. H2 metabolism in methanogens becomes increasingly important in the Power-to-Gas renewable energy conversion and storage technologies.

Results
The early response of the mixed mesophilic microbial community to H2 gas injection was investigated with the goal of uncovering the first responses of the microbial community in the CH4 formation and CO2 mitigation Power-to-Gas process. The overall microbial composition changes, following a 10 min excessive bubbling of H2 through the reactor, was investigated via metagenome and metatranscriptome sequencing. The overall composition and taxonomic abundance of the biogas producing anaerobic community did not change appreciably 2 hours after the H2 treatment, indicating that this time period was too short to display differences in the proliferation of the members of the microbial community. There was, however, a substantial increase in the expression of genes related to hydrogenotrophic methanogenesis of certain groups of Archaea. As an early response to H2 exposure the activity of the hydrogenotrophic methanogenesis in the genus Methanoculleus was upregulated but the hydrogenotrophic pathway in genus Methanosarcina was downregulated. The RT-qPCR data corroborated the metatranscriptomic

Results
H2 injection also altered the metabolism of a number of microbes belonging in the kingdom Bacteria. Many Bacteria possess the enzyme sets for the Wood-Ljungdahl pathway. These and the homoacetogens are partners for syntrophic community interactions between the distinct kingdoms of Archaea and Bacteria.

Conclusions
External H2 regulates the functional activity of certain Bacteria and Archaea. The syntrophic cross-kingdom interactions in H2 metabolism are important for the efficient operation of the Power-to-Gas process. Therefore, mixed communities are recommended for the large scale Power-to-Gas process rather than single hydrogenotrophic methanogen strains. Fast and reproducible response from the microbial community can be exploited in turn-off and turn-on of the Power-to-Gas microbial cell factories.
A novel strategy to identify candidate diagnostic and prognostic biomarkers for gastric cancer
Authors: Liu Lei , Pang Honglin , He Qiao , Pan Biran , Sun Xiaobin , Shan Jing , Wu Liping , Wu Kaiwen , Yao Xue , Guo Yuanbiao 
Published: July 2021

Abstract
Background
Gastric cancer (GC) is one of the most common cancer worldwide. It is essential to identify non-invasive diagnostic and prognostic biomarkers of GC. The aim of the present study was to screen candidate biomarkers associated with the pathogenesis and prognosis of GC by a novel strategy.

Methods
The expression level of gene higher in cancer than in adjacent non-cancer tissue was defined as “positive”, and the top 5% genes with “positive rate” were filtered out as candidate diagnostic biomarkers in three Gene Expression Omnibus (GEO) datasets. Further, a prognostic risk model was constructed by multivariate Cox regression analysis in GEO dataset and validated in The Cancer Genome Atlas (TCGA). The expression level of candidate biomarkers was determined in serum and serum-derived exosomes of GC patients. Moreover, the effect of biomarkers in exosomes on migration of GC cells was analyzed by transwell assay.

Results
Ten candidate biomarkers (AGT, SERPINH1, WNT2, LIPG, PLAU, COL1A1, MMP7, MXRA5, CXCL1 and COL11A1) were identified with efficient diagnostic value in GC. A prognostic gene signature consisted of AGT, SERPINH1 and MMP7 was constructed and showed a good performance in predicting overall survivals in TCGA. Consistently, serum levels of the three biomarkers also showed high sensitivity and specificity in distinguishing GC patients from controls. In addition, the expression level of the three biomarkers were associated with malignant degree and decreased after surgery in GC patients. Moreover, the expression level of AGT and MMP7 in exosomes correlated positively with serum level. The exosomes derived from serum of GC patients can promote migration of SGC‐7901 cells. After neutralized the expression level of three proteins in exosomes with antibodies, the migration of GC cells was obviously suppressed.

Conclusions
Our findings provided a novel strategy to identify diagnostic biomarkers based on public datasets, and suggested that the three-gene signature was a candidate diagnostic and prognostic biomarker for patients with GC.
Circ_0001721 enhances doxorubicin resistance and promotes tumorigenesis in osteosarcoma through miR-758/TCF4 axis
Authors: Guan Huapeng , Xu Hao , Chen Jinshui , Wu Weishan , Chen Dongfeng , Chen Yungang , Sun Jianzhong 
Published: July 2021

Abstract
Background
Osteosarcoma (OS) is a common type of bone malignancy that often occurs in children and adolescents. Chemoresistance is a huge barrier to cancer therapy. This study aimed to investigate the role and potential mechanism of circ_0001721 in doxorubicin (DXR) resistance and OS development.

Methods
The levels of circ_0001721, miR-758 and transcription factor 4 (TCF4) were detected by quantitative real-time polymerase chain reaction or western blot assay. Cell Counting Kit-8 (CCK-8) assay was used to calculate the half inhibition concentration (IC50) of DXR and assess cell viability. Cell migration and invasion were evaluated by transwell assay. Cell apoptosis was monitored by flow cytometry. The levels of multidrug resistance-related and Wnt/β-catenin pathway-related proteins were measured by western blot assay. The interaction among circ_0001721, miR-758 and TCF4 were confirmed by dual-luciferase reporter assay, RNA immunoprecipitation assay or RNA pull-down assay. The xenograft model was established to analyze tumor growth in vivo.

Results
Circ_0001721 and TCF4 were upregulated, whereas miR-758 was down-regulated in DXR-resistant OS tissues and cells. Circ_0001721 silence reduced DXR resistance of KHOS/DXR and MG63/DXR cells. Circ_0001721 regulated DXR resistance via sponging miR-758. Moreover, miR-758 modulated DXR resistance by targeting TCF4. Besides, circ_0001721 knockdown inhibited tumor growth in vivo.

Conclusion
Circ_0001721 potentiated DXR resistance and facilitated the progression of OS by regulating miR-758/TCF4 axis, which provides promising therapeutic targets for OS treatment.
DNA double-strand break repair gene mutation and the risk of papillary thyroid microcarcinoma: a case–control study
Authors: Qin Jiali , Fan Jie , Li Gang , Liu Shanting , Liu Zhensheng , Wu Yao 
Published: July 2021

Abstract
Objective
To study the relationship between DNA double-strand break (DSB) repair gene mutations and the risk of papillary thyroid microcarcinoma (PTMC).

Methods
One hundred patients with PTMC or benign thyroid nodules (BTNs) at Henan Cancer Hospital were retrospectively analyzed. The DSB repair capacity of peripheral blood T lymphocytes in the two groups was assessed by flow cytometry. Data were compared using Student’s t-test to evaluate the relationship between DSB repair capacity and the risk of PTMC. Factors influencing DSB repair capacity were analyzed by multivariate logistic regression analysis. The relationship between PTMC and DSB repair capacity was analyzed by univariate analysis. Targeted next-generation DNA sequencing was applied to screen and analyze DSB repair genes related to PTMC.

Results
The DSB repair capacity was 31.30% in the PTMC group and 44.40% in the BTN group, with that of the former being significantly lower (P < 0.05). Multivariate logistic regression analysis of age, sex, obesity status, radiation and other factors showed that radiation exposure was positively correlated with reduced DSB repair capacity(OR = 3.642; 95% CI 1.484–8.935, P = 0.020). Moreover, univariate analysis showed that a reduction in DSB repair capacity was a risk factor for PTMC(OR = 2.333; 95% CI 1.027–5.300, P = 0.043).Targeted next-generation DNA sequencing was performed on the DSB repair genes discovered, and those that were mutated in association with PTMC were Rad50 and FANCA; Rad51 mutations were related to BTN.

Conclusion
Radiation exposure is positively associated with induced DSB repair gene mutations, which may cause a reduced capacity for DSB repair and eventually lead to PTMC.
Fatty acid oxidation: driver of lymph node metastasis
Authors: Li Mao , Xian Hong-chun , Tang Ya-Jie , Liang Xin-hua , Tang Ya-ling 
Published: July 2021

AbstractFatty acid oxidation (FAO) is the emerging hallmark of cancer metabolism because certain tumor cells preferentially utilize fatty acids for energy. Lymph node metastasis, the most common way of tumor metastasis, is much indispensable for grasping tumor progression, formulating therapy measure and evaluating tumor prognosis. There is a plethora of studies showing different ways how tumor cells metastasize to the lymph nodes, but the role of FAO in lymph node metastasis remains largely unknown. Here, we summarize recent findings and update the current understanding that FAO may enable lymph node metastasis formation. Afterward, it will open innovative possibilities to present a distinct therapy of targeting FAO, the metabolic rewiring of cancer to terminal cancer patients.
Health and socio-demographic implications of the Covid-19 second pandemic wave in Israel, compared with the first wave
Authors: Birenbaum-Carmeli Daphna , Chassida Judith 
Published: July 2021

Abstract
Background
Israel’s containment of the first wave of Covid-19 was relatively successful. Soon afterwards, however, in the summer months, a harsher pandemic wave developed, resulting in many more seriously ill and dead Israelis. Israel was the world’s first country to impose a second general lockdown. The present study outlines the early months of Israel’s second pandemic wave, until the imposition of the second general lockdown, and their impact on various communities. The investigation is conducted in conjunction with five sociodemographic variables: population density, socioeconomic status, rate of elderly population, minority status (Jewish / Arab identity) and religiosity (Ultra-Orthodox vs. other Jewish communities).

Methods
The analysis is based on a cross sectional study of morbidity rates, investigated on a residential community basis. Following the descriptive statistics, we move on to present a multivariate analysis to explore associations between the five aforementioned sociodemographic variables and Covid-19 morbidity in Israel in the early second pandemic wave vs. the first Covid-19 outbreak.

Results
Both the descriptive statistics and regressions show morbidity rates to be significantly and positively associated with communities’ population density and significantly and negatively associated with socioeconomic status (SES) and the size of elderly population. These results differ from Wave I morbidity, which was not significantly associated with SES. Another difference vis-a-vis Wave I is the rise of morbidity in Arab communities that led to the disappearance of the previously observed significant negative association of morbidity with minority (Arab) status. Exceptional morbidity was found in Ultra-Orthodox Jewish communities.

Conclusion
The second wave of Covid-19 in Israel has profoundly affected marginalized communities characterized by high residential density, low SES and minority status. Other marginalized and disempowered communities have also been badly hit. While acknowledging the potential contribution of various possible causes, we highlight the policy response of Israel’s government during the early weeks of the second Covid-19 outbreak, suggesting that the severe second wave might possibly be associated with belated, undecided government response during this period.
RGD-modified multifunctional nanoparticles encapsulating salvianolic acid A for targeted treatment of choroidal neovascularization
Authors: Zhang Junxiu , Zhu Jingyi , Zhao Lingzhou , Mao Ke , Gu Qing , Li Dongli , Zhao Jinhua , Wu Xingwei 
Published: July 2021

Abstract
Background
The development of alternative anti-angiogenesis therapy for choroidal neovascularization (CNV) remains a great challenge. Nanoparticle systems have emerged as a new form of drug delivery in ocular diseases. Here, we report the construction and characterization of arginine-glycine-aspartic acid (RGD)-conjugated polyethyleneimine (PEI) as a vehicle to load antioxidant salvianolic acid A (SAA) for targeted anti-angiogenesis therapy of CNV. In this study, PEI was consecutively modified with polyethylene glycol (PEG) conjugated RGD segments, 3-(4′-hydroxyphenyl) propionic acid-Osu (HPAO), and fluorescein isothiocyanate (FI), followed by acetylation of the remaining PEI surface amines to generate the multifunctional PEI vehicle PEI.NHAc-FI-HPAO-(PEG-RGD) (for short, RGD-PEI). The formed RGD-PEI was utilized as an effective vehicle platform to load SAA.

Results
We showed that RGD-PEI/SAA complexes displayed desirable water dispersibility, low cytotoxicity, and sustainable release of SAA under different pH conditions. It could be specifically taken up by retinal pigment epithelium (RPE) cells which highly expressed ɑvβ5 integrin receptors in vitro and selectively accumulated in CNV lesions in vivo. Moreover, the complexes displayed specific therapeutic efficacy in a mouse model of laser induced CNV, and the slow elimination of the complexes in the vitreous cavity was verified by SPECT imaging after 131I radiolabeling. The histological examinations further confirmed the biocompatibility of RGD-PEI/SAA.

Conclusions
The results suggest that the designed RGD-PEI/SAA complexes may be a potential alternative anti-angiogenesis therapy for posterior ocular neovascular diseases.

Graphic abstract
Validation and reliability testing of the Breast-Q latissimus dorsi questionnaire: cross-cultural adaptation and psychometric properties in a Swedish population
Authors: Kamya Lynne , Hansson Emma , Weick Linn , Hansson Emma 
Published: July 2021

Abstract
Background
The main aim of post-mastectomy breast reconstruction is to improve the patient’s quality of life, which makes high-quality and validated patient-reported outcome measurements essential. None of the established instruments include evaluation of donor-site morbidity, such as impact on upper extremity and back function, when a latissimus dorsi (LD) muscle is used; and BREAST-Q LD questionnaire was therefore recently developed for this purpose. The aim of this study was to translate into Swedish and culturally adapt the BREAST-Q LD questionnaire’s two subscales, appearance and function, and perform a psychometric evaluation of the subscales in a Swedish population of patients.

Methods
This was a cross-sectional study. The questionnaire was translated according to established guidelines. The questionnaires were sent to all patients operated using an LD flap between 2007 and 2017. Internal consistency was assessed using Cronbach’s α. Inter-item correlations and corrected item-total correlations were calculated using the Pearson’s correlation coefficient. Convergent validity was evaluated by comparing the BREAST-Q LD questionnaire to the Western Ontario Osteoarthritis of the Shoulder Index, using the Spearman correlation coefficient. Test–retest reliability was tested with intraclass correlation coefficients (ICCs), and the coefficient of variation and Bland–Altman plots were drawn. Floor and ceiling effects were calculated. Known-group validation was tested by comparing scores from the patients and from normal controls using the Mann–Whitney U-test and by calculating eta squared effect size.

Results
The questionnaires were sent to 176 eligible patients and 125 responded (71%). The patients had been operated a mean of 6.6 years ago, and most (92%) had previous radiation. Internal consistency was satisfactory for both subscales. The correlation coefficients between questions were r > 0.30 for all items of both scales. The corrected item-total correlation coefficient ranged from 0.62 to 0.90. As hypothesised, the function scale was correlated with the WOOS “Physical symptoms” subscale. Reliability was adequate according to the ICCs. The ceiling effect threshold for the appearance scale was reached and that for the back scale was almost reached. There were significant differences between patients and controls, in the hypothesised direction.

Conclusions
The results of this study support a good internal consistency, convergent validity, test–retest reliability and known-group validation for the Swedish BREAST-Q LD questionnaire. However, it may be difficult to discriminate between patients with very mild and those with no symptoms using the appearance scale.
Trial registration: ClinicalTrials.Gov identifier NCT04526561.
Down-regulation of S100P induces apoptosis in endometrial epithelial cell during GnRH antagonist protocol
Authors: Zhang Dan , Han Mi , Zhou Mingjuan , Liu Mengyu , Li Yan , Xu Bufang , Zhang Aijun 
Published: July 2021

Abstract
Background
The gonadotropin-releasing hormone (GnRH) antagonist protocol for in vitro fertilization (IVF) often leads to lower pregnancy rates compared to the GnRH agonist protocol. Decreased endometrial receptivity is one reason for the lower success rate, but the mechanisms underlying this phenomenon remain poorly understood. The S100 calcium protein P (S100P) is a biomarker for endometrial receptivity. Both GnRH antagonist and S100P are involved in mediating cell apoptosis. However, the involvement of S100P in reduced endometrial receptivity during the GnRH antagonist protocol remains unclear.

Methods
Endometrial tissue was collected at the time of implantation window from patients undergoing the GnRH agonist (GnRH-a) or GnRH antagonist (GnRH-ant) protocols, as well as from patients on their natural cycles. Endometrial cell apoptosis and expression levels of S100P, HOXA10, Bax, and Bcl-2 were assessed. Ishikawa cells were cultured to evaluate the effects that GnRH antagonist exposure or S100P up- or down- regulation had on apoptosis.

Results
Endometrial tissue from patients in the GnRH-ant group showed elevated apoptosis and decreased expression of the anti-apoptotic marker Bcl-2. In addition, endometrial expression of S100P was significantly reduced in the GnRH-ant group, and expression of HOXA10 was lower. Immunofluorescence colocalization analysis revealed that S100P was mainly distributed in the epithelium. In vitro experiments showed that knockdown of S100P in Ishikawa cells induced apoptosis, decreased expression of Bcl-2, while overexpression of S100P caused the opposite effects and decreased expression of Bax. Furthermore, endometrial epithelial cells exposed to GnRH antagonist expressed lower levels of S100P and Bcl-2, increased expression of Bax, and had higher rates of apoptosis. The increased apoptosis induced by GnRH antagonist treatment could be rescued by overexpression of S100P.

Conclusions
We found that GnRH antagonist treatment induced endometrial epithelial cell apoptosis by down-regulating S100P, which was detrimental to endometrial receptivity. These results further define a mechanistic role for S100P in contributing to endometrial apoptosis during GnRH antagonist treatment, and suggest that S100P is a potential clinical target to improve the success of IVF using the GnRH antagonist protocol.