bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perceptions and experiences with district health information system software to collect and utilize health data in Bangladesh: a qualitative exploratory study
Authors: Begum Tahmina , Khan Shaan Muberra , Adamou Bridgit , Ferdous Jannatul , Parvez Muhammad Masud , Islam Mohammad Saiful , Kumkum Feroza Akhter , Rahman Aminur , Anwar Iqbal 
Published: May 2020

Abstract
Background
Accurate and high-quality data are important for improving program effectiveness and informing policy.
In 2009 Bangladesh’s health management information system (HMIS) adopted the District Health Information Software, Version 2 (DHIS2) to capture real-time health service utilization data. However, routinely collected data are being underused because of poor data quality and reporting. We aimed to understand the facilitators and barriers to implementing DHIS2 as a way to retrieve meaningful and accurate data for reproductive, maternal, newborn, child, and adolescent health (RMNCAH) services.

Methods
This qualitative study was conducted in two districts of Bangladesh from September 2017 to 2018. Data collection included key informant interviews (n = 11), in-depth interviews (n = 23), and focus group discussions (n = 2). The study participants were involved with DHIS2 implementation from the community level to the national level. The data were analyzed thematically.

Results
DHIS2 could improve the timeliness and completeness of data reporting over time. The reported facilitating factors were strong government commitment, extensive donor support, and positive attitudes toward technology among staff. Quality checks and feedback loops at multiple levels of data gathering points are helpful for minimizing data errors. Introducing a dashboard makes DHIS2 compatible to use as a monitoring tool. Barriers to effective DHIS2 implementation were lack of human resources, slow Internet connectivity, frequent changes to DHIS2 versions, and maintaining both manual and electronic system side-by-side. The data in DHIS2 remains incomplete because it does not capture data from private health facilities. Having two parallel HMIS reporting the same RMNCAH indicators threatens data quality and increases the reporting workload.

Conclusion
The overall insights from this study are expected to contribute to the development of effective strategies for successful DHIS2 implementation and building a responsive HMIS. Focused strategic direction is needed to sustain the achievements of digital data culture. Periodic refresher trainings, incentives for increased performance, and an automated single reporting system for multiple stakeholders could make the system more user-friendly. A national electronic health strategy and implementation framework can facilitate creating a culture of DHIS2 use for planning, setting priorities, and decision making among stakeholder groups.
Multilocus sequence typing characterizes diversity of Ureaplasma diversum strains, and intra-species variability induces different immune response profiles
Authors: Andrade Yasmin M. F. S. , Santos-Junior Manoel N. , Rezende Izadora S. , Barbosa Maysa S. , Amorim Aline T. , Silva Ícaro B. S. , Queiroz Ellunny C. , Bastos Bruno L. , Campos Guilherme B. , Timenetsky Jorge , Marques Lucas M. 
Published: May 2020

Abstract
Background
Ureaplasma diversum is a pathogen found in the genital tract of cattle and associated with genital disorders such as infertility, placentitis, abortion, birth of weak calves, low sperm motility, seminal vesiculitis and epididymitis. There are few studies evaluating the genetic diversity of U. diversum strains and their influence on the immune response in cattle. Therefore, to better understand genetic relationships of the pathogenicity of U. diversum, a multilocus sequence typing (MLST) scheme was performed to characterize the ATCC 49782 strain and another 40 isolates recovered from different Brazilian states.

Results
Primers were designed for housekeeping genes ftsH, polC, rpL22, rpoB, valS and ureA and for virulence genes, phospholipase D (pld), triacylglycerol lipase (tgl), hemolysin (hlyA), MIB-MIP system (mib,mip), MBA (mba), VsA (VsA) and ribose transporter (tABC). PCRs were performed and the targeted gene products were purified and sequenced. Sequence types (STs), and clonal complexes (CCs) were assigned and the phylogenetic relationship was also evaluated. Thus, a total of 19 STs and 4 CCs were studied. Following the molecular analysis, six isolates of U. diversum were selected, inoculated into bovine monocyte/macrophage culture and evaluated for gene expression of the cytokines TNF-α, IL-1, IL-6, IL-10 and IL-17. Differences were detected in the induction of cytokines, especially between isolates 198 and BA78, promoted inflammatory and anti-inflammatory profiles, respectively, and they also differed in virulence factors.

Conclusion
It was observed that intra-species variability between isolates of U. diversum can induce variations of virulent determinants and, consequently, modulate the expression of the triggered immune response.
Validation of genome-wide association study-identified single nucleotide polymorphisms in a case-control study of pancreatic cancer from Taiwan
Authors: Shan Yan-Shen , Chen Li-Tzong , Wu Jin-Shang , Chang Yin-Fan , Lee Chih-Ting , Wu Chih-Hsing , Chiang Nai-Jung , Huang Hsin-En , Yen Chia-Jui , Chao Ying-Jui , Tsai Hui-Jen , Chen Chiung-Yu , Kang Jui-Wen , Kuo Chin-Fu , Tsai Chia-Rung , Weng Ya-Ling , Yang Han-Chien , Liu Hui-Chin , Chang Jeffrey S. 
Published: May 2020

AbstractBackgroundDue to differences in genetic background, it is unclear whether the genetic loci identified by the previous genome-wide association studies (GWAS) of pancreatic cancer also play significant roles in the development of pancreatic cancer among the Taiwanese population.MethodsThis study aimed to validate the 25 pancreatic cancer GWAS-identified single nucleotide polymorphisms (SNPs) in a case-control study (278 cases and 658 controls) of pancreatic cancer conducted in Taiwan. Statistical analyses were conducted to determine the associations between the GWAS-identified SNPs and pancreatic cancer risk. Gene-environment interaction analysis was conducted to evaluate the interactions between SNPs and environmental factors on pancreatic cancer risk.ResultsAmong the 25 GWAS-identified SNPs, 7 (rs2816938 (~ 11 kb upstream ofNR5A2), rs10094872 (~ 28 kb upstream ofMYC), rs9581943 (200 bp upstream ofPDX1) and 4 chromosome 13q22.1 SNPs: rs4885093, rs9573163, rs9543325, rs9573166) showed a statistically significant association with pancreatic cancer risk in the current study. Additional analyses showed two significant gene-environment interactions (between poor oral hygiene andNR5A2rs2816938 and between obesity andPDX1rs9581943) on the risk of pancreatic cancer.ConclusionsThe current study confirmed the associations between 7 of the 25 GWAS-identified SNPs and pancreatic risk among the Taiwanese population.Furthermore, pancreatic cancer was jointly influenced by lifestyle and medical factors, genetic polymorphisms, and gene-environment interaction. Additional GWAS is needed to determine the genetic polymorphisms that are more relevant to the pancreatic cancer cases occurring in Taiwan.
Nanos3, a cancer-germline gene, promotes cell proliferation, migration, chemoresistance, and invasion of human glioblastoma
Authors: Zhang Fengyu , Liu Ruilai , Liu Cheng , Zhang Haishi , Lu Yuan 
Published: May 2020

Abstract
Background
Radiotherapy, chemotherapy, and surgery have made crucial strides in glioblastoma treatment, yet they often fail; thus, new treatment and new detection methods are needed. Aberrant expression of Nanos3 has been functionally associated with various cancers. Here, we sought to identify the clinical significance and potential mechanisms of Nanos3 in human glioblastoma.

Methods
Nanos3 expression was studied in nude mouse glioblastoma tissues and glioblastoma cell lines by immunohistochemistry, Western blot, and RT-PCR. Clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 gene editing assay was performed to generate the Nanos3 knockdown glioblastoma cell lines. The effects of Nanos3 on glioblastoma cells proliferation, migration, invasion, chemoresistance, germ cell characteristics, and tumor formation were analyzed by CCK8, transwell, cell survival experiments and alkaline phosphatase staining in vitro and in nude mouse models in vivo. Correlation between the expression of stemness proteins and the expression of Nanos3 was evaluated by Western blot.

Results
We found that Nanos3 was strongly expressed in both glioblastoma cell lines and tissues. Western blot and sequencing assays showed that the Nanos3 knockdown glioblastoma cell lines were established successfully, and we discovered that Nanos3 deletion reduced the proliferation, migration, and invasion of glioblastoma cells in vitro (P < 0.05). Nanos3 knockdown enhanced the sensitivity of glioblastoma cells to doxorubicin (DOX) and temozolomide (TMZ) (P < 0.05), and Nanos3+/− glioblastoma cell lines did not show the characteristics of the germline cells. In addition, Nanos3 deletion inhibited subcutaneous xenograft tumor growth in vivo (P < 0.001). Moreover, the oncogenesis germline protein levels of CD133, Oct4, Ki67, and Dazl decreased significantly in glioblastoma cells following Nanos3 knockdown.

Conclusions
Both in vitro and in vivo assays suggest that Nanos3, which is a cancer-germline gene, initiates the tumorigenesis of glioblastoma via acquiring the oncogenesis germline traits. These data demonstrate that ectopic germline traits are necessary for glioblastoma growth.
The differences in self-perceptions of aging, health-related quality of life and their association between urban and rural Chinese older hypertensive patients
Authors: Hou Yunying , Wu Qing , Zhang Dandan , Jin Xiaohong , Wu Wenya , Wang Xiaohua 
Published: May 2020

Abstract
Background
Most hypertensive clients are elderly, whose health-related quality of life (HRQL) may be associated with self-perceptions of aging (older individuals’ beliefs about their own aging). Meanwhile, culture and health disparities between rural and urban populations are substantial. Whether there are differences in self-perceptions of aging, HRQL, and their association among elderly hypertensive clients in urban and rural areas remains unknown. The objective of this study was to investigate and compare self-perceptions of aging and HRQL and their association among urban and rural older Chinese hypertensive clients.

Methods
A cross-sectional investigation was conducted in 15 urban community clinics and 22 village clinics from Suzhou, China. Older hypertensive adults were invited to complete a self-administered questionnaire addressing socio-demographic and clinical information, HRQL and self-perceptions of aging.

Results
There were 492 urban participants and 537 rural participants included in the analyses. The physical (40.0 ± 12.1 vs. 30.9 ± 8.9, P <  0.001) and mental (51.5 ± 8.3 vs. 46.0 ± 7.8, P <  0.001) HRQL scores of urban participants were all higher than those of rural ones. Urban participants’ scores on dimensions of “timeline cyclical”, “consequences negative”, and “control negative” of self-perceptions of aging questionnaire (APQ) were lower than those of rural participants (P <  0.001, respectively), while the scores on dimensions of “consequences positive” and “control positive” were higher (P <  0.001, respectively). Adjusted multivariate linear regression showed that participants who had worse self-perceptions of aging had poorer HRQL. Some APQ dimensions associated with urban or rural hypertensive elders’ HRQL were different.

Conclusions
Older hypertensive clients in rural areas have poorer self-perceptions of aging and HRQL than those in urban areas. Health care professionals should pay more attention to HRQL and self-perceptions of aging of older hypertensive clients in rural areas.
Preoperative squamous cell carcinoma antigen and albumin serum levels predict the survival of patients with stage T1-3N0M0 esophageal squamous cell carcinoma: a retrospective observational study
Authors: Wu Lei-Lei , Liu Xuan , Huang Wei , Lin Peng , Long Hao , Zhang Lan-Jun , Ma Guo-Wei 
Published: May 2020

Abstract
Background
This study aimed to explore the significance of preoperative levels of squamous cell carcinoma antigen (SCC-Ag) and albumin on the cancer-specific survival (CSS) of patients with stage T1-3N0M0 in esophageal squamous cell cancer (ESCC).

Methods
The data of 308 patients who underwent esophagectomy between 1996 and 2011 were analyzed. SCC-Ag and albumin levels were measure 1 week before surgery. The optimal cutoff levels of SCC-Ag and albumin were determined using the X-Tile software, which were 1.0 μg/L and 39.8 g/L, respectively. The associations between SCC-Ag and albumin levels and clinicopathological characteristics were assessed using the χ2 test, Student’s t-test and Fisher’s exact test. Cox univariable and multivariable analyses were computed to identify SCC-Ag and albumin levels as independent prognostic factors related to the CSS of patients with ESCC. We used the Kaplan-Meier survival curve to determine the significance of SCC-Ag and albumin level on ESCC in the long-term follow-up.

Results
The 5-year CSS rate for the entire cohort was 65.0%. There was a significant difference in CSS between the low and high SCC-Ag level groups (hazard ratio [HR], 1.828, 95% confidence interval [CI], 1.203–2.778; P = 0.005). Patients with ESCC with low albumin level had a worse CSS than those with high albumin level (HR, 0.540; 95% CI, 0.348–0.838; P = 0.006). Patients with both high SCC-Ag and low albumin levels had worse 5-year CSS than patients with low SCC-Ag and high albumin levels (P < 0.05).

Conclusions
Preoperative serum SCC-Ag and albumin levels can predict survival in patients ESCC with stage T1-3N0M0. Patients with ESCC with high SCC-Ag and low albumin levels may have a poor survival outcome.
TRUST4RD: tool for reducing uncertainties in the evidence generation for specialised treatments for rare diseases
Authors: Annemans Lieven , Makady Amr 
Published: May 2020

Abstract
Background
Many treatments developed for rare diseases will have an Orphan Medicinal Product (OMP) designation, indicating that they are likely to deliver benefit in an area of high unmet need. Their approval may be based on a small or uncontrolled trial, as randomised controlled trials (RCTs) of sufficient size are often difficult to conduct, or repeat, as a result of the rarity of the condition, sparsity of patients, or for ethical reasons. Furthermore, many products are given a conditional marketing authorisation, requiring additional evidence to be collected after product launch. This is even more challenging with the advent of advanced therapeutic medicinal products, which use novel scientific approaches like gene or somatic cell therapy.

Issue
Given the high unmet need associated with these products, there is pressure for Health Technology Assessment (HTA)/reimbursement bodies to enable rapid access to effective treatments. However, there is often only limited evidence available for assessment.

Methods
TRUST4RD proposes an approach to identify uncertainties of most concern for decision-makers by developing an iterative and informed dialogue amongst stakeholders (including manufacturers, clinicians, patients, regulatory- and HTA agencies and payers), so that potential approaches to resolution can be discussed. As evidence is generated, uncertainties are reviewed and prioritised, and evidence-generation plans revised or clarified accordingly. The aim is to develop – both pre- and post HTA submission – a better understanding of evidence requirements versus evidence-generation trade-offs as an evidence base grows and the potential value of a product becomes clearer.

Conclusion
TRUST4RD presents guidance on defining uncertainties and evidence gaps in the assessment of value and value for money of specialised treatments for rare diseases. It also provides guidance on the potential of Real World Evidence (RWE) to help address such uncertainties, including the typology of evidence uncertainties, the importance of different uncertainties and the data sources available to address them before and after HTA submission. In making use of the guidance, authorisation and reimbursement discussions on such treatments can be embedded in an evidence-rich context, thereby ensuring value to all parties, particularly to patients.
Surgical management of sarcoma in adolescent and young adult patients
Authors: Hashimoto Kazuhiko , Nishimura Shunji , Oka Naohiro , Akagi Masao 
Published: May 2020

Abstract
Objective
To examine the clinical features and outcomes of adolescent and young adult sarcoma patients who underwent surgical management and clarify important factors associated with prognosis. We reviewed 18 young adult sarcoma patients sarcoma patients treated surgically in our hospital. The tumor site, histology, grade, stage, and American Society of Anesthesiologists-Physical Status before surgery, operation time, intraoperative blood loss, complications, surgical margin, local recurrence, metastasis, and outcomes were investigated. The 3-year survival rate was also calculated. We compared survival based on age, grade, and surveyed features of poor outcome cases.

Results
The 3-year survival rate was 61.3%. There was no significant difference in survival based on age, grade, operation time, or intraoperative blood loss. Three of five patients who died of the disease had stage ≥ IV at diagnosis. All patients with R1 surgical margins developed recurrence and all those with an American Society of Anesthesiologists-Physical Status ≥ 2 died. Patients with late-stage sarcomas, R1 tumor margin, or high American Society of Anesthesiologists-Physical Status score had poor prognoses. To achieve a favorable outcome in adolescent and young adult sarcoma patients, early detection and obtaining R0 ≥ surgical margin are essential.
Hepatitis C virus relapse after successful treatment with direct-acting antivirals, followed by sarcomatous changes in hepatocellular carcinoma: a case report
Authors: Kurokawa Ken , Ohki Takamasa , Kato Jun , Fukumura Yukiyo , Imai Makoto , Shibata Chikako , Arai Junya , Kondo Mayuko , Takagi Kaoru , Kojima Kentaro , Seki Michiharu , Mori Masaya , Toda Nobuo , Tagawa Kazumi 
Published: May 2020

Abstract
Background
Combination therapy of interferon and ribavirin has traditionally been used to eradicate hepatitis C virus. The sustained virologic response achieved with interferon-related therapy is persistent, and late relapses after achieving sustained virologic response at 24 weeks using this therapy are reportedly rare (< 1%). In 2014, interferon-free therapy with direct-acting antivirals was developed, and the rate of sustained virologic response was improved. However, the persistence thereof remains uncertain, and the appropriate follow-up period for hepatitis C virus-positive patients is under discussion.

Case presentation
A 74-year-old Japanese man who had hepatitis C virus–related hepatocellular carcinoma and was successfully treated with radiofrequency ablation four times underwent direct-acting antiviral therapy with daclatasvir and asunaprevir; sustained virologic response at 24 weeks was confirmed. However, although he had no high risk factors for reinfection, hepatitis C virus ribonucleic acid was detected again 6 months after achieving sustained virologic response at 24 weeks. Moreover, he developed active hepatitis with an increased viral load. Five months after development of hepatitis, recurrent hepatocellular carcinoma emerged in segment II, where we had performed radiofrequency ablation 17 months previously. The recurrent hepatocellular carcinoma enlarged quite rapidly and induced multiple peritoneal disseminations and lung metastases. He died 3 months after the abrupt recurrence. A sarcomatous change in the hepatocellular carcinoma was identified during the autopsy.

Conclusions
Although sustained virologic response at 24 weeks has generally been regarded to denote complete eradication of hepatitis C virus, we present a patient in whom hepatitis C virus recurred 6 months after achieving sustained virologic response at 24 weeks with direct-acting antiviral therapy. In addition, a sarcomatous change in hepatocellular carcinoma emerged 5 months after active hepatitis developed due to late hepatitis C virus relapse in this case. The sarcomatous change in hepatocellular carcinoma is generally thought to be related to anticancer therapies, such as radiofrequency ablation. However, in this case, late viral relapse and active hepatitis in addition to the previous radiofrequency ablation could have been the trigger. There may be a need for follow-up of hepatitis C virus ribonucleic acid beyond sustained virologic response at 24 weeks with direct-acting antiviral therapy, owing to the possibility of late viral relapse and tumorigenesis.
Co-transplantation with adipose-derived cells to improve parathyroid transplantation in a mice model
Authors: Cui Qiuxia , Zhang Dan , Kong Deguang , Tang Jianing , Liao Xing , Yang Qian , Ren Jiangbo , Gong Yan , Wu Gaosong 
Published: May 2020

Abstract
Background
Accidentally removed parathyroid glands are still challenging in neck surgery, leading to hypoparathyroidism characterized with abnormally low levels of parathyroid hormone. Parathyroid auto-transplantation is usually applied in compensation. To improve the efficiency of parathyroid transplantation, we introduced a method by co-transplanting with adipose-derived cells, including stromal vascular fractions (SVFs) and adipose-derived stem cells (ADSCs), and investigated the underlying molecular mechanisms involved in parathyroid transplantation survival.

Methods
Rat and human parathyroid tissues were transplanted into nude mice as parathyroid transplantation model to examine the effects of SVFs and ADSCs on grafts angiogenesis and survival rates, including blood vessel assembly and parathyroid hormone levels. Several angiogenic factors, such as vascular endothelial growth factor (VEGF)-A and fibroblast growth factor (FGF) 2, were assessed in parathyroid grafts. The effects of hypoxia were investigated on ADSCs. The modulatory roles of the eyes absent homolog 1 (EYA1), which is vital in parathyroid development, was also investigated on angiogenic factor production and secretion by ADSCs. All experimental data were statistically processed. Student’s t test was used to assess significant differences between 2 groups. For multiple comparisons with additional interventions, two-way ANOVA followed by Tukey’s post hoc test was performed. P < 0.05 was considered as significant.

Results
SVFs improve rat parathyroid transplantation survival and blood vessel assembly, as well as FGF2 and VEGF-A expression levels in parathyroid transplantation mice. Functional human parathyroid grafts have higher microvessel density and increased VEGF-A expression. The supernatant of ADSCs induced tubule formation and migration of human endothelial cells in vitro. Hypoxia had no effect on proliferation and apoptosis of human ADSCs but induced higher angiogenic factor levels of VEGF-A and FGF2, modulated by EYA1, which was confirmed by parathyroid glands transplantation in mice.

Conclusions
Adipose-derived cells, including ADSCs and SVFs, improve parathyroid transplantation survival via promoting angiogenesis through EYA1-regulating angiogenetic factors in vitro and in vivo. Our studies proved an effective method to improve the parathyroid autotransplantation, which is promising for clinical patients with hypoparathyroidism when parathyroid glands were accidentally injured, removed, or devascularized.