bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distance to primary care facilities and healthcare utilization for preschool children in rural northwestern Burkina Faso: results from a surveillance cohort
Authors:   for the Étude CHAT Study Group, Oldenburg Catherine E. , Sié Ali , Ouattara Mamadou , Bountogo Mamadou , Boudo Valentin , Kouanda Idrissa , Lebas Elodie , Brogdon Jessica M. , Lin Ying , Nyatigo Fanice , Arnold Benjamin F. , Lietman Thomas M. 
Published: March 2021

Abstract
Background
Delays in care-seeking for childhood illness may lead to more severe outcomes. We evaluated whether community distance from a primary healthcare facility was associated with decreased healthcare utilization in a rural district of northwestern Burkina Faso.

Methods
We conducted passive surveillance of all government-run primary healthcare facilities in Nouna District, Burkina Faso from March 1 through May 31, 2020. All healthcare visits for children under 5 years of age were recorded on a standardized form for sick children. We recorded the age, sex, and community of residence of the child as well as any diagnoses and treatments administered. We calculated healthcare utilization per 100 child-months by linking the aggregate number of visits at the community level to the community’s population of children under 5 months per a census that was conducted from August 2019 through February 2020. We calculated the distance between each community and its corresponding healthcare facility and assessed the relationship between distance and the rate of healthcare utilization.

Results
In 226 study communities, 12,676 primary healthcare visits were recorded over the three-month period. The median distance between the community and primary healthcare facility was 5.0 km (IQR 2.6 to 6.9 km), and median number of healthcare visits per 100 child-months at the community level was 6.7 (IQR 3.7 to 12.3). The rate of primary healthcare visits declined with increasing distance from clinic (Spearman’s rho − 0.42, 95% CI − 0.54 to − 0.31, P < 0.0001). This relationship was similar for cause-specific clinic visits (including pneumonia, malaria, and diarrhea) and for antibiotic prescriptions.

Conclusions
We documented a distance decay effect between community distance from a primary healthcare facility and the rate of healthcare visits for children under 5. Decreasing distance-related barriers, for example by increasing the number of facilities or targeting outreach to more distant communities, may improve healthcare utilization for young children in similar settings.
Vegetable intake and the risk of bladder cancer in the BLadder Cancer Epidemiology and Nutritional Determinants (BLEND) international study
Authors: Yu Evan Yi-Wen , Wesselius Anke , Mehrkanoon Siamak , Goosens Mieke , Brinkman Maree , van den Brandt Piet , Grant Eric J. , White Emily , Weiderpass Elisabete , Le Calvez-Kelm Florence , Gunter Marc J. , Huybrechts Inge , Riboli Elio , Tjonneland Anne , Masala Giovanna , Giles Graham G. , Milne Roger L. , Zeegers Maurice P. 
Published: March 2021

Abstract
Background
Although a potential inverse association between vegetable intake and bladder cancer risk has been reported, epidemiological evidence is inconsistent. This research aimed to elucidate the association between vegetable intake and bladder cancer risk by conducting a pooled analysis of data from prospective cohort studies.

Methods
Vegetable intake in relation to bladder cancer risk was examined by pooling individual-level data from 13 cohort studies, comprising 3203 cases among a total of 555,685 participants. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs), were estimated using Cox proportional hazards regression models stratified by cohort for intakes of total vegetable, vegetable subtypes (i.e. non-starchy, starchy, green leafy and cruciferous vegetables) and individual vegetable types. In addition, a diet diversity score was used to assess the association of the varied types of vegetable intake on bladder cancer risk.

Results
The association between vegetable intake and bladder cancer risk differed by sex (P-interaction = 0.011) and smoking status (P-interaction = 0.038); therefore, analyses were stratified by sex and smoking status. With adjustment of age, sex, smoking, energy intake, ethnicity and other potential dietary factors, we found that higher intake of total and non-starchy vegetables were inversely associated with the risk of bladder cancer among women (comparing the highest with lowest intake tertile: HR = 0.79, 95% CI = 0.64–0.98, P = 0.037 for trend, HR per 1 SD increment = 0.89, 95% CI = 0.81–0.99; HR = 0.78, 95% CI = 0.63–0.97, P = 0.034 for trend, HR per 1 SD increment = 0.88, 95% CI = 0.79–0.98, respectively). However, no evidence of association was observed among men, and the intake of vegetable was not found to be associated with bladder cancer when stratified by smoking status. Moreover, we found no evidence of association for diet diversity with bladder cancer risk.

Conclusion
Higher intakes of total and non-starchy vegetable are associated with reduced risk of bladder cancer for women. Further studies are needed to clarify whether these results reflect causal processes and potential underlying mechanisms.
The importance of CDC27 in cancer: molecular pathology and clinical aspects
Authors: Kazemi-Sefat Golnaz Ensieh , Keramatipour Mohammad , Talebi Saeed , Kavousi Kaveh , Sajed Roya , Kazemi-Sefat Nazanin Atieh , Mousavizadeh Kazem 
Published: March 2021

AbstractBackgroundCDC27 is one of the core components of Anaphase Promoting complex/cyclosome. The main role of this protein is defined at cellular division to control cell cycle transitions. Here we review the molecular aspects that may affect CDC27 regulation from cell cycle and mitosis to cancer pathogenesis and prognosis.Main textIt has been suggested that CDC27 may play either like a tumor suppressor gene or oncogene in different neoplasms. Divergent variations inCDC27DNA sequence and alterations in transcription ofCDC27have been detected in different solid tumors and hematological malignancies. ElevatedCDC27expression level may increase cell proliferation, invasiveness and metastasis in some malignancies. It has been proposed thatCDC27upregulation may increase stemness in cancer stem cells. On the other hand, downregulation ofCDC27may increase the cancer cell survival, decrease radiosensitivity and increase chemoresistancy. In addition,CDC27downregulation may stimulate efferocytosis and improve tumor microenvironment.ConclusionCDC27 dysregulation, either increased or decreased activity, may aggravate neoplasms. CDC27 may be suggested as a prognostic biomarker in different malignancies.
Evaluation of exosome derivatives as bio-informational reprogramming therapy for cancer
Authors: Gonzalez Michael J. , Kweh Mercedes F. , Biava Pier Mario , Olalde Jose , Toro Alondra P. , Goldschmidt-Clermont Pascal J. , White Ian A. 
Published: March 2021

AbstractExosomes are nanoparticle sized (100 ± 50 nm) extracellular vesicles (ECVs) that play important roles in cell-to-cell communication. They do this by utilizing their natural ability to shuttle signaling molecules across the cellular microenvironment and promote paracrine signaling. Currently, exosomes are being explored for their potential as therapeutic agents for various degenerative diseases including cancer. The rationale behind their therapeutic ability is that they can transfer signaling biomolecules, and subsequently induce metabolic and physiological changes in diseased cells and tissues. In addition, exosomes can be used as a drug delivery system and may be very effective at reducing toxicity and increasing bioavailability of therapeutic molecules and drugs. Although exosomes were first believed to be a waste product of the cell, current research has demonstrated that these particles can serve as modulators of the immune system, act as cancer biomarkers, cause re-differentiation of cancer cells, and induce apoptosis in diseased cells. Extensive research has been performed specifically using amniotic fluid-derived extracellular vesicles, named “cytosomes”. While the use of cytosomes in clinical application is still in the early stages, researchers have shown great potential for these EVs in regenerative medicine as immune modulators, in controlling microbial infection and by inducing tissue repair through the activation of endogenous, tissue-specific stem cells. This review emphasizes the capabilities of specific subsets of extracellular vesicles that can potentially be used for cancer therapy, principally as a source of bi-informational reprogramming for malignant cells.
Radiotherapy of oligometastatic prostate cancer: a systematic review
Authors: Rogowski Paul , Roach Mack , Schmidt-Hegemann Nina-Sophie , Trapp Christian , von Bestenbostel Rieke , Shi Run , Buchner Alexander , Stief Christian , Belka Claus , Li Minglun 
Published: March 2021

AbstractBackgroundDue to improved imaging sensitivity, the term “oligometastatic” prostate cancer disease is diagnosed more often, leading to an increasing interest in metastasis-directed therapy (MDT). There are two types of radiation based MDT applied when treating oligometastatic disease: (1) stereotactic body radiation therapy (SBRT) generally used for bone metastases; or (2) SBRT for isolated nodal oligometastases combined with prophylactic elective nodal radiotherapy. This review aims to summarize current evidence data, which may shed light on the optimal management of this heterogeneous group of patients.MethodsA systematic review of the Medline database through PubMed was performed according to PRISMA guidelines. All relevant studies published up to November 2020 were identified and screened. Fifty-six titles were included. Besides outcome parameters, different prognostic and predictive factors were assessed, including site of metastases, time between primary treatment and MDT, use of systemic therapies, hormone sensitivity, as well as pattern of recurrence.FindingsEvidence consists largely of retrospective case series and no consistent precise definition of oligometastasis exists, however, most investigators seem to acknowledge the need to distinguish between patients presenting with what is frequently called “synchronous” versus “metachronous” oligometastatic disease. Available data on radiotherapy as MDT demonstrate high local control rates and a small but relevant proportion of patients without progressive disease after 2 years. This holds true for both hormone sensitive and castration resistant prostate cancer diseases. The use of68Ga-PSMA PET/CT for staging increased dramatically. Radiation doses and field sizes varied considerably among the studies. The search for relevant prognostic and predictive factors is ongoing.ConclusionsTo our best knowledge this review on oligometastatic prostate cancer included the largest number of original articles. It demonstrates the therapeutic potential and challenges of MDT for oligometastatic prostate cancer. Prospective studies are under way and will provide further high-level evidence.
Focal adhesion kinase inhibition synergizes with nab-paclitaxel to target pancreatic ductal adenocarcinoma
Authors: Le Large T. Y. S. , Bijlsma M. F. , El Hassouni B. , Mantini G. , Lagerweij T. , Henneman A. A. , Funel N. , Kok B. , Pham T. V. , de Haas R. , Morelli L. , Knol J. C. , Piersma S. R. , Kazemier G. , van Laarhoven H. W. M. , Giovannetti E. , Jimenez C. R. 
Published: March 2021

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is a very lethal disease, with minimal therapeutic options. Aberrant tyrosine kinase activity influences tumor growth and is regulated by phosphorylation. We investigated phosphorylated kinases as target in PDAC.

Methods
Mass spectrometry-based phosphotyrosine proteomic analysis on PDAC cell lines was used to evaluate active kinases. Pathway analysis and inferred kinase activity analysis was performed to identify novel targets. Subsequently, we investigated targeting of focal adhesion kinase (FAK) in vitro with drug perturbations in combination with chemotherapeutics used against PDAC. Tyrosine phosphoproteomics upon treatment was performed to evaluate signaling. An orthotopic model of PDAC was used to evaluate the combination of defactinib with nab-paclitaxel.

Results
PDAC cell lines portrayed high activity of multiple receptor tyrosine kinases to various degree. The non-receptor kinase, FAK, was identified in all cell lines by our phosphotyrosine proteomic screen and pathway analysis. Targeting of this kinase with defactinib validated reduced phosphorylation profiles. Additionally, FAK inhibition had anti-proliferative and anti-migratory effects. Combination with (nab-)paclitaxel had a synergistic effect on cell proliferation in vitro and reduced tumor growth in vivo.

Conclusions
Our study shows high phosphorylation of several oncogenic receptor tyrosine kinases in PDAC cells and validated FAK inhibition as potential synergistic target with Nab-paclitaxel against this devastating disease.
The impact of Pegylated liposomal doxorubicin in recurrent ovarian cancer: an updated meta-analysis of randomized clinical trials
Authors: Li Xin-Ru , Zhu Yi , Zhang Guo-Nan , Huang Jian-Ming , Pei Li-Xia 
Published: March 2021

Abstract
Background
Previous meta-analysis studies suggested that pegylated liposomal doxorubicin (PLD) may improve the survival rate of patients with recurrent ovarian cancer. The aim of the present meta-analysis, then, was to further update the role of PLD in the treatment of recurrent ovarian cancer.

Methods
We performed a literature search using the electronic databases Medicine, EMBASE, Web of Science, and the Cochrane Library to 27 July 2020. We only restricted the randomized clinical trials. Study-specific hazard ratios and 95% confidence interval (HR/95% CI) and risk ratios and 95% confidence interval (RR/95% CI) were pooled using a random-effects model.

Results
Ten studies (12 trials) were included after screening 940 articles. We categorized the eligible studies into two groups: the doublet regimens (four trials, 1767 patients) showed that PLD plus carbo provided superior progression-free survival (PFS) (HR, 0.85; 95% CI, 0.74–0.97) and similar overall survival (OS) (HR, 1.00; 95% CI, 0.88–1.14) compared to paclitaxel (PAC) plus carboplatin (carbo). PLD plus carbo was associated with significantly more anemia and thrombocytopenia, and other side effects were well tolerated. The monotherapy regimens (eight trials, 1980 patients) showed that PLD possessed a similar PFS (HR, 1.02; 95% CI, 0.90–1.16) and OS (HR, 0.88; 95% CI, 0.77–1.01) relative to other monotherapies. PLD alone was also more associated with mucositis/stomatitis and hand-foot syndrome, while other side effects were well tolerated.

Conclusions
In platinum-sensitive recurrent ovarian cancer, PLD plus carbo was more effective than PAC plus carbo, while in platinum-resistant or -refractory recurrent ovarian cancer, PLD exhibited similar survival to other monotherapies. Regarding side effects, PLD plus carbo and mono chemotherapy were both well tolerated.
Definition and prevalence of familial short stature
Authors: Grigoletto Veronica , Occhipinti Alessandro Agostino , Pellegrin Maria Chiara , Sirchia Fabio , Barbi Egidio , Tornese Gianluca 
Published: March 2021

AbstractObjectiveTo verify the prevalence of novel definitions of familial short stature on a cross-sectional cohort of children referred for short stature when their height and that of both parents were measured.MethodsWe consecutively enrolled 65 individuals referred for short stature when both parents were present. We defined “target height-related short stature” (TH-SS) when child’s height is ≤ − 2 SDS and included in the range of target height; suspected “autosomal dominant short stature” (AD-SS) when child height and at least one parent height are ≤ − 2 SDS; “constitutional familial short stature” (C-FSS) when a child with TH-SS does not have any parents with height ≤ − 2 SDS.ResultsOf 65 children referred for SS, 48 individuals had a height ≤ − 2 SDS. Based on the parents’ measured heights, 24 children had TH-SS, 16 subjects AD-SS, and 12 individuals C-FSS. If we had considered only the parents’ reported height, 3 of 24 children with TH-SS, 9 of 16 with AD-SS, and 10 of 12 with C-FSS would have been lost.ConclusionWe suggest novel definitions to adequately detect and approach the cases of FSS since C-FSS (25%) might not need any specific investigation, while on the contrary, AD-SS (33%) should undergo genetic evaluation. Moreover, this study underlines that adequate measurement and consideration of children’s and parents’ heights (individually and together) are crucial in the clinical evaluation of every child with short stature.
Stable DNMT3L overexpression in SH-SY5Y neurons recreates a facet of the genome-wide Down syndrome DNA methylation signature
Authors: Laufer Benjamin I. , Gomez J. Antonio , Jianu Julia M. , LaSalle Janine M. 
Published: March 2021

AbstractBackgroundDown syndrome (DS) is characterized by a genome-wide profile of differential DNA methylation that is skewed towards hypermethylation in most tissues, including brain, and includes pan-tissue differential methylation. The molecular mechanisms involve the overexpression of genes related to DNA methylation on chromosome 21. Here, we stably overexpressed the chromosome 21 geneDNA methyltransferase 3L(DNMT3L) in the human SH-SY5Y neuroblastoma cell line and assayed DNA methylation at over 26 million CpGs by whole genome bisulfite sequencing (WGBS) at three different developmental phases (undifferentiated, differentiating, and differentiated).ResultsDNMT3Loverexpression resulted in global CpG and CpG island hypermethylation as well as thousands of differentially methylated regions (DMRs). TheDNMT3LDMRs were skewed towards hypermethylation and mapped to genes involved in neurodevelopment, cellular signaling, and gene regulation. ConsensusDNMT3LDMRs showed that cell lines clustered by genotype and then differentiation phase, demonstrating sets of common genes affected across neuronal differentiation. The hypermethylatedDNMT3LDMRs from all pairwise comparisons were enriched for regions of bivalent chromatin marked by H3K4me3 as well as differentially methylated sites from previous DS studies of diverse tissues. In contrast, the hypomethylatedDNMT3LDMRs from all pairwise comparisons displayed a tissue-specific profile enriched for regions of heterochromatin marked by H3K9me3 during embryonic development.ConclusionsTaken together, these results support a mechanism whereby regions of bivalent chromatin that lose H3K4me3 during neuronal differentiation are targeted by excess DNMT3L and become hypermethylated. Overall, these findings demonstrate thatDNMT3Loverexpression during neurodevelopment recreates a facet of the genome-wide DS DNA methylation signature by targeting known genes and gene clusters that display pan-tissue differential methylation in DS.
A systematic review of the cost-effectiveness of ultrasound in emergency care settings
Authors: Lentz Brian , Fong Tiffany , Rhyne Randall , Risko Nicholas 
Published: March 2021

AbstractBackgroundThe use of ultrasound (US) in emergency departments (ED) has become widespread. This includes both traditional US scans performed by radiology departments as well as point-of-care US (POCUS) performed by bedside clinicians. There has been significant interest in better understanding the appropriate use of imaging and where opportunities to enhance cost-effectiveness may exist. The purpose of this systematic review is to identify published evidence surrounding the cost-effectiveness of US in the ED and to grade the quality of that evidence.MethodsWe performed a systematic review of the literature following Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Studies were considered for inclusion if they were: (1) economic evaluations, (2) studied the clinical use of ultrasound, and (3) took place in an emergency care setting. Included studies were critically appraised using the Consolidated Health Economic Evaluation Reporting Standards checklist.ResultsWe identified 631 potentially relevant articles. Of these, 35 studies met all inclusion criteria and were eligible for data abstraction. In general, studies were supportive of the use of US. In particular, 11 studies formed a strong consensus that US enhanced cost-effectiveness in the investigation of pediatric appendicitis and 6 studies supported enhancements in the evaluation of abdominal trauma. Across the studies, weaknesses in methodology and reporting were common, such as lack of sensitivity analyses and inconsistent reporting of incremental cost-effectiveness ratios.ConclusionsThe body of existing evidence, though limited, generally demonstrates that the inclusion of US in emergency care settings allows for more cost-effective care. The most definitive evidence for improvements in cost-effectiveness surround the evaluation of pediatric appendicitis, followed by the evaluation of abdominal trauma. POCUS outside of trauma has had mixed results.
Short-term balance training and acute effects on postural sway in balance-deficient older adults: a randomized controlled trial
Authors: Sörlén Niklas , Hult Andreas , Nordström Peter , Nordström Anna , Johansson Jonas 
Published: March 2021

Abstract
Background
We aimed to determine the effectiveness of 4 weeks of balance exercise compared with no intervention on objectively measured postural sway.

Methods
This was a single-center parallel randomized controlled, open label, trial. A six-sided dice was used for allocation at a 1:1-ratio between exercise and control. The trial was performed at a university hospital clinic in Sweden and recruited community-dwelling older adults with documented postural instability. The intervention consisted of progressively challenging balance exercise three times per week, during 4 weeks, with follow-up at week five. Main outcome measures were objective postural sway length during eyes open and eyes closed conditions.

Results
Sixty-five participants aged 70 years (balance exercise n = 32; no intervention n = 33) were randomized. 14 participants were excluded from analysis because of early dropout before follow-up at week five, leaving 51 (n = 22; n = 29) participants for analysis. No significant differences were detected between the groups in any of the postural sway outcomes. Within-group analyses showed significant improvements in hand grip strength for the intervention group, while Timed Up & Go improvements were comparable between groups but only statistically significant in the control group.

Conclusions
Performing balance exercise over a four-week intervention period did not acutely improve postural sway in balance-deficient older adults. The lower limit in duration and frequency to achieve positive effects remains unclear.

Trial registration
Clinical trials NCT03227666, July 24, 2017, retrospectively registered.