bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of pregnancy-related referrals from rural health facilities to two central hospitals in Harare, Zimbabwe: a prospective descriptive study
Authors: Busumani William , Mundagowa Paddington T. 
Published: March 2021

AbstractBackgroundBetween the years 2000 and 2017, the global maternal mortality rate dropped by 38% however, 94% of maternal deaths still emanated from low-to middle-income countries. Rural women are at a significantly higher risk of dying from pregnancy when compared to their urban counterparts. Early detection of complications and prompt referral to higher levels of care can reduce the associated maternal and perinatal mortality. This study aimed to determine the maternal and perinatal outcomes of pregnancy-related referrals from rural health facilities to central hospitals in Harare, Zimbabwe.MethodsA prospective descriptive study was conducted using a sample of 206 patients. All mothers who were referred from rural healthcare facilities were recruited for participation. Data were extracted from patient notes using a structured questionnaire and missing information was obtained from the mother after she had recovered. Bivariate analysis was done using IBM SPSS.ResultsThe average age of study participants was 27.4 ± 7.7 years. 87.4% had booked for antenatal care and 81.6% presented to the tertiary facility with their referral notes. The major reasons for referring patients were previous cesarean section (20.4%) and hypertensive disorders in pregnancy (18.4%). There were nine maternal deaths thus a case fatality rate of 4.4% while the perinatal mortality rate was 151/1000 live births. Young mothers were at a higher risk of having adverse perinatal outcomes while primiparous mothers were more likely to have a blood transfusion. Mothers who traveled for > 100 km to the tertiary facility and those who did not attend any antenatal visit were more likely to need blood transfusion. Delivering at the rural health facility was significantly associated with receiving a blood transfusion at the tertiary facility. Mothers who did not attend antenatal visits were more likely to have negative perinatal outcomes.ConclusionThe proportion of obstetric patients being referred from rural facilities to tertiary institutions for complications reveals how primary and secondary healthcare facilities in Zimbabwe are falling short of offering the services they should be offering. Equipping these facilities with skilled human resources as well as contemporary equipment could help decongest the central hospitals consequently reducing the adverse maternal and perinatal outcomes.
Defining safety net hospitals in the health services research literature: a systematic review and critical appraisal
Authors: Hefner Jennifer L. , Hogan Tory Harper , Opoku-Agyeman William , Menachemi Nir 
Published: March 2021

Abstract
Background
The aim of this study was to identify the range of ways that safety net hospitals (SNHs) have been empirically operationalized in the literature and determine the extent to which patterns could be identified in the use of empirical definitions of SNHs.

Methods
We conducted a PRISMA guided systematic review of studies published between 2009 and 2018 and analyzed 22 articles that met the inclusion criteria of hospital-level analyses with a clear SNH definition.

Results
Eleven unique SNH definitions were identified, and there were no obvious patterns in the use of a definition category (Medicaid caseload, DSH payment status, uncompensated care, facility characteristics, patient care mix) by the journal type where the article appeared, dataset used, or the year of publication.

Conclusions
Overall, there is broad variability in the conceptualization of, and variables used to define, SNHs. Our work advances the field toward the development of standards in measuring, operationalizing, and conceptualizing SNHs across research and policy questions.
The transcriptional trajectories of pluripotency and differentiation comprise genes with antithetical architecture and repetitive-element content
Authors: Telonis Aristeidis G. , Rigoutsos Isidore 
Published: March 2021

Abstract
Background
Extensive molecular differences exist between proliferative and differentiated cells. Here, we conduct a meta-analysis of publicly available transcriptomic datasets from preimplantation and differentiation stages examining the architectural properties and content of genes whose abundance changes significantly across developmental time points.

Results
Analysis of preimplantation embryos from human and mouse showed that short genes whose introns are enriched in Alu (human) and B (mouse) elements, respectively, have higher abundance in the blastocyst compared to the zygote. These highly expressed genes encode ribosomal proteins or metabolic enzymes. On the other hand, long genes whose introns are depleted in repetitive elements have lower abundance in the blastocyst and include genes from signaling pathways. Additionally, the sequences of the genes that are differentially expressed between the blastocyst and the zygote contain distinct collections of pyknon motifs that differ between up- and down-regulated genes. Further examination of the genes that participate in the stem cell-specific protein interaction network shows that their introns are short and enriched in Alu (human) and B (mouse) elements. As organogenesis progresses, in both human and mouse, we find that the primarily short and repeat-rich expressed genes make way for primarily longer, repeat-poor genes. With that in mind, we used a machine learning-based approach to identify gene signatures able to classify human adult tissues: we find that the most discriminatory genes comprising these signatures have long introns that are repeat-poor and include transcription factors and signaling-cascade genes. The introns of widely expressed genes across human tissues, on the other hand, are short and repeat-rich, and coincide with those with the highest expression at the blastocyst stage.

Conclusions
Protein-coding genes that are characteristic of each trajectory, i.e., proliferation/pluripotency or differentiation, exhibit antithetical biases in their intronic and exonic lengths and in their repetitive-element content. While the respective human and mouse gene signatures are functionally and evolutionarily conserved, their introns and exons are enriched or depleted in organism-specific repetitive elements. We posit that these organism-specific repetitive sequences found in exons and introns are used to effect the corresponding genes’ regulation.
H3K27 modifiers regulate lifespan in C. elegans in a context-dependent manner
Authors: Guillermo Abigail R. R. , Chocian Karolina , Gavriilidis Gavriil , Vandamme Julien , Salcini Anna Elisabetta , Mellor Jane , Woollard Alison 
Published: March 2021

Abstract
Background
Evidence of global heterochromatin decay and aberrant gene expression in models of physiological and premature ageing have long supported the “heterochromatin loss theory of ageing”, which proposes that ageing is aetiologically linked to, and accompanied by, a progressive, generalised loss of repressive epigenetic signatures. However, the remarkable plasticity of chromatin conformation suggests that the re-establishment of such marks could potentially revert the transcriptomic architecture of animal cells to a “younger” state, promoting longevity and healthspan. To expand our understanding of the ageing process and its connection to chromatin biology, we screened an RNAi library of chromatin-associated factors for increased longevity phenotypes.

Results
We identified the lysine demethylases jmjd-3.2 and utx-1, as well as the lysine methyltransferase mes-2 as regulators of both lifespan and healthspan in C. elegans. Strikingly, we found that both overexpression and loss of function of jmjd-3.2 and utx-1 are all associated with enhanced longevity. Furthermore, we showed that the catalytic activity of UTX-1, but not JMJD-3.2, is critical for lifespan extension in the context of overexpression. In attempting to reconcile the improved longevity associated with both loss and gain of function of utx-1, we investigated the alternative lifespan pathways and tissue specificity of longevity outcomes. We demonstrated that lifespan extension caused by loss of utx-1 function is daf-16 dependent, while overexpression effects are partially independent of daf-16. In addition, lifespan extension was observed when utx-1 was knocked down or overexpressed in neurons and intestine, whereas in the epidermis, only knockdown of utx-1 conferred improved longevity.

Conclusions
We show that the regulation of longevity by chromatin modifiers can be the result of the interaction between distinct factors, such as the level and tissue of expression. Overall, we suggest that the heterochromatin loss model of ageing may be too simplistic an explanation of organismal ageing when molecular and tissue-specific effects are taken into account.
Frequency and functional translation of low muscle mass in overweight and obese patients with COPD
Authors: Machado Felipe V. C. , Spruit Martijn A. , Groenen Miriam T. J. , Houben-Wilke Sarah , van Melick Paula P. , Hernandes Nidia A. , Schols Annemie M. W. J. , Pitta Fabio , Wouters Emiel F. M. , Franssen Frits M. E. 
Published: March 2021

Abstract
Background
Cut offs for fat-free mass index (FFMI) and appendicular skeletal muscle mass index (ASMI) are available for diagnosing low muscle mass in patients with COPD. This study aimed to investigate: (1) the frequency of low muscle mass (FFMI and ASMI) applying different cut-offs and (2) the functional translation (clinical impact) of low muscle mass, in patients with COPD stratified into BMI categories.

Methods
Patients with COPD were assessed regarding body composition, exercise capacity, quadriceps muscle strength, symptoms of anxiety and depression, dyspnea and quality of life upon referral to pulmonary rehabilitation. The proportion of patients with low muscle mass was compared among BMI categories. Clinical outcomes between patients with normal and low muscle mass within each BMI category were compared.

Results
469 patients with COPD were included for analyses. The frequency of patients classified as low FFMI varied significantly according to the choice of cut-off (32 to 54%; P < 0.05), whereas the frequency of patients with low ASMI was 62%. When applying age-gender-BMI-specific cut-offs, 254 patients (54%) were classified as low FFMI. The choice of the cut-off affected the frequency of patients with low muscle mass in all BMI categories. Overweight and obese patients with low muscle mass were more frequently males and presented worse pulmonary function, exercise capacity and muscle strength compared with overweight and obese patients with normal muscle mass.

Conclusions
Approximately half of the overweight and obese patients with COPD have low muscle mass when applying age-gender-BMI-specific cut-offs. Low muscle mass is associated with worse functional outcomes in overweight and obese COPD patients.
Identification of a tumor microenvironment-related gene signature to improve the prediction of cervical cancer prognosis
Authors: Chen Qian , Qiu Bingqing , Zeng Xiaoyun , Hu Lang , Huang Dongping , Chen Kaihua , Qiu Xiaoqiang 
Published: March 2021

Abstract
Background
Previous studies have found that the microenvironment of cervical cancer (CESC) affects the progression and treatment of this disease. Thus, we constructed a multigene model to assess the survival of patients with cervical cancer.

Methods
We scored 307 CESC samples from The Cancer Genome Atlas (TCGA) and divided them into high and low matrix and immune scores using the ESTIMATE algorithm for differential gene analysis. Cervical cancer patients were randomly divided into a training group, testing group and combined group. The multigene signature prognostic model was constructed by Cox analyses. Multivariate Cox analysis was applied to evaluate the significance of the multigene signature for cervical cancer prognosis. Prognosis was assessed by Kaplan–Meier curves comparing the different groups, and the accuracy of the prognostic model was analyzed by receiver operating characteristic-area under the curve (ROC-AUC) analysis and calibration curve. The Tumor Immune Estimation Resource (TIMER) database was used to analyze the relationship between the multigene signature and immune cell infiltration.

Results
We obtained 420 differentially expressed genes in the tumor microenvironment from 307 patients with cervical cancer. A three-gene signature (SLAMF1, CD27, SELL) model related to the tumor microenvironment was constructed to assess patient survival. Kaplan–Meier analysis showed that patients with high risk scores had a poor prognosis. The ROC-AUC value indicated that the model was an accurate predictor of cervical cancer prognosis. Multivariate cox analysis showed the three-gene signature to be an independent risk factor for the prognosis of cervical cancer. A nomogram combining the three-gene signature and clinical features was constructed, and calibration plots showed that the nomogram resulted in an accurate prognosis for patients. The three-gene signature was associated with T stage, M stage and degree of immune infiltration in patients with cervical cancer.

Conclusions
This research suggests that the developed three-gene signature may be applied as a biomarker to predict the prognosis of and personalized therapy for CESC.
Validation of SYBR green I based closed‐tube loop‐mediated isothermal amplification (LAMP) assay for diagnosis of knowlesi malaria
Authors: Lai Meng Yee , Ooi Choo Huck , Lau Yee Ling 
Published: March 2021

AbstractBackgroundAs an alternative to PCR methods, LAMP is increasingly being used in the field of molecular diagnostics. Under isothermal conditions at 65 °C, the entire procedure takes approximately 30 min to complete. In this study, we establish a sensitive and visualized LAMP method in a closed-tube system for the detection ofPlasmodium knowlesi.MethodsA total of 71 malaria microscopy positive blood samples collected in blood spots were obtained from the Sarawak State Health Department. Using18s rRNAas the target gene, nested PCR and SYBR green I LAMP assay were performed following the DNA extraction. The colour changes of LAMP end products were observed by naked eyes.ResultsLAMP assay demonstrated a detection limit of 10 copies/µL in comparison with 100 copies/µL nested PCR. Of 71P. knowlesiblood samples collected, LAMP detected 69 microscopy-positive samples. LAMP exhibited higher sensitivity than nested PCR assay. The SYBR green I LAMP assay was 97.1% sensitive (95% CI 90.2–99.7%) and 100% specific (95% CI 83.2–100%). Without opening the cap, incorporation of SYBR green I into the inner cap of the tube enabled the direct visualization of results upon completion of amplification. The positives instantaneously turned green while the negatives remained orange.ConclusionsThese results indicate that SYBR green I LAMP assay is a convenient diagnosis tool for the detection ofP. knowlesiin remote settings.
Thrombotic antiphospholipid syndrome in a child with human immunodeficiency virus: a rare case report
Authors: Dong Rong-Jing , Lei Su-Yun , Li Jun , Yang Xin-Ping , Li Yu-Ye , Zhang Yun-Gui 
Published: March 2021

Abstract
Background
Antiphospholipid syndrome (APS) is a non-inflammatory autoimmune disorder induced by antiphospholipid antibodies, which occurs exceedingly rarely in pediatric population and even more rarely reported in HIV positive children.

Case summary
A case of 11 years old boy had a sudden onset of swelling in his left lower leg along with pain which were worsening gradually. Initially, topical ointment was applied for 1 month which were ineffective in reducing pain and swelling. Instead, the symptoms were aggravated and suddenly spread to the proximal thigh, accompanied by dyskinesia of left lower leg. Both color doppler ultrasonography and vascular CT scan of left lower leg revealed deep venous thrombosis. His serum anti-phospholipid antibodies (aPLs) were tested positive. He was a known case of HIV virological failure with substantial HIV viral load (VL) despite receiving regular antiretroviral therapy (ART). His symptoms improved after giving aggressive antithrombotic and high dose corticosteroid treatments.

Conclusion
When pediatric patients develop thrombotic disease, APS also needs to be ruled out. The autoantibodies levels should be routinely tested to look for recurrent thrombosis in children with HIV/AIDS.
What do Australian adults eat for breakfast? A latent variable mixture modelling approach for understanding combinations of foods at eating occasions
Authors: Leech Rebecca M. , Boushey Carol J. , McNaughton Sarah A. 
Published: March 2021

Abstract
Background
The patterning of food intake at eating occasions is a poorly understood, albeit important, step towards achieving a healthy dietary pattern. However, to capture the many permutations of food combinations at eating occasions, novel analytic approaches are required. We applied a latent variable mixture modelling (LVMM) approach to understand how foods are consumed in relation to each other at breakfast.

Methods
Dietary intake at breakfast (n = 8145 occasions) was assessed via 24-h recall during the 2011–12 Australian National Nutrition and Physical Activity Survey (n = 3545 men and n = 4127 women, ⩾19 y). LVMM was used to determine breakfast food profiles based on 35 food group variables, reflecting compliance with Australian Dietary Guidelines. F and adjusted-chi2 tests assessed differences in timing of consumption and participant characteristics between the breakfast profiles. Regression models, adjusted for covariates, were used to examine associations between breakfast food profiles and objective adiposity measures (BMI and waist circumference).

Results
Five distinct profiles were found. Three were similar for men and women. These were labelled: “Wholegrain cereals and milks” (men: 16%, women: 17%), “Protein-foods” (men and women: 11%) and “Mixed cereals and milks” (men: 33%, women: 37%). Two “Breads and spreads” profiles were also found that were differentiated by their accompanying beverages (men) or type of grain (women). Profiles were found to vary by timing of consumption, participant characteristics and adiposity indicators. For example, the “Protein-foods” profile occurred more frequently on weekends and after 9 am. Men with a “Bread and spreads (plus tea/coffee)” profile were older (P < 0.001) and had lower income and education levels (P < 0.05), when compared to the other profiles. Women with a “Protein-foods” profile were younger (P < 0.001) and less likely to be married (P < 0.01). Both men and women with a “Wholegrain cereals and milks” profile had the most favourable adiposity estimates (P < 0.05).

Conclusions
We identified five breakfast food profiles in adults that varied by timing of consumption, participant characteristics and adiposity indicators. LVMM was a useful approach for capturing the complexity of food combinations at breakfast. Future research could collect contextual information about eating occasions to understand the complex factors that influence food choices.
Multi-omics characterization and validation of invasiveness-related molecular features across multiple cancer types
Authors: Bi Guoshu , Liang Jiaqi , Zheng Yuansheng , Li Runmei , Zhao Mengnan , Huang Yiwei , Zhan Cheng , Xu Songtao , Fan Hong 
Published: March 2021

Abstract
Background
Tumor invasiveness reflects many biological changes associated with tumorigenesis, progression, metastasis, and drug resistance. Therefore, we performed a systematic assessment of invasiveness-related molecular features across multiple human cancers.

Materials and methods
Multi-omics data, including gene expression, miRNA, DNA methylation, and somatic mutation, in approximately 10,000 patients across 30 cancer types from The Cancer Genome Atlas, Gene Expression Omnibus, PRECOG, and our institution were enrolled in this study.

Results
Based on a robust gene signature, we established an invasiveness score and found that the score was significantly associated with worse prognosis in almost all cancers. Then, we identified common invasiveness-associated dysregulated molecular features between high- and low-invasiveness score group across multiple cancers, as well as investigated their mutual interfering relationships thus determining whether the dysregulation of invasiveness-related genes was caused by abnormal promoter methylation or miRNA expression. We also analyzed the correlations between the drug sensitivity data from cancer cell lines and the expression level of 685 invasiveness-related genes differentially expressed in at least ten cancer types. An integrated analysis of the correlations among invasiveness-related genetic features and drug response were conducted in esophageal carcinoma patients to outline the complicated regulatory mechanism of tumor invasiveness status in multiple dimensions. Moreover, functional enrichment suggests the invasiveness score might serve as a predictive biomarker for cancer patients receiving immunotherapy.

Conclusion
Our pan-cancer study provides a comprehensive atlas of tumor invasiveness and may guide more precise therapeutic strategies for tumor patients.
Variability in phenotype and response to treatment in chronic nonbacterial osteomyelitis; the Irish experience of a national cohort
Authors: O’Leary Daire , Wilson Anthony G. , MacDermott Emma-Jane , Lowry Clodagh , Killeen Orla G. 
Published: March 2021

Abstract
Background
Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory disease affecting bone with considerable phenotypic heterogeneity and variable association with other autoinflammatory conditions. Disease pathogenesis is incompletely understood, and treatment protocols vary between physicians with no clinical treatment guidelines available prior to 2017. Although CNO was previously considered benign, it is now clear that long-term sequelae do occur.
The aim of this study is to provide a detailed phenotypic description of children and adolescents with CNO who attended tertiary paediatric rheumatology services in Ireland between September 2017 and September 2019, their disease course, treatment and outcomes.

Methods
This study involved retrospective review of clinical notes, laboratory, radiology and histology results of Irish children and adolescents with CNO who are currently attending tertiary paediatric rheumatology services. The Bristol diagnostic criteria were applied retrospectively; only patients who met these criteria were included. Criteria for remission and partial response were based on the Childhood Arthritis and Rheumatology Research Alliance (CARRA) criteria for treatment failure.

Results
Forty-four children and adolescents were recruited. Demographics in terms of age of onset, gender and number of sites were similar to those previously reported. Overall, 18/44 (40.9%) had extraosseous manifestations associated with CNO; 12/44 (27.2%) had cutaneous involvement. All patients received a regular nonsteroidal anti-inflammatory drug (NSAID) after diagnosis with 27/44 (61.4%) requiring at least 1 second-line medication. Second-line agents used in this cohort were bisphosphonates, methotrexate and TNF-blockers. No patients received systemic corticosteroids.

Conclusion
This national cohort showed a high prevalence of extraosseous involvement and a low response rate to NSAID treatment. This may reflect a more inflammatory phenotype and highlights the need to define different subtypes of CNO.