bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laminin G1 residues of protein S mediate its TFPI cofactor function and are competitively regulated by C4BP
Authors: Teraz-Orosz Adrienn , Gierula Magdalena , Petri Anastasis , Jones David , Keniyopoullos Renos , Folgado Patricia Badia , Santamaria Salvatore , Crawley James T. B. , Lane David A. , Ahnström Josefin 
Published: November 2021

AbstractProtein S is a cofactor in the tissue factor pathway inhibitor (TFPI) anticoagulant pathway. It enhances TFPIα-mediated inhibition of factor (F)Xa activity and generation. The enhancement is dependent on a TFPIα-protein S interaction involving TFPIα Kunitz 3 and protein S laminin G-type (LG)-1. C4b binding protein (C4BP), which binds to protein S LG1, almost completely abolishes its TFPI cofactor function. However, neither the amino acids involved in TFPIα enhancement nor the mechanisms underlying the reduced TFPI cofactor function of C4BP-bound protein S are known. To screen for functionally important regions within protein S LG1, we generated 7 variants with inserted N-linked glycosylation attachment sites. Protein S D253T and Q427N/K429T displayed severely reduced TFPI cofactor function while showing normal activated protein C (APC) cofactor function and C4BP binding. Based on these results, we designed 4 protein S variants in which 4 to 6 surface-exposed charged residues were substituted for alanine. One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. The C4BP β-chain was expressed to determine the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S, C4BP β-chain-bound protein S had severely reduced TFPI cofactor function. These results show that protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 are critical for protein S-mediated enhancement of TFPIα and that binding of the C4BP β-chain blocks this function.
Complete mitochondrial genomes reveal robust phylogenetic signals and evidence of positive selection in horseshoe bats
Authors: Zhang Lin , Sun Keping , Csorba Gábor , Hughes Alice Catherine , Jin Longru , Xiao Yanhong , Feng Jiang 
Published: November 2021

Abstract
Background
In genus Rhinolophus, species in the Rhinolophus philippinensis and R. macrotis groups are unique because the horseshoe bats in these group have relatively low echolocation frequencies and flight speeds compared with other horseshoe bats with similar body size. The different characteristics among bat species suggest particular evolutionary processes may have occurred in this genus. To study the adaptive evidence in the mitochondrial genomes (mitogenomes) of rhinolophids, especially the mitogenomes of the species with low echolocation frequencies, we sequenced eight mitogenomes and used them for comparative studies of molecular phylogeny and adaptive evolution.

Results
Phylogenetic analysis using whole mitogenome sequences produced robust results and provided phylogenetic signals that were better than those obtained using single genes. The results supported the recent establishment of the separate macrotis group. The signals of adaptive evolution discovered in the Rhinolophus species were tested for some of the codons in two genes (ND2 and ND6) that encode NADH dehydrogenases in oxidative phosphorylation system complex I. These genes have a background of widespread purifying selection. Signals of relaxed purifying selection and positive selection were found in ND2 and ND6, respectively, based on codon models and physicochemical profiles of amino acid replacements. However, no pronounced overlap was found for non-synonymous sites in the mitogenomes of all the species with low echolocation frequencies. A signal of positive selection for ND5 was found in the branch-site model when R. philippinensis was set as the foreground branch.

Conclusions
The mitogenomes provided robust phylogenetic signals that were much more informative than the signals obtained using single mitochondrial genes. Two mitochondrial genes that encoding proteins in the oxidative phosphorylation system showed some evidence of adaptive evolution in genus Rhinolophus and the positive selection signals were tested for ND5 in R. philippinensis. These results indicate that mitochondrial protein-coding genes were targets of adaptive evolution during the evolution of Rhinolophus species, which might have contributed to a diverse range of acoustic adaptations in this genus.
Deep transcriptomic study reveals the role of cell wall biosynthesis and organization networks in the developing shell of peanut pod
Authors: Gupta Kapil , Gupta Shubhra , Faigenboim-Doron Adi , Patil Abhinandan Surgonda , Levy Yael , Carrus Scott Cohen , Hovav Ran 
Published: November 2021

AbstractBackgroundPeanut (Arachis hypogaeaL.) belongs to an exceptional group of legume plants, wherein the flowers are produced aerially, but the pods develop under the ground. In such a unique environment, the pod’s outer shell plays a vital role as a barrier against mechanical damage and soilborne pathogens. Recent studies have reported the uniqueness and importance of gene expression patterns that accompany peanut pods’ biogenesis. These studies focused on biogenesis and pod development during the early stages, but the late developmental stages and disease resistance aspects still have gaps. To extend this information, we analyzed the transcriptome generated from four pod developmental stages of two genotypes, Hanoch (Virginia-type) and IGC53 (Peruvian-type), which differs significantly in their pod shell characteristics and pathogen resistance.ResultsThe transcriptome study revealed a significant reprogramming of the number and nature of differentially expressed (DE) genes during shell development. Generally, the numbers of DE genes were higher in IGC53 than in Hanoch, and the R5-R6 transition was the most dynamic in terms of transcriptomic changes. Genes related to cell wall biosynthesis, modification and transcription factors (TFs) dominated these changes therefore, we focused on their differential, temporal and spatial expression patterns. Analysis of the cellulose synthase superfamily identified specificCellulose synthase(CesAs)andCellulose synthase-like(Csl)genes and their coordinated interplay with other cell wall-related genes during the peanut shell development was demonstrated. TFs were also identified as being involved in the shell development process, and their pattern of expression differed in the two peanut genotypes. The shell component analysis showed that overall crude fiber, cellulose, lignin, hemicelluloses and dry matter increased with shell development, whereas K, N, protein, and ash content decreased. Genotype IGC53 contained a higher level of crude fiber, cellulose, NDF, ADF, K, ash, and dry matter percentage, while Hanoch had higher protein and nitrogen content.ConclusionsThe comparative transcriptome analysis identified differentially expressed genes, enriched processes, and molecular processes like cell wall biosynthesis/modifications, carbohydrate metabolic process, signaling, transcription factors, transport, stress, and lignin biosynthesis during the peanut shell development between two contrasting genotypes. TFs and other genes like chitinases were also enriched in peanut shells known for pathogen resistance against soilborne major pathogens causing pod wart disease and pod damages. This study will shed new light on the biological processes involved with underground pod development in an important legume crop.
Demographic, tumour, and treatment characteristics of female patients with breast cancer in Sri Lanka; results from a hospital-based cancer registry
Authors: Wijeratne Don Thiwanka , Gunasekera Sanjeeva , Booth Christopher M. , Promod Hasitha , Jalink Matthew , Jayarajah Umesh , Seneviratne Sanjeewa 
Published: November 2021

Abstract
Background
Although breast cancer is the most common cancer among Sri Lankan women, there is little published data on patient characteristics and treatment in the local context. We aimed to describe disease characteristics and management in a large contemporary cohort of women with breast cancer at the National Cancer Institute of Sri Lanka (NCISL).

Methods
All women with invasive primary breast cancers diagnosed during 2016–2020 were identified from the NCISL breast cancer registry. The NCISL sees approximately 40% of all cancer patients in Sri Lanka. Cancer stage at diagnosis was defined according to the Tumour, Node, and Metastasis (TNM) staging system and the Estrogen (ER) and progesterone (PR) receptor status was determined based on the results of immunohistochemistry tests. Descriptive statistics were used to describe the study cohort and treatment patterns.

Results
Over 5100 patients were diagnosed with breast cancer during the study period at the NCISL. The mean age of the women was 56 (SD 12) years. Common co-morbidities were hypertension (n = 1566, 30%) and diabetes mellitus (n = 1196, 23%). Two thirds (66%) of the cancers were early stage (stage I & II) at diagnosis. ER/PR positivity rate was 72% and HER-2 positivity rate was 22%. Two thirds of the women had undergone mastectomy while 68% had undergone axillary clearance. The rate of chemotherapy delivery was 91% for women with node positive disease while 77% of eligible women (i.e., after wide local excision or with > 3 positive lymph nodes) had received adjuvant radiotherapy. Endocrine therapy was initiated in 88% of eligible women with hormone receptor positive disease while rate of trastuzumab use was 59% among women with HER2 positive breast cancer.

Conclusions
High percentage of advanced breast cancer at diagnosis and high prevalence of comorbidities are some of the major challenges faced in the management of breast cancer in Sri Lanka. Given that stage at diagnosis is the most important prognostic factor determining survival, greater efforts are needed to promote early diagnosis of breast cancer. Considerable lapses in the concordance between guideline recommendations and the delivery of cancer care warrants closer assessment and intervention.
Developing a prioritisation framework for patients in need of coronary artery angiography
Authors: Doshmangir Leila , Pourasghar Faramarz , Sharghi Rahim , Rezapour Ramin , Gordeev Vladimir Sergeevich 
Published: November 2021

Abstract
Background
Effective waiting list management and comprehensive prioritisation can provide timely delivery of appropriate services to ensure that the patient needs are met and increase equity in the provision of health services. We developed a prioritisation framework for patients in need of coronary artery angiography (CAA).

Methods
We used a multi-methods approach to elicit effective factors that affect CAA patient prioritisation. Qualitative data wase collected using semi-structured interviews with 15 experts. The final set of factors was selected using experts’ consensus through modifed Delphi technique. The framework was finalised during expert panel meetings.

Results
212 effective factors were identified based on the literature review, interviews, and expert panel discussion of them, 37 factors were selected for modifed Delphi study. Following two rounds of Delphi discussions, seven final factors were selected and weighed by ten experts using pair-wise comparisons. The following weights were given: the severity of pain and symptoms (0.22), stress testing (0.18), background diseases (0.15), number of myocardial infarctions (0.15), waiting time (0.10), reduction of economic and social performance (0.12), and special conditions (0.08).

Conclusion
Clinical effective factors were important for CAA prioritisation framework. Using this framework can potentially lead to improved accountability and justice in the health system.
Spirometric reference equations for Cameroonians aged 4 to 89 years derived using lambda, mu, sigma (LMS) method
Authors: Pefura-Yone Eric Walter , Balkissou Adamou Dodo , Poka-Mayap Virginie , Djenabou Amadou , Massongo Massongo , Ofimboudem Nguetsa Arsene , Mayoh-Nguemfo Catherine Fanny , Tsala Antoinette Ghislaine , Hadjara Halidou , Amougou Francine 
Published: November 2021

Abstract
Background
Spirometric reference values are well known in several ethnic groups but the normative spirometric values of blacks living in Africa have been less studied. The purpose of this study is to establish normative spirometric equations from a representative population of Cameroonian children and adults and compare these equations with those developed by the Global Lung Initiative (GLI) and in Nigerians.

Methods
Spirometric data from healthy Cameroonians aged 4–89 years randomly collected between 2014 and 2018 were used to derive reference equations using generalized additive model for location (mu), shape (lambda) and scale (sigma).

Results
A total of 625 children and adolescents (290 males and 335 females) and 1152 adults (552 males and 600 females) were included in the study. The prediction equation for spirometric index was written as: M = Exp[a0 + a1*ln (Height) + a2*ln (Age) + Mspline, Mspline was age related spline contribution]. Applying the GLI standards for African Americans resulted in overall values greater than those found in our study for forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC). These values were very close in children and adolescents while the values obtained with the GLI equations for African Americans were significantly higher in adults. FEV1/FVC ratio in our study was similar for adult males but lower in adult females (88% vs 85%, difference =  + 3.5%) when applying Nigerian standards.

Conclusions
FEV1 and FVC of the Cameroonian infant and adolescent population are very close to those of black Americans. However, FEV1 and FVC of Cameroonian adults are significantly lower than those of black American adults. These equations should allow a more suitable interpretation of spirometry in the Cameroonian population.
Midwives’ strategies for coping with barriers to providing quality maternal and neonatal care: a Glaserian grounded theory study
Authors: Ismaila Yakubu , Bayes Sara , Geraghty Sadie 
Published: November 2021

Abstract
Background
Midwives face direct and indirect barriers in their workplaces that have negative consequences on their ability to provide quality care to women and neonates, however, they still carry on with their duties. This study aimed at investigating the coping strategies that Ghanaian midwives adopt to be able to complete their work.

Methods
Glaserian Grounded theory was used in this study. Data were collected through non-participant observations and semi-structured interviews. The study participants included 29 midwives who worked in labour/birthing environments and a pharmacist, a social worker, a national Health Insurance Scheme manager and a health services manager.

Findings
The midwives’ motivation due to their strong desire to save the lives of women and neonates and their strong affection for the midwifery profession was identified to help them cope with the barriers that they faced in their workplaces. The midwives’ motivation was found to spur actions such as improvising, taking control of the birthing process and the birthing environment and the maintenance of social and professional networks to help them to complete their duties.

Conclusion
Ghanaian midwives face myriad barriers in their workplaces; however, they are able to adopt coping strategies that enable them to complete their duties. The provision of care resources for maternity services in the country will reduce the barriers that the midwives face and improve the quality of maternal and neonatal care. In the short term however, pre and post midwifery educational programmes should focus on developing resilience in the midwifery workforce to help midwives cope more effectively with the challenges that they face in their workplaces.
Emergency hospital admissions among older adults living alone in the community
Authors: Barrenetxea Jon , Tan Kelvin Bryan , Tong Rachel , Chua Kevin , Feng Qiushi , Koh Woon-Puay , Chen Cynthia 
Published: November 2021

Abstract
Background
Among older adults, living alone is often associated with higher risk of Emergency Department (ED) admissions. However, older adults living alone are very heterogeneous in terms of health. As more older adults choose to live independently, it remains unclear if the association between living alone and ED admissions is moderated by health status. We studied the association between living alone and ED admission outcomes (number of admissions, inpatient days and inpatient costs) among older adults with and without multimorbidity.

Methods
We used data from 16,785 individuals of the third follow-up of the Singapore Chinese Health Study, a population-based cohort of older Singapore Chinese (mean age: 73(61-96) years). Participants were interviewed face-to-face from 2014 to 2016 for sociodemographic/health factors and followed-up for one year on ED admission outcomes using Singapore Ministry of Health’s Mediclaim Database. We first applied multivariable logistic regression and two-part models to test if living alone is a risk factor for ED admission outcomes. We then ran stratified and joint effect analysis to examine if the associations between living alone and ED admission outcomes were moderated by multimorbidity.

Results
Compared to living with others, living alone was associated with higher odds of ED admission [Odds Ratio (OR) 1.28, 95 % Confidence Interval(CI) 1.08-1.51)], longer inpatient days (+0.61, 95 %CI 0.25-0.97) and higher inpatient costs (+322 USD, 95 %CI 54-591). The interaction effects of living arrangement and multimorbidity on ED admissions and inpatient costs were not statistically different, whereas the interaction between living arrangements and multimorbidity on inpatient days was borderline significant (p-value for interaction=0.050). Compared to those living with others and without multimorbidity, the relative mean increase was 1.13 inpatient days (95 %CI 0.39-1.86) for those living alone without multimorbidity, and 0.73 inpatient days ( 95 %CI 0.29-1.17) for those living alone with multimorbidity.

Conclusions
Older adults living alone were at higher risk of ED admission and higher inpatient costs regardless of multimorbidity, while those living alone without multimorbidity had the longest average inpatient days. To enable aging in place while avoiding ED admissions, interventions could provide instrumental support and regular health monitoring to older adults living alone, regardless of their health status.
Reduced risk of recurrent pneumothorax for sirolimus therapy after surgical pleural covering of entire lung in lymphangioleiomyomatosis
Authors: Sakurai Teiko , Arai Toru , Hirose Masaki , Kojima Kensuke , Sakamoto Tetsuki , Matsuda Yoshinobu , Sugimoto Chikatoshi , Yoon Hyung-Eun , Inoue Yoshikazu 
Published: November 2021

Abstract
Background
Patients with lymphangioleiomyomatosis (LAM) frequently experience pneumothorax. Although sirolimus is the standard therapy for LAM, its effect on pneumothorax is controversial. Recently, total pleural covering (TPC) and modified TPC (mTPC) were introduced as surgical treatment options for pneumothorax for patients with LAM. However, the effect of sirolimus on the recurrence of pneumothorax in patients who underwent the treatments is still uncertain. We hypothesized that some clinical factors including sirolimus treatment could predict postoperative recurrence of pneumothorax. In order to clarify this hypothesis, we retrospectively analyzed the clinical data from 18 consecutive patients with LAM who underwent 24 surgical pleural covering of entire lung (SPC) as 17 TPC and 7 mTPC against pneumothoraces from surgical database between January 2005 and January 2019, and we determined the predictors of postoperative recurrence.

Results
Of the 24 surgeries of SPC, 14 surgeries (58.3%) had a history of two or more ipsilateral pneumothoraces, and 11 surgeries (45.8%) had a history of ipsilateral pleural procedures before SPC. Sixteen surgeries (66.6%) in 12 patients received treatment of sirolimus after SPC (sirolimus group). With a median follow-up time of 69.0 months after SPC, four surgeries (16.6%) in three patients had a postoperative recurrence, and the 5-year recurrence-free survival (RFS) after SPC was 82.9%. In patients with postoperative recurrence, serum level of vascular endothelial growth factors D was significantly higher than that in those with non-recurrence (3260.5 vs. 892.7 pg/mL, p = 0.02), and the rate of sirolimus treatment in the recurrence group was significantly lower than that in the no-recurrence group (0 vs. 80%, p = 0.006). The log-rank test showed that the RFS of the sirolimus group (sirolimus use after SPC) was significantly better than that of the non-sirolimus group (p = 0.001), and no significant difference was observed for other factors.

Conclusion
We first reported sirolimus might effectively suppress the recurrence of pneumothoraces in LAM patients who received SPC. Sirolimus induction after SPC (TPC or mTPC) might be a feasible option for frequent pneumothorax in LAM.
Comparison of trapping methods for use in surveys for potential Culicoides vectors of orbiviruses
Authors: Becker Michael , Park Jeong-Seok , Gentry Glen , Husseneder Claudia , Foil Lane 
Published: November 2021

AbstractBackgroundBluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV) are orbiviruses that can cause fatal vector-borne diseases in white-tailed deer (Odocoileus virginianus). Trapping methods for collecting potentialCulicoidesvectors of orbiviruses were compared to optimize surveillance studies.MethodsThe number of captured midges and the virus infection rates of midge pools were compared for dry ice-baited Centers for Disease Control and Prevention (CDC) traps with or without black light. The number of individual midges of differentCulicoidesspecies captured at different crepuscular and nocturnal periods using rotator traps also was determined. The number of species/specimens ofCulicoideswas measured using five different trap methods including three animal-baited methods, a CDC trap with black light, and a CDC trap with no light.ResultsIn trial one, there was no significant difference (P = 0.37) in the proportion of BTV-infected flies caught in traps with light compared to traps without light. However, there was a significant difference (P = 0.026) for EHDV-infected flies, and 89% were captured in traps with light. In trial two, more specimens ofC. debilipalpiswere captured in the morning hours (06:00–08:00) than in the evening hours (18:00–20:00). For trial three, the animal-baited traps did not capture any species ofCulicoidesthat were not captured in the CDC light traps. There was no significant difference (P = 0.22) in total specimens captured among all five trap types.ConclusionsSpecimens ofCulicoidesinfected with BTV were not repelled by light traps in the first trial, while the majority of the specimens positive for EHDV were caught in traps with light. For the second trial, specimens ofC. debilipalpiswere most abundant during early morning hours, and thus spray applications of insecticides for control of that species may be more effective at sunrise rather than sunset. For objective three, no animal-baited trapping method collected different species of midges when compared to the CDC traps with light, which is unlike certain studies conducted in other geographical regions.Graphical abstract