bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinimetric analysis of outcome measures for airway clearance in people with cystic fibrosis: a systematic review
Authors: Stanford Gemma E. , Jones Mandy , Charman Susan C. , Bilton Diana , Usmani Omar S. , Davies Jane C. , Simmonds Nicholas J. 
Published: September 2022

Background: Airway clearance techniques (ACTs) are integral to cystic fibrosis (CF) management. However, there is no consensus as to which outcome measures (OMs) are best for assessing ACT efficacy. Objectives: To summarise OMs that have been assessed for their clinimetric properties (including validity, feasibility, reliability, and reproducibility) within the context of ACT research in CF. Design and Methods: A systematic review was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) standards. Any parallel or cross-over randomised controlled trial (RCT) investigating outcome measures for ACT in the CF population were eligible for inclusion. The search was performed in five medical databases, clinicaltrials.gov, and abstracts from international CF conferences. The authors planned to independently assess study quality and risk of bias using the COnsensus-based Standards for the selection of health status Measurement InstrumeNts (COSMIN) risk of bias checklist with external validity assessment based upon study details (participants and study intervention). Two review authors (GS and MJ) independently screened search results against inclusion criteria, and further data extraction were planned but not required. Results: No completed RCTs from the 187 studies identified met inclusion criteria for the primary or post hoc secondary objective. Two ongoing trials were identified. Discussion and conclusion: This empty systematic review highlights that high-quality RCTs are urgently needed to investigate and validate the clinimetric properties of OMs used to assess ACT efficacy. With the changing demographics of CF combined with the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies, an accurate assessment of the current benefit of ACT or the effect of ACT withdrawal is a high priority for clinical practice and future research; OMs which have been validated for this purpose are essential. Registration: This systematic review was registered on the PROSPERO database (CRD42020206033).
Prevalence of pulmonary tuberculosis and associated factors among adults living with HIV/AIDS attending public hospitals in Shashamene Town, Oromia Region, South Ethiopia
Authors: Gisso Belayneh Tadesse , Hordofa Mesfin Worku , Ormago Moges Desta 
Published: September 2022

Objective: This study was aimed to assess the prevalence of pulmonary tuberculosis and its associated factors among adults living with HIV/AIDS attending Public Hospitals, Shashamene Town, Oromia Region, South Ethiopia. Methods: A cross-sectional study was conducted from November 2020 to February 2021 among Adults Living with HIV/AIDS attending Public Hospitals in Shashamene Town, Oromia Region, South Ethiopia. A sputum sample was collected and analyzed using Xpert MTB/RIF assay and blood sample was collected to count CD4 using BD FACSPresto analyzer. Semi-structured questionnaires were used to collect data. SPSS version 25 software was used for statistical analysis and a p value of <0.05 was considered as statistically significant. Results: In this study, the overall prevalence of pulmonary tuberculosis among adults living with HIV/AIDS attending the Public Hospitals was 23.5% (5% confidence interval: 18.26, 29.13). Variables such as age range of 50–64 years, female gender, occupation with house wife, and World Health Organization stage (III and IV) were significantly associated with prevalence of tuberculosis infection. Conclusion: The prevalence of tuberculosis in our study site was high. There is a need for regular screening of people living with HIV/AIDS for TB using highly sensitive method like Xpert MTB/RIF assay to know their TB status as well as early commencement of anti-TB.
Thinking outside Earth’s box—how might heredity and evolution differ on other worlds?
Authors: Noor Mohamed A. F. 
Published: September 2022

AbstractScholars and the public conceive of extraterrestrial life through the lens of "life as we know it" on Earth. However, assumptions based on centuries of study around heredity and evolution on Earth may not apply to life truly independent forms of life, and some perspectives accepted or ruled out in the nineteenth century may need to be re-evaluated for life outside of Earth. In honor of the 200th birthday of Mendel, and to provide raw material for the creativity of storytellers, filmmakers, and the public, this thought experiment essay revisits a handful of classic concepts and approaches, as well as some unusual forms of life on Earth, to posit whether different types of genetics and evolution may exist in truly independent extraterrestrial forms. While fundamental evolutionary processes like natural selection and genetic drift are likely to still apply at least similarly in independent life forms, inheritance may be quite radically different from that envisioned by Mendel and others since.
OsFTL4, an FT-like Gene, Regulates Flowering Time and Drought Tolerance in Rice (Oryza sativa L.)
Authors: Gu Houwen , Zhang Kunming , Chen Jie , Gull Sadia , Chen Chuyan , Hou Yafei , Li Xiangbo , Miao Jun , Zhou Yong , Liang Guohua 
Published: September 2022

AbstractThe initiation of flowering in cereals is a critical process influenced by environmental and endogenous signals. Flowering Locus T-like (FT-like) genes encode the main signals for flowering. Of the 13 FT-like genes in the rice genome, Hd3a/OsFTL2 and RFT1/OsFTL3 have been extensively studied and revealed to be critical for flowering. In this study, a rice FT-like gene, OsFTL4, was functionally characterized. Specifically, osftl4 mutants were generated using a CRISPR/Cas9 system. Compared with the wild-type control (Guangluai 4), the osftl4-1 and osftl4-2 mutants flowered 9.6 and 5.8 days earlier under natural long-day and short-day conditions, respectively. Additionally, OsFTL4 was mainly expressed in the vascular tissue, with the resulting OsFTL4 protein localized in both the nucleus and cytoplasm. Furthermore, OsFTL4 was observed to compete with Hd3a for the interaction with multiple 14-3-3 proteins. An analysis of the effects of simulated drought stress suggested that silencing OsFTL4 enhances drought tolerance by decreasing stomatal conductance and water loss. These results indicate that OsFTL4 helps integrate the flowering process and the drought response in rice.
The proportion and phenotypic changes of CD4+CD25−Foxp3+ T cells in patients with untreated rheumatoid arthritis
Authors: Ju Bomiao , Zhu Li , Wang Jing , Zheng Jian , Hao Zhiming , Luo Jing , Zhang Jing , Hu Nan , An Qi , Feng Xiuyuan , Huo Yongwei , He Lan 
Published: September 2022

Abstract
Objective
CD4+CD25+Foxp3+ regulatory T (Treg) cell-mediated immunosuppression is an essential mechanism of rheumatoid arthritis (RA). However, little is known regarding the specific role of CD4+CD25−Foxp3+ Treg cells in RA. This study aimed to investigate the frequency of circulating CD4+CD25−Foxp3+ Treg cells and their role in RA.

Methods
Sixty-one untreated RA patients and 40 healthy controls (HCs) were enrolled in this study. The proportion of CD4+CD25−Foxp3+ T cells and CD4+CD25+Foxp3+ Tregs; the levels of CTLA4, GITR, Helios, and ICOS; and the production of IL-17A, IFN-γ, and IL-10 were assessed by flow cytometry. The correlation of CD4+CD25–Foxp3+ T cells and CD4+CD25+Foxp3+ Tregs with the clinical indicators was conducted by Spearman correlation analysis.

Results
The proportion of CD4+CD25–Foxp3+ T cells was elevated in RA and positively correlated with disease activity. CD4+CD25–Foxp3+ T cells expressed less Helios and produced more IFN-γ than conventional Tregs in RA. Additionally, the proportion of CD4+CD25–Foxp3+ T cells was positively correlated with DAS28 score, IgG titer, and anti-CCP titer.

Conclusions
These data indicate that CD4+CD25−Foxp3+ T cells in RA exhibit several different functional properties from conventional Tregs and are correlated with RA disease activity.
Comparative study of a modified double-lumen tube ventilation control connector and traditional connector in clinical use: a randomised-controlled trial
Authors: Liu Chang , Zhao Yuanyu , Li You , Guan Huiwen , Feng Junjie , Cheng Shengquan , Wang Xin , Wang Yue , Sun Xufang 
Published: September 2022

Abstract
Background
A Y-shaped rotatable connector (YRC) for double-lumen tubes (DLT) is invented and compared with the traditional connector (Y-shaped connector, YC).

Methods
Sixty patients with ASA grade I-III, aged ≥ 18 years, who needed to insert a DLT for thoracic surgery were recruited and assigned into the YRC group (n = 30) and the YC group (n = 30) randomly. The primary endpoints included the inhaled air concentration (Fi) and the exhaled air concentration (Et) of sevoflurane before and after the switch between two-lung ventilation and one-lung ventilation at different times, positioning time, and switching time. The secondary endpoints were the internal gas volume of the two connectors, airway pressure, and the sputum suction time.

Results
The Et and Fi of the YRC group and the YC group were significantly different (all p < 0.05) at 5s, 10s, and 30s after the patient switched from two-lung ventilation to one-lung ventilation. The positioning time of the YRC group was less than YC group (89.75 ± 14.28 s vs 107.80 ± 14.96 s, p < 0.05), as well as the switching time (3.60 ± 1.20 s vs 9.05 ± 2.53 s, p < 0.05) and the internal gas volume (17.20 ml vs 24.12 ml). There was no difference in airway pressure and the sputum suction time in two groups.

Conclusion
Compared with YC, YRC was beneficial for maintaining depth of anesthesia, improves efficiency for the switch between one-lung and two-lung ventilation, and shortens the tube positioning time.
Family functioning and health-related quality of life of inpatients with coronary heart disease: a cross-sectional study in Lanzhou city, China
Authors: Zhang Hongchen , Wang Yanhong , Cai Xiaoqing , Tang Nan , Wei Siqi , Yang Yanwei 
Published: September 2022

Abstract
Background
A key outcome in coronary heart disease (CHD) is Health Related Quality of Life (HRQoL), and family functioning is important in the management of CHD. But few studies have examined both together, and little is known about them among inpatients with CHD in less developed areas of China. Therefore, this study aimed to assess the HRQoL and family functioning status of inpatients with CHD in Lanzhou from Northwest China, and identify the factors that affect their HRQoL.

Methods
A cross‑sectional study was conducted in 224 CHD inpatients at one major hospital. Sociodemographic data and disease information of CHD inpatients were collected by face-to-face using a structured questionnaire and data were also obtained from patient medical records. HRQoL was measured using the Sickness Impact Profile (SIP). Family functioning was measured using the family APGAR index. Multiple binary logistic regression analysis (MBLRA) was used to explore potential risk factors associated with HRQoL, and Pearson’s correlations were used to assess the relationship between family functioning and HRQoL.

Results
The overall, physical and psychosocial SIP scores were 25.03 ± 8.52, 18.61 ± 9.90 and 28.08 ± 9.64, respectively. The total family APGAR score was 6.11 ± 2.45. MBLRA found older age, poorer cardiac function and more severe disease were associated with poorer HRQoL, while better family functioning, higher monthly income, and urban living were associated with better HRQoL. Family functioning was weakly to moderately correlated with total and psychosocial HRQoL.

Conclusions
Older and less affluent inpatients with lower educational level, less family support and more severe CHD have poorest quality of life, and health care providers should consider interventions to support them.
Impact of metal artifact reduction algorithm on gross tumor volume delineation in tonsillar cancer: reducing the interobserver variation
Authors: Fukugawa Yoshiyuki , Toya Ryo , Matsuyama Tomohiko , Watakabe Takahiro , Shimohigashi Yoshinobu , Kai Yudai , Matsumoto Tadashi , Oya Natsuo 
Published: September 2022

Abstract
Background
Patients with tonsillar cancer (TC) often have dental fillings that can significantly degrade the quality of computed tomography (CT) simulator images due to metal artifacts. We evaluated whether the use of the metal artifact reduction (MAR) algorithm reduced the interobserver variation in delineating gross tumor volume (GTV) of TC.

Methods
Eighteen patients with TC with dental fillings were enrolled in this study. Contrast-enhanced CT simulator images were reconstructed using the conventional (CTCONV) and MAR algorithm (CTMAR). Four board-certified radiation oncologists delineated the GTV of primary tumors using routine clinical data first on CTCONV image datasets (GTVCONV), followed by CTCONV and CTMAR fused image datasets (GTVMAR) at least 2 weeks apart. Intermodality differences in GTV values and Dice similarity coefficient (DSC) were compared using Wilcoxon’s signed-rank test.

Results
GTVMAR was significantly smaller than GTVCONV for three observers. The other observer showed no significant difference between GTVCONV and GTVMAR values. For all four observers, the mean GTVCONV and GTVMAR values were 14.0 (standard deviation [SD]: 7.4) cm3 and 12.1 (SD: 6.4) cm3, respectively, with the latter significantly lower than the former (p < 0.001). The mean DSC of GTVCONV and GTVMAR was 0.74 (SD: 0.10) and 0.77 (SD: 0.10), respectively, with the latter significantly higher than that of the former (p < 0.001).

Conclusions
The use of the MAR algorithm led to the delineation of smaller GTVs and reduced interobserver variations in delineating GTV of the primary tumors in patients with TC.
Experience and confidence in health technologies: evidence from malaria testing and treatment in Western Kenya
Authors: Mangeni Judith N. , Abel Lucy , Taylor Steve M. , Obala Andrew , O’Meara Wendy Prudhomme , Saran Indrani 
Published: September 2022

Abstract
Background
Low adoption of effective health technologies increases illness morbidity and mortality worldwide. In the case of malaria, effective tools such as malaria rapid diagnostic tests (RDTs) and artemisinin-combination therapies (ACTs) are both under-used and used inappropriately. Individuals’ confidence in RDTs and ACTs likely affects the uptake of these tools.

Methods
In a cohort of 36 households (280 individuals) in Western Kenya observed for 30 months starting in June 2017, we examined if experience with RDTs and ACTs changes people’s beliefs about these technologies and how those beliefs affect treatment behavior. Household members requested a free RDT from the study team any time they suspected a malaria illness, and positive RDT results were treated with a free ACT. We conducted annual, monthly, and sick visit surveys to elicit beliefs about the accuracy of malaria RDT results and the effectiveness of ACTs. Beliefs were elicited on a 5-point Likert scale from “very unlikely” to “very likely.”

Results
Over the study period, the percentage of survey respondents that said a hypothetical negative RDT result was “very likely” to be correct increased from approximately 55% to 75%. Controlling for initial beliefs, people who had been tested at least once with an RDT in the past year had 3.6 times higher odds (95% CI [1 1.718 7.679], P = 0.001) of saying a negative RDT was “very likely” to be correct. Confidence in testing was associated with treatment behavior: those who believed a negative RDT was “very likely” to be correct had 1.78 times higher odds (95% CI [1.079 2.934], P = 0.024) of adhering to a negative RDT result (by not taking ACTs) than those who were less certain about the accuracy of negative RDTs. Adherence to a negative test also affected subsequent beliefs: controlling for prior beliefs, those who had adhered to their previous test result had approximately twice the odds (OR = 2.19, 95% CI [1.661 2.904], P < 0.001) of saying that a hypothetical negative RDT was “very likely” to be correct compared to those who had not adhered.

Conclusions
Our results suggest that greater experience with RDTs can not only increase people’s confidence in their accuracy but also improve adherence to the test result.
BertSRC: transformer-based semantic relation classification
Authors: Lee Yeawon , Son Jinseok , Song Min 
Published: September 2022

AbstractThe relationship between biomedical entities is complex, and many of them have not yet been identified. For many biomedical research areas including drug discovery, it is of paramount importance to identify the relationships that have already been established through a comprehensive literature survey. However, manually searching through literature is difficult as the amount of biomedical publications continues to increase. Therefore, the relation classification task, which automatically mines meaningful relations from the literature, is spotlighted in the field of biomedical text mining. By applying relation classification techniques to the accumulated biomedical literature, existing semantic relations between biomedical entities that can help to infer previously unknown relationships are efficiently grasped. To develop semantic relation classification models, which is a type of supervised machine learning, it is essential to construct a training dataset that is manually annotated by biomedical experts with semantic relations among biomedical entities. Any advanced model must be trained on a dataset with reliable quality and meaningful scale to be deployed in the real world and can assist biologists in their research. In addition, as the number of such public datasets increases, the performance of machine learning algorithms can be accurately revealed and compared by using those datasets as a benchmark for model development and improvement. In this paper, we aim to build such a dataset. Along with that, to validate the usability of the dataset as training data for relation classification models and to improve the performance of the relation extraction task, we built a relation classification model based on Bidirectional Encoder Representations from Transformers (BERT) trained on our dataset, applying our newly proposed fine-tuning methodology. In experiments comparing performance among several models based on different deep learning algorithms, our model with the proposed fine-tuning methodology showed the best performance. The experimental results show that the constructed training dataset is an important information resource for the development and evaluation of semantic relation extraction models. Furthermore, relation extraction performance can be improved by integrating our proposed fine-tuning methodology. Therefore, this can lead to the promotion of future text mining research in the biomedical field.
Identification and functional characterization of BICD2 as a candidate disease gene in an consanguineous family with dilated cardiomyopathy
Authors: Luo Kai , Zheng Chenqing , Luo Rong , Cao Xin , Sun Huajun , Ma Huihui , Huang Jichang , Yang Xu , Wu Xiushan , Li Xiaoping 
Published: September 2022

Abstract
Background
Familial dilated cardiomyopathy (DCM) is a genetic cardiomyopathy that is associated with reduced left ventricle function or systolic function. Fifty-one DCM-causative genes have been reported, most of which are inherited in an autosomal dominant manner. However, recessive DCM-causative gene is rarely observed.

Methods
Whole-exome sequencing (WES) was performed in a consanguineous family with DCM to identify candidate variants. Sanger sequencing was utilized to confirm the variant. We then checked the DCM candidate gene in 210 sporadic DCM cases. We next explored BICD2 function in both embryonic and adult bicd2-knockout zebrafish models. In vivo cardiac function of bicd2-knockout fish was detected by echocardiography and RNA-seq.

Results
We identified an autosomal recessive and evolutionarily conserved missense variant, NM_001003800.1:c.2429G > A, in BICD2, which segregated with the disease phenotype in a consanguineous family with DCM. Furthermore, we confirmed the presence of BICD2 variants in 3 sporadic cases. Knockout of bicd2 resulted in partial embryonic lethality in homozygotes, suggesting a vital role for bicd2 in embryogenesis. Heart dilation and decreased ejection fraction, cardiac output and stroke volume were observed in bicd2-knockout zebrafish, suggesting a phenotype similar to human DCM. Furthermore, RNA-seq confirmed a larger transcriptome shift in in bicd2 homozygotes than in heterozygotes. Gene set enrichment analysis of bicd2-deficient fish showed the enrichment of altered gene expression in cardiac pathways and mitochondrial energy metabolism.

Conclusions
Our study first shows that BICD2 is a novel candidate gene associated with familial DCM, and our findings will facilitate further insights into the molecular pathological mechanisms of DCM.
Beyond the vaccines: a glance at the small molecule and peptide-based anti-COVID19 arsenal
Authors: Nepali Kunal , Sharma Ram , Sharma Sachin , Thakur Amandeep , Liou Jing-Ping 
Published: September 2022

AbstractUnprecedented efforts of the researchers have been witnessed in the recent past towards the development of vaccine platforms for the control of the COVID-19 pandemic. Albeit, vaccination stands as a practical strategy to prevent SARS-CoV-2 infection, supplementing the anti-COVID19 arsenal with therapeutic options such as small molecules/peptides and antibodies is being conceived as a prudent strategy to tackle the emerging SARS-CoV-2 variants. Noteworthy to mention that collective efforts from numerous teams have led to the generation of a voluminous library composed of chemically and mechanistically diverse small molecules as anti-COVID19 scaffolds. This review article presents an overview of medicinal chemistry campaigns and drug repurposing programs that culminated in the identification of a plethora of small molecule-based anti-COVID19 drugs mediating their antiviral effects through inhibition of proteases, S protein, RdRp, ACE2, TMPRSS2, cathepsin and other targets. In light of the evidence ascertaining the potential of small molecule drugs to approach conserved proteins required for the viral replication of all coronaviruses, accelerated FDA approvals are anticipated for small molecules for the treatment of COVID19 shortly. Though the recent attempts invested in this direction in pursuit of enrichment of the anti-COVID-19 armoury (chemical tools) are praiseworthy, some strategies need to be implemented to extract conclusive benefits of the recently reported small molecule viz. (i) detailed preclinical investigation of the generated anti-COVID19 scaffolds (ii) in-vitro profiling of the inhibitors against the emerging SARS-CoV-2 variants (iii) development of assays enabling rapid screening of the libraries of anti-COVID19 scaffold (iv) leveraging the applications of machine learning based predictive models to expedite the anti-COVID19 drug discovery campaign (v) design of antibody–drug conjugates.