bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between serum bone biomarker levels and therapeutic response to abatacept in patients with rheumatoid arthritis (RA): a multicenter, prospective, and observational RA ultrasound cohort study in Japan
Authors: Kawashiri Shin-ya , Endo Yushiro , Nishino Ayako , Okamoto Momoko , Tsuji Sosuke , Takatani Ayuko , Shimizu Toshimasa , Sumiyoshi Remi , Koga Tomohiro , Iwamoto Naoki , Ichinose Kunihiro , Tamai Mami , Nakamura Hideki , Origuchi Tomoki , Aramaki Toshiyuki , Ueki Yukitaka , Yoshitama Tamami , Eiraku Nobutaka , Matsuoka Naoki , Okada Akitomo , Fujikawa Keita , Hamada Hiroaki , Nagano Shuji , Tada Yoshifumi , Kawakami Atsushi 
Published: June 2021

Abstract
Background
To evaluate the effect of treatment on serum bone biomarkers and explore whether serum bone biomarkers are associated with therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept.

Methods
We enrolled 59 RA patients treated with abatacept from a multicenter, exploratory, short-term, prospective and observational ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) therapy. We evaluated the patients’ clinical disease activity and musculoskeletal ultrasound (MSUS) scores. The serum concentrations of five bone biomarkers were evaluated (dickkopf-1 [Dkk-1], sclerostin [SOST], osteocalcin [OC], osteopontin [OPN], and osteoprotegerin [OPG]) by multiplex bead assays at baseline, 3, and 6 months: the change over 6 months was defined as the Δ value. ‘Power Doppler (PD) responder’ was defined as a patient whose Δtotal PD score over 6 months was greater than the median change.

Results
Abatacept significantly improved the clinical disease activity and MSUS score over 6 months. Serum OPG was significantly elevated at 6 months after the abatacept introduction (p = 0.016). The ΔSOST and ΔOPG were significantly greater in the PD responders versus the non-PD responders (p = 0.0041 and 0.0073, respectively). The serum Dkk-1 at baseline was significantly lower in the PD responders (n = 30) vs. the non-PD responders (n = 29) (p = 0.026). A multivariate logistic regression analysis showed that the serum Dkk-1 at baseline (odds ratio 0.50, 95% confidence interval [CI] 0.23–0.91, p = 0.043) was an independent predictor of PD responder status.

Conclusion
Serum levels of bone biomarkers may be useful for predicting RA patients’ therapeutic responses to abatacept.

Trial registration
Name of the registry: Assessment of therapeutic responsiveness by imaging of the joints in patients with rheumatoid arthritis; A observational cohort study
Trial registration number: UMIN000012524
Date of registration: 12/9/2013
URL of trial registry record: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000014657
The theorisation of ‘best interests’ in bioethical accounts of decision-making
Authors: Birchley Giles 
Published: June 2021

Abstract
Background
Best interests is a ubiquitous principle in medical policy and practice, informing the treatment of both children and adults. Yet theory underlying the concept of best interests is unclear and rarely articulated. This paper examines bioethical literature for theoretical accounts of best interests to gain a better sense of the meanings and underlying philosophy that structure understandings.

Methods
A scoping review of was undertaken. Following a literature search, 57 sources were selected and analysed using the thematic method.

Results
Three themes emerged. The first placed best interests within the structure of wider theory, noting relationships with consequentialism, deontology, prudential value theory, rights and political philosophy. The second mapped a typology of processes of decision-making, among which best interests was ambiguously positioned. It further indicated factors that informed best interests decision-making, primarily preferences, dignity and quality of life. The final theme considered best interests from a relational perspective.

Conclusions
Characterisation of best interests as strictly paternalist and consequentialist is questionable: while accounts often suggested a consequentialist basis for best interests, arguments appeared philosophically weak. Deontological accounts, found in law and Kantianism, and theories of political liberalism influenced accounts of best interests, with accounts often associating best interests with negative patient preferences (i.e. individual refusals). There was much more emphasis on negative interests than positive interests. Besides preference, factors like dignity and quality of life were held to inform best interests decisions, but generally were weakly defined. To the extent that preferences were unable to inform decision making, decisions were either made by proxy authority or by an intersubjective process of diffuse authority. Differing approaches reflect bifurcations in liberal philosophy between new liberalism and neo-liberalism. Although neither account of authority appears dominant, bias to negative interests suggests that bioethical debate tends to reflect the widespread ascendancy of neo-liberalism. This attitude was underscored by the way relational accounts converged on private familial authority. The visible connections to theory suggest that best interests is underpinned by socio-political trends that may set up frictions with practice. How practice negotiates these frictions remains a key question.
Neuroticism, resilience, and social support: correlates of severe anxiety among hospital workers during the COVID-19 pandemic in Nigeria and Botswana
Authors: Olashore Anthony A. , Akanni Oluyemi O. , Oderinde Kehinde O. 
Published: June 2021

Abstract
Background
The role of healthcare workers (HCWs) during the COVID-19 pandemic may make them more susceptible to anxiety than the general population. This study aimed to determine the prevalence of anxiety and evaluate the potential effects of resilience, neuroticism, social support, and other sociodemographic factors on anxiety among HCWs from two African countries.

Methods
A cross-sectional survey of 373 HCWs was conducted in Botswana and Nigeria, using an anxiety rating scale, neuroticism subscale of Big Five Inventory, Oslo social support scale, and Resilience Scale. Data collection was done between May 1 and September 30, 2020.

Results
The participants’ mean age (SD) was 38.42 (8.10) years, and 65.1% were females. Forty-nine (13.1%) of the HCWs reported clinical anxiety. In the final model of hierarchical multiple regression, neuroticism (B = 0.51, t = 10.59, p = p < 0.01), resilience (B = 0.34, t = − 7.11, p < 0.01), and social support (B = 0.079, t = − 2.11, p = 0.035) were associated with severe anxiety, after controlling for the significant sociodemographic factors.

Conclusions
Severe anxiety exists among HCWs in Africa, although the rate was lower than reported elsewhere. Neuroticism, resilience, and social support may be vital targets for psychological intervention in a pandemic as COVID-19; thus, their roles should be further explored.
Less airway inflammation and goblet cell metaplasia in an IL-33-induced asthma model of leptin-deficient obese mice
Authors: Kurokawa Atsushi , Kondo Mitsuko , Arimura Ken , Ashino Shigeru , Tagaya Etsuko 
Published: June 2021

Abstract
Background
Obesity-associated asthma is a phenotype of severe asthma. Late-onset, non-eosinophilic and female-dominant phenotype is highly symptomatic and difficult to treat. Leptin, an adipokine, exerts an immunomodulatory effect. IL-33 associated with innate immunity induces type 2 inflammation and is present in adipose tissue. The purpose of this study was to elucidate the pathogenesis of obesity-associated asthma by focusing on the interaction between leptin and IL-33.

Methods
In leptin-deficient obese (ob/ob) and wild-type mice, IL-33 was instilled intranasally on three consecutive days. In part of the mice, leptin was injected intraperitoneally prior to IL-33 treatment. The mice were challenged with methacholine, and airway hyperresponsiveness (AHR) was assessed by resistance (Rrs) and elastance (Ers) of the respiratory system using the forced oscillation technique. Cell differentiation, IL-5, IL-13, eotaxin, keratinocyte-derived chemokine (KC) in bronchoalveolar lavage fluid (BALF) and histology of the lung were analyzed. For the in vitro study, NCI-H292 cells were stimulated with IL-33 in the presence or absence of leptin. Mucin-5AC (MUC5AC) levels were measured using an enzyme-linked immunosorbent assay.

Results
Ob/ob mice showed greater Rrs and Ers than wild-type mice. IL-33 with leptin, but not IL-33 alone, enhanced Ers rather than Rrs challenged with methacholine in ob/ob mice, whereas it enhanced Rrs alone in wild-type mice. IL-33-induced eosinophil numbers, cytokine levels in BALF, eosinophilic infiltration around the bronchi, and goblet cell metaplasia were less in ob/ob mice than in wild-type mice. However, leptin pretreatment attenuated these changes in ob/ob mice. MUC5AC levels were increased by co-stimulation with IL-33 and leptin in vitro.

Conclusions
Ob/ob mice show innate AHR. IL-33 with leptin, but not IL-33 alone, induces airway inflammation and goblet cell metaplasia and enhances AHR involving peripheral airway closure. This is presumably accelerated by mucus in ob/ob mice. These results may explain some aspects of the pathogenesis of obesity-associated asthma.
Advances in aptamer screening and aptasensors’ detection of heavy metal ions
Authors: Guo Wenfei , Zhang Chuanxiang , Ma Tingting , Liu Xueying , Chen Zhu , Li Song , Deng Yan 
Published: June 2021

AbstractHeavy metal pollution has become more and more serious with industrial development and resource exploitation. Because heavy metal ions are difficult to be biodegraded, they accumulate in the human body and cause serious threat to human health. However, the conventional methods to detect heavy metal ions are more strictly to the requirements by detection equipment, sample pretreatment, experimental environment, etc. Aptasensor has the advantages of strong specificity, high sensitivity and simple preparation to detect small molecules, which provides a new direction platform in the detection of heavy metal ions. This paper reviews the selection of aptamers as target for heavy metal ions since the 21th century and aptasensors application for detection of heavy metal ions that were reported in the past five years. Firstly, the selection methods for aptamers with high specificity and high affinity are introduced. Construction methods and research progress on sensor based aptamers as recognition element are also introduced systematically. Finally, the challenges and future opportunities of aptasensors in detecting heavy metal ions are discussed.
Thrombosis and bleeding outcomes in the treatment of cerebral venous thrombosis in cancer
Authors: Abelhad Nadia I , Qiao Wei , Garg Naveen , Rojas-Hernandez Cristhiam M. 
Published: June 2021

Abstract
Background
There is a need for clinical outcome data of cerebral venous thrombosis (CVT) in cancer patients. We examined the recanalization, thrombosis recurrence and major bleeding during CVT treatment in a cancer exclusive adult population.

Methods
We performed a retrospective review of cancer associated CVT identified through an institutional data warehouse. The primary endpoint was radiological and comprised the evaluation of thrombus recanalization at 12 months. Secondary endpoints were clinical and included rates of bleeding complications and recurrence of CVT. Variables were compared across subgroups of study outcomes. The backward stepdown procedure was used to identify variables for the final logistic model regarding thrombosis and bleeding outcomes.

Results
The population included forty-five patients, slightly predominant of male adults (55.6%) with a median age of 54.5 years. Solid malignancies comprised 64.4% of cases. A total of 33 cases were treated with anticoagulation. CVT recanalization was documented in almost 60% of cases. The cerebral venous thrombosis recurrence or propagation rate at 12 months was 15.6%. Major bleeding complications were observed in 15 patients.

Conclusions
Our findings are suggestive of a narrow therapeutic index of anticoagulation in cancer-CVT. Careful monitoring of anticoagulation effect and bleeding complications are of utmost clinical relevance in cancer patients. Further larger and controlled studies are needed to confirm our observations.
A potential association between immunosenescence and high COVID-19 related mortality among elderly patients with cardiovascular diseases
Authors: Wang Yuanyuan , Pang Shu-Chao , Yang Ying 
Published: June 2021

AbstractElderly patients with cardiovascular diseases account for a large proportion of Corona virus Disease 2019(COVID-19)related deaths. COVID-19, as a new coronavirus, mainly targets the patient’s lung triggering a cascade of innate and adaptive immune responses in the host. The principal causes of death among COVID-19 patients, especially elderly subjects with cardiovascular diseases, are acute respiratory distress syndrome(ARDS), multiple organ dysfunction syndrome (MODS), and microvascular thrombosis. All prompted by an excessive uncontrolled systemic inflammatory response. Immunosenescence, characterized by systemic and chronic inflammation as well as innate/adaptive immune imbalance, presents both in the elderly and cardiovascular patients. COVID-19 infection further aggravates the existing inflammatory process and lymphocyte depletion leading to uncontrollable systemic inflammatory responses, which is the primary cause of death. Based on the higher mortality, this study attempts to elucidate the pathophysiological mechanisms of COVID-19 in elderly subjects with cardiovascular diseases as well as the cause of the high mortality result from COVID-19.
LazyB: fast and cheap genome assembly
Authors: Gatter Thomas , von Löhneysen Sarah , Fallmann Jörg , Drozdova Polina , Hartmann Tom , Stadler Peter F. 
Published: June 2021

Abstract
Background
Advances in genome sequencing over the last years have lead to a fundamental paradigm shift in the field. With steadily decreasing sequencing costs, genome projects are no longer limited by the cost of raw sequencing data, but rather by computational problems associated with genome assembly. There is an urgent demand for more efficient and and more accurate methods is particular with regard to the highly complex and often very large genomes of animals and plants. Most recently, “hybrid” methods that integrate short and long read data have been devised to address this need.

Results
is such a hybrid genome assembler. It has been designed specificially with an emphasis on utilizing low-coverage short and long reads. starts from a bipartite overlap graph between long reads and restrictively filtered short-read unitigs. This graph is translated into a long-read overlap graph G. Instead of the more conventional approach of removing tips, bubbles, and other local features, stepwisely extracts subgraphs whose global properties approach a disjoint union of paths. First, a consistently oriented subgraph is extracted, which in a second step is reduced to a directed acyclic graph. In the next step, properties of proper interval graphs are used to extract contigs as maximum weight paths. These path are translated into genomic sequences only in the final step. A prototype implementation of , entirely written in python, not only yields significantly more accurate assemblies of the yeast and fruit fly genomes compared to state-of-the-art pipelines but also requires much less computational effort.

Conclusions
is new low-cost genome assembler that copes well with large genomes and low coverage. It is based on a novel approach for reducing the overlap graph to a collection of paths, thus opening new avenues for future improvements.

Availability
The prototype is available at https://github.com/TGatter/LazyB.
Patient-derived tumor models: a more suitable tool for pre-clinical studies in colorectal cancer
Authors: Rizzo Giulia , Bertotti Andrea , Leto Simonetta Maria , Vetrano Stefania 
Published: June 2021

AbstractColorectal cancer (CRC), despite the advances in screening and surveillance, remains the second most common cause of cancer death worldwide. The biological inadequacy of pre-clinical models to fully recapitulate the multifactorial etiology and the complexity of tumor microenvironment and human CRC’s genetic heterogeneity has limited cancer treatment development. This has led to the development of Patient-derived models able to phenocopy as much as possible the original inter- and intra-tumor heterogeneity of CRC, reflecting the tumor microenvironment’s cellular interactions. Implantation of patient tissue into immunodeficient mice hosts and the culture of tumor organoids have allowed advances in cancer biology and metastasis. This review highlights the advantages and limits of Patient-derived models as innovative and valuable pre-clinical tools to study progression and metastasis of CRC, develop novel therapeutic strategies by creating a drug screening platform, and predict the efficacy of clinical response to therapy.
Circ-PNPT1 contributes to gestational diabetes mellitus (GDM) by regulating the function of trophoblast cells through miR-889-3p/PAK1 axis
Authors: Zhang Li , Zeng Ming , Tang Fei , Chen Jun , Cao Dongmei , Tang Ze-nan 
Published: June 2021

Abstract
Background
Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy. CircRNA polyribonucleotide nucleotidyltransferase 1 (circ-PNPT1) has been found to be abnormally expressed in GDM patients. However, function and mechanism of circ-PNPT1 in GDM remain largely undefined.

Methods
Levels of circ-PNPT1, microRNA (miR)-889-3p and PAK1 (p21 (RAC1) activated kinase 1) were detected using quantitative real-time polymerase chain reaction and Western blot assays. Cell viability, apoptosis, migration and invasion were determined using cell counting kit-8 assay, flow cytometry, transwell and wound healing assays, respectively. The binding interaction between miR-889-3p and circ-PNPT1 or PAK1 was verified using dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. Exosomes were obtained from culture media by the use of commercial kits and qualified by transmission electron microscopy (TEM).

Results
Circ-PNPT1 was highly expressed in the placental tissues of GDM and high glucose (HG)-induced trophoblast cells. Knockdown of circ-PNPT1 reversed HG-induced arrest of trophoblast cell viability, migration, invasion and the promotion of cell apoptosis. Mechanistically, we confirmed circ-PNPT1 could promote the expression of PAK1, the target of miR-889-3p, by directly sponging miR-889-3p, and circ-PNPT1 regulated HG-induced trophoblast cell dysfunction by miR-889-3p/PAK1 axis. Further studies showed circ-PNPT1 was packaged into exosomes and could be internalized by surrounding trophoblast cells.

Conclusion
Circ-PNPT1 promoted HG-induced trophoblast cell biological dysfunction through miR-889-3p/PAK1 axis. Meanwhile, it could be transferred from HG-induced trophoblast cells to surrounding untreated cells via exosomes.
Interventions directed at men for preventing intimate partner violence: a systematic review protocol
Authors: Idriss-Wheeler Dina , Hajjar Julia , Yaya Sanni 
Published: June 2021

Abstract
Background
Intimate partner violence (IPV) is a population health problem linked to a myriad of negative psychological, physical, emotional, sexual and reproductive health outcomes for women. The movement towards working with boys and men over the past couple of decades has increased the number of interventions specifically directed at men who perpetrate violence against a female partner. There is little evidence-based research on key characteristics of effective interventions directed at men to reduce or prevent IPV against female partners. The objective of this systematic review is to identify interventions specifically directed at males , as the perpetrators of violence against women, that have proven to be effective in preventing or reducing intimate partner violence.

Methods
The following electronic databases will be used to search for peer-reviewed studies: MEDLINE (OVID), Embase (OVID), PsycInfo (OVID), CINAHL (EBSCO), Global Health (EBSCO), Gender Watch (ProQuest), Web of Science (Web of Knowledge), PROSPERO, Cochrane Central Register of Controlled Trials Database (Ovid) and SCOPUS. We will include randomized control trials, non-randomized studies of interventions published in peer-reviewed journals and relevant unpublished manuscripts, books/chapters and clinical or programme study reports. Studies have to demonstrate direction of effect (i.e. pre-post intervention/difference between groups) in terms of prevention or reduction in the outlined outcomes. Primary outcomes include change in behaviour and knowledge of male perpetrator regarding the impact of IPV on women as well as women’s experience of IPV. Secondary outcomes include change in behaviours around substance use and social activities, decrease in negative mental health outcomes and interactions with law enforcement. Studies will be screened, appraised and extracted by two reviewers; any conflicts will be resolved through discussion. Narrative synthesis will be used to analyse and present findings. If sufficient and comparable data is available, a meta-analysis will be conducted.

Discussion
This review will provide synthesized evidence on interventions directed at males to reduce or prevent their perpetration of intimate partner violence against female partners. Implications for practice will include key characteristics of interventions proven to be effective based on evidence synthesis and certainty of findings. Recommendations for further research will also be considered.

Systematic review registration
This protocol was submitted for registration in the International Prospective Register of Systematic Reviews (PROSPERO) on September 4, 2020.