bluuebunny/crossref_metadata_2025_split huggingface dataset:
A lung adenocarcinoma patient with co-mutations of MET and EGFR exon20 insertion responded to crizotinib
Authors: Chen Yan , Jiang Bo , He Yuange , Zhang Chu , Zhou Wenjie , Fang Cheng , Gu Dejian , Zhang Minxia , Ji Mei , Shi Juntao , Yang Xin 
Published: June 2022

AbstractBackgroundTargeted therapy has revolutionized the treatment of patients with malignancies harboring mutations in driver genes and has brought a favorable survival benefit to the population with actionable oncogenic mutations. In recent years, theMETexon14 skipping mutation has been recognized as a potentially promising therapeutic target in non-small cell lung cancer (NSCLC). These changes are mutually exclusive with molecular drivers such asEGFR, KRAS, HER-2,BRAF, ALKandROS1. The prevalence rate of coexistingMETexon 14 mutations andEGFRsensitive mutations (L858R, exon 19 deletions) in Chinese population was reported to be 0.2% (3/1590). However, the coexistence ofMETexon 14 mutations withEGFRexon 20 insertion mutations has never been reported and the management of this subtype is not identified.Case presentationA 69-year-old male with a right lung adenocarcinoma (T4N2M0, IIIB) was confirmed to be positive forMETexon 14 skipping (c.3028_3028+1delGGinsTT, 44.4%),METamplification (copy number 4.4), andEGFRexon 20 insertion (p. N771_H773dup, 22.1%) mutations. After the progression of one cycle of chemotherapy (Pemetrexed 0.8 g d1), the patient was subsequently accepted treatment with Crizotinib (250 mg twice a day) and achieved an important clinical remission for six months until the development of brain metastases. Then, he was submitted to a cycle of anti-programmed cell death-1 (PD-1) therapy after failure of Crizotinib and eventually acquired resistance despite of the high expression of programmed death ligand-1 (PD-L1) and tumor mutational burden (TMB) status.ConclusionThis case report provides treatment strategies for epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)-untreated lung adenocarcinoma patients simultaneously carryingMETalterations andEGFRexon 20 insertion mutations. In addition, the signatures of PD-L1 or TMB expression were not the candidate for predicting the efficacy of immunotherapy in this context.
‘You say you are a TB doctor, but actually, you do not have any power’: health worker (de)motivation in the context of integrated, hospital-based tuberculosis care in eastern China
Authors: Zou Guanyang , McPake Barbara , Kielmann Karina 
Published: June 2022

Abstract
Background
In China, tuberculosis (TB) care, traditionally provided through the Centre for Disease Control (CDC), has been integrated into ‘designated’ public hospitals at County level, with hospital staff taking on delivery of TB services supported by CDC staff. Little is known about the impact of this initiative on the hospital-based health workers who were delegated to manage TB. Drawing on a case study of two TB ‘designated’ hospitals in Zhejiang province, we explored factors influencing hospital-based health workers’ motivation in the context of integrated TB service delivery.

Methods
We conducted 47 in-depth interviews with health officials, TB/hospital managers, clinicians, radiologists, laboratory staff and nurses involved in the integrated model of hospital-based TB care. Thematic analysis was used to develop and refine themes, code the data and assist in interpretation.

Results
Health workers tasked with TB care in ‘designated’ hospitals perceived their professional status to be low, related to their assessment of TB treatment as lacking need for professional skills, their limited opportunities for professional development, and the social stigma surrounding TB. In both sites, the integrated TB clinics were under-staffed: health workers providing TB care reported heavy workloads, and expressed dissatisfaction with a perceived gap in their salaries compared with other clinical staff. In both sites, health workers were concerned about poor infection control and weak risk management assessment systems.

Conclusions
Inadequate attention to workforce issues for TB control in China, specifically the professional status, welfare, and development as well as incentivization of infectious disease control workers has contributed to dissatisfaction and consequently poor motivation to serve TB patients within the integrated model of TB care. It is important to address the failure to motivate health workers and maximize public good-oriented TB service provision through improved government funding and attention to the professional welfare of health workers providing TB care in hospitals.
Exosome-mediated lncRNA SND1-IT1 from gastric cancer cells enhances malignant transformation of gastric mucosa cells via up-regulating SNAIL1
Authors: Jin Guohua , Zhang Jianguang , Cao Tingting , Chen Bang , Tian Yu , Shi Yang 
Published: June 2022

Abstract
Background
Gastric cancer (GC), as one of the most common malignancies across the globe, is the fourth leading cause of cancer-related deaths. Though a large body of research has been conducted to develop the therapeutic methods of GC, the survival rate of advanced patients is still poor. We aimed to dig into the potential regulatory mechanism of GC progression.

Methods
Bioinformatics tools and fundamental assays were performed at first to confirm the candidate genes in our study. The functional assays and mechanism experiments were conducted to verify the regulatory mechanisms of the genes underlying GC progression.

Results
Long non-coding RNA (lncRNA) SND1 intronic transcript 1 (SND1-IT1) is highly expressed in exosomes secreted by GC cells. SND1-IT1 was verified to bind to microRNA-1245b-5p (miR-1245b-5p) through competitive adsorption to promote ubiquitin specific protease 3 (USP3) messenger RNA (mRNA) expression. SND1-IT1 was validated to recruit DEAD-box helicase 54 (DDX54) to promote USP3 mRNA stability. SND1-IT1 induces malignant transformation of GES-1 cells through USP3. USP3 mediates the deubiquitination of snail family transcriptional repressor 1 (SNAIL1).

Conclusions
Exosome-mediated lncRNA SND1-IT1 from GC cells enhances malignant transformation of GES-1 cells via up-regulating SNAIL1.

Graphical Abstract
Fertility and contraception among women of reproductive age following a disaster: a scoping review
Authors: Strid Penelope , Snead Margaret Christine , Galang Romeo R. , Bish Connie L. , Ellington Sascha R. 
Published: June 2022

Abstract
Background
The prevalence and severity of disasters triggered by natural hazards has increased over the last 20 years. Women of reproductive age may encounter unique reproductive health challenges following a disaster. In this scoping review we identify gaps in literature to inform future research and search for potential associations between disasters by natural hazards and post-disaster fertility and contraception among women of reproductive age.

Methods
Medline (OVID), Embase (OVID), PsycInfo (OVID), CINAHL (Ebsco), Scopus, Environmental Science Collection (ProQuest Central), and Sociological Abstracts (ProQuest Central) were searched for articles published from 1980 through March 3, 2022 in English or Spanish language. Search terms were related to fertility, contraception, and disasters. We included original research that described a discrete natural hazard exposure, a population of women of reproductive age (15–49 years), and outcomes of fertility or contraception use or access, with pre- and post-disaster measures.

Results
Among 9788 citations, after initial exclusion 5121 remained for title and abstract review. One hundred and eighteen citations underwent full-text review and 26 articles met the inclusion criteria. Following critical appraisal, 20 articles were included in this review. Eighteen articles described outcomes related to fertility, five articles described contraception access, and three articles described contraception use.

Conclusions
Clearly defined exposure measures, robust analyses, and methodical post-disaster assessment periods, may address the current gaps within disaster research on fertility and contraception among women of reproductive age. Consistent patterns in fertility following a disaster triggered by natural hazards were not identified between or within disaster types. Studies that assessed contraception found no change in use, while some studies found a decrease in contraceptive access overall.
Aryl hydrocarbon receptor activation-mediated vascular toxicity of ambient fine particulate matter: contribution of polycyclic aromatic hydrocarbons and osteopontin as a biomarker
Authors: Ho Chia-Chi , Wu Wei-Te , Lin Yi-Jun , Weng Chen-Yi , Tsai Ming-Hsien , Tsai Hui-Ti , Chen Yu-Cheng , Yet Shaw-Fang , Lin Pinpin 
Published: June 2022

Abstract
Background
Exposure to ambient fine particulate matter (PM2.5) is associated with vascular diseases. Polycyclic aromatic hydrocarbons (PAHs) in PM2.5 are highly hazardous; however, the contribution of PM2.5-bound PAHs to PM2.5-associated vascular diseases remains unclear. The ToxCast high-throughput in vitro screening database indicates that some PM2.5-bound PAHs activate the aryl hydrocarbon receptor (AhR). The present study investigated whether the AhR pathway is involved in the mechanism of PM2.5-induced vascular toxicity, identified the PAH in PM2.5 that was the major contributor of AhR activation, and identified a biomarker for vascular toxicity of PM2.5-bound PAHs.

Results
Treatment of vascular smooth muscle cells (VMSCs) with an AhR antagonist inhibited the PM2.5-induced increase in the cell migration ability; NF-κB activity; and expression of cytochrome P450 1A1 (CYP1A1), 1B1 (CYP1B1), interleukin-6 (IL-6), and osteopontin (OPN). Most PM2.5-bound PAHs were extracted into the organic fraction, which drastically enhanced VSMC migration and increased mRNA levels of CYP1A1, CYP1B1, IL-6, and OPN. However, the inorganic fraction of PM2.5 moderately enhanced VSMC migration and only increased IL-6 mRNA levels. PM2.5 increased IL-6 secretion through NF-κB activation; however, PM2.5 and its organic extract increased OPN secretion in a CYP1B1-dependent manner. Inhibiting CYP1B1 activity and silencing OPN expression prevented the increase in VSMC migration ability caused by PM2.5 and its organic extract. The AhR activation potencies of seven PM2.5-bound PAHs, reported in the ToxCast database, were strongly correlated with their capabilities of enhancing the migration ability of VSMCs. Benzo(k)fluoranthene (BkF) contributed the most to the AhR agonistic activity of ambient PM2.5-bound PAHs. The association between PM2.5-induced vascular toxicity, AhR activity, and OPN secretion was further verified in mice; PM2.5-induced intimal hyperplasia in pulmonary small arteries and OPN secretion were alleviated in mice with low AhR affinity. Finally, urinary concentrations of 1-hydroxypyrene, a major PAH metabolite, were positively correlated with plasma OPN levels in healthy humans.

Conclusions
The present study offers in vitro, animal, and human evidences supporting the importance of AhR activation for PM2.5-induced vascular toxicities and that BkF was the major contributor of AhR activation. OPN is an AhR-dependent biomarker of PM2.5-induced vascular toxicity. The AhR activation potency may be applied in the risk assessment of vascular toxicity in PAH mixtures.
Comprehensive benchmarking of CITE-seq versus DOGMA-seq single cell multimodal omics
Authors: Xu Zhongli , Heidrich-O’Hare Elisa , Chen Wei , Duerr Richard H. 
Published: June 2022

AbstractThe recently developed method TEA-seq and similar DOGMA-seq single cell trimodal omics assays provide unprecedented opportunities for understanding cell biology, but independent evaluation is lacking. We explore the utility of DOGMA-seq compared to the bimodal CITE-seq assay in activated and stimulated human peripheral blood T cells. We find that single cell trimodal omics measurements after digitonin (DIG) permeabilization were generally better than after an alternative “low-loss lysis” (LLL) permeabilization condition. Next, we find that DOGMA-seq with optimized DIG permeabilization and its ATAC library provides more information, although its mRNA and cell surface protein libraries have slightly inferior quality, compared to CITE-seq.
Molecular characterization and determination of the biochemical properties of cathepsin L of Trichinella spiralis
Authors: Liu Ruo Dan , Meng Xiang Yu , Li Chen Le , Long Shao Rong , Cui Jing , Wang Zhong Quan 
Published: June 2022

AbstractCathepsin L is an important cysteine protease, but its function inT. spiralisremains unclear. The aim of this research was to explore the biological characteristics ofT. spiraliscathepsin L (TsCatL) and its role inT. spiralis-host interactions. Bioinformatic analysis revealed the presence of the cysteine protease active site residues Gln, Cys, His and Asn in mature TsCatL, as well as specific motifs of cathepsin L similar to ERFNIN and GYLND in the prepeptide of TsCatL. Molecular docking of mature TsCatL and E64 revealed hydrophobic effects and hydrogen bonding interactions. Two domains of TsCatL (TsCatL2) were cloned and expressed, and recombinant TsCatL2 (rTsCatL2) was autocatalytically cleaved under acidic conditions to form mature TsCatL. TsCatL was transcribed and expressed in larvae and adults and located in the stichosome, gut and embryo. Enzyme kinetic tests showed that rTsCatL2 degraded the substrate Z-Phe-Arg-AMC under acidic conditions, which was inhibited by E64 and PMSF and enhanced by EDTA, L-cysteine and DTT. The kinetic parameters of rTsCatL2 were a Km value of 48.82 μM and Vmax of 374.4 nM/min at pH 4.5, 37 °C and 5 mM DTT. In addition, it was shown that rTsCatL2 degraded haemoglobin, serum albumin, immunoglobulins (mouse IgG, human IgG and IgM) and extracellular matrix components (fibronectin, collagen I and laminin). The proteolytic activity of rTsCatL2 was host specific and significantly inhibited by E64. rTsCatL2 possesses the natural activity of a sulfhydryl-containing cysteine protease, and TsCatL is an important digestive enzyme that seems to be important for the nutrient acquisition, immune evasion and invasion ofTrichinellain the host.
Clinical yarning with Aboriginal and/or Torres Strait Islander peoples—a systematic scoping review of its use and impacts
Authors: Burke Alexander W. , Welch Susan , Power Tamara , Lucas Cherie , Moles Rebekah J. 
Published: June 2022

Abstract
Objectives
To explore how clinical yarning has been utilised as a health intervention for Aboriginal and/or Torres Strait Islander peoples and if there are any reported impacts yarning might have on health outcomes.

Study design
Systematic scoping review of published literature.

Data sources
A one-word search term “yarning” was applied in Scopus, EMBASE, CINAHL, MEDLINE, International Pharmaceutical Abstracts, Australian Public Affairs Information Service-Health, and the Aboriginal and/or Torres Strait Islander Health Bibliography databases. Databases were searched from inception to May 20, 2020.

Study selection
Studies were included where clinical yarning had been used as a health intervention. Inclusion and exclusion criteria were developed and applied according to PRISMA systematic and scoping review reporting methods.

Data synthesis
A total of 375 manuscripts were found from the initial data search. After removal of duplicates and removal of manuscripts based on abstract review, a total of 61 studies underwent full-text review. Of these, only five met the inclusion criteria of utilising yarning as a clinical intervention. Four of these studies described consumer self-reported health outcomes, with only one study looking at improvements in objective physiological health outcomes.

Conclusions
Whilst clinical yarning may be a culturally appropriate intervention in healthcare, there are limited studies that have measured the impact of this intervention. Further research may be needed to ascertain the true benefits of this intervention.
Determinants of COVID-19 vaccine behaviour intentions among the youth in Kenya: a cross-sectional study
Authors: Osur Joachim O. , Chengo Rehema , Muinga Evelyne , Kemboi Jackline , Sidibe Myriam , Rarieya Maggie 
Published: June 2022

Abstract
Introduction
COVID-19 has become a public health concern globally with increased numbers of cases of the disease and deaths reported daily. The key strategy for the prevention of COVID-19 disease is to enhance mass COVID-19 vaccination. However, mass vaccination faces challenges of hesitation to acceptance of the vaccine in the community. The youth may not be among the vulnerable population to severe COVID-19 disease but are highly susceptible to contracting the virus and spreading it. The aim of the study was to assess COVID-19 vaccine youth behavior intentions and their determinants in Kenya.

Methods
The study used a mixed method design, employing a cross-sectional survey and focused group discussions across 47 counties in Urban, Peri-Urban and Rural settings of Kenya. The interviewees were youths aged 18–35, registered in online platforms/peer groups that included Shujaaz, Brck Moja, Aiffluence, Y Act and Heroes for Change. Quantitative data was collected using Google forms. A total of 665 interviews were conducted. Quantitative data was analysed using STATA version 16. In this paper we report quantitative study findings.

Results
The findings of the study indicated that only 42% of the youth were ready to be vaccinated, with 52% adopting a wait and see approach to what happens to those who had received the vaccine and 6% totally unwilling to be vaccinated. The determinants of these behavior intentions included: the perceived adverse effects of the vaccine on health, inadequate information about the COVID-19 vaccine, conflicting information about COVID-19 vaccine from the social media, religious implications of the vaccine, impact of education level on understanding of the vaccine, perceived risk of contracting the COVID-19 disease, efficacy of the COVID-19 vaccine, COVID-19 affecting women than men and trust in the ministry of health to lead COVID-19 interventions. Significantly it was found that hesitancy is higher among females, protestants and those with post-secondary education. Lack of information and concerns around vaccine safety and effectiveness were main cause of COVID-19 vaccine hesitancy. Social media was the major source of information contributing to hesitancy. Other contributors to hesitancy included low trust in the MoH and belief that mass vaccination is not helpful.

Conclusion
Vaccine hesitancy remains high among the youth but the causes of it are modifiable and health systems need to have evidence based engagements with the youth to reduce vaccine hesitancy.
International comparison of physicians’ attitudes toward refusal of treatment by patients with anorexia nervosa: a case-based vignette study
Authors: Takimoto Yoshiyuki 
Published: June 2022

Abstract
Background
This study investigated the attitudes of physicians in Japan, the United Kingdom (UK), and the United States (US) toward refusal of treatment for anorexia nervosa.

Methods
A questionnaire survey was administered to physicians treating patients with eating disorder (Japan, n = 55; UK, n = 84; US, n = 82) to evaluate their treatment strategies for fictitious cases of refusal of treatment for anorexia nervosa.

Results
For acute patients, 53 (96.3%) physicians in Japan, 65 (77.4%) in the UK, and 54 (65.9%) in the US chose compulsory treatment if the patient’s family requested treatment, while 46 (83.6%) physicians in Japan, 53 (63.1%) in the UK, and 47 (57.3%) in the US chose compulsory treatment if the family left the decision to the patient. For severe and enduring anorexia nervosa, 53 (96.3%) physicians in Japan, 62 (73.8%) in the UK, and 57 (69.5%) in the US chose compulsory treatment if the patient’s family requested treatment, while 38 (69.1%) physicians in Japan, 56 (66.7%) in the UK, and 55 (67.1%) in the US chose compulsory treatment if the family left the decision to the patient.

Conclusions
Physicians in all three countries tended to choose compulsory treatment irrespective of disease duration or whether the patient’s family requested treatment or not. This may indicate that medical practitioners value the ethical obligation of beneficence, giving priority to the protection of life. Attitudes toward refusal of treatment during a life crisis tend to vary among medical professionals, particularly if the patient’s family does not request treatment.
Pathological and neurophysiological outcomes of seeding human-derived tau pathology in the APP-KI NL-G-F and NL-NL mouse models of Alzheimer’s Disease
Authors: Tok S. , Maurin H. , Delay C. , Crauwels D. , Manyakov N. V. , Van Der Elst W. , Moechars D. , Drinkenburg W. H. I. M. 
Published: June 2022

AbstractThe two main histopathological hallmarks that characterize Alzheimer’s Disease are the presence of amyloid plaques and neurofibrillary tangles. One of the current approaches to studying the consequences of amyloid pathology relies on the usage of transgenic animal models that incorporate the mutant humanized form of the amyloid precursor protein (hAPP), with animal models progressively developing amyloid pathology as they age. However, these mice models generally overexpress the hAPP protein to facilitate the development of amyloid pathology, which has been suggested to elicit pathological and neuropathological changes unrelated to amyloid pathology. In this current study, we characterized APP knock-in (APP-KI) animals, that do not overexpress hAPP but still develop amyloid pathology to understand the influence of protein overexpression. We also induced tau pathology via human-derived tau seeding material to understand the neurophysiological effects of amyloid and tau pathology. We report that tau-seeded APP-KI animals progressively develop tau pathology, exacerbated by the presence of amyloid pathology. Interestingly, older amyloid-bearing, tau-seeded animals exhibited more amyloid pathology in the entorhinal area, isocortex and hippocampus, but not thalamus, which appeared to correlate with impairments in gamma oscillations before seeding. Tau-seeded animals also featured immediate deficits in power spectra values and phase-amplitude indices in the hippocampus after seeding, with gamma power spectra deficits persisting in younger animals. Both deficits in hippocampal phase-amplitude coupling and gamma power differentiate tau-seeded, amyloid-positive animals from buffer controls. Based on our results, impairments in gamma oscillations appear to be strongly associated with the presence and development of amyloid and tau pathology, and may also be an indicator of neuropathology, network dysfunction, and even potential disposition to the future development of amyloid pathology.