bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of workplace‐based assessment tools to support postgraduate training of provisionally registered pharmacists in Australia
Authors: Maundu Josephine , Galbraith Kirsten , Croft Hayley , Clark Bronwyn , Kirsa Sue , Wilkinson Glenys , Abeyaratne Carmen 
Published: October 2022

AbstractThe Australian Pharmacy Council (APC) is the national accreditation authority for pharmacy education and training in Australia. In 2020, APC published revised Accreditation Standards and a new Performance Outcomes Framework (POF). The POF details expected performance for pharmacy students at the point of graduation and for pharmacy graduates on completion of postgraduate training. The APC and the pharmacist regulator, the Pharmacy Board of Australia collaborated on a project to develop workplace‐based assessment (WBA) tools for use in assessing performance of pharmacy graduates in the postgraduate training period. The objectives of the project were to; identify and develop an initial suite of WBA tools; develop accompanying guidance and supporting documentation; seek feedback from stakeholders; and pilot the WBA tools in community and hospital settings. The WBA tools were developed through consultative process overseen by a group of education experts (a Technical Working Group) and a governance group. The latter comprising members from the Pharmacy Board and APC. The Technical Working Group agreed on the tools to develop based on an available Intern Year Assessment Blueprint and the tools were then drafted by a consultant. APC held consultative forums and a pilot study to gather feedback from intern pharmacists and preceptors. The project resulted in development of a suite of three types of WBA tools; Entrustable Professional Activities (EPAs), Case Based Discussions (CbD), and In Training Assessment (ITA) activities covering six areas of focus. All types of tools that were initially agreed upon were made available for use. The WBA tools address 15 performance outcomes in the POF. Future direction will involve further evaluation of the tools in diverse practice settings and expansion of the current suite of tools to cover additional performance outcomes.
Longitudinal associations between adolescent out‐of‐school time and adult substance use
Authors: Hsieh Ta‐yang , Simpkins Sandra D. , Vandell Deborah Lowe 
Published: October 2022

AbstractIntroductionBased on Bronfenbrenner's bioecological theory and Bornstein's specificity principle, the purpose of this study was to examine adolescents' time in out‐of‐school settings as a precursor of three types of problematic substance use in adulthood (i.e., binge drinking, regular marijuana use, and use of illicit drugs).MethodAdolescents (N = 978) reported the time they spent in four common out‐of‐school settings at ages 15 and 18: unsupervised time with peers, organized sports, other organized activities, and paid employment. At age 26, participants reported binge drinking, marijuana use, and illicit drug use.Results and ConclusionsAdolescents' time in out‐of‐school settings during high school predicted age 26 substance use over and above family and adolescent factors, including adolescents' substance use during high school. Adolescents' unsupervised time with peers increased the odds and frequency of binge drinking and regular marijuana use at age 26. Time in high school organized sports increased the odds of binge drinking at age 26, but not marijuana or illicit drug use. Time spent in other organized activities, such as community service and the arts, lowered the odds of illicit drug use whereas paid employment in high school was not related to age 26 substance use. Aligned with Bornstein's specificity principle, time spent in specific out‐of‐school settings during adolescence were differentially related to substance use problems in early adulthood, with some activities serving as a risk factor and other activities serving as a protective factor for young adults.
Development of chitosan‐polygalacturonic acid polyelectrolyte complex fibrous scaffolds using the hydrothermal treatment for bone tissue engineering
Authors: Wasupalli Geeta Kumari , Verma Devendra 
Published: October 2022

AbstractAn ideal bone regeneration scaffold system needs to meet the high compressive properties of the bone. The stiffness of the scaffold extracellular matrix determines the cell's fate via cell adhesion migration and differentiation in‐vitro and in‐vivo. This study aims to investigate the effect of hydrothermal treatment on polyelectrolyte complex (PEC) fibrous biomaterials and its effect on scaffold morphology, cell viability, and function in‐vitro. FTIR analysis revealed the ability of the thermal treatment to set the interaction of HAp with polymeric PEC fibers. FESEM analysis showed that with an increase in temperature, the interconnectivity and pore size increased (control—82.38 ± 12.92 μm; at 120°C—335.48 ± 85.10 μm). Mechanical tests showed that the scaffolds heated at 90°C showed the highest stiffness in both dry and wet states (dry state: 1.82 ± 0.07 MPa, wet state: 122 ± 1.78 kPa). Additionally, the hydrothermal treatment also improved the aqueous stability as well as swelling capacity. According to the experimental findings, hydrothermal treatment is a useful technique for crosslinker‐free gelation with improved mechanical strength and nanofibrous structure. Furthermore, the cell adhesion, proliferation, and osteogenic differentiation of the MG63 cells on the hydrogel scaffolds in‐vitro were evaluated by MTT assay, confocal imaging, alkaline phosphatase assay, and collagen estimation. The in‐vitro study showed that scaffolds fabricated at 90°C promoted better MG63 cell attachment, proliferation, and differentiation. These results suggest the potential use of hydrothermal treated chitosan‐polygalacturonic acid (PgA) fibrous scaffolds in bone tissue engineering.
Effect of Osteoblast‐Specific Deletion of the Proton Receptor OGR1
Authors: Krieger Nancy S , Chen Luojing , Becker Jennifer , Chan Michaela , Bushinsky David A 
Published: October 2022

ABSTRACTMetabolic acidosis (MET) stimulates bone resorption through inhibition of osteoblast (OB) bone formation and stimulation of osteoclast (OC) bone resorption. We found that OGR1, a G protein‐coupled proton (H+)‐sensing receptor, was critical for initial H+ signaling in the OB. In mice with a global deletion of OGR1, we demonstrated that loss of OGR1 impairs H+‐induced bone resorption, leading to increased bone density through effects on both the OB and OC. Using an OC‐specific deletion of OGR1, we found that MET directly activates OGR1 in the OC. To determine if the response of OGR1 to MET in the OB is independent of a response in OCs and to characterize direct activation of OGR1 in the OB, we studied female mice with an OB‐specific deletion of OGR1 (OB‐cKO) and differentiated osteoblasts derived from marrow of OB‐cKO and wild‐type (WT) mice. In OB‐cKO mice, we found increased bone area in both tibial and femoral cortical bone. Specific loss of OB OGR1 increased in vitro mineralization, alkaline phosphatase activity, and expression of osteoblast‐specific genes compared with WT with no alteration in OC activity. MET stimulation of OB cox2 and fgf23 gene expression was inhibited in OB‐cKO OB. These results indicate that MET activation of OGR1 in the OB is independent of the response in the OC and that OGR1 in both cell types is required for a complete response to MET. Characterization of the role of OGR1 in MET‐induced bone resorption will improve our understanding of bone loss associated with metabolic acidosis in patients with chronic kidney disease. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
The abnormal level and prognostic potency of multiple inflammatory cytokines in PCI‐treated STEMI patients
Authors: Zhang Jing , Xu Huichuan , Yao Mingyan , Jia Hongdan , Cong Hongliang 
Published: October 2022

AbstractObjectiveInflammatory cytokines modulate atherogenesis and plaque rupture to involve in ST‐segment elevation myocardial infarction (STEMI) progression. The present study determined eight inflammatory cytokine levels in 212 percutaneous coronary intervention (PCI)‐treated STEMI patients, aiming to comprehensively investigate their potency in estimating major adverse cardiac event (MACE) risk.MethodsSerum tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, IL‐8, IL‐10, IL‐17A, vascular cell adhesion molecule‐1 (VCAM‐1), and intercellular adhesion molecule‐1 (ICAM‐1) of 212 PCI‐treated STEMI patients and 30 angina pectoris patients were determined using enzyme‐linked immunosorbent assay.ResultsTNF‐α (52.5 (43.9–62.6) pg/ml versus 46.4 (39.0–59.1) pg/ml, p = 0.031), IL‐8 (61.6 (49.6–81.7) pg/ml versus 46.7 (32.5–63.1) pg/ml, p = 0.001), IL‐17A (57.4 (45.7–77.3) pg/ml versus 43.2 (34.2–64.6) pg/ml, p = 0.001), and VCAM‐1 (593.6 (503.4–811.4) ng/ml versus 493.8 (390.3–653.7) ng/ml, p = 0.004) levels were elevated in STEMI patients compared to angina pectoris patients, while IL‐1β (p = 0.069), IL‐6 (p = 0.110), IL‐10 (p = 0.052), and ICAM‐1 (p = 0.069) were of no difference. Moreover, both IL‐17A high (vs. low) (p = 0.026) and VCAM‐1 high (vs. low) (p = 0.012) were linked with increased cumulative MACE rate. The multivariable Cox's analysis exhibited that IL‐17A high (vs. low) (p = 0.034) and VCAM‐1 high (vs. low) (p = 0.014) were independently associated with increased cumulative MACE risk. Additionally, age, diabetes mellitus, C‐reactive protein, multivessel disease, stent length, and stent type were also independent factors for cumulative MACE risk.ConclusionIL‐17A and VCAM‐1 high level independently correlate with elevated MACE risk in STEMI patients, implying its potency in identifying patients with poor prognoses.
ATM‐ and ATR‐induced primary ciliogenesis promotes cisplatin resistance in pancreatic ductal adenocarcinoma
Authors: Chao Yu‐Ying , Huang Bu‐Miin , Peng I‐Chen , Lee Pei‐Rong , Lai Yi‐Shyun , Chiu Wen‐Tai , Lin Yi‐Syuan , Lin Shih‐Chieh , Chang Jung‐Hsuan , Chen Pai‐Sheng , Tsai Shaw‐Jenq , Wang Chia‐Yih 
Published: October 2022

AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers because of its late diagnosis and chemoresistance. Primary cilia, the cellular antennae, are observed in most human cells to maintain development and differentiation. Primary cilia are gradually lost during the progression of pancreatic cancer and are eventually absent in PDAC. Here, we showed that cisplatin‐resistant PDAC regrew primary cilia. Additionally, genetic or pharmacological disruption of primary cilia sensitized PDAC to cisplatin treatment. Mechanistically, ataxia telangiectasia mutated (ATM) and ATM and RAD3‐related (ATR), tumor suppressors that initiate DNA damage responses, promoted the excessive formation of centriolar satellites (EFoCS) and autophagy activation. Disruption of EFoCS and autophagy inhibited primary ciliogenesis, sensitizing PDAC cells to cisplatin treatment. Collectively, our findings revealed an unexpected interplay among the DNA damage response, primary cilia, and chemoresistance in PDAC and deciphered the molecular mechanism by which ATM/ATR‐mediated EFoCS and autophagy cooperatively regulate primary ciliogenesis.
CD133‐Src‐TAZ signaling stimulates ductal fibrosis following DDC diet‐induced liver injury
Authors: Oh Ho Taek , Heo Woong , Yoo Gi Don , Kim Kyung Min , Hwang Jun‐Ha , Hwang Eun Sook , Ko Jesang , Ko Young‐Gyu , Hong Jeong‐Ho 
Published: October 2022

AbstractChronic liver injury follows inflammation and liver fibrosis; however, the molecular mechanism underlying fibrosis has not been fully elucidated. In this study, the role of ductal WW domain‐containing transcription regulator 1 (WWTR1)/transcriptional coactivator with PDZ‐binding motif (TAZ) was investigated after liver injury. Ductal TAZ‐knockout (DKO) mice showed decreased liver fibrosis following a Diethyl 1,4‐dihydro‐2,4,6‐trimethyl‐3,5‐pyridinedicarboxylate (DDC) diet compared to wild‐type (WT) mice, as evidenced by decreased expression levels of fibrosis inducers, including connective tissue growth factor (Ctgf)/cellular communication network factor 2 (CCN2), cysteine‐rich angiogenic inducer 61 (Cyr61/CCN1), and transforming growth factor beta 1 (Tgfb1), in DKO mice. Similarly, TAZ‐knockout (KO) cholangiocyte organoids showed decreased expression of fibrosis inducers. Additionally, the culture supernatant of TAZ‐KO cholangiocyte organoids decreased the fibrogenic gene expression in liver stellate cells. Further studies revealed that prominin 1 (PROM1/CD133) stimulated TAZ for fibrosis. After the administration of DDC diet, fibrosis was decreased in CD133‐KO (CD133‐KO) mice compared to that in WT mice. Similarly, CD133‐KO cholangiocyte organoids showed decreased Ctgf, Cyr61, and Tgfb1 expression levels compared to WT cholangiocyte organoids. Mechanistically, CD133 stabilized TAZ via Src activation. Inhibition of Src decreased TAZ levels. Similarly, CD133‐knockdown HCT116 cells showed decreased TAZ levels, but reintroduction of active Src recovered the TAZ levels. Taken together, our results suggest that TAZ facilitates liver fibrosis after a DDC diet via the CD133‐Src‐TAZ axis.
Circadian clock‐mediated nuclear receptors in cancer
Authors: Niu Ya , Tang Shuang 
Published: October 2022

AbstractCircadian system coordinates the daily periodicity of physiological and biochemical functions to adapt to environmental changes. Circadian disruption has been identified to increase the risk of cancer and promote cancer progression, but the underlying mechanism remains unclear. And further mechanistic understanding of the crosstalk between clock components and cancer is urgent to achieve clinical anticancer benefits from chronochemotherapy. Recent studies discover that several nuclear receptors regulating circadian clock, also play crucial roles in mediating multiple cancer processes. In this review, we aim to summarize the latest developments of clock‐related nuclear receptors in cancer biology and dissect mechanistic insights into how nuclear receptors coordinate with circadian clock to regulate tumorigenesis and cancer treatment. A better understanding of circadian clock‐related nuclear receptors in cancer could help prevent tumorigenesis and improve anticancer efficacy.
Metabolic labeling of cardiomyocyte‐derived small extracellular‐vesicle (sEV) miRNAs identifies miR‐208a in cardiac regulation of lung gene expression
Authors: Han Chaoshan , Yang Junjie , Zhang Eric , Jiang Ying , Qiao Aijun , Du Yipeng , Zhang Qinkun , An Junqing , Sun Jiacheng , Wang Meimei , Nguyen Thanh , Lal Hind , Krishnamurthy Prasanna , Zhang Jianyi , Qin Gangjian 
Published: October 2022

AbstractToxoplasma gondii uracil phosphoribosyltransferase (UPRT) converts 4‐thiouracil (4TUc) into 4‐thiouridine (4TUd), which is incorporated into nascent RNAs and can be biotinylated, then labelled with streptavidin conjugates or isolated via streptavidin‐affinity methods. Here, we generated mice that expressed T. gondii UPRT only in cardiomyocytes (CMUPRT mice) and tested our hypothesis that CM‐derived miRNAs (CMmiRs) are transferred into remote organs after myocardial infarction (MI) by small extracellular vesicles (sEV) that are released from the heart into the peripheral blood (PBsEV). We found that 4TUd was incorporated with high specificity and sensitivity into RNAs isolated from the hearts and PBsEV of CMUPRT mice 6 h after 4TUc injection. In PBsEV, 4TUd was incorporated into CM‐specific/enriched miRs including miR‐208a, but not into miRs with other organ or tissue‐type specificities. 4TUd‐labelled miR208a was also present in lung tissues, especially lung endothelial cells (ECs), and CM‐derived miR‐208a (CMmiR‐208a) levels peaked 12 h after experimentally induced MI in PBsEV and 24 h after MI in the lung. Notably, miR‐208a is expressed from intron 29 of α myosin heavy chain (αMHC), but αMHC transcripts were nearly undetectable in the lung. When PBsEV from mice that underwent MI (MI‐PBsEV) or sham surgery (Sham‐PBsEV) were injected into intact mice, the expression of Tmbim6 and NLK, which are suppressed by miR‐208a and cooperatively regulate inflammation via the NF‐κB pathway, was lower in the lungs of MI‐PBsEV–treated animals than the lungs of animals treated with Sham‐PBsEV or saline. In MI mice, Tmbim6 and NLK were downregulated, whereas endothelial adhesion molecules and pro‐inflammatory cells were upregulated in the lung; these changes were significantly attenuated when the mice were treated with miR‐208a antagomirs prior to MI surgery. Thus, CMUPRT mice enables us to track PBsEV‐mediated transport of CMmiRs and identify an miR‐208a‐mediated mechanism by which myocardial injury alters the expression of genes and inflammatory response in the lung.
Summary of the experiences, knowledge, medical management, and family communication of monoallelic MUTYH carriers
Authors: McKenna Danielle B. , Sanchez Pauleen , Powers Jacquelyn , Brower Jamie , Wang Louise , Mueller Rebecca , Symecko Heather , Hamilton Jada G. , Wildman Temima , Domchek Susan M. , Couch Fergus J. , Garber Judy E. , Offit Kenneth , Robson Mark E. , Katona Bryson W. 
Published: October 2022

AbstractGermline genetic testing for inherited cancer risk is increasingly being performed with multigene panel testing with MUTYH often included on colorectal cancer‐ and polyposis‐focused panels, as well as on broader pan‐cancer panels. With up to 1%–2% of the general population being monoallelic MUTYH carriers, pathogenic/likely pathogenic (P/LP) variants in MUTYH are one of the most common findings on multigene cancer panels. However, little is known about patient experience and understanding of monoallelic MUTYH P/LP variants, nor whether such findings influence medical management recommendations and familial communication, which this study aims to better understand. Monoallelic P/LP MUTYH carriers were recruited from the Prospective Registry of Multiplex Testing (PROMPT) and completed a cross‐sectional self‐report survey on sociodemographic characteristics, medical and family history, experiences with MUTYH genetic testing, genetics and MUTYH knowledge, perceived cancer risk, and familial communication. Of 115 eligible PROMPT participants, 49 (43%) completed the survey who were primarily female (94%), white (96%), had a history of cancer (61%), and a median age of 51.4 years. Most participants (61%) reported satisfaction with how their healthcare provider managed their genetic test result and care, and 65% of survey participants reported their provider recommended colonoscopy based on their genetic test results. Participants' responses also reflected variable levels of knowledge regarding cancer risks and screening recommendations for MUTYH carriers. The majority (98%) of participants shared their genetic test results with at least some of their relatives; however, only 13% of eligible relatives reportedly underwent cascade testing. Taken together, this study provides needed insight into the overall experiences of monoallelic MUTYH carriers and highlights numerous areas for improvement in clinician education, communication, and management of these individuals.
Patient and provider perceptions of a community‐based accompaniment intervention for adolescents transitioning to adult HIV care in urban Peru: a qualitative analysis
Authors: Galea Jerome T. , Wong Milagros , Ninesling Brennan , Ramos Alicia , Senador Liz , Sanchez Hugo , Kolevic Lenka , Matos Eduardo , Sanchez Eduardo , Errea Renato A. , Lindeborg Andrew , Benites Carlos , Lecca Leonid , Shin Sonya , Franke Molly F. 
Published: October 2022

AbstractIntroductionAdolescents living with HIV (ALWH) experience higher mortality rates compared to other age groups, exacerbated by the suboptimal transition from paediatric to adult HIV care, during which decreased adherence to antiretroviral therapy (ART) and unsuppressed viremia are frequent. Care transition—a process lasting months or years—ideally prepares ALWH for adult care and can be improved by interventions that are youth‐friendly and address psychosocial issues affecting ART adherence; however, such interventions are infrequently operationalized. Community‐based accompaniment (CBA), in which laypeople provide individualized support and health system navigation, can improve health outcomes among adults with HIV. Here, we describe patient and provider perceptions of a novel HIV CBA intervention called “PASEO” for ALWH in Lima, Peru.MethodsPASEO consisted of six core elements designed to support ALWH during and after the transition to adult HIV care. During 2019–2021, community‐based health workers provided tailored accompaniment for ALWH aged 15–21 years over 9 months, after which adolescent participants were invited to provide feedback in a focus group or in‐depth interview. HIV care personnel were also interviewed to understand their perspectives on PASEO. A semi‐structured interview guide probing known acceptability constructs was used. Qualitative data were analysed using a framework analysis approach and emergent themes were summarized with illustrative quotes.ResultsWe conducted five focus groups and 11 in‐depth interviews amongN= 26 ALWH and nine key‐informant interviews with HIV care personnel. ALWH participants included males, females and one transgender female, and those with both early childhood and recent HIV infection. ALWH praised PASEO, attributing increased ART adherence to the project. Improved mental health, independence, self‐acceptance and knowledge on how to manage their HIV were frequently cited. HIV professionals similarly voiced strong support for PASEO. Both ALWH and HIV professionals expressed hope that PASEO would be scaled. HIV professionals voiced concerns regarding financing PASEO in the future.ConclusionsA multicomponent CBA intervention to increase ART adherence among ALWH in Peru was highly acceptable by ALWH and HIV programme personnel. Future research should determine the efficacy and economic impact of the intervention.