tbuckley/cabot-search huggingface dataset:
A needs-based workforce model to deliver tertiary-level community mental health care for distressed infants, children, and adolescents in South Australia: a mixed-methods study
Authors: Leonie Segal, Sophie Guy, Matthew Leach, Aaron Groves, Catherine Turnbull, Gareth Furber
Journal: The Lancet Public Health (2018)

BackgroundHigh-quality mental health services for infants, children, adolescents, and their families can improve outcomes for children exposed to early trauma. We sought to estimate the workforce needed to deliver tertiary-level community mental health care to all infants, children, adolescents, and their families in need using a generalisable model, applied to South Australia (SA).MethodsWorkforce estimates were determined using a workforce planning model. Clinical need was established using data from the Longitudinal Study of Australian Children and the Young Minds Matter survey. Care requirements were derived by workshopping clinical pathways with multiprofessional panels, testing derived estimates through an online survey of clinicians.FindingsPrevalence of tertiary-level need, defined by severity and exposure to childhood adversities, was estimated at 5–8% across infancy and childhood, and 16% in mid-adolescence. The derived care pathway entailed reception, triage, and follow-up (mean 3 h per patient), core clinical management (mean 27 h per patient per year), psychiatric oversight (mean 4 h per patient per year), specialised clinical role (mean 12 h per patient per year), and socioeconomic support (mean 12 h per patient per year). The modelled clinical full-time equivalent was 947 people and budget was AU$126 million, more than five times the current service level.InterpretationOur novel needs-based workforce model produced actionable estimates of the community workforce needed to address tertiary-level mental health needs in infants, children, adolescents, and their families in SA. A considerable expansion in the skilled workforce is needed to support young people facing current distress and associated family-based adversities. Because mental illness is implicated in so many burgeoning social ills, addressing this shortfall could have wide-ranging benefits.FundingNational Health and Medical Research Council (Australia), Department of Health SA.
GATA6 suppression enhances lung specification from human pluripotent stem cells
Authors: Chia-Min Liao, Somdutta Mukherjee, Amita Tiyaboonchai, Jean Ann Maguire, Fabian L. Cardenas-Diaz, Deborah L. French, Paul Gadue
Journal: Journal of Clinical Investigation (2018)

The transcription factor GATA6 has been shown to be important for lung development and branching morphogenesis in mouse models, but its role in human lung development is largely unknown. Here, we studied the role of GATA6 during lung differentiation using human pluripotent stem cells. We found that the human stem cell lines most efficient at generating NKX2.1+ lung progenitors express lower endogenous levels of GATA6 during endoderm patterning and that knockdown of GATA6 during endoderm patterning increased the generation of these cells. Complete ablation of GATA6 resulted in the generation of lung progenitors displaying increased cell proliferation with up to a 15-fold expansion compared with control cells, whereas the null cell line displayed a defect in further development into mature lung cell types. Furthermore, transgenic expression of GATA6 at the endoderm anteriorization stage skewed development toward a liver fate at the expense of lung progenitors. Our results suggest a critical dosage effect of GATA6 during human endoderm patterning and a later requirement during terminal lung differentiation. These studies offer an approach of modulating GATA6 expression to enhance the production of lung progenitors from human stem cell sources.
Advances and Biomedical Applications of Polypeptide Hydrogels Derived from α‐Amino Acid <i>N</i>‐Carboxyanhydride (NCA) Polymerizations
Authors: Xianfeng Zhou, Zhibo Li
Journal: Advanced Healthcare Materials (2018)

Abstract Polypeptide hydrogels, having the ability to mimic certain properties of natural, native extracellular matrix components, are being actively designed and described for various applications in the construction of tissue engineering scaffolds, living cell encapsulation, and drug delivery systems. Compared to conventional hydrogels, polypeptide hydrogels possess biocompatibility, biodegradability, bioactivity, functional diversity, and structural advantage based on the unique secondary structures (α‐helix and β‐sheet). Furthermore, the progresses in functional N ‐carboxyanhydride polymerization combined with advanced orthogonal conjugation techniques significantly promote the development of the polypeptide materials. This progress report focuses on the recent advances in designing and engineering polypeptide hydrogels obtained from ring opening polymerization, highlighting the precise manipulation of their properties for biomedical applications.
Clinical Implications of Revised Pooled Cohort Equations for Estimating Atherosclerotic Cardiovascular Disease Risk
Authors: Steve Yadlowsky, Rodney A. Hayward, Jeremy B. Sussman, Robyn L. McClelland, Yuan-I Min, Sanjay Basu
Journal: Annals of Internal Medicine (2018)

Background: The 2013 pooled cohort equations (PCEs) are central in prevention guidelines for cardiovascular disease (CVD) but can misestimate CVD risk. Objective: To improve the clinical accuracy of CVD risk prediction by revising the 2013 PCEs using newer data and statistical methods. Design: Derivation and validation of risk equations. Setting: Population-based. Participants: 26 689 adults aged 40 to 79 years without prior CVD from 6 U.S. cohorts. Measurements: Nonfatal myocardial infarction, death from coronary heart disease, or fatal or nonfatal stroke. Results: The 2013 PCEs overestimated 10-year risk for atherosclerotic CVD by an average of 20% across risk groups. Misestimation of risk was particularly prominent among black adults, of whom 3.9 million (33% of eligible black persons) had extreme risk estimates (<70% or >250% those of white adults with otherwise-identical risk factor values). Updating these equations improved accuracy among all race and sex subgroups. Approximately 11.8 million U.S. adults previously labeled high-risk (10-year risk ≥7.5%) by the 2013 PCEs would be relabeled lower-risk by the updated equations. Limitations: Updating the 2013 PCEs with data from modern cohorts reduced the number of persons considered to be at high risk. Clinicians and patients should consider the potential benefits and harms of reducing the number of persons recommended aspirin, blood pressure, or statin therapy. Our findings also indicate that risk equations will generally become outdated over time and require routine updating. Conclusion: Revised PCEs can improve the accuracy of CVD risk estimates. Primary Funding Source: National Institutes of Health.
Shear-induced integrin signaling in platelet phosphatidylserine exposure, microvesicle release, and coagulation
Authors: Aiming Pang, Yujie Cui, Yunfeng Chen, Ni Cheng, M. Keegan Delaney, Minyi Gu, Aleksandra Stojanovic-Terpo, Cheng Zhu, Xiaoping Du
Journal: Blood (2018)
The unmet needs of GI cancer patients: A call to action.
Authors: Martha Raymond
Journal: Journal of Clinical Oncology (2018)

167 Background: Gastrointestinal (GI) cancers are the most common and deadliest type of cancer in the United States. Understanding the need for increased GI cancer patient education, the GI Cancers Alliance created an online unmet needs survey with goals that included: determining gaps in support services, better understanding needs in patient education, and gaining insight into psychosocial concerns. Methods: 507 GI cancer survivors completed the anonymous survey. The qualitative/quantitative survey was open for a 6 week period during October &amp; November 2016. Survey respondents reported being diagnosed with one of the following GI cancer primary tumor types: Esophagus (6%), Liver (8%), Bile Duct (7%), Pancreas (6%), Gallbladder (2%), Stomach (16%), Ileum (3%), Appendix (3%), GI Carcinoid Tumor (2%), Colon (25%), Rectum (13%), Anus (6%), Did not know primary location (3%). Results: Of the 507 respondents, 84% of patients/survivors reported difficulty adjusting to a new normal as a GI cancer survivor. 59% reported they did not have adequate support (family, friends, professional, spiritual or thru advocacy organizations) to help cope with their diagnosis. Anxiety (67%), Fear (66%) and Depression (59%) were common emotions reported during the cancer continuum. Less than half (40%) of respondents described themselves as empowered patients, comfortable advocating for themselves regarding their healthcare and treatment decisions. 92% of patients surveyed did not have a Survivorship Care Plan (SCP). More than half (52%) of all respondents had not heard of or didn’t know the purpose of having a SCP. Conclusions: Our data underscores the unmet needs of GI cancer survivors, including gaps in support services and patient education. As an initial step to help meet these needs, we created a customizable SCP specific to GI cancers and will launch an online GI Cancer Resource Library. Future directions include systematic distribution of the SCP and continued expansion of GI cancer education and empowerment initiatives.
Fiber Intake and Colorectal Cancer
Authors: Tomohiro Kurokawa, Tetsuya Tanimoto, Giichiro Tsurita
Journal: JAMA Oncology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Health Status Disparities by Sex, Race/Ethnicity, and Socioeconomic Status in Outpatients With Heart Failure
Authors: Yevgeniy Khariton, Michael E. Nassif, Laine Thomas, Gregg C. Fonarow, Xiaojuan Mi, Adam D. DeVore, Carol Duffy, Puza P. Sharma, Nancy M. Albert, J. Herbert Patterson, Javed Butler, Adrian F. Hernandez, Fredonia B. Williams, Kevin McCague, John A. Spertus
Journal: JACC Heart Failure (2018)

This study sought to describe the health status of outpatients with heart failure and reduced ejection fraction (HFrEF) by sex, race/ethnicity, and socioeconomic status (SES).
Autophagy Regulates the Liver Clock and Glucose Metabolism by Degrading CRY1
Authors: Miriam Toledo, Ana Batista-Gonzalez, Emilio Merheb, Marie Louise Aoun, Elena Tarabra, Daorong Feng, Jaakko Sarparanta, Paola Merlo, Francesco Botrè, Gary J. Schwartz, Jeffrey E. Pessin, Rajat Singh
Journal: Cell Metabolism (2018)
RNA m6A methylation participates in regulation of postnatal development of the mouse cerebellum
Authors: Chunhui Ma, Mengqi Chang, Hongyi Lv, Zhi-Wei Zhang, Weilong Zhang, Xue He, Gaolang Wu, Shunli Zhao, Yao Zhang, Di Wang, Xufei Teng, Chunying Liu, Qing Li, Arne Klungland, Yamei Niu, Shuhui Song, Wei-Min Tong
Journal: Genome biology (2018)

N6-methyladenosine (m6A) is an important epitranscriptomic mark with high abundance in the brain. Recently, it has been found to be involved in the regulation of memory formation and mammalian cortical neurogenesis. However, while it is now established that m6A methylation occurs in a spatially restricted manner, its functions in specific brain regions still await elucidation. We identify widespread and dynamic RNA m6A methylation in the developing mouse cerebellum and further uncover distinct features of continuous and temporal-specific m6A methylation across the four postnatal developmental processes. Temporal-specific m6A peaks from P7 to P60 exhibit remarkable changes in their distribution patterns along the mRNA transcripts. We also show spatiotemporal-specific expression of m6A writers METTL3, METTL14, and WTAP and erasers ALKBH5 and FTO in the mouse cerebellum. Ectopic expression of METTL3 mediated by lentivirus infection leads to disorganized structure of both Purkinje and glial cells. In addition, under hypobaric hypoxia exposure, Alkbh5-deletion causes abnormal cell proliferation and differentiation in the cerebellum through disturbing the balance of RNA m6A methylation in different cell fate determination genes. Notably, nuclear export of the hypermethylated RNAs is enhanced in the cerebellum of Alkbh5-deficient mice exposed to hypobaric hypoxia. Together, our findings provide strong evidence that RNA m6A methylation is controlled in a precise spatiotemporal manner and participates in the regulation of postnatal development of the mouse cerebellum.
Phase II national clinical trial of prophylactic irradiation to the contralateral breast for BRCA mutation carriers treated for early breast cancer (EBC).
Authors: Ella Evron, Merav A. Ben David, Hadassah Goldberg, Georgeta Fried, Bella Kaufman, Rafi Catane, Rephael Pfeffer, David Geffen, Tami Karni, Roxolyana Abdah-Bortnyak, Ora Rosengarten, Diana Matceyevsky, Moshe J. Inbar, Abraham Kuten, Benjamin W. Corn
Journal: Journal of Clinical Oncology (2018)

514 Background: Women who carry germ line mutations in BRCA1/2 face a very high risk of breast and ovarian cancer. Recommendations for BRCA mutation carriers advocate intensified screening and BSO. Risk-reducing bilateral mastectomy is considered by healthy BRCA mutation carriers and by carrier patients who already developed breast cancer. Yet, the procedure is disfiguring. Women fear its effects on body image, sexuality and sensation and seek alternative preventive measures. Most studies found that breast conserving therapy was associated with similar risk of ipsilateral cancer recurrence in BRCA carriers compared to non-carriers. However, the risk of subsequent contralateral (CLT) breast cancer in carriers was markedly increased. In Israel, BRCA associated breast cancer is relatively common. Accordingly, a national protocol was devised for this enriched population. Methods: In this IRB-approved trial, the choice of prophylactic irradiation to the CLT breast, in addition to radiation of the involved side, was offered to BRCA carrier patients treated for EBC who declined CLT mastectomy. Radiation to both sides was delivered by the same schedule and dose. The primary end point was CLT breast cancer. Results: Between May 2007 and October 2017, 162 patients were enrolled. 81 opted for standard treatment including surgery and radiation to the involved side only (control group) and 81 chose additional radiation to the CLT breast (intervention group). At a median follow up of 60 months, 9 patients developed CLT breast cancer in the control group within a median of 24 months, as compared to 2 patients in the intervention group who developed CLT breast cancer 80, 109 months after bilateral breast irradiation (log-rank P = 0.027). One patient developed sarcoma in the muscle behind a CLT breast, 5 years after bilateral irradiation. There was no increase in other early or late radiation toxicities among the intervention group. Conclusions: Among BRCA carrier patients treated for EBC, the addition of CLT breast irradiation significantly reduces the risk of subsequent CLT breast cancer and constitutes a viable option for high-risk women declining mastectomy. Clinical trial information: NCT00496288.
A single centre study investigating the risk of recurrence for adjuvant hormone receptor positive breast cancer patients with mental health conditions.
Authors: Hilary Martin, Andrew D. Redfern
Journal: Journal of Clinical Oncology (2018)

e12552 Background: Mental health conditions are associated with poorer health outcomes. Much of the focus in the association between adjuvant breast cancer outcomes and mental health have focussed on the interaction between specific antidepressants and tamoxifen. The influence of mental health conditions overall and breast cancer outcome have been less well studied. Methods: This was a single centre retrospective study of data from 1921 women treated with curative intent for hormone receptor positive breast cancer. Demographic data was obtained on this cohort from case notes, as well as treatment and outcome details. Patients were identified as having a mental health condition based on case notes and medication charts. For the purpose of analysis only those on medication for a mental health condition at time of diagnosis of breast cancer were included in this study. Medications included both antipsychotics and antidepressant medications. Cox univariate and multivariate analysis was undertaken. Results: Of the 1921 patients in this cohort, 251 (13.1%) were on medication for mental health condition at the time of diagnosis of breast cancer. On univariate Cox regression analysis, those with a mental health condition were at increased risk of disease recurrence, with a hazard ratio 1.49 (95% CI 1.08 to 2.07, p = 0.016) and, on adjusted analysis the risk of recurrence for those with a mental health condition had a risk of recurrence more than double that of those without a mental health condition (HR 2.59, 95% CI 1.65-4.08, p < 0.001). Conclusions: Risk of recurrence was significantly higher for patients with mental health conditions treated with curative intent. Further research is required to identify the mechanisms underlying this poorer outcome. Such research can then be utilised to guide interventions to reduce the risk of recurrence for this group.
DNA damage predicts prognosis and treatment response in colorectal liver metastases superior to immunogenic cell death and T cells
Authors: Johannes Laengle, Judith Stift, Agnes Bilecz, Brigitte Wolf, Andrea Beer, Balazs Hegedus, Stefan Stremitzer, Patrick Starlinger, Dietmar Tamandl, Dietmar Pils, Michael Bergmann
Journal: Theranostics (2018)

Preclinical models indicate that DNA damage induces type I interferon (IFN), which is crucial for the induction of an anti-tumor immune response.In human cancers, however, the association between DNA damage and an immunogenic cell death (ICD), including the release and sensing of danger signals, the subsequent ER stress response and a functional IFN system, is less clear.Methods: Neoadjuvant-treated colorectal liver metastases (CLM) patients, undergoing liver resection in with a curative intent, were retrospectively enrolled in this study (n=33).DNA damage (γH2AX), RNA and DNA sensors (RIG-I, DDX41, cGAS, STING), ER stress response (p-PKR, p-eIF2α, CALR), type I and type II IFN-induced proteins (MxA, GBP1), mature dendritic cells (CD208), and cytotoxic and memory T cells (CD3, CD8, CD45RO) were investigated by an immunohistochemistry whole-slide tissue scanning approach and further correlated with recurrence-free survival (RFS), overall survival (OS), radiographic and pathologic therapy response.Results: γH2AX is a negative prognostic marker for RFS (HR 1.32, 95% CI 1.04-1.69,p=0.023) and OS (HR 1.61, 95% CI 1.23-2.11,p<0.001).A model comprising of DDX41, STING and p-PKR predicts radiographic therapy response (AUC=0.785,p=0.002).γH2AX predicts prognosis superior to the prognostic value of CD8.CALR positively correlates with GBP1, CD8 and cGAS.A model consisting of γH2AX, p-eIF2α, DDX41, cGAS, CD208 and CD45RO predicts pathological therapy response (AUC=0.944,p<0.001). Conclusion:In contrast to preclinical models, DNA damage inversely correlated with ICD and its associated T cell infiltrate and potentially serves as a therapeutic target in CLM.
Identification of an Amino Acid Motif in <scp>HLA</scp>–<scp>DR</scp>β1 That Distinguishes Uveitis in Patients With Juvenile Idiopathic Arthritis
Authors: Anne‐Mieke J. W. Haasnoot, Marco W. Schilham, Sylvia Kamphuis, Petra C. E. Hissink Muller, Arnd Heiligenhaus, Dirk Foell, Kirsten Minden, Roel A. Ophoff, Timothy R. D. J. Radstake, Anneke I. Den Hollander, Tjitske H. C. M. Reinards, Sanne Hiddingh, Nicoline E. Schalij‐Delfos, Esther P. A. H. Hoppenreijs, Marion A. J. van Rossum, Carine Wouters, Rotraud K. Saurenmann, J. Merlijn van den Berg, Nico M. Wulffraat, Rebecca ten Cate, Joke H. de Boer, Sara L. Pulit, Jonas J. W. Kuiper
Journal: Arthritis & Rheumatology (2018)

Objective Uveitis is a visually debilitating disorder that affects up to 30% of children with the most common forms of juvenile idiopathic arthritis ( JIA ). The disease mechanisms predisposing only a subgroup of children to uveitis are unknown. This study was undertaken to identify genetic susceptibility loci for uveitis in JIA , using a genome‐wide association study in 522 children with JIA . Methods Two cohorts of JIA patients with ophthalmologic follow‐up data were genotyped. Data were then imputed using a genome‐wide imputation reference panel, and an HLA ‐specific reference panel was used for imputing amino acids and HLA types in the major histocompatibility complex ( MHC ). After imputation, genome‐wide and MHC ‐specific analyses were performed, and a reverse immunology approach was utilized to model antigen presentation at 13 common HLA – DR β1 alleles. Results Presence of the amino acid serine at position 11 (serine 11) in HLA – DR β1 was associated with an increased risk of uveitis in JIA patients (odds ratio [ OR ] 2.60, P = 5.43 × 10 −10 ) and was specific to girls ( P females = 7.61 × 10 −10 versus P males = 0.18). Serine 11 resides in the YST motif in the peptide‐binding groove of HLA – DR β1; all 3 amino acids in this motif are in perfect linkage disequilibrium and show identical association with disease. Quantitative prediction of binding affinity revealed that HLA – DR β1 alleles with the YST motif could be distinguished on the basis of discernable peptide‐binding preferences. Conclusion These findings highlight a genetically distinct, sexually dimorphic feature of JIA with uveitis as compared to JIA without uveitis. The association could be indicative of the potential involvement of antigen presentation by HLA – DR β1 in the development of uveitis in JIA . The results of this study may advance our progress toward improved treatments for, and possible prevention of, the sight‐threatening complications of uveitis in children with JIA .
Percutaneous Revascularization for Ischemic Ventricular Dysfunction: Rationale and Design of the REVIVED-BCIS2 Trial
Authors: Divaka Perera, Tim Clayton, Mark C. Petrie, John P. Greenwood, Peter D. O’Kane, Richard Evans, Mark Sculpher, Theresa Mcdonagh, Anthony Gershlick, Mark de Belder, Simon Redwood, Gerald Carr-White, Michael Marber
Journal: JACC Heart Failure (2018)
Non-medical health professionals get chance to train as GPs in Scotland
Authors: Bryan Christie
Journal: BMJ (2018)

Experienced nurses and other health professionals will get the opportunity to train as family doctors in Scotland in an innovative approach to filling GP vacancies.

The Scottish government is funding a range of new university courses to encourage recruitment into general practice as part of wider efforts to increase the GP workforce by 800 doctors over the next decade.

Medical schools were asked to put forward proposals for new …