tbuckley/cabot-search huggingface dataset:
Core elements for the implementation of primary care-based prostate cancer follow-up: A process evaluation of a randomized controlled trial.
Authors: Barbara M. Wollersheim, Kristel M. van Asselt, Emine Akdemir, Shifra Crouse, Floris J. Pos, Henk G. van der Poel, Lonneke V van de Poll-Franse, Annelies H. Boekhout
Journal: Journal of Clinical Oncology (2021)

242 Background: To improve the quality and efficiency of prostate cancer survivorship care, a randomized controlled trial (RCT) is currently comparing the safety and effectiveness of specialist- (usual care) versus primary care-based (intervention) prostate cancer follow-up. This process evaluation assessed the reach and identified constructs for the implementation of primary care-based follow-up in a RCT setting. Methods: A mixed-methods approach was used through the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework and the Consolidated Framework for Implementation Research (CFIR). We used quantitative data to evaluate the reach of the RCT and qualitative data (interviews) to indicate the perspectives of patients, general practitioners (GPs) and specialists. Thematic analysis was used to analyze the interview transcripts. Results: In total, 569 patients with localized prostate cancer from 12 hospitals were invited to participate in the trial. 18 patients were not eligible, 145 patients declined (of whom most preferred follow-up in the hospital), whereas 21 GPs declined to participate. Finally, 385 patients were randomized to specialist- (n=192) or to primary care-based (n=193) follow-up. In addition, we interviewed 15 patients, 10 GPs and 8 specialists. Participants identified several advantages of primary care- versus specialist-based follow-up: it is closer to home, more accessible, the relationship is more personal, and the hospital can focus on patients undergoing active treatment. Nevertheless, participants also identified challenges: evidence-based guidelines should be implemented, communication and collaboration between primary and secondary care should be accessible and transparent, quality indicators (i.e. PSA levels) should be collected, and GPs expect compensation (money or extra capacity). Conclusions: If the RCT shows that primary care- is equally effective as specialist-based follow-up, this study could enable the transition of prostate cancer follow-up to primary care by presenting information on the reach of an RCT and by providing advantages and challenges of primary care-based prostate cancer follow-up.
Nuclear dynamics and stress responses in Alzheimer’s disease
Authors: Artemis Iatrou, Eric M. Clark, Yanling Wang
Journal: Molecular Neurodegeneration (2021)

Abstract In response to extracellular and intracellular stressors, the nucleus and nuclear compartments undergo distinct molecular changes to maintain cell homeostasis. In the context of Alzheimer’s disease, misfolded proteins and various cellular stressors lead to profound structural and molecular changes at the nucleus. This review summarizes recent research on nuclear alterations in AD development, from the nuclear envelope changes to chromatin and epigenetic regulation and then to common nuclear stress responses. Finally, we provide our thoughts on the importance of understanding cell-type-specific changes and identifying upstream causal events in AD pathogenesis and highlight novel sequencing and gene perturbation technologies to address those challenges.
P16.13 MenImmune: Evaluation of immune-related and prognostic biomarkers in meningioma
Authors: M Truffelli, M Grassi, P Fiaschi, L Roccatagliata, E Bennicelli, L Barletta, E Cella, L Valle, G Zona, G Gaggero
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Meningiomas are the most common group of adult central nervous system primary tumor. The major known predictors for meningioma recurrence are extent of surgical resection and histological grade. Although grading system is the actual standard for risk classification, there are several exceptions in the clinical behavior. Recent studies have shown that meningiomas can express PD-L1, a known therapeutic target for checkpoint inhibitors. Tumor microenvironment and hormonal setting are known to influence the immune system response. The only standard therapeutic strategies nowadays are surgery and radiotherapy. Meningiomas microenvironment needs to be further studied looking for new therapeutic targets. New prognostic tools combining histological and radiological features (RF) are needed to better address the treatment strategy. ELIGIBILITY CRITERIA Patients diagnosed with meningioma who underwent surgery at the Department of Neurosurgery of the IRCCS Ospedale Policlinico San Martino of Genoa from 1998. - Availability of magnetic resonance imaging (MRI) at diagnosis. - Availability of histological samples. OBJECTIVES Identification and prevalence of immune-related biomarkers and their correlation with morphological and hormonal features. - Survival analyses in the study population and according to the different characteristics analyzed. - The identification of specific clinical, histological and RF of meningiomas and their inclusion in a prognostic signature. STUDY DESIGN This is a retrospective-prospective monocentric study designed to analyze clinical, radiological and histological features of meningioma patients. - Clinical data will be collected from the electronic patient records. - Analyses will be conducted on a cohort of patients enriched with higher grade meningioma to balance the proportion between high and low grade histologies. - Histological specimen will be blindly reviewed and reclassified according to histological type, morphological features and WHO 2016 criteria. - The MRI features will be analyzed at diagnosis. STUDY ANALYSIS We retrospectively enrolled 50 patients with available radiological, histological and clinical data.- All histopathological specimens will be examined with slides obtained from material fixed in 10% neutral buffered formalin, included in kerosene, sectioned at 3 µm and stained with hematoxylin-eosin. - We will look for the presence of estrogens and progesterone receptors. - Concerning immune-related biomarkers we will further assess PD-L1 positivity (cut-off: positive 1%, negative &amp;lt;1%), MSI status and the inflammatory infiltrate with immunohistochemistry, in particular TILs (CD45, CD3, CD4, CD8, FOXP3, CTLA4), B cell (CD20), TAM (CD68). - All histological and radiological data will be analyzed and correlated with the clinical characteristics of meningioma patients and their outcomes.
Trends in diagnosis and treatment of early breast cancer (eBC) in the United States (US) during the COVID-19 era.
Authors: Benjamin Ackerman, Catherine Keane, Julia A. Beaver, Paul Gustav Kluetz, Donna Rivera, Prashni Paliwal, Harpreet Singh, Philani Mpofu, Laleh Amiri-Kordestani, Shrujal S. Baxi
Journal: Journal of Clinical Oncology (2021)

227 Background: Recent studies have demonstrated a decline in cancer screening and diagnosis during the COVID-19 pandemic. This study explored trends in the diagnosis and management of eBC at a sample of cancer clinics across the US early on in the pandemic. Methods: Patients were selected from the Flatiron Health Research Database (FHRD), an electronic health record-derived de-identified database comprising approximately 280 US cancer clinics (̃800 sites of care). Eligible patients had an ICD code for breast cancer, at least two clinical encounters, and a confirmed eBC (Stage I-III) diagnosis from unstructured documents. Patients were selected into two cohorts based on diagnosis date: a) COVID-19 era cohort diagnosed between February 1, 2020 through June 30, 2020 and b) pre-COVID-19 era cohort diagnosed from February 1, 2019 through June 30, 2019. Descriptive statistics were used to assess diagnosis trends in each time frame. Initial treatment received following eBC diagnosis was categorized as surgery, radiation or systemic therapy and was compared between the two cohorts. Initial treatment modalities for each cohort were further stratified by clinical stage and biomarker subtype (HER2+, HR+/HER2-, triple negative [TN] or unknown). Results: A total of 278 and 253 patients were selected for the pre-COVID-19 era and COVID-19 era cohorts, with a median age at diagnosis of 65 and 64 years, respectively. A 35% decrease in the number of eBC diagnoses was observed in April/May 2020 compared to March 2020, yet this reduction in diagnoses was not observed during the equivalent months in the pre-COVID-19 era cohort. Compared to the pre-COVID-19 era, a greater proportion of patients diagnosed with eBC during the COVID-19 era initiated systemic therapy as their first treatment modality (16.5% vs 29.6%) including patients with HER2+ (27.5% vs. 60%), HR+/HER2- (13.5% vs. 24.9%) and TN (30.8% vs. 40.0%) disease. This trend was observed in patients with stage I (11.7% vs. 24.1%) or II (55.9% vs. 73.0%) but not in patients with stage III (81.2% vs. 77.3%) eBC. Notably, among patients with HR+/HER2- eBC who received systemic therapy as their first treatment, endocrine therapy was most commonly used in keeping with recent recommendations from professional societies due to COVID-related anticipated surgical delays. Conclusions: This study demonstrates that COVID-19 was associated with a decreased incidence of eBC which could be, at least in part, attributed to previously reported delays in routine screening and pandemic healthcare utilization. Further efforts are required to understand who was affected by these delays and the impact on cancer outcomes. Follow-up data are needed to understand if the observed trends in cancer screening and treatment persist and their impact on long-term cancer outcomes.
Harnessing the power of anticipation to manage respiratory-related brain suffering and ensuing dyspnoea: insights from the neurobiology of the respiratory nocebo effect
Authors: Fabien Vinckier, Sophie Betka, Nathalie Nion, Laure Serresse, Thomas Similowski
Journal: European Respiratory Journal (2021)

<b>The mere expectation of dyspnoea contributes to shape the lives of patients with chronic respiratory diseases: approaches addressing anticipatory mechanisms will provide new therapeutic avenues for persistent dyspnoea in the near future</b> https://bit.ly/3mkv6US
Team debriefings in healthcare: aligning intention and impact
Authors: Michaela Kolbe, Sven Schmutz, Julia Carolin Seelandt, Walter J Eppich, Jan B Schmutz
Journal: BMJ (2021)

### What you need to know

The covid-19 pandemic has renewed focus on debriefings to improve performance among healthcare providers: debriefings help teams learn quickly and manage patients more safely.1234 However, in some circumstances, debriefings may harm more than help. In this article we introduce debriefing and its benefits, highlight the potential consequences when debriefing intentions blur, and offer guidance to navigate shifting debriefing objectives, for example during instances of clinicians’ distress related to patient care.

Team debriefings (also known as after action reviews) are guided meetings during which members discuss, interpret, and learn from recent events.56 Debriefings will typically include both retrospective (eg, collaborative sense making in information-rich and ambiguous environments) and prospective reflection (eg, sustaining positive performance, planning treatments, anticipating problems).57 They foster reflection on clinical practice for the individual and the team. Various debriefing tools and structures are in use, such as TALK (Target, Analysis, Learning, Key Actions),8 PEARLS (Promoting Excellence and Reflective Learning in Simulation),9 and REFLECT (Review the event, Encourage team participation, Focused feedback, Listen to each other, Emphasise key points, Communicate clearly, Transform the future). …
Abstract 15668: Distinct Types of Plexiform Lesions in Pulmonary Arterial Hypertension Identified by Synchrotron-Based Phase Contrast Micro-CT
Authors: Christian Westöö, Christian Norvik, Niccolò Peruzzi, Goran Lovric, Oscar van der Have, Ida Jeremiasen, Rajmund Mokso, Vinicio A De Jesus Perez, Hans Brunnström, Martin Bech, Csaba Galambos, Karin Tran-Lundmark
Journal: Circulation (2019)

In pulmonary arterial hypertension (PAH), plexiform lesions are associated with severe arterial obstruction and right ventricular failure. Exploring the structure and position of plexiform lesions ...
Commentaire du travail de Pohl H et al., pp. 891
Authors: Gilles Lesur
Journal: Endoscopy (2015)

See also: Cap-assisted colonoscopy and detection of Adenomatous Polyps (CAP) study: a randomized trialEndoscopy 2015; 47(10): 891-897DOI: 10.1055/s-0034-1392261
Structure-guided discovery of potent and oral soluble epoxide hydrolase inhibitors for the treatment of neuropathic pain
Authors: Fangyu Du, Ruolin Cao, Lu Chen, Jianwen Sun, Yajie Shi, Yang Fu, Bruce D. Hammock, Zhonghui Zheng, Zhongbo Liu, Guoliang Chen
Journal: Acta Pharmaceutica Sinica B (2021)

Soluble epoxide hydrolase (sEH) is related to arachidonic acid cascade and is over-expressed in a variety of diseases, making sEH an attractive target for the treatment of pain as well as inflammatory-related diseases. A new series of memantyl urea derivatives as potent sEH inhibitors was obtained using our previous reported compound 4 as lead compound. A preferential modification of piperidinyl to 3-carbamoyl piperidinyl was identified for this series via structure-based rational drug design. Compound A20 exhibited moderate percentage plasma protein binding (88.6%) and better metabolic stability in vitro. After oral administration, the bioavailability of A20 was 28.6%. Acute toxicity test showed that A20 was well tolerated and there was no adverse event encountered at dose of 6.0 g/kg. Inhibitor A20 also displayed robust analgesic effect in vivo and dose-dependently attenuated neuropathic pain in rat model induced by spared nerve injury, which was better than gabapentin and sEH inhibitor (±)-EC-5026. In one word, the oral administration of A20 significantly alleviated pain and improved the health status of the rats, demonstrating that A20 was a promising candidate to be further evaluated for the treatment of neuropathic pain.
Regulatory regions in natural transposable element insertions drive interindividual differences in response to immune challenges in Drosophila
Authors: Anna Ullastres, Miriam Merenciano, Josefa González
Journal: Genome biology (2021)

Abstract Background Variation in gene expression underlies interindividual variability in relevant traits including immune response. However, the genetic variation responsible for these gene expression changes remains largely unknown. Among the non-coding variants that could be relevant, transposable element insertions are promising candidates as they have been shown to be a rich and diverse source of cis -regulatory elements. Results In this work, we use a population genetics approach to identify transposable element insertions likely to increase the tolerance of Drosophila melanogaster to bacterial infection by affecting the expression of immune-related genes. We identify 12 insertions associated with allele-specific expression changes in immune-related genes. We experimentally validate three of these insertions including one likely to be acting as a silencer, one as an enhancer, and one with a dual role as enhancer and promoter. The direction in the change of gene expression associated with the presence of several of these insertions is consistent with an increased survival to infection. Indeed, for one of the insertions, we show that this is the case by analyzing both natural populations and CRISPR/Cas9 mutants in which the insertion is deleted from its native genomic context. Conclusions We show that transposable elements contribute to gene expression variation in response to infection in D. melanogaster and that this variation is likely to affect their survival capacity. Because the role of transposable elements as regulatory elements is not restricted to Drosophila , transposable elements are likely to play a role in immune response in other organisms as well.
Repurposing non-oncology small-molecule drugs to improve cancer therapy: Current situation and future directions
Authors: Leilei Fu, Wenke Jin, Jiahui Zhang, Lingjuan Zhu, Jia Lu, Yongqi Zhen, Lan Zhang, Liang Ouyang, Bo Liu, Haiyang Yu
Journal: Acta Pharmaceutica Sinica B (2021)

Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy, with potentially lower overall costs and shorter timelines. Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers, with the aid of some new emerging technologies, such as omics sequencing and artificial intelligence to overcome the bottleneck of drug repurposing. Therefore, in this review, we focus on summarizing the therapeutic potential of non-oncology drugs, including cardiovascular drugs, microbiological drugs, small-molecule antibiotics, anti-viral drugs, anti-inflammatory drugs, anti-neurodegenerative drugs, antipsychotic drugs, antidepressants, and other drugs in human cancers. We also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer therapies. Taken together, these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.
Ethnic minority women and babies: outcomes worsen, and CQC demands action
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Ethnic inequalities in outcomes among women and babies have been exacerbated by the covid-19 pandemic and must be tackled immediately, England’s healthcare regulator has warned.

In a report published on 21 September the Care Quality Commission outlined its findings from visits to nine maternity services in England that took place as the country was emerging from the third lockdown between March and June 2021. The CQC said that while many maternity units across England were providing good care it had concerns about leadership and oversight of risk, team working, culture, and the extent to which some services were engaging with and listening to the needs of their local population.

Between 2014 and 2016 the CQC rated half of all …
COVID-19 and advance care planning: A unique opportunity.
Authors: Aliya Gessling, Mary Rank, Deborah Larson, Ann Soloway, Jessica Langston, Quy Tran
Journal: Journal of Clinical Oncology (2021)

32 Background: Advance Care Planning (ACP) is a process to document patient preferences for future health care. Conversations between healthcare providers, patients, and loved-ones are required to reflect a patient’s values, goals, and ultimately their choices for life-sustaining treatments (LST). The COVID-19 pandemic has highlighted the critical importance of these discussions and the need for improved patient engagement. Methods: As COVID-19 infections surged, the VA Northern California Health Care System (VA NCHCS) Hospice and Palliative Care Section (HPCS) partnered with Patient Aligned Care Teams to expand urgent outreach to high-risk patients needing LST documentation. High risk was defined as age &gt; 80, COPD or asthma diagnosis, or Care Assessment Need Score &gt; 80 (CAN Score models risk of hospitalization or death within 1 year). An experienced HPCS Nurse Practitioner (NP) contacted these identified patients to 1.) provide COVID-19 education, 2.) conduct a high-quality goals of care conversation, and 3.) complete LST documentation and other ACP needs. A representative cohort was then followed up to evaluate concordance of treatment with their documented preferences. Results: Between March 2020 and September 2020, 910 patients were identified as high risk. Of these patients, 294 agreed to participate in the telehealth visit and complete LST documentation. Importantly, 108 (37%) patients chose DNR and other LST limitations. In addition, 142 (48%) patients created POLST documentation and 128 (43%) completed Advance Directives. Over 70% of patients who were hospitalized in the VA received care concordant with the newly documented LST preferences. A follow up survey of 29 participants found the outreach impactful and their preferences documented correctly. Conclusions: Prior studies have demonstrated success at educating primary providers to conduct ACP discussions, but given the limitations imposed by COVID-19 restrictions, this novel and highly cost-effective process of coupling a highly trained HPCS NP with a primary care team to perform ACP was piloted with success. After only a single ACP discussion, patients were able to formalize their limits to treatment and subsequent care aligned with these preferences. Patients also found this focused ACP discussion meaningful. This pathway will be integrated within the VA NCHCS as a long-term approach to continued ACP outreach.
Pemphigus. Skin failure mediated by autoantibodies
Authors: J. R. Stanley
Journal: JAMA (1990)

<h3>SELECTED CASES</h3><h3>Case 1.—</h3> A 47-year-old woman presented to the National Institutes of Health Clinical Center for evaluation of a 3-year history of painful oral erosions (Fig 1, top left). During the previous 2 months her oral erosions were so extensive and severe that she could not eat well and lost approximately 9 kg. In the last month she also noted erosions on the skin of her trunk and extremities. A skin biopsy specimen revealed an intraepidermal blister with acantholysis (loss of cell-to-cell adhesion) just above the basal cell layer (Fig 1, top right). The results of direct immunofluorescence of perilesional skin were positive for IgG on the cell surface of keratinocytes throughout the epidermis. Indirect immunofluorescence showed a serum IgG that bound to the epithelial cell surface of monkey esophagus at a titer of 160. Pemphigus vulgaris (PV) was diagnosed, and the patient was treated daily with 80 mg
Brazilian glomerulonephritis: analysis of a regional multicentre study in state of São Paulo
Authors: P. Malafronte, Y. A. Sens, Viktória Woronik, M. S. M. Marrocos, Rui Toledo Barros, G. M. Kirstajn, M. A. R. Alves, V. A. Soares, R. A. M. Cadaval, R. R. Bergamo, J. E. Romão, O. M. Vieira Neto
Journal: Journal of the American Society of Nephrology (2001)