tbuckley/cabot-search huggingface dataset:
Association Between Antipsychotic Use and COVID-19 Mortality Among People With Serious Mental Illness
Authors: Katlyn Nemani, Sarah Conderino, Julia Marx, Lorna E. Thorpe, Donald C. Goff
Journal: JAMA Psychiatry (2021)

Schizophrenia spectrum disorders are associated with increased mortality in the setting of COVID-19 infection. 1-3Among several possible explanations for this increased risk is the role of adverse effects of antipsychotic medication, which has not been systematically examined in this population.Our goal was to investigate whether antecedent antipsychotic use was associated with mortality among patients with serious mental illness diagnosed with COVID-19.Methods | We conducted a retrospective cohort study using the New York University Langone Health electronic health record Table 1.Characteristics of Study Population by Antipsychotic Use Characteristic Antipsychotic use, No. (%) (N = 464)
Screening for Chlamydial and Gonococcal Infections
Authors: Amy Cantor, Tracy Dana, Jessica C. Griffin, Heidi D. Nelson, Chandler Weeks, Kevin L. Winthrop, Roger Chou
Journal: JAMA (2021)

<h3>Importance</h3> The 2014 US Preventive Services Task Force (USPSTF) recommendation statement supported the effectiveness of screening for chlamydia and gonorrhea in asymptomatic, sexually active women 24 years or younger and in older women at increased risk for infection, although evidence for screening in men was insufficient. <h3>Objective</h3> To update the 2014 USPSTF review on screening for chlamydial and gonococcal infection in adults and adolescents, including those who are pregnant. <h3>Data Sources</h3> Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Ovid MEDLINE (January 1, 2014, through May 28, 2020) with surveillance through May 21, 2021. <h3>Study Selection</h3> Randomized clinical trials and observational studies of screening effectiveness, accuracy of risk stratification and alternative screening methods, accuracy of tests, and screening harms. <h3>Data Extraction and Synthesis</h3> One investigator abstracted data; a second checked accuracy. Two investigators independently assessed study quality. <h3>Main Outcomes and Measures</h3> Complications of infection; infection transmission or acquisition; diagnostic accuracy of anatomical site–specific testing and collection methods; screening harms. <h3>Results</h3> Twenty-seven studies were included (N = 179 515). Chlamydia screening compared with no screening was significantly associated with reduced risk of pelvic inflammatory disease (PID) in 2 of 4 trials and with reduced hospital-diagnosed PID (0.24% vs 0.38%); relative risk, 0.6 [95% CI, 0.4-1.0]), but not clinic-diagnosed PID or epididymitis, in the largest trial. In studies of risk prediction instruments in asymptomatic women, age younger than 22 years demonstrated comparable accuracy to extensive criteria. Sensitivity of chlamydial testing was similar at endocervical (89%-100%) and self- and clinician-collected vaginal (90%-100%) sites for women and at meatal (100%), urethral (99%), and rectal (92%) sites for men but lower at pharyngeal sites (69.2%) for men who have sex with men. Sensitivity of gonococcal testing was 89% or greater for all anatomical samples. False-positive and false-negative testing rates were low across anatomical sites and collection methods. <h3>Conclusions and Relevance</h3> Screening for chlamydial infection was significantly associated with a lower risk of PID in young women. Risk prediction criteria demonstrated limited accuracy beyond age. Testing for asymptomatic chlamydial and gonococcal infections was highly accurate at most anatomical sites, including urine and self-collected specimens. Effectiveness of screening in men and during pregnancy, optimal screening intervals, and adverse effects of screening require further evaluation.
P10.02 Combined methods of a micropump system and a chronic cranial window allows tumor observation with multi photon laser scanning microscopy under continuous treatment
Authors: S Weil, E Jung, D Domínguez Azorín, J Higgins, J Reckless, N Ramsden, P Keller, D Grainger, W Wick, F Winkler
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Glioblastomas are notoriously therapy resistant tumors. As opposed to other tumor entities, no major advances in therapeutic success have been made in the past decades. This has been calling for a deeper biological understanding of the tumor, its growth and resistance patterns. We have been using a xenograft glioma model, where human glioblastoma cells are implanted under chronic cranial windows and studied longitudinally over many weeks and months using multi photon laser scanning microscopy (MPLSM). To test the effect of (new) drugs, a stable and direct delivery system avoiding the blood-brain-barrier has come into our interest. MATERIAL AND METHODS We implanted cranial windows and fluorescently labeled human glioblastoma stem-like cells into NMRI nude mice to follow up on the tumor development in our MPLSM model. After tumor establishment, an Alzet® micropump was implanted to directly deliver agents via a catheter system continuously over 28 days directly under the cranial window onto the brain surface. Using the MPLSM technique, the continuous delivery and infusion of drugs onto the brain and into the tumor was measured over many weeks in detail using MPLSM. RESULTS The establishment of the combined methods allowed reliable concurrent drug delivery over 28 days bypassing the blood-brain-barrier. Individual regions and tumor cells could be measured and followed up before, and after the beginning of the treatment, as well as after the end of the pump activity. Fluorescently labelled drugs were detectable in the MPLSM and its distribution into the brain parenchyma could be quantified. After the end of the micropump activity, further MPLSM measurements offer the possibility to observe long term effects of the applied drug on the tumor. CONCLUSION The combination of tumor observation in the MPSLM and concurrent continuous drug delivery is a feasible and reliable method for the investigation of (novel) anti-tumor agents, especially drugs that are not blood-brain-barrier penetrant. Morphological or even functional changes of individual tumor cells can be measured under and after treatment. These techniques can be used to test new drugs targeting the tumor, its tumor microtubes and tumor cells networks, and measure the effects longitudinally.
On the Lack of Native Hawaiian and Pacific Islander Individuals in the Physician Workforce
Authors: Westley S. Mori
Journal: JAMA Network Open (2021)

The popular conception of the Hawaiian islands as a paradise is a foil to a stark reality-Native Hawaiian and other Pacific Islander individuals experience among the worst health outcomes across all racial and ethnic groups.The relative unawareness to the plight of this population's health metrics may be in part due to the historical, although imprecise, practice in health outcomes research of grouping Native Hawaiian and other Pacific Islander individuals with Asian American individuals, who themselves represent a heterogeneous group that generally shares little culturally with Native Hawaiian and other Pacific Islander individuals.Moreover, many studies may exclude Native Hawaiian and other Pacific Islander individuals completely.When Native Hawaiian and other Pacific
Author Correction: Chromatin lncRNA Platr10 controls stem cell pluripotency by coordinating an intrachromosomal regulatory network
Authors: Zhonghua Du, Xue Wen, Yichen Wang, Lin Jia, Shilin Zhang, Yudi Liu, Lei Zhou, Hui Li, Wang Yang, Cong Wang, Jingcheng Chen, Yajing Hao, Daniela Salgado Figueroa, Huiling Chen, Dan Li, Naifei Chen, Ilkay Celik, Yanbo Zhu, Zi Yan, Changhao Fu, Shanshan Liu, Benzheng Jiao, Zhuo Wang, Hui Zhang, Günhan Gülsoy, Jianjun Luo, Baoming Qin, Sujun Gao, Philipp Kapranov, Miguel A. Esteban, Songling Zhang, Wei Li, Ferhat Ay, Runsheng Chen, Andrew R. Hoffman, Jiuwei Cui, Ji-Fan Hu
Journal: Genome biology (2021)
Outcomes of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome
Authors: Roxane Labrosse, Julia I. Chu, Myriam A. Armant, John K. Everett, Danilo Pellin, Niharika Kareddy, Andrew L. Frelinger, Lauren A. Henderson, Amy E. O’Connell, Amlan Biswas, Jet Coenen-van der Spek, Alexandra Miggelbrink, Claudia Fiorini, Hriju Adhikari, Charles C. Berry, Vito Adrian Cantu, Johnson Fong, Jason Jaroslavsky, Derin F. Karadeniz, Quan-Zhen Li, Shantan Reddy, Aoife M. Roche, Chengsong Zhu, Jennifer S. Whangbo, Colleen Dansereau, Brenda Mackinnon, Emily Morris, Stephanie M. Koo, Wendy B. London, Safa Baris, Ahmet Ozen, Elif Karakoc-Aydiner, Jenny M. Despotovic, Lisa R. Forbes Satter, Akihiko Saitoh, Yuta Aizawa, Alejandra King, Mai Anh Thi Nguyen, Vy Do Uyen Vu, Scott B. Snapper, Anne Galy, Luigi D. Notarangelo, Frederic D. Bushman, David A. Williams, Sung-Yun Pai
Journal: Blood (2023)
Gut epithelial IL-27 confers intestinal immunity through the induction of intraepithelial lymphocytes
Authors: Chia-Hao Lin, Mei-Chi Chen, Ling-Li Lin, David A. Christian, Booki Min, Christopher A. Hunter, Li-Fan Lu
Journal: The Journal of Experimental Medicine (2021)

IL-27 controls a diverse range of immune responses in many disease settings. Here, we identify intestinal epithelial cells (IECs) as one of the major IL-27 cellular sources in the gut-associated tissue. Unlike IL-27 secreted by innate immune cells, gut epithelial IL-27 is dispensable for T-bet+ regulatory T cell (T reg cell) differentiation or IL-10 induction. Rather, IEC-derived IL-27 specifically promotes a distinct CD8αα+CD4+ intraepithelial lymphocyte (IEL) population that acquires their functional differentiation at the intestinal epithelium. Loss of IL-27 in IECs leads to a selective defect in CD8αα+CD4+ IELs over time. Consequently, mice with IEC-specific IL-27 ablation exhibited elevated pathogen burden during parasitic infection, and this could be rescued by transfer of exogenous CD8αα+CD4+ IELs. Collectively, our data reveal that in addition to its known regulatory properties in preventing immune hyperactivity, gut epithelial IL-27 confers barrier immunity by inducing a specific IEL subset and further suggest that IL-27 produced by different cell types plays distinct roles in maintaining intestinal homeostasis.
Pembrolizumab with low-dose carboplatin for recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer: survival and immune correlates
Authors: John B Liao, William R Gwin, Renata R Urban, Katie M Hitchcock-Bernhardt, Andrew L Coveler, Doreen M Higgins, Jennifer S Childs, Hania N Shakalia, Ron E Swensen, Sasha E Stanton, Anna V Tinker, Tanya A Wahl, Richard G Ancheta, Kathryn F McGonigle, James Y Dai, Mary L Disis, Barbara A Goff
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Anti-programmed death 1 (PD1)/programmed cell death ligand 1 (PD-L1) therapies have shown modest activity as monotherapy in recurrent ovarian cancer. Platinum chemotherapies induce T-cell proliferation and enhance tumor recognition. We assessed activity and safety of pembrolizumab with carboplatin in recurrent platinum-resistant ovarian cancer. Patients and methods This phase I/II, single-arm clinical trial studied concurrent carboplatin and pembrolizumab in recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer. Primary platinum refractory patients were excluded. Patients were treated after progression on subsequent non-platinum systemic therapy after becoming platinum resistant or refractory. Pembrolizumab 200 mg was given on day 1 and carboplatin area under the curve 2 on days 8 and 15 of a 3-week cycle until progression. Imaging was assessed by blinded independent review. PD-L1 expression was assessed by immunohistochemistry. Flow cytometry on peripheral blood mononuclear cells was performed for CD3, CD4, CD8, PD1, CTLA4 and Ki67. Results The most common treatment-related adverse events were lymphopenia (18%) and anemia (9%) with most being grade 1 or 2 (93%). Of 29 patients treated, 23 patients were evaluable for best objective response: 10.3% (95% CI 2.2 to 27.4) had partial response (PR), 51.7% (95% CI 32.5 to 70.6) had stable disease (SD). 56.5% of patients had decreases in target lesions from baseline. All PD-L1-positive patients achieved PR (3/7, 42.8%) or SD (4/7, 57.2%). Median progression-free survival was 4.63 months (95% CI 4.3 to 4.96). Median OS was 11.3 months (95% CI 6.094 to 16.506). Peripheral CD8+PD1+Ki67+ T cells expanded after 3 (p=0.0015) and 5 (p=0.0023) cycles. CTLA4+PD1+CD8+ T cells decreased through the course of treatment up to the 12th cycle (p=0.004). When stratified by ratio of peripheral CD8+PD1+Ki67+ T cells to tumor burden at baseline, patients with a ratio ≥0.0375 who had a significantly longer median OS of 18.37 months compared with those with a ratio &lt;0.0375 who had a median OS of 8.72 months (p=0.0099). No survival advantage was seen with stratification by tumor burden alone (p=0.24) or by CD8+PD1+Ki67+ T cells alone (p=0.53). Conclusions Pembrolizumab with carboplatin was well-tolerated and active in recurrent platinum-resistant ovarian cancer. A ratio of peripheral T-cell exhaustion to radiographic tumor burden may identify patients more likely to benefit from this chemoimmunotherapy. Trial registration number NCT03029598 .
P07.02 Robot-assisted stereotactic brain biopsy combined with cortical mapping using navigated transcranial magnetic stimulation
Authors: G E D Petrescu, R Radu, C Gorgan, A Giovani, F M Brehar, R M Gorgan
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Frame-based stereotactic biopsy has been for decades the gold-standard method for taking samples of brain tumors for the histopathological diagnostic in cases when surgery was contraindicated. However, novel frameless techniques have been developed in order to facilitate the procedure for the neurosurgeon, and for the patient as well. Preoperative cortical mapping techniques enable the planning of the trajectory with the sparing of eloquent areas. MATERIAL AND METHODS A preoperative cortical mapping using navigated transcranial magnetic stimulation was performed in the case of a 37-year-old male that presented with headache. The MRI scan revealed multiple lesions located frontal lobe and temporal lobe on the right hemisphere and frontal and occipital lobes on the left hemisphere. The results of the preoperative cortical mapping were integrated into the neuronavigation system and used for the planning of the frameless based stereotactic brain biopsy. A biopsy procedure was performed using a robotic arm according to the planned trajectory. RESULTS The targeted lesion was the right frontal one. The planned trajectory took into account the results from the cortical mapping using nTMS, and the eloquent areas were avoided. The robotic arm guided the procedure and aligned to the entry point and trajectory. According to the histopathological result the lesion was a grade II diffuse astrocytoma. There were no perioperative complications. CONCLUSION To our knowledge, this is the first report that describes the use of a robot-guided frameless brain biopsy system combined with the preoperative mapping of the eloquent cortical areas using navigated transcranial magnetic stimulation. This approach is a safe one and carries less burden for the patient as well as for the surgeon.
Gene expression ratio of deoxycytidine kinase (dCK) to cytidine deaminase (CDA) corresponds with cytotoxicity in solid tumors in vitro
Authors: Stacy Shord, Shitalben Patel
Journal: Cancer Research (2008)

116  Purpose: Gemcitabine (GEM) and paclitaxel (PAC) were commonly administered together to patients with advanced breast, lung and ovarian cancer. This combination only provided marginal benefit compared to either agent alone and appeared inferior to other combinations. However, this combination could prove beneficial in some patients if appropriately selected based on histological or molecular markers. Our preliminary data indicated PAC reduced the systemic clearance and volume of distribution of GEM in humans and the production of its metabolites in primary human cells. We investigated the sequence-dependence of this combination and the effects of PAC on the gene expression and activity of dCK and CDA, two enzymes responsible for the metabolism of GEM.  Experimental Design: Five cell lines were used in this study: adenocarcinoma, T47D:A18 (breast), A2780 (ovarian), H838 (lung); squamous cell carcinoma, H460 (lung); and large cell carcinoma, H520 (lung). The IC50 for GEM and PAC was determined in each cell line in a separate study. Cytotoxicity, by direct cell count, and flow cytometry analysis were assessed after treatment with sequential PAC→GEM and GEM→PAC. Each cell line was treated with PAC or GEM at 24 h intervals for a total drug exposure of 48 h. The type of drug interaction was assessed by the combination index (CI). The gene expression for dCK and CDA were measured using quantitative real-time PCR (TaqMan) and the activity for dCK was measured using a radiolabeled assay with and without PAC.  Results: GEM→PAC was favored compared to PAC→GEM in 4 of the 5 cell lines as demonstrated by decreased cell viability at the IC50 of GEM and PAC. Sequence dependent changes noted in flow cytometry analysis; greater G2 + M phase arrest with PAC→GEM and greater S phase arrest with GEM→PAC, as anticipated. The CI indicated: strong antagonism (T47D:A18), nearly additive (H460), synergism (H520) and high synergism (A2780, H838). PAC increased dCK activity by 30% to 70% in 4 of the 5 cell lines (A2780, H520, H460, T47D:A18). dCK and CDA mRNA levels were significantly decreased in 2 of the 5 cell lines (p=0.02, H460, H520). A ratio of dCK to CDA > 1 corresponded with synergism; a ratio = 1 corresponded with nearly additive and a ratio
Challenges and opportunities of alternative payment models for physicians/quality officers in community/academic oncology practice sites via a national prospective survey.
Authors: Aditi Kharat, Rupesh Panchal, Sabrina Ilham, Madeline Brendle, Trang Au, Ronda Copher, David Huggar, Ali McBride, Connor Willis, Diana I. Brixner
Journal: Journal of Clinical Oncology (2021)

46 Background: Alternative payment models (APMs) aim to address the rising cost of cancer care ($173 billion in 2020) by promoting high-value care. This study explored the challenges and opportunities associated with implementation of APMs in oncology practice sites across the U.S. Methods: A novel survey was created through literature review and a focus group of content experts and researchers. This survey was distributed electronically (Qualtrics) to oncology/hematology physicians (MDs) and quality officers (QOs) at U.S academic (AC) and community (CO) cancer centers from August 2020 to November 2020. Each participant reported on their center’s experience with APMs. A descriptive analysis was conducted. Results: A total of 136 sites were contacted and 28 sites (13AC/15CO) participated (21% response rate). There were 30 (67%) sites that implemented an APM, the most common was the CMS Oncology Care Models (CMS OCM) (87%, n=26), which typically took 6 months or less for implementation (66%, n=20) and was reported to improve benchmark performance (63%, n=10). The most common reasons APMs were not implemented were administrative complexity (53%, n=8); difficulty with alignment of multiple payers to APM (47%, n=7); and need for a median of 5 full-time hires. A larger number of QOs indicated participation in CMS OCM compared to MDs [94% (n=15) vs. 76% (n=11)]. The biggest difficulty experienced by MDs was adoption of innovation at site’s financial risk (43%, n=6) compared to QOs who focused on administrative and financial burden (43%, n=7). Community cancer sites were more likely to use APMs (100%, n=23) compared to AC sites (31%, n=7). The largest difficulty experienced by CO sites was adoption of innovations at their own financial risk (26%, n=6) compared to high costs, administrative burden and lack of payer engagement (29%, n=2 each) for AC sites. The most common challenge with incentives among CO sites was concerns with risk adjustment of quality measures (57%, n=13) compared to increased complexity of incentive compensation (57%, n=4) for AC sites. CO sites indicated that quality measure performance reviews were primarily conducted by administrative staff compared to clinical leaders for AC sites. Conclusions: Administrative burden and access to appropriate patient data inhibit the impact of APMs. MDs are primarily concerned about the penalties and financial risk, whereas QOs focus on administrative complexities. For CO and AC sites, the adoption and implementation of APMs to improve cost and care delivery was not without significant challenges. This study demonstrates the multifaceted impact APMs have on care delivery.
Fever, arthritis, and painful skin nodules
Authors: Yu-Pei Lin, Chi-Sheng Chiou
Journal: BMJ (2021)

A woman in her 40s presented to the emergency department with a 3 day history of fever (~39°C), bilateral swelling of the ankle joints, and multiple severely painful skin nodules on her shins (fig 1). She had applied a topical steroid to the leg lesions but this had not helped.



Fig 1 
Multiple severely painful skin nodules on the shins



For the previous five years she had recurrent oral ulcerations (more than four episodes per year) and several instances of vulval ulceration. During this time, she had tried stress relief for the oral ulcers and topical antifungal, antiviral, and steroid ointments three times a day for two weeks for the vulval lesions. However, response to these treatments was poor and the ulcerations still occurred intermittently.

On examination, the erythematous shin nodules measured 1-2 cm in diameter and were firm and severely …
P-195 Gastric adenocarcinoma classification: Association with clinicopathological features and overall survival in Moroccan patients
Authors: J. Nshizirungu, E. Van Cutsem, S. Bennis, I. Mellouki, M. Sekal, D. Benajah, N. Lahmidani, H. El Bouhaddouti, K. Majdoub, S. Ibrahimi, S. Celeiro, M. Viana-Pereira, R. Reis
Journal: Annals of Oncology (2021)