tbuckley/cabot-search huggingface dataset:
Machine learning and health need better values
Authors: Marzyeh Ghassemi, Shakir Mohamed
Journal: npj Digital Medicine (2022)

Health care is a human process that generates data from human lives, as well as the care they receive. Machine learning has worked in health to bring new technology into this sociotechnical environment, using data to support a vision of healthier living for everyone. Interdisciplinary fields of research like machine learning for health bring different values and judgements together, requiring that those value choices be deliberate and measured. More than just abstract ideas, our values are the basis upon which we choose our research topics, set up research collaborations, execute our research methodologies, make assessments of scientific and technical correctness, proceed to product development, and finally operationalize deployments and describe policy. For machine learning to achieve its aims of supporting healthier living while minimizing harm, we believe that a deeper introspection of our field's values and contentions is overdue. In this perspective, we highlight notable areas in need of attention within the field. We believe deliberate and informed introspection will lead our community to renewed opportunities for understanding disease, new partnerships with clinicians and patients, and allow us to better support people and communities to live healthier, dignified lives.
Socially assistive robots for people with dementia: Systematic review and meta-analysis of feasibility, acceptability and the effect on cognition, neuropsychiatric symptoms and quality of life
Authors: Clare Yu, Andrew Sommerlad, Lena Sakure, Gill Livingston
Journal: Ageing Research Reviews (2022)

There is increasing interest in using robots to support dementia care but little consensus on the evidence for their use. The aim of the study is to review evidence about feasibility, acceptability and clinical effectiveness of socially assistive robots used for people with dementia.We conducted a systematic review and meta-analysis. We searched MEDLINE, EMBASE, PsychINFO, CINHAL, IEEE Xplore Digital Library, and EI Engineering Village from inception to 04 - 02-2022 - included primary studies assessing feasibility, acceptability, or effectiveness of socially assistive robots for people with dementia. Two independent reviewers screened studies for eligibility, and assessed quality. Narrative synthesis prioritized higher quality studies, and random-effect meta-analyses compared robots with usual care (UC) or active control (AC) immediately after the intervention (short-term; ST) or long-term (LT) on cognition, neuropsychiatric symptoms, and quality of life.66 studies and four categories of robots were eligible: Companion robots (Pet and humanoid companion robots), telepresence communication robots, homecare assistive robots and multifunctional robots. PARO (companion robot seal) was feasible and acceptable but limited by its weight, cost, and sound. On meta-analysis, PARO had no ST or LT compared to UC or AC over 5-12 weeks on agitation (ST vs UC, 4 trials, 153 participants: pooled standardized mean difference (SMD) 0.25; - 0.57 to 0.06; LT vs UC; 2 trials, 77 participants, SMD = -0.24; - 0.94, 0.46), cognition (ST vs UC, 3 trials, 128 participants: SMD= 0.03; -0.32, 0.38), overall neuropsychiatric symptoms (ST vs UC, 3 trials, 169 participants: SMD= -0.01; -0.32, 0.29; ST vs AC, 2 trials, 145 participants: SMD =0.02, -0.71, 0.85), apathy (ST vs AC, 2 trials, 81 participants: SMD= 0.14; 0.29, 0.58), depression (ST vs UC, 4 trials, 181 participants; SMD= 0.08; -0.52, 0.69; LT vs UC: 2 trials, 77 participants: SMD =0.01; -0.75, 0.77), anxiety (ST vs UC: 2 trials, 104 participants, SMD= 0.24; -0.85, 1.33) and quality of life (ST vs UC, 2 trials, 127 participants: SMD=-0.05; -0.52, 0.42; ST vs AC: 2 trials, 159 participants, SMD =-0.36, -0.76, 0.05). Robotic animals, humanoid companion robots, telepresence robots and multifunctional robots were feasible and acceptable. However, humanoid companion robots have speech recognition problems, and telepresence robots and multifunctional robots were often difficult to use. There was mixed evidence about the feasibility of homecare robots. There was little evidence on any of these robots' effectiveness.Although robots were generally feasible and acceptable, there is no clear evidence that people with dementia derive benefit from robots for cognition, neuropsychiatric symptoms, or quality of life. We recommend that future research should use high quality designs to establish evidence of effectiveness.
Risk Assessment in Population-Based Breast Cancer Screening
Authors: Mikael Eriksson, Emily F. Conant, Despina Kontos, Per Hall
Journal: Journal of Clinical Oncology (2022)

Yala et al 1 reported on the multinational validation of the Mirai artificial intelligence-based mammographybased breast cancer risk model.The study included 62,185 screening mammograms and 3,815 incident cancers diagnosed within 5 years of study entry.Concordance indices ranged from 0.75-0.84for the 5-year risk model across seven screening sites.It was concluded that the risk tool could offer broad and equitable improvements in breast care.The authors advance the important inclusion of imagebased data to further refine existing models for the assessment of breast cancer risk.The identification of women who, after a negative screen, may benefit from supplemental screening could lead to earlier detection of breast cancers and potentially improved prognoses as previously described. 2The goal of equitable improvements in care is also essential for broad implementation.We, therefore, read this study with great interest and applaud the authors for their undertaking.However, there are several aspects of this study that require clarification.
One Cell At a Time (OCAT): a unified framework to integrate and analyze single-cell RNA-seq data
Authors: Chloe X. Wang, Lin Zhang, Bo Wang
Journal: Genome biology (2022)

Abstract Integrative analysis of large-scale single-cell RNA sequencing (scRNA-seq) datasets can aggregate complementary biological information from different datasets. However, most existing methods fail to efficiently integrate multiple large-scale scRNA-seq datasets. We propose OCAT, One Cell At a Time, a machine learning method that sparsely encodes single-cell gene expression to integrate data from multiple sources without highly variable gene selection or explicit batch effect correction. We demonstrate that OCAT efficiently integrates multiple scRNA-seq datasets and achieves the state-of-the-art performance in cell type clustering, especially in challenging scenarios of non-overlapping cell types. In addition, OCAT can efficaciously facilitate a variety of downstream analyses.
Enrollment of Black Participants in Pivotal Clinical Trials Supporting US Food and Drug Administration Approval of Chimeric Antigen Receptor–T Cell Therapy for Hematological Malignant Neoplasms
Authors: Samer Al Hadidi, Carolina Schinke, Sharmilan Thanendrarajan, Maurizio Zangari, Frits van Rhee
Journal: JAMA Network Open (2022)

Disparities that affect Black persons with various hematological malignant neoplasms are substantial, yet little is known about disparities related to the use of US Food and Drug Administration (FDA)-approved chimeric antigen receptor-T cell (CAR-T) therapy.To examine the enrollment of Black participants in clinical trials that resulted in a subsequent FDA approval of CAR-T products in hematological malignant neoplasms.A cross-sectional study was performed using publicly available data on drug products and demographic subgroups from Drugs@fda in the period of August 2017 to May 2021. Data analysis included patients with large B cell lymphoma, follicular lymphoma, mantle cell lymphoma, acute lymphoblastic leukemia, and multiple myeloma who were enrolled into 7 clinical trials that investigated various CAR-T products. The study was conducted from July 1, 2021, to November 30, 2021.Frequencies of participation of Black participants were calculated with adjustment for disease prevalence.Of the 1057 enrolled patients included in the study, CAR-T products were given to 746 patients (71%), and efficacy was reported for 729 enrolled patients (69%) across all the approved CAR-T products and indications. Most patients (1015 patients [96%]) were enrolled in the US. Black participants were included in the racial category other in the study that supported tisagenlecleucel approval in acute lymphoblastic leukemia; otherwise, their enrollment was specified either in the study publication and/or the demographic subgroup information available under the FDA product labeling information. The number of Black participants who received the CAR-T product and had reported efficacy varied between studies (range, 1-12 participants [2%-5%]). Adjusted prevalence measures showed the lowest participation to prevalence ratio of 0.2 for multiple myeloma and 0.6 for large B cell lymphoma.The findings of this study suggest that there are substantial disparities affecting Black patients across all approved CAR-T products used to treat hematological malignant neoplasms with otherwise limited effective treatment options. The study findings might aid policy discussions regarding the immediate need of regulations that enforce certain thresholds of Black patients' enrollment before granting FDA approval.
Adverse effects of COVID-19 mRNA vaccines: the spike hypothesis
Authors: Ioannis P. Trougakos, Evangelos Terpos, Harry Alexopoulos, Marianna Politou, Dimitrios Paraskevis, Andreas Scorilas, Efstathios Kastritis, Evangelos Andreakos, Meletios A. Dimopoulos
Journal: Trends in Molecular Medicine (2022)
Evaluation of the Mexican warning label nutrient profile on food products marketed in Mexico in 2016 and 2017: A cross-sectional analysis
Authors: Alejandra Contreras-Manzano, Carlos Cruz-Casarrubias, Ana Munguía, Alejandra Jáuregui, Jorge Vargas-Meza, Claudia Nieto, Lizbeth Tolentino-Mayo, Simón Barquera
Journal: PLoS Medicine (2022)

Different nutrient profiles (NPs) have been developed in Latin America to assess the nutritional quality of packaged food products. Recently, the Mexican NP was developed as part of the new warning label regulation implemented in 2020, considering 5 warning octagons (calories, sugar, sodium, saturated fats, and trans fats) and 2 warning rectangles (caffeine and non-nutritive sweeteners). The objective of this cross-sectional study was to evaluate the Mexican NP and other NPs proposed or used in Latin America against the Pan American Health Organization (PAHO) model.
Neuroinflammation associated with ultrasound-mediated permeabilization of the blood–brain barrier
Authors: Olive Jung, Alec Thomas, Scott R. Burks, Michael L. Dustin, Joseph A. Frank, Marc Ferrer, Eleanor Stride
Journal: Trends in Neurosciences (2022)

The blood-brain barrier (BBB) continues to represent one of the most significant challenges for successful drug-based treatments of neurological disease. Mechanical modulation of the BBB using focused ultrasound (FUS) and microbubbles (MBs) has shown considerable promise in enhancing the delivery of therapeutics to the brain, but questions remain regarding possible long-term effects of such forced disruption. This review examines the evidence for inflammation associated with ultrasound-induced BBB disruption and potential strategies for managing such inflammatory effects to improve both the efficacy and safety of therapeutic ultrasound in neurological applications.
Hippocampal place codes are gated by behavioral engagement
Authors: Noah L. Pettit, Xintong C. Yuan, Christopher D. Harvey
Journal: Nature Neuroscience (2022)

Abstract As animals explore an environment, the hippocampus is thought to automatically form and maintain a place code by combining sensory and self-motion signals. Instead, we observed an extensive degradation of the place code when mice voluntarily disengaged from a virtual navigation task, remarkably even as they continued to traverse the identical environment. Internal states, therefore, can strongly gate spatial maps and reorganize hippocampal activity even without sensory and self-motion changes.
Utility of the Treatment-Related Mortality (TRM) score to predict outcomes of adults with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation
Authors: Lucas C. Zarling, Megan Othus, Brenda M. Sandmaier, Filippo Milano, Gary Schoch, Chris Davis, Marie Bleakley, H. Joachim Deeg, Frederick R. Appelbaum, Rainer Storb, Roland B. Walter
Journal: Leukemia (2022)
Usefulness of 68Ga-Pentixafor PET/CT on Diagnosis and Management of Cushing Syndrome
Authors: Jie Ding, Anli Tong, Marcus Hacker, Ming Feng, Li Huo, Xiang Li
Journal: Clinical Nuclear Medicine (2022)

This pilot study investigated the performance of C-X-C motif chemokine receptor 4 (CXCR4) molecular imaging ( 68 Ga-pentixafor PET/CT) in Cushing syndrome (CS) and the correlation between CXCR4 signaling interactions and glucose metabolism in adrenocorticotropin-cortisol pathway.We retrospectively evaluated 31 patients (16 patients with CS and 15 patients with nonfunctioning pituitary or adrenal adenomas). All patients underwent 68 Ga-pentixafor PET/CT, and 11 with pituitary adenoma also underwent 18 F-FDG PET/CT. The diagnosis accuracy of 68 Ga-pentixafor PET/CT was calculated. The correlation between radiouptake along the pituitary-adrenal axis and hormone levels was calculated.Patients with Cushing disease characterized a focal uptake in adrenocorticotropic hormone-producing pituitary adenoma (ACTH-PA). In ACTH-independent CS, there was increased uptake of 68 Ga-pentixafor in adrenal lesions but not in the pituitary fossa. The nonfunctioning pituitary or adrenal adenomas showed negative 68 Ga-pentixafor signal. The one patient with metastatic ectopic ACTH syndrome had multiple 68 Ga-pentixafor-avid lesions. Using the threshold of SUV max >8.5 in the adrenal lesions, the sensitivity and specificity of 68 Ga-pentixafor PET/CT to diagnose cortisol-producing adenoma were 100% and 84.9%. A cutoff SUV max value of 3.0 on 68 Ga-pentixafor PET/CT had 100% sensitivity and specificity for differentiating ACTH-PA. The corresponding hormone level was significantly correlated with uptake of 68 Ga-pentixafor in pituitary adenoma and adrenal tissue but not with glucose metabolism.We have characterized the performance of 68 Ga-pentixafor in different subtypes of CS. 68 Ga-pentixafor PET/CT is promising in the differential diagnosis of both ACTH-independent and ACTH-dependent CS. Activated CXCR4 molecular signaling along the pituitary-adrenal axis was found in patients with Cushing disease.
Selection, Effectiveness, and Adverse Effects of Contraception
Authors: Ekaterina Skaritanov, Gianna Wilkie, Lara C. Kovell
Journal: JAMA (2022)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Tislelizumab Versus Chemotherapy as Second-Line Treatment for Advanced or Metastatic Esophageal Squamous Cell Carcinoma (RATIONALE-302): A Randomized Phase III Study
Authors: Lin Shen, Ken Kato, Sung-Bae Kim, Jaffer A. Ajani, Kuaile Zhao, Zhiyong He, Xinmin Yu, Yongqian Shu, Qi Luo, Jufeng Wang, Zhendong Chen, Zuoxing Niu, Longzhen Zhang, Tienan Yi, Jong-Mu Sun, Jianhua Chen, Guohua Yu, Chen-Yuan Lin, Hiroki Hara, Qing Bi, Taroh Satoh, Roberto Pazo-Cid, Hendrick-Tobias Arkenau, Christophe Borg, Florian Lordick, Liyun Li, Ningning Ding, Aiyang Tao, Jingwen Shi, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2022)

Patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) have poor prognosis. For these patients, treatment options are limited after first-line systemic therapy.In this open-label phase III clinical study, patients with advanced or metastatic ESCC, whose tumor progressed after first-line systemic treatment, were randomly assigned (1:1) to receive intravenous tislelizumab, an anti-programmed cell death protein 1 antibody, 200 mg every 3 weeks or chemotherapy (investigator's choice of paclitaxel, docetaxel, or irinotecan). The primary end point was overall survival (OS) in all patients. The key secondary end point was OS in patients with programmed death-ligand 1 tumor area positivity (TAP) score ≥ 10%.In total, 512 patients across 11 countries/regions were randomly assigned. At final analysis, conducted after 410 death events occurred, OS was significantly longer with tislelizumab versus chemotherapy in all patients (median, 8.6 v 6.3 months; hazard ratio [HR], 0.70 [95% CI, 0.57 to 0.85]; one-sided P = .0001), and in patients with TAP ≥ 10% (median, 10.3 months v 6.8 months; HR, 0.54 [95% CI, 0.36 to 0.79]; one-sided P = .0006). Survival benefit was consistently observed across all predefined subgroups, including those defined by baseline TAP score, region, and race. Treatment with tislelizumab was associated with higher objective response rate (20.3% v 9.8%) and a more durable antitumor response (median, 7.1 months v 4.0 months) versus chemotherapy in all patients. Fewer patients experienced ≥ grade 3 treatment-related adverse events (18.8% v 55.8%) with tislelizumab versus chemotherapy.Tislelizumab significantly improved OS compared with chemotherapy as second-line therapy in patients with advanced or metastatic ESCC, with a tolerable safety profile. Patients with programmed death-ligand 1 TAP ≥ 10% also demonstrated statistically significant survival benefit with tislelizumab versus chemotherapy.
Cyclin-dependent kinase inhibitor fadraciclib (CYC065) depletes anti-apoptotic protein and synergizes with venetoclax in primary chronic lymphocytic leukemia cells
Authors: Rong Chen, Yuling Chen, Ping Xiong, Daniella Zheleva, David Blake, Michael J. Keating, William G. Wierda, William Plunkett
Journal: Leukemia (2022)

Abstract Fadraciclib (CYC065) is a second-generation aminopurine CDK2/9 inhibitor with increased potency and selectivity toward CDK2 and CDK9 compared to seliciclib (R-roscovitine). In chronic lymphocytic leukemia (CLL), a disease that depends on the over-expression of anti-apoptotic proteins for its survival, inhibition of CDK9 by fadraciclib reduced phosphorylation of the C-terminal domain of RNA polymerase II and blocked transcription in vitro; these actions depleted the intrinsically short-lived anti-apoptotic protein Mcl-1 and induced apoptosis. While the simulated bone marrow and lymph node microenvironments induced Mcl-1 expression and protected CLL cells from apoptosis, these conditions did not prolong the turnover rate of Mcl-1, and fadraciclib efficiently abrogated the protective effect. Further, fadraciclib was synergistic with the Bcl-2 antagonist venetoclax, inducing more profound CLL cell death, especially in samples with 17p deletion. While fadraciclib, venetoclax, and the combination each had distinct kinetics of cell death induction, their activities were reversible, as no additional cell death was induced upon removal of the drugs. The best combination effects were achieved when both drugs were maintained together. Altogether, this study provides a rationale for the clinical development of fadraciclib in CLL, either alone or in combination with a Bcl-2 antagonist.
Ceramide-induced integrated stress response overcomes Bcl-2 inhibitor resistance in acute myeloid leukemia
Authors: Alexander C. Lewis, Victoria S. Pope, Melinda N. Tea, Manjun Li, Gus O. Nwosu, Thao M. Nguyen, Craig T. Wallington-Beddoe, Paul A. B. Moretti, Dovile Anderson, Darren J. Creek, Maurizio Costabile, Saira R. Ali, Chloe A. L. Thompson-Peach, B. Kate Dredge, Andrew G. Bert, Gregory J. Goodall, Paul G. Ekert, Anna L. Brown, Richard D’Andrea, Nirmal Robinson, Melissa R. Pitman, Daniel Thomas, David M. Ross, Briony L. Gliddon, Jason A. Powell, Stuart M. Pitson
Journal: Blood (2022)

Inducing cell death by the sphingolipid ceramide is a potential anticancer strategy, but the underlying mechanisms remain poorly defined. In this study, triggering an accumulation of ceramide in acute myeloid leukemia (AML) cells by inhibition of sphingosine kinase induced an apoptotic integrated stress response (ISR) through protein kinase R-mediated activation of the master transcription factor ATF4. This effect led to transcription of the BH3-only protein Noxa and degradation of the prosurvival Mcl-1 protein on which AML cells are highly dependent for survival. Targeting this novel ISR pathway, in combination with the Bcl-2 inhibitor venetoclax, synergistically killed primary AML blasts, including those with venetoclax-resistant mutations, as well as immunophenotypic leukemic stem cells, and reduced leukemic engraftment in patient-derived AML xenografts. Collectively, these findings provide mechanistic insight into the anticancer effects of ceramide and preclinical evidence for new approaches to augment Bcl-2 inhibition in the therapy of AML and other cancers with high Mcl-1 dependency.