tbuckley/cabot-search huggingface dataset:
CD8-Targeted IL2 Unleashes Tumor-Specific Immunity in Human Cancer Tissue by Reviving the Dysfunctional T-cell Pool
Authors: Paulien Kaptein, Nadine Slingerland, Christina Metoikidou, Felix Prinz, Simone Brokamp, Mercedes Machuca-Ostos, Guido de Roo, Ton N.M. Schumacher, Yik A. Yeung, Kelly D. Moynihan, Ivana M. Djuretic, Daniela S. Thommen
Journal: Cancer Discovery (2024)

Abstract Tumor-specific CD8+ T cells are key effectors of antitumor immunity but are often rendered dysfunctional in the tumor microenvironment. Immune-checkpoint blockade can restore antitumor T-cell function in some patients; however, most do not respond to this therapy, often despite T-cell infiltration in their tumors. We here explored a CD8-targeted IL2 fusion molecule (CD8–IL2) to selectively reactivate intratumoral CD8+ T cells in patient-derived tumor fragments. Treatment with CD8–IL2 broadly armed intratumoral CD8+ T cells with enhanced effector capacity, thereby specifically enabling reinvigoration of the dysfunctional T-cell pool to elicit potent immune activity. Notably, the revival of dysfunctional T cells to mediate effector activity by CD8–IL2 depended on simultaneous antigen recognition and was quantitatively and qualitatively superior to that achieved by PD-1 blockade. Finally, CD8–IL2 was able to functionally reinvigorate T cells in tumors resistant to anti–PD-1, underscoring its potential as a novel treatment strategy for patients with cancer. Significance: Reinvigorating T cells is crucial for response to checkpoint blockade therapy. However, emerging evidence suggests that the PD-1/PD-L1 axis is not the sole impediment for activating T cells within tumors. Selectively targeting cytokines toward specific T-cell subsets might overcome these barriers and stimulate T cells within resistant tumors. See related article by Moynihan et al., p. 1206 (32).
LiFT (a Lithium Fiber‐Based Test): An At‐Home Companion Diagnostics for a Safer Lithium Therapy in Bipolar Disorder
Authors: Farbod Amirghasemi, Sina Khazaee Nejad, Ruitong Chen, Ali Soleimani, Victor Ong, Nika Shroff, Tanya Eftekhari, Kara Ushijima, Alar Ainla, Steven Siegel, Maral P. S. Mousavi
Journal: Advanced Healthcare Materials (2024)

Abstract This work presents LiFT (a lithium fiber‐based test), a low‐cost electrochemical sensor that can measure lithium in human saliva and urine with FDA‐required accuracy. Lithium is used for the treatment of bipolar disorder, and has a narrow therapeutic window. Close monitoring of lithium concentration in biofluids and adjustment of drug dosage can minimize the devastating side effects. LiFT is an inexpensive, yet accurate and simple‐to‐operate lithium sensor for frequent at‐home testing for early identification of lithium toxicity. The low cost and high accuracy of LiFT are enabled through an innovative design and the use of ubiquitous materials such as yarn and carbon black for fabrication. LiFT measures Li + through potentiometric recognition using a lithium selective sensing membrane that is deposited on the ink‐coated yarn. A detection limit of 0.97 µM is obtained with a sensitivity of 59.07±1.25 mV/decade for the Li + sensor in deionized water. Moreover, the sodium correction extended LiFT's linear range in urine and saliva to 0.5 mM. The LiFT platform sends the test results to the patient's smartphone, which subsequently can be shared with the patient's healthcare provider to expedite diagnosis and prevention of acute lithium toxicity.
IL2 Targeted to CD8+ T Cells Promotes Robust Effector T-cell Responses and Potent Antitumor Immunity
Authors: Kelly D. Moynihan, Manu P. Kumar, Hussein Sultan, Danielle C. Pappas, Terrence Park, S. Michael Chin, Paul Bessette, Ruth Y. Lan, Henry C. Nguyen, Nathan D. Mathewson, Irene Ni, Wei Chen, Yonghee Lee, Sindy Liao-Chan, Jessie Chen, Ton N.M. Schumacher, Robert D. Schreiber, Yik A. Yeung, Ivana M. Djuretic
Journal: Cancer Discovery (2024)

Abstract IL2 signals pleiotropically on diverse cell types, some of which contribute to therapeutic activity against tumors, whereas others drive undesired activity, such as immunosuppression or toxicity. We explored the theory that targeting of IL2 to CD8+ T cells, which are key antitumor effectors, could enhance its therapeutic index. To this aim, we developed AB248, a CD8 cis-targeted IL2 that demonstrates over 500-fold preference for CD8+ T cells over natural killer and regulatory T cells (Tregs), which may contribute to toxicity and immunosuppression, respectively. AB248 recapitulated IL2’s effects on CD8+ T cells in vitro and induced selective expansion of CD8+T cells in primates. In mice, an AB248 surrogate demonstrated superior antitumor activity and enhanced tolerability as compared with an untargeted IL2Rβγ agonist. Efficacy was associated with the expansion and phenotypic enhancement of tumor-infiltrating CD8+ T cells, including the emergence of a “better effector” population. These data support the potential utility of AB248 in clinical settings. Significance: The full potential of IL2 therapy remains to be unlocked. We demonstrate that toxicity can be decoupled from antitumor activity in preclinical models by limiting IL2 signaling to CD8+ T cells, supporting the development of CD8+ T cell–selective IL2 for the treatment of cancer. See related article by Kaptein et al. p. 1226.
An early and trustable indicator suggestive of non-tuberculosis mycobacteria isolation in a high tuberculosis burden setting
Authors: Qian Liang, Xiaoyi Jiang, Junnan Jia, Liping Zhao, Yunxu Li, Fen Wang, Lingling Dong, Yi Xue, Guanglu Jiang, Hairong Huang
Journal: Journal of Infection (2024)

BackgroundDistinguishing between non-tuberculous mycobacterial (NTM) lung infections and pulmonary tuberculosis becomes challenging due to their similar clinical manifestations and radiological images. Consequently, instances of delayed diagnosis or misdiagnosis are highly frequent. A feasible and reliable indicator of the existence of NTM in the early stages of the disease would help to solve this dilemma.MethodsIn this study, we evaluated the potential of smear-positive and Xpert assay (Cepheid, USA) negative outcomes as an early indicator of possible NTM infection in a high TB burden setting retrospectively and prospectively.ResultsDuring the study period, 12·77% (138/1081) of the smear-positive cases yielded negative outcomes with the simultaneous Xpert assay. From the 110 patients who yielded smear-positive/Xpert-negative outcomes and cultivated strain as well, 105 (95·45%) were proved to have NTM isolated. By incorporating an additional criterion of a negative result from the Interferon-gamma release assay, the accuracy of the screening method reached 100%. Regarding the NTM presence prediction value, smear-positive/Xpert-negative has a sensitivity of 24·86% (45/181) in all NTM isolated cases but 93·75%~96·55% accuracy in retrospective study or 93·75% accuracy in prospective study in smear-positive NTM isolated cases. In addition, the specificity was ~99·47% (943/948) in smear-positive tuberculosis cases.ConclusionThe clue of the presence of NTM could be obtained on the first day of the hospital visit due to the point of care (POC) feature of smear testing and Xpert assay. About one-fourth of the NTM-isolated patients would benefit from this rapid, convenient, and reliable screening strategy in the given circumstance. Smear-positive/Xpert-negative outcome is an early, trustable indicator that is indicative of NTM isolation.
A Wood‐Derived Periosteum for Spatiotemporal Drug Release: Boosting Bone Repair through Anisotropic Structure and Multiple Functions
Authors: Tianyi Sun, Chunhua Chen, Kun Liu, Lin Li, Ruixi Zhang, Wei Wen, Shan Ding, Mingxian Liu, Changren Zhou, Binghong Luo
Journal: Advanced Healthcare Materials (2024)

Abstract Existing artificial periostea face many challenges, including difficult‐to‐replicate anisotropy in mechanics and structure, poor tissue adhesion, and neglected synergistic angiogenesis and osteogenesis. Here, inspired by natural wood (NW), a wood‐derived elastic artificial periosteum is developed to mimic the structure and functions of natural periosteum, which combines an elastic wood (EW) skeleton, a polydopamine (PDA) binder layer, and layer‐by‐layer (LBL) biofunctional layers. Specifically, EW derived from NW is utilized as the anisotropic skeleton of artificial periosteum to guide cell directional behaviors, moreover, it also shows a similar elastic modulus and flexibility to natural periosteum. To further enhance its synergistic angiogenesis and osteogenesis, surface LBL biofunctional layers are designed to serve as spatiotemporal release platforms to achieve sequential and long‐term release of pamidronate disodium (PDS) and deferoxamine (DFO), which are pre‐encapsulated in chitosan (CS) and hyaluronic acid (HA) solutions, respectively. Furthermore, the combined effect of PDA coating and LBL biofunctional layers enables the periosteum to tightly adhere to damaged bone tissue. More importantly, this novel artificial periosteum can boost angiogenesis and bone formation in vitro and in vivo. This study opens up a new path for biomimetic design of artificial periosteum, and provides a feasible clinical strategy for bone repair.
Excessive Exogenous Gonadotropins and Genetic and Pregnancy Outcomes After Euploidy Embryo Transfer
Authors: Tianxiang Ni, Wei Zhou, Yingbo Liu, Weiran Cui, Yang Liu, Juanjuan Lu, Qian Zhang, Zi-Jiang Chen, Yan Li, Junhao Yan
Journal: JAMA Network Open (2024)

Importance The safety of exogenous gonadotropin treatment, based on its effect on embryos and pregnancy outcomes, remains inconclusive. Objective To evaluate the associations of different doses and durations of gonadotropins with embryonic genetic status and pregnancy outcomes after euploid embryo transfer in couples with infertility. Design, Setting, and Participants This study was a post hoc analysis of a multicenter randomized clinical trial (RCT) conducted at 14 reproductive centers throughout China from July 2017 to June 2018 that evaluated the cumulative live birth rate with or without preimplantation genetic testing for aneuploidy (PGT-A) among couples with infertility and good prognosis. The PGT-A group from the original RCT was selected for secondary analysis. Patients were divided into 4 groups according to the total dosage of exogenous gonadotropins and treatment duration: group 1 (≤1500 IU and &amp;amp;lt;10 days), group 2 (≤1500 IU and ≥10 days), group 3 (&amp;amp;gt;1500 IU and &amp;amp;lt;10 days), and group 4 (&amp;amp;gt;1 500 IU and ≥10 days). Group 1 served as the control group. Data were analyzed from June through August 2023. Interventions Blastocyst biopsy and PGT-A. Main outcomes and measures The primary outcomes were embryonic aneuploidy, embryonic mosaicism, and cumulative live birth rates after euploid embryo transfer. Results A total of 603 couples (mean [SD] age of prospective mothers, 29.13 [3.61] years) who underwent PGT-A were included, and 1809 embryos were screened using next-generation sequencing. The embryo mosaicism rate was significantly higher in groups 2 (44 of 339 embryos [13.0%]; adjusted odds ratio [aOR], 1.69 [95% CI, 1.09-2.64]), 3 (27 of 186 embryos [14.5%]; aOR, 1.98 [95% CI, 1.15-3.40]), and 4 (82 of 651 embryos [12.6%]; aOR, 1.60 [95% CI, 1.07-2.38]) than in group 1 (56 of 633 embryos [8.8%]). There were no associations between gonadotropin dosage or duration and the embryo aneuploidy rate. The cumulative live birth rate was significantly lower in groups 2 (83 of 113 couples [73.5%]; aOR, 0.49 [95% CI, 0.27-0.88]), 3 (42 of 62 couples [67.7%]; aOR, 0.41 [95% CI, 0.21-0.82]), and 4 (161 of 217 couples [74.2%]; aOR, 0.53 [95% CI, 0.31-0.89]) than in group 1 (180 of 211 couples [85.3%]). Conclusions and relevance In this study, excessive exogenous gonadotropin administration was associated with increased embryonic mosaicism and decreased cumulative live birth rate after euploid embryo transfer in couples with a good prognosis. These findings suggest that consideration should be given to minimizing exogenous gonadotropin dosage and limiting treatment duration to improve embryo outcomes and increase the live birth rate. Trial Registration ClinicalTrials.gov Identifier: NCT03118141
Pulmonary Vein Isolation With or Without Left Atrial Appendage Ligation in Atrial Fibrillation
Authors: Dhanunjaya R. Lakkireddy, David J. Wilber, Suneet Mittal, David Tschopp, Christopher R. Ellis, Abdi Rasekh, Troy Hounshell, Rudy Evonich, Sheetal Chandhok, Ronald D. Berger, Rodney Horton, Michael H. Hoskins, Hugh Calkins, Steven J. Yakubov, Pamela Simons, Benjamin R. Saville, Randall J. Lee
Journal: JAMA (2024)

Left atrial appendage elimination may improve catheter ablation outcomes for atrial fibrillation.
Automated Text Message–Based Program and Use of Acute Health Care Resources After Hospital Discharge
Authors: Eric Bressman, Judith A. Long, Robert E. Burke, Aiden Ahn, Katherine Honig, Jarcy Zee, Nancy McGlaughlin, Mohan Balachandran, David A. Asch, Anna U. Morgan
Journal: JAMA Network Open (2024)

Importance Postdischarge outreach from the primary care practice is an important component of transitional care support. The most common method of contact is via telephone call, but calls are labor intensive and therefore limited in scope. Objective To test whether a 30-day automated texting program to support primary care patients after hospital discharge reduces acute care revisits. Design, Setting, and Participants A 2-arm randomized clinical trial was conducted from March 29, 2022, through January 5, 2023, at 30 primary care practices within a single academic health system in Philadelphia, Pennsylvania. Patients were followed up for 60 days after discharge. Investigators were blinded to assignment, but patients and practice staff were not. Participants included established patients of the study practices who were aged 18 years or older, discharged from an acute care hospitalization, and considered medium to high risk for adverse health events by a health system risk score. All analyses were conducted using an intention-to-treat approach. Intervention Patients in the intervention group received automated check-in text messages from their primary care practice on a tapering schedule for 30 days following discharge. Any needs identified by the automated messaging platform were escalated to practice staff for follow-up via an electronic medical record inbox. Patients in the control group received a standard transitional care management telephone call from their practice within 2 business days of discharge. Main Outcomes and Measures The primary study outcome was any acute care revisit (readmission or emergency department visit) within 30 days of discharge. Results Of the 4736 participants, 2824 (59.6%) were female; the mean (SD) age was 65.4 (16.5) years. The mean (SD) length of index hospital stay was 5.5 (7.9) days. A total of 2352 patients were randomized to the intervention arm and 2384 were randomized to the control arm. There were 557 (23.4%) acute care revisits in the control group and 561 (23.9%) in the intervention group within 30 days of discharge (risk ratio, 1.02; 95% CI, 0.92-1.13). Among the patients in the intervention arm, 79.5% answered at least 1 message and 41.9% had at least 1 need identified. Conclusions and Relevance In this randomized clinical trial of a 30-day postdischarge automated texting program, there was no significant reduction in acute care revisits. Trial Registration ClinicalTrials.gov Identifier: NCT05245773
Mental Health Care Utilization Among Parents of Children With Cancer
Authors: Xin Hu, Scott D. Grosse, Xuesong Han, Jordan Gilleland Marchak, Xu Ji
Journal: JAMA Network Open (2024)

Importance Caring for children diagnosed with cancer may adversely affect the mental health (MH) of parents. Objective To characterize utilization of MH services among parents of children with vs without cancer using nationwide commercial claims data. Design, Setting, and Participants For this cross-sectional study, the Merative MarketScan Commercial Claims Database was used to identify continuously insured families of children treated for cancer (aged ≤21 years at diagnosis) during 2010 to 2018, compared with families who matched eligibility criteria but did not have a child with a cancer history. Parents were assessed from 18 months before to 12 months after their child’s cancer diagnosis. Analyses were conducted from February 2022 to September 2023. Exposures Children’s cancer diagnosis. Main Outcomes and Measures Outcomes included parents’ MH-related visits during the first year following their child’s cancer diagnosis. Logistic regressions compared outcomes between families of children with vs without cancer, adjusting for sociodemographic and clinical factors. Results This study included 4837 families of children with cancer (4210 mothers and 4016 fathers) and 24 185 families of children without cancer (21 444 mothers and 19 591 fathers) with continuous insurance enrollment. Most household leads were aged 35 to 54 years (3700 [76.5%] in families of children with cancer vs 17 812 [73.6%] in families of children without cancer) and resided in urban areas (4252 [87.9%] vs 21 156 [87.5%]). The probabilities of parents having anxiety-related visits (10.6% vs 7.0%), depression-related visits (8.4% vs 6.1%), and any MH-related visits (18.1% vs 13.3%) were higher in families of children with vs without cancer. Adjusted analyses showed absolute increases of 3.2 percentage points (95% CI, 2.3 to 4.0; 45.7% relative increase), 2.2 percentage points (95% CI, 1.4 to 3.0; 36.1% relative increase), and 4.2 percentage points (95% CI, 3.1 to 5.3; 31.3% relative increase) in the probabilities of 1 or both parents having anxiety-related visits, depression-related visits, and any MH-related visits, respectively, among families of children with vs without cancer. Such differences were greater in magnitude among mothers than fathers. Conclusions and Relevance In this cohort study of privately insured parents, those caring for children with cancer had a higher likelihood of utilizing MH care than other parents. These findings underline the importance of interventions toward targeted counseling and support to better meet MH care needs among parents and caregivers of children with cancer.
Health Care Delivery Innovations—Implementation Matters in Understanding What Works
Authors: Teryl K. Nuckols
Journal: JAMA Network Open (2024)

Eric Bressman, MD, MSHP; Judith A. Long, MD; Robert E. Burke, MD, MS; Aiden Ahn, BA; Katherine Honig, BA; Jarcy Zee, PhD; Nancy McGlaughlin, RN, MSN; Mohan Balachandran, MA, MS; David A. Asch, MD, MBA; Anna U. Morgan, MD, MSc, MSHP
Dietary Sodium and Blood Pressure—Reply
Authors: Deepak K. Gupta, Cora E. Lewis, Norrina B. Allen
Journal: JAMA (2024)

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 Journals 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 2024 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
Blood Pressure Self-Management After Hypertensive Pregnancy
Authors: Weixiu Li
Journal: JAMA (2024)

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 Journals 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 2024 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
Screening Recommendations and Treatments for Postpartum Depression—Reply
Authors: Tiffany A. Moore Simas, Anna Whelan, Nancy Byatt
Journal: JAMA (2024)

In Reply In reply to our review of screening and treatment for postpartum depression,1 we appreciate the comments from Dr Nitzan and colleagues highlighting skin-to-skin contact or kangaroo mother care as potential approaches for preventing and treating postpartum depression.
Blood Pressure Self-Management After Hypertensive Pregnancy—Reply
Authors: Jamie Kitt, Richard J. McManus, Paul Leeson
Journal: JAMA (2024)

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 Journals 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 2024 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