tbuckley/cabot-search huggingface dataset:
CTNI-02. NERATINIB FOR TREATMENT OF LEPTOMENINGEAL METASTASES FROM HER2-POSITIVE BREAST CANCER IN EXTENDED ACCESS PROGRAM: PRELIMINARY RESULTS
Authors: Alessia Pellerino, Rosa Palmiero, Francesco Bruno, Erminia Muscolino, Federica Franchino, Roberta Rudà, Riccardo Soffietti
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION The aim of the study was to evaluate the activity of neratinib in LM from HER2-positive BC after the failure of multiple lines of treatment. PATIENTS AND METHODS Inclusion criteria were as follows: age ≥ 18 years; histological diagnosis of primary HER2-positive BC; newly-diagnosed LM (LANO criteria); KPS ≥ 60; coexistence of BM that have or not received radiotherapy; life expectancy ≥ 3 months; previous drugs, including capecitabine, trastuzumab, T-DM1, pertuzumab, and hormone therapy, were allowed, with the exclusion of lapatinib or other investigational agents. Neratinib was administered 240 mg daily continuously. Primary endpoint was the OS. Secondary endpoints were progression-free survival (PFS), neurological benefit, radiological response rate, and tolerability. RESULTS Nine patients with LM have been enrolled with a median age of 44 years, and a median KPS of 80. Median time since LM onset from the diagnosis of primary BC was 42 months, and patients underwent a median number of adjuvant treatments before LM of 3. Three patients developed LM alone, and other 6 had LM associated with multiple BM. Six-months and 1-year OS were 66.7% and 22.3%, respectively, with a median OS of 8 months (95%CI 3-13*). Median PFS was 3.5 months (95%CI 2-6) after the start of treatment. A neurological improvement was reported in 2/9 patients (22.2%), while in other 4/9 patients (44.5%) was achieved a neurological stabilization lasting for a median time of 5 months (95%CI 2-19). The best radiological response was a stable disease in 5/9 patients (55.6%), while no complete or partial were achieved according to LANO criteria. A CSF clearance was observed in 1 patient only (11.1%). Grade III-IV adverse events were not reported, and 2 patients only (22.2%) had mild diarrhea correlated with neratinib. CONCLUSIONS Neratinib might be a safe and effective treatment in LM from heavily pretreated HER2-positive BC.
In vivo therapeutic genome editing via CRISPR/Cas9 magnetoplexes for myocardial infarction
Authors: Hanseul Park, Dongyoon Kim, Byounggook Cho, Junho Byun, Yong Sook Kim, Youngkeun Ahn, Jin Hur, Yu-Kyoung Oh, Jongpil Kim
Journal: Biomaterials (2021)
Therapeutic advances in non‐small cell lung cancer: Focus on clinical development of targeted therapy and immunotherapy
Authors: Yuan Cheng, Tao Zhang, Qing Xu
Journal: MedComm (2021)

Lung cancer still contributes to nearly one-quarter cancer-related deaths in the past decades, despite the rapid development of targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC). The development and availability of comprehensive genomic profiling make the classification of NSCLC more precise and personalized. Most treatment decisions of advanced-stage NSCLC have been made based on the genetic features and PD-L1 expression of patients. For the past 2 years, more than 10 therapeutic strategies have been approved as first-line treatment for certain subgroups of NSCLC. However, some major challenges remain, including drug resistance and low rate of overall survival. Therefore, we discuss and review the therapeutic strategies of NSCLC, and focus on the development of targeted therapy and immunotherapy in advanced-stage NSCLC. Based on the latest guidelines, we provide an updated summary on the standard treatment for NSCLC. At last, we discussed several potential therapies for NSCLC. The development of new drugs and combination therapies both provide promising therapeutic effects on NSCLC.
LBA1 BNT211: A phase I/II trial to evaluate safety and efficacy of CLDN6 CAR-T cells and CARVac-mediated in vivo expansion in patients with CLDN6+ advanced solid tumors
Authors: J. Haanen, A. Mackensen, C. Koenecke, W. Alsdorf, A. Desuki, E. Wagner-Drouet, D. Heudobler, P. Borchmann, E. Wiegert, C. Schulz, B. Rengstl, L. Preußner, Ö. Türeci, U. Sahin
Journal: Annals of Oncology (2021)
Nicotine Pouch Unit Sales in the US From 2016 to 2020
Authors: Mary Hrywna, M. Jane Lewis, Pamela M. Ling
Journal: JAMA (2021)

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
Prediction of biochemical nonresolution in patients with chronic drug‐induced liver injury: A large multicenter study
Authors: Chun‐Yan Wang, Ya Deng, Ping Li, Sujun Zheng, Guofeng Chen, Guangde Zhou, Jing Xu, Yan‐Ping Chen, Zheng Wang, Xueyuan Jin, Jin‐Mo Tang, Kun‐Peng Hu, Jing‐Feng Bi, Ping Zhang, Chun‐Xia Li, Ang Huang, Gui‐Ji Lv, Xiao‐He Xiao, Zhengsheng Zou, Dong Ji
Journal: Hepatology (2021)

To clarify high-risk factors and develop a nomogram model to predict biochemical resolution or biochemical nonresolution (BNR) in patients with chronic DILI.
Optimized Dosing: The Next Step in Precision Medicine in Non-Small-Cell Lung Cancer
Authors: René J. Boosman, Jacobus A. Burgers, Egbert F. Smit, Neeltje Steeghs, Anthonie J. van der Wekken, Jos H. Beijnen, Alwin D. R. Huitema, Rob ter Heine
Journal: Drugs (2021)
Benefit of a Live Donor for Patients With Hepatocellular Carcinoma on the Waiting List—Reply
Authors: Quirino Lai, Gonzalo Sapisochin, Jan Paul Lerut
Journal: JAMA Surgery (2021)

In Reply We thank Zhang et al for their Letter on our article1 on the beneficial intention-to-treat effect of living donor liver transplant (LDLT) when compared with deceased donor liver transplant (DDLT) in the setting of patients with hepatocellular cancer (HCC).
Reply to W. E. Rosa et al and T. N. Townsend et al
Authors: Andrea C. Enzinger, Kaushik Ghosh, Nancy L. Keating, David M. Cutler, Mary Beth Landrum, Alexi A. Wright
Journal: Journal of Clinical Oncology (2021)

In response to our article, 1 Dr Rosa et al 2 provide a sobering reminder of the vast global inequities in opioid access.Less than 0.04% of the global prescription opioid supply is distributed to low-income countries, 3 and more than 70% of patients with cancer live in countries where opioid analgesics are almost entirely unavailable. 4These disturbing figures underpin unimaginable suffering for millions of patients in low-and middle-income countries.We share the authors' concerns that well-intended but short-sighted opioid policies could hamper efforts to provide quality palliative care globally.Rosa et al 2 cite a specific instance in which US lawmakers pressured the WHO to withdraw two opioid prescribing guidelines considered important to global pain management efforts.Although the involved lawmakers alleged improper pharmaceutical industry influence on the guidelines, we share the authors' conviction that patients with cancer in low-and middleincome countries should not be burdened by corrective actions aimed primarily at recalibrating US opioid prescribing.Similarly, US patients with cancer-particularly those with end-stage cancers-should be spared from these burdens.US opioid policy should be squarely focused on preventing and treating opioid misuse disorder and reducing opioid overdose deaths.Although the authors correctly remind us that most opioid overdose deaths are the result of illicitly trafficked synthetic opioids, prescription opioids play an important role in the development of opioid misuse disorder.Policies to minimize inappropriate opioid prescribing are clearly vital to combatting the ongoing US opioid epidemic.It is less clear how policies can be crafted to have this effect while simultaneously protecting opioid access for patients with greatest need-whether at home or abroad.
The importance of saturating density dependence for population-level predictions of SARS-CoV-2 resurgence compared with density-independent or linearly density-dependent models, England, 23 March to 31 July 2020
Authors: Emily S Nightingale, Oliver J Brady, Laith Yakob
Journal: Eurosurveillance (2021)

BackgroundPopulation-level mathematical models of outbreaks typically assume that disease transmission is not impacted by population density ('frequency-dependent') or that it increases linearly with density ('density-dependent').AimWe sought evidence for the role of population density in SARS-CoV-2 transmission.MethodsUsing COVID-19-associated mortality data from England, we fitted multiple functional forms linking density with transmission. We projected forwards beyond lockdown to ascertain the consequences of different functional forms on infection resurgence.ResultsCOVID-19-associated mortality data from England show evidence of increasing with population density until a saturating level, after adjusting for local age distribution, deprivation, proportion of ethnic minority population and proportion of key workers among the working population. Projections from a mathematical model that accounts for this observation deviate markedly from the current status quo for SARS-CoV-2 models which either assume linearity between density and transmission (30% of models) or no relationship at all (70%). Respectively, these classical model structures over- and underestimate the delay in infection resurgence following the release of lockdown.ConclusionIdentifying saturation points for given populations and including transmission terms that account for this feature will improve model accuracy and utility for the current and future pandemics.
Lifestyle Modification Is Appropriate as Primary Prevention—Reply
Authors: Romit Bhattacharya, Pradeep Natarajan
Journal: JAMA Cardiology (2021)

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 Cardiology 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 Cardiology journal
Bacteria and bacterial derivatives as delivery carriers for immunotherapy
Authors: Sae-Ryung Kang, Dinh-Huy Nguyen, Su Woong Yoo, Jung-Joon Min
Journal: Advanced Drug Delivery Reviews (2021)

There is growing interest in the role of microorganisms in human health and disease, with evidence showing that new types of biotherapy using engineered bacterial therapeutics, including bacterial derivatives, can address specific mechanisms of disease. The complex interactions between microorganisms and metabolic/immunologic pathways underlie many diseases with unmet medical needs, suggesting that targeting these interactions may improve patient treatment. Using tools from synthetic biology and chemical engineering, non-pathogenic bacteria or bacterial products can be programmed and designed to sense and respond to environmental signals to deliver therapeutic effectors. This review describes current progress in biotherapy using live bacteria and their derivatives to achieve therapeutic benefits against various diseases.
Feasibility of conservative fluid administration and deresuscitation compared with usual care in critical illness: the Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) randomised clinical trial
Authors: Jonathan A. Silversides, Ross McMullan, Lydia M. Emerson, Ian Bradbury, Jonathan Bannard-Smith, Tamas Szakmany, John Trinder, Anthony J. Rostron, Paul Johnston, Andrew J. Ferguson, Andrew J. Boyle, Bronagh Blackwood, John C. Marshall, Daniel F. McAuley
Journal: Intensive Care Medicine (2021)
Treatment Outcomes Associated With Dupilumab Use in Patients With Atopic Dermatitis
Authors: Bruce Strober, Usha G. Mallya, Min Yang, Sohini Ganguli, Abhijit Gadkari, Jessie Wang, Debra Sierka, Dimittri Delevry, Alexa B. Kimball
Journal: JAMA Dermatology (2021)

Clinical trial populations may not reflect clinical practice: knowledge generated in other settings can inform clinical decision-making.To evaluate self-reported disease control and quality of life after initiating dupilumab treatment in patients with atopic dermatitis (AD) in the the clinical setting.This cohort study using an online survey administered prior to (baseline) and at 1, 2, 3, 6, 9, and 12 months after dupilumab initiation included adults with moderate-to-severe AD who initiated treatment with dupilumab through the US patient support program and agreed to participate in the study. Data were collected between January 2018 and January 2020 and the analysis was completed in May 2020.Clinically driven treatment with dupilumab.Disease control measured by the Atopic Dermatitis Control Tool (ADCT); concomitant AD therapies; satisfaction with therapy; skin symptoms (skin pain/soreness, hot/burning feeling, sensitivity to touch) assessed using numerical rating scales; flares; health-related quality of life assessed using the Dermatology Life Quality Index; sleep problems assessed using the ADCT item and a stand-alone question; and the AD-specific Work Productivity and Activity Impairment Questionnaire.Of 699 patients who initiated dupilumab (431 [61.7%] female, 515 [73.7%] White), 632 and 483 completed the survey at months 1 and 12, respectively. As-observed results showed that most patients achieved adequate disease control (ADCT total score) at month 1 with further improvement at month 12 (385 of 632 patients [60.9%] and 374 of 483 [77.4%] for the 2 time points, respectively, vs 41 of 699 [5.3%] at baseline; both P < .001). Use of other AD therapies was reduced at each follow-up vs baseline, including topical and systemic corticosteroids, which were reduced at month 12 to 40.4% (195 of 483 patients) and 6.2% (30 of 483 patients), respectively, from 68.1% (476 of 699) and 34.9% (244 of 699), respectively, at baseline (both P < .001 vs baseline). Patient satisfaction with AD treatment was higher than baseline (120 of 699 [17.7%]) at each follow-up to 85.1% (411 of 483) at month 12 (P < .001). At each follow-up, patients reported reductions in flares, itch, skin symptoms, and improved sleep, health-related quality of life, and daily activities vs baseline. Results were consistent based on observed data and imputed data using pattern mixture models for missing data.Consistent with patient-reported outcomes in clinical trials, this cohort study found that dupilumab treatment was associated with rapid and sustained disease control for up to 12 months as demonstrated by statistically significant improvements relative to baseline on all patient-reported outcomes including treatment satisfaction.
Long-Term Exposure to Low-Level NO2 and Mortality among the Elderly Population in the Southeastern United States
Authors: Yaoyao Qian, Haomin Li, Andrew Rosenberg, Qiulun Li, Jeremy Sarnat, Stefania Papatheodorou, Joel Schwartz, Donghai Liang, Yang Liu, Pengfei Liu, Liuhua Shi
Journal: Environmental Health Perspectives (2021)

Background: Mounting evidence has shown that long-term exposure to fine particulate matter [PM ≤2.5μm in aerodynamic diameter (PM2.5)] and ozone (O3) can increase mortality. However, the health effects associated with long-term exposure to nitrogen dioxide (NO2) are less clear, in particular the evidence is scarce for NO2 at low levels that are below the current international guidelines. Methods: We constructed a population-based full cohort comprising all Medicare beneficiaries (aged ≥65, N=13,590,387) in the southeastern United States from 2000 to 2016, and we then further defined the below-guideline cohort that included only those who were always exposed to low-level NO2, that is, with annual means below the current World Health Organization guidelines (i.e., ≤21 ppb). We applied previously estimated spatially and temporally resolved NO2 concentrations and assigned annual means to study participants based on their ZIP code of residence. Cox proportional hazards models were used to examine the association between long-term exposure to low-level NO2 and all-cause mortality, adjusting for potential confounders. Results: About 71.1% of the Medicare beneficiaries in the southeastern United States were always exposed to low-level NO2 over the study period. We observed an association between long-term exposure to low-level NO2 and all-cause mortality, with a hazard ratio (HR)= 1.042 (95% CI: 1.040, 1.045) in single-pollutant models and a HR= 1.047 (95% CI: 1.045, 1.049) in multipollutant models (adjusting for PM2.5 and O3), per 10-ppb increase in annual NO2 concentrations. The penalized spline indicates a linear exposure–response relationship across the entire NO2 exposure range. Medicare enrollees who were White, female, and residing in urban areas were more vulnerable to long-term NO2 exposure. Conclusion: Using a large and representative cohort, we provide epidemiological evidence that long-term exposure to NO2, even below the national and global ambient air quality guidelines, was approximately linearly associated with a higher risk of mortality among older adults, independent of PM2.5 and O3 exposure. Improving air quality by reducing NO2 emissions, therefore, may yield significant health benefits. https://doi.org/10.1289/EHP9044
The enhancing effect and promoting mechanisms of the stereoisomeric monoterpene alcohol esters as enhancers for drugs with different physicochemical properties
Authors: Heping Wang, Yan Li, Chunyan Wang, Jing Wang, Bo Ren, Xiaona Li, Mingzhu Li, Dandan Geng, Chensi Wu, Ligang Zhao
Journal: Asian Journal of Pharmaceutical Sciences (2021)

To explore the structure-activity connections of amphiphilic permeation enhancers containing the length of the hydrophobic chains as well as the properties of the polar head, O-acylgeraniol and O-acylnerol derivatives were synthesized from geraniol/nerol (cis-isomer of geraniol) and pharmaceutical excipient acids in this research. Their promotion of the percutaneous absorption of three drugs as the model, flurbiprofen (FP), isosorbide dinitrate (ISDN) and donepezil (DNP), which were selected based on their physicochemical properties, was tested by in vitro skin penetration and in vivo. Molecular simulation, ATR-FTIR, CLSM and histological observation were implement to evaluate the mode of action of the enhancers. The results indicated that (E)-3,7-dimethyl-2,6-octadien-1-yl tetradecanoate (GER-C14, trans-) achieved the highest enhancement ability for the three drugs; additionally, the in vivo results obtained were in good correlation with the in vitro data. Molecular docking results suggested that enhancers loosen the hydrogen bonds between ceramides, and the results of molecular simulation indicated that GER-C14, NER-C14 could insert into the middle of the lipid bilayer to form an independent phase. According to ATR-FTIR and histological evaluation, the enhancers extracted lipids and influenced the protein region, thereby disturbing the skin array. In addition, CLSM described the dynamic effects of enhancers on lipids between stratum corneum (SC) cells. In conclusion, GER-C14 had a better penetration promotion effect, which broadened our understanding of stereoisomeric penetration enhancers.
Endothelial cell-derived angiopoietin-like protein 2 supports hematopoietic stem cell activities in bone marrow niches
Authors: Zhuo Yu, Wenqian Yang, Xiaoxiao He, Chiqi Chen, Wenrui Li, Limin Zhao, Ligen Liu, Junling Liu, Li Xie, Yaping Zhang, Junke Zheng
Journal: Blood (2021)

Bone marrow niche cells have been reported to fine-tune hematopoietic stem cell (HSC) stemness via direct interaction or secreted components. Nevertheless, how niche cells control HSC activities remains largely unknown. We previously showed that angiopoietin-like protein 2 (ANGPTL2) can support the ex vivo expansion of HSCs by binding to human leukocyte immunoglobulin-like receptor B2. However, how ANGPTL2 from specific niche cell types regulates HSC activities under physiological conditions is still not clear. Herein, we generated an Angptl2-flox/flox transgenic mouse line and conditionally deleted Angptl2 expression in several niche cells, including Cdh5+ or Tie2+ endothelial cells, Prx1+ mesenchymal stem cells, and Pf4+ megakaryocytes, to evaluate its role in the regulation of HSC fate. Interestingly, we demonstrated that only endothelial cell-derived ANGPTL2 and not ANGPTL2 from other niche cell types plays important roles in supporting repopulation capacity, quiescent status, and niche localization. Mechanistically, ANGPTL2 enhances peroxisome-proliferator-activated receptor D (PPARD) expression to transactivate G0s2 to sustain the perinuclear localization of nucleolin to prevent HSCs from entering the cell cycle. These findings reveal that endothelial cell-derived ANGPTL2 serves as a critical niche component to maintain HSC stemness, which may benefit the understanding of stem cell biology in bone marrow niches and the development of a unique strategy for the ex vivo expansion of HSCs.
Targeting regulated cell death in tumor nanomedicines
Authors: Qinghu Zeng, Xiangyi Ma, Yangmeihui Song, Qiqing Chen, Qiuling Jiao, Liqiang Zhou
Journal: Theranostics (2021)

Nanomedicines hold great potential in anticancer therapy by modulating the biodistribution of nanomaterials and initiating targeted oxidative stress damage, but they are also limited by the inherent self-protection mechanism and the evolutionary treatment resistance of cancer cells. New emerging explorations of regulated cell death (RCD), including processes related to autophagy, ferroptosis, pyroptosis, and necroptosis, substantially contribute to the augmented therapeutic efficiency of tumors by increasing the sensitivity of cancer cells to apoptosis. Herein, paradigmatic studies of RCD-mediated synergistic tumor nanotherapeutics are introduced, such as regulating autophagy-enhanced photodynamic therapy (PDT), targeting ferroptosis-sensitized sonodynamic therapy (SDT), inducing necroptosis-augmented photothermal therapy (PTT), and initiating pyroptosis-collaborative chemodynamic therapy (CDT), and the coordination mechanisms are discussed in detail. Multiangle analyses addressing the present challenges and upcoming prospects of RCD-based nanomedicines have also been highlighted and prospected for their further strengthening and the broadening of their application scope. It is believed that up-and-coming coadjutant therapeutic methodologies based on RCDs will considerably impact precision nanomedicine for cancer.