tbuckley/cabot-search huggingface dataset:
Effects of a Mindfulness-Based Intervention versus Health Self-Management on Subclinical Anxiety in Older Adults with Subjective Cognitive Decline: The SCD-Well Randomized Superiority Trial
Authors: Natalie L. Marchant, Thorsten Barnhofer, Roxane Coueron, Miranka Wirth, Antoine Lutz, Eider M. Arenaza-Urquijo, Fabienne Collette, Géraldine Poisnel, Harriet Demnitz-King, Ann-Katrin Schild, Nina Coll-Padros, Floriane Delphin-Combe, Tim Whitfield, Marco Schlosser, Julie Gonneaud, Julien Asselineau, Zuzana Walker, Pierre Krolak-Salmon, José Luis Molinuevo, Eric Frison, Gael Chételat, Frank Jessen, Olga M. Klimecki
Journal: Psychotherapy and Psychosomatics (2021)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Older adults experiencing subjective cognitive decline (SCD) have a heightened risk of developing dementia and frequently experience subclinical anxiety, which is itself associated with dementia risk. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To understand whether subclinical anxiety symptoms in SCD can be reduced through behavioral interventions. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; SCD-Well is a randomized controlled trial designed to determine whether an 8-week mindfulness-based intervention (caring mindfulness-based approach for seniors; CMBAS) is superior to a structurally matched health self-management program (HSMP) in reducing subclinical anxiety. Participants were recruited from memory clinics at 4 European sites. The primary outcome was change in anxiety symptoms (trait subscale of the State-Trait Anxiety Inventory; trait-STAI) from pre- to postintervention. Secondary outcomes included a change in state anxiety and depression symptoms postintervention and 6 months postrandomization (follow-up). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; One hundred forty-seven participants (mean [SD] age: 72.7 [6.9] years; 64.6% women; CMBAS, &lt;i&gt;n&lt;/i&gt; = 73; HSMP, &lt;i&gt;n&lt;/i&gt; = 74) were included in the intention-to-treat analysis. There was no difference in trait-STAI between groups postintervention (adjusted change difference: –1.25 points; 95% CI –4.76 to 2.25) or at follow-up (adjusted change difference: –0.43 points; 95% CI –2.92 to 2.07). Trait-STAI decreased postintervention in both groups (CMBAS: –3.43 points; 95% CI –5.27 to –1.59; HSMP: –2.29 points; 95% CI –4.14 to –0.44) and reductions were maintained at follow-up. No between-group differences were observed for change in state anxiety or depression symptoms. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; A time-limited mindfulness intervention is not superior to health self-management in reducing subclinical anxiety symptoms in SCD. The sustained reduction observed across both groups suggests that subclinical anxiety symptoms in SCD are modifiable. &lt;b&gt;&lt;i&gt;ClinicalTrials.gov identifier:&lt;/i&gt;&lt;/b&gt; NCT03005652.
Abstract PO-070: Boost tumor response to radiation therapy: What can we learn from PTEN-deficient models?
Authors: Xinyi Fan, Miaoyan Qiu, Silvia C. Formenti, Wen H. Shen
Journal: Clinical Cancer Research (2021)

Abstract PTEN is among the most frequently mutated genes in nearly all types of cancer. TCGA studies reported mutation or deletion of the PTEN gene in 11% of breast invasive carcinoma and 9% of colorectal adenocarcinoma. Cancer-associated PTEN deficiency is associated with worse prognosis as well as tumor resistance to therapies, including chemotherapy and immunotherapy. However, it is largely controversial, as there is no consensus regarding how PTEN deficiency alters tumor response to radiation therapy (RT). RT elicits anti-cancer efficacy through both cell-autonomous and non-cell-autonomous mechanisms by disrupting the cancer genome and by promoting immune responses. Similarly, loss of PTEN results in genomic instability and immune deregulation, which may lead to a tumor-specific net outcome of growth and response to RT. In order to characterize a pan-cancer phenotype of RT sensitivity, we created multiple isogenic pairs of tumor cells of different tissue origins. Our studies, using both a breast cancer model and a colon cancer model, demonstrate that PTEN deficiency confers an enhanced RT efficacy through a non-cell autonomous mechanism. Specifically, orthotopically implanted tumors lacking PTEN regressed significantly following single-dose RT that was less effective in suppressing PTEN-proficient tumors. A more efficient regimen (3*8Gy) became ablative and achieved 100% tumor-free survival only in the hosts of PTEN-deficient tumors. The RT sensitivity manifested in PTEN-mutant tumors in vivo is likely due to enhanced immunogenicity, because in vitro, PTEN-deficient cancer cells not only lost such vulnerability but often exhibited RT resistance. Our data suggest that PTEN-deficient tumor phenotypes may be exploited to achieve the highest cancer elimination rate, using a combinatorial strategy to promote non-cell-autonomous immunogenicity and to concurrently overcome cell-autonomous RT resistance. Citation Format: Xinyi Fan, Miaoyan Qiu, Silvia C. Formenti, Wen H. Shen. Boost tumor response to radiation therapy: What can we learn from PTEN-deficient models? [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-070.
Co-opting regulation bypass repair as a gene-correction strategy for monogenic diseases
Authors: Jingjie Hu, Rebecca A. Bourne, Barbara C. McGrath, Alice Lin, Zifei Pei, Douglas R. Cavener
Journal: Molecular Therapy (2021)

With the development of CRISPR-Cas9-mediated gene-editing technologies, correction of disease-causing mutations has become possible. However, current gene-correction strategies preclude mutation repair in post-mitotic cells of human tissues, and a unique repair strategy must be designed and tested for each and every mutation that may occur in a gene. We have developed a novel gene-correction strategy, co-opting regulation bypass repair (CRBR), which can repair a spectrum of mutations in mitotic or post-mitotic cells and tissues. CRBR utilizes the non-homologous end joining (NHEJ) pathway to insert a coding sequence (CDS) and transcription/translation terminators targeted upstream of any CDS mutation and downstream of the transcriptional promoter. CRBR results in simultaneous co-option of the endogenous regulatory region and bypass of the genetic defect. We validated the CRBR strategy for human gene therapy by rescuing a mouse model of Wolcott-Rallison syndrome (WRS) with permanent neonatal diabetes caused by either a large deletion or a nonsense mutation in the PERK (EIF2AK3) gene. Additionally, we integrated a CRBR GFP-terminator cassette downstream of the human insulin promoter in cadaver pancreatic islets of Langerhans, which resulted in insulin promoter regulated expression of GFP, demonstrating the potential utility of CRBR in human tissue gene repair. With the development of CRISPR-Cas9-mediated gene-editing technologies, correction of disease-causing mutations has become possible. However, current gene-correction strategies preclude mutation repair in post-mitotic cells of human tissues, and a unique repair strategy must be designed and tested for each and every mutation that may occur in a gene. We have developed a novel gene-correction strategy, co-opting regulation bypass repair (CRBR), which can repair a spectrum of mutations in mitotic or post-mitotic cells and tissues. CRBR utilizes the non-homologous end joining (NHEJ) pathway to insert a coding sequence (CDS) and transcription/translation terminators targeted upstream of any CDS mutation and downstream of the transcriptional promoter. CRBR results in simultaneous co-option of the endogenous regulatory region and bypass of the genetic defect. We validated the CRBR strategy for human gene therapy by rescuing a mouse model of Wolcott-Rallison syndrome (WRS) with permanent neonatal diabetes caused by either a large deletion or a nonsense mutation in the PERK (EIF2AK3) gene. Additionally, we integrated a CRBR GFP-terminator cassette downstream of the human insulin promoter in cadaver pancreatic islets of Langerhans, which resulted in insulin promoter regulated expression of GFP, demonstrating the potential utility of CRBR in human tissue gene repair.
Abstract 16590: Does Use of Intra-Aortic Balloon Pump Improves Outcome in Patients Admitted With Acute Coronary Syndrome and Cardiogenic Shock: An Nationwide Inpatient Sample Analysis
Authors: Neel Patel, Dhrubajyoti Bandyopadhyay, sandipan chakraborty, Birendra Amgai, Adrija Hajra, Zeel Patel, Soniya Koirala, Wilbert S Aronow, Ahmed Bakhit, mazin Khalid
Journal: Circulation (2020)

Introduction: Intra-aortic balloon pump (IABP) has been shown to have a neutral effect on patients having cardiogenic shock (CS) in acute coronary syndrome (ACS). However, subgroup analysis of certain studies has shown a beneficial effect of IABP on selected populations presenting with CS. Hypothesis: IABP is associated with improved survival and less in-hospital complications in patients with ACS and CS. Methods: Nationwide Inpatient Sample 2016 and 2017 had been retrospectively analyzed to identify all patients presenting with ACS and CS (n=79260) with appropriate ICD-10-CM codes. Patients with cardiac arrest, tamponade or pulmonary embolism, free wall rupture, ventricular septal defect, severe peripheral artery disease, aortic regurgitation, age greater than 90 or less than 18 have been excluded (n=14055) to include a final population of 65,180. Among them, IABP was used in 22,725 patients. Propensity score matching using the kernel method was used to generate an adjusted odds ratio (OR). Multiple imputations are used to generate missing variables. Results: 34% of patients presenting with CS required IABP in our analysis. Patients requiring IABP are younger and more likely to be male. Patients requiring IABP have higher prevalence of hypertension, obesity, dyslipidemia, and CAD. On propensity-matched analysis, the risk of all-cause in-hospital mortality is similar between two groups regardless of IABP use (p = 0.18). IABP appears to be protective for acute kidney injury (AKI) in non-propensity matched analysis (p = 0.007). There is a higher incidence of mechanical ventilation, bleeding, blood transfusion, coronary artery dissection, hemodialysis requirement, and respiratory failure in the IABP cohort. IABP appears to be protective for complete heart block (CHB) (p = 0.016). Conclusion: IABP use is associated with increased in-hospital complications without any mortality benefit. There appears to be some benefit towards the prevention of AKI and CHB.
Leave no one behind: ensuring access to COVID-19 vaccines for refugee and displaced populations
Authors: Monette Zard, Ling San Lau, Diana M. Bowser, Fouad M. Fouad, Diego I. Lucumí, Goleen Samari, Arturo Harker, Donald S. Shepard, Wu Zeng, Rachel T. Moresky, Mhd Nour Audi, Claire M. Greene, S. Patrick Kachur
Journal: Nature Medicine (2021)
Global environmental change and planetary health in the curriculum of undergraduate health professionals in Latin America: a review
Authors: Yasna Palmeiro-Silva, Maria Teresa Ferrada, Ignacio Silva, Jorge Ramirez
Journal: The Lancet Planetary Health (2021)

BackgroundPeople living in Latin America are already affected by global environmental changes and several health inequities, increasing the risk of poor health. Health professionals have a key role in tackling these threats and their consequences by providing direct care and advocating for public health policies. Hence, health professionals should be taught about global environmental changes, climate change, and policy advocacy, which could be included under the planetary health frame. Unfortunately, whether these ideals have been included in the undergraduate curriculum in Latin American universities is unclear. We aimed to analyse the incorporation of courses on climate change, environmental health, and planetary health in the curriculum of undergraduate health professionals in Latin America.MethodsIn this review, we did a documentary analysis of the curriculum of undergraduate health professional programmes that had been published on each university website. We selected the ten best Latin American universities for each country according to the QS Latin American University 2020, Times Higher Education World University 2020, and Academic Ranking of World Universities 2019 rankings. Between April 6 and May 5, 2020, we reviewed the curriculum of the nursing, medicine, nutrition, and psychology courses at these universities, looking for the phrases "climate change", "environmental health", and "planetary health" in the names of the courses offered.FindingsWe included 161 universities and reviewed 392 courses. We identified 276 (70%) courses that incorporated public health or epidemiology, or both; however, only 118 (30%) courses covered environmental health, and only two (1%) courses were on climate change. None of the universities included in our review offered a planetary health course.InterpretationOur findings imply that new Latin American health professionals are receiving insufficient training on environmental matters, which comprise roughly 25% of the global burden of disease. As we enter the Anthropocene epoch and rapid global environmental changes, health professionals need to be aware of the challenges and actively involved in the responses to protect the population and the environment. The planetary health approach facilitates this awareness and preparation. Planetary health education includes concepts regarding the holistic association between global environmental changes, natural systems, human health, and sustainability, among others, encompassing a broader perspective than just environmental healthFundingNone.
Relationship between TNFa and iron metabolism in differentiating human monocytic THP-1 cells
Authors: A. Scaccabarozzi, P. Arosio, G. Weiss, L. Valenti, P. Dongiovanni, A. L. Fracanzani, M. Mattioli, S. Levi, G. Fiorelli, S. Fargion
Journal: Blood (2000)
Functional identification of the terpene synthase family involved in diterpenoid alkaloids biosynthesis in Aconitum carmichaelii
Authors: Liuying Mao, Baolong Jin, Lingli Chen, Mei Tian, Rui Ma, Biwei Yin, Haiyan Zhang, Juan Guo, Jinfu Tang, Tong Chen, Changjiangsheng Lai, Guanghong Cui, Luqi Huang
Journal: Acta Pharmaceutica Sinica B (2021)

Aconitum carmichaelii is a high-value medicinal herb widely used across China, Japan, and other Asian countries. Aconitine-type diterpene alkaloids (DAs) are the characteristic compounds in Aconitum. Although six transcriptomes, based on short-read next generation sequencing technology, have been reported from the Aconitum species, the terpene synthase (TPS) corresponding to DAs biosynthesis remains unidentified. We apply a combination of Pacbio isoform sequencing and RNA sequencing to provide a comprehensive view of the A. carmichaelii transcriptome. Nineteen TPSs and five alternative splicing isoforms belonging to TPS-b, TPS-c, and TPS-e/f subfamilies were identified. In vitro enzyme reaction analysis functional identified two sesqui-TPSs and twelve diTPSs. Seven of the TPS-c subfamily genes reacted with GGPP to produce the intermediate ent-copalyl diphosphate. Five AcKSLs separately reacted with ent-CPP to produce ent-kaurene, ent-atiserene, and ent-13-epi-sandaracopimaradie: a new diterpene found in Aconitum. AcTPSs gene expression in conjunction DAs content analysis in different tissues validated that ent-CPP is the sole precursor to all DAs biosynthesis, with AcKSL1, AcKSL2s and AcKSL3-1 responsible for C20 atisine and napelline type DAs biosynthesis, respectively. These data clarified the molecular basis for the C20-DAs biosynthetic pathway in A. carmichaelii and pave the way for further exploration of C19-DAs biosynthesis in the Aconitum species.
Covid-19: EU investigates four reports of blood clots after Janssen vaccine
Authors: Elisabeth Mahase
Journal: BMJ (2021)

The European Medicines Agency is investigating four reported cases of unusual blood clots with low platelets in people who have received the Janssen (Johnson & Johnson) covid-19 vaccine.Three cases have been reported during the vaccine rollout in the US, while one case occurred in a clinical trial.One case was fatal.The EMA and the UK Medicines and Healthcare Products Regulatory Agency has investigated similar cases in people who had received the Oxford University-AstraZeneca vaccine.No link has been found between this vaccine and the blood clot cases, with the EMA concluding that they were a "possible" side effect but "extremely rare."The EMA and MHRA said that no restrictions were needed in relation to the vaccine's rollout and that its benefits outweighed the risks. 1 Like the AstraZeneca vaccine, the Janssen vaccine uses a viral vector platform.In Janssen's case researchers used adenovirus type 26, the same as used in Russia's Gamaleya Research Institute vaccine.In its latest announcement the EMA's Pharmacovigilance Risk Assessment Committee said, "These reports point to a 'safety signal,' but it is currently not clear whether there is a causal association between vaccination with [Janssen's vaccine] and these conditions." 2 While rollout of the vaccine has not yet started in the EU, it was expected to begin in the next few weeks.The EMA's committee said it would decide whether regulatory action was needed once evaluation had concluded but said this "usually consists of an update to the product information."1
The Global Extent of Undetected Glaucoma in Adults
Authors: Zhi Soh, Marco Yu, Bjorn Kaijun Betzler, Shivani Majithia, Sahil Thakur, Yih Chung Tham, Tien Yin Wong, Tin Aung, David S. Friedman, Ching-Yu Cheng
Journal: Ophthalmology (2021)
Alzheimerの危険因子年齢,APOE遺伝子型および性は異なる分子経路を駆動する【JST・京大機械翻訳】
Authors: Zhao Na, Ren Yingxue, Yamazaki Yu, Qiao Wenhui, Li Fuyao, M Felton Lindsey, Mahmoudiandehkordi Siamak, Kueider-Paisley Alexandra, Sonoustoun Berkiye, Arnold Matthias, Shue Francis, Zheng Jiaying, N Attrebi Olivia, A Martens Yuka, Li Zonghua, Bastea Ligia, D Meneses Axel, Chen Kai, Thompson J. Will, St John-Williams Lisa, Tachibana Masaya, Aikawa Tomonori, Oue Hiroshi, Job Lucy, Yamazaki Akari, Liu Chia-Chen, Storz Peter, W Asmann Yan, Ertekin-Taner Niluefer, Kanekiyo Takahisa, Kaddurah-Daouk Rima, Bu Guojun
Journal: Neuron (2020)
AAV9-mediated FIG4 delivery prolongs life span in Charcot-Marie-Tooth disease type 4J mouse model
Authors: Maximiliano Presa, Rachel M. Bailey, Crystal Davis, Tara Murphy, Jenn Cook, Randy Walls, Hannah Wilpan, Laurent Bogdanik, Guy M. Lenk, Robert W. Burgess, Steven J. Gray, Cathleen Lutz
Journal: Journal of Clinical Investigation (2021)

Charcot-Marie-Tooth disease type 4J (CMT4J) is caused by recessive, loss-of-function mutations in FIG4, encoding a phosphoinositol(3,5)P2-phosphatase. CMT4J patients have both neuron loss and demyelination in the peripheral nervous system, with vacuolization indicative of endosome/lysosome trafficking defects. Although the disease is highly variable, the onset is often in childhood and FIG4 mutations can dramatically shorten life span. There is currently no treatment for CMT4J. Here, we present the results of preclinical studies testing a gene-therapy approach to restoring FIG4 expression. A mouse model of CMT4J, the Fig4–pale tremor (plt) allele, was dosed with a single-stranded adeno-associated virus serotype 9 (AAV9) to deliver a codon-optimized human FIG4 sequence. Untreated, Fig4plt/plt mice have a median survival of approximately 5 weeks. When treated with the AAV9-FIG4 vector at P1 or P4, mice survived at least 1 year, with largely normal gross motor performance and little sign of neuropathy by neurophysiological or histopathological evaluation. When mice were treated at P7 or P11, life span was still significantly prolonged and peripheral nerve function was improved, but rescue was less complete. No unanticipated adverse effects were observed. Therefore, AAV9-mediated delivery of FIG4 is a well-tolerated and efficacious strategy in a mouse model of CMT4J.
Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer 2 Fertility preservation for male patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group
Authors: Renee L. Mulder, Anna Font-Gonzalez, D.M. Green, E.A.H. Loeffen, M.M. Hudson, J.J. Loonen, L.B. Kenney, M.D. van de Wetering
Journal: The Lancet Oncology (2021)
SMARCA4 and Other SWItch/Sucrose NonFermentable Family Genomic Alterations in NSCLC: Clinicopathologic Characteristics and Outcomes to Immune Checkpoint Inhibition
Authors: Joao V. Alessi, Biagio Ricciuti, Liam F. Spurr, Hersh Gupta, Yvonne Y. Li, Carolyn Glass, Mizuki Nishino, Andrew D. Cherniack, James Lindsay, Bijaya Sharma, Kristen D. Felt, Scott J. Rodig, Michael L. Cheng, Lynette M. Sholl, Mark M. Awad
Journal: Journal of Thoracic Oncology (2021)
Abstract IA-013: Integrating radiation therapy with immunotherapy
Authors: Marka Crittenden
Journal: Clinical Cancer Research (2021)

Abstract We have shown that when studied in isolation, radiation therapy functions poorly as an endogenous vaccine, and that many of the promising therapeutic approaches of radiation in combination with immunotherapy depends on a pre-existing immune response. Therefore, focusing primarily on radiation as an in situ vaccine strategy may yield limited results. We have identified that the ability of radiation therapy to function as a vaccine is dependent on its ability to activate the cDC1 subpopulation of dendritic cells in the tumor and that a lack of endogenous adjuvant and/or active suppression following radiation resulting in lack of maturation of cDC1 may be a major factor that limits control of poorly radioimmunogenic tumors. However, where radiation therapy and immunotherapy combinations work well, radiation therapy cannot be adequately replaced by a potent tumor vaccine, demonstrating that radiation therapy provides critical effects beyond priming new T cell responses. In addition to potential vaccine effects of radiation, it also modifies the cancer cells in the field to make them a better target for control by immune cells. We recently demonstrated that one of the major roles that radiation can play in controlling tumors when combined with immunotherapy is to increase the susceptibility of surviving cancer cells to CD8+ T cells through induction of MHC-I through genetic upregulation of the MHC-I transactivator NLRC5. These data support the critical role of local modulation by radiation in improved tumor control with combination immunotherapy. Citation Format: Marka Crittenden. Integrating radiation therapy with immunotherapy [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr IA-013.