tbuckley/cabot-search huggingface dataset:
CanDirect: Effectiveness of a Telephone-Supported Depression Self-Care Intervention for Cancer Survivors
Authors: Jane McCusker, Jennifer M. Jones, Madeline Li, Rosana Faria, Mark J. Yaffe, Sylvie D. Lambert, Antonio Ciampi, Eric Belzile, Manon de Raad
Journal: Journal of Clinical Oncology (2021)

PURPOSE Depression in post-treatment cancer survivors is common and can impair quality of life. CanDirect is a novel, telephone-delivered depression self-care intervention for cancer survivors. We conducted a randomized controlled superiority trial to compare CanDirect with usual care (UC) in this population. METHODS Participants completing cancer treatment within the past 10 years who had mild-moderate depressive symptoms with or without major depression were recruited from clinical and community settings in Quebec and Ontario. Permuted block random assignment allocated participants to CanDirect plus UC or to UC alone. Assessments of depression severity (Center for Epidemiological Studies-Depression scale [CES-D]; primary outcome) and secondary outcomes health-related quality of life (Short Form Survey-12 mental and physical component summaries), anxiety symptoms (Hospital Anxiety and Depression Scale), activation (Patient Activation Measure), depression diagnosis (Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-IV), and health services (self-report) were conducted at baseline, as well as 3 and 6 months (primary time point). Analyses of outcomes were adjusted for covariates using linear regression and missing data by inverse probability weighting. RESULTS Participants recruited between September 2016 and October 2018 were randomly assigned to CanDirect (n = 121) or UC (n = 124). Among 245 participants randomly assigned, 218 (89.0%) completed the primary outcome at 6 months. CanDirect participants reported less severe depressive symptoms on the CES-D than UC participants at 6 months, adjusted effect size (ES) 0.61 (95% CI, 0.33 to 0.88). CanDirect participants also had significantly greater quality of life, lower anxiety, more activation, and lower rates of depression diagnoses, compared with UC. Exploratory analysis suggested that sex was a modifier of the primary outcome (interaction term P value = .03); the intervention was less effective in men (ES, 0.12; 95% CI, −0.45 to 0.69). CONCLUSION The findings suggest that CanDirect is an effective method of managing mild-moderate depression symptoms in cancer survivors.
Ultra high-risk PFA ependymoma is characterized by loss of chromosome 6q
Authors: Lorena V Baroni, Lakshmikirupa Sundaresan, Ayala Heled, Hallie Coltin, Kristian W Pajtler, Tong Lin, Thomas E Merchant, Roger McLendon, Claudia Faria, Molly Buntine, Christine L White, Stefan M Pfister, Mark R Gilbert, Terri S Armstrong, Eric Bouffet, Sachin Kumar, Michael D Taylor, Kenneth D Aldape, David W Ellison, Nicholas G Gottardo, Marcel Kool, Andrey Korshunov, Jordan R Hansford, Vijay Ramaswamy
Journal: Neuro-Oncology (2021)

Within PF-EPN-A, 1q gain is a marker of poor prognosis, however, it is unclear if within PF-EPN-A additional cytogenetic events exist which can refine risk stratification.Five independent non-overlapping cohorts of PF-EPN-A were analyzed applying genome-wide methylation arrays for chromosomal and clinical variables predictive of survival.Across all cohorts, 663 PF-EPN-A were identified. The most common broad copy number event was 1q gain (18.9%), followed by 6q loss (8.6%), 9p gain (6.5%), and 22q loss (6.8%). Within 1q gain tumors, there was significant enrichment for 6q loss (17.7%), 10q loss (16.9%), and 16q loss (15.3%). The 5-year progression-free survival (PFS) was strikingly worse in those patients with 6q loss, with a 5-year PFS of 50% (95% CI 45%-55%) for balanced tumors, compared with 32% (95% CI 24%-44%) for 1q gain only, 7.3% (95% CI 2.0%-27%) for 6q loss only and 0 for both 1q gain and 6q loss (P = 1.65 × 10-13). After accounting for treatment, 6q loss remained the most significant independent predictor of survival in PF-EPN-A but is not in PF-EPN-B. Distant relapses were more common in 1q gain irrespective of 6q loss. RNA sequencing comparing 6q loss to 6q balanced PF-EPN-A suggests that 6q loss forms a biologically distinct group.We have identified an ultra high-risk PF-EPN-A ependymoma subgroup, which can be reliably ascertained using cytogenetic markers in routine clinical use. A change in treatment paradigm is urgently needed for this particular subset of PF-EPN-A where novel therapies should be prioritized for upfront therapy.
Physical activity self-reports: past or future?
Authors: Matteo C Sattler, Barbara E Ainsworth, Lars B Andersen, Charlie Foster, Maria Hagströmer, Johannes Jaunig, Paul Kelly, Harold W Kohl III, Charles E Matthews, Pekka Oja, Stephanie A Prince, Mireille N M van Poppel
Journal: British Journal of Sports Medicine (2021)

The measurement of physical activity (PA) is fundamental to health-related research, practice and policy. For decades, self-report measures have provided unique insights into the role of PA for human health and society. In fact, studies, in which participants reported their behaviours—or the behaviours of others—using diaries, logs, questionnaires and recalls, have historically provided the evidence that underpins global PA guidelines.1 Self-reports have been used extensively in various settings, including population surveillance, observational and intervention studies and routine assessment as part of healthcare.

The field of PA measurement is rapidly evolving. We have a wealth of measurement instruments and achieved remarkable advancements in the use of device-based information such as raw accelerometry, novel algorithms for pattern recognition and worldwide initiatives for data harmonisation.2 3 The technological evolution has changed the practice of PA self-reports as well, and led to electronic surveys and ecological momentary assessments (EMAs) for the measurement of PA in natural environments and in ‘real time’.

Despite significant improvements, an established standard for the measurement of PA does not exist due to the complexity of the behaviour.4 PA is multifaceted and encompasses different domains (eg, leisure, occupation, transport, household), dimensions (eg, frequency, duration, intensity, …
LIX1-like protein promotes liver cancer progression via miR-21-3p-mediated inhibition of fructose-1,6-bisphosphatase
Authors: Jie Zou, Xiaoyun Zhu, Dejuan Xiang, Yanqiu Zhang, Jie Li, Zhigui Su, Lingyi Kong, Hao Zhang
Journal: Acta Pharmaceutica Sinica B (2021)

Limb and CNS expressed 1 like (LIX1L) is over-expressed in several types of tumors. However, the function of LIX1L in glucose metabolism and hepatocellular carcinoma (HCC) progression remains elusive. Here we report that LIX1L is over-expressed in human HCC tissues, which predicts unfavorable prognosis. LIX1L deficiency in vivo significantly attenuated liver cancer initiation in mice. Functional studies indicated that LIX1L overexpression elevated proliferation, migratory, invasive capacities of HCC cells in vitro, and promoted liver cancer growth and metastasis in vivo. LIX1L knockdown up-regulated fructose-1,6-bisphosphatase (FBP1) expression to reduce glucose consumption as well as lactate production. Mechanistically, LIX1L increased miR-21-3p expression, which targeted and suppressed FBP1, thereby promoting HCC growth and metastasis. MiR-21-3p inhibitor could abrogate LIX1L induced enhancement of cell migration, invasion, and glucose metabolism. Inhibition of miR-21-3p suppressed tumor growth in an orthotopic tumor model. Our results establish LIX1L as a critical driver of hepatocarcinogenesis and HCC progression, with implications for prognosis and treatment.
Triglyceride‐To‐High-Density-Lipoprotein-Cholesterol Ratio as a Predictor for Metabolic Syndrome According to Obesity Onset in Women With Severe Obesity
Authors: Nayra Figueiredo, Marcela De Oliveira Queiroz, Karem Lays Soares Lopes, Luciana Oliveira e Silva, Valeria De Souza Abreu, Juarez Távora de Siqueira Júnior, Ana Raimunda Dâmaso, Maria Aderuza Horst, João Felipe Mota, Flavia Campos Corgosinho
Journal: Metabolism (2021)
Dasiglucagon, a Ready-To-Use Glucagon Analog, For Rapid And Effective Treatment of Severe Hypoglycemia: a Phase 3, Randomized Controlled Trial in Children With Type 1 Diabetes
Authors: Tadej Battelino, Ramin Tehranchi, Timothy Bailey, Klemen Dovc, Anita Melgaard, Jenine Y. Stone, Stephanie Woerner, Thekla von dem Berg, Linda A. DiMeglio, David Kendall, Thomas Danne
Journal: Metabolism (2021)
Maturation of Nasopharyngeal and Oral Microbiome in Chinese Infants
Authors: Ting Fan Leung, Yu Ping Song, Miss, Yehao Chen, Shuk Man Li, Kate Ching Ching Chan, Agnes Sze Yin Leung, Brian Hei Long Tong, Apple Chung Man Yeung, Nam Sze Cheng, Cecily Woon Wa Leung, Mei Kam Chang, Wing Hung Tam, Zigui Chen, Paul Kay Sheung Chan
Journal: Journal of Allergy and Clinical Immunology (2021)
Updating Reports of Phase 3 Clinical Trials for Cancer
Authors: Elena Elimova, Stephanie Moignard, Xuan Li, Manshu Yu, Wei Xu, Bostjan Seruga, Ian F. Tannock
Journal: JAMA Oncology (2021)

Phase 3 randomized clinical trials (RCTs) are usually reported after a predetermined number of events (death or disease progression) have occurred, when survival curves remain poorly defined. Updated reports are important in providing mature data.To evaluate the proportion of phase 3 RCTs for cancer that are updated and the factors that are associated with updating them and, for updated trials, to compare initial and updated results.This study identified reports of 2-group RCTs with a sample size of at least 100, published in 6 major journals between 1990 and 2010, that evaluated drug treatments for breast, lung, or prostate cancer. PubMed and abstracts of large cancer conferences were searched to identify updated (or earlier) reports of the same trials published up to 2019. Logistic regression was used to identify factors associated with the provision of updated reports. The hazard ratios defining the relative treatment effects for the primary and secondary end points between the initial and updated reports were compared.Proportion of RCTs whose results are updated, factors associated with updating, and change in hazard ratio for the primary end point between initial and updated reports.A total of 207 RCTs met the inclusion criteria, and 41 (20%) were found to have updated reports. The factors significantly associated with an update included positive trial results (odds ratio [OR], 8.7 [95% CI, 3.3-23.3]), larger trial size (OR, 1.0006 [95% CI, 1.0000-1.0012]), evaluation of hormonal agents (OR, 5.8 [95% CI, 1.6-21.8]) or targeted agents (OR, 4.3 [95% CI, 1.3-14.6]) compared with chemotherapy, and evaluation of adjuvant therapy rather than therapy for advanced disease (OR, 8.0 [95% CI, 2.9-21.9]). For 31 trials for which initial and updated hazard ratios for the primary end point were available, the median hazard ratio increased from 0.66 (95% CI, 0.22-1.20) to 0.74 (95% CI, 0.32-1.19) (P < .001), indicating a decreased level of effectiveness.Only 20% of reports of phase 3 clinical trials for breast, lung, and prostate cancer were updated. Original reports of such trials are based on relatively few events, and their results are immature; more mature data indicate a decreased level of effect in updated trials. Updated reporting to provide mature, long-term results of clinical trials should be mandated.
Impact of Baseline Blood Eosinophil Count on Flare Reduction in Mepolizumab-Treated Patients With Hypereosinophilic Syndrome
Authors: Marc Rothenberg, Florence Roufosse, Stanislas Faguer, Gerald Gleich, Jean-Emmanuel Kahn, Jonathan Steinfeld, Namhee Kwon, Jane Bentley, Steve Yancey
Journal: Journal of Allergy and Clinical Immunology (2021)
Cancer-Associated Fibroblasts Promote Aggressive Gastric Cancer Phenotypes via Heat Shock Factor 1–Mediated Secretion of Extracellular Vesicles
Authors: Nil Grunberg, Meirav Pevsner-Fischer, Tal Goshen-Lago, Judith Diment, Yaniv Stein, Hagar Lavon, Shimrit Mayer, Oshrat Levi-Galibov, Gil Friedman, Yifat Ofir-Birin, Li-Jyun Syu, Cristina Migliore, Eyal Shimoni, Salomon M. Stemmer, Baruch Brenner, Andrzej A. Dlugosz, David Lyden, Neta Regev-Rudzki, Irit Ben-Aharon, Ruth Scherz-Shouval
Journal: Cancer Research (2021)

Gastric cancer is the third most lethal cancer worldwide, and evaluation of the genomic status of gastric cancer cells has not translated into effective prognostic or therapeutic strategies. We therefore hypothesize that outcomes may depend on the tumor microenvironment (TME), in particular, cancer-associated fibroblasts (CAF). However, very little is known about the role of CAFs in gastric cancer. To address this, we mapped the transcriptional landscape of human gastric cancer stroma by microdissection and RNA sequencing of CAFs from patients with gastric cancer. A stromal gene signature was associated with poor disease outcome, and the transcription factor heat shock factor 1 (HSF1) regulated the signature. HSF1 upregulated inhibin subunit beta A and thrombospondin 2, which were secreted in CAF-derived extracellular vesicles to the TME to promote cancer. Together, our work provides the first transcriptional map of human gastric cancer stroma and highlights HSF1 and its transcriptional targets as potential diagnostic and therapeutic targets in the genomically stable tumor microenvironment. SIGNIFICANCE: This study shows how HSF1 regulates a stromal transcriptional program associated with aggressive gastric cancer and identifies multiple proteins within this program as candidates for therapeutic intervention. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/7/1639/F1.large.jpg.
Dietary betaine prevents obesity through gut microbiota-drived microRNA-378a family
Authors: Jingjing Du, Peiwen Zhang, Jiang Luo, Linyuan Shen, Shunhua Zhang, Hao Gu, Jin He, Linghui Wang, Xue Zhao, Mailing Gan, Liu Yang, Lili Niu, Ye Zhao, Qianzi Tang, Guoqing Tang, Dongmei Jiang, Yanzhi Jiang, Mingzhou Li, Anan Jiang, Long Jin, Jideng Ma, Surong Shuai, Lin Bai, Jinyong Wang, Bo Zeng, De Wu, Xuewei Li, Li Zhu
Journal: Gut Microbes (2021)

Betaine is a natural compound present in commonly consumed foods and may have a potential role in the regulation of glucose and lipids metabolism. However, the underlying molecular mechanism of its action remains largely unknown. Here, we show that supplementation with betaine contributes to improved high-fat diet (HFD)-induced gut microbiota dysbiosis and increases anti-obesity strains such as
Surgeon Technical Skills, a Potential Confounder in Clinical Trials
Authors: Xiaojie Wang, Zhifang Zheng, Pan Chi
Journal: JAMA Surgery (2021)

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Repeated centralized multidisciplinary team assessment of resectability, clinical behavior, and outcomes in 1086 Finnish metastatic colorectal cancer patients (RAXO): A nationwide prospective intervention study
Authors: Pia Osterlund, Tapio Salminen, Leena-Maija Soveri, Raija Kallio, Ilmo Kellokumpu, Annamarja Lamminmäki, Päivi Halonen, Raija Ristamäki, Eila Lantto, Aki Uutela, Emerik Osterlund, Ali Ovissi, Arno Nordin, Eetu Heervä, Kaisa Lehtomäki, Jari Räsänen, Maija Murashev, Laura Aroviita, Antti Jekunen, Reneé Lindvall-Andersson, Paul Nyandoto, Juha Kononen, Anna Lepistö, Tuija Poussa, Timo Muhonen, Annika Ålgars, Helena Isoniemi
Journal: The Lancet Regional Health - Europe (2021)

Resection of colorectal cancer (CRC) metastases provides good survival but is probably underused in real-world practice.A prospective Finnish nationwide study enrolled treatable metastatic CRC patients. The intervention was the assessment of resectability upfront and twice during first-line therapy by the multidisciplinary team (MDT) at Helsinki tertiary referral centre. The primary outcome was resection rates and survival.In 2012-2018, 1086 patients were included. Median follow-up was 58 months. Multiple metastatic sites were present in 500 (46%) patients at baseline and in 820 (76%) during disease trajectory. In MDT assessments, 447 (41%) were classified as resectable, 310 (29%) upfront and 137 (18%) after conversion therapy. Six-hundred and ninety curative intent resections or local ablative therapies (LAT) were performed in 399 patients (89% of 447 resectable). Multiple metastasectomies for multisite or later developing metastases were performed in 148 (37%) patients. Overall, 414 liver, 112 lung, 57 peritoneal, and 107 other metastasectomies were performed. Median OS was 80·4 months in R0/1-resected (HR 0·15; CI95% 0·12-0·19), 39·1 months in R2-resected/LAT (0·39; 0·29-0·53) patients, and 20·8 months in patients treated with "systemic therapy alone" (reference), with 5-year OS rates of 66%, 40%, and 6%, respectively.Repeated centralized MDT assessment in real-world metastatic CRC patients generates high resectability (41%) and resection rates (37%) with impressive survival, even when multisite metastases are present or develop later.The funders had no role in the study design, analysis, and interpretation of the data or writing of this report.
Secreted modular calcium-binding protein 1 binds and activates thrombin to account for platelet hyperreactivity in diabetes
Authors: Fredy Delgado Lagos, Amro Elgheznawy, Anastasia Kyselova, Dagmar Meyer zu Heringdorf, Corina Ratiu, Voahanginirina Randriamboavonjy, Alexander W. Mann, Beate Fisslthaler, Mauro Siragusa, Ingrid Fleming
Journal: Blood (2021)
Epigenetic signatures in cancer: proper controls, current challenges and the potential for clinical translation
Authors: Daniela Mancarella, Christoph Plass
Journal: Genome Medicine (2021)

Abstract Epigenetic alterations are associated with normal biological processes such as aging or differentiation. Changes in global epigenetic signatures, together with genetic alterations, are driving events in several diseases including cancer. Comparative studies of cancer and healthy tissues found alterations in patterns of DNA methylation, histone posttranslational modifications, and changes in chromatin accessibility. Driven by sophisticated, next-generation sequencing-based technologies, recent studies discovered cancer epigenomes to be dominated by epigenetic patterns already present in the cell-of-origin, which transformed into a neoplastic cell. Tumor-specific epigenetic changes therefore need to be redefined and factors influencing epigenetic patterns need to be studied to unmask truly disease-specific alterations. The underlying mechanisms inducing cancer-associated epigenetic alterations are poorly understood. Studies of mutated epigenetic modifiers, enzymes that write, read, or edit epigenetic patterns, or mutated chromatin components, for example oncohistones, help to provide functional insights on how cancer epigenomes arise. In this review, we highlight the importance and define challenges of proper control tissues and cell populations to exploit cancer epigenomes. We summarize recent advances describing mechanisms leading to epigenetic changes in tumorigenesis and briefly discuss advances in investigating their translational potential.
Efficacy of Omalizumab against Aspirin-hypersensitivity and Overproduction of Cysteinyl Leukotrienes in Aspirin-exacerbated Respiratory Disease: A Randomized Trial
Authors: Hiroaki Hayashi, Yuma Fukutomi, Chihiro Mitsui, Keiichi Kajiwara, Kentaro Watai, Yosuke Kamide, Maki Iwata, Kisako Nagayama, Yuto Nakamura, Yuto Hamada, Yasuhiro Tomita, Kiyoshi Sekiya, Takahiro Tsuburai, Akio Mori, Kenji Izuhara, Keiko Wakahara, Naozumi Hashimoto, Yoshinori Hasegawa, Masami Taniguchi
Journal: Journal of Allergy and Clinical Immunology (2021)
Understanding the impact of the COVID-19 pandemic on physical and mental health
Authors: Shu Cao, Hena Din, Christopher Warren, Jessica Fitzpatrick, Tina Hernandez-Boussard, Manisha Desai, Sharon Chinthrajah, Kari Nadeau
Journal: Journal of Allergy and Clinical Immunology (2021)

The COVID-19 pandemic has contributed to 800,000 deaths and millions of hospitalizations globally. However, little is known regarding long-term symptom trends among recovering patients nor its mental health impact. Individuals testing positive for COVID-19 at Stanford Hospital were recruited into a year-long observational study. Recruited individuals were invited to enroll family members irrespective of suspected COVID status. All participants underwent COVID-19 testing and completed questionnaires assessing COVID-19-related symptomatology, testing methods, preventative behaviors, comorbidities, and psychosocial factors. From April 8 to August 20, 156 participants (4-86 years-old) were enrolled a median of 25 days post-COVID-19 testing (55% female, 32% Hispanic, median age=42). Most (60%) participants had mild COVID-19 symptoms (i.e. symptoms resolving without clinical intervention) while 17% were hospitalized. Median symptom duration was 13 days. Fatigue was most commonly reported (49%). Although symptoms resolved for all patients by 2 months post-initial test, at 4 months symptoms reappeared in 3% of participants, including fatigue, body aches, shortness-of-breath, and trouble breathing. 17% of participants reported greater anxiety due to the pandemic. Median PROMIS global mental and physical health T-scores were 54.1 and 53.3, respectively. Hispanic participants reported poorer physical (p=0.01) and mental health (p=0.03) vs. non-Hispanic participants. Participants initially testing negative to COVID-19 (N=25) reported better physical health vs. those testing positive (N=131);(p=0.02), however mental health T-scores were comparable (p=.34). Preliminary data from this diverse cohort of families impacted by COVID-19, indicate that COVID-19 can lead to substantial, sustained physical and mental health burden—which may be greater among Hispanic patients.