tbuckley/cabot-search huggingface dataset:
Psycho-Oncology: Cancer patients with past suicide attempts, or a family history of suicide.
Authors: Daniela Gercovich, Ernesto Gil Deza, Flavio Tognelli, Carlos Fernando Garcia Gerardi, Claudia Lorena Acuna, Cesar Gonzalez, Eduardo L. Morgenfeld, Mirta Morgenfeld, Edgardo G. J. Rivarola, Felipe G. Gercovich
Journal: Journal of Clinical Oncology (2019)

e23173 Background: “The suicide rate in cancer patients is twice that observed in the general population in the United States” (JNCI vol 100, 24, page 1750, 2008). This paper focuses ona population with great psychological risk: cancer patients (Pt) with previous suicide attempts (SA) or a family history of suicide (FS); both grouped under SAFS for the purpose of this study. Methods: Between 9/26/2012 and 11/28/2018 all new patients (Pt) admitted to IOHM filled out a Past Medical History Form (PMHF) (ASCO 2013 ABST. e17539) with their preexisting clinical conditions. The database was locked and anonymized. Those with a history of SAFS before cancer diagnosis were selected. Results: Out of 15,617 Pt, 184 Pt (1.2%) were SAFS(141 Pt were SA, 39 Pt were FS and 4 Pt were both). The relative risk ofSA was ten times larger for those with FS. Psychiatric Medication: Antipsychotics: 15Pt (8%), Antidepressants: 23 Pt (12%) and Benzodiazepines 45 Pt(24%), No treatment 101 Pt (55%). Population Characteristics: Sex: F:144 Pt . M: 40 Pt. Age: 56y (r = 26-88). Tumor Dx: Breast (65 Pt ) - Gastrointestinal (24 Pt) - Urological (21 Pt ) - Lung (21 Pt ) -Gynecological (19 Pt) - Hematological (11 Pt) -Head &amp;Neck (8 Pt) - Endocrine (7 Pt) - Other (8 Pt). Stages: Early (0-I-II-III): 130 Pt, Advanced: 54 Pt. Ob-Gyn history:25 Pt (17%) nulliparous, 18 Pt (12%) with one child, 77 Pt (53%) with 2 or 3 children and 24 Pt (17%) with more than 3 children; 62 Pt (43%) had previous abortions. Average severe comorbidities (respiratory and psychiatric) was 3 per Pt (r = 0-18). Toxic habits: Smoking: 120 Pt (65%), Alcohol: 37 Pt (20%) and Illicit Drugs: 4 Pt (2%). Follow-up: 19 months (r = 0-70). No Pt had any SA, or commited suicide, during the follow-up.Living patients:177 (96%). Conclusions: 1) In our vast cohort, 184 Pt (1.2%) were identified as highly vulnerable psychiatric Pt due to SAFS. 2) Given the high psychological risk and stressful cancer diagnosis, 83 Pt (45%) were prescribed psychiatric drugs. 3) Follow-up of SAFS Pt by a multidisciplinary team is requiredfor adequate Pt and family support.
The impact of blinding on patient-reported outcomes (PROs) in randomized controlled trials of immune checkpoint inhibitors versus traditional chemotherapies.
Authors: James Dickerson, Evan Thomas Hall, Surbhi Singhal, Brooke Peterson Gabster, Lidia Schapira
Journal: Journal of Clinical Oncology (2019)

e23160 Background: Immune checkpoint inhibitors (ICIs) have been met with a wave of excitement due to their novel mechanism. We hypothesized that this may impact how patients (via PROs) report treatment tolerability in comparison to traditional therapies. We sought to examine if there was a notable difference in PROs in blinded vs unblinded trials of ICIs. Methods: We systematically searched PubMed, CINAHL, Embase, Web of Science, and Scopus in August 2018 for publications with quantitative PRO data comparing ICIs to cytotoxic chemotherapy. Case series, narrative reviews, and publications lacking original data were excluded. Eligible publications were reviewed to assess if patients were blinded to the agent received, and a comparison for common PRO metrics was performed. Results: Of the 1,450 unique references identified, eight met inclusion criteria: 1 double blinded placebo-controlled trial and 7 trials where patients were aware of the assigned arm. The blinded trial had quantitative PRO data in the form of the European Organisation for Research and Treatment of Cancer (EORTC) global health status (GHS) score and patient reported symptom burden at week 12. Most (6 of 7; 86%) unblinded trials reported the GHS at either week 12 or 15, and patient symptom burden at these time points as well (5 of 7; 71%). For the EORTC GHS, the blinded trial showed no inter-arm difference at week 12. 4 of 6 (67%) open label trials noted statistically significant differences in GHS favoring the ICI arm. For symptom burden at week 12 or 15, there was no difference found in the blinded study. In unblinded trials, there were domains where patients receiving ICIs reported a statistically significant lower symptom burden than those receiving chemotherapy: fatigue (4 of 5 trials favoring ICIs; 80%), dyspnea (2 of 5; 40%), insomnia (1 of 4; 25%), appetite loss (1 of 4; 25%), and diarrhea (1 of 5; 20%). There were no differences in pain (n = 5), nausea/vomit (n = 5), and constipation (n = 5). Conclusions: We found a trend towards more favorable reporting on common symptoms in unblinded studies of patients receiving ICIs. Our analysis is limited by the lack of available comparisons in the published literature.
Laparoscopic extralevator abdominoperineal resection versus laparoscopic abdominoperineal resection for lower rectal cancer: A retrospective comparative study from China
Authors: Xinyu Qi, Maoxing Liu, Fei Tan, Kai Xu, Zhendan Yao, Nan Zhang, Hong Yang, Chenghai Zhang, Jiadi Xing, Ming Cui, Xiangqian Su
Journal: International Journal of Surgery (2019)

This study was performed to compare the short- and long-term outcomes of laparoscopic extralevator abdominoperineal resection (LELAPR) versus laparoscopic abdominoperineal resection (LAPR) in patients with lower rectal cancer. Consecutive patients who underwent LELAPR or LAPR in our unit from September 2009 to December 2015 were retrospectively reviewed. The patients' clinicopathological data and short- and long-term outcomes were compared and analyzed. Of the 111 patients included in this study, 58 (52%) patients underwent LAPR and 53 (48%) LELAPR. A negative circumferential resection margin was achieved in all the two groups of patients. The LELAPR group had a longer operation time (P = 0.049), more intraoperative blood loss (P = 0.037), shorter hospitalization after surgery (P = 0.002), fewer lymph nodes harvested (P = 0.001), fewer positive lymph nodes (P = 0.002), and a shorter maximum tumor diameter (P < 0.001) compared with the LAPR group. There were also lower rates of intraoperative perforation (P = 0.039) and death (P = 0.013) in the LELAPR group. However, there were no significant differences in the rates of local recurrence (P = 0.144), metastasis (P = 0.111), overall survival (P = 0.404), disease-free survival (P = 0.515), or progression-free survival (P = 0.210) between the two groups. There were no significant differences in postoperative complications including postoperative hernia (P = 0.918), urinary retention (P = 0.579), intestinal obstruction (P = 1.0), and perineal wound complications (P = 0.252). Compared with LAPR, the LELAPR approach significantly reduced the rate of intraoperative perforation and postoperative death without increasing postoperative complications. LELAPR was beneficial to patients with ulcerative, anterior and advanced lower rectal cancer.
Predicitve factors of cisplatin (CDDP) discontinuation in concurrent chemoradiotherapy (CCRT) to locally advanced head and neck cancer patients.
Authors: Kenji Nakano, Yasuyoshi Sato, Yukiko Sato, Takashi Toshiyasu, Takao Asari, Wataru Shimbashi, Toru Sasaki, Hirofumi Fukushima, Hiroyuki Yonekawa, Hiroki Mitani, Masahiko Oguchi, Kazuyoshi Kawabata, Shunji Takahashi
Journal: Journal of Clinical Oncology (2013)

e17006 Background: CCRT is a standard therapy for locally advanced head and neck cancer patients, but some patients have intolerance to high dose density of CDDP. Predictive factors for CDDP discontinuation need to be investigated for making appropriate treatment decisions. Methods: We retrospectively analyzed nonmetastatic head and neck cancer patients treated with CCRT with CDDP (80 mg/m2 per 3 weeks) from November 2005 to April 2012 in our institute. Radiation therapy was performed as three-dimensional radiotherapy or intensity-modified radiotherapy (IMRT). Results: A total of 164 patients received CCRT, of which 89 (54 %) were Stage IV;. Primary sites were as follows; oral cavity 7, oropharynx 52, hypopharynx 53, larynx 14, nasopharynx 30, paranasal sinus/nasal cavity 3, and unknown primary 5. IMRT was performed to 54 (33 %) patients. Median follow-up time was 19 months (range 1-69 months); 1-year overall survival (OS) and progression free survival (PFS) were 90 % and 78 %. Non-Stage IV; and high creatinine clearance (&gt;70 ml/min) were associated with longer OS in Cox proportional hazard model. As for CDDP treatment, 75 (46 %) patients completed 3 cycles of CDDP, 69 (42 %) patients received 2 cycles, and 20 (12 %) patients received only 1 cycle. The main reasons for CDDP discontinuation were infection (24 patients) and renal dysfunction (18 patients). In logistic regression analysis, male sex, younger age (&lt; 61 years) and high body mass index (BMI) (&gt;25) were associated with 3 cycles completion of CDDP statistically significantly (p = .002, odds ratio 6.622; p = .006, odds ratio 2.602; p = .035, odds ratio 2.655, respectively). Conclusions: In CCRT to head and neck cancer patients, infection and renal dysfunction were the main reasons for CDDP discontinuation. Sex, age and BMI could be predictive of CDDP completion/discontinuation.
Visible light-induced apoptosis activatable nanoparticles of photosensitizer-DEVD-anticancer drug conjugate for targeted cancer therapy
Authors: Wooram Um, Jooho Park, Hokyung Ko, Seungho Lim, Hong Yeol Yoon, Man Kyu Shim, Sangmin Lee, Young Ji Ko, Min Ju Kim, Jae Hyung Park, Dong-Kwon Lim, Youngro Byun, Ick Chan Kwon, Kwangmeyung Kim
Journal: Biomaterials (2019)
Diindolylmethane (DIM), formed spontaneously from Indole-3-carbinol (I3C), is the dominant anti-proliferative indole in cell culture media after adding I3C.
Authors: Michael A. Zeligs, H. Leon Bradlow
Journal: Cancer Research (2006)

5597  Over 150 studies, utilizing I3C added to cultures of breast, prostate, cervical, ovarian, colon and thyroid cancer cells, have attributed observed growth-inhibitory and pro-apoptotic activity to I3C. Prior studies have documented conversion of I3C into DIM in aqueous acid and in vivo in the acidic gastric milieu, yet there has been little study of the spontaneous conversion of I3C into DIM in pH 7 cell culture media. Direct anti-proliferative activity using DIM as the starting agent has now been observed in vitro and in in vivo in models of breast, prostate, cervical, endometrial, ovarian, colon and thyroid cancer. This suggests that DIM, and possibly other non-DIM condensation products from I3C (Linear and Cyclic Trimers), are the actual indoles responsible for previously reported anti-cancer activity from I3C. To address the question of whether DIM may be contributing to activity previously reported for I3C in vitro, we studied the conversion of I3C into DIM under typical cell culture conditions. We added pure I3C in DMSO to samples of a variety of tissue culture medias in sterile tubes. These were placed in a tissue culture incubator at 37 C°. After 24, 36, 48, 72, or 96 hrs the tubes were removed and the media extracted twice with 2 ml of chloroform. The chloroform was evaporated in vacuo and the residue taken up in EtOAc. Aliquots were spotted on 20x20 cm TLC plates and developed in EtOAc:Hexane. The plates were then dried, developed with PMA and then scanned. The intensity of the I3C/DIM spots was quantified using image-J software^. The TLC results are summarized below, expressed as ratios of signal intensities for DIM to I3C. *media + 25% serum; ^ media + 5% serum; ^^ average of two serum studies The results show that I3C readily converts into DIM in tissue culture media. DIM predominating after 24 hrs. Because of the greater relative potency of DIM to I3C previously reported, DIM may be the major active compound responsible for anti-cancer effects in I3C cell culture experiments. ^ Rasband, W.S., ImageJ, NIH, http://rsb.info.nih.gov/ij/, 1997-2005
Dermal adipose tissue has high plasticity and undergoes reversible dedifferentiation in mice
Authors: Zhuzhen Zhang, Mengle Shao, Chelsea Hepler, Zhenzhen Zi, Shangang Zhao, Yu A. An, Yi Zhu, Alexandra L. Ghaben, May-yun Wang, Na Li, Toshiharu Onodera, Nolwenn Joffin, Clair Crewe, Qingzhang Zhu, Lavanya Vishvanath, Ashwani Kumar, Chao Xing, Qiong A. Wang, Laurent Gautron, Yingfeng Deng, Ruth Gordillo, Ilja Kruglikov, Christine M. Kusminski, Rana K. Gupta, Philipp E. Scherer
Journal: Journal of Clinical Investigation (2019)

Dermal adipose tissue (also known as dermal white adipose tissue and herein referred to as dWAT) has been the focus of much discussion in recent years. However, dWAT remains poorly characterized. The fate of the mature dermal adipocytes and the origin of the rapidly reappearing dermal adipocytes at different stages remain unclear. Here, we isolated dermal adipocytes and characterized dermal fat at the cellular and molecular level. Together with dWAT's dynamic responses to external stimuli, we established that dermal adipocytes are a distinct class of white adipocytes with high plasticity. By combining pulse-chase lineage tracing and single-cell RNA sequencing, we observed that mature dermal adipocytes undergo dedifferentiation and redifferentiation under physiological and pathophysiological conditions. Upon various challenges, the dedifferentiated cells proliferate and redifferentiate into adipocytes. In addition, manipulation of dWAT highlighted an important role for mature dermal adipocytes for hair cycling and wound healing. Altogether, these observations unravel a surprising plasticity of dermal adipocytes and provide an explanation for the dynamic changes in dWAT mass that occur under physiological and pathophysiological conditions, and highlight the important contributions of dWAT toward maintaining skin homeostasis.
Abstract 13106: Heart Rate Recovery and Chronotropic Response in Patients With Hypertrophic Cardiomyopathy
Authors: hongchang luo, Veronica L Dimaano, Jackie Kembro, Hulya Yalcin, Theodore Abraham, Roselle M Abraham
Journal: Circulation (2013)

Background: Alterations in heart rate variability, abnormalities in catecholamine re-uptake by myocardial sympathetic nerve terminals and marked peripheral vasodilation during exercise have been re...
Suppression of HIF2 signalling attenuates the initiation of hypoxia-induced pulmonary hypertension
Authors: Cheng-Jun Hu, Jens M. Poth, Hui Zhang, Amanda Flockton, Aya Laux, Sushil Kumar, Brittany McKeon, Gary Mouradian, Min Li, Suzette Riddle, Steven C. Pugliese, R. Dale Brown, Eli M. Wallace, Brian B. Graham, Maria G. Frid, Kurt R. Stenmark
Journal: European Respiratory Journal (2019)

Most published studies addressing the role of hypoxia inducible factors (HIFs) in hypoxia-induced pulmonary hypertension development employ models that may not recapitulate the clinical setting, including the use of animals with pre-existing lung/vascular defects secondary to embryonic HIF ablation or activation. Furthermore, critical questions including how and when HIF signalling contributes to hypoxia-induced pulmonary hypertension remain unanswered.Normal adult rodents in which global HIF1 or HIF2 was inhibited by inducible gene deletion or pharmacological inhibition (antisense oligonucleotides (ASO) and small molecule inhibitors) were exposed to short-term (4 days) or chronic (4-5 weeks) hypoxia. Haemodynamic studies were performed, the animals euthanised, and lungs and hearts obtained for pathological and transcriptomic analysis. Cell-type-specific HIF signals for pulmonary hypertension initiation were determined in normal pulmonary vascular cells in vitro and in mice (using cell-type-specific HIF deletion).Global Hif1a deletion in mice did not prevent hypoxia-induced pulmonary hypertension at 5 weeks. Mice with global Hif2a deletion did not survive long-term hypoxia. Partial Hif2a deletion or Hif2-ASO (but not Hif1-ASO) reduced vessel muscularisation, increases in pulmonary arterial pressures and right ventricular hypertrophy in mice exposed to 4-5 weeks of hypoxia. A small molecule HIF2 inhibitor (PT2567) significantly attenuated early events (monocyte recruitment and vascular cell proliferation) in rats exposed to 4 days of hypoxia, as well as vessel muscularisation, tenascin C accumulation and pulmonary hypertension development in rats exposed to 5 weeks of hypoxia. In vitro, HIF2 induced a distinct set of genes in normal human pulmonary vascular endothelial cells, mediating inflammation and proliferation of endothelial cells and smooth muscle cells. Endothelial Hif2a knockout prevented hypoxia-induced pulmonary hypertension in mice.Inhibition of HIF2 (but not HIF1) can provide a therapeutic approach to prevent the development of hypoxia-induced pulmonary hypertension. Future studies are needed to investigate the role of HIFs in pulmonary hypertension progression and reversal.
Pulmonary fibrosis linked to variants in the<i>ACD</i>gene, encoding the telomere protein TPP1
Authors: Thijs W. Hoffman, Joanne J. van der Vis, Jasper J. van der Smagt, Maarten P.G. Massink, Jan C. Grutters, Coline H.M. van Moorsel
Journal: European Respiratory Journal (2019)

<b>Pulmonary fibrosis is associated with mutations in the <i>ACD</i> gene, encoding the telomere protein TPP1. Potentially disease-causing variants were found in 5% of a cohort of 60 unrelated patients with pulmonary fibrosis who were referred for genetic screening.</b>http://bit.ly/2Mw9Cn0
Antibody-drug conjugates in clinical trials for lymphoid malignancies and multiple myeloma
Authors: Bo Yu, Delong Liu
Journal: Journal of Hematology & Oncology (2019)

Antibody-drug conjugates (ADC) represent a distinct family of chemoimmunotherapy agents. ADCs are composed of monoclonal antibodies conjugated to cytotoxic payloads via specialized chemical linkers. ADCs therefore combine the immune therapy with targeted chemotherapy. Due to the distinct biomarkers associated with lymphocytes and plasma cells, ADCs have emerged as a promising treatment option for lymphoid malignancies and multiple myeloma. Several ADCs have been approved for clinical applications: brentuximab vedotin, inotuzumab ozogamicin, moxetumomab pasudotox, and polatuzumab vedotin. More novel ADCs are under clinical development. In this article, we summarized the general principles for ADC design, and updated novel ADCs under various stages of clinical trials for lymphoid malignancies and multiple myeloma.
Emotions in the development of moral norms within cooperative relationships
Authors: Jeremy I M Carpendale, Beau Wallbridge
Journal: Behavioral and Brain Sciences (2019)

We support May's criticism of attempts to reduce morality to being primarily based on evolved emotional reactions. However, we question the clarity and consistence of his own position and suggest taking a developmental approach. We focus on providing a developmental approach to the role of emotions in the social origin of moral norms.
Helen Salisbury: Trust and truth telling
Authors: Helen Salisbury
Journal: BMJ (2019)

When my patients tell me their symptoms they put their trust in me: they trust me to listen attentively, to examine carefully, and to investigate as thoroughly as necessary. They trust me to keep their confidences and to follow up as promised. Above all, when they ask me a question they trust me to tell them the truth as far as I know it. If I fall short in any of these areas I am likely to lose their trust—and then I’m not much use to anyone. I also risk losing …
Rationalization, controversy, and the entanglement of moral-social cognition: A “critical pessimist” take
Authors: Robin Zheng
Journal: Behavioral and Brain Sciences (2019)

Abstract I raise two worries about the Debunker's and Defeater Dilemmas, respectively, and I argue that moral cognition is inextricable from social cognition, which tends to rationalize deep social inequality. I thus opine that our moral-social capacities fare badly in profoundly unjust social contexts such as our own.
Dendrimer-Functionalized Superparamagnetic Nanobeacons for Real-Time Detection and Depletion of HSP90α mRNA and MR Imaging
Authors: Zhongyuan Chen, Yueting Peng, Xiaoxue Xie, Yi Feng, Tingting Li, Shun Li, Xiang Qin, Hong Yang, Chunhui Wu, Chuan Zheng, Jie Zhu, Fengming You, Yiyao Liu
Journal: Theranostics (2019)

Background & Aims: The use of antisense oligonucleotide-based nanosystems for the detection and regulation of tumor-related gene expression is thought to be a promising approach for cancer diagnostics and therapies.Herein, we report that a cubic-shaped iron oxide nanoparticle (IONC) core nanobeacon is capable of delivering an HSP90α mRNA-specific molecular beacon (HSP90-MB) into living cells and enhancing T 2 -weighted MR imaging in a tumor model.Methods: The nanobeacons were built with IONC, generation 4 poly(amidoamine) dendrimer (G4 PAMAM), Pluronic P123 (P123) and HSP90-MB labeled with a quencher (BHQ1) and a fluorophore (Alexa Fluor 488).Results: After internalization by malignant cells overexpressing HSP90α, the fluorescence of the nanobeacon was recovered, thus distinguishing cancer cells from normal cells.Meanwhile, MB-mRNA hybridization led to enzyme activity that degraded DNA/RNA hybrids and resulted in downregulation of HSP90α at both the mRNA and protein levels.Furthermore, the T 2 -weighted MR imaging ability of the nanobeacons was increased after PAMAM and P123 modification, which exhibited good biocompatibility and hemocompatibility.Conclusions: The nanobeacons show promise for applicability to tumor-related mRNA detection, regulation and multiscale imaging in the fields of cancer diagnostics and therapeutics.
Genomic and Phenotypic Analyses Reveal Mechanisms Underlying Homing Ability in Pigeon
Authors: Yong Shao, Hang-Yu Tian, Jing-Jing Zhang, Hamed Kharrati-Koopaee, Xing Guo, Xiao-Lin Zhuang, Ming-Li Li, Hojat Asadollahpour Nanaie, Elahe Dehghani Tafti, Bahador Shojaei, Mohammad Reza Namavar, Narges Sotoudeh, Adeola Oluwakemi Ayoola, Jia-Li Li, Bin Liang, Ali Esmailizadeh, Shu Wang, Dong-Dong Wu
Journal: Molecular Biology and Evolution (2019)

Abstract The homing pigeon was selectively bred from the domestic pigeon for a homing ability over long distances, a very fascinating but complex behavioral trait. Here, we generate a total of 95 whole genomes from diverse pigeon breeds. Comparing the genomes from the homing pigeon population with those from other breeds identifies candidate positively selected genes, including many genes involved in the central nervous system, particularly spatial learning and memory such as LRP8. Expression profiling reveals many neuronal genes displaying differential expression in the hippocampus, which is the key organ for memory and navigation and exhibits significantly larger size in the homing pigeon. In addition, we uncover a candidate gene GSR (encoding glutathione-disulfide reductase) experiencing positive selection in the homing pigeon. Expression profiling finds that GSR is highly expressed in the wattle and visual pigment cell layer, and displays increased expression levels in the homing pigeon. In vitro, a magnetic field stimulates increases in calcium ion concentration in cells expressing pigeon GSR. These findings support the importance of the hippocampus (functioning in spatial memory and navigation) for homing ability, and the potential involvement of GSR in pigeon magnetoreception.
How is mindreading really like reading?
Authors: Ian A. Apperly
Journal: Behavioral and Brain Sciences (2019)

Abstract I suggest an alternative basis for Heyes’ analogy between cultural learning of mindreading and text reading. Unlike text reading, mindreading does not entail decoding of observable stimuli. Like text reading, mindreading requires relevant inferences. Identification of relevant inferences is a deeply challenging problem, and the most important contribution of cultural learning to mindreading may be an apprenticeship in thinking like a mindreader.