tbuckley/cabot-search huggingface dataset:
Classical social reward signatures in infants with later ASD
Authors: Teodora Gliga, Mayada Elsabbagh
Journal: Behavioral and Brain Sciences (2019)

Abstract Autistic individuals can be socially motivated. We disagree with the idea that self-report is sufficient to understand their social drive. Instead, we underscore evidence for typical non-verbal signatures of social reward during the early development of autistic individuals. Instead of focusing on whether or not social motivation is typical, research should investigate the factors that modulate social drives.
Прогнозування ефективності терапії алкогольного цирозу печінки
Authors: O.Ye. Samogalska, T.B. Lazarchuk, O.V. Babyak, I.M. Vitruk
Journal: GASTROENTEROLOGY (2013)

Для створення прогностичної таблиці ефективності терапії алкогольного цирозу печінки проаналізували 21 показник лабораторних досліджень. Для прогнозування ефективності терапії використовували інтегральну оцінку — сума балів по 15 прогностичних показниках. Сума балів, що перевищувала +13, свідчить про високу ймовірність успішності стандартної терапії. При сумі балів менше –13 імовірність неуспіху становить 95 %. Якщо сума балів перебуває в проміжку від +13 до –13, то інформації недостатньо для ухвалення конкретного рішення. Визначення високого ризику неефективності стандартної терапії допускає розробку індивідуальної програми лікування хворих на алкогольний цироз печінки з розрахуванням індексу маси тіла.
Reconciling autistic individuals’ self-reported social motivation with diminished social reward responsiveness in neuroimaging
Authors: Lisa D. Yankowitz, Caitlin C. Clements
Journal: Behavioral and Brain Sciences (2019)

Abstract The self-report of some autistic individuals that they experience social motivation should not be interpreted as a refutation of neuroimaging evidence supporting the social motivation hypothesis of autism. Neuroimaging evidence supports subtle differences in unconscious reward processing, which emerge at the group level and which may not be perceptible to individuals, but which may nonetheless impact an individual's behavior.
Planned Parenthood president forced out as organisation faces US government funding cuts
Authors: Janice Hopkins Tanne
Journal: BMJ (2019)

The president and chief executive of Planned Parenthood, Leana Wen, left her job on Tuesday over “philosophical differences” about the organisation’s direction. Wen, the former health commissioner of Baltimore, Maryland, had been in the job for only eight months.

Her departure comes as the organisation—which provides family planning advice and services to women on low incomes, and is a favourite target of President Donald Trump and anti-abortion groups—faces cuts of nearly $60m (£48m; €54m) in government funding.

Although abortion remains legal in the US, state restrictions mean that it is increasingly difficult for women to access.1 Contraception has also been …
Endocrine therapy use among Medicaid-insured breast cancer survivors with hormone receptor-positive tumors.
Authors: Racquel Elizabeth Kohler, Stephanie B. Wheeler, Katherine Elizabeth Reeder-Hayes, Ravi K. Goyal, Kristen Hassmiller Lich, Timothy Smith, Cathy Melvin, Alexis Moore, Hyman Bernard Muss
Journal: Journal of Clinical Oncology (2012)

6017 Background: Estrogen receptor positive (ER+) and progesterone receptor positive (PR+) cancers account for the majority of breast cancer diagnoses and deaths. Among women with ER+ or PR+ breast cancers, endocrine therapy (ET) is the cornerstone of adjuvant therapy and reduces 5-year risk of recurrence by as much as 40%. Observational studies in Medicare and privately-insured populations suggest that ET is underutilized. We sought to characterize ET use in a low-income Medicaid-insured population in North Carolina. Methods: We used Medicaid claims data matched to NC Central Cancer Registry records for women ages 18-64 diagnosed with in situ, stage I or II breast cancer from 2003-2007. We excluded dual eligibles and included only cases enrolled in Medicaid for at least 12 of the 15 months following the index diagnosis. We defined our outcome as receipt of any ET medication (tamoxifen, letrozole, exemestane, or anastroxole) in prescription claims during the 15-month period post-diagnosis, among women with ER+ or PR+ disease. In multivariate logistic regressions, independent variables included age, race, tumor characteristics, receipt of other breast cancer treatments, co-morbidity, rural/urban residence, reason for Medicaid eligibility, involvement in the Breast and Cervical Cancer Control Program (BCCCP), patient-centered medical home enrollment, and diagnosis year. Results: Of the 269 women who met inclusion/exclusion criteria and were ER+ or PR+, only 45% filled a prescription for ET during the study period. In multivariate analyses, being involved in the CDC-affiliated BCCCP was significantly associated with higher likelihood of receipt of guideline-recommended endocrine therapy (Marginal Effect: 0.299, p&lt;0.01), but other independent variables were not significantly correlated with receipt of ET. Conclusions: Results suggest that ET is substantially underutilized in this low-income, vulnerable population and that intervention efforts to improve ET use may be important. Qualitative research is needed to understand the more nuanced, behavioral reasons for ET underuse, which may be related to symptom burden, cost, and patient-provider communication.
Eosinophil extracellular traps activate type 2 innate lymphoid cells through stimulating airway epithelium in severe asthma
Authors: Youngwoo Choi, Young‐Min Kim, Hee‐Ra Lee, Jiyeong Mun, Soyoon Sim, Dong‐Hyun Lee, Duy Le Pham, Seung‐Hyun Kim, Yoo Seob Shin, Seung‐Woo Lee, Hae‐Sim Park
Journal: Allergy (2019)

Abstract Background Activated eosinophils release extracellular traps (EETs), which contribute to airway inflammation in severe asthma (SA). However, the role of EETs in innate immunity has not yet been completely determined. The present study aimed to demonstrate the mechanism of airway inflammation in SA mediated by EETs. Methods Peripheral counts of EET + eosinophils and type 2 innate lymphoid cells (ILC2s) were evaluated in patients with SA (n = 13), nonsevere asthma (NSA, n = 17), and healthy control subjects (HC, n = 8). To confirm the effect of EETs, airway hyperresponsiveness (AHR) and adapted/innate immune responses were assessed in mice. Furthermore, the effects of anti‐IL‐33/TSLP antibody were tested. Results The numbers of EET + eosinophils and ILC2s were significantly elevated in SA, with a positive correlation between these two cells ( r = .539, P &lt; .001). When mice were injected with EETs, we observed significant increases in epithelium‐derived cytokines (IL‐1α, IL‐1β, CXCL‐1, CCL24, IL‐33, and TSLP) and eosinophil/neutrophil count in bronchoalveolar lavage fluid (BALF) as well as an increased proportion of IL‐5‐ or IL‐13‐producing ILC2s in the lungs. When Rag1 −/− mice receiving ILC2s were treated with EETs, increased AHR and IL‐5/IL‐13 levels in BALF were noted, which were effectively suppressed by anti‐IL‐33 or anti‐TSLP antibody. Conclusion EETs could enhance innate and type 2 immune responses in SA, in which epithelium‐targeting biologics (anti‐IL‐33/TSLP antibody) may have a potential benefit.
Cancer risks, beliefs, and health care access among the underprivileged.
Authors: Jean F. Morere, Jérôme Viguier, Xavier B. Pivot, Jean-Yves Blay, Yvan Coscas, Christine Lhomel, François Eisinger
Journal: Journal of Clinical Oncology (2013)

6563 Background: One goal of the current French National Cancer Plan is to reduce health inequities in cancer control. In the present work, an underprivileged population was explored to analyze exposure to cancer risk factors and cancer screening attendance in order to highlight ways to improve cancer control. Methods: Within the nationwide observational study EDIFICE 3, conducted by phone interviews among a representative sample of 1603 subjects aged between 40 and 75 years old, we used the “EPICES” validated questionnaire to examine the association of underserved status with cancer risk factors, beliefs, and health care access. Results: Based on EPICES score, underserved subjects represent 33% of the sample. These subjects subjectively perceive a higher risk of cancer compared to non-underserved subjects (21% vs 14% respectively, p&lt;0.01). They more often consider that the cancer always has an external cause (18% vs 12%, p&lt;0.01), rely less on information from the general practitioner (48% vs 56%, p&lt;0.01) and lay press (28% vs 37%, p&lt;0.05). They trust the national health system less (average score from 1 to 10; 6.0 vs 6.3, p &lt;0.05). They also have more cancer risk factors: BMI (26.0 vs 24.8, p&lt;0.01), active smoking (38% vs 23%, p&lt;0.01) and less practicing sport (42% vs 77%, p&lt;0.01). They have more comorbidities: average (2.2 vs 1.8, p&lt;0.01), at least one (76% vs 65%, p&lt;0.01), anxiety (27% vs 12%, p&lt;0.01), hypertension (24% vs 19%, p&lt;0.05) and cardiovascular disease (13% vs 9%, p&lt;0.05). Among persons with a cancer, underserved subjects have a higher rate of lung cancer (10% of cancers vs 1%, p&lt;0.05). However, no difference in cancer screening attendance was observed between underserved and non-underserved subjects: colorectal cancer (60% vs 60%); breast cancer (94% vs 97%) and prostate cancer (46% vs 52%). Access to healthcare is not an issue (consultations with a general practitioner more frequent for underserved group: 5.4 vs 3.7 per year, p&lt;0.01). Conclusions: To reduce inequities in cancer control, as screening attendance is not discriminating, the effort for upstream interventions should be focused on prevention. Cancer risk factors such as smoking, overweight and a sedentary life style are appropriate targets for communication campaigns.
Radioimmunotherapy efficiency and safety in consolidation and relapse treatment of aggressive B-cell non-Hodgkin lymphoma: An updated analysis of 230 patients of the international RIT-network.
Authors: Karin Hohloch, Henrike Katharina Lankeit, Pier Luigi Zinzani, Michael Lorsbach, Christiane Windemuth-Kiesselbach, Lorenz H. Trumper
Journal: Journal of Clinical Oncology (2012)

8052 Background: In aggressive lymphoma, few reliable clinical data about the use of radioimmunotherapy exist. Pts. with DLBCL registered in the international RIT-Network (RIT-NT) were analyzed with regard to Indication, line of therapy and outcome. Methods: The RIT-NT recruited 1111 pts. between Dec. 2006 and 2010. It is a web-based registry that collects observational data from RIT-treated patients with malignant lymphoma. 232 pts. with DLBCL registered in the database were evaluated in the analysis. Results: 232 pts with DLBCL are registered, 17 pts were excluded. Histologic subtypes: 190 DLBCL, 15 primary mediastinal, 9 large cell anaplastic, 1 intravascular. Median age was 62 years (range 17-88), 27% of pts &gt;70 years old. Stage I 16pts, II 54 pts, III 60 pts, IV 68 pts; 6 extranodal involvement, for 11 pts. stage is not documented. 187 pts had 1-3 previous chemotherapies (Ctx), 21 pts 4-6 previous Ctx, 1 pts had 7 previous Ctx, for 6 pts. previous Ctx is not documented. 15 pts. had previous RIT and 24 pts a stem cell transplantation prior to RIT. 6 pts had bone marrow infiltration prior to RIT, 3 with more than 25%. 87 pts had RIT as first line (8 pts. conditioning, 68 pts consolidation, 1 primary therapy, 10 other), and 84 pts received RIT in relapse (2d to 8 th. line therapy) (2 pts. conditioning, 31 pts consolidation, 26 recurrence, 19 therapy refractory, 6 other). Grade IV° hematotoxicity occured for neutrophils and platelets, grade III° for hemoglobin after RIT. Median time to recovery of blood count was 81 days (range 0-600 days). ORR was 63,3 %; CR 54,4%; PR 8,8%, SD 0,9%, PD 23,7%, N.D. 12%. CR rate first line was 76,3 %, for relapse 44,3%. Mean overall survival (OS) in first line was 26,5 months 14,3 months for pts. treated in relapse or refractory disease. Conclusions: Most pts. with DLBCL in the RIT-N received RIT as consolidation after first line therapy with excellent CR rates and OS compared to published data from risk groups . In relapsed DLBCL RIT is a safe and feasible treatment leading to satisfactory response rates with low toxicity. A prospective randomized phase III trial in front line DLBCL is currently planned (ZEST).
Image Gallery: Nodular pretibial myxoedema
Authors: J.‐W. Liu, D.‐L. Ma
Journal: British Journal of Dermatology (2019)

Funding sources: none. Conflicts of interest: none to declare. Dear Editor, A 39‐year‐old man presented to our clinic with symmetric, indurated, nonpitting cerebriform nodules with a peau d'orange appearance and hypertrichosis on both legs of three 3 years’ duration (Fig. 1a, b). Four years earlier, he had received radioactive iodine treatment for Graves’ disease. The treatment was successful, and he had stopped regular follow‐up after 11 months. Laboratory tests were consistent with hyperthyroidism at the time of presentation. A skin biopsy taken from a nodule on the right lower extremity stained with alcian blue demonstrated abundant deposition of mucin throughout the dermis (Fig. 1a, b). The patient was then diagnosed with nodular pretibial myxoedema (PM). Treatment with methimazole and propranolol was started, and the patient responded well. Topical halometasone ointment was applied directly to the nodules at night and covered with a plastic film. After 5 months of treatment, the nodules had markedly flattened. PM can occur in patients with various types of thyroid function status, hyperthyroidism, hypothyroidism or even euthyroidism. Occlusive dressing with corticosteroids is a safe and effective treatment.1
Partha Kar: Is genuine patient choice possible in the NHS?
Authors: Partha Kar
Journal: BMJ (2019)

Patient choice. Patient empowerment. As doctors we may say that we welcome, want, or support these things—but how much do we mean it? How much does the system actually allow it? How often are we doing any more than the bare minimum to tick a box, in terms of providing patient choice? The uncomfortable answer is that we’ve only just moved beyond paying it lip service.

But giving choice to patients can be tricky. If we say that the patient knows best, we’re bound to spark a debate with colleagues. And the extent to which any …
Safety and Benefit of Using Liver Grafts From Older Donors
Authors: Pablo Beltran Miranda, Miguel Angel Gomez Bravo, Francisco Javier Padillo Ruiz
Journal: JAMA Surgery (2019)

To the Editor We read with great interest the results of the cohort study by Haugen et al1 about liver transplant trends from 2003 to 2016 and the outcomes of older donors. We congratulate the authors for the extensive review and important results.
Meta-analysis of sweetened carbonated beverage consumption and cancer risk.
Authors: Alice Koechlin, Philippe Autier, Peter Boyle
Journal: Journal of Clinical Oncology (2013)

e12548 Background: There is speculation of possible links between sweetened carbonated beverage consumption and the risk of developing cancer. The aim of this study was to examine the association between sweetened, carbonated beverage consumption and cancer risk. Methods: PRISMA guidelines of meta-analyses were followed as closely as possible. Over 50 independent estimates of risk were available, 11 for colas specifically. A random effects meta-analysis was performed with tests for publication bias (Begg, Egger, Macaskill) performed as well as Higgins and Thompson’s I 2 measure of the percentage of heterogeneity between studies which could not be explained by chance. Results: Overall the different sites of cancer, the summary relative risk (SRR) when all 56 independent estimates were considered together was SRR=1.04 (95% CI (0.96, 1.13)). On this overall scale, there appears to be no association between consumption of soft-drinks and the risk of cancer. When individual cancer sites were considered, there was no significant increase, or decrease in the meta-analysis estimate of risk of cancer of the pancreas, bladder, kidney, oesophageal squamous cell or adenocarcinoma, colon, gastric cardia, gastric non-cardia, prostate, breast, larynx and ovary nor from the oral cavity, pharynx, glioma, leukaemia or non-Hodgkin’s lymphoma where only one study was available. There was no evidence in a sensitivity analysis from those studies which reported results separately for coke, pepsi or other colas of an associated risk of pancreas cancer (SRR=1.00, 95% CI (0.61; 1.65)) based on three studies. The results for all other forms of cancers were greatly hampered by poor methodology and small numbers of studies (mainly one report on each cancer site studied). Conclusions: Overall, the findings are reassuring regarding the association between soft drinks, including colas and cancer risk, although the quality of many of the studies is quite poor by acceptable, modern standards and no study has been conducted with use of carbonated beverages as a primary hypothesis.
Dose Optimization for Anticancer Drug Combinations: Maximizing Therapeutic Index via Clinical Exposure-Toxicity/Preclinical Exposure-Efficacy Modeling
Authors: Dean C. Bottino, Mayankbhai Patel, Ekta Kadakia, Jilai Zhou, Chirag Patel, Rachel Neuwirth, Natasha Iartchouk, Rachael Brake, Karthik Venkatakrishnan, Arijit Chakravarty
Journal: Clinical Cancer Research (2019)

Recommended phase II dose (RP2D) determination for combination therapy regimens is a constrained optimization problem of maximizing antitumor activity within the constraint of clinical tolerability to provide a wide therapeutic index. A methodology for addressing this problem was developed and tested using clinical and preclinical data from combinations of the investigational drugs TAK-117, a PI3Kα inhibitor, and TAK-228, a TORC1/2 dual inhibitor.Utilizing free fraction-corrected average concentrations, [Formula: see text] and [Formula: see text], which are the primary pharmacokinetic predictors of single-agent preclinical antitumor activity, a preclinical exposure-efficacy surface was characterized, allowing for nonlinear interactions between growth rate inhibition of the agents on a MDA-MB-361 cell line xenograft model. Logistic regression was used to generate an exposure-effect surface for [Formula: see text] and [Formula: see text] versus clinical toxicity outcomes [experiencing a dose-limiting toxicity (DLT)] in single-agent and combination dose-escalation studies. A maximum tolerated exposure curve was defined at which DLT probability was 25%; predicted antitumor activity along this curve was used to determine optimal RP2D.The toxicity constraint curve determined from early clinical data predicted that any clinically tolerable combination was unlikely to result in greater antitumor activity than either single-agent TAK-117 or TAK-228 administered at their respective MTDs. Similar results were obtained with 10 other cell lines, with one agent or the other predicted to outperform the combination.This methodology represents a general, principled way of evaluating and selecting optimal RP2D combinations in oncology. The methodology will be retested upon availability of clinical data from TAK-117/TAK-228 combination phase II studies.See related commentary by Mayawala et al., p. 6564.
Adhesive Small-Bowel Obstruction—Surgery for All?
Authors: Nahum Beglaibter, Haggi Mazeh
Journal: JAMA Surgery (2019)

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CT response assessment combining reduction in size and arterial enhancement correlates with time to progression in metastatic renal cancer patients treated with TKIs
Authors: P. D. Nathan, A. Vinayan, D. Stott, V. Goh
Journal: Journal of Clinical Oncology (2009)

e16062 Background: Targeted therapy is now the standard of care in advanced Renal Carcinoma (RCC). Response assessment by RECIST criteria is insensitive as treated tumours often have only a modest change in size despite the induction of significant necrosis and does not correlate with time to progression (TTP). The Choi criteria (10% size reduction or 15% contrast enhancement reduction) are routinely used in the assessment of GIST tumours treated with targeted agents. We report the use of combined size and density assessment in RCC metastases treated with either sunitinib or cediranib. Methods: CT scans from 32 patients with metastatic RCC treated with either sunitinib (18) or cediranib (14) were assessed. Scans from 10 patients were not evaluable as non-contrast enhanced scans were performed due to impaired renal function. Scans from a further 2 patients were excluded as they ceased treatment due to toxicity rather than progression. Scans from 20 evaluable patients at baseline and 12 weeks on treatment were assessed using RECIST, Choi, and modified criteria in which both a 10% decrease in size and 15% decrease in enhancement in the arterial phase were required to define a response (PR). A total of 60 lesions were assessed. Response assessment was performed using each of the three methods and correlated with time to disease progression (itself RECIST defined). Statistical analysis was performed using the Mann-Whitney U test. Results: There was no difference in TTP between RECIST defined PR (346.8 days) and SD (328.5 days) (P=0.965). TTP in Choi defined PR (358.4 days) and SD (189.6 days) groups showed improved but non-significant separation of TTP duration (P=0.266). TTP in PR (421.5 days) and SD (200.3 days) groups defined by a combined assessment of reduction in size and enhancement showed greatly improved separation (P=0.064). Conclusions: A combined reduction in both size and arterial phase enhancement of RCC metastases treated with TKIs correlates with time to progression. RECIST and standard Choi criteria appear inferior. No significant financial relationships to disclose.