tbuckley/cabot-search huggingface dataset:
P14.53 Deconstructing pathologically increased MEG network clustering in glioma patients
Authors: S D Kulik, J Derks, T Numan, A Hillebrand, P C de Witt Hamer, M Klein, J J G Geurts, J C Reijneveld, C J Stam, M M Schoonheim, L Douw
Journal: Neuro-Oncology (2019)

Abstract Introduction Functional brain networks in glioma patients are characterized by higher global clustering than healthy controls, indicating stronger connectivity in triads of brain regions when averaging across the entire brain. However, this could be due to either primary increased local clustering of (peri)tumor regions or higher local clustering throughout the entire brain. METHODS Magnetoencephalography recordings of 71 glioma patients and 53 HCs were analyzed by calculating functional connectivity with the phase lag index between source-localized time series of 78 cortical regions of the automated anatomical labelling atlas. Per participant, we calculated (1) global average clustering, (2) local clustering of tumor and non-tumor regions, and (3) Euclidean distance between tumor centroids and of all other region centroids. RESULTS Glioma patients had higher global average clustering (p=0.002) than HCs. This increase was indeed global: there was no difference between tumor and non-tumor regions (p=0.154) and no association between distance and local clustering (p=0.759). When splitting patients into high (top 25%, n=18) and normal global clustering (other 75%, n=53) to more specifically pick up on the determinants of pathological global average clustering, again no localized or distance-dependent effects were found. High clustering patients were younger than patients with normal global clustering (p=0.027). Posthoc analysis into tumor localization preference for particular network regions in the entire patient cohort revealed greater tumor occurrence in regions with high clustering in HC (p&lt;0.001), while patients with high global clustering showed tumors localized in regions with lower clustering in HC (p=0.032). CONCLUSION The functional brain network of a subset of (relatively young) glioma patients is disturbed on a global level, suggesting that treatment thereof might benefit patients. Moreover, our exploratory analyses suggest that gliomas occur more often in normally highly clustered regions, but that tumors occurring in less clustered regions are associated with more extensive global network alterations. These findings may speculatively indicate that patients with and without such pathologically altered global clustering represent distinct phenotypes (both in terms of age and tumor localization) and may also need to be treated as such.
Results of a phase II study of carboplatin and etoposide in patients with progressive metastatic castration refractory prostate cancer (mCRPC) and neuro-endocrine differentiation
Authors: A. Flechon, D. Pouessel, C. Ferlay, D. Perol, P. Beuzeboc, G. Gravis, F. Joly, S. Oudard, G. Deplanque, J. Droz, S. Culine
Journal: Journal of Clinical Oncology (2009)

e16073 Background: Neuro-endocrine differentiation is often observed in the evolution of mCRPC. We assessed the efficacy and toxicity of a platin-based chemotherapy regimen in patients with mCPRC and neuro-endocrine differentiation defined by: either increased circulating neuro-endocrine markers (chromogranin A: CgA, Neuron Specific Enolase: NSE) more than 1.5 X normal serum values and/or visceral metastases confirmed with immunihistochemical proof of neuro-endocrine differentiation on pathological sample. Methods: Sixty patients were included (Simon optimal two stages design with P0 = 20%, P1 = 40%, α = 5% and power 90% for a total of 54 evaluable patients) and were treated by the combination of carboplatin AUC 4 d1 IV and etoposide 100 mg/m 2 /d d1–3 IV every 3 weeks for a maximum of 6 cycles. Efficacy endpoints included PSA and neuro-endocrine marker response rate (defined as a decrease of 50% or greater of the baseline serum value), objective response rate (according to RECIST criteria), and toxicity. Results: Sixty patients were included between April 2005 to January 2008, median age was 67 (range: 45–80). Sixty-seven per cent patients received prior chemotherapy. Patients had bone metastases (78%), lymph nodes involvement (49%), lung metastases (35%), hepatic involvement (33%) and other localizations (17%). The objective response rate was 33% in the 48 assessable patients. A neuro-endocrine response was observed in 28% of 32 evaluable patients for neuro-endocrine marker level (CgA 6%, NSE 25% and both 3%). The PSA response rate was 9%. The most common grade 3–4 treatment-related toxicities were neutropenia (67%), thrombocytopenia (31%), anemia (27%), asthenia (14%) nausea and vomiting grade (12%). There were 6% febrile neutropenia, with one related toxic death. The median follow-up is 9 months. The median response duration was 1.8 months (range: 0.2–13.4 months). The median overall survival is 10 months. Conclusions: Despite an absolute response rate in accordance with the study assumptions, the benefit-risk ratio of this regimen seems unfavourable due to observed toxicities. Another trials must be conducted in order to define a group of patients which may benefit of this regimen. No significant financial relationships to disclose.
The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta‐review of meta‐analyses of randomized controlled trials
Authors: Joseph Firth, Scott B. Teasdale, Kelly Allott, Dan Siskind, Wolfgang Marx, Jack Cotter, Nicola Veronese, Felipe Schuch, Lee Smith, Marco Solmi, André F. Carvalho, Davy Vancampfort, Michael Berk, Brendon Stubbs, Jerome Sarris
Journal: World Psychiatry (2019)

The role of nutrition in mental health is becoming increasingly acknowledged. Along with dietary intake, nutrition can also be obtained from “nutrient supplements”, such as polyunsaturated fatty acids (PUFAs), vitamins, minerals, antioxidants, amino acids and pre/probiotic supplements. Recently, a large number of meta‐analyses have emerged examining nutrient supplements in the treatment of mental disorders. To produce a meta‐review of this top‐tier evidence, we identified, synthesized and appraised all meta‐analyses of randomized controlled trials (RCTs) reporting on the efficacy and safety of nutrient supplements in common and severe mental disorders. Our systematic search identified 33 meta‐analyses of placebo‐controlled RCTs, with primary analyses including outcome data from 10,951 individuals. The strongest evidence was found for PUFAs (particularly as eicosapentaenoic acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention‐deficit/hyperactivity disorder, whereas there was no evidence for schizophrenia. Folate‐based supplements were widely researched as adjunctive treatments for depression and schizophrenia, with positive effects from RCTs of high‐dose methylfolate in major depressive disorder. There was emergent evidence for N‐acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. All nutrient supplements had good safety profiles, with no evidence of serious adverse effects or contraindications with psychiatric medications. In conclusion, clinicians should be informed of the nutrient supplements with established efficacy for certain conditions (such as eicosapentaenoic acid in depression), but also made aware of those currently lacking evidentiary support. Future research should aim to determine which individuals may benefit most from evidence‐based supplements, to further elucidate the underlying mechanisms.
Cancer-specific mortality and competing causes of death in older adults: A prospective, multicenter cohort study (ELCAPA-19).
Authors: Deborah Assouan, Elena Paillaud, Philippe Caillet, Emmanuelle Kempf, Helene Vincent, Etienne Brain, Godelieve Rochette de Lempdes, Cyril Touboul, Claudia Martinez-Tapia, Mylene Allain, Sylvie Bastuji-Garin, Olivier Hanon, Marie Laurent, Florence Canoui-Poitrine
Journal: Journal of Clinical Oncology (2019)

11547 Background: Among older adults with cancer, comorbidities compete with cancer as the cause of death. The objectives were to quantify the proportion and rate of cancer-specific death in older patients with cancer, and to analyze the associations between geriatric factors and cancer death. Methods: Between January 2007 and December 2014, older patients with cancer were prospectively included by the ELCAPA cohort study’s eight investigating centers. Competing risk methods were used to estimate 6-month and 3-year cancer mortality rates and to probe associations between geriatric factors and cancer death. Results: A total of 1678 patients were included (mean ± standard deviation age: 81.3 ± 5.8; women: 49%). The most common cancers were colorectal (19%), breast (17%) and urinary (15%) cancers and 49% had metastasis. After a median follow-up period of 34 months, a total of 948 deaths were observed. Of the 282 deaths in non-metastatic patients, 203 (72%; 95% confidence interval (CI): [66%-77%]) were attributable to cancer. This proportion was 92% (89–94; N = 448/498) for metastatic patients. The 6-month and 3-year cancer mortality rates was respectively 12% (9–15) and 34% (29-38) for non-metastatic tumors and 45% (41–49) and 83% (80–87) for metastatic stage tumors. At 6 months, the geriatric factors independently associated with cancer death were a dependency in activities of daily living (ADL) score ≤ 5 (adjusted subhazard ratio: 2.11 (95%CI: [1.68–2.64]), mobility impairment (Timed Get Up and Go (TGUG) test time &gt; 20 s (1.40 [1.05–1.87]) or inability to perform the TGUG (2.41 [1.67–3.48])) and comorbidities (total Cumulative Index Rating Scale-Geriatric score ≥13) (1.59 [1.23–2.06]). At 3 years, the independently associated factors were ADL ≤ 5 (1.60, [1.34–1.91]), TGUG &gt; 20 s (1.28, [1.04–1.59]) or inability to perform TGUG (2.02 [1.47–2.79]), and cognitive impairment (1.23 [1.01–1.50]). Conclusions: Most older adults with cancer die from this disease and not from other comorbidities. However, geriatric parameters (dependency, impaired mobility, comorbidities, and cognitive impairment) are independently associated with cancer death. These geriatric impairments should be taken into account when assessing the cancer patient’s prognosis in clinical practice. Clinical trial information: NCT02884375.
A payment of ecosystem services programme leveraging ecological restoration, public health, and livelihood in a family farm-dominated landscape
Authors: Abdon Schmitt Filho, Joshua Farley, Paulo Sinisgalli, Lui Schmitt
Journal: The Lancet Planetary Health (2019)

Society must increase food production and restore vital ecosystem services or suffer unacceptable consequences. Unfortunately, conventional agriculture might be the single greatest threat to ecosystem function. At the same time, reducing ecologically harmful agricultural inputs or restoring farmlands to native ecosystems threatens food production. We fell into this predicament because we designed agricultural and economic systems that failed to account for ecosystem services, and the path forward requires redesigning both systems. Agroecology—which applies ecological principles to design sustainable farming methods that can increase food production, wean us away from non-renewable and harmful agricultural inputs, and restore ecosystem services—promises to be an appropriate redesign of agricultural systems. In Santa Rosa de Lima (Santa Catarina, Brazil), we are working with small family farmers, local and state government, and non-government organisations to develop multifunction riparian forests (MultRF) and High biodiversity silvopastoral systems (SPSnuclei) that achieve these goals, as well as the policies required for the adoption and dissemination. Appropriate policies must recognise that agricultural land can be managed for multiple ecosystem services, some of which directly benefit the farmer and market production, while others flow to society as a whole at different spatial levels, and hence are public goods. Ongoing research suggests that MultRFs and SPSnuclei can generate crucial ecosystem services like controlling blackflies, but incur initial investments. Farmers cannot be expected to prioritise the needs of society over those of their family, even when the former is socially optimal. This paper describes a pilot project for payments for ecosystem services for an agroecology scheme in Santa Rosa de Lima Southern Brazil, designed as participatory action research by the Silvopastoral and Ecological Restoration Lab (Universidade Federal de Santa Catarina) to address these challenges. Funding CAPES & CNPq & Gund IE. Contributors All cited authors were fully involved on the design of the PSA program discussed. Declaration of interests We declare no competing interests.
Posttraumatic Stress Disorder Is Associated with Increased Risk of Ovarian Cancer: A Prospective and Retrospective Longitudinal Cohort Study
Authors: Andrea L. Roberts, Tianyi Huang, Karestan C. Koenen, Yongjoo Kim, Laura D. Kubzansky, Shelley S. Tworoger
Journal: Cancer Research (2019)

Ovarian cancer is the deadliest gynecologic cancer. Chronic stress accelerates tumor growth in animal models of ovarian cancer. We therefore postulated that posttraumatic stress disorder (PTSD) may be associated with increased risk of ovarian cancer. We used data from the Nurses' Health Study II, a longitudinal cohort study with 26 years of follow-up, conducted from 1989 to 2015 with 54,710 subjects. Lifetime PTSD symptoms were measured in 2008. Self-reported ovarian cancer was validated with medical records. Risk of ovarian cancer was estimated with Cox proportional hazards models and further adjusted for known ovarian cancer risk factors (e.g., hormonal factors) and health risk factors (e.g., smoking). Fully prospective secondary analyses examined incident ovarian cancer occurring after PTSD assessment in 2008. In addition, we examined associations by menopausal status. During follow-up, 110 ovarian cancers were identified. Women with high PTSD symptoms had 2-fold greater risk of ovarian cancer versus women with no trauma exposure [age-adjusted HR = 2.10; 95% confidence interval (CI), 1.12-3.95]. Adjustment for health and ovarian cancer risk factors moderately attenuated this association (HR = 1.86; 95% CI, 0.98-3.51). Associations were similar or moderately stronger in fully prospective analyses (age-adjusted HR = 2.38; 95% CI, 0.98-5.76, N cases = 50) and in premenopausal women (HR = 3.42; 95% CI, 1.08-10.85). In conclusion, we show that PTSD symptoms are associated with increased risk of ovarian cancer. Better understanding of the underlying molecular mechanisms could lead to interventions that reduce ovarian cancer risk in women with PTSD and other stress-related mental disorders. SIGNIFICANCE: PTSD is associated with ovarian cancer risk, particularly in premenopausal women. Understanding the underlying molecular mechanisms will aid in formulating ways to reduce ovarian cancer risk associated with chronic stress.
Fluorescence Lifetime-Based Tumor Contrast Enhancement Using an EGFR Antibody–Labeled Near-Infrared Fluorophore
Authors: Rahul Pal, Homan Kang, Hak Soo Choi, Anand T.N. Kumar
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Imaging techniques for highly specific detection of cancer cells in vivo can have applications ranging from preclinical drug discovery studies to clinical cancer diagnosis and surgical therapy. Although fluorescence imaging using cancer-targeted antibodies has shown promise, nonspecific probe accumulation in tissue results in significant background fluorescence, reducing detection sensitivity using traditional intensity–based continuous-wave (CW) fluorescence imaging. Here we demonstrate that fluorescence lifetime (FLT) imaging can provide significant tumor contrast enhancement over CW intensity in preclinical models of human breast cancer. Experimental Design: Mice bearing MDA-MB-231 tumors were injected with anti-EGFR antibody conjugated to the fluorescent dye IRDye 800CW (anti-EGFR-800). Time domain fluorescence imaging was performed in vivo and in situ up to 48 hours after dye injection. Results: Mice injected with anti-EGFR-800 showed a significantly longer FLT (0.7 ± 0.03 ns) compared with the FLT of nonspecific probe uptake in liver (0.63 ± 0.05 ns), providing a dramatic improvement in sensitivity and specificity compared with CW intensity. IgG antibody–conjugated IRDye 800CW did not show an increased FLT compared with normal tissue, suggesting that the FLT increase of anti-EGFR-800 in tumors was associated with receptor expression. Using serial surgery, we show that FLT allows the detection of smaller residual tumors in the surgical bed than possible using CW intensity. Conclusions: Our data suggest that FLT can significantly enhance tumor contrast using fluorescently labeled antibodies, thereby accelerating the efficient clinical application of these probes for margin assessment in image-guided surgery and for highly specific detection of tumor receptors in vivo.
Safety and efficacy of AMG 714 in patients with type 2 refractory coeliac disease: a phase 2a, randomised, double-blind, placebo-controlled, parallel-group study
Authors: Christophe Cellier, Gerd Bouma, Tom van Gils, Sherine Khater, Georgia Malamut, Laura Crespo, Pekka Collin, Peter H R Green, Sheila E Crowe, Wayne Tsuji, Eric Butz, Nadine Cerf-Bensussan, Elizabeth Macintyre, Jane R Parnes, Francisco Leon, Olivier Hermine, Chris J Mulder, Bana Jabri, Joseph Murray, Anthony DiMarino, Ciaran P Kelly, Valerie Byrnes, David Sanders, Knut EA Lundin, Michael Schumann, Hetty Bontkes, Bertrand Meresse, Garbiñe Roy Ariño, Govind Bhagat, Keijo Viiri, Samuli Rounioja, Jack Bui, Raquel Perez Maseda, Carlota García-Hoz, Amelie Trinquand, George Vlad, Marios Hadjivassiliou, Michel Azizi, Anne Blanchard, Beth Llewellyn, Ashleigh Palmer, Ralph Raymond
Journal: The Lancet. Gastroenterology & hepatology (2019)
Dermal papilla cell culture under hypoxia
Authors: M. Zheng, Y.‐J. Jang, N. Choi, D.‐Y. Kim, T.W. Han, J. H. Yeo, J. Lee, J.‐H. Sung
Journal: British Journal of Dermatology (2019)

Hair loss is most frequently associated with aging or hormonal imbalances, which result in follicular stem cells not being able to regenerate hair follicles (HFs). Many patients take medication or have hair transplantation to resolve hair loss, but there are limitations such as cost, side effects, and so on. Hair transplantation is a common way to treat severe hair loss. However, hair transplantation is based on redistribution of hair follicles without any new follicle formation. Lots of researchers have focused on developing methods to regenerate new hair follicles. Reduced HFs results in progressive hair thinning/loss, and is associated with a failure to maintain the right number of dermal papilla cells (DPC), which specifies hair size, shape and lifecycle. DPCs play a key role in hair regeneration. Therefore, tremendous efforts have been made to promote DPCs’ ability to induce new hair growth. This study looked at how to use hypoxia, a cue that regulates many processes in the body, to improve culture conditions (how the cells are grown in the lab) for DPCs, to help produce DPCs in vitro (in the lab) and maintain their hair inductivity in vivo (in people).
National Trends in the Provision of Human Milk at Hospital Discharge Among Very Low-Birth-Weight Infants
Authors: Margaret G. Parker, Lucy T. Greenberg, Erika M. Edwards, Danielle Ehret, Mandy B. Belfort, Jeffrey D. Horbar
Journal: JAMA Pediatrics (2019)

Human milk confers important health benefits to very low-birth-weight (VLBW) infants (≤1500 g). The extent to which the use of human milk has changed over time and the factors associated with human milk use nationally in this population are poorly understood.
Molecular imaging of bacterial infections: Overcoming the barriers to clinical translation
Authors: Alvaro A. Ordonez, Mark A. Sellmyer, Gayatri Gowrishankar, Camilo A. Ruiz-Bedoya, Elizabeth W. Tucker, Christopher J. Palestro, Dima A. Hammoud, Sanjay K. Jain
Journal: Science Translational Medicine (2019)

Molecular imaging could fulfill unmet clinical needs for diagnosing and monitoring bacterial infections, if translational barriers are addressed.
Quantifying the consumption, nutrition, and greenhouse gas emission effects of dietary guidelines in China: a modelling study
Authors: Sabina Ciorasteanu
Journal: The Lancet Planetary Health (2019)

BackgroundThe rapid nutrition transition China is now ongoing; the so-called westernisation of diets has been negatively affecting both human health and that of the environment. Against this backdrop, the Chinese government released new Dietary Guidelines (CDG) in 2016 and has been actively promoting them since. Our research makes use of quantitative modelling and aims to determine whether adjusting the average Chinese diet, so that it fulfils dietary requirements, could lead to nutritional and environmental co-benefits. Moreover, we want to determine the maximum reduction in greenhouse gas emissions (GHGEs) that could be achieved while simultaneously consuming a healthy diet.MethodsA diet optimisation model is used to simulate, quantify and compare the effects on the consumption of 19 food groups, and associated levels of GHGEs, resulting from two different scenarios: consumers complying with either the CDG or the WHO dietary norms. Subsequent simulations set maximum emission limits for the optimised diets and progressively reduce emissions by 5%. Four waves of consumption and price survey data from the China Health and Nutrition Survey are used in the analysis, while LCA estimates of GHGEs are compiled from the appropriate literature.FindingsPreliminary results show that outcomes under the two scenarios differ significantly, both nutritionally and in terms of GHGEs. Adopting the CDG would lead to a considerable intensification of emissions for both men and women, while adhering to the WHO norms would marginally increase emissions for women and slightly decrease emissions for men. However, we find a 10% reduction in GHGEs relative to current levels could be achieved, under both scenarios, through healthy and realistic dietary change. The maximum decrease in emissions achievable in the CDG model is 15%. The WHO models with a more drastic decrease in emissions (30% and 40%) involve major dietary change and lead to less balanced and varied diets compared with existing ones.InterpretationOur quantitative estimates show the potential for dietary guidelines to lead to environmental and health co-benefits, but only if they are specifically formulated to include environmental considerations. Achieving a major reduction in GHGEs through diets involves clear trade-offs between nutritional and environmental considerations.FundingNone.
Differences in Predictors of Mortality and Resource Utilization Among Adult Patients with Acute Lymphocytic Leukemia and Acute Myeloid Leukemia
Authors: Manoj P Rai, Heather Laird-Fick, Prabhjot Singh Bedi, Justin D. Kaner, Samanjit Kaur Kandola, Shilpa Kavuturu, Nishant Tageja, Marwan S Abougergi, Stanley M. Marks, James B. Bussel
Journal: Blood (2018)