tbuckley/cabot-search huggingface dataset:
Nutrition for women and children—Are we doing the right things in the right way?
Authors: Lars Åke Persson, Kathleen M. Rasmussen, Huixia Yang
Journal: PLoS Medicine (2019)

The recent 2019 report on the State of Food Security and Nutrition in the World paints a picture of some progress, but also highlights alarming developments in certain areas [1].After a period of decline, hunger is now increasing, and over 2 billion people do not have regular access to safe, nutritious and sufficient food.Hunger has also increased in middle-income countries.Anemia in women continues to be a widespread problem, and there is a gender gap with more women than men being food insecure.One in seven newborns suffered from low birth weight in 2015; there has been no improvement in recent years.The number of children with stunted linear growth has decreased, but this progress is insufficient to meet the 2030 target of halving the total number of stunted children.Currently, almost 150 million children are stunted, and 50 million suffer from wasting.At the same time, overweight and obesity are increasing in all regions of the world, especially among school-age children and adults.Many low-and middle-income countries suffer a double burden of malnutrition, with maternal and child malnutrition a particular problem, alongside increasing occurrence of adult overweight, insulin resistance, diabetes, and cardiovascular diseases [2].In the accompanying PLOS Medicine Special Issue on Maternal and Child Health & Nutrition, important research contributions are provided from three crosscutting perspectives: the ongoing social and nutritional transitions in societies, the womanand-child continuum of health and nutrition care, and that of the Developmental Origins of Health and Disease (DOHaD).The risk of next-generation overweight and obesity is increased when the mother is obese before conception [3].Countries with an ongoing rapid nutritional transition, for example Bangladesh, show drastic increases in overweight and obesity in women of reproductive age [4].This has severe adverse effects for women's health, pregnancy outcomes, and the longterm health of their offspring.In the Special Issue, a number of scientific contributions on the mother-and-child dyad focus on weight change, overweight, obesity and related conditions and outcomes [5][6][7][8].Two studies address how women could be helped to achieve an appropriate weight before pregnancy, and whether achieving that weight improves outcomes.When women with obesity had bariatric surgery to induce weight loss before pregnancy, Zainab Akhter and colleagues show in their systematic review and meta-analysis that the odds of a number of adverse birth outcomes increased [6].In a study on the ELFE birth cohort in France, Marion Lecourgille ´and colleagues considered the role of weight change in women either above or below the upper end of normal body mass index.In both groups, they found that gestational weight gain mediated the effects of pre-pregnancy weight change on infant birth weight [7].
Hemoglobin Utilization in Asplenic and Non-Splenectomized Transfusion Dependent Thalassemia Patients Supported with Pathogen Reduced Red Blood Cell Concentrates in a Phase 3 Study (SPARC)
Authors: Yesim Aydinok, Antonio Piga, Raffaella Origa, Nina Mufti, Anna Erikson, Anne North, Katie Waldhaus, Christine Ernst, Jin-Sying Lin, Norman Huang, Richard J. Benjamin, Laurence Corash
Journal: Blood (2018)
P025 Disturbed sexual functioning in female patients with systemic sclerosis
Authors: B Hermankova, M Spiritovic, H Smucrova, S Oreska, H Storkanova, K Pavelka, J Vencovsky, L Senolt, R Becvar, M Tomcik
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> Systemic sclerosis (SSc) is a chronic autoimmune disease leading to various physical and psychological impairments including sexual dysfunction. <h3>Objectives</h3> The aim of this study was to assess sexual functions/quality of life and pelvic floor function in female SSc patients compared to age-/sex-matched healthy controls (HC), and to analyze the potential impact of disease activity, fatigue, physical activity and depression. <h3>Methods</h3> In total, 41 women with SSc (mean age: 50.9, disease duration: 5.8 years, lcSSc/dcSSc: 18/23, mRSS: 13.6, ESSG activity index: 2.5), who fulfilled the ACR/EULAR 2013 criteria, and 41 healthy controls (mean age: 50.9) without rheumatic diseases filled in 12 well-established and validated questionnaires assessing sexual function/quality of life, pelvic floor function, fatigue, physical activity and depression. We used the following questionnaires: Female Sexual Function Index (FSFI), Brief Index of Sexual Function for Women (BISF-W), Sexual Quality of Life Questionnaire (SQoL-F), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), Pelvic Floor Distress Inventory Questionnaire (PFIQ7), Fatigue Impact Scale (FIS), Beck's Depression Inventory II (BDI II), Health Assessment Questionnaire (HAQ), Scleroderma Health Assessment Questionnaire (SHAQ) and Human Activity Profile (HAP). <h3>Results</h3> Compared to HC, patients with SSc had significantly higher prevalence and greater severity of sexual dysfunction (FSFI, BISF-W: in all subscales as well as total scores), dysfunction of pelvic floor (PISQ-12, PFIQ7), and worse sexual quality of life (SQol-F) (table). Worse scores in SSc patients were associated with higher disease activity [ESSG activity index: SQol-F (r=−0.364, p=0.0443)], greater fatigue [FIS correlated negatively with both FSFI, and BISF-W], more severe depression [BDI-II: FSFI (r=−0.553, p=0.0002), BISF-W (r=−0.514, p=0.0007)], deteriorated quality of life [SHAQ: FSFI (r=−0.536, p=0.0003), BISF-W (r=−0.563, p=0.0001), SQol-F (r=−0.338, p=0.0382), PISQ-12 (r=0.563, p=0.0051)], and worse ability to perform physical activities [HAP: FSFI (r=0.407, p=0.0082), BISF-W (r=0.409, p=0.0078)]. <h3>Conclusions</h3> Women with SSc reported significantly impaired sexual function, sexual quality of life and pelvic floor function than age-matched healthy controls. Worse scores in SSc were associated with disease activity, physical activity, fatigue, depression and quality of life. <h3>Acknowledgements</h3> Supported by AZV-16-33574A, MHCR 023728, and SVV – 2 60 373. <h3>Disclosure of Interest</h3> None declared.
Sorafenib Population Pharmacokinetics and Skin Toxicities in Children and Adolescents with Refractory/Relapsed Leukemia or Solid Tumor Malignancies
Authors: Hiroto Inaba, John C. Panetta, Stanley B. Pounds, Lei Wang, Lie Li, Fariba Navid, Sara M. Federico, Eric D. Eisenmann, Aksana Vasilyeva, Yong-Dong Wang, Sheila Shurtleff, Ching-Hon Pui, Tanja A. Gruber, Raul C. Ribeiro, Jeffrey E. Rubnitz, Sharyn D. Baker
Journal: Clinical Cancer Research (2019)

To determine the pharmacokinetics and skin toxicity profile of sorafenib in children with refractory/relapsed malignancies.Sorafenib was administered concurrently or sequentially with clofarabine and cytarabine to patients with leukemia or with bevacizumab and cyclophosphamide to patients with solid tumor malignancies. The population pharmacokinetics (PPK) of sorafenib and its metabolites and skin toxicities were evaluated.In PPK analysis, older age, bevacizumab and cyclophosphamide regimen, and higher creatinine were associated with decreased sorafenib apparent clearance (CL/f; P < 0.0001 for all), and concurrent clofarabine and cytarabine administration was associated with decreased sorafenib N-oxide CL/f (P = 7e-4). Higher bilirubin was associated with decreased sorafenib N-oxide and glucuronide CL/f (P = 1e-4). Concurrent use of organic anion-transporting polypeptide 1B1 inhibitors was associated with increased sorafenib and decreased sorafenib glucuronide CL/f (P < 0.003). In exposure-toxicity analysis, a shorter time to development of grade 2-3 hand-foot skin reaction (HFSR) was associated with concurrent (P = 0.0015) but not with sequential (P = 0.59) clofarabine and cytarabine administration, compared with bevacizumab and cyclophosphamide, and with higher steady-state concentrations of sorafenib (P = 0.0004) and sorafenib N-oxide (P = 0.0275). In the Bayes information criterion model selection, concurrent clofarabine and cytarabine administration, higher sorafenib steady-state concentrations, larger body surface area, and previous occurrence of rash appeared in the four best two-predictor models of HFSR. Pharmacokinetic simulations showed that once-daily and every-other-day sorafenib schedules would minimize exposure to sorafenib steady-state concentrations associated with HFSR.Sorafenib skin toxicities can be affected by concurrent medications and sorafenib steady-state concentrations. The described PPK model can be used to refine exposure-response relations for alternative dosing strategies to minimize skin toxicity.
The Game Is Afoot
Authors: Nicholas Yozamp, Jason L. Hornick, Christopher P. Chiodo, Amy L. Miller, Joseph Loscalzo
Journal: New England Journal of Medicine (2020)

A 63-year-old woman presented with several months of pain in both ankles. She had had a fracture of the left tibial plateau 2 years earlier, followed by a fracture of the left medial femoral condyle. She reported no fevers, weight loss, or pain elsewhere.
Does health-related quality of life (HRQL) improve for patients who respond to chemotherapy? Analysis of patients with advanced pancreas cancer (APC) receiving gemcitabine on Cancer and Leukemia Group B (CALGB) study #80303
Authors: D. Romanus, L. Archer, X. Wang, R. Goldberg, M. Mulcahy, H. Kindler, D. Schrag
Journal: Journal of Clinical Oncology (2007)

9008 Background: Gemcitabine chemotherapy for APC is palliative and confers only modest survival advantage. Therefore HRQL concerns are of paramount importance. Methods: We compared HRQL scores based on response to chemotherapy at the first interval restaging (8 weeks). We evaluated HRQL at baseline on paper, and then q8 weeks by phone using the EQ5D instrument in patients with APC participating in a double-blind, randomized trial comparing overall survival for gemcitabine with bevacizumab (GB) or placebo (GP). The EQ5D is a HRQL measure whose composite (C) and visual analog scale (VAS) scores respectively reflect societal and patient valuations. Results: Among 552 patients starting protocol treatment, characteristics did not differ between 359 who did and 193 who didn’t complete baseline assessments. Patients who didn’t complete 8 week assessments were more likely to have died, progressed or discontinued protocol therapy. Changes in EQ5D scores from baseline to 8 weeks did not differ by treatment arm (p-values=0.84, 0.79 for C and VAS scales, Wilcoxon rank sum test). At 8 weeks, all patients and those with progressive disease had a modest decline in VAS scores (p-values≤0.02, Wilcoxon signed rank test). Comparisons of changes from baseline in C scores at 8 week follow-up revealed no differences within other response group strata (all p-values &gt; 0.05). Conclusions: Based on this preliminary analysis, gemcitabine therapy was not associated with higher HRQL scores, nor was there any strong association between tumor response and HRQL. To increase data representativeness, future APC trials should assess HRQL more often than every 8 weeks. HRQL Scores Based on Gemcitabine Response Strata. Values are Mean (SD) [Table: see text] [Table: see text]
Treatment of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) Post-Hematopoietic Stem Cell Transplantation (HSCT) in Patients with Neuroblastoma: Final Data from the Defibrotide Expanded-Access Program
Authors: Stephan A Grupp, Brandon Triplett, Araz Marachelian, Sonata Jodele, Robert J. Ryan, Robin L. Hume, William Martin Tappe, Paul G Richardson
Journal: Blood (2017)
Effect of Low-Dose Supplementation of Arginine Vasopressin on Need for Blood Product Transfusions in Patients With Trauma and Hemorrhagic Shock
Authors: Carrie A. Sims, Daniel Holena, Patrick Kim, Jose Pascual, Brian Smith, Neils Martin, Mark Seamon, Adam Shiroff, Shariq Raza, Lewis Kaplan, Elena Grill, Nicole Zimmerman, Christopher Mason, Benjamin Abella, Patrick Reilly
Journal: JAMA Surgery (2019)

Current therapies for traumatic blood loss focus on hemorrhage control and blood volume replacement. Severe hemorrhagic shock, however, is associated with a state of arginine vasopressin (AVP) deficiency, and supplementation of this hormone may decrease the need for blood products in resuscitation.To determine whether low-dose supplementation of AVP in patients with trauma (hereinafter referred to as trauma patients) and with hemorrhagic shock decreases their need for transfused blood products during resuscitation.This randomized, double-blind placebo-controlled clinical trial included adult trauma patients (aged 18-65 years) who received at least 6 U of any blood product within 12 hours of injury at a single urban level 1 trauma center from May 1, 2013, through May 31, 2017. Exclusion criteria consisted of prehospital cardiopulmonary resuscitation, emergency department thoracotomy, corticosteroid use, chronic renal insufficiency, coronary artery disease, traumatic brain injury requiring any neurosurgical intervention, pregnancy, prisoner status, or AVP administration before enrollment. Data were analyzed from May 1, 2013, through May 31, 2017, using intention to treat and per protocol.After administration of an AVP bolus (4 U) or placebo, participants received AVP (≤0.04 U/min) or placebo for 48 hours to maintain a mean arterial blood pressure of at least 65 mm Hg.The primary outcome was total volume of blood product transfused. Secondary end points included total volume of crystalloid transfused, vasopressor requirements, secondary complications, and 30-day mortality.One hundred patients underwent randomization (49 to the AVP group and 51 to the placebo group). Patients were primarily young (median age, 27 years [interquartile range {IQR}, 22-25 years]) and male (n = 93) with penetrating trauma (n = 79). Cohort characteristics before randomization were well balanced. At 48 hours, patients who received AVP required significantly less blood products (median, 1.4 [IQR, 0.5-2.6] vs 2.9 [IQR, 1.1-4.8] L; P = .01) but did not differ in requirements for crystalloids (median, 9.9 [IQR, 7.9-13.0] vs 11.0 [8.9-15.0] L; P = .22) or vasopressors (median, 400 [IQR, 0-5900] vs 1400 [IQR, 200-7600] equivalent units; P = .22). Although the groups had similar rates of mortality (6 of 49 [12%] vs 6 of 51 [12%]; P = .94) and total complications (24 of 44 [55%] vs 30 of 47 [64%]; P = .37), the AVP group had less deep venous thrombosis (5 of 44 [11%] vs 16 of 47 [34%]; P = .02).Low-dose AVP during the resuscitation of trauma patients in hemorrhagic shock decreases blood product requirements. Additional research is necessary to determine whether including AVP improves morbidity or mortality.ClinicalTrials.gov identifier: NCT01611935.
Effect of oxaliplatin-containing neoadjuvant chemotherapy on tumor volume in locally advanced rectal cancer and sensitivity of surviving tumor cells to radiotherapy.
Authors: Kjersti Flatmark, Knut Hakon Hole, Marie Gron Saelen, Torveig Weum Abrahamsen, Karianne Giller Fleten, Kathrine Roe, Svein Dueland, Therese Seierstad, Anne Hansen Ree
Journal: Journal of Clinical Oncology (2013)

3547 Background: The use of oxaliplatin (OXA) is well established in adjuvant and palliative treatment of colorectal cancer (CRC), but its role in neoadjuvant treatment of locally advanced rectal cancer (LARC) is controversial. Data from the ACCORD 12/0405, STAR-01 and NSABBP R-04 trials suggest no additional clinical benefit of adding OXA to fluoropyrimidine-based preoperative chemoradiotherapy (CRT) in LARC. However, the possibility of reducing risk of systemic recurrence and the use of OXA-containing neoadjuvant chemotherapy (NACT) in liver metastasis warrant further clarification of the role of OXA in neoadjuvant treatment of LARC. Methods: We report results from a non-randomized phase II trial of neoadjuvant treatment of 72 LARC patients, receiving two courses of the Nordic FLOX regimen prior to CRT (25 x 2 Gy; weekly OXA; daily capecitabine). Tumor volumes were calculated from MRI scans taken before and after NACT and 4 weeks after CRT completion. Using OXA resistant human CRC cell lines, the impact of previous OXA exposure on radiosensitivity (1-5 Gy) was examined. Results: Median baseline tumor volume was 16.6 cm 3 (1.1-293 cm 3 ). All tumors, except one, responded to NACT, leaving a median tumor volume of 5.3 cm 3 (0.2-157 cm 3 ), representing a median volume reduction of 63%. In all but three patients, additional tumor volume reduction was observed following subsequent CRT (median tumor volume 5.3 cm 3 ; 0.02-119 cm 3 ; median volume reduction of 68%). Exposure of cell lines to increasing concentrations of OXA resulted in resistance towards the drug. OXA resistant models exhibited increased radiosensitivity compared to OXA sensitive counterparts. Conclusions: OXA-containing NACT led to substantial tumor volume reduction. Additional tumor volume reduction was observed in almost all cases, suggesting that pretreatment with OXA-containing NACT did not preclude tumor response to CRT. Results from experimental models rather suggest that pretreatment with OXA might enhance radiosensitivity of surviving OXA resistant cells. Taken together, our results are in favor of continued exploration of OXA-containing NACT in LARC. Clinical trial information: NCT00278694.
Genomic GPS: using genetic distance from individuals to public data for genomic analysis without disclosing personal genomes
Authors: Kunhee Kim, Hyungryul Baik, Chloe Soohyun Jang, Jin Kyung Roh, Eleazer Eskin, Buhm Han
Journal: Genome biology (2019)

Genomic global positioning system (GPS) applies the multilateration technique commonly used in the GPS to genomic data. In the framework we present here, investigators calculate genetic distances from their samples to reference samples, which are from data held in the public domain, and share this information with others. This sharing enables certain types of genomic analysis, such as identifying sample overlaps and close relatives, decomposing ancestry, and mapping of geographical origin without disclosing personal genomes. Thus, our method can be seen as a balance between open data sharing and privacy protection.
Clinical characteristics of nonosteogenic, non-Ewing’s sarcoma of the bone: Experience at the Toronto Sarcoma Program.
Authors: Zachary William Neil Veitch, Peter Charles Ferguson, Anthony Griffin, Kanan Alshammari, Esmail Mutahar Al-Ezzi, Eoghan Ruadh Malone, Elizabeth Demicco, Brendan Dickson, Charles N. Catton, Peter W. M. Chung, Abha A. Gupta, Albiruni Ryan Abdul Razak, Jay Wunder
Journal: Journal of Clinical Oncology (2019)

11029 Background: Non-osteogenic sarcoma of the bone is a rare entity comprising a heterogenous group of malignant tumors. Clinical characteristics and outcome data are sparse in the literature. We evaluated the characteristics and long-term outcomes of patients (pts) with this disease. Methods: Pts with non-osteogenic sarcoma of the bone treated at the Toronto Sarcoma Program from 1987-2017 were identified from our institutional sarcoma database. Patient characteristics (ie: age, gender, tumor size, histology, grade, necrosis, tumor location), treatment modality (ie: surgical management, chemotherapy, radiotherapy), and survival information were collected. Survival was estimated by Kaplan-Meier (log-rank). Multi-variate analysis (MVA) was used to evaluate characteristics for sarcoma specific survival. Results: Of 130 pts identified, 106 had non-metastatic disease with a median age of 46 (range 18-89). Male-to-female predominance was 1.5:1. Common histologies were undifferentiated pleomorphic sarcoma (UPS; 42%), leiomyosarcoma (21%), and fibrosarcoma (11%). Tumors were generally high grade (59%) and &gt; 5 cm in size (73%). The majority of pts received chemotherapy (68%), with Cisplatin/Doxorubicin based regimens (95%). R0 resection was achieved in 85% of cases. Survival for the entire cohort, showed a median (m)DFS of 8.13 years (95%CI:2.52-18.02), and a mOS of 11.72 (95%CI:7.00-not reached [NR]). Median sarcoma specific survival was NR, however 15- and 25-year survivals were 60.4% and 52.6% respectively. MVA demonstrated axial tumor location (HR = 13.03; p = 0.005), no chemotherapy (HR = 4.50; p = 0.017) and tumor grade (G2: HR = 36.21; p = 0.012; G3: HR = 20.30; p = 0.015) as risk factors for sarcoma specific death. Tumor size &gt; 10cm (p = 0.085) and necrosis &gt; 90% (p = 0.082) trended towards significance. Conclusions: Non-osteogenic sarcoma of the bone is a rare tumor entity, with a predominant UPS histology. Patient outcomes are reasonable, with measurable long-term survival. Axial tumor location, absence of chemotherapy, and high-grade disease predict for worse survival outcome. Further evaluation with larger data series is warranted to more fully understand this disease.
Are Adverse Reproductive Outcomes Associated With the Illness or Its Treatment (or Both)?
Authors: Katherine L. Wisner, Kimberly A. Yonkers
Journal: JAMA Psychiatry (2019)

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Molecular Evolution of Auxin-Mediated Root Initiation in Plants
Authors: Jie Yu, Yuyun Zhang, Wu Liu, Hua Wang, Shaoting Wen, Yijing Zhang, Lin Xu
Journal: Molecular Biology and Evolution (2019)

The root originated independently in euphyllophytes (ferns and seed plants) and lycophytes; however, the molecular evolutionary route of root initiation remains elusive. By analyses of the fern Ceratopteris richardii and seed plants, here we show that the molecular pathway involving auxin, intermediate-clade WUSCHEL-RELATED HOMEOBOX (IC-WOX) genes, and WUSCHEL-clade WOX (WC-WOX) genes could be conserved in root initiation. We propose that the "auxin>IC-WOX>WC-WOX" module in root initiation might have arisen in the common ancestor of euphyllophytes during the second origin of roots, and that this module has further developed during the evolution of different root types in ferns and seed plants.