bluuebunny/crossref_metadata_2025_split huggingface dataset:
Our Essential and Endangered Dentist–Scientist Workforce
Authors: D’Souza R.N. , Colombo J.S. , Embree M.C. , Myers J.M. , DeRouen T.A. 
Published: October 2016

Future advances in dental medicine rely on a robust and stable pipeline of dentist–scientists who are dedicated to research inspired by the patients’ condition. The biomedical research community faces external and internal pressures that have been building over years. This is now threatening the current and future status of basic, translational and patient-oriented research by dentist–scientists who study dental, oral and craniofacial diseases, population sciences, and prevention. The dental academic, research and practicing communities can no longer ignore the warning signs of a system that is under considerable stress. Here, the authors report findings of the Physician–Scientist Workforce Working Group, charged by the National Institutes of Health (NIH) Director, to perform quantitative and qualitative analyses on dentist–scientists by addressing the size, composition and activities of the group, relative to other health professions. From 1999 to 2012, trends in the numbers of grant applications and awards to dentist–scientists point to an overall decline. Disturbing are the low numbers of new investigators who apply for Early Career NIH Programs. While more seasoned dentist researchers enjoy greater success, the average age of first-time funded dentists is 52.7 y for females and 54.6 y for males, with a relatively low number of applications submitted and funded. These new data led the panel to stress the need to expand the capacity of the dentist–scientist workforce to leverage technologies and research opportunities that benefit the profession at-large. Suggestions were made to invest in developing clinical research faculty, including those with foreign degrees, through new training mechanisms. The creation of new alliances between national organizations like the American Association for Dental Research, the American Dental Education Association and the American Dental Association will undoubtedly lead to bold and concerted actions that must be pursued with a sense of urgency. A more supportive culture within dental schools and universities for dentist–scientists is needed, as their success is critical to the future career choices of their mentees. Knowledge Transfer Statement: Advances in dental medicine rely on a pipeline of dentist–scientists who are dedicated to research inspired by the patients’ condition. Despite the recent advancement in technology and innovation, the dental community can no longer ignore the various pressures that threaten the future of the dentist–scientist profession. Here, the authors report findings of the Physician-Scientist Workforce Working Group of NIH that were published in 2014, and draw attention to the key issues threatening the NIH-funded pool of dentist–scientists.
Upper extremity recovery after ischaemic and haemorrhagic stroke: Part of the SALGOT study
Authors: Persson Hanna C , Opheim Arve , Lundgren-Nilsson Åsa , Alt Murphy Margit , Danielsson Anna , Sunnerhagen Katharina S 
Published: October 2016

Introduction The purpose was to explore if there are differences in extent of change in upper extremity motor function and activity capacity, in persons with ischaemic versus haemorrhagic stroke, during the first year post stroke. Patients and methods One hundred seventeen persons with stroke (ischaemic n = 98, haemorrhagic n = 19) and reduced upper extremity function 3 days after onset were consecutively included to the Stroke Arm Longitudinal Study at the University of Gothenburg (SALGOT) from a stroke unit. Upper extremity motor function (Fugl-Meyer Assessment Scale for Upper Extremity (FMA-UE)) and activity capacity (Action Research Arm Test (ARAT)) were assessed at 6 assessments during the first year; age and initial stroke severity were recorded. Differences between groups in extent of change over time of upper extremity motor function and activity capacity were analysed with mixed models repeated measurements method. Results Significant improvements were found in function and activity in both groups within the first month ( p = 0.001). Higher age and more severe stroke had a negative impact on recovery in both groups. Larger improvements of function and activity were seen in haemorrhagic stroke compared to ischaemic, both from 3 days to 3- and 12 months, and from 1 month to 3 months. Both groups reached similar levels of function and activity at 3 months post stroke. Conclusion Although persons with haemorrhagic stroke had initially lower scores than those with ischaemic stroke, they had a larger improvement within the first 3 months, and thereafter both groups had similar function and activity.
Metformin improves defective hematopoiesis and delays tumor formation in Fanconi anemia mice
Authors: Zhang Qing-Shuo , Tang Weiliang , Deater Matthew , Phan Ngoc , Marcogliese Andrea N. , Li Hui , Al-Dhalimy Muhsen , Major Angela , Olson Susan , Monnat Raymond J. , Grompe Markus 
Published: October 2016

Key Points
The widely used diabetes drug metformin improves hematopoiesis and delays tumor formation in a preclinical murine model of FA. Metformin reduces DNA damage in human FA patient–derived cells.
Targeting BTK through microRNA in chronic lymphocytic leukemia
Authors: Bottoni Arianna , Rizzotto Lara , Lai Tzung-Huei , Liu Chaomei , Smith Lisa L. , Mantel Rose , Reiff Sean , El-Gamal Dalia , Larkin Karilyn , Johnson Amy J. , Lapalombella Rosa , Lehman Amy , Plunkett William , Byrd John C. , Blachly James S. , Woyach Jennifer A. , Sampath Deepa 
Published: October 2016

Key Points
Inhibition of HDAC reverses epigenetic silencing to upregulate miRs that target BTK and suppress its downstream prosurvival signaling. We identified a rationale for the dual targeting of BTK when combined with ibrutinib and a strategy to eliminate the C481S-mutant BTK clone.
Mice lacking the conserved transcription factor Grainyhead-like 3 (Grhl3) display increased apposition of the frontal and parietal bones during embryonic development
Authors: Goldie Stephen J. , Arhatari Benedicta D. , Anderson Peter , Auden Alana , Partridge Darren D. , Jane Stephen M. , Dworkin Sebastian 
Published: October 2016

Abstract
Background
Increased apposition of the frontal and parietal bones of the skull during embryogenesis may be a risk factor for the subsequent development of premature skull fusion, or craniosynostosis. Human craniosynostosis is a prevalent, and often serious embryological and neonatal pathology. Other than known mutations in a small number of contributing genes, the aetiology of craniosynostosis is largely unknown. Therefore, the identification of novel genes which contribute to normal skull patterning, morphology and premature suture apposition is imperative, in order to fully understand the genetic regulation of cranial development.

Results
Using advanced imaging techniques and quantitative measurement, we show that genetic deletion of the highly-conserved transcription factor Grainyhead-like 3 (Grhl3) in mice (Grhl3
−/−
) leads to decreased skull size, aberrant skull morphology and premature apposition of the coronal sutures during embryogenesis. Furthermore, Grhl3
−/−
mice also present with premature collagen deposition and osteoblast alignment at the sutures, and the physical interaction between the developing skull, and outermost covering of the brain (the dura mater), as well as the overlying dermis and subcutaneous tissue, appears compromised in embryos lacking Grhl3. Although Grhl3
−/−
mice die at birth, we investigated skull morphology and size in adult animals lacking one Grhl3 allele (heterozygous; Grhl3
+/−
), which are viable and fertile. We found that these adult mice also present with a smaller cranial cavity, suggestive of post-natal haploinsufficiency in the context of cranial development.

Conclusions
Our findings show that our Grhl3 mice present with increased apposition of the frontal and parietal bones, suggesting that Grhl3 may be involved in the developmental pathogenesis of craniosynostosis.
Effects of recall time on cause-of-death findings using verbal autopsy: empirical evidence from rural South Africa
Authors: Hussain-Alkhateeb Laith , Petzold Max , Collinson Mark , Tollman Stephen , Kahn Kathleen , Byass Peter 
Published: October 2016

Abstract
Background
Verbal autopsy (VA) is a widely used technique for assigning causes to non-medically certified deaths using information gathered from a close caregiver. Both operational and cultural factors may cause delays in follow-up of deaths. The resulting time lag—from death to VA interview—can influence ways in which terminal events are remembered, and thus affect cause-of-death assignment. This study investigates the impact of recall period on causes of death determined by VA.

Methods
A total of 10,882 deaths from the Agincourt Health and Demographic Surveillance System (HDSS) with complete VAs, including recall period, were incorporated in this study. To measure seasonal effect, cause specific mortality fractions (CSMFs) were calculated and compared by every cause for VAs undertaken within six months of death and those undertaken from six to 12 months of death. All causes were classified into eight broad categories and entered in a multiple logistic regression to explore outcome by recall period in relation to covariates.

Results
The majority of deaths (83 %) had VAs completed within 12 months. There was a tendency towards longer recall periods for deaths of those under one year or over 65 years of age. Only the acute respiratory, diarrhoeal and other unspecified non-communicable disease groups showed a CSMF ratio significantly different from unity at the 99 % confidence level between the two recall periods. Only neonatal deaths showed significantly different OR for recall exceeding 12 months (OR 1.69; p value = 0.004) and this increased when adjusting for background factors (OR 2.58; p value = 0.000).

Conclusion
A recall period of up to one year between death and VA interview did not have any consequential effects on the cause-of-death patterns derived, with the exception of neonatal causes. This is an important operational consideration given the planned widespread use of the VA approach in civil registration, HDSS sites and occasional surveys.
Medicare D Subsidies and Racial Disparities in Persistence and Adherence With Hormonal Therapy
Authors: Biggers Alana , Shi Yushu , Charlson John , Smith Elizabeth C. , Smallwood Alicia J. , Nattinger Ann B. , Laud Purushottam W. , Neuner Joan M. 
Published: October 2016

Purpose To investigate the role of out-of-pocket cost supports through the Medicare Part D Low-Income Subsidy on disparities in breast cancer hormonal therapy persistence and adherence by race or ethnicity. Methods A nationwide cohort of women age ≥ 65 years with a breast cancer operation between 2006 and 2007 and at least one prescription filled for oral breast cancer hormonal therapy was identified from all Medicare D enrollees. The association of race or ethnicity with nonpersistence (90 consecutive days with no claims for a hormonal therapy prescription) and nonadherence (medication possession rate < 80%) was examined. Survival analyses were used to account for potential differences in age, comorbidity, or intensity of other treatments. Results Among the 25,111 women in the study sample, 77% of the Hispanic and 70% of the black women received a subsidy compared with 21% of the white women. By 2 years, 69% of black and 70% of Hispanic patients were persistent compared with 61% of white patients. In adjusted analyses, patients in all three unsubsidized race or ethnicity groups had greater discontinuation than subsidized groups (white patients: hazard ratio [HR], 1.83; 95% CI, 1.70 to 1.95; black patients: HR, 2.09; 95% CI, 1.73 to 2.51; Hispanic patients: HR, 3.00; 95% CI, 2.37 to 3.89). Racial or ethnic persistence disparities that were present for unsubsidized patients were not present or reversed among subsidized patients. All three subsidized race or ethnicity groups also had higher adherence than all three unsubsidized groups, although with the smallest difference occurring in black women. Conclusion Receipt of a prescription subsidy was associated with substantially improved persistence to breast cancer hormonal therapy among white, black, and Hispanic women and lack of racial or ethnic disparities in persistence. Given high subsidy enrollment among black and Hispanic women, policies targeted at low-income patients have the potential to also substantially reduce racial and ethnic disparities.
Addition of Androgens Improves Survival in Elderly Patients With Acute Myeloid Leukemia: A GOELAMS Study
Authors: Pigneux Arnaud , Béné Marie C. , Guardiola Philippe , Recher Christian , Hamel Jean-Francois , Sauvezie Mathieu , Harousseau Jean-Luc , Tournilhac Olivier , Witz Francis , Berthou Christian , Escoffre-Barbe Martine , Guyotat Denis , Fegueux Nathalie , Himberlin Chantal , Hunault Mathilde , Delain Martine , Lioure Bruno , Jourdan Eric , Bauduer Frederic , Dreyfus Francois , Cahn Jean-Yves , Sotto Jean-Jacques , Ifrah Norbert 
Published: October 2016

Purpose Elderly patients with acute myeloid leukemia (AML) have a poor prognosis, and innovative maintenance therapy could improve their outcomes. Androgens, used in the treatment of aplastic anemia, have been reported to block proliferation of and initiate differentiation in AML cells. We report the results of a multicenter, phase III, randomized open-label trial exploring the benefit of adding androgens to maintenance therapy in patients 60 years of age or older. Patients and Methods A total of 330 patients with AML de novo or secondary to chemotherapy or radiotherapy were enrolled in the study. Induction therapy included idarubicin 8 mg/m2 on days 1 to 5, cytarabine 100 mg/m2 on days 1 to 7, and lomustine 200 mg/m2 on day 1. Patients in complete remission or partial remission received six reinduction courses, alternating idarubicin 8 mg/m2 on day 1, cytarabine 100 mg/m2 on days 1 to 5, and a regimen of methotrexate and mercaptopurine. Patients were randomly assigned to receive norethandrolone 10 or 20 mg/day, according to body weight, or no norethandrolone for a 2-year maintenance therapy regimen. The primary end point was disease-free survival by intention to treat. Secondary end points were event-free survival, overall survival, and safety. This trial was registered at www.ClinicalTrials.gov identifier NCT00700544. Results Random assignment allotted 165 patients to each arm; arm A received norethandrolone, and arm B did not receive norethandrolone. Complete remission or partial remission was achieved in 247 patients (76%). The Schoenfeld time-dependent model showed that norethandrolone significantly improved survival for patients still in remission at 1 year after induction. In arms A and B, respectively, 5-year disease-free survival was 31.2% and 16.2%, event-free survival was 21.5% and 12.9%, and overall survival was 26.3% and 17.2%. Norethandrolone improved outcomes irrelevant to all prognosis factors. Only patients with baseline leukocytes > 30 × 109/L did not benefit from norethandrolone. Conclusion This study demonstrates that maintenance therapy with norethandrolone significantly improves survival in elderly patients with AML without increasing toxicity.
Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation
Authors: Herrera Alex F. , Mei Matthew , Low Lawrence , Kim Haesook T. , Griffin Gabriel K. , Song Joo Y. , Merryman Reid W. , Bedell Victoria , Pak Christine , Sun Heather , Paris Tanya , Stiller Tracey , Brown Jennifer R. , Budde Lihua E. , Chan Wing C. , Chen Robert , Davids Matthew S. , Freedman Arnold S. , Fisher David C. , Jacobsen Eric D. , Jacobson Caron A. , LaCasce Ann S. , Murata-Collins Joyce , Nademanee Auayporn P. , Palmer Joycelynne M. , Pihan German A. , Pillai Raju , Popplewell Leslie , Siddiqi Tanya , Sohani Aliyah R. , Zain Jasmine , Rosen Steven T. , Kwak Larry W. , Weinstock David M. , Forman Stephen J. , Weisenburger Dennis D. , Kim Young , Rodig Scott J. , Krishnan Amrita , Armand Philippe 
Published: October 2016

PurposeDouble-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL.MethodsPatients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed.ResultsA total of 117 patients were included; 44% had DEL and 10% had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% ( P = .049), and the 4-year OS was 56% versus 67% ( P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% ( P = .013), and 4-year OS was 25% versus 61% ( P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS, 0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response ( v complete response) at transplant were associated with inferior OS.ConclusionDEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT.
Body Composition Changes After Very-Low-Calorie Ketogenic Diet in Obesity Evaluated by 3 Standardized Methods
Authors: Gomez-Arbelaez Diego , Bellido Diego , Castro Ana I. , Ordoñez-Mayan Lucia , Carreira Jose , Galban Cristobal , Martinez-Olmos Miguel A. , Crujeiras Ana B. , Sajoux Ignacio , Casanueva Felipe F. 
Published: October 2016

AbstractContext:Common concerns when using low-calorie diets as a treatment for obesity are the reduction in fat-free mass, mostly muscular mass, that occurs together with the fat mass (FM) loss, and determining the best methodologies to evaluate body composition changes.Objective:This study aimed to evaluate the very-low-calorie ketogenic (VLCK) diet-induced changes in body composition of obese patients and to compare 3 different methodologies used to evaluate those changes.Design:Twenty obese patients followed a VLCK diet for 4 months. Body composition assessment was performed by dual-energy X-ray absorptiometry (DXA), multifrequency bioelectrical impedance (MF-BIA), and air displacement plethysmography (ADP) techniques. Muscular strength was also assessed. Measurements were performed at 4 points matched with the ketotic phases (basal, maximum ketosis, ketosis declining, and out of ketosis).Results:After 4 months the VLCK diet induced a −20.2 ± 4.5 kg weight loss, at expenses of reductions in fat mass (FM) of −16.5 ± 5.1 kg (DXA), −18.2 ± 5.8 kg (MF-BIA), and −17.7 ± 9.9 kg (ADP). A substantial decrease was also observed in the visceral FM. The mild but marked reduction in fat-free mass occurred at maximum ketosis, primarily as a result of changes in total body water, and was recovered thereafter. No changes in muscle strength were observed. A strong correlation was evidenced between the 3 methods of assessing body composition.Conclusion:The VLCK diet-induced weight loss was mainly at the expense of FM and visceral mass; muscle mass and strength were preserved. Of the 3 body composition techniques used, the MF-BIA method seems more convenient in the clinical setting.
The impact of FOXO on dopamine and octopamine metabolism in Drosophila under normal and heat stress conditions
Authors: Gruntenko Nataly E. , Adonyeva Natalya V. , Burdina Elena V. , Karpova Evgenia K. , Andreenkova Olga V. , Gladkikh Daniil V. , Ilinsky Yury Y. , Rauschenbach Inga Yu 
Published: October 2016

ABSTRACT
The forkhead boxO transcription factor (FOXO) is a component of the insulin signalling pathway and plays a role in responding to adverse conditions, such as oxidative stress and starvation. In stressful conditions, FOXO moves from the cytosol to the nucleus where it activates gene expression programmes. Here, we show that FOXO in Drosophila melanogaster responds to heat stress as it does to other stressors. The catecholamine signalling pathway is another component of the stress response. In Drosophila, dopamine and octopamine levels rise steeply under heat, nutrition and mechanical stresses, which are followed by a decrease in the activity of synthesis enzymes. We demonstrate that the nearly twofold decline of FOXO expression in foxoBG01018 mutants results in dramatic changes in the metabolism of dopamine and octopamine and the overall response to stress. The absence of FOXO increases tyrosine decarboxylase activity, the first enzyme in octopamine synthesis, and decreases the enzymatic activity of enzymes in dopamine synthesis, alkaline phosphatase and tyrosine hydroxylase, in young Drosophila females. We identified the juvenile hormone as a mediator of FOXO regulation of catecholamine metabolism. Our findings suggest that FOXO is a possible trigger for endocrinological stress reactions.
Control of apico–basal epithelial polarity by the microtubule minus-end-binding protein CAMSAP3 and spectraplakin ACF7
Authors: Noordstra Ivar , Liu Qingyang , Nijenhuis Wilco , Hua Shasha , Jiang Kai , Baars Matthijs , Remmelzwaal Sanne , Martin Maud , Kapitein Lukas C. , Akhmanova Anna 
Published: October 2016

ABSTRACT
The microtubule cytoskeleton regulates cell polarity by spatially organizing membrane trafficking and signaling processes. In epithelial cells, microtubules form parallel arrays aligned along the apico–basal axis, and recent work has demonstrated that the members of CAMSAP/Patronin family control apical tethering of microtubule minus ends. Here, we show that in mammalian intestinal epithelial cells, the spectraplakin ACF7 (also known as MACF1) specifically binds to CAMSAP3 and is required for the apical localization of CAMSAP3-decorated microtubule minus ends. Loss of ACF7 but not of CAMSAP3 or its homolog CAMSAP2 affected the formation of polarized epithelial cysts in three-dimensional cultures. In short-term epithelial polarization assays, knockout of CAMSAP3, but not of CAMSAP2, caused microtubule re-organization into a more radial centrosomal array, redistribution of Rab11-positive (also known as Rab11A) endosomes from the apical cell surface to the pericentrosomal region and inhibition of actin brush border formation at the apical side of the cell. We conclude that ACF7 is an important regulator of apico–basal polarity in mammalian intestinal cells and that a radial centrosome-centered microtubule organization can act as an inhibitor of epithelial polarity.