bluuebunny/crossref_metadata_2025 huggingface dataset:
Apolipoprotein ε4 allele is associated with frailty syndrome: results from the hellenic longitudinal investigation of ageing and diet study
Authors: Mourtzi Niki , Ntanasi Eva , Yannakoulia Mary , Kosmidis Mary , Anastasiou Costas , Dardiotis Efthimios , Hadjigeorgiou Giorgos , Sakka Paraskevi , Scarmeas Nikolaos
Published: July 2019

Apolipoprotein (APOE) ε4 allele has been associated with a number of age-related diseases but previous studies failed to identify any link with Frailty syndrome. The aim of the present study is to investigate the association between APOE ε4 allele and frailty syndrome. We operationalised Frailty according to the Fried definition, and we determined the APOE genotype in 1234 participants of the hellenic longitudinal investigation of ageing and diet study. Logistic regression analyses were performed to examine the association between APOE ε4 allele and frailty. Models were adjusted for age, education, sex, presence (or absence) of hypertension, diabetes, myocardial infraction, coronary disease, congestive heart failure, arrhythmia or other heart disease, family history of dementia and current smoking. The same models were performed after exclusion of patients with dementia and participants with APOE ε2/ε4 genotype. In the fully adjusted model, carriers of APOE ε4 allele had 2.753 higher odds of frailty relative to non-carriers. After trichotomization of APOE genotype, APOE ε4 heterozygotes had 2.675 higher risk of frailty compared to non-carriers while exclusion of patients with dementia or/and APOE ε2/ε4 genotype did not alter the association. The APOE ε4 allele may be a significant biomarker of frailty with diagnostic and prognostic capacity.
Optimization of the Order Menu in the Electronic Health Record Facilitates Test Patterns Consistent With Recommendations in the Choosing Wisely Initiative
Authors: Barry Courtney , Kaufman Steven , Feinstein David , Kim Nami , Gandhi Snehal , Nikolic Dejan , Edmonston Tina Bocker , Bierl Charlene
Published: July 2019

Objectives

Thyroid and rheumatologic autoimmune testing are areas where evidence-based guidance from specialty organizations and Choosing Wisely support utilizing screening tests for autoimmune and thyroid disorders prior to more specialized testing. Adjustment of the orderable options in the electronic health record (EHR) can influence ordering patterns without requiring manual review or additional effort by the clinician.

Methods

The menu was adjusted to reflect recommendations from Choosing Wisely to favor screening tests that automatically reflex to specialized testing on primary care providers’ preference lists. Effectiveness was evaluated by reviewing total orders for individual tests.

Results

Shifts in ordering from individual screening tests (antinuclear antibody and thyrotropin) to ones that reflexed to specialized testing were observed in parallel with significant reductions in the corresponding specialized testing.

Conclusions

Optimization of the EHR laboratory ordering menu can be used to shift ordering patterns toward Choosing Wisely recommendations.
From Pleasure to Pain, and Back Again: The Intricate Relationship Between Alcohol and Nociception
Authors: Robins Meridith T , Heinricher Mary M , Ryabinin Andrey E
Published: July 2019

Aims

A close and bidirectional relationship between alcohol consumption and pain has been previously reported and discussed in influential reviews. The goal of the present narrative review is to provide an update on the developments in this field in order to guide future research objectives.

Methods

We evaluated both epidemiological and neurobiological literature interrogating the relationship between alcohol use and pain for the presence of significant effects. We outlined studies on interactions between alcohol use and pain using both self-reports and objective experimental measures and discussed potential underlying mechanisms of these interactions.

Results

Epidemiological, preclinical and clinical literature point to three major interactions between alcohol use and pain: (a) alcohol use leading to hyperalgesia, (b) alcohol use moderating pain and hyperalgesia and (c) chronic pain as a risk factor predisposing to alcohol relapse. Neurobiological studies using animal models to assess these interactions have transitioned from mostly involuntary modes of experimenter-controlled alcohol administration to self-administration procedures, and increasingly indicate that neuronal circuits implicated in both withdrawal and anticipation stages of alcohol use disorder also have a role in chronic pain. Mechanistically, alterations in GABA, glutamate, the corticotropin-releasing factor system, endogenous opioids and protein kinase C appear to play crucial roles in this maladaptive overlap.

Conclusions

Many of the principles explaining the interactions between alcohol and pain remain on a strong foundation, but continuing progress in modeling these interactions and underlying systems will provide a clearer basis for understanding, and ultimately treating, the damaging aspects of this interaction.
Critical assessment of bioinformatics methods for the characterization of pathological repeat expansions with single-molecule sequencing data
Authors: Chiara Matteo , Zambelli Federico , Picardi Ernesto , Horner David S , Pesole Graziano
Published: July 2019

A number of studies have reported the successful application of single-molecule sequencing technologies to the determination of the size and sequence of pathological expanded microsatellite repeats over the last 5 years. However, different custom bioinformatics pipelines were employed in each study, preventing meaningful comparisons and somewhat limiting the reproducibility of the results. In this review, we provide a brief summary of state-of-the-art methods for the characterization of expanded repeats alleles, along with a detailed comparison of bioinformatics tools for the determination of repeat length and sequence, using both real and simulated data. Our reanalysis of publicly available human genome sequencing data suggests a modest, but statistically significant, increase of the error rate of single-molecule sequencing technologies at genomic regions containing short tandem repeats. However, we observe that all the methods herein tested, irrespective of the strategy used for the analysis of the data (either based on the alignment or assembly of the reads), show high levels of sensitivity in both the detection of expanded tandem repeats and the estimation of the expansion size, suggesting that approaches based on single-molecule sequencing technologies are highly effective for the detection and quantification of tandem repeat expansions and contractions.
Prevention of Criminal Offending: The Intervening and Protective Effects of Education for Aggressive Youth
Authors: Kennedy-Turner Kathleen , Serbin Lisa A , Stack Dale M , Dickson Daniel J , Ledingham Jane E , Schwartzman Alex E
Published: July 2019

Children from poor neighbourhoods showing early aggressive behaviour are at risk for criminal offending. The role of education as a mediator, neighbourhood disadvantage and aggression as moderators for criminal offending were examined in a lower-income, community sample (n = 3,521; 48% males), across a 40-year period from childhood to mid-adulthood. Educational attainment accounted for 15–59% of the effect from childhood risk factors. Aggression was found to be a moderator such that aggressive children with low education had the highest odds of criminal offending. A protective effect was found where aggressive children who managed to obtain more education had reduced odds of offending. Research conceptualizing education as a ‘control’ variable does not address its role in the processes leading to criminal offending.
Association of non-invasive measures of subclinical atherosclerosis and arterial stiffness with mortality and major cardiovascular events in chronic kidney disease: systematic review and meta-analysis of cohort studies
Authors: Kouis Panayiotis , Kousios Andreas , Kanari Athina , Kleopa Daphne , Papatheodorou Stephania I , Panayiotou Andrie G
Published: July 2019

Background

Non-invasive cardiovascular disease (CVD) risk prediction, in subclinical stages, aiming to stratify patients and tailor interventions remains an unmet need in chronic kidney disease (CKD). In this meta-analysis, we summarize the association of carotid intima–media thickness (cIMT), coronary artery calcium score (CACS) and pulse wave velocity (PWV) with all-cause mortality, cardiovascular (CV) mortality and CV events in non-dialysis CKD and patients on haemodialysis.

Methods

Systematic review and meta-analysis of prospective cohort studies.

Results

Out of 27 984 records, a total of 45 studies were eligible for quantitative synthesis; 11 for cIMT, 18 for CACS and 16 for PWV involving 2235, 4904 and 5717 patients, respectively. Meta-analysis was possible from pooled data of five cIMT studies (708 subjects), eight CACS studies (862 subjects) and nine PWV studies (1508 subjects). In dialysis patients, cIMT was associated with all-cause mortality [relative risk (RR) per unit increase: 1.08, 95% confidence interval (CI) 1.00–1.17, I2: 68%] and CV mortality (RR: 1.29, 95% CI 1.14–1.47, I2: 0%). High versus low CACS was associated with all-cause mortality (RR: 2.51, 95% CI 1.66–3.79, I2: 5.7%) and CV events (RR: 3.77 95% CI 2.16–6.58, I2: 20.2%). High versus low PWV was associated with all-cause (RR: 5.34, 95% CI 3.01–9.47, I2: 0%) and CV mortality (RR: 8.55, 95% CI 4.37–16.73, I2: 0%). The combined estimated for all-cause mortality per 1 m/s increment unit in PWV was 1.25 (95% CI 1.17–1.34, I2: 0%) and for CV mortality was 1.24 (95% CI 1.16–1.34, I2: 15.5%). In non-dialysis patients, CACS was associated with CV events (RR: 4.02, 95% CI 1.57–10.29, I2: 63.4%). High versus low PWV was associated with all-cause mortality (RR: 2.52, 95% CI 1.40–4.55, I2: 62.6%).

Conclusions

Non-invasive measures of atherosclerosis and arterial stiffening are associated with all-cause and CV mortality as well as CV events among patients with all stages of CKD. These markers could be considered for the evaluation of CV morbidity and mortality risks. Moreover, the results of this meta-analysis support the study of interventions, with effect on these markers of vascular disease, on long-term CVD outcomes.
Renal outcomes of radioligand therapy: experience of 177lutetium—prostate-specific membrane antigen ligand therapy in metastatic castrate-resistant prostate cancer
Authors: Gallyamov Marat , Meyrick Danielle , Barley Jerome , Lenzo Nat
Published: July 2019

Background

Radioligand therapy (RLT) with 177lutetium (Lu)-labelled prostate-specific membrane antigen (PSMA) ligands has been increasingly used in recent years for therapy of metastatic castrate-resistant prostate cancer (mCRPC). Studies have revealed that 177Lu-PSMA ligand therapy is well tolerated and appears to cause fewer adverse effects than current standard of care third-line treatments. Notably, since 177Lu-PSMA agents are predominantly excreted by kidneys, there are concerns relating to their potential nephrotoxicity and renal outcomes. Although many recent studies have focused on mostly nephrotoxic adverse reactions at up to 3-month follow-up, assessment of renal outcomes after 177Lu-PSMA RLT in longer term follow-up is lacking. The aim of this study was to assess the influence of 177Lu-PSMA RLT on renal function in patients treated for mCRPC at >3 months post-therapy.

Methods

In this retrospective cohort study, we assessed 195 men with progressive mCRPC who had received therapy with 177Lu-PSMA as second- or third-line after standard therapeutic interventions. Patients underwent investigations with 68Ga-PSMA-ligand positron emission tomography/computed tomography scan to confirm PSMA-expressing mCRPC. Eligible patients were required to have estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2, an Eastern Cooperative Oncology Group performance status score <3, no severe liver injury (as characterized by liver function tests) and no significant bone marrow dysfunction. Enrolled patients received two to five cycles of intravenous 177Lu-PSMA I&T or 177Lu-PSMA-617, at 6- to 10-week intervals. Renal outcomes were assessed according to Kidney Disease: Improving Global Outcomes guidelines as incidence of acute kidney injury (AKI), acute kidney disease (AKD) or chronic kidney disease (CKD). All assessments and tests were undertaken between therapy cycles and at follow-up of at least 3 months.

Results

Of 195 assessed men with mCRPC, 110 patients aged [mean ± SD (range)] 70 ± 8 (53–92) years were recruited into this study with median follow-up of 8 (interquartile range 5–12, minimum 3, maximum 29) months and mean baseline eGFR 81 ± 13 mL/min/1.73 m2. Pre-existing CKD was identified in 12% of patients. None of the patients experienced an AKI during RLT. Two AKD and three CKD G3a cases were identified. Analysis of possible impact of prior CKD and major risk factors (hypertension, diabetes, history of AKI) on incidence of AKD or CKD demonstrated relative risk 4.2 [95% confidence interval (CI) 1.23–14.29] and 1.91 (95% CI 1.14–3.12), respectively. However, Fisher’s exact test did not reveal statistical significance of the impact of both conditions.

Conclusions

Current Lu-PSMA RLT protocols appear to carry a mild nephrotoxic risk with the rate of about 4.5%. Prior CKD is potentially the most significant risk factor of post-RLT renal dysfunction.
Transcatheter aortic valve implantation after aortic valve neocuspidization using autologous pericardium: a case report
Authors: Tada Norio , Tanaka Naoyuki , Abe Kazuo , Hata Masaki
Published: July 2019

Background

Aortic valve neocuspidization (AVNeo), a novel surgical procedure used in the treatment of aortic valve diseases, including aortic stenosis (AS), involves the replacement of three aortic valve cusps by glutaraldehyde-treated autologous pericardium. Although reoperation risk is low, no case report on the deterioration of the AVNeo has yet been published.

Case summary

An 80-year-old woman who underwent AVNeo for severe degenerative tricuspid AS 6 years previously complained of shortness of breath. Echocardiographic assessment revealed the reconstructed aortic valve leaflet was elongated, thickened, and marginally calcified resulting in recurrent severe AS. Transcatheter aortic valve implantation using balloon-expandable transcatheter heart valve was successfully performed.

Discussion

To our knowledge, this is the first case report regarding the structural deterioration of the AVNeo resulting in restenosis 6 years after the first surgery. Transcatheter aortic valve implantation is possibly a suitable approach for post-procedural recurrence after AVNeo to avoid redo open-heart surgery which would be of prohibitive risk especially in an elderly population.
Interactions between dark septate endophytes, ectomycorrhizal fungi and root pathogens in vitro
Authors: Berthelot Charlotte , Leyval Corinne , Chalot Michel , Blaudez Damien
Published: July 2019

Dark septate endophytes (DSEs) are widely distributed worldwide and can promote plant growth. Therefore, they are considered potentially important plant allies, especially in stressful environments. Previous studies have reported that DSEs cohabit roots with other microorganisms such as ectomycorrhizal (ECM), endophytic and pathogenic fungi/oomycetes. However, interactions between different DSE species have not yet been reported, and studies on the interactions between DSEs and other fungi are scarce. Using a simple and reproducible pairwise growth assay in vitro, we studied the synergistic/antagonistic interactions between eight DSEs, two ECM fungi and three root pathogens. Most of the DSE/DSE outcomes were neutral. Interestingly, we identified several DSE strains acting in synergy with other strains, as well as strains that could potentially act as biocontrol agents. Notably, three metal-tolerant DSE strains, namely, Cadophora sp., Leptodontidium sp. and Phialophora mustea, could decrease the growth of the root phytopathogens Pythium intermedium, Phytophthora citricola and Heterobasidion annosum. The present data are discussed in the general context of the use of fungal consortia as inocula in the tree-based phytomanagement of marginal lands.
Are health workers reduced to being drug dispensers of antiretroviral treatment? A randomized cross-sectional assessment of the quality of health care for HIV patients in northern Uganda
Authors: Seeberger Ulrike G , Valadez Joseph J
Published: July 2019

High quality of care (QoC) for antiretroviral treatment (ART) is essential to prevent treatment failure. Uganda, as many sub-Saharan African countries, increased access to ART by decentralizing provision to districts. However, little is known whether this rapid scale-up maintained high-quality clinical services. We assess the quality of ART in the Acholi and Lango sub-regions of northern Uganda to identify whether the technical quality of critical ART sub-system needs improvement. We conducted a randomized cross-sectional survey among health facilities (HF) in Acholi (n = 11) and Lango (n = 10). Applying lot quality assurance sampling principles with a rapid health facility assessment tool, we assessed ART services vis-à-vis national treatment guidelines using 37 indicators. We interviewed health workers (n = 21) using structured questionnaires, directly observed clinical consultations (n = 126) and assessed HF infrastructure, human resources, medical supplies and patient records in each health facility (n = 21). The district QoC performance standard was 80% of HF had to comply with each guideline. Neither sub-region complied with treatment guidelines. No HF displayed adequate: patient monitoring, physical examination, training, supervision and regular monitoring of patients’ immunology. The full range of first and second line antiretroviral (ARV) medication was not available in Acholi while Lango had sufficient stocks. Clinicians dispensed available ARVs without benefit of physical examination or immunological monitoring. Patients reported compliance with drug use (>80%). Patients’ knowledge of preventing HIV/AIDS transmission concentrated on condom use; otherwise it was poor. The poor ART QoC in northern Uganda raises major questions about ART quality although ARVs were dispensed. Poor clinical care renders patients’ reports of treatment compliance as insufficient evidence that it takes place. Further studies need to test patients’ immunological status and QoC in more regions of Uganda and elsewhere in sub-Saharan Africa to identify topical and geographical areas which are priorities for improving HIV care.
Effect of Cognitive Behavioral Therapy on Clinical Disease Course in Adolescents and Young Adults With Inflammatory Bowel Disease and Subclinical Anxiety and/or Depression: Results of a Randomized Trial
Authors: van den Brink Gertrude , Stapersma Luuk , Bom Anna Sophia , Rizopolous Dimitris , van der Woude C Janneke , Stuyt Rogier J L , Hendriks Danielle M , van der Burg Joyce A T , Beukers Ruud , Korpershoek Thea A , Theuns-Valks Sabine D M , Utens Elisabeth M W J , Escher Johanna C
Published: July 2019

Background

Anxiety and depressive symptoms are prevalent in patients with inflammatory bowel disease (IBD) and may negatively influence disease course. Disease activity could be affected positively by treatment of psychological symptoms. We investigated the effect of cognitive behavioral therapy (CBT) on clinical disease course in 10–25-year-old IBD patients experiencing subclinical anxiety and/or depression.

Methods

In this multicenter parallel group randomized controlled trial, IBD patients were randomized to disease-specific CBT in addition to standard medical care (CBT + care us usual [CAU]) or CAU only. The primary outcome was time to first relapse in the first 12 months. Secondary outcomes were clinical disease activity, fecal calprotectin, and C-reactive protein (CRP). Survival analyses and linear mixed models were performed to compare groups.

Results

Seventy patients were randomized (CBT+CAU = 37, CAU = 33), with a mean age of 18.3 years (±50% < 18 y, 31.4% male, 51.4% Crohn’s disease, 93% in remission). Time to first relapse did not differ between patients in the CBT+CAU group vs the CAU group (n = 65, P = 0.915). Furthermore, clinical disease activity, fecal calprotectin, and CRP did not significantly change over time between/within both groups. Exploratory analyses in 10–18-year-old patients showed a 9% increase per month of fecal calprotectin and a 7% increase per month of serum CRP in the CAU group, which was not seen in the CAU+CBT group.

Conclusions

CBT did not influence time to relapse in young IBD patients with subclinical anxiety and/or depression. However, exploratory analyses may suggest a beneficial effect of CBT on inflammatory markers in children.
Algebras with Irreducible Module Varieties III: Birkhoff Varieties
Authors: Bobiński Grzegorz
Published: July 2019

We study a family of affine varieties arising from a version of an old problem due to Birkhoff asking for the classification of embeddings of finite abelian $p$-groups. We show that all of these varieties are irreducible and have a dense orbit.
Re-evaluating herd protection by Vi typhoid vaccine in a cluster randomized trial
Authors: Ali Mohammad , Sur Dipika , Kanungo Suman , Qadri Firdausi , Kim Deok Ryun , Islam Taufiqul , Im Justin , Ahmmed Faisal , Chon Yun , Khan Ashraful Islam , Zaman K , Marks Florian , Dutta Shanta , Bhattacharya Sujit K , Clemens John D
Published: July 2019

Background

In a cluster randomized trial (CRT) of a Vi polysaccharide vaccine against typhoid in the slums of Kolkata we found evidence of vaccine herd protection. However, transmission of typhoid into clusters from the outside likely occurred in this densely populated setting, which could have diminished our estimates of vaccine herd protection.

Methods

Eighty clusters (40 in each arm) were randomised to receive a single dose of either Vi or inactivated hepatitis A vaccine. We analysed protection for the entire cluster and for subclusters consisting of residents of the innermost households.

Results

During 2 y of follow-up, total protection was 61% (95% CI 41 to 75), overall protection was 57% (95% CI 37 to 71) and indirect protection was 44% (95% CI 2 to 69). Analyses of the innermost 75% and 50% of households of the clusters showed similar findings. However, in the innermost 25% of households of the clusters, total protection was 82% (95% CI 48 to 94) and overall protection was 66% (95% CI 27 to 84). There was not a sufficient sample size to demonstrate such a trend for indirect protection in these innermost households.

Conclusions

The findings suggest that analyses of the entire cluster may have led to underestimation of herd protection against typhoid by Vi vaccine and that restriction of the analyses to the inner subclusters may have led to a more accurate estimation of vaccine herd effects.
Health informatics and health equity: improving our reach and impact
Authors: Veinot Tiffany C , Ancker Jessica S , Bakken Suzanne
Published: July 2019

Health informatics studies the use of information technology to improve human health. As informaticists, we seek to reduce the gaps between current healthcare practices and our societal goals for better health and healthcare quality, safety, or cost. It is time to recognize health equity as one of these societal goals—a point underscored by this Journal of the American Medical Informatics Association Special Focus Issue, “Health Informatics and Health Equity: Improving our Reach and Impact.” This Special Issue highlights health informatics research that focuses on marginalized and underserved groups, health disparities, and health equity. In particular, this Special Issue intentionally showcases high-quality research and professional experiences that encompass a broad range of subdisciplines, methods, marginalized populations, and approaches to disparities. Building on this variety of submissions and other recent developments, we highlight contents of the Special Issue and offer an assessment of the state of research at the intersection of health informatics and health equity.
US Copyright Office finds Yeezy Boost 350 creative, original and separable: registration granted
Authors: Key Thomas
Published: July 2019

Letter from Karyn Temple, Register of Copyrights and Director, US Copyright Office, to Joseph Petersen, Kilpatrick Townsend & Stockton LLP (8 May 2019)

After refusing to register the Yeezy Boost 350 designs twice—initially as inseparable useful articles and later for want of originality and creativity—the US Copyright Office granted registration to the shoe designs.
Pathological Findings in Male Patients With Anti-N-methyl-d-Aspartate Receptor Encephalitis
Authors: Hirano Makito , Itoh Tatsuki , Fujimura Harutoshi , Inoue Kimiko , Samukawa Makoto , Nose Kazuhiro , Sakamoto Hikaru , Maekura Shunji , Ueno Shuichi , Satou Takao , Nishioka Tsukasa , Kusunoki Susumu , Nakamura Yusaku
Published: July 2019

Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is the most common type of autoimmune encephalitis. The disease predominantly affects women (1:5–1:10), with only 3 reports of autopsy findings in women being published to date. The present study reports findings from the first autopsy performed on a man with anti-NMDAR encephalitis. The patient had some scattered lesions in the limbic system with neuronal loss, gliosis, and microglial activation. The temporal and frontal cortices showed additional patchy demyelination. T-lymphocyte infiltration was detectable in the fusiform gyrus lesion. These findings were partly similar to those reported in female patients. Although clinical differences based on the sex of the patient are reported for this disease, the observed pathological similarities potentially help to establish common therapeutic strategies for all patients. Severe testicular damage was additionally observed in the male patient in this study. Biopsy-proven severe testicular damage was also confirmed in another, previously fertile man who became azoospermic. Moreover, serum follicle-stimulating hormone levels, which often increased in response to disturbed spermatogenesis, were elevated, and testosterone/luteinizing hormone ratio reflecting Leydig cell function was low in all 5 male patients in this study. Overall, these findings suggest similar brain pathology in patients of both sexes and severe testicular damage in male patients.
Robotic cholecystectomy and cholecystoenteric fistula closure in a female with remote cholangitis
Authors: Baratta Vanessa M , Kurbatov Vadim , Le Blanc Justin M , Bowker Brennan , Yavorek George
Published: July 2019

Cholecystocolic fistula (CCF), a connection between the gallbladder and neighboring colon, is a rare entity with little consensus as to the optimal surgical management. Existing case reports have described both open and laparoscopic repairs. We describe the first reported case of a successful robotic repair of a CCF in a 50-year-old woman diagnosed with cholangitis 5 years prior to surgery. The patient had a longitudinal follow-up by a single surgeon, allowing for early diagnosis and repair. This case also includes radiographic imaging over 5 years during the index hospitalization and preoperative workup. This allows for a glimpse into the natural pathogenesis of this disease. After robotic surgery, the patient made a complete recovery with no postoperative complications.
The Management of Newly-Diagnosed Non-muscle Invasive Bladder Cancer in Veterans Integrated Services Network 02 of the Veterans Health Administration
Authors: Caputo Joseph M , Moran George , Muller Benjamin , Keller Alison T , Li Gen , Anderson Christopher B
Published: July 2019

Introduction

Over 1,500 bladder cancers were diagnosed among US Veterans in 2010, the majority of which were non-muscle invasive bladder cancer (NMIBC). Little is known about NMIBC treatment within the Veterans Health Administration. The objective of the study was to assess the quality of care for Veterans with newly-diagnosed NMIBC within Veterans Integrated Service Network (VISN) 02.

Materials and Methods

We used ICD-9 and ICD-10 codes to identify patients with newly-diagnosed bladder cancer from 1/2016–8/2017. We risk-stratified the patients into low, intermediate, and high-risk based on the 2016 American Urological Association Guidelines on NMIBC. Our primary objectives were percentages of transurethral resection of bladder tumors (TURBTs) with detrusor, repeat TURBT in high-risk and T1 disease, high-risk NMIBC treated with induction intravesical therapy (IVT), and responders treated with maintenance IVT. We performed logistic regression for association between distance to diagnosing hospital and receipt of induction IVT in high-risk patients.

Results

There were 121 newly-diagnosed NMIBC patients; 16% low-risk, 28% intermediate-risk, and 56% high-risk. Detrusor was present in 80% of all initial TURBTs and 84% of high-risk patients. Repeat TURBT was performed in 56% of high-risk NMIBC and 60% of T1. Induction IVT was given to 66% of high-risk patients and maintenance IVT was given to 59% of responders. On multivariate logistic regression, distance to medical center was not associated with receipt of induction IVT (OR = 0.99, 95% CI [0.97,1.01], p = 0.52).

Conclusions

We observed high rates of sampling of detrusor in the first TURBT specimen, utilization of repeat TURBT, and administration of induction and maintenance intravesical BCG for high-risk patients among a regional cohort of US Veterans with NMIBC. While not a comparative study, our findings suggest high quality NMIBC care in VA VISN 02.
Postpartum Fitness and Body Mass Index Changes in Active Duty Navy Women
Authors: Rogers Amy E , Khodr Zeina G , Bukowinski Anna T , Conlin Ava Marie S , Faix Dennis J , Garcia Shawn M S
Published: July 2019

Introduction

Active duty Navy women participate in biannual Physical Fitness Assessments (PFAs), which include height and weight measurements and a Physical Readiness Test (PRT). PFAs are waived during pregnancy and resume the cycle after 6 months following maternity leave. The purpose of this study was to compare changes in PFA results over time between women who had or did not have a live birth during the follow-up period, and identify characteristics of women with lower PFA results postpartum.

Materials and Methods

This longitudinal study included 14,142 active duty Navy women, aged 19–40 years, with PFA results during July 2011–June 2015. Multivariable logistic regression, Stuart-Maxwell tests, and mixed effects modeling were used to examine changes in PRT scores and body mass index over time between women with and without a live birth during follow-up. All data were analyzed in 2017. This study was approved by the institutional review boards at the Uniformed Services University Office of Research and the Naval Health Research Center, and informed consent was waived in accordance with 32 CFR § 219.116(d).

Results

Postpartum women had increased odds of PRT failures (AOR = 3.88, 95% CI: 1.44–10.40) and lower PRT scores (AOR = 1.47, 95% CI: 1.12–1.92) up to 2.5 years postpartum, versus women without a live birth. Being enlisted, obese/overweight prepregnancy, and younger were risk factors for suboptimal PFA outcomes. Mean core strength and cardiovascular endurance, but not upper body strength, scores were significantly lower in postpartum women at 1 year postpartum versus women without a live birth.

Conclusions

Our findings show that additional interventions may be needed to assist women in returning to prepregnancy fitness up to 1 year postpartum. Future studies should examine additional factors that may improve postpartum fitness in addition to enhancing maternity leave policies.
Virologic Suppression in U.S. Navy Personnel Living with HIV Infection and Serving in Operational Assignments
Authors: Woodson Sarah E , Barba Laura C , Beckett Charmagne
Published: July 2019

Introduction

Current United States Navy policy supports the continuation of duty for active duty (AD) service members living with HIV infection. The creation of this policy is instrumental to prevent exclusion and to promote career expansion and promotional opportunities for AD service members infected with HIV. The established instruction parallels the HIV care continuum, a widely accepted public health model. No studies have been done to determine whether allowing service members to fill operational and Outside the Continental United States (OCONUS) assignments disrupts this continuum of care. This retrospective study aims to evaluate how an operational or OCONUS assignment impacts the ability of an HIV AD service members to receive the standard of care HIV medical treatment and maintain viral suppression.

Materials/Methods

A retrospective chart review was performed on the health records of 20 United States AD Navy service members with HIV who were placed in OCONUS or large ship assignments per current U.S. Navy policy. Health records were reviewed during the service member’s assignment. Viral loads were documented immediately prior and at 6 months after starting their new assignment. Changes to anti-retroviral medications and the medical treatment facility, including the specialty of the treating provider were recorded.

Results

The results demonstrate no significant change in the service member’s viral load during the first 6 months in an operational or OCONUS assignment. Members still had access to care including medications and specialty providers based on the locality.

Conclusion

All service members within this review were able to maintain viral suppression despite the location of their assignments. This limited study suggests that care is accessible and the standard HIV care continuum is maintained while deployed or stationed overseas.
Testing modified gravity with wide binaries in Gaia DR2
Authors: Pittordis Charalambos , Sutherland Will
Published: July 2019

Several recent studies have shown that very wide binary stars can potentially provide an interesting test for modified-gravity theories which attempt to emulate dark matter; these systems should be almost Newtonian according to standard dark-matter theories, while the predictions for MOND-like theories are distinctly different, if the various observational issues can be overcome. Here we explore an observational application of the test from the recent Gaia DR2 data release: we select a large sample of ∼24 000 candidate wide binary stars with distance $\lt 200 \, {\rm pc}$ and magnitudes G < 16 from Gaia DR2, and estimated component masses using a main-sequence mass–luminosity relation. We then compare the frequency distribution of pairwise relative projected velocity (relative to circular-orbit value) as a function of projected separation; these distributions show a clear peak at a value close to Newtonian expectations, along with a long ‘tail’ which extends to much larger velocity ratios; the ‘tail’ is considerably more numerous than in control samples constructed from DR2 with randomized positions, so its origin is unclear. Comparing the velocity histograms with simulated data, we conclude that MOND-like theories without an external field effect (ExFE) are strongly inconsistent with the observed data since they predict a peak-shift in clear disagreement with the data; testing MOND-like theories with an ExFE is not decisive at present, but has good prospects to become decisive in future with improved modelling or understanding of the high-velocity tail, and additional spectroscopic data.
NGC 326: X-shaped no more
Authors: Hardcastle M J , Croston J H , Shimwell T W , Tasse C , Gürkan G , Morganti R , Murgia M , Röttgering H J A , van Weeren R J , Williams W L
Published: July 2019

We present new 144-MHz Low-Frequency Array (LOFAR) observations of the prototypical ‘X-shaped’ radio galaxy NGC 326, which show that the formerly known wings of the radio lobes extend smoothly into a large-scale, complex radio structure. We argue that this structure is most likely the result of hydrodynamical effects in an ongoing group or cluster merger, for which pre-existing X-ray and optical data provide independent evidence. The large-scale radio structure is hard to explain purely in terms of jet reorientation due to the merger of binary black holes, a previously proposed explanation for the inner structure of NGC 326. For this reason, we suggest that the simplest model is one in which the merger-related hydrodynamical processes account for all the source structure, though we do not rule out the possibility that a black hole merger has occurred. Inference of the black hole–black hole merger rate from observations of X-shaped sources should be carried out with caution in the absence of deep, sensitive low-frequency observations. Some X-shaped sources may be signposts of cluster merger activity, and it would be useful to investigate the environments of these objects more generally.
Impact of galaxy mergers on the colours of cluster galaxies
Authors: Oh Sree , Kim Keunho , Lee Joon Hyeop , Kim Minjin , Sheen Yun-Kyeong , Rhee Jinsu , Ree Chang H , Jeong Hyunjin , Ho Luis C , Kyeong Jaemann , Sung Eon-Chang , Park Byeong-Gon , Yi Sukyoung K
Published: July 2019

We examine the ultraviolet and optical colours of 906 cluster galaxies from the KASI-Yonsei Deep Imaging Survey of Clusters (KYDISC). The sample has been divided into two categories, morphologically disturbed and undisturbed galaxies, based on the visual signatures related to recent mergers. We find that galaxies with signatures of recent mergers show significantly bluer colours than undisturbed galaxies. Disturbed galaxies populate more on the cluster outskirts, suggesting recent accretion into the cluster environment, which implies that disturbed galaxies can be less influenced by the environmental quenching process and remain blue. However, we still detect bluer colours of disturbed galaxies in all locations (cluster core and outskirts) for the fixed morphology, which is difficult to understand just considering the difference in time since infall into a cluster. Moreover, blue disturbed galaxies show features seemingly related to recent star formation. Therefore, we suspect that mergers make disturbed galaxies keep their blue colour longer than undisturbed galaxies under the effect of the environmental quenching through either merger-induced star formation or central gas concentration which is less vulnerable for gas stripping.
Do the planets in the HD 34445 system really exist?
Authors: Georgakarakos Nikolaos , Dobbs-Dixon Ian
Published: July 2019

In 2010 the first planet was discovered around star HD 34445. Recently, another five planets were announced orbiting the same star. It is a rather dense multiplanet system with some of its planets having separations of fractions of an au and minimum masses ranging from Neptune to sub-Jupiter ones. Given the number of planets and the various uncertainties in their masses and orbital elements, the HD 34445 planetary system is quite interesting as there is the potential for mean motion and secular resonances that could render the outcome of its dynamical evolution and fate an open question. In this paper we investigate the dynamical stability of the six-planet system in order to check the validity of the orbital solution acquired. This is achieved by a series of numerical experiments, where the dynamical evolution of the system is tested on different time-scales. We vary the orbital elements and masses of the system within the error ranges provided. We find that for a large area of the parameter space we can produce stable configurations and therefore conclude it is very likely that the HD 34445 planetary system is real. Some discussion about the potential habitability of the system is also done.
Speciation in Howea Palms Occurred in Sympatry, Was Preceded by Ancestral Admixture, and Was Associated with Edaphic and Phenological Adaptation
Authors: Osborne Owen G , Ciezarek Adam , Wilson Trevor , Crayn Darren , Hutton Ian , Baker William J , Turnbull Colin G N , Savolainen Vincent
Published: July 2019

Howea palms are viewed as one of the most clear-cut cases of speciation in sympatry. The sister species Howea belmoreana and H. forsteriana are endemic to the oceanic Lord Howe Island, Australia, where they have overlapping distributions and are reproductively isolated mainly by flowering time differences. However, the potential role of introgression from Australian mainland relatives had not previously been investigated, a process that has recently put other examples of sympatric speciation into question. Furthermore, the drivers of flowering time-based reproductive isolation remain unclear. We sequenced an RNA-seq data set that comprehensively sampled Howea and their closest mainland relatives (Linospadix, Laccospadix), and collected detailed soil chemistry data on Lord Howe Island to evaluate whether secondary gene flow had taken place and to examine the role of soil preference in speciation. D-statistics analyses strongly support a scenario whereby ancestral Howea hybridized frequently with its mainland relatives, but this only occurred prior to speciation. Expression analysis, population genetic and phylogenetic tests of selection, identified several flowering time genes with evidence of adaptive divergence between the Howea species. We found expression plasticity in flowering time genes in response to soil chemistry as well as adaptive expression and sequence divergence in genes pleiotropically linked to soil adaptation and flowering time. Ancestral hybridization may have provided the genetic diversity that promoted their subsequent adaptive divergence and speciation, a process that may be common for rapid ecological speciation.
Metabolic alterations of uterine grafts after extended cold ischemic storage: experimental study in ewes
Authors: Tholance Yannick , Tricard Jeremy , Chianea Thierry , Marquet Pierre , Ponsonnard Sébastien , Sturtz Franck , Piccardo Alessandro , Gauthier Tristan
Published: July 2019

Uterine transplantation from a deceased donor could become an available option for widely treating uterine infertility. However, this procedure requires more precise knowledge about the graft’s tolerance to extended cold ischemia. Here, we sought to assess the uterine metabolic alterations after extended cold ischemic storage in a model of auto-transplantation in ewe. A total of 14 uterine auto-transplantations were performed, divided into 2 groups: 7 after 3 h of cold ischemia time (CIT) and 7 after 24 h. Venous uterine blood was collected before uterus retrieval and during reperfusion (30, 60 and 90 min); thereafter, blood gases, lactate, glucose and amino acids (AAs) were analyzed. Apoptosis analyses were performed before uterus retrieval and following reperfusion in uterus biopsies. A total of 12 uterine auto-transplantations were successfully performed and 7 ewes were alive ≥8 days after transplantation. After reperfusion, a decrease in pH, a rise of lactate and lactate/glucose ratio and a delayed decrease of pO2 were found in the 3 h CIT group. No significant variation of these parameters was observed in the 24 h CIT group. Significant decreases of AAs were observed during reperfusion and these decreases were more pronounced and concerned a larger number of compounds in the 24 h CIT group than in the 3 h CIT group. There was no significant uterine apoptotic signal in either group. Overall, these results suggest that extended CIT storage delayed restoration of aerobic glycolysis and induced an increase in AA requirements of the uterus after reperfusion. However, this biochemical alteration did not reduce success rate for uterine transplantation.
A role for the Saccharomyces cerevisiae ABCF protein New1 in translation termination/recycling
Authors: Kasari Villu , Pochopien Agnieszka A , Margus Tõnu , Murina Victoriia , Turnbull Kathryn , Zhou Yang , Nissan Tracy , Graf Michael , Nováček Jiří , Atkinson Gemma C , Johansson Marcus J O , Wilson Daniel N , Hauryliuk Vasili
Published: July 2019

Translation is controlled by numerous accessory proteins and translation factors. In the yeast Saccharomyces cerevisiae, translation elongation requires an essential elongation factor, the ABCF ATPase eEF3. A closely related protein, New1, is encoded by a non-essential gene with cold sensitivity and ribosome assembly defect knock-out phenotypes. Since the exact molecular function of New1 is unknown, it is unclear if the ribosome assembly defect is direct, i.e. New1 is a bona fide assembly factor, or indirect, for instance due to a defect in protein synthesis. To investigate this, we employed yeast genetics, cryo-electron microscopy (cryo-EM) and ribosome profiling (Ribo-Seq) to interrogate the molecular function of New1. Overexpression of New1 rescues the inviability of a yeast strain lacking the otherwise strictly essential translation factor eEF3. The structure of the ATPase-deficient (EQ2) New1 mutant locked on the 80S ribosome reveals that New1 binds analogously to the ribosome as eEF3. Finally, Ribo-Seq analysis revealed that loss of New1 leads to ribosome queuing upstream of 3′-terminal lysine and arginine codons, including those genes encoding proteins of the cytoplasmic translational machinery. Our results suggest that New1 is a translation factor that fine-tunes the efficiency of translation termination or ribosome recycling.
DNA sequence models of genome-wide Drosophila melanogaster Polycomb binding sites improve generalization to independent Polycomb Response Elements
Authors: Bredesen Bjørn André , Rehmsmeier Marc
Published: July 2019

Polycomb Response Elements (PREs) are cis-regulatory DNA elements that maintain gene transcription states through DNA replication and mitosis. PREs have little sequence similarity, but are enriched in a number of sequence motifs. Previous methods for modelling Drosophila melanogaster PRE sequences (PREdictor and EpiPredictor) have used a set of 7 motifs and a training set of 12 PREs and 16-23 non-PREs. Advances in experimental methods for mapping chromatin binding factors and modifications has led to the publication of several genome-wide sets of Polycomb targets. In addition to the seven motifs previously used, PREs are enriched in the GTGT motif, recently associated with the sequence-specific DNA binding protein Combgap. We investigated whether models trained on genome-wide Polycomb sites generalize to independent PREs when trained with control sequences generated by naive PRE models and including the GTGT motif. We also developed a new PRE predictor: SVM-MOCCA. Training PRE predictors with genome-wide experimental data improves generalization to independent data, and SVM-MOCCA predicts the majority of PREs in three independent experimental sets. We present 2908 candidate PREs enriched in sequence and chromatin signatures. 2412 of these are also enriched in H3K4me1, a mark of Trithorax activated chromatin, suggesting that PREs/TREs have a common sequence code.
DNA complexes with human apurinic/apyrimidinic endonuclease 1: structural insights revealed by pulsed dipolar EPR with orthogonal spin labeling
Authors: Krumkacheva Olesya A , Shevelev Georgiy Yu , Lomzov Alexander A , Dyrkheeva Nadezhda S , Kuzhelev Andrey A , Koval Vladimir V , Tormyshev Victor M , Polienko Yuliya F , Fedin Matvey V , Pyshnyi Dmitrii V , Lavrik Olga I , Bagryanskaya Elena G
Published: July 2019

A DNA molecule is under continuous influence of endogenous and exogenous damaging factors, which produce a variety of DNA lesions. Apurinic/apyrimidinic sites (abasic or AP sites) are among the most common DNA lesions. In this work, we applied pulse dipolar electron paramagnetic resonance (EPR) spectroscopy in combination with molecular dynamics (MD) simulations to investigate in-depth conformational changes in DNA containing an AP site and in a complex of this DNA with AP endonuclease 1 (APE1). For this purpose, triarylmethyl (TAM)-based spin labels were attached to the 5′ ends of an oligonucleotide duplex, and nitroxide spin labels were introduced into APE1. In this way, we created a system that enabled monitoring the conformational changes of the main APE1 substrate by EPR. In addition, we were able to trace substrate-to-product transformation in this system. The use of different (orthogonal) spin labels in the enzyme and in the DNA substrate has a crucial advantage allowing for detailed investigation of local damage and conformational changes in AP-DNA alone and in its complex with APE1.