bluuebunny/crossref_metadata_2025_split huggingface dataset:
Telomeres Increasingly Develop Aberrant Structures in Aging Humans
Authors: Boccardi Virginia , Cari Luigi , Nocentini Giuseppe , Riccardi Carlo , Cecchetti Roberta , Ruggiero Carmelinda , Arosio Beatrice , Paolisso Giuseppe , Herbig Utz , Mecocci Patrizia 
Published: November 2018

Abstract
Telomeres progressively shorten with age, and it has been proposed that critically short and dysfunctional telomeres contribute to aging and aging-associated diseases in humans. For many years it was thought that telomere erosion was strictly a consequence of the “end replication problem,” or the inability of replicative polymerases to completely duplicate linear DNA ends. It is becoming increasingly evident, however, that telomere shortening of cultured human cells is also caused because of other replication defects in telomeric repeats, those that cause fragile telomeres and other aberrant telomeric structures that can be detected on metaphase chromosomes. Whether these replication defects contribute to telomere erosion also in human tissues is currently unknown. By analyzing peripheral blood mononuclear cells from a total of 35 healthy subjects ranging in age from 23 to 101 years, we demonstrated that telomeres increasingly display aberrant structures with advancing donor age. Although the percentages of fragile telomeres increased only until adulthood, the percentages of chromosomes displaying sister telomere loss and sister telomere chromatid fusions increased consistently throughout the entire human life span. Our data, therefore, suggest that telomeric replication defects other than the end replication problem contribute to aging-associated telomere erosion in humans.
In Vivo Imaging With Confirmation by Histopathology for Increased Rigor and Reproducibility in Translational Research: A Review of Examples, Options, and Resources
Authors: Gabrielson Kathleen , Maronpot Robert , Monette Sébastien , Mlynarczyk Coraline , Ramot Yuval , Nyska Abraham , Sysa-Shah Polina 
Published: November 2018

Abstract
Preclinical noninvasive imaging can be an indispensable tool for studying animal models of disease. In vivo imaging to assess anatomical, functional, and molecular features requires verification by a comparison to the macroscopic and microscopic morphological features, since all noninvasive in vivo imaging methods have much lower resolution than standard histopathology. Comprehensive pathological evaluation of the animal model is underutilized; yet, many institutions have veterinary or human pathologists with necessary comparative pathology expertise. By performing a rigorous comparison to gross or histopathology for image interpretation, these trained individuals can assist scientists with the development of the animal model, experimental design, and evaluation of the in vivo imaging data. These imaging and pathology corroboration studies undoubtedly increase scientific rigor and reproducibility in descriptive and hypothesis-driven research. A review of case examples including ultrasound, nuclear, optical, and MRI is provided to illustrate how a wide range of imaging modalities data can be confirmed by gross or microscopic pathology. This image confirmation and authentication will improve characterization of the model and may contribute to decreasing costs and number of animals used and to more rapid translation from preclinical animal model to the clinic.
Of Mice, Dogs, Pigs, and Men: Choosing the Appropriate Model for Immuno-Oncology Research
Authors: Overgaard Nana H , Fan Timothy M , Schachtschneider Kyle M , Principe Daniel R , Schook Lawrence B , Jungersen Gregers 
Published: November 2018

AbstractThe immune system plays dual roles in response to cancer. The host immune system protects against tumor formation via immunosurveillance; however, recognition of the tumor by immune cells also induces sculpting mechanisms leading to a Darwinian selection of tumor cell variants with reduced immunogenicity. Cancer immunoediting is the concept used to describe the complex interplay between tumor cells and the immune system. This concept, commonly referred to as the three E’s, is encompassed by 3 distinct phases of elimination, equilibrium, and escape. Despite impressive results in the clinic, cancer immunotherapy still has room for improvement as many patients remain unresponsive to therapy. Moreover, many of the preclinical results obtained in the widely used mouse models of cancer are lost in translation to human patients.To improve the success rate of immuno-oncology research and preclinical testing of immune-based anticancer therapies, using alternative animal models more closely related to humans is a promising approach. Here, we describe 2 of the major alternative model systems: canine (spontaneous) and porcine (experimental) cancer models. Although dogs display a high rate of spontaneous tumor formation, an increased number of genetically modified porcine models exist. We suggest that the optimal immuno-oncology model may depend on the stage of cancer immunoediting in question. In particular, the spontaneous canine tumor models provide a unique platform for evaluating therapies aimed at the escape phase of cancer, while genetically engineered swine allow for elucidation of tumor-immune cell interactions especially during the phases of elimination and equilibrium.
Applied Institutional Approaches for the Evaluation and Management of Zoonoses in Contemporary Laboratory Animal Research Facilities
Authors: Colby Lesley A , Zitzow Lois 
Published: November 2018

AbstractZoonoses, diseases transmitted between animals and humans, have been a concern in laboratory animal medicine for decades. Exposure to zoonotic organisms not only poses health risks to personnel and research animals but may also affect research integrity. Early laboratory animal programs were ineffective at excluding and preventing transmission of zoonotic diseases: the health status of the animals were often unknown, endemic diseases occurred frequently, housing conditions were less controlled, and veterinary care programs were decentralized. Over time, these conditions improved, but despite this, zoonotic diseases remain a contemporary concern. To reduce the incidence of zoonoses, management should perform an accurate risk assessment that takes into account the type of research performed, animal species used, animal sources, and housing conditions. Specific research practices, such as the use of biological materials, can also affect the risk assessment and should be considered. Once identified, the characteristics of significant zoonotic organisms can be examined. In addition, personnel attitudes and training, facility design and management, equipment availability, personal protective equipment used, standard operating procedures, and the institution’s vermin control program can impact the risk assessment. The effectiveness of the occupational health and safety program at managing risks of zoonoses should also be examined. Risk assessment, in the context of zoonotic disease prevention, is a complex exercise and is most effective when a team approach is used and includes research, husbandry, veterinary, and biosafety personnel.
Vanishing of Symplectic Homology and Obstruction to Flexible Fillability
Authors: Zhou Zhengyi 
Published: November 2018

Abstract
For any asymptotically dynamically convex contact manifold $Y$, we show that $SH_{\ast }(W)=0$ is a property independent of the choice of topologically simple (i.e., $c_1(W)=0$ and $\pi _{1}(Y)\rightarrow \pi _1(W)$ is injective) Liouville filling $W$. In particular, if $Y$ is the boundary of a flexible Weinstein domain, then any topologically simple Liouville filling $W$ has vanishing symplectic homology. As a consequence, we answer a question of Lazarev partially: a contact manifold $Y$ admitting flexible fillings determines the integral cohomology of all the topologically simple Liouville fillings of $Y$. The vanishing result provides an obstruction to flexible fillability. As an application, we show that all Brieskorn manifolds of dimension $\ge 5$ cannot be filled by flexible Weinstein manifolds.
Resilience in Displacement and the Protection of Civilians in South Sudan
Authors: Munive Jairo 
Published: November 2018

Abstract
The United Nations Mission in South Sudan (UNMISS) was established in 2011. As violence erupted in 2013, the peacekeeping mission allowed tens of thousands of civilians into its bases, leading to the establishment of Protection of Civilians (POC) sites that today shelter more than 200,000 people. The argument of this article is that the creation of the POC sites became constitutive of a broader set of controversies surrounding the building or otherwise of resilience among displaced civilians. The UNMISS is pushing to offer as few services as possible and is focusing on the delivery of traditional humanitarian assistance to encourage return. Conversely, the humanitarian community is pushing for the expansion of services beyond life-saving short-term interventions and towards building the capacity of Internally Displaced People (IDPs) to resist adverse shocks in the future. This article concludes that contestations over the politics of resilience have become a driver of tension and friction between the peacekeeping mission and the humanitarians.
Emerging evidence of an effect of salt on innate and adaptive immunity
Authors: Evans Rhys D R , Antonelou Marilina , Henderson Scott , Walsh Stephen B , Salama Alan D 
Published: November 2018

AbstractSalt intake as part of a western diet currently exceeds recommended limits, and the small amount found in the natural diet enjoyed by our Paleolithic ancestors. Excess salt is associated with the development of hypertension and cardiovascular disease, but other adverse effects of excess salt intake are beginning to be recognized, including the development of autoimmune and inflammatory disease. Over the last decade there has been an increasing body of evidence demonstrating that salt affects multiple components of both the innate and adaptive immune systems. In this review we outline the recent laboratory, animal and human data, highlighting the effect of salt on immunity, with a particular focus on the relevance to inflammatory kidney disease.
Effect of Commonly Used Pediatric Antibiotics on Gut Microbial Diversity in Preschool Children in Burkina Faso: A Randomized Clinical Trial
Authors: Oldenburg Catherine E , Sié Ali , Coulibaly Boubacar , Ouermi Lucienne , Dah Clarisse , Tapsoba Charlemagne , Bärnighausen Till , Ray Kathryn J , Zhong Lina , Cummings Milo E , Lebas Elodie , Lietman Thomas M , Keenan Jeremy D , Doan Thuy 
Published: November 2018

Abstract

Background
Exposure to antibiotics may result in alterations to the composition of intestinal microbiota. However, few trials have been conducted, and observational studies are subject to confounding by indication. We conducted a randomized controlled trial to determine the effect of 3 commonly used pediatric antibiotics on the intestinal microbiome in healthy preschool children.

Methods
Children aged 6–59 months were randomized (1:1:1:1) to a 5-day course of 1 of 3 antibiotics, including amoxicillin (25 mg/kg/d twice-daily doses), azithromycin (10 mg/kg dose on day 1 and then 5 mg/kg once daily for 4 days), cotrimoxazole (240 mg once daily), or placebo. Rectal swabs were obtained at baseline and 5 days after the last dose and were processed using 16S rRNA gene sequencing. The prespecified primary outcome was inverse Simpson’s α-diversity index.

Results
Post-treatment Simpson’s diversity was significantly different across the 4 arms (P = .003). The mean Simpson’s α-diversity among azithromycin-treated children was significantly lower than in placebo-treated children (6.6; 95% confidence interval [CI], 5.5–7.8; vs 9.8; 95% CI, 8.7–10.9; P = .0001). Diversity in children treated with amoxicillin (8.3; 95% CI, 7.0–9.6; P = .09) or cotrimoxazole (8.3; 95% CI, 8.2–9.7; P = .08) was not significantly different than placebo.

Conclusions
Azithromycin affects the composition of the pediatric intestinal microbiome. The effect of amoxicillin and cotrimoxazole on microbiome composition was less clear.

Clinical Trials Registration
clinicaltrials.gov NCT03187834.
A Pilot Randomized Controlled Trial Comparing Mindfulness Meditation, Cognitive Therapy, and Mindfulness-Based Cognitive Therapy for Chronic Low Back Pain
Authors: Day Melissa A , Ward L Charles , Ehde Dawn M , Thorn Beverly E , Burns John , Barnier Amanda , Mattingley Jason B , Jensen Mark P 
Published: November 2018

AbstractObjectiveThis pilot trial compared the feasibility, tolerability, acceptability, and effects of group-delivered mindfulness meditation (MM), cognitive therapy (CT), and mindfulness-based cognitive therapy (MBCT) for chronic low back pain (CLBP).SettingUniversity of Queensland Psychology Clinic.SubjectsParticipants were N = 69 (intent-to-treat [ITT] sample) adults with CLBP.DesignA pilot, assessor-blinded randomized controlled trial.MethodsParticipants were randomized to treatments. The primary outcome was pain interference; secondary outcomes were pain intensity, physical function, depression, and opioid medication use. The primary study end point was post-treatment; maintenance of gains was evaluated at three- and six-month follow-up.ResultsRatings of acceptability, and ratios of dropout and attendance showed that MBCT was acceptable, feasible, and well tolerated, with similar results found across conditions. For the ITT sample, large improvements in post-treatment scores for pain interference, pain intensity, physical function, and depression were found (P < 0.001), with no significant between-group differences. Analysis of the follow-up data (N = 43), however, revealed that MBCT participants improved significantly more than MM participants on pain interference, physical function, and depression. The CT group improved more than MM in physical function. The MBCT and CT groups did not differ significantly on any measures.ConclusionsThis is the first study to examine MBCT for CLBP management. The findings show that MBCT is a feasible, tolerable, acceptable, and potentially efficacious treatment option for CLBP. Further, MBCT, and possibly CT, could have sustained benefits that exceed MM on some important CLBP outcomes. A future definitive randomized controlled trial is needed to evaluate these treatments and their differences.
Using codesign to develop a culturally tailored, behavior change mHealth intervention for indigenous and other priority communities: A case study in New Zealand
Authors: Verbiest Marjolein E A , Corrigan Callie , Dalhousie Sally , Firestone Ridvan , Funaki Tevita , Goodwin Debbie , Grey Jacqui , Henry Akarere , Humphrey Gayl , Jull Andrew , Vano Mereaumate , Pekepo Crystal , Morenga Lisa Te , Whittaker Robyn , Mhurchu Cliona Ni 
Published: November 2018

Abstract
The obesity rate in New Zealand is one of the highest worldwide (31%), with highest rates among Māori (47%) and Pasifika (67%). Codesign was used to develop a culturally tailored, behavior change mHealth intervention for Māori and Pasifika in New Zealand. The purpose of this article is to provide an overview of the codesign methods and processes and describe how these were used to inform and build a theory-driven approach to the selection of behavioral determinants and change techniques. The codesign approach in this study was based on a partnership between Māori and Pasifika partners and an academic research team. This involved working with communities on opportunity identification, elucidation of needs and desires, knowledge generation, envisaging the mHealth tool, and prototype testing. Models of Māori and Pasifika holistic well-being and health promotion were the basis for identifying key content modules and were applied to relevant determinants of behavior change and theoretically based behavior change techniques from the Theoretical Domains Framework and Behavior Change Taxonomy, respectively. Three key content modules were identified: physical activity, family/whānau [extended family], and healthy eating. Other important themes included mental well-being/stress, connecting, motivation/support, and health literacy. Relevant behavioral determinants were selected, and 17 change techniques were mapped to these determinants. Community partners established that a smartphone app was the optimal vehicle for the intervention. Both Māori and Pasifika versions of the app were developed to ensure features and functionalities were culturally tailored and appealing to users. Codesign enabled and empowered users to tailor the intervention to their cultural needs. By using codesign and applying both ethnic-specific and Western theoretical frameworks of health and behavior change, the mHealth intervention is both evidence based and culturally tailored.
Low Anterior Resection Syndrome and Quality of Life After Sphincter-Sparing Rectal Cancer Surgery: A Long-term Longitudinal Follow-up
Authors: Pieniowski Emil H.A. , Palmer Gabriella J. , Juul Therese , Lagergren Pernilla , Johar Asif , Emmertsen Katrine J. , Nordenvall Caroline , Abraham-Nordling Mirna 
Published: November 2018

BACKGROUND:Despite low anterior resection syndrome being a well-known consequence of sphincter-preserving rectal cancer surgery, the long-term effect on bowel function and quality of life is not fully understood.OBJECTIVE:This study aimed to elucidate whether symptoms of low anterior resection syndrome change over time and if the correlation to quality of life is equivalent when measured at 2 time points.DESIGN:This prospective cohort study included measurements at 2 time points (5 years between; range, 7.1–16.1 years from surgery to second follow-up).SETTINGS:This multicenter study included patients from Sweden and Denmark.PATIENTS:Patients were included if they were ≥18 years of age and underwent curative rectal cancer surgery with either total or partial mesorectal excision.MAIN OUTCOME MEASURES:Outcomes were measured with the low anterior resection syndrome questionnaire including a question assessing the impact of bowel function on quality of life and with the validated quality-of-life questionnaire EORTC QLQ-C30.RESULTS:In total, 282 patients were included and there were no statistically significant differences in the distribution among the 3 groups (no, minor, and major low anterior resection syndrome) when comparing time points follow-up 1 with follow-up 2 (p= 0.455). At follow-up 2, 138 patients (49%) still experienced major impairment. No both statistically and clinically significant differences were seen in the mean score of EORTC QLQ-C30 when comparing the same low anterior resection syndrome group at follow-up 1 and follow-up 2, and the impact on quality of life was comparable. Global health status/quality of life was impaired in the major low anterior resection syndrome group at both follow-up 1 (p< 0.001) and follow-up 2 (p< 0.001).LIMITATIONS:The study design prevents an evaluation of causality.CONCLUSIONS:Difficulties with low anterior resection syndrome and the impact on patients’ quality of life persist over time. SeeVideo Abstractat http://links.lww.com/DCR/A762.
Emergent Colon Resections: Does Surgeon Specialization Influence Outcomes?
Authors: Kulaylat Audrey S. , Pappou Emmanouil , Philp Matthew M. , Kuritzkes Benjamin A. , Ortenzi Gail , Hollenbeak Christopher S. , Choi Christine , Messaris Evangelos 
Published: November 2018

BACKGROUND:
Relationships between high-volume surgeons and improved postoperative outcomes have been well documented. Colorectal procedures are often performed by general surgeons, particularly in emergent settings, and may form a large component of their practice. The influence of subspecialized training on outcomes after emergent colon surgery, however, is not well described.

OBJECTIVE:
The purpose of this study was to determine whether subspecialty training in colorectal surgery is associated with differences in postoperative outcomes after emergency colectomy.

DESIGN:
This was a retrospective cohort study.

SETTINGS:
Three tertiary care hospitals participating in the National Surgical Quality Improvement Project were included.

PATIENTS:
Patients undergoing emergent colon resections were identified at each institution and stratified by involvement of either a colorectal surgeon or a general or acute care surgeon.

MAIN OUTCOME MEASURES:
Propensity score matching was used to isolate the effect of surgeon specialty on the primary outcomes, including postoperative morbidity, mortality, length of stay, and the need for unplanned major reoperation, in comparable cohorts of patients.

RESULTS:
A total of 889 cases were identified, including 592 by colorectal and 297 by general/acute care surgeons. After propensity score matching, cases performed by colorectal surgeons were associated with significantly lower rates of 30-day mortality (6.7% vs 16.4%; p = 0.001), postoperative morbidity (45.0% vs 56.7%; p = 0.009), and unplanned major reoperation (9.7% vs 16.4%; p = 0.04). In addition, length of stay was ≈4.4 days longer among patients undergoing surgery by general/acute care surgeons (p < 0.001).

LIMITATIONS:
This study was limited by its retrospective design, with potential selection bias attributed to referral patterns.

CONCLUSIONS:
After controlling for underlying disease states and illness severity, emergent colon resections performed by colorectal surgeons were associated with significantly lower rates of postoperative morbidity and mortality when compared with noncolorectal surgeons. These findings may have implications for referral patterns for institutions. See Video Abstract at http://links.lww.com/DCR/A767.
Hepatitis A Outbreak Among Men Who Have Sex With Men, Yokohama, Japan, January to May 2018
Authors: Yoshimura Yukihiro , Horiuchi Hiroshi , Sawaki Kenji , Miyata Nobuyuki , Kumazaki Makoto , Usuku Shuzo , Tachikawa Natsuo 
Published: November 2018

Abstract
Between January and May in 2018, 17 male cases of hepatitis A were reported in Yokohama, Japan. Of these, 14 identified as men who have sex with men. The viral sequence in this outbreak was same as that of the recent European and Taiwanese outbreaks strain.
Designing and conducting proof-of-concept chronic pain analgesic clinical trials
Authors: Campbell Claudia M. , Gilron Ian , Doshi Tina , Raja Srinivasa 
Published: November 2018

Abstract

Introduction:
The evolution of pain treatment is dependent on successful development and testing of interventions. Proof-of-concept (POC) studies bridge the gap between identification of a novel target and evaluation of the candidate intervention's efficacy within a pain model or the intended clinical pain population.

Methods:
This narrative review describes and evaluates clinical trial phases, specific POC pain trials, and approaches to patient profiling.

Results:
We describe common POC trial designs and their value and challenges, a mechanism-based approach, and statistical issues for consideration.

Conclusion:
Proof-of-concept trials provide initial evidence for target use in a specific population, the most appropriate dosing strategy, and duration of treatment. A significant goal in designing an informative and efficient POC study is to ensure that the study is safe and sufficiently sensitive to detect a preliminary efficacy signal (ie, a potentially valuable therapy). Proof-of-concept studies help avoid resources wasted on targets/molecules that are not likely to succeed. As such, the design of a successful POC trial requires careful consideration of the research objective, patient population, the particular intervention, and outcome(s) of interest. These trials provide the basis for future, larger-scale studies confirming efficacy, tolerability, side effects, and other associated risks.