bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modifying Risks in Ventral Hernia Patients With Prehabilitation
Authors: Liang Mike K. , Bernardi Karla , Holihan Julie L. , Cherla Deepa V. , Escamilla Richard , Lew Debbie F. , Berger David H. , Ko Tien C. , Kao Lillian S. 
Published: July 2018

Objective:
The aim of this study was to determine whether preoperative nutritional counseling and exercise (prehabilitation) in obese patients with ventral hernia repair (VHR) results in more hernia-free and complication-free patients.

Background:
Obesity and poor fitness are associated with complications following VHR. These issues are prevalent in low socioeconomic status patients.

Methods:
This was a blinded, randomized controlled trial at a safety-net academic institution. Obese patients (BMI 30 to 40) seeking VHR were randomized to prehabilitation versus standard counseling. VHR was performed once preoperative requirements were met: 7% total body weight loss or 6 months of counseling and no weight gain. Primary outcome was the proportion of hernia-free and complication-free patients. Secondary outcomes were wound complications at 1 month postoperative and weight loss measures. Univariate analysis was performed.

Results:
Among 118 randomized patients, prehabilitation was associated with a higher percentage of patients who lost weight and achieved weight loss goals; however, prehabilitation was also associated with a higher dropout rate and need for emergent repair. VHR was performed in 44 prehabilitation and 34 standard counseling patients. There was a trend toward less wound complication in prehabilitation patients (6.8% vs 17.6%, P = 0.167). The prehabilitation group was more likely to be hernia-free and complication-free (69.5% vs 47.5%, P = 0.015).

Conclusions:
It is feasible to implement a prehabilitation program for obese patients at a safety-net hospital. Prehabilitation patients have a higher likelihood of being hernia-free and complication-free postoperatively. Although further trials and long-term outcomes are needed, prehabilitation may benefit obese surgical patients, but there may be increased risks of dropout and emergent repair.

Clinical Trial Registration:
This trial was registered with clinicaltrials.gov (NCT02365194)
Is it Time to Abandon the Milan Criteria?
Authors: Halazun Karim J. , Tabrizian Parissa , Najjar Marc , Florman Sander , Schwartz Myron , Michelassi Fabrizio , Samstein Benjamin , Brown Robert S. , Emond Jean C. , Busuttil Ronald W. , Agopian Vatche G. 
Published: July 2018

Objectives:
European liver transplant (LT) centers have moved away from using the Milan Criteria (MC) for hepatocellular carcinoma (HCC) patient selection, turning to models including tumor biological indices, namely alpha-fetoprotein (AFP). We present the first US model to incorporate an AFP response (AFP-R), with comparisons to MC and French-AFP models (F-AFP).

Methods:
AFP-R was measured as differences between maximum and final pre-LT AFP in HCC patients undergoing LT at 3 US centers (2001 to 2013). Cox and competing risk-regression analyses identified predictors of recurrence-free survival (RFS).

Results:
Of 1450 patients, 235 (16.2%) were outside MC. Tumor size, number, and AFP-R were independent predictors of RFS and were assigned weighted points based on Cox-regression analysis. An AFP-R consistently < 200 ng/mL predicted the best outcome. A 3-tiered competing-risk RFS model, the New York/California (NYCA) score, was developed, accurately discriminating between groups (P < 0.001), and correlating with overall survival (P < 0.001). Two hundred one of 235 patients outside MC (85.5%) would be recategorized into NYCA low/acceptable-risk groups. The c-statistic for our NYCA score is 0.731 compared with 0.613 for MC and 0.658 for F-AFP (P < 0.0001).

Conclusion:
Incorporation of AFP-R into HCC selection criteria allows for MC expansion. As United Network for Organ Sharing considers adding AFP to selection algorithms, the NYCA score provides an objective, user-friendly tool for centers to appropriately risk-stratify patients.
Frailty as a Predictor of Death or New Disability After Surgery
Authors: McIsaac Daniel I. , Taljaard Monica , Bryson Gregory L. , Beaulé Paul E. , Gagné Sylvain , Hamilton Gavin , Hladkowicz Emily , Huang Allen , Joanisse John A. , Lavallée Luke T. , MacDonald David , Moloo Husein , Thavorn Kednapa , van Walraven Carl , Yang Homer , Forster Alan J. 
Published: July 2018

Objective:
To compare the accuracy of the modified Fried Index (mFI) and the Clinical Frailty Scale (CFS) to predict death or patient-reported new disability 90 days after major elective surgery.

Background:
The association of frailty with patient-reported outcomes, and comparisons between preoperative frailty instruments are poorly described.

Methods:
This was a prospective multicenter cohort study. We determined frailty status in individuals ≥65 years having elective noncardiac surgery using the mFI and CFS. Outcomes included death or patient-reported new disability (primary); safety incidents, length of stay (LOS), and institutional discharge (secondary); ease of use, usefulness, benefit, clinical importance, and feasibility (tertiary). We measured the adjusted association of frailty with outcomes using regression analysis and compared true positive and false positive rates (TPR/FPR).

Results:
Of 702 participants, 645 had complete follow up. The CFS identified 297 (42.3%) with frailty, the mFI 257 (36.6%); 72 (11.1%) died or experienced a new disability. Frailty was significantly associated with the primary outcome (CFS adjusted odds ratio, OR, 2.51, 95% confidence interval, CI, 1.50–4.21; mFI adjusted-OR 2.60, 95% CI 1.57–4.31). TPR and FPR were not significantly different between instruments. Frailty was the only significant predictor of death or new disability in a multivariable analysis. Need for institutional discharge, costs and LOS were significantly increased in individuals with frailty. The CFS was easier to use, required less time and had less missing data.

Conclusions:
Older people with frailty are significantly more likely to die or experience a new patient-reported disability after surgery. Clinicians performing frailty assessments before surgery should consider the CFS over the mFI as accuracy was similar, but ease of use and feasibility were higher.
Leadership in American Surgery
Authors: Pories Susan E. , Turner Patricia L. , Greenberg Caprice C. , Babu Maya A. , Parangi Sareh 
Published: July 2018

Objective:
To celebrate the increasing representation of women as leaders in American surgery and provide suggestions for increasing diversity in leadership.

Background:
Women were barred from entering the practice of medicine or surgery until the mid 1800's when Elizabeth Blackwell led the way as the first woman admitted to medical school. Although the numbers of women practicing medicine and surgery have increased exponentially since Dr Blackwell graduated, the number of women in leadership positions has remained low until recently.

Methods:
An analysis of the literature on the history of women in surgery and the websites of the major surgical societies.

Results:
More women are now rising to leadership positions in surgery, both in academics and within surgical organizations. The American College of Surgeons and many other surgical societies, as well as an increasing number of academic departments of surgery have realized that women can be inspiring and capable leaders. However, increasing the number of under-represented minority women in leadership positions remains an opportunity for improvement.

Conclusions:
Great progress has been made in the advancement of women into leadership positions in surgery. To continue this trend and increase the number of under-represented minority women in surgery will require attention to recruitment, mentorship, and sponsorship.
Consolidation alters motor sequence-specific distributed representations
Authors: Pinsard Basile , Boutin Arnaud , Gabitov Ella , Lungu Ovidiu , Benali Habib , Doyon Julien 
Published: July 2018

AbstractFMRI studies investigating the acquisition of sequential motor skills in humans have revealed learning-related functional reorganizations of the cortico-striatal and cortico-cerebellar motor systems in link with the hippocampus. Yet, the functional significance of these activity level changes is not fully understood as they convey the evolution of both sequence-specific knowledge and unspecific task expertise. Moreover, these changes do not specifically assess the occurrence of learning-related plasticity. To address these issues, we investigated local circuits tuning to sequence-specific information using multivariate distances between patterns evoked by consolidated or newly acquired motor sequences production. Results reveal that representations in dorsolateral striatum, prefrontal and secondary motor cortices are greater when executing consolidated sequences than untrained ones. By contrast, sequence representations in the hippocampus and dorsomedial striatum are less engaged. Our findings show, for the first time in humans, that complementary sequence-specific motor representations evolve distinctively during critical phases of skill acquisition and consolidation.
Fine-scale Inference of Ancestry Segments without Prior Knowledge of Admixing Groups
Authors: Salter-Townshend Michael , Myers Simon 
Published: July 2018

ABSTRACTWe present an algorithm for inferring ancestry segments and characterizing admixture events, which involve an arbitrary number of genetically differentiated groups coming together. This allows inference of the demographic history of the species, properties of admixing groups, identification of signatures of natural selection, and may aid disease gene mapping. The algorithm employs nested hidden Markov models to obtain local ancestry estimation along the genome for each admixed individual. In a range of simulations, the accuracy of these estimates equals or exceeds leading existing methods that return local ancestry. Moreover, and unlike these approaches, we do not require any prior knowledge of the relationship between sub-groups of donor reference haplotypes and the unseen mixing ancestral populations. Instead, our approach infers these in terms of conditional “copying probabilities”. In application to the Human Genome Diversity Panel we corroborate many previously inferred admixture events (e.g. an ancient admixture event in the Kalash). We further identify novel events such as complex 4-way admixture in San-Khomani individuals, and show that Eastern European populations possess 1 – 5% ancestry from a group resembling modern-day central Asians. We also identify evidence of recent natural selection favouring sub-Saharan ancestry at the HLA region, across North African individuals. We make available anRandC++ software library, which we term MOSAIC (which stands for MOSAIC Organises Segments of Ancestry In Chromosomes).
Predicting HIV Incidence in the SEARCH Trial: A Mathematical Modelling Study
Authors: Jewell Britta L. , Bershteyn Anna 
Published: July 2018

ABSTRACTIntroductionSEARCH is one of four randomized-controlled trials (RCTs) investigating the strategy of community-based treatment-as-prevention (TasP) for the reduction of HIV incidence in sub-Saharan Africa. SEARCH takes place among 32 pair-matched rural communities in three regions of East Africa and exceeded the UNAIDS 90-90-90 targets for HIV testing, linkage to care, and viral suppression in the intervention arm. We used mathematical modeling to estimate expected 3-year cumulative HIV incidence in both arms of the trial, using different assumptions about two main sources of uncertainty: scale-up of antiretroviral therapy (ART) in the control arm, and the degree of mixing between SEARCH residents and non-residents.MethodsWe used the HIV modelling software EMOD-HIV to configure and calibrate a new model of the SEARCH communities. The 32 trial communities were clustered into six nodes (three for the control arm and three for the intervention arm) using k-means clustering based on community HIV prevalence, male circumcision rates, mobility, and geographic region. The model was parameterized using data on demographics, HIV prevalence, male circumcision rates, and viral suppression data collected at trial baseline in 2013, and calibrated to nodespecific and age-specific HIV prevalence, ART coverage, and population size. Using data on ART scale-up in subsequent follow-up years in the trial, we varied linkage to ART in the control arm and the degree of external mixing between SEARCH residents and non-residents.ResultsIf no external mixing and no additional control arm ART linkage occurred, we estimate the trial would report a relative risk (RR) of 0.60 (95% CI 0.54-0.67, p<0.001), with all simulations showing a significant result. However, if SEARCH residents mixed equivalently with non-residents and ART linkage in the control arm also increased such that the control arm also exceeded the 73% viral suppression target, the RR is estimated to be 0.96 (95% CI 0.87-1.06, p=0.458) and 72% of simulations are non-significant. Given our “best guess” assumptions about external mixing and year 3 data on ART linkage in the control arm, the RR is estimated to be 0.90 (95% CI 0.81-1.00, p=0.05), with 49% non-significant simulations.ConclusionThe SEARCH trial is predicted to show a 4-40% reduction in cumulative 3-year incidence, but between 18-72% of simulations were non-significant if either or both ART linkage in the control arm and external mixing are substantial. Despite achieving the 90-90-90 targets, our “best guess” is that the SEARCH trial has an equal probability of reporting a non-significant reduction in HIV incidence as it does a significant reduction.
Diversity-dependent plant-soil feedbacks underlie long-term plant diversity effects on primary productivity
Authors: Guerrero-Ramírez Nathaly R. , Reich Peter B. , Wagg Cameron , Ciobanu Marcel , Eisenhauer Nico 
Published: July 2018

AbstractAlthough diversity-dependent plant-soil feedbacks (PSFs) may contribute significantly to plant diversity effects on ecosystem functioning, the influence of underlying abiotic and biotic mechanistic pathways have been little explored to date. Here, we assessed such pathways with a PSF experiment using soil conditioned for ≥12 years from two grassland biodiversity experiments. Model plant communities differing in diversity were grown in soils conditioned by plant communities with either low- or high-diversity (soil history). Our results reveal that plant diversity can modify plant productivity through both diversity-mediated plant-plant and plant-soil interactions, with the main driver (current plant diversity or soil history) differing with experimental context. The underlying mechanisms of PSFs were explained to a significant extent by both abiotic and biotic pathways (specifically, nematode richness and soil nitrogen availability). Thus, effects of plant diversity loss on ecosystem functioning may persist or even increase over time because of biotic and abiotic soil legacy effects.
Body mass aging trajectory is modulated by environmental conditions but independent of lifespan
Authors: Briga Michael , Jimeno Blanca , Verhulst Simon 
Published: July 2018

AbstractHow lifespan associates with aging trajectories of health and disease is an urgent question in societies with increasing lifespan. Body mass declines with age are associated with decreased organismal functioning in many species. We tested whether two factors that decreased lifespan in zebra finches, sex and manipulated environmental quality, accelerated the onset and/or rate of within-individual body mass declines. We subjected 597 birds for nine years to experimentally manipulated foraging costs (harsh = H, benign = B) during development and in adulthood in a 2×2 design. This yielded four treatment combinations (HH, HB, BH, BB). Harsh environments during development and in adulthood decreased average body mass additively. In males, the aging trajectory was quadratic, with a maximum between 3.5 and 4 years, and independent of the environment (HH=HB=BH=BB). In females, the shape of the aging trajectory differed between environments: a quadratic trajectory as in males in the benign adult environment (HB=BB), a linear decline when benign development was followed by harsh adulthood (BH) and a linear increase when in a lifelong harsh environment (HH). We found no evidence for an association between lifespan and body mass aging trajectories either between or within experimental groups. However, females lived shorter than males, and their body mass decline started earlier for most treatment combinations. Thus, we conclude that foraging conditions can affect the shape of body mass aging trajectories, but these are independent of lifespan.
Counterconditioning following memory retrieval diminishes reinstatement of appetitive memories in humans
Authors: Gera Rani , Barak Segev , Schonberg Tom 
Published: July 2018

AbstractAppetitive memories play a crucial role in learning and behavior but under certain circumstances become maladaptive and play a vital part in addiction and other psychopathologies. In recent years, scientific research demonstrated the ability of memories to be modified following their reactivation through memory retrieval, in a process termed memory reconsolidation. Several non-pharmacological behavioral manipulations yielded mixed results in their capacity to alter maladaptive memories in humans. Here, aiming to translate promising findings observed in rodents to humans, we constructed a novel three-day procedure to test the efficacy of aversive counterconditioning to alter appetitive memories when given following memory retrieval. On Day1 we used appetitive conditioning to form appetitive memories. On Day2, we retrieved these appetitive memories for half of the participants (Retrieval group). Subsequently, all participants underwent counterconditioning. On Day3, we tried to reinstate Day1 appetitive memories. We observed a significant reduction in the reinstatement of the original appetitive memory when counterconditioning was induced following memory retrieval. We provide here a novel human paradigm that models several memory processes, and demonstrate memory attenuation when counterconditioned after its retrieval. This paradigm can be used to study complex appetitive memory dynamics, e.g., memory reconsolidation, and their underlying brain mechanisms.
Frictional effects on RNA folding: Speed limit and Kramers turnover
Authors: Hori Naoto , Denesyuk Natalia A. , Thirumalai D. 
Published: July 2018

AbstractWe investigated frictional effects on the folding rates of a human Telomerase hairpin (hTR HP) and H-type pseudoknot from the Beet Western Yellow Virus (BWYV PK) using simulations of the Three Interaction Site (TIS) model for RNA. The heat capacity from TIS model simulations, calculated using temperature replica exchange simulations, reproduces nearly quantitatively the available experimental data for the hTR HP. The corresponding results for BWYV PK serve as predictions. We calculated the folding rates (kFs) from more than 100 folding trajectories for each value of the solvent viscosity (η) at a fixed salt concentration of 200 mM. Using the theoretical estimate ( where N is number of nucleotides) for folding free energy barrier, kF data for both the RNAs are quantitatively fit using one dimensional Kramers’ theory with two parameters specifying the curvatures in the unfolded basin and the barrier top. In the high-friction regime (η ≳ 10−5 Pa·s), for both HP and PK, kFs decrease as 1/η whereas in the low friction regime kFs increase as η increases, leading to a maximum folding rate at a moderate viscosity (~ 10−6 Pa·s), which is the Kramers turnover. From the fits, we find that the speed limit to RNA folding at water viscosity is between (1 − 4)μs, which is in accord with our previous theoretical prediction as well as results from several single molecule experiments. Both the RNA constructs fold by parallel pathways. Surprisingly, we find that the flux through the pathways could be altered by changing solvent viscosity, a prediction that is more easily testable in RNA than proteins.
Assessing protein dynamics on low complexity single-strand DNA curtains
Authors: Schaub Jeffrey M. , Zhang Hongshan , Soniat Michael M. , Finkelstein Ilya J. 
Published: July 2018

AbstractSingle-stranded DNA (ssDNA) is a critical intermediate in all DNA transactions. As ssDNA is more flexible than double-stranded (ds)DNA, interactions with ssDNA-binding proteins (SSBs) may significantly compact or elongate the ssDNA molecule. Here, we develop and characterize low-complexity ssDNA curtains, a high-throughput single-molecule assay to simultaneously monitor protein binding and correlated ssDNA length changes on supported lipid bilayers. Low-complexity ssDNA is generated via rolling circle replication of short synthetic oligonucleotides, permitting control over the sequence composition and secondary structure-forming propensity. One end of the ssDNA is functionalized with a biotin, while the second is fluorescently labeled to track the overall DNA length. Arrays of ssDNA molecules are organized at microfabricated barriers for high-throughput single-molecule imaging. Using this assay, we demonstrate thatE. coliSSB drastically and reversibly compacts ssDNA templates upon changes in NaCl concentration. We also examine the interactions between a phosphomimetic RPA and ssDNA. Our results indicate that RPA-ssDNA interactions are not significantly altered by these modifications. We anticipate low-complexity ssDNA curtains will be broadly useful for single-molecule studies of ssDNA-binding proteins involved in DNA replication, transcription and repair.
Tsc1-mTOR signaling controls the structure and function of midbrain dopamine neurons
Authors: Kosillo Polina , Doig Natalie M. , Agopyan-Miu Alexander H.C.W. , Ahmed Kamran , Conyers Lisa , Threlfell Sarah , Magill Peter J. , Bateup Helen S. 
Published: July 2018

SummarymTOR complex 1 (mTORC1) is a central coordinator of cell growth and metabolism. Mutations in regulators of mTORC1 cause syndromic disorders with a high prevalence of cognitive and psychiatric conditions. To elucidate the cellular origins of these manifestations, we conditionally deleted the gene encoding the mTORC1 negative regulator Tsc1 from mouse midbrain dopamine neurons, which modulate motor, affective, and cognitive behaviors that are frequently affected in psychiatric disorders. Loss of Tsc1 and constitutive activation of mTORC1 strongly impacted the properties of dopamine neurons, causing somatodendritic hypertrophy, reduced intrinsic excitability, altered axon terminal ultrastructure, and severely impaired dopamine release. These perturbations were associated with selective deficits in cognitive flexibility, which could be prevented by genetic reduction of the obligatory mTORC1 protein Raptor. Our results establish a critical role for mTORC1 in setting the functional properties of midbrain dopamine neurons, and indicate that dopaminergic dysfunction may underlie cognitive inflexibility in mTOR-related syndromes.