bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Persistence of Initial Treatment for HIV Infection With Modern Antiretroviral Therapy
Authors: Davy-Mendez Thibaut , Eron Joseph J. , Zakharova Oksana , Wohl David A. , Napravnik Sonia 
Published: June 2017

Background:
Initiating antiretroviral therapy (ART) early improves clinical outcomes and prevents transmission. Guidelines for first-line therapy have changed with the availability of newer ART agents. In this study, we compared persistence and virologic responses with initial ART according to the class of anchor agent used.

Setting:
An observational clinical cohort study in the Southeastern United States.

Methods:
All HIV-infected patients participating in the UNC Center for AIDS Research Clinical Cohort (UCHCC) and initiating ART between 1996 and 2014 were included. Separate time-to-event analyses with regimen discontinuation and virologic failure as outcomes were used, including Kaplan–Meier survival curves and adjusted Cox proportional hazards models.

Results:
One thousand six hundred twenty-four patients were included (median age of 37 years at baseline, 28% women, 60% African American, and 28% white). Eleven percent initiated integrase strand transfer inhibitor (INSTI), 33% non–nucleoside reverse transcriptase inhibitor (NNRTI), 20% boosted protease inhibitor, 27% other, and 9% NRTI only regimens. Compared with NNRTI-containing regimens, INSTI-containing regimens had an adjusted hazard ratio of 0.49 (95% confidence interval, 0.35 to 0.69) for discontinuation and 0.70 (95% confidence interval, 0.46 to 1.06) for virologic failure. All other regimen types were associated with increased rates of discontinuation and failure compared with NNRTI.

Conclusions:
Initiating ART with an INSTI-containing regimen was associated with lower rates of regimen discontinuation and virologic failure.
Antiretroviral Prescription and Viral Suppression in a Representative Sample of HIV-Infected Persons in Care in 4 Large Metropolitan Areas of the United States, Medical Monitoring Project, 2011–2013
Authors: Wohl Amy Rock , Benbow Nanette , Tejero Judith , Johnson Christopher , Scheer Susan , Brady Kathleen , Gagner Alexandra , Hughes Alison , Eberhart Michael , Mattson Christine , Skarbinski Jacek 
Published: June 2017

Background:
Comparisons of antiretroviral therapy (ART) prescription and viral suppression among people in HIV care across US metropolitan areas are limited. Medical Monitoring Project, 2011–2013, data were used to describe and compare associations between sociodemographics and ART prescription and viral suppression for persons receiving HIV care.

Setting:
Chicago, Los Angeles County (LAC), Philadelphia, and San Francisco in the United States.

Methods:
Bivariate and multivariable methods were used.

Results:
The proportion of patients prescribed ART (91%–93%) and virally suppressed (79%–88%) was consistent although more persons were virally suppressed in San Francisco compared with the other areas, and a smaller proportion was virally suppressed in Philadelphia compared with Chicago. In the combined cohort, persons aged 30–49 years were less likely than persons 50+ (adjusted prevalence ratio (aPR) –0.97, confidence interval (CI): 0.94 to 0.99); persons reporting non-injection drug use were less likely than non-users (aPR = 0.94, CI: 0.90 to 0.98); and Hispanics were more likely than whites (aPR – 1.04, CI: 1.01 to 1.08) to be prescribed ART. Blacks (aPR = 0.93; CI: 0.87 to 0.99) and homeless persons (aPR = 0.87; CI: 0.80 to 0.95) were less likely to be virally suppressed in the combined cohort. In LAC, persons aged 30–49 years were less likely than those 50+ to be prescribed ART (aPR = 0.94, CI: 0.90 to 0.98). Younger persons (18–29) (aPR = 0.77; CI: 0.60 to 0.99) and persons with less than a high school education (aPR = 0.80; CI: 0.67 to 0.95) in Philadelphia, blacks (aPR = 0.90; CI: 0.83 to 0.99) and men who have sex with women only (aPR = 0.89; CI: 0.80 to 0.99) in Chicago, and homeless individuals in LAC (aPR = 0.80; CI: 0.67 to 0.94) were less likely to be virally suppressed.

Conclusion:
Data highlight the need to increase ART prescription to achieve viral suppression among younger persons, noninjection drug users, blacks, and homeless persons in US metropolitan areas and underscores the importance of region-specific strategies for affected subgroups.
Risk of Post-transplant Hepatocellular Carcinoma Recurrence Is Higher in Recipients of Livers From Male Than Female Living Donors
Authors: Han Sangbin , Yang Ju Dong , Sinn Dong Hyun , Kim Jong Man , Choi Gyu Sung , Jung Gangha , Ahn Joong Hyun , Kim Seonwoo , Ko Justin S. , Gwak Mi Sook , Kwon Choon Hyuck D. , Leise Michael D. , Gwak Geum-Youn , Heimbach Julie K. , Kim Gaab Soo 
Published: June 2017

Objective:
To evaluate the relationship between donor sex and hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation.

Background:
HCC shows a male predominance in incidence and recurrence after tumor resection due to sex differences in hepatic sex hormone receptors. There have been no studies evaluating the importance of donor sex on post-transplant HCC recurrence.

Methods:
Of 384 recipients of livers, from living donors, for HCC: 104/120 who received grafts from female donors were matched with 246/264 who received grafts from male donors using propensity score matching, with an unfixed matching ratio based on factors like tumor biology. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence.

Results:
The median follow-up time was 39 months. Before matching, recurrence probability at 1/2/5 years after transplantation was 6.1/9.7/12.7% in recipients with female donors and 11.7/19.2/25.3% in recipients with male donors. Recurrence risk was significantly higher with male donors in univariable analysis (hazard ratio [HR] = 2.04 [1.15–3.60], P = 0.014) and multivariable analysis (HR=2.10 [1.20–3.67], P = 0.018). In the matched analysis, recurrence risk was also higher with male donors (HR=1.92 [1.05–3.52], P = 0.034): both in intrahepatic recurrence (HR=1.92 [1.05–3.51], P = 0.034) and extrahepatic recurrence (HR=1.93 [1.05–3.52], P = 0.033). Multivariable analysis confirmed the significance of donor sex (HR=2.08 [1.11–3.91], P = 0.023). Interestingly, the significance was lost when donor age was >40 years. Two external cohorts validated the significance of donor sex.

Conclusions:
Donor sex appears to be an important graft factor modulating HCC recurrence after living donor liver transplantation.
Open versus Laparoscopic Surgery for Advanced Low Rectal Cancer
Authors: Hida Koya , Okamura Ryosuke , Sakai Yoshiharu , Konishi Tsuyoshi , Akagi Tomonori , Yamaguchi Tomohiro , Akiyoshi Takashi , Fukuda Meiki , Yamamoto Seiichiro , Yamamoto Michio , Nishigori Tatsuto , Kawada Kenji , Hasegawa Suguru , Morita Satoshi , Watanabe Masahiko 
Published: June 2017

Background:
Laparoscopic surgery for rectal cancer is widely performed all over the world and several randomized controlled trials have been reported. However, the usefulness of laparoscopic surgery compared with open surgery has not been demonstrated sufficiently, especially for the low rectal area.

Objective:
The aim of this study was to investigate the hypothesis that laparoscopic primary tumor resection is safe and effective when compared with the open approach for locally advanced low rectal cancer.

Patients and Methods:
Data from patients with clinical stage II to III low rectal cancer below the peritoneal reflection were collected and analyzed. The operations were performed from 2010 to 2011. Short-term outcomes and long-term prognosis were analyzed with propensity score matching.

Results:
Of 1608 cases collated from 69 institutes, 1500 cases were eligible for analysis. The cases were matched into 482 laparoscopic and 482 open cases. The mean height of the tumor from the anal verge was 4.6 cm. Preoperative treatment was performed in 35% of the patients. The conversion rate from laparoscopic to open surgery was 5.2%. Estimated blood loss during laparoscopic surgery was significantly less than that during open surgery (90 vs 625 mL, P < 0.001). Overall, the occurrence of complications after laparoscopic surgeries was less than that after open surgeries (30.3% vs 39.2%, P = 0.005). Three-year overall survival rates were 89.9% [95% confidence interval (95% CI) 86.7–92.4] and 90.4% (95% CI 87.4–92.8) in the laparoscopic and open groups, respectively, and no significant difference was seen between the 2 groups. No significant difference was observed in recurrence-free survival (RFS) between the 2 groups (3-year RFS: 70.9%, 68.4 to 74.2 vs 71.8%, 67.5 to 75.7).

Conclusion:
Laparoscopic surgery could be considered as a treatment option for advanced, low rectal cancer below the peritoneal reflection, based on the short-term and long-term results of this large cohort study (UMIN-ID: UMIN000013919).
Immediate Impact of Centralization on Abdominal Aortic Aneurysm Repair Outcomes for a Vascular Network in the South West of England
Authors: Leighton Philippa , Doe Matthew , Pathak Samir , AlDuwaisan Abdullah , Brooks Marcus 
Published: June 2017

Objective:
Our aim was to assess the short-term impact of centralization on the outcomes of patients undergoing abdominal aortic aneurysm repair in a vascular network in the South West of England.

Background:
The centralization of vascular services has been implemented nationally across the National Health Service to improve patient outcomes. The full impact of these major changes has not yet been fully analyzed.

Methods:
A retrospective cohort study examining outcomes of patients undergoing abdominal aortic aneurysm repair, based on prospectively entered National Vascular Registry data, pre and post centralization in the South West of England. The primary outcome was mortality at 30 days. Secondary measures included 30-day morbidity, length of hospital stay, and length of intensive care unit stay.

Results:
The 30-day mortality was unchanged pre and post-centralization (11% vs 12%, P = 0.84). The 30-day morbidity rate was also unchanged (24% vs 25%, P = 0.83), as was length of intensive care unit stay (3 vs 3 days, P = 0.74). Overall length of stay was not significantly different (8 vs 6 days, P = 0.76). Subgroup analysis of patients with elective, ruptured, and symptomatic aneurysm repair demonstrated no differences in 30-day mortality. There was a significantly shorter stay post-centralization for patients with symptomatic aneurysms (6 vs 12 days pre-centralization, P = 0.012).

Conclusions:
The process of centralization of abdominal aortic aneurysm repair in a vascular network was safe for patients and had no immediate impact on outcomes. Longer-term outcome measures and financial data will be required to further assess the benefit of centralization.
The Surgeon Volume-outcome Relationship
Authors: Modrall J. Gregory , Minter Rebecca M. , Minhajuddin Abu , Eslava-Schmalbach Javier , Joshi Girish P. , Patel Shivani , Rosero Eric B. 
Published: June 2017

Objective:
Increasing surgeon volume may improve outcomes for index operations. We hypothesized that there may be surrogate operative experiences that yield similar outcomes for surgeons with a low-volume experience with a specific index operation, such as esophagectomy.

Background:
The relationship between surgeon volume and outcomes has potential implications for credentialing of surgeons. Restrictions of privileges based on surgeon volume are only reasonable if there is no substitute for direct experience with the index operation. This study was aimed at determining whether there are valid surrogates for direct experience with a sample index operation—open esophagectomy.

Methods:
The Nationwide Inpatient Sample (2003–2009) was utilized. Surgeons were stratified into low and high-volume groups based on annual volume of esophagectomy. Surrogate volume was defined as the aggregate annual volume per surgeon of upper gastrointestinal operations including excision of esophageal diverticulum, gastrectomy, gastroduodenectomy, and repair of diaphragmatic hernia.

Results:
In all, 26,795 esophagectomies were performed nationwide (2003–2009), with a crude inhospital mortality rate of 5.2%. Inhospital mortality decreased with increasing volume of esophagectomies performed annually: 7.7% and 3.8% for low and high-volume surgeons, respectively (P < 0.0001). Among surgeons with a low-volume esophagectomy experience, increasing volume of surrogate operations improved the outcomes observed for esophagectomy: 9.7%, 7.1%, and 4.3% for low, medium, and high-surrogate-volume surgeons, respectively (P = 0.016).

Conclusions:
Both operation-specific volume and surrogate volume are significant predictors of inhospital mortality for esophagectomy. Based on these observations, it would be premature to limit hospital privileges based solely on operation-specific surgeon volume criteria.
Robotic Versus Video-assisted Lobectomy/Segmentectomy for Lung Cancer
Authors: Liang Hengrui , Liang Wenhua , Zhao Lei , Chen Difei , Zhang Jianrong , Zhang Yiyin , Tang Shiyan , He Jianxing 
Published: June 2017

Objective: To compare the safety/efficacy of the robotic-assisted lobectomy/segmentectomy (RAL/S) with the video-assisted lobectomy/segmentectomy (VAL/S) for radical lung cancer resection.

Background:
It remains uncertain whether the newly developed RAL/S is comparable with the VAL/S.

Methods:
A comprehensive search of online databases was performed. Perioperative outcomes were synthesized. Cumulative meta-analysis was performed to evaluate the temporal trend of pooled outcomes. Specific subgroups (propensity score matching studies, pure lobectomy studies) were examined.

Results:
Analysis of 14 studies including a total of 7438 patients was performed. RAL/S was performed on 3239 patients, whereas the other 4199 patients underwent VAL/S. The 30-day mortality [0.7% vs 1.1%; odds ratio (OR) 0.53, P = 0.045] and conversion rate to open surgery (10.3% vs 11.9%; OR 0.57, P < 0.001) were significantly lower in patients who underwent RAL/S than VAL/S. Meanwhile, the postoperative complications (27.5% vs 28.2%; OR 0.95, P = 0.431), operation time [176.63 vs 162.74 min; standardized mean difference (SMD) 0.30, P = 0.086], duration of hospitalization (4.90 vs 5.23 days; SMD −0.08, P = 0.292), days to tube removal (4.10 vs 3.53 days; SMD 0.25, P = 0.120), retrieved lymph node (11.96 vs 10.67; SMD 0.46, P = 0.381), and retrieved lymph node station (4.98 vs 4.32; SMD 0.83, P = 0.261) were similar between the 2 groups. The cumulative meta-analyses suggested that the relative effects between 2 groups have already stabilized. All outcomes of subgroup and overall analyses were similar.

Conclusions:
This up-to-date meta-analysis confirms that RAL/S is a feasible and safe alternative to VAL/S for radical resection of lung cancer. Future studies should focus on the long-term benefits and cost effectiveness of RAL/S compared with VAL/S.
Falls and Physical Activity in Persons With Mild to Moderate Dementia Participating in an Intensive Motor Training
Authors: Zieschang Tania , Schwenk Michael , Becker Clemens , Uhlmann Lorenz , Oster Peter , Hauer Klaus 
Published: June 2017

Background:
Physical activity is beneficial in people with dementia. As physical activity increases risk exposure for falls, safety concerns arise. Prior exercise trials in people with dementia have not measured physical activity. Falls in relation to exposure time rather than person-years as outcome measure has been promoted but not investigated in people with dementia.

Methods:
Patients with mild to moderate dementia (n=110) were randomized to an intensive, progressive strength and functional training intervention or to a low-intensity group training for 12 weeks each. Physical activity was measured with a standardized questionnaire. Falls were documented prospectively by calendars for 12 months.

Results:
During the intervention, physical activity was significantly higher in the intervention group (P<0.001) without an increased fall rate (intervention group vs. control group: 2.89 vs. 1.94; incidence rate ratio, 1.49; 95% confidence interval, 0.66-3.36; P=0.333). In the subgroup of multiple fallers, the number of falls per 1000 hours of activity was significantly lower in the intervention group (8.85 vs. 18.67; P=0.017).

Conclusions:
Increased physical activity during exercise intervention was safe in people with mild to moderate dementia. Fall rate adjusted for physical activity is a useful and sensitive outcome measure in addition to fall rate per person-years.
Quantifying uncertainty in the inference of generalized coalescents
Authors: Wallstrom Timothy C. , Bhattacharya Tanmoy , Wilkins Jon F. 
Published: June 2017

AbstractWe develop inference methods for generalized coalescent models, such as theΛ- andΞ-coalescents, which have recently been proposed for populations with broad offspring distributions, repeated selective sweeps, or strong selection. These are all populations that may not be adequately described by the usual Kingman coalescent. A roadblock to the application of such models has been the lack of effective tools for inferring an appropriate model, which stems from difficulties in evaluating the associated likelihoods. We overcome these difficulties by introducing estimators that are both computationally tractable and statistically efficient. We use these estimators to obtain point estimates and confidence intervals for the parameters of the coalescent models, and p-values for the hypothesis that the population is described by the Kingman coalescent. Our approach is based on the theory of unbiased estimating equations, which is more general than composite likelihood and may be applicable in other areas of statistical genetics. Our main focus is on inference from linked site-frequency spectra using parameterized families ofΛ-coalescents. We show that useful inferences may be made from non-singleton data alone if singletons are suspect due to sequencing or data-cleaning errors, although the data requirements are greatly increased. We apply our method to mitochondrial sequence data from Gadus morhua, the Atlantic cod.
Hands-free control of heterologous gene expression in batch cultures
Authors: Borkowski Olivier , Endy Drew , Subsoontorn Pakpoom 
Published: June 2017

AbstractBackgroundAutonomous cell-based control of heterologous gene expression can simplify batch-culture bioprocessing by eliminating external monitoring and extrinsic control of culture conditions. Existing approaches use auto-induction media, synthetic cell-cell communication systems, or application-specific biosensors. A simpler, resource-efficient, and general-purpose expression control system responsive to common changes during batch culture would be useful.ResultsWe used nativeE.colipromoters and recombinase-based switches to repurpose endogenous transcription signals for control of heterologous gene expression. Specifically, natural changes in transcription from endogenous promoters result in recombinase expression at different phases of batch culture. So-expressed recombinases invert a constitutive promoter regulating expression of arbitrary heterologous genes. We realized reversible and single-use switching, reduced static and dynamic cell-to-cell variation, and overall expression amplification. We used “off-the-shelf” genetic parts and abstraction-based composition frameworks to realize reliable forward engineering of our synthetic genetic systems.ConclusionWe engineered autonomous control systems for regulating heterologous gene expression. Our system uses generic endogenous promoters to sense and control heterologous expression during growth-phase transitions. Our system does not require specialized auto-induction media, production or activation of quorum sensing, or the development of application-specific biosensors. Cells programmed to control themselves could simplify existing bioprocess operations and enable the development of more powerful synthetic genetic systems.
Impact of domain knowledge on blinded predictions of binding energies by alchemical free energy calculations
Authors: Mey Antonia S J S , Jiménez Jordi Juárez , Michel Julien 
Published: June 2017

AbstractThe drug design data resource (D3R) consortium organises blinded challenges to address the latest advances in computational methods for ligand pose prediction, affinity ranking, and free energy calculations. Within the context of the second D3R Grand Challenge several blinded binding free energies predictions were made for two congeneric series of FXR inhibitors with a semi-automated alchemical free energy calculations workflow featuring the FESetup and SOMD tools. Reasonable performance was observed in retrospective analyses of literature datasets. Nevertheless blinded predictions on the full D3R datasets were poor due to difficulties encountered with the ranking of compounds that vary in their net-charge. Performance increased for predictions that were restricted to subsets of compounds carrying the same net-charge. Disclosure of X-ray crystallography derived binding modes maintained or improved the correlation with experiment in a subsequent rounds of predictions. The best performing protocols on D3R set1 and set2 were comparable or superior to predictions made on the basis of analysis of literature SARs only, and comparable or slightly inferior, to the best submissions from other groups.
Addressing the looming identity crisis in single cell RNA-seq
Authors: Crow Megan , Paul Anirban , Ballouz Sara , Huang Z. Josh , Gillis Jesse 
Published: June 2017

AbstractSingle cell RNA-sequencing technology (scRNA-seq) provides a new avenue to discover and characterize cell types, but the experiment-specific technical biases and analytic variability inherent to current pipelines may undermine the replicability of these studies. Meta-analysis of rapidly accumulating data is further hampered by the use of ad hoc naming conventions. Here we demonstrate our replication framework, MetaNeighbor, that allows researchers to quantify the degree to which cell types replicate across datasets, and to rapidly identify clusters with high similarity for further testing. We first measure the replicability of neuronal identity by comparing more than 13 thousand individual scRNA-seq transcriptomes, sampling with high specificity from within the data to define a range of robust practices. We then assess cross-dataset evidence for novel cortical interneuron subtypes identified by scRNA-seq and find that 24/45 cortical interneuron subtypes have evidence of replication in at least one other study. Identifying these putative replicates allows us to re-analyze the data for differential expression and provide lists of robust candidate marker genes. Across tasks we find that large sets of variably expressed genes can identify replicable cell types and subtypes with high accuracy, suggesting a general route forward for large-scale evaluation of scRNA-seq data.