bluuebunny/crossref_metadata_2025 huggingface dataset:
What Kinds of Posterior Cruciate Ligament Bundles Are Preserved in Cruciate-Retaining Total Knee Arthroplasty? A Three-Dimensional Morphology Study
Authors: Inou Yoshinori , Tomita Tetsuya , Kiyotomo Dai , Yoshikawa Hideki , Sugamoto Kazuomi
Published: November 2018

In this study, the effects of tibial bone cutting on the attachment area of the posterior cruciate ligament (PCL), including both the anterolateral bundle (ALB) and posteromedial bundle (PMB), in cruciate-retaining total knee arthroplasty (CR-TKA) were simulated using a three-dimensional (3D) model of the tibial reconstruction. A total of 40 knees with medial osteoarthritis in patients scheduled for TKA were evaluated. Following surface registration of 3D computed tomography (CT) and 3D magnetic resonance imaging (MRI) models of the tibia with the PCL, the area of PCL attachment was calculated. Tibial bone cutting in the 3D CT model was simulated at 8 and 10 mm distal to the center of the lateral articular surfaces of the tibia and with posterior tibial slope angles of 0, 7, and 10 degrees. The percentages of the ALB and PMB tibial attachment areas that remained after cutting at 8 mm were, respectively, 21.8 ± 19.7% and 86.3 ± 17.7% with 0 degrees, 9.5 ± 10.4% and 64.1 ± 23.6% with 7 degrees, and 8.1 ± 6.7% and 51 ± 25.3% with 10 degrees. These results suggest that only half of the PCL attachment area was left after the bone cut simulation. Complete preservation of the ALB and PMB attachment areas requires appropriate selection of surgical procedures and devices.
Cognitive Training for Robotic Arm-Assisted Unicompartmental Knee Arthroplasty through a Surgical Simulation Mobile Application
Authors: Vestermark George L. , Bhowmik-Stoker Manoshi , Springer Bryan D.
Published: November 2018

Advances in mobile device technology combined with the implementation of surgical simulation have led to the development of novel applications (apps) as a potential learning tool for surgical trainees. Touch Surgery (TS) (Kinosis Limited, London, United Kingdom) is a mobile-based app that combines cognitive task analysis with a virtual reality medium to familiarize the user with a surgical procedure through interactive rehearsal. The purpose of this study was to compare the educational efficacy of the TS app with a traditional paper-based learning program in performing a robotic arm-assisted unicompartmental knee arthroplasty. Twelve participants (four interns, four residents, four adult reconstructive fellows) were randomized to a paper-based technique guide or learning modules from the Mako Partial Knee (Stryker, Mahwah, NJ) TS app. Trainees were subjected to a baseline pretest. After preparing with the allocated training tool, participants completed an immediate posttest followed by a retention test administered 3 weeks later. The TS simulation group demonstrated greater improvement (22% score increase; p = 0.001) in posttest assessment compared with the control group (10% score increase; p = 0. 09). The TS simulation group demonstrated better information recall compared with the control group based on the score differential following the 3-week retention test. This randomized comparative study demonstrated that the TS app was better than traditional paper-based learning for both immediate posttest performance and long-term information recall of the Mako robotic arm-assisted unicompartmental knee arthroplasty. Surgical simulation apps may be an effective learning tool for surgical trainees.
First-Trimester Uterine Artery Doppler for the Prediction of Preeclampsia in Nulliparous Women: The Great Obstetrical Syndrome Study
Authors: Demers Suzanne , Boutin Amélie , Gasse Cédric , Drouin Olivier , Girard Mario , Bujold Emmanuel
Published: November 2018

Objective This study aimed to estimate the performance of first-trimester uterine artery (UtA) pulsatility index (PI) for the prediction of preeclampsia (PE).

Study Design We conducted a prospective cohort study of nulliparous women with singleton gestation at 11 to 13 6/7 weeks. UtA-Doppler's was performed on both UtAs and the mean UtA-PI was reported in multiple of median (MoM) adjusted for gestational age. Using receiver operating characteristic curves and their area under the curves (AUC); we calculated the performance of UtA-PI for the prediction of PE. Proportional hazard models were used to develop prediction models combining UtA-PI and maternal characteristics.

Results Out of 4,676 participants with completed follow-up, 232 (4.9%) developed PE, including 202 (4.3%) term and 30 (0.6%) preterm PE. Mean UtA-PI decreased with gestational age between 11 and 13 6/7 weeks (p < 0.001). First-trimester UtA-PI was associated with preterm (AUC: 0.69; 95% CI [confidence interval]: 0.57–0.80) but not with term (AUC: 0.52; 95% CI: 0.48–0.56) PE. UtA-PI combined with maternal characteristics could predict 45% of preterm PE at a false positive rate of 10%.

Conclusion First-trimester UtA-PI decreases with gestational age between 11 and 13 6/7 weeks and is associated with the risk of preterm but not term PE.
Manipulation under Anesthesia: Does Polyethylene Thickness Matter?
Authors: Feng James E. , Anoushiravani Afshin A. , Ziegler Jacob , Schwarzkopf Ran , Long William J.
Published: November 2018

Total knee arthroplasty (TKA) has been established as the most effective treatment for end-stage, symptomatic osteoarthritis of the knee. However, improper polyethylene size selection has been proposed to predispose patients to postoperative stiffness following TKA. The aim of this study is to evaluate if there is a correlation between the use of the thinnest tibial implant thickness and implant manufacturer with the likelihood of undergoing manipulation under anesthesia (MUA). A retrospective review of unilateral TKAs performed between January 2012 and November 2015 was performed. Each knee implant system was normalized by total tibial component thickness for each individual implant system (metal back plus polyethylene) and reaggregated to assess the difference in MUA rates when comparing the thinnest tibial component thickness against the next two sizes. Subset analysis was performed comparing the thinnest tibial component thickness for each individual implant system versus (1) all other tibial component sizes and (2) tibial components one and two sizes larger. A total of 2,728 patients were retrospectively evaluated, of which 71 (2.60%) underwent MUA. Combined tibial component thickness ranged from 8 to 21 mm. When aggregated together to compare the MUA rate between the thinnest liner and the next two sizes, no statistically significant difference was observed (p = 1). Subset analysis demonstrated inconsistent significant differences in MUA rates. Our results suggest that the polyethylene liner thickness alone is not a predictor of postoperative knee stiffness necessitating MUA. When selecting a polyethylene liner, a proper fit maximizing flexion/extension stability is the most crucial factor.
Vitamin K Antagonists, Non–Vitamin K Antagonist Oral Anticoagulants, and Vascular Calcification in Patients with Atrial Fibrillation
Authors: Peeters Frederique , Dudink Elton , Kimenai Dorien , Weijs Bob , Altintas Sibel , Heckman Luuk , Mihl Casper , Schurgers Leon , Wildberger Joachim , Meex Steven , Kietselaer Bas , Crijns Harry
Published: November 2018

Background Vitamin K antagonists (VKAs) are associated with coronary artery calcification in low-risk populations, but their effect on calcification of large arteries remains uncertain. The effect of non–vitamin K antagonist oral anticoagulants (NOACs) on vascular calcification is unknown. We investigated the influence of use of VKA and NOAC on calcification of the aorta and aortic valve.

Methods In patients with atrial fibrillation without a history of major adverse cardiac or cerebrovascular events who underwent computed tomographic angiography, the presence of ascending aorta calcification (AsAC), descending aorta calcification (DAC), and aortic valve calcification (AVC) was determined. Confounders for VKA/NOAC treatment were identified and propensity score adjusted logistic regression explored the association between treatment and calcification (Agatston score > 0). AsAC, DAC, and AVC differences were assessed in propensity score–matched groups.

Results Of 236 patients (33% female, age: 58 ± 9 years), 71 (30%) used VKA (median duration: 122 weeks) and 79 (34%) used NOAC (median duration: 16 weeks). Propensity score–adjusted logistic regression revealed that use of VKA was significantly associated with AsAC (odds ratio [OR]: 2.31; 95% confidence interval [CI]: 1.16–4.59; p = 0.017) and DAC (OR: 2.38; 95% CI: 1.22–4.67; p = 0.012) and a trend in AVC (OR: 1.92; 95% CI: 0.98–3.80; p = 0.059) compared with non-anticoagulation. This association was absent in NOAC versus non-anticoagulant (AsAC OR: 0.51; 95% CI: 0.21–1.21; p = 0.127; DAC OR: 0.80; 95% CI: 0.36–1.76; p = 0.577; AVC OR: 0.62; 95% CI: 0.27–1.40; p = 0.248). A total of 178 patients were propensity score matched in three pairwise comparisons. Again, use of VKA was associated with DAC (p = 0.043) and a trend toward more AsAC (p = 0.059), while use of NOAC was not (AsAC p = 0.264; DAC p = 0.154; AVC p = 0.280).

Conclusion This cross-sectional study shows that use of VKA seems to contribute to vascular calcification. The calcification effect was not observed in NOAC users.
Tigecycline Use in Neonates: 5-Year Experience of a Tertiary Center
Authors: Gunel Mehmet , Ozbek Erdal , İpek Mehmet
Published: November 2018

The off-label use of tigecycline to treat serious infections has been reported in pediatric patients. We report four newborn infants diagnosed with sepsis caused by extensively drug-resistant Klebsiella pneumoniae and successfully treated with tigecycline. If no alternative drugs are available, tigecycline may be considered as an option for nosocomial infections even in newborn infants. However, further reports are needed to establish its efficacy and safety.
Longitudinal Measurements of Resting Energy Expenditure by Indirect Calorimetry in Healthy Term Infants during the First 2 Months of Life
Authors: Verma Sourabh , Bailey Sean M. , Mally Pradeep V. , Howell Heather B.
Published: November 2018

Objective To determine longitudinal measurements of resting energy expenditure (REE) by indirect calorimetry (IC) in healthy term infants during the first 2 months of life.

Study Design An outpatient prospective pilot study was performed in healthy term infants to estimate REE by measuring expired gas fractions of oxygen (O2) and carbon dioxide (CO2) with IC in a respiratory and metabolic steady state.

Results A total of 30 measurements were performed. Fourteen subjects completed measurements at both 1 and 2 months of life, and two subjects had only measurements made at 1 month of life. Mean REE values were 64.1 ± 12.7 and 58.4 ± 14.3 kcal/kg/d at 1 and 2 months of age, respectively. Mean O2 consumption and CO2 production measurements were 9.3 ± 2.0 and 7.7 ± 1.2 mL/kg/min and 8.1 ± 2.2 and 6.4 ± 1.1 mL/kg/min at 1 and 2 months of age, respectively.

Conclusion This pilot study demonstrates longitudinal measurements of REE by IC in healthy term infants during the first 2 months of life. We also demonstrate that, overall, there is consistency in REE values in this population, with a likely decrease in individual longitudinal measurements over the first 2 months of life.
Assessing Maternal and Fetal Risks Associated with Prolonged Induction of Labor
Authors: Triebwasser Jourdan , VanArtsdalen Jamie , Kobernik Emily , Seiler Kristian , Langen Elizabeth
Published: November 2018

Objective To assess whether prolonged induction of labor was associated with increased maternal or neonatal morbidity.

Study Design We performed a retrospective cohort study of women undergoing induction of labor at a single institution. We included women with singletons ≥ 36 weeks with initial cervical dilation ≤4 cm. Prolonged induction of labor was defined as lasting > 36 hours from the time of initial method to delivery. A 2-to-1 propensity score-matched analysis was performed between women with and those without prolonged induction of labor. Maternal outcomes were cesarean delivery, chorioamnionitis, endometritis, postpartum hemorrhage, severe perineal laceration, and length of postpartum admission. Neonatal outcomes included Apgar scores, umbilical artery pH, and neonatal intensive care admission.

Results Among 2,021 women, 407 (20.1%) had a prolonged induction. In unadjusted analyses, prolonged induction of labor was associated with increased cesarean delivery and chorioamnionitis. After 2-to-1 propensity score matching, there were 267 women with prolonged induction and 424 controls. Women with prolonged induction of labor had higher rates of cesarean delivery (35.6 vs. 16%, p < 0.001), chorioamnionitis (14.2 vs. 4.7%, p < 0.001), endometritis (6.4 vs. 1.9%, p = 0.002), and postpartum hemorrhage (18.8 vs. 11.9%, p = 0.008). There were no significant differences in neonatal outcomes.

Conclusion Overall length of induction impacts maternal outcome.
What you hear is (not always) what you get
Authors: Lipski John M.
Published: November 2018

The present study offers data from native Spanish speakers who possess receptive competence in Palenquero, a Spanish-lexified
creole spoken in the Afro-Colombian village of San Basilio de Palenque. Until recently Palenquero was endangered, but language
revitalization activities are now underway in Palenque. These efforts are resulting in young L2 Palenquero speakers and receptive
bilinguals, who do not actively use the language but who are exposed to it within the community and through occasional classes.
This study, based on experimental research conducted in Palenque, examines receptive bilinguals' grasp of Palenquero subject-verb
structures as a demonstration of how the divergence between active and receptive bilinguals' grammars can go undetected within the
speech community. Receptive bilinguals sometimes produce referential null subjects instead of overt pronouns even in the absence
of other disambiguating cues. Receptive bilinguals also do not systematically differentiate Palenquero pre-verbal particles, in a
fashion suggestive of a maximally simplified subject-verb configuration.
The Inventory of Callous-Unemotional Traits: Reliability, Convergent Validity, and Predictive Validity for Reoffending in Adolescents on Probation
Authors: Bhanwer Aisha K. , Viljoen Jodi L. , Shaffer Catherine S. , Douglas Kevin S.
Published: November 2018

This prospective study assessed the reliability and validity of the Inventory of Callous-Unemotional Traits (ICU) in a sample of 70 adolescent offenders. With the exception of the Unemotional subscale, ICU scores showed acceptable reliability. ICU total and Callousness scores demonstrated moderate associations with the Antisocial Process Screening Device and the Psychopathy Checklist: Youth Version. The ICU also demonstrated moderate predictive accuracy for violent reoffending over an 18-month follow-up period. While these findings provide some support for the ICU’s validity, more research is needed to determine if it is appropriate for use in applied settings with adolescent offenders.
Unusual Location for a Periorbital Dermoid Cyst
Authors: Scofield-Kaplan Stacy M. , Sobti Deepak , Evers Bret M. , Hogan R. Nick , Mancini Ronald
Published: November 2018

Dermoid cysts in the orbit classically present in children as a mass in the superotemporal or superonasal orbit along the zygomatico-frontal or fronto-ethmoidal suture lines. The presence of a dermoid cyst in the superficial eyelid, not associated with the tarsus, has only been reported once previously. The authors present a case of a 60-year-old man with a painless right lower eyelid mass inferonasally that was completely excised and found to be a dermoid cyst. The presence of a dermoid cyst involving the superficial lower eyelid is very rare. Furthermore, dermoid cysts in adults typically present in the setting of trauma, which was absent in this case. Therefore, it is important to consider dermoid cysts in the differential diagnosis of eyelid lesions in adults.
Calcium priming of the central venous catheter prevents a drop in ionized calcium concentration during Regional Citrate Anticoagulation
Authors: Roveri Giulia , Busana Mattia , Lusardi Andrea Clarissa , Ferrari Federica , Trevisan Giacomo , Di Girolamo Luca , Dei Poli Marco , Resta Marco Vittorio
Published: November 2018

During citrate-based Continuous Renal Replacement Therapy (CRRT), an infusion of calcium is necessary to replace the calcium lost in the effluent. The replacement takes place through a central venous catheter (CVC) that is primed with saline solution. Thus, we hypothesized a potential systemic anticoagulation caused by the unchelated citrate reaching the patient at the start of CRRT because of 0.42 ml of line dead space. In this pilot study, two subpopulations of 7 patients who underwent Continuous Veno-Venous Hemodiafiltration (150 ml/min of blood flow, 1500 ml/h dialysate flow, 1500 ml/h of citrate predilution) were studied. One had the CVC primed with saline, the second with calcium chloride 10%. Calcium replacement rate was 6.3 ± 0.2 ml/h. Ionized calcium concentration was studied over time in the two groups and in the group with saline priming we detected a transient period of hypocalcemia (ionized calcium concentration [iCa] < 1.00 mmol/l for the first 2 hours). In the subpopulation with the calcium priming, this was not present. No significant effect on filter life emerged. Priming of the catheter with calcium seems effective in avoiding a potential issue regarding citrate accumulation at the start of CRRT. More studies are needed to assess the clinical significance of this finding.
Prediction of Lumbar Disk Herniation and Clinical Outcome Using Quantitative Magnetic Resonance Imaging
Authors: Raudner Marcus , Schreiner Markus M. , Juras Vladimir , Weber Michael , Stelzeneder David , Kronnerwetter Claudia , Windhager Reinhard , Trattnig Siegfried
Published: November 2018

Objectives

The aim of this study was to assess the predictive value of T2 mapping at baseline with regard to the development of disk herniation and clinical outcome at a 5-year follow-up in patients with low back pain.

Materials and Methods

Twenty-five symptomatic patients (13 male; mean age, 44.0 years; range, 24–64 years at baseline) were examined at 3 T magnetic resonance imaging, with a 5-year follow-up. Region of interest analysis was performed on 125 lumbar intervertebral disks on 2 central sagittal T2 maps. Absolute T2 relaxation times and a T2 value ratio of the posterior annulus fibrosus as a percentage of the nucleus pulposus (NPAF) were evaluated for each disk. All disks were graded morphologically using the Pfirrmann score. Roland-Morris Disability Questionnaires (RMDQ) and a visual analogue scale (VAS) were assessed for each patient at follow-up as a clinical end point and compared with diagnosed lumbar disk herniation. Statistical analysis was conducted by a biomedical statistician.

Results

Using the baseline NPAF ratio, follow-up development of herniation was predicted with an area under the curve (AUC) of 0.893 in a receiver operating characteristic curve. The same was done using the baseline nucleus pulposus T2, resulting in an AUC of 0.901. Baseline and follow-up NPAF, as well as baseline and follow-up nucleus pulposus T2, differed significantly (P < 0.001) between disks with no herniation, disks with herniation at baseline, and disks with new herniation at follow-up. Difference was still significant (all P < 0.001), when only testing for difference in degenerated discs with Pfirrmann score III to V. Calculating sensitivity and specificity for herniation prediction only in discs with Pfirmann III to V using a receiver operating characteristic, AUC was 0.844 with baseline herniations excluded.

The lowest baseline nucleus pulposus T2 per patient correlated significantly with follow-up RMDQ (r = −0.517; P = 0.008) and VAS (r = −0.494; P = 0.012). The highest baseline NPAF correlated significantly with RMDQ (r = 0.462; P = 0.020), but not VAS (r = 0.279; P = 0.177).

Conclusions

Quantitative T2 mapping may serve as a clinically feasible, noninvasive imaging biomarker that can indicate disks at risk for herniation and correlates with clinical outcome and subjective patient burden in a representative cohort of patients with low back pain.
Nonshaven Follicular Unit Extraction
Authors: Park Jae Hyun , You Seung Hyun , Kim Na Rae
Published: November 2018

Nonshaven follicular unit extraction (NS-FUE) is the most state-of-the-art surgical technique in the field of follicular unit hair transplantation. It is particularly appealing because donor area shaving, one of the most serious impediments for the patient, can be omitted. In this article, we present our surgical approach for NS-FUE. We selectively used the direct or the pretrimming method of NS-FUE according to indication, determined by considering the location and purpose of transplantation, the condition of the recipient site, and the patient's preference. A total of 658 patients underwent NS-FUE. Of these, 17 had pubic atrichia, 2 had pubic atrichia and also received hairline correction surgery, 6 received eyebrow transplantation, 19 had female pattern hair loss, 362 had male pattern baldness (MPB), 2 had MPB and also required eyebrow transplantation, 3 received hair transplantation for MPB and scalp scar, 9 underwent male hairline correction surgery, 192 underwent female hairline surgery, and 46 received hair transplantation for scalp scar. The average numbers of transplanted grafts were 573 for atrichia, 1300 for atrichia and hairline correction performed successively, 240 for eyebrow transplantation, 996 for female pattern hair loss, 1408 for MPB (with a maximum of 3000), 1050 for MPB and eyebrow transplantation, 998 for female pattern hair loss (with a maximum of 1910), and 141 for scalp scar. On average, the total transection rate was 8.2%, and the calculated density was 2.2.
Multimodal Patient Blood Management Program Based on a Three-pillar Strategy
Authors: Althoff Friederike C. , Neb Holger , Herrmann Eva , Trentino Kevin M. , Vernich Lee , Füllenbach Christoph , Freedman John , Waters Jonathan H. , Farmer Shannon , Leahy Michael F. , Zacharowski Kai , Meybohm Patrick , Choorapoikayil Suma
Published: November 2018

Objectives:

To determine whether a multidisciplinary, multimodal Patient Blood Management (PBM) program for patients undergoing surgery is effective in reducing perioperative complication rate, and thereby is effective in improving clinical outcome.

Background:

PBM is a medical concept with the focus on a comprehensive anemia management, to minimize iatrogenic (unnecessary) blood loss, and to harness and optimize patient-specific physiological tolerance of anemia.

Methods:

A systematic review and meta-analysis was performed. Eligible studies had to address each of the 3 PBM pillars with at least 1 measure per pillar, for example, preoperative anemia management plus cell salvage plus rational transfusion strategy. The study protocol has been registered with PROSPERO (CRD42017079217).

Results:

Seventeen studies comprising 235,779 surgical patients were included in this meta-analysis (100,886 pre-PBM group and 134,893 PBM group). Implementation of PBM significantly reduced transfusion rates by 39% [risk ratio (RR) 0.61, 95% confidence interval (CI) 0.55–0.68, P < 0.00001], 0.43 red blood cell units per patient (mean difference −0.43, 95% CI −0.54 to −0.31, P < 0.00001), hospital length of stay (mean difference −0.45, 95% CI −0.65 to −0.25, P < 0,00001), total number of complications (RR 0.80, 95% CI 0.74–0.88, P <0.00001), and mortality rate (RR 0.89, 95% CI 0.80–0.98, P = 0.02).

Conclusions:

Overall, a comprehensive PBM program addressing all 3 PBM pillars is associated with reduced transfusion need of red blood cell units, lower complication and mortality rate, and thereby improving clinical outcome. Thus, this first meta-analysis investigating a multimodal approach should motivate all executives and health care providers to support further PBM activities.
Tamsulosin to Prevent Postoperative Urinary Retention After Female Pelvic Reconstructive Surgery
Authors: Chapman Graham C. , Sheyn David , Petrikovets Andrey , Mahajan Sangeeta T. , El-Nashar Sherif , Pollard Robert , Mangel Jeffrey M.
Published: November 2018

Objective

This study aimed to determine the effect of tamsulosin on postoperative urinary retention in female patients after pelvic reconstructive surgery.

Methods

Data were obtained from a retrospective, matched cohort of female patients who were admitted after pelvic reconstructive surgery at a single academic institution. Patients who received tamsulosin were compared with those who did not at a 1:4 ratio, matched by surgical procedure. Patients were excluded if they were discharged on the day of surgery or if an intraoperative complication necessitated prolonged postoperative bladder drainage. Information on demographics, preoperative diagnoses, prolapse stage, preoperative voiding dysfunction, urodynamic findings, intraoperative details, postoperative complications, and voiding outcomes up to 6 weeks after surgery was gathered. The primary outcome was postoperative urinary retention, defined by failure of an active voiding trial.

Results

Patients underwent surgery between January 2016 and March 2018. We identified 35 patients who received tamsulosin and matched to 140 controls. Patients in the tamsulosin group were younger; groups were otherwise similar. Patients who received tamsulosin after surgery were less likely to develop postoperative urinary retention (2.9% vs 24.3%, P = 0.004). After controlling for confounders, multivariable logistic regression identified tamsulosin use as the only independent predictor of postoperative urinary retention with a significant protective effect (odds ratio, 0.09; 95% confidence interval, 0.01–0.67; P = 0.03).

Conclusions

Prophylactic tamsulosin use may be effective in preventing postoperative urinary retention in female patients undergoing pelvic reconstructive surgery.
Steatosis in Liver Transplantation: Current Limitations and Future Strategies
Authors: Linares Ivan , Hamar Matyas , Selzner Nazia , Selzner Markus
Published: November 2018

In parallel with the pandemic of obesity and diabetes, the prevalence of nonalcoholic fatty liver disease has progressively increased. Nonalcoholic steatohepatitis (NASH), a subtype of nonalcoholic fatty liver disease has also augmented considerably being currently cirrhosis due to NASH the second indication for liver transplantation in the United States. Innovative treatments for NASH have shown promising results in phase 2 studies and are being presently evaluated in phase 3 trials. On the other hand, the high mortality on the liver transplant waitlist and the organ shortage has obligated the transplant centers to consider suboptimal grafts, such as steatotic livers for transplantation. Fatty livers are vulnerable to preservation injury resulting in a higher rate of primary nonfunction, early allograft dysfunction and posttransplant vascular and biliary complications. Macrosteatosis of more than 30% in fact is an independent risk factor for graft loss. Therefore, it needs to be considered into the risk assessment scores. Growing evidence supports that moderate and severe macrosteatotic grafts can be successfully used for liver transplantation with careful recipient selection. Protective strategies, such as machine-based perfusion have been developed in experimental setting to minimize preservation-related injury and are now on the verge to move into the clinical implementation. This review focuses on the current and potential future treatment of NASH and the clinical practice in fatty liver transplantation, highlights its limitations and optimal allocation, and summarizes the advances of experimental protective strategies, and their potential for clinical application to increase the acceptance and improve the outcomes after liver transplantation with high-grade steatotic livers.
Ethnic and Age Disparities in Outcomes Among Liver Transplant Waitlist Candidates
Authors: Mustian Margaux N. , Shelton Brittany A. , MacLennan Paul A. , Reed Rhiannon D. , White Jared A. , Eckhoff Devin E. , Locke Jayme E. , Allman Richard M. , Gray Stephen H.
Published: November 2018

Background.

Despite the increasing prevalence of end-stage liver disease in older adults, there is no consensus to determine suitability for liver transplantation (LT) in the elderly. Disparities in LT access exist, with a disproportionately lower percentage of African Americans (AAs) receiving LT. Understanding waitlist outcomes in older adults, specifically AAs, will identify opportunities to improve LT access for this vulnerable population.

Methods.

All adult, liver-only white and AA LT waitlist candidates (January 1, 2003 to October 1, 2015) were identified in the Scientific Registry of Transplant Recipients. Age and race categories were defined: younger white (age <60 years), younger AA, older white (age, ≥60 years), and older AA. Outcomes were delisting, transplantation, and mortality and were modeled using Fine and Gray competing risks.

Results.

Among 101 805 candidates, 58.4% underwent transplantation, 14.7% died while listed, and 21.4% were delisted. Among those delisted, 36.1% died, whereas 7.4% were subsequently relisted. Both older AAs and older whites were more likely than younger whites to be delisted and to die after delisting. Older whites had higher incidence of waitlist mortality than younger whites (subdistribution hazard ratio, 1.07; 95% confidence interval, 1.01-1.13). All AAs and older whites had decreased incidence of LT, compared with younger whites.

Conclusions.

Both older age and AA race were associated with decreased cumulative incidence of transplantation. Independent of race, older candidates had increased incidences of delisting and mortality after delisting than younger whites. Our findings support the need for interventions to ensure medical suitability for LT among older adults and to address disparities in LT access for AAs.
Nanopore native RNA sequencing of a human poly(A) transcriptome
Authors: Workman Rachael E. , Tang Alison D. , Tang Paul S. , Jain Miten , Tyson John R. , Zuzarte Philip C. , Gilpatrick Timothy , Razaghi Roham , Quick Joshua , Sadowski Norah , Holmes Nadine , Goes de Jesus Jaqueline , Jones Karen L. , Snutch Terrance P. , Loman Nicholas , Paten Benedict , Loose Matthew , Simpson Jared T. , Olsen Hugh E. , Brooks Angela N. , Akeson Mark , Timp Winston
Published: November 2018

High throughput cDNA sequencing technologies have dramatically advanced our understanding of transcriptome complexity and regulation. However, these methods lose information contained in biological RNA because the copied reads are often short and because modifications are not carried forward in cDNA. We address these limitations using a native poly(A) RNA sequencing strategy developed by Oxford Nanopore Technologies (ONT). Our study focused on poly(A) RNA from the human cell line GM12878, generating 9.9 million aligned sequence reads. These native RNA reads had an aligned N50 length of 1294 bases, and a maximum aligned length of over 21,000 bases. A total of 78,199 high-confidence isoforms were identified by combining long nanopore reads with short higher accuracy Illumina reads. We describe strategies for assessing 3′ poly(A) tail length, base modifications and transcript haplotypes from nanopore RNA data. Together, these nanopore-based techniques are poised to deliver new insights into RNA biology.

DISCLOSURES

MA holds shares in Oxford Nanopore Technologies (ONT). MA is a paid consultant to ONT. REW, WT, TG, JRT, JQ, NJL, JTS, NS, AB, MA, HEO, MJ, and ML received reimbursement for travel, accommodation and conference fees to speak at events organised by ONT. NL has received an honorarium to speak at an ONT company meeting. WT has two patents (8,748,091 and 8,394,584) licensed to Oxford Nanopore. JTS, ML and MA received research funding from ONT.
Novel autoregulatory cases of alternative splicing coupled with nonsense-mediated mRNA decay
Authors: Pervouchine Dmitri , Popov Yaroslav , Berry Andy , Borsari Beatrice , Frankish Adam , Guigó Roderic
Published: November 2018

Nonsense-mediated decay (NMD) is a eukaryotic mRNA surveillance system that selectively degrades transcripts with premature termination codons (PTC). Many RNA-binding proteins (RBP) regulate their expression levels by a negative feedback loop, in which RBP binds its own pre-mRNA and causes alternative splicing to introduce a PTC. We present a bioinformatic framework to identify novel such autoregulatory feedback loops by combining eCLIP assays for a large panel of RBPs with the data on shRNA inactivation of NMD pathway, and shRNA-depletion of RBPs followed by RNA-seq. We show that RBPs frequently bind their own pre-mRNAs and respond prominently to NMD pathway disruption. Poison and essential exons, i.e., exons that trigger NMD when included in the mRNA or skipped, respectively, respond oppositely to the inactivation of NMD pathway and to the depletion of their host genes, which allows identification of novel autoregulatory mechanisms for a number of human RBPs. For example, SRSF7 binds its own pre-mRNA and facilitates the inclusion of two poison exons; SFPQ binding promotes switching to an alternative distal 3’-UTR that is targeted by NMD; RPS3 activates a poison 5’-splice site in its pre-mRNA that leads to a frame shift; U2AF1 binding activates one of its two mutually exclusive exons, leading to NMD; TBRG4 is regulated by cluster splicing of its two essential exons. Our results indicate that autoregulatory negative feedback loop of alternative splicing and NMD is a generic form of post-transcriptional control of gene expression.
Consequences of breed formation on patterns of genomic diversity and differentiation: the case of highly diverse peripheral Iberian cattle
Authors: da Fonseca Rute R. , Ureña Irene , Afonso Sandra , Pires Ana Elisabete , Jørsboe Emil , Chikhi Lounes , Ginja Catarina
Published: November 2018

Background

Iberian primitive breeds exhibit a remarkable phenotypic diversity over a very limited geographical space. While genomic data are accumulating for most commercial cattle, it is still lacking for these primitive breeds. Whole genome data is key to understand the consequences of historic breed formation and the putative role of earlier admixture events in the observed diversity patterns.

Results

We sequenced 48 genomes belonging to eight Iberian native breeds and found that the individual breeds are genetically very distinct with FST values ranging from 4 to 16% and have levels of nucleotide diversity similar or larger than those of their European counterparts, namely Jersey and Holstein. All eight breeds display significant gene flow or admixture from African taurine cattle and include mtDNA and Y‐chromosome haplotypes from multiple origins. Furthermore, we detected a very low differentiation of chromosome X relative to autosomes within all analyzed taurine breeds, potentially reflecting male‐biased gene flow.

Conclusions

Our results show that an overall complex history of admixture resulted in unexpectedly high levels of genomic diversity for breeds with seemingly limited geographic ranges that are distantly located from the main domestication center for taurine cattle in the Near East. This is likely to result from a combination of trading traditions and breeding practices in Mediterranean countries. We also found that the levels of differentiation of autosomes vs sex chromosomes across all studied taurine and indicine breeds are likely to have been affected by widespread breeding practices associated with male-biased gene flow.
Mesenchymal stem cell derived exosomes enhance lymphangiogenesis via exosomal transfer of Ang-2/Tie2
Authors: Zhao Ting , Yan Zhixin , Liu Jinwen , Sun Hui , Chen Yifei , Tao Yan , Xu Wenrong , Qian Hui , Yan Yongmin
Published: November 2018

Mesenchymal stem cell derived exosomes (MSC-Ex) are nanosized membrane-bound extracellular vesicles found in MSC conditioned medium, that have yielded beneficial effects in several experimental models of organ injury. However, the therapeutic value and mechanism of MSC-Ex in lymphedema is poorly understood. Here we find that human umbilical cord MSCs derived exosomes (hucMSC-Ex) treatment contributed to the regeneration of LYVE-1 positive lymphatic vessels and reduction of lymphedema in a mouse model of tail lymphedema. Following uptake, exosomal lymphangiogenic factors (angiopoietin (Ang)-2 and Tie2) are taken up by HDLECs and promoted HDLECs proliferation, migration, and tube formation in vitro. We also find that exosomal Ang-2 and Tie2 exert a prolymphangiogenic effect on HDLECs through upregulating Prox1 and VEGFR3/p-Akt expression. In conclusion, our result unravel a previously unappreciated prolymphangiogenic role of hucMSC-Ex in lymphedema therapy and provide a new mechanism of Ang-2 in therapeutic lymphangiogenesis.
Dynamic Graphical Models of Molecular Kinetics
Authors: Olsson Simon , Noé Frank
Published: November 2018

Most current molecular dynamics simulation and analysis methods rely on the idea that the molecular system can be characterized by a single global state, e.g., a Markov State in a Markov State Model (MSM). In this approach, molecules can be extensively sampled and analyzed when they only possess a few metastable states, such as small to medium-sized proteins. However this approach breaks down in frustrated systems and in large protein assemblies, where the number of global meta-stable states may grow exponentially with the system size. Here, we introduce Dynamic Graphical Models (DGMs), which build upon the idea of Ising models, and describe molecules as assemblies of coupled subsystems. The switching of each sub-system state is only governed by the states of itself and its neighbors. DGMs need many fewer parameters than MSMs or other global-state models, in particular we do not need to observe all global system configurations to estimate them. Therefore, DGMs can predict new, previously unobserved, molecular configurations. Here, we demonstrate that DGMs can faithfully describe molecular thermodynamics and kinetics and predict previously unobserved metastable states for Ising models and protein simulations.
A Neurophysiological Measure of Reward Sensitivity and its Limited Association with Anhedonia in Adolescents and Young Adults
Authors: Frank David W. , Stevens Elise M. , Versace Francesco
Published: November 2018

Anhedonia (i.e., the attenuated ability to enjoy pleasurable stimuli) characterizes multiple mood disorders, but its neurophysiological underpinnings are not yet clear. Here, we measured event-related potentials in 116 adolescents and young adults engaged in a signal detection task designed to objectively characterize the anhedonic phenotype. In line with previous studies, the behavioral results showed that approximately 35% of the sample did not develop a response bias towards the more frequently rewarded stimuli (a sign of low hedonic capacity). The event-related potentials (ERPs) evoked by the reward feedback stimuli delivered during the task showed that individuals that did not develop a response bias had significantly less cortical positivity at Fz from 224 ms to 316 ms post feedback onset compared to those that developed a response bias during the task. However, further analyses showed that this between groups difference was relatively weak, as it disappeared when we controlled for response-locked ERPs. Furthermore, the response bias observed in the signal detection task was not strongly associated with self-reported ratings of hedonic capacity. We conclude that even though the signal detection task may be used as a reward sensitivity measure in neurotypical adolescents and young adults, this task may only be able to detect clinically significant levels of anhedonia in this particular population.
ChIPulate : A comprehensive ChIP-seq simulation pipeline
Authors: Datta Vishaka , Hannenhalli Sridhar , Siddharthan Rahul
Published: November 2018

ChIP-seq (Chromatin Immunoprecipitation followed by sequencing) is a high-throughput technique to identify genomic regions that are bound in vivo by a particular protein, e.g., a transcription factor (TF). Biological factors, such as chromatin state, indirect and cooperative binding, as well as experimental factors, such as antibody quality, cross-linking, and PCR biases, are known to affect the outcome of ChIP-seq experiments. However, the relative impact of these factors on inferences made from ChIP-seq data is not entirely clear. Here, via a detailed ChIP-seq simulation pipeline, ChIPulate, we assess the impact of various biological and experimental sources of variation on several outcomes of a ChIP-seq experiment, viz., the recoverability of the TF binding motif, accuracy of TF-DNA binding detection, the sensitivity of inferred TF-DNA binding strength, and number of replicates needed to confidently infer binding strength. We find that the TF motif can be recovered despite poor and non-uniform extraction and PCR amplification efficiencies. The recovery of the motif is however affected to a larger extent by the fraction of sites that are either cooperatively or indirectly bound. Importantly, our simulations reveal that the number of ChIP-seq replicates needed to accurately measure in vivo occupancy at high-affinity sites is larger than the recommended community standards. Our results establish statistical limits on the accuracy of inferences of protein-DNA binding from ChIP-seq and suggest that increasing the mean extraction efficiency, rather than amplification efficiency, would better improve sensitivity. The source code and instructions for running ChIPulate can be found athttps://github.com/vishakad/chipulate.
Community rescue in experimental phytoplankton communities facing severe herbicide pollution
Authors: V. Fugère , M.-P Hébert , N.B. Costa , C.C.Y. Xu , R.D.H. Barrett , B.E. Beisner , G. Bell , G.F. Fussmann , B.J. Shapiro , V. Yargeau , A. Gonzalez
Published: November 2018

Evolutionary rescue occurs when adaptation prevents local extinction in deteriorating environments. Laboratory experiments with microorganisms have shown that the likelihood of evolutionary rescue is greatest in large populations that have previously experienced sublethal doses of stress. To assess this result in natural communities, we conducted a mesocosm experiment with semi-natural phytoplankton communities exposed to glyphosate, a widely used herbicide. We tested whether community biomass and pre-exposure to sublethal stress would facilitate community rescue after severe contamination. Exposure to sublethal stress, but not community biomass, facilitated rescue significantly–even though it led to biodiversity loss. Furthermore, glyphosate had modest effects on community composition, suggesting that community resistance to glyphosate was primarily driven by changes in resistance within taxa, not by community turnover. Our results expand the scope of community evolutionary rescue theory to complex ecosystems and confirm that prior stress exposure is a key predictor of rescue.
Reannotation of the ribonucleotide reductase in a cyanophage reveals life history strategies within the virioplankton
Authors: Harrison Amelia O. , Moore Ryan M. , Polson Shawn W. , Wommack K. Eric
Published: November 2018

Ribonucleotide reductases (RNRs) are ancient enzymes that catalyze the reduction of ribonucleotides to deoxyribonucleotides. They are required for virtually all cellular life and are prominent within viral genomes. RNRs share a common ancestor and must generate a protein radical for direct ribonucleotide reduction. The mechanisms by which RNRs produce radicals are diverse and divide RNRs into three major classes and several subclasses. The diversity of radical generation methods means that cellular organisms and viruses typically contain the RNR best-suited to the environmental conditions surrounding DNA replication. However, such diversity has also fostered high rates of RNR misannotation within subject sequence databases. These misannotations have resulted in incorrect translative presumptions of RNR biochemistry and have diminished the utility of this marker gene for ecological studies of viruses. We discovered a misannotation of the RNR gene within theProchlorococcusphage P-SSP7 genome, which caused a chain of misannotations within commonly observed RNR genes from marine virioplankton communities. These RNRs are found in marine cyanopodo- and cyanosiphoviruses and are currently misannotated as Class II RNRs, which are O2-independent and require cofactor B12. In fact, these cyanoviral RNRs are Class I enzymes that are O2-dependent and may require a di-metal cofactor made of Fe, Mn, or a combination of the two metals. The discovery of an overlooked Class I β subunit in the P-SSP7 genome, together with phylogenetic analysis of the α and β subunits confirms that the RNR from P-SSP7 is a Class I RNR. Phylogenetic and conserved residue analyses also suggest that the P-SSP7 RNR may constitute a novel Class I subclass. The reannotation of the RNR clade represented by P-SSP7 means that most lytic cyanophage contain Class I RNRs, while their hosts, B12-producingSynechococcusandProchlorococcus, contain Class II RNRs. By using a Class I RNR, cyanophage avoid a dependence on host-produced B12, a more effective strategy for a lytic virus. The discovery of a novel RNR β subunit within cyanopodoviruses also implies that some unknown viral genes may be familiar cellular genes that are too divergent for homology-based annotation methods to identify.
Atomic view into Plasmodium actin polymerization, ATP hydrolysis, and phosphate release
Authors: Kumpula Esa-Pekka , López Andrea J. , Tajedin Leila , Han Huijong , Kursula Inari
Published: November 2018

Plasmodium actins form very short filaments and have a non-canonical link between ATP hydrolysis and polymerization. Long filaments are detrimental to the parasites, but the structural factors constraining Plasmodium microfilament lengths are currently unknown. Using high-resolution crystallography, we show that magnesium binding activates the Plasmodium actin I monomer before polymerization by a slight flattening, which is reversed upon phosphate release. A coordinated potassium ion resides in the active site during hydrolysis and leaves together with the phosphate, a process governed by the position of the Arg178/Asp180-containing A-loop. Asp180 interacts with either Lys270 or His74, depending on protonation, while Arg178 links the inner and outer domains. Hence, the A-loop is a switch between stable and non-stable filament conformations. Our data provide a comprehensive model for polymerization, phosphate release, and the inherent instability of parasite microfilaments.