bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations Between Polycystic Ovary Syndrome and Adverse Obstetric and Neonatal Outcomes: A Population Study of 9.1 Million Births
Authors: Mills Ginevra , Badeghiesh Ahmad , Suarthana Eva , Baghlaf Haitham , Dahan Michael H.
Published: November 2020

(Abstracted from Hum Reprod 2020;35(8):1914–1921)

Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology that may be associated with an increased risk of requiring cesarean section (C/S), experiencing preterm delivery (PTD), having small-for-gestational-age (SGA) infants, and undergoing induction of labor. This syndrome is commonly associated with insulin resistance (IR) and is indicated to be independently associated with gestational diabetes mellitus, hypertensive disorders of pregnancy, and preeclampsia.
Influence of Cardiopulmonary Resuscitation Coaching on Interruptions in Chest Compressions During Simulated Pediatric Cardiac Arrest*
Authors: Kessler David O. , Grabinski Zoe , Shepard Lindsay N. , Jones Sara I. , Lin Yiqun , Duff Jonathan , Tofil Nancy M. , Cheng Adam
Published: November 2020

Objectives:

To determine the impact of a cardiopulmonary resuscitation coach on the frequency and duration of pauses during simulated pediatric cardiac arrest.

Design:

This is a secondary analysis of video data collected from a prospective multicenter trial. Forty simulated pediatric cardiac arrest scenarios (20 noncoach and 20 coach teams), each lasting 18 minutes in duration, were reviewed by three clinical experts to document events surrounding each pause in chest compressions.

Setting:

Four pediatric academic medical centers from Canada and the United States.

Subjects:

Two-hundred healthcare providers in five-member interprofessional resuscitation teams that included either a cardiopulmonary resuscitation coach or a noncoach clinical provider.

Interventions:

Teams were randomized to include either a trained cardiopulmonary resuscitation coach or an additional noncoach clinical provider.

Measurements and Main Results:

The frequency, duration, and associated factors with each interruption in chest compressions were recorded and compared between the groups with and without a cardiopulmonary resuscitation coach, using t tests, Wilcoxon rank-sum tests, or chi-squared tests, depending on the distribution and types of outcome variables. Mixed-effect linear models were used to explore the effect of cardiopulmonary resuscitation coaching on pause durations, accounting for multiple measures of pause duration within teams. A total of 655 pauses were identified (noncoach n = 304 and coach n = 351). Cardiopulmonary resuscitation-coached teams had decreased total mean pause duration (98.6 vs 120.85 s, p = 0.04), decreased intubation pause duration (median 4.0 vs 15.5 s, p = 0.002), and similar mean frequency of pauses (17.6 vs 15.2, p = 0.33) when compared with noncoach teams. Teams with cardiopulmonary resuscitation coaches are more likely to verbalize the need for pause (86.5% vs 73.7%, p < 0.001) and coordinate change of the compressors, rhythm check, and pulse check (31.7% vs 23.2%, p = 0.05). Teams with cardiopulmonary resuscitation coach have a shorter pause duration than non-coach teams, adjusting for number and types of tasks performed during the pause.

Conclusions:

When compared with teams without a cardiopulmonary resuscitation coach, the inclusion of a trained cardiopulmonary resuscitation coach leads to improved verbalization before pauses, decreased pause duration, shorter pauses during intubation, and better coordination of key tasks during chest compression pauses.
The Effect of Alpha Lipoic Acid on the Recovery of Sciatic Nerve Injury in Rats
Authors: Kurt Oktay Kubra Neslihan , Akpinar Pinar , Unlu Ozkan Feyza , Aktas Ilknur , Ersoy Canillioglu Yasemin , Erkanli Senturk Gozde
Published: November 2020

Objective

The aim of this study was to investigate the regenerative effects of alpha lipoic acid on the recovery of sciatic nerve crush injury (SNCI) in rats.

Design

This was a randomized, experimental, and sham-controlled study. The sciatic nerves of 28 rats in four groups were traumatized for 60 secs: G1, sham operated + saline; G2, SNCI + saline; G3, SNCI + alpha lipoic acid 50 mg/kg/day; and G4, SNCI + alpha lipoic acid 100 mg/kg/day. Sciatic functional index values were measured on day 0, 1, 7, 14, 21, and 28. Sciatic nerve stimulation threshold values were recorded on day 1, 14, and 28. End-point histopathologic evaluation was conducted.

Results

The mean sciatic functional index value of G2 but not G3/G4 on day 7 was significantly lower than on day 0 (P = 0.035, P = 0.447/P = 0.800). The mean sciatic functional index value of G2 but not G3/G4 increased significantly between day 7 and 14 (P = 0.035, P = 0.447/P = 0.438). The day 14 mean sciatic nerve stimulation threshold values of G3/G4 but not G2 were decreased significantly compared with those on day 1 (P = 0.022/P = 0.022, P = 0.933). The mean sciatic nerve stimulation threshold values of G3/G4 on day 14 were similar to those on day 0 (P = 0.106/P = 0.418). Regeneration in muscle and nerve connective tissues and nerve structures was observed in G3/G4. Inflammation in the muscle and nerve tissues of G4 was suppressed down to similar levels of G1. Myelinated nerve fibers were less degenerated in G3/G4.

Conclusion

Alpha lipoic acid has the potential to accelerate the process of nerve healing in the context of SNCI in rats.
Validation of the Trust in the Surgical Decision Scale
Authors: Brodney Suzanne , Sepucha Karen , Fowler Floyd J. , Valentine K. D. , Barry Michael J.
Published: November 2020

Objective:

To develop and validate a short measure of trust in the surgical decision making process.

Summary of Background Data:

Having a reliable and valid measure of trust is important to assess the quality of the patient-surgeon relationship when decisions about surgical procedures are made.

Methods:

A previously published 10-item trust scale was qualitatively tested with patients, and a revised set of 14 items was tested using a web-based survey of 300 people who had hip, knee or back surgery in the past 2 years. The 14 items were evaluated using patterns of correlations and relevance to medical decision making to create a 5-item version. A 5-item subset was compared to the 14-item version to assess reliability and validity of patient's trust in the surgical decision making process.

Results:

Of the 300 participants, 32% had hip surgery, 33% had knee surgery, and 34% back surgery. Mean age was 53 years, 45% female, 80% White, and 36% had a high school degree or less. The item intercorrelations for the 14 items were 0.43–0.72 and 0.58–0.71 for the 5 items. Correlation between the versions was 0.96 (P < 0.01). The 14- and 5-item versions were positively correlated with participants’ shared decision making process scores (0.42 and 0.41, both P = 0.01), internal consistency reliability scores were 0.95 and 0.89, respectively, and were negatively correlated with their Decision Regret scores (–0.51 and –0.48, both P = 0.01).

Conclusion:

The 5-item Trust in the Surgical Decision Scale has strong evidence of validity and reliability for patients who underwent common orthopedic procedures.
Bariatric Surgery in Medicare Patients
Authors: Chao Grace F. , Chhabra Karan R. , Yang Jie , Thumma Jyothi R. , Arterburn David E. , Ryan Andrew M. , Telem Dana A. , Dimick Justin B.
Published: November 2020

Objective:

To compare safety and healthcare utilization after sleeve gastrectomy versus Roux-en-Y gastric bypass in a national Medicare cohort.

Summary Background Data:

Though bariatric surgery is increasing among Medicare beneficiaries, no long-term, national studies examining comparative effectiveness between procedures exist. Bariatric outcomes are needed for shared decision-making and coverage policy concerns identified by the cMS Medicare Evidence Development and Coverage Advisory Committee.

Methods:

Retrospective instrumental variable analysis of Medicare claims (2012–2017) for 30,105 bariatric surgery patients entitled due to disability or age. We examined clinical safety outcomes (mortality, complications, and reinterventions), healthcare utilization [Emergency Department (ED) visits, rehospitalizations, and expenditures], and heterogeneity of treatment effect. We compared all outcomes between sleeve and bypass for each entitlement group at 30 days, 1 year, and 3 years.

Results:

Among the disabled (n = 21,595), sleeve was associated with lower 3-year mortality [2.1% vs 3.2%, absolute risk reduction (ARR) 95% confidence interval (CI): –2.2% to –0.03%], complications (22.2% vs 27.7%, ARR 95%CI: –8.5% to –2.6%), reinterventions (20.1% vs 27.7%, ARR 95%CI: –10.7% to –4.6%), ED utilization (71.6% vs 77.1%, ARR 95%CI: –8.5% to –2.4%), and rehospitalizations (47.4% vs 52.3%, ARR 95%Ci: –8.0% to –1.7%). Cumulative expenditures were $46,277 after sleeve and $48,211 after bypass (P = 0.22). Among the elderly (n = 8510), sleeve was associated with lower 3-year complications (20.1% vs 24.7%, ARR 95%CI: –7.6% to –1.7%), reinterventions (14.0% vs 21.9%, ARR 95%CI: –10.7% to –5.2%), ED utilization (51.7% vs 57.2%, ARR 95%CI: –9.1% to –1.9%), and rehospitalizations (41.8% vs 45.8%, ARR 95%Ci: –7.5% to –0.5%). Expenditures were $38,632 after sleeve and $39,270 after bypass (P = 0.60). Procedure treatment effect significantly differed by entitlement for mortality, revision, and paraesophageal hernia repair.

Conclusions:

Bariatric surgery is safe, and healthcare utilization benefits of sleeve over bypass are preserved across both Medicare elderly and disabled subpopulations.
Association Between Preoperative HbA1c Levels and Complications after Esophagectomy
Authors: Okamura Akihiko , Yamamoto Hiroyuki , Watanabe Masayuki , Miyata Hiroaki , Kanaji Shingo , Kamiya Kinji , Kakeji Yoshihiro , Doki Yuichiro , Kitagawa Yuko
Published: November 2020

Objective:

To elucidate the association between preoperative hemoglobin A1c (HbAlc) levels and short-term outcomes after oncologic esophagectomy.

Summary Background Data:

Although diabetes mellitus is associated with an increased risk of postoperative morbidity in several types of surgery, the association of diabetes mellitus with short-term outcomes after esophagectomy has shown conflicting results.

Methods:

We analyzed 15,801 patients who underwent oncologic esophagectomy between 2015 and 2017 from the National Clinical Database. We evaluated the associations between preoperative HbA1c levels and short-term outcomes, using multivariable logistic regression and restricted cubic spline models.

Results:

The cohort included 12,074, 1361, 1097, 909, and 360 patients with HbA1c levels of ≤5.9%, 6.0% to 6.4%, 6.5% to 6.9%, 7.0% to 7.9%, and ≥8.0%, respectively. There were value-dependent associations between HbA1c values and odds ratios for anastomotic leakage, surgical site infections, pneumonia, and composite outcomes. Compared with the HbA1c category of ≤5.9%, the categories of 7.0% to 7.9% and ≥8.0% were at higher risk for anastomotic leakage (P < 0.001 and 0.031, respectively), the category of ≥8.0% was at higher risk for surgical site infections (P = 0.001), the categories of 6.5% to 6.9% and 7.0% to 7.9% were at higher risk for pneumonia (P = 0.016 and 0.002, respectively), and the categories of 7.0 to 7.9 and > 8.0% were at higher risk for composite outcomes (P < 0.001 and 0.001, respectively).

Conclusions:

Preoperative HbA1c levels are associated with the risk of postoperative complications after esophagectomy, and the threshold values differed among the outcomes. Preoperative HbA1c is useful in predicting the risk of postoperative complications.
Thoracic Endovascular Aortic Repair Practice in 13 Countries
Authors: Hellgren Tina , Beck Adam W. , Behrendt Christian-Alexander , Becker Daniel , Beiles Barry , Boyle Jonathan R. , Jormalainen Mikko , Koncar Igor , Lopez Espada Cristina , Setacci Carlo , Settembre Nicla , Sutzko Danielle C. , Szeberin Zoltan , Thomson Ian , Venermo Maarit , Mani Kevin
Published: November 2020

Objective:

To assess practice patterns and short-term outcome after thoracic endovascular aortic repair (TEVAR), based on an international vascular registry collaboration.

Summary Background Data:

TEVAR has become the primary surgical treatment modality for descending aortic pathologies, and has expanded to new patient cohorts, including the elderly.

Methods:

Data on thoracic aortic aneurysms (TAA), type B aortic dissections (TBAD), and traumatic aortic injuries (TAI) treated with TEVAR from 2012 to 2016 were retrieved from registries and centers in 13 countries.

Results:

Nine-thousand five-hundred eighteen TEVAR for TAA (n= 4436), TBAD (n= 3976) and TAI (n= 1106) were included. The distribution of TEVAR procedures per pathology varied, with TAA repair constituting from 40% of TEVARs in the US to 72% in the UK (P< 0.001).

Mean intact TAA (iTAA) diameter varied from 59 (US) to 69 mm (Nancy, France) (P< 0.001), 25.3% of patients having a diameter of <60 mm. Perioperative mortality after iTAA repair was 4.9%; combined mortality, stroke, paraplegia, and renal replacement therapy outcome was 12.8%. 18.6% of iTAA patients were ≥80 years old. Mortality was higher in this group (7.2%) than in patients <80 (3.8%) (P< 0.001). After rTAA repair, perioperative mortality was 26.8%.

Mortality was 9.7% after acute (within 14 days from onset of dissection) and 3.0% after chronic TBAD repair (P< 0.001). Mortality after TAI was 7.8%, and depended on injury severity (grade IV (free rupture) 20.9%).

Conclusions:

This registry collaboration provides a unique platform to evaluate cross-border patterns of use and outcomes of TEVAR. A common core dataset is proposed, to achieve harmonization of registry-based quality outcome measures for TEVAR.
Outcomes of Laparoscopic Redo Fundoplication in Patients With Failed Antireflux Surgery
Authors: Schlottmann Francisco , Laxague Francisco , Angeramo Cristian A. , Sadava Emmanuel E. , Herbella Fernando A. M. , Patti Marco G.
Published: November 2020

Objective:

The aim of this meta-analysis was to summarize the current available evidence regarding the surgical outcomes of laparoscopic redo fundoplication (LRF).

Summary of Background Data:

Although antireflux surgery is highly effective, a minority of patients will require a LRF due to recurrent symptoms, mechanical failure, or intolerable side-effects of the primary repair.

Methods:

A systematic electronic search on LRF was conducted in the Medline database and Cochrane Central Register of Controlled Trials. Conversion and postoperative morbidity were used as primary endpoints to determine feasibility and safety. Symptom improvement, QoL improvement, and recurrence rates were used as secondary endpoints to assess efficacy. Heterogeneity across studies was tested with the Chi-square and the proportion of total variation attributable to heterogeneity was estimated by the inconsistency (I
2) statistic. A random-effect model was used to generate a pooled proportion with 95% confidence interval (CI) across all studies.

Results:

A total of 30 studies and 2,095 LRF were included. The mean age at reoperation was 53.3 years. The weighted pooled proportion of conversion was 6.02% (95% CI, 4.16%–8.91%) and the meta-analytic prevalence of major morbidity was 4.98% (95% CI, 3.31%–6.95%). The mean follow-up period was 25 (6–58) months. The weighted pooled proportion of symptom and QoL improvement was 78.50% (95% CI, 74.71%–82.03%) and 80.65% (95% CI, 75.80%–85.08%), respectively. The meta-analytic prevalence estimate of recurrence across the studies was 10.71% (95% CI, 7.74%–14.10%).

Conclusions:

LRF is a feasible and safe procedure that provides symptom relief and improved QoL to the vast majority of patients. Although heterogeneously assessed, recurrence rates seem to be low. LRF should be considered a valuable treatment modality for patients with failed antireflux surgery.
Evaluating the association between American Association for the Surgery of Trauma emergency general surgery anatomic severity grades and clinical outcomes using national claims data
Authors: Scott John W. , Staudenmayer Kristan , Sangji Naveen , Fan Zhaohui , Hemmila Mark , Utter Garth
Published: November 2020

BACKGROUND

Emergency general surgery (EGS) encompasses a heterogeneous population of acutely ill patients, and standardized methods for determining disease severity are essential for comparative effectiveness research and quality improvement initiatives. The American Association for the Surgery of Trauma (AAST) has developed a grading system for the anatomic severity of 16 EGS conditions; however, little is known regarding how well these AAST EGS grades can be approximated by diagnosis codes in administrative databases.

METHODS

We identified adults admitted for 16 common EGS conditions in the 2012 to 2017q3 National Inpatient Sample. Disease severity strata were assigned using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes based on AAST EGS anatomic severity grades. We evaluated whether assigned EGS severity (multiple strata or dichotomized into less versus more complex) were associated with in-hospital mortality, complications, length of stay, discharge disposition, and costs. Analyses were adjusted for age, sex, comorbidities, hospital traits, geography, and year.

RESULTS

We identified 10,886,822 EGS admissions. The number of anatomic severity strata derived from ICD-9/10-CM codes varied by EGS condition and by year. Four conditions mapped to four strata across all years. Two conditions mapped to four strata with ICD-9-CM codes but only two or three strata with ICD-10-CM codes. Others mapped to three or fewer strata. When dichotomized into less versus more complex disease, patients with more complex disease had worse outcomes across all 16 conditions. The addition of multiple strata beyond a binary measure of complex disease, however, showed inconsistent results.

CONCLUSION

Classification of common EGS conditions according to anatomic severity is feasible with International Classification of Diseases codes. No condition mapped to five distinct severity grades, and the relationship between increasing grade and outcomes was not consistent across conditions. However, a standardized measure of severity, even if just dichotomized into less versus more complex, can inform ongoing efforts aimed at optimizing outcomes for EGS patients across the nation.

LEVEL OF EVIDENCE

Prognostic, level III.
Immunosuppression Regimen Use and Outcomes in Older and Younger Adult Kidney Transplant Recipients: A National Registry Analysis
Authors: Lentine Krista L. , Cheungpasitporn Wisit , Xiao Huiling , McAdams-DeMarco Mara , Lam Ngan N. , Segev Dorry L. , Bae Sunjae , Ahn JiYoon B. , Hess Gregory P. , Caliskan Yasar , Randall Henry B. , Kasiske Bertram L. , Schnitzler Mark A. , Axelrod David A.
Published: November 2020

Background.

Although the population of older transplant recipients has increased dramatically, there are limited data describing the impact of immunosuppression regimen choice on outcomes in this recipient group.

Methods.

National data for US Medicare-insured adult kidney recipients (N = 67 362; 2005–2016) were examined to determine early immunosuppression regimen and associations with acute rejection, death-censored graft failure, and mortality using multivariable regression analysis in younger (18–64 y) and older (>65 y) adults.

Results.

The use of antithymocyte globulin (TMG) or alemtuzumab (ALEM) induction with triple maintenance immunosuppression (reference) was less common in older compared with younger (36.9% versus 47.0%) recipients, as was TMG/ALEM + steroid avoidance (19.2% versus 20.1%) and mammalian target of rapamycin inhibitor (mTORi)-based (6.7% versus 7.7%) treatments. Conversely, older patients were more likely to receive interleukin (IL)-2-receptor antibody (IL2rAb) + triple maintenance (21.1% versus 14.7%), IL2rAb + steroid avoidance (4.1% versus 1.8%), and cyclosporine-based (8.3% versus 6.6%) immunosuppression. Compared with older recipients treated with TMG/ALEM + triple maintenance (reference regimen), those managed with TMG/ALEM + steroid avoidance (adjusted odds ratio [aOR], 0.440.520.61) and IL2rAb + steroid avoidance (aOR, 0.390.550.79) had lower risk of acute rejection. Older patients experienced more death-censored graft failure when managed with Tac + antimetabolite avoidance (adjusted hazard [aHR], 1.411.782.25), mTORi-based (aHR, 1.702.142.71), and cyclosporine-based (aHR, 1.411.782.25) regimens, versus the reference regimen. mTORi-based and cyclosporine-based regimens were associated with increased mortality in both older and younger patients.

Conclusions.

Lower-intensity immunosuppression regimens (eg, steroid-sparing) appear beneficial for older kidney transplant recipients, while mTORi and cyclosporine-based maintenance immunosuppression are associated with higher risk of adverse outcomes.
Optimization of enzyme treatment conditions for extraction of
dietary fiber from Opuntia humifusa stem
Authors: Jang Eun Jin , Kim Ja Min , Yoon Kyung Young , Kim Seong-Ho
Published: November 2020

This study aimed to optimize the hydrolysis conditions required for extraction of
dietary fiber from Opuntia humifusa stem using
Viscozyme® (MilliporeSigma, St. Louis, MO, USA) with
response surface methodology (RSM). A central composite design was applied to
examine the effects of the independent variables, enzyme concentration
(0.5-2.5%, X1) and reaction time (1-5h, X2). The
hydrolysis conditions were optimized using total yield, total dietary fiber
(TDF), water-soluble dietary fiber (SDF), and water-insoluble dietary fiber
(IDF) contents of hydrolysates as dependent variables. The total yield was
39.9-53.2% and the coefficient (R2) of the derived equation
from the response surface regression for total yield was 0.9073. The TDF and SDF
contents in all hydrolysates were 29.02-43.82% and 27.25-40.68%,
respectively, which were within the 1% level. The IDF contents in all
hydrolysates were 0.98-3.80% (R2 0.8886) and with in 5%
significance. The optimal hydrolysis conditions comprised 1.0-1.8%
Viscozyme® and an incubation period of 1.0-1.8 h. Our
results suggested that O. humifusa could be a source that might
extend the application of dietary fiber in functional food industries.
DrugOrchestra: Jointly predicting drug response, targets, and side effects via deep multi-task learning
Authors: Jiang Yuepeng , Rensi Stefano , Wang Sheng , Altman Russ B.
Published: November 2020

Massively accumulated pharmacogenomics, chemogenomics, and side effect datasets offer an unprecedented opportunity for drug response prediction, drug target identification and drug side effect prediction. Existing computational approaches limit their scope to only one of these three tasks, inevitably overlooking the rich connection among them. Here, we propose DrugOrchestra, a deep multi-task learning framework that jointly predicts drug response, targets and side effects. DrugOrchestra leverages pre-trained molecular structure-based drug representation to bridge these three tasks. Instead of directly fine-tuning on an individual task, DrugOrchestra uses deep multi-task learning to obtain a phenotype-based drug representation by simultaneously fine-tuning on drug response, target and side effect prediction. By coupling these three tasks together, DrugOrchestra is able to make predictions for unseen drugs by only knowing their molecular structures. We constructed a heterogeneous drug discovery dataset of over 21k drugs by integrating 8 datasets across three tasks. Our method obtained significant improvement in comparison to methods that were trained on a single task or a single dataset. We further revealed the transferability across 8 datasets and 3 tasks, providing novel insights for understanding drug mechanisms.

Availability

https://github.com/jiangdada1221/DrugOrchestra
COAL_PHYRE: A Composite Likelihood Method for Estimating Species Tree Parameters from Genomic Data Using Coalescent Theory
Authors: Guerra Geno , Nielsen Rasmus
Published: November 2020

2

Genome-scale data are increasingly being used to infer phylogenetic trees. A major challenge in such inferences is that different regions of the genome may have local topologies that differ from the species tree due to incomplete lineage sorting (ILS). Another source of gene tree discrepancies is estimation errors arising from the randomness of the mutational process during sequence evolution. There are two major groups of methods for estimating species tree from whole-genome data: a set of full likelihood methods, which model both sources of variance, but do not scale to large numbers of independent loci, and a class of faster approximation methods which do not model the mutational variance.

To bridge the gap between these two classes of methods, we present COAL_PHYRE (COmposite Approximate Likelihood for PHYlogenetic REconstruction), a composite likelihood based method for inferring population size and divergence time estimates of rooted species trees from aligned gene sequences. COAL_PHYRE jointly models coalescent variation across loci using the MSC and variation in local gene tree reconstruction using a normal approximation. To evaluate the accuracy and speed of the method, we compare against BPP, a powerful MCMC full-likelihood method, as well as ASTRAL-III, a fast approximate method. We show that COAL_PHYRE’s divergence time and population size estimates are more accurate than ASTRAL, and comparable to those obtained using BPP, with an order of magnitude decrease in computational time. We also present results on previously published data from a set of Gibbon species to evaluate the accuracy in topology and parameter inference on real data, and to illustrate the method’s ability to analyze data sets which are prohibitively large for MCMC methods.
Bell-shaped dose response for a system with no IFFLs
Authors: Sontag Eduardo D.
Published: November 2020

It is well known that the presence of an incoherent feedforward loop (IFFL) in a network may give rise to a steady state non-monotonic dose response. This note shows that the converse implication does not hold. It gives an example of a three-dimensional system that has no IFFLs, yet its dose response is bell-shaped. It also studies under what conditions the result is true for two-dimensional systems, in the process recovering, in far more generality, a result given in the T-cell activation literature.
Meta-Prism 2.0: Enabling algorithm for ultra-fast, accurate and memory-efficient search among millions of microbial community samples
Authors: Kang Kai , Chong Hui , Ning Kang
Published: November 2020

Motivation

Microbial community samples and sequencing data have been accumulated at a speed faster than ever, with tens of thousands of samples been sequenced each year. Mining such a huge amount of multi-source heterogeneous data is becoming more and more difficult. Among several sample mining bottlenecks, efficient and accurate search of samples is one of the most prominent: Faced with millions of samples in the data repository, traditional sample comparison and search approaches fall short in speed and accuracy.

Results

Here we proposed Meta-Prism 2.0, a microbial community sample search method based on smart pair-wise sample comparison, which pushed the time and memory efficiency to a new limit, without the compromise of accuracy. Based on memory-saving data structure, time-saving instruction pipeline, and boost scheme optimization, Meta-Prism 2.0 has enabled ultra-fast, accurate and memory-efficient search among millions of samples. Meta-Prism 2.0 has been put to test on several datasets, with largest containing one million samples. Results have shown that firstly, as a distance-based method, Meta-Prism 2.0 is not only faster than other distance-based methods, but also faster than unsupervised methods. Its 0.00001s per sample pair search speed, as well as 8GB memory needs for searching against one million samples, have enabled it to be the most efficient method for sample comparison. Additionally, Meta-Prism 2.0 could achieve the comparison accuracy and search precision that are comparable or better than other contemporary methods. Thirdly, Meta-Prism 2.0 can precisely identify the original biome for samples, thus enabling sample source tracking.

Conclusion

In summary, Meta-Prism 2.0 can perform accurate searches among millions of samples with very low memory cost and fast speed, enabling knowledge discovery from samples at a massive scale. It has changed the traditional resource-intensive sample comparison and search scheme to a cheap and effective procedure, which could be conducted by researchers everyday even on a laptop, for insightful sample search and knowledge discovery. Meta-Prism 2.0 could be accessed at:https://github.com/HUST-NingKang-Lab/Meta-Prism-2.0.
Cognitive Aids for Operating Room Crises – A Thematic Analysis of Implementer Experiences
Authors: Henrich Natalie , Benotti Emily , Berry William , Hannenberg Alexander , Hepner David , Karlage Ami , Goldhaber-Fiebert Sara
Published: November 2020

Background

Strategies for the implementation of evidence-based interventions have proliferated, but it remains unclear how these strategies are operationalized for different types of interventions and contexts. Here, we examine seven implementation strategies--initially developed for implementing the World Health Organization (WHO) Surgical Safety Checklist (SSC)--for implementing cognitive aids for operating room (OR) crises.

Methods

We conducted semi-structured interviews with implementers of these aids exploring the use of each of the strategies previously studied with WHO SSC implementation as well as barriers and facilitators to implementation. We conducted a thematic analysis to identify and describe the use of the strategies. We mapped barriers and factors helping facilitate (facilitators) onto corresponding constructs from the Consolidated Framework for Implementation Research.

Results

We conducted interviews with 37 implementers across the United States. Most interviewees identified similar strategies in their implementation process, and none offered additional strategies that fell outside existing categories. There was substantial variation among implementers in how the strategies were deployed. Many of the barriers and facilitators were common across implementations.

Conclusion

Interviewees used a core set of strategies to implement cognitive aids for OR crises, but there was substantial variation in how implementers used these strategies, suggesting the flexibility of the strategies and the value of deliberately adapting strategies to local context. The transferability of implementation strategies from the WHO SSC to other OR-based cognitive aids demonstrates the utility of informing novel implementations with prior successful ones that share similar attributes with respect to intervention and/or context.
PALM: Patient-centered Treatment Ranking via Large-scale Multivariate Network Meta-analysis
Authors: Duan Rui , Tong Jiayi , Lin Lifeng , Levine Lisa D , Sammel Mary D , Stoddard Joel , Li Tianjing , Schmid Christopher H , Chu Haitao , Chen Yong
Published: November 2020

The growing number of available treatment options have led to urgent needs for reliable answers when choosing the best course of treatment for a patient. As it is often infeasible to compare a large number of treatments in a single randomized controlled trial, multivariate network meta-analyses (NMAs) are used to synthesize evidence from existing trials of a subset of the available treatments, where outcomes related to both efficacy and safety are considered simultaneously. However, these large-scale multiple-outcome NMAs have created challenges to existing methods due to the increasingly complexity of the unknown correlation structures between different outcomes and treatment comparisons. In this paper, we proposed a new framework for PAtient-centered treatment ranking via Large-scale Multivariate network meta-analysis, termed as PALM, which includes a parsimonious modeling approach, a fast algorithm for parameter estimation and inference, a novel visualization tool for comparing treatments with multivariate outcomes termed as the star plot, as well as personalized treatment ranking procedures taking into account the individual’s considerations on multiple outcomes. In application to an NMA that compares 14 treatment options for labor induction over five modalities, we provided a comprehensive illustration of the proposed framework and demonstrated its computational efficiency and practicality. Our analysis leads to new insights on comparing these 14 treatment options based on joint inference of multiple outcomes that cannot be obtained from univariate NMAs, and novel visualizations of evidence to support patient-centered clinical decision making.
Preliminary Minimum Reporting Requirements for Reporting In-Vivo Neural Interface Research: I. Implantable Neural Interfaces
Authors: Eiber Calvin D. , Delbeke Jean , Cardoso Jorge , de Neeling Martijn , John Sam E. , Lee Chang Won , Skefos Jerry , Sun Argus , Prodanov Dimiter , McKinney Zach
Published: November 2020

The pace of research and development in neuroscience, neurotechnology, and neurorehabilitation is rapidly accelerating, with the number of publications doubling every 4.2 years. Maintaining this progress requires technological standards and scientific reporting guidelines to provide frameworks for communication and interoperability. The present lack of such standards for neurotechnologies limits the transparency, reproducibility, and meta-analysis of this growing body of research, posing an ongoing barrier to research, clinical, and commercial objectives.

Continued neurotechnological innovation requires the development of some minimal standards to promote integration between this broad spectrum of technologies and therapies. To preserve design freedom and accelerate the translation of research into safe and effective technologies with maximal user benefit, such standards must be collaboratively co-developed by a full spectrum of neuroscience and neurotechnology stakeholders. This paper summarizes the preliminary recommendations of IEEE Working Group P2794, developing a Reporting Standard forin-vivoNeural Interface Research (RSNIR).

Impact Statement

This work provides a preliminary set of reporting guidelines for implantable neural interface research, developed by IEEE WG P2794 in open collaboration between a range of stakeholders to accelerate the research, development, and integration of innovative neurotechnologies.
Enhanced olfactory memory performance in trap-design Y-mazes allows the study of novel memory phenotypes inDrosophila
Authors: Mohandasan Radhika , Iqbal Fathima Mukthar , Thakare Manikrao , Sridharan Madhav , Das Gaurav
Published: November 2020

The neural basis of behaviour is identified by systematically disrupting the activity of specific neurons and screening for loss in phenotype. Robust, high-scoring behavioural assays are thus necessary for identifying the neural circuits of novel behaviours. Here, we report the design and use of a Y-maze based classical olfactory learning and memory assay inDrosophila. Appetitive memory scores in our Y-mazes are considerably better and longer-lasting than that from a commonly used T-maze design. We found that the mechanism that traps flies in their choice of an odour is mainly responsible for the improving scores in the Y-mazes. Using Y-mazes, we could assay significant 24 h gustatory aversive memories in flies. These aversive memories are susceptible to protein synthesis inhibitor cycloheximide (CXM) and therefore embodies long-term memory (LTM). When anaesthesia resistant memory (ARM) deficientradishmutant flies are trained with dry sucrose, 24 h memory is severely disrupted. However, when we trained with 2 M sucrose-agar and tested in Y-mazes,radishmutants exhibited a residual 24 appetitive memory. This memory is not ARM, and we show that it is not CXM sensitive LTM either. It could be a third form of appetitive consolidated memory in flies. The Y-maze assembly described here is particularly sensitive and will thus enable the study of new memory phenotypes inDrosophila.
Proteomics on longitudinal serum samples differentiates localized and disseminated Lyme disease
Authors: Fatou Benoit , Smolen Kinga K. , Belperron Alexia A. , Wurie Zainab , Kleinstein Steven H. , Montgomery Ruth R. , Levy Ofer , Bockenstedt Linda K. , Steen Hanno
Published: November 2020

Lyme disease (LD) is the most prevalent vector-borne disease in North America, with ~300,000 new cases annually in the USA alone. LD is most often recognized by the appearance of the skin lesion erythema migrans (EM) at the tick bite site but also can present with signs of disseminated infection manifesting as multiple EM lesions and/or involvement of the heart, nervous system or joints. In this study, we examined the serum proteome of study participants presenting with either a single EM (localized LD) or early disseminated infection (disseminated LD). Samples collected at the time of diagnosis and at convalescent time points were assessed using our in-house developed MStern blotting-based serum proteomics platform. After technical validation of our platform, the temporal analysis from diagnosis to clinical resolution of the infection demonstrates LD stage-associated pathways activation such as a temporary upregulation of acute phase response specific to the participants with disseminated LD. In addition, we identified the members of the serum amyloid A protein family as potentially promising candidate biomarkers to identify those with disseminated LD. The results of this pilot study demonstrate the feasibility of using our time- and cost-effective sample sparing MStern blotting-based serum proteomics platform to efficiently interrogate proteome changes over time in those suffering infections such as LD. These observations establish a new approach to human serum proteomics, provide fresh insight into the host immune responses associated with disease severity (localized versus disseminated infection) and suggest novel biomarker candidate panels for LD stages.

Importance

We investigated the proteome changes ofBorrelia burgdorferi-infected participants with either a single erythema migrans or early disseminated Lyme disease infection. Using our in-house time-and cost-effective proteomics platform, the temporal analysis from diagnosis to clinical resolution of the infection shows a temporary upregulation of the acute phase response specific to the participants with disseminated infection. Finally, specific protein panels were identified as possible biomarker candidates to categorize those having an initial diagnosis of disseminated manifestation using a reference cohort of acute localized infection and a clinically resolved convalescent phase disease samples from the same Lyme disease participants.
Diet and heat - one neuronal subset two responses
Authors: Prince Elodie , Kretzschmar Jenny , Trautenberg Laura C. , Brankatschk Marko
Published: November 2020

The Insulin signal cascade is one of the best studied metabolic circuits, and shows a remarkable high molecular and functional conservation across the animal kingdom. Insulin-producing cells respond directly to nutritional cues in circulation and receive modulatory input from connected neuronal networks. Neuronal control is rapid and integrates a wide range of variables including dietary change or environmental temperature. However, despite various detailed studies that demonstrated the potential of neuronal regulation the physiological relevance of this circuit remains elusive.

InDrosophila, Insulin-like peptide 7 (dIlp7)-producing neurons are wired with Insulin-producing cells. We found a dual role for this neuronal subset: a.) activated dilp7-producing neurons are required to facilitate development at high temperatures, and if confronted with calorie-rich food that represses neuronal activity b.) their product, dIlp7, regulates Insulin signalling levels. Our work shows that Insulin-producing cells not simply integrate signals from circulating nutritional cues and neuronal inputs, but switch to neuronal control in response to dietary composition.
Dehydration risk, not ambient incubation, limits nest attendance at high temperatures
Authors: Bourne Amanda R. , Ridley Amanda R. , McKechnie Andrew E. , Spottiswoode Claire N. , Cunningham Susan J.
Published: November 2020

High air temperatures have measurable negative impacts on reproduction in wild animal populations, including during incubation in birds. Understanding the mechanisms driving these impacts requires comprehensive knowledge of animal physiology and behaviour under natural conditions. We used a novel combination of a non-invasive doubly-labelled water technique and behaviour observations in the field to examine effects of temperature, rainfall, and group size on physiology and behaviour during incubation in southern pied babblersTurdoides bicolor, a cooperatively-breeding passerine endemic to a semi-arid region in southern Africa. The proportion of time that clutches of eggs were incubated declined as air temperatures increased, traditionally interpreted as a benefit of ambient incubation. However, we show that a) clutches were less likely to hatch when exposed to high air temperatures; b) pied babbler groups incubated their nests almost constantly (97% of daylight hours) except on hot days; c) operative temperatures in unattended nests were substantially higher than air temperatures and frequently exceeded 40.5°C, above which bird embryos are at risk of death; d) pied babblers incubating for long periods of time failed to maintain water balance on hot days but not cool days; and e) pied babblers from incubating groups did not maintain body mass on hot days. These results suggest that, rather than taking advantage of opportunities for ambient incubation, pied babblers leave the nests during hot periods to avoid dehydration as a consequence of incubating at high operative temperatures. As mean air temperatures increase and extreme heat events become more frequent under climate change, birds will likely incur greater water costs during incubation, leading to compromised nest attendance and increased likelihood of eggs overheating, with implications for nest success and, ultimately, population persistence.
Mechanical Efficiency Investigation of an ankle-assisted robot for human walking with a backpack-load
Authors: Wang Zhihou , Huang Guowei , Liu Biao , Zhou Zikang , Liang Binghong , Liu Youwei , Xie Longhan
Published: November 2020

Lower limb assistive robots have a wide range of applications in medical rehabilitation, hiking, and the military. The purpose of this work is to investigate the efficiency of wearable assistive devices under different weight-bearing walking conditions. We designed an experimental platform, with a lightweight ankle-assisted robot weighing 5.2 kg and carried mainly on the back. Eight subjects were tested in three experimental conditions: free walk with load (FWL), power-off with load (POFL), and power-on with load (PONF) for different levels of force at a walking speed of 3.6 km/h. We recorded the metabolic expenditure and kinematics of the subjects under three levels of weight-bearing (equal to 10%, 20%, and 30% of body mass). The critical forces from the fit of the assistive force and metabolic depletion curves were 130 N, 160 N and 215 N at three different load levels. The intrinsic weight of our device increases mechanical work at the ankle as the load weight rises, with 2.08 J, 2.43 J, 2.73 J for one leg during a gait cycle. The ratio of the mechanical work input by the robot to the mechanical work output by the weight of the device decreases (0.904, 0.717, and 0.513 with different load carriages), verifying that the walking assistance efficiency of such devices decreases as the weight rises. In terms of mechanical work in the ankle joint, our results confirm that the efficiency of the ankle-assisted walking robot decreases as weight bearing increases, which provides important guidance for the lightweight design of portable weight-bearing walking robots.
Reef development and Sea level changes driveAcanthasterPopulation Expansion in the Indo-Pacific region
Authors: Pretorius P.C. , Hoareau T.B.
Published: November 2020

Molecular clock calibration is central in population genetics as it provides an accurate inference of demographic history, whereby helping with the identification of driving factors of population changes in an ecosystem. This is particularly important for coral reef species that are seriously threatened globally and in need of conservation. Biogeographic events and fossils are the main source of calibration, but these are known to overestimate timing and parameters at population level, which leads to a disconnection between environmental changes and inferred reconstructions. Here, we propose the Last Glacial Maximum (LGM) calibration that is based on the assumptions that reef species went through a bottleneck during the LGM, which was followed by an early yet marginal increase in population size. We validated the LGM calibration using simulations and genetic inferences based on Extended Bayesian Skyline Plots. Applying it to mitochondrial sequence data of crown-of-thorns starfishAcanthaster spp., we obtained mutation rates that were higher than phylogenetically based calibrations and varied among populations. The timing of the greatest increase in population size differed slightly among populations, but all started between 10 and 20 kya. Using a curve-fitting method, we showed thatAcanthasterpopulations were more influenced by sea-level changes in the Indian Ocean and by reef development in the Pacific Ocean. Our results illustrate that the LGM calibration is robust and can probably provide accurate demographic inferences in many reef species. Application of this calibration has the potential to help identify population drivers that are central for the conservation and management of these threatened ecosystems.
Preclinical validation of a second generation leishmanization vaccine against vector transmitted fatal visceral leishmaniasis
Authors: Karmakar Subir , Ismail Nevien , Oliveira Fabiano , Oristian James , Zhang Wen Wei , Kaviraj Swarnendu , Singh Kamaleshwar P. , Mondal Abhishek , Das Sushmita , Pandey Krishna , Bhattacharya Parna , Volpedo Greta , Gannavaram Sreenivas , Satoskar Monika , Satoskar Sanika , Sastry Rajiv M. , Meneses Claudio , Hamano Shinjiro , Das Pradeep , Matlashewski Greg , Singh Sanjay , Kamhawi Shaden , Dey Ranadhir , Valenzuela Jesus G. , Satoskar Abhay , Nakhasi Hira L.
Published: November 2020

Visceral Leishmaniasis (VL) is fatal if untreated. There is no licensed vaccine available against human leishmaniasis. We recently demonstrated protection in mice againstL. majorinfection using a CRISPR genome edited attenuatedLeishmania majorstrain (LmCen−/−). Here, as a pre-clinical step, we evaluated the protective efficacy ofLmCen−/−against VL induced by sand fly transmittedLeishmania donovaniin hamsters. Intradermal immunization of hamsters withLmCen−/−did not develop any lesion; while still priming a pro-inflammatory immune response. When challenged withL. donovanieither by intradermal needle injection or by infected sand flies,LmCen−/−-immunized hamsters were protected, not showing spleen or liver pathology averting VL fatality compared to control animals. Spleen cells fromLmCen−/−immunized and infected sand fly challenged hamsters produced significantly higher Th1-associated cytokines and chemokines including IFN-γ and TNF-α, and significantly reduced expression of the anti-inflammatory cytokines IL-10 and IL-21, compared to non-immunized challenged animals. We further developed a GLP-gradeLmCen−/−which showed equal protection as laboratory-gradeLmCen−/−parasites in hamsters. Importantly, GLP-gradeLmCen−/−parasites also induced a proinflammatory immune response in the PBMCs isolated from healthy people living in non-endemic and endemic for VL as well as cured VL people living in endemic region. Together, this study demonstrates that theLmCen−/−parasites are safe and efficacious against VL and it is a strong candidate vaccine to be tested in a human clinical trial.