bluuebunny/crossref_metadata_2025 huggingface dataset:
HPTN 067/ADAPT: Correlates of Sex-Related Pre-exposure Prophylaxis Adherence, Thai Men Who Have Sex With Men, and Transgender Women, 2012–2013
Authors: Holtz Timothy H. , Chitwarakorn Anupong , Hughes James P. , Curlin Marcel E. , Varangrat Anchalee , Li Maoji , Amico K. Rivet , Mock Philip A. , Grant Robert M. ,   the Thai HPTN 067/ADAPT Study Team
Published: September 2019

Background:

We identified correlates of sex-related pre-exposure prophylaxis (PrEP) adherence in HPTN067/ADAPT, a phase 2, open-label feasibility study of daily and nondaily regimens of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)-based PrEP, among Thai men who have sex with men (MSM), and transgender women (TGW), Bangkok.

Methods:

Participants were randomly assigned to one of three self-administered dosing regimens for 24 weeks: daily, time-driven, or event-driven. Demographic and behavioral information was obtained at screening. Pill-container opening was recorded with electronic dose monitoring, and self-reported information on PrEP use, sex events, and substance use was obtained during weekly interviews to confirm dose data. Sex-related PrEP adherence was calculated as the proportion of sex events covered by PrEP use (at least one tablet taken within 4 days before sex and at least one tablet taken within 24 hours after sex) to total sex events. We used multivariate modeling with sex event as the unit of analysis to evaluate correlates associated with sex-related PrEP adherence.

Results:

Among 178 MSM and TGW, sex-related PrEP adherence was similar in the daily and time-driven arms (P = 0.79), both significantly greater than the event-driven arm (P = 0.02 compared to daily). Sex-related PrEP adherence by those reporting stimulant use (74.2%) was similar to those reporting other nonalcohol drug use (76.3%, P = 0.80), but lower than those reporting no substance use (84.6%, P = 0.04). In a multivariable model, randomization to the event-driven arm, a higher prestudy number of reported sex events, and use of stimulant drugs were associated with significantly lower sex-related PrEP adherence.

Conclusion:

Adherence was influenced by treatment schedule and adversely affected by nonalcoholic substance use. Regardless of these factors, Thai MSM and TGW maintained high adherence levels to oral PrEP dosing regimens and coverage of sexual exposures.
Bilirubin-Related Differential Striatal [18F]FP-CIT Uptake in Parkinson Disease
Authors: Lee Dong Yun , Oh Minyoung , Kim Soo-Jong , Oh Jungsu S. , Chung Sun Ju , Kim Jae Seung
Published: September 2019

Purpose of the Report

Oxidative stress is a leading factor in the pathogenesis of idiopathic Parkinson disease (IPD). Two intrinsic antioxidative molecules, bilirubin and uric acid, are known to protect dopaminergic neurons from oxidative stress in IPD. The objective of this study was to determine the relationship between basal serum levels of 2 molecules and dopaminergic deficit assessed by dopamine transporter imaging with 18F-fluorinated-N-3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl)nortropane ([18F]FP-CIT) PET/CT in patients with early-stage drug-naive IPD.

Methods

Cases of IPD patients who possess the levels of uric acid and bilirubin within a month from [18F]FP-CIT PET/CT from January 2011 to December 2016 were retrospectively reviewed. As a control, the same criteria applied to patients with essential tremor (ET). PET images were analyzed using volume-of-interest templates for 12 striatal subregions and 1 occipital area, and the specific-to-nonspecific binding ratio (SNBR) was calculated.

Results

One hundred five patients with drug-naive, early-stage IPD and 62 patients with ET were finally included. Levels of bilirubin were significantly higher in the IPD group than in controls (P = 0.026), and bilirubin level was the factor showing the most correlations with SNBR in IPD (P < 0.001), whereas uric acid showed no such difference or relationship. Furthermore, levels of bilirubin showed a positive correlation with SNBR in more affected posterior putamen in the IPD group (Pearson correlation coefficient, ρ = 0.456; P < 0.001), but a negative one in the ET group (ρ = −0.440, P < 0.001).

Conclusions

Bilirubin, not uric acid, was the most significant antioxidant marker for dopaminergic deficit in early-stage drug-naive IPD assessed by [18F]FP-CIT PET/CT.
Circumferential Negative Intermittent Pressure to the Midarm Does Not Impair Digital O2 Saturation
Authors: Aljomah Ahmed S. , Hammami Muhammad M.
Published: September 2019

Background

Circumferential negative pressure wound therapy is commonly used to manage wounds and enhance the healing process. A theoretical concern was recently raised that circumferential negative pressure wound therapy may have a negative effect on perfusion distally.

Methods

In a randomized study, we applied circumferential negative pressure (125 mm Hg) to the midarm of 13 healthy volunteers through InfoV.A.C. Therapy Unit device. The pressure was applied intermittently (5 minutes on and 2 minutes off) for 9 hours. The same device without negative pressure was applied to the contralateral midarm as control. Bilateral index finger O2 saturation (Spo
2) was measured every 30 minutes using digital pulse oximetry.

Results

Mean (SD) age of the volunteers was 32.2 (9.5) years, and 61.5% were male. Mean (SD) area under the curve from time 0 to 9 hours of Spo
2 was 890.56 (6.69) and 889.71 (6.23) %xh in the intervention and control arms, respectively (P = 0.35). O2 saturation was ≥94% at all observation times in both arms, and no adverse events were identified.

Conclusions

Circumferential negative intermittent pressure of 125 mm Hg applied to the midarm of healthy volunteers for 9 hours does not adversely affect digital Spo
2.
Cranioplasty With Autogenous Frozen and Autoclaved Bone: Management and Treatment Outcomes
Authors: Sahoo Nanda Kishore , Thakral Ankur , Janjani Lalit
Published: September 2019

Cranioplasty is a widely employed procedure for restoration of calvarial form and shape. The use of autogenous bone flap offers biological reconstruction with minimal donor site morbidity. One of the options to re-use bone autograft is low temperature preservation followed by autoclaving during cranioplasty. A retrospective evaluation of 12 patients with a mean age of 32.58 ± 10.04 years who underwent frozen autogenous autoclaved bone cranioplasty was done. Cranial bone flaps were removed during the initial craniectomy and stored at 4°C for 20 minutes followed by preservation at −40°C in the deep freezer of the blood bank. Cranioplasty subsequently was performed at a mean time period of 172.17 ± 26.20 days by thawing the bone at room temperature followed by autoclaving at 121°C under 15 psi for 40 minutes. Data regarding patients’ characteristics and complications were recorded. Clinical outcomes based on skull shape and symmetry, cosmesis and scars were analyzed by a panel of 4 raters, including 3 doctors and 1 patient. Radiological outcomes were analyzed based on remaining bone thickness and bone gap widening. The present study revealed functionally, structurally, and cosmetically satisfying results. All the cases had satisfactory healing and no incidence of bone graft infection. The skull shape and symmetry, cosmesis and scars revealed excellent to moderate improvement in three-fourth of the patients. Radiological outcomes revealed none of the patients had severe resorption requiring surgical revision with excellent to good implant alignment in 92% of cases. It was concluded that frozen autogenous cranial bone flaps sterilized by autoclaving is safe and effective material for cranioplasty.
Nasal Reconstruction Following a Dog Bite
Authors: Senturk Erol , Dagistanli Nurtac , Calim Omer Faruk , Ozturan Orhan
Published: September 2019

Bite wounds in the nose region may lead to serious esthetic problems and functional losses. The authors describe a dog bite to his nose, resulting in a defect involving the entire tip of the nose and a part of the surrounding subunits. He was repaired with forehead flap and auricular conchal cartilage acutely. To the authors’ knowledge, there are very few cases of acute repair in the literature. The authors also made a literature review on this subject.
Cone-Beam Computed Tomographic Evaluation of Styloid Process in Patients With Temporomandibular Disorders and Asymptomatic Individuals
Authors: Şahin Onur , Kalabalik Fahrettin , Tatar Birkan , Odabaşi Onur
Published: September 2019

Objectives:

Elongated styloid processes (ESP) may show clinical symptoms that are readily confused with symptoms associated with temporomandibular disorders (TMDs). The purpose of study was to compare the prevalance and characteristics of ESP in patients with TMD and asymptomatic individuals are examined by cone beam computed tomography.

Methods:

Angulations and length of the styloid process (SP) were evaluated in CBCT images of 100 patients with TMD symptoms and 100 control patients, retrospectively. Differences between the patient and control groups were assessed by analysis independent sample t test. Pearson correlation test was used to evaluate between length and angulation of SP relationship.

Results:

The mean length of SP in the TMD group was 38.19 ± 8.6 mm for the right and 38.99 ± 8.1 mm for the right side. The mean length of SP in the control group was 36.80 ± 6.3 for the right side and 36.18 ± 6.5 mm for the left side. The mean anterior angulation of the SP in the TMD group was 22.08 ± 5.5 degree in the TMD group and 23.97 ± 4.1 degree in the control group. The mean medial angulation of the SP in the TMD group was 30.57 ± 4.9 degree and 29.89 ± 4.4 degree in the control group. There was no significant difference in length and angle between the groups (P > 0.05).

Conclusion:

No correlation was found in terms of length and angulations of SP between TMD and control groups.
Reconstruction of a Large Posttraumatic Mandibular Defect Using Bone Tissue Engineering With Fresh-Frozen Humeral Allograft Seeded With Autologous Bone Marrow Aspirate and Vascularized With a Radial Forearm Flap
Authors: Schlund Matthias , Nicot Romain , Depeyre Arnaud , Alkasbi Juma , Ferri Joël
Published: September 2019

Introduction:

Currently, vascularized autologous bone transplantation is considered the gold standard for large mandibular continuity defect reconstruction. Donor site morbidity is a major concern. Therefore, bone tissue engineering (BTE) seems to be the ideal solution. Fresh-frozen bone allograft is the closest material to autologous bone. The purpose of this clinical report is to show a new technique of large mandibular continuity defect reconstruction using a fresh-frozen humeral allograft seeded with autologous iliac bone marrow aspirate and vascularized with a radial forearm flap.

Methods:

A 33-year-old man presented with severe cranio-facial trauma resulting in several fractures of the facial skeleton including a comminuted mandibular fracture from left parasymphysis to left angle, which caused a large continuity defect.

Results:

Result at 6 months was aesthetically and functionally satisfactory with osseointegration of the bone graft.

Discussion:

The authors chose to use iliac bone marrow aspirate to seed the allograft scaffold since hematopoietic stem cells and mesenchymal stem cell are able to differentiate into osteoblasts, ease of harvest of the iliac crest and its low rate of morbidity. Contemporary biomaterials used for BTE are bioceramic but bone is still the better scaffold to engineer bone and only allografting avoids donor site morbidity. Vascularization is one of the main challenges of BTE; insertion of autologous vascular bundles from pedicle or free flaps is 1 solution. The authors chose the radial forearm flap since the pedicle is long and the authors did not need a great amount of soft tissue.
The Diagnostic and Prognostic Value of suPAR in Patients with Sepsis: A Systematic Review and Meta-Analysis
Authors: Huang Qiangru , Xiong Huaiyu , Yan Peijing , Shuai Tiankui , Liu Jingjing , Zhu Lei , Lu Jiaju , Yang Kehu , Liu Jian
Published: September 2019

Background:

Soluble urokinase-type plasminogen activator receptor (suPAR) has the potential to diagnose infectious diseases. Due to the lack of reliable biomarkers and the importance of timely diagnosis for sepsis treatment, we conducted this systematic review and meta-analysis to evaluate the value of suPAR diagnosis and prognosis for sepsis.

Methods:

PubMed, Embase, Web of Science, and Cochrane Library databases were searched for studies, which reported the value of suPAR diagnosis and/or prognosis in patients with sepsis.

Results:

A total of 30 studies involving 6,906 patients were included. Sensitivity and specificity of suPAR for diagnosing sepsis were 0.76 [95% confidence interval (CI), 0.63–0.86] and 0.78 (95% CI, 0.72–0.83), respectively. The area under the summary receiver-operating characteristic curve (AUC) was 0.83 (95% CI, 0.80–0.86). Pooled sensitivity and specificity for predicting mortality were 0.74 (95% CI, 0.67–0.80) and 0.70 (95% CI, 0.63–0.76), respectively, with AUC of 0.78 (95% CI, 0.74–0.82). In addition, AUC for differentiating sepsis from systemic inflammatory response syndrome (SIRS) was 0.81 (95% CI, 0.77–0.84), and the sensitivity and specificity were 0.67 (95% CI, 0.58–0.76) and 0.82 (95% CI, 0.73–0.88), respectively.

Conclusion:

suPAR is a feasible biomarker for timely diagnosis and prognosis of sepsis. Compared with effective value of procalcitonin (PCT) identified by previous meta-analysis, suPAR has similar clinical guiding value, whereas suPAR exhibits higher specificity, which can facilitate the deficiencies of PCT. suPAR also shows a diagnostic value in differentiating sepsis from SIRS. Considering the lack of biomarkers for sepsis and the similar clinical value of suPAR and PCT, suPAR should be considered as a biomarker in clinical practice for sepsis.
Association of Vitamin D Deficiency with Profound Cardiogenic Shock in Patients Resuscitated From Sudden Cardiac Arrest
Authors: Cha Jung-Joon , Wi Jin
Published: September 2019

Background:

Vitamin D deficiency is associated with various cardiovascular diseases, including sudden cardiac arrest (SCA). Profound cardiogenic shock is associated with morbidity and mortality in patients with SCA. This study investigated the association of vitamin D deficiency with profound cardiogenic shock in patients resuscitated from SCA.

Patients and Methods:

We enrolled patients who were successfully resuscitated from out-of-hospital cardiac arrests of a presumed cardiac cause. Profound cardiogenic shock was defined as refractory hypotension requiring high-dose vasopressor infusion (norepinephrine >0.5 mcg/kg/min) despite adequate intravascular volume replacement. Vitamin D levels were measured as plasma 25(OH)D concentrations and severe vitamin D deficiency was defined as 25(OH)D <10 ng/mL.

Results:

A total of 237 subjects (179 men (76%), mean age 56.5 ± 16.5 years) were included in this study. The first monitored rhythm was shockable in 160 subjects (68%). Mean arrest time and CPR times were 25.6 ± 15.7 and 22.8 ± 15.0 min, respectively. Profound cardiogenic shock was observed in 100 subjects (42%). The mean vitamin D level was 12.3 ± 6.7 ng/mL, and vitamin D deficiency was diagnosed in 109 subjects (46%). In profound cardiogenic shock subjects, vitamin D levels were significantly lower (10.7 ± 7.0 vs. 13.4 ± 6.2 ng/mL,P = 0.002) and severe vitamin D deficiency was observed more frequently (63% vs. 34%,P < 0.001). Subjects with profound cardiogenic shock were likely to have longer arrest times (29.5 ± 17.0 vs. 22.7 ± 14.0 min,P = 0.001), left ventricular systolic dysfunction (LVEF < 40%, 73% vs. 38%,P < 0.001), and baseline renal dysfunction (65% vs. 37%,P < 0.001). Multivariate logistic analysis indicated that vitamin D deficiency was significantly associated with profound cardiogenic shock after SCA (OR 2.71, 95% CI 1.42–5.18,P = 0.003) after adjusting for confounding variables.

Conclusions:

Severe vitamin D deficiency was strongly associated with profound cardiogenic shock and mortality in patients resuscitated from SCA.
Towards Successes in the Management of Nonconvulsive Status Epilepticus: Tracing the Detection-to-Needle Trajectories
Authors: Baang Hae Young , Swingle Nicholas , Sajja Kalyan , Madhavan Deepak , Shostrom Valerie K. , Taraschenko Olga
Published: September 2019

Purpose:

Data on the timeliness of emergent medication delivery for nonconvulsive status epilepticus (NCSE) are currently lacking.

Methods:

Retrospective chart reviews (between 2015 and 2018) and analyses of all patients with NCSE were performed at the University of Nebraska Medical Center, a level 4 epilepsy center, to determine the latencies to order and administration of the first, second, and third antiepileptic drugs (AEDs). Recurrent NCSE cases were considered independently and classified as comatose and noncomatose.

Results:

There were 77 occurrences of NCSE in 53 patients. The first, second, and third AEDs were delivered with substantial delays at median times of 80 (25%–75% interquartile range, 44–166), 126 (interquartile range, 67–239), and 158 minutes (interquartile range, 89–295), respectively, from seizure detection. The median times to the order of the first and second AEDs were 33 and 134.5 minutes longer in comatose NCSE patients compared with those with noncomatose forms, respectively (P = 0.001 and 0.004, respectively). The median times between the AED orders and their administration in these two groups were the same (P = 0.60 and 0.37, respectively). With bivariate analysis, the median latencies to administration of the first, second, and third AEDs were significantly increased by 33, 109.5, and 173 minutes, respectively, in patients who died within 30 days compared with those who survived (P = 0.047, P = 0.02, P = 0.0007, respectively).

Conclusions:

The administration of the first, second, and third AEDs for NCSE was delayed. Slow initiation of acute treatment in comatose patients was caused by delays in the placement of the medication order.
High-Density Adaptive Ten Ten: Proposal for Electrode Nomenclature for High-Density EEG
Authors: Heine Walter , Dobrota Mary-Ann , Schomer Donald , Wigton Rebekah , Herman Susan
Published: September 2019

Purpose:

High-density EEG (HD-EEG) systems and electrical source imaging techniques have revolutionized our ability to assess the potential sources of epileptiform activity and other EEG features. Nonetheless, clinical use of HD-EEG is hampered by the lack of a standardized electrode nomenclature system and the inherent difficulties encountered in visually reviewing recordings. Inefficient visual review of HD-EEG remains a major barrier to incorporating these techniques into routine clinical care.

Methods:

Extension of the 10-10 is first defined by the addition of 2 reference curves: the −10% and −20% axial reference curves. Electrode positions over the face are named based on facial bony structures (N = nasion, Z = zygomatic prominence, M = mandible) and over the back of the head on posterior landmarks (I = inion, S = subinion, B = Base). Then, following the 10% incremental distance rule, we define additional electrode positions. Electrodes with nonstandard positions are clustered around the closest 10-10 electrode, deemed their cardinal point.

Results:

The 256-electrode Geodesic Sensor Net mapped to 96 of the 120 extended 10-10 cardinal electrodes.

Conclusions:

Electrode position nomenclature that builds upon the international standard 10-10 system allows electroencephalographers to identify spatial areas of interest in HD-EEG relative to positions in routine use. A standard viewing montage for HD-EEG and its application with electrical source imaging boost efficiency when reviewing data and improve accuracy in recognizing epileptiform discharges. Additionally, our proposed system is not limited to a specific HD-EEG system, electrode count, or electrode layout.
Determinants of first aid knowledge and basic practice among elementary school teachers in Debre Tabor City, Northwest Ethiopia
Authors: Taklual Wubet , Mekie Maru , Yenew Chalachew
Published: September 2019

Background

Unpremeditated injuries are the leading causes of morbidity and mortality in pediatrics population, especially in low and middle-income countries. Giving immediate help for an injured child is a crucial step for saving the child from further disability and/or death. This study aimed to assess the determinant factors of first aid knowledge and basic practice among elementary school teachers in Debre Tabor, Ethiopia.

Method

Institution based cross-sectional study was employed in Debre Tabor City. Single population proportion formula was used for sample size calculation and a total of 216 elementary school teachers were included in study. Simple random sampling technique with proportional allocation was applied for selections of the study participant. Data entry was done by Epi data version 3.1 and the data was exported to SPSS version 21 for analysis. Binary and multivariable logistic regression analysis were performed to identify determinants of knowledge on first aid. Crude and adjusted odds ratios were used to determine the significance and strength of association at 95% confidence interval.

Result

Our study revealed that 45.8% of the subjects were knowledgeable on first aid. More than 75% of study participant reported that they have encountered a child who need first aid. Among this 64% of them provide first aid. The multivariable analysis revealed that service year (AOR=3.51, 95%CI: (1.06, 11.59)), educational status (AOR=12.15, 95%CI: (3.17, 46.67)), previous first aid training (AOR=0.43, 95%CI: (0.21, 0.87)) and information about first aid (AOR=0.12, 95%CI ;(0.03, 0.48)) were found to be significantly associated with having knowledge on first aid.

Conclusion

School teachers have low knowledge on first aid. Educational status, service year, previous first aid training and information on first aid were the predictor of first aid knowledge. Introducing essential first aid training in the curriculum during teachers’ training shall be considered.
Input dose differentiation by NF-κB
Authors: Son Minjun , Wang Andrew , Tu Hsiung-Lin , Metzig Marie O , Patel Parthiv , Husain Kabir , Lin Jing , Murugan Arvind , Hoffmann Alexander , Tay Savaş
Published: September 2019

Cells receive a wide range of dynamic signaling inputs during immune regulation, but how gene regulatory networks measure and interpret such dynamic inputs is not understood. Here, we used microfluidic live-cell analysis and mathematical modeling to study how NF-κB pathway in single-cells responds to time-varying immune inputs such as increasing, decreasing or fluctuating cytokine signals. Surprisingly, we found that NF-κB acts as a differentiator, responding strictly to the absolute difference in cytokine concentration, and not to the concentration itself. Our analyses revealed that negative feedbacks by the regulatory proteins A20 and IκBα enable dose differentiation by providing short-term memory of prior cytokine level and continuously resetting kinase cycling and receptor levels. Investigation of NF-κB target gene expression showed that cells create unique transcriptional responses under different dynamic cytokine profiles. Our results demonstrate how cells use simple network motifs and transcription factor dynamics to efficiently extract information from complex signaling environments.
Distinguishing pedigree relationships using multi-way identical by descent sharing and sex-specific genetic maps
Authors: Qiao Ying , Sannerud Jens , Basu-Roy Sayantani , Hayward Caroline , Williams Amy L.
Published: September 2019

The proportion of samples with one or more close relatives in a genetic dataset increases rapidly with sample size, necessitating relatedness modeling and enabling pedigree-based analyses. Despite this, relatives are generally unreported and current inference methods typically detect only the degree of relatedness of sample pairs and not pedigree relationships. We developed CREST, an accurate and fast method that identifies the pedigree relationships of close relatives. CREST utilizes identical by descent (IBD) segments shared between a pair of samples and their mutual relatives, leveraging the fact that sharing rates among these individuals differ across pedigree configurations. Furthermore, CREST exploits the profound differences in sex-specific genetic maps to classify pairs as maternally or paternally related—e.g., paternal half-siblings—using the locations of autosomal IBD segments shared between the pair. In simulated data, CREST correctly classifies 91.5-99.5% of grandparent-grandchild (GP) pairs, 70.5-97.0% of avuncular (AV) pairs, and 79.0-98.0% of half-siblings (HS) pairs compared to PADRE’s rates of 38.5-76.0% of GP, 60.5-92.0% of AV, 73.0-95.0% of HS pairs. Turning to the real 20,032 sample Generation Scotland (GS) dataset, CREST correctly determines the relationship of 99.0% of GP, 85.7% of AV, and 95.0% of HS pairs that have sufficient mutual relative data, completing this analysis in 10.1 CPU hours including IBD detection. CREST’s maternal and paternal relationship inference is also accurate, as it flagged five pairs as incorrectly labeled in the GS pedigrees— three of which we confirmed as mistakes, and two with an uncertain relationship—yielding 99.7% of HS and 93.5% of GP pairs correctly classified.
Reference glycan structure libraries of primary human cardiomyocytes and pluripotent stem cell-derived cardiomyocytes reveal cell-type and culture stage-specific glycan phenotypes
Authors: Ashwood Christopher , Waas Matthew , Weerasekera Ranjuna , Gundry Rebekah L.
Published: September 2019

Cell surface glycoproteins play critical roles in maintaining cardiac structure and function in health and disease and the glycan-moiety attached to the protein is critical for proper protein folding, stability and signaling. However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart. In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM). Altogether, we established the first reference structure libraries of the cardiac glycome containing 265N-andO-glycans. Comparing theN-glycome of CM enriched from primary heart tissue to that of heart tissue homogenate, 21 structures significantly differed, and the high mannose class is increased in enriched CM. Moreover, by comparing primary CM to hiPSC-CM collected during 20-100 days of differentiation, dynamic changes in the glycan profile throughoutin vitrodifferentiation were observed and differences between primary and hiPSC-CM were revealed. Namely, >30% of theN-glycome significantly changed across these time-points of differentiation and only 23% of theN-glycan structures were shared between hiPSC-CM and primary CM. These observations are an important complement to current genomic, transcriptomic, and proteomic profiling and reveal new considerations for the use and interpretation of hiPSC-CM models for studies of human development, disease, and drug testing. Finally, these data are expected to support future regenerative medicine efforts by informing targets for evaluating the immunogenic potential of hiPSC-CM and harnessing differences between immature, proliferative hiPSC-CM and adult primary CM.
Meta-16S rRNA gene phylogenetic reconstruction reveals astonishing diversity of the cosmopolitan myxobacteria
Authors: Liu Yang , Yao Qing , Zhu Hong-Hui
Published: September 2019

Numerous ecological studies for myxobacteria have been conducted well, but their true diversity hidden in plain sight remains to be explored. To bridge this gap, we here implemented a comprehensive survey of diversity and distribution of myxobacteria by using 4997 publicly available 16S rRNA gene sequences (≥1200 bp) collected from several hundreds of sites across multiple countries and regions. In the study, the meta-16S rRNA gene phylogenetic reconstruction clearly revealed that these sequences were classified to 998 species, 445 genera, 58 families, and 20 suborders, highlighting a considerable taxonomic diversity of myxobacteria, the great majority of which belonged to new taxa. Most cultured myxobacteria including the well-described type strains were strongly inclined to locate on the shallow branches of the phylogenetic tree; on the contrary, the majority of uncultured myxobacteria the deep branches. The geographical analysis of sequences based on their environmental categories clearly demonstrated that myxobacteria showed a nearly cosmopolitan distribution, despite the presence of some habitat-specific taxa, especially at genus and species levels. Among all abundant suborders, members of Suborder_4, Suborder_15, and Suborder_17 were more widely distributed in marine environments, the remaining suborders preferred to reside in terrestrial ecosystems, particularly in soils, indicating a potential selectivity of geographical distribution. In conclusion, this study profiles a clear framework of diversity and distribution of the cosmopolitan myxobacteria and sheds light on the isolation of the uncultured myxobacteria.

IMPORTANCE

Myxobacteria are an attractive bacterial group ubiquitous in soil and aquatic environments. However, the biodiversity and ecological preferences of myxobacteria remain poorly understood across heterogeneous environments. We analyzed thousands of publicly available and high-quality 16S rRNA gene sequences of myxobacteria by using the phylogenetic reconstruction. The study presented an astonishing diversity than that expected from the previous studies. This study further demonstrated that the culturability of myxobacteria was perfectly comparable to its phylogeny in the phylogenetic tree. The geographical analysis clearly indicated that myxobacteria showed a nearly cosmopolitan distribution, while some taxa exhibited obvious preferences for specific environmental conditions. Together, our study provides novel insights into the diversity, distributions, and ecological preferences of of myxobacteria from diverse environments and lays the foundation for innovation of isolation techniques and the discovery of new secondary metabolites.
Potential of genomic selection for improvement of resistance to Ostreid Herpes virus in Pacific oyster (Crassostrea gigas)
Authors: Gutierrez Alejandro P. , Symonds Jane , King Nick , Steiner Konstanze , Bean Tim P. , Houston Ross D.
Published: September 2019

In genomic selection (GS), genome-wide SNP markers are used to generate genomic estimated breeding values (gEBVs) for selection candidates. The application of GS in shellfish looks promising and has the potential to help in dealing with one of the main issues currently affecting Pacific oyster production worldwide, which is the “summer mortality syndrome”. This causes periodic mass mortality in farms worldwide and has mainly been attributed to a specific variant of the Ostreid herpesvirus (OsHV-1-μvar). In the current study, we evaluated the potential of genomic selection for host resistance OsHV in Pacific oysters, and compared it to pedigree-based approaches. An OsHV-1 disease challenge was performed using an immersion-based virus exposure treatment for oysters for seven days. 768 samples were genotyped using the medium density SNP array for oysters. GWAS was performed for the survival trait using a GBLUP approach in BLUPF90 software. Heritability ranged from 0.25±0.05 to 0.37±0.05 (mean±s.e) based on pedigree and genomic information, respectively. Genomic prediction was more accurate than pedigree prediction, and SNP density reduction had little impact on prediction accuracy until marker densities dropped below ∼500 SNPs. This demonstrates the potential for GS in Pacific oyster breeding programs and importantly, demonstrates that a low number of SNPs might suffice to obtain accurate gEBVs, thus potentially making the implementation of GS more cost effective.
Streptococcus pyogenes Cas9 displays biased one-dimensional diffusion on dsDNA to search for a target
Authors: Yang Mengyi , Zhang Lijingyao , Sun Ruirui , Zhong Weixiong , Yang Yuzhuo , Chen Chunlai
Published: September 2019

The RNA-guided Streptococcus pyogenes Cas9 (spCas9) is a sequence-specific DNA endonuclease that works as one of the most powerful genetic editing tools. However, how the Cas9 locates its target among huge amounts of dsDNAs remains controversial. Here, combining biochemical and single-molecule assays, we revealed that Cas9 uses both three-dimensional and one-dimensional diffusion to find its target. We further observed a surprising biased one-dimensional diffusion of Cas9 from 3’ to 5’ end of the non-target strand under physiological salt condition, whereas low ionic concentration or mutations on PAM recognition residues induce unbiased one-dimensional diffusion of Cas9 along dsDNA. We quantified the diffusion length of 27 bp, which accelerates the target search efficiency of Cas9 by ∼ 10 folds. Our results reveal a unique searching mechanism of Cas9 at physiological salt conditions, and provide important guidance for both in-vitro and in-vivo applications of Cas9.
Evidence of Absence Treated as Absence of Evidence: The Effects of Variation in the Number and Distribution of Gaps Treated as Missing Data on the Results of Standard Maximum Likelihood Analysis
Authors: Machado Denis Jacob , Castroviejo-Fisher Santiago , Grant Taran
Published: September 2019

We evaluated the effects of variation in the number and distribution of gaps (i.e., no base; coded as IUPAC “.” or “–”) treated as missing data (i.e., any base, coded as “?” or IUPAC “N”) in standard maximum likelihood (ML) analysis. We obtained alignments with variable numbers and arrangements of gaps by aligning seven diverse empirical datasets under different gap opening costs using MAFFT. We selected the optimal substitution model for each alignment using the corrected Akaike Information Criterion (AICc) in jModelTest2 and searched for the optimal trees for each alignment using default search parameters and the selected models in GARLI. We also employed a Monte Carlo approach to randomly insert gaps (treated as missing data) into an empirical dataset to understand more precisely the effects of their variable numbers and distributions. To compare alignments quantitatively, we used several measures to quantify the number and distribution of gaps in all alignments (e.g., alignment length, total number of gaps, total number of characters containing gaps, number of gap openings). We then used these variables to derive four indices (ranging from 0 to 1) that summarize the distribution of gaps both within and among terminals, including an index that takes into account their optimization on the tree. Our most important observation is that ML scores correlate negatively with gap opening costs, and the amount of missing data. These variables also cause unpredictable effects on tree topologies. We discuss the implications of our results for the traditional and tree-alignment approaches in ML.
Neuromodulation and Differential Learning Across Mosquito Species
Authors: Wolff Gabriella H. , Lahondère Chloé , Vinauger Clément , Riffell Jeffrey A.
Published: September 2019

Mosquitoes can learn to change their host-feeding behaviors, such as shifting activity times to avoid bednets or switching from biting animals to biting humans, leading to the transfer of zoonotic diseases. Dopamine is critical for insect learning, but its role in the antennal lobe remains unclear, and it is unknown whether different mosquito species learn the same odor cues. We assayed aversive olfactory learning and dopaminergic brain innervation in four mosquito species with different host preferences and report here that they differentially learn odors salient to their preferred host and innervation patterns vary across species. Using genetically-encoded GCaMP6sAedes aegypti, we mapped odor-evoked antennal lobe activity and report that glomeruli tuned to “learnable” odors have significantly higher dopaminergic innervation. Changes in dopamine expression in the antennal lobes of diverse invertebrate species may be an evolutionary mechanism to adapt olfactory learning circuitry without changing brain structure and for mosquitoes an ability to adapt to other hosts when their preferred are no longer present.
Predicting Alzheimer’s disease progression using deep recurrent neural networks
Authors: Nguyen Minh , He Tong , An Lijun , Alexander Daniel C. , Feng Jiashi , Yeo B.T. Thomas ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: September 2019

Early identification of individuals at risk of developing Alzheimer’s disease (AD) dementia is important for developing disease-modifying therapies. In this study, given multimodal AD markers and clinical diagnosis of an individual from one or more timepoints, we seek to predict the clinical diagnosis, cognition and ventricular volume of the individual for every month (indefinitely) into the future. We proposed and applied a minimal recurrent neural network (minimalRNN) model to data from The Alzheimer’s Disease Prediction Of Longitudinal Evolution (TADPOLE) challenge, comprising longitudinal data of 1677 participants (Marinescu et al. 2018) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We compared the performance of the minimalRNN model and four baseline algorithms up to 6 years into the future. Most previous work on predicting AD progression ignore the issue of missing data, which is a prevalent issue in longitudinal data. Here, we explored three different strategies to handle missing data. Two of the strategies treated the missing data as a “preprocessing” issue, by imputing the missing data using the previous timepoint (“forward filling”) or linear interpolation (“linear filling). The third strategy utilized the minimalRNN model itself to fill in the missing data both during training and testing (“model filling”). Our analyses suggest that the minimalRNN with “model filling” compared favorably with baseline algorithms, including support vector machine/regression, linear state space (LSS) model, and long short-term memory (LSTM) model. Importantly, although the training procedure utilized longitudinal data, we found that the trained minimalRNN model exhibited similar performance, when using only 1 input timepoint or 4 input timepoints, suggesting that our approach might work well with just cross-sectional data. An earlier version of our approach was ranked 5th (out of 53 entries) in the TADPOLE challenge in 2019. The current approach is ranked 2nd out of 63 entries as of June 3rd, 2020.
No division of labour, and subfertile foundresses, in a phyllode-gluing Acacia thrips
Authors: Gilbert James D. J.
Published: September 2019

Behavioural variation is a hallmark of animal societies, which commonly contain breeders and nonbreeders, and helpers and nonhelpers. In some cases labour is divided with nonbreeders “helping” – gaining indirectly, via genetic benefits, or directly, e.g. by augmenting group size. Conversely, they may benefit by not helping, conserving energy for breeding later. However, subordinate behaviour after inheriting a breeding position is rarely evaluated.

In the Australian interior, Acacia thripsDunatothrips aneurae(Thysanoptera) glueAcaciaphyllodes together into “domiciles”. Foundresses, usually sisters, build domiciles singly or communally. Some co-foundresses are nonreproductive, and their role is currently unknown. I experimentally rejected the idea that they substantially “help” by contributing to domicile repair. Nonreproductives were less likely to repair damage than reproductives. Alternatively, they may be waiting to inherit the domicile, or simply of too poor quality to reproduce or help. To test these alternatives, in the field, I allowed repairer or nonrepairer females to “inherit” a domicile by removing their nestmate(s). Thus isolated, “nonrepairer” females took much longer to repair domiciles than “repairers”, control singletons or pairs. Although ovarian condition was equivalent across groups, after 21 days nonrepairers actually laid fewer eggs compared to other groups.

Thus, labour was not divided: instead reproduction and helping covaried, probably depending on female quality and the outcome of intra-domicile competition. Nonreproductive nonhelpers were not waiting to breed. Their role, and their net effect on colony productivity, remains to be shown. They are likely subfertile, and may make the “best of a bad job” by gaining indirect benefits to the best of their limited ability.
Post-replicative pairing of sister ter regions in Escherichia coli involves multiple activities of MatP
Authors: Crozat Estelle , Tardin Catherine , Salhi Maya , Rousseau Philippe , Lablaine Armand , Bertoni Tommaso , Holcman David , Sclavi Bianca , Cicuta Pietro , Cornet François
Published: September 2019

The ter region of the bacterial chromosome, where replication terminates, is the last to be segregated before cell division in Escherichia coli. Delayed segregation is controlled by the MatP protein, which binds to specific sites (matS) within ter, and interacts with other proteins such as ZapB. Here, we investigate the role of MatP by combining short-time mobility analyses of the ter locus with biochemical approaches. We find that ter mobility is similar to that of a non-ter locus, except when sister ter loci are paired after replication. This effect depends on MatP, the persistence of catenanes, and ZapB. We characterise MatP/DNA complexes and conclude that MatP binds DNA as a tetramer, but bridging matS sites in a DNA-rich environment remains infrequent. We propose that tetramerisation of MatP links matS sites with ZapB and/or with non-specific DNA to promote optimal pairing of sister ter regions until cell division.
Analysis of genes within the schizophrenia-linked 22q11.2 deletion identifies interaction of night owl/LZTR1 and NF1 in GABAergic sleep control
Authors: Maurer Gianna W. , Malita Alina , Nagy Stanislav , Koyama Takashi , Werge Thomas M. , Halberg Kenneth A. , Texada Michael J. , Rewitz Kim
Published: September 2019

The human 22q11.2 chromosomal deletion is one of the strongest identified genetic risk factors for schizophrenia. Although the deletion spans a number of genes, the contribution of each of these to the 22q11.2 deletion syndrome (DS) is not known. To investigate the effect of individual genes within this interval on the pathophysiology associated with the deletion, we analyzed their role in sleep, a behavior affected in virtually all psychiatric disorders, including the 22q11.2 DS. We identified the gene LZTR1 (night owl, nowl) as a regulator of sleep in Drosophila. Neuronal loss of nowl causes short and fragmented sleep, especially during the night. In humans, LZTR1 has been associated with Ras-dependent neurological diseases also caused by Neurofibromin-1 (Nf1) deficiency. We show that Nf1 loss leads to a night-time sleep phenotype nearly identical to that of nowl loss, and that nowl negatively regulates Ras and interacts with Nf1 in sleep regulation. We also show that nowl is required for metabolic homeostasis, suggesting that LZTR1 may contribute to the genetic susceptibility to obesity associated with the 22q11.2 DS. Furthermore, knockdown of nowl or Nf1 in GABA-responsive sleep-promoting neurons elicits the sleep-fragmentation phenotype, and this defect can be rescued by increased GABAA receptor signaling, indicating that Nowl promotes sleep by decreasing the excitability of GABA-responsive wake-driving neurons. Our results suggest that nowl/LZTR1 may be a conserved regulator of GABA signaling and sleep that contributes to the 22q11.2 DS.
GeneWalk identifies relevant gene functions for a biological context using network representation learning
Authors: Ietswaart Robert , Gyori Benjamin M. , Bachman John A. , Sorger Peter K. , Churchman L. Stirling
Published: September 2019

The primary bottleneck in high-throughput genomics experiments is identifying the most important genes and their relevant functions from a list of gene hits. Existing methods such as Gene Ontology (GO) enrichment analysis provide insight at the gene set level. For individual genes, GO annotations are static and biological context can only be added by manual literature searches. Here, we introduce GeneWalk (github.com/churchmanlab/genewalk), a method that identifies individual genes and their relevant functions under a particular experimental condition. After automatic assembly of an experiment-specific gene regulatory network, GeneWalk quantifies the similarity between vector representations of each gene and its GO annotations through representation learning, yielding annotation significance scores that reflect their functional relevance for the experimental context. We demonstrate the use of GeneWalk analysis of RNA-seq and nascent transcriptome (NET-seq) data from human cells and mouse brains, validating the methodology. By performing gene- and condition-specific functional analysis that converts a list of genes into data-driven hypotheses, GeneWalk accelerates the interpretation of high-throughput genetics experiments.
Simplification of ribosomes in bacteria with tiny genomes
Authors: Nikolaeva Daria D. , Gelfand Mikhail S. , Garushyants Sofya K.
Published: September 2019

The ribosome is an essential cellular machine performing protein biosynthesis. Its structure and composition are highly conserved in all species. However, some bacteria have been reported to have an incomplete set of ribosomal proteins. We have analyzed ribosomal protein composition in 214 small bacterial genomes (< 1 Mb) and found that although the ribosome composition is fairly stable, some ribosomal proteins may be absent, especially in bacteria with dramatically reduced genomes. The protein composition of the large subunit is less conserved than that of the small subunit. We have identified the set of frequently lost ribosomal proteins and demonstrated that they tend to be situated on the ribosome surface and have fewer contacts to other ribosome components. Moreover, some proteins are lost in an evolutionary correlated manner. The reduction of rRNA is also common in bacteria with tiny genomes with deletions mostly occurring in free loops. Finally, the loss of the anti-Shine-Dalgarno sequence is associated with the genome reduction, the number of lost ribosomal proteins, and with the loss of bL9 and TF.