bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Calcium Scoring Between 64-Multidetector Computed Tomography and 320-Multidetector Computed Tomography Using a Cardiac Phantom: Achieving Consistent Image Quality With Dose Optimization
Authors: Tsai Sung-Yi , Ding Xiao-Hua , Jin Shih-Chun , Yi Dong-Bo , Chen Jyh-Cheng
Published: January 2020

The purpose of this study was to evaluate the relationship between radiation dose and noise level on various coronary calcium scoring protocols between 64-multidetector computed tomography (MDCT) and 320-MDCT. The cardiac QRM phantoms (1 small size and 1 medium size) were used in this study. Lower-dose imaging protocols were proposed for optimization with the parameters of 120 kVp and 10 mAs for small-size phantom (0.336 mSv) in 64-MDCT imaging and small-size phantom (0.2 mSv) in 320-MDCT case, and 120 kVp and 80 mAs for medium-size phantom (2.73 mSv) in 64-MDCT imaging and medium-size phantom (1.58 mSv) in 320-MDCT case. Our results suggest that people can apply lower-dose protocols in the clinical use for early diagnosis of coronary disease without sacrificing diagnostic accuracy.
Cultured Epidermal Autograft for Total Scalp Reconstruction in a Neonate Following Necrotizing Fasciitis
Authors: Kimia Rotem , Azoury Saïd C. , Allukian Myron , Nguyen Phuong D.
Published: January 2020

Necrotizing fasciitis in the pediatric population is a particularly difficult diagnostic and management challenge. Options for soft tissue reconstruction of wounds following surgical debridement have been historically limited, yet recent advancements in bioengineered tissue and matrices have introduced alternative methods of treatment for these patients. We present a case of neonatal necrotizing fasciitis of the scalp requiring full-thickness surgical debridement, which was successfully reconstructed using Epicel cultured epidermal autograft (CEA). A 4-day-old female neonate (gestational age 40 weeks) presented with scalp erythema, blistering, and sepsis following peripartum fetal scalp electrode monitoring. She underwent surgical excision of the scalp to healthy bleeding tissue resulting in a defect of approximately 97% of the scalp, measuring 18 × 19 cm including 4 × 3.5 cm of exposed bone at the occiput. Initial provisional coverage of the defect was obtained with Integra collagen matrix bilayer dressing to stimulate granulation over exposed bone. Concurrently, a 2 × 4-cm excisional biopsy of the left groin skin was obtained for CEA in vitro expansion over 21 days. Then, autograft sheets were applied to achieve total scalp coverage. Clinical assessments at 1 week, 1 month, and 2 months postoperatively exhibited, approximately, 60% take, 80% take, and 90% take, respectively. Scalp involvement in neonatal necrotizing infections is a notably rare presentation as surmised by our review of the literature, and to our knowledge, this is the first report on the use of Integra and CEA for near-total neonatal scalp coverage.
Long-term Outcomes of Endoscopic Resection for Gastric Subepithelial Tumors
Authors: Li D.M. , Ren L.L. , Jiang Y.P.
Published: January 2020

Objective:

The purpose of the current study was to analyze the safety and efficacy of endoscopic resection for gastric subepithelial tumors (SETs) using long-term patient outcome data.

Patients and Methods:

A retrospective analysis of 73 consecutive patients with gastric SETs was performed from June 2014 to December 2016. The treatment methods included submucosal dissection, submucosal excavation or endoscopic full-thickness resection (EFTR). In addition to epidemiological data (sex and age), tumor size, surgical parameters, length of stay, complications, costs, and endoscopic, clinicopathologic, and follow-up data were analyzed to compare treatments.

Results:

The complete resection rate was 97.3% (71/73). Three patients experienced complications (4.1%), including 2 with delayed perforation and 1 with perioperative infection. The median postoperative feeding time was 3 days, and the median postoperative hospital stay was 5 days. The median follow-up period was 19 months, with no patient death or tumor recurrence. Among the 38 patients with gastrointestinal stromal tumors, the complete resection rate was 97.4% (37/38). The complete resection and complication rates between the endoscopic submucosal excavation (ESE) group and the EFTR group were not statistically significant. There was no recurrence or metastasis detected among either group; however, the ESE group had earlier postoperative feeding, a shorter postoperative hospital stay, and less hospitalization expenses.

Conclusions:

Endoscopic resection for gastric SETs (<3 cm) is safe and feasible concerning medium-term and long-term effects. Compared with the EFTR group, the ESE group had earlier postoperative feeding, a shorter postoperative hospital stay, and less hospitalization expenses. Even so, gastric SETs with malignant potential are at risk of recurrence. Larger prospective multicenter studies are warranted.
Association of More Intensive Induction With Less Acute Rejection Following Intestinal Transplantation: Results of 445 Consecutive Cases From a Single Center
Authors: Vianna Rodrigo , Farag Ahmed , Gaynor Jeffrey J. , Selvaggi Gennaro , Tekin Akin , Garcia Jennifer , Beduschi Thiago
Published: January 2020

Background.

In intestinal transplantation, acute cellular rejection (ACR) remains a significant challenge to achieving long-term graft survival. It is still not clear which are the most important prognostic factors.

Methods.

We performed a Cox multivariable analysis of the hazard rates of developing any ACR, severe ACR, and cause-specific graft loss during the first 60 months posttransplant among 445 consecutive intestinal transplant recipients at our institution since 1994. Of particular interest was to determine the prognostic influence of induction type: rabbit antithymocyte globulin (rATG; 2 mg/kg × 5)/rituximab (150 mg/m2 × 1; begun in 2013), alemtuzumab (2001–2011), and less intensive forms.

Results.

First ACR and severe ACR occurred in 61.3% (273/445) and 22.2% (99/445) of cases. The following 3 multivariable predictors were associated with significantly lower hazard rates of developing ACR and severe ACR: transplant type modified multivisceral or full multivisceral (P = 0.0009 and P < 0.000001), rATG/rituximab induction (P < 0.000001 and P < 0.01), and alemtuzumab induction (P = 0.004 and P = 0.07). For both ACR and severe ACR, the protective effects of rATG/rituximab and alemtuzumab were highly significant (P ≤ 0.000005 for ACR; P ≤ 0.01 for severe ACR) but only during the first 24 days posttransplant (when the ACR hazard rate was at its peak). The prognostic effects of rATG/rituximab and alemtuzumab on ACR/severe ACR disappeared beyond 24 days posttransplant (ie, nonproportional hazards). While significant protective effects of both rATG/rituximab and alemtuzumab existed during the first 6 months posttransplant for the hazard rate of graft loss-due-to-rejection (P = 0.01 and P = 0.003), rATG/rituximab was additionally associated with a consistently lower hazard rate of graft loss-due-to-infection (P = 0.003). All significant effects remained after controlling for the propensity-to-be-transplanted since 2013.

Conclusions.

More intensive induction was associated with a significant lowering of ACR risk, particularly during the early posttransplant period.
Impaired Exercise Tolerance Early After Heart Transplantation Is Associated With Development of Cardiac Allograft Vasculopathy
Authors: Yu Mingxi D. , Liebo Max J. , Lundgren Scott , Salim Ahmed M. , Joyce Cara , Zolty Ronald , Moulton Michael J. , Um John Y. , Lowes Brian D. , Raichlin Eugenia
Published: January 2020

Background.

Exercise performance remains limited in some patients after heart transplantation (HTx). The goal of this study was to assess for association between cardiopulmonary exercise test performance at 1 year after HTx and future development of cardiac allograft vasculopathy (CAV).

Methods.

Overall 243 HTx recipients performed cardiopulmonary exercise testing at 1 year after HTx. During the median follow-up period of 31 (interquartile range 19;61) months, 76 (32%) patients were diagnosed with CAV (CAV group).

Results.

The CAV group patients had lower exercise capacity (5.2 ± 1.9 versus 6.5 ± 2.2 metabolic equivalents; P = 0.001) and duration (9.6 ± 3.5 versus 11.4 ± 4.8 min; P = 0.008), lower peak oxygen consumption (VO2) (18.4 ± 5.4 versus 21.4 ± 6.1 mL/kg/min; P = 0.0005), lower normalized peak VO2 (63% ± 18% versus 71% ± 19%; P = 0.007), and higher minute ventilation (VE)/carbon dioxide production (VCO2) (34 ± 5 versus 32 ± 5, P = 0.04). On Cox proportional hazards regression analysis, normalized peak VO2 ≤60%, and VE/VCO2 ≥34 were associated with a high hazard for CAV (HR = 1.8 [95% CI 1.10-4.53, P = 0.03] and 2.5 [95% CI 1.01-8.81, P = 0.04], respectively). The subgroup of patients with both normalized peak VO2 ≤60% and VE/VCO2 ≥34 was at highest risk for development of CAV (HR = 5.2, 95% CI 2.27-15.17, P = 0.001).

Conclusions.

Normalized peak VO2 ≤60% and VE/VCO2 ≥34 at 1 year after HTx are associated with the development of CAV.
Identifying medullary bone in extinct avemetatarsalians: challenges, implications and perspectives
Authors: Canoville Aurore , Schweitzer Mary H. , Zanno Lindsay
Published: January 2020

Medullary bone (MB) is a sex-specific tissue produced by female birds during the laying cycle, and it is hypothesized to have arisen within Avemetatarsalia, possibly outside Avialae. Over the years, researchers have attempted to define a set of criteria from which to evaluate the nature of purported MB-like tissues recovered from fossil specimens. However, we argue that the prevalence, microstructural and chemical variability of MB in Neornithes is, as of yet, incompletely known and thus current diagnoses of MB do not capture the extent of variability that exists in modern birds. Based on recently published data and our own observations of MB distribution and structure using computed tomography and histochemistry, we attempt to advance the discourse on identifying MB in fossil specimens. We propose: (i) new insights into the phylogenetic breadth and structural diversity of MB within extant birds; (ii) a reevaluation and refinement of the most recently published list of criteria suggested for confidently identifying MB in the fossil record; (iii) reconsideration of some prior identifications of MB-like tissues in fossil specimens by taking into account the newly acquired data; and (iv) discussions on the challenges of characterizing MB in Neornithes with the goal of improving its diagnosis in extinct avemetatarsalians.

This article is part of the theme issue ‘Vertebrate palaeophysiology’.
Case study of radial fibrolamellar bone tissues in the outer cortex of basal sauropods
Authors: Jentgen-Ceschino Benjamin , Stein Koen , Fischer Valentin
Published: January 2020

The histology of sauropod long bones often appears uniform and conservative along their evolutionary tree. One of the main aspects of their bone histology is to exhibit a fibrolamellar complex in the cortex of their long bones. Here, we report another bone tissue, the radial fibrolamellar bone (RFB), in the outer cortex of the humeri of a young adult cf.
Isanosaurus
(Early to Late Jurassic, Thailand) and an adult
Spinophorosaurus nigerensis
(Early to Middle Jurassic, Niger) that do not exhibit any pathological feature on the bone surface. Its location within the cortex is unexpected, because RFB is a rapidly deposited bone tissue that would rather be expected early in the ontogeny. A palaeopathological survey was conducted for these sampled specimens. Observed RFB occurrences are regarded as spiculated periosteal reactive bone, which is an aggressive form of periosteal reaction. A ‘hair-on-end’ pattern of neoplasmic origin (resembling a Ewing's sarcoma) is favoured for cf.
Isanosaurus
, while a sunburst pattern of viral or neoplasmic origin (resembling an avian osteopetrosis or haemangioma) is favoured for
Spinophorosaurus
. This study highlights the importance of bone histology in assessing the frequency and nature of palaeopathologies.

This article is part of the theme issue ‘Vertebrate palaeophysiology’.
Investigation of a bone lesion in a gorgonopsian (Synapsida) from the Permian of Zambia and periosteal reactions in fossil non-mammalian tetrapods
Authors: Kato Kyle M. , Rega Elizabeth A. , Sidor Christian A. , Huttenlocker Adam K.
Published: January 2020

While only distantly related to mammals, the anatomy of Permian gorgonopsians has shed light on the functional biology of non-mammalian synapsids and on the origins of iconic ‘mammal-like’ anatomical traits. However, little is known of gorgonopsian behaviour or physiology, which would aid in reconstructing the paleobiological context in which familiar mammalian features arose. Using multi-modal imaging, we report a discrete osseous lesion in the forelimb of a late Permian-aged gorgonopsian synapsid, recording reactive periosteal bone deposition and providing insights into the origins and diversity of skeletal healing responses in premammalian synapsids. We suggest that the localized lesion on the anterolateral (preaxial) shaft of the left radius represents acute periostitis and, conservatively, most likely developed as a subperiosteal haematoma with subsequent bone deposition and limited internal remodelling. The site records an inner zone of reactive cortical bone forming irregular to radial bony spicules and an outer, denser zone of slowed subperiosteal bone apposition, all of which likely occurred within a single growing season. In surveys of modern reptiles—crocodylians, varanids—such haematomas are rare compared to other documented osteopathologies. The extent and rapidity of the healing response is reminiscent of mammalian and dinosaurian bone pathologies, and may indicate differing behaviour or bone physiology compared to non-dinosaurian reptiles. This report adds to a growing list of putative disease entities recognized in early synapsids and broadens comparative baselines for pathologies and the evolution of bone response to disease in mammalian forebears.

This article is part of the theme issue ‘Vertebrate palaeophysiology’.
Inferring the physiological regimes of extinct vertebrates: methods, limits and framework
Authors: Padian Kevin , de Ricqlès Armand
Published: January 2020

What can we know of the physiological regimes of ancient vertebrates? Essential to the exploration of this question are several epistemological tools: (i) a phylogenetic framework for interpreting whole animals and individual tissues, (ii) reliable knowledge of variation in populations and among climates and geographies, (iii) an understanding of phenotypic variation during ontogeny and between sexes, and (iv) a sense of the patterns of body size change, both phyletically and ontogenetically. Palaeobiologists are historically bound to a dichotomous set of terms developed long ago to describe the relatively depauperate living vertebrate fauna. This system sees only binary categories of five major groupings: the ‘cold-blooded’ fishes, amphibians, and reptiles, and the ‘warm-blooded’ birds and mammals. The integration of histoanatomical data with patterns of size, growth and phylogeny provides an opportunity to re-imagine not only vertebrate palaeophysiology, but vertebrate physiology in general. Here, we discuss how four ‘signals’ or ‘influences’ on bone tissues—phylogeny, ontogeny, mechanics and environment—can help to address these questions.

This article is part of the theme issue ‘Vertebrate palaeophysiology’.
Large-scale and significant expression from pseudogenes in Sodalis glossinidius – a facultative bacterial endosymbiont
Authors: Goodhead Ian , Blow Frances , Brownridge Philip , Hughes Margaret , Kenny John , Krishna Ritesh , McLean Lynn , Pongchaikul Pisut , Beynon Rob , Darby Alistair C.
Published: January 2020

The majority of bacterial genomes have high coding efficiencies, but there are some genomes of intracellular bacteria that have low gene density. The genome of the endosymbiont

Sodalis glossinidius

contains almost 50 % pseudogenes containing mutations that putatively silence them at the genomic level. We have applied multiple ‘omic’ strategies, combining Illumina and Pacific Biosciences Single-Molecule Real-Time DNA sequencing and annotation, stranded RNA sequencing and proteome analysis to better understand the transcriptional and translational landscape of

Sodalis

pseudogenes, and potential mechanisms for their control. Between 53 and 74 % of the

Sodalis

transcriptome remains active in cell-free culture. The mean sense transcription from coding domain sequences (CDSs) is four times greater than that from pseudogenes. Comparative genomic analysis of six Illumina-sequenced

Sodalis

isolates from different host Glossina species shows pseudogenes make up ~40 % of the 2729 genes in the core genome, suggesting that they are stable and/or that

Sodalis

is a recent introduction across the genus Glossina as a facultative symbiont. These data shed further light on the importance of transcriptional and translational control in deciphering host–microbe interactions. The combination of genomics, transcriptomics and proteomics gives a multidimensional perspective for studying prokaryotic genomes with a view to elucidating evolutionary adaptation to novel environmental niches.
Portable Objective Diagnostics using Visual Evoked Potentials for Age-related Macular Degeneration
Authors: Versek Craig , Banijamali S. Mohammad Ali , Bex Peter J. , Lashkari Kameran , Kamarthi Sagar V. , Sridhar Srinivas
Published: January 2020

Delayed Dark Adapted vision Recovery (DAR) is a biomarker for Age-related Macular Degeneration (AMD), however its measurement is burdensome for patients and examiners. We developed a portable, wireless, quick-setup system that employs a headset with a smartphone to deliver controlled photobleach and monocular pattern reversal stimuli, while using custom electroencephalography (EEG) electrodes and electronics in order to measure objective Dark Adapted Visual Evoked Potentials (DAVEP) at multiple locations of the visual field - all in one comfortable 20-minute session, without requiring subject reporting. DAVEP responses post photobleach (up to 15 minutes), were measured concurrently in both eyes of 13 patients with AMD and 8 others not diagnosed with AMD. New, unexpected features at high latencies were observed in the DAVEP responses to scotopic stimulus intensities. The amplitude recovery of the DAVEP response was significantly delayed in AMD patients compared with controls. We developed DAVEP1 scores, a simple metric for DAR, using it to successfully identify all 100% of AMD subjects and classify 90% of subject eyes correctly. Deficits in DAR in patients with AMD can be identified using this objective VEP based system and the DAVEP1 metric, a promising new objective biomarker for this disease that can be easily tested in a clinic.
A Cross-Sectional Survey on Smartphone Usage Pattern, the Level of Mobile Phone Dependence and Psychosocial Effects among Undergraduate Students in a Malaysian University
Authors: Nasser Nisha Syed , Ling Loh Jia , Rashid Aida Abdul , Sharifat Hamed , Ahmad Umar , Ibrahim Buhari , Mustafa Salasiah , Kee Hoo Fan , Mooi Ching Siew , Suppiah Subapriya
Published: January 2020

Objective

Problematic smartphone use (PSU) is the development of pathological dependence at the expense of performing activities of daily living, thus having a negative health and psychosocial impact on the users. Previous PSU studies focused on medical students and little is known regarding its effect on students undergoing other fields of study. The objective of this study is to identify the pattern of smartphone usage and determine the psychosocial factors affecting PSU among undergraduate students in Malaysia and compare the pattern among different fields of study.

Method

A prospective cross-sectional study was conducted using validated Smartphone Addiction Scale–Malay version (SAS-M) questionnaire. One-way ANOVA was used to determine the correlation between the patterns of smartphone usage among the students categorised by their ethnic groups, hand dominance and by their field of study. MLR analysis was applied to predict PSU based on socio-demographic data, smartphone usage patterns, psychosocial factors and field of study.

Results

A total of 1060 students completed the questionnaire. The majority of students had PSU (60.7%). Students used smartphones predominantly to access SNAs, namely Instagram. Longer duration on the smartphone per day (≥ 9 hours), age at first using a smartphone and depression carried higher risk of developing PSU, whereas the field of study (science vs. arts based) did not contribute to an increased risk of developing PSU.

Conclusion

Findings from this study can help better inform university administrators about at-risk groups of undergraduate students who may benefit from targeted intervention designed to reduce their addictive behavior patterns.
A Combined HLA Molecular Mismatch and Expression Analysis for Evaluating HLA-DPB1 de novo Donor-Specific Antibody Risk in Pediatric Solid Organ Transplantation: Implications for Solid Organ & Hematopoietic Stem Cell Transplantation
Authors: Shieh Mengkai , Hayeck Tristan J. , Dinh Anh , Duke Jamie L. , Chitnis Nilesh , Mosbruger Timothy , Morlen Ryan P. , Ferriola Deborah , Kneib Carolina , Hu Taishan , Huang Yanping , Monos Dimitri S.
Published: January 2020

Background

HLA molecular mismatch (MM) has been shown to be a risk factor for de novo donor-specific antibody (dnDSA) development in solid organ transplantation (SOT). HLA expression differences have also been associated with adverse outcomes in hematopoietic cell transplantation. We sought to study both MM and expression in assessing dnDSA risk.

Methods

One-hundred-and-three HLA-DP-mismatched SOT pairs were retrospectively analysed. MM was computed using amino acids (aa), eplets and, supplementarily, Grantham/Epstein scores. DPB1 alleles were classified as rs9277534-A (low-expression) or -G (high-expression)–linked. To determine the associations between risk factors and dnDSA, logistic regression, linkage disequilibrium (LD) and population-based analyses were performed.

Results

A high-risk AA:GX (recipient:donor) expression combination (X=A or G) demonstrated strong association with DP-dnDSA (p=0.001). MM was also associated with DP-dnDSA when evaluated by itself (eplet_p=0.007, aa_p=0.003, Grantham_p=0.005, Epstein_p=0.004). When attempting to determine the relative individual effects of the risk factors in multivariable analysis, only AA:GX expression status retained a strong association (RR=18.6, p=0.007 with eplet; RR=15.8, p=0.02 with aa), while MM was no longer significant (eplet_p=0.56, aa_p=0.51). Importantly, these risk factors are correlated, due to LD between the expression-tagging SNP and polymorphisms along HLA-DPB1.

Conclusions

The MM and expression risk factors each appear to be strong predictors of DP-dnDSA and to possess clinical utility; however, the two risk factors are closely correlated. These metrics may represent distinct ways of characterizing a common overlapping dnDSA risk profile, but they are not independent. Further, we demonstrate the importance and detailed implications of LD effects in risk assessment of dnDSA and possibly transplantation overall.
Geographical and environmental contributions to genomic divergence in mangrove forests
Authors: da Silva Michele Fernandes , Cruz Mariana Vargas , de Deus Vidal Júnior João , Zucchi Maria Imaculada , Mori Gustavo Maruyama , de Souza Anete Pereira
Published: January 2020

Assessing the relative importance of geographical and environmental factors to the spatial distribution of genetic variation can provide information about the processes that maintain genetic variation in natural populations. With a globally wide but very restricted habitat distribution, mangrove trees are a useful model for studies aiming to understand the contributions of these factors. Mangroves occur along the continent–ocean interface of tropical and subtropical latitudes, regions considered inhospitable to many other types of plants. Here, we used landscape genomics approaches to investigate the relative contributions of geographical and environmental variables to the genetic variation of two black mangrove species,Avicennia schauerianaandAvicennia germinans, along the South American coast. Using single nucleotide polymorphisms, our results revealed an important role of ocean currents and geographical distance in the gene flow ofA. schauerianaand an isolation-by-environment pattern in the organization of the genetic diversity ofA. germinans. Additionally, forA. germinans, we observed significant correlations between genetic variation with evidence of selection and the influence of precipitation regimens, solar radiation and temperature patterns. These discoveries expand our knowledge about the evolution of mangrove trees and provide important information to predict future responses of coastal species to the expected global changes during this century.
On mechanisms of light-induced deformations in photoreceptors
Authors: Boyle Kevin C. , Chen Zhijie Charles , Ling Tong , Pandiyan Vimal Prabhu , Kuchenbecker James , Sabesan Ramkumar , Palanker Daniel
Published: January 2020

Photoreceptors in the retina convert light into electrical signals through a phototransduction cycle that consists of multiple electrical and biochemical events. Phase-resolved optical coherence tomography (pOCT) measurements of the optical path length (OPL) change in the cone photoreceptor outer segments after a light stimulus (optoretinogram) reveal a fast, ms-scale contraction by tens of nm, followed by a slow (hundreds of ms) elongation reaching hundreds of nm. Ultrafast measurements with a line-scan pOCT system show that the contractile response amplitude increases logarithmically with the number of incident photons, and its peak shifts earlier at higher stimulus intensities.

We present a model that accounts for these features of the contractile response. Conformational changes in opsins after photoisomerization result in the fractional shift of charge across the disk membrane, leading to a transmembrane voltage change, known as the early receptor potential (ERP). Lateral repulsion of the ions on both sides of the membrane affects its surface tension and leads to its lateral expansion. Since the volume of the disks does not change much on a ms time scale, their lateral expansion leads to an axial contraction of the outer segment. With increasing stimulus intensity and resulting tension, the area expansion coefficient of the disk membrane also increases as thermally-induced fluctuations are pulled flat, resisting further expansion. This results in a logarithmic saturation of the deformation and a peak shift to earlier with brighter stimuli. Slow expansion of the photoreceptors is explained by the influx of water due to osmotic changes during phototransduction. Both effects closely match measurements in healthy human volunteers.
TarDict: RandomForestClassifier-based software predict Drug-Tartget interaction
Authors: Habib Peter T. , Alsamman Alsamman M. , Hassanein Sameh E. , Hamwieh Aladdin
Published: January 2020

Predicting the target of unknown or/and drugs under investigation from data of already identified drugs is very important not only for the understanding of various drug and molecular interaction processes but also for the development of novel drugs. Here we introduce TarDict, a RandomForestClassifier based-software predict the target pathway or protein based on SMILES of chemical. TarDict receives SMILES and returns a list of the possible similar drug, then export list to the user the target that drug contribute in. Training data set of 20442 entry and testing reveal %95 accuracy.
A critical re-evaluation of fMRI signatures of motor sequence learning
Authors: Berlot Eva , Popp Nicola J. , Diedrichsen Jörn
Published: January 2020

Despite numerous studies, there is little agreement about what brain changes accompany motor sequence learning, partly because of a general publication bias that favors novel results. We therefore decided to systematically reinvestigate proposed functional magnetic resonance imaging correlates of motor learning in a preregistered longitudinal study with four scanning sessions over 5 weeks of training. Activation decreased more for trained than untrained sequences in premotor and parietal areas, without any evidence of learning-related activation increases. Premotor and parietal regions also exhibited changes in the fine-grained, sequence-specific activation patterns early in learning, which stabilized later. No changes were observed in the primary motor cortex (M1). Overall, our study provides evidence that human motor sequence learning occurs outside of M1. Furthermore, it shows that we cannot expect to find activity increases as an indicator for learning, making subtle changes in activity patterns across weeks the most promising fMRI correlate of training-induced plasticity.
Molecular profiling of innate immune response mechanisms in ventilator-associated pneumonia
Authors: Pathak Khyatiben V. , McGilvrey Marissa I. , Hu Charles K. , Mansfield Krystine Garcia- , Lewandoski Karen , Eftekhari Zahra , Yuan Yate-Ching , Zenhausern Frederic , Menashi Emmanuel , Pirrotte Patrick
Published: January 2020

Ventilator-associated pneumonia (VAP) is a common hospital-acquired infection, leading to high morbidity and mortality. Currently, bronchoalveolar lavage (BAL) is utilized in hospitals for VAP diagnosis and guiding treatment options. While BAL collection procedures are invasive, alternatives such as endotracheal aspirates (ETA) may be of diagnostic value, however, their utility has not been thoroughly explored. Longitudinal ETA and BAL were collected from 16 intubated patients up to 15 days, of which 11 developed VAP. We conducted a comprehensive LC-MS/MS based proteome and metabolome characterization of longitudinal ETA and BAL to detect host and pathogen responses to VAP infection. We discovered a diverse ETA proteome of the upper airways reflective of a rich and dynamic host-microbe interface. Prior to VAP diagnosis by microbial cultures from BAL, patient ETA presented characteristic signatures of reactive oxygen species and neutrophil degranulation, indicative of neutrophil mediated pathogen processing as a key host response to the VAP infection. Along with an increase in amino acids, this is suggestive of extracellular membrane degradation resulting from proteolytic activity of neutrophil proteases. Days prior to VAP diagnosis, detection of pathogen peptides with species level specificity in ETA may increase specificity over culture-based diagnosis. Our findings suggest that ETA may provide early mechanistic insights into host-pathogen interactions associated with VAP infection and therefore facilitate its diagnosis and treatment.

Graphical abstract
C-terminal eYFP fusion impairsEscherichia coliMinE function
Authors: Palanisamy Navaneethan , Öztürk Mehmet Ali , Di Ventura Barbara
Published: January 2020

TheEscherichia coliMin system plays an important role in the proper placement of the septum ring (Z-ring) at mid-cell during cell division. MinE forms a pole-to-pole spatial oscillator together with the membrane-bound ATPase MinD, which results in MinD having a concentration gradient with maxima at the poles and minimum at mid-cell. MinC, the direct inhibitor of the Z-ring initiator protein FtsZ, forms a complex with MinD at the membrane, thus mirroring MinD polar gradients. Therefore, MinC-mediated FtsZ inhibition occurs away from mid-cell. The existence of the oscillations was revealed by performing time-lapse microscopy with fluorescently-labeled Min proteins. These fusion proteins have been since then widely used to study properties of the Min system. Here we show that, despite permitting oscillations to occur in a range of protein concentrations, the enhanced yellow fluorescent protein (eYFP) C-terminally fused to MinE impairs its function. Combiningin vivo, in vitroandin silicoapproaches, we demonstrate that the eYFP compromises MinE ability to displace MinC from MinD, to stimulate MinD ATPase activity and to directly bind to the membrane. Moreover, we reveal that MinE-eYFP is prone to aggregation. Taken together, our results indicate that this fusion is functionally impaired and should be used with caution in cell biological studies.
Polymorphism of fecundity genes (BMP15andGDF9) and their association with litter size in Bangladeshi prolific Black Bengal goat
Authors: Das A. , Shaha M. , Gupta M. Das , Dutta Avijit , Miazi O. F.
Published: January 2020

Identification of prolificacy associated genetic markers remains vital in goat breeding industry since an increase in litter size can generate significant profit. Black Bengal is a prolific goat breed in Bangladesh. There are no inland reports on polymorphisms associated with fertility of Black Bengal goats in Bangladesh. In this study, we investigated two major fecundity genes-bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) in order to detect any possible mutations in these two genes in Bangladeshi Black Bengal goats. We identified six single nucleotide polymorphisms (SNP), of which five (C735A, C743A, G754T, C781A, and C808G) inBMP15exon 2 and one (T1173A) inGDF9exon 2. We also studied their association with litter size. Association analysis results show that polymorphism at the 735, 754 and 781 nucleotide positions ofBMP15exon 2 had significant association with litter size in Black Bengal goat. The effect of parity was also highly significant (p <0.001) on litter size. This study explored, for the first time, SNP loci in fecundity genes in Bangladeshi prolific Black Bengal goats. Further studies with a high number of genetically unrelated animals for assessing the association of these loci and others in the fecundity genes with litter size may be useful.
Cannabis use is associated with sexually dimorphic changes in executive control of visuospatial decision-making
Authors: Banks Parker J. , Bennett Patrick J. , Sekuler Allison B. , Gruber Aaron J.
Published: January 2020

When the outcome of a choice is less favourable than expected, humans and animals typically shift to an alternate choice option. Several lines of evidence indicate that this “lose-shift” responding is an innate sensorimotor response strategy that is normally suppressed by executive function. Therefore, the lose-shift response provides a covert gauge of cognitive control over choice mechanisms. We report here that the spatial position, rather than visual features, of choice targets drives the lose-shift effect. Furthermore, the ability to inhibit lose-shift responding to gain reward is different among male and female habitual cannabis users. Increased self-reported cannabis use was concordant with suppressed response flexibility and an increased tendency to lose-shift in women, which reduced performance in a choice task in which random responding is the optimal strategy. On the other hand, increased cannabis use in men was concordant with reduced reliance on spatial cues during decision-making, and had no impact on the number of correct responses. These data (63,600 trials from 106 participants) provide strong evidence that spatial-motor processing is an important component of economic decision-making, and that its governance by executive systems is different in men and women who use cannabis frequently.
Damage Repair Versus Aging in Biofilms
Authors: Wright Robyn J. , Clegg Robert J. , Coker Timothy L. R. , Kreft Jan-Ulrich
Published: January 2020

The extent of senescence due to damage accumulation (or aging) is evidently evolvable as it varies hugely between species and is not universal, suggesting that its fitness advantages depend on life history and environment. In contrast, repair of damage is present in all organisms studied. Repair and segregation of damage have not always been considered as alternatives, despite the fundamental trade-off between investing resources into repair or growth. For unicellular organisms, unrepaired damage could be divided asymmetrically between daughter cells, leading to aging of one and rejuvenation of the other. Repair of unicells has been shown to be advantageous in well-mixed environments such as chemostats. However, most microorganisms live in spatially structured systems such as biofilms with gradients of environmental conditions and cellular physiology as well as clonal population structure. We asked whether this clonal structure might favor aging by damage segregation as this can be seen as a division of labor strategy, akin to the germline soma division in multicellular organisms. We used an individual-based model with a newly developed adaptive repair strategy where cells respond to their current intracellular damage levels by investing into repair machinery accordingly. We found that the new adaptive repair strategy was advantageous whenever efficient and optimal, both in biofilms and chemostats. Thus, biofilms do not favor a germline soma-like division of labor between daughter cells in terms of damage segregation. We suggest that damage segregation is only beneficial when active and effective, extrinsic mortality is high and a degree of multicellularity is present.

IMPORTANCE

Damage is an inevitable consequence of life, leading to a trade-off between allocating resources into damage repair or into growth whilst allowing aging,i.e., segregation of damage upon cell division. Few studies considered repair as an alternative to aging. Moreover, all previous studies merely considered well-mixed environments, although the vast majority of unicellular organisms live in spatially structured environments, exemplified by biofilms, and fitness advantages in well-mixed systems often turn into disadvantages in spatially structured systems. We compared the fitness consequences of aging versus damage repair in biofilms with an individual-based model implementing an adaptive repair mechanism based on sensing damage. We found that aging is not beneficial. Instead, it is useful as a stress response to deal with damage that failed to be repaired when (i) clearly asymmetric cell division is feasible; (ii) extrinsic mortality is high; and (iii) a degree of multicellularity is present.
In vitrocharacterization of protein effector export in the bradyzoite stage ofToxoplasma gondii
Authors: Mayoral Joshua , Shamamian Peter , Weiss Louis M.
Published: January 2020

The ubiquitous parasiteToxoplasma gondiiexhibits an impressive ability to maintain a chronic infection of its host for prolonged periods. Despite this, little is known regarding if and howT. gondiibradyzoites, a quasi-dormant life-stage residing within intracellular cysts, manipulate the host cell so as to maintain a persistent infection. A previous proteomic study of the cyst wall, an amorphous layer of proteins that forms underneath the cyst membrane, identified MYR1 as a putative cyst wall proteinin vitro. As MYR1 is known to be involved in the translocation of parasite derived effector proteins into the host cell, we sought to determine whether parasites transitioning toward the bradyzoite life stage retain the capacity to translocate proteins via this pathway. By epitope tagging the endogenous loci of four known effectors that translocate from the parasitophorous vacuole into the host cell nucleus, we show by immunofluorescence that most effectors accumulate in the host nucleus at early but not late timepoints post-infection during the tachyzoite to bradyzoite transition and when parasites farther along the bradyzoite differentiation continuum invade a new host cell. We demonstrate that the suppression of interferon-gamma (IFN-γ) signaling, previously shown to be mediated by the effector TgIST, also occurs in the context of prolonged infection with bradyzoites, and that TgIST export is a process that occurs beyond the early stages of host cell infection. These findings have important implications as to how this highly successful parasite maintains a persistent infection of its host.

IMPORTANCE

Toxoplasmabradyzoites persist within tissue cysts and are refractory to current treatments, serving as a reservoir for acute complications in settings of compromised immunity. Much remains to be understood regarding how this life-stage successfully establishes and maintains a persistent infection. In this study, we investigated whether the export of parasite effector proteins into the host cell occurs during the development ofin vitrotissue cysts. We quantified the presence of four previously described effectors in host cell nuclei at different timepoints post-bradyzoite differentiation and found that they accumulate largely during the early stages of infection. Despite a decline in nuclear accumulation, we found that one of these effectors still mediates its function after prolonged infection with bradyzoites and provide evidence that this effector is exported beyond early infection stages. These findings suggest that effector export from within developing tissue cysts provides one potential mechanism by which this parasite achieves chronic infection.
Diagnostic accuracy of physical examination to detect the pelvic fractures among the blunt trauma patients; systematic review and meta-analysis
Authors: Okada Yohei , Nishioka Norihiro , Tsujimoto Yasushi
Published: January 2020

Background

The study aims to perform systematic review and meta-analysis to identify the diagnostic accuracy of physical examination for pelvic fracture among the blunt trauma patients.

Method

We will perform a systematic review and meta-analysis for diagnostic test accuracy (DTA). We will include all reports on the diagnostic accuracy of physical examinations for detecting pelvic fractures. We will include the studies designed as prospective or retrospective observational (cohort or cross-sectional) studies or secondary analysis of randomized controlled trials. The target participants are blunt trauma patients with potential pelvic injury. The target condition is pelvic fracture. The index test being investigated is physical examination for pelvic fracture. The reference standard is X-ray or computed tomography to confirm the target condition. We will search MEDLINE, EMBASE and The Cochrane Library inclusive of Cochrane Controlled Trials Register. Two authors will independently screen the study eligibility and extract data. Screening will be a two-step process with initial title/abstract screening followed by full-text screening. We will evaluate the risk of bias independently by two investigators and reported according to the QUADAS-2 tool. In the meta-analysis, we will use a bivariate random-effects model to report the summary receiver operating characteristic (SROC) point (summary values for sensitivity and specificity) and the 95% confidence region around the summary ROC point.

Trial registration

This review is submitted with University hospital medical information network clinical trial registry (UMIN-CTR) [UMIN000038785].
Dissecting the collateral damage of antibiotics on gut microbes
Authors: Maier Lisa , Goemans Camille V. , Pruteanu Mihaela , Wirbel Jakob , Kuhn Michael , Cacace Elisabetta , Banerjee Tisya , Anderson Exene Erin , Milanese Alessio , Löber Ulrike , Forslund Sofia K. , Patil Kiran Raosaheb , Zeller Georg , Bork Peer , Typas Athanasios
Published: January 2020

Antibiotics are used for fighting pathogens, but also target our commensal bacteria as a side effect, disturbing the gut microbiota composition and causing dysbiosis and disease1-3. Despite this well-known collateral damage, the activity spectrum of the different antibiotic classes on gut bacteria remains poorly characterized. Having monitored the activities of >1,000 marketed drugs on 38 representative species of the healthy human gut microbiome4, we here characterize further the 144 antibiotics therein, representing all major classes. We determined >800 Minimal Inhibitory Concentrations (MICs) and extended the antibiotic profiling to 10 additional species to validate these results and link to available data on antibiotic breakpoints for gut microbes. Antibiotic classes exhibited distinct inhibition spectra, including generation-dependent effects by quinolones and phylogeny-independence by β-lactams. Macrolides and tetracyclines, two prototypic classes of bacteriostatic protein synthesis inhibitors, inhibited almost all commensals tested. We established that both kill different subsets of prevalent commensal bacteria, and cause cell lysis in specific cases. This species-specific activity challenges the long-standing divide of antibiotics into bactericidal and bacteriostatic, and provides a possible explanation for the strong impact of macrolides on the gut microbiota composition in animals5-8and humans9-11. To mitigate the collateral damage of macrolides and tetracyclines on gut commensals, we exploited the fact that drug combinations have species-specific outcomes in bacteria12and sought marketed drugs, which could antagonize the activity of these antibiotics in abundant gut commensal species. By screening >1,000 drugs, we identified several such antidotes capable of protecting gut species from these antibiotics without compromising their activity against relevant pathogens. Altogether, this study broadens our understanding of antibiotic action on gut commensals, uncovers a previously unappreciated and broad bactericidal effect of prototypical bacteriostatic antibiotics on gut bacteria, and opens avenues for preventing the collateral damage caused by antibiotics on human gut commensals.
Increased likelihood of heat-induced large wildfires in the Mediterranean Basin
Authors: Ruffault J , Curt T , Moron V , Trigo RM , Mouillot F , Koutsias N , Pimont F , Martin-StPaul NK , Barbero R , Dupuy J-L , Russo A , Belhadj-Kheder C
Published: January 2020

Wildfire activity is expected to increase across the Mediterranean Basin because of climate change. However, the effects of future climate changes on the combinations of atmospheric conditions that promote large wildfires remain largely unknown. Using a fire-weather based classification of wildfires, we show that future climate scenarios point to an increase in the frequency and severity of two heat-induced fire-weather types that have been responsible for a majority of record-breaking wildfire events. Heat-induced fire-weather types are characterized by compound dry warm conditions and occur in the summer during heatwaves, either under moderate (sudden heatwavetype) or intense (hot droughttype) drought. Heat-induced fire weather is projected to increase in frequency by 14% by the end of the century (2071-2100) under the RCP4.5 scenario, and by 30% under the RCP8.5. These findings suggest that the frequency and extent of large wildfires will increase throughout the Mediterranean Basin, with far-reaching impacts.
Cell-type specific impact of glucocorticoid receptor activation on the developing brain
Authors: Cruceanu Cristiana , Dony Leander , Krontira Anthi C. , Fischer David S. , Roeh Simone , Di Giaimo Rossella , Kyrousi Christina , Arloth Janine , Czamara Darina , Martinelli Silvia , Wehner Stefanie , Breen Michael S. , Koedel Maik , Sauer Susann , Rex-Haffner Monika , Cappello Silvia , Theis Fabian J. , Binder Elisabeth B.
Published: January 2020

A fine-tuned balance of glucocorticoid receptor (GR) activation is essential for organ formation, with disturbances influencing health outcomes. Excess GR-activationin uterohas been linked to brain-related negative outcomes, with unclear underlying mechanisms, especially regarding cell-type specific effects. To address this, we used anin vitromodel of fetal human brain, induced pluripotent-stem-cell-derived cerebral organoids, and mapped GR-activation effects using single-cell transcriptomics across development. Interestingly, neurons showed targeted regulation of differentiation- and maturation-related transcripts, suggesting a delay of these processes upon GR-activation. Uniquely in neurons, differentially-expressed transcripts were significantly enriched for genes associated with behavior-related phenotypes and disorders. This suggests that aberrant GR-activation could impact proper neuronal maturation, leading to increased disease susceptibility, through neurodevelopmental processes at the interface of genetic susceptibility and environmental exposure.