bluuebunny/crossref_metadata_2025 huggingface dataset:
Apparent Diffusion Coefficient of the Placenta and Fetal Organs in Intrauterine Growth Restriction
Authors: Abdel Razek Ahmed Abdel Khalek , Thabet Mahmoud , Salam Eman Abdel
Published: February 2019

Purpose

This study aimed to assess apparent diffusion coefficient (ADC) of the placenta and fetal organs in intrauterine growth restriction (IUGR).

Materials and methods

A prospective study of 30 consecutive pregnant women (aged 21–38 years with mean age of 31.5 years and a mean gestational week of 35 ± 2.3) with IUGR and 15 age-matched pregnant women was conducted. All patients and controls underwent diffusion-weighted magnetic resonance imaging. The ADCs of the placenta and fetal brain, kidney, and lung were calculated and correlated with neonates needing intensive care unit (ICU) admission.

Results

There was a significant difference in ADC of the placenta and fetal brain, lung, and kidney (P = 0.001, 0.001, 0.04, and 0.04, respectively) between the patients and the controls. The cutoff ADCs of the placenta and fetal brain, lung, and kidney used to detect IUGR were 1.45, 1.15, 1.80, and 1.40 × 10−3 mm2/s, respectively, with areas under the curve (AUCs) of 0.865, 0.858, 0.812, and 0.650, respectively, and accuracy values of 75%, 72.5%, 72.5%, and 70%, respectively. Combined ADC of the placenta and fetal organs used to detect IUGR revealed an AUC of 1.00 and an accuracy of 100%. There was a significant difference in ADC of the placenta and fetal brain, lung, and kidney between neonates needing admission and those not needing ICU admission (P = 0.001, 0.001, 0.002, and 0.002, respectively). The cutoff ADCs of the placenta and fetal brain, lung, and kidney used to define neonates needing ICU were 1.35, 1.25, 1.95, and 1.15 × 10−3 mm2/s with AUCs of 0.955, 0.880, 0.884, and 0.793, respectively, and accuracy values of 86.7%, 46.7%, 76.7%, and 70%, respectively. Combined placental and fetal brain ADC used to define neonates needing ICU revealed an AUC of 0.968 and an accuracy of 93.3%.

Conclusion

Combined ADC of the placenta and fetal organs can detect IUGR, and combined ADC of the placenta and fetal brain can define fetuses needing ICU.
“Nightmares–Family Medicine” Course Is an Effective Acute Care Teaching Tool for Family Medicine Residents
Authors: Gilic Filip , Schultz Karen , Sempowski Ian , Blagojevic Ana
Published: February 2019

Introduction

Simulation is an effective method for teaching acute care skills but has not been comprehensively evaluated with family medicine (FM) residents. We developed a comprehensive simulation-based approach for teaching acute care skills to FM residents and assessed it for effectiveness.

Method

We compared the effectiveness of our standard acute care simulation training [Acute Care Rounds (ACR)] to a more comprehensive simulation-based acute care program, Nightmares–Family Medicine (NM). We used a self-reported comfort scale as well as video-captured performance on an acute care Objective Structured Clinical Examination (OSCE). Seventy-seven of our FM residents in their postgraduate year 1 between July 2012 and June 2015 participated in the study. Wilcoxon matched pairs and one-tailed t tests analysis was used for analyzing the comfort scale, Whitney-Mann, and χ2 for the OSCE performance.

Results

Nightmares–Family Medicine's initial 2-day session significantly improved the resident's self-assessment scores on all 20 items of the questionnaire (P < 0.05). Time-matched ACR improved 11 of 20 items (P < 0.05) level. Follow-up NM sessions improved 5 to 8 of 20 items (P < 0.05). Follow-up ACR sessions improved 1 to 5 of 20 items (P < 0.05). The means taken at the end of postgraduate year 1 year were higher for 13 of 20 items in the NM group (P < 0.05) as compared with ACR group. The NM group scored significantly higher on both the mean scores of OSCE individual categories (P < 0.01) and the Global Assessment Score (P < 0.05). Significantly less NM residents failed the OSCE (n = 1/30, 3.3% vs n = 8/37, 21.6%, P < 0.05).

Conclusions

“Nightmares–Family Medicine” course is very effective at teaching acute care skills to FM residents and more so than our previous curriculum.
Prehospital trauma experience of the Israel defense forces on the Syrian border 2013–2017
Authors: Benov Avi , Shkolnik Irena , Glassberg Elon , Nadler Roy , Gendler Sami , Antebi Ben , Chen Jacob , Fink Noam , Bader Tarif
Published: February 2019

BACKGROUND

The Israeli Defense Force Medical Corps (IDF-MC) is routinely collecting prehospital data to establish a prehospital registry. Since February 2013, Israel has been providing medical care to Syrian refugees. This unique humanitarian aid begins in prehospital settings and typically culminates in Israeli civilian hospitals. This report describes the accumulated experience of the IDF-MC to provide Syrian refugees with prehospital treatment.

METHODS

Care provided by IDF-MC medical teams, including prehospital casualty care, is regularly documented and after-action reports are conducted. Records of casualties arriving at the Israeli-Syrian border from February 16, 2013, to December 31, 2017, were prospectively extracted from the IDF Trauma Registry. Patients who did not have a casualty card were excluded. The database included demographic information, injury signature and treatment given.

RESULTS

During the study period, 2,785 Syrian casualties were treated, of whom 2,339 were trauma victims. The most common mechanism of injury was penetrating (60.4%). Prehospital lifesaving interventions included 127 endotracheal intubations, 30 cricothyroidotomies, 55 chest decompressions, and 58 tourniquets for extremity hemorrhage control. Remote Damage Control Resuscitation included reconstituted freeze-dried plasma (n = 75) and tranexamic acid (n = 222 casualties) with no adverse effects.

CONCLUSION

The experience of the IDF-MC teams in caring for civilian casualties along a hostile international border is unique. In this capacity, the IDF-MC has demonstrated effectiveness in providing lifesaving and resuscitative interventions including tranexamic acid and freeze-dried plasma. In this experience, tourniquets have been effective in controlling hemorrhage when applied early and endotracheal intubation and cricothyroidotomy have provided effective airway options in select patients. Prehospital combat casualty care presents a significant challenge both in terms of providing adequate care and in terms of data collection and analysis. The experience described in this article is one example of effective, ongoing prehospital data gathering process. Efforts to provide medical relief to victims of the Syrian civil war continue to this day. While we hope for a better future, as long as these lessons continue to accumulate, it is our obligation to use them to support improvement of trauma care and hopefully save more lives.

LEVEL OF EVIDENCE

Therapeutic, level III.
The promising future of drones in prehospital medical care and its application to battlefield medicine
Authors: Braun Jonathan , Gertz S. David , Furer Ariel , Bader Tarif , Frenkel Hagay , Chen Jacob , Glassberg Elon , Nachman Dean
Published: February 2019

Unmanned aerial vehicles, commonly referred to as drones, have been made widely available in recent years leading to an exponential growth in their roles and applications. The rapidly developing field of medical drones is on the verge of revolutionizing prehospital medicine enabling advanced health care delivery to once-inaccessible patients. The aim of this review is to clarify the basic technical properties of currently available medical drones and review recent advances and their usefulness in military and civilian health care missions. A thorough search was conducted using conventional medical literature databases and nonmedical popular search engines. The results indicate increasingly rapid incorporation of unmanned aerial vehicles into search and rescue missions, telemedicine assignments, medical supply routes, public health surveillance, and disaster management. Medical drones appear to be of great benefit for improving survivability of deployed forces on and off the battlefield. The emerging aerial medical delivery systems appear to provide particularly promising solutions for bridging some of the many serious gaps between third world health care systems and their western counterparts and between major metropolitan centers and distant rural communities. The global nature of drone-based health care delivery needs points to a need for an international effort between collaborating civilian and military medical forces to harness the currently available resources and novel emerging technologies for broader lifesaving capabilities.

LEVEL OF EVIDENCE

Level V.
Psychiatric outcome at least 20 years after trauma: A survey on the status of subjective general health and psychiatric symptoms with a focus on posttraumatic stress disorder
Authors: Halvachizadeh Sascha , Teuber Henrik , Allemann Florin , Luidl Anna Theresa , von Känel Roland , Zelle Boris , Tiziani Simon , Rauen Katrin , Pape Hans-Christoph , Pfeifer Roman
Published: February 2019

BACKGROUND

Information on long-term psychiatric sequelae after severe trauma is sparse. We therefore performed a survey addressing several symptoms related to posttraumatic stress disorder (PTSD) in patients who sustained multiple injuries more than 20 years after trauma.

METHODS

Patients injured between January 1, 1973, and December 31, 1990, were contacted at least 20 years later. We included multiply injured patients aged between 3 and 60 years from a single level 1 trauma center. A questionnaire based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnostic criteria for PTSD, including individual symptoms related to intrusion, avoidance, and hyperarousal was sent to all patients.

RESULTS

A total of 359 patients (56.35%) received a questionnaire. Of these, 337 patients (93.87%) returned the questionnaire and were included in the study (223 males [66.17%] and 114 females [33.82%]). Mean ± SD follow-up was 29.5 ± 8.5 years. Nearly half the study population (47.18%) experienced lasting psychiatric sequelae, such as intrusive recollection (n = 65, 19.28%), avoidance (n = 92, 27.29%), or hyperarousal (n = 95, 28.18%) at least monthly. Ten patients (2.96%) fulfilled all Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnostic criteria for PTSD. A total of 131 patients (38.87%) reported fair or poor general health status. There was no difference in injury severity in patients with or without PTSD (injury severity score, 8.33 vs. 20.36, respectively; p = 0.52) or PTSD-related symptoms including intrusion (19.88 vs. 20.32, p = 0.74), avoidance (19.99 vs. 20.3, p = 0.79), and hyperarousal (19.36 vs. 20.68, p = 0.26).

CONCLUSION

At least 20 years after injury, no correlation was found between the development of psychiatric complications and the severity of injury. While the rate of full-blown PTSD was low, nearly half the study population regularly suffered from at least one psychiatric symptom attributable to the initial trauma. Awareness for the development of psychiatric complications and early initiation of psychiatric counseling are advisable.

LEVEL OF EVIDENCE

Prognostic and epidemiologic, level II.
Glass Slippers and Glass Cliffs: Fitting In and Falling Off
Authors: Krishnan Nithya , Biggerstaff Deborah , Szczepura Ala , Dolton Monica , Livingston Sondra , Hattersley John , Eris Josette , Ascher Nancy , Higgins Robert , Braun Hillary , Wood Kathryn , Raymond Neil
Published: February 2019

Background.

A glass ceiling effect exists for women in male-dominated professions. Recent studies also show a glass-cliff effect where senior women can more easily fall from positions of leadership. Transplantation remains a male-dominated specialty. This study investigated gender and the perception of adverse clinical incidents in transplantation.

Methods.

Prospective randomised web-based survey involving five clinical scenarios presenting two versions of episodes with errors or mistakes, with either a male or female as a randomly named protagonist (Set1 and Set2). To address unconscious bias, the study was described as examining actions following clinical adverse incidents in transplantation. Each scenario was followed by 2 closed questions: (1) clinical performance rating and (2) selection of action required. Reasoning was invited (open-text comments). Responses were analyzed using quantitative and qualitative methods.

Results.

One hundred ninety-one invitees responded; 134 completed questionnaires. There were no statistically significant differences (P > 0.05) in responses between sets for performance ratings or recommended actions. However, for “first solo laparoscopic surgery” scenario, there was some indication that “No Action” was more likely if surgeon was male (P = 0.056). Male responses rated female performance as significantly worse (P = 0.035) for the laboratory-based scenario. One hundred two participants provided open-text comments. Thematic analysis identified 7 themes. Acceptable levels of risk theme demonstrated engendered leadership beliefs, that is, when clinical judgment proved incorrect, males described as forceful but females as needing support. In cases where things went wrong, respondents were more likely to comment females should not have decided to proceed.

Conclusions.

While gender may no longer be an overt issue in perceived performance of senior staff in transplantation, respondents’ use of language and their choice of words display elements of unconscious (covert) engendered views.
Inhibition of Cyclin-dependent Kinase 2 Signaling Prevents Liver Ischemia and Reperfusion Injury
Authors: Xu Jin , Xue Zhengze , Zhang Cheng , Liu Yuan , Busuttil Ronald W. , Zhang Jiamin , Kupiec-Weglinski Jerzy W. , Ji Haofeng
Published: February 2019

Background.

Liver ischemia and reperfusion injury (IRI) is a major complication of liver transplant, hepatectomy, and hemorrhagic shock. The cyclin-dependent kinase 2 (CDK2) acts as a pivotal regulator of cell cycle and proliferation.

Methods.

This study evaluated the modulation and therapeutic potential of CDK2 inhibition in a mouse model of partial liver warm IRI.

Results.

Liver IR-triggered intrinsic CDK2 expression, peaking by 0.5 hour of reperfusion and maintaining a high-level throughout 1 to 24 hours. Roscovitine, a specific CDK2 inhibitor, prevented liver IR-mediated damage with abolished serum alanine aminotransferase levels and reserved liver pathology. CDK2 inhibition-mediated liver protection was accompanied by decreased macrophage/neutrophil infiltration, diminished hepatocyte apoptosis, abolished toll like receptor 4 signaling and downstream gene inductions (C-X-C motif ligand-10, Tumor necrosis factor-α, interleukin-1β, and interleukin-6), yet augmented interleukin-10 expression. In vitro, CDK2 inhibition by Roscovitine suppressed macrophage TLR4 activation and further depressed downstream inflammatory signaling (myeloid differentiation factor 88, interferon regulatory transcription factor 3, p38, c-Jun N-terminal kinase, and extracellular-regulated kinase).

Conclusions.

Our novel findings revealed the critical role of CDK2 in hepatic cytoprotection and homeostasis against liver IRI. As CDK2 inhibition regulated local immune response and prevented hepatocyte death, this study provided the evidence for new treatment approaches to combat IRI in liver transplant.
The Role of the Family in Deceased Organ Procurement: A Guide for Clinicians and Policymakers
Authors: Delgado Janet , Molina-Pérez Alberto , Shaw David , Rodríguez-Arias David
Published: February 2019

Families play an essential role in deceased organ procurement. As the person cannot directly communicate his or her wishes regarding donation, the family is often the only source of information regarding consent or refusal. We provide a systematic description and analysis of the different roles the family can play, and actions the family can take, in the organ procurement process across different jurisdictions and consent systems. First, families can inform or update healthcare professionals about a person’s donation wishes. Second, families can authorize organ procurement in the absence of deceased’s preferences and the default is not to remove organs, and oppose donation where there is no evidence of preference but the default is to presume consent; in both cases, the decision could be based on their own wishes or what they think the deceased would have wanted. Finally, families can overrule the known wishes of the deceased, which can mean preventing donation, or permitting donation when the deceased refused it. We propose a schema of 4 levels on which to map these possible family roles: no role, witness, surrogate, and full decisional authority. We conclude by mapping different jurisdictions onto this schema to provide a more comprehensive understanding of the consent system for organ donation and some important nuances about the role of families. This classificatory model aims to account for the majority of the world’s consent systems. It provides conceptual and methodological guidance that can be useful to researchers, professionals, and policymakers involved in organ procurement.
Genetic Variants Associated With Immunosuppressant Pharmacokinetics and Adverse Effects in the DeKAF Genomics Genome-wide Association Studies
Authors: Oetting William S. , Wu Baolin , Schladt David P. , Guan Weihua , van Setten Jessica , Keating Brendan J. , Iklé David , Remmel Rory P. , Dorr Casey R. , Mannon Roslyn B. , Matas Arthur J. , Israni Ajay K. , Jacobson Pamala A.
Published: February 2019

Background.

The immunosuppressants tacrolimus and mycophenolate are important components to the success of organ transplantation, but are also associated with adverse effects, such as nephrotoxicity, anemia, leukopenia, and new-onset diabetes after transplantation. In this report, we attempted to identify genetic variants which are associated with these adverse outcomes.

Methods.

We performed a genome-wide association study, using a genotyping array tailored specifically for transplantation outcomes containing 722 147 single nucleotide polymorphisms, and 2 cohorts of kidney allograft recipients—a discovery cohort and a confirmation cohort—to identify and then confirm genetic variants associated with immunosuppressant pharmacokinetics and adverse outcomes.

Results.

Several genetic variants were found to be associated with tacrolimus trough concentrations. We did not confirm variants associated with the other phenotypes tested although several suggestive variants were identified.

Conclusions.

These results show that adverse effects associated with tacrolimus and mycophenolate are complex, and recipient risk is not determined by a few genetic variants with large effects with but most likely are due to many variants, each with small effect sizes, and clinical factors.
Analysis of 75 Candidate SNPs Associated With Acute Rejection in Kidney Transplant Recipients: Validation of rs2910164 in MicroRNA MIR146A
Authors: Oetting William S. , Schladt David P. , Dorr Casey R. , Wu Baolin , Guan Weihua , Remmel Rory P. , Iklé David , Mannon Roslyn B. , Matas Arthur J. , Israni Ajay K. , Jacobson Pamala A.
Published: February 2019

Background.

Identifying kidney allograft recipients who are predisposed to acute rejection (AR) could allow for optimization of clinical treatment to avoid rejection and prolong graft survival. It has been hypothesized that a part of this predisposition is caused by the inheritance of specific genetic variants. There are many publications reporting a statistically significant association between a genetic variant, usually in the form of a single-nucleotide polymorphism (SNP), and AR. However, there are additional publications reporting a lack of this association when a different cohort of recipients is analyzed for the same single-nucleotide polymorphism.

Methods.

In this report, we attempted to validate 75 common genetic variants, which have been previously reported to be associated with AR, using a large kidney allograft recipient cohort of 2390 European Americans and 482 African Americans.

Results.

Of those variants tested, only 1 variant, rs2910164, which alters the expression of the microRNAMIR146A, was found to exhibit a significant association within the African American cohort. Suggestive variants were found in the genesCTLAandTLR4.

Conclusions.

Our results show that most variants previously reported to be associated with AR were not validated in our cohort. This shows the importance of validation when reporting the associations with complex clinical outcomes such as AR. Additional work will need to be done to understand the role of MIR146A in the risk of AR in kidney allograft recipients.
The Proportional Relationship Between Pretransplant WT1 mRNA Levels and Risk of Mortality After Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Not in Remission
Authors: Ido Kentaro , Nakamae Mika , Koh Hideo , Okamura Hiroshi , Nanno Satoru , Nishimoto Mitsutaka , Takeoka Yasunobu , Hirose Asao , Nakashima Yasuhiro , Hashimoto Yoshinori , Nakane Takahiko , Hino Masayuki , Nakamae Hirohisa
Published: February 2019

Background.

The relationship between the expression levels of Wilms’ tumor-1 gene (WT1) mRNA in peripheral blood before allogeneic hematopoietic cell transplantation (allo-HCT) and risk of mortality in acute myeloid leukemia (AML) patients in noncomplete remission (non-CR) remains quite elusive.

Methods.

We retrospectively assessed the impact of the pretransplant WT1 mRNA level on survival after allo-HCT in non-CR AML patients.

Results.

A total of 125 AML patients, including 46 non-CR patients (36.8%), were analyzed. On multivariate analysis of non-CR AML patients, WT1 mRNA ≥5000 copies/μg RNA was significantly related to increased risk of mortality (hazard ratio, 2.7; 95% confidence interval, 1.3-5.5; P = 0.008). Furthermore, in the entire cohort, log10-transformed WT1 mRNA before allo-HCT was found to be significantly associated with the increased risk of mortality irrespective of whether the disease status was CR or non-CR, using Akaike’s information criterion. As the pretransplant WT1 mRNA level elevated, the hazard ratio of mortality monotonically increased in a nonlinear manner regardless of remission status, suggesting that WT1 mRNA level in peripheral blood might reflect tumor burden.

Conclusions.

This study demonstrated that the pretransplant WT1 mRNA level was a powerful prognostic factor in allo-HCT even for non-CR AML patients, and there may be a WT1 mRNA threshold in non-CR patients for benefiting from allo-HCT.
Greater Susceptibility for Metabolic Syndrome in Pediatric Solid Organ and Stem Cell Transplant Recipients
Authors: Blöte Ricarda , Memaran Nima , Borchert-Mörlins Bianca , Thurn-Valsassina Daniela , Goldschmidt Imeke , Beier Rita , Sauer Martin , Müller Carsten , Sarganas Giselle , Oh Jun , Büscher Rainer , Kemper Markus J. , Sugianto Rizky I. , Epping Jelena , Schmidt Bernhard M.W. , Melk Anette
Published: February 2019

Background.

Cardiovascular comorbidity is of increasing importance after transplantation. Metabolic syndrome (MS) contributes to the risk for cardiovascular sequelae. Our aim was to assess the risk for MS in pediatric solid organ and stem cell transplant recipients by comparing them with matched untransplanted peers in a multicenter study.

Methods.

We prospectively assessed MS in 295 pediatric transplant recipients and compared them with 1475 age- and sex-matched controls.

Results.

Posttransplant metabolic syndrome (PTMS) was most frequent in lung (43%) and kidney (39%), followed by liver (16%) and stem cell (13%) recipients, compared with nontransplanted peers (4%; P < 0.01). The risk of displaying PTMS was almost 22-fold higher after lung (95% confidence interval, CI, 8.2-57.4), 16-fold higher after kidney (95% CI, 9.1-28.9), 5-fold higher after liver (95% CI, 2.1-10.1), and 4-fold higher after stem cell (95% CI, 1.4-9.5) transplantation. The contribution of individual components leading to MS differed depending on transplant type. In the combined analysis of all transplant groups, older age, less physical activity, calcineurin or mammalian target of rapamycin inhibitor-based immunosuppression, and hypovitaminosis D were associated with PTMS.

Conclusions.

By investigating a large group of patients, our study not only shows a high prevalence of PTMS but also identifies kidney and lung transplant patients as being at a particularly high risk. Moreover, knowledge on the factors associated with PTMS allows for individualized treatment approaches as well as potential preventive measures.
Subclinical Inflammation in Renal Transplantation
Authors: Rush David N. , Gibson Ian W.
Published: February 2019

The standardization of renal allograft pathology began in 1991 at the first Banff Conference held in Banff, Alberta, Canada. The first task of transplant pathologists, clinicians, and surgeons was to establish diagnostic criteria for T-cell–mediated rejection (TCMR). The histological threshold for this diagnosis was arbitrarily set at “i2t2”: a mononuclear interstitial cell infiltrate present in at least 25% of normal parenchyma and >4 mononuclear cells within the tubular basement membrane of nonatrophic tubules. TCMR was usually found in dysfunctional grafts with an elevation in the serum creatinine; however, our group and others found this extent of inflammation in “routine” or “protocol” biopsies of normally functioning grafts: “subclinical” TCMR. The prevalence of TCMR is higher in the early months posttransplant and has decreased with the increased potency of current immunosuppressive agents. However, the pathogenicity of lesser degrees of inflammation under modern immunosuppression and the relation between ongoing inflammation and development of donor-specific antibody has renewed our interest in subclinical alloreactivity. Finally, the advances in our understanding of pretransplant risk assessment, and our increasing ability to monitor patients less invasively posttransplant, promises to usher in the era of precision medicine.
Bacillus aciditolerans sp. nov., isolated from paddy soil
Authors: Ding Meng-Jiao , Shang Nian-Jie , Xiao Zhi-xin , Shao Fei , Liu Li , Huang Ying , Zhou Lu-kuo , Zhou Ji-Heng , Zhang Yi
Published: February 2019

A Gram-stain-positive, motile, rod-shaped bacterial strain, YN-1T, was isolated from a rice field in the town of Jietou, Yunnan Province, PR China. Colonies were circular, 1–2 mm in diameter, creamy white, with slightly irregular margins. The isolate grew optimally at 37 °C, pH 7.0 and with 1.0 % (w/v) NaCl. On the basis of the results of 16S rRNA gene sequence similarity comparisons, YN-1T clustered together with other species of the genus

Bacillus

and showed highest similarities with

Bacillus onubensis

0911MAR22V3T (98.0 %),

Bacillus humi

LMG22167T (97.5 %), '

Bacillus timonensis

'
10403023 (97.4 %) and '

Bacillus
sinesaloumensis' P3516 (97.1 %). However, the DNA–DNA hybridization values between YN-1T and closely related strains of species of the genus

Bacillus

were well below 47 %, indicating that they represent different taxa. The average nucleotide identity and the Genome-to-Genome Distance Calculator also revealed low relatedness (below 95 and 70 %, respectively) between YN-1T and type strains of closely related species of the genus
Bacillus
. The DNA G+C content of the strain was 40 mol%. The major cellular fatty acids were iso-C15 : 0, anteiso-C15 : 0, and C16 : 0. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids, three unidentified aminophospholipids and two other unidentified lipids. Physiological and biochemical test results were also different from those of the most closely related species. On the basis of the phenotypic, genetic and chemotaxonomic data, strain YN-1T is considered to represent a novel species of the genus

Bacillus

, for which the name

Bacillus
aciditolerans sp. nov. is proposed, with strain YN-1T (=CCTCC AB 2017280T=JCM 32973T) as the type strain.
Single cell ATAC-seq identifies broad changes in neuronal abundance and chromatin accessibility in Down Syndrome
Authors: Spektor Roman , Yang Jee Won , Lee Seoyeon , Soloway Paul D.
Published: February 2019

Down Syndrome (DS) is caused by triplication of chr21 and is associated with cognitive impairment, Alzheimer’s Disease, and other developmental alterations. The Ts65Dn mouse model for DS has triplication of sequences syntenic with human chr21, and traits resembling those seen in humans with DS. We performed single-cell combinatorial indexing assay for transposase accessible chromatin using sequencing (sci-ATAC-seq) on cortices of adult Ts65Dn mice and control littermates. Analyses of 13,766 cells revealed 26 classes of cells. The most abundant class of excitatory neurons was reduced by 17% in Ts65Dn mice, and three of the four most common classes of interneurons were increased by 50%. Ts65Dn mice display changes in accessibility at binding motifs for transcription factors that are determinants of neuronal lineage, and others encoded within triplicated regions. These studies define previously uncharacterized cellular and molecular features of DS, and potential mechanisms underlying the condition.
The great tit HapMap project: a continental-scale analysis of genomic variation in a songbird
Authors: Spurgin Lewis G. , Bosse Mirte , Adriaensen Frank , Albayrak Tamer , Barboutis Christos , Belda Eduardo , Bushuev Andrey , Cecere Jacopo G. , Charmantier Anne , Cichon Mariusz , Dingemanse Niels J. , Doligez Blandine , Eeva Tapio , Erikstad Kjell Einar , Fedorov Vyacheslav , Griggio Matteo , Heylen Dieter , Hille Sabine , Hinde Camilla A. , Ivankina Elena , Kempenaers Bart , Kerimov Anvar , Krist Milos , Kvist Laura , Laine Veronika N. , Mänd Raivo , Matthysen Erik , Nager Ruedi , Nikolov Boris P. , Norte A. Claudia , Orell Markku , Ouyang Jenny , Petrova-Dinkova Gergana , Richner Heinz , Rubolini Diego , Slagsvold Tore , Tilgar Vallo , Török János , Tschirren Barbara , Vágási Csongor I. , Yuta Teru , Groenen Martien A.M. , Visser Marcel E. , van Oers Kees , Sheldon Ben C. , Slate Jon
Published: February 2019

A major aim of evolutionary biology is to understand why patterns of genomic diversity vary among populations and species. Large-scale genomic studies of widespread species are useful for studying how the environment and demographic history shape patterns of genomic divergence, and with the continually decreasing cost of sequencing and genotyping, such studies are now becoming feasible. Here, we carry out one of the most geographically comprehensive surveys of genomic variation in a wild vertebrate to date; the great tit (Parus major) HapMap project. We screenedca500,000 SNP markers across 647 individuals from 29 populations, spanning almost the entire geographic range of the European great tit subspecies. We found that genome-wide variation was consistent with a recent colonisation across Europe from a single refugium in South-East Europe, with bottlenecks and reduced genetic diversity in island populations. Differentiation across the genome was highly heterogeneous, with clear “islands of differentiation” even among populations with very low levels of genome-wide differentiation. Low local recombination rate in the genome was a strong predictor of high local genomic differentiation (FST), especially in island and peripheral mainland populations, suggesting that the interplay between genetic drift and recombination is a key driver of highly heterogeneous differentiation landscapes. We also detected genomic outlier regions that were confined to one or more peripheral great tit populations, most likely as a result of recent directional selection at the range edges of this species. Haplotype-based measures of selection were also related to recombination rate, albeit less strongly, and highlighted population-specific sweeps that likely resulted from positive selection. These regions under positive selection contained candidate genes associated with morphology, thermal adaptation and colouration, providing promising avenues for future investigation. Our study highlights how comprehensive screens of genomic variation in wild organisms can provide unique insights into evolution.
Comprehensive bioinformatics analysis ofL1CAMgene revealed Novel Pathological mutations associated with L1 syndrome
Authors: Murshed Naseem S. , Mustafa Mujahed I. , Abdelmoneim Abdelrahman H. , Mahmoud Thwayba A. , Elfadol Nafisa M. , Hassan Mohamed A.
Published: February 2019

Background

Mutations in the human L1CAM gene cause a group of neurodevelopmental disorders known as L1 syndrome (CRASH syndrome). The L1CAM gene provides instructions for producing the L1 protein, which is found all over the nervous system on the surface of neurons. L1 syndrome involves a variety of characteristics but the most common characteristic is muscle stiffness. Patients with L1 syndrome can also suffer from difficulty speaking, seizures, and underdeveloped or absent tissue connecting the left and right halves of the brain.

Method

The human L1CAM gene was studied from dbSNP/NCBI, 1499 SNPs were Homo sapiens; of which 450 were missense mutations. This selected for Comprehensive bioinformatics analysis by several in silico tools to investigate the effect of SNPs on L1CAM protein’s structure and function.

Results

34 missense mutations (26 novel mutations) out of 450 nsSNPs that are found to be the most deleterious that effect on the L1CAM structural and functional level.

Conclusion

Better understanding of L1 syndrome caused by mutations in L1CAM gene was achieved using Comprehensive bioinformatics analysis. These findings describe 35 novel L1 mutations which improve our understanding on genotype-phenotype correlation. And can be used as diagnostic markers for L1 syndrome and besides in cancer diagnosis specifically in breast cancer.
Structure of the human frataxin-bound iron-sulfur cluster assembly complex provides insight into its activation mechanism
Authors: Fox Nicholas G. , Yu Xiaodi , Feng Xidong , Bailey Henry J. , Martelli Alain , Nabhan Joseph F. , Strain-Damerell Claire , Bulawa Christine , Yue Wyatt W. , Han Seungil
Published: February 2019

Iron-sulfur clusters (ISC) are essential in all life forms and carry out many crucial cellular functions. The core machinery for de novo ISC biosynthesis, located in the mitochondria matrix, is a five-protein complex containing the cysteine desulfurase NFS1 that is activated by frataxin (FXN), scaffold protein ISCU, accessory protein ISD11, and acyl-carrier protein ACP. Deficiency in FXN leads to the loss-of-function neurodegenerative disorder Friedreich’s ataxia (FRDA). Recently crystal structures depicting the inactive 3- and 4-way sub-complexes of the ISC biosynthesis machinery, lacking the key activator FXN, have been determined. Here, the 3.2 Å resolution cryo-electron microscopy structure of the FXN-bound active human complex, containing two copies of the NFS1-ISD11-ACP-ISCU-FXN hetero-pentamer, delineates for the first time in any organism the interactions of FXN with the component proteins. FXN binds at the interface of two NFS1 and one ISCU subunits, modifying the local environment of a bound zinc ion that would otherwise inhibit NFS1 activity in complexes without FXN. Our structure sheds light on how FXN facilitates ISC production through unlocking the zinc inhibition and stabilizing key loop conformations of NFS1 and ISCU at the protein-protein interfaces, and offers an explanation of how FRDA clinical mutations affect complex formation and FXN activation.
Feeding Kinematics And Morphology Of The Alligator Gar (Atractosteus Spatula, Lacépède, 1803): Feeding Mechanics Of Atractosteus Spatula
Authors: Lemberg Justin B. , Shubin Neil H. , Westneat Mark W.
Published: February 2019

Modern (lepisosteid) gars are a small clade of seven species and two genera that occupy an important position on the actinopterygian phylogenetic tree as members of the Holostei (Amia+ gars), sister-group of the teleost radiation. Often referred to as “living fossils,” these taxa preserve many plesiomorphic characteristics used to interpret and reconstruct early osteichthyan feeding conditions. Less attention, however, has been paid to the functional implications of gar-specific morphology, thought to be related to an exclusively ram-based, lateral-snapping mode of prey capture. Previous studies of feeding kinematics in gars have focused solely on members of the narrow-snoutedLepisosteusgenus, and here we expand that dataset to include a member of the broad-snouted sister-genus and largest species of gar, the alligator gar (Atractosteus spatula, Lacépède, 1803). High-speed videography reveals that the feeding system of alligator gars is capable of rapid expansion from anterior-to-posterior, precisely timed in a way that appears to counteract the effects of a bow-wave during ram-feeding and generate a unidirectional flow of water through the feeding system. Reconstructed cranial anatomy based on contrast-enhanced micro-CT data show that a lateral-sliding palatoquadrate, flexible intrasuspensorial joint, pivoting interhyal, and retractable pectoral girdle are all responsible for increasing the range of motion and expansive capabilities of the gar cranial linkage system. Muscular reconstructions and manipulation experiments show that, while the sternohyoideus is the primary input to the feeding system (similar to other “basal” actinopterygians), additional input from the hyoid constrictors and hypaxials play an important role in decoupling and modulating between the dual roles of the sternohyoideus: hyoid retraction (jaw opening) and hyoid rotation (pharyngeal expansion) respectively. The data presented here demonstrate an intricate feeding mechanism, capable of precise control with plesiomorphic muscles, that represents one of the many ways the ancestral osteichthyan feeding mechanism has been modified for prey capture.

RESEARCH HIGHLIGHTS

Alligator gars use a surprisingly expansive cranial linkage system for prey capture that relies on specialized joints for increased mobility and is capable of precise modulation from anterior to posterior using plesiomorphic osteichthyan musculature.
Evaluation of methods to assign cell type labels to cell clusters from single-cell RNAsequencing data
Authors: Díaz-Mejía J. Javier , Meng Elaine C. , Pico Alexander R. , MacParland Sonya A. , Ketela Troy , Pugh Trevor J. , Bader Gary D. , Morris John H.
Published: February 2019

Identification of cell type subpopulations from complex cell mixtures using single-cell RNA-sequencing (scRNA-seq) data includes automated computational steps like data normalization, dimensionality reduction and cell clustering. However, assigning cell type labels to cell clusters is still conducted manually by most researchers, resulting in limited documentation, low reproducibility and uncontrolled vocabularies. Two bottlenecks to automating this task are the scarcity of reference cell type gene expression signatures and that some dedicated methods are available only as web servers with limited cell type gene expression signatures. In this study, we benchmarked four methods (CIBERSORT, GSEA, GSVA, and ORA) for the task of assigning cell type labels to cell clusters from scRNA-seq data. We used scRNA-seq datasets from liver, peripheral blood mononuclear cells and retinal neurons for which reference cell type gene expression signatures were available. Our results show that, in general, all four methods show a high performance in the task as evaluated by Receiver Operating Characteristic curve analysis (average AUC = 0.94, sd = 0.036), whereas Precision-Recall curve analyses show a wide variation depending on the method and dataset (average AUC = 0.53, sd = 0.24). CIBERSORT and GSVA were the top two performers. Additionally, GSVA was the fastest of the four methods and was more robust in cell type gene expression signature subsampling simulations. We provide an extensible framework to evaluate other methods and datasets at https://github.com/jdime/scRNAseq_cell_cluster_labeling.
Amplification-free Library Preparation Improves Quality of Hi-C Analysis
Authors: Niu Longjian , Shen Wei , Huang Yingzhang , He Na , Zhang Yuedong , Sun Jialei , Wan Jing , Jiang Daxin , Yang Manyun , Tse Yu Chung , Li Li , Hou Chunhui
Published: February 2019

PCR amplification of Hi-C libraries introduces unusable duplicates and results in a biased representation of chromatin interactions. We present a simplified, fast, and economically efficient Hi-C library preparation procedure that generates sufficient non-amplified ligation products for deep sequencing from 30 million Drosophila cells. Comprehensive analysis of the resulting data indicates that amplification-free Hi-C preserves higher complexity of chromatin interaction and lowers sequencing depth dramatically for the same number of unique paired reads. For human cells which has a large genome, this method recovers an amount of ligated fragments enough for direct high-throughput sequencing without amplification on as low as 250 thousand of cells. Comparison with published in situ Hi-C on millions of human cells reveals that amplification introduces distance-dependent amplification bias, which results in increasing background noise level against genomic distance. With amplification bias avoided, our method may produce a chromatin interaction network more faithfully reflecting the real three-dimensional genomic architecture.
A global survey of mycobacterial diversity in soil
Authors: Walsh Corinne M. , Gebert Matthew J. , Delgado-Baquerizo Manuel , Maestre Fernando T. , Fierer Noah
Published: February 2019

Mycobacteriumis a diverse bacterial genus ubiquitous in many soil and aquatic environments. Members of this genus have been associated with human and other animal diseases, including the nontuberculous mycobacteria (NTM), which are of growing relevance to public health worldwide. Although soils are often considered an important source of environmentally-acquired NTM infections, the biodiversity and ecological preferences of soil mycobacteria remain largely unexplored across contrasting climates and ecosystem types. Using a culture-independent approach by combining 16S rRNA marker gene sequencing with mycobacterial-specific hsp65 gene sequencing, we analyzed the diversity, distributions, and environmental preferences of soil-dwelling mycobacteria in 143 soil samples collected from across the globe. The surveyed soils harbored highly diverse mycobacterial communities that span the full-extent of the known mycobacterial phylogeny, with most soil mycobacteria belonging to previously undescribed lineages. While the genusMycobacteriumtended to have higher relative abundances in cool, wet, and acidic soil environments, several individual mycobacterial clades had contrasting environmental preferences. We identified the environmental preferences of many mycobacterial clades, including the clinically-relevantM. aviumcomplex that was more commonly detected in wet and acidic soils. However, most of the soil mycobacteria detected were not closely related to known pathogens, calling into question previous assumptions about the general importance of soil as a source of NTM infections. Together this work provides novel insights into the diversity, distributions and ecological preferences of soil mycobacteria, and lays the foundation for future efforts to link mycobacterial phenotypes to their distributions.

Importance

Mycobacteria are common inhabitants of soil, and while most members of the bacterial genus are innocuous, some mycobacteria can cause environmentally-acquired infections of humans and other animals. Human infections from nontuberculous mycobacteria (NTM) are increasingly prevalent worldwide, and some areas appear to be ‘hotspots’ for NTM disease. While exposure to soil is frequently implicated as an important mode of NTM transmission, the diversity, distributions and ecological preferences of soil mycobacteria remain poorly understood. We analyzed 143 soils from across the globe and found that the genusMycobacteriumand lineages within the genus often exhibited predictable preferences for specific environmental conditions. Soils harbor large amounts of previously-undescribed mycobacterial diversity, and lineages that include known pathogens were rarely detected in soil. Together these findings suggest that soil is an unlikely source of many mycobacterial infections. The biogeographical patterns we documented lend insight into the ecology of this important group of soil-dwelling bacteria.
RUNX/CBFβ transcription factor complexes promote the phenotypic plasticity of metastatic breast cancer cells
Authors: Ran Ran , Harrison Hannah , Ariffin Nur Syamimi , Ayub Rahna , Pegg Henry J , Deng Wensheng , Mastro Andrea , Ottewell Penny D. , Fowles Anna M. , Blyth Susan M. Mason Karen , Holen Ingunn , Shore Paul
Published: February 2019

Epithelial to mesenchymal transition (EMT) is a dynamic process that drives cancer cell plasticity and is thought to play a major role in metastasis. Here we show that the plasticity of metastatic breast cancer cells can be promoted by the activity of the RUNX transcription factors. We demonstrate that the RUNX co-regulator CBFβ is essential to maintain the mesenchymal phenotype of triple-negative breast cancer cells and that CBFβ-depleted cells undergo a mesenchymal to epithelial transition (MET) and re-organise into acini-like structures, reminiscent of those formed by epithelial breast cells. We subsequently show, using an inducible CBFβ system, that the MET can be reversed, thus demonstrating the plasticity of RUNX/CBFβ-mediated EMT. Moreover, the MET can be reversed by expression of the EMT transcription factor Slug whose expression is dependent on CBFβ, RUNX1 and RUNX2. Finally, we demonstrate that loss of CBFβ inhibits the ability of metastatic breast cancer cells to invade bone cell cultures and suppresses their ability to form bone metastasesin vivo. Together our findings demonstrate that the RUNX/CBFβ complexes can determine the plasticity of the metastatic cancer cell phenotypes, suggesting that their regulation in different micro-environments may play a key role in the establishment of metastatic tumours.
High-coverage, long-read sequencing of Han Chinese trio reference samples
Authors: Wang Ying-Chih , Olson Nathan D , Deikus Gintaras , Shah Hardik , Wenger Aaron M , Trow Jonathan , Xiao Chunlin , Sherry Stephen , Salit Marc L. , Zook Justin M , Smith Melissa , Sebra Robert
Published: February 2019

Single-molecule long-read sequencing datasets were generated for a son-father-mother trio of Han Chinese descent that is part of the Genome In a Bottle (GIAB) consortium portfolio. The dataset was generated using the Pacific Biosciences Sequel System. The son and each parent were sequenced to an average coverage of 60 and 30, respectively, with N50 subread lengths between 16 and 18 kb. Raw reads and reads aligned to both the GRCh37 and GRCh38 are available at the NCBI GIAB ftp site (ftp://ftp-trace.ncbi.nlm.nih.gov/giab/ftp/data/ChineseTrio/) and the raw read data is archived in NCBI SRA (SRX4739017, SRX4739121, and SRX4739122). This dataset is available for anyone to develop and evaluate long-read bioinformatics methods.