bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights into the red algae and eukaryotic evolution from the genome of
Porphyra umbilicalis
(Bangiophyceae, Rhodophyta)
Authors: Brawley Susan H. , Blouin Nicolas A. , Ficko-Blean Elizabeth , Wheeler Glen L. , Lohr Martin , Goodson Holly V. , Jenkins Jerry W. , Blaby-Haas Crysten E. , Helliwell Katherine E. , Chan Cheong Xin , Marriage Tara N. , Bhattacharya Debashish , Klein Anita S. , Badis Yacine , Brodie Juliet , Cao Yuanyu , Collén Jonas , Dittami Simon M. , Gachon Claire M. M. , Green Beverley R. , Karpowicz Steven J. , Kim Jay W. , Kudahl Ulrich Johan , Lin Senjie , Michel Gurvan , Mittag Maria , Olson Bradley J. S. C. , Pangilinan Jasmyn L. , Peng Yi , Qiu Huan , Shu Shengqiang , Singer John T. , Smith Alison G. , Sprecher Brittany N. , Wagner Volker , Wang Wenfei , Wang Zhi-Yong , Yan Juying , Yarish Charles , Zäuner-Riek Simone , Zhuang Yunyun , Zou Yong , Lindquist Erika A. , Grimwood Jane , Barry Kerrie W. , Rokhsar Daniel S. , Schmutz Jeremy , Stiller John W. , Grossman Arthur R. , Prochnik Simon E.
Published: July 2017

Significance

Fossil evidence shows that red algae (Rhodophyta) are one of the most ancient multicellular lineages. Their ecological, evolutionary, and commercial importance notwithstanding, few red algal nuclear genomes have been sequenced. Our analyses of the
Porphyra umbilicalis
genome provide insights into how this macrophyte thrives in the stressful intertidal zone and into the basis for its nutritional value as human food. Many of the novel traits (e.g., cytoskeletal organization, calcium signaling pathways) we find encoded in the
Porphyra
genome are extended to other red algal genomes, and our unexpected findings offer a potential explanation for why the red algae are constrained to small stature relative to other multicellular lineages.
Specific emotional schema of death-related images vs unpleasant images / Esquema emocional específico de imágenes relacionadas con la muerte frente a imágenes desagradables
Authors: Martí-García Celia , Fernández-Alcántara Manuel , Schmidt-Riovalle Jacqueline , Cruz-Quintana Francisco , García-Caro M. Paz , Pérez-García Miguel
Published: July 2017

Understanding the specific emotional responses elicited by death and how it differs from other unpleasant stimuli is essential for understanding people’s behaviour. In study I, 113 students viewed a set of unpleasant images or images of death. Death images rated lower arousal ( p = .020, d = 0.31, CI [−.06 to .80]) and lower control ( p = .015, d = 0.68, 95% CI [.23 to .93]) than unpleasant pictures. The results also indicated that viewing death-related images did not induce a state of anxiety; in study II, 84 students (42 participants with prior experience related to death) viewed pleasant, neutral, unpleasant and death images. The participants with prior experience reported lower arousal for death-related images ( p = .004, d = 0.87, 95% CI [.45 to 1.36]). In both studies, images of death induced a specific emotional schema according to Izard’s theory that can be modulated by having previous experience.
In situ synchrotron X-ray study of bainite transformation kinetics in a low-carbon Si-containing steel
Authors: Guo L. , Bhadeshia H. K. D. H. , Roelofs H. , Lembke M. I.
Published: July 2017

The bainite transformation in a low-carbon Si-containing steel has been studied in situ by synchrotron X-rays. While the austenite is homogeneous prior to transformation, the carbon distribution becomes nonuniform as bainite plates form. This is because of the different degrees of physical isolation of films and blocks of residual austenite. The method for converting dilatational strain into bainite volume fraction, using lattice strain as a reference, during isothermal transformation was found to overestimate it. The bainitic and martensitic ferrite did not exhibit a tetragonal unit cell due to the low-carbon content of the steel and the high transformation temperature.
Against Selective Realism(s)
Authors: Tulodziecki Dana
Published: July 2017

It has recently been suggested that realist responses to historical cases featured in pessimistic meta-inductions are not as successful as previously thought. In response, selective realists have updated the basic divide et impera strategy specifically to take such cases into account and to argue that more modern realist accounts are immune to the historical challenge. Using a case study—that of the nineteenth-century zymotic theory of disease—I argue that these updated proposals fail and that even the most sophisticated recent realist accounts remain vulnerable to the challenge from history.
An Amish founder mutation disrupts a PI(3)P-WHAMM-Arp2/3 complex–driven autophagosomal remodeling pathway
Authors: Mathiowetz Alyssa J. , Baple Emma , Russo Ashley J. , Coulter Alyssa M. , Carrano Eric , Brown Judith D. , Jinks Robert N. , Crosby Andrew H. , Campellone Kenneth G.
Published: July 2017

Actin nucleation factors function to organize, shape, and move membrane-bound organelles, yet they remain poorly defined in relation to disease. Galloway-Mowat syndrome (GMS) is an inherited disorder characterized by microcephaly and nephrosis resulting from mutations in the WDR73 gene. This core clinical phenotype appears frequently in the Amish, where virtually all affected individuals harbor homozygous founder mutations in WDR73 as well as the closely linked WHAMM gene, which encodes a nucleation factor. Here we show that patient cells with both mutations exhibit cytoskeletal irregularities and severe defects in autophagy. Reintroduction of wild-type WHAMM restored autophagosomal biogenesis to patient cells, while inactivation of WHAMM in healthy cell lines inhibited lipidation of the autophagosomal protein LC3 and clearance of ubiquitinated protein aggregates. Normal WHAMM function involved binding to the phospholipid PI(3)P and promoting actin nucleation at nascent autophagosomes. These results reveal a cytoskeletal pathway controlling autophagosomal remodeling and illustrate several molecular processes that are perturbed in Amish GMS patients.
Childlessness and vulnerability of older people in China
Authors: Feng Zhixin
Published: July 2017

Background

the number of childless older people is increasing in China, but relatively little is known about the role of childlessness in health outcomes. This study investigates the relationship between childlessness and three health outcomes: difficulty with Instrumental Activities of Daily Living (IADLs), self-rated health and depression.

Methods

this study includes 13,171 individuals aged 50 and above from national survey data of the second wave of the China Family Panel Study (2012). Binary/multinomial logistic and ordinary least squares regression models are presented.

Results

childless individuals whose children have all died exhibit worse health outcomes than individuals with children, but this effect is influenced by demographic characteristics, socio-economic status and social security. On the other hand, individuals who are childless due to other reasons (involuntary or voluntary) are less likely to report difficulty with IADLs and to report depression than older people with all children alive after controlling for demographic and socio-economic and social security factors.

Conclusions

the death of a child has an adverse effect on people’s health for both childless people whose children have all died and those who have lost a child but have other children alive. These two groups are in the most vulnerable position, which could also suggest that their children have died because they grew up in a vulnerable family. The government needs to improve the social security for these two groups and provide social services (particularly mental health services) to older people who have lost a child; these could contribute to alleviating some of the adverse effects of the death of a child.
ggseqlogo: a versatile R package for drawing sequence logos
Authors: Wagih Omar
Published: July 2017

Sequence logos have become a crucial visualization method for studying underlying sequence patterns in the genome. Despite this, there remains a scarcity of software packages that provide the versatility often required for such visualizations. ggseqlogo is an R package built on the ggplot2 package that aims to address this issue. ggseqlogo offers native illustration of publication-ready DNA, RNA and protein sequence logos in a highly customizable fashion with features including multi-logo plots, qualitative and quantitative colour schemes, annotation of logos and integration with other plots. The package is intuitive to use and seamlessly integrates into R analysis pipelines.

Availability and implementation

ggseqlogo is released under the GNU licence and is freely available via CRAN-The Comprehensive R Archive Network https://cran.r-project.org/web/packages/ggseqlogo. A detailed tutorial can be found at https://omarwagih.github.io/ggseqlogo.
Microbiome Alterations Are Correlated with Occurrence of Postharvest Stem-End Rot in Mango Fruit
Authors: Diskin Sonia , Feygenberg Oleg , Maurer Dalia , Droby Samir , Prusky Dov , Alkan Noam
Published: July 2017

During storage and ripening, mango fruit develop stem-end rots (SER) that reduce quality, causing significant losses of harvested fruit. The presented results indicate that pathogens, endophytically colonizing the fruit’s stem end, awaken during fruit ripening and cause SER. The main pathogens causing SER in mango grown in Israel were found to be Alternaria alternata and Lasiodiplodia theobromae. Confocal analysis of the sliced stems indicated that the pathogens endophytically colonize the phloem of the fruit’s stem end; they branch into the fruit parenchyma when the pathogen switches to its actively pathogenic stage. We show that the stem ends are also colonized by other microorganisms, including fungi, yeast, and bacteria, which do not cause any apparent symptoms and are considered as true endophytes. Stem-end microbiomes of red (resistant) compared with green (susceptible) mango stored at optimal and suboptimal temperatures were deep sequenced for fungi and bacteria using internal transcribed spacer and 16S, respectively. Our results showed that both fungal and bacterial community changes are dependent on fruit peel color, storage duration, and storage temperature. The stem-end microbiota seems to be very dynamic in terms of interactions and changes. For example, in susceptible fruits, as green mango compared with red mango and in fruit after storage compared with harvested fruit, the abundance of Alternaria (Pleosporaceae) pathogens increased. This increase in pathogenic fungi was correlated with the increased occurrence of SER. In those two scenarios, before the rot developed, the increased amount of fungi was correlated with an increased abundance of chitin-degrading Chitinophagaceae bacteria. In summary, our results show that various conditions modify the microbial community at the stem end and can reduce postharvest SER.
Effect of Intrathecal Bupivacaine Dose on the Success of External Cephalic Version for Breech Presentation
Authors: Chalifoux Laurie A. , Bauchat Jeanette R. , Higgins Nicole , Toledo Paloma , Peralta Feyce M. , Farrer Jason , Gerber Susan E. , McCarthy Robert J. , Sullivan John T.
Published: July 2017

Background

Breech presentation is a leading cause of cesarean delivery. The use of neuraxial anesthesia increases the success rate of external cephalic version procedures for breech presentation and reduces cesarean delivery rates for fetal malpresentation. Meta-analysis suggests that higher-dose neuraxial techniques increase external cephalic version success to a greater extent than lower-dose techniques, but no randomized study has evaluated the dose–response effect. We hypothesized that increasing the intrathecal bupivacaine dose would be associated with increased external cephalic version success.

Methods

We conducted a randomized, double-blind trial to assess the effect of four intrathecal bupivacaine doses (2.5, 5.0, 7.5, 10.0 mg) combined with fentanyl 15 μg on the success rate of external cephalic version for breech presentation. Secondary outcomes included mode of delivery, indication for cesarean delivery, and length of stay.

Results

A total of 240 subjects were enrolled, and 239 received the intervention. External cephalic version was successful in 123 (51.5%) of 239 patients. Compared with bupivacaine 2.5 mg, the odds (99% CI) for a successful version were 1.0 (0.4 to 2.6), 1.0 (0.4 to 2.7), and 0.9 (0.4 to 2.4) for bupivacaine 5.0, 7.5, and 10.0 mg, respectively (P = 0.99). There were no differences in the cesarean delivery rate (P = 0.76) or indication for cesarean delivery (P = 0.82). Time to discharge was increased 60 min (16 to 116 min) with bupivacaine 7.5 mg or higher as compared with 2.5 mg (P = 0.004).

Conclusions

A dose of intrathecal bupivacaine greater than 2.5 mg does not lead to an additional increase in external cephalic procedural success or a reduction in cesarean delivery.
Trends and territorial inequalities of incidence and survival of childhood leukaemia and their relations to socioeconomic status in Hungary, 1971–2015
Authors: Jakab Zsuzsanna , Juhasz Attila , Nagy Csilla , Schuler Dezso , Garami Miklos
Published: July 2017

The Hungarian Childhood Cancer Registry, a population-based national registry of the Hungarian Paediatric Haemato-Oncology Network founded in 1971, monitors the incidence and mortality of childhood cancer. Our aims were to carry out a longitudinal study to investigate the trends and spatial inequalities of incidence and survival of leukaemia, and the association between survival and deprivation in Hungary. All cases of childhood leukaemia and myelodysplasia were analysed (3157 cases, 1971–2015, age: 0–14 years). Time trends and the annual percentage change in direct standardized incidence and mortality were assessed. Survival and association with deprivation were assessed using the Kaplan–Meier method and Cox regression. Incidence rates of leukaemia (23.5–56.0/million) increased with an average annual percent change (AAPC) of 1%, determined by an increase in the incidence of acute lymphoblastic leukaemia (14.6–39.2/million, AAPC: 1.25%). Kaplan–Meier analysis showed a significant improvement in overall survival over the study period. Starting from 25% of cases surviving 5 years in the 70s; the overall 5-year survival reached 80% by 2010. Survival differences were observed with sex, leukaemia type and age at diagnosis. A reverse association was found in the survival probability of leukaemia by degree of deprivation. The Cox proportional hazards model verified a significant reverse association with deprivation [hazard ratio=1.08 (1.04–1.12)]. This is the first nationwide study to confirm the prognostic role of deprivation on the basis of a large cohort of patients with childhood leukaemia during a 45-year period. To maintain further improvement in treatment results, it is important to detect inequalities. Our results showed that deprivation may also be important in the survival of leukaemia.
The bidirectional relationship between vasomotor symptoms and depression across the menopausal transition: a systematic review of longitudinal studies
Authors: Natari Rifani B. , Clavarino Alexandra M. , McGuire Treasure M. , Dingle Kaeleen D. , Hollingworth Samantha A.
Published: July 2017

Objective:

To explore the nature of the bidirectional relationship between vasomotor symptoms (VMS) and depression, and to determine whether hot flashes and night sweats differentially affect the association between VMS and depression through their effect on sleep disruption.

Methods:

Multiple databases were searched from 1961 until July 31, 2016, and a manual search of reference lists of identified articles was conducted. Sixteen articles that involved 10,008 participants were identified and analyzed.

Results:

The methods of analyses and measurement of VMS and depression varied across the studies. Two studies explored the bidirectional association, but only one was significant in both directions (odds ratio [OR] depression to VMS 3.06, 95% confidence interval [CI] 1.43-6.58; OR VMS to depression 8.88, 95% CI 2.57-30.68). In both cases, the association between VMS leading to depressive symptoms was stronger than the opposite. Eleven studies examined VMS leading to depression, but only five showed a significant effect (OR 1.57-1.81, P ≤ 0.02). Treating VMS and depressive symptoms as continuous variables (n = 3) diminished the relationship. Three studies showed a significant association of depression leading to VMS (OR 1.62-1.94, P ≤ 0.01). We found little evidence for a specific effect of night sweats on the association between VMS and depressive symptoms. The effect might not be related to sleep disruption.

Conclusions:

There is a bidirectional association between VMS and depressive symptoms. The menopausal transition appears to increase the risk of recurrent episodes of depression that might not be explained only by VMS. Further investigation is needed to explain the differential effect of night sweats and hot flashes on depression.
COMPARATIVE ANALYSIS OF RETINAL REATTACHMENT SURGERY WITH OR WITHOUT INTERNAL LIMITING MEMBRANE PEELING TO PREVENT POSTOPERATIVE MACULAR PUCKER
Authors: Forlini Matteo , Date Purva , Ferrari Luisa Micelli , Lorusso Massimo , Lecce Gabriella , Verdina Tommaso , Neri Giovanni , Benatti Caterina , Rossini Paolo , Bratu Adriana , D'Eliseo Domenico , Ferrari Tommaso Micelli , Cavallini Gian Maria
Published: July 2017

Purpose:

To determine whether internal limiting membrane (ILM) peeling during pars plana vitrectomy for rhegmatogenous retinal detachment reduces the incidence of epiretinal membrane (ERM) formation.

Methods:

In this retrospective study, preoperative, intraoperative, and postoperative data from all eyes undergoing pars plana vitrectomy for rhegmatogenous retinal detachment between January 2007 and December 2013 was analyzed. All cases with at least 1-year of follow-up were included. Data collection included vision, intraoperative complications, occurrence of ERM, and spectral domain optical coherence tomography characteristics. The OCTs were retrieved for all eyes and were graded by a single masked grader.

Results:

Out of 159 eyes recruited, ILM peeling was done in 78 eyes (49%). Overall occurrence of ERM was 20%. Seven eyes (9%) in ILM peeling group and 25 eyes in the non-ILM peeling group (31%) showed ERM (P = 0.001). Postoperative vision was significantly better in eyes that had ILM peeling (0.48 ± 0.4 logarithm of the minimum angle of resolution [20/63] vs. 0.77 ± 0.6 logarithm of the minimum angle of resolution [20/125], P = 0.003). In multivariable models adjusting for type of tamponade, ILM peeling reduced the likelihood of ERM formation by 75% (P = 0.01).

Conclusion:

Internal limiting membrane peeling during pars plana vitrectomy for rhegmatogenous retinal detachment significantly reduces ERM formation in the postoperative period and is associated with better visual and anatomical outcomes.
Incidence of Active Tuberculosis and Cohort Retention Among Adolescents in Western Kenya
Authors: Nduba Videlis , van’t Hoog Anna H. , Mitchell Ellen M. H. , Borgdorff Martien , Laserson Kayla F.
Published: July 2017

Setting:

Siaya County, with the highest tuberculosis notification rates in Kenya.

Objectives:

To determine the incidence of active tuberculosis and 1-year cohort retention in 12–18-year-old adolescents, in preparation for phase III tuberculosis vaccine trials.

Methods:

Adolescents were enrolled and followed up for 1–2 years to determine tuberculosis incidence. Adolescents with a positive tuberculin skin test, history of cohabitation with a tuberculosis case or at least 1 tuberculosis symptom received clinical and sputum examination and a chest radiograph. Definite tuberculosis cases were bacteriologically confirmed and clinical cases diagnosed by a clinician based on a suggestive chest radiograph and having clinical symptoms. Risk factors were explored using Poisson regression.

Results:

Among 4934 adolescents without tuberculosis at baseline, 26 tuberculosis cases were identified during follow-up with a corresponding incidence density of 4.4 [95% confidence interval (CI): 3.0–6.4] events per 1000 person-years of observation, 12 definite tuberculosis cases; incidence density of 2.0 (95% CI: 0.9–3.1). Having previous tuberculosis (rate ratio: 12.5; CI: 1.8–100) and presence of tuberculin skin test conversion (rate ratio: 3.4; CI: 1.5–7.7) were significantly associated with higher risk of tuberculosis. Overall (4086/4925), 83.0% of adolescents were retained in the study after 1 year of follow-up. Being female, older, out of school and being orphaned were significant risk factors for loss to follow-up.

Conclusion:

The tuberculosis incidence in adolescents will help inform future tuberculosis vaccine trial sample size calculations for this setting. The predictive factors for tuberculosis and retention can be further explored in future trials.
Central-peripheral Temperature Monitoring as a Marker for Diagnosing Late-onset Neonatal Sepsis
Authors: Leante-Castellanos José Luis , Martínez-Gimeno Antonio , Cidrás-Pidré Manuel , Martínez-Munar Gerardo , García-González Ana , Fuentes-Gutiérrez Carmen
Published: July 2017

Background:

The prognosis for late-onset sepsis depends largely on a timely diagnosis. We assess central-peripheral temperature difference monitoring as a marker for late-onset neonatal sepsis diagnosis.

Methods:

We performed a prospective, observational study focusing on a cohort of 129 very low–birth-weight infants. Thermal gradient alteration was defined as a difference of > 2°C maintained during 4 hours. We then determined its association with the late-onset sepsis variable through logistic regression.

Results:

We enrolled 129 preterm babies in 52 months. Thermal gradient alterations showed an adjusted odds ratio for late-onset sepsis of 23.60 (95% confidence interval [CI], 6.80–81.88), with a sensitivity of 83% and negative predictive value of 94%. In 71% of cases, thermal gradient alteration was the first clinical sign of sepsis, while C-reactive protein was < 1.5 mg/dL in 64% of cases and procalcitonin < 2 ng/mL in 36%. These figures indicate potential for early diagnosis.

Conclusions:

Sustained increases of central-peripheral temperature differences are an early sign of evolving late-onset sepsis.
Zika Virus-associated Ocular and Neurologic Disorders
Authors: Şahiner Fatih , Siğ Ali Korhan , Savaşçi Ümit , Tekin Kemal , Akay Fahrettin
Published: July 2017

Background:

It has been approximately 70 years since the discovery of the Zika virus (ZIKV). It had been established that the virus causes mild infections and is confined to Africa and Asia; however, major changes in the clinical and epidemiologic patterns of ZIKV infection have occurred in recent years. The virus has attracted intense interest because of the possible association of several autoimmune and neurodevelopmental disorders.

Methods:

We present a summary of the articles that attempt to explain the ZIKV unknowns and strengthen the association with some disorders that are thought to be related to ZIKV, by describing the discovery milestones from the initial identification of the virus to the present day.

Results:

New evidence strengthens the association between ZIKV infections and Guillain–Barré syndrome (GBS), microcephaly and various neurodevelopmental and ophthalmologic disorders as a result of numerous new clinical and experimental studies.

Conclusions:

The World Health Organization declared the end of the “Public Health Emergency of International Concern” in December 2016, but ZIKV and associated consequences remain a significant enduring public health challenge.
Late-Onset Hiv Encephalopathy In Children With Long-Standing Virologic Suppression Followed By Slow Spontaneous Recovery Despite no Change In Antiretroviral Therapy
Authors: Innes Steve , van Toorn Ronald , Otwombe Kennedy , Dobbels Els , van Zyl Gert , Cotton Mark F. , Laughton Barbara
Published: July 2017

We describe 4 Children with HIV Early Antiretroviral Therapy trial participants with late-onset HIV encephalopathy despite long-standing viral suppression in blood and undetectable HIV DNA and RNA polymerase chain reaction in cerebrospinal fluid. Extensive investigations revealed no alternative etiology. Reassuringly, all 4 experienced slow spontaneous recovery despite no change in antiretroviral therapy. Virally suppressed HIV-infected children remain at risk for fluctuating neurologic signs and symptoms.
Passive Transcutaneous Bone Conduction Hearing Implants: A Systematic Review
Authors: Cooper Timothy , McDonald Brendan , Ho Allan
Published: July 2017

Objective:

To systematically review the literature on currently available passive transcutaneous bone conduction hearing implants (pTCBI) with regard to complications, audiological outcomes, and quality-of-life scores.

Data Sources:

MEDLINE, EMBASE, Scopus, and Cochrane Library.

Study Selection:

All identified English-language articles reporting on the implantation of currently available pTCBI's and their complications. Both pediatric and adult patients were included. No limitation was placed on study design or level of evidence.

Data Extraction:

Complications, audiological outcomes including mean pure-tone average gain and mean speech reception threshold gain, and quality-of-life outcomes.

Data Synthesis:

Twenty-six articles were included in the review. Four hundred eighty-two pTCBIs have been reported in the literature. Major complications including skin breakdown, wound dehiscence, hematoma, seroma, and inability to use the device occurred in 5.2% of patients. Minor complications including pain and self-resolving erythema at the implant site occurred in 13.1% of the patients. The weighted mean pure-tone average gain of the two included devices was 28.4 ± 2.1 dB and the mean speech reception threshold gain was 32.9 ± 3.9 dB. Favorable quality-of-life scores have been demonstrated with pTCBIs.

Conclusion:

pTCBIs are a viable alternative to percutaneous devices in a carefully selected group of patients. These devices have demonstrated good audiological outcomes, low morbidity, and high patient satisfaction.
Maternal Hepatitis B Virus Infection and Pregnancy Outcomes
Authors: Wan Zhihua , Zhou Aifen , Zhu Huiping , Lin Xiaofang , Hu Dan , Peng Songxu , Zhang Bin , Du Yukai
Published: July 2017

Goals:

To examine the impact of maternal hepatitis B virus infection on pregnancy outcomes.

Background:

Studies regarding hepatitis B virus infection and pregnancy outcomes are limited with inconsistent results, and none of them have evaluated the effect of maternal viral load in pregnancy on pregnancy outcomes.

Study:

A hospital-based case-control study was conducted. In total, 1728 hepatitis B surface antigen (HBsAg)-positive women who delivered consecutively at Wuhan Women and Children Medical and Healthcare Center, Wuhan, China, from June 2008 to May 2015, were compared with 1497 HBsAg-negative women giving birth in the same hospital during the same period who were randomly identified and selected from the computerized medical record database in parallel. Univariate and multivariate logistic regression models were constructed.

Results:

After adjusting for confounding variables, maternal HBsAg carriage was associated with increased risk of pregnancy-induced hypertension [adjusted odds ratio (aOR)=2.20; 95% confidence interval (CI), 1.30-3.73], fetal distress (aOR=1.40; 95% CI, 1.09-1.78), cesarean delivery (aOR=1.70; 95% CI, 1.45-1.99), and macrosomia (aOR=1.68; 95% CI, 1.19-2.37). Moreover, maternal viral load in the second trimester was significantly associated with risk of preterm birth (aOR for each log10 copy/mL increase, 1.18; 95% CI, 1.01-1.39) among HBsAg carriers after adjustment for maternal age, employment, parity, history of abortion, and prenatal body mass index.

Conclusions:

Maternal HBsAg carriage was associated with several adverse pregnancy outcomes. Furthermore, hepatitis B viral activity in pregnancy might have certain effects on pregnancy outcomes. Careful surveillance of maternal HBsAg status as well as viral activity in the second trimester among HBsAg carriers is warranted.
Obesity and pancreatitis
Authors: Khatua Biswajit , El-Kurdi Bara , Singh Vijay P.
Published: July 2017

Purpose of review

The obesity pandemic poses a unique set of problems for acute pancreatitis – both by increasing acute pancreatitis incidence, and worsening acute pancreatitis severity. This review explores these associations, underlying mechanisms, and potential therapies.

Recent findings

We review how the obesity associated increase in gallstones, surgical, and endoscopic interventions for obesity management, diabetes, and related medications such as incretin-based therapies and hypertriglyceridemia may increase the incidence of acute pancreatitis. The mechanism of how obesity may increase acute pancreatitis severity are discussed with a focus on cytokines, adipokines, damage-associated molecular patterns and unsaturated fatty acid-mediated lipotoxicity. The role of obesity in exacerbating pancreatic necrosis is discussed; focusing on obesity-associated pancreatic steatosis. We also discuss how peripancreatic fat necrosis worsens organ failure independent of pancreatic necrosis. Last, we discuss emerging therapies including choice of intravenous fluids and the use of lipase inhibitors which have shown promise during severe acute pancreatitis.

We discuss how obesity may contribute to increasing acute pancreatitis incidence, the role of lipolytic unsaturated fatty acid release in worsening acute pancreatitis, and potential approaches, including appropriate fluid management and lipase inhibition in improving acute pancreatitis outcomes.
Prevention of hemolytic disease of the fetus and newborn: what have we learned from animal models?
Authors: Cruz-Leal Yoelys , Marjoram Danielle , Lazarus Alan H.
Published: July 2017

Purpose of review

This review aims to highlight recent advances in our understanding of how anti-red blood cell (RBC) antibodies prevent erythrocyte immunization with an emphasis on new murine models.

Recent findings

New murine models with clinically relevant human erythrocyte antigens have been used to understand the alloimmunization process and its inhibition. The search to elucidate the mechanism of action of IgG-mediated inhibition of erythrocyte alloimmunization has provided new evidence in support of a potential role for epitope masking, immune deviation and/or antigen modulation in this process. In addition, recent evidence suggests that blends of monoclonal antibodies targeting nonoverlapping epitopes on the RBC surface can improve the efficacy of monoclonal antibodies approaching that of polyclonal IgG.

Animal models with defined alloantigens have helped to identify important mechanistic components that lead to alloimmunization and its inhibition by IgG. A better understanding of the underlying mechanisms leading to hemolytic disease of the fetus and newborn is required to develop the most effective prevention strategies for future patients.
Wnt signaling in cardiovascular disease: opportunities and challenges
Authors: Gay Austin , Towler Dwight A.
Published: July 2017

Purpose of review

Cardiometabolic diseases increasingly afflict our aging, dysmetabolic population. Complex signals regulating low-density lipoprotein receptor-related protein (LRP) and frizzled protein family members – the plasma membrane receptors for the cadre of Wnt polypeptide morphogens – contribute to the control of cardiovascular homeostasis.

Recent findings

Both canonical (β-catenin-dependent) and noncanonical (β-catenin-independent) Wnt signaling programs control vascular smooth muscle (VSM) cell phenotypic modulation in cardiometabolic disease. LRP6 limits VSM proliferation, reduces arteriosclerotic transcriptional reprogramming, and preserves insulin sensitivity while LRP5 restrains foam cell formation. Adipose, skeletal muscle, macrophages, and VSM have emerged as important sources of circulating Wnt ligands that are dynamically regulated during the prediabetes−diabetes transition with cardiometabolic consequences. Platelets release Dkk1, a LRP5/LRP6 inhibitor that induces endothelial inflammation and the prosclerotic endothelial−mesenchymal transition. By contrast, inhibitory secreted frizzled-related proteins shape the Wnt signaling milieu to limit myocardial inflammation with ischemia-reperfusion injury. VSM sclerostin, an inhibitor of canonical Wnt signaling in bone, restrains remodeling that predisposes to aneurysm formation, and is downregulated in aneurysmal vessels by epigenetic methylation.

Components of the Wnt signaling cascade represent novel targets for pharmacological intervention in cardiometabolic disease. Conversely, strategies targeting the Wnt signaling cascade for other therapeutic purposes will have cardiovascular consequences that must be delineated to establish clinically useful pharmacokinetic–pharmacodynamic relationships.
Localized muscle vibration reverses quadriceps muscle hypotrophy and improves physical function: a clinical and electrophysiological study
Authors: Benedetti Maria Grazia , Boccia Gennaro , Cavazzuti Lorenzo , Magnani Elena , Mariani Elisabetta , Rainoldi Alberto , Casale Roberto
Published: July 2017

Quadriceps weakness has been associated with knee osteoarthritis (OA). High-frequency localized muscle vibration (LMV) has been proposed recently for quadriceps strengthening in patients with knee OA. The purpose of this study was (a) to investigate the clinical effectiveness of high-frequency LMV on quadriceps muscle in patients with knee OA and (b) to disentangle, by means of surface electromyography (sEMG), the underlying mechanism. Thirty patients, aged between 40 and 65 years, and clinically diagnosed with knee OA were included in this randomized, controlled, single-blinded pilot study. Participants were randomly assigned to two groups: a study group treated with LMV, specifically set for muscle strengthening (150 Hz), by means of a commercial device VIBRA, and a control group treated with neuromuscular electrical stimulation. Clinical outcome was measured using the Western Ontario and McMaster Universities Osteoarthritis Index, Visual Analogue Scale, knee range of motion, Timed Up and Go test, and Stair climbing test. To assess changes in muscle activation and fatigue a subgroup of 20 patients was studied with the use of sEMG during a sustained isometric contraction. The LMV group showed a significant change in Western Ontario and McMaster Universities Osteoarthritis Index score, Visual Analogue Scale score, Timed Up and Go test, Stair Climbing Test, and knee flexion. These improvements were not significant in patients treated with neuromuscular electrical stimulation. sEMG analysis suggested an increased involvement of type II muscle fibers in the group treated with LMV. In conclusion, the present study supports the effectiveness of local vibration in muscle function and clinical improvement of patients with knee OA.
Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas
Authors: Casar-Borota Olivera , Botling Johan , Granberg Dan , Stigare Jerker , Wikström Johan , Boldt Henning Bünsow , Kristensen Bjarne Winther , Pontén Fredrik , Trouillas Jacqueline
Published: July 2017

Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown. Facing a difficult diagnostic case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None of the pituitary tumors expressed serotonin, suggesting that serotonin immunoreactive sellar tumors represent primary or secondary NETs of nonpituitary origin. Normal expression of ATRX and DAXX in pituitary tumors suggests that ATRX and DAXX do not play a role in the pathogenesis of pituitary endocrine tumors that remain localized to the sellar and perisellar region. A lack of ATRX or DAXX in a sellar NET suggests a nonpituitary NET, probably of pancreatic origin. One of the 2 examined corticotroph carcinomas, however, demonstrated negative ATRX immunolabeling due to an ATRX gene mutation. Further studies on a larger cohort of pituitary carcinomas are needed to clarify whether ATRX mutations may contribute to the metastatic potential in a subset of pituitary NETs.
Teaching Incision and Drainage
Authors: Adams Cynthia M. , Nigrovic Lise E. , Hayes Gavin , Weinstock Peter H. , Nagler Joshua
Published: July 2017

Objectives

Incision and drainage (I&D) of skin abscesses is an important procedural skill for pediatric emergency medicine providers. Practical skills training using simulation provides an opportunity to learn and gain confidence with this invasive procedure. Our objective was to assess the perceived educational value of 2 versions of an abscess model as part of an educational workshop for teaching I&D.

Methods

A combined didactic and practical skills workshop was developed for use at 2 national conferences. The didactic content was created through an iterative process. To facilitate hands-on training, 2 versions of an abscess model were created: 1 constructed from a negative mold and the other using a 3-dimensional printer. Participants were surveyed regarding prior experience with I&D, procedural confidence, and perceptions of the educational utility of the models.

Results

Seventy physicians and 75 nurse practitioners participated in the study. Procedural confidence improved after training using each version of the model, with the greatest improvements noted among novice learners. Ninety-four percent of physicians, and 99% of nurse practitioners rated the respective models as either “educational” or “very educational,” and 97% and 100%, respectively, would recommend the abscess models to others.

Conclusions

A combined didactic and practical skills educational workshop using novel abscess models was effective at improving learners' confidence. Our novel models provide an effective strategy for teaching procedural skills such as I&D and demonstrate a novel use of 3-dimensional printers in medical education. Further study is needed to determine if these educational gains translate into improvement in clinical performance or patient outcomes.
Does the Application of Heat Gel Pack After Eutectic Mixture of Local Anesthetic Cream Improve Venipuncture or Intravenous Cannulation Success Rate in Children? A Randomized Control Trial
Authors: Schreiber Silvana , Cozzi Giorgio , Patti Giuseppa , Taddio Andrea , Montico Marcella , Pierobon Chiara , Barbi Egidio
Published: July 2017

Objective

Needle-related procedures are the most common sources of pain for children in the hospital setting. The most used topical anesthetic, eutectic mixture of local anesthetic (EMLA) cream, may cause transient vasoconstriction. It has been postulated that this vasoconstriction may decrease vein visualization. The application of heat gel pack after removal of EMLA cream in the site of venipuncture counteracts the vasoconstriction, improving vein visualization. We assessed using a prospective randomized controlled trial whether the application of heat gel pack increases the needle procedure success rate. The primary study outcome was procedural success rate at the first attempt.

Methods

The study enrolled 400 children, 200 of whom applied heat gel pack after removing EMLA (treatment group) and 200 did not (control group). Procedural success rate at the first attempt, vein perception before procedure, procedural pain, and adverse events were recorded in both groups.

Results

Eighty-eight percent of the procedures were successful at the first attempt in the treatment group and 89% in the control group (P = 0.876). Vein perception was not significantly different in the 2 groups (P = 0.081). Pain score after the procedure was similar in the 2 groups.

Conclusions

This study shows that the application of heat gel pack after removal of EMLA cream does not improve venipuncture or intravenous cannulation success rate.
Identification of Hypotensive Emergency Department Patients with Cardiogenic Etiologies
Authors: Henning Daniel J. , Kearney Kathleen E. , Hall Michael Kennedy , Mahr Claudius , Shapiro Nathan I. , Nichol Graham
Published: July 2017

Objective:

Identify predictors of cardiogenic etiology among emergency department (ED) patients with hypotension, and use these predictors to create a clinical tool to discern cardiogenic etiology of hypotension.

Methods:

This secondary analysis evaluated a prospective cohort of consecutive patients with hypotension in an urban, academic, tertiary care ED from November 2012 to September 2013. We included adults with hypotension, defined as a new vasopressor requirement, systolic blood pressure (SBP) < 90 mm Hg after at least 1 L of crystalloid or 2 units packed red blood cells, or SBP < 90 mm Hg and fluids withheld due to concern for fluid overload. The primary outcome was cardiogenic etiology, adjudicated by two physician chart review, with 25% paired chart review (kappa = 0.92). We used multivariable logistic regression to predict cardiogenic etiology, utilizing clinical data abstracted from the electronic medical record. We created a prediction score from significant covariates and calculated its test characteristics for cardiogenic hypotension.

Results:

Of 700 patients with hypotension, 107 (15.3%, 95% CI: 12.6%–18.0%) had cardiogenic etiology. Independent predictors of cardiogenic etiology were shortness of breath (OR 4.1, 95% CI: 2.5–6.7), troponin > 0.1 ng/mL (37.5, 7.1–198.2), electrocardiographic ischemia (8.9, 4.0–19.8), history of heart failure (2.0, 1.1–3.3), and absence of fever (4.5, 2.3–8.7) (area under the curve [AUC] = 0.83). The prediction score created from these predictors yielded 78% sensitivity and 77% specificity for cardiogenic etiology (AUC = 0.827).

Conclusions:

Clinical predictors offer reasonable ED screening sensitivity for cardiogenic hypotension, while demonstrating sufficient specificity to facilitate early cardiac interventions.
Antithrombin III Attenuates AKI Following Acute Severe Pancreatitis
Authors: Kong Yiwei , Yin Jianyong , Cheng Dongsheng , Lu Zeyuan , Wang Niansong , Wang Feng , Liang Mingyu
Published: July 2017

Background:

Antithrombin III (ATIII), the predominant coagulation factor inhibitor, possesses anti-inflammatory properties and exerts renoprotective effects on renal ischemia-reperfusion injury in animal models. However, the ATIII's protective effects of ATIII on acute kidney injury (AKI) following severe acute pancreatitis (SAP) need to be confirmed.

Methods:

We assessed the association between ATIII activities and the incidence of AKI in patients with SAP, and explored therapeutic effects and potential mechanisms of ATIII on kidney injury in sodium taurocholate induced SAP rat model. Rats were intravenously injected with ATIII (500 μg/kg) before or after the induction of SAP.

Results:

The results demonstrated ATIII did not attenuate pancreatic injury, but significantly ameliorate renal dysfunction and renal histological injury. ATIII administration alleviated renal inflammation response, oxidative stress, and cell apoptosis. Moreover, ATIII attenuated tumor necrosis factor α (TNFα)-stimulated intercellular cell adhesion molecule 1(ICAM-1) and monocyte chemotactic protein 1 (MCP-1) upregulation in cultured renal tubular epithelial cells.

Conclusion:

ATIII appears to ameliorate SAP-induced kidney injury by inhibiting inflammation, oxidative stress, and apoptosis. ATIII supplementation may have a potential prophylactic and therapeutic effect on SAP induced AKI.
Songbird organotypic culture as anin vitromodel for interrogating sparse sequencing networks
Authors: Shen Jun , Blute Todd A. , Liberti William A. , Yen William , Liberti Derek C. , Kotten Darrell N. , Cruz-Martín Alberto , Gardner Timothy J.
Published: July 2017

Sparse sequences of neuronal activity are fundamental features of neural circuit computation; however, the underlying homeostatic mechanisms remain poorly understood. To approach these questions, we have developed a method for cellular-resolution imaging in organotypic cultures of the adult zebra finch brain, including portions of the intact song circuit. Thesein vitronetworks can survive for weeks, and display mature neuron morphologies. Neurons within the organotypic slices exhibit a diversity of spontaneous and pharmacologically induced activity that can be easily monitored using the genetically encoded calcium indicator GCaMP6. In this study, we primarily focus on the classic song sequence generator HVC and the surrounding areas. We describe proof of concept experiments including physiological, optical, and pharmacological manipulation of these exposed networks. This method may allow the cellular rules underlying sparse, stereotyped neural sequencing to be examined with new degrees of experimental control.

Highlights

Organotypic brain slices from adult zebra finch (Taeniopygia guttata), expressing the calcium indicator GCaMP6, can be cultured and maintained for at least several weeks and display spontaneous and evoked calcium transients.
GAS Power Calculator: web-based power calculator for genetic association studies
Authors: Johnson Jennifer Li , Abecasis Gonçalo R.
Published: July 2017

Motivation:

Statistical power calculations are crucial in designing genetic association studies. They help guide tradeoffs between large sample sizes and detailed assessments of genotype and phenotype, help determine which studies are viable, and help interpret research findings. To facilitate widespread use of power analysis in the design and interpretation of genetic studies, it is important to enable users to calculate power and visualize the effect of different models and design choices in convenient, interactive tools that are easily accessible.

Results:

We developed the Genetic Association Study (GAS) Power Calculator to provide users with a simple interface that can be compute the power of genetic association studies in a convenient browser based interface.

Availability:

The GAS Power Calculator can be accessed from the web interface at http://csg.sph.umich.edu/abecasis/gas_power_calculator/. Source code is available at https://github.com/jenlij/GAS-power-calculator.
Evolutionary rewiring of the human regulatory network by waves of genome expansion
Authors: Marnetto Davide , Mantica Federica , Molineris Ivan , Grassi Elena , Pesando Igor , Provero Paolo
Published: July 2017

Genome expansion is believed to be an important driver of the evolution of gene regulation. To investigate the role of newly arising sequence in rewiring the regulatory network we estimated the age of each region of the human genome by applying maximum parsimony to genome-wide alignments with 100 vertebrates. We then studied the age distribution of several types of functional regions, with a focus on regulatory elements. The age distribution of regulatory elements reveals the extensive use of newly formed genomic sequence in the evolution of regulatory interactions. Many transcription factors have expanded their repertoire of targets through waves of genomic expansions that can be traced to specific evolutionary times. Repeated elements contributed a major part of such expansion: many classes of such elements are enriched in binding sites of one or a few specific transcription factors, whose binding sites are localized in specific portions of the element and characterized by distinctive motif words. These features suggest that the binding sites were available as soon as the new sequence entered the genome, rather than being created later by accumulation of point mutations. By comparing the age of regulatory regions to the evolutionary shift in expression of nearby genes we show that rewiring through genome expansion played an important role in shaping the human regulatory network.