bluuebunny/crossref_metadata_2025 huggingface dataset:
POPdemog: visualizing population demographic history from simulation scripts
Authors: Zhou Ying , Tian Xiaowen , Browning Brian L , Browning Sharon R
Published: March 2018

We present POPdemog, an R package which converts coalescent simulation program input parameters into a visual representation of the demographic model. This package is useful for preparing figures, for checking that demographic simulation parameters have been correctly specified, and for understanding demographic models that other researchers have used to simulate genetic data. The POPdemog package supports the ms, msa, msHot, MaCS, msprime, scrm and Cosi2 programs, and includes options for customizing the output figures.

Availability and implementation

The POPdemog package and its tutorial can be freely downloaded from https://github.com/YingZhou001/POPdemog.

Supplementary information

Supplementary data are available at Bioinformatics online.
SPV: a JavaScript Signaling Pathway Visualizer
Authors: Calderone Alberto , Cesareni Gianni
Published: March 2018

The visualization of molecular interactions annotated in web resources is useful to offer to users such information in a clear intuitive layout. These interactions are frequently represented as binary interactions that are laid out in free space where, different entities, cellular compartments and interaction types are hardly distinguishable. Signaling Pathway Visualizer is a free open source JavaScript library, which offers a series of pre-defined elements, compartments and interaction types meant to facilitate the representation of signaling pathways consisting of causal interactions without neglecting simple protein–protein interaction networks.

Availability and implementation

Freely available under Apache version 2 license; Source code: https://github.com/Sinnefa/SPV_Signaling_Pathway_Visualizer_v1.0. Language: JavaScript; Web technology: Scalable Vector Graphics; Libraries: D3.js.
Dietary Patterns and Physical Activity Correlate With Total Cholesterol Independently of Lipid-Lowering Drugs and Antiretroviral Therapy in Aging People Living With Human Immunodeficiency Virus
Authors: Marzel Alex , Kouyos Roger D , Reinschmidt Sara , Balzer Katharina , Garon Fabienne , Spitaleri Monica , Matthes Nicolas , Suter Paolo , Weber Rainer , Staehelin Cornelia , Lecompte Thanh Doco , Tarr Philip , Kovari Helen ,   Swiss HIV Cohort Study, Aubert V , Battegay M , Bernasconi E , Böni J , Braun D L , Bucher H C , Calmy A , Cavassini M , Ciuffi A , Dollenmaier G , Egger M , Elzi L , Fehr J , Fellay J , Furrer H , Fux C A , Günthard H F , Haerry D , Hasse B , Hirsch H H , Hoffmann M , Hösli I , Kahlert C , Kaiser L , Keiser O , Klimkait T , Kouyos R D , Kovari H , Ledergerber B , Martinetti G , de Tejada B Martinez , Marzolini C , Metzner K J , Müller N , Nicca D , Pantaleo G , Paioni P , Rauch A , Rudin C , Scherrer A U , Schmid P , Speck R , Stöckle M , Tarr P , Trkola A , Vernazza P , Wandeler G , Weber R , Yerly S
Published: March 2018

Background

Hypercholesterolemia is a well established risk factor for coronary heart disease and is highly prevalent among human immunodeficiency virus (HIV)-positive persons. Antiretroviral therapy (ART) can both directly modify total cholesterol and have drug-drug interactions with statins. This makes investigating modifiable behavioral predictors of total cholesterol a pertinent task.

Methods

To explore the association between diet and physical activity with cross-sectionally measured total cholesterol, we administered a validated Food-Frequency-Questionnaire to participants of the Swiss HIV Cohort Study ≥45 years old. Linear mixed-effects models were applied to explore the associations between dietary patterns and physical activity with total cholesterol, after adjustment for clinical and demographic covariates.

Results

In total, 395 patients were included. Forty percent (158 of 395) had elevated total cholesterol (>5.2 mmol/L), and 41% (164 of 395) were not regularly physically active. In multivariable analysis, 2 factors were positively associated with total cholesterol; female sex (β = 0.562; 95% confidence interval [CI], 0.229–0.896) and the combined consumption of meat, refined/milled grains, carbonated beverages, and coffee (β = 0.243; 95% CI, 0.047–0.439). On the other hand, regular physical activity (β = −0.381; 95% CI, −0.626 to −0.136), lipid-lowering drugs (β = −0.443; 95% CI −0.691 to −0.196), ART containing tenofovir (β = −0.336; 95% CI −0.554 to −0.118), and black ethnicity (β = −0.967; 95% CI −1.524 to −0.410) exhibited a negative association.

Conclusions

We found independent associations between certain dietary patterns and physical activity with total cholesterol. Increasing physical activity might achieve cardiovascular and other health benefits in HIV-positive individuals. The clinical relevance of the identified dietary patterns requires further investigation in prospective cohort studies and randomized controlled trials.
Cadaveric Nerve and Artery Proximity to Sacrospinous Ligament Fixation Sutures Placed by a Suture-Capturing Device
Authors: Katrikh Aaron Z. , Ettarh Rajuno , Kahn Margie A.
Published: March 2018

(Abstracted from Obstet Gynecol 2017;130:1033–1038)

A common choice for apical suspension is use of sacrospinous ligament fixation procedures, in which the vaginal vault is anchored to the ligament. There is no consensus on the recommended number and placement of sutures during the fixation procedure; placement varies from the lateral third of the sacrospinous ligament close to the ischial spine and as far away medially as 4 cm.
Re-emergence of Congenital Syphilis in Ohio
Authors: Cooper Joshua M. , Porter Makeda , Bazan José A. , Nicholson Lisa M. , Sánchez Pablo J.
Published: March 2018

Background:

The recent occurrence of congenital syphilis in Columbus, OH, raised concern for an increase in syphilis among women and infants. The objectives were to examine the rates of syphilis among men, women and infants in Ohio from 2003 to 2016 and compare these rates to the rest of the United States.

Methods:

This retrospective study evaluated cases of syphilis among men, women and infants from 2003 to 2016 using data from the Ohio Department of Health and the Centers for Disease Control and Prevention.

Results:

In Ohio from 2003 to 2016, the number of all syphilis cases among women significantly increased from 153 (2.6/100,000) to 294 (5.2/100,000), respectively (b = 0.26; P = 0.001; 95% confidence interval [CI]: 0.137–0.382). From 2003 to 2016, congenital syphilis in Ohio also increased significantly from 3 (2/100,000) to 13 cases (9.3/100,000), respectively (b = 1.05; P ≤ 0.001; 95% CI: 0.687–1.408). The increase in congenital syphilis mirrored the increase in all cases of syphilis in women but not with the rates of primary and secondary syphilis. Among men, cases of primary and secondary syphilis increased significantly in Ohio and the rest of the United States, from 156 (2.8/100,000) and 5956 (4.2/100,000) in 2003 to 622 (10.5/100,000) and 24,724 (15.6/100,000) in 2016, respectively (Ohio: b = 0.55; P < 0.001; 95% CI: 0.426–0.679; United States: b = 0.77; P < 0.001; 95% CI: 0.629–0.916).

Conclusions:

The association of congenital syphilis with all syphilis cases in women highlights the importance of reporting all cases and not just primary and secondary syphilis. The increase in congenital syphilis reinforces the recommendation for repeat maternal screening during pregnancy.
Antibiotic Recommendations for Acute Otitis Media and Acute Bacterial Sinusitis
Authors: Wald Ellen R. , DeMuri Gregory P.
Published: March 2018

There has been a substantial change in the prevalence and microbiologic characteristics of cases of acute otitis media secondary to the widespread use of pneumococcal conjugate vaccines. Current trends in nasopharyngeal colonization and the microbiology of acute otitis media support a change in the recommendation for antibiotic management of acute otitis media and acute bacterial sinusitis in children.
Hospitalization Rate and Population-based Incidence of Hospitalization for Community-acquired Pneumonia Among Children in Suzhou, China
Authors: Shan Wei , Shi Ting , Zhang Xiyan , Xue Jian , Wang Yin , Yu Jia , Huang Yukai , Lin Sheng , Zhao Genming , Tian Jianmei , Zhang Tao
Published: March 2018

Background:

Data on hospitalization burden of community-acquired pneumonia (CAP) in children are very limited in China. This study aimed to estimate the hospitalization rate (HR) and population-based incidence of hospitalization of CAP for children <15 years of age in Suzhou, China.

Methods:

This was a retrospective study of children hospitalized in Soochow University Affiliated Children’s Hospital from January 2010 to December 2014. Children who were residents of downtown Suzhou, 29 days to <15 years of age, with discharge diagnosis codes (International Classification of Diseases, 10th revision) including J09–J18 and J20–J22 were included. All-cause clinical community-acquired pneumonia (CCAP) and radiographically confirmed pneumonia (RCAP) were identified based on individual medical chart review. The HR and population-based cumulative incidence of hospitalization (HI) were calculated.

Results:

Among 184,734 children <15 years of age admitted to Soochow University Affiliated Children’s Hospital during the study period, 31,302 children were identified as having CCAP and 24,218 (77.4%) children confirmed as having RCAP. CCAP hospitalization occurred year round and peaked during winter and early spring. The overall HRs for CCAP and RCAP were 189.0 [95% confidence interval (CI): 187.1–190.9] and 146.2 (95% CI: 144–148) per 1000 hospitalizations, respectively, and the HIs per 100,000 children annually were CCAP, 3235.8 (95% CI: 3207.3–3264.2) and RCAP, 2503.5 (95% CI: 2478.3–2528.6). For children <5 years of age, the HR for CCAP was 248.4 (95% CI: 245.9–250.9) and RCAP was 194.0 (95% CI: 191.4–196.3) per 1000 hospitalizations; the HI for CCAP was 6956.2 (95% CI: 6892.8–7019.6) and 5431.9 (95% CI: 5375.4–5488.4) per 100,000 children for RCAP. The highest HR and HI were observed in children 29 days to <6 months of age: HR for CCAP was 407.4 (95% CI: 400.9–413.9) per 1000 hospitalizations and HI for CCAP was 11,203.7 (95% CI: 11,026.8–11,380.6) per 100,000 children annually.

Conclusions:

There is a considerable burden of CAP among children <15 years of age in Suzhou, particularly among children 29 days to <6 months of age and during winter and early spring. These data provide valuable information to monitor CAP trends over time in children of Suzhou, China.
The marketing of testosterone treatments for age-related low testosterone or ‘Low T’
Authors: Mintzes Barbara
Published: March 2018

Purpose of review

To summarize the research evidence on promotion of testosterone for ‘Low T’, or age-related hypogonadism.

Recent findings

Marketing of testosterone for ‘Low T’ has relied on strategies that are inadequately regulated to prevent off-label promotion, such as unbranded ‘disease-awareness’ advertising campaigns targeting the general public, sponsored continuing medical education (CME) and ghostwriting. A recent US analysis of television advertising exposure levels versus insurance claims found that both unbranded ‘disease-awareness’ advertising and branded ads were associated with increased rates of testosterone testing, treatment initiation, and treatment without prior testing. Exposés of sponsored CME and ghostwriting indicate misrepresentation of the research evidence on the sequelae of untreated low testosterone and on treatment efficacy. In the United States, advertising to the general public ceased in 2014 after the Food and Drug Administration changed product labeling to clarify that testosterone is only indicated for pathological hypogonadism. Unbranded ‘disease-awareness’ advertising to the general public and ‘Low T’ messages for health professionals have continued elsewhere.

The review of the experience of promotion of testosterone for ‘Low T’ and research evidence on effects of advertising targeting the public highlights the need for improved regulation of unbranded ‘disease awareness’ advertising to ensure adequate protection of public.
DAISY Nurses—Recognizing Clinical Expertise Through Certification
Authors: Sweeney Cynthia Divens
Published: March 2018

The DAISY Foundation is dedicated to recognizing nurses who provide compassionate, skilled, and extraordinary nursing care. Nominations for The DAISY Award are typically submitted in the form of a story. Stories are an opportunity to share with others what compassionate and extraordinary nursing care looks like and to recognize the individual nurses who provide that care. Clinical competence delivered with compassion is a hallmark of DAISY Award recipients. Professional certification provides an additional form of recognition of a nurse's clinical competence.
The Imperative of Solving Nurses’ Usability Problems With Health Information Technology
Authors: Staggers Nancy , Elias Beth L. , Makar Ellen , Alexander Gregory L.
Published: March 2018

BACKGROUND

Health information technology (IT) usability issues are a key concern for nurse executives and nurses.

OBJECTIVES

The aims of this study are to understand usability pain points faced by nurses regarding the use of health IT, identify their impact and importance, discuss responsibilities, and develop possible solutions to improve the health IT-user experience for nurses.

METHODS

Twenty-seven experts were interviewed including nursing leaders, informaticists, executives, engineers, researchers, and human factors experts across acute care, long-term care, and vendor settings. Semistructured questions guided the interviews, and content analysis was used to identify themes.

RESULTS

Four themes emerged: 1) user experience pain points, 2) importance of the issues, 3) the responsibility gap, and 4) acting on usability issues.

CONCLUSION

Nurses continue to endure significant health IT-usability issues that negatively impact patients, nurses, and healthcare organizations. Solutions include enhancing the voice of nursing at the national and local levels, creating a digital strategy for nursing, providing incentives to improve usability in health IT, and accelerating the understanding of nurses' work intended to inform and translate nurses' work into health IT design.
The Effects of Social Influence on Nurses' Hand Hygiene Behaviors
Authors: Piras Susan E. , Minnick Ann , Lauderdale Jana , Dietrich Mary S. , Vogus Timothy J.
Published: March 2018

OBJECTIVE

The aim of this article is to describe the associations of nurses' hand hygiene (HH) attitudes, subjective norms, and perceived behavioral control with observed and self-reported HH behavior.

BACKGROUND

Hand hygiene is an essential strategy to prevent healthcare-associated infections. Despite tremendous efforts, nurses' HH adherence rates remain suboptimal.

METHODS

This quantitative descriptive study of ICU nurses in the southeastern United States was guided by the theory of planned behavior. The self-administered Patient Safety Opinion Survey and iScrub application, which facilitates observation, comprised the data set.

RESULTS

Nurses' observed HH median was 55%; tendency to self-report was a much higher 90%. Subjective norm and perceived control scores were associated with observed and self-reported HH (P < .05) but not attitude scores or reports of intention.

CONCLUSIONS

Nurses' subjective norm and perceived control are associated with observed and self-reported HH performance. Healthcare workers overestimate their HH performance. Findings suggest future research to explore manipulators of these variables to change nurses' HH behavior.
Developing and Testing an International Audit of Nursing Quality Indicators for Older Adults With Fragility Hip Fracture
Authors: MacDonald Valerie , Maher Ann Butler , Mainz Hanne , Meehan Anita J. , Brent Louise , Hommel Ami , Hertz Karen , Taylor Anita , Sheehan Katie Jane
Published: March 2018

BACKGROUND:

Fragility hip fracture in older adults often has poor outcomes, but these outcomes can be improved with attention to specific quality care indicators.

PURPOSE:

The International Collaboration of Orthopaedic Nursing (ICON) developed an audit process to identify the extent to which internationally accepted nursing quality care indicators for older adults with fragility hip fracture are reflected in policies, protocols, and processes guiding acute care.

METHODS:

A data abstraction tool was created for each of 12 quality indicators. Data were collected using a mixed-methods approach with unstructured rounds. A rationale document providing evidence for the quality indicators and a user evaluation form were included with the audit tool. A purposeful sample of 35 acute care hospitals representing 7 countries was selected.

RESULTS:

Thirty-five hospitals (100%) completed the survey. Respondents viewed the content as relevant and applicable for the defined patient population. Although timing and frequency of implementation varied among and within countries, the identified quality indicators were reflected in the majority of policies, protocols, or processes guiding care in the hospitals surveyed.

CONCLUSION:

Developing and testing an audit of nurse-sensitive quality indicators for older adults with fragility hip fracture demonstrate international consensus on common core best practices to ensure optimal acute care.
The FL/AC Ratio for Prediction of Shoulder Dystocia in Women With Gestational Diabetes
Authors: Duryea Elaine L. , Casey Brian M. , McIntire Donald D. , Twickler Diane M.
Published: March 2018

(Abstracted from J Matern Fetal Neonatal Med 2017;30(19):2378–2381)

Shoulder dystocia in vaginal deliveries can result in neonatal brachial plexus palsy (NBPP), requiring multiple surgical interventions and resulting in severe long-term disability. Sonographic predictors of shoulder dystocia are of particular interest in women with gestational diabetes mellitus (GDM) as GDM increases the risk of shoulder dystocia.
Premature Ovarian Insufficiency in Childhood Cancer Survivors: A Report From the St. Jude Lifetime Cohort
Authors: Chemaitilly Wassim , Li Zhenghong , Krasin Matthew J. , Brooke Russell J. , Wilson Carmen L. , Green Daniel M. , Klosky James L. , Barnes Nicole , Clark Karen L. , Farr Jonathan B. , Fernandez-Pineda Israel , Bishop Michael W. , Metzger Monika , Pui Ching-Hon , Kaste Sue C. , Ness Kirsten K. , Srivastava Deo Kumar , Robison Leslie L. , Hudson Melissa M. , Yasui Yutaka , Sklar Charles A.
Published: March 2018

(Abstracted from J Clin Endocrinol Metab 2017;102:2242–2250)

Survivors of childhood cancer are at an increased risk of premature ovarian insufficiency (POI) because of the vulnerability of the ovaries to pelvic radiotherapy, alkylating agent chemotherapy, and other gonadotoxic treatment modalities. Although POI can occur early, during, or immediately following cancer treatment completion, it more commonly develops in the years following completion of cancer treatment but prior to age 40 years.
Efficacy of Bedside Respiratory Muscle Training in Patients With Stroke
Authors: Yoo Hyun-Joon , Pyun Sung-Bom
Published: March 2018

Objective

Inspiratory and expiratory muscles are important for effective respiratory function. This study aimed to investigate the efficacy of bedside respiratory muscle training on pulmonary function and stroke-related disabilities in stroke rehabilitation.

Design

Patients with stroke (N = 40) in a rehabilitation unit were randomly assigned to either the intervention group (n
1 = 20) or the control group (n
2 = 20). Both groups participated in a conventional stroke rehabilitation program. During the study period, the intervention group received bedside respiratory muscle training twice a day for 3 wks. The respiratory muscle training consisted of (1) a breath stacking exercise, (2) inspiratory muscle training, and (3) expiratory muscle training. The primary outcomes were measures of pulmonary function: forced vital capacity, forced expiratory volume in 1 sec, and peak flow. Secondary outcomes were stroke-related disabilities assessed using the National Institutes of Health Stroke Scale, Modified Barthel Index, Berg Balance Scale, Fugl-Meyer Assessment, the Korean Mini-Mental State Examination, and pneumonia incidence.

Results

Pulmonary function was significantly improved in the intervention group after 3 wks of respiratory muscle training (P < 0.05). This improvement in pulmonary function was independent of the improvement in stroke-related disabilities.

Conclusion

Three weeks of respiratory muscle training had significant effects on pulmonary function in stroke survivors.

To Claim CME Credits

Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME

CME Objectives

Upon completion of this article, the reader should be able to: (1) Appreciate the respiratory function changes that occur in patients following a stroke; (2) Describe appropriate inspiratory and expiratory muscle training techniques to improve pulmonary function in patients following a stroke; (3) Enhance ability to implement inpatient; and (4) Determine appropriate respiratory training programs for patients following stroke.

Level

Advanced

Accreditation

The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Cystic Progression of a Cavernous Malformation at the Level of the Trigeminal Root Entry Zone Presenting With Sudden Onset of Trigeminal Neuralgia
Authors: Giacobbo Scavo Carlo , Roperto Raffaelino , Cacciotti Guglielmo , Mastronardi Luciano
Published: March 2018

Background:

Cavernous malformations (CM) in the cerebellopontine angle (CPA) are rare, and most of them are solid and extend from the internal auditory canal into the CPA. In contrast, cystic CM arising in the CPA and not involving the internal auditory canal and dura of the skull base are extremely rare. The authors present an uncommon large cystic progression of a cavernous malformation at the level of the trigeminal root entry zone evolving to severe trigeminal neuralgia and brainstem compression.

Methods:

A 62-year-old female presented a sudden onset of left trigeminal neuralgia, caused by a large cystic lesion at the level of the root entry zone of the left 5th nerve. On neurological examination, she showed slight gait ataxia and hypoesthesia on the left hemiface (on the first and second trigeminal branches). Other cranial nerves were in order. Magnetic resonance imaging showed a large cystic intracranial mass, with a small solid portion, leading to brainstem compression.

Results:

Microsurgical removal of the lesion was performed via retrosigmoid approach, with intraoperative monitoring of somato-sensory evoked potentials, facial, and cochlear nerves. The posterior-medial portion of the lesion was solid, whereas the main portion was cystic, containing xanthochromic fluid. The small solid lesion continued with a thin capsule of a large cyst adherent to brainstem, cerebellar hemisphere, and trigeminal nerve entry zone. A big draining vein arising from the solid part of the lesion runned parallel to brainstem. The mass was piecemeal totally removed.

After surgery the patient recovered both left trigeminal neuralgia and hypoesthesia; ataxia was significantly relieved too. Postoperative magnetic resonance imaging confirmed the total removal. Histopathological features were consistent with a CM. At 6-month follow-up, patient's symptoms at the presentation had resolved.

Conclusion:

The authors present a very rare patient of large cystic cavernous malformation at the level of the trigeminal root entry zone presenting with sudden onset of trigeminal neuralgia. Even if it has not established imaging features, a cystic cavernoma of the cerebello-pontine angle may be suspected when a cystic mass is present, not involving the internal acoustic meatus nor the skull base dura mater. Careful microneurosurgical technique and monitoring of cranial nerves allow good long-term results.
Evaluation of Fibrin Clot Attachment on Titanium Laser-Conditioned Surface Using Scanning Electron Microscopy
Authors: Sinjari Bruna , Traini Tonino , Caputi Sergio , Mortellaro Carmen , Scarano Antonio
Published: March 2018

Objectives:

The study aimed to evaluate the effects of different titanium surface treatments on blood clot extension (bce).

Methods:

A total of 54 titanium disks with machined surface (M), laser-conditioned surface (L), and grit-blasted surface (S) were used in the present study. The surface characteristics such as contact angles and the microroughness were determined on each group (n = 4). To evaluate the bce, 0.1 mL of human blood was dropped onto the surface of each specimen and left for 7 minutes at room temperature. After fixation, dehydration, and gold sputtering treatments, the specimens were observed under scanning electron microscope. The bce values were expressed as percentage of specimen surface covered by blood clot.

Results:

The surface roughness (Ra ± standard deviation [SD]) was 0.75 ± 0.02 μm for M, 0.25 ± 0.02 μm for L, and 1.30 ± 0.03 μm for S. The contact angles measured in static conditions (WCA ± SD) were 71 ± 5.4° for M, 107 ± 6.6° for L, and 91 ± 7.2° for S. Regarding the bce (bce ± SD) of M samples (65.5 ± 4.3%) was statistically lower compared with both L (83.4 ± 5.1%) and S samples (72.4 ± 4.7%) (P < 0.05). Meanwhile, the L group showed the higher bce value.

Conclusion:

The present results suggest that the laser-conditioned surface may increase the wettability and bce.
Subunit Reconstruction of Mid-Facial Defects With Free Style Facial Perforator Flaps
Authors: Dölen Utku Can , Baltu Yahya , Aydin Orhan
Published: March 2018

Introduction:

Reconstruction of facial defects is not only important for cosmesis but also for the function. Local flaps are considered the best reconstruction method for facial defects. The authors want to show the feasibility of free style facial perforator flap for the reconstruction of moderate sized mid-facial defects.

Methods:

Free style facial artery and lateral nasal artery perforator flaps were performed in 22 patients (11 males and 11 females) who had removal of facial tumor between March 2015 and December 2016

Results:

The median age of patients was 62 years (range: 35–84). The mean follow-up period was 12.6 months (range: 5–24). Pathology results were basal cell carcinoma in 13 patients, squamous cell carcinoma in 6 patients, and other skin tumors in 3 patients. The defect size ranged from 2 × 2 to 5 × 5 cm. No major or minor complication happened but 1 flap had venous congestion that healed without any intervention

Conclusion:

Free style facial perforator flaps are highly reliable flaps with wide range of motion. In addition, they provide single-stage closure with esthetic subunit reconstruction. With the current knowledge of reconstruction and skills of microsurgery, they can be easily the first choice for the closure of mid-facial defects.
Transcriptome Landscape of Human Oocytes and Granulosa Cells Throughout Folliculogenesis
Authors: Zhang Yaoyao , Yan Zhiqiang , Qin Qingyuan , Nisenblat Vicki , Yu Yang , Wang Tianren , Lu Cuiling , Yang Ming , Yang Shuo , Yao Ying , Zhu Xiaohui , Xia Xi , Dang Yujiao , Ren Yixin , Yuan Peng , Li Rong , Liu Ping , Guo Hongyan , Han Jinsong , He Haojie , Wu Yu , Li Meng , Zhang Kun , Wang Yiting , Qiao Jie , Yan Jie , Yan Liying
Published: March 2018

Folliculogenesis is a highly regulated process that involves bidirectional interactions of the oocytes and surrounding granulosa cells (GCs). Little is unknown, however, about the transcriptomic profiles of human oocytes and GCs throughout folliculogenesis. Here we performed a high resolution RNA-Seq of human oocytes and GCs at each follicular stage, which revealed unique transcriptional profiles, stage-specific signature genes, oocyte- and GC-derived genes that reflect ovarian reserve. We identified reciprocal cell-to-cell interactions between oocytes and GCs, including NOTCH, TGF-β signaling and gap junctions and determined the expression patterns of maternal-effect genes involved in folliculogenesis and early embryogenesis. Finally, we demonstrated robust differences between human and mice oocyte transcriptomes. This is the first comprehensive overview of the transcriptomic signatures governing the stepwise human folliculogenesis in-vivo that provides a valuable resource for basic and translational research in human reproductive biology.
A novel time-stamp mechanism transforms egocentric encounters into an allocentric spatial representation
Authors: Wallach Avner , Harvey-Girard Erik , Jun James Jaeyoon , Longtin André , Maler Leonard
Published: March 2018

Learning the spatial organization of the environment is essential for most animals’ survival. This often requires the animal to derive allocentric information about the environment from egocentric sensory and motor experience. The neural circuits and mechanisms underlying this transformation are currently unknown. We addressed this problem in electric fish, which can precisely navigate in complete darkness and whose requisite brain circuitry is relatively simple. We conducted the first neural recordings in the preglomerular complex, the thalamic region exclusively connecting the optic tectum with the spatial learning circuits in the dorsolateral pallium. While tectal egocentric information was eliminated in preglomerular neurons, the time-intervals between object encounters were precisely encoded. We show that this highly-reliable temporal information, combined with a speed signal, can permit accurate path-integration that then enables computing allocentric spatial relations. Our results suggest that similar mechanisms are involved in spatial learning via sequential encounters in all vertebrates.
More is less: increased processing of unwanted memories facilitates forgetting
Authors: Wang Tracy H. , Placek Katerina , Lewis-Peacock Jarrod A.
Published: March 2018

The intention to forget can produce long-lasting effects. This ability has been linked to suppression of both rehearsal and retrieval of unwanted memories – processes that are mediated by prefrontal cortex and hippocampus. Here, we describe an alternative account of deliberate forgetting in which the intention to forget is associated with increased engagement with the unwanted information. We used pattern classifiers to decode functional magnetic resonance imaging (fMRI) data from a task in which participants viewed a series of pictures and were instructed to remember or forget each one. Pictures followed by a forget instruction elicited higher levels of processing in ventral temporal cortex compared to those followed by a remember instruction. This boost in processing led to more forgetting, particularly for items that showed moderate (vs. weak or strong) activation. This result is consistent with the non-monotonic plasticity hypothesis, which predicts weakening and forgetting of memories that are moderately activated.
Methylthioadenosine reduces host inflammatory response by suppressingSalmonellavirulence
Authors: Bourgeois Jeffrey S. , Zhou Daoguo , Thurston Teresa L. M. , Gilchrist James J. , Koa Dennis C.
Published: March 2018

In order to deploy virulence factors at appropriate times and locations, microbes must rapidly sense and respond to various metabolite signals. Previously we showed transient elevation of the methionine-derived metabolite methylthioadenosine (MTA) in serum during systemicSalmonella entericaserovar Typhimurium (S.Typhimurium) infection. Here we explored the functional consequences of increased MTA concentrations onS.Typhimurium virulence. We found that MTA—but not other related metabolites involved in polyamine synthesis and methionine salvage—reduced motility, host cell pyroptosis, and cellular invasion. Further, we developed a genetic model of increased bacterial endogenous MTA production by knocking out the master repressor of the methionine regulon,metJ. Like MTA treatedS.Typhimurium, the ΔmetJmutant displayed reduced motility, host cell pyroptosis, and invasion. These phenotypic effects of MTA correlated with suppression of flagellar andSalmonellapathogenicity island-1 (SPI-1) networks. ΔmetJ S.Typhimurium had reduced virulence in oral infection of C57BL/6 mice. Finally, ΔmetJbacteria induced a less severe inflammatory cytokine response in a mouse sepsis model. These data provide a possible bacterial mechanism for our previous findings that pretreating mice with MTA dampens inflammation and prolongs survival. Together, these data indicate that exposure ofS.Typhimurium to MTA or disruption of the bacterial methionine metabolism pathway is sufficient to suppress SPI-1 mediated processes, motility, andin vivovirulence.

Significance

Salmonella entericaserovar Typhimurium (S. Typhimurium) is a leading cause of gastroenteritis and bacteremia worldwide. Widespread multi-drug resistance, inadequate diagnostics, and the absence of a vaccine for use in humans, all contribute to the global burden of morbidity and mortality associated withS.Typhimurium infection. Here we find that increasing the concentration of the methionine derived metabolite methylthioadenosine, either inS.Typhimurium or in its environment, is sufficient to suppress virulence processes. These findings could be leveraged to inform future therapeutic interventions againstS.Typhimurium aimed at manipulating either host or pathogen methylthioadenosine production.
Enrichment of gene variants associated with treatable genetic disorders in psychiatric populations
Authors: Sriretnakumar Venuja , Harripaul Ricardo , Vincent John B. , Kennedy James L. , So Joyce
Published: March 2018

Purpose

Many genetic conditions can mimic mental health disorders, with psychiatric symptoms that are difficult to treat with standard psychotropic medications. This study tests the hypothesis that psychiatric populations are enriched for pathogenic variants associated with selected treatable genetic disorders.

Methods

Using next-generation sequencing, 2046 psychiatric patients were screened for variants in genes associated with four inborn errors of metabolism (IEMs), Niemann-Pick disease type C (NPC), Wilson disease (WD), homocystinuria (HOM), and acute intermittent porphyria (AIP).

Results

Among the 2046 cases, carrier rates of 0·83%, 0·98%, 0·20%, and 0·24% for NPC, WD, HOM, and AIP were seen respectively. An enrichment of known and likely pathogenic variants in the genes associated with NPC and AIP was found in the psychiatric cohort, and especially in schizophrenia patients.

Conclusion

The results of this study support that rare genetic disease variants, such as those associated with IEMs, may contribute to the pathogenesis of psychiatric disorders. IEMs should be considered as possible causative factors for psychiatric presentations, especially in psychotic disorders, such as schizophrenia, and in the context of poor treatment response.
Inhibition of norepinephrine signaling during a sensitive period disrupts locus coeruleus circuitry and emotional behaviors in adulthood
Authors: Meng Qingyuan , Garcia-Garcia Alvaro L. , Dranovsky Alex , Leonardo E. David
Published: March 2018

Deficits in arousal and stress responsiveness span numerous psychiatric developmental disorders including depression and anxiety. Arousal is supported by norepinephrine (NE) released from locus coeruleus (LC) neurons onto cortical and limbic areas. During development, the NE system matures in concert with increased exploration of the animal’s environment. While several psychiatric medications target the LC-NE system, the possibility that its modulation during discreet developmental periods can have long-lasting consequences for mental health has not been explored. We used a pharmacogenetic strategy in mice to reversibly inhibit NE signaling during brief developmental periods to determine the long-lasting impact on adult circuits mediating emotional behavior. We also examine whether disruption of NE signaling during development results in permanent changes within the adult LC-NE system. Finally, we test whether developmental exposure to the α-2 receptor agonist guanfacine recapitulates the effect seen with our pharmacogenetic strategy. Our results reveal a sensitive period (postnatal days 10-21) during which alterations in NE signaling result in long-term changes in adult emotional behavior. Changes in NE signaling during this sensitive period results in changes in stress-related LC neuron activity, alterations in α-2 autoreceptor function, and circuit-specific molecular changes in LC-NE target regions in adulthood. Treating animals with guanfacine during the sensitive period produced similar results. Our findings indicate an early critical role for NE in sculpting brain circuits that support adult emotional function.
Human activity is altering the world’s zoogeographical regions
Authors: Bernardo-Madrid Rubén , Calatayud Joaquín , González-Suarez Manuela , Rosvall Martin , Lucas Pablo M. , Rueda Marta , Antonelli Alexandre , Revilla Eloy
Published: March 2018

Human activity leading to both species introductions and extinctions is widely known to influence diversity patterns on local and regional scales. Yet, it is largely unknown whether the intensity of this activity is enough to affect the configuration of biodiversity at broader levels of spatial organization. Zoogeographical regions, or zooregions, are surfaces of the Earth defined by characteristic pools of species, which reflect ecological, historical, and evolutionary processes acting over millions of years. Consequently, it is widely assumed that zooregions are robust and unlikely to change on a human timescale. Here, however, we show that human-mediated introductions and extinctions can indeed reconfigure the currently recognized zooregions of amphibians, mammals, and birds. In particular, introductions homogenize the African and Eurasian zooregions in mammals; reshape boundaries with the reallocation of Oceania to the New World zooregion in amphibians; and divide bird zooregions by increasing biotic heterogeneity. Furthermore, the combined effect of amphibian introductions and extinctions has the potential to divide two zooregions largely representing the Old and the New World. Interestingly, the robustness of zooregions against changes in species composition may largely explain such zoogeographical changes. Altogether, our results demonstrate that human activities can erode the higher-level organization of biodiversity formed over millions of years. Comparable reconfigurations have previously been detectable in Earth’s history only after glaciations and mass extinction events, highlighting the profound and far-reaching impact of ongoing human activity and the need to protect the uniqueness of biotic assemblages from the effects of future species introductions and extinctions.
A Polygenic Score for Higher Educational Attainment is Associated with Larger Brains
Authors: Elliott Maxwell L. , Belsky Daniel W , Anderson Kevin , Corcoran David L. , Ge Tian , Knodt Annchen , Prinz Joseph A. , Sugden Karen , Williams Benjamin , Ireland David , Poulton Richie , Caspi Avshalom , Holmes Avram , Moffitt Terrie , Hariri Ahmad R
Published: March 2018

People who score higher on intelligence tests tend to have larger brains. Twin studies suggest the same genetic factors influence both brain size and intelligence. This has led to the hypothesis that genetics influence intelligence partly by contributing to development of larger brains. We tested this hypothesis with molecular genetic data using discoveries from a genome-wide association study (GWAS) of educational attainment, a correlate of intelligence. We analyzed genetic, brain imaging, and cognitive test data from the UK Biobank, the Dunedin Study, the Brain Genomics Superstruct Project (GSP), and the Duke Neurogenetics Study (DNS) (combined N=8,271). We measured genetics using polygenic scores based on published GWAS. We conducted meta-analysis to test associations among participants’ genetics, total brain volume (i.e., brain size), and cognitive test performance. Consistent with previous findings, participants with higher polygenic scores achieved higher scores on cognitive tests, as did participants with larger brains. Participants with higher polygenic scores also had larger brains. We found some evidence that brain size partly mediated associations between participants’ education polygenic scores and their cognitive test performance. Effect-sizes were larger in the population-based UK Biobank and Dunedin samples than in the GSP and DNS samples. Sensitivity analysis suggested this effect-size difference partly reflected restricted range of cognitive performance in the GSP and DNS samples. Recruitment and retention of population-representative samples should be a priority for neuroscience research. Findings suggest promise for studies integrating GWAS discoveries with brain imaging data to understand neurobiology linking genetics with individual differences in cognitive performance.
Nanoscale spatio-temporal diffusion modes measured by simultaneous confocal and STED imaging
Authors: Schneider Falk , Waithe Dominic , Galiani Silvia , de la Serna Jorge Bernadino , Sezgin Erdinc , Eggeling Christian
Published: March 2018

The diffusion dynamics in the cellular plasma membrane provides crucial insights into the molecular interactions, organization and bioactivity. Fluorescence correlation spectroscopy combined with super-resolution stimulated emission depletion nanoscopy (STED-FCS) measures such dynamics with high spatial and temporal resolution and reveals nanoscale diffusion characteristics by measuring the molecular diffusion in conventional confocal mode and super-resolved STED mode sequentially. However, to directly link the spatial and the temporal information, a method that simultaneously measures the diffusion in confocal and STED modes is needed. Here, to overcome this problem, we establish an advanced STED-FCS measurement method; line interleaved excitation scanning STED-FCS (LIESS-FCS) which discloses the molecular diffusion modes at different spatial positions with a single measurement. It relies on fast beam-scanning along a line with alternating laser illumination that yields, for each pixel, the apparent diffusion coefficients for two different observation spot sizes (conventional confocal and super-resolved STED). We demonstrate the potential of the LIESS-FCS approach with simulations and experiments on lipid diffusion in model and live cell plasma membranes. We also apply LIESS-FCS to investigate the spatio-temporal organization of GPI-anchored proteins in the plasma membrane of live cells which interestingly show multiple diffusion modes at different spatial positions.
SSMART: Sequence-structure motif identification for RNA-binding proteins
Authors: Munteanu Alina , Mukherjee Neelanjan , Ohler Uwe
Published: March 2018

Motivation

RNA-binding proteins (RBPs) regulate every aspect of RNA metabolism and function. There are hundreds of RBPs encoded in the eukaryotic genomes, and each recognize its RNA targets through a specific mixture of RNA sequence and structure properties. For most RBPs, however, only a primary sequence motif has been determined, while the structure of the binding sites is uncharacterized.

Results

We developed SSMART, an RNA motif finder that simultaneously models the primary sequence and the structural properties of the RNA targets sites. The sequence-structure motifs are represented as consensus strings over a degenerate alphabet, extending the IUPAC codes for nucleotides to account for secondary structure preferences. Evaluation on synthetic data showed that SSMART is able to recover both sequence and structure motifs implanted into 3‘UTR-like sequences, for various degrees of structured/unstructured binding sites. In addition, we successfully used SSMART on high-throughput in vivo and in vitro data, showing that we not only recover the known sequence motif, but also gain insight into the structural preferences of the RBP.

Availability

SSMART is freely available at https://ohlerlab.mdc-berlin.de/software/SSMART_137/

Contact

uwe.ohler@mdc-berlin.de
Urothelial organoids originate from Cd49fHighstem cells and display Notch-dependent differentiation capacity
Authors: Santos Catarina P. , Lapi Eleonora , Álvaro-Espinosa Laura , Fernández-Barral Asunción , Barbáchano Antonio , Megías Diego , Muñoz Alberto , Real Francisco X
Published: March 2018

The urothelium is a specialized stratified epithelium with unique structural and functional features. Understanding the mechanisms involved in urothelial stem cell biology and differentiation has been limited by the lack of methods for unlimited propagation. Here, we establish normal mouse urothelial organoid (NMU-o) cultures that can be maintained uninterruptedly for >1 year. Organoid growth is dependent on EGF and Wnt activators. High CD49f/ITGA6 expression features a subpopulation of organoid-forming urothelial stem cells expressing basal markers. On induction of differentiation, multilayered organoids show reduced layer number, acquire barrier function, and activate the urothelial program, including expression of uroplakins and tight junction components. Combined pharmacological modulation of PPARγ and EGFR was most potent driving cell differentiation. Transcriptome analysis of organoids widely validates the system, highlights the transcriptional networks involved, and reveals NOTCH signaling as a novel pathway required for normal urothelial organoid differentiation.
Model-based Pavlovian control of attention to threat
Authors: Talmi D , Slapkova M , Wieser MJ
Published: March 2018

Signals for reward or punishment attract attention preferentially, a principle termed ‘value-modulated attention capture’ (VMAC). The mechanisms that govern the allocation of attention resources can be productively described with a terminology that is more often applied to the control of overt behaviours, namely, the distinction between instrumental and Pavlovian control, and between model-free and model-based control. While instrumental control of VMAC can be either model-free or model-based, it is not known whether Pavlovian control of VMAC can be model-based. To decide whether this is possible we measured Steady-State Visual Evoked Potentials (SSVEPs) while 20 healthy adults took part in a novel task. During the learning stage participants underwent aversive threat conditioning with two CSs, one that predicted pain (CS+) and one that predicted safety (CS-). Instructions given prior to the test stage in the task allowed participants to infer whether novel, ambiguous CSs (new CS+/ new CS-) were threatening or safe. Correct inference required combining stored internal representations and new propositional information, the hallmark of model-based control. SSVEP amplitudes quantified the amount of attention allocated to novel CSs on their very first presentation, before they were ever reinforced. We found that SSVEPs were higher for new CS+ than new CS-. Because task design precluded model-free or instrumental control this result demonstrates a model-based Pavlovian control of VMAC. It confirms, in the domain of internal resource allocation, the model-based Pavlovian control of incentive behaviour and underlines the potential transformative role of information as an emotion regulation technique.