bluuebunny/crossref_metadata_2025 huggingface dataset:
Osteoma Cutis Arising in Common Blue Nevus (Blue Osteonevus): A Clinicopathologic, Immunohistochemical, and Dermoscopic Study
Authors: López-Robles Joaquín , Pérez-Plaza Alejandra , Requena Luis , Santonja Carlos
Published: June 2018

Osteonevus of Nanta is a rare histopathologic variant of melanocytic nevus that results from ossification of the dermis between dermal nests of melanocytes. Most cases described in the literature have been associated with long-standing intradermal nevi and were often located in the upper part of the body. We report a lesion on the shoulder of an elderly man showing the association of a common blue nevus and osteoma cutis, an exceptional feature which has been previously reported in 2 instances. We also describe for the first time the dermoscopic appearance of this “blue osteonevus.”
Impact of Dermoscopy and Reflectance Confocal Microscopy on the Histopathologic Diagnosis of Lentigo Maligna/Lentigo Maligna Melanoma
Authors: Mataca Ema , Migaldi Mario , Cesinaro Anna M.
Published: June 2018

Background:

Equivocal pigmented lesions of the head are usually biopsied to avoid inappropriate treatment. Clinical approach has evolved from simple visual examination to sophisticated techniques for selecting the biopsy sites.

Objective:

This study aimed to retrospectively evaluate the efficiency of dermoscopy (DE) and reflectance confocal microscopy (RCM) in sampling a histopathologically representative focus of lentigo maligna/lentigo maligna melanoma.

Methods:

Punch biopsies and surgical excisions of 72 patients, 37 men and 35 women (median age 70.6 years, range 39–90 years), affected by lentigo maligna/lentigo maligna melanoma of the head, sent from a single dermatology clinic, were reviewed for the presence of 5 histopathologic criteria: atypical junctional melanocytes, increased junctional melanocytes, follicular colonization, pagetoid spread and melanocytic junctional nests, plus other minor features. Forty-two patients were biopsied under DE and 30 under RCM guidance.

Results:

Accuracy of the 2 techniques in sampling a representative tissue overlapped in most cases, although RCM selected sites to biopsy with more histopathologic criteria, in particular pagetoid spread and melanocytic nests. Interestingly, with RCM, inflammation and melanophages were observed more in biopsy than in excision. False positive cases were not registered.

Conclusion:

Compared with the sampling at naked eye, our results show that DE and RCM help selecting the most appropriate areas for biopsies, thus allowing not only more robust histopathologic diagnoses, but also a more accurate microstaging of tumor.
Adverse events related to Trendelenburg position during laparoscopic surgery: recommendations and review of the literature
Authors: Arvizo Cynthia , Mehta Sumit T. , Yunker Amanda
Published: June 2018

Purpose of review

Laparoscopy is routinely performed for the treatment and management of gynaecologic disorders. During gynaecologic laparoscopy, the patient is placed in the Trendelenburg position to optimize visualization and access to the pelvis. The Trendelenburg position may result in complications in many organ systems.

Recent findings

Trendelenburg positioning may cause rare, potentially life-threatening complications of the respiratory and cardiovascular systems. Case reports of visual field loss and cognitive aberrations following Trendelenburg positioning have been published. Few intervention studies have been performed evaluating attenuation of changes in intraocular pressure and haemodynamics.

This review summarizes possible complications related to the Trendelenburg position and current evidence regarding interventions to minimize the risk of complications.
Spontaneous Coronary Artery Dissection (SCAD)
Authors: Wagers Tina Pittman , Stevens Courtney J. , Ross Kaitlin V. , Leon Katherine Kelly , Masters Kevin S.
Published: June 2018

Purpose:

Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic type of acute myocardial infarction that primarily affects young, healthy women without typical risk factors for heart disease. Few investigations have examined psychosocial variables in this population and none have looked at patient perceptions of the experience and stresses associated with having a SCAD event or the resources currently available to SCAD survivors. This investigation describes survivors' subjective experiences of SCAD. Participants also provided information about types and helpfulness of resources available to them post-SCAD, including cardiac rehabilitation.

Methods:

Participants were recruited online and completed a one-time questionnaire.

Results:

Participants (n = 409) completed a questionnaire concerning their experiences with their SCAD event in the 1 y and 2 wk prior to the SCAD event. Their responses reflected moderate to high perceptions of stress. Participants experienced the SCAD event as highly stressful and frightening and their heart health presents as a moderate-severe source of current, post-diagnosis stress. Spontaneous coronary artery dissection–based informational support was frequently rated as inadequate, whereas other supportive resources varied in their helpfulness and accessibility. Participants reported positive experiences in cardiac rehabilitation and strong interest in SCAD-specific, professionally led, online patient education and support groups.

Conclusions:

This study is the largest to date investigation of SCAD survivors and their experiences in this understudied and perhaps underrecognized condition. Opportunities for researchers and providers to develop, tailor, and disseminate SCAD-specific interventions are discussed.
Injectable Corticosteroids in Sport
Authors: Olafsen Nathan P. , Herring Stanley A. , Orchard John W.
Published: June 2018

Objective:

To review the literature guiding all aspects of the use of injectable corticosteroids for painful musculoskeletal conditions, with a focus on the treatment of athletes.

Data Sources:

An extensive search of the literature was completed including search terms of corticosteroid, steroid, athlete, and injection, among others. Additional articles were used after being identified from previously reviewed articles.

Main Results:

Injections of corticosteroids for a variety of painful conditions of the extremities and the axial spine have been described. Numerous minor and major complications have been reported, including those with a high degree of morbidity. There is a dearth of published research on the use of corticosteroid injections in athletes, with most of the research on this topic focused on older, nonathlete populations. Generally, these injections are well tolerated and can provide short-term pain improvement with little or no long-term benefits.

Conclusions:

Corticosteroid injections should be used cautiously in athletes and only after a full consideration of the pharmacology, pathogenesis of disease, potential benefits, complications, factors specific to the athlete, and rules of athletic governing bodies. Corticosteroid injections are just one component of a comprehensive rehabilitation plan available to the physician providing care to athletes.
Phototherapy on Management of Creatine Kinase Activity in General Versus Localized Exercise: A Systematic Review and Meta-Analysis
Authors: Machado Aryane Flauzino , Micheletti Jéssica Kirsch , Lopes Jaqueline Santos Silva , Vanderlei Franciele Marques , Leal-Junior Ernesto Cesar Pinto , Netto Junior Jayme , Pastre Carlos Marcelo
Published: June 2018

Objective:

The main focus of this systematic review was to determine the efficacy of phototherapy in the management of creatine kinase (CK) activity after exercise and furthermore to identify for which exercise model protocol phototherapy provides the best results.

Design:

Meta-analysis comparing phototherapy with a control condition.

Setting:

The MEDLINE, EMBASE, SPORTDiscus, PEDro, and CENTRAL databases were searched from their earliest records to October 03, 2016. Data were pooled in a meta-analysis and described as standardized mean difference (SMD) with 95% confidence intervals (CIs) using a random effects model.

Participants:

Healthy subjects (no restrictions were applied, eg, age, sex, and exercise level).

Intervention:

Phototherapy (low-level laser therapy and/or light-emitting diode therapy) before or after exercise and a placebo or control condition.

Main Outcome Measures:

Creatine kinase activity (no restriction to any analysis, eg, serum, plasma, or capillary blood).

Results:

Fourteen studies were included for review. The results revealed that phototherapy has a more positive effect than control condition in management of CK activity [SMD = 0.77, 95% CI (0.32 to 1.22); P = 0.0007; I2 = 72%]. In exploratory analysis, the results showed that phototherapy was effective only in the exercise protocol with localized exercise with large effect size [localized exercise: SMD = 0.89, 95% CI (0.26 to 1.51); P = 0.0002; I2 = 76%; general exercise: SMD = 0.61, 95% CI (−0.05 to 1.26); P = 0.07; I2 = 67%].

Conclusions:

The available evidence suggest that phototherapy has beneficial effects on the management of CK activity and demonstrate a possible relationship based on damage caused by exercise, providing a greater effect in studies that used localized exercise.
Concussion Symptom Profiles Among Child, Adolescent, and Young Adult Athletes
Authors: Howell David R. , Kriz Peter , Mannix Rebekah C. , Kirchberg Tyler , Master Christina L. , Meehan William P.
Published: June 2018

Objectives:

(1) To examine how age influences initial symptom presentation following concussion; and (2) to determine whether specific symptom profiles are associated with duration of postconcussion symptoms, and whether they vary by age group.

Design:

A total of 689 patients (20% children 7-12 years of age, 69% adolescents 13-18 years of age, and 11% young adults 19-30 years of age) were seen and diagnosed with a concussion within 21 days after injury. Patients completed the Post-Concussion Symptom Scale (PCSS) and were followed until they no longer required care.

Setting:

Two specialty care sport concussion clinical practices.

Main outcome measures:

Overall PCSS score was obtained, as well as severity ratings from somatic, vestibular–ocular, cognitive, sleep, and emotional symptom domains. We also calculated total symptom duration time.

Results:

No significant main effect of age, or age by sex associations were identified among the symptom domains. Females endorsed a higher somatic symptom severity rating than males (9.8 ± 6.7 vs 8.1 ± 6.7; P = 0.03). For patients between 7 and 12 years of age, higher somatic [β-coefficient = 1.57, 95% confidence interval (CI), 1.47-1.67] and cognitive (β-coefficient = 2.50, 95% CI, 2.32-2.68) symptom severities were associated with longer duration of concussion symptoms. Among adolescents, longer total symptom duration was associated with more severe somatic (β-coefficient = 1.25, 95% CI, 0.34-2.15) and vestibular–ocular (β-coefficient = 2.36, 95% CI, 1.49-3.23) symptoms.

Conclusions:

Within 21 days after concussion, symptom-reporting behavior seems to be similar across the age spectrum, but the relationship between symptom profiles and time to symptom resolution varies by age. Although overall symptom ratings are beneficial in determining clinical pathways, symptom domain use may provide a beneficial method to determine individualized patient care that differs between children and adolescents after concussion.
Abdominal Obesity is More Predictive of Advanced Colorectal Neoplasia Risk Than Overall Obesity in Men
Authors: Kim Nam Hee , Jung Yoon Suk , Park Jung Ho , Park Dong Il , Sohn Chong Il
Published: June 2018

Goals:

We aimed to ascertain whether waist circumference (WC) is associated with risk of colorectal neoplasia (CRN), independent of body mass index (BMI).

Background:

Although several studies have reported the association between abdominal obesity, measured by WC, and CRN, it remains unclear whether their association is biased by BMI.

Study:

A cross-sectional study was performed on 154,552 asymptomatic examinees who underwent colonoscopy for a health check-up.

Results:

The mean age was 42.6 years, and the proportion of males was 65.2%. The prevalence rate of CRN in subjects in WC quartiles 1, 2, 3, and 4 was 15.6%, 18.1%, 20.4%, and 22.0% among men and 7.8%, 9.4%, 12.2%, and 15.8% among women, respectively. WC and BMI were independent risk factors for overall CRN and nonadvanced CRN in both men and women. In men, the association of BMI with advanced CRN was attenuated to null after adjusting for WC [Q2, Q3, and Q4 vs. Q1; odds ratios (95% confidence intervals), 0.93 (0.79-1.10), 0.85 (0.71-1.03), and 0.99 (0.80-1.22), respectively; P
trend=0.822], whereas the association of WC with advanced CRN significantly persisted even after adjusting for BMI [Q2, Q3, and Q4 vs. Q1; 1.20 (1.02-1.42), 1.45 (1.20-1.75), and 1.64 (1.32-2.04), respectively; P
trend<0.001]. In women, neither WC nor BMI was associated with the risk of advanced CRN.

Conclusions:

Abdominal obesity is associated with an increased risk of advanced CRN, independent of overall obesity (BMI) in men. Our findings suggest that abdominal obesity is more strongly predictive of advanced CRN than overall obesity in men.
Why Effective Interventions Do Not Work for All Patients
Authors: Edlind Merritt , Mitra Nandita , Grande David , Barg Frances K. , Carter Tamala , Turr Lindsey , Glanz Karen , Long Judith A. , Kangovi Shreya
Published: June 2018

Background:

Half of all Americans have a chronic disease. Promoting healthy behaviors to decrease this burden is a national priority. A number of behavioral interventions have proven efficacy; yet even the most effective of these has high levels of nonresponse.

Objectives:

In this study, we explore variation in response to an evidence-based community health worker (CHW) intervention for chronic disease management.

Research Design:

We used a convergent parallel design that combined a randomized controlled trial with a qualitative process evaluation that triangulated chart abstraction, in-depth interviews and participant observation.

Subjects:

Eligible patients lived in a high-poverty region and were diagnosed with 2 or more of the following chronic diseases: diabetes, obesity, hypertension or tobacco dependence. There were 302 patients in the trial, 150 of whom were randomly assigned to the CHW intervention. Twenty patients and their CHWs were included in the qualitative evaluation.

Results:

We found minimal differences between responders and nonresponders by sociodemographic or clinical characteristics. A qualitative process evaluation revealed that health behavior change was challenging for all patients and most experienced failure (ie, gaining weight or relapsing with cigarettes) along the way. Responders seemed to increase their resolve after failed attempts at health behavior change, while nonresponders became discouraged and “shut down.”

Conclusions:

Failure is a common and consequential aspect of health behavior change; a deeper understanding of failure should inform chronic disease interventions.
Associations of CAHPS Composites With Global Ratings of the Doctor Vary by Medicare Beneficiaries’ Health Status
Authors: Hays Ron D. , Mallett Joshua S. , Haas Ann , Kahn Katherine L. , Martino Steven C. , Gaillot Sarah , Elliott Marc N.
Published: June 2018

Research Objective:

Care coordination among health care providers is essential for high-quality care and it is strongly associated with overall ratings of doctors. Care coordination may be especially important for sicker and chronically ill patients because of the multiple providers involved in their care. This study examines whether the association of care coordination with global ratings of one’s personal doctor varies by number of chronic conditions and self-rated health.

Study Design:

We used nationally representative Medicare Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey data to evaluate care coordination, doctor communication, getting needed care, getting care quickly, count of 6 chronic conditions (angina, cancer, chronic obstructive pulmonary disease, diabetes, heart attack, stroke), self-rated general health (5-point scale, poor to excellent, scored linearly), and interactions among them as predictors of the CAHPS global rating of personal doctor (scored 0–100 with 100 being best possible personal doctor) using linear regression models. The analytic sample included 242,871 Medicare fee-for-service and managed care beneficiaries in 2013: 56% female; 14% 18–64, 47% 65–74, 27% 75–84, and 11% 85 and older; and 48% high school education or less.

Results:

The CAHPS composites (of care coordination, doctor communication, getting needed care, and getting care quickly) and number of chronic conditions were significantly positively associated with ratings of personal doctor (P<0.05). Care coordination and doctor communication had a stronger association with positive ratings of the personal doctor among those with worse self-rated health (P<0.001).

Discussion:

Results were consistent with the hypothesis that patients in worse health weigh care coordination more heavily in global physician assessments than patients in better health. Emphasis on improving care coordination, especially for patients in poorer health, may improve patients’ overall assessments of their providers. The study provides further evidence for the importance of care coordination experiences in the era of patient-centered care.
Hopelessness, Death Anxiety, and Social Support of Hospitalized Patients With Gynecologic Cancer and Their Caregivers
Authors: Uslu-Sahan Fatma , Terzioglu Fusun , Koc Gulten
Published: June 2018

Background

Gynecologic cancer can create hopelessness and death anxiety and alter the lifestyle of the affected women and their caregivers. Perceived social support may facilitate coping with this illness.

Objective

The aim of this study was to determine whether hospitalized patients with gynecologic cancer and their caregivers differ in feelings of hopelessness and death anxiety and how those conditions may be related to their social support.

Methods

Two hundred patients with gynecologic cancer and their 200 caregivers from 1 university hospital were enrolled in this descriptive correlational study. Study measures included a demographic form, the Perceived Social Support Scale, the Beck Hopelessness Scale, and the Thorson-Powell's Death Anxiety Scale. Data were analyzed using Student t test, Pearson correlation test, and linear regression analyses.

Results

Patients had higher hopelessness and death anxiety compared with caregivers (P < .001). Patients' perceived social support explained 35% of the total variance in hopelessness and 28% of the variance in death anxiety; caregivers' perceived social support explained 40% of the total variance in hopelessness and 12% of the variance in death anxiety.

Conclusion

Patients felt hopelessness and death anxiety in greater rates than caregivers. Social support had a significant effect on hopelessness and death anxiety of patients and their caregivers.

Implications for Practice

Nurses, who are the healthcare professionals spending time with patients and families from diagnosis forward, need to evaluate patients and their caregivers for hopelessness and death anxiety and consider their social support systems during this evaluation.
Effectiveness of App-Based Self-acupressure for Women With Menstrual Pain Compared to Usual Care: A Randomized Pragmatic Trial
Authors: Blödt Susanne , Pach Daniel , von Eisenhart-Rothe Sanna , Lotz Fabian , Roll Stephanie , Icke Katja , Witt Claudia M.
Published: June 2018

(Abstracted from Am J Obstet Gynecol 2018;218:227.e1–227.e9)

Up to 81% of women of reproductive age are affected by primary dysmenorrhea. Approximately 15% of patients experience severe menstrual pain, which has a significant impact on their quality of life.
Inherited Metabolic Disorders: Implications for the Obstetrician-Gynecologist
Authors: Hopkins Maeve K. , Dugoff Lorraine , Kuller Jeffrey A.
Published: June 2018

Importance

Inherited metabolic disorders, or inborn errors of metabolism, can result in significant morbidity and mortality. Advances in genetic testing, including newborn screening and prenatal carrier screening, continue to increase awareness and highlight the importance of these conditions. Increasingly, women born with these conditions are surviving to adulthood, and many become pregnant. The practicing obstetrician-gynecologist should be familiar with the most common and the most relevant inherited metabolic disorders affecting women.

Objective

The objective of this review is to define inherited metabolic disorders that have relevance to the obstetrician-gynecologist. We discuss the diagnosis, presentation, epidemiology, and special concerns to the obstetrician-gynecologist managing patients affected by these conditions.

Evidence Acquisition

A MEDLINE search of “inherited metabolic disorders” and “inborn errors of metabolism” and specific conditions reported in the review was performed.

Results

The evidence cited in this review includes 8 case reports or case series, 4 text books, 1 systematic review, 1 American College of Obstetricians and Gynecologists committee opinion, and 18 additional peer-reviewed journal articles that were original research or expert opinion summaries.

Conclusions and Relevance

Inherited metabolic disorders manifest in diverse ways that have clinical implications for the obstetrician-gynecologist. Knowledge of these disorders and their pathophysiology and genetic basis can improve care provided for women affected by this diverse group of conditions. It is critical to assemble a multidisciplinary team of providers to optimize care for patients with inherited metabolic disorders.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the learner should be better able to compare selected types of inherited metabolic disorders regarding their impact on reproductive endocrinology, pregnancy, and gynecology; apply the basic principles of Mendelian inheritance when taking a family history and refer women with a personal or family history of inherited metabolic disorders to the appropriate genetics services and specialists; educate patients and other health care providers about the association of delayed menstruation, infertility, premature ovarian insufficiency, and high-risk pregnancy in women with a personal or family history of inherited metabolic disorders; and provide general preconception counseling to women with a known diagnosis of selected inherited metabolic disorders and appropriately refer them to a specialized team during gestation and postpartum.
Leak Compensation During Volume Guarantee With the Dräger Babylog VN500 Neonatal Ventilator*
Authors: Szakmar Eniko , Morley Colin J. , Belteki Gusztav
Published: June 2018

Objectives:

To investigate how compensating for endotracheal tube leaks by targeting the leak-compensated tidal volume affects measured physiologic and ventilator variables during neonatal mechanical ventilation.

Design:

Retrospective observational study.

Setting:

A level III Neonatal ICU.

Patients:

We enrolled 30 neonates who were ventilated using synchronized intermittent positive pressure mode with volume guarantee and had at least 12 hours of continuous detailed recording of ventilation variables.

Interventions:

Infants were treated using the Dräger VN500 ventilator (Dräger, Lübeck, Germany), which uses a proprietary algorithm to measure and compensate for endotracheal tube leaks. Eleven were ventilated without leak compensation and 19 with leak compensation.

Measurements and Main Results:

Detailed ventilation data were collected and analyzed at 1 Hz, with intermittent blood gas values. The percentage of leak was less than 20% in 73% of leak-compensated inflations, and the volume of the leak compensation was less than 1 mL/kg in 97.3% of inflations. Between the two groups, ventilation variables were comparable, except the percentage of leak that was significantly (p = 0.005) higher in the recordings with leak compensation. Without leak compensation, the mean expired tidal volume was maintained very close to the set level up to 50% leak, but with leaks greater than 50%, it declined progressively. With leak compensation, the mean leak-compensated expired tidal volume was well maintained even with leak greater than 90% although with large variability. Without leak compensation, the difference between the maximum allowed inflating pressure and the peak inflating pressure decreased progressively as the leak increased. This did not occur with leak compensation. The median Pco
2 was slightly higher with leak compensation.

Conclusions:

During volume guarantee ventilation with a Dräger VN500 ventilator, without leak compensation the expired tidal volume declined after 50% leak. With leak compensation, the tidal volume was maintained even with a large leak. With leak compensation, there was a more stable peak inflating pressure, although the Pco
2 was slightly higher.
Cluster Analysis Using Anti–Aminoacyl-tRNA Synthetases and SS-A/Ro52 antibodies in Patients With Polymyositis/Dermatomyositis
Authors: Ohashi Keiji , Sada Ken-Ei , Nakai Yu , Matsushima Shun , Asano Yosuke , Hayashi Keigo , Yamamura Yuriko , Hiramatsu Sumie , Miyawaki Yoshia , Morishita Michiko , Katsuyama Takayuki , Katsuyama Eri , Watanabe Haruki , Tatebe Noriko , Narazaki Mariko , Matsumoto Yoshinori , Sunahori Watanabe Katsue , Kawabata Tomoko , Wada Jun
Published: June 2018

Objective

Although several autoantibodies have been identified for polymyositis/dermatomyositis (PM/DM) diagnosis, the clinical impact of these antibodies is yet to be elucidated.

Methods

Patients with PM/DM at Okayama University Hospital from 2012 to 2016 were historically enrolled, and antibody profiles were analyzed using line immunoassay. Hierarchical cluster analysis was performed based on serological analysis of anti-aminoacyl-tRNA synthetase (ARS) antibodies, including anti-Jo-1, PL-7, PL-12, EJ, OJ, and SS-A/Ro-52 antibodies. Clinical symptoms and relapse proportions were compared among these clusters.

Results

Sixty-one patients were enrolled in this study: 28 were diagnosed with PM, and 33 were diagnosed with DM. The following 3 clusters were determined: 1 (n = 10), anti-Jo-1 and anti-SS-A/Ro-52 antibodies double positive (10/10, 100%); 2 (n = 24), anti-SS-A/Ro-52 antibody positive (20/24, 83%), anti-Jo-1 antibody negative (24/24, 100%), and anti-ARS antibodies (excluding anti-Jo-1 antibody) positive (15/24, 63%); and 3 (n = 27), anti-Jo-1 and anti-SS-A/Ro52 antibodies double negative (26/27, 96%). The proportion of patients who relapsed was significantly lower in cluster 3 than it was in clusters 1 and 2 (risk ratio, 0.37; 95% confidence interval, 0.17-0.83; p = 0.026 and risk ratio, 0.42; 95% confidence interval, 0.20-0.89; P = 0.019, respectively). There was no difference in the proportion of relapsed patients between clusters 1 and 2.

Conclusions

Our cluster analysis shows that anti-SS-A/Ro52 or any anti-ARS antibodies or both might be relevant to clinical outcomes.
Diagnostic Criteria and Treatment Algorithm for Susac Syndrome
Authors: Egan Robert A.
Published: June 2018

Background:

Susac syndrome (SS) classically presents with the clinical triad of retinal artery occlusion, sensorineural hearing loss, and encephalopathy and the neuroimaging triad of white matter lesions, deep gray matter lesions, and leptomeningeal disease. However, patients can present with an incomplete clinical or neuroimaging triads making diagnosis difficult in certain situations. A standard treatment paradigm also is lacking in this illness. It is important for neuro-ophthalmologists to recognize clinical and radiographic findings that are pathognomonic for this syndrome and have a basic understanding of the available treatment options.

Evidence Acquisition:

Review of medical literature.

Results:

A definite diagnosis of SS is made when the clinical triad or the neuroimaging triad is present. There are numerous reports of 2 other imaging findings in this condition: arteriolar wall hyperfluorescence (AWH) on fluorescein angiography in retinal arterioles remote from retinal ischemia and central callosal lesions on MRI. Both of these imaging findings are diagnostic of SS. Gass plaques in retinal arterioles are almost always seen in the acute phase of the illness but are not pathognomonic for SS. The most common medications used in this syndrome are corticosteroids and intravenous immunoglobulin. A number of other medications have been used including mycopheolate, rituximab, azathioprine, and cyclophosphamide.

Conclusions:

In the absence of the clinical triad or magnetic resonance imaging triad for SS, AWH remote from retinal vascular injury and central callosal lesions are confirmatory of the diagnosis because they have never been described in any other condition. The presence of Gass plaques in retinal arterioles should strongly suggest the diagnosis. Despite the lack of clinical trial data, patients with SS must be treated promptly and aggressively. In more fulminant cases, addition of mycophenolate mofetil or rituximab is required, followed by cyclophosphamide when disease is refractory to other medications.
Genetic analysis of invasive Escherichia coli in Scotland reveals determinants of healthcare-associated versus community-acquired infections
Authors: Goswami Cosmika , Fox Stephen , Holden Matthew , Connor Martin , Leanord Alistair , Evans Thomas J.
Published: June 2018

Bacteraemia caused by Escherichia coli is a growing problem with a significant mortality. The factors that influence the acquisition and outcome of these infections are not clear. Here, we have linked detailed genetic data from the whole-genome sequencing of 162 bacteraemic isolates collected in Scotland, UK, in 2013–2015, with clinical data in order to delineate bacterial and host factors that influence the acquisition in hospital or the community, outcome and antibiotic resistance. We identified four major sequence types (STs) in these isolates: ST131, ST69, ST73 and ST95. Nearly 50 % of the bacteraemic isolates had a urinary origin. ST69 was genetically distinct from the other STs, with significantly less sharing of accessory genes and with a distinct plasmid population. Virulence genes were widespread and diversely distributed between the dominant STs. ST131 was significantly associated with hospital-associated infections (HAIs), and ST69 with those from the community. However, there was no association of ST with outcome, although patients with HAI had a higher immediate mortality compared to those with community-associated infections (CAIs). Genome-wide association studies revealed genes involved in antibiotic persistence as significantly associated with HAIs and those encoding elements of a type VI secretion system with CAIs. Antibiotic resistance was common, and there were networks of correlated resistance genes and phenotypic antibiotic resistance. This study has revealed the complex interactions between the genotype of E. coli and its ability to cause bacteraemia, and some of the determinants influencing hospital or community acquisition. In part, these are shaped by antibiotic usage, but strain-specific factors are also important.
Extrastriate Connectivity of the Mouse Dorsal Lateral Geniculate Thalamus
Authors: Bienkowski Michael S. , Benavidez Nora L. , Wu Kevin , Gou Lin , Becerra Marlene , Dong Hong-Wei
Published: June 2018

The mammalian visual system is one of the most well-studied brain systems. Visual information from the retina is relayed to the dorsal lateral geniculate nucleus of the thalamus (LGd). The LGd then projects topographically to primary visual cortex (VISp) to mediate visual perception. In this view, the VISp is a critical network hub where visual information must traverse LGd-VISp circuits to reach higher-order ‘extrastriate’ visual cortices. However, decades of conflicting reports in a variety of mammals support or refute the existence of extrastriate LGd connections that can bypass the VISp. Here, we provide evidence of bidirectional extrastriate connectivity with the mouse LGd. Using small, discrete coinjections of anterograde and retrograde tracers within the thalamus and cortex, our cross-validated approach identified bidirectional thalamocortical connectivity between LGd and extrastriate visual cortices. Our findings support the existence of extrastriate LGd circuits and provide novel understanding of LGd organization in rodent visual system.
Reparametrizing the Sigmoid Model of Gene Regulation for Bayesian Inference
Authors: Modrák Martin
Published: June 2018

This poster describes a novel reparametrization of a fre-quently used non-linear ordinary differential equation (ODE) model of gene regulation. We show that in its commonly used form, the model cannot reliably distinguish between both quantitatively and qualitatively different parameter combinations. The proposed reparametrization makes inference over the model stable and amenable to fully Bayesian treatment with state of the art Hamiltonian Monte Carlo methods.

Complete source code and a more detailed explanation of the model is available at https://github.com/cas-bioinf/genexpi-stan.
A deep learning approach to pattern recognition for short DNA sequences
Authors: Busia Akosua , Dahl George E. , Fannjiang Clara , Alexander David H. , Dorfman Elizabeth , Poplin Ryan , McLean Cory Y. , Chang Pi-Chuan , DePristo Mark
Published: June 2018

Motivation

Inferring properties of biological sequences--such as determining the species-of-origin of a DNA sequence or the function of an amino-acid sequence--is a core task in many bioinformatics applications. These tasks are often solved using string-matching to map query sequences to labeled database sequences or via Hidden Markov Model-like pattern matching. In the current work we describe and assess an deep learning approach which trains a deep neural network (DNN) to predict database-derived labels directly from query sequences.

Results

We demonstrate this DNN performs at state-of-the-art or above levels on a difficult, practically important problem: predicting species-of-origin from short reads of 16S ribosomal DNA. When trained on 16S sequences of over 13,000 distinct species, our DNN achieves read-level species classification accuracy within 2.0% of perfect memorization of training data, and produces more accurate genus-level assignments for reads from held-out species thank-mer, alignment, and taxonomic binning baselines. Moreover, our models exhibit greater robustness than these existing approaches to increasing noise in the query sequences. Finally, we show that these DNNs perform well on experimental 16S mock community dataset. Overall, our results constitute a first step towards our long-term goal of developing a general-purpose deep learning approach to predicting meaningful labels from short biological sequences.

Availability

TensorFlow training code is available through GitHub (https://github.com/tensorflow/models/tree/master/research). Data in TensorFlow TFRecord format is available on Google Cloud Storage (gs://brain-genomics-public/research/seq2species/).

Contact

seq2species-interest@google.com

Supplementary information

Supplementary data are available in a separate document.
A Continuous-Time Semi-Markov Model for Animal Movement in a Dynamic Environment
Authors: Johnson Devin S. , Pelland Noel A. , Sterling Jeremy T.
Published: June 2018

We consider an extension to discrete-space continuous-time models animal movement that have previously be presented in the literature. The extension from a continuous-time Markov formulation to a continuous-time semi-Markov formulation allows for the inclusion of temporally dynamic habitat conditions as well as temporally changing movement responses by animals to that environment. We show that with only a little additional consideration, the Poisson likelihood approximation for the Markov version can still be used within the multiple imputation framework commonly employed for analysis of telemetry data. In addition, we consider a Bayesian model selection methodology with the imputation framework. The model selection method uses a Laplace approximation to the posterior model probability to provide a computationally feasible approach. The full methodology is then used to analyze movements of 15 northern fur seal (Callorhinus ursinus) pups with respect to surface winds, geostrophic currents, and sea surface temperature. The highest posterior model probabilities belonged to those models containing only winds and current, SST did not seem to be a significant factor for modeling their movement.
A systems view of spliceosomal assembly and branchpoints with iCLIP
Authors: Briese Michael , Haberman Nejc , Sibley Christopher R. , Chakrabarti Anob M. , Wang Zhen , König Julian , Perera David , Wickramasinghe Vihandha O. , Venkitaraman Ashok R. , Luscombe Nicholas M. , Smith Christopher W. , Curk Tomaž , Ule Jernej
Published: June 2018

Studies of spliceosomal interactions are challenging due to their dynamic nature. Here we employed spliceosome iCLIP, which immunoprecipitates SmB along with snRNPs and auxiliary RNA binding proteins (RBPs), to map human spliceosome engagement with snRNAs and pre-mRNAs. This identified over 50,000 branchpoints (BPs) that have canonical sequence and structural features. Moreover, it revealed 7 binding peaks around BPs and splice sites, each precisely overlapping with binding profiles of specific splicing factors. We show how the binding patterns of these RBPs are affected by the position and strength of BPs. For example, strong or proximally located BPs preferentially bind SF3 rather than U2AF complex. Notably, these effects are partly neutralized during spliceosomal assembly in a way that depends on the core spliceosomal protein PRPF8. These insights exemplify spliceosome iCLIP as a broadly applicable method for transcriptomic studies of splicing mechanisms.
Modulating long-range energetics via helix stabilization: a case study using T4 lysozyme
Authors: Rosemond Sabriya N. , Hamadani Kambiz M. , Cate Jamie H.D. , Marqusee Susan
Published: June 2018

Cooperative protein folding requires distant regions of a protein to interact and provide mutual stabilization. The mechanism of this long-distance coupling remains poorly understood. Here, we use T4 lysozyme (T4L*) as a model to investigate long-range communications across a globular protein. T4L* is composed of two structurally distinct subdomains, although it behaves in a two-state manner at equilibrium. The subdomains of T4L* are connected via two topological connections: the N-terminal helix that is structurally part of the C-terminal subdomain (the A-helix) and a long helix that spans both subdomains (the C-helix). To understand the role that the C-helix plays in cooperative folding, we analyzed a circularly permuted version of T4L* (CP13*), whose subdomains are connected only by the C-helix. We demonstrate that when isolated as individual fragments, both subdomains of CP13* can fold autonomously into marginally stable conformations. The energetics of the N-terminal subdomain depend on the formation of a salt bridge known to be important for stability in the full-length protein. We show that the energetic contribution of the salt bridge to the stability of the N-terminal fragment increases when the C-helix is stabilized, such as occurs upon folding of the C-terminal subdomain. These results suggest a model where long-range energetic coupling is mediated by helix stabilization.
A Moment-Based Maximum Entropy Model for Fitting Higher-Order Interactions in Neural Data
Authors: Cayco-Gajic N. Alex , Zylberberg Joel , Shea-Brown Eric
Published: June 2018

Correlations in neural activity have been demonstrated to have profound consequences for sensory encoding. To understand how neural populations represent stimulus information, it is therefore necessary to model how pairwise and higher-order spiking correlations between neurons contribute to the collective structure of population-wide spiking patterns. Maximum entropy models are an increasingly popular method for capturing collective neural activity by including successively higher-order interaction terms. However, incorporating higher-order interactions in these models is difficult in practice due to two factors. First, the number of parameters exponentially increases as higher orders are added. Second, because triplet (and higher) spiking events occur infrequently, estimates of higher-order statistics may be contaminated by sampling noise. To address this, we extend previous work on the Reliable Interaction class of models [1] to develop a normalized variant that adaptively identifies the specific pairwise and higher-order moments that can be estimated from a given dataset for a specified confidence level. The resulting “Reliable Moment” model is able to capture cortical-like distributions of population spiking patterns. Finally, we show that, compared with the Reliable Interaction model, the Reliable Moment model infers fewer strong spurious higher-order interactions and is better able to predict the frequencies of previously unobserved spiking patterns.
Yeast replicative aging leads to permanent cell cycle arrest in G1 effectuated by the start repressor Whi5
Authors: Yang Jing , Wang Ziwei , Liu Xili , Li Hao , Ouyang Qi
Published: June 2018

Yeast replicative aging has been a canonical model for aging research. Since replicative aging eventually leads to permanent cell cycle arrest, a fundamental question is how cells sense the signals from aging and communicate that to the cell cycle control machineries. Using microfluidic devices to track individual mother cells labeled by two different cell cycle markers Whi5-tdTomato and Myo1-EGFP, we measured the length of different cell cycle phases as a function of age and the distribution of cell death in different cell cycle phases. We found that the majority of the cells died in the G1 phase, and their G1 cell cycle length increased drastically in the last few cell divisions. This increase of G1 length correlates with the increase of the nuclear concentration of Whi5, which is a major transcriptional suppressor of the cell cycle start check point. Interestingly, this correlation is apparent only above a threshold concentration of Whi5. We show that in response to external stress, Whi5 concentration increases and cell growth slows down in a Whi5 dependent manner, and that Whi5 deletion significantly extends the lifespan. Together these data suggest the existence of a programmed control to arrest cell cycle in G1 in response to stress signals due to aging, and that Whi5 is a major mediator of this process. Our findings may have important implications in understanding senescence and cancer in mammalian cells, which have a parallel G1/S control system with Rb (a well known tumor suppressor) as the analog of Whi5.

Significance statement

In this work, we used microfluidic devices to track individual mother cells labeled by two cell cycle markers Whi5-tdTomato and Myo1-EGFP. We found that aging leads to significant lengthening of G1 phase in old cells and the eventual permanent cell cycle arrest in G1, and Whi5 plays an important role in implementing such a program. We show that oxidative stress can lead to the increase of Whi5 expression and the slow-down of cell division. Furthermore, Whi5 deletion significantly extends the lifespan. The result suggest the existence of a programmed control to arrest cell cycle in G1 in response to stress signals due to aging, and that Whi5 is a major mediator of this process.
Cross-platform meta-analysis reveals common matrisome variation associated with tumor genotypes and immunophenotypes in human cancers
Authors: Bin Lim Su , Jin Tan Swee , Lim Wan-Teck , Lim Chwee Teck
Published: June 2018

Background

Recent sequencing efforts unveil genomic landscapes of the tumor microenvironment. Yet, little is known about the extent to which matrisome pattern is conserved in progressive tumors across diverse cancer types, and thus its clinical impact remains largely unexplored.

Findings

Using a newly generated, unified data resource, we conducted cross-platform assessment of a measure of altered extra-cellular matrix (ECM) composition and remodeling associated with tumor progression, termed as the matrisome index (TMI). Parallel analyses with TCGA in over 30,000 patient-derived biopsies revealed that TMI is closely associated with mutational load, tumor histopathology, and predictive of patient outcomes. We found an enrichment of specific tumor-infiltrating immune cell populations, signatures predictive of immunotherapy resistance, and several immune checkpoints in tumors with high TMI, suggesting potential role of ECM interaction with immunophenotyes and tumor immune escape mechanisms. Both epithelial cancer cells and carcinoma-associated fibroblasts are potential cellular contributors of such deregulated matrisome.

Conclusions

Despite wide spectrum of genetic heterogeneity and dynamic nature, matrisome abnormalities are integral to disease progression. Our resource of a curated compendium of 8,386 genome-wide profiles, molecular and clinical associations, and matrisome-tumor genotype-immunophenotype relationships identify potentially actionable immune targets that may guide personalized immunotherapy.
Local adaptation and sexual selection drive intra-island diversification in a songbird lineage: differential divergence in autosomes and sex chromosomes
Authors: Bourgeois Yann XC , Bertrand Joris AM , Delahaie Boris , Holota Hélène , Thébaud Christophe , Milá Borja
Published: June 2018

Recently diverged taxa showing marked phenotypic and ecological diversity are optimal systems to test the relative importance of two major evolutionary mechanisms, adaptation to local ecological conditions by natural selection, or mechanisms of reproductive isolation such as assortative mating mediated by sexually selected mating signals or post-zygotic incompatibilities. Whereas local adaptation is expected to affect many loci throughout the genome, traits acting as mating signals are expected to be located on sex chromosomes and have a simple genetic basis. We used genome-wide markers to test these predictions in Reunion Island’s gray-white eye (Zosterops borbonicus), which has recently diversified into five distinct plumage forms. Two of them correspond to a polymorphic highland population that is separated by a steep ecological gradient from three distinct lowland forms that show narrow contact zones in plumage color traits, yet no association with environmental variables. An analysis of population structure using genome-wide SNP loci revealed two major clades corresponding to highland and lowland forms, respectively, with the latter separated further into three independent lineages corresponding to plumage forms. Coalescent tests of alternative demographic scenarios provided support for divergence of highland and lowland lineages with an intensification of gene flow in the last 60,000 years. Landscapes of genomic variation revealed that signatures of selection associated with elevation are found at multiple regions across the genome, whereas most loci associated with the lowland forms are located on the Z sex chromosome. A gene ontology analysis identified TYRP1, a Z-linked color gene, as a likely candidate locus underlying color variation among lowland forms. Our results are consistent with the role of natural selection in driving the divergence of locally adapted highland populations, and the role of sexual selection in differentiating lowland forms through reproductive isolation mechanisms, showing that both modes of lineage divergence can take place at very small geographic scales in birds.