bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced Antifungal Susceptibility of Vulvovaginal Candida Species at Normal Vaginal pH Levels: Clinical Implications
Authors: Spitzer Mark , Wiederhold Nathan P.
Published: February 2018

Objective

The aims of the study were to assess for differences in antifungal in vitro potency at pH 7 and pH 4 and to discuss any potential clinical implications of that difference.

Materials and Methods

A retrospective analysis of 217 first positive yeast cultures from 217 patients. Yeast isolates underwent antifungal susceptibility testing, with minimum inhibitory concentrations (MICs) (microgram per milliliter) measured at pH 7 and pH 4 for fluconazole, itraconazole, miconazole, clotrimazole, terconazole, and nystatin. Only the first isolates collected from each patient were included in the analysis.

Results

Yeast first isolates included 173 Candida albicans, 15 Candida glabrata, and 29 isolates from 8 other species. Geometric mean (GM) MIC values for all antifungals were significantly higher when tested at pH 4 (p < .001 for all comparisons). For C. albicans, the largest GM MIC differences were observed for terconazole (0.17 pH 7 vs 6.17 pH 4) and clotrimazole (0.04 vs 0.24). For terconazole, 97.7% of the isolates had a MIC of 1 or less at pH 7 but 83.2% had a MIC of 4 or higher at pH 4. For C. glabrata, terconazole (GM MIC = 0.26 pH 7 vs >64 pH 4), clotrimazole (0.13 vs 6.96), miconazole (0.06 vs 0.76), and fluconazole (3.17 vs 26.6) were most affected. All C. glabrata isolates had a MIC of 1 or less for terconazole at pH 7 and one had a MIC of 8 at pH 4, whereas all the rest were highly resistant (MIC > 64).

Conclusions

Antifungals have reduced in vitro potency when tested at lower pH. Candida glabrata is more affected than C. albicans. The impact may be greatest for the antifungal terconazole and against C. glabrata isolates.
The safety and efficacy of ledipasvir/sofosbuvir with or without ribavirin in the treatment of orthotopic liver transplant recipients with recurrent hepatitis C: real-world data
Authors: Pyrsopoulos Nikolaos , Trilianos Panagiotis , Lingiah Vivek A. , Fung Phoenix , Punnoose Merlin
Published: February 2018

Background

Recurrent hepatitis C (RHC) in orthotopic liver transplantation (OLT) population is associated with accelerated rates of fibrosis, low efficacy and decreased tolerability with traditional therapies.

Aim

The aim of this study was to evaluate the safety and efficacy of ledipasvir/sofosbuvir (LED/SOF) with or without ribavirin (RBV) in OLT patients with RHC.

Patients and methods

Patients at least 3 months post-OLT and with documented RHC were treated with LED/SOF with or without RBV for either 12 or 24 weeks. End-of-treatment and sustained virological response 12 weeks after the completion of treatment were documented. Patients were closely monitored for treatment-related adverse effects and the potential need for adjustment in their immunosuppression.

Results

Seventy-one patients were included in the study. Median age was 62 years. Median time from OLT was 55 months. Twenty-six (36.6%) patients were treatment-naive and 45 (63.4%) had previously failed interferon-based therapies. The majority of patients (57.7%) had stage F0–F2 fibrosis. Sixty-seven (94.3%) patients completed 12 weeks of LED/SOF with RBV, three patients completed 12 or 24 weeks of LED/SOF without RBV, and one patient completed only 8 weeks of LED/SOF without RBV owing to severe allograft dysfunction. Sustained virological response was near universal in our cohort (98.5%) regardless of genotype, fibrosis stage, and regimen or treatment duration. Most commonly reported side effects were malaise and gastrointestinal upset. No patient required adjustment in immunosuppression and no episodes of rejection were documented during treatment.

Conclusion

The combination of LED/SOF with RBV for 12 weeks or LED/SOF for 24 weeks is very effective and safe in treating OLT recipients with RHC.
Relationships Between Early Nutrition and Blood Glucose Concentrations in Very Preterm Infants
Authors: Tottman Anna C. , Bloomfield Frank H. , Cormack Barbara E. , Harding Jane E. , Mohd Slim M. Atif , Weston Abigail F. , Alsweiler Jane M.
Published: February 2018

Objectives:

The aim of the study was to determine whether changes to early nutrition are associated with levels of glycemia in very preterm infants.

Methods:

A retrospective, observational study of infants <1500 g or <30 weeks’ gestation admitted to Neonatal Intensive Care, National Women's Hospital, New Zealand, before (Old Protocol) and after (New Protocol) a change in nutritional protocol. Nutritional intakes were calculated and averaged by day for postnatal days 1 to 7 (week 1) and 1 to 28 (month 1). Relationships between glycemia measures, macronutrient intakes, and achievement of 10% enteral feeds (≥10% total intake) were explored using logistic regression.

Results:

Old Protocol (n = 190) and New Protocol (n = 267) groups had similar baseline characteristics. In week 1, New Protocol infants received more protein, less fat, and carbohydrate, had lower mean blood glucose concentrations (BGCs) (mean ± SD 4.9 ± 1.2 vs 5.6 ± 1.4 mmoll/L, P < 0.0001), less hyperglycemia (BGC > 8.5 mmol/L, 71 [27%] vs 80 [42%], P = 0.0005), but similar hypoglycemia (BGC < 2.6). In month 1, New Protocol infants also had less hyperglycemia (105 [39%] vs 96 [51%], P = 0.02) and lower mean BGC (5.0 ± 1.1 vs 5.5 ± 1.1 mmol/L, P < 0.0001), but insulin usage was similar. After adjustment for birth weight z score and gestational age, hyperglycemia was significantly associated with week 1 intakes (g · kg−1 · day−1) of protein (odds ratio [95% confidence intervals] 0.47 [0.23–0.79], P = 0.004), fat (0.54 [0.40–0.74], P < 0.0001), and carbohydrate (1.25 [1.09–1.44], P < 0.0001). These relationships were similar for month 1. Each additional day to achieve 10% enteral feeds was associated with increased odds of hypoglycemia (1.09 [1.00–1.18], P = 0.04) and hyperglycemia (1.16 [1.06–1.28], P = 0.002).

Conclusions:

In very preterm infants, macronutrient balance and small, early enteral feeds may assist glycemic control.
Fertility Preservation Toolkit: A Clinician Resource to Assist Clinical Discussion and Decision Making in Pediatric and Adolescent Oncology
Authors: Kemertzis Matthew A. , Ranjithakumaran Harene , Hand Meredith , Peate Michelle , Gillam Lynn , McCarthy Maria , Super Leanne , McQuillan Sarah , Drew Sarah , Jayasinghe Yasmin , Orme Lisa
Published: February 2018

Purpose:

Fertility preservation (FP) discussions in children with cancer presents unique challenges due to ethical considerations, lack of models-of-care, and the triadic nature of discussions. This study evaluated a fertility toolkit for clinicians involved in FP discussions with pediatric, adolescent, and young adult patients and parents.

Materials and Methods:

A survey-based, longitudinal study of clinicians at The Royal Children’s Hospital Melbourne involved in FP discussions undertaken at 3 time-points: 2014, alongside an education session for baseline assessment of oncofertility practices (survey 1); after each toolkit use to evaluate case-specific implementation (survey 2); 2016, to evaluate impact on clinical practice (survey 3).

Results:

Fifty-nine clinicians completed survey 1. Over 66% reported baseline dissatisfaction with the existing FP system; 56.7% were not confident in providing up-to-date information. Only 34.5% “often” or “always” provided verbal information; 14.0% “often” or “always” provided written information. Survey 2 was completed after 11 consultations. All clinicians were satisfied with the discussions and outcomes using the toolkit. Thirty-nine clinicians completed survey 3. Over 70% felt confident providing up-to-date FP knowledge, 67.7% “often” or “always” provided verbal information, and 35.4% “often” or “always” provided written information.

Conclusions:

Clinicians desire improvement in FP practice. The toolkit provided significant perceived and actual benefits.
Clinical and Serological Predictors of Suicide in Schizophrenia and Major Mood Disorders
Authors: Dickerson Faith , Origoni Andrea , Schweinfurth Lucy A.B. , Stallings Cassie , Savage Christina L.G. , Sweeney Kevin , Katsafanas Emily , Wilcox Holly C. , Khushalani Sunil , Yolken Robert
Published: February 2018

Persons with serious mental illness are at high risk for suicide, but this outcome is difficult to predict. Serological markers may help to identify suicide risk. We prospectively assessed 733 persons with a schizophrenia spectrum disorder, 483 with bipolar disorder, and 76 with major depressive disorder for an average of 8.15 years. The initial evaluation consisted of clinical and demographic data as well as a blood samples from which immunoglobulin G antibodies to herpes viruses and Toxoplasma gondii were measured. Suicide was determined using data from the National Death Index. Cox proportional hazard regression models examined the role of baseline variables on suicide outcomes. Suicide was associated with male sex, divorced/separated status, Caucasian race, and elevated levels of antibodies to Cytomegalovirus (CMV). Increasing levels of CMV antibodies were associated with increasing hazard ratios for suicide. The identification of serological variables associated with suicide might provide more personalized methods for suicide prevention.
The Effect of Oral Phenazopyridine on Perioperative Voiding After Midurethral Slings (EPIPhANy Study)
Authors: Dueñas-Garcia Omar Felipe , Sierra Tania , Taylor Danielle , Leung Katherine , Hall Cynthia D. , Flynn Michael K.
Published: February 2018

Objective

To determine the effect of preoperative oral phenazopyridine on postoperative voiding dysfunction in women undergoing a retropubic midurethral sling.

Methods

A single-institution randomized clinical trial was performed from September 2015 to March 2017, comparing 200 mg of oral phenazopyridine versus no phenazopyridine in patients undergoing a retropubic midurethral sling under general anesthesia with no concomitant procedures. A power calculation indicated that we required at least 40 subjects per arm. Preoperative demographics, intraoperative medications, blood loss, and complications were recorded. A standardized voiding trial was performed before discharge. Voiding dysfunction was determined by the proportion of subjects who failed a postoperative voiding trial. Pain scores were obtained before and 2 to 3 hours after the surgical procedure. Patient characteristics and surgical data were compared using χ2, Fisher exact test, or Wilcoxon rank sum test.

Results

Ninety-two subjects were enrolled in the study. Three patients cancelled their surgery and 1 had an intraoperative urethral injury, leaving 88 patients for the final analysis (44 per arm). Patient demographics showed no differences between groups. Phenazopyridine did not reduce the proportion of patients who failed the voiding trial (27%) compared with subjects who did not receive the medication (21%) (P = 0.453). Postoperative visual analog pain scores were higher in those not receiving phenazopyridine (1.76 vs 1.21, P = 0.046), but after adjusting for the difference in preoperative and postoperative pain scores, the groups showed no difference (P = 0.087).

Conclusions

Our prospective trial shows that phenazopyridine has no effect on short-term postoperative voiding dysfunction. This condition appears to be multifactorial, and further research is needed.
FACE: Female Pelvic Medicine and Reconstructive Surgery Awareness Campaign: Increasing Exposure
Authors: Barr Susan A. , Crisp Catrina C. , White Amanda B. , Malik Shazia A. , Kenton Kimberly
Published: February 2018

Objective

The aims of this study are to identify screening, treatment, and referral practices of primary care physicians (PCPs) for patients with pelvic floor disorders (PFDs) and evaluate awareness of the Female Pelvic Medicine and Reconstructive Surgery (FPMRS) subspecialty.

Methods

We conducted a cross-sectional survey of PCPs using a random sample of 1005 American College of Physicians members, stratified by demographic region. Electronic survey content included awareness of FPMRS certification, comfort diagnosing and treating PFDs, and PFD referral patterns for PCPs.

Results

The 399 survey respondents were predominately male and of diverse ages, geographic distribution, and experience level.

Forty-eight percent were aware of the FPMRS subspecialty, 31% of FPMRS board certification, and 25% of American Urogynecologic Society. Less than one third screened for PFDs, only two thirds were comfortable diagnosing urinary complaints, and even fewer felt comfortable diagnosing pelvic organ prolapse and fecal incontinence (FI).

Eighty-five percent recommended pelvic floor exercises for stress urinary incontinence and referred to urology (29%) or FPMRS (25%) as second-line therapy, whereas 55% recommended medication/fiber for FI and referred to gastroenterology/colorectal surgery (31%) and FPMRS (2%) as second-line therapy.

Primary care physicians referred to colorectal surgery for FI (60%), to Ob/Gyn for obstetric anal sphincter injury (38%) and pelvic organ prolapse (57%), and to urology for microscopic hematuria (80%), overactive bladder (60%), recurrent urinary tract infection (75%), stress urinary incontinence (48%), and voiding dysfunction (84%).

Conclusions

Most PCPs do not routinely screen for PFDs, and fewer feel comfortable treating. The majority is unaware of FPMRS and American Urogynecologic Society and more commonly refers PFD patients to other specialists.
Pelvic Organ Prolapse and Urinary Incontinence in Women After Bariatric Surgery: 5-Year Follow-up
Authors: Gabriel Iwona , Tavakkoli Ali , Minassian Vatche A.
Published: February 2018

Objective

The objective of this study was to determine if weight loss surgery is associated with decreased prevalence of urinary incontinence (UI) and pelvic organ prolapse (POP) symptoms.

Methods

A survey was conducted among previously morbidly obese women who underwent bariatric surgery at Brigham and Women's Hospital, Boston from 2007 to 2015. In addition to the Pelvic Floor Distress Inventory 20, we collected demographic and clinical data including symptoms of and treatment for UI and POP before surgery. Participants were divided into 4 quartiles based on self-reported postsurgical weight loss: less than 26.1 kg, 26.1 to 36.2 kg, 36.3 to 46.2 kg, and greater than 46.2 kg. Cox proportional hazard ratios were used to estimate risk of UI and POP by quartile. Kruskal-Wallis test was used to compare bother scores between the groups.

Results

A total of 447 women responded to the survey. Mean follow-up from surgery was 5 years. Women with Roux-en-Y gastric bypass had significantly greater weight loss than gastric banding or sleeve gastrectomy. The adjusted hazard ratios of current UI, stress UI, urgency UI, and prolapse decreased with increasing weight loss quartile (P trend <0.005). Based on the Pelvic Floor Distress Inventory 20, prevalence of POP symptoms was 26% with a mean bother score of 50. Although symptom bother by quartile of weight loss was not statistically significant, the trend (from the first to fourth quartile) for the mean values of Urogenital Distress Inventory 6 (from 13 to 9) and Pelvic Organ Prolapse Distress Inventory 6 (from 26 to 20) showed an improvement in bother symptoms.

Conclusions

There exists an inverse relationship between amount of weight loss and subsequent POP and UI symptoms 5 years after bariatric surgery.
A Systematic Review of Frailty Assessments in Women With Pelvic Floor Disorders: Are We Following the American College of Surgeons National Surgical Quality Improvement Program/American Geriatric Society Guidelines?
Authors: Zeno Aldene , Alvarez Pedro , Yazdany Tajnoos
Published: February 2018

Introduction

Associations between frailty and women with pelvic floor disorders (PFDs) are not well understood. This study seeks to describe studies among women with PFD and the associated frailty assessments as recommended in the American College of Surgeons National Surgical Quality Improvement Program/American Geriatric Society (ACS NSQIP/AGS) guidelines.

Methods

This systematic review was registered with PROSPERO using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The GRADE (Grading of Recommendations, Assessment, Development and Evaluations) criteria are applied to assess study quality. Data synthesis is descriptive. Outcomes of interest include the ratio of studies adhering to the ACS NSQIP/AGS guidelines and evidence for frailty assessments versus usual care for women with PFDs.

Results

Twenty studies regarding frailty and PFDs were included for systematic review. Studies were categorized as relating to (1) epidemiology, (2) frailty and incontinence, (3) postoperative morbidity, and (4) surgical choice. Most studies (5/20) did not define frailty or failed to follow the ACS NSQIP/AGS guidelines. All studies were of very low to low quality. Collectively, each category generated very low GRADE quality evidence of frailty and the relationship to PFDs.

Conclusions

Most studies regarding frailty among women with PFDs did not define frailty as recommended in the ACS NSQIP/AGS guidelines. The evidence regarding PFDs and frailty is of very low quality. This is the first systematic review regarding frailty assessments specifically among women with PFDs. Paucity of data regarding frailty in women with PFDs, particularly with regard to surgical choice and surgical counseling, highlights the need for further study in this area.
Sequence of Pelvic Examination Affects Patient-Reported Pain
Authors: Rinko Rebecca , Yu Ian , Bakillah Emna , Alper Lauren , Delaney Colleen , Su Marisa , Dawson Melissa , Gracely Edward J. , Whitmore Kristene E.
Published: February 2018

Objective

The purpose of this trial is to compare patient-reported pain based on the sequence of the pelvic examination and to assess the relationship between pain during the examination and quality of life, self-esteem, and sexual function.

Methods

A randomized controlled trial of women presenting for annual gynecologic examinations. Women were assigned to either group A: a Q-tip touch test, speculum examination, then bimanual examination or group B: Q-tip touch test, bimanual examination, then speculum examination. The primary outcome was visual analog scales to assess pain at baseline and after each portion of the examination. Secondary outcomes were responses to questionnaires for self-esteem, quality of life, and sexual function.

Results

Of 200 women who enrolled, 192 (96%) completed all visual analog scale data points. Each portion of the examination caused minimal pain over baseline in each group. Pain during the speculum examination was higher than pain during the bimanual examination in both groups (P = 0.007 and P < 0.001). Group B, however, had significantly higher pain scores after the speculum examination than group A (P = 0.044). The groups did not differ on bimanual pain scores (P = 0.76). Pain scores were not statistically different when analyzed by age, parity, sexual activity, sexual orientation, education, or previous hysterectomy. Within both groups, patients who documented having any pain after the speculum examination or the bimanual examination were also more likely to have lower quality of life scores (P < 0.001 and P < 0.001).

Conclusions

Pain associated with the speculum examination was lower in those undergoing speculum before bimanual examination. Speculum pain was greater than bimanual pain in both groups. Most patients reported minimal or no pain during the different portions of the examination.
The Utility of Preoperative Laboratory Testing Before Urogynecologic Surgery
Authors: Husk Katherine E. , Willis-Gray Marcella G. , Dieter Alexis A. , Wu Jennifer M.
Published: February 2018

Objectives

National guidelines for preoperative laboratory testing are based on limited, low-quality evidence. The role of age as a risk factor for testing is unclear. We sought to compare the prevalence of abnormal preoperative laboratory results in older vs younger urogynecologic surgical patients.

Methods

In this retrospective cohort study of women undergoing urogynecologic surgery, we compared older (age, ≥65 years) with younger (age, 50–64 years) women. Our primary outcome was the prevalence of an abnormal preoperative laboratory result.

Results

We included 317 women, with 167 (52.7%) in the older cohort (ages, 65–91 years; mean, 73.3 ± 5.6 years) and 150 (47.3%) in the younger cohort (ages, 50–64 years; mean, 57.3 ± 4.1 years). Overall, 18.3% of participants had at least one abnormal preoperative laboratory, with older women more likely to have an abnormal result (28.7% vs 10.7%, P < 0.001). Compared with the younger cohort, older women had higher rates of abnormal hemoglobin (13.8% vs 6.0%, P = 0.02) and creatinine values (10.8% vs 2.7%, P = 0.005), with no significant differences for platelets (3.0% vs 1.3%, P = 0.53), sodium (3.0% vs 0.7%, P = 0.22), or potassium (6.0% vs 3.3%, P = 0.27). After adjusting for potential confounders, older age remained associated with an abnormal preoperative result (odds ratio, 3.6; 95% confidence interval, 1.9–7.1).

Conclusions

In our sample, women 65 years or older had a greater than 25% chance of having an abnormal preoperative laboratory result and were at higher risk compared with younger women. Age 65 years or greater should be considered as a criterion for preoperative laboratory testing in urogynecologic patients.
Operating Room Efficiency: Examining the Impact of Personnel Handoffs
Authors: Geynisman-Tan Julia , Brown Oluwateniola , Mueller Margaret , Bochenska Katarzyna , Collins Sarah , Lewicky-Gaupp Christina , Kenton Kimberly
Published: February 2018

Objectives

This study aimed to determine if personnel handoffs or number of learners in the operating room (OR) are associated with longer OR times in women having pelvic organ prolapse surgery.

Methods

A retrospective review of women undergoing prolapse surgery in 2016 was conducted. Demographics; procedure; OR, anesthetic, and surgical time; number of handoffs between anesthesia members, circulators, and surgical technologies; and number of learners were abstracted.

Results

One hundred forty-eight women underwent pelvic organ prolapse surgery. Mean age was 54 ± 14 years, and most women were healthy and white. Procedures performed were as follows: 31% laparoscopic sacrocolpoexies (LASCs), 28% robotic sacrocolpopexies (RASCs), 19% colpocleises, and 22% native tissue reconstructions. For minimally invasive sacrocolpopexies (LASC + RASC), mean OR time was 270 ± 65 minutes. Median anesthesia, surgical technology, and circulator handoffs for sacrocolpopexies were 2 (interquartile range, 0–4), 1 (0–3), and 2 (2–6). Median number of learners in the OR for sacrocolpopexies was 4 (interquartile range, 1–7). Patient comorbidities and American Society of Anesthesiologists class were not associated with longer OR times (P = 0.9 and P = 0.4). Longer OR times were positively correlated with increasing numbers of anesthesia, surgical technology, and circulator handoffs, but not with the number of learners (Spearman ρ = 0.34, P = 0.001; ρ = 0.34, P < 0.001; ρ = 0.59, P < 0.001, and ρ = 0.16, P = 0.43). For LASC, every technology handoff was associated with 23 additional minutes of OR time (P = 0.004). For RASC, every technology handoff was associated with 31 additional minutes of OR time (P = 0.007), and each circulator handoff was associated with 15 additional minutes (P = 0.05).

Conclusion

Handoffs between OR personnel are associated with longer OR times, independent of patient factors.
Dextromethorphan/Quinidine in Migraine Prophylaxis: An Open-label Observational Clinical Study
Authors: Berkovich Regina R. , Sokolov Alexey Y. , Togasaki Daniel M. , Yakupova Aida A. , Cesar Paul-Henry , Sahai-Srivastava Soma
Published: February 2018

Objective

This study aimed to assess potential efficacy and safety of dextromethorphan/quinidine (DMQ) in prophylactic treatment of migraine in patients with multiple sclerosis (MS) with superimposed pseudobulbar affect (PBA).

Methods

Multiple sclerosis patients with superimposed PBA and comorbid migraine were enrolled into this open-label observational study at the University of Southern California Comprehensive MS Center. The baseline characteristics included, among other data, frequency and severity of acute migraine attacks and use of migraine relievers. The DMQ was used exclusively per its primary indication — PBA symptoms control — 20/10 mg orally, twice a day for the mean of 4.5 months (the shortest exposure registered was 3 months and the longest, 6 months). To determine whether treatment caused an effect on migraine frequency and severity, the baseline and posttreatment values were compared using nonparametric sign test.

Results

Thirty-three MS subjects with PBA, who also suffered from migraines, were identified. Twenty-nine subjects had improvement in headache frequency, 4 had no change, and none had worsening (P < 0.001 as compared with the baseline). Twenty-eight subjects had improvement in headache severity, 5 had no change, and none had worsening (P < 0.001).

Conclusions

Our pilot study results provide evidence that DMQ shows promise as a candidate for larger clinical studies evaluating its efficacy for the prevention of migraine headaches.
A novel and highly efficient esterification process using triphenylphosphine oxide with oxalyl chloride
Authors: Jia Mingzhu , Jiang Lixue , Niu Fanfan , Zhang Yu , Sun Xiaoling
Published: February 2018

Triphenylphosphine oxide (TPPO) and oxalyl chloride ((COCl)
2
) are used as novel and high-efficiency coupling reagents for the esterification of alcohols with carboxylic acids via the TPPO/(COCl)
2
system at room temperature for 1 h. The reaction represents the first TPPO-promoted esterification under mild and neutral conditions with excellent yields. Furthermore, we proposed a plausible mechanism with the help of
31
P NMR spectroscopy.
The hemodynamic initial-dip consists of both volumetric and oxymetric changes correlated to localized spiking activity
Authors: Zaidi Ali Danish , Birbaumer Niels , Fetz Eberhard , Logothetis Nikos , Sitaram Ranganatha
Published: February 2018

The “initial-dip” is a transient decrease frequently observed in functional neuroimaging signals, immediately after stimulus onset, and is believed to originate from a rise in deoxy-hemoglobin (HbR) caused by local neural activity. It has been shown to be more spatially specific than the hemodynamic response, and is believed to represent focal neuronal activity. However, despite being observed in various neuroimaging modalities (such as fMRI, fNIRS, etc), its origins are disputed and its neuronal correlates unknown. Here, we show that the initial-dip is dominated by a decrease in total-hemoglobin (HbT). We also find a biphasic response in HbR, with an early decrease and later rebound. However, HbT decreases were always large enough to counter spiking-induced increases in HbR. Moreover, the HbT-dip and HbR-rebound were strongly coupled to highly localized spiking activity. Our results suggest that the HbT-dip helps prevent accumulation of spiking-induced HbR-concentration in capillaries by flushing out HbT, probably by active venule dilation.
Epigenetic Profiling for the Molecular Classification of Metastatic Brain Tumors
Authors: Orozco Javier I. J. , Knijnenburg Theo A. , Manughian-Peter Ayla O. , Salomon Matthew P. , Barkhoudarian Garni , Jalas John R. , Wilmott James S. , Hothi Parvinder , Wang Xiaowen , Takasumi Yuki , Buckland Michael E. , Thompson John F. , Long Georgina V. , Cobbs Charles S. , Shmulevich Ilya , Kelly Daniel F. , Scolyer Richard A. , Hoon Dave S. B. , Marzese Diego M.
Published: February 2018

Optimal treatment of brain metastases is often hindered by limitations in diagnostic capabilities. To meet these challenges, we generated genome-scale DNA methylomes of the three most frequent types of brain metastases: melanoma, breast, and lung cancers (n=96). Using supervised machine learning and integration of multiple DNA methylomes from normal, primary, and metastatic tumor specimens (n=1,860), we unraveled epigenetic signatures specific to each type of metastatic brain tumor and constructed a three-step DNA methylation-based classifier (BrainMETH) that categorizes brain metastases according to the tissue of origin and therapeutically-relevant subtypes. BrainMETH predictions were supported by routine histopathologic evaluation. We further characterized and validated the most predictive genomic regions in a large cohort of brain tumors (n=165) using quantitative methylation-specific PCR. Our study highlights the importance of brain tumor-defining epigenetic alterations, which can be utilized to further develop DNA methylation profiling as a critical tool in the histomolecular stratification of patients with brain metastases.
EcRBPome: a comprehensive database of all known E. coli RNA-binding proteins
Authors: Ghosh Pritha , Guita Niang , Offmann Bernard , Sowdhamini R.
Published: February 2018

Background

The repertoire of RNA-binding proteins (RBPs) in bacteria play crucial role for their survival, and interactions with the host machinery, but there is little information, record or characterisation in bacterial genomes. As a first step towards this, we have chosen the bacterial model system Escherichia coli, and organised all RBPs in this organism into a comprehensive database named EcRBPome.

Results

EcRBPome contains RBPs recorded from 166 complete E. coli proteomes available in the RefSeq database (as of May 2016). The database provides various features related to the E. coli RBPs, like their domain architectures, PDB structures, GO and EC annotations etc. It provides the assembly, bioproject and biosample details of each strain, as well as cross-strain comparison of occurrences of various RNA-binding domains (RBDs). The percentage of RBPs, the abundance of the various RBDs harboured by each strain have been graphically represented in this database and available alongside other files for user download.

Conclusion

To the best of our knowledge, this is the first database of its kind and we hope that it will be of great use to the biological community. Database URL: http://caps.ncbs.res.in/ecrbpome
Genie: An interactive real-time simulation for teaching genetic drift
Authors: Castillo Andreina I. , Roos Ben H. , Rosenberg Michael S. , Cartwright Reed A. , Wilson Melissa A.
Published: February 2018

Neutral evolution is a fundamental concept in evolutionary biology but teaching this and other non-adaptive concepts is specially challenging. Here we present Genie, a browser-based educational tool that facilitates demonstration of concepts such as genetic drift, population isolation, gene flow, and genetic mutation. Because it does not need to be downloaded and installed, Genie can scale to large groups of students and is useful for both in-person and online instruction. Genie was used to teach genetic drift to Evolution students at Arizona State University during Spring 2016 and Spring 2017. The effectiveness of Genie to teach key genetic drift concepts and misconceptions was assessed with the Genetic Drift Inventory developed by Price et al. (2014). Overall, Genie performed comparably to that of traditional static methods across all evaluated classes. We have empirically demonstrated that Genie can be successfully integrated with traditional instruction to reduce misconceptions about genetic drift.
eTumorMetastasis, a network-based algorithm predicts clinical outcomes using whole-exome sequencing data of cancer patients
Authors: Milanese Jean-Sébastien , Tibiche Chabane , Zaman Naif , Zou Jinfeng , Han Pengyong , Meng Zhiganag , Nantel Andre , Droit Arnaud , Wang Edwin
Published: February 2018

Continual reduction in sequencing cost is expanding the accessibility of genome sequencing data for routine clinical applications. However, the lack of methods to construct machine learning-based predictive models using these datasets has become a crucial bottleneck for the application of sequencing technology in clinics. Here we developed a new algorithm, eTumorMetastasis, which transforms tumor functional mutations into network-based profiles, and identify network operational gene signatures (NOG signatures) which model the tipping point at which a tumor cell shifts from a state that doesn’t favor recurrences to one that does. We showed that NOG signatures derived from genomic mutations of tumor founding clones (i.e., the ‘most recent common ancestor’ of the cells within a tumor) significantly distinguished recurred and non-recurred breast tumors. These results imply that somatic mutations of tumor founders are association with tumor recurrence and can be used to predict clinical outcomes. Finally, the concepts underlying the eTumorMetastasis pave the way for the application of genome sequencing in predictions for other complex genetic diseases.
Influenza A virus environmental persistence is driven by the hemagglutinin and the neuraminidase
Authors: Labadie Thomas , Batéjat Christophe , Manuguerra Jean-Claude , Leclercq India
Published: February 2018

The transmission routes of Influenza A viruses (IAVs) submit virus particles to a wide range of environmental conditions that affect their transmission. In water, temperature, salinity and pH are important factors modulating viral persistence in a strain-dependant manner, and the viral factors driving IAV persistence remained to be described. We used an innovative method based on a real-time cell system analysis to quantify viral decay in an environmental model. Thus, we identified the viral hemagglutinin (HA) and neuraminidase (NA) as the main proteins driving the environmental persistence by comparing the inactivation slopes of several reassortant viruses. We also introduced synonymous and non-synonymous mutations in the HA or in the NA that modulated IAV persistence. Our results demonstrate that HA stability and expression level, as well as calcium-binding sites of the NA protein are molecular determinants of viral persistence.

Finally, IAV particles could not trigger membrane fusion after environmental exposure, stressing the importance of the HA and the NA for environmental persistence.
Adaptive planning in human search
Authors: Krusche Moritz J. F. , Schulz Eric , Guez Arthur , Speekenbrink Maarten
Published: February 2018

How do people plan ahead when searching for rewards? We investigate planning in a foraging task in which participants search for rewards on an infinite two-dimensional grid. Our results show that their search is best-described by a model which searches at least 3 steps ahead. Furthermore, participants do not seem to update their beliefs during planning, but rather treat their initial beliefs as given, a strategy similar to a heuristic called root-sampling. This planning algorithm corresponds well with participants’ behavior in test problems with restricted movement and varying degrees of information, outperforming more complex models. These results enrich our understanding of adaptive planning in complex environments.
Problematic usage of the Zhang and Luck mixture model
Authors: Ma Wei Ji
Published: February 2018

A common method, due to Zhang and Luck (2008), for analyzing delayed-estimation data with a circular stimulus variable is to fit a mixture of a Von Mises distribution and a uniform distribution. The uniform distribution represents random guesses, presumably made when an item is not kept in memory. When I generate synthetic data from a variable-precision model with zero guessing, the method estimates the guess rate to be nonzero and often high. This is due to model mismatch: the fitted model is not matched to the data-generating (true) model. In real data, this could be a problem if one considers the variable-precision model a plausible candidate model and draws conclusions based on the estimated guess rates. I describe five solutions to this problem: analyzing the residual, ruling out the variable-precision model, robust inference, fitting a hybrid model, and using model-free statistics. I hope that these solutions can contribute to good data analysis practices in the study of working memory.
GLUE: A flexible software system for virus sequence data
Authors: Singer Joshua B , Thomson Emma C , McLauchlan John , Hughes Joseph , Gifford Robert J
Published: February 2018

Background

Virus genome sequences, generated in ever-higher volumes, can provide new scientific insights and inform our responses to epidemics and outbreaks. To facilitate interpretation, such data must be organised and processed within scalable computing resources that encapsulate virology expertise. GLUE (Genes Linked by Underlying Evolution) is a data-centric bioinformatics environment for building such resources. The GLUE core data schema organises sequence data along evolutionary lines, capturing not only nucleotide data but associated items such as alignments, genotype definitions, genome annotations and motifs. Its flexible design emphasises applicability to different viruses and to diverse needs within research, clinical or public health contexts.

Results

HCV-GLUE is a case study GLUE resource for hepatitis C virus (HCV). It includes an interactive public web application providing sequence analysis in the form of a maximum-likelihood-based genotyping method, antiviral resistance detection and graphical sequence visualisation. HCV sequence data from GenBank is categorised and stored in a large-scale sequence alignment which is accessible via web-based queries. Whereas this web resource provides a range of basic functionality, the underlying GLUE project can also be downloaded and extended by bioinformaticians addressing more advanced questions.

Conclusion

GLUE can be used to rapidly develop virus sequence data resources with public health, research and clinical applications. This streamlined approach, with its focus on reuse, will help realise the full value of virus sequence data.
Structural diversity across arbuscular mycorrhizal, ectomycorrhizal, and endophytic plant—fungus networks
Authors: Toju Hirokazu , Sato Hirotoshi , Yamamoto Satoshi , Tanabe Akifumi S.
Published: February 2018

Background

Below-ground linkage between plant and fungal communities is one of the major drivers of terrestrial ecosystem dynamics. However, we still have limited knowledge of how such plant–fungus associations vary in their community-scale properties depending on fungal functional groups and geographic locations.

Methods

Based on high-throughput sequencing of root-associated fungi in eight forests along the Japanese Archipelago, we performed a comparative analysis of arbuscular mycorrhizal, ectomycorrhizal, and saprotrophic/endophytic associations across a latitudinal gradient from cool-temperate to subtropical regions.

Results

In most of the plant–fungus networks analyzed, host–symbiont associations were significantly specialized but lacked “nested” architecture, which has been commonly reported in plant–pollinator and plant–seed disperser networks. Meanwhile, the structure of arbuscular mycorrhizal networks was differentiated from that of ectomycorrhizal and saprotrophic/endophytic networks, characterized by high connectance. Our data also suggested that geographic factors affected the organization of plant–fungus network structure. For example, the southernmost subtropical site analyzed in this study displayed lower network-level specificity of host–symbiont associations and higher (but still low) nestedness than northern localities.

Conclusions

Our comparative analyses suggest that arbuscular mycorrhizal, ectomycorrhizal, and saprotrophic/endophytic plant–fungus associations often lack nested network architecture, while those associations can vary, to some extent, in their community-scale properties along a latitudinal gradient. Overall, this study provides a basis for future studies that will examine how different types of plant–fungus associations collectively structure terrestrial ecosystems.
Big and Small Cerebral Asymmetries
Authors: Eckert Mark A. , Vaden Kenneth I. ,   Dyslexia Data Consortium
Published: February 2018

Letter Highlights

Deformation-based asymmetries replicate previously observed grey matter asymmetries and characterize white matter asymmetries.

Increased sensitivity to structural asymmetries in some brain regions depends on smaller-scale normalization or deformation parameters.

Tuning deformation parameters can provide more precise asymmetry measures for understanding the mechanisms and functional significance of cerebral asymmetries.
Sound induces change in orientation preference of V1 neurons: Audio-visual cross-influence
Authors: Chanauria Nayan , Bharmauria Vishal , Bachatene Lyes , Cattan Sarah , Rouat Jean , Molotchnikoff Stéphane
Published: February 2018

In the cortex, demarcated unimodal sensory regions often respond to unforeseen sensory stimuli and exhibit plasticity. The goal of the current investigation was to test evoked responses of primary visual cortex (V1) neurons when an adapting auditory stimulus is applied in isolation. Using extracellular recordings in anesthetized cats, we demonstrate that, unlike the prevailing observation of only slight modulations in the firing rates of the neurons, sound imposition in isolation entirely shifted the peaks of orientation tuning curves of neurons in both supra- and infragranular layers of V1. Our results suggest that neurons specific to either layer dynamically integrate features of sound and modify the organization of the orientation map of V1. Intriguingly, these experiments present novel findings that the mere presentation of a prolonged auditory stimulus may drastically recalibrate the tuning properties of the visual neurons and highlight the phenomenal neuroplasticity of V1 neurons.

Highlights

Prolonged application of sound shifts preferred orientation of neurons in area 17 of cats.

Orientation tuning shifts in the individual neurons in supra- and infragranular layers of V1.

Supra- and infragranular layers of V1 operate together but also as distinct compartments following sound adaptation.

Visual cortex is specifically and dynamically impacted by non-visual stimuli.

Sound adaptation certainly modifies the organization of orientation maps in V1.
AlignmentViewer: Sequence Analysis of Large Protein Families
Authors: Reguant Roc , Antipin Yevgeniy , Sheridan Rob , Luna Augustin , Sander Chris
Published: February 2018

AlignmentViewer is multiple sequence alignment viewer for protein families with flexible visualization, analysis tools and links to protein family databases. It is directly accessible in web browsers without the need for software installation, as it is implemented in JavaScript, and does not require an internet connection to function. It can handle protein families with tens of thousands of sequences and is particularly suitable for evolutionary coupling analysis, facilitating the computation of protein 3D structures and the detection of functionally constrained interactions.

Availability and Implementation

AlignmentViewer is open source software under the MIT license. The viewer is at http://alignmentviewer.org and the source code, documentation and issue tracking, for co-development, are at https://github.com/dfci/alignmentviewer

Contact

alignment.viewer@gmail.com, reaches all authors
CRISPR-DT: designing gRNAs for the CRISPR-Cpf1 system with improved target efficiency and specificity
Authors: Zhu Houxiang , Liang Chun
Published: February 2018

The CRISPR-Cpf1 system has been successfully applied in genome editing. However, target efficiency of the CRISPR-Cpf1 system varies among different gRNA sequences. We reanalyzed the published CRISPR-Cpf1 gRNAs data and found many sequence and structural features related to their target efficiency. Using machine learning technology, a SVM model was created to predict target efficiency for any given gRNAs. We have developed the first web service application, CRISPR-DT (CRISPR DNA Targeting), to help users design optimal gRNAs for the CRISPR-Cpf1 system by considering both target efficiency and specificity. CRISPR-DT is available athttp://bioinfolab.miamioh.edu/CRISPR-DT.
Survey of human chromosome 21 gene expression effects on early development in Danio rerio
Authors: McGuire Edie Sarah , Zaghloul Norann A , Leitch Carmen C , Klinedinst Donna K , Lebron Janette , Thole Joey F , McCallion Andrew S , Katsanis Nicholas , Reeves Roger H.
Published: February 2018

Trisomy for human chromosome 21 (Hsa21) results in Down syndrome (DS), one of the most genetically complex conditions compatible with human survival. Assessment of the physiological consequences of dosage-driven overexpression of individual Hsa21 genes during early embryogenesis and the resulting contributions to DS pathology in mammals are not tractable in a systematic way. A recent study looked loss-of-function of C. elegans orthologues of Hsa21 genes and identified ten candidates with behavioral phenotypes, but the equivalent over-expression experiment has not been done. We turned to zebrafish as a developmental model and, using a number of surrogate phenotypes, we screened Hsa21 genes for dosage sensitive effects on early embyrogenesis. We prepared a library of 164 cDNAs of conserved protein coding genes, injected mRNA into early embryos and evaluated up to 5 days post-fertilization (dpf). Twenty-four genes produced a gross morphological phenotype, 11 of which could be reproduced reliably. Seven of these gave a phenotype consistent with down regulation of the sonic hedgehog (Shh) pathway; two showed defects indicative of defective neural crest migration; one resulted consistently in pericardial edema; and one was embryonic lethal. Combinatorial injections of multiple Hsa21 genes revealed both additive and compensatory effects, supporting the notion that complex genetic relationships underlie end phenotypes of trisomy that produce DS. Together, our data suggest that this system is useful in the genetic dissection of dosage-sensitive gene effects on early development and can inform the contribution of both individual loci and their combinatorial effects to phenotypes relevant to the etiopathology of DS.