bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of laparoscopic versus open simple nephrectomy in patients with xanthogranulomatous pyelonephritis: A singlecenter analysis of outcomes and predictors of surgical approaches and complications
Authors: Chiancone Francesco , Persico Francesco , Fabiano Marco , Meccariello Clemente , Giannella Riccardo , Fedelini Maurizio , Lughezzani Giovanni , Fedelini Paolo
Published: November 2021

Background

The aim of this study was to compare the outcomes of open simple nephrectomy and laparoscopic simple nephrectomy in patients with xanthogranulomatous pyelonephritis (XGP) in a single-institutional retrospective study and to identify predictive factors of surgical approaches and complications.

Materials and methods

We retrospectively analyzed the data of 67 consecutive patients with a histopathological diagnosis of XGP who underwent either open simple nephrectomy (ON) or laparoscopic simple nephrectomy (LN) from January 2014 to April 2020. The primary endpoint was the evaluation of perioperative outcomes and complications. Secondary endpoints were to define factors influencing the surgical approach and the likelihood of postoperative complications.

Results

Overall, 44 out of 67 patients (65.67%) underwent ON, while 23 (34.33%) underwent LN. Patients in the ON group experienced more postoperative pain according to the visual analogic scale (p = 0.032). Moreover, time to deambulation and time to return to full daily activities, assessed according to the 12-Item Short Form Survey physical and mental component summary scores questionnaires, were significantly shorter in the LN group (p = 0.021, p < 0.001, and p < 0.001, respectively). Of note, there were no significant differences in intraoperative and postoperative complication rates among the groups (p = 0.258 and p = 0.317, respectively). No conversion to open surgery was described. Logistic regression analysis demonstrated that urgency (p = 0.025) was the only predictor associated with a higher risk of intraoperative complications. However, no independent factors associated with postoperative complications or with the surgical approach of choice were found.

Conclusions

Based on our results, laparoscopic treatment of XGP represents a feasible alternative to ON, resulting in less postoperative pain and faster recovery. In skilled hands, LN should be considered as the treatment of choice for XGP.
Menopausal symptoms among Chinese and Japanese women: differences and similarities
Authors: Su Jing , Jogamoto Akiko , Yoshimura Hiroyuki , Yang Lu Jun
Published: November 2021

Objectives:

This study aimed to identify the characteristics of menopausal symptoms among Japanese and Chinese women and to determine the correlation between menopausal symptoms and self-efficacy.

Methods:

We surveyed 40- to 59-year-old women, 329 of whom were from an urban area in Northwest China (Xi’an) and 310 were from an urban area in Western Japan (Ehime), using a menopausal symptoms inventory and a self-efficacy scale. Comparison analysis was conducted among pre-, peri-, and postmenopausal status, within and between the two cultural groups. Following a two-way ANOVA, multiple comparisons were performed using the Tukey-Kramer test. The correlation between severity of menopause symptoms and self-efficacy scores was evaluated using canonical correlation analysis.

Results:

The most frequently reported symptoms were fatigue (93.6%) among Japanese women and memory loss (76.6%) among Chinese women. Japanese women showed significantly higher severity scores across all factors than Chinese, sexual function: 19.58 (SE = 0.73) versus 15.04 (SE = 0.67); mental health condition: 35.44 (SE = 1.15) versus 27.12 (SE = 0.95); interpersonal anxiety: 27.45 (SE = 0.95) versus 21.92 (SE = 0.86); autonomic balance: 42.76 (SE = 1.27) versus 35.75 (SE = 1.17); other subjective symptoms: 39.68 (SE = 1.20) versus 33.07 (SE = 1.12) in the premenopausal group (P < 0.01); and mental health conditions 35.14 (SE = 1.41) versus 29.60 (SE = 1.25), interpersonal anxiety: 27.34 (SE = 1.18) versus 20.79 (SE = 1.02), autonomic balance factors: 45.81 (SE = 1.79) versus 38.05 (SE = 1.67) in the postmenopausal group (P < 0.01). No significant differences of the factors among menopausal stages within Japanese women were found. Among Chinese women, peri- and postmenopausal women showed significantly higher severity scores on sexual function, while perimenopausal women scored higher on mental health conditions and autonomic balance factors (P < 0.01). A negative correlation was found between menopausal symptoms and self-efficacy among both Japanese and Chinese women (P < 0.01).

Conclusions:

Japanese women reported more severe symptoms compared with their Chinese counterparts, and for Chinese women, symptoms might be specifically associated with menopausal status. Menopausal experience is associated with self-efficacy and vice versa.
Access Drives Health System Transformation and Growth
Authors: Sussman Jason H.
Published: November 2021

Healthcare is in the midst of a “great disintermediation.” New care delivery models are offering novel ways of accessing care and moving the US healthcare system from a hospital-centric to a consumer-centric focus. This transformation is opening new opportunities for technology-enabled, risk-ready innovators intent on disrupting traditional ties among health systems, primary care physicians, and consumers.
Frugal Method of Notch Modification of Scleral Contact Lenses in the Setting of Complex Ocular Surface Anatomy
Authors: Patel Raj P. , Samples Jeffrey S. , Riaz Kamran M.
Published: November 2021

Scleral contact lenses (ScCLs) have gained popularity as a treatment of refractive errors in patients with complex anterior segment pathology. Patients with mechanical abnormalities of the ocular surface may be unsuccessful with traditional ScCL fitting. Scleral contact lens modifications, such as notching and microvaulting, typically incur additional financial costs and require the services of professional laboratories. We describe a frugal method of ScCL notch modification that can be performed by a practitioner using readily available tools in a single office visit. Two patients with abnormal ocular surface anatomy were fit with the practitioner-modified ScCL and achieved successful visual rehabilitation. We offer this method as a potentially economical and effective technique to achieve successful ScCL fitting in this challenging patient population with pathologies that may preclude standard ScCL usage.
Changes in Tear Meniscus Analysis of Children Who Have Type 1 Diabetes Mellitus, With and Without Vitamin D Deficiency
Authors: Aksoy Aydemir Gozde , Aydemir Emre , Asik Abdulvahit
Published: November 2021

Purpose:

The aim of this study was to quantitatively evaluate dry eye test parameters of pediatric patients with and without vitamin D deficiency (VDD) in type 1 diabetes mellitus.

Methods:

In this prospective cross-sectional study, the Ocular Surface Disease Index, Schirmer test, tear film breakup time, corneal staining score, and anterior segment optical coherence tomography were used to determine the dry eye test parameters of pediatric patients with type 1 diabetes mellitus (T1-DMPs) (group 1) and a healthy pediatric control group (group 2). Group 1 was divided into 2 subgroups based on their vitamin D status: group 1a, who had a VDD, and group 1b, who had vitamin D levels that were within the normal range.

Results:

This study compared 90 eyes of 90 pediatric T1-DMPs with 80 eyes of 80 healthy controls. The demographic characteristics of the groups were similar (P > 0.05). The tear film breakup time, Schirmer test, corneal staining score, and values of the tear meniscus height and area were observed to have been lower in the patients in group 1a than the healthy pediatric control group, at P < 0.001. The same parameters were statistically significantly lower in the patients in group 1a when compared with group 1b (P < 0.05 for both).

Conclusions:

The tear measurements of the pediatric T1-DMPs were lower than those in the healthy pediatric control group. The accompanying VDD made this situation more pronounced.
Upper Eyelid Contour Changes After Orbital Decompression in Graves Orbitopathy
Authors: Cruz Antonio A. V. , Equitério Bruna , Diniz Stefania B. , Garcia Denny M. , Rootman Daniel B. , Goldberg Robert A. , Galindo-Ferreiro Alicia , Marqués-Fernández Victoria , Sales-Sanz Marco
Published: November 2021

Purpose:

To evaluate the effect of orbital decompression on the upper eyelid contour.

Methods:

A paired cross-sectional analysis of the upper eyelid contour was performed for 103 eyes of 66 patients who underwent orbital decompression. A control group of 26 normal subjects was also included. The eyelid contour of all participants were measured with Bézier lines adjusted to the eyelid contour and 9 midpupil eyelid margin (MPD) distances from a horizontal line bisecting the pupil. One central, corresponding to the margin reflex distance (MRD 1), and 8 equally distributed medially and laterally at 20% of the interval between the lines. Patients were classified as with flare if the height of the most lateral MPD relative to the MRD 1 was above the upper limit of the controls.

Results:

Preoperatively 63 of the 103 contours were classified as flare + (F+). After decompression MRD1 showed a mean decrease of 0.4 mm and the location of the contour shifted 0.8 mm medially. These changes were not correlated with proptosis reduction. Orbital decompression decreased the lateral curvature of the contours especially for the F+ lids. In 40% of the F+ eyelids the flare sign disappeared after decompression.

Conclusions:

Orbital decompression affects the lateral eyelid contour and diminishes the amount of lateral eyelid retraction surgery necessary to correct the flare sign. In 40% of the patients, the eyelid contour is normalized with proptosis reduction only.
Developmental Outcomes of Children Served in a Part C Early Intervention Program
Authors: Elbaum Batya , Celimli-Aksoy Seniz
Published: November 2021

In the United States, early intervention (EI) programs under Part C of the Individuals with Disabilities Education Act serve thousands of infants and toddlers with or at risk for developmental delays. Despite this, few studies have investigated the developmental progress and outcomes of children served, especially in relation to the heterogeneity of children's diagnoses and identified areas of delay. In this study, we classified children into 9 subgroups based on their medical diagnosis or, for children without a specific diagnosis, their identified areas of developmental delay. We then analyzed data from the developmental assessment administered to each child on program entry and exit. Multivariate analyses of children's pre- and postscores in 5 domains (cognitive, motor, adaptive, communication, and personal–social) confirmed the distinctiveness of each subgroup's developmental profile on entry into EI as well as significant differences across subgroups in children's pattern of developmental change while in services. Across subgroups, the percentage of children who were within age norms in all measured domains at the time they transitioned out of the program ranged from 10% to 49%. The results add to our understanding both of children's improvements while in EI and the variation in outcomes for meaningfully defined subgroups of children.
Occupation-Based Developmentally Supportive Care for Infants With Congenital Heart Disease in the Hospital Environment
Authors: Kelso Damond Grace
Published: November 2021

Congenital heart disease (CHD), the result of structural changes to the heart present at birth, is the most common congenital birth condition. As survival rates for infants with complex CHD have increased in recent years, risk for neurodevelopmental challenges has also increased. Early referral to developmentally supportive care is recommended as best practice; however, there is limited information about how to best support occupations of infants with CHD as early as possible while still in the hospital. Recommendations for developmentally supportive care structured around occupations of infancy, existing developmental care models, and current evidence are reviewed and discussed for infants hospitalized following cardiac surgery. Key occupations of infancy discussed include movement and sensory exploration, procurement (communication of needs), sleep, feeding, and social interaction and play. Future work is recommended to develop occupation-based training and education resources for interprofessional hospital staff about developmentally supportive care for the hospitalized infant with CHD.
Characteristics of Adults With Diagnosed HIV Who Experienced Housing Instability: Findings From the Centers for Disease Control and Prevention Medical Monitoring Project, United States, 2018
Authors: Marcus Ruthanne , Tie Yunfeng , Dasgupta Sharoda , Beer Linda , Padilla Mabel , Fagan Jennifer , Prejean Joseph
Published: November 2021

People living with HIV (PLWH) who experience homelessness have poorer clinical outcomes than people with HIV who are not homeless; however, there is limited information on PLWH who experience other forms of housing instability. We used interviews and medical record abstraction data from the Medical Monitoring Project, collected 2018–2019 (N = 4,050), to describe sociodemographic characteristics and clinical outcomes of adults with HIV by whether people experienced unstable housing in the past 12 months. Overall, 21% were unstably housed, of which 55.2% were unstably housed but not homeless. People who were unstably housed were more likely to be younger, have lower educational attainment, be previously incarcerated, live at or below the poverty level, and have poorer mental health and clinical outcomes, independent of homelessness. Interventions to address housing instability, integrated with clinical care, could benefit not just PLWH who are homeless but also those who are unstably housed.
The Utility of Pathology Reports to Identify Persons With Cancer Recurrence
Authors: Warren Joan L. , Noone Anne-Michelle , Stevens Jennifer , Wu Xiao-Cheng , Hsieh Mei-chin , Mumphrey Brent J. , Schmidt Rodney , Coyle Linda , Shields Rusty , Mariotto Angela B.
Published: November 2021

Background:

Cancer recurrence is an important measure of the impact of cancer treatment. However, no population-based data on recurrence are available. Pathology reports could potentially identify cancer recurrences. Their utility to capture recurrences is unknown.

Objective:

This analysis assesses the sensitivity of pathology reports to identify patients with cancer recurrence and the stage at recurrence.

Subjects:

The study includes patients with recurrent breast (n=214) or colorectal (n=203) cancers.

Research Design:

This retrospective analysis included patients from a population-based cancer registry who were part of the Patient-Centered Outcomes Research (PCOR) Study, a project that followed cancer patients in-depth for 5 years after diagnosis to identify recurrences.

Measures:

Information abstracted from pathology reports for patients with recurrence was compared with their PCOR data (gold standard) to determine what percent had a pathology report at the time of recurrence, the sensitivity of text in the report to identify recurrence, and if the stage at recurrence could be determined from the pathology report.

Results:

One half of cancer patients had a pathology report near the time of recurrence. For patients with a pathology report, the report’s sensitivity to identify recurrence was 98.1% for breast cancer cases and 95.7% for colorectal cancer cases. The specific stage at recurrence from the pathology report had a moderate agreement with gold-standard data.

Conclusions:

Pathology reports alone cannot measure population-based recurrence of solid cancers but can identify specific cohorts of recurrent cancer patients. As electronic submission of pathology reports increases, these reports may identify specific recurrent patients in near real-time.
School-based health centers as a context to engage and serve communities
Authors: Cutuli J.J.
Published: November 2021

Purpose of review

School-based health centers (SBHCs) primarily serve underserved students and families through removing barriers to care. The number of SBHCs have increased dramatically with investments from state-funding and federal-funding programs, including expanded funding from the American Rescue Plan. This article reviews findings on the perceived importance of school and community partnership. It also provides a critical review of the evidence base on impact on health, mental health, and education indicators.

Recent findings

Recent findings underscore the importance of SBHCs engaging the school and community to build trust while identifying and responding to needs. Engagement supports planning, implementing, and sustaining SBHCs. Studies of impact find that SBHCs increase participation in preventive and routine health and decrease emergency department utilization and hospitalization. However, additional research needs to rigorously test for effects of SBHCs on symptoms and indicators of wellbeing, especially with respect to mental health and education.

SBHCs increase participation of students from marginalized groups in preventive and routine care. School and community engagement are vital aspects of SBHCs, likely removing barriers related to trust. Additional rigorous evidence is needed testing efficacy of SBHCs when it comes to improving health, mental health, and education.
Features and management of men with pN1 cM0 prostate cancer after radical prostatectomy and lymphadenectomy: a systematic review of population-based evidence
Authors: Laine Charles , Gandaglia Giorgio , Valerio Massimo , Heidegger Isabel , Tsaur Igor , Olivier Jonathan , Ceci Francesco , van den Bergh Roderick C.N. , Kretschmer Alexander , Thibault Constance , Chiu Peter K. , Tilki Derya , Kasivisvanathan Veeru , Preisser Felix , Zattoni Fabio , Fankhauser Christian , Kesch Claudia , Puche-Sanz Ignacio , Moschini Marco , Pradere Benjamin , Ploussard Guillaume , Marra Giancarlo
Published: November 2021

Purpose of review

To investigate the features and optimal management of pN+ cM0 prostate cancer (PCa) according to registry-based studies.

Recent findings

Up to 15% of PCa patients harbor lymph node invasion (pN+) at radical prostatectomy plus lymph node dissection. Nonetheless, the optimal management strategy in this setting is not well characterized.

We performed a systematic review including n = 13 studies. Management strategies comprised 13 536 men undergoing observation, 11 149 adjuvant androgen deprivation therapy (aADT), 7,075 adjuvant radiotherapy (aRT) +aADT and 705 aRT. Baseline features showed aggressive PCa in the majority of men. At a median follow-up ranging 48–134months, Cancer-related death was 5% and overall-mortality 16.6%. aADT and aRT alone had no cancer-specific survival or overall survival advantages over observation only and over not performing aRT, respectively. aADT plus aRT yielded a survival benefit compared to observation and aADT, which in one study, were limited to certain intermediate-risk categories. Age, Gleason, Charlson score, positive surgical margins, pathological stage, and positive nodes number, but not prostate specific antigen, were most relevant prognostic factors. Our work further confirmed pN+ PCa is a multifaceted disease and will help future research in defining its optimal management based on different risk categories to maximize survival and patient's quality of life.
Success with dorsal root entry zone lesioning after a failed trial of spinal cord stimulation in a patient with pain due to brachial plexus avulsion
Authors: Lopez Lucia , Sdrulla Andrei D.
Published: November 2021

Pain caused by brachial plexopathy (BP) represents a challenging clinical problem with few effective therapeutic options. Here, we present a patient with severe, painful BP after a high-impact motor vehicle accident who failed conservative treatments. A trial of cervical spinal cord stimulation was completed using multiple waveforms (tonic, BurstDR, and 10 kHz) over 14 days with only 30% to 40% pain reduction. Subsequently, he underwent dorsal root entry zone lesioning with a significant decrease in his pain 1 year later. Surgical exploration revealed extensive damage and avulsion of his cervical roots that was not observed on a previous brachial plexus magnetic resonance imaging. We discuss the etiology and diagnosis of traumatic BP, possible reasons for the failed spinal cord stimulation trial, and implications for management.
Machine Learning Estimation of Low-Density Lipoprotein Cholesterol in Women With and Without HIV
Authors: Dong Tony , Rana Mariam N. , Longenecker Chris T. , Rajagopalan Sanjay , Kim Chang H. , Al-Kindi Sadeer G.
Published: November 2021

Introduction:

Low-density lipoprotein cholesterol (LDL-C) is typically estimated from total cholesterol, high-density lipoprotein cholesterol, and triglycerides. The Friedewald, Martin–Hopkins, and National Institutes of Health equations are widely used but may estimate LDL-C inaccurately in certain patient populations, such as those with HIV. We sought to investigate the utility of machine learning for LDL-C estimation in a large cohort of women with and without HIV.

Methods:

We identified 7397 direct LDL-C measurements (5219 from HIV-infected individuals, 2127 from uninfected controls, and 51 from seroconvertors) from 2414 participants (age 39.4 ± 9.3 years) in the Women's Interagency HIV Study and estimated LDL-C using the Friedewald, Martin–Hopkins, and National Institutes of Health equations. We also optimized 5 machine learning methods [linear regression, random forest, gradient boosting, support vector machine (SVM), and neural network] using 80% of the data (training set). We compared the performance of each method using root mean square error, mean absolute error, and coefficient of determination (R2) in the holdout (20%) set.

Results:

SVM outperformed all 3 existing equations and other machine learning methods, achieving the lowest root mean square error and mean absolute error, and the highest R2 (11.79 and 7.98 mg/dL, 0.87, respectively, compared with those obtained using the Friedewald equation: 12.45 and 9.14 mg/dL, 0.87). SVM performance remained superior in subgroups with and without HIV, with nonfasting measurements, in LDL <70 mg/dL and triglycerides > 400 mg/dL.

Conclusions:

In this proof-of-concept study, SVM is a robust method that predicts directly measured LDL-C more accurately than clinically used methods in women with and without HIV. Further studies should explore the utility in broader populations.
Relationships Between Age, Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1), and Mortality Among Critically Ill Adults: A Cohort Study
Authors: Sathe Neha A. , Bhatraju Pavan K. , Mikacenic Carmen , Morrell Eric D. , Mabrey F. Linzee , Liles W. Conrad , Wurfel Mark M.
Published: November 2021

Background:

Innate immune dysregulation may contribute to age-related differences in outcomes among critically ill adults. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is an important innate immune marker with prognostic value in sepsis, but age-related differences have not been studied.

Methods:

This was a prospective cohort from a large tertiary care hospital enrolling adults from both medical and trauma-surgical intensive care units (ICUs). Plasma sTREM-1 was measured in participants within 24 h of ICU admission. We analyzed associations between age (≤50 and >50 years) and sTREM-1 using linear regression. We then examined associations between sTREM-1 and both 28-day mortality and persistent organ dysfunction (defined as need for dialysis, vasopressors, or invasive mechanical ventilation) 7 days following admission using relative risk regression.

Results:

Of 231 critically ill adults, older patients (n = 122) had higher prevalence of chronic disease and sepsis on enrollment than younger patients, but acute illness severity was similar. Age over 50 was associated with 27% higher sTREM-1 concentrations (95% CI 6%–53%), adjusted for sex and Charlson comorbidity index (CCI). Two-fold higher sTREM-1 was associated with 2.42-fold higher risk for mortality (95% CI 1.57, 3.73) and 1.86-fold higher risk for persistent organ dysfunction (95% CI 1.45, 2.39), adjusted for sex, CCI, and age.

Conclusions:

sTREM-1 was elevated among critically ill older adults, and strongly associated with both death and persistent organ dysfunction. Immune responses associated with sTREM-1 may contribute to age-related differences in ICU outcomes, warranting further study as a potential therapeutic target in older adults.
National adherence to the ASGE-SAGES guidelines for managing suspected choledocholithiasis: An EAST multicenter study
Authors: Tracy Brett M. , Poulose Benjamin K. , Paterson Cameron W. , Mendoza April E. , Gaitanidis Apostolos , Saxe Jonathan M. , Young Andrew J. , Zielinski Martin D. , Sims Carrie A. , Gelbard Rondi B.
Published: November 2021

BACKGROUND

The American Society for Gastrointestinal Endoscopy and Society of American Gastrointestinal and Endoscopic Surgeons provide guidelines for managing suspected common bile duct (CBD) stones. We sought to evaluate adherence to the guidelines among patients with choledocholithiasis and/or acute biliary pancreatitis (ABP) and to evaluate the ability of these guidelines to predict choledocholithiasis.

METHODS

We prospectively identified patients undergoing same-admission cholecystectomy for choledocholithiasis and/or ABP from 2016 to 2019 at 12 United States medical centers. Predictors of suspected CBD stones were very strong (CBD stone on ultrasound; bilirubin >4 mg/dL), strong (CBD > 6 mm; bilirubin ≥1.8 to ≤4 mg/dL), or moderate (abnormal liver function tests other than bilirubin; age >55 years; ABP). Patients were grouped by probability of CBD stones: high (any very strong or both strong predictors), low (no predictors), or intermediate (any other predictor combination). The management of each probability group was compared with the recommended management in the guidelines.

RESULTS

The cohort was comprised of 844 patients. High-probability patients had 64.3% (n = 238/370) deviation from guidelines, intermediate-probability patients had 29% (n = 132/455) deviation, and low-probability patients had 78.9% (n = 15/19) deviation. Acute biliary pancreatitis increased the odds of deviation for the high- (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.06–2.8; p = 0.03) and intermediate-probability groups (OR, 1.6; 95% CI, 1.07–2.42; p = 0.02). Age older than 55 years (OR, 2.19; 95% CI, 1.4–3.43; p < 0.001) also increased the odds of deviation for the intermediate group. A CBD greater than 6 mm predicted choledocholithiasis in the high (adjusted OR (aOR), 2.16; 95% CI, 1.17–3.97; p = 0.01) and intermediate group (aOR, 2.78; 95% CI, 1.59–4.86; p < 0.001). Any very strong predictor (aOR, 2.43; 95% CI, 1.76–3.37; p < 0.0001) and both strong predictors predicted choledocholithiasis (aOR, 2; 95% CI, 1.35–2.96; p < 0.001).

CONCLUSION

Almost 45% of patients with suspected CBD stones were managed discordantly from the American Society for Gastrointestinal Endoscopy and Society of American Gastrointestinal and Endoscopic Surgeons guidelines. We believe these guidelines warrant revision to better reflect the ability of the clinical variables at predicting choledocholithiasis.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.
Advanced neuroimaging techniques in epilepsy
Authors: Duncan John S. , Trimmel Karin
Published: November 2021

Purpose of review

We review significant advances in epilepsy imaging in recent years.

Recent findings

Structural MRI at 7T with optimization of acquisition and postacquisition image processing increases the diagnostic yield but artefactual findings remain a challenge. MRI analysis from multiple sites indicates different atrophy patterns and white matter diffusion abnormalities in temporal lobe and generalized epilepsies, with greater abnormalities close to the presumed seizure source. Structural and functional connectivity relate to seizure spread and generalization; longitudinal studies are needed to clarify the causal relationship of these associations. Diffusion MRI may help predict surgical outcome and network abnormalities extending beyond the epileptogenic zone. Three-dimensional multimodal imaging can increase the precision of epilepsy surgery, improve seizure outcome and reduce complications. Language and memory fMRI are useful predictors of postoperative deficits, and lead to risk minimization. FDG PET is useful for clinical studies and specific ligands probe the pathophysiology of neurochemical fluxes and receptor abnormalities.

Improved structural MRI increases detection of abnormalities that may underlie epilepsy. Diffusion, structural and functional MRI indicate the widespread associations of epilepsy syndromes. These can assist stratification of surgical outcome and minimize risk. PET has continued utility clinically and for research into the pathophysiology of epilepsies.
Learning from the comorbidities of epilepsy
Authors: Shlobin Nathan A. , Sander Josemir W.
Published: November 2021

Purpose of review

Comorbidities are a common feature in epilepsy, but neither the entire spectrum nor the significance of such comorbidities has been fully explored. We review comorbidities associated with epilepsy and their associated burden, provide an overview of relationships, and discuss a new conceptualization of the comorbidities.

Recent findings

The epidemiology of the comorbidities of epilepsy and effects on health outcomes, healthcare use, and healthcare expenditures have been partly delineated. Distinct mechanisms of the associations have been suggested but not entirely ascertained. Movement from conceptualizing epilepsy as a condition to a symptom-complex has occurred.

Comorbidities are common among people with epilepsy and are associated with poorer clinical outcomes and quality of life, greater use of health resources, and increased expenditure. Becoming aware of the associated mechanisms and their uncertainty is central to understanding the relationships between epilepsy and comorbid health conditions, which have implications for diagnosis and screening, medical management, and surgical management. Conceptualizing comorbidities of epilepsy as precipitating factors and epilepsy as the symptom will improve the understanding of epilepsy and catalyze research and improvements in clinical practice.
Anemia and Idiopathic Intracranial Hypertension: A Systematic Review and Meta-analysis
Authors: Yu Caberry W. , Waisberg Ethan , Kwok Jason M. , Micieli Jonathan A.
Published: November 2021

Background:

Idiopathic intracranial hypertension (IIH) is a condition typically affecting young, obese women. Although anemia is recognized as a risk factor of IIH from case reports, their relationship remains controversial as several comparative studies showed no significant association. This study aimed to examine the relationship between anemia and IIH.

Methods:

MEDLINE, Embase, Cochrane Library, and grey literature were searched to September 2020. Primary studies on patients with diagnoses of anemia of any kind and IIH were included. Primary outcomes included the total number of cases of anemia and IIH. A meta-analysis on the prevalence of anemia in IIH compared with control patients was conducted. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to rate the quality of evidence.

Results:

Overall, 62 cases and 5 observational or case–control studies were included. Pooled incidence of anemia in patients with IIH was 195/1,073 (18.2%). Patients with IIH (n = 774) had a significantly higher prevalence of anemia compared with controls (n = 230,981) (RR 1.44 [95% confidence interval 1.08–1.92]). Patients were 67.7% females and had a mean age of 22.4 years. The mean opening pressure was 37.9 cmH2O. Anemia was most commonly caused by iron deficiency (51.6%) and aplastic anemia (19.4%). Most patients (59.7%) showed improvement or resolution with anemia treatment only without intracranial pressure-lowering therapy. Evidence was limited because of high risk of reporting bias from the large number of case reports and case–control studies.

Conclusions:

Anemia is significantly more common in IIH compared with control patients, and case reports suggest a direct relationship. Complete blood counts should be considered in all patients with papilledema, particularly in atypical presentations (male, nonobese, nonperipapillary retinal hemorrhages, prominent risk factor for anemia) or in treatment-refractory IIH.
Sociodemographic and cultural determinants of mood disorders
Authors: D’cruz Migita M. , Chaturvedi Santosh K.
Published: November 2021

Purpose of review

The present review aims to examine, summarize and update information on the sociodemographic and cultural determinants of mood disorders.

Recent findings

Known sociodemographic and cultural determinants continue to be good predictors of the risk of developing a mood disorder over the lifetime. Polygenic risk scores do not appear to offer any advantages over these determinants at present. There is also new and emerging understanding of the role of lifestyle and environmental factors in mediating vulnerability to mood disorder. The influence of ethnicity and migration, on the other hand, is far more complex than initially envisaged.

Recent evidence on sociodemographic determinants of mood disorders confirms associations derived from existing literature. There is also new and emerging evidence on how quality of sleep, diet and the environment influence risk of mood disorders. Culture and ethnicity, depending on context, may contribute to both vulnerability and resilience. Socioeconomic deprivation may be the final common pathway through which several sociodemographic and cultural determinants of mood disorders act.
Immune escape facilitation by mutations of epitope residues in RdRp of SARS-CoV-2
Authors: Gupta Aayatti Mallick , Mandal SasthiCharan , Mandal Sukhendu , Chakrabarti Jaydeb
Published: November 2021

SARS-CoV-2 has considerably higher mutation rate. SARS-CoV-2 possesses a RNA dependent RNA polymerase (RdRp) which helps to replicate its genome. The mutation P323L in RdRp is associated with the loss of a particular epitope (321-327) from this protein which may influence the pathogenesis of the concern SARS-CoV-2 through the development of antibody escape variants. We consider the effect of mutations in some of the epitope regions including the naturally occurring mutation P323L on the structure of the epitope and their interface with paratope using all-atom molecular dynamics (MD) simulation studies. P323L mutations cause conformational changes in the epitope region by opening up the region associated with increase in the radius of gyration and intramolecular hydrogen bonds, making the region less accessible. Moreover, the fluctuations in the dihedral angles in the epitope:paratope (IgG) interface increase which destabilize the interface. Such mutations may help in escaping antibody mediated immunity of the host.
The impact of Fisher’s Reproductive Compensation on raising equilibrium frequencies of semi-dominant, non-lethal mutations under mutation/selection balance
Authors: Hastings Ian M.
Published: November 2021

Fisher’s reproductive compensation (fRC) occurs when a species’ demography means the death of an individual allows increased survival of his/her relatives, usually assumed to be full sibs. This likely occurs in many species, including humans. Several important recessive human genetic diseases cause early foetal/infant death allowing fRC to act on these mutations. The impact of fRC on these genetic conditions has been calculated and shown to be substantial as quantified by ω, the fold increase in equilibrium frequencies of the mutation under fRC compared to its absence i.e. ω=1.22 and ω=1.33 for autosomal and sex-linked loci, respectively. However, the impact of fRC on the frequency of the much large class of semi-dominant, non-lethal mutations is unknown. This is calculated here by a mixture of simulation and algebra and shown that ω=2-h*s and ω≈2-0.19s-0.85h*s for autosomal and sex-linked loci respectively where h is dominance (varied between 0.05 and 0.95) and s is selection coefficient (varied between 0.05 and 0.9). These results show that the actions of fRC can almost double equilibrium frequency of mutations with low values of h and/or s. The dynamics of fRC acting on this type of mutation are also identified and discussed.
Simultaneous assessment of eight phosphorylated STAT residues in T-cells by flow cytometry.
Authors: Monk Emily , Vassallo Melinda , Burke Paulo , Weber Jeffrey , Chattopadhyay Pratip , Woods David
Published: November 2021

Signal transducer and activator of transcription (STAT) proteins are a family of transcription factors controlling functions in immune responses and other cell types. Given their importance, we developed a flow cytometry panel to assess eight phosphorylated STAT residues in human T-cells, including six tyrosine residues across six STAT proteins (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT6) and additional serine residues on STAT1 and STAT3. We applied this protocol to test the in vitro induction of pSTATs in response to CD3/CD28 activation and a panel of recombinant cytokines. We also assessed the pSTAT expression profiles of naive CD4+ T-cells polarized to Th1, Th2, Th17 or iTregs. pSTAT1(S727), pSTAT2(Y689) and pSTAT3(S727) were constitutively expressed in most T-cells, even in the absence of stimulation. For pSTAT1(S727) and pSTAT3(S727), we observed two positive states, high and low. Conversely, expression of pSTAT1(Y701), pSTAT3(Y705), pSTAT4(Y693) and pSTAT6(Y641) were absent in resting T-cells and only expressed with CD3/CD28 activation or with specific cytokines. Variable frequencies of pSTAT5a(Y694) expression were observed in resting T-cells, which increased with activation or specific cytokine stimulation (e.g. IL-2). IFN-beta stimulation enhanced frequencies of expressing cells for all pSTATs. Correlations among several pSTATs, particularly pSTAT1(S727)high and pSTAT3(S727)high were observed. While polarization resulted in increases in canonically associated pSTATs, other non-canonical pSTAT changes were also observed. Collectively, we developed, optimized, and tested a sensitive and rapid approach for simultaneously assessing phosphorylation of six STAT proteins. Using this approach, we made several novel observations of T-cell pSTAT induction in response to stimuli.
Perceived facial happiness during conversation correlates with insular and hypothalamus activity for humans, not robots: An investigation of the somatic marker hypothesis applied to social interactions
Authors: Chaminade Thierry , Spatola Nicolas
Published: November 2021

The somatic marker hypothesis posits that perceiving emotions entails reenacting markers of self emotions, in particular in the autonomous nervous system. Well studied in decision-making tasks, it has not been tested in a social cognitive neuroscience framework, and in particular for the automatic processing of positive emotions during natural interactions. Here, we address this question using a unique corpus of brain activity recorded during unconstrained conversations between participants and a human or a humanoid robot. fMRI recordings are used to test whether activity in the most important brain regions in relation to the autonomic system, the amygdala, hypothalamus and insula, is affected by the level of happiness expressed by the human and robot agents. Results indicate that for the hypothalamus and the insula, in particular the anterior agranular region strongly involved in processing social emotions, activity in the right hemisphere increases with the level of happiness expressed by the human, but not the robot. Results indicate that perceiving positive emotions in social interactions induces the local brain responses predicted by the somatic marker hypothesis, but only when the interacting agent is a real human.
Effect of therapeutic ultrasound on the mechanical and biological properties of fibroblasts
Authors: Cárdenas-Sandoval Rosy P. , Pastrana-Rendón Homero F. , Ávila-Bernal Alba G. , Ramírez-Martínez Angélica M. , Navarrete-Jimenez Myriam L. , Ondo-Mendez Alejandro O. , Garzón-Alvarado Diego A.
Published: November 2021

Conventional doses of therapeutic ultrasound alter the mechanical behavior of ligament fibroblasts to improve the regenerative and remodeling stages of the wound healing process. Using a multidisciplinary approach, we applied ultrasound doses of 1.0 and 2.0 W/cm2at 1 MHz frequency for five days on ligament fibroblasts. Atomic force microscopy showed a decrease in cell elastic modulus for both doses, but the treated cells were still viable based on flow cytometry. Finite element method analysis exhibited visible cytoskeleton displacements and decreased harmonics in treated cells. Colorimetric assay revealed increased cell proliferation, while scratch assay showed increased migration at low doses. An increase in collagen and fibronectin was detected by enzyme-linked immunoassay at high doses, and β-actin expression for both treatments was visualized through immunofluorescence imaging. Both doses of ultrasound altered the fibroblast mechanical properties due to cytoskeletal reorganization and enhanced the early and late stages of cell repair.
A computationally efficient clustering linear combination approach to jointly analyze multiple phenotypes for GWAS
Authors: Wang Meida , Zhang Shuanglin , Sha Qiuying
Published: November 2021

There has been an increasing interest in joint analysis of multiple phenotypes in genome-wide association studies (GWAS) because jointly analyzing multiple phenotypes may increase statistical power to detect genetic variants associated with complex diseases or traits. Recently, many statistical methods have been developed for joint analysis of multiple phenotypes in genetic association studies, including the Clustering Linear Combination (CLC) method. The CLC method works particularly well with phenotypes that have natural groupings, but due to the unknown number of clusters for a given data, the final test statistic of CLC method is the minimum p-value among all p-values of the CLC test statistics obtained from each possible number of clusters. Therefore, a simulation procedure must be used to evaluate the p-value of the final test statistic. This makes the CLC method computationally demanding. We develop a new method called computationally efficient CLC (ceCLC) to test the association between multiple phenotypes and a genetic variant. Instead of using the minimum p-value as the test statistic in the CLC method, ceCLC uses the Cauchy combination test to combine all p-values of the CLC test statistics obtained from each possible number of clusters. The test statistic of ceCLC approximately follows a standard Cauchy distribution, so the p-value can be obtained from the cumulative density function without the need for the simulation procedure. Through extensive simulation studies and application on the COPDGene data, the results demonstrate that the type I error rates of ceCLC are effectively controlled in different simulation settings and ceCLC either outperforms all other methods or has statistical power that is very close to the most powerful method with which it has been compared.
A flexible workflow for building spectral libraries from narrow window data independent acquisition mass spectrometry data
Authors: Heil Lilian R. , Fondrie William E. , McGann Christopher D. , Federation Alexander J. , Noble William S. , MacCoss Michael J. , Keich Uri
Published: November 2021

Advances in library-based methods for peptide detection from data independent acquisition (DIA) mass spectrometry have made it possible to detect and quantify tens of thousands of peptides in a single mass spectrometry run. However, many of these methods rely on a comprehensive, high quality spectral library containing information about the expected retention time and fragmentation patterns of peptides in the sample. Empirical spectral libraries are often generated through data-dependent acquisition and may suffer from biases as a result. Spectral libraries can be generated in silico but these models are not trained to handle all possible post-translational modifications. Here, we propose a false discovery rate controlled spectrum-centric search workflow to generate spectral libraries directly from gas-phase fractionated DIA tandem mass spectrometry data. We demonstrate that this strategy is able to detect phosphorylated peptides and can be used to generate a spectral library for accurate peptide detection and quantitation in wide window DIA data. We compare the results of this search workflow to other library-free approaches and demonstrate that our search is competitive in terms of accuracy and sensitivity. These results demonstrate that the proposed workflow has the capacity to generate spectral libraries while avoiding the limitations of other methods.
The effects of sequence length and composition of random sequence peptides on the growth of E. coli cells
Authors: Fajardo C. R. Johana , Tautz Diethard
Published: November 2021

We study the potential for the de novo evolution of genes from random nucleotide sequences using libraries of E. coli expressing random sequence peptides. We assess the effects of such peptides on cell growth by monitoring frequency changes of individual clones in a complex library through four serial passages. Using a new analysis pipeline that allows to trace peptides of all lengths, we find that over half of the peptides have consistent effects on cell growth. Across nine different experiments, around 16 % of clones increase in frequency and 36 % decrease, with some variation between individual experiments. Shorter peptides (8–20 residues), are more likely to increase in frequency, longer ones are more likely to decrease. GC content, amino acid composition, intrinsic disorder and aggregation propensity show slightly different patterns between peptide groups. Sequences that increase in frequency tend to be more disordered with lower aggregation propensity. This coincides with the observation that young genes with more disordered structures are better tolerated in genomes. Our data indicate that random sequences can be a source of evolutionary innovation, since a large fraction of them are well tolerated by the cells or can provide a growth advantage.
Cholinergic control of striatal GABAergic microcircuits
Authors: Kocaturk S. , Shah F. , Guven B. , Tepper J.M. , Assous M.
Published: November 2021

Abstract

Cholinergic interneurons (CINs) are essential elements of striatal circuits and behaviors. While acetylcholine signaling via muscarinic receptors (mAChRs) have been well studied, more recent data indicate that postsynaptic nicotinic receptors (nAChRs) located on GABAergic interneurons (GINs) are equally critical. One demonstration is that CINs stimulation induces large disynaptic inhibition of SPNs mediated by nAChR activation of striatal GINs. While these circuits are ideally positioned to modulate striatal output activity, the neurons involved are not definitively identified due largely to an incomplete mapping of CINs-GINs interconnections. Here, we show that CINs optogenetic activation evokes an intricate dual mechanism involving co-activation of pre- and postsynaptic mAChRs and nAChRs on four GINs populations. Using multi-optogenetics, we demonstrate the participation of tyrosine hydroxylase-expressing GINs in the disynaptic inhibition of SPNs likely via heterotypic electrical coupling with neurogliaform interneurons. Altogether, our results highlight the importance of CINs in regulating GINs microcircuits via complex synaptic/heterosynaptic mechanisms.