bluuebunny/crossref_metadata_2025 huggingface dataset:
Type 1 diabetes induced by immune checkpoint inhibitors
Authors: Zhang Rui , Cai Xiao-Ling , Liu Liu , Han Xue-Yao , Ji Li-Nong
Published: August 2020

With the increasing use of immune checkpoint inhibitors (ICI) including anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1) in cancers, ICI-induced type 1 diabetes has been reported throughout the world. In this review, we aim to summarize the characteristics of this disease and discuss the mechanism of it. As an immune-related adverse event, type 1 diabetes developed after the administration of anti-PD-1 or anti-PD-ligand 1 (PD-L1) in the combination with or without anti-CTLA-4. It usually presented with acute onset, and 62.1% of the reported cases had diabetic ketoacidosis. Only a third of them had positive autoantibodies associated with type 1 diabetes. Susceptible HLA genotypes might be associated. T-cell-stimulation by blocking of the interaction of PD-1 and PD-L1 in pancreatic β cells was the main mechanism involved in the pathology. Insulin was the only effective treatment of ICI-induced type 1 diabetes. In conclusions, ICI-induced type 1 diabetes is a potentially life-threating adverse event after the immunotherapy of cancers. Screening and early recognition is important. Further investigation of the mechanism may help to better understand the pathology of type 1 diabetes.
Reflections on the Impending Lawsuits by Governments Against Pharmaceutical Opioid Producers in Canada
Authors: Fischer Benedikt , Haines-Saah Rebecca
Published: August 2020

Canada has experienced an unprecedented opioid-related public health crisis. Several Canadian (provincial) governments are preparing lawsuits against pharmaceutical opioid manufacturers towards liability and reparations for the extensive costs of opioid-related harms. We briefly examine these efforts on ethical, practical and commonsensical grounds. Specifically, the opioid drugs fuelling the crisis were actively approved by public regulators, and governments for long neglected explicit warnings about and failed to implement crucial interventions towards the emerging opioid crisis when needed. The opioid crisis arose out of interactive dynamics (of actions and non-actions) by multiple protagonists neither accounted for nor corrected by one-sided responsibility assignments.

Le Canada a connu une crise sans précédent au niveau de la santé publique liée aux opioïdes. Plusieurs gouvernements canadiens (provinciaux) préparent des poursuites contre les fabricants d’opioïdes pharmaceutiques pour responsabilité civile et réparation en raison des coÛts élevés des méfaits liés aux opioïdes. Nous avons examiné ces efforts aux niveaux éthique, pratique et logique. Plus précisément, les médicaments opioïdes qui alimentent la crise ont été activement approuvés par les régulateurs publics, et les gouvernements ont longtemps négligés les avertissements explicites. De plus, ils n’ont pas réussi à mettre en œuvre des interventions cruciales contre la crise des opioïdes émergente en cas de besoin. La crise des opioïdes est née de la dynamique interactive (des actions et des non-actions) de multiples protagonistes. Elle n’a été ni expliquée ni corrigée par des attributions de blâmes unilatérales.
Female reproductive health and cognitive function
Authors: Tsai Chia-Kuang , Chen Yuan-Yuei , Chou Chung-Hsing , Kao Tung-Wei , Liang Chih-Sung , Yang Fu-Chi , Wang Chung-Ching , Lee Jiunn-Tay , Chen Wei-Liang
Published: August 2020

Objective:

The impact of sex hormones milieu on women's cognitive performance at different reproductive stages has caused increased caution. Our research aims to explore whether parity is negatively correlated with cognitive function.

Methods:

There were 1,093 postmenopausal participants recruited from the Health and Nutrition Examination Survey dataset. Cognitive functioning was evaluated by digit symbol substitution test (DSST). We performed log transformation to normalize the distributions of the DSST values.

Results:

Participants were categorized into tertile groups based on the number of pregnancies. Using the zero to one pregnancy group as the reference, there was a reduced DSST scores with β values of −0.13 (95% confidence interval [CI] −0.23 to −0.03; P = 0.008) in the ≥5 pregnancies group after adjusting for socioeconomic, medical disease, lifestyle, and reproductive components. Moreover, women who had their last pregnancy after 28 years old and education less than 12 years also was correlate with cognitive malfunction after adjusting relevant covariates (both P 
< 0.001).

Conclusions:

Women with at least five pregnancies had poorer cognitive performance. Last pregnancy after 28 years old and education less than 12 years also was associated with poorer DSST scores.

Video Summary:

http://links.lww.com/MENO/A634.
Breast effects of oral, combined 17β-estradiol, and progesterone capsules in menopausal women: a randomized controlled trial
Authors: Liu James H. , Black Denise R. , Larkin Lisa , Graham Shelli , Bernick Brian , Mirkin Sebastian
Published: August 2020

Objective:

To evaluate the effect of a single-capsule, bioidentical 17β-estradiol (E2) and progesterone (P4) hormone therapy on mammograms and breasts in postmenopausal women after 1 year of use.

Methods:

In the 12-month, phase 3, randomized, double-blind, placebo-controlled, multicenter REPLENISH trial, postmenopausal women (40-65 y) with moderate to severe vasomotor symptoms and a uterus were randomized to four active daily dose groups of E2/P4 (TX-001HR) or a placebo group. Mammograms were performed and read locally at screening (or ≤6 months before first dose) and at study end using BI-RADS classification. Incidence of abnormal mammograms and breast adverse events was evaluated.

Results:

All but 8 (0.4%) mammograms at screening were normal (BI-RADS 1 or 2). At 1 year, 39 (2.9%) of the 1,340 study-end mammograms were abnormal (BI-RADS 3 or 4); incidence was 1.7% to3.7% with active doses and 3.1% with placebo. Breast cancer incidence was 0.36% with active doses and 0% with placebo. Breast tenderness was reported at frequencies of 2.4% to 10.8% with active doses versus 0.7% with placebo, and led to eight study discontinuations (1.6% of discontinuations in active groups).

Conclusions:

In this phase 3 trial of a combined E2/P4, results of secondary outcomes suggest that E2/P4 may not be associated with increased risk of abnormal mammograms versus placebo, and the incidence of breast tenderness was low relative to most of the rates reported in other studies using hormone therapy.
Ischemic optic neuropathy after Descemet-stripping automated endothelial keratoplasty
Authors: Rosenberg Christopher R. , Weissbart Sarah B. , Sibony Patrick A.
Published: August 2020

An 82-year-old woman presented with a failed Descemet-stripping automated endothelial keratoplasty (DSAEK) in her right eye performed a month earlier. The patient underwent uneventful repeat DSAEK. Six days after the procedure, the patient was found to have an afferent pupillary defect and optic nerve swelling in her right eye on fundoscopy and optical coherence tomography. A comprehensive workup, including bilateral temporal artery biopsies and magnetic resonance imaging, for vasculitic etiologies was negative. A diagnosis of nonarteritic anterior ischemic optic neuropathy (NAION) was made. Although NAION has been reported after various ocular surgeries, to the authors' knowledge, this is the first reported case of NAION after uneventful corneal transplantation. Therefore, NAION should be considered a rare complication of corneal transplantation surgery. Meticulous preoperative and postoperative evaluation, including an attentive pupillary and dilated fundus examination, are essential in assessing a patient's risk factors for this condition and monitoring for its occurrence in the perioperative period.
Relative Cost Differences of Initial Treatment Strategies for Newly Diagnosed Opioid Use Disorder
Authors: Larochelle Marc R. , Wakeman Sarah E. , Ameli Omid , Chaisson Christine E. , McPheeters Jeffrey T. , Crown William H. , Azocar Francisca , Sanghavi Darshak M.
Published: August 2020

Background:

Relative costs of care among treatment options for opioid use disorder (OUD) are unknown.

Methods:

We identified a cohort of 40,885 individuals with a new diagnosis of OUD in a large national de-identified claims database covering commercially insured and Medicare Advantage enrollees. We assigned individuals to 1 of 6 mutually exclusive initial treatment pathways: (1) Inpatient Detox/Rehabilitation Treatment Center; (2) Behavioral Health Intensive, intensive outpatient or Partial Hospitalization Services; (3) Methadone or Buprenorphine; (4) Naltrexone; (5) Behavioral Health Outpatient Services, or; (6) No Treatment. We assessed total costs of care in the initial 90 day treatment period for each strategy using a differences in differences approach controlling for baseline costs.

Results:

Within 90 days of diagnosis, 94.8% of individuals received treatment, with the initial treatments being: 15.8% for Inpatient Detox/Rehabilitation Treatment Center, 4.8% for Behavioral Health Intensive, Intensive Outpatient or Partial Hospitalization Services, 12.5% for buprenorphine/methadone, 2.4% for naltrexone, and 59.3% for Behavioral Health Outpatient Services. Average unadjusted costs increased from $3250 per member per month (SD $7846) at baseline to $5047 per member per month (SD $11,856) in the 90 day follow-up period. Compared with no treatment, initial 90 day costs were lower for buprenorphine/methadone [Adjusted Difference in Differences Cost Ratio (ADIDCR) 0.65; 95% confidence interval (CI), 0.52–0.80], naltrexone (ADIDCR 0.53; 95% CI, 0.42–0.67), and behavioral health outpatient (ADIDCR 0.54; 95% CI, 0.44–0.66). Costs were higher for inpatient detox (ADIDCR 2.30; 95% CI, 1.88–2.83).

Conclusion:

Improving health system capacity and insurance coverage and incentives for outpatient management of OUD may reduce health care costs.
Scalp Staples Placed in a Pediatric Emergency Department
Authors: Quinn Bruce J. , Mancinelli Andrea , Rooney-Otero Kathleen , Martin Michelle , Ghavi Lila N. , Wojewoda Eva M. , Rogers Brent D.
Published: August 2020

Objectives

Scalp lacerations are a common occurrence in the pediatric population. A preferred method of closure in a busy pediatric emergency department (PED) is skin staples, because of their ease of use and rapid application. However, using skin staples also demands that the child have a follow-up visit for their removal. This study examines whether caregivers can be taught how to safely remove their child's skin staples at home, obviating the need for a return clinic visit and its associated costs.

Methods

This is a prospective, convenience study of 30 children older than 4 years presenting with a scalp laceration that the attending physician chose to close with skin staples. Caregivers of enrolled children completed an initial survey and received training in skin staple removal in the PED. Upon discharge, caregivers were given the staple removal device and specific instructions indicating the date for staple removal and how to access an online video reviewing proper staple removal technique. Caregivers were contacted after anticipated staple removal for completion of a follow-up survey. We recorded caregiver success rate at staple removal and measured potential benefits with regard to lost wages, transportation costs, and missed school time. Data were analyzed using descriptive statistics.

Results

Twenty-eight (93%) of 30 enrolled caregivers were successful in completely removing their child's staples; one caregiver did not attempt removal and another was lost to follow-up. Twenty-five caregivers (83%) completed follow-up surveys. All caregivers reported that if given a future choice, they would prefer to remove their child's staples at home rather than return to a clinic and all said that they would be “very comfortable” if they needed to remove staples again in the future. Sixty-four percent of caregivers estimated that it would have taken greater than 2 hours to attend a clinic for staple removal. Thirty-two percent of caregivers would have lost greater than US $100 in wages. Eighty-eight percent of children would have missed school time, with 46% having to miss an entire school day.

Conclusions

Caregivers who were taught how to remove their child's scalp staples in the PED before discharge were highly successful at home. Ninety-three percent of enrolled patients had their staples completely removed and no complications were reported. Benefits included avoiding lost wages, lost time attending a follow-up clinic, and lost time from school. Staple removal is a simple technique that can easily be taught to caregivers in a matter of minutes and lead to greater patient and parent satisfaction.
Defining the Histologic Support Structures of the Nasal Ala and Soft Triangle: Toward Understanding the Cause of Iatrogenic Alar Retraction
Authors: Dowlatshahi A. Samandar , Constantian Mark B. , Deng April , Fudem Gary
Published: August 2020

Background:

As rhinoplasty techniques have evolved to more extensive dissections, the incidence of iatrogenic deformities, such as alar rim retraction, has risen. Its mechanism is presently unknown. This study examined the microscopic anatomy of the nasal ala to define architectural support elements at the histologic level to determine why rhinoplasty dissection creates such deformities.

Methods:

Eight cadaveric noses were harvested and sectioned through the soft triangle and ala. Various tissue stains were performed. Slides were examined using light microscopy. Anatomical features pertaining to cartilage, skin, mucosa, elastic fibers, and muscle were documented.

Results:

Four male and four female noses were sectioned. The median cadaver age was 64 years (range, 47 to 83 years). On Elastica van Gieson stain, distinct elastic fibers span from the vestibular lining to the caudal margin of the lower lateral cartilage, and from the caudal edge of the lower lateral cartilage to the external alar skin. In the nasal ala midsection, trichrome stains reveal that skeletal muscle is located far beyond the lower lateral cartilage, close to the free alar margin. The soft triangle shows a distinct microanatomical structure, with heavy longitudinal condensations of elastin. These histologic findings have not been previously reported.

Conclusions:

A distinct anatomical alar wall endoskeleton has been identified. It is obligatorily disrupted by specific rhinoplasty maneuvers when dissection is carried out over the lateral crura and into areas without cartilaginous support. This microanatomy may explain factors that contribute to postoperative alar wall retraction. Leaving this area undisturbed or performing adjunctive measures with rhinoplasty can provide structural support to the external valves, thus minimizing the risk of deformity.
The Impact of Markers of HIV Infection on Change in Liver Stiffness in People With HIV and Hepatitis C Virus Co-infection After Treatment and Cure of Hepatitis C
Authors: van Santen Daniela K. , Agius Paul A. , Sasadeusz Joseph , Fairley Christopher K. , Sievert William , Gane Edward , Iser David , O'Reilly Mark , Medland Nicholas A. , Moore Richard , Hellard Margaret E. , Hoy Jennifer F. , Doyle Joseph S. ,   on behalf of the Co-EC Study Group
Published: August 2020

Background:

Markers of HIV disease severity are associated with increased liver fibrosis in HIV/Hepatitis C virus (HCV) co-infected individuals. HCV treatment may reverse liver fibrosis, but evidence among HIV/HCV-co-infected populations and the impact of HIV parameters on fibrosis regression is limited. We aimed to assess the influence of surrogate markers of HIV-infection and other determinants of liver stiffness before HCV treatment and changes after HCV cure in people living with HIV.

Methods:

We used data from an HCV treatment implementation study aiming for HCV micro-elimination among gay and bisexual men with HIV in Melbourne, Australia (co-EC Study). We obtained liver stiffness measurements (LSM) before and after direct-acting antiviral treatment using transient elastography (FibroScan). Linear mixed models were used to evaluate determinants of pretreatment LSM and changes in LSM following cure with duration in years between pre- and post-LSM assessment as main exposure variable.

Results:

At least one LSM was available in 173 participants, and 98 participants had 2 LSMs. Median pre- and post-treatment LSMs were 5.7 and 5.1 kPa, respectively. Median time between transient elastography measurements was 1.3 years (interquartile range = 0.9–2.1). In multivariable analysis, longer duration of known HIV infection, a lower CD4 and CD8 T-cell count and hazardous alcohol consumption were associated with higher LSM values before treatment initiation. Successfully treated patients had a 6% (95% confidence interval = −10% to −2%) annual decrease (0.34 kPa predicted decrease) in LSM following cure. Changes in LSM values did not depend on any of the pretreatment HIV markers or other factors.

Conclusion:

Low levels of liver stiffness were observed before treatment initiation and a small decrease (6%) in LSM following HCV cure in people living with HIV. No clear predictors affecting change in LSM following cure were found in this study, including markers of HIV infection. However, markers of advanced HIV immunodeficiency and hazardous alcohol consumption remained associated with higher LSM values even after HCV cure.
Texture Analysis as a Radiomic Marker for Differentiating Benign From Malignant Adrenal Tumors
Authors: Yu HeiShun , Parakh Anushri , Blake Michael , McDermott Shaunagh
Published: August 2020

Objective

The aim of this study was to evaluate the use of texture analysis for differentiation between benign from malignant adrenal lesions on contrast-enhanced abdominal computed tomography (CT).

Methods

After institutional review board approval, a retrospective analysis was performed, including an electronic search of pathology records for all biopsied adrenal lesions. Patients were included if they also had a contrast-enhanced abdominal CT in the portal venous phase. Computed tomographic images were manually segmented, and texture analysis of the segmented tumors was performed. Texture analysis results of benign and malignant tumors were compared, and areas under the curve (AUCs) were calculated.

Results

One hundred twenty-five patients were included in the analysis. Excellent discriminators of benign from malignant lesions were identified, including entropy and standard deviation. These texture features demonstrated lower values for benign lesions compared with malignant lesions. Entropy values of benign lesions averaged 3.95 using a spatial scaling factor of 4 compared with an average of 5.08 for malignant lesions (P< .0001). Standard deviation values of benign lesions averaged 19.94 on the unfiltered image compared with an average of 34.32 for malignant lesions (P< .0001). Entropy demonstrated AUCs ranging from 0.95 to 0.97 for discriminating tumors, with sensitivities and specificities ranging from 81% to 95% and 88% to 100%, respectively. Standard deviation demonstrated AUCs ranging from 0.91 to 0.94 for discriminating tumors, with sensitivities and specificities ranging from 73% to 93% and 86% to 95%, respectively.

Conclusion

Texture analysis offers a noninvasive tool for differentiating benign from malignant adrenal tumors on contrast-enhanced CT images. These results support the further development of texture analysis as a quantitative biomarker for characterizing adrenal tumors.
Head Ultrasound Resistive Indices Are Associated With Brain Injury on Diffusion Tensor Imaging Magnetic Resonance Imaging in Neonates With Hypoxic-Ischemic Encephalopathy
Authors: Snyder Elizabeth J. , Perin Jamie , Chavez-Valdez Raul , Northington Frances J. , Lee Jennifer K. , Tekes Aylin
Published: August 2020

Background

Neonatal hypoxic-ischemic encephalopathy (HIE) is associated with dysfunctional cerebral autoregulation. Resistive index (RI) measured in the anterior cerebral artery on transfontanellar head ultrasound is a noninvasive measure of blood flow and may indicate autoregulation dysfunction. We tested whether RI was associated with brain injury on diffusion tensor imaging magnetic resonance imaging (MRI).

Materials and Methods

Seventy-five neonates who underwent therapeutic hypothermia for HIE were enrolled. Resistive index values were obtained from head ultrasound performed at the end of therapeutic hypothermia. Apparent diffusion coefficient scalars were measured on MRIs performed before day of life 10.

Results

Lower RI was associated with lower apparent diffusion coefficient in the centrum semiovale, basal ganglia, thalamus, and posterior limb of the internal capsule. Combining RI and Apgar scores improved the ability to distinguish injury severity on MRI relative to either metric alone.

Conclusions

Low RI correlated with worse brain injury on diffusion tensor imaging and may serve as an early marker of brain injury in cooled HIE neonates.
Covid-19: Correlation of Early Chest Computed Tomography Findings With the Course of Disease
Authors: Erturk Sukru Mehmet , Durak Gorkem , Ayyildiz Hakan , Comert Rana Gunoz , Medetalibeyoglu Alpay , Senkal Naci , Uysal Emre , Tunaci Atadan
Published: August 2020

Objective

To investigate the role of chest computed tomography (CT) examinations acquired early after initial onset of symptoms in predicting disease course in coronavirus disease 2019.

Methods

Two hundred sixty-two patients were categorized according to intensive care unit (ICU) admission, survival, length of hospital stay, and reverse transcriptase-polymerase chain reaction positivity. Mean time interval between the onset of symptoms and CT scan was 5.2 ± 2.3 days. Groups were compared using Student t test, Mann-Whitney U, and Fisher exact tests.

Results

In the ICU (+) and died groups, crazy paving (64% and 57.1%), bronchus distortion (68% and 66.7%), bronchiectasis-bronchiolectasis (80% and 76.2%), air trapping (52% and 52.4%) and mediastinal-hilar lymph node enlargement (52% and 52.4%) were significantly more encountered (P < 0,05). These findings were correlated with longer hospital stays (P < 0.05). There were no differences between reverse transcriptase-polymerase chain reaction-positive and -negative patients except bronchiectasis-bronchiolectasis.

Conclusion

Computed tomography examinations performed early after the onset of symptoms may help in predicting disease course and planning of resources, such as ICU beds.
Superficial Peroneal Neurocutaneous Flap for Coverage of Donor Site Defect After the Combined Transfer of Toe and Dorsal Foot Flap
Authors: Wang Chunyang , Yang Weichao , Zhang Feng , Lineaweaver William C. , Wen Gen , Chai Yimin
Published: August 2020

Background

Reconstruction of digital loss with soft tissue defects remains a tough challenge. Although a combined flap of toe and dorsal foot skin provides a good option for “like-for-like” hand reconstruction, the disappointed donor site morbidity prevents it from popularity. In this study, we presented experiences of the superficial peroneal neurocutaneous (SPNC) flap for donor site closure after the combined toe and dorsal foot flap transfer.

Methods

Superficial peroneal neurocutaneous flaps were used to cover foot donor site defects in 9 patients. The flaps harvested from feet including 3 cases of wrap-around flap with dorsal foot flap, 4 cases of 2nd toe flap with dorsal foot flap, 2 cases of 2nd and 3rd toe flap with dorsal foot flap. The flap size, operation time, and complications were documented, and the donor sites were evaluated by the subjective outcome measure, the foot evaluation questionnaire, and the Vancouver Scar Scale.

Results

All flaps but one survived completely without complications. Marginal necrosis occurred in the distal part of the flap in one case, which was treated by daily dressings. The skin grafts on the lower leg healed uneventfully. The average operation time of flap transfer was 40 minutes. Follow-up ranged from 9 to 16 months, and patients were content with the results of the foot donor site according to the outcome measures. All the patients were able to wear normal shoes walking and running with a normal gait, and none sustained complications of skin erosion or ulceration. Protective sensibility was obtained in all the flaps. Two patients complained of cold intolerance and 2 could not wear a thong sandal. The donor site scars on the lower leg were measured 3.2 on average on the Vancouver Scar Scale.

Conclusions

The SPNC flap is a practical procedure for donor site closure on the foot, especially when extra dorsal foot skin is elevated with a toe flap for hand reconstruction.
Considerations for Continuing Simulation Training During Infectious Outbreaks
Authors: Ong Say Yang , Ashokka Balakrishnan , Khoo Deborah , Kelly Michelle A.
Published: August 2020

Summary Statement

Healthcare simulation training can be significantly disrupted by infectious disease outbreaks, yet it is a key component in several important medical education activities, such as resuscitation refresher training and high-stakes prelicensure healthcare examinations. This article details the strategic and tactical considerations for continuing simulation training during infectious disease outbreaks. A framework of graded responses, titrated to outbreak severity, is provided from the perspective of an academic medical center managing simulation training during the early stage of the now global coronavirus disease 2019 outbreak.
Distinct cortical systems reinstate the content and context of episodic memories
Authors: Kragel James E. , Ezzyat Youssef , Lega Bradley C. , Sperling Michael R. , Worrell Gregory A. , Gross Robert E. , Jobst Barbara C. , Sheth Sameer A. , Zaghloul Kareem A. , Stein Joel M. , Kahana Michael J.
Published: August 2020

Episodic recall depends upon the reinstatement of cortical activity present during the formation of a memory. We identified dissociable cortical networks via functional connectivity that uniquely reinstated semantic content and temporal context of previously studied stimuli during free recall. Network-specific reinstatement predicted the temporal and semantic organization of recall sequences, demonstrating how specialized cortical systems enable the human brain to target specific memories.
IMPACT OF COVID-19 PANDEMIC LED LOCKDOWN ON THE LIFESTYLE OF ADOLESCENTS AND YOUNG ADULTS
Authors: Roy Shubhajeet , Tiwari Sunita , Kanchan Shweta , Bajpai Prashant
Published: August 2020

OBJECTIVE

This study was designed to study affect of COVID 19 pandemic on lifestyle of young adults and adolescent.

METHOD

Online survey, was conducted in about 1000 respondents in the age group of 13–25 years.

RESULTS

Questionnaire based survey showed mean sleeping duration changing from 6.85hours to 8.17hours, average screen time becoming 5.12hours from 3.5hours, 51.9% subjects experiencing increased stress levels, 76.4% subjects experiencing increased food intake and 38.6% subjects had decreased levels of physical activity as per self-monitoring.

CONCLUSION

These changes might have long lasting effect on their physical, mental and social health and need counteractive measures to help young people lead a healthy lifestyle during the epidemic and beyond.
Impact of bariatric surgery on multiple health outcomes: a protocol for umbrella review of systematic review and meta-analysis
Authors: Seo Kim Min , Yeob Kim Jong , Park Sungsoo
Published: August 2020

The number of bariatric surgery rises as the prevalence of obesity and metabolic comorbidities consistently increases[1]. Although bariatric surgery was originally developed for glycemic control and weight reduction, increasing evidence suggested extra-metabolic health outcomes are followed by bariatric surgery; incidences on diverse types of cancer[2], perinatal outcomes[3], sexual function[4], and even degree of physical activity[5] are known to be altered after bariatric surgery. We aim to conduct umbrella review for metabolic and other multiple health outcomes following bariatric surgery, and systematically appraise the context and quality of the relevant evidence.

Contact

minseolike@naver.com; crossing96@yonsei.ac.kr
ELAVL1 Primarily Couples mRNA Stability with the 3’UTRs of Interferon Stimulated Genes
Authors: Rothamel Katherine , Arcos Sarah , Kim Byungil , Reasoner Clara , Mukherjee Neelanjan , Ascano Manuel
Published: August 2020

Upon detection of a pathogen, the innate immune system triggers signaling events leading to the transcription of mRNAs that encode for pro-inflammatory and anti-microbial effectors. RNA-binding proteins (RBPs) interact with these functionally critical mRNAs and temporally regulate their fates at the post-transcriptional level. One such RBP is ELAVL1, which is known to bind to introns and 3’UTRs. While significant progress has been made in understanding how ELAVL1 regulates mRNAs, how its target repertoire and binding affinity changes within an immunological context remains poorly understood. Here, we overlap four distinct high-throughput approaches to define its cell-type and context-dependent targets and determine its regulatory impact during immune activation. ELAVL1 overwhelmingly binds to intronic sites in a naïve state, but during an innate immune response, ELAVL1 targets the 3’UTR - binding both previously and newly expressed mRNAs. We find that ELAVL1 mediates the RNA stability of genes that regulate the pathways involved in pathogen sensing and cytokine production. Our findings reveal the importance of examining RBP regulatory impact under dynamic transcriptomic events to best understand their post-transcriptional regulatory roles within specific biological circuitries.
TOLLIP resolves lipid-induced EIF2 signaling in alveolar macrophages for durableMycobacterium tuberculosisprotection
Authors: Venkatasubramanian Sambasivan , Plumlee Courtney , Dill-McFarland Kim , Pearson Gemma L. , Cohen Sara B. , Lietzke Anne , Pacheco Amanda , Hinderstein Sarah A. , Emery Robyn , Soleimanpour Scott A. , Altman Matthew , Urdahl Kevin B. , Shah Javeed A.
Published: August 2020

Relative deficiency of TOLLIP expression in monocytes is associated with increased tuberculosis (TB) susceptibility in genetic studies, despite antagonizing host innate immune pathways that controlMycobacterium tuberculosis(Mtb) infection. In this study, we investigated the mechanisms by which TOLLIP influences Mtb immunity.Tollip-/-mice developed worsened disease, consistent with prior genetic observations, and developed large numbers of foam cells. Selective TOLLIP deletion in alveolar macrophages (AM) was sufficient to induce lipid accumulation and increased Mtb persistence 28 days after infection, despite increased antimicrobial responses. We analyzed sorted, Mtb-infectedTollip-/-AM from mixed bone marrow chimeric mice to measure global gene expression 28 days post-infection. We found transcriptional profiles consistent with increased EIF2 signaling. Selective lipid administration toTollip-/-macrophages induced lipid accumulation, and Mtb infection of lipid laden,Tollip-/-macrophages induced cellular stress and impaired Mtb control. EIF2 activation induced increased Mtb replication within macrophages, irrespective of TOLLIP expression, and EIF2 kinases were enriched in human caseous granulomas. Our findings define a critical checkpoint for TOLLIP to prevent lipid-induced EIF2 activation and demonstrate an important mechanism for EIF2 signaling to permit Mtb replication within macrophages.
State-dependent changes in perception and coding in the mouse somatosensory cortex
Authors: Lee Conrad CY , Kheradpezhouh Ehsan , Diamond Mathew E. , Arabzadeh Ehsan
Published: August 2020

An animal’s behavioral state is reflected in the dynamics of cortical population activity and its capacity to process sensory information. To better understand the relationship between behavioral states and information processing, mice are trained to detect varying amplitudes of whisker-deflection under two-photon calcium imaging. Layer 2/3 neurons (n=1436) in the vibrissal primary somatosensory cortex are imaged across different behavioral states, defined based on detection performance (low to high-state) and pupil diameter. The neurometric curve in each behavioral state mirrors the corresponding psychometric performance, with calcium signals predictive of the animal’s choice outcome. High behavioral states are associated with lower network synchrony, extending over shorter cortical distances. The decrease of correlations in variability across neurons in the high state results in enhanced information transmission capacity at the population level. The observed state-dependent changes suggest that the coding regime within the first stage of cortical processing may underlie adaptive routing of relevant information through the sensorimotor system.

Highlights

Network synchrony and pupil diameter are coupled to changes in behavioral state.

High behavioral state results in enhanced information transmission capacity at the population level, with neurometric curve in each behavioral state mirroring the corresponding psychometric performance

Behavioral state and calcium signal in primary somatosensory cortex predict choice outcome.

eTOC

In Brief

Lee et al. investigates the relationship between behavioral states and information processing in the primary somatosensory cortex. They demonstrate increases in behavioral state results in decrease cortical variability, enhanced information transmission capacity and stimulus encoding at the population level.
TaxonTableTools - A comprehensive, platform-independent graphical user interface software to explore and visualise DNA metabarcoding data
Authors: Macher Till-Hendrik , Beermann Arne J. , Leese Florian
Published: August 2020

DNA metabarcoding is increasingly used in research and application to assess biodiversity. Powerful analysis software exists to process raw data. However, when it comes to the translation of sequence read data into biological information many end users with limited bioinformatic expertise struggle with the downstream analysis and explore data only to a minor extent. Thus, there is a growing need for easy-to-use, graphical user interface (GUI) analysis software to analyse and visualise DNA metabarcoding data. We here present TaxonTableTools (TTT), a new platform independent GUI software that aims to fill this gap by providing simple and reproducible analysis and visualisation workflows. TTT uses a so-called “TaXon table” as input. This format can easily be generated within TTT from two input files: a read table and a taxonomy table that can be obtained by various published metabarcoding pipelines. TTT analysis and visualisation modules include e.g. Venn diagrams to compare taxon overlap among replicates, samples or among different analysis methods. It analyses and visualises basic statistics such as read proportion per taxon as well as more sophisticated visualisation such as interactive Krona charts for taxonomic data exploration. Various ecological analyses such as alpha or beta diversity estimates, and rarefaction analysis ordination plots can be produced directly. Data can be explored also in formats required by traditional taxonomy-based analyses of regulatory bioassessment programs. TTT comes with a manual and tutorial, is free and publicly available through GitHub (https://github.com/TillMacher/TaxonTableTools) and the Python package index (https://pypi.org/project/taxontabletools/).
Versatile, Multivalent Nanobody Cocktails Efficiently Neutralize SARS-CoV-2
Authors: Xiang Yufei , Nambulli Sham , Xiao Zhengyun , Liu Heng , Sang Zhe , Duprex W. Paul , Schneidman-Duhovny Dina , Zhang Cheng , Shi Yi
Published: August 2020

The outbreak of COVID-19 has severely impacted global health and the economy. Cost-effective, highly efficacious therapeutics are urgently needed. Here, we used camelid immunization and proteomics to identify a large repertoire of highly potent neutralizing nanobodies (Nbs) to the SARS-CoV-2 spike (S) protein receptor-binding domain (RBD). We discovered multiple elite Nbs with picomolar to femtomolar affinities that inhibit viral infection at sub-ng/ml concentration, more potent than some of the best human neutralizing antibodies. We determined a crystal structure of such an elite neutralizing Nb in complex with RBD. Structural proteomics and integrative modeling revealed multiple distinct and non-overlapping epitopes and indicated an array of potential neutralization mechanisms. Structural characterization facilitated the bioengineering of novel multivalent Nb constructs into multi-epitope cocktails that achieved ultrahigh neutralization potency (IC50s as low as 0.058 ng/ml) and may prevent mutational escape. These thermostable Nbs can be rapidly produced in bulk from microbes and resist lyophilization, and aerosolization. These promising agents are readily translated into efficient, cost-effective, and convenient therapeutics to help end this once-in-a-century health crisis.
Mutation ofIDR1enhances drought tolerance by reducing ROS production and activating ROS scavenging in rice
Authors: Zu Xiaofeng , Lu Yanke , Wang Qianqian , La Yumei , Tan Feng , Niu Jiayu , Xia Huihui , Hong Xinyue , Wu Yufeng , Zhou Shaoxia , Li Kun , Chen Huhui , Qiang Sheng , Rui Qi , Wang Huaqi , La Honggui
Published: August 2020

To discover new mutant alleles conferring enhanced tolerance to drought stress, we screened a mutagenized rice population (cv. IAPAR9) and identified a mutant, namedidr1-1(for increased drought resistance 1-1), with obviously increased drought tolerance under upland field conditions. Theidr1-1mutant possessed a significantly enhanced ability to tolerate high-drought stress in different trials. Map-based cloning revealed that the gene LOC_Os05g26890 (corresponding toD1orRGA1gene), residing in the mapping region ofIDR1locus, carried a single-base deletion in theidr1-1mutant, which caused a frameshift and premature translation termination. Complementation tests indicated that such a mutation was indeed responsible for the elevated drought tolerance inidr1-1mutant. IDR1 protein was localized in nucleus and to plasma membrane or cell periphery. Further investigations indicated that the significantly increased drought tolerance inidr1-1mutant stemmed from a range of physiological and morphological changes occurring in such a mutant, including greater leaf potentials, increased proline contents, heightened leaf thickness, and upregulation of antioxidant-synthesizing and drought-induced genes, etc., under drought-stressed conditions. Especially, ROS production from NADPH oxidases and chloroplasts might be remarkably impaired, while ROS-scavenging ability appeared to be markedly enhanced as a result of significantly elevated expression of a dozen ROS-scavenging enzyme genes inidr1-1mutant under drought-stressed conditions. Besides, IDR1 physically interacted with TUD1, andidr1-1mutant showed impaired EBR responsiveness. Altogether, these results suggest that mutation of IDR1 leads to alterations of multiple layers of regulations, which ultimately confers obviously enhanced drought tolerance to theidr1-1mutant.

One-sentence summary

Mutation ofIDR1significantly enhances drought tolerance in an upland cultivar IAPAR9 by decreasing apoplastic and chloroplastic ROS production and increasing ROS-scavenging ability
Leptin signaling regulates physiological damage and host-pathogen cooperation
Authors: Sanchez Karina K. , Troha Katia , Stengel Sarah , Ayres Janelle S.
Published: August 2020

To combat infections, hosts employ a combination of antagonistic and cooperative defense strategies. The former refers to pathogen killing mediated by resistance mechanisms, while the latter refers to physiological defense mechanisms that promote host health during infection independent of pathogen killing, leading to an apparent cooperation between the host and the pathogen. Previous work has shown that leptin, a pleiotropic hormone that plays a central role in regulating appetite and energy metabolism, is indispensable for resistance mechanisms, while a role for leptin signaling in cooperative host-pathogen interactions remains unknown. Using a mouse model ofYersinia pseudotuberculosis(Yptb) infection, the causative agent of Far East scarlet-like fever, we unexpectedly found that genetic inhibition of leptin signaling conferred protection fromYptbinfection due to increased host-pathogen cooperation rather than greater resistance defenses. The protection againstYptbinfection was not due to differences in food consumption, lipolysis or fat mass. Furthermore, we found that the survival advantage was associated with increased liver damage and dysfunction. Our work reveals an additional level of complexity for the role of leptin in infection defense and suggests that in some contexts, in addition to tolerating the pathogen, tolerating organ damage and dysfunction is more beneficial for survival than preventing the damage.
A functional chromogen geneCfrom wild rice is involved in a different anthocyanin biosynthesis pathway inindicaandjaponica
Authors: Qiao Weihua , Wang Yanyan , Xu Rui , Yang Ziyi , Sun Yan , Su Long , Zhang Lizhen , Wang Junrui , Huang Jingfen , Zheng Xiaoming , Liu Shijia , Tian Yunlu , Chen Liangming , Liu Xi , Lan Jinhao , Yang Qingwen
Published: August 2020

Accumulation of anthocyanin is a desirable trait to be selected in rice domestication, but the molecular mechanism of anthocyanin biosynthesis in rice remains largely unknown. In this study, a novel allele of chromogen geneC,OrC1, fromOryza rufipongonwas cloned and identified as a determinant regulator of anthocyanin biosynthesis. AlthoughOrC1functions in purple apiculus, leaf sheath and stigma inindicabackground, it only promotes purple apiculus injaponica. Transcriptome analysis revealed thatOrC1regulates flavonoid biosynthesis pathway and activates a few bHLH and WD40 genes of ternary MYB-bHLH-WD40 complex inindica. Differentially expressed genes and metabolites were found in theindicaandjaponicabackgrounds, indicating thatOrC1activated the anthocyanin biosynthetic genesOsCHI,OsF3H,OsANS,OsINSandOsANRand produced six metabolites independently. Artificial selection and domestication ofC1gene in rice occurred on the coding region in the two subspecies independently. Our results reveal the regulatory system and domestication ofC1, provide new insights into MYB transcript factor involved in anthocyanin biosynthesis, and show the potential of engineering anthocyanin biosynthesis in rice.

Author summary

Accumulation of anthocyanin is a selection trait in rice domestication, whereas the mechanisms regulating the anthocyanin biosynthetic pathway in rice remain unresolved. Here, a novel allele of chromogen gene C from wild rice (Oryza rufipongon) was identified as a determinant regulator of anthocyanin biosynthesis. A key question is to what extent the involvement of the C1 gene can explain coloration variability of cultivated rice, where anthocyanin accumulation has been eliminated by artificial selection. Our results reveal the functional chromogen gene C from wild rice causes different coloration phenotypes, regulates various anthocyanin biosynthetic genes and produces different metabolites inindicaandjaponica. Artificial selection and domestication of the C1 gene in rice only occurs within the coding region of the two subspecies independently.
Dipeptidyl peptidase 9 triggers BRCA2 degradation by the N-degron pathway to promote DNA-damage repair
Authors: Silva-Garcia Maria , Bolgi Oguz , Ross Breyan , Pilla Esther , Kari Vijayalakshmi , Killisch Markus , Stark Nadine , Lenz Christof , Spitzner Melanie , Gorrell Mark D. , Grade Marian , Urlaub Henning , Dobbelstein Matthias , Huber Robert , Geiss-Friedlander Ruth
Published: August 2020

Dipeptidyl peptidase 9(DPP9) is a serine protease cleaving N-terminal dipeptides preferentially post-proline with (patho)physiological roles in the immune system and cancer. Only few DPP9 substrates are known. Here we identify an association of human DPP9 with the tumour suppressor BRCA2, a key player in repair of DNA double-strand breaks that promotes the formation of RAD51 filaments. This interaction is triggered by DNA-damage and requires access to the DPP9 active-site. We present crystallographic structures documenting the N-terminal Met1-Pro2of a BRCA21-40peptide captured in the DPP9 active-site. Mechanistically, DPP9 targets BRCA2 for degradation by the N-degron pathway, and promotes RAD51 foci formation. Both processes are phenocopied by BRCA2 N-terminal truncation mutants, indicating that DPP9 regulates both stability and the cellular stoichiometric interactome of BRCA2. Consistently, DPP9-deprived cells are hypersensitive to DNA-damage. Together, we identify DPP9 as a regulator of BRCA2, providing a possible explanation for DPP9 involvement in cancer development.
Contextual Prediction Errors Reorganize Episodic Memories in Time
Authors: Yazin Fahd , Das Moumita , Banerjee Arpan , Roy Dipanjan
Published: August 2020

Episodic memories are contextual experiences ordered in time. This is underpinned by associative binding between events within the same contexts. The role of prediction errors in strengthening declarative memory is well established but has not been investigated in the time dimension of complex episodic memories. Here we used 3-day movie viewing paradigm to test the hypothesis that contextual prediction errors leads to temporal organization of sequential memory processing. Our main findings uncover that prediction errors lead to changes in temporal organization of events, secondly, new unexpected sequences show as high accuracy as control sequences viewed repeatedly, and these effects are specifically due to prediction errors, and not novel associations. A drift-diffusion modelling further revealed a lower decision threshold for the newer, unexpected sequences compared to older sequences reflected by their faster recall leads to reorganization of episodes in time. Moreover, we found individual decision threshold could significantly predict their relative speed of sequence memory recall. Taking together our results suggest a temporally distinct role for prediction errors in ordering sequences of events in episodic memory.
A Connectome-Based Approach to Assess Motor Outcome after Neonatal Arterial Ischemic Stroke
Authors: Harrach Mariam Al , Pretzel Pablo , Groeschel Samuel , Rousseau François , Dhollander Thijs , Hertz-Pannier Lucie , Lefevre Julien , Chabrier Stéphane , Dinomais Mickael ,   on behalf of the AVCnn study group
Published: August 2020

Objective

studies of motor outcome after Neonatal Arterial Ischemic Stroke (NAIS) often rely on lesion mapping using MRI. However, clinical measurements indicate that motor deficit can be different than what would solely be anticipated by the lesion extent and location. Because this may be explained by the cortical disconnections between motor areas due to necrosis following the stroke, the investigation of the motor network can help in the understanding of visual inspection and outcome discrepancy. In this study, we propose to examine the structural connectivity between motor areas in NAIS patients compared to healthy controls in order to define the cortical and subcortical connections that can reflect the motor outcome

Methods

30 healthy controls and 32 NAIS patients with and without Cerebral Palsy (CP) underwent MRI acquisition and manual assessment. The connectome of all participants was obtained from T1-weighted and diffusion-weighted imaging.

Results

significant disconnections in the lesioned and contra-lesioned hemispheres of patients were found. Furthermore, significant correlations were detected between the structural connectivity metric of specific motor areas and manuality assessed by the Box and Block Test (BBT) scores in patients.

Interpretation

using the connectivity measures of these links the BBT score can be estimated using a multiple linear regression model. In addition, the presence or not of CP can also be predicted using the KNN classification algorithm. According to our results, the structural connectome can be an asset in the estimation of gross manual dexterity and can help uncover structural changes between brain regions related to NAIS.