bluuebunny/crossref_metadata_2025 huggingface dataset:
Media attention and policy response: 21st century chemical regulation in the USA
Authors: Matus Kira J M , Bernal Marie N
Published: June 2020

This article explores the relationship between media coverage of chemical hazards, scientific understandings of chemical risk, and policy change in the USA at the state level from 1990 to 2010. We observe that media coverage compounded by scientific development, especially in relation to a greater understanding of chemical hazards and approaches to its management, affected public perception of health and environmental risk, aiding in a shift of expectations about necessary levels of statutory protection from the states. We also note the emergence of effective framings of chemical risk around impacts on vulnerable populations, such as children, where media attention and policy action created important coalitions of support. The resulting increased state-, county-, and city-level policy action eventually led to support and momentum policy change at the federal level. This study helps to clarify how media attention to chemical hazards may play an important role in influencing eventual policy responses and risk management approaches.
Gestational sleep deprivation is associated with higher offspring body mass index and blood pressure
Authors: Harskamp-van Ginkel Margreet W , Ierodiakonou Despo , Margetaki Katerina , Vafeiadi Marina , Karachaliou Marianna , Kogevinas Manolis , Vrijkotte Tanja G M , Chatzi Leda
Published: June 2020

Study Objectives

The objective of this study was to evaluate the association between gestational sleep deprivation and childhood adiposity and cardiometabolic profile.

Methods

Data were used from two population-based birth cohorts (Rhea study and Amsterdam Born Children and their Development study). A total of 3,608 pregnant women and their children were followed up until the age of 11 years. Gestational sleep deprivation was defined as 6 or fewer hours of sleep per day, reported by questionnaire. The primary outcomes included repeated measures of body mass index (BMI), waist circumference, body fat, serum lipids, systolic and diastolic blood pressure (DBP) levels in childhood. We performed a pooled analysis with adjusted linear mixed effect and Cox proportional hazards models. We tested for mediation by birthweight, gestational age, and gestational diabetes.

Results

Gestational sleep deprivation was associated with higher BMI (beta; 95% CI: 0.7; 0.4, 1.0 kg/m2) and waist circumference (beta; 95% CI: 0.9; 0.1, 1.6 cm) in childhood, and increased risk for overweight or obesity (HR; 95% CI: 1.4; 1.1, 2.0). Gestational sleep deprivation was also associated with higher offspring DBP (beta; 95% CI: 1.6; 0.5, 2.7 mmHg). The observed associations were modified by sex (all p-values for interaction < 0.05); and were more pronounced in girls. Gestational diabetes and shorter gestational age partly mediated the seen associations.

Conclusions

This is the first study showing that gestational sleep deprivation may increase offspring’s adiposity and blood pressure, while exploring possible mechanisms. Attention to glucose metabolism and preterm birth might be extra warranted in mothers with gestational sleep deprivation.
Bioactivity of Circulatory Factors After Pulmonary Exposure to Mild or Stainless Steel Welding Fumes
Authors: Kodali Vamsi , Shoeb Mohammad , Meighan Terence G , Eye Tracy , Friend Sherri A , Hubczak John , Kashon Michael L , Zeidler-Erdely Patti C , Antonini James M , Erdely Aaron
Published: June 2020

Studies suggest that alterations in circulating factors are a driver of pulmonary-induced cardiovascular dysfunction. To evaluate, if circulating factors effect endothelial function after a pulmonary exposure to welding fumes, an exposure known to induce cardiovascular dysfunction, serum collected from Sprague Dawley rats 24 h after an intratracheal instillation exposure to 2 mg/rat of 2 compositionally distinct metal-rich welding fume particulates (manual metal arc welding using stainless steel electrodes [MMA-SS] or gas metal arc welding using mild steel electrodes [GMA-MS]) or saline was used to test molecular and functional effects of in vitro cultures of primary cardiac microvascular endothelial cells (PCMEs) or ex vivo organ cultures. The welding fumes elicited significant pulmonary injury and inflammation with only minor changes in measured serum antioxidant and cytokine levels. PCME cells were challenged for 4 h with serum collected from exposed rats, and 84 genes related to endothelial function were analyzed. Changes in relative mRNA patterns indicated that serum from rats exposed to MMA-SS, and not GMA-MS or PBS, could influence several functional aspects related to endothelial cells, including cell migration, angiogenesis, inflammation, and vascular function. The predictions were confirmed using a functional in vitro assay (scratch assay) as well as an ex vivo multicellular environment (aortic ring angiogenesis assay), validating the concept that endothelial cells can be used as an effective screening tool of exposed workers for determining bioactivity of altered circulatory factors. Overall, the results indicate that pulmonary MMA-SS fume exposure can cause altered endothelial function systemically via altered circulating factors.
Compartment Syndrome in Operatively Managed Pediatric Monteggia Fractures and Equivalents
Authors: Kopriva John , Awowale John , Whiting Paul , Livermore Andrew , Siy Alex , Hetzel Scott , Noonan Kenneth
Published: June 2020

Background:

Acute compartment syndrome (ACS) is not commonly associated with pediatric Monteggia fractures or Monteggia equivalents (MF/ME). The aims of this study were: (1) To document a rate of ACS among children with operatively managed MF/ME, comparing this to the rate of ACS in classically associated Type 3 supracondylar humerus (T3-SCH) fractures at the same institution; (2) To determine which patients with MF/ME are at highest risk for ACS.

Methods:

Children ages 2 to 12 with MF/ME requiring operative management at an academic institution over a 14-year period were identified. The Monteggia fractures were characterized using the Bado classification; equivalent injuries were identified according to established criteria. Similarly, all patients with T3-SCH fractures managed over the same period were identified. Record review included demographic, procedural, and radiographic variables. Statistical analysis compared the rates of ACS in both groups and determined risk factors associated with developing ACS in patients with MF/ME.

Results:

The rate of ACS in MF/ME was 9 of the 59 (15.3%), which was significantly higher than the rate of ACS in T3-SCH fractures 2 of the 230 (0.9%) (P=0.001). Comparing MF/ME with ACS to those without; there was no difference in sex (P=1.00), Bado Type (P=0.683), or Monteggia fracture versus equivalent (P=0.704). MF/ME with preoperative vascular deficits (22.2%) and those undergoing intramedullary fixation of the radius were more likely to develop ACS (P=0.021 and 0.015, respectively), and there was a trend toward higher rates of ACS among MF/ME with preoperative neurological deficits (P=0.064).

Conclusions:

Patients with operatively managed MF/ME had a significantly higher rate of ACS compared with patients with T3-SCH fractures. With no predisposition based on Bado classification or Monteggia fracture versus equivalent, all operatively managed MF/ME appear to be at risk for ACS. Patients with preoperative neurovascular deficits and those undergoing intramedullary radial fixation develop ACS at higher rates. Careful assessment of the forearm for signs and symptoms of ACS both before and after fixation is critical.

Level of Evidence:

Level III—retrospective case control.
Early Plastic Surgery Involvement Improves Outcomes in Total Joint Arthroplasty Patients With Soft Tissue Complications
Authors: Vajapey Sravya P. , Chandawarkar Rajiv , Glassman Andrew H.
Published: June 2020

The authors reviewed the outcomes of patients who have undergone total hip or knee arthroplasty and concurrent soft tissue reconstruction at our institution and describe our combined orthoplastic approach to such patients. This was a retrospective series of 8 patients who underwent the soft tissue reconstruction procedure before or after joint replacement by a single orthopedic surgeon in collaboration with a single plastic surgeon. Five men and 3 women met inclusion criteria. Flap reconstruction was performed in 7 of 8 cases, skin grafting in 3 of 8 cases, and complex wound closure in 1 of 8 cases. The majority of patients had 1 or 2 risk factors for developing wound complications. Five had a good outcome at the final follow-up and 3 had poor outcomes. Of 5 patients who had good outcomes, 4 underwent plastic surgery evaluation for prophylactic soft tissue reconstruction because of prior failed arthroplasty procedure, soft tissue scarring, atrophy, or previous infection. Of 3 with poor outcomes, 2 underwent plastic surgery evaluation for a salvage procedure after they developed soft tissue complications. Joint arthroplasty patients undergoing early plastic surgery evaluation for prophylactic soft tissue reconstruction had better outcomes compared with patients undergoing evaluation for a salvage procedure after soft tissue complications have developed.
Effect of sustained intensive therapy with disease modifying anti-rheumatic drugs in rheumatoid arthritis: a 5-year real-world consecutive study
Authors: Cai Yue-Ming , Li Ru , Ye Hua , He Jing , Sun Xiao-Lin , Jin Jia-Yang , Liu Jia-Jia , Gan Yu-Zhou , You Xu-Jie , Xu Jing , Shi Lian-Jie , Cheng Gong , Wang Qing-Wen , Li Zhan-Guo
Published: June 2020

Background

Intensive therapy with disease modifying anti-rheumatic drugs (DMARDs) has been reported to improve the outcomes of rheumatoid arthritis (RA). However, real-world study on the effect of intensive therapy on RA sustained remission is still lacking. This study aimed to investigate the outcome of sustained intensive DMARD therapy (SUIT) for RA in a real-world 5-year consecutive cohort.

Methods

Based on a consecutive cohort of 610 out-patients with RA, remission of RA was assessed in 541 patients from 2012 to 2017, by dividing into SUIT, non-SUIT, and intermittent SUIT (Int-SUIT) groups. Changes in the disease activity scores were evaluated by 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR), 28-joint disease activity score based on C-reactive protein (DAS28-CRP), and clinical deep remission criteria (CliDR). Cumulative remission rates between different groups were compared using Kaplan-Meier curves and predictive factors of sustained remission were identified by univariate and multivariate logistic regression analysis.

Results

The remission rates of the SUIT group decreased from 12.0% (65/541) to 5.6% (20/359) based on DAS28-ESR, from 14.0% (76/541) to 7.2% (26/359) based on DAS28-CRP, and from 8.5% (46/541) to 3.1% (11/359) based on CliDR, respectively, with a gradually decreasing trend during the 5 years. The SUIT regimen led to a significantly higher cumulative remission rate than non-SUIT regimen based on DAS28-ESR (39.7% vs. 19.5%, P = 0.001), DAS28-CRP (42.0% vs. 19.6%, P = 0.001), and CliDR (24.5% vs. 8.7%, P = 0.001). The cumulative remission rates of patients treated with SUIT regimen were significantly higher than those treated with Int-SUIT regimen based on DAS28-ESR (39.7% vs. 25.7%, P = 0.043) and CliDR (24.5% vs. 14.2%, P = 0.047), but there was no significant difference between the two groups based on DAS28-CRP (42.0% vs. 27.4%, P = 0.066). Multivariate logistic regression analysis showed that the use of SUIT regimen was an independent favorable predictor according to different remission definitions (for DAS28-ESR: odds ratio [OR], 2.215, 95% confidence interval [CI]: 1.271–3.861, P = 0.005; for DAS28-CRP: OR, 1.520, 95% CI: 1.345–1.783, P = 0.002; for CliDR: OR, 1.525, 95% CI: 1.314–1.875, P = 0.013).

Conclusion

Sustained intensive treatment of RA is an optimal strategy in daily practice and will lead to an increased remission rate.
Drug-induced priapism
Authors: Pucci Mark , Roussak Penelope , Pang David , Darrad Maitrey
Published: June 2020

Drug-induced priapism is a rare but serious condition associated with a variety of prescribed and illicit drugs. The most common causes include antipsychotics, oral phosphodiesterase type 5 inhibitors, the antidepressant trazodone, and alpha-adrenoceptor antagonists prescribed for hypertension or lower urinary tract symptoms (such as prazosin and tamsulosin). Risk factors include predisposing conditions such as sickle cell disease, spinal cord injury, and history of previous priapism. When patients present to the Emergency Department with priapism, a thorough drug history should be carried out, including use of recreational drugs and drugs obtained without prescription.
Association Between Dry Eye and Polycystic Ovary Syndrome: Subclinical Inflammation May Be Part of the Process
Authors: Asfuroğlu Yonca , Kan Özgür , Asfuroğlu Mahmut , Baser Emre
Published: June 2020

Purpose:

To evaluate the changes in tear function in patients with polycystic ovary syndrome (PCOS) and establish whether there is a correlation between hormonal levels, novel hematologic biomarkers, and dry eye parameters.

Material and Method:

Forty-seven patients with PCOS and 43 age-matched patients with unexplained infertility were included in the control group. Follicle-stimulating hormone, luteinizing hormone, estradiol, thyroid-stimulating hormone, prolactin, dehydroepiandrosterone sulfate (DHEA-S), 17-OH progesterone, fasting and postprandial glucose, fasting insulin, and cholesterol metabolites were evaluated in both groups. In addition, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio were obtained from a complete blood count. The Ocular Surface Disease Index (OSDI) questionnaire was administered, and all patients underwent tear break-up time (BUT) and Schirmer I tests. Bivariate correlations were investigated using Spearman correlation coefficient analysis.

Results:

The mean age of the PCOS group and the control group was 27.66±3.96 years and 29.28±6.83 years, respectively. Schirmer I test scores and BUT values were significantly lower and OSDI results were significantly higher in the PCOS group (P=0.003, P<0.001, and P=0.004). An inverse correlation was found between DHEA-S and BUT values in the PCOS group (r=−0.296, P=0.043). Similarly, a negative correlation was also present between NLR and BUT values in the PCOS group (r=−0.322, P=0.027).

Conclusions:

Dry eye can be well established by sensitive tests in patients with PCOS. The severity of dry eye may be correlated with the level of inflammation and hyperandrogenism.
Prevention of Acquisition of Cytomegalovirus Infection in Pregnancy Through Hygiene-based Behavioral Interventions: A Systematic Review and Gap Analysis
Authors: Barber Victoria , Calvert Anna , Vandrevala Tushna , Star Caroline , Khalil Asma , Griffiths Paul , Heath Paul T. , Jones Christine E.
Published: June 2020

Background:

Congenital cytomegalovirus infection is the most common nongenetic cause of sensorineural hearing loss in childhood and an important cause of neurodisability. There is no licensed cytomegalovirus (CMV) vaccine and no antenatal treatment for congenital CMV that is routinely recommended in clinical practice in the United Kingdom.

Objectives:

To review the published literature for studies that evaluated preventative hygiene-based interventions in pregnancy for their impact on knowledge about CMV prevention, the uptake of preventative behaviors or the acquisition of CMV in pregnancy.

Search Strategy:

Searches were carried out in Medical Literature Analysis and Retrieval System Online and Cumulative Index of Nursing and Allied Health Literature databases.

Selection Criteria:

All human studies, limited to women of childbearing age were included.

Data Collection and Analysis:

Two reviewers independently assessed the quality of the methods and results of included articles. Extracted data were classified using Cochrane guidelines.

Main Results:

Seven studies met the inclusion criteria. These show that preventative measures are acceptable to pregnant women, can impact their behavior and have the potential to reduce CMV in pregnancy. They are limited by several factors; sample size, nonrandomized trial design and interventions that are beyond routine clinical practice.

Conclusions:

An effective intervention that changes behavior in pregnancy and reduces the risk of CMV acquisition is needed as part of routine care. There is currently insufficient evidence about the form that this intervention should take.

Registration:

PROSPERO registration number: CRD42017069666.
Impact of a Point-of-care Respiratory PCR Panel in a Pediatric Clinic on Postvisit Communication and Follow-up Visits
Authors: Fenton Jesse , Posa Molly , Kelly Maria , Rand Kenneth H. , Beal Stacy G.
Published: June 2020

While the FilmArray Respiratory Panel EZ has been proven to reduce inappropriate antibiotic use in the outpatient pediatric setting, it is unclear whether its implementation will also reduce downstream health costs such as provider visits and telephone calls. This analysis will help pediatricians make more informed decisions on the implementation and judicious use of the Respiratory Panel EZ in their clinical practice.
The Role of Children in the Dynamics of Intra Family Coronavirus 2019 Spread in Densely Populated Area
Authors: Somekh Eli , Gleyzer Alexadra , Heller Eli , Lopian Miriam , Kashani-Ligumski Lior , Czeiger Shelly , Schindler Yehudit , Lessing Joseph. B. , Stein Michal
Published: June 2020

We examined the dynamics of coronavirus 2019 (COVID-19) transmission within families. Our investigation demonstrated significantly lower rates of COVID-19 positivity in children compared with adults residing in the same household. Children of 5–17 years of age were 61% and children of 0–4 years of age were 47% less likely to have positive polymerase chain reaction results compared with adults residing in the same household.
COVID-19-Associated Myocarditis in an Adolescent
Authors: Trogen Brit , Gonzalez Francisco J. , Shust Gail F.
Published: June 2020

A 17-year-old obese male was admitted to the pediatric intensive care unit after presenting with fluid-responsive septic shock following 7 days of fever, gastrointestinal symptoms and neck pain. Initial workup was positive for SARS-CoV-2 and elevated troponin I and brain natriuretic peptide. Echocardiography and cardiac magnetic resonance imaging confirmed acute myocarditis. One week after discharge, repeat echocardiogram demonstrated improved heart function with only residual myocardial dysfunction.
Malassezia Hepatic Abscess in a Neonate
Authors: Cantey Joseph B. , Dallas Steven D. , Cigarroa Francisco G. , Quinn Amy F.
Published: June 2020

Malassezia sp. require exogenous lipid for growth and can cause disseminated infection in neonates requiring intravenous lipid infusions. Usually, Malassezia infection in neonates presents as fungemia or hematogenous dissemination into bone or lungs. We present a presumed case of Malassezia liver abscess associated with lipid infusion via a mispositioned umbilical venous catheter.
Differences between Breast Cancer Reconstruction and Institutionally Established Normative Data Using the BREAST-Q Reconstruction Module: A Comparative Study
Authors: Klifto Kevin M. , Aravind Pathik , Major Melissa , Payne Rachael M. , Shen Wen , Rosson Gedge D. , Cooney Carisa M. , Manahan Michele A.
Published: June 2020

Background:

Evidence is limited for BREAST-Q scores in women without breast cancer or breast surgery to establish baseline values for clinical interpretation. The primary aim of this study was to compare differences in breast satisfaction and quality of life in women without breast cancer and without breast surgery to patients undergoing breast reconstruction using the BREAST-Q.

Methods:

The authors performed a single-center, patient-reported outcomes comparative study. A sample of 300 women attending gynecology appointments completed a study-specific demographics form and preoperative BREAST-Q reconstruction module. Eligible women had no history of breast cancer or breast surgery and were not currently pregnant (control group). The authors compared prospectively collected control group data to demographics and preoperative and 12-month postoperative BREAST-Q scores in 300 breast reconstruction patients, retrospectively selected from a prospectively collected registry.

Results:

Control group BREAST-Q scores were higher in Satisfaction with Breasts (mean, 59.3 versus 55.3; p < 0.042) and Physical Well-being Chest scores (mean, 84.1 versus 78.8; p < 0.001), and lower for Physical Well-being Abdomen scores (mean, 81.9 versus 88.7; p < 0.001) when compared to breast reconstruction patients’ preoperative scores. When compared with breast reconstruction patients’ 12-month postoperative scores, control group scores were lower in Satisfaction with Breasts (mean, 59.3 versus 65.5; p < 0.002) and Psychosocial Well-being (mean, 69.5 versus 76.2; p < 0.001) and higher in Physical Well-being Chest (mean, 84.1 versus 78.2; p < 0.001).

Conclusions:

The authors found differences in preoperative and 12-month postoperative BREAST-Q scores between breast reconstruction patients and a comparable control population. Establishing normative BREAST-Q data could serve as an important baseline for breast outcomes research and better understanding of patients’ ability to recover quality of life following reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
Rhinoplasty Refinements: Revision Rhinoplasty Using Fresh Frozen Costal Cartilage Allograft
Authors: Rohrich Rod J. , Shanmugakrishnan R. Raja , Mohan Raja
Published: June 2020

A crooked nose is challenging for a surgeon and needs to be treated using a systematic approach. Correction of nasal deformities such as a retracted columella in a revision rhinoplasty may need additional cartilage to correct the framework. Fresh frozen cartilage graft has been used as an extended spreader graft and a columellar strut graft to correct this problem. This option prevents donor-site morbidity associated with harvesting autologous cartilage.
The SPF-SPLF Graft: Building the Ideal Dorsum in Revision Rhinoplasty
Authors: Robotti Enrico , Leone Francesco
Published: June 2020

Achieving a natural appearing dorsum in secondary rhinoplasty remains an elusive goal. An inherent contradiction exists between the two most usually used techniques: solid rib segment and diced cartilage fascia constructs. The former will often cause edge visibility, in addition to potential warping and distortion; the latter prevents from both but may generate obtuse, ill-defined borders with poor shape control, possible contour asymmetries, and often a tubular appearance. A solution to the equation can be found in an innovative technique that combines three elements: perichondrium, rectus fascia, and a rib lamination. The combination is called the sandwich of perichondrium and fascia (SPF) or the sandwich of perichondrium, rib lamination, and fascia (SPLF). As a single unit over the entire dorsum, the issues of junction irregularity inherent in the use of separate graft segments, and of asymmetries in the dorsal contour because of inadequate distribution of diced cartilage, are avoided. In a greater than 18-month experience on 23 cases at the time of writing, the SPF-SPLF graft has proved to be an ideal solution. Adequate edge definition and elegant related shadowing are provided, precise tailoring is attained, and proper height of the dorsum contour is reestablished, following adequate reconstruction of the underlying dorsal plateau. The gradual flow from SPF to SPLF is logical and progressive according to need, and proper fixation ensures long-term stability of the hybrid construct. All three elements required are harvested from the same donor site with a resulting minimal scar.
Galectin-1 and Galectin-3 Expression in Lesional Skin of Patients With Systemic Sclerosis—Association With Disease Severity
Authors: Mora Gabriela Fernanda , Zubieta Mariana Rodríguez
Published: June 2020

Galectin-1 (Gal-1) and galectin-3 (Gal-3) are carbohydrate-binding proteins involved in normal processes, autoimmunity, and cancer. Increased serum Gal-3 levels in scleroderma were associated with active disease, vasculopathy, and mortality.

Objectives

The aim of this study was to evaluate Gal-1 and Gal-3 expression in the lesional skin of patients with scleroderma regarding disease severity and organ involvement.

Methods

A cross-sectional study was conducted on patients diagnosed as systemic sclerosis (SSc), after informed consent. Clinical and serological profiles were reviewed from medical records. Lesional skin biopsies were taken by losange incision from patients. Samples were analyzed by immunohistochemistry and compared with normal skin of a healthy patient. Parametric statistical analysis was done with Student t test and Pearson coefficient. Significance was established as p ≤ 0.05 with a 95% confidence interval.

Results

Biopsies of 10 patients and a healthy control (9 female, 1 male) were analyzed. The mean age was 54.5 years (18–74 years). Four of 10 patients had diffuse, 4 had limited scleroderma, 1 had overlap syndrome, and 1 had sclerodermiform graft-versus-host disease. The mean fibroblasts count per field was 13.2 in scleroderma versus 7.2 in normal skin. The mean expression of Gal-1 in scleroderma fibroblasts was 13% (0%–56%) and 47.5% for Gal-3 (6.5%–95.5%); in normal skin, the mean expression was 91% (90%–95%) for Gal-1 and 97% (89%–100%) for Gal-3. A higher Gal-3 expression in scleroderma (within its lower expression compared with normal skin) was associated with pulmonary artery hypertension (p = 0.004) and to a higher modified Rodnan's skin score (p = 0.0003). In a similar manner, anti–centromere antibodies were associated with a higher Gal-1 expression in SSc skin fibroblasts (p = 0.04).

Conclusions

Gal-1 and Gal-3 had a lower expression in scleroderma lesional skin compared with a normal control. We found a significant correlation between a higher Gal-3 expression (within the lower ones compared with normal skin) in fibroblasts from SSc patients and severe disease (pulmonary hypertension and a higher modified Rodnan's skin score) compared with patients with lower expression of this protein. Similarly, the presence of anti–centromere antibodies was associated with a higher expression of Gal-1 within this group of patients.
Increased immediate early gene activation in the basolateral amygdala following persistent peripheral inflammation.
Authors: Morales-Medina Julio Cesar , Rastogi Ashutosh , Mintz Eric , Caldwell Heather K.
Published: June 2020

Chronic pain results in a variety of neural adaptations, many of which are maladaptive and result in hypersensitivity to pain. In humans, this hypersensitivity can be debilitating and treatment options are limited. Fortunately, there are numerous animal models that mimic clinical populations and have the potential to aid in the evaluation of underlying mechanisms and ultimately the development of better treatments. One of these is the complete Freund’s adjuvant (CFA)-model of chronic inflammatory pain. In rodents, this model requires the injection of CFA into the hindpaw, muscle, or joint, which induces inflammation similar to what might be found in individuals with rheumatoid arthritis or tendonitis. While the mechanistic effects CFA on the spinal cord are well established, less is known about the effects of CFA on the brain. Thus, in this study, neuronal activation, as measured by c-Fos immunocytochemistry, in brain regions important to control of pain was evaluated. Animals that received CFA treatment, and tested 3 days later for mechanical allodynia and edema, had an increase in the number of c-Fos immunopositive cells in the basolateral amygdala, but not in any of the other brain regions that were evaluated. Given that the basolateral amygdala is known to be important for pain-related emotional responses, these data suggest that the CFA-model may provide an opportunity to further explore how pain affects this brain region at a mechanistic level, which in turn may shed light on what may be occurring in clinical populations.
Reclassification of Friedmanniella endophytica, Lysinimicrobium sediminis and Lechevalieria rhizosphaerae as Microlunatus kandeliicorticis nom. nov., Demequina sediminis comb. nov. and Lentzea rhizosphaerae comb. nov., respectively
Authors: Yang Ling-Ling , Zhi Xiao-Yang
Published: June 2020

According to Rule 37a of the International Code of Nomenclature of Prokaryotes, the name of a taxon must be changed if the nomenclatural type of the taxon is excluded. Recently, in a transfer of actinobacterial species, three species –

Friedmanniella endophytica

Tuo et al. 2016,

Lysinimicrobium sediminis

Hamada et al. 2017 and

Lechevalieria rhizosphaerae

Zhao et al. 2017 – were not transferred with their type species. Therefore, to resolve these nomenclatural issues, Microlunatus kandeliicorticis nom. nov., Demequina sediminis comb. nov. and Lentzea rhizosphaerae comb. nov. are proposed, respectively.
Flavobacterium alkalisoli sp. nov., isolated from rhizosphere soil of Suaeda salsa
Authors: Xu Lian , Wang Hai-Tao , Zhang Jin-Xin , Zhang Hui , Wang Shuai , Sun Ji-Quan
Published: June 2020

A Gram-negative, strictly aerobic, gliding motility, none-spore forming, yellow, rods bacterial strain, designated XS-5T, was isolated from rhizosphere soil of Suaeda salsa, in Tumd Right Banner, Inner Mongolia, PR China. A phylogenetic tree based on the 16S rRNA gene sequences and the phylogenomic tree both showed that strain XS-5T clustered with

Flavobacterium beibuense

F44-8T (shared 97.2 % of 16S rRNA gene similarity) and

Flavobacterium rakeshii

FCS-5T (97.6 %), and shared <96.0 % of 16S rRNA gene similarities with all other type strains. Strain XS-5T contained MK-6 as the major respiratory quinone. Its major polar lipids were phosphatidylethanolamine, an unidentified aminolipid and an unidentified lipid; and the major fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, C16 : 0, iso-C15 : 0 3-OH, Summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1
 ω7c), and Summed feature 9 (iso-C17 : 1
 ω9c and/or C16 : 0 10-methyl). The genome consisted of a 3 985 855 bp circular chromosome, with a G+C content of 37.9 mol%, predicting 3616 coding sequences genes, 45 tRNA genes and three rRNA operons. The average nucleotide identity, amino acid identity and digital DNA–DNA hybridization values of strain XS-5T to

F. beibuense

F44-8T and

F. rakeshii

FCS-5T were 79.2 and 79.2 %, 81.7 and 81.6 %, 22.3 and 22.2 %, respectively. The results of phylogenetic, physiological and biochemical tests allowed the discrimination of strain XS-5T from its phylogenetic relatives. Flavobacterium alkalisoli sp. nov. is therefore proposed with strain XS-5T (=CGMCC 1.17077T=KCTC 72459T) as the type strain.
An exploration of the SARS-CoV-2 spike receptor binding domain (RBD) – a complex palette of evolutionary and structural features
Authors: Sanyal Dwipanjan , Chowdhury Sourav , Uversky Vladimir N. , Chattopadhyay Krishnananda
Published: June 2020

SARS-CoV-2 spike protein (S) is associated with the entry of virus inside the host cell by recruiting its loop dominant receptor binding domain (RBD) and interacting with the host ACE2 receptor. Our study deploying a two-tier approach encompassing evolutionary and structural analysis provides a comprehensive picture of the RBD, which could be of potential use for better understanding the RBD and address its druggability issues. Resorting to an ensemble of sequence space exploratory tools including co-evolutionary analysis and deep mutational scans we provide a quantitative insight into the evolutionarily constrained subspace of the RBD sequence space. Guided by structure network analysis and Monte Carlo simulation we highlight regions inside the RBD, which are critical for providing structural integrity and conformational flexibility of the binding cleft. We further deployed fuzzy C-means clustering by plugging the evolutionary and structural features of discrete structure blocks of RBD to understand which structure blocks share maximum overlap based on their evolutionary and structural features. Deploying this multi-tier interlinked approach, which essentially distilled the evolutionary and structural features of RBD, we highlight discrete region, which could be a potential druggable pocket thereby destabilizing the structure and addressing evolutionary routes.
The Sequenced Genomes of Non-Flowering Land Plants Reveal the (R)Evolutionary History of Peptide Signaling
Authors: Furumizu Chihiro , Krabberød Anders K. , Hammerstad Marta , Alling Renate M. , Wildhagen Mari , Sawa Shinichiro , Aalen Reidunn B.
Published: June 2020

An understanding of land plant evolution is a prerequisite for in-depth knowledge of plant biology. Here we extract and explore information hidden in the increasing number of sequenced plant genomes, from bryophytes to angiosperms, to elucidate a specific biological question – how peptide signaling evolved. To conquer land and cope with changing environmental conditions, plants have gone through transformations that must have required a revolution in cell-to-cell communication. We discuss peptides mediating endogenous and exogenous changes by interaction with receptors activating intracellular molecular signaling. Signaling peptides were discovered in angiosperms and operate in tissues and organs like flowers, seeds, vasculature, and 3D meristems that are not universally conserved across land plants. Nevertheless, orthologues of angiosperm peptides and receptors have been identified in non-flowering plants. These discoveries provoke questions regarding the co-evolution of ligands and their receptors, and whetherde novointeractions in peptide signaling pathways may have contributed to generate novel traits in land plants. The answers to such questions will have profound implications for the understanding of evolution of cell-to-cell communication and the wealth of diversified terrestrial plants. Under this perspective we have generated, analyzed and reviewed phylogenetic, genomic, structural, and functional data to elucidate the evolution of peptide signaling.
Natural genetic variation determines microglia heterogeneity in wild-derived mouse models of Alzheimer’s disease
Authors: Yang Hongtian Stanley , Onos Kristen D. , Choi Kwangbom , Keezer Kelly J. , Skelly Daniel A. , Carter Gregory W. , Howell Gareth R.
Published: June 2020

Microglia are now considered drivers of Alzheimer’s disease (AD) pathology. However, single-cell RNA-sequencing (scRNA-seq) of microglia in mice, a key preclinical model organsim, have shown mixed results regarding translatability to human studies. To address this, scRNA-seq of microglia from C57BL/6J (B6) and wild-derived strains WSB/EiJ, CAST/EiJ and PWK/PhJ carryingAPP/PS1was performed and demonstrated that genetic diversity significantly altered features and dynamics of microglia in baseline neuroimmune functions and in response to amyloidosis. There was significant variation in abundance of microglial subpopulations, including numbers of disease-associated microglia and interferon-responding microglia across the strains. Further, for each subpopulation, significant gene expression differences were observed between strains, and relative to B6 that included nineteen genes previously associated with human AD includingApoe, Trem2, Bin1andSorl1. This resource will be critical in the development of appropriately targeted therapeutics for AD and a range of other neurological diseases.
Intestinal-derived FGF15 preserves muscle and bone mass following sleeve gastrectomy
Authors: Bozadjieva Kramer Nadejda , Shin Jae Hoon , Shao Yikai , Gutierrez-Aguilar Ruth , Li Ziru , Heppner Kristy M. , Chiang Samuel , Vargo Sara G. , Granger Katrina , Sandoval Darleen A. , MacDougald Ormond A , Seeley Randy J.
Published: June 2020

Bariatric surgeries such as the Vertical Sleeve Gastrectomy (VSG) are invasive, but provide the most effective long-term metabolic improvements in obese and Type 2 diabetic patients. These powerful effects of manipulating the gastrointestinal tract point to an important role of gastrointestinal signals in regulating both energy balance and metabolism. To that end, we have used mouse models of VSG to identify key gut signals that mediate these beneficial effects. Preliminary data from our rodent model of VSG led us to hypothesize a potential role for the hormone Fibroblast-Growth Factor15/19 (mouse/human ortholog) which pharmacologically can regulate many aspects of energy homeostasis and glucose handling. FGF15 is expressed in ileal enterocytes of the small intestine and is released postprandially. Like many other gut hormones, postprandial plasma levels in humans and ileal FGF15 expression in mice increase after VSG. We generated intestinal-specific FGF15 knock out (VilCreERT2; Fgf15f/f) mice and controls, which were maintained on 60% high-fat diet. Interestingly, ablation of intestinal FGF15 in adult mice results in little change to body weight or glucose regulation when challenged with a high-fat diet. Unlike what we had predicted, intestinal-specific FGF15 knock out mice lost more weight after VSG and this was a result of increased lean tissue loss compared to control mice. Further, the loss of bone mineral density observed after VSG in control mice was increased in intestinal-specific FGF15 knock out mice. Finally the effect of VSG to reduce hepatic cholesterol was also absent in intestinal-specific FGF15 knock out mice. These data point to an important role for intestinal FGF15 to protect the organism from deleterious effects of rapid weight loss that occurs after VSG.
Resuscitation of the microbial seed bank alters plant-soil interactions
Authors: Kuo Venus , Lehmkuhl Brent K. , Lennon Jay T.
Published: June 2020

While microorganisms are recognized for driving belowground processes that influence the productivity and fitness of plant populations, the vast majority of bacteria and fungi in soil belong to a seed bank consisting of dormant individuals. Still, plant performance may be affected by microbial dormancy through its effects on the activity, abundance, and diversity of soil microorganisms. To test how microbial seed banks influence plant-soil interactions, we purified recombinant resuscitation promoting factor (Rpf), a bacterial protein that terminates dormancy. Then, in a factorially designed experiment, we applied the Rpf to soil containing field mustard (Brassica rapa), an agronomically important plant species. Plant biomass was ~33 % lower in the Rpf treatment compared to plants grown with an unmanipulated microbial seed bank. In addition, Rpf reduced soil respiration, decreased bacterial abundance, and increased fungal abundance. These effects of Rpf on plant performance were accompanied by shifts in bacterial community composition, which may have diluted mutualists or resuscitated pathogens. Our findings suggest that changes in microbial seed banks may influence the magnitude and direction of plant-soil feedbacks in ways that affect above- and below-ground biodiversity and function.
Frequent assembly of chimeric complexes in the protein interaction network of an interspecies yeast hybrid
Authors: Dandage Rohan , Berger Caroline M. , Gagnon-Arsenault Isabelle , Moon Kyung-Mee , Stacey Richard Greg , Foster Leonard J. , Landry Christian R.
Published: June 2020

Hybrids between species often show extreme phenotypes, including some that take place at the molecular level. In this study, we investigated the phenotypes of an interspecies diploid hybrid in terms of protein-protein interactions inferred from protein correlation profiling. We used two yeast species,Saccharomyces cerevisiaeandSaccharomyces uvarum, which are interfertile, but yet have proteins diverged enough to be differentiated using mass spectrometry. Most of the protein-protein interactions are similar between hybrid and parents, and are consistent with the assembly of chimeric complexes, which we validated using an orthogonal approach for prefoldin complex. We also identify instances of altered protein-protein interactions in the hybrid, for instance in complexes related to proteostasis and in mitochondrial protein complexes. Overall, this study uncovers likely frequent occurrence of chimeric protein complexes with few exceptions, which may result from incompatibilities or imbalances between the parental proteins.
Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α
Authors: Mann Shivani N. , Hadad Niran , Nelson-Holte Molly , Rothman Alicia R. , Sathiaseelan Roshini , Ali-Mondal Samim , Agbaga Martin-Paul , Unnikrishnan Archana , Subramaniam Malayannan , Hawse John , Huffman Derek M. , Freeman Willard M. , Stout Michael B.
Published: June 2020

Metabolic dysfunction underlies several chronic diseases, many of which are exacerbated by obesity. Dietary interventions can reverse metabolic declines and slow aging, although compliance issues remain paramount. 17α-estradiol treatment improves metabolic parameters and slows aging in male mice. The mechanisms by which 17α-estradiol elicits these benefits remain unresolved. Herein, we show that 17α-estradiol elicits similar genomic binding and transcriptional activation through estrogen receptor α (ERα) to that of 17β-estradiol. In addition, we show that the ablation of ERα completely attenuates the beneficial metabolic effects of 17α-E2 in male mice. Our findings suggest that 17α-E2 acts primarily through the liver and hypothalamus to improve metabolic parameters in male mice. Lastly, we also determined that 17α-E2 improves metabolic parameters in male rats, thereby proving that the beneficial effects of 17α-E2 are not limited to mice. Collectively, these studies suggest ERα may be a drug target for mitigating chronic diseases in male mammals.
CASTLE: Cell Adhesion with Supervised Training and Learning Environment
Authors: Gilbert S G , Krautter F , Cooper D , Chimen M , Iqbal A J , Spill F
Published: June 2020

Different types of microscopy are used to uncover signatures of cell adhesion and mechanics. Automating the identification and analysis often involve sacrificial routines of cell manipulation such asin vitrostaining. Phase-contrast microscopy (PCM) is rarely used in automation due to the difficulties with poor quality images. However, it is the least intrusive method to provide insights into the dynamics of cells, where other types of microscopy are too destructive to monitor. In this study, we propose an efficient workflow to automate cell counting and morphology in PCM images. We introduce Cell Adhesion with Supervised Training and Learning Environment (CASTLE), available as a series of additional plugins to ImageJ. CASTLE combines effective techniques for phase-contrast image processing with statistical analysis and machine learning algorithms to interpret the results. The proposed workflow was validated by comparing the results to a manual count and manual segmentation of cells in images investigating different adherent cell types, including monocytes, neutrophils and platelets. In addition, the effect of different molecules on cell adhesion was characterised using CASTLE. For example, we demonstate that Galectin-9 leads to differences in adhesion of leukocytes. CASTLE also provides information using machine learning techniques, namely principal component analysis andk-means clustering, to distinguish morphology currently inaccessible with manual methods. All scripts and documentation is open-source and available at the corresponding GitLab project.
SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes
Authors: Jungreis Irwin , Sealfon Rachel , Kellis Manolis
Published: June 2020

Despite its overwhelming clinical importance, the SARS-CoV-2 gene set remains unresolved, hindering dissection of COVID-19 biology. Here, we use comparative genomics to provide a high-confidence protein-coding gene set, characterize protein-level and nucleotide-level evolutionary constraint, and prioritize functional mutations from the ongoing COVID-19 pandemic. We select 44 complete Sarbecovirus genomes at evolutionary distances ideally-suited for protein-coding and non-coding element identification, create whole-genome alignments, and quantify protein-coding evolutionary signatures and overlapping constraint. We find strong protein-coding signatures for all named genes and for 3a, 6, 7a, 7b, 8, 9b, and also ORF3c, a novel alternate-frame gene. By contrast, ORF10, and overlapping-ORFs 9c, 3b, and 3d lack protein-coding signatures or convincing experimental evidence and are not protein-coding. Furthermore, we show no other protein-coding genes remain to be discovered. Cross-strain and within-strain evolutionary pressures largely agree at the gene, amino-acid, and nucleotide levels, with some notable exceptions, including fewer-than-expected mutations in nsp3 and Spike subunit S1, and more-than-expected mutations in Nucleocapsid. The latter also shows a cluster of amino-acid-changing variants in otherwise-conserved residues in a predicted B-cell epitope, which may indicate positive selection for immune avoidance. Several Spike-protein mutations, including D614G, which has been associated with increased transmission, disrupt otherwise-perfectly-conserved amino acids, and could be novel adaptations to human hosts. The resulting high-confidence gene set and evolutionary-history annotations provide valuable resources and insights on COVID-19 biology, mutations, and evolution.
Single cell profiling of total RNA using Smart-seq-total
Authors: Isakova Alina , Neff Norma , Quake Stephen R.
Published: June 2020

The ability to interrogate total RNA content of single cells would enable better mapping of the transcriptional logic behind emerging cell types and states. However, current RNA-seq methods are unable to simultaneously monitor both short and long, poly(A)+ and poly(A)-transcripts at the single-cell level, and thus deliver only a partial snapshot of the cellular RNAome. Here, we describe Smart-seq-total, a method capable of assaying a broad spectrum of coding and non-coding RNA from a single cell. Built upon the template-switch mechanism, Smart-seq-total bears the key feature of its predecessor, Smart-seq2, namely, the ability to capture full-length transcripts with high yield and quality. It also outperforms current poly(A)–independent total RNA-seq protocols by capturing transcripts of a broad size range, thus, allowing us to simultaneously analyze protein-coding, long non-coding, microRNA and other non-coding RNA transcripts from single cells. We used Smart-seq-total to analyze the total RNAome of human primary fibroblasts, HEK293T and MCF7 cells as well as that of induced murine embryonic stem cells differentiated into embryoid bodies. We show that simultaneous measurement of non-coding RNA and mRNA from the same cell enables elucidation of new roles of non-coding RNA throughout essential processes such as cell cycle or lineage commitment. Moreover, we show that cell types can be distinguished based on the abundance of non-coding transcripts alone.