bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin II for Near Drowning: A Case Series
Authors: Smith Susan E. , Butler Sydney A. , Martin Joshua , Gerard Daniel , Sikora Newsome Andrea
Published: May 2021

Objective:

This case series describes the effect of angiotensin II administration on hemodynamics in patients with parenchymal lung injury due to submersion injury.

Case Summary:

A 33-year-old female and a 72-year-old female were both brought to the emergency department after incidents of near drowning. Upon arrival to the emergency department, both patients were hemodynamically unstable and were eventually intubated for airway protection. Imaging done by conventional chest radiograph for both patients revealed bilateral pulmonary edema. Due to their hemodynamic status, vasopressors were initiated for both patients and were quickly titrated, leading to the initiation of angiotensin II. In one patient, angiotensin II was initiated early in shock and resulted in rapid improvement of hemodynamics. In the other patient, angiotensin II was initiated later and a more muted response was observed.

Conclusions:

In patients with near drowning, angiotensin II appeared to improve hemodynamic status rapidly. This is the first case series to report the use of this new vasoactive agent in this population and poses noteworthy mechanistic considerations.
Glycogen Debrancher Enzyme Deficiency Myopathy
Authors: Sadeh Menachem , Yosovich Keren , Dabby Ron
Published: May 2021

Glycogen storage disease type III is a rare inherited disease caused by decreased activity of glycogen debranching enzyme. It affects primarily the liver, cardiac muscle, and skeletal muscle. Pure involvement of the skeletal muscle with adult onset is extremely rare. We report on a patient with myopathy due to glycogen storage disease III, and describe the clinical features, and pathologic and genetic findings.
Preliminary report of post-Ophira mini sling implantation voiding pattern: What to learn from pressure-flow studies?
Authors: Gon Lucas Mira , Andrade Danilo Leite , Palma Paulo , Reis Leonardo O. , Riccetto Cássio Luis Zanettini
Published: May 2021

Background:

The study is amined to correlate the voiding pattern after successful mini sling Ophira implantation with postoperative symptoms and satisfaction, in addition to identifying obstructions.

Materials and methods:

From 2012 to 2015 in a single institution, all consecutive patients who had stress urinary incontinence treated by using the mini sling Ophira had a pre- and 12 months postoperative urodynamic test. The International Consultation on Incontinence Questionnaire – Urinary Incontinence – Short Form (ICIQ-UI-SF) and the International Consultation on Incontinence Questionnaire – Overactive Bladder (ICIQ-OAB) translated into Portuguese, were given. Patients were objectively considered cured when presenting no urinary incontinence at the Valsalva test and subjectively cured when the ICIQ-UI-SF was zero.

Results:

Questionnaire scores were obtained from 29 patients and urodynamic data from 20 patients. Mini sling Ophira implantation resulted in a significant improvement of urinary symptoms evidenced by a significant mean reduction in ICIQ-UI-SF from 16 to 5 (p < 0.0001) and ICIQ-OAB from 8 to 4 (p = 0.0001). The subjective and objective cure rates were 55% and 45%, respectively. The urodynamic changes were not related to success even when adjusted for age, hormonal status, or anterior pelvic organ prolapse. The mean maximum flow decreased to 4.9 mL/s (95% CI: 0.62–10.8; p = 0.035), and the mean detrusor pressure at maximum flow increased to 11.4 cmH2O (95% CI: 4–18; p = 0.0078).

Conclusions:

Mini sling Ophira implantation decreased maximum urinary flow and increased the detrusor pressure at the maximum urinary flow and these urodynamic changes were not related to success.
Quercetin, Perillyl Alcohol, and Berberine Ameliorate Right Ventricular Disorders in Experimental Pulmonary Arterial Hypertension: Effects on miR-204, miR-27a, Fibrotic, Apoptotic, and Inflammatory Factors
Authors: Rajabi Soodeh , Najafipour Hamid , Jafarinejad-Farsangi Saeideh , Joukar Siyavash , Beik Ahmad , Askaripour Majid , Jafari Elham , Safi Zohreh
Published: May 2021

Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease causing right ventricular (RV) hypertrophy, failure, and death. Some miRNAs are involved in the pathophysiology of PAH. As the current treatments cannot prevent the progression of the disease, we investigated whether 3 plant derivatives, namely perillyl alcohol (PA), quercetin (QS), and berberine (BBR), can improve RV function and affect the expression of miR-204, miR-27a, and biochemical factors in monocrotaline-induced PAH (MCT-PAH). Thirty-six rats were divided into control (CTL), MCT, MCT+Veh (vehicle), MCT+PA, MCT+QS, and MCT + BBR groups (n = 6 each). After inducing PAH using MCT (60 mg/kg), PA (50 mg/kg), QS (30 mg/kg), and BBR (30 mg/kg) were administrated daily for 3 weeks. miR-204 expression, total antioxidant capacity, and antiapoptotic protein Bcl-2 significantly declined in the RV of PAH rats, and PA, QS, and BBR treatment significantly compensated for these decreases. Proapoptotic protein Bax and p21 cell cycle inhibitor increased in the RV. All 3 herbal derivatives compensated for Bax increase, and BBR caused a decrease in p21. TNFα, IL-6, and malondialdehyde increased in the RV, and PA, QS, and BBR significantly counterbalanced these increases. miR-27a expression was not affected by MCT and plant derivatives. Overall, PA, QS, and BBR improved ventricular disorders in rats with PAH by decreasing inflammation, apoptosis, and fibrosis and increasing the antioxidant-to-oxidant ratio. Therefore, these herbal derivatives may be considered as target therapeutic goals for this disease either alone or in combination with current medications.
Quality metrics in minimally invasive gynecologic surgery
Authors: Khalil Susan , Kossl Kelsey , Pasik Sara , Brodman Michael , Ascher-Walsh Charles
Published: May 2021

Purpose of review

Quality improvement and patient safety are relevant to the advancement of clinical care, particularly in the field of minimally invasive gynecologic surgery (MIGS). Although safety and feasibility of MIGS have been established, identification of quality metrics in this field is also necessary.

Recent findings

Surgical quality improvement has focused on national overarching measures to reduce mortality, surgical site infections (SSIs), and complications. Quality improvement in minimally invasive surgery has additionally led to advancements in postoperative patient recovery and long-term outcomes. Process measures in minimally invasive surgery include use of bundles and enhanced recovery after surgery (ERAS) programs. However, procedure-specific quality metrics for MIGS outcomes are poorly defined at this time.

Quality metrics in minimally invasive gynecology are well defined for structural measures and select process measures. Creation of relevant benchmarks for outcome measures in minimally invasive gynecologic surgery are needed.
Malnutrition, Family Support, and Possible Sarcopenia in Patients Undergoing Transcatheter Aortic Valve Implantation
Authors: Hsu Ching-I , Wei Jeng , Tung Heng-Hsin , Peng Li-Ning , Chen Liang-Kung , Liu Chieh-Yu
Published: May 2021

Background

Possible sarcopenia, aortic valve stenosis, and malnutrition are important issues that afflict older adults.

Objective

The aims of this study were to compare the differences in nutritional status and family support in older adults with possible sarcopenia and those without sarcopenia after undergoing transcatheter aortic valve implantation (TAVI) and to identify the predictors of malnutrition and demonstrate changes in heart function over time after undergoing TAVI.

Methods

A case-control design was conducted. Possible sarcopenia was identified by measuring calf circumference, grip strength, and gait speed. The Mini Nutritional Assessment-Short Form and numerical family support rating scale were used to collect data. Left ventricular ejection fraction and New York Heart Association (NYHA) functional class were assessed at 5 time points to evaluate heart function.

Results

Eighty-one participants were categorized into those without sarcopenia (34) and those with possible sarcopenia (47). Logistic linear regression showed albumin and possible sarcopenia to be predictors of malnutrition (odds ratio, 5.5; 95% confidence interval, 1.02–30.19). Family support was associated with nutrition status (P = .019). For patient heart function, the results of NYHA functional class and left ventricular ejection fraction improved over time after TAVI. The improvement in NYHA functional class at T2 was significantly different between the 2 groups compared with that at T0.

Conclusions

The nutrition level was higher among participants without sarcopenia than those with possible sarcopenia. Approximately 90% of the participants indicated that they had high family support. Demographic factors and albumin levels could be used to evaluate risk of malnutrition. Patients without possible sarcopenia showed greater improvement in NYHA class.
Effect of Exenatide Use on Cognitive and Affective Functioning in Obese Patients With Type 2 Diabetes Mellitus
Authors: Eren-Yazicioglu Candan Yasemin , Kara Buket , Sancak Seda , Uysal Sanem Pinar , Yazici Dilek , Okuroglu Nalan , Whitton Alexis E. , Rutherford Ashleigh V. , Yapici-Eser Hale
Published: May 2021

Purpose/Background

Glucagon-like peptide-1 (GLP-1) is a molecule used to treat type 2 diabetes mellitus (T2DM). Given their widespread expression in the nervous system, GLP-1 receptors also play a role in regulating mood and cognitive function. Here, we aimed to compare obese patients with T2DM, with or without exenatide (a GLP-1R agonist) use on cognitive and affective functioning.

Methods/Procedures

A total of 43 patients with T2DM (23 on exenatide and 20 without exenatide) were evaluated with the Snaith-Hamilton Pleasure Scale, Cognitive Failures Questionnaire, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7, Childhood Trauma Questionnaire, Perceived Stress Scale (PSS), and Chronic Stress Scale, in addition to laboratory-based measures of reward learning (the probabilistic reward task) and working memory (Letter-N-Back task).

Findings/Results

Patients on exenatide had higher body mass index (BMI) (37.88 ± 5.44 vs 35.29 ± 6.30; P = 0.015), PHQ-9 (9.70 ± 4.92 vs 6.70 ± 4.66; P = 0.026), and PSS (29.39 ± 6.70 vs 23.35 ± 7.69; P = 0.015) scores. Other stress scales (Childhood Trauma Questionnaire and Chronic Stress Scale), Generalized Anxiety Disorder-7 scores, response bias, or discriminability as assessed by probabilistic reward task and self-report (Cognitive Failures Questionnaire) and laboratory-based (Letter-N-Back) cognitive measures were not significantly different between groups (both Ps > 0.05). Multivariate linear regression analyses adding BMI and PSS as covariates revealed that although BMI had no effect (P = 0.5), PSS significantly predicted PHQ-9 scores (P = 0.004). Mediation analysis showed that exenatide users reported higher PSS, with greater PSS associated with higher PHQ-9 levels (b = 0.236). There was no evidence on exenatide directly influencing PHQ-9 independent of PSS (c′ = 1.573; P = 0.305; 95% bootstrap confidence interval, −1.487 to 4.634).

Implications/Conclusions

Based on previous research and our findings, exenatide use might be mediating depression scores through disrupting stress responses.
Identification of a Risk Profile for New-Onset Diabetes After Acute Pancreatitis
Authors: Firkins Stephen A. , Hart Phil A. , Papachristou Georgios I. , Lara Luis F. , Cruz-Monserrate Zobeida , Hinton Alice , Conwell Darwin L. , Bradley David P. , Krishna Somashekar G.
Published: May 2021

Objectives

There is a paucity of studies evaluating predictors of new-onset diabetes mellitus (DM) after acute pancreatitis (AP-related DM). We used a population-based database to evaluate predictors of AP-related DM.

Methods

The Nationwide Readmissions Database (2010–2014) was used to identify all nondiabetic adults with an index primary diagnosis of AP. Multiple exclusions were applied to identify cohorts with and without AP-related DM. A case-control study was conducted to identify risk factors for developing AP-related DM within the calendar year.

Results

We identified 2510 subjects with AP-related DM and 40,308 controls with AP who did not develop DM. Multivariable analysis revealed that increasing age (50–64 years; adjusted odds ratio [aOR], 1.35; 95% confidence interval [CI], 1.14–1.60), male sex (aOR, 1.2; 95% CI, 1.03–1.40), lowest income quartile (aOR, 1.48; 95% CI, 1.18–1.84), Elixhauser comorbidity index of 3 or higher (aOR, 1.47; 95% CI, 1.23–1.75), components of metabolic syndrome (aOR, 2.12; 95% CI, 1.21–3.70), severe AP (aOR, 1.60; 95% CI, 1.34–1.90), and recurrent AP (aOR, 1.46; 95% CI, 1.24–1.72) were independently associated with increased risk of AP-related DM.

Conclusions

These population-level variables predictive of developing AP-related DM can potentially identify patients who may benefit from closer follow-up, intensive education, and implementation of preventative strategies.
Patients With Coronavirus Disease 2019 Interstitial Pneumonia Exhibit Pancreatic Hyperenzymemia and Not Acute Pancreatitis
Authors: Pezzilli Raffaele , Centanni Stefano , Mondoni Michele , Rinaldo Rocco F. , Davì Matteo , Stefanelli Rossana , Melzi d'Eril Gianvico , Barassi Alessandra
Published: May 2021

Objectives

Gastrointestinal manifestations of coronavirus disease 19 (COVID-19) have been well established, but pancreatic involvement is under debate. Our aims were to evaluate the presence of acute pancreatitis in COVID-19 patients and to assess the frequency of pancreatic hyperenzymemia.

Methods

From April 1, 2020, to April 30, 2020, 110 consecutive patients (69 males, 41 females; mean age, 63.0 years; range, 24–93 years) met these criteria and were enrolled in the study. The clinical data and serum activity of pancreatic amylase and lipase were assayed in all patients using commercially available kits.

Results

None of the patients studied developed clinical signs or morphological alterations compatible with acute pancreatitis. However, it was found that 24.5% of the patients had amylase values above 53 IU/L and 16.4% had lipase values above 300 IU/L. Only 1 patient (0.9%) had both amylase and lipase values in excess of 3-fold the upper normal limit without clinical signs of pancreatitis.

Conclusions

The presence of pancreatic hyperenzymemia in a patient with COVID-19 requires the management of these patients be guided by clinical evaluation and not merely by evaluation of the biochemical results.
Gastrointestinal Factors Associated With Hospitalization in Infants With Cystic Fibrosis: Results From the Baby Observational and Nutrition Study
Authors: Sathe Meghana , Huang Rong , Heltshe Sonya , Eng Alexander , Borenstein Elhanan , Miller Samuel I. , Hoffman Lucas , Gelfond Daniel , Leung Daniel H. , Borowitz Drucy , Ramsey Bonnie , Freeman A. Jay
Published: May 2021

Objectives:

To identify factors that increase the risk of gastrointestinal-related (GI-related) hospitalization of infants with cystic fibrosis (CF) during the first year of life.

Methods:

The Baby Observational and Nutrition Study was a longitudinal, observational cohort of 231 infants diagnosed with CF by newborn screening. We performed a post-hoc assessment of the frequency and indications for GI-related admissions during the first year of life.

Results:

Sixty-five participants had at least one admission in the first 12 months of life. High pancreatic enzyme replacement therapy (PERT) dosing (>2000 lipase units/kg per meal; hazard ratio [HR] = 14.75, P = 0.0005) and use of acid suppressive medications (HR = 4.94, P = 0.01) during the study period were positively associated with subsequent GI-related admissions. High levels of fecal calprotectin (fCP) (>200 μg/g) and higher relative abundance of fecal Klebsiella pneumoniae were also positively associated with subsequent GI-related admissions (HR = 2.64, P = 0.033 and HR = 4.49, P = 0.002, respectively). During the first 12 months of life, participants with any admission had lower weight-for-length z scores (WLZ) (P = 0.01). The impact of admission on WLZ was particularly evident in participants with a GI-related admission (P < 0.0001).

Conclusions:

Factors associated with a higher risk for GI-related admission during the first 12 months include high PERT dosing, exposure to acid suppressive medications, higher fCP levels, and/or relative abundance of fecal K pneumoniae early in life. Infants with CF requiring GI-related hospitalization had lower WLZ at 12 months of age than those not admitted as well as those admitted for non-GI-related indications.
Midfacial Degloving Technique for Free Flap Reconstruction of Nasal and Anterior Skull Base Defects
Authors: Roubaud Margaret S. , Patel Sneha D. , Hanasono Matthew M.
Published: May 2021

Traditionally, surgical access for extirpation and reconstruction of midfacial tumors requires external incisions that can cause a myriad of complications, especially in irradiated patients. The modern midfacial degloving approach involves hidden, sublabial and intranasal incisions that provide reliable access for free flap reconstruction of nasal and maxillofacial tumors. Seven patients with a history of radiation therapy underwent free flap reconstruction of the midface. Five patients underwent the technique in a delayed manner, and the remaining two underwent reconstruction immediately at the time of resection. Five patients underwent free radial forearm fasciocutaneous free flaps and two underwent reconstruction with anterolateral thigh perforator flaps. Bone and/or rib cartilage grafting was used in all patients. All patients underwent successful free flap reconstruction of the midface without external incisions. The most common complication was postoperative infection requiring oral or intravenous antibiotics. No patients sustained loss of their grafts or hardware in the postoperative period. The midfacial degloving technique provides satisfactory exposure to the nasal cavity, midface, orbits, and skull base for free flap reconstruction, without disrupting the external soft tissue. The authors describe a novel use of the midfacial degloving technique to provide safe and reliable results with improved cosmetic outcome.
The Evolution of Migraine Surgery: Two Decades of Continual Research. My Current Thoughts
Authors: Guyuron Bahman
Published: May 2021

A mere serendipitous finding has culminated in a life-changing development for patients and a colossally fulfilling field for many surgeons. The surgical treatment of migraine headaches has been embraced by many plastic surgeons after numerous investigations ensuring that the risks are minimal and the rewards inestimable. Seldom has a plastic surgery procedure been the subject of such scrutiny. Through retrospective, prospective pilot, prospective randomized, prospective randomized with sham surgery, and 5-year follow-up studies, the safety, efficacy, and longevity of the given operation have been confirmed. Although the first decade of this journey was focused on investigating effectiveness and risk profile, the second decade was largely devoted to improving results, reducing invasiveness, and shortening recovery. Multiple publications in peer-reviewed journals over the past 20 years, several independent studies from reputable surgeons at recognized centers, and over 40 studies from the author’s center have established the surgical treatment of headaches as a standard practice.
Career Development in Plastic Surgery
Authors: Carbullido M. Kristine , Hornacek Michael , Reid Chris M. , Gosman Amanda
Published: May 2021

Professional development as a plastic surgeon is a critical component of a balanced and rewarding career. The phase of career plays an important role in what opportunities are available and what decisions must be made to affect the trajectory of the surgeon’s life and practice. Engagement and proactive strategic planning can help identify these points in a career. The goal of this article is to describe some of the fundamental choices in professional development, discuss recent literature related to the phases of career progression, and present the construct of career as a continuum integrated with life goals. Foundational career planning has roots even before becoming a resident or fellow, with increasing attention paid during medical school and undergraduate years. Mentorship and leadership roles, and work-life balance challenges, grow with entry into practice. Career sustainment with continuing education, ergonomic resources, and transition to retirement become important considerations for the experienced surgeon. Career success is a diverse vision, with composition unique to the individual surgeon. Understanding the merit of different career directions will help the surgeon take full advantage of the plethora of opportunities available in the plastic surgery specialty. Importantly, this planning and engagement has contributed to the decreased rate of burnout seen in plastic surgery.
A Multicentric Prospective Cohort Study of Modified Lateral Intercostal Artery Perforator Flap in Partial Breast Reconstruction
Authors: Neamonitou Foteini , Thekkinkattil Dinesh , Sukumar Aiswarya , Prusty Lydia , Vidya Raghavan
Published: May 2021

Background

Oncoplastic breast surgery is well established in many parts of the world and is gaining popularity in the rest of the world. The cornerstone in oncoplastic breast surgery is to respect oncological principles during cancer resection maintaining good aesthetic and cosmetic outcome. With the advancement in local, regional, and systemic treatment for breast cancer, survival has improved, and patients live longer. It is utmost essential to help our patients to maintain a good quality of life. Aesthetic and cosmetic outcomes have a significant impact on patient's psychosocial, emotional, and sexual well-being.

Oncoplastic techniques have evolved over the last decade with the increasing use of perforator flaps to enable partial breast reconstruction. We report the findings of a prospective cohort study using modified lateral intercostal artery perforator in partial breast reconstruction. This modified technique offers a less visible scar and good access to the axilla without any need for repositioning the patient during the operative procedure.

Methods

A retrospective review of a prospectively maintained database of patients who underwent partial breast reconstruction with a modified lateral intercostal artery perforator flap was carried out between July 2016 and January 2020 in 2 oncoplastic breast units. The study had local approval from the respective audit departments. Patient demographics, operative data, surgical complications, and outcomes were collected and analyzed.

Results

Forty-one patients underwent the procedure between July 2016 and January 2020. The median age of the population data was 58 years (interquartile range, 9 years). There were 10 active smokers (24.4%), and 3 patients had diabetes mellitus (7.3%). Overall, 3 patients (7.1%) developed seroma, 1 had a hematoma (2.4%), and 1 had a locoregional recurrence (2.4%). Two patients (4.9%) underwent margin re-excision for close margins. Most patients (92%) had the procedure carried out as day-case surgery. None of the patients developed wound infection, necrosis, or flap loss. The results were comparable across the 2 participating units.

Conclusions

The data suggest that modified intercostal artery perforator flap is an excellent oncoplastic technique for volume replacement in partial breast reconstruction with a short learning curve and minimal perioperative morbidity.
Neutralizing Ljungan virus antibodies in children with newly diagnosed type 1 diabetes
Authors: Lundstig Annika , McDonald Sharia L. , Maziarz Marlena , Weldon William C. , Vaziri-Sani Fariba , Lernmark Åke , Nilsson Anna-Lena
Published: May 2021

Ljungan virus (LV), a Parechovirus of the Picornavirus family, first isolated from a bank vole at the Ljungan river in Sweden, has been implicated in the risk for autoimmune type 1 diabetes. An assay for neutralizing Ljungan virus antibodies (NLVA) was developed using the original 87–012 LV isolate. The goal was to determine NLVA titres in incident 0–18 years old newly diagnosed type 1 diabetes patients (n=67) and school children controls (n=292) from Jämtland county in Sweden. NLVA were found in 41 of 67 (61 %) patients compared to 127 of 292 (44 %) controls (P=0.009). In the type 1 diabetes patients, NLVA titres were associated with autoantibodies to glutamic acid decarboxylase (GADA) (P=0.023), but not to autoantibodies against insulin (IAA) or islet antigen-2 (IA-2A). The NLVA assay should prove useful for further investigations to determine levels of LV antibodies in patients and future studies to determine a possible role of LV in autoimmune type 1 diabetes.
Deep Neural Networks for Human’s Fall-risk Prediction using Force-Plate Time Series Signal
Authors: Savadkoohi M. , Oladunni T. , Thompson L.A.
Published: May 2021

Early and accurate identification of the balance deficits could reduce falls, in particular for older adults, a prone population. Our work investigates deep neural networks’ capacity to identify human balance patterns towards predicting fall-risk. Human balance ability can be characterized based on commonly-used balance metrics, such as those derived from the force-plate time series. We hypothesized that low, moderate, and high risk of falling can be characterized based on balance metrics, derived from the force-plate time series, in conjunction with deep learning algorithms. Further, we predicted that our proposed One-One-One Deep Neural Networks algorithm provides a considerable increase in performance compared to other algorithms. Here, an open source force-plate dataset, which quantified human balance from a wide demographic of human participants (163 females and males aged 18-86) for varied standing conditions (eyes-open firm surface, eyes-closed firm surface, eyes-open foam surface, eyes-closed foam surface) was used. Classification was based on one of the several indicators of fall-risk tied to the fear of falling: the clinically-used Falls Efficacy Scale (FES) assessment. For human fall-risk prediction, the deep learning architecture implemented comprised of: Recurrent Neural Network (RNN), Long-Short Time Memory (LSTM), One Dimensional Convolutional Neural Network (1D-CNN), and a proposed One-One-One Deep Neural Network. Results showed that our One-One-One Deep Neural Networks algorithm outperformed the other aforementioned algorithms and state-of-the-art models on the same dataset. With an accuracy, precision, and sensitivity of 99.9%, 100%, 100%, respectively at the 12th epoch, we found that our proposed One-One-One Deep Neural Network model is the most efficient neural network in predicting human’s fall-risk (based on the FES measure) using the force-plate time series signal. This is a novel methodology for an accurate prediction of human risk of fall.
COVID-19 Mitigation Practices and COVID-19 Rates in Schools: Report on Data from Florida, New York and Massachusetts
Authors: Oster Emily , Jack Rebecca , Halloran Clare , Schoof John , McLeod Diana
Published: May 2021

This paper reports on the correlation of mitigation practices with staff and student COVID-19 case rates in Florida, New York, and Massachusetts during the 2020-2021 school year. We analyze data collected by the COVID-19 School Response Dashboard and focus on student density, ventilation upgrades, and masking. We find higher student COVID-19 rates in schools and districts with lower in-person density but no correlations in staff rates. Ventilation upgrades are correlated with lower rates in Florida but not in New York. We do not find any correlations with mask mandates. All rates are lower in the spring, after teacher vaccination is underway.
Allosteric receptor modulation uncovers an FFAR2 antagonist as a positive orthosteric modulator/agonist in disguise
Authors: Lind Simon , Hoffmann Dagny Olofsson , Forsman Huamei , Dahlgren Claes
Published: May 2021

Two earlier described Free Fatty Acid Receptor 2 (FFAR2)-specific antagonists (CATPB and GLPG0974) have different receptor-interaction characteristics at the molecular/functional level. The inhibitory effect of the two antagonists, on the novel receptor-cross-talk activation signals generated by the ATP-receptor, show that both antagonists inhibit the effect of the positive allosteric FFAR2 modulators (PAMs) AZ1729 and Cmp58. No neutrophil activation was induced by AZ1729 or Cmp58 alone, but together they were co-agonistic PAMs and activated the superoxide generating NADPH-oxidase in neutrophils. This response was inhibited by CATPB but not by GLPG0974; in contrast, GLPG0974 acted as a positive modulator that increased the potency but not the efficacy of the response. At the signaling level, GLPG0974 changed the biased signaling induced by the co-agonistic PAMs, to include a rise in the cytosolic concentration of free calcium ions (Ca2+). This effect was reciprocal, i.e., GLPG0974 triggers a rise in intracellular Ca2+, demonstrating that GLPG0974 may act as an FFAR2 agonist. In summary, by studying the effects of the FFAR2 ligand GLPG0974 on neutrophils activation induced by the co-agonists AZ1729 and Cmp58, we reveal that GLPG0974 in addition to be an antagonist, displays also agonistic and positive FFAR2 modulating functions that affects the NADPH-oxidase activity and the receptor down-stream signaling induced by the two co-agonistic PAMs.
Surface Engineering of FLT4-Targeted Nanocarriers Enhances Cell-Softening Glaucoma Therapy
Authors: Vincent Michael P. , Stack Trevor , Vahabikashi Amir , Li Guorong , Perkumas Kristin M. , Ren Ruiyi , Gong Haiyan , Stamer W. Daniel , Johnson Mark , Scott Evan A.
Published: May 2021

Primary open-angle glaucoma is associated with elevated intraocular pressure (IOP) that damages the optic nerve and leads to gradual vision loss. Several agents that reduce the stiffness of pressure-regulating Schlemm’s canal endothelial cells, in the conventional outflow pathway of the eye, lower IOP in glaucoma patients and are approved for clinical use. However, poor drug penetration and uncontrolled biodistribution limit their efficacy and produce local adverse effects. Compared to other ocular endothelia, FLT4/VEGFR3 is expressed at elevated levels by Schlemm’s canal endothelial cells and can be exploited for targeted drug delivery. Here, we validate FLT4 receptors as a clinically relevant target on Schlemm’s canal cells from glaucomatous human donors and engineer polymeric self-assembled nanocarriers displaying lipid-anchored targeting ligands that optimally engage this receptor. Targeting constructs were synthesized as lipid-PEGX-peptide, differing in the number of PEG spacer units (x), and were embedded in micelles. We present a novel proteolysis assay for quantifying ligand accessibility that we employ to design and optimize our FLT4-targeting strategy for glaucoma nanotherapy. Peptide accessibility to proteases correlated with receptor-mediated targeting enhancements. Increasing the accessibility of FLT4-binding peptides enhanced nanocarrier uptake by Schlemm’s canal cells while simultaneously decreasing uptake by off-target vascular endothelial cells. Using a paired longitudinal IOP studyin vivo, we show this enhanced targeting of Schlemm’s canal cells translates to IOP reductions that are sustained for a significantly longer time as compared to controls. Histological analysis of murine anterior segment tissue confirmed nanocarrier localization to Schlemm’s canal within one hour after intracameral administration. This work demonstrates that steric effects between surface-displayed ligands and PEG coronas significantly impact targeting performance of synthetic nanocarriers across multiple biological scales. Minimizing the obstruction of modular targeting ligands by PEG measurably improved the efficacy of glaucoma nanotherapy and is an important consideration for engineering PEGylated nanocarriers for targeted drug delivery.
Transient nuclear deformation primes epigenetic state and promotes cell reprogramming
Authors: Song Yang , Soto Jennifer , Chen Binru , Zhao Weikang , Hoffman Tyler , Zhu Ninghao , Peng Qin , Ly Chau , Wong Pak Kin , Wang Yingxiao , Rowat Amy C. , Kurdistani Siavash K , Li Song
Published: May 2021

Cell reprogramming has wide applications in tissue regeneration, disease modeling and personalized medicine, but low reprogramming efficiency remains a challenge. In addition to biochemical cues, biophysical factors can modulate the epigenetic state and a variety of cell functions. However, how biophysical factors help overcome the epigenetic barrier for cell reprogramming are not well understood. Here we utilized microfluidic channels to induce a transient deformation of the cell nucleus, which caused the disassembly of the nuclear lamina and a downregulation of DNA methylation and histone (H3K9) for 12-24 hours. These global decreases of heterochromatin marks at the early stage of cell reprogramming strikingly enhanced the conversion of fibroblasts into neurons and induced pluripotent stem cells. Consistently, inhibition of DNA methylation and H3K9 methylation partially mimicked the effects of mechanical squeezing on iN reprogramming efficiency. Knocking down lamin A had similar effects to squeezing on enhancing the reprogramming efficiency. Based on these findings, we developed a scalable microfluidic system that enabled a continuous cell processing to effectively prime the epigenetic state for cell reprogramming, demonstrating the potential of mechano-biotechnology for cell engineering.
Identification of shared and differentiating genetic risk for autism spectrum disorder, attention deficit hyperactivity disorder and case subgroups
Authors: Mattheisen Manuel , Grove Jakob , Als Thomas D , Martin Joanna , Voloudakis Georgios , Meier Sandra , Demontis Ditte , Bendl Jaroslav , Walters Raymond , Carey Caitlin E , Rosengren Anders , Strom Nora , Hauberg Mads Engel , Zeng Biao , Hoffman Gabriel , Bybjerg-Grauholm Jonas , Bækvad-Hansen Marie , Agerbo Esben , Cormand Bru , Nordentoft Merete , Werge Thomas , Mors Ole , Hougaard David M , Buxbaum Joseph D , Faraone Stephen V , Franke Barbara , Dalsgaard Søren , Mortensen Preben B , Robinson Elise B , Roussos Panos , Neale Benjamin M , Daly Mark J , Børglum Anders D
Published: May 2021

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable neurodevelopmental disorders with a considerable overlap in their genetic etiology. We dissected their shared and distinct genetic architecture by cross-disorder analyses of large data sets, including samples with information on comorbid diagnoses. We identified seven loci shared by the disorders and the first five genome-wide significant loci differentiating the disorders. All five differentiating loci showed opposite allelic directions in the two disorders separately as well as significant associations with variation in other traits e.g. educational attainment, items of neuroticism and regional brain volume. Integration with brain transcriptome data identified and prioritized several significantly associated genes. Genetic correlation of the shared liability across ASD-ADHD was strong for other psychiatric phenotypes while the ASD-ADHD differentiating liability correlated most strongly with cognitive traits. Polygenic score analyses revealed that individuals diagnosed with both ASD and ADHD are double-burdened with genetic risk for both disorders and show distinctive patterns of genetic association with other traits when compared to the ASD-only and ADHD-only subgroups. The results provide novel insights into the biological foundation for developing just one or both of the disorders and for driving the psychopathology discriminatively towards either ADHD or ASD.
Covid19 Pandemic Policy Monitor (COV-PPM): European level tracking of non-pharmaceutical interventions
Authors: Bozorgmehr Kayvan , Rohleder Sven , Duwendag Stella , Mohsenpour Amir , Saint Victoria , Gold Andreas , Kaur Sukhvir , Nutsch Niklas , Costa Diogo
Published: May 2021

The Covid-19 Pandemic Policy Monitor (COV-PPM) prospectively documents the measures taken to contain SARS-Cov-2 transmission across countries in EU27, EEA and UK. In Germany, measures have also been documented at the federal state and, partially, at the district levels. Non-pharmaceutical interventions (NPIs) implemented since March 2020 have been retrieved and updated weekly from official governments webpages, Ministries of Health, National (Public) Health Institutes or Administrations. NPI categories refer to restrictions, closures or changes in functioning implemented in thirteen domains: public events (gatherings in indoor or outdoor spaces); public institutions (kindergartens, schools, universities); public transport (trains, buses, trams, metro); citizens movement/mobility (e.g. pedestrians, cars, ships); border closures (air, land or sea, all incoming travels, from high-risk regions, only non-nationals); measures to improve the healthcare system (e.g. human resources or technical reinforcement, redistribution, material or infrastructural); measures for risk/vulnerable groups (e.g. elderly, chronically ill, pregnant); economic measures (e.g. lay-off rules establishment, actions to avoid job-loss, tax relaxation); testing policies (e.g. testing criteria changes); nose and mouth protection rules, vaccination and others/miscellaneous measures.
A cross-sectional study of the mismatch between telecommuting preference and frequency associated with psychological distress among Japanese workers in the COVID-19 pandemic
Authors: Otsuka Souhei , Ishimaru Tomohiro , Nagata Masako , Tateishi Seiichiro , Eguchi Hisashi , Tsuji Mayumi , Ogami Akira , Matsuda Shinya , Fujino Yoshihisa ,   for the CORoNaWork Project
Published: May 2021

Objective

To examine how the mismatch between telecommuting preference and telecommuting frequency was associated with psychological distress during the COVID-19 pandemic.

Methods

Data from 33,302 workers throughout Japan were obtained using an Internet survey. Among 33,302 participants, 20,395 who telecommuted were included in the analysis. Participants’ telecommuting preference and frequency during the COVID-19 pandemic were determined using a questionnaire. Psychological distress was assessed using Kessler 6 (K6).

Results

Among participants who did and did not prefer to telecommute, those who telecommuted four or more days per week had an OR of psychological distress of 0.67 (p<0.001) and 1.87 (p=0.001), respectively, compared with those who rarely telecommuted.

Conclusions

The association between telecommuting and psychological distress differs depending on telecommuting preference.
Performance of the TaqMan™ COVID-19 Pooling Kit for detection of SARS-CoV-2 in Asymptomatic and Symptomatic populations at an Institution of Higher Education
Authors: Ganz Troy , Sanderson Sarah , Baush Connor , Mejia Melanie , Gandhi Manoj , Auclair Jared
Published: May 2021

Clinical evidence for asymptomatic cases of coronavirus disease (COVID-19) has reinforced the significance of effective surveillance testing programs. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) assays are considered the ‘gold standard’ for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. However, the labor and resource requirements can be prohibitive with respect to large testing volumes associated with the pandemic. Pooled testing algorithms may serve to increase testing capacity with more efficient resource utilization. Due to the lack of carefully curated cohorts, there is limited evidence for the applicability of RT-PCR pooling in asymptomatic COVID-19 cases. In this study, we compared the analytical sensitivity of the TaqMan™ SARS-CoV-2 Pooling Assay to detect one positive sample in a pool of five anterior nare swabs in symptomatic and asymptomatic cohorts at an institute of higher education. Positive pools were deconvoluted and each individual sample was retested using the TaqPath™ COVID-19 Combo Kit. Both assays target the open reading frame (ORF) 1ab, nucleocapsid (N), and spike (S) gene of the strain that originated in Wuhan, Hubei, China. Qualitative results demonstrated absolute agreement between pooled and deconvoluted samples in both cohorts. Independent t-test performed on Ct shifts confirmed an insignificant difference between cohorts with p-values of 0.306 (Orf1ab), 0.147 (N), and 0.052 (S). All negative pools were correctly reported as negative. Thus, pooled PCR testing up to five samples is a valid method for surveillance testing of students and staff in a university setting, especially when the prevalence is expected to be low.
Defensive nymphs in the water-repellent gall of the social aphid Colophina monstrifica (Hemiptera: Aphididae: Eriosomatinae)
Authors: Uematsu Keigo , Aoki Shigeyuki , Yang Man-Miao
Published: May 2021

The aphid Colophina monstrifica forms woolly colonies with sterile soldiers on the secondary host Clematis uncinata in Taiwan. However, the gall or primary-host generation of C. monstrifica has not been found to date. We successfully induced galls of the species on trees of Zelkova serrata through attaching its eggs onto the trees, and also found a few naturally formed galls on another Z. serrata tree. The identity of the aphids was confirmed by examining their morphology and mitochondrial DNA sequences. First- and second-instar nymphs in the galls exhibited attacking behavior toward artificially introduced moth larvae. Observations with a scanning electron microscope revealed that the gall inner surface was densely covered with minute trichomes. This indicates the water repellency of the inner surface, and strongly suggests that young nymphs of C. monstrifica dispose of honeydew globules outside the gall, as known in the congener C. clematis.
Stem cells commit to differentiation following multiple induction events in the Drosophila testis
Authors: Yuen Alice C , Hillion Kenzo-Hugo , Amoyel Marc
Published: May 2021

How and when potential becomes restricted in differentiating stem cell daughters is poorly understood. While it is thought that signals from the niche are actively required to prevent differentiation, another model proposes that stem cells can reversibly transit between multiple states, some of which are primed, but not committed, to differentiate. In the Drosophila testis, somatic cyst stem cells (CySCs) generate cyst cells, which encapsulate the germline to support its development. We find that CySCs are maintained independently of niche self-renewal signals if activity of the PI3K/Tor pathway is inhibited. Conversely, PI3K/Tor is not sufficient alone to drive differentiation, suggesting that it acts to license cells for differentiation. Indeed, we find that the germline is required for differentiation of CySCs in response to PI3K/Tor elevation, indicating that final commitment to differentiation involves several steps and intercellular communication. We propose that CySC daughter cells are plastic, that their fate depends on the availability of neighbouring germ cells, and that PI3K/Tor acts to induce a primed state for CySC daughters to enable coordinated differentiation with the germline.
Hiding in plain sight: genetic deaf-blindness is not always Usher syndrome
Authors: Medina Genevieve , Perry Julia , Oza Andrea , Kenna Margaret
Published: May 2021

Hearing loss (HL) is the most common congenital sensory impairment. Usher syndrome (USH) is the leading genetic etiology of congenital deafness combined with progressive vision loss, and individuals presenting with these symptoms are often assumed to have USH. This can be an erroneous assumption, as there are additional genetic causes of deaf-blindness. Our objective is to describe and accurately diagnose non-USH genetic causes of deaf-blindness. We present three children with hearing and vision loss with clinical and genetic findings suggestive of USH. However, ongoing clinical assessment did not completely support an USH diagnosis, and exome analysis was pursued for all three individuals. Updated genetic testing showed pathogenic variants in ALMS1 in the first individual and TUBB4B in the second and third. Although HL in all three was consistent with USH type 2, vision impairment with retinal changes was noted by age 2 yr, which is unusual for USH. In all three the updated genotype more accurately fit the clinical phenotype. Because USH is the most common form of genetic deaf-blindness, individuals with HL, early vision impairment, and retinal dysfunction are often assumed to have USH. However, additional genes associated with HL and retinal impairment include ALMS1, TUBB4B, CEP78, ABHD12, and PRPS1. Accurate genetic diagnosis is critical to these individuals’ understanding of their genetic conditions, prognosis, vision and hearing loss management, and future access to molecular therapies. If clinically or genetically USH seems uncertain, updated genetic testing for non-USH genes is essential.
I broke the glass ceiling, now what? Overview of metaphors to explain gender inequality in organizations
Authors: Grangeiro Rebeca da Rocha , Silva Lucas Emmanuel Nascimento , Esnard Catherine
Published: May 2021

Purpose

This paper aims to identify and systematically summarize the relevant research on metaphors that are used to explain gender inequalities in the organizational context.

Design/methodology/approach

The researchers conducted a systematic literature review using bibliometric techniques and content analysis.

Findings

The systematic literature review identified a total of 1,269 papers in 688 journals written by 2,441 authors. The first paper was published in 1971 and the publication growth can be observed in the five decades analyzed. The Gender in Management: An International Journal, was the journal that published more papers about this thematic. Michelle Ryan was the most influential researcher regarding the number of papers and citations she had. The content analysis performed with the 27 most influential papers showed 4 research streams (metaphors; gender and leadership; challenges, stereotypes and toxic environment; and gender in the academy). Concerning the metaphors explored in those papers, the glass ceiling is the most prominent. Furthermore, 26 kinds of barriers were identified regarding the challenges that women face to reach positions of power.

Practical implications

The scrutiny of the metaphors and barriers enable access to what is being a hindrance to female progression in the organizational structure. So, this study may instrumentalize organizations and women to improve gender diversity practices in the workplace.

Originality/value

The value of the paper lays in the extensive literature review, using a bibliometric approach and content analysis.