bluuebunny/crossref_metadata_2025 huggingface dataset:
Emergency department visits and inpatient hospitalizations among older patients with brain metastases: a dual population- and institution-level analysis
Authors: Lamba Nayan , Catalano Paul J , Whitehouse Colleen , Martin Kate L , Mendu Mallika L , Haas-Kogan Daphne A , Wen Patrick Y , Aizer Ayal A
Published: May 2021

Background

Older patients with brain metastases (BrM) commonly experience symptoms that prompt acute medical evaluation. We characterized emergency department (ED) visits and inpatient hospitalizations in this population.

Methods

We identified 17 789 and 361 Medicare enrollees diagnosed with BrM using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2010-2016) and an institutional database (2007-2016), respectively. Predictors of ED visits and hospitalizations were assessed using Poisson regression.

Results

The institutional cohort averaged 3.3 ED visits/1.9 hospitalizations per person-year, with intracranial disease being the most common reason for presentation/admission. SEER-Medicare patients averaged 2.8 ED visits/2.0 hospitalizations per person-year. For patients with synchronous BrM (N = 7834), adjusted risk factors for ED utilization and hospitalization, respectively, included: male sex (rate ratio [RR] = 1.15 [95% CI = 1.09-1.22], P < .001; RR = 1.21 [95% CI = 1.13-1.29], P < .001); African American vs white race (RR = 1.30 [95% CI = 1.18-1.42], P < .001; RR = 1.25 [95% CI = 1.13-1.39], P < .001); unmarried status (RR = 1.07 [95% CI = 1.01-1.14], P = .02; RR = 1.09 [95% CI = 1.02-1.17], P = .01); Charlson comorbidity score >2 (RR = 1.27 [95% CI = 1.17-1.37], P < .001; RR = 1.36 [95% CI = 1.24-1.49], P < .001); and receipt of non-stereotactic vs stereotactic radiation (RR = 1.44 [95% CI = 1.34-1.55, P < .001; RR = 1.49 [95% CI = 1.37-1.62, P < .001). For patients with metachronous BrM (N = 9955), ED visits and hospitalizations were more common after vs before BrM diagnosis (2.6 vs 1.2 ED visits per person-year; 1.8 vs 0.9 hospitalizations per person-year, respectively; RR = 2.24 [95% CI = 2.15-2.33], P < .001; RR = 2.06 [95% CI = 1.98-2.15], P < .001, respectively).

Conclusions

Older patients with BrM commonly receive hospital-level care secondary to intracranial disease, especially in select subpopulations. Enhanced care coordination, closer outpatient follow-up, and patient navigator programs seem warranted for this population.
Autonomous algorithmic collusion: economic research and policy implications
Authors: Assad Stephanie , Calvano Emilio , Calzolari Giacomo , Clark Robert , Denicolò Vincenzo , Ershov Daniel , Johnson Justin , Pastorello Sergio , Rhodes Andrew , Xu Lei , Wildenbeest Matthijs
Published: May 2021

Markets are being populated with new generations of pricing algorithms, powered with artificial intelligence (AI), that have the ability to autonomously learn to operate. This ability can be both a source of efficiency and cause of concern for the risk that algorithms autonomously and tacitly learn to collude. In this paper we explore recent developments in the economic literature and discuss implications for policy.
MODELING AND EXPERIMENTS TO ESTIMATE RADON EMANATION FACTOR IN SOIL—GRAIN SIZE AND MOISTURE EFFECT
Authors: Chitra N , Sundar S Bala , Valan I Inigo , Subramanian V , Jose M T , Venkatraman B
Published: May 2021

The influence of soil grain size on its radon emanation mechanism was investigated by developing a Monte-Carlo model. The proposed model supplements the previous formulations by accounting for the effect elicited by specific surface area of the sample. The specific surface area of a sample is governed by its grain size and it strongly influences the emanation rate which is a surface phenomenon. The emanation study was further extended to include the moisture effect. Experiments were carried out with two soil samples; Soil-2 and Soil-4 collected from different terrains, to analyze the role played by moisture in the emanation mechanism. The above model was augmented with provisions to include the moisture input. The model could reproduce the experimental results. There is an abrupt increase in the emanation factor when the moisture content changes from 0 to 2%. Thereafter, the increase is gradual and finally becomes steady when the moisture level reaches 10%. Soil-2 and Soil-4 showed sizeable difference in their radon emanation factor values. This could be explained based on the parent226Ra distribution pattern which stems from the mineralogical composition of the samples. Quartz was predominantly found in Soil-2, whereas Soil-4 shows peaks corresponding to minerals namely ilmenite, Rutile and Zircon confirming relatively higher concentration of heavy minerals than Soil-2. The emanation factor values of the individual minerals reported in the literature were used to decide upon the 226Ra distribution depth and with this input the model to ascertain the experimental observations.
Macrophage Activation Syndrome in a Child with Juvenile Idiopathic Arthritis Secondary to SARS-CoV-2
Authors: Akturk Hacer , Tanyildiz Murat , Erbey Fatih , Tasdemir Mehmet , Celikyurt Aydın , Gonen Emel , Bilge Ilmay
Published: May 2021

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a pandemic affecting many countries and millions of people. Physicians have encountered some rare and challenging cases related to SARS-CoV-2, a novel virus with still many unknowns. In order to share our experience of a such clinical picture, we present here a child with SARS-CoV-2-induced macrophage activation syndrome in the setting of juvenile idiopathic arthritis.
Variant Median Nerve Anatomy: Ultrasound Evidence of a Pseudoconduction Block
Authors: Abrams Rory M. C. , Pedowitz Elizabeth J. , Simpson David M. , Shin Susan C.
Published: May 2021

Introduction:

A conduction block at a noncompressible site warrants further investigation.

Methods and materials:

A 36-year-old woman with a history of Hodgkin lymphoma and chemotherapy-induced polyneuropathy developed bilateral hand numbness and paresthesias. Workup revealed bilateral carpal tunnel syndrome and an apparent superimposed conduction block of the median nerve in the forearm. Given the history of cancer, there was concern for an infiltrative or an immune-mediated process.

Results:

Neuromuscular ultrasound demonstrated that the median nerve descended the upper extremity along an atypical path, deep along the posteromedial aspect of the upper arm, and relatively medially in the forearm. Ultrasound-directed nerve stimulation revealed there was no conduction block. This anatomical variant has been rarely described and has not been reported previously to mimic conduction block or been documented via ultrasound.

Conclusions:

This case demonstrates that neuromuscular ultrasound may supplement the electrodiagnostic study and limit confounding technical factors because of rare anatomic variation.
Prevalence of Screen Time Among Children Aged 2 to 5 Years in Chandigarh, a North Indian Union Territory
Authors: Kaur Nimran , Gupta Madhu , Malhi Prahbhjot , Grover Sandeep
Published: May 2021

Objective:

To estimate the prevalence of screen time (ST) and its associated effects, including emotional and behavioral changes, sleep disturbances, and physical activity levels, in children aged 2 to 5 years.

Methods:

We conducted a cross-sectional study among 400 randomly selected children aged 2 to 5 years in Chandigarh, North India. We used a validated, pretested, semistructured digital-screen exposure and physical activity questionnaire; an abbreviated standard Child Sleep Habit Questionnaire; and a standard Preschool Child Behavior Checklist. We considered ST as excessive if it was more than 1 hour per day as per the American Academy of Pediatrics 2016 guidelines. IBM SPSS Statistics for Macintosh, version 25.0, was used to perform linear regression model analysis and stepwise binary multivariate logistic regression.

Results:

Approximately 59.5% of children (mean age 3.5 ± 0.9 years) had excessive ST. ST was higher on weekdays (58.5%) compared with the weekends (56.8%). Higher ST correlated positively with the mother's level of education (r = +0.219) and higher per capita family income (r = +0.227). Screen time was also positively correlated with attending daycare centers (adjusted odd's ratio [aOR] = 1.82, confidence interval [CI] = 1.18–2.81), caregivers ST of more than 2 hours (aOR = 1.68, CI = 1.12–2.56), and the absence of digital-media rules at home (aOR = 3.3, CI = 0.92–11.65). It was negatively correlated (i.e., protective) with lower mother's education (i.e., up to middle school) (aOR = 0.62, CI = 0.41–0.96) and watching educational digital-media content (aOR = 0.53, CI = 0.33–0.87).

Conclusion:

We observed a high prevalence of excessive ST among children aged 2 to 5 years. Screen time was significantly associated with being in daycare centers, higher caregivers' ST, lower mothers' educational status, and educational digital content.
Racial and ethnic disparities in access to minimally invasive gynecologic surgery for benign pathology
Authors: Barnes Whitney A. , Carter-Brooks Charelle M. , Wu Catherine Z. , Acosta Danilo A. , Vargas Maria V.
Published: May 2021

Purpose of review

To review current US literature and describe the extent, source, and impact of disparities that exist among Black, Indigenous, and people of color (BIPOC) in surgical route and outcomes for hysterectomy, myomectomy, and endometriosis surgery.

Recent findings

Despite the nationwide trend toward minimally invasive surgery (MIS), BIPOC women are disproportionally less likely to undergo MIS hysterectomy and myomectomy and have higher rates of perioperative complications. African American women, in particular, receive significantly disparate care. Contemporary literature on the prevalence of endometriosis in BIPOC women is lacking. Further, there is little data on the racial and ethnic differences in endometriosis surgery access and outcomes.

Racial and ethnic disparities in access to minimally invasive gynecologic surgery for benign pathology exist and these differences are not fully accounted for by patient, socioeconomic, or healthcare infrastructure factors. Initiatives that incentivize hiring surgeons trained to perform complex gynecologic surgery, standardized pathways for route of surgery, quality improvement focused on increased hospital MIS volume, and hospital-based public reporting of MIS volume data may be of benefit for minimizing disparities. Further, initiatives to reduce disparities need to address racism, implicit bias, and healthcare structural issues that perpetuate disparities.
Evaluating the prediction accuracy of the Hill-RBF 3.0 formula using a heteroscedastic statistical method
Authors: Tsessler Maria , Cohen Shir , Wang Li , Koch Douglas D. , Zadok David , Abulafia Adi
Published: May 2021

Purpose:

To evaluate the accuracy of the Hill-RBF 3 formula, with and without direct measurements of total corneal power, using a heteroscedastic statistical method for analysis.

Setting:

Department of Ophthalmology, Shaare Zedek Medical Center, Jerusalem, Israel.

Design:

Retrospective, consecutive case series.

Methods:

Records of consecutive patients who underwent routine cataract surgery between February 2018 and June 2020 were retrospectively reviewed. The prediction accuracy of the Hill-RBF 3.0 formula was compared with that of the Barrett Universal II, Emmetropia Verifying Optical 2.0, Haigis, Hill-RBF 2.0, Hoffer Q, Holladay 1, Holladay 2, Kane, Olsen, and SRK/T formulas, based on biometry measurements by swept-source optical coherence tomography (SS-OCT) with standard keratometry (K), SS-OCT with total keratometry (TK), and an optical low-coherence reflectometer (OLCR). Statistical analysis was applied according to a heteroscedastic statistical method with SD of prediction errors as the main parameter for formula performance.

Results:

The study included 153 eyes of 153 patients. The SD values that were obtained by Hill-RBF 3.0 (0.266 to 0.285 diopters [D]) were significantly lower compared with those by Hill-RBF 2.0 (0.290 to 0.309 D), Hoffer Q (0.387 to 0.407 D), Holladay 1 (0.367 to 0.385 D), Holladay 2 (0.386 to 0.401 D), and SRK/T (0.377 to 0.399 D) formulas (P < .036). The prediction accuracy of the Hill-RBF 3.0 was similar across the SS-OCT (K), SS-OCT (TK), and OLCR methods of measurement (P > .51).

Conclusions:

The Hill-RBF 3.0 was more accurate than the Hill-RBF 2.0 and older generation formulas and had similar prediction accuracy compared with new generation formulas. The use of TK did not provide significant improvement to its prediction accuracy.
Organizational Justice and Cognitive Failures in Japanese Employees
Authors: Inoue Akiomi , Eguchi Hisashi , Kachi Yuko , Tsutsumi Akizumi
Published: May 2021

Objective:

We examined the association of organizational justice (ie, procedural justice and interactional justice) with cognitive failures, and the mediation effect of psychological distress on this association in Japanese employees.

Methods:

A total of 189 men and 35 women from two sites of a manufacturing company in Japan were surveyed using a self-administered web-based questionnaire. A multiple mediation analysis was conducted.

Results:

A significant negative total effect of procedural justice on cognitive failures was observed (c = −0.180 [95% confidence interval: −0.315 to −0.044]). Furthermore, the mediation effect of psychological distress was significant (c–c′ = −0.213 [95% confidence interval: −0.323 to −0.115]). Similar patterns were observed for interactional justice.

Conclusions:

Employees may be more likely to experience cognitive failures in daily activities in work settings where organizational justice is lower, which seems to be explained by psychological distress.
Comparing Vestibule Examination Techniques: Light Touch, Serial Forces, and the Lidocaine Test
Authors: Stenson Amy L. , Leclair Catherine M. , Goetsch Martha F.
Published: May 2021

Objective

The purpose of this study was to compare techniques and pain scales that assess tenderness in the vulvar vestibule in provoked vestibulodynia, using the cotton swab test and a vulvalgesiometer, and assess topical lidocaine solution with each.

Materials and Methods

This randomized study at a specialty vulvar clinic evaluated tender vestibules of reproductive-aged women with vestibulodynia using light rolling cotton swab touch at 6 sites and evaluated the vulvalgesiometer at 2 sites, randomizing the order of the initial tool. Participants reported pain using the Numerical Rating Scale 0–10 and the Verbal Pain Scale 0–3. With the vulvalgesiometer, the pain tolerance threshold was measured using forces of 10, 25, 50, 100, 200, and 300 g. After both initial tests, lidocaine 4% topical solution was applied for 3 minutes, and the swab test and vulvalgesiometer were repeated in the order initially performed, constituting the lidocaine test. Data analysis used t tests, Fisher exact tests, Wilcoxon signed rank tests, and Spearman rank correlation.

Results

Sixteen patients completed the study, 8 starting with each instrument. Light swab touch evoked significant pain, and lidocaine reduced pain to zero or mild levels. The pain threshold was 25 g, and only 38% could tolerate testing past 100 g without lidocaine. The Verbal Pain Scale correlated well with the Numerical Rating Scale.

Conclusions

Light rolling cotton swab touch using the 4-item verbal scale can map vestibulodynia tenderness that can be extinguished by lidocaine, consistent with distinguishing a mucosal condition. Forces by vulvalgesiometer of greater than 100–200 g may evoke pain other than mucosal allodynia.
Mycophenolate Mofetil Hepatotoxicity Associated With Mitochondrial Abnormality in Liver Transplant Recipients and Mice
Authors: Warren Mikako , Mitsinikos Tania , Yanni George , Sasaki Mika , Sasaki Atsuo T. , Thomas Dan
Published: May 2021

Objectives:

Mycophenolate mofetil (MMF) is a widely used immunosuppressive agent. MMF hepatotoxicity has been reported in non-transplant and renal transplant patients with minimal histologic description. This is the first study describing detailed histology and ultrastructure of MMF hepatotoxicity.

Methods:

Four liver-transplant recipients (Cases 1–4) were suspected to have MMF hepatotoxicity. Cases 1–3 (two females and one male; 4–17 years) had multiple biopsies for liver function test (LFT) abnormalities. Case 4 (female; 16 years) had a surveillance biopsy. Electron-microscopic examination (EM) was requested on Cases 1–3 for unexplained, persistent LFT elevation and histologic abnormalities despite therapy and Case 4 for unexplained histologic abnormalities despite a stable clinical course. To confirm the pathologic changes in the human allografts, livers from MMF-treated and untreated mice were also reviewed.

Results:

While the allograft biopsies showed nonspecific histologic changes, EM revealed unequivocal mitochondrial abnormalities similar to those seen in primary and secondary mitochondrial disorders. In Cases 1 and 2, LFTs improved after stopping and reducing MMF, respectively. In Case 3, pre- and post-MMF treatment biopsies were performed and only the post-MMF biopsy demonstrated mitochondrial abnormalities. Mitochondrial abnormality in Case 4 was subclinical. The mouse study confirmed that MMF caused various stress changes in the mitochondria; number of mitochondria/cell (mean ± standard deviation; untreated group: 58.25 ± 8.426; MMF-treated group: 76.37 ± 18.66), number of lipid droplets/cell (untreated: 0.9691 ± 1.150; MMF-treated: 3.649 ± 4.143) and sizes of mitochondria (μm, untreated: 0.8550 ± 0.3409; MMF-treated: 0.9598 ± 0.5312) were significantly increased in hepatocytes in the MMF-treated mice compared with the untreated mice (P < 0.0001).

Conclusions:

Although MMF is safe for the majority of patients, MMF can cause mitochondrial stress, which may trigger more severe mitochondrial abnormalities in a small subset. MMF hepatotoxicity should be considered for MMF-treated patients with unexplained, persistent LFT abnormalities and nonspecific histologic findings. EM should be requested for these cases.
Factors Affecting Selenium Status in Infants on Parenteral Nutrition Therapy
Authors: Rao Anita , Jericho Hilary , Patton Tiffany , Sriram Sudhir , Hebert Taylor , Weinstein Dana , Pompeii-Wolfe Cecelia , Wroblewski Kristen , Sentongo Timothy
Published: May 2021

Introduction:

Selenium is an essential micronutrient that must be supplemented in infants and young children on exclusive parenteral nutrition (PN). We examined selenium status and clinical factors associated with a deficiency in infants on PN.

Methods:

This was a retrospective cohort study of pediatric patients receiving PN with routine monitoring of selenium status. Deficiency was diagnosed using age-based norms of plasma selenium status. Associations between selenium deficiency and the following clinical factors were examined: birthweight status: extremely low birthweight (ELBW) versus very low birthweight (VLBW) versus low birthweight (LBW) versus normal birthweight (NBW), serum albumin status, presence of cholestasis, and co-administration of enteral feeds.

Results:

A total of 42 infants were included with gestational age [median (interquartile range)] 28 weeks (25,34). The prevalence of selenium deficiency was 80% and the prevalence of albumin deficiency was 87.5%. The odds of selenium deficiency were higher in ELBW infants (odds ratio = 17.84, 95% confidence interval [4.04–78.72], P < 0.001) and VLBW infants (odds ratio = 16.26, 95% confidence interval [1.96–135.04], P < 0.001) compared to NBW infants. The odds of selenium deficiency were 5-fold higher in patients with low serum albumin (odds ratio = 5.33, 95% confidence interval [1.39–20.42], P = 0.015). There were no associations seen between selenium status and presence of cholestasis or co-administration of enteral feeds.

Conclusion:

In this cohort of infants on PN therapy, the main clinical factors associated with selenium deficiency were presence of hypoalbuminemia and history of ELBW or VLBW. These findings support dual measurement of serum albumin and serum selenium to improve interpretation of selenium status.
Investigation of the Orbital Arterial Distribution Using Image Superimposition to Determine Safe Zones for Retrobulbar Injection and to Prevent Filler Complications
Authors: Shin Hyun-Jin , Lee Shin-Hyo , Park Jung-Ah , Koh Ki-Seok , Song Wu-Chul
Published: May 2021

Background:

Retrobulbar filler injection has recently been considered an ideal method for orbital volume enhancement due to its nontoxic, easily reversible, and noninvasive characteristics. This study determined the arterial distribution in the orbit with the aim of defining a safety zone for retrobulbar filler injections used to enhance the orbital volume.

Methods:

Twenty-seven orbits of 24 formalin-embalmed cadavers were dissected. The orbital arteries were identified after removal of the eyeball, extraocular muscles, and connective tissues. The course of each orbital artery was then recorded in each specimen, and all of the courses were then superimposed to determine the arterial distribution in the orbit.

Results:

The superimposition of lined images based on the orbital vasculature of each specimen revealed that the arterial density was highest in the superonasal region and lowest in the inferotemporal region. In particular, orbital arteries were scarce at 8 o’clock and 4 o’clock in the right and left orbits, respectively, and an artery-free zone was demonstrated in the outer part of those directions.

Conclusions:

When performing a transcutaneous retrobulbar injection of filler for orbital volume enhancement, the relative safety zone could be considered to be located at 8 o’clock and 4 o’clock in the right and left orbits, respectively. The detailed topographic information about the arterial distribution in the orbit, provided by the present study, may help oculofacial surgeons to avoid injury to major vessels and decrease the risk of retrobulbar hemorrhage and vision-threatening complications.
Sensibility, Sensation, and Nerve Regeneration after Reconstructive Genital Surgery: Evolving Concepts in Neurobiology
Authors: Calotta Nicholas A. , Kuzon William , Dellon A. Lee , Monstrey Stan , Coon Devin
Published: May 2021

Background:

Sensory recovery following phalloplasty and vaginoplasty for gender dysphoria is essential to the overall success of gender-confirming surgery. Anecdotal evidence suggests that superior reinnervation results are seen in genitoplasty compared to other peripheral nerve repair scenarios. Despite these observed differences, the quality of available literature is poor.

Methods:

The authors reviewed the body of English language literature regarding sensory outcomes following genitoplasty for gender confirmation.

Results:

The available body of literature discussing the basic science and clinical science aspects of sensory recovery following gender-confirming genitoplasty is small. Available data show that sensory recovery following vaginoplasty produces high rates of reported orgasmic ability, largely through the neoclitoris, and a neovagina with vibratory and pressure sensation similar to that of the native vagina. Phalloplasty sensory outcomes are variable, with the largest series reporting return of sensation in the neophallus that is slightly less than what is measured in control men. Erogenous sensation, including the ability to orgasm, is present in nearly all patients after several months.

Conclusions:

Existing series indicate that genitoplasty patients experience faster and more complete recovery than any other peripheral nerve regeneration scenarios. However, there are many potential confounding factors in assessment and reporting, and more consistent and reproducible measure endpoints measures are needed. Further research is needed to better understand both the basic science and clinical science of peripheral nerve regeneration in genitoplasty, which may change fundamental aspects of current paradigms of peripheral nerve regeneration.
Applying Principles of Breast Revision to Managing Aesthetic Patients with Textured Implants
Authors: Gabriel Allen , O’Rorke Erin , Maxwell G. Patrick
Published: May 2021

Textured breast implants have garnered increased attention recently because of their risk of breast implant–associated anaplastic large cell lymphoma (BIA-ALCL), an uncommon and treatable type of T-cell lymphoma. Treatment involves bilateral en bloc capsulectomy, which is curative in the majority of cases. At present, there is no defined management approach for aesthetic patients asymptomatic for BIA-ALCL requesting the removal of their textured implants, particularly as it relates to the management of the capsule. It is unclear if en bloc capsulectomy is necessary in these patients as it is in patients with BIA-ALCL. In the absence of clear guidance on the management of the capsule in asymptomatic patients, the basic principles of breast revision surgery can be applied to these patients.
Revisional Breast Surgery: Are Surgical Plans Changed if the Patient Has a Textured Device?
Authors: Nava Maurizio , De Vita Roy , Catanuto Giuseppe , Tunesi Gianfranco , Rocco Nicola
Published: May 2021

The authors reviewed the available evidence on revision surgery following implant-based breast surgery with the aim of investigating whether any difference in the surgical approach should be proposed if the patient has a textured device. They included in their review 31 studies presenting different approaches for revision surgery following implant-based breast surgery (both aesthetic and reconstructive), with a level of evidence ranging from 4 to 5. None of the included studies proposed different surgical approaches for revision surgery in patients carrying textured devices. The authors conclude that no different surgical attitudes in revision surgery following implant-based breast surgery should be adopted if the patient has a textured device according to the available evidence, when a correct approach is performed to face the complication or adverse event, following a thorough preoperative study of the patient with the proper diagnostic tools.
Detection of SARS-CoV-2 in saliva using tailed amplicon sequencing
Authors: Garoutte Aaron , Santiago-Rodriguez Tasha M. , Fehling Heather L. , Iwasiow Rafal
Published: May 2021

The most recent virus from the Coronaviridae family infecting humans, SARS-CoV-2, has resulted in a global pandemic. As part of the surveillance efforts, SARS-CoV-2 genomes are increasingly being made publicly available. Methods that include both short- and long-read sequencing have been used to elucidate SARS-CoV-2 genomes; however, many of these untargeted approaches may require deeper sequencing for greater genome coverage. For this reason, sequence capture or amplicon-based approaches for SARS-CoV-2 genome sequencing have been developed. The present study evaluated a modified sequence capture approach, namely, tailed amplicon sequencing, to determine SARS-CoV-2 near complete genome sequences from the saliva of infected individuals. Particularly, the suitability of saliva samples stored at room temperature using OMNIgene®•ORAL OME-505 was evaluated. The tailed amplicon sequencing approach poses the additional advantage of being a cost-effective method for library preparation. Different known SARS-CoV-2 variants were identified across the infected subjects, with an average of > 99.4% genome coverage. This methodology also enabled robust genomic surveillance using phylogenetic analyses. The present study supports the suitability of saliva stored at room temperature using collection devices for SARS-CoV-2 variant detection. Importantly, the present study supports the use of tailed amplicon sequencing approaches as an alternative, cost-effective method for SARS-CoV-2 detection in saliva for genomic surveillance.
Intersections between copper, β-arrestin-1, calcium, FBXW7, CD17, insulin resistance and atherogenicity mediate depression and anxiety due to type 2 diabetes mellitus: a nomothetic network approach
Authors: Al-Hakeim Hussein Kadhem , Hadi Hadi Hassan , Jawad Ghoufran Akeel , Maes Michael
Published: May 2021

Background

Type 2 diabetes mellitus (T2DM) is frequently accompanied by affective disorders with a prevalence of comorbid depression of around 25%. Nevertheless, the biomarkers of affective symptoms including depression and anxiety due to T2DM are not well established.

Aims

This study was conducted to delineate the serum biomarkers predicting affective symptoms due to T2DM above and beyond the effects of insulin resistance and atherogenicity.

Methods

The present study delineated the effects of serum levels of copper, zinc, β-arrestin-1, FBXW7, lactosylceramide (LacCer), serotonin, albumin, calcium, magnesium, IR and atherogenicity on severity of depression and anxiety in 58 men with T2DM and 30 healthy male controls. Severity of affective symptoms was assessed using the Hamilton Depression and Anxiety rating scales.

Results

We found that 61.7% of the variance in affective symptoms was explained by the multivariate regression on copper, β-arrestin-1, calcium, and insulin resistance coupled with atherogenicity, while 44.4% of the variance in the latter was explained by copper, β-arrestin-1, LacCer (all positively) and calcium and FBXW7 (both negatively). Copper and LacCer (positive) and calcium and BXW7 (inverse) had significant specific indirect effects on affective symptoms which were mediated by insulin resistance and atherogenicity. Copper, β-arrestin-1, and calcium were associated with affective symptoms above and beyond the effects of insulin resistance and atherogenicity.

Discussion

T2DM and affective symptoms share common pathways namely increased atherogenicity, insulin resistance, copper, and β-arrestin-1, and lowered calcium, whereas copper, β-arrestin-1, calcium, LacCer, and FBXW7 may modulate depression and anxiety symptoms by affecting T2DM.
RT-qPCR half reaction optimization for the detection of SARS-CoV-2
Authors: Wink Priscila Lamb , Volpato Fabiana , de Lima-Morales Daiana , Paiva Rodrigo Minuto , Willig Julia Biz , Bock Hugo , de Paris Fernanda , Luís Barth Afonso
Published: May 2021

BACKGROUND

The main laboratory test for the diagnosis of COVID-19 is the reverse transcription real-time polymerase chain reaction (RT-qPCR). However, the RT-qPCR is an expensive method due to the number of tests required.

OBJECTIVES

To evaluate an alternative RT-qPCR approach for the detection of SARS-CoV-2 sing half of the total volume currently recommended by the US Centers for Disease Control and Prevention.

METHODS

The analytical limit of detection (LoD) and the reaction efficiency using half volumes of RT-qPCR assay were evaluated for both the N1 and N2 regions by using a synthetic control RNA. A panel of 76 SARS-CoV-2-positive and 26 SARS-CoV-2-negative clinical samples were evaluated to establish the clinical sensitivity and specificity.

FINDINGS

The RT-qPCR assay efficiency was 105% for both the half and standard reactions considering the N2 target and 84% (standard) and 101% (half) for N1. The RT-qPCR half reaction LoD for N1 and N2 were 20 and 80 copies/µL, respectively. Clinical sensitivity and specificity were 100%. The half reaction presented a decrease of up to 5.5 cycle thresholds when compared with the standard RT-qPCR.

CONCLUSIONS

The use of RT-qPCR half reaction proved to be a feasible and economic strategy for detection of SARS-CoV-2 RNA.

Sponsorship

This work was supported by FAPERGS (20/2551-0000265-9) and by Fundo de Incentivo a Pesquisa e Eventos do Hospital de Clínicas de Porto Alegre (FIPE/HCPA) (Project no. 2020-0163).
Characterization of the Second Wave of the COVID-19 Pandemic in India: A Google Trends Analysis
Authors: Visaria Aayush , Polamarasetti Pooja , Reddy Shivani , Ali Alizah , Hameed Fariha R. , James Joel , Akhtar Moizz , Islam Sumaiya , Raju Priyanka , Thawani Rajat
Published: May 2021

Background

The second wave of the COVID-19 pandemic has led to considerable morbidity and mortality in India, in part due to lack of healthcare access, low health literacy, and poor disease surveillance. In this retrospective, descriptive ecological study, we utilized Google Trends (GT) to characterize the second COVID-19 wave and its association with official case counts based on search terms related to symptoms, testing, disease complications, medications, preventive behaviors, and healthcare utilization.

Methods

GT is a publicly available, online tracking system of Google searches. Searches are presented as relative search volumes (RSV) from 0 (least) to 100 (most number of searches). We performed pre-defined Web searches in India from 2/12/2021 to 5/09/2021. We characterized the peak RSV, RSV doubling rates, and Spearman rank correlation of selected search terms with official case counts. We also used date-adjusted linear regression to estimate the association between highly correlated search terms and official case counts. We then qualitatively classified public search queries into thematic groups to better understand public awareness and needs related to COVID-19.

Results

We observed that searches for symptoms (most searched terms in order: fever, cough, headache, fatigue, chest pain), disease states (infection, pneumonia), COVID-19-related medications (remdesivir, ivermectin, azithromycin, Fabiflu, dexamethasone), testing modalities (PCR, CT Scan, D-dimer, C-reactive protein, oxygen saturation), healthcare utilization (oxygen cylinders, hospital, physician), and preventive behaviors (lockdown, mask, pulse oximetry, hand sanitizer, quarantine) all demonstrated increases, in line with increases in official case counts. Symptoms, PCR testing, outpatient medications, and preventive behaviors peaked around April 24th, approximately two weeks prior to the peak RSV in official case counts. Contrarily, healthcare utilization factors, including searches for hospital, physicians, beds, disease states, and inpatient medications did not peak until the first week of May. There were highly significant correlations between ‘Coronavirus Disease 2019’ (r=0.959), ‘fever’ (r=0.935), ‘pulse oximetry’ (r=0.952), ‘oxygen saturation’ (r=0.944), ‘C-reactive protein’ (r=0.955), ‘D-Dimer’ (r=0.945), & ‘Fabiflu’ (r=0.943) and official case counts.

Conclusion

GT search terms related to symptoms, testing, and medications are highly correlated with official case counts in India, suggesting need for further studies examining GT’s potential use as a disease surveillance and public informant tool for public health officials.
Epidemiological characteristics of three SARS-CoV-2 variants of concern and implications for future COVID-19 pandemic outcomes
Authors: Yang Wan , Shaman Jeffrey
Published: May 2021

Three SARS-CoV-2 variants classified as variants of concern – B.1.1.7, B.1.351, and P.1 – have spread globally. To characterize their viral and epidemiological properties in support of public health planning, we develop and apply a model-inference system to estimate the changes in transmissibility and immune escape for each variant, based on case and mortality data from the country where each variant emerged. Accounting for under-detection of infection, disease seasonality, concurrent non-pharmaceutical interventions, and mass-vaccination, we estimate that B.1.1.7 has a 46.6% (95% CI: 32.3 – 54.6%) increase in transmissibility but nominal immune escape from protection induced by prior wild-type infection; B.1.351 has a 32.4% (95% CI: 14.6 – 48.0%) increase in transmissibility and 61.3% (95% CI: 42.6 – 85.8%) immune escape; and P.1 has a 43.3% (95% CI: 30.3 – 65.3%) increase in transmissibility and 52.5% (95% CI: 0 – 75.8%) immune escape. Model simulations indicate that B.1.351 and P.1 could supplant B.1.1.7 dominance and lead to increased infections. Our findings highlight the importance of preventing the spread of B.1.351 and P.1, in addition to B.1.1.7, via continued preventive measures, prompt mass-vaccination of all populations, continued monitoring of vaccine efficacy, and possible updating of vaccine formulations to ensure high efficacy.
AnmO2l: An open-source pulse-dose oxygen conserving device for the COVID-19 crisis
Authors: Li Honquan , Krishnamurthy Deepak , Kothari Anesta , Li Ethan , Lipnick Michael , Gaba David , Fanning Ruth , Prakash Manu
Published: May 2021

The surge of COVID-19 cases in India and around the world has resulted in acute oxygen shortage. Oxygen therapy through nasal cannula with flow rates of 1-6 L/min is an effective treatment for many COVID-19 patients in non-critical conditions and may help prevent disease progression. The same treatment is also used in post-acute care for recovering COVID-19 patients. Here we describe a simple, open source, and rapidly manufacturable oxygen conservation device for use with dual-port nasal cannula that can extend the life of current oxygen supply by almost two to three times, which we hope will help towards coping with the ongoing crisis.
Demographic disparities in clinical outcomes of COVID-19: data from a statewide cohort in South Carolina
Authors: Yang Xueying , Zhang Jiajia , Chen Shujie , Olatosi Bankole , Bruner Larisa , Diedhiou Abdoulaye , Scott Cheryl , Mansaray Ali , Weissman Sharon , Li Xiaoming
Published: May 2021

Background

Current literature examining the clinical characteristics of COVID-19 patients under-represent COVID-19 cases who were either asymptomatic or had a mild illness.

Objective

To generate a state-level description and examine the demographic disparities of clinical outcomes of COVID-19.

Design

Statewide population-based cohort study

Setting

COVID-19 surveillance facilities in South Carolina

Patients

Adults COVID-19 cases reported to the SC DHEC by Case Report Form during March 04–December 31, 2020

Measurements

The primary predictors were socio-demographic characteristics. The outcomes were COVID-19 disease severity, hospitalization, and mortality, which collected from the standardized CRF.

Results

Among a total of 280,177 COVID-19 cases, 5.2% (14,451) were hospitalized and 1.9% (5,308) died. Individuals who were older, male gender, Blacks, Hispanic or Latino, and residing in small towns had higher odds for hospitalization and death from COVID-19 (Ps<0.0001). Regarding disease severity, 144,157 (51.5%) were asymptomatic, while 34.4% and 14.2% had mild and moderate/severe symptoms, respectively. Older individuals (OR: 1.14, 95%CI: 1.11, 1.18), Hispanic or Latino (OR: 2.07; 95%CI: 1.96, 2.18), and people residing in small towns (OR: 1.15; 95%CI: 1.08, 1.23) had higher odds of experiencing moderate/severe symptoms, while male and Asian (vs Whites) patients had lower odds of experiencing moderate/severe symptoms.

Limitations

Potential misclassification of outcomes due to missing data; other variables were not evaluated, such as comorbidities.

Conclusion

As the first statewide population-based study using data from multiple healthcare systems with a long follow-up period in the US, we provide a more generalizable picture of COVID-19 symptoms and clinical outcomes. The findings from this study reinforce the fact that rural residence, racial and ethnic social determinants of health, unfortunately, remain predictors of poor health outcomes for COVID-19 patients.
Arousal state affects perceptual decision-making by modulating hierarchical sensory processing in a large-scale visual system model
Authors: Sörensen Lynn K. A. , Bohté Sander M. , Slagter Heleen A. , Scholte H. Steven
Published: May 2021

Arousal levels strongly affect task performance. Yet, what arousal level is optimal for a task depends on its difficulty. Easy task performance peaks at higher arousal levels, whereas performance on difficult tasks displays an inverted U-shape relationship with arousal, peaking at medium arousal levels, an observation first made by Yerkes and Dodson in 1908. It is commonly proposed that the noradrenergic locus coeruleus system regulates these effects on performance through a widespread release of noradrenaline resulting in changes of cortical gain. This account, however, does not explain why performance decays with high arousal levels only in difficult, but not in simple tasks. Here, we present a mechanistic model that revisits the Yerkes-Dodson effect from a sensory perspective: a deep convolutional neural network augmented with a global gain mechanism reproduced the same interaction between arousal state and task difficulty in its performance. Investigating this model revealed that global gain states differentially modulated sensory information encoding across the processing hierarchy, which explained their differential effects on performance on simple versus difficult tasks. These findings offer a novel hierarchical sensory processing account of how, and why, arousal state affects task performance.

Author’s summary

Over a hundred years ago, it was first observed that the effect of arousal on performance depends on task difficulty: the Yerkes-Dodson effect. Difficult tasks are best solved at intermediate arousal levels, whereas easy tasks benefit from a high arousal state. Current theories on how arousal affects neural processing cannot explain this effect of task difficulty. Here, we implement a key effect of arousal on cortical processing, a change in neuronal gain, in a computational model of visual processing capable of object recognition. Across a series of experiments, we find that our model can reproduce the Yerkes-Dodson effect behaviorally and that this effect can be explained by where in the processing hierarchy different arousal states optimize sensory information encoding.
Genetic analysis of Caenorhabditis elegans pry-1/Axin suppressors identifies genes involved in reproductive structure development, stress response, and aging
Authors: Mallick Avijit , Jhaveri Nikita , Jeon Jihae , Chang Yvonne , Shah Krupali , Hosein Hannah , Gupta Bhagwati P.
Published: May 2021

The Axin family of scaffolding proteins regulates a wide array of developmental and post-developmental processes in eukaryotes. Studies in the nematode, Caenorhabditis elegans, have shown that the Axin homolog, PRY-1, plays essential roles in multiple tissues. To understand the genetic network of pry-1, we focused on a set of genes that are differentially expressed in the pry-1-mutant transcriptome and are linked to reproductive structure development. Eight of the genes (ard-1, rpn-7, cpz-1, his-7, cdk-1, rnr-1, clsp-1, and spp-1), when knocked down by RNA interference, efficiently suppressed the plate-level multivulva phenotype of pry-1 mutants. In every case, other than clsp-1 and spp-1, the ectopic vulval precursor cell (VPC) induction was also inhibited. The suppressor genes are members of known gene families in eukaryotes and perform essential functions. Our genetic interaction experiments revealed that except for clsp-1, the genes participate in one or more pry-1-mediated biological events. While four of them (cpz-1, his-7, cdk-1, and rnr-1) function in VPC induction, stress response, and aging, the other three (spp-1, ard-1, and rpn-7) are specific to one or more of these processes. Further analysis of the genes involved in aging showed that his-7, cdk-1, and rnr-1 also interacted with daf-16/FOXO. The results of genetic epistasis experiments suggested that his-7 functions upstream of daf-16, whereas cdk-1 and rnr-1 act downstream of the pry-1-daf-16 pathway. Altogether, these findings demonstrate the important role of pry-1 suppressors in C. elegans. Given that all of the genes described in this study are conserved, future investigations of their interactions with Axin and their functional specificity promises to uncover the genetic network of Axin under normal and disease states.
Predicting T cell receptor antigen specificity from structural features derived from homology models of receptor-peptide-major histocompatibility complexes
Authors: Milighetti Martina , Shawe-Taylor John , Chain Benjamin M
Published: May 2021

1

The physical interaction between the T cell receptor (TCR) and its cognate antigen causes T cells to activate and participate in the immune response. Understanding this physical interaction is important in predicting TCR binding to a target epitope, as well as potential cross-reactivity. Here, we propose a way of collecting informative features of the binding interface from homology models of T cell receptor-peptide-major histocompatibility complex (TCR-pMHC) complexes. The information collected from these structures is sufficient to discriminate binding from non-binding TCR-pMHC pairs in multiple independent datasets. The classifier is limited by the number of crystal structures available for the homology modelling and by the size of the training set. However, the classifier shows comparable performance to sequence-based classifiers requiring much larger training sets.
Neuroimaging Measures of Iron and Gliosis Explain Memory Performance in Aging
Authors: Venkatesh Anu , Daugherty Ana M. , Bennett Ilana J.
Published: May 2021

Evidence from animal and histological studies have indicated that accumulation of iron in the brain results in reactive gliosis that contributes to cognitive deficits. The current study extends these findings to human cognitive aging and suggests that magnetic resonance imaging (MRI) techniques like quantitative relaxometry can be used to study iron and its effects in vivo. The effects of iron on microstructure and memory performance were examined using a combination of quantitative relaxometry and multi-compartment diffusion imaging in 35 young (21.06 ± 2.18 years) and 28 older (72.58 ± 6.47 years) adults, who also completed a memory task. Replicating past work, results revealed age-related increases in iron content (R2 *) and diffusion, and decreases in memory performance. Independent of age group, iron content was significantly related to restricted (intracellular) diffusion in regions with low-moderate iron (hippocampus, caudate) and to all diffusion metrics in regions with moderate-high iron (putamen, globus pallidus). This pattern is consistent with different stages of iron-related gliosis, ranging from astrogliosis that may influence intracellular diffusion to microglial proliferation and increased vascular permeability that may influence all sources of diffusion. Further, hippocampal restricted diffusion was significantly related to memory performance, with a third of this effect related to iron content; consistent with the hypothesis that higher iron-related astrogliosis in the hippocampus is associated with poorer memory performance. These results demonstrate the sensitivity of MRI to iron-related gliosis and extends our understanding of its impact on cognition by showing that this relationship also explains individual differences in memory performance.
Diel light cycles affect phytoplankton competition in the global ocean
Authors: Tsakalakis Ioannis , Follows Michael J. , Dutkiewicz Stephanie , Follett Christopher L. , Vallino Joseph J.
Published: May 2021

Light, essential for photosynthesis, is present in two periodic cycles in nature: seasonal and diel. Although seasonality of light is typically resolved in ocean ecosystem and biogeochemistry models because of its significance for seasonal succession and biogeography of phytoplankton, the diel light cycle is generally not resolved. Here we use a three-dimensional global ocean model and compare high temporal resolution simulations with and without diel light cycles. The model simulates 15 phytoplankton types of different cell size, encompassing two broad ecological strategies: small cells with high nutrient affinity (gleaners) and larger cells with high maximal growth rate (opportunists). Both are grazed by zooplankton and limited by nitrogen, phosphorus and iron. Simulations show that diel cycles of light induce diel cycles in phytoplankton populations and limiting nutrients in the global ocean. Diel nutrient cycles are associated with higher concentration of limiting nutrients by up to 200% at low latitudes (-40° to 40°), a process that increases opportunists’ biomass by up to 50%. Size classes with the highest maximal growth rates from both gleaner and opportunist groups are favored the most by diel light cycles. This mechanism weakens as latitude increases because the effects of the seasonal cycle dominate over those of the diel cycle. The present work shows that resource competition under diel light cycles has a significant impact on phytoplankton biogeography, indicating the necessity of resolving diel processes in global ocean models.