bluuebunny/crossref_metadata_2025 huggingface dataset:
The Lines That Held Us: Assessing Racial and Socioeconomic Disparities in SARS-CoV-2 Testing
Authors: Hsiao Chu J , Patel Aditi G M , Fasanya Henrietta O , Stoffel Michelle R , Beal Stacy G , Winston-McPherson Gabrielle N , Campbell Sean T , Cotten Steven W , Crews Bridgit O , Kuan Kevin , Lapedis Cathryn J , Mathias Patrick C , Peck Palmer Octavia M , Greene Dina N
Published: June 2021

Background

Racial disparities in SARS-CoV-2 prevalence are apparent. Race is a sociocultural construct, necessitating investigation into how sociocultural factors contribute.

Methods

This cross-sectional study linked laboratory data of adult patients between February 29 and May 15, 2020 with socio-demographics variables from the 2018 American Community Survey (ACS). Medical sites included healthcare organizations in Michigan, New York, North Carolina, California, Florida, Pennsylvania, and Washington. Race was treated as a proxy for racism and not biological essentialism. Laboratory data included patient age, sex, race, ethnicity, test result, test location, and residential ZIP code. ACS data included economic and educational variables contributing to an SES Index, population density, proportion Medicaid, and racial composition for corresponding ZIP code. Associations between race/socioeconomic variables and test results were examined using odds ratios (OR).

Results

Of 126 452 patients [mean (SD) age 51.9 (18.4) years; 52 747 (41.7%) men; 68 856 (54.5%) White and 27 805 (22.0%) Black], 18 905 (15.0%) tested positive. Of positive tests, 5238 (SD 27.7%) were White and 7223 (SD 38.2%) were Black. Black race increased the odds of a positive test; this finding was consistent across sites [OR 2.11 (95% CI 1.95–2.29)]. When subset by race, higher SES increased the odds of a positive test for White patients [OR 1.10 (95% CI 1.05–1.16)] but decreased the odds for Black patients [OR 0.92 (95% CI 0.86–0.99)]. Black patients, but not White patients, who tested positive overwhelmingly resided in more densely populated areas.

Conclusions

Black race was associated with SARS-CoV-2 positivity and the relationship between SES and test positivity differed by race, suggesting the impact of socioeconomic status on test positivity is race-specific.
Evaluation of Three Commercial and Two Non-Commercial Immunoassays for the Detection of Prior Infection to SARS-CoV-2
Authors: Nilles Eric J , Karlson Elizabeth W , Norman Maia , Gilboa Tal , Fischinger Stephanie , Atyeo Caroline , Zhou Guohai , Bennett Christopher L , Tolan Nicole V , Oganezova Karina , Walt David R , Alter Galit , Simmons Daimon P , Schur Peter , Jarolim Petr , Woolley Ann E , Baden Lindsey R
Published: June 2021

Background

Serological testing provides a record of prior infection with SARS-CoV-2, but assay performance requires independent assessment.

Methods

We evaluated 3 commercial (Roche Diagnostics pan-IG, and Epitope Diagnostics IgM and IgG) and 2 non-commercial (Simoa and Ragon/MGH IgG) immunoassays against 1083 unique samples that included 251 PCR-positive and 832 prepandemic samples.

Results

The Roche assay registered the highest specificity 99.6% (3/832 false positives), the Ragon/MGH assay 99.5% (4/832), the primary Simoa assay model 99.0% (8/832), and the Epitope IgG and IgM 99.0% (8/830) and 99.5% (4/830), respectively. Overall sensitivities for the Simoa, Roche pan-IG, Epitope IgG, Ragon/MGH IgG, and Epitope IgM were 92.0%, 82.9%, 82.5%, 64.5% and 47.0%, respectively. The Simoa immunoassay demonstrated the highest sensitivity among samples stratified by days postsymptom onset (PSO), <8 days PSO (57.69%) 8–14 days PSO (93.51%), 15–21 days PSO (100%), and > 21 days PSO (95.18%).

Conclusions

All assays demonstrated high to very high specificities while sensitivities were variable across assays.
Design, development, and deployment of an indication- and kidney function-based decision support tool to optimize treatment and reduce medication dosing errors
Authors: Hirsch Jamie S , Brar Rajdeep , Forrer Christopher , Sung Christine , Roycroft Richard , Seelamneni Pradeep , Dabir Hemala , Naseer Ambareen , Gautam-Goyal Pranisha , Bock Kevin R , Oppenheim Michael I
Published: June 2021

Delivering clinical decision support (CDS) at the point of care has long been considered a major advantage of computerized physician order entry (CPOE). Despite the widespread implementation of CPOE, medication ordering errors and associated adverse events still occur at an unacceptable level. Previous attempts at indication- and kidney function-based dosing have mostly employed intrusive CDS, including interruptive alerts with poor usability. This descriptive work describes the design, development, and deployment of the Adult Dosing Methodology (ADM) module, a novel CDS tool that provides indication- and kidney-based dosing at the time of order entry. Inclusion of several antimicrobials in the initial set of medications allowed for the additional goal of optimizing therapy duration for appropriate antimicrobial stewardship. The CDS aims to decrease order entry errors and burden on providers by offering automatic dose and frequency recommendations, integration within the native electronic health record, and reasonable knowledge maintenance requirements. Following implementation, early utilization demonstrated high acceptance of automated recommendations, with up to 96% of provided automated recommendations accepted by users.
Kimura’s disease: a rare cause of chronic neck lymphadenopathy
Authors: Kok Kenneth Y Y , Lim Edwin C C
Published: June 2021

Kimura’s disease is a rare chronic inflammatory disorder of unknown etiology which typically presents with subcutaneous nodules in the head and neck region and is frequently associated with regional lymphadenopathy or salivary gland enlargement. Peripheral blood eosinophilia and elevated serum immunoglobulin E levels are constant features of the disease. We present herein a 31-year-old male patient who presented with chronic neck lymphadenopathy. Kimura’s disease was diagnosed on fine needle aspiration cytology, the patient initially decided not to have further intervention. He presented 6 years later with lymphadenopathy and was treated with surgery. The diagnosis of Kimura’s disease was confirmed on histopathology. This patient had the disease for 6 years and did not have the typical features of peripheral eosinophilia and raise serum IgE level.
Diagnostic Evaluation of Hypoglycemia Due To an Insulinoma in a Deployed Infantryman: Significance of Neuroglycopenia and the Role of the Military Health System
Authors: Olatunbosun Samuel T , Alaketu Ayodeji F , McDermott Joseph H , Elsayed von Bayreuth Al M
Published: July 2021

Insulinoma, the prototype of endogenous hyperinsulinemic hypoglycemia, is a very rare condition, with an incidence of four cases per million person-years. Its rate of occurrence in the U.S. military population is unknown. Two cases of insulinomas involving active duty service members have been published. However, there has been no reported case of an insulinoma in a deployed service member. We report the case of a 21-year-old infantryman with clinical hypoglycemia of insidious onset, manifesting with overt neuroglycopenic symptoms during his deployment as a combatant soldier, and the ultimate diagnosis of an insulinoma as the underlying cause. The series of multiple clinical evaluations and the unique circumstances leading to the formal evaluation of the patient’s hypoglycemia and treatment are chronicled. The significance of neuroglycopenia and the diagnostic approach to any suspected case of hypoglycemia, the potential challenges and opportunities, and educational aspects of evaluation and management of the insulinoma are elaborated. The potential role of the Military Health System in facilitating the detection and treatment of this rare condition in the service member is discussed as well.
An inventory of atomic species in the atmosphere of WASP-121b using UVES high-resolution spectroscopy
Authors: Merritt Stephanie R , Gibson Neale P , Nugroho Stevanus K , de Mooij Ernst J W , Hooton Matthew J , Lothringer Joshua D , Matthews Shannon M , Mikal-Evans Thomas , Nikolov Nikolay , Sing David K , Watson Chris A
Published: June 2021

Ultrahot Jupiters (UHJs) present excellent targets for atmospheric characterization. Their hot dayside temperatures (T ≳ 2200 K) strongly suppress the formation of condensates, leading to clear and highly inflated atmospheres extremely conducive to transmission spectroscopy. Recent studies using optical high-resolution spectra have discovered a plethora of neutral and ionized atomic species in UHJs, placing constraints on their atmospheric structure and composition. Our recent work has presented a search for molecular features and detection of Fe i in the UHJ WASP-121b using Very Large Telescope (VLT)/UV–Visual Echelle Spectrograph (UVES) transmission spectroscopy. Here, we present a systematic search for atomic species in its atmosphere using cross-correlation methods. In a single transit, we uncover potential signals of 17 atomic species that we investigate further, categorizing five as strong detections, three as tentative detections, and nine as weak signals worthy of further exploration. We confirm previous detections of Cr i, V i, Ca i, K i, and exospheric H i and Ca ii made with the High Accuracy Radial velocity Planet Searcher (HARPS) and the Echelle SPectrograph for Rocky Exoplanets and Stable Spectroscopic Observations (ESPRESSO), and independently re-recover our previous detection of Fe i at 8.8σ using both the blue and red arms of the UVES data. We also add a novel detection of Sc ii at 4.2σ. Our results further demonstrate the richness of UHJs for optical high-resolution spectroscopy.
Endoscopic Third Ventriculostomy With “Rescue” Fourth Ventriculocisternostomy: 2-Dimensional Operative Video
Authors: Goldberg Jacob L , Carnevale Joseph A , Rapoport Benjamin , Garton Andrew L A , Bander Evan , Souweidane Mark M
Published: June 2021

This case of endoscopic third ventriculostomy (ETV) and flexible endoscopy for lysis of fourth ventricle adhesions for obstructive hydrocephalus illustrates a key anatomical variant (anastomosis of posterior communicating arteries) that increases the difficulty of ETV and should be recognized preoperatively. The video further demonstrates flexible endoscopy for lysis of a fourth ventricular web and excellent third and fourth ventricular anatomy. This patient presented with normal pressure hydrocephalus-like symptoms and magnetic resonance imaging suggestive of a fourth ventricular outflow obstruction. An ETV would be an ideal intervention with a high chance of success
1
and avoiding a ventriculoperitoneal shunt or a more invasive suboccipital craniectomy for fourth ventricle exploration; however, variant anatomy and resultant medialization of the bilateral posterior communicating arteries put their location directly beneath the tuber cinereum. After discussing the risks and benefits of the proposed procedure, the patient consented to proceeding with the surgery. Patient is not identifiable either by clinical vignette or through this operative video, which is entirely intraventricular. The care rendered was standard (nonexperimental). The patient did sign consent for filming and production of the educational video submitted.

 Here, we present operative video from our ETV, demonstrating an inability to confirm adequate fenestration and subsequent flexible endoscopy for fourth ventriculocisternostomy.
The efficacy of systemic glucocorticosteroids for pain in rheumatoid arthritis: a systematic literature review and meta-analysis
Authors: McWilliams Daniel F , Thankaraj Divya , Jones-Diette Julie , Morgan Rheinallt , Ifesemen Onosi S , Shenker Nicholas G , Walsh David A
Published: June 2021

Objectives

Glucocorticosteroids (GCs) are recommended to suppress inflammation in people with active RA. This systematic review and meta-analysis aimed to quantify the effects of systemic GCs on RA pain.

Methods

A systematic literature review of randomized controlled trials (RCTs) in RA comparing systemic GCs to inactive treatment. Three databases were and spontaneous pain and evoked pain outcomes were extracted. Standardized mean differences (SMDs) and mean differences were meta-analysed. Heterogeneity (I2, tau statistics) and bias (funnel plot, Egger’s test) were assessed. Subgroup analyses investigated sources of variation. This study was pre-registered (PROSPERO CRD42019111562).

Results

A total of 18 903 titles, 880 abstracts and 226 full texts were assessed. Thirty-three RCTs suitable for the meta-analysis included 3123 participants. Pain scores (spontaneous pain) decreased in participants treated with oral GCs; SMD = −0.65 (15 studies, 95% CI −0.82, −0.49, P <0.001) with significant heterogeneity (I2 = 56%, P =0.0002). Efficacy displayed time-related decreases after GC initiation. Mean difference visual analogue scale pain was −15 mm (95% CI −20, −9) greater improvement in GC than control at ≤3 months, −8 mm (95% CI −12, −3) at >3–6 months and −7 mm (95% CI −13, 0) at >6 months. Similar findings were obtained when evoked pain outcomes were examined. Data from five RCTs suggested improvement also in fatigue during GC treatment.

Conclusion

Oral GCs are analgesic in RA. The benefit is greatest shortly after initiation and GCs might not achieve clinically important pain relief beyond 3 months. Treatments other than anti-inflammatory GCs should be considered to reduce the long-term burden of pain in RA.
Growth indices, intestinal histomorphology, and blood profile of rabbits fed probiotics- and prebiotics-supplemented diets
Authors: Nwachukwu Chinwe Uchechi , Aliyu Karimat Imam , Ewuola Emmanuel Olubisi
Published: June 2021

In a 12-week feeding trial, 32 rabbits (Chinchilla × New Zealand White; 56 days old; 691 ± 1 g body weight) were used to investigate the effect of pro- and prebiotics as growth enhancer on the growth performance, intestinal mucosal development, hematological and serum biochemical responses of rabbits. The dietary Biotronic® prebiotics and Biovet®-YC probiotics were added at 400 mg/kg and 50 mg/kg, respectively. The rabbits were housed individually and randomly assigned to four dietary treatments (n = 8/group; 50:50 bucks to does) including a control diet (diet 1), diet 2 (control + Biotronic® prebiotics), diet 3 (control + Biovet®-YC probiotics) and diet 4 (control + symbiotics [Biotronic® prebiotics and Biovet®-YC probiotics]). Body weight (BW), average daily gain (ADG), dry matter intake (DMI), and feed conversion ratio (FCR) were monitored. Five rabbits per treatment were used for organ assessment and intestinal histomorphology after feeding trial. Blood samples were collected for hematological and serum biochemical analysis. Results showed that supplementation of Biotronic® prebiotics and symbiotics in rabbit diet significantly (P < 0.05) increased final BW and ADG compared to Biovet®-YC probiotic and control diets. Kidney, lung, esophagus, gastro-intestinal tract, small and large intestines were significantly (P < 0.05) influenced by dietary treatments. Ileal mucosal assessment revealed that villus height (VH), villus width, villus density, crypt depth (CD), and VH:CD ratio of rabbits fed Biotronic® prebiotic and symbiotic diets were similar and significantly (P < 0.05) higher than those rabbits fed control and Biovet®-YC probiotic diets. Packed cell volume of rabbits fed symbiotic and control diets was significantly (P < 0.05) higher than those fed Biotronic® prebiotic and Biovet®-YC probiotic diets. This study suggests that Biotronic® prebiotics and its combination with Biovet®-YC probiotics are good alternative growth promoting feed additives in rabbit nutrition. They improved performance, intestinal development and blood profiles and aid feed digestion, nutrient absorption and utilization in rabbits.
Challenges of Assessing Resident Competency in Well-Being: Development of the Psychiatry Milestones 2.0 Well-Being Subcompetency
Authors: Houston L. Joy , DeJong Sandra M. , Brenner Adam M. , Macaluso Matthew , Kinzie J. Mark , Arbuckle Melissa R. , Janssen Furhut , Cowley Deborah S. , Bentman Adrienne L.
Published: June 2021

Burnout and depression are major problems facing physicians, with 300–400 physicians dying by suicide each year. In an effort to address this issue, the Accreditation Council for Graduate Medical Education (ACGME) revised the Common Program Requirements for residency and fellowship programs to include a strong emphasis on well-being, and this revision has been extended to including a subcompetency on well-being in the Milestones 2.0. The Psychiatry Milestones 2.0 Work Group was convened to draft updated psychiatry milestones. As part of the open feedback period, the American Association of Directors of Psychiatric Residency Training submitted an organizational letter outlining several points to consider regarding the original draft of the well-being subcompetency. The ACGME was receptive to this feedback and allowed the Psychiatry Milestones 2.0 Work Group to revise the subcompetency. Current research indicates that burnout is largely driven by systemic factors, but well-being literature and initiatives often focus on individual factors and responsibility for burnout rather than systemic change. Program directors tasked with assessing resident well-being can additionally encounter several professionalism concerns, including how to (1) define a subcompetency within a competency that itself has not been well defined; (2) decide the appropriate balance between individual and systemic responsibility for well-being; (3) consider mental health as a parameter of well-being; (4) balance roles as physicians, psychiatrists, and training directors in thinking about the mental health of residents without overstepping boundaries and while maintaining privacy, confidentiality, and resident safety; and (5) measure well-being in a sociocultural context. This article describes how these considerations were incorporated into the revision of the Psychiatry Milestones 2.0 version of the well-being subcompetency, which has subsequently been made available to other specialty work groups for potential use as they develop their specialty-specific Milestones 2.0.
The relationship between falling and fear of falling among community-dwelling elderly
Authors: Chen Wei-Cheng , Li Yang-Tzu , Tung Tao-Hsin , Chen Chieh , Tsai Ching-Yao
Published: June 2021

Researchers have repeatedly examined the relationship between a previous experience of a fall and subsequent fear of falling (FOF); however, few studies have investigated the effects of falling along various timelines among older adults. The objective of this study was to determine whether experiencing a fall in the previous month or the previous year led to FOF among the elderly.

The National Health and Aging Trends Study (NHATS) in the U.S. collected information indicative of basic trends in the behavior of individuals aged 65 years and older. In the current study, we applied multiple logistic regression analysis of results from round 7 of the NHATS with the aim of identifying the risk factors associated with FOF among 5559 participants aged 65 years or older.

FOF was reported by 48.8% of those who experienced a fall in the previous year and 46.8% experienced a fall in the previous month. The results of regression analysis revealed that after adjusting for sex, age, related chronic disease, activities of daily living, and instrumental activities of daily living, FOF was significantly associated with experiencing a fall during the previous month (OR = 2.29, 95% CI: 1.78–2.95) or during the previous year (OR = 2.60, 95% CI: 2.16–3.14).

Our results indicate that experiences of falling during the previous month or the previous year were both significantly associated with a fear of falling, and caregivers should keep this in mind when dealing with community-living elderly individuals.
Effect of inflammatory bowel disease and related medications on COVID-19 incidence, disease severity, and outcome: the Israeli experience
Authors: Richter Vered , Bermont Anton , Cohen Daniel L , Broide Efrat , Shirin Haim
Published: June 2021

Objectives

The coronavirus disease 2019 (COVID-19) pandemic raised concerns among inflammatory bowel disease (IBD) patients fearing an increased risk of infection and poor outcomes. We aimed to evaluate the incidence of COVID-19 among IBD patients; its influence on disease severity and outcome; its relationship to medication use and how the pandemic affected IBD management.

Methods

An anonymous questionnaire was posted online to members of the Israel Crohn’s Disease and Ulcerative Colitis Foundation (November 2020–January 2021). The questionnaire addressed the course of IBD disease and COVID-19 infection over the past year.

Results

Total 2152 IBD patients completed the questionnaire. Of which 104 (4.8%) had been infected with COVID-19, significantly lower than the ‘expected’ infected cases among the Israeli population (P = 0.033). The median age of participants was 39 years; 60.5% were female. Most patients (75.6%) had no comorbidities other than IBD. No correlation was found between IBD type or disease severity and COVID-19 infection. Most IBD patients reported mild COVID-19 disease, regardless of the type of IBD medications. Multivariable logistic regression analysis revealed that younger age, elevated BMI and diabetes were independent risk factors for COVID-19 infection. IBD treatment methods including 5-aminosalicylic acid, smoking and hypertension were protective factors. In total 25.2% of COVID-19 patients discontinued their IBD treatment, compared to 8.5% of non-COVID-19-infected patients. IBD flares were significantly higher in those who discontinued treatment (P < 0.001).

Conclusions

IBD patients do not have an increased risk for COVID-19, regardless of IBD activity or treatment. Patients should be encouraged to continue effective IBD therapy, including biologics and steroids, to minimize active IBD.
Disruptions in Care and Support for Homebound Adults in Home-Based Primary Care in New York City During the COVID-19 Pandemic
Authors: Federman Alex D. , Leff Bruce , Brody Abraham A. , Lubetsky Sara , Siu Albert L. , Ritchie Christine S. , Ornstein Katherine A.
Published: June 2021

Homebound older adults are a highly vulnerable population, yet little is known about their experiences with healthcare during the COVID-19 pandemic. We interviewed patients in home-based primary care (HBPC) in New York City by telephone in May and June of 2020. Interviews covered social supports, household activities, self-care, and medical care, and asked participants to compare current with prepandemic experiences. Among 70 participants, 37% were Black and 32% were Hispanic. Disruptions in the home included greater difficulty accessing paid caregivers (13.9%) and food (35.3%) than before the pandemic, and unaddressed household chores (laundry, 81.4%; food preparation, 11.4%). Black study participants were more likely than White and Hispanic participants to report disruptions in accessing medical care (13 [50.0%] vs. 3 [14.3%] vs. 6 [27.3%], respectively, p = 0.02), as well as food preparation and medication taking. Black patients in HBPC are at risk of disparities in healthcare and social support during the COVID-19 pandemic.
Global tropical reef fish richness could decline by around half if corals are lost
Authors: Strona Giovanni , Lafferty Kevin D. , Fattorini Simone , Beck Pieter S. A. , Guilhaumon François , Arrigoni Roberto , Montano Simone , Seveso Davide , Galli Paolo , Planes Serge , Parravicini Valeriano
Published: June 2021

Reef fishes are a treasured part of marine biodiversity, and also provide needed protein for many millions of people. Although most reef fishes might survive projected increases in ocean temperatures, corals are less tolerant. A few fish species strictly depend on corals for food and shelter, suggesting that coral extinctions could lead to some secondary fish extinctions. However, secondary extinctions could extend far beyond those few coral-dependent species. Furthermore, it is yet unknown how such fish declines might vary around the world. Current coral mass mortalities led us to ask how fish communities would respond to coral loss within and across oceans. We mapped 6964 coral-reef-fish species and 119 coral genera, and then regressed reef-fish species richness against coral generic richness at the 1° scale (after controlling for biogeographic factors that drive species diversification). Consistent with small-scale studies, statistical extrapolations suggested that local fish richness across the globe would be around half its current value in a hypothetical world without coral, leading to more areas with low or intermediate fish species richness and fewer fish diversity hotspots.
Breath biomarkers of insulin resistance in pre-diabetic Hispanic adolescents with obesity
Authors: Khan Mohammad S. , Cuda Suzanna , Karere Genesio M. , Cox Laura , Bishop Andrew C.
Published: June 2021

Background

Insulin Resistance (IR) affects a quarter of the world’s adult population and is a major factor in the pathogenesis of cardio-metabolic disease. Non-invasive sampling of exhaled breath contains metabolic markers indicative of underlying systemic metabolic abnormality.

Method

In this pilot study, we implemented a non-invasive breathomics approach, combined with random forest machine learning, to investigate metabolic markers from pre-diabetic Hispanic adolescents with obesity as indicators of abnormal metabolic regulation.

Findings

Exhaled breath collection using the ReCIVA breathalyzer is feasible in an adolescent population. We have identified a signature of breath metabolites (breath-IR model) which correlates with Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (R = 0.95,p<0.001). A strong correlation was also observed between the breath-IR model and the blood glycemic profile (fasting insulin R=0.91,p<0.001 and fasting glucose R=0.80,p<0.001). Among tentatively identified metabolites, limonene, undecane, and 2,7-dimethyl-undecane, significantly cluster individuals based on HOMA-IR (p=0.003,p=0.002, andp<0.001, respectively). Our breath-IR model differentiates between adolescents with and without IR with an area under the receiver operating characteristic curve of 0.87, after cross-validation.

Interpretation

Identification of a breath metabolite signature indicative of IR in prediabetic Hispanic adolescents with obesity provides evidence of the utility of exhaled breath metabolomics for assessing systemic metabolic dysregulation. A simple and non-invasive breath-based test has utility as a diagnostic tool for monitoring IR progression, potentially allowing for earlier detection of IR and implementation of early interventions to prevent onset of type 2 diabetes mellitus.

Funding

This study was funded by The Healthy Babies Project, Texas Biomedical Research Institute, San Antonio, TX.
Resurgence of SARS-CoV-2 in India: Potential role of the B.1.617.2 (Delta) variant and delayed interventions
Authors: Salvatore Maxwell , Bhattacharyya Rupam , Purkayastha Soumik , Zimmermann Lauren , Ray Debashree , Hazra Aditi , Kleinsasser Michael , Mellan Thomas , Whittaker Charlie , Flaxman Seth , Bhatt Samir , Mishra Swapnil , Mukherjee Bhramar
Published: June 2021

India has seen a surge of SARS-CoV-2 infections and deaths in early part of 2021, despite having controlled the epidemic during 2020. Building on a two-strain, semi-mechanistic model that synthesizes mortality and genomic data, we find evidence that altered epidemiological properties of B.1.617.2 (Delta) variant play an important role in this resurgence in India. Under all scenarios of immune evasion, we find an increased transmissibility advantage for B.1617.2 against all previously circulating strains. Using an extended SIR model accounting for reinfections and wanning immunity, we produce evidence in support of how early public interventions in March 2021 would have helped to control transmission in the country. We argue that enhanced genomic surveillance along with constant assessment of risk associated with increased transmission is critical for pandemic responsiveness.

One Sentence Summary

Altered epidemiological characteristics of B.1.617.2 and delayed public health interventions contributed to the resurgence of SARS-CoV-2 in India from February to May 2021.
Glycoproteome remodelling in MLL-rearranged B-cell precursor acute lymphoblastic leukemia
Authors: Oliveira Tiago , Zhang Mingfeng , Joo Eun Ji , Abdel-Azim Hisham , Chen Chun-Wei , Yang Lu , Chou Chih-Hsing , Qin Xi , Chen Jianjun , Alagesan Kathirvel , Almeida Andreia , Jacob Francis , Packer Nicolle H , von Itzstein Mark , Heisterkamp Nora , Kolarich Daniel
Published: June 2021

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with mixed-lineage leukemia gene rearrangement (MLL-r) is a poor-prognosis subtype for which additional therapeutic targets are urgently needed. Currently no multi omics data set for primary MLL r patient cells exists that integrates transcriptomics, proteomics and glycomics to gain an inclusive picture of theranostic targets.

Methods

We have integrated transcriptomics, proteomics and glycomics to i) obtain the first inclusive picture of primary patient BCP-ALL cells and identify molecular signatures that distinguish leukemic from normal precursor B-cells and ii) better understand the benefits and limitations of the applied technologies to deliver deep molecular sequence data across major cellular biopolymers.

Results

MLL-r cells feature an extensive remodelling of their glycocalyx, with increased levels of Core 2-type O-glycans and complex N-glycans as well as significant changes in sialylation and fucosylation. Notably, glycosaminoglycan remodelling from chondroitin sulfate to heparan sulfate was observed. A survival screen, to determine if glycan remodelling enzymes are redundant, identified MGAT1 and NGLY1, essential components of the N-glycosylation/degradation pathway, as highly relevant within this in vitro screening. OGT and OGA, unique enzymes that regulate intracellular O-GlcNAcylation, were also indispensable. Transcriptomics and proteomics further identified Fes and GALNT7-mediated glycosylation as possible therapeutic targets. While there is overall good correlation between transcriptomics and proteomics data, we demonstrate that a systematic combined multi-omics approach delivers important diagnostic information that is missed when applying a single omics technology.

Conclusions

Apart from confirming well-known MLL-r BCP-ALL glycoprotein markers, our integrated multi-omics workflow discovered previously unidentified diagnostic/therapeutic protein targets.

Graphical abstract
Comparative of the Effectiveness of Different Objective Method for Infraclavicular Brachial Plexus Block Success; Which One of Them is A Reliable and Early Indicator?
Authors: Şengel Abdulhakim , Karahan Mahmut Alp , Altay Nuray , Binici Orhan , Pehlivan Veli Fahri , Atlas Ahmet
Published: June 2021

BACKGROUND

Traditional methods that evaluate the success of peripheral nerve block have been replaced by methods that allow objective evaluations over time. Multiple objective techniques for peripheral nerve block have been discussed in the literature.

OBJECTIVE

This study aims to investigate whether perfusion index (PI), non-invasive tissue hemoglobin monitoring (SpHb), tissue oxygen saturation (StO2), tissue hemoglobin index (THI) and body temperature are reliable and objective methods to evaluate the adequacy of infraclavicular blockage.

DESIGN

A prospective observational study.

SETTING

Single center, Department of Anesthesiology, Harran University Medical Faculty, Turkey, from February 2019 to December 2019.

PATIENTS

A total of 100 patients scheduled to undergo forearm surgery.

INTERVENTION

Ultrasound-guided infraclavicular block (ICB) in 100 patients undergoing forearm surgery.

MAIN OUTCOME MEASURES

PI, SpHb, StO2, THI and Body Temperature measurements were recorded 5 min before the block procedure, right after the procedure, and until the 25th minute after the procedure at 5-min intervals. These values were compared between the blocked limbs and non-blocked limbs while being statistically compared between the successful and failed block groups.

RESULTS

Although there were significant differences between the groups of blocked extremity and non-blocked extremity in terms of StO2 (P = 0.001), THI (P = 0.001), PI (P = 0.001) and body temperature (P = 0.001), there was no significant difference between these groups in terms of SpHb (P > 0.05). Moreover, a significant difference was detected between the groups of successful block and failed block in terms of StO2 (P = 0.002), PI (P = 0.002) and body temperature (P = 0.005), while there was no significant difference between these groups in terms of THI (P > 0.05) and SpHb (P > 0.05).

CONCLUSION

StO2, PI and body temperature measurements are the simple, objective, noninvasive techniques to be used to evaluate success of block procedures. According to The receiver operating characteristic (ROC) analysis, StO2 is the specific parameter with the highest sensitivity among these parameters.

TRIAL REGISTRATION

ACTRN12621000588897
Minimizing the infected peak utilizing a single lockdown: a technical result regarding equal peaks
Authors: Greene James M. , Sontag Eduardo D.
Published: June 2021

Due to the usage of social distancing as a means to control the spread of the novel coronavirus disease COVID-19, there has been a large amount of research into the dynamics of epidemiological models with time-varying transmission rates. Such studies attempt to capture population responses to differing levels of social distancing, and are used for designing policies which both inhibit disease spread but also allow for limited economic activity. One common criterion utilized for the recent pandemic is the peak of the infected population, a measure of the strain placed upon the health care system; protocols which reduce this peak are commonly said to ‘flatten the curve.” In this work, we consider a very specialized distancing mandate, which consists of one period of fixed length of distancing, and addresses the question of optimal initiation time. We prove rigorously that this time is characterized by an equal peaks phenomenon: the optimal protocol will experience a rebound in the infected peak after distancing is relaxed, which is equal in size to the peak when distancing is commenced. In the case of a non-perfect lockdown (i.e. disease transmission is not completely suppressed), explicit formulas for the initiation time cannot be computed, but implicit relations are provided which can be pre-computed given the current state of the epidemic. Expected extensions to more general distancing policies are also hypothesized, which suggest designs for the optimal timing of non-overlapping lockdowns.
Interrogation of genome-wide, experimentally dissected gene regulatory networks reveals mechanisms underlying dynamic cellular state control
Authors: Tan Xiangtian , Worley Jeremy , Turunen Mikko , Wong Kelly , Fernández Ester Calvo , Paull Evan , Jones Sunny , Wang Junqiang , Noh Heeju , Salvatori Beatrice , Chavez Alejandro , Califano Andrea
Published: June 2021

Pooled CRISPRi-mediated silencing of >1,000 transcriptional regulators expressed in single colorectal adenocarcinoma cells, followed by single-cell RNA-seq profiling at two timepoints, 1 day and 4 days, allowed reverse engineering the underlying tumor context-specific, causal regulatory network. Furthermore, the availability of experimentally derived, highly multiplexed gene reporter assays for each regulator, as identified by this analysis, allowed accurate assessment of differential protein activity following silencing of each regulator, thus providing proof-of-concept for generating comprehensive, tissue-specific networks of transcriptional and post-translational interactions. Analysis of this causal network allowed elucidation of complex autoregulatory mechanisms that have eluded previous computational approaches and supported systematic elucidation of cooperative mechanisms, where one regulatory protein can modulate the activity of another regulatory protein, as well as transcriptional mimicry, where one regulatory protein can phenocopy others.
A chromosome-level genome sequence of a model chrysanthemum: evolution and reference for hexaploid cultivated chrysanthemum
Authors: Nakano Michiharu , Hirakawa Hideki , Fukai Eigo , Toyoda Atsushi , Kajitani Rei , Minakuchi Yohei , Itoh Takehiko , Higuchi Yohei , Kozuka Toshiaki , Bono Hidemasa , Shirasawa Kenta , Shiraiwa Ippei , Sumitomo Katsuhiko , Hisamatsu Tamotsu , Shibata Michio , Isobe Sachiko , Taniguchi Kenji , Kusaba Makoto
Published: June 2021

Chrysanthemums are one of the most industrially important cut flowers worldwide. However, their segmental allopolyploidy and self-incompatibility have prevented the application of genetic analysis and modern breeding strategies. We thus developed a model strain, Gojo-0 (Chrysanthemum seticuspe), which is a diploid and self-compatible pure line. Here, we present the 3.05 Gb chromosome-level reference genome sequence, which covered 97% of the C. seticuspe genome. The genome contained more than 80% interspread repeats, of which retrotransposons accounted for 72%. We identified recent segmental duplication and retrotransposon expansion in C. seticuspe, contributing to a relatively large genome size. Furthermore, we identified aretrotransposon, SbdRT, which was enriched in gene-dense genome regions and had experienced a very recent transposition burst. We also demonstrated that the chromosome-level genome sequence facilitates positional cloning in C. seticuspe. The genome sequence obtained here can greatly contribute as a reference for chrysanthemum in front-line breeding including genome editing.
GuideMaker: Software to design CRISPR-Cas guide RNA pools in non-model genomes
Authors: Poudel Ravin , Rodriguez Lidimarie Trujillo , Reisch Christopher R. , Rivers Adam R.
Published: June 2021

Background

CRISPR-Cas systems have expanded the possibilities for gene editing in bacteria and eukaryotes. There are many excellent tools for designing the CRISPR-Cas guide RNAs for model organisms with standard Cas enzymes. GuideMaker is intended as a fast and easy-to-use design tool for atypical projects with 1) non-standard Cas enzymes, 2) non-model organisms, or 3) projects that need to design a panel of guide RNAs (gRNA) for genome-wide screens.

Findings

GuideMaker can rapidly design gRNAs for gene targets across the genome from a degenerate protospacer adjacent motif (PAM) and a GenBank file. The tool applies Hierarchical Navigable Small World (HNSW) graphs to speed up the comparison of guide RNAs. This allows the user to design gRNAs targeting all genes in a typical bacterial genome in about 1-2 minutes.

Conclusions

Guidemaker enables the rapid design of genome-wide gRNA for any CRISPR-Cas enzyme in non-model organisms. While GuideMaker is designed with prokaryotic genomes in mind, it can efficiently process smaller eukaryotic genomes as well. GuideMaker is available as command-line software, a stand-alone web application, and a tool in the CyCverse Discovery Environment. All versions are available under a Creative Commons CC0 1.0 Universal Public Domain Dedication.
A centronuclear myopathy-causing mutation in dynamin-2 perturbs the actin-dependent structure of dendritic spines leading to excitatory synaptic defects in a murine model of the disease
Authors: Arriagada-Diaz Jorge , Gómez Bárbara , Prado-Vega Lorena , Mattar-Araos Michelle , Labraña-Allende Marjorie , Hinostroza Fernando , Gajardo Ivana , Guerra-Fernández María José , Bevilacqua Jorge A. , Cárdenas Ana M. , Bitoun Marc , Ardiles Alvaro O. , Gonzalez-Jamett Arlek M.
Published: June 2021

Dynamin-2 is a large GTP-ase, member of the dynamin superfamily, that regulates membrane remodeling and cytoskeleton dynamics. In the mammalian nervous system dynamin-2 modulates synaptic vesicle (SV)-recycling at the nerve terminals and receptor-trafficking to and from postsynaptic densities (PSDs). Mutations in dynamin-2 cause autosomal dominant centronuclear myopathy (CNM), a congenital neuromuscular disorder characterized by progressive weakness and atrophy of distal skeletal muscles. Cognitive defects have also been reported in dynamin-2-linked CNM patients suggesting a concomitant impairment of the central nervous system. Here we addressed the mechanisms that lead to cognitive defects in dynamin-2-linked CNM using a knock-in mouse model that harbors the p.R465W mutation in dynamin-2, the most common causing CNM. Our results show that these mice exhibit reduced capability to learn and acquire spatial and recognition memory, impaired long-term potentiation of the excitatory synaptic strength and perturbed dendritic spine morphology, which seem to be associated with actin defects. Together, these data reveal for the first time that structural and functional synaptic defects underlie cognitive defects in the CNM context. In addition our results contribute to the still scarce knowledge about the importance of dynamin-2 at central synapses.
THERAPEUTIC EFFECTS OF HYPOXIC AND PRO-INFLAMMATORY PRIMING OF MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES IN INFLAMMATORY ARTHRITIS
Authors: Kay Alasdair G. , Treadwell Kane , Roach Paul , Morgan Rebecca , Lodge Rhys , Hyland Mairead , Piccinini Anna M. , Forsyth Nicholas , Kehoe Oksana
Published: June 2021

Novel biological therapies have revolutionised the management of Rheumatoid Arthritis (RA) but no cure currently exists. Mesenchymal stem cells (MSCs) immunomodulate inflammatory responses through paracrine signalling, including via secretion of extracellular vesicles (EVs) in the cell secretome. We evaluated the therapeutic potential of MSCs-derived small EVs in an antigen-induced model of arthritis (AIA).

EVs isolated from MSCs cultured normoxically (21% O2, 5% CO2), hypoxically (2% O2, 5% CO2) or with a pro-inflammatory cytokine cocktail were applied into the AIA model. Disease pathology was assessed post-arthritis induction through swelling and histopathological analysis of synovial joint structure. Activated CD4+ T cells from healthy mice were cultured with EVs or MSCs to assess deactivation capabilities prior to application of standard EVs in vivo to assess T cell polarisation within the immune response to AIA.

All EVs treatments reduced knee-joint swelling whilst only normoxic and pro-inflammatory primed EVs improved histopathological outcomes. In vitro culture with EVs did not achieve T cell deactivation. Polarisation towards CD4+ helper cells expressing IL17a (Th17) was reduced when normoxic and hypoxic EV treatments were applied in vitro. Normoxic EVs applied into the AIA model reduced Th17 polarisation and improved Th17:Treg homeostatic balance.

Priming of MSCs in EV production can be applied to alter the therapeutic efficacy however normoxic EVs present the optimal strategy for broad therapeutic benefit. The varied outcomes observed in MSCs priming may promote EVs optimised for therapies targeted for specific therapeutic priorities. EVs present an effective novel technology with potential for cell-free therapeutic translation.
Inoculum origin, incubation temperature and mild hydrostatic pressure modulate growth and activity of anaerobic saline communities
Authors: Kraho Vikuonuo , Liu Yi
Published: June 2021

This manuscript has been removed owing to an apparent copyright violation
Epigenetic Regulation of Nuclear Lamina-Associated Heterochromatin by HAT1 and the Acetylation of Newly Synthesized Histones
Authors: Popova Liudmila V. , Nagarajan Prabakaran , Lovejoy Callie M. , Sunkel Benjamin D. , Gardner Miranda L. , Wang Meng , Freitas Michael A. , Stanton Benjamin Z. , Parthun Mark R.
Published: June 2021

During S phase, eukaryotic cells must faithfully duplicate both the sequence of the genome and the regulatory information found in the epigenome. A central component of the epigenome is the pattern of histone post-translational modifications that play a critical role in the formation of specific chromatin states. During DNA replication, parental nucleosomes are disrupted and re-deposited on the nascent DNA near their original location to preserve the spatial memory of the epigenetic modifications. Newly synthesized histones must also be incorporated into the nascent chromatin to maintain nucleosome density. Transfer of modification patterns from parental histones to new histones is a fundamental step in epigenetic inheritance. Whether new histones play an active or passive role in epigenetic inheritance is unknown. Here we report that HAT1, which acetylates lysines 5 and 12 of newly synthesized histone H4 during replication-coupled chromatin assembly, regulates the epigenetic inheritance of chromatin states. HAT1 regulates the accessibility of large domains of heterochromatin termed HAT1-dependent Accessibility Domains (HADs). HADs are mega base-scale domains that comprise ~10% of the mouse genome. HAT1 functions as a global negative regulator of H3 K9me2/3 and HADs correspond to the regions of the genome that display HAT1-dependent increases in H3 K9me3 peak density. HADs display a high degree of overlap with a subset of Lamin-Associated Domains (LADs). HAT1 is required to maintain nuclear structure and integrity. These results indicate that HAT1 and the acetylation of newly synthesized histones are critical regulators of the epigenetic inheritance of heterochromatin and suggest a new mechanism for the epigenetic regulation of nuclear lamina-heterochromatin interactions.
Plant lipid metabolism in susceptible and tolerant soybean (Glycine max) cultivars in response to Phytophthora sojae colonization and infection
Authors: Adigun Oludoyin Adeseun , Pham Thu Huong , Grapov Dmitry , Nadeem Muhammad , Jewell Linda Elizabeth , Cheema Mumtaz , Galagedara Lakshman , Thomas Raymond
Published: June 2021

Soybean is one of the most cultivated crops globally and a staple food for much of the world’s population. The annual global crop losses due to infection by the Phytophthora sojae are currently estimated at approximately $2B USD, yet we have limited understanding of the role of lipid metabolism in the adaptative strategies used to limit infection and crop loss. We employed a multi-modal lipidomics approach to investigate how soybean cultivars remodel their lipid metabolism to successfully limit infection by Phytophthora sojae. Both the tolerant and susceptible soybean cultivars showed alterations in lipid metabolism in response to Phytophthora sojae infection. Relative to non-inoculated controls, induced accumulation of stigmasterol was observed in the susceptible cultivar whereas, induced accumulation of phospholipids and glycerolipids occurred in tolerant soybean cultivar. We have generated a comprehensive metabolic map of susceptible and tolerant soybean root and stem lipid metabolism to identify lipid modulators of host immune or tolerance response to Phytophthora sojae infection and identified potential pathways and unique lipid biomarkers like TG(15:0/22:0/22:5), TG(10:0/10:0/10:0), TG(10:0/10:0/14:0), DG(18:3/18:3), DG(16:0/18:3) and DG(24:0/18:2) as possible targets for the development of future plant protection solutions.