bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient brain connectivity reconfiguration predicts higher marital quality and lower depression
Authors: Ma Shan-Shan , Zhang Jin-Tao , Wang Luo-Bin , Song Kun-Ru , Yao Shu-Ting , Fang Ren-Hui , Hu Yi-Fan , Jiang Xin-Ying , Potenza Marc N , Fang Xiao-Yi
Published: August 2021

Social information processing is important for successful romantic relationships and protection against depression, and depends on functional connectivity (FC) within and between large-scale networks. Functional architecture evident at rest is adaptively reconfigured during a task, and there were two possible associations between brain reconfiguration and behavioral performance during neurocognitive tasks (efficiency effect and distraction-based effect). This study examined the relationships between brain reconfiguration during social information processing and relationship-specific and more general social outcomes in marriage. Resting-state FC was compared with FC during social information processing (watching relationship-specific and general emotional stimuli) of 29 heterosexual couples, and the FC similarity (reconfiguration efficiency) was examined in relation to marital quality and depression 13 months later. The results indicated that wives’ reconfiguration efficiency (globally and in visual association network) during relationship-specific stimuli processing was related to their own marital quality. Higher reconfiguration efficiency (globally and in medial frontal, frontal-parietal, default mode, motor/sensory and salience networks) in wives during general emotional stimuli processing was related to their lower depression. These findings suggest efficiency effects on social outcomes during social cognition, especially among married women. The efficiency effects on relationship-specific and more general outcomes are, respectively, higher during relationship-specific stimuli or general emotional stimuli processing.
Cognitive throughput and working memory raw scores consistently differentiate resilient and vulnerable groups to sleep loss
Authors: Brieva Tess E , Casale Courtney E , Yamazaki Erika M , Antler Caroline A , Goel Namni
Published: August 2021

Study Objectives

Substantial individual differences exist in cognitive deficits due to sleep restriction (SR) and total sleep deprivation (TSD), with various methods used to define such neurobehavioral differences. We comprehensively compared numerous methods for defining cognitive throughput and working memory resiliency and vulnerability.

Methods

Forty-one adults participated in a 13-day experiment: 2 baseline, 5 SR, 4 recovery, and one 36 h TSD night. The Digit Symbol Substitution Test (DSST) and Digit Span Test (DS) were administered every 2 h. Three approaches (Raw Score [average SR performance], Change from Baseline [average SR minus average baseline performance], and Variance [intraindividual variance of SR performance]), and six thresholds (±1 standard deviation, and the best/worst performing 12.5%, 20%, 25%, 33%, 50%) classified Resilient/Vulnerable groups. Kendall’s tau-b correlations compared the group categorizations’ concordance within and between DSST number correct and DS total number correct. Bias-corrected and accelerated bootstrapped t-tests compared group performance. 

Results

The approaches generally did not categorize the same participants into Resilient/Vulnerable groups within or between measures. The Resilient groups categorized by the Raw Score approach had significantly better DSST and DS performance across all thresholds on all study days, while the Resilient groups categorized by the Change from Baseline approach had significantly better DSST and DS performance for several thresholds on most study days. By contrast, the Variance approach showed no significant DSST and DS performance group differences.

Conclusion

Various approaches to define cognitive throughput and working memory resilience/vulnerability to sleep loss are not synonymous. The Raw Score approach can be reliably used to differentiate resilient and vulnerable groups using DSST and DS performance during sleep loss.
Student experiences of online study groups and drop-in mathematics support during COVID-19
Authors: Mac an Bhaird Ciarán , McGlinchey Aisling , Mulligan Peter , O’Malley James , O’Neill Rachel
Published: August 2021

In this paper, we consider the changes to mathematics learning support (MLS) at Maynooth University due to the COVID-19 pandemic, including the provision of novel online study groups aimed at increasing student engagement and interaction. We briefly outline the local, national and international impact of COVID-19 on MLS and then focus on the results of a student survey. Respondents who regularly used online MLS were broadly positive about their experiences. They cited, in particular, the influence of tutors and the scheduled study groups, which provided structure and motivation as well as the opportunity to work with others and ask questions in less intimidating small groups. However, some respondents highlighted factors that impacted negatively on their engagement. These included low attendance or interaction from peers, timetabling issues or busy schedules, lack of awareness of the details of the services and increased feelings of discomfort and anxiety in an online environment. We consider how this student feedback may influence our future online and in-person supports.
Interpreting merger clauses in contracts governed by the CISG: delineating the scope for the use of extrinsic evidence
Authors: Suresh Aditya
Published: August 2021

Under Article 8(3) of the United Nations Convention on Contracts for the International Sale of Goods (CISG), parties’ statements, prior negotiations and other external circumstances may be used to assess the presence of subjective or objective intent that can, in turn, be used to interpret contractual terms in international sales contracts governed by the CISG. However, parties to the contract can, through the adoption of an ‘entire agreement’ or ‘merger’ clause, opt out of this rule under Article 8(3) and restrict these interpretative tools in any manner as they see fit, depending on the requirements of their contract. Since the CISG does not explicitly address merger clauses and their effects, the CISG Advisory Council, in its Opinion no. 3, has provided a test to determine how the scope of a merger clause is to be determined. However, this test presents certain conceptual and practical limitations that render it inadequate for use in international commercial contracts. This article aims to analyse this test and the methods that have been used to interpret merger clauses under other uniform legal instruments and cases in common law jurisdictions. On this basis, the article proposes a test that attempts to fully capture the conceptual intent behind including merger clauses while ensuring that the parties are in the driver’s seat while determining their scope and effect.
Transpanting the Unidroit Contract Principles into the Qatar Financial Center: a fresh paradigm for wholesale legal transplants?
Authors: Bantekas Ilias
Published: August 2021

The Qatar Financial Center (QFC) decided to adopt a set of Contract Regulations that are effectively the equivalent of its contracts statute. The QFC does not have a civil code. The Regulations are largely predicated on the Unidroit Principles of International Commercial Contracts (PICC). Even so, its drafters introduced, in addition, elements peculiar to the common law of contracts that are not found in the PICC, and the QFC Court, which is largely composed of a common law-inclined bench, has made it clear in many of its cases that common law judgments and English statutes can and will serve as authority in the interpretation of the Contract Regulations. The situation is further complicated by the fact that the Regulations are meant to apply in a broader legal system (that of Qatar), which recognizes several elements of Islamic law in the context of public policy—although generally Islamic law plays a very minor role, if at all, in the ordinary Qatari law of contracts. Despite the complexity underlying the Contract Regulations, its relevant success—to date—is firmly premised on the fact that the process of legal transplantation was not undertaken in a vacuum, but, rather, it is a ‘living instrument’ that is acceptable and, above all, useful to its stakeholders. Much like other contract law-related legal transplants taking root in other special economic zones, so too the QFC Contract Regulations represent an excellent paradigm as to how wholesale legal transplants can be undertaken.
La liberté des parties dans le droit de la médiation OHADA
Authors: Gouambe Simplice
Published: August 2021

La consécration de la liberté des parties dans la recherche de la solution à leur différend se manifeste en deux temps : premièrement, lors de la mise en place de la médiation, les parties ont le choix de recourir ou non à la médiation, elles doivent de commun accord procéder à la désignation du médiateur et à la fixation de sa mission. Deuxièmement, lors de la mise en œuvre de la médiation, la liberté des parties se manifeste plus dans la conduite du processus qu’au dénouement de la médiation. Toutefois, cette liberté est ébranlée par certaines obligations de nature substantielle ou de nature processuelle qui pèsent sur les parties.

Mots-clés

liberté, différend, processus de médiation, patrimonialité de la cause, ordre public.
Retour sur la cohabitation entre le droit CEMAC et le droit OHADA dans la liquidation des établissements de crédit en Afrique centrale
Authors:  Camille Tchotchou Petche Kamga
Published: August 2021

La liquidation des compartiments bancaire et non bancaire des établissements de crédit se caractérise par un dualisme juridique. Au premier compartiment est appliqué le droit CEMAC, tandis que le second compartiment est soumis au droit OHADA. Ce dualisme juridique est marqué par la prééminence de la réglementation bancaire CEMAC en raison de la spécificité de l’activité bancaire. Toutefois, cette prééminence n’est pas sans ambages. La réglementation bancaire CEMAC s’entremêle dans le processus de liquidation du compartiment non bancaire, pourtant dédié au droit OHADA, et de ce fait, relègue celui-ci à une position subsidiaire dans son « propre empire ». Cet imbroglio juridique crée une situation d’inconfort juridique pour toute personne qui sera chargée d’assurer la liquidation d’un établissement de crédit. Elle devra faire preuve de subtilité et de sagacité pour démêler et identifier, à chaque étape de la procédure, la véritable règle applicable.

Mots-clésdroit CEMAC, droit OHADA, liquidation, procédures collectives, établissements de crédit

Summary

The liquidation of the banking and non-banking compartments of credit institutions is characterized by legal dualism. CEMAC law is applied to the first compartment and the second compartment is subject to OHADA law. This legal dualism is marked by the pre-eminence of the CEMAC banking regulations due to the specificity of the banking activity. However, this pre-eminence is not without ambiguity. The CEMAC banking regulations are interwoven in the process of liquidating the non-banking compartment, which is nevertheless dedicated to OHADA law, and therefore relegates it to a subsidiary position in its “own empire”. This legal imbroglio creates a situation of legal discomfort for anyone who will be responsible for liquidating a credit institution. He will have to show subtlety and sagacity to disentangle and identify, at each stage of the procedure, the real applicable rule.
How Academic Medicine Can Help Confront the Opioid Crisis
Authors: Volkow Nora D. , McLellan Tom , Blanco Carlos
Published: August 2021

The United States is in the midst of a devastating overdose and addiction crisis involving opioids as well as other drugs. Yet, despite the existence of effective treatments for opioid use disorder, only a minority of people who need treatment for this or other substance use disorders receive it. Besides the terrible human and economic costs of overdose deaths and the other health consequences of addiction, untreated substance use has wide-ranging impacts across health care. Academic medicine can help address this crisis by increasing the preparedness of the current and future clinical workforce to detect and treat substance misuse and addiction through increased attention to these topics in medical and nursing schools and in residency programs. In this commentary, the authors explore the barriers to treatment for substance misuse and addiction and the role of academic medicine in improving treatment outcomes through training, clinical care, health service delivery, and research.
Hallucinogen Persisting Perception Disorder Following Recreational Dextromethorphan Use
Authors: Rymowicz Robert , Tsuang Tiffany
Published: August 2021

Introduction:

Hallucinogen persisting perception disorder (HPPD) is a rarely diagnosed disorder characterized by continuous sensory disturbances following the use of hallucinogenic substances. Its cause remains unknown, and treatments remain elusive, although previous case reports have detailed attempts at treatment with a variety of psychoactive medications. No previous case reports have discussed the emergence of HPPD following dextromethorphan use, or its treatment with ropinirole.

Case:

We present the case of a 20-year-old male who developed HPPD after repeated recreational dextromethorphan use at supratherapeutic dosages, leading to the acute onset of visual snow, motional trails, the persistence of afterimages, the perception of halos around lights, tinnitus, and depersonalization and derealization. The client found these symptoms to be greatly distressing, and he had worsening of symptoms when treated with antipsychotic medications. After he was treated with lamotrigine and clonazepam, he had some improvement of symptoms. To treat additional visual symptoms, the patient was given ropinirole, a dopamine agonist, which made him feel better with less visual disturbances. Ultimately he had to discontinue all medications due to intolerability to side effects.

Conclusions:

The lack of effective treatments for HPPD and a general lack of awareness among patients and providers leads to underdiagnosis and incorrect management. Ropinirole may offer a novel treatment for patients with HPPD, and more research is needed to determine the suitability of dopamine agonists in the treatment for HPPD.
Prevalence of Open-angle Glaucoma in the Faroese Population
Authors: Holm Elin , Holm Malan , Vilhelmsen Kaj , Andorsdottir Gudrid , Vorum Henrik , Simpson Allie , Roos Benjamin R. , Fingert John H. , Rosenberg Thomas
Published: August 2021

Purpose:

The Faroe Islands are home to 50,000 genetically isolated people in the North Atlantic. The prevalence of open-angle glaucoma (OAG) in the Faroese population is unknown. Consequently, we conducted a survey to determine the prevalence of OAG in the Faroese population. We also investigated the role of known glaucoma-causing genes in Faroese OAG.

Materials and Methods:

We conducted a prospective survey of known and newly diagnosed glaucoma patients at the Faroese National Hospital, Landssjukrahusid, Tórshavn between October 1, 2015 to December 31, 2017. In addition we reviewed the only eye care provider in the Faroese Islands by scrutinizing electronic medical records between 2009 and June 15, 2014, October 1, 2015 and the partly overlapping prescriptions for ocular hypotensive medications in 2016 to identify patients with either a diagnosis of glaucoma, a diagnosis of ocular hypertension or a prescription for ocular hypotensive medications. Next, we prospectively confirmed diagnoses with complete eye examinations. Patient DNA samples were tested for variations in known glaucoma-causing genes [myocilin (MYOC), optineurin (OPTN), and TANK binding kinase 1 (TBK1)].

Results:

We determined the age-related prevalence of OAG January 1, 2017 in individuals 40 years or older to be 10.7/1000 (1.07%) and highly age-related. A diagnosis of OAG was present in 264 patients, of whom 211 (79.9%) had primary OAG (including normal tension glaucoma), 49 (18.6%) had pseudoexfoliation glaucoma, and 4 (1.5%) had pigmentary glaucoma. Among patients receiving medications for glaucoma, nearly 50% had primary OAG, while the majority of the rest had ocular hypertension or secondary glaucoma. No disease-causing variants were detected in MYOC, OPTN, or TBK1.

Conclusions:

The calculated prevalence of OAG in the Faroe Islands was 1.07%. The absence of MYOC, OPTN, or TBK1 disease-causing variants in Faroese primary OAG patients suggests that a different, potentially unique set of genes may be contributing to the pathogenesis of glaucoma in this population.
Nonbite Transmission of Pasteurella Causing Epiglottitis in an Immunocompetent Patient
Authors: Bell Erin , Hartley Molly , Cullen Joan , Banjade Rashmi
Published: August 2021

Pasteurella infections commonly manifest as localized skin infections; however, more invasive infections can also occur. Pasteurella epiglottitis is a rare infection associated with nonbite transmission, including food and beverages contaminated with animal saliva. Fewer than 20 cases of Pasteurella epiglottitis have been reported in the literature.
A Polyp Worth Removing
Authors: Karnes William E. , Johnson David A. , Berzin Tyler M. , Gross Seth A. , Vargo John J. , Sharma Prateek , Zachariah Robin , Samarasena Jason B. , Anderson Joseph C.
Published: August 2021

Leaving no significant polyp behind while avoiding risks due to unnecessary resections is a commonsense strategy to safely and effectively prevent colorectal cancer (CRC) with colonoscopy. It also alludes to polyps worth removing and, therefore, worth finding. The majority of “worthy” precancerous polyps are adenomas, which for over 2 decades, have received the most attention in performance research and metrics. Consequently, the detection rate of adenomas is currently the only validated, outcome-based measure of colonoscopy demonstrated to correlate with reduced risk of postcolonoscopy CRC. However, a third or more of postcolonoscopy CRCs originate from sessile serrated polyps (SSPs), which are notoriously difficult to find, diagnose and completely resect. Among serrated polyps, the agreement among pathologists differentiating SSPs from non-neoplastic hyperplastic polyps is moderate at best. This lack of ground truth precludes SSPs from consideration in primary metrics of colonoscopy quality or performance of novel polyp detection technologies. By instead leveraging the distinct endoscopic and clinical features of serrated polyps, including those considered important due to proximal location and larger size, clinically significant serrated polyps represent serrated polyps worth removing, enriched with subtle precancerous SSPs. With the explosion of technologies to assist polyp detection, now is the time to broaden benchmarks to include clinically significant serrated polypss alongside adenomas, a measure that is relevant both for assessing the performance of endoscopists, and for assessing new polyp detection technologies.
Impact of Trauma Type on Startle Reactivity to Predictable and Unpredictable Threats
Authors: Kreutzer Kayla A. , Gorka Stephanie M.
Published: August 2021

Trauma exposure has been repeatedly linked to psychophysiological threat reactivity, although the directionality of this association has been inconsistent. Several factors likely contribute to inconsistent findings including type of trauma and threat paradigm. The present study therefore examined the impact of trauma type on psychophysiological reactivity to predictable (P-) and unpredictable (U-) threat in young adults (N = 112). Participants were classified into three groups: history of interpersonal or noninterpersonal trauma, or no history of trauma. Startle eyeblink potentiation was recorded during a well-validated threat-of-shock paradigm. Results indicated individuals with interpersonal trauma exposure displayed exaggerated startle reactivity to U-threat (only) compared with both other groups. In contrast, individuals with noninterpersonal trauma exhibited blunted startle reactivity to U-threat (only) compared with both other groups. Findings reveal that trauma and threat type influence threat reactivity and that those with a history of interpersonal trauma may uniquely display exaggerated sensitivity to stressors that are uncertain.
Resilience and Hope Among Yazidi Women Released From ISIS Enslavement
Authors: Taha Perjan Hashim , Nguyen Thomas P. , Slewa-Younan Shameran
Published: August 2021

This study aimed to explore the levels of resilience and hope among Yazidi women who survived captivity by Islamic State of Iraq and Syria (ISIS) and to examine its relationship with posttraumatic stress disorder (PTSD), generalized anxiety, and depressive symptoms. In this cross-sectional study, 139 formerly enslaved Yazidi women were assessed. The mean scores of resilience and hope were below the suggested cutoff means (M = 2.47, SD = 0.48, R = 1–5) and (M = 31.6, SD = 11.7, R = 8–64), respectively. Sociodemographic variables were not related to resilience and hope, other than those women who stayed in captivity for more than a 3-year period who reported significantly lower levels of hope (M = 28.36, SD = 11.69). Formerly enslaved Yazidi women who display higher levels of PTSD, generalized anxiety, and depression exhibit significantly lower levels of resilience and hope. Resilience and hope are therefore important concepts to explore in traumatized populations.
Long Sleep Duration Associated With Cognitive Impairment in Chinese Community-Dwelling Older Adults
Authors: Zhang Hui , Ma Weibo , Chen Yaoxin , Wang Feng , Wang Jingru , Han Peipei , Wang Yiwen , Zhang Chenyu , Xie Fandi , Niu Shumeng , Hu Hao , Wang Hong , Guo Qi
Published: August 2021

We aimed to examine the association between sleep duration and impaired cognitive function in different cognitive domains in Chinese community-dwelling older adults. A total of 1591 participants (≥60 years) were divided into five groups: ≤6 hours (very short sleep duration), >6 to 7 hours (short sleep duration), ≥7 to 8 hours (moderate sleep duration), >8 to 9 hours (moderately long sleep duration), and >9 hours (long sleep duration), according to sleep duration. Cognitive function was assessed using the Mini-Mental State Examination. Long sleep duration significantly increased the likelihood of cognitive impairment. In addition to attention, long sleep duration was negatively related to poorer global cognition and other cognitive domain functions. With the stratification of age groups, long sleep duration was negatively associated with other cognitive domain functions except delayed recall in older elderly (≥75 years) people, but not in younger elderly (60–74 years) people. Long sleep duration was associated with higher rates of cognitive impairment, poorer global cognition, and declined orientation, memory, language ability, and executive function in Chinese community-dwelling older adults, which was more significant in older elderly people.
Association Between Histopathology and Magnetic Resonance Imaging Texture in Grading Gliomas Based on Intraoperative Magnetic Resonance Navigated Stereotactic Biopsy
Authors: Rui Wenting , Pang Haopeng , Xie Qian , Wang Yin , Duan Shaofeng , Ren Yan , Yao Zhenwei
Published: August 2021

Objective

To explore the value of magnetic resonance imaging (MRI) textures and its correlation with histopathological malignancy of gliomas by magnetic resonance (MR) navigated stereotactic biopsy.

Methods

A total of 36 diffuse glioma cases and 64 puncture targets were included. All patients underwent a preoperative MR scan and intraoperative MR-navigated stereotactic biopsy. The histopathological diagnosis was grade II or grade III diffuse glioma. Regions of interest consistent with puncture targets were delineated on T1-weighted brain volume with gadolinium contrast enhancement images, and textures were extracted using Omni Kinetics software. Mann-Whitney rank sum test was used to analyze texture differences between grade II and grade III samples. False discovery rate (FDR) correction was applied to correct for multiple comparisons. Receiver operating characteristic curves evaluated the diagnostic value of textural analysis for grading gliomas. Correlation between MRI textures and histopathology was examined by Spearman correlation test.

Results

Texture features, including max intensity, 95th quantile, range, variance, standard deviation, sum variance, and cluster prominence were higher in grade III glioma targets than grade IIs, grade II gliomas showed increased uniformity and short run low gray-level emphasis values (P and qFDRcorr < 0.05). Area under the curve was 0.887 (95% confidence interval, 0.805–0.969; P < 0.001) with combined textures in glioma grading. The listed first-order and gray-level cooccurrence matrix textures were correlated with Ki-67 labeling index. Gray-level cooccurrence matrix and gray-level run length matrix textures were correlated with isocitrate dehydrogenase 1 mutation.

Conclusions

Textures on T1-weighted brain volume with gadolinium contrast enhancement images differ between grade III and II gliomas and are correlated with Ki-67 labeling index and isocitrate dehydrogenase 1 mutation.
A Pilot Study on Feasibility of Ultrashort Echo Time T2* Cartilage Mapping in the Sacroiliac Joints
Authors: Wong Tony T. , Quarterman Patrick , Duong Phuong , Rasiej Michael J. , Wang Runsheng , Jaramillo Diego , Jambawalikar Sachin R.
Published: August 2021

Purpose

Assess feasibility of ultrashort echo time (UTE) T2* cartilage mapping in sacroiliac (SI) joints

Methods

Prospective magnetic resonance imagings with UTE T2* cartilage maps obtained on 20 SI joints in 10 subjects. Each joint was segmented into thirds by 2 radiologists. The UTE T2* maps were analyzed; reliability and differences in UTE T2* values between radiologists were assessed.

Results

Mean UTE T2* value was 10.44 ± 0.60 ms. No difference between right/left SI joints (median, 10.52 vs 10.45 ms; P = 0.940), men/women (median, 10.34 vs. 10.57 ms; P = 0.174), or different anatomic regions (median range 10.55–10.69 ms; P = 0.805). Intraclass correlation coefficients were 0.94 to 0.99 (intraobserver) and 0.91 to 0.96 (interobserver). Mean bias ± standard deviation on Bland-Altman was −0.137 ± 0.196 ms (limits of agreement −0.521 and 0.247) without proportional bias (β = 0.148, P = 0.534).

Conclusions

The UTE T2* cartilage mapping in the SI joints is feasible with high reader reliability.
Pathogenesis of Alzheimer’s disease: Involvement of the Choroid Plexus
Authors: Čarna Maria , Onyango Isaac G. , Katina Stanislav , Holub Dušan , Nezvedova Marketa , Jha Durga , Nedelska Zuzana , Lacovich Valentina , Vyvere Thijs Vande , Houbrechts Ruben , Garcia-Mansfield Krystine , Sharma Ritin , David-Dirgo Victoria , Vyhnalek Martin , Texlova Kateřina , Chaves Hernan , Bakkar Nadine , Pertierra Lucia , Vinkler Mojmir , Markova Hana , Laczo Jan , Sheardova Kateřina , Frič Jan , Pompeano Antonio , Forte Giancarlo , Kaňovsky Petr , Belaškova Silvie , Damborsky Jiři , Hort Jakub , Seyfried Nicholas T. , Bowser Robert , Sevlever Gustavo , Rissman Robert A. , Smith Richard A. , Hajduch Marian , Pirrotte Patrick , Spačil Zdeněk , Dammer Eric B. , Limbäck-Stokin Clara , Stokin Gorazd B.
Published: August 2021

Aging and Alzheimer’s disease (AD), a major age-related disorder, are both characterized by inflammatory changes in the cerebrospinal fluid (CSF). The origin and the mechanisms underlying these inflammatory changes, however, remain poorly understood. Here, we report that aging elicits inflammatory changes in the CSF that become accentuated uniquely in AD compared to other inflammatory and neurodegenerative disorders. We show that the choroid plexus (ChP), which produces CSF, gains a pro-inflammatory profile, exhibits perturbed metabolism and contributes to the CSF changes observed in AD. We then use MRI imaging to establish a correlation between cognitive decline and increased volume of significantly remodelled ChP in patients with AD, and provide clinical relevance to the identified ChP pathology. These findings collectively suggest that ChP, unable to resolve inflammatory insults efficiently over the lifetime, participates in the inflammation and the pathogenesis of AD.
Association of E484K and L452R spike protein mutations with SARS-CoV-2 infection in vaccinated persons---Maryland, January – May 2021
Authors: Feder Kenneth A. , Patel Ami , Vepachedu Venkata R. , Dominguez Catherine , Keller Eric N. , Klein Liore , Kim Curi , Blood Tim , Hyun Judie , Williams Theo , Feldman Katherine A. , Mostafa Heba H. , Morris C. Paul , Ravel Jacques , Duwell Monique , Blythe David , Myers Robert
Published: August 2021

Background

The E484K and L452R amino acid substitutions on the spike protein of SARS-CoV-2 are associated with reduced neutralization by antibodies from acquired immunity. This study examines the respective association of these mutations with infection in persons who had previously received a COVID-19 vaccine.

Methods

Genetic sequences from SARS-CoV-2 specimens collected from Maryland residents and reported to Maryland Department of Health were linked to vaccination history. The prevalence of infections in fully vaccinated persons -- defined as being at least two weeks past receiving the final scheduled dose of a COVID-19 vaccine series -- was compared between infections caused by viruses carrying E484K to those not carrying E484K, and between infections caused by viruses carrying L452R to those not carrying L452R, using logistic regression to adjust for confounding.

Results

Of 9,048 sequenced SARS-CoV-2 specimens examined, 265 (2.9%) were collected from fully vaccinated persons. In adjusted analysis, the E484K substitution was associated with an increase in the odds of the sequenced specimen being collected from a fully vaccinated person (OR 1.96, 95% CI, 1.36 to 2.83). The L452R mutation was not significantly associated with infections in vaccinated persons (OR 1.07, 95% CI, 0.69 to 1.68).

Conclusion

Though more than 97% of SARS-CoV-2 infections were in persons who were not fully vaccinated, the E484K mutation was associated with increased odds of SARS-CoV-2 infection in vaccinated persons. Linking vaccination and sequencing data can help identify and estimate the impact SARS-CoV-2 mutations may have on vaccine effectiveness.

In viruses sequenced for Maryland’s routine SARS-CoV-2 genomic surveillance, the spike protein amino acid substitution E484K was more prevalent in viruses that infected vaccinated people than in viruses that infected people who were not vaccinated.
Peanut oral immunotherapy differentially suppresses clonally distinct subsets of T helper cells
Authors: Monian Brinda , Tu Ang A. , Ruiter Bert , Morgan Duncan M. , Petrossian Patrick M. , Smith Neal P. , Gierahn Todd M. , Ginder Julia H. , Shreffler Wayne G. , Love J. Christopher
Published: August 2021

Food allergy affects an estimated 8% of children in the US, with increasing severity and global prevalence1. Oral immunotherapy (OIT) is a recently approved treatment with outcomes ranging from sustained tolerance to food allergen to no apparent benefit2,3. The immunological underpinnings that influence clinical outcomes of OIT still remain largely unresolved. Using single-cell RNA sequencing and paired TCRα/β sequencing, we assessed the transcriptomes of CD154+ and CD137+ peanut-reactive T helper cells from 12 peanut-allergic patients longitudinally throughout OIT. We observed expanded populations of cells expressing Th1, Th2, and Th17 signatures that further separated into six clonally distinct subsets, including a Tfh1-like, a Tfh2-like, a Th2A-like, and a Th2reg-like subset. Four of these subsets demonstrated convergence of TCR sequences, suggesting antigen-driven T cell fate. Although we observed suppression during OIT of Th2 and Th1 gene signatures within effector clonotypes, Tfh clonotypes were unaffected. We also did not observe significant clonal deletion or induction among the antigen-reactive T cells characterized. Positive outcomes were associated with larger decrease of Th2 signatures in Th2A-like cells, while treatment failure was associated with high baseline inflammatory gene signatures that were unmodulated by OIT. These signatures, including expression of OX40, OX40L, STAT1, and GPR15, were most clearly present in Th1 and Th17 clonotypes, but were also more broadly detected across the CD154+ CD4 population. These results demonstrate that differential clinical response is associated both with pre-existing trait characteristics of the CD4 immune compartment and with susceptibility to modulation by OIT.

Conflict of Interest Statement

A.A.T., T.M.G., J.C.L., and the Massachusetts Institute of Technology have filed patents related to the single-cell sequencing methods used in this work. J.C.L. has interests in Sunflower Therapeutics PBC, Pfizer, Honeycomb Biotechnologies, OneCyte Biotechnologies, SQZ Biotechnologies, Alloy Therapeutics, QuantumCyte, Amgen, and Repligen. J.C.L.’s interests are reviewed and managed under Massachusetts Institute of Technology’s policies for potential conflicts of interest. J.C.L. receives sponsored research support at MIT from Amgen, the Bill & Melinda Gates Foundation, Biogen, Pfizer, Roche, Takeda, and Sanofi. The spouse of J.C.L. is an employee of Sunflower Therapeutics PBC. T.M.G. is currently an employee of Honeycomb Biotechnologies, Inc. A.A.T. is currently an employee of Immunitas Therapeutics, Inc. W.G.S. is a consultant of Aimmune Therapeutics.
Airway-specific autoantibodies identify a subset of patients with fibrotic interstitial lung disease
Authors: Boustani Karim , Ghai Poonam , Invernizzi Rachele , Hewitt Richard J. , Maher Toby M. , Li Quan-Zhen , Molyneaux Philip L. , Harker James A.
Published: August 2021

Background

Fibrotic interstitial lung disease (fILD) has previously been associated with the presence of autoantibody. While studies have focused on systemic autoimmunity, the role of local autoantibodies in the airway remains unknown. We therefore extensively characterised the airway and peripheral autoantibody profiles in patients with fILD and assessed association with disease severity and outcome.

Methods

Bronchoalveolar lavage (BAL) was collected from a cohort of fILD patients and total airway antibody concentrations were quantified. An autoantigen microarray was used to measure IgG and IgA autoantibodies against 124 autoantigens in BAL from 40 idiopathic pulmonary fibrosis (IPF), 20 chronic hypersensitivity pneumonitis (CHP), 20 connective tissue disease-associated ILD (CTD-ILD) patients and 20 controls.

Results

A subset of patients with fILD but not healthy controls had a local autoimmune signature in their airways that was not present systemically, regardless of disease. The proportion of patients with IPF with a local autoantibody signature was comparable to that of CTD-ILD, which has a known autoimmune pathology, identifying a potentially novel subset of patients. The presence of an airway autoimmune signature was not associated with reduced survival probability or changes in lung function in the cohort as a whole. Patients with IPF had increased airway total IgA and IgG1 while subjects with CHP had increased airway IgA, IgG1 and IgG4. In patients with CHP, increased airway total IgA was associated with reduced survival probability.

Conclusion

The presence of airway autoantibodies identifies a unique subset of patients with fILD and the mechanisms by which these autoantibodies contribute to disease requires further investigation.
Development of a Post-Acute Sequelae of COVID-19 (PASC) Symptom Lexicon Using Electronic Health Record Clinical Notes
Authors: Wang Liqin , Foer Dinah , MacPhaul Erin , Lo Ying-Chih , Bates David W. , Zhou Li
Published: August 2021

Objective

To develop a comprehensive post-acute sequelae of COVID-19 (PASC) symptom lexicon from clinical notes to support PASC symptom identification and research.

Methods

We identified 26,117 COVID-19 positive patients from the Mass General Brigham’s electronic health records (EHR) and extracted 328,879 clinical notes from their post-acute infection period (day 51-110 from first positive COVID-19 test). The PASC symptom lexicon incorporated Unified Medical Language System® (UMLS) Metathesaurus concepts and synonyms based on selected semantic types. The MTERMS natural language processing (NLP) tool was used to automatically extract symptoms from a development dataset. The lexicon was iteratively revised with manual chart review, keyword search, concept consolidation, and evaluation of NLP output. We assessed the comprehensiveness of the lexicon and the NLP performance using a validation dataset and reported the symptom prevalence across the entire corpus.

Results

The PASC symptom lexicon included 355 symptoms consolidated from 1,520 UMLS concepts. NLP achieved an averaged precision of 0.94 and an estimated recall of 0.84. Symptoms with the highest frequency included pain (43.1%), anxiety (25.8%), depression (24.0%), fatigue (23.4%), joint pain (21.0%), shortness of breath (20.8%), headache (20.0%), nausea and/or vomiting (19.9%), myalgia (19.0%), and gastroesophageal reflux (18.6%).

Discussion and Conclusion

PASC symptoms are diverse. A comprehensive PASC symptom lexicon can be derived using a data-driven, ontology-driven and NLP-assisted approach. By using unstructured data, this approach may improve identification and analysis of patient symptoms in the EHR, and inform prospective study design, preventative care strategies, and therapeutic interventions for patient care.
Age-specific rate of severe and critical SARS-CoV-2 infections estimated with multi-country seroprevalence studies
Authors: Herrera-Esposito Daniel , de los Campos Gustavo
Published: August 2021

Knowing the age-specific rates at which individuals infected with SARS-CoV-2 develop severe and critical disease is essential for designing public policy, for epidemic modeling, and for individual risk evaluation. In this study, we present the first estimates of these rates using multi-country serology studies, and data on hospital admissions and mortality from early to mid-2020. We integrated data from those sources using a Bayesian model that accounts for the high heterogeneity between data sources and for the uncertainty associated to the estimates reported from each data source. Our results show that the risk of severe and critical disease increases exponentially with age, but much less steeply than the risk of fatal illness. Importantly, the estimated rate of severe disease outcome in adolescents is between one and two orders of magnitude larger than the reported rate of vaccine side-effects, showing how these estimates are relevant for health policy. Finally, we validate our results by showing that they are in close agreement with the estimates obtained from an indirect method that uses reported infection fatality rates estimates and hospital mortality data.
Decline in pneumococcal disease in young children during the COVID-19 pandemic associated with suppression of seasonal respiratory viruses, despite persistent pneumococcal carriage: A prospective cohort study
Authors: Danino Dana , Ben-Shimol Shalom , van der Beek Bart Adriaan , Givon-Lavi Noga , Avni Yonat Shemer , Greenberg David , Weinberger Daniel M. , Dagan Ron
Published: August 2021

Background

Invasive pneumococcal disease (IPD) declined during the COVID-19 pandemic. Previous studies hypothesized that this was due to reduced pneumococcal transmission resulting from non-pharmacological interventions. We used multiple ongoing cohort surveillance projects in children <5 years to test this hypothesis.

Methods

The first SARS-CoV-2 cases were detected in February-2020, resulting in a full lockdown, followed by several partial restrictions. Data from ongoing surveillance projects captured the incidence dynamics of community-acquired alveolar pneumonia (CAAP), non-alveolar lower respiratory infections necessitating chest X-rays (NA-LRI), nasopharyngeal pneumococcal carriage in non-respiratory visits, nasopharyngeal respiratory virus detection (by PCR), and nationwide invasive pneumococcal disease (IPD). Monthly rates (January-2020 through February-2021 vs. mean monthly rates 2016-2019 [expected rates]) adjusted for age and ethnicity, were compared.

Findings

CAAP and bacteremic pneumococcal pneumonia were strongly reduced (incidence rate ratios, [IRRs] 0η07 and 0η19, respectively); NA-LRI and non-pneumonia IPD were also reduced, with a lesser magnitude (IRRs, 0η46 and 0η42, respectively). In contrast, pneumococcal carriage prevalence was only slightly reduced and density of colonization and pneumococcal serotype distributions were similar to previous years. The pneumococcus-associated disease decline was temporally associated with a full suppression of RSV, influenza viruses, and hMPV, often implicated as co-pathogens with pneumococcus. In contrast, adenovirus, rhinovirus, and parainfluenza activities were within or above expected levels.

Interpretation

Reductions in pneumococcal and pneumococcus-associated diseases occurring during the COVID-19 pandemic were not predominantly related to reduced pneumococcal transmission and carriage but were strongly associated with the complete disappearance of specific respiratory viruses.

Funding

Partially funded by Pfizer, Inc.
Rapid comparative evaluation of SARS-CoV-2 rapid point-of-care antigen tests
Authors: Denzler Anna , Jacobs Max L. , Witte Victoria , Schnitzler Paul , Denkinger Claudia M. , Knop Michael
Published: August 2021

Background

Currently, more than 500 different AgPOCTs for SARS-CoV-2 diagnostics are on sale (July 2021), for many of which no data about sensitivity other than self-acclaimed values by the manufacturers are available. In many cases these do not reflect real-life diagnostic sensitivities. Therefore, manufacturer-independent quality checks of available AgPOCTs are needed, given the potential implications of false-negative results.

Objective

The objective of this study was to develop a scalable approach for direct comparison of the analytical sensitivities of commercially available SARS-CoV-2 antigen point-of-care tests (AgPOCTs) in order to rapidly identify poor performing products.

Methods

We present a methodology for quick assessment of the sensitivity of SARS-CoV-2 lateral flow test stripes suitable for quality evaluation of many different products. We established reference samples with high, medium and low SARS-CoV-2 viral loads along with a SARS-CoV-2 negative control sample. Test samples were used to semi-quantitatively assess the analytical sensitivities of 32 different commercial AgPOCTs in a head-to-head comparison.

Results

Among 32 SARS-CoV-2 AgPOCTs tested, we observe sensitivity differences across a broad range of viral loads (∼7.0*108to ∼1.7*105SARS-CoV-2 genome copies per ml). 23 AgPOCTs detected the Ct25 test sample (∼1.4*106copies/ ml), while only five tests detected the Ct28 test sample (∼1.7*105copies/ ml). In the low range of analytical sensitivity we found three saliva spit tests only delivering positive results for the Ct21 sample (∼2.2*107copies/ ml). Comparison with published data support our AgPOCT ranking. Importantly, we identified an AgPOCT offered in many local drugstores and supermarkets, which did not reliably recognize the sample with highest viral load (Ct16 test sample with ∼7.0*108copies/ ml) leading to serious doubts in its usefulness in SARS-CoV-2 diagnostics.

Conclusion

The rapid sensitivity assessment procedure presented here provides useful estimations on the analytical sensitivities of 32 AgPOCTs and identified a widely-spread AgPOCT with concerningly low sensitivity.
BIOCHEMICAL AND HAEMATOLOGICAL CHANGES ASSOCIATED WITH TRANSPLACENTAL CONGENITAL MALARIA IN KOGI STATE, NORTHCENTRAL NIGERIA
Authors: Akor Shedrack Egbunu , Musa Dickson Achimugu , Akogu SPO , Matthew Akpa , Friday Emmanuel Titus , Idachaba Timothy , Onoja Patience , Abdul Ameh Simon
Published: August 2021

Background

Transplacental congenital malaria is a vertical transplacental transmission of malaria parasites from the mother to the baby in utero or perinatally during labor. Cord blood that conveyed oxygen and nutrients from mother to fetus and return with carbon dioxide and other waste materials can transmit malaria pathogen. This study is aim to establish early diagnosis of transplacental congenital malaria using cord blood biochemical and haematological indices. Cord blood from 164 babies delivered at three hospitals in Kogi State between January and December, 2020 were microscopically investigated for malaria parasite. Biochemical and Haematological analyses were done using SYSMEX XP-300, Roche 9180 and VIS Spectrophotometer model 721. The data obtained were expressed as mean ±standard deviation using SPSS 23. The indicator level of statistical significance was set at p<0.05. The results showed significant (p<0.05) decreased in values of WBC, platelet, sodium, potassium, urea, creatinine, RBC, PCV, haemoglobin and MCHC in malaria infected cord blood in comparison to malaria negative control group. Significant (P<0.05) increased activities of liver enzymes (AST, ALT, ALP), total protein, bicarbonate and chloride in malaria infected cord blood when compared with malaria negative group. However, no statistically significant difference in lymphocyte, MCV, MCH, neutrophil and mixed of both malaria infected and malaria negative cord blood. This study suggests that cord blood biochemical and haematological indices can be used to diagnose and manage transplacental congenital malaria in fetus and neonates.