bluuebunny/crossref_metadata_2025_split huggingface dataset:
PET/CT Imaging for Langerhans Cell Histiocytosis Involving Only Posterior Elements of the Cervical Vertebra
Authors: Zhang Wenjie , Xie Hangyu , Su Minggang 
Published: April 2021

Abstract
Langerhans cell histiocytosis only involving the posterior elements of the spine is rare. We report the case of a 7-year-old boy who has pain and restricted motion of his neck. 18F-FDG PET/CT revealed an osteolytic lesion in the posterior elements of the fourth cervical vertebra. The lesion has high 18F-FDG uptake with an SUVmax of 8.01. An operation was performed, and the final pathological finding revealed Langerhans cell histiocytosis.
18F-FET PET/CT in Early Subventricular Zone Recurrence of Adult Glioblastoma
Authors: Dissaux Gurvan , Dissaux Brieg , Bourhis David , Schick Ulrike , Querellou Solène 
Published: April 2021

Abstract
Glioma stem cells (GSCs) are the source of tumor recurrence in glioblastoma and are capable of whole tumor regeneration once the treatment has concluded. Compelling evidence from the last decade suggests that GSC may arise from neural stem cells residing in the adult subventricular zone (SVZ). We report the findings of an 18F-FET PET/CT showing pathological uptake in SVZ with a tumor-background ratio of greater than 1.6, giving evidence for glioblastoma recurrence. This case highlights the particular attention to be paid to the SVZ given the possible development of GSC.
Breast Metastasis of Primary Peritoneal Carcinoma Demonstrated on FDG PET/CT
Authors: Gungor Serkan , Girgin Rabia Burcin 
Published: April 2021

Abstract
Primary serous peritoneal carcinomas (PSPCs) are rare, and dissemination other than intraperitoneal implantation is even rarer. Breast is an extremely unusual location of metastasis for PSPC. The distinction of breast metastasis of PSPC from primary breast cancer is crucial because the treatment and the prognosis are entirely different. Here we present a case of breast and axillary lymph node metastases from PSPC that were identified on staging FGD PET/CT.
The Effect of Zolpidem on Language Function of Patients With Nonfluent Variant of Frontotemporal Dementia: A Pilot Study
Authors: Sayadnasiri Mohammad , Dieji Bahamn , Noroozi Mehdi , Rezaei Omid 
Published: April 2021

Objective
Primary progressive aphasia (PPA), as the language variant of frontotemporal dementia, is a neurodegenerative disease with an insidious course that has no appropriate treatment yet. The present study evaluated the effect of zolpidem on improving language function in patients with nonfluent variant PPA (nfv-PPA).

Methods
In this interventional pilot study, patients diagnosed with nfv-PPA were evaluated for language function through the Persian Aphasia Test. Patients were then treated with zolpidem with a maximum dose of 10 mg twice daily and reevaluated after 6 weeks using the Persian Aphasia Test. Data were compared by paired samples t test. Values of P ≤ 0.05 were considered significant.

Results
Thirteen (8 men) patients completed the study. The mean age of the patients was 58.5 ± 4.5 years. Changes were statistically significant in none of the 6 subtests including spontaneous speech content, speech fluency, auditory comprehension, sequential command comprehension, repetition, and naming.

Conclusion
The study showed that zolpidem did not affect the improvement of language function in patients with nfv-PPA. Thus, traditional language structures do not seem to be sensitive to the modulatory effects of zolpidem. Studies with larger sample sizes will help support this hypothesis.
A novel variant of interest of SARS-CoV-2 with multiple spike mutations detected through travel surveillance in Africa
Authors: de Oliveira Tulio , Lutucuta Silvia , Nkengasong John , Morais Joana , Paixão Joana Paula , Neto Zoraima , Afonso Pedro , Miranda Julio , David Kumbelembe , Inglês Luzia , Raisa Rivas Carralero Amilton Pereira Agostinho Paulo , Freitas Helga Reis , Mufinda Franco , Tessema Sofonias Kifle , Tegally Houriiyah , San Emmanuel James , Wilkinson Eduan , Giandhari Jennifer , Pillay Sureshnee , Giovanetti Marta , Naidoo Yeshnee , Katzourakis Aris , Ghafari Mahan , Singh Lavanya , Tshiabuila Derek , Martin Darren , Lessells Richard J 
Published: April 2021

AbstractAt the end of 2020, the Network for Genomic Surveillance in South Africa (NGS-SA) detected a SARS-CoV-2 variant of concern (VOC) in South Africa (501Y.V2 or PANGO lineage B.1.351)1. 501Y.V2 is associated with increased transmissibility and resistance to neutralizing antibodies elicited by natural infection and vaccination2,3. 501Y.V2 has since spread to over 50 countries around the world and has contributed to a significant resurgence of the epidemic in southern Africa. In order to rapidly characterize the spread of this and other emerging VOCs and variants of interest (VOIs), NGS-SA partnered with the Africa Centres for Disease Control and Prevention and the African Society of Laboratory Medicine through the Africa Pathogen Genomics Initiative to strengthen SARS-CoV-2 genomic surveillance across the region.
“Maternal and offspring genetic risk score (GRS) analyses of fetal alcohol exposure and ADHD risk in offspring”
Authors: Haan Elis , Sallis Hannah M. , Ystrom Eivind , Njølstad Pål Rasmus , Andreassen Ole A. , Reichborn-Kjennerud Ted , Munafò Marcus R. , Havdahl Alexandra , Zuccolo Luisa 
Published: April 2021

AbstractBackgroundStudies investigating the effects of prenatal alcohol exposure on childhood ADHD symptoms using conventional observational designs have reported inconsistent findings, which may be affected by unmeasured confounding and maternal and fetal ability to metabolise alcohol. We used genetic variants from alcohol metabolising genes (alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)) as proxies for fetal alcohol exposure to investigate their association with offspring ADHD risk around age 7-8.MethodsWe used data from three longitudinal pregnancy cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC), Generation R study (GenR) and the Norwegian Mother, Father and Child Cohort study (MoBa). Genetic risk scores (GRS) for alcohol use and metabolism using 36 single nucleotide polymorphisms (SNPs) from ADH/ALDH genes were calculated for mothers (NALSPAC=8,196; NMOBA=13,614), fathers (NMOBA=13,935) and offspring (NALSPAC=8,237; NMOBA=14,112; NGENR=2,661). Associations between maternal GRS and offspring ADHD risk were tested in the full sample to avoid collider bias. Offspring GRS analyses were stratified by maternal drinking status. Results: The pooled estimate in maternal GRS analyses adjusted for offspring GRS in ALSPAC and MoBa was OR=0.99, 95%CI 0.97-1.02. The pooled estimate in offspring GRS analyses stratified by maternal drinking status across the cohorts was: ORDRINKING=0.98, 95%CI 0.94-1.02; ORNO DRINKING=0.99, 95%CI 0.97-1.02. These findings remained similar after accounting for maternal genotype data in ALSPAC and maternal and paternal genotype data in MoBa.ConclusionsWe did not find evidence for a causal effect of fetal alcohol exposure on ADHD risk in offspring. The results may be affected by low power and outcome assessment.
Characterizing the countrywide epidemic spread of influenza A(H1N1)pdm09 virus in Kenya between 2009 and 2018
Authors: Owuor D. Collins , de Laurent Zaydah R. , Kikwai Gilbert K. , Mayieka Lillian M. , Ochieng Melvin , Müller Nicola F. , Otieno Nancy A. , Emukule Gideon O. , Hunsperger Elizabeth N. , Garten Rebecca , Barnes John R. , Chaves Sandra S. , Nokes D. James , Agoti Charles N. 
Published: April 2021

ABSTRACTBackgroundThe spatiotemporal patterns of spread of influenza A(H1N1)pdm09 viruses on a countrywide scale are unclear in many tropical/subtropical regions mainly because spatiotemporally representative sequence data is lacking.MethodsWe isolated, sequenced, and analyzed 383 influenza A(H1N1)pdm09 viral genomes isolated from hospitalized patients between 2009 and 2018 from seven locations across Kenya. Using these genomes and contemporaneously sampled global sequences, we characterized the spread of the virus in Kenya over several seasons using phylodynamic methods.ResultsThe transmission dynamics of influenza A(H1N1)pdm09 virus in Kenya was characterized by: (i) multiple virus introductions into Kenya over the study period, although these were remarkably few, with only a few of those introductions instigating seasonal epidemics that then established local transmission clusters; (ii) persistence of transmission clusters over several epidemic seasons across the country; (iii) seasonal fluctuations in effective reproduction number (Re) associated with lower number of infections and seasonal fluctuations in relative genetic diversity after an initial rapid increase during the early pandemic phase, which broadly corresponded to epidemic peaks in the northern and southern hemispheres; (iv) high virus genetic diversity with greater frequency of seasonal fluctuations in 2009-11 and 2018 and low virus genetic diversity with relatively weaker seasonal fluctuations in 2012-17; and (v) virus migration from multiple geographical regions to multiple geographical destinations in Kenya.ConclusionConsiderable influenza virus diversity circulates within Africa, as demonstrated in this report, including virus lineages that are unique to the region, which may be capable of dissemination to other continents through a globally migrating virus population. Further knowledge of the viral lineages that circulate within understudied low-to-middle income tropical and subtropical regions is required to understand the full diversity and global ecology of influenza viruses in humans and to inform vaccination strategies within these regions.
Increased household secondary attacks rates with Variant of Concern SARS-CoV-2 index cases
Authors: Buchan Sarah A. , Tibebu Semra , Daneman Nick , Whelan Michael , Vanniyasingam Thuva , Murti Michelle , Brown Kevin A. 
Published: April 2021

AbstractIMPORTANCEHigher secondary attack rates related to variant of concern (VOC) index cases have been reported, but have not been explored within households, which continue to be an important source of coronavirus disease 2019 (COVID-19) transmissionOBJECTIVETo compare secondary attack rates in households with VOC versus non-VOC index cases.DESIGNA retrospective cohort study of household index cases reported from February 7 – 27, 2021. A propensity-score matched cohort was derived to calculate adjusted estimates.SETTINGOntario, Canada.PARTICIPANTSA population-based cohort of all private households with index cases. We excluded cases in congregate settings, as well as households with one individual or with >1 case with the same earliest symptom onset date.EXPOSUREVOC status, defined as either individuals confirmed as B.1.1.7 using whole genome sequencing or those that screened positive for the N501Y mutation using real-time PCR.MAIN OUTCOME AND MEASUREHousehold secondary attack rate, defined as the number of household secondary cases that occurred 1-14 days after the index case divided by the total number of household secondary contacts.RESULTSWe included 1,259 index VOC and non-VOC cases in the propensity score-matched analysis. The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49), similar to the unadjusted estimate. In stratified analyses, the higher secondary attack rate for VOC compared to non-VOC index cases was accentuated for asymptomatic index cases (RR=1.91, 95% CI 0.96-3.80) and presymptomatic cases (RR=3.41, 95%CI 1.13-10.26)CONCLUSIONS AND RELEVANCEThis study provides strong evidence of increased transmissibility in households due to VOCs and suggests that asymptomatic and pre-symptomatic transmission may be of particular importance for VOCs. Our study suggests that more aggressive public health measures will be needed to control VOCs and that ongoing research is needed to understand mechanisms of VOC transmissibility to curb their associated morbidity and mortality.
HBACopy Number and Kidney Disease Risk among Black Americans: a Longitudinal Cohort Study
Authors: Ruhl A. Parker , Jeffries Neal , Yang Yu , Naik Rakhi P. , Patki Amit , Pecker Lydia H. , Mott Bryan T. , Zakai Neil A. , Winkler Cheryl A. , Kopp Jeffrey B. , Lange Leslie A. , Irvin Marguerite R. , Gutierrez Orlando M. , Cushman Mary , Ackerman Hans C. 
Published: April 2021

ABSTRACTBackgroundAlpha globin gene (HBA)copy number is variable among people of African descent.HBAlimits endothelial nitric oxide signaling and variation in gene copy number could modify kidney disease risk in this population.ObjectiveTo examine the association ofHBAcopy number with chronic kidney disease (CKD) and end-stage kidney disease (ESKD). We hypothesized that higherHBAcopy number would be associated with greater CKD prevalence and ESKD incidence.DesignProspective, longitudinal cohort from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study which enrolled participants from 2003 through 2007 and conducted follow-up through June 2014. Data were analyzed from January 2018 through January 2021.SettingCommunity-dwelling participants enrolled throughout the contiguous United StatesParticipantsBlack Americans age 45 years and olderMeasurementsHBAcopy number was measured using droplet-digital PCR on genomic DNA; copy number ranged from 2 to ≥ 5 copies. The prevalence ratio (PR) of CKD and relative risk (RR) of incident reduced estimated glomerular filtration rate (eGFR) were calculated using modified Poisson multivariable regression employing a log-linear effect ofHBAallele count. The hazard ratio (HR) of incident ESKD was calculated using Cox proportional hazards multivariable regression.ResultsAmong 9,918 participants,HBAgene copy number frequencies were 4%, 28%, 67%, and 1% for 2, 3, 4, and ≥5 copies, respectively. After adjusting for demographic, clinical, and genetic risk factors, each additional copy ofHBAwas associated with 14% greater prevalence of CKD (PR = 1.14, 95% CI 1.07 to 1.21;P< 0.0001). While there was no significant association with incident reduced eGFR (RR = 1.06, 95% CI 0.94 to 1.18; p = 0.36), the hazard of incident ESKD was 28% higher for each additional copy ofHBA(HR = 1.28, 95% CI 1.01 to 1.61;P= 0.04).LimitationsThis study did not identify the mechanism by whichHBAcopy number modifies kidney disease risk. This study focused on Black Americans, a population with a high frequency of the 3.7 kb gene deletion; it is unknown whetherHBAmodifies kidney disease risk in other populations with the 3.7 kb deletion.ConclusionsIncreasingHBAcopy number was associated with greater prevalent CKD and incident ESKD in a national longitudinal study of Black Americans.Funding SourceNational Institutes of Health
Validity and cultural generalisability of a 5-minute AI-based, computerised cognitive assessment in Mild Cognitive Impairment and Alzheimer’s Dementia
Authors: Modarres Hadi , Kalafatis Chris , Apostolou Panos , Marefat Haniye , Khanbagi Mahdiyeh , Karimi Hamed , Vahabi Zahra , Aarsland Dag , Khaligh-Razavi Seyed-Mahdi 
Published: April 2021

AbstractINTRODUCTIONEarly detection and monitoring of mild cognitive impairment (MCI) and Alzheimer’s Disease (AD) patients are key to tackling dementia and providing benefits to patients, caregivers, healthcare providers and society. We developed the Integrated Cognitive Assessment (ICA); a 5-minute, language independent computerised cognitive test that employs an Artificial Intelligence (AI) model to improve its accuracy in detecting cognitive impairment. In this study, we aimed to evaluate the generalisability of the ICA in detecting cognitive impairment in MCI and mild AD patients.METHODSWe studied the ICA in a total of 230 participants. 95 healthy volunteers, 80 MCI, and 55 participants with mild AD completed the ICA, the Montreal Cognitive Assessment (MoCA) and Addenbrooke’s Cognitive Examination (ACE) cognitive tests.RESULTSThe ICA demonstrated convergent validity with MoCA (Pearson r = 0.58, p<0.0001) and ACE (r = 0.62, p<0.0001). The ICA AI model was able to detect cognitive impairment with an AUC of 81% for MCI patients, and 88% for mild AD patients. The AI model demonstrated improved performance with increased training data and showed generalisability in performance from one population to another. The ICA correlation of 0.17 (p=0.01) with education years is considerably smaller than that of MoCA (r=0.34, p<0.0001) and ACE (r=0.41, p<0.0001) which displayed significant correlations. In a separate study the ICA demonstrated no significant practice effect observed over the duration of the study.DISCUSSIONThe ICA can support clinicians by aiding accurate diagnosis of MCI and AD and is appropriate for large-scale screening of cognitive impairment. The ICA is unbiased by differences in language, culture and education.
Dorsomedial striatal activity tracks completion of behavioral sequences
Authors: Vandaele Youna , Ottenheimer David J , Janak Patricia H 
Published: April 2021

AbstractFor proper execution of goal-directed behaviors, individuals require both a general representation of the goal and an ability to monitor their own progress toward that goal. Here, we examine how dorsomedial striatum (DMS), a region pivotal for forming associations among stimuli, actions, and outcomes, encodes the execution of goal-directed action sequences that require self-monitoring of behavior. We trained rats to complete a sequence of at least 5 consecutive lever presses (without visiting the reward port) to obtain a reward and recorded the activity of individual cells in DMS while rats performed the task. We found that the pattern of DMS activity gradually changed during the execution of the sequence, permitting accurate decoding of sequence progress from neural activity at a population level. Moreover, this sequence-related activity was blunted on trials where rats did not complete a sufficient number of presses. Overall, these data suggest a link between DMS activity and the execution of behavioral sequences that require monitoring of ongoing behavior.
Endoplasmic reticulum phospholipid scramblase activity revealed after protein reconstitution into giant unilamellar vesicles containing a photostable lipid reporter
Authors: Mathiassen Patricia P. M. , Menon Anant K. , Günther Pomorski Thomas 
Published: April 2021

AbstractTransbilayer movement of phospholipids in biological membranes is mediated by a diverse set of lipid transporters. Among them are scramblases that facilitate a rapid bi-directional movement of lipids without metabolic energy input. Here, we established a new fluorescence microscopy-based assay for detecting phospholipid scramblase activity of membrane proteins upon their reconstitution into giant unilamellar vesicles formed from proteoliposomes by electroformation. The assay is based on chemical bleaching of fluorescence of a photostable ATTO-dye labeled phospholipid with the membrane-impermeant reductant sodium dithionite. We demonstrate that this new methodology is suitable for the study of the scramblase activity of the yeast endoplasmic reticulum at single vesicle level.
Ultrapotent bispecific antibodies neutralize emerging SARS-CoV-2 variants
Authors: Cho Hyeseon , Gonzales-Wartz Kristina Kay , Huang Deli , Yuan Meng , Peterson Mary , Liang Janie , Beutler Nathan , Torres Jonathan L. , Cong Yu , Postnikova Elena , Bangaru Sandhya , Talana Chloe Adrienna , Shi Wei , Yang Eun Sung , Zhang Yi , Leung Kwanyee , Wang Lingshu , Peng Linghang , Skinner Jeff , Li Shanping , Wu Nicholas C. , Liu Hejun , Dacon Cherrelle , Moyer Thomas , Cohen Melanie , Zhao Ming , Lee F. Eun-Hyung , Weinberg Rona S. , Douagi Iyadh , Gross Robin , Schmaljohn Connie , Pegu Amarendra , Mascola John R. , Holbrook Michael , Nemazee David , Rogers Thomas F. , Ward Andrew B. , Wilson Ian A. , Crompton Peter D. , Tan Joshua 
Published: April 2021

AbstractThe emergence of SARS-CoV-2 variants that threaten the efficacy of existing vaccines and therapeutic antibodies underscores the urgent need for new antibody-based tools that potently neutralize variants by targeting multiple sites of the spike protein. We isolated 216 monoclonal antibodies targeting SARS-CoV-2 from plasmablasts and memory B cells of COVID-19 patients. The three most potent antibodies targeted distinct regions of the RBD, and all three neutralized the SARS-CoV-2 variants B.1.1.7 and B.1.351. The crystal structure of the most potent antibody, CV503, revealed that it binds to the ridge region of SARS-CoV-2 RBD, competes with the ACE2 receptor, and has limited contact with key variant residues K417, E484 and N501. We designed bispecific antibodies by combining non-overlapping specificities and identified five ultrapotent bispecific antibodies that inhibit authentic SARS-CoV-2 infection at concentrations of <1 ng/mL. Through a novel mode of action three bispecific antibodies cross-linked adjacent spike proteins using dual NTD/RBD specificities. One bispecific antibody was >100-fold more potent than a cocktail of its parent monoclonalsin vitroand prevented clinical disease in a hamster model at a 2.5 mg/kg dose. Notably, six of nine bispecific antibodies neutralized B.1.1.7, B.1.351 and the wild-type virus with comparable potency, despite partial or complete loss of activity of at least one parent monoclonal antibody against B.1.351. Furthermore, a bispecific antibody that neutralized B.1.351 protected against SARS-CoV-2 expressing the crucial E484K mutation in the hamster model. Thus, bispecific antibodies represent a promising next-generation countermeasure against SARS-CoV-2 variants of concern.
Rab40/Cullin5 complex regulates EPLIN and actin cytoskeleton dynamics during cell migration and invasion
Authors: Linklater Erik S , Duncan Emily D , Han Ke-Jun , Kaupinis Algirdas , Valius Mindaugas , Lyons Traci R , Prekeris Rytis 
Published: April 2021

ABSTRACTRab40b is a SOCS box containing protein that regulates the secretion of MMPs to facilitate extracellular matrix remodeling during cell migration. Here we show that Rab40b interacts with Cullin5 via the Rab40b SOCS domain. We demonstrate that loss of Rab40b/Cullin5 binding decreases cell motility and invasive potential, and show that defective cell migration and invasion stem from alteration to the actin cytoskeleton, leading to decreased invadopodia formation, decreased actin dynamics at the leading edge, and an increase in stress fibers. We also show that these stress fibers anchor at less dynamic, more stable focal adhesions. Mechanistically, changes in the cytoskeleton and focal adhesion dynamics are mediated in part by EPLIN, which we demonstrate to be a binding partner of Rab40b and a target for Rab40b/Cullin5 dependent localized ubiquitylation and degradation. Thus, we propose a model where the Rab40b/Cullin5 dependent ubiquitylation regulates EPLIN localization to promote cell migration and invasion by altering focal adhesion and cytoskeletal dynamics.