bluuebunny/crossref_metadata_2025_split huggingface dataset:
The mitochondrial stress-induced protein carboxyl-terminal alanine and threonine tailing (msiCAT-tailing) promotes glioblastoma tumorigenesis by modulating mitochondrial functions
Authors: Cai Ting , Zhang Bei , Reddy Esha , Wu Yuanna , Tang Yinglu , Mondal Isha , Wang Jerry , Ho Winson S , Lu Rongze Olivia , Wu Zhihao 
Published: May 2024

AbstractThe rapid and sustained proliferation in cancer cells requires accelerated protein synthesis. Accelerated protein synthesis and disordered cell metabolism in cancer cells greatly increase the risk of translation errors. ribosome-associated quality control (RQC) is a recently discovered mechanism for resolving ribosome collisions caused by frequent translation stalls. The role of the RQC pathway in cancer initiation and progression remains controversial and confusing. In this study, we investigated the pathogenic role of mitochondrial stress-induced protein carboxyl-terminal terminal alanine and threonine tailing (msiCAT-tailing) in glioblastoma (GBM), which is a specific RQC response to translational arrest on the outer mitochondrial membrane. We found that msiCAT-tailed mitochondrial proteins frequently exist in glioblastoma stem cells (GSCs). Ectopically expressed msiCAT-tailed mitochondrial ATP synthase F1 subunit alpha (ATP5α) protein increases the mitochondrial membrane potential and blocks mitochondrial permeability transition pore (MPTP) formation/opening. These changes in mitochondrial properties confer resistance to staurosporine (STS)-induced apoptosis in GBM cells. Therefore, msiCAT-tailing can promote cell survival and migration, while genetic and pharmacological inhibition of msiCAT-tailing can prevent the overgrowth of GBM cells.HighlightsThe RQC pathway is disturbed in glioblastoma (GBM) cellsmsiCAT-tailing on ATP5α elevates mitochondrial membrane potential and inhibits MPTP openingmsiCAT-tailing on ATP5α inhibits drug-induced apoptosis in GBM cellsInhibition of msiCAT-tailing impedes overall growth of GBM cells
Comparison of MR coil options for concurrent TMS-fMRI
Authors: Jackson J. B. , Scrivener C. L. , Mada M. , Woolgar A. 
Published: May 2024

AbstractConcurrent transcranial magnetic stimulation (TMS) with functional magnetic resonance imaging (fMRI) is increasingly being used to study how TMS affects neural processing in local and remote connected brain regions. However, there are many technical challenges that arise when operating this unique combination of techniques. One such challenge is MR head coil compatibility and the image resolution that can be achieved. Here we compare the temporal-signal-to noise-ratio (tSNR) between 3 different MR head coils that can be used with TMS. We show that the 7-channel TMS-dedicated surface coils result in a very high tSNR directly under the TMS and the supplementary coil in comparison to the TxRx and the Magnetica. However, there is low tSNR elsewhere. This field inhomogeneity may not be suitable for all research questions, for example where the aim is to look at distributed neural responses. In these cases, an MR coil with a more homogeneous tSNR such as the Magnetica, may be more appropriate.
Nationwide upsurge in invasive disease in the context of longitudinal surveillance of carriage and invasiveStreptococcus pyogenes2009-2023, the Netherlands: a molecular epidemiological study
Authors: Rümke Lidewij W. , Davies Matthew A. , Vestjens Stefan M.T. , van der Putten Boas C.L. , Bril-Keijzers Wendy C.M. , van Houten Marlies A. , Rots Nynke Y. , Wijmenga-Monsuur Alienke J. , van der Ende Arie , de Gier Brechje , Vlaminckx Bart J.M. , van Sorge Nina M. 
Published: May 2024

ABSTRACTBackgroundSince 2022, many countries reported an upsurge in invasive group A streptococcal (iGAS) infections. We explored whether changes inS. pyogenescarriage rates or emergence of more virulent strains, such asemm1 variants M1UKand M1DK, contributed to the 2022/2023 surge in the Netherlands.MethodsWe determinedemm(sub)type distribution for 2,698 invasive and 351S. pyogenescarriage isolates collected between January 2009 - March 2023. Genetic evolution ofemm1 was analyzed by whole-genome sequencing of 497emm1 isolates.FindingsThe nationwide iGAS upsurge coincided with a sharp increase ofemm1.0 from 18% (18/100) of invasive isolates in Q1 2022 to 58% (388/670) in Q1 2023 (Fisher’s exact, p<0.0001). M1UKbecame dominant among invasiveemm1 isolates in 2016 and further expanded from 72% in Q1 2022 to 96% in Q1 2023. Phylogenetic comparison revealed evolution and clonal expansion of four new M1UKclades in 2022/2023. DNase Spd1 and superantigen SpeC were acquired in 9% (46/497) ofemm1 isolates.S. pyogenescarriage rates andemm1 proportions in carriage isolates remained stable during this surge and the expansion of M1UKin iGAS was not reflected in carriage isolates.InterpretationDuring the 2022/2023 iGAS surge in the Netherlands, expansion of four new M1UKclades was observed among invasive isolates but not carriage isolates, suggesting increased virulence and fitness of M1UKcompared to contemporary M1 strains. The emergence of more virulent clades has important implications for public health strategies such as antibiotic prophylaxis for close contacts of iGAS patients.
Characterization of pediatric urinary microbiome at species-level resolution indicates variation due to sex, age, and urologic history
Authors: Kelly Maryellen S , Dahl Erin M , Jeries Layla , Sysoeva Tatyana A , Karstens Lisa 
Published: May 2024

Extended SummaryBackgroundRecently, associations between recurrent urinary tract infections (UTI) and the urinary microbiome (urobiome) composition have been identified in adults. However, little is known about the urobiome in children. We aimed to characterize the urobiome of children with species-level resolution and to identify associations based on UTI history.Study designFifty-four children (31 females and 21 males) from 3 months to 5 years of age participated in the study. Catheterized urine specimens were obtained from children undergoing a clinically indicated voiding cystourethrogram. To improve the analysis of the pediatric urobiome, we used a novel protocol using filters to collect biomass from the urine coupled with synthetic long-read 16S rRNA gene sequencing to obtain culture-independent species-level resolution data. We tested for differences in microbial composition between sex and history of UTIs using non-parametric tests on individual bacteria and alpha diversity measures.ResultsWe detected bacteria in 61% of samples from 54 children (mean age 40.7 months, 57% females). Similar to adults, urobiomes were distinct across individuals and varied by sex. The urobiome of females showed higher diversity as measured by the inverse Simpson and Shannon indices but not the Pielou evenness index or number of observed species (p = 0.05, p=0.04, p = 0.35, and p = 0.11, respectively). Additionally, several species were significantly overrepresented in females compared to males, including those from the generaAnaerococcus, Prevotella,andSchaalia(p = 0.03, 0.04, and 0.02, respectively). Urobiome diversity increased with age, driven mainly by males. Comparison of children with a history of 1, 2, or 3+ UTIs revealed that urobiome diversity significantly decreases in the group that experienced 3+ UTIs as measured by the Simpson, Shannon, and Pielou indices (p = 0.03, p = 0.05, p = 0.01). Several bacteria were also found to be reduced in abundance.DiscussionIn this study, we confirm that urobiome can be identified from catheter-collected urine specimens in infants as young as 3 months, providing further evidence that the pediatric bladder is not sterile. In addition to confirming variations in the urobiome related to sex, we identify age-related changes in children under 5 years of age, which conflicts with some prior research. We additionally identify associations with a history of UTIs.ConclusionsOur study provides additional evidence that the pediatric urobiome exists. The bacteria in the bladder of children appear to be affected by early urologic events and warrants future research.
A qualitative study of emergency nurses’ perspectives on intranasal ketamine for procedural sedation in children
Authors: Wonnacott David , Scott Shannon D. , Flynn Rachel , Ali Samina , Van Der Vaart Everly , Poonai Naveen 
Published: May 2024

ABSTRACTPurposeThere is mounting evidence supporting a role for intranasal (IN) ketamine for procedural sedation in children due to its less invasive delivery. Drug administration and monitoring is largely performed by nurses and clinical uptake requires understanding their perceptions. We explored nursing perspectives of IN ketamine for procedural sedation in children to understand facilitators and barriers and inform institutional guidelines.Design and MethodsFrom January to February, 2018, we conducted 2 focus groups with 8 registered nurses in a Canadian tertiary care paediatric ED. Following professional transcription, data were analyzed using an inductive qualitative approach.ResultsSeven of 8 participants had experience administering IN ketamine to children for procedural sedation. Nurses perceived that IN ketamine had the potential to reduce children’s distress and improve nursing resource use. Perceived barriers included: 1) uncertainty regarding sedation effectiveness and incorporation into institutional sedation protocols, 2) perceptions that IN ketamine produced a relatively lighter, slower-onset, and less titratable sedation, and 3) healthcare providers’ lack of familiarity with IN ketamine and reluctance to change their current approach to sedation.ConclusionsWe identified barriers to adoption of IN ketamine such as uncertainty regarding its pharmacodynamic properties, safety, and impact on workflow, along with facilitators such as fewer adverse events and nursing resources, and less procedural distress for children.Practice ImplicationsProvider education should focus on IN ketamine’s pharmacodynamic properties and development of institutional sedation guidelines that define indications for use, support engagement of child life specialists, and operationalize the type and duration of monitoring requirements.CLINICIAN’S CAPSULEWhat is known about the topic?Intranasal ketamine is an emerging agent for procedural sedation and analgesia in the emergency department due to ease of administration.What did this study ask?What are paediatric nurses’ perspectives on intranasal ketamine for procedural sedation among children in the emergency department?What did this study find?Nurses identified advantages to intranasal ketamine but expressed considerable uncertainty regarding its pharmacodynamic properties and its incorporation into clinical practice.Why does this study matter to clinicians?Provider education may overcome some uncertainty and should focus on intranasal ketamine’s pharmacodynamic properties and incorporation into institutional sedation protocols.MeetingsPediatric Academic Societies (Baltimore, Maryland, April 30, 2019); Canadian Association of Emergency Physicians (Halifax, Nova Scotia, May 29, 2019); Canadian Paediatric Society (Toronto, Ontario, June 7, 2019)
Preliminary findings from the Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE I) Study: a Randomized Controlled Trial
Authors: Cowling Benjamin J. , Wong Sook-San , Santos Jefferson J. S. , Touyon Lisa , Ort Jordan , Ye Naiqing , Kwok Natalie K. M. , Ho Faith , Cheng Samuel M. S. , Ip Dennis K. M. , Peiris Malik , Webby Richard J. , Wilson Patrick C. , Valkenburg Sophie A. , Tsang John S. , Leung Nancy H. L. , Hensley Scott E. , Cobey Sarah 
Published: May 2024

ABSTRACTBackgroundStudies have reported that repeated annual vaccination may influence the effectiveness of the influenza vaccination in the current season. The mechanisms underlying these differences are unclear but might include “focusing” of the adaptive immune response to older strains.MethodsWe established a 5-year randomized placebo-controlled trial of repeated influenza vaccination (Flublok, Sanofi Pasteur) in adults 18-45 years of age. Participants were randomized equally between five groups, with planned annual receipt of vaccination (V) or saline placebo (P) as follows: P-P-P-P-V, P-P-P-V-V, P-P-V-V-V, P-V-V-V-V, or V-V-V-V-V. Serum samples were collected each year just before vaccination and after 30 and 182 days. A subset of sera were tested by hemagglutination inhibition assays, focus reduction neutralization tests and enzyme-linked immunosorbent assays against vaccine strains.ResultsFrom 23 October 2020 through 11 March 2021 we enrolled and randomized 447 adults. We selected sera from 95 participants at five timepoints from the first two study years for testing. Among vaccinated individuals, antibody titers increased between days 0 and 30 against each of the vaccine strains, with substantial increases for first-time vaccinees and smaller increases for repeat vaccinees, who had higher pre-vaccination titers in year 2. There were statistically significant reductions in the proportion of participants achieving a four-fold greater rise in antibody titer for the repeat vaccinees for A(H1N1), B/Victoria and B/Yamagata, but not for influenza A(H3N2). There were no statistically significant differences between groups in geometric mean titers at day 30 or the proportions of participants with antibody titers ≥40 at day 30 for any of the vaccine strains.ConclusionsIn the first two years, repeat vaccinees and first-time vaccinees had similar post-vaccination geometric mean titers to all four vaccine strains, indicative of similar levels of clinical protection. The vaccine strains of A(H1N1) and A(H3N2) were updated in year 2, providing an opportunity to explore antigenic distances between those strains in humans in subsequent years.
Mass drug administration coverage and determinants of drug uptake for elimination of Onchocerciasis in Ulanga District
Authors: Mhiche Ambakisye , Gasarasi Dinah , Kabona George , Hussein Ally , Abade Ahmed Mohamed 
Published: May 2024

AbstractBackgroundOnchocerciasis remain to be an important public health problem targeted for elimination in Tanzania. Ulanga District was known for its high endemicity since 1960s and has been implementing MDA through Community Directed Treatment with Ivermectin (CDTI) strategy since 1998. However, current reports indicate high prevalence of Onchocerciasis in both human and vector species probably because of poor treatment coverage indicating limited evidence for transmission. This study was conducted to assess treatment coverage and explore determinants of drug uptake during MDA program.MethodsA cross-sectional community-based study using multistage cluster sampling was carried out in Ulanga District, Morogoro Tanzania from April-June 2019. Study participants were randomly selected from households and interviewed using a structured questionnaire. Modified Poisson regression was performed to determine independent factors associated with MDA uptake.ResultsA total of 502 participants were recruited during the study period with a response rate of 96%. The majority (67%) were females, and the mean age of the study participants was 37.8 ±15 years with an age range of 25–34 (25.5 %). MDA coverage for the studied villages was as follows; Mawasiliano (68%) Uponera (83%), Isongo (84%) and Togo (79%). The drug uptake for all villages was below the optimal coverage recommended by WHO (85%) for successful transmission interruption. Having an age of ≤ 24 years [Adjusted Prevalence Ration (APR) = 3.9(95% CI:1.9-8.3), p < 0.05)], Living in the village for at least a year [APR = 3.4 (95% CI:2.4-4.8), p <0.05)] and believing IVM prevent Onchocerciasis [APR = 13.4(95% CI:2.9-60.9)], p<0.05) were associated with increased chances of Ivermectin uptake during MDA. In addition, decreased drug uptake [APR = 12(95% CI: 2.4-60.9), p<0.05)] was attributable to fear of restriction to drinking alcohol after taking drugs.ConclusionLow coverage below the WHO optimal recommended coverage has been demonstrated in the studied villages. This implies low drug uptake, delayed interruption of transmission and Onchocerciasis elimination. These findings, therefore, emphasize the need to intensify the MDA awareness campaigns targeting less compliant groups in the community to reinforce the benefits of ivermectin in Onchocerciasis control and address the community misconceptions about MDA.
Transcranial Focused Ultrasound Targeting the Default Mode Network for the Treatment of Depression
Authors: Schachtner Jessica N. , Dahill-Fuchel Jacob F. , Allen Katja E. , Bawiec Christopher R. , Hollender Peter J. , Ornellas Sarah B. , Konecky Soren D. , Achrol Achal S. , Allen John J.B. 
Published: May 2024

AbstractImportanceUp to 50% of individuals fail to respond to current depression treatments. Repetitive negative thought and default mode network hyperconnectivity are central in depression and can be targeted using novel neuromodulation techniques.ObjectiveThis study assessed whether non-invasive transcranial focused ultrasound to the default mode network can decrease depression symptoms and repetitive negative thought, and improve quality of life.DesignThis open-label case series began in August 2023, with a six-month follow-up period (current).SettingA community-based study at the University of Arizona.ParticipantsTwenty individuals aged 18 – 45 were enrolled from among 247 screened. Exclusion criteria included history of psychosis/mania, acute suicidality, MRI contraindications, pregnancy, and medical and neurological factors that may complicate diagnosis or brain function.InterventionUp to three weeks of transcranial ultrasound (11 sessions) targeting the anterior medial prefrontal cortex; ten minutes per session.Main Outcomes and MeasuresDepression severity (Beck Depression Inventory – II and the Hamilton Depression Rating Scale), repetitive negative thought (Perseverative Thinking Questionnaire), and quality of life (World Health Organization Quality of Life survey) were outcomes.ResultsThis sample was young (mean 30.4 years ± 10.0), predominantly female (75%), with moderate to severe depression and high comorbidity. Fifty percent of participants endorsed current psychiatric medication use. Ten percent of subjects dropped out of the study. Significant decreases in depression occurred on self-report, 11.3 (p < 0.001, CI = −14.68, −8.15) and interview ratings, 4.3 (p < 0.001, CI = −6.21, −2.43). Repetitive negative thought decreased by 8.53 (p <0.001, CI = −11.01, −5.79). Physical and psychological well-being improved by 7.6 (p < 0.001, CI = 3.62, 11.63) and 11.9 points (p < 0.001, CI = 7.51, 16.21), respectively. Environment satisfaction increased by 5.0 (p = 0.001, CI = 2.24, 7.56).Conclusions and RelevanceTranscranial ultrasound holds promise as a treatment for depression.Trial RegistrationAltering Default Mode Network Activity with Transcranial Focused Ultrasound to Reduce Depressive Symptoms (DMNtFUS). Registration number: 019782-00001 Clinical trials ID:NCT06320028URL:https://clinicaltrials.gov/study/NCT06320028?intr=Ultrasound&cond=depression&locStr=Arizona&country=United%20States&state=Arizona&rank=1
Estimates of Actual and Potential Lives Saved in the United States from the use of COVID-19 Convalescent Plasma
Authors: Dragotakes Quigly , Johnson Patrick W. , Buras Matthew R. , Carter Rickey E. , Joyner Michael J. , Bloch Evan , Gebo Kelly A. , Hanley Daniel F. , Henderson Jeffrey P. , Pirofski Liise-anne , Shoham Shmuel , Senefeld Jonathon W. , Tobian Aaron AR , Wiggins Chad C. , Wright R. Scott , Paneth Nigel S. , Sullivan David J. , Casadevall Arturo 
Published: May 2024

AbstractIn the Spring of 2020, the United States of America (USA) deployed COVID-19 convalescent plasma (CCP) to treat hospitalized patients. Over 500,000 patients were treated with CCP during the first year of the pandemic. In this study, estimated the number of actual inpatient lives saved by CCP treatment in the USA based upon CCP weekly use, weekly national mortality data, and CCP mortality reduction data from meta-analyses of randomized controlled trials and real-world data. We also estimate the potential number of lives saved if CCP had been deployed for 100% of hospitalized patients or used in 15% to 75% of outpatients. Depending on the assumptions modeled in stratified analyses, CCP was estimated to have saved between 16,476 and 66,296 lives. The CCP ideal use might have saved as many as 234.869 lives while preventing 1,136,133 hospitalizations. CCP deployment was a successful strategy for ameliorating the impact of the COVID-19 pandemic in the USA. This experience has important implications for convalescent plasma used in future infectious disease emergencies.Significance statementWhen the COVID-19 pandemic struck in 2020, the population lacked immunity, no validated therapies were available, and mortality was high. COVID-19 convalescent plasma (CCP) was authorized in the United States for treatment of hospitalized patients based on historical evidence of convalescent plasma (CP) efficacy and findings from a nationwide registry suggesting that it reduced mortality. However, this decision was controversial because it was not based on evidence from randomized controlled clinical trials. In this study, we leveraged CCP use and mortality data combined with CCP efficacy data to show that CCP reduced mortality and saved tens of thousands of lives the first year of the pandemic. This provides a powerful basis to consider CP deployment in future infectious disease emergencies.