bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammation and autoreactivity define a discrete subset of patients with post-acute sequelae of COVID-19, or long-COVID
Authors: Woodruff Matthew C. , Bonham Kevin S. , Anam Fabliha A. , Walker Tiffany A. , Ishii Yusho , Kaminski Candice Y. , Ruunstrom Martin C. , Truong Alexander D. , Dixit Adviteeya N. , Han Jenny E. , Ramonell Richard P. , Haddad Natalie S. , Rudolph Mark E. , Jenks Scott A. , Khosroshahi Arezou , Lee F. Eun-Hyung , Sanz Ignacio 
Published: September 2021

AbstractWhile significant attention has been paid to the immunologic determinants of disease states associated with COVID-191,2, their contributions to post-acute sequelae of COVID-19 (PASC) remain less clear3-5. Due to the wide array of PASC presentations6, it is critical to understand if specific features of the disease are associated with discrete immune processes, and whether those processes may be therapeutically targeted. To this end, we performed wide immunologic and serological characterization of patients in the early recovery phase of COVID-19 across a breadth of symptomatic presentations. Using high-parameter proteomics screening and applied machine learning (ML), we identify clear signatures of immunologic activity between PASC patients and uncomplicated recovery, dominated by inflammatory cytokine signaling, neutrophil activity, and markers of cell death. Consistent with disease complexity, heterogeneity in plasma profiling reveals distinct PASC subsets with striking divergence in these ongoing inflammatory processes, here termed plasma quiescent (plaq) and inflammatory (infl) PASC. In addition to elevated inflammatory blood proteomics, inflPASC patients display positive clinical tests of acute inflammation including C-reactive protein and fibrinogen, increased B cell activity with extrafollicular involvement coupled with elevated targeting of viral nucleocapsid protein and clinical autoreactivity. Further, the unique plasma signatures of PASC patients allowed for the creation of refined models with high sensitivity and specificity for the positive identification of inflPASC with a streamlined assessment of 12 blood markers. Additionally, refined ML modeling highlights the unexpected significance of several markers of potential diagnostic or therapeutic use for PASC in general, including the peptide hormone, epiregulin. In all, this work identifies clear biological signatures of PASC with potential diagnostic and therapeutic potential and establishes clear disease subtypes that are both easily identifiable and highly relevant to ongoing efforts in both therapeutic targeting and epidemiological investigation of this highly complex disease.
Postnatal maternal depressive symptoms and behavioural outcomes in term- and preterm-born toddlers
Authors: Kleine I , Vamvakas G , Lautarescu A , Falconer S , Chew A , Counsell SJ , Pickles A , Edwards AD , Nosarti C 
Published: September 2021

AbstractObjectivesTo examine the association between maternal depressive symptoms in the immediate postnatal period and offspring’s mental health in a large cohort of term- and preterm-born toddlers.Design and ParticipantsData were drawn from the Developing Human Connectome Project. Maternal postnatal depressive symptoms were assessed at term, and children’s outcomes were evaluated at a median corrected age of 18.4 months (range 17.3 – 24.3).Exposure and outcomesPreterm birth was defined as <37 weeks completed gestation. Maternal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale (EPDS). Toddlers’ outcome measures were parent-rated Child Behaviour Checklist 11/2-5 Total (CBCL) and Quantitative Checklist for Autism in Toddlers (Q-CHAT) scores. Toddlers’ cognition was assessed with the Bayley Scales of Infant and Toddler Development – Third Edition (Bayley-III).ResultsHigher maternal EPDS scores were associated with toddlers’ higher CBCL (B=0.93, 95% CI 0.43-1.44, p<0.001, f2=0.05) and Q-CHAT scores (B=0.27, 95% CI 0.03-0.52, p=.031, f2=0.01). Higher maternal EPDS scores were not associated with toddlers’ cognitive outcomes. Maternal EPDS, toddlers’ CBCL and Q-CHAT scores did not differ between preterm (n=97; 19.1% of the total sample) and term participants.ConclusionsOur findings indicate that children whose mothers had increased depressive symptoms in the early postnatal period, including subclinical symptoms, exhibit more maternally-reported behavioural problems in toddlerhood. These associations were independent of gestational age. Further research is needed to confirm the clinical significance of these findings.Strengths and limitations of this studyProspective study with a large sample, using multiple imputation to reduce non-response bias.Maternal depressive symptoms assessed as a continuous variable, providing more nuanced information about the significance of subclinical symptoms.Maternal depressive symptoms assessed earlier than in previous studies, enabling recognition of early screening opportunities for families.Potential shared method variance bias through parent-completed child behavioural assessments.Unknown paternal and parental factors, such as comorbid psychiatric conditions, that may confound our findings.
The Impact of New SARS-CoV-2 Variants on Vaccine Breakthrough: A Pilot Study on Spreading Infection in the Communities
Authors: Ayass Mohamad Ammar , Zhang Jin , Zhu Kevin , Cao Wanying , Griko Natalya , Pashkov Victor , Dai Jun , Tripathi Trivendra , Mosleh Lina Abi 
Published: September 2021

AbstractBackgroundCoronavirus disease 2019 (COVID-19) vaccines are effective at helping protect against severe disease and death from variants; however, incident of breakthrough infection in vaccinated patients has been increased. Therefore, we aimed to assess the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) new variants of concern in the communities and investigate vaccine breakthrough cases on our laboratory (Ayass Bioscience LLC) confirmed detection of COVID-19 variants in Dallas-Fort Worth (DFW), Texas.MethodsEpidemiologic study has been performed at our laboratory. We studied the viral whole-genome sequence and genotyping analysis on 166 symptomatic cases of COVID-19 which were randomly selected from nasal swab positive cases assessed from June 1st to August 30th, 2021, by reverse transcription polymerase chain reaction (RT-PCR) cycle threshold (CT) values. COVID-19 variants were identified to be dominated by B.1.617.2 (89.2%) and followed by AY.3 (1.8%), B.1.1.7 (4.8%), a combination of B.1.526.1 and B.1.617.2 (3%), B.1.621 (0.6%), and P.2 (0.6%).ResultThe CT values showed significant difference among the three age groups: <30 years, 31-60 years, and >60 years by one-way ANOVA (N1: F (2, 118) =4.96, p=0.009; N2: F (2, 118) =4.95, p=0.009). No significant difference was observed by symptom, status of immunization, or vaccine manufacturer. A two-way ANOVA was performed to examine the effect of gender and variant group (Delta and other variants) on the CT values. The analyses revealed a statistically significant interaction between the effect of gender and variant group (N1, F (1.117) = 3.906, p = 0.05; N2, F (1, 117) = 7.402, p = 0.008).ConclusionOur study shows that Delta, the dominant variant of COVID-19, is spreading in the communities, and vaccine breakthrough cases occurred in the majority of Delta variant (91%) followed by AY.3 (5%), B.1.1.7 (2%) and 2% of the double variant of B.1.526.1 and B.1.617.2. The incidence of the breakthrough cases was not linked to a specific manufacturer. The CT value is likely to associate with age. This study also supports our laboratory’s ongoing efforts to sequence the SARS-CoV-2 virus from positive patient samples to identify the new viral variants and possible vaccine breakthrough mutations in the community.
Quantification and prognostic significance of interferon-γ secreting SARS-CoV-2 responsive T cells in hospitalised patients with acute COVID-19
Authors: Pan Daniel , Kim Jee Whang , Nazareth Joshua , Assadi Sara , Bellass Adam , Leach Jack , Brosnan James G , Ahmed Adam , Starcevic Fleur , Sze Shirley , Martin Christopher A , Williams Caroline M , Barer Michael R , Sahota Amandip , Patel Prashanth , Tattersall Andrea , Cooper Andrea , Pareek Manish , Haldar Pranabashis 
Published: September 2021

AbstractLittle is known about T-cell responses during acute coronavirus disease-2019 (COVID-19). We measured T-cell interferon gamma (IFN-γ) responses to spike 1 (S1), spike 2 (S2), nucleocapsid (N) and membrane (M) SARS-CoV-2 antigens using the T-SPOT® Discovery SARS-CoV-2 assay, a proven EliSPOT technology, in 114 hospitalised adult COVID-19 patients and assessed their association with clinical disease phenotype. T-SPOT® Discovery SARS-CoV-2 responses were detectable within 2 days of a positive PCR and did not correlate with vaccination status or symptom duration. Higher responses to S1 protein associated with a higher symptom burden, and serum IL-6 levels. Despite treatment with dexamethasone this subgroup was also at greater risk of requiring continuous positive airway pressure (CPAP) in the days following sampling. Higher T-cell responses measured using T-SPOT® Discovery SARS-CoV-2 associate with progressive disease in acute COVID-19 disease and may have utility as a prognostic biomarker that should be evaluated in larger cohorts.
Young Zambian infants with symptomatic RSV and pertussis infections are frequently prescribed inappropriate antibiotics
Authors: Gunning CE , Rohani P , Mwananyanda L , Kwenda G , Mupila Z , Gill CJ 
Published: September 2021

AbstractPediatric community-acquired pneumonia (CAP) remains a pressing global health concern, particulary in low-resource settings where diagnosis and treatment rely on empiric, symptoms-based guidelines such as the WHO’s Integrated Management of Childhood Illness (IMCI). This study details the delivery of IMCI-based health care in a cohort of 1,320 young infants and their mothers in a low-resource urban community in Lusaka, Zambia. We prospectively monitored mother/infant pairs across infants’ first four months of life, recording symptoms of respiratory infection and antibiotics prescriptions (predominantly penicillins), and tested nasopharyngeal (NP) samples for Respiratory syncytial virus (RSV) and Bordetella pertussis. Symptoms and antibiotics use were more common in infants (43% and 15.7%) than in mothers (16.6% and 8%), while RSV and B. pertussis were observed at similar rates in infants (2.7% and 32.5%) and mothers (2% and 35.5%), albeit frequently at very low levels. In infants, we observed strong associations between symptoms, pathogen detection, and antibiotics use. Critically, we demonstrate that non-macrolide antibiotics were commonly prescribed for pertussis infections, some of which persisted across many weeks. We speculate that improved diagnostic specificity and/or clinician education paired with timely, appropriate treatment of pertussis could substantially reduce the burden of this disease while reducing the off-target use of penicillins.
Connecting Artificial Intelligence and Primary Care Challenges: Findings from a Multi-Stakeholder Collaborative Consultation
Authors: Kueper Jacqueline K. , Terry Amanda L. , Bahniwal Ravninder , Meredith Leslie , Beleno Ron , Brown Judith Belle , Dang Janet , Leger Daniel , McKay Scott , Ryan Bridget L. , Zwarenstein Merrick , Lizotte Daniel J. 
Published: September 2021

ABSTRACTDespite widespread advancements in and envisioned uses for artificial intelligence (AI), few examples of successfully implemented AI innovations exist in primary care (PC) settings.ObjectivesTo identify priority areas for AI and PC in Ontario, Canada.MethodsA collaborative consultation event engaged multiple stakeholders in a nominal group technique process to generate, discuss, and rank ideas for how AI can support Ontario PC.ResultsThe consultation process produced nine ranked priorities: 1) preventative care and risk profiling, 2) patient self-management of condition(s), 3) management and synthesis of information, 4) improved communication between PC and AI stakeholders, 5) data sharing and interoperability, 6-tie) clinical decision support, 6-tie) administrative staff support, 8) practitioner clerical and routine task support, and 9) increased mental health care capacity and support. Themes emerging from small group discussions about barriers, implementation issues, and resources needed to support the priorities included: equity and the digital divide; system capacity and culture; data availability and quality; legal and ethical issues; user-centered design; patient-centredness; and proper evaluation of AI-driven tool implementation.DiscussionFindings provide guidance for future work on AI and PC. There are immediate opportunities to use existing resources to develop and test AI for priority areas at the patient, provider, and system level. For larger-scale, sustainable innovations, there is a need for longer-term projects that lay foundations around data and interdisciplinary work.ConclusionStudy findings can be used to inform future research and development of AI for PC, and to guide resource planning and allocation.SUMMARYWhat is already known?–The field of artificial intelligence and primary care is underdeveloped.What does this paper add?–An environmental scan without geographic location restriction identified 110 artificial intelligence-driven tools with potential relevance to primary care that existed around the time of the study.–A multi-stakeholder consultation session identified nine priorities to guide future work on artificial intelligence and primary care in Ontario, Canada.–Priorities for artificial intelligence and primary care include provider, patient, and system level uses as well as foundational areas related to data and interdisciplinary communication.
Effect of Long-Term Caloric Restriction on DNA Methylation Measures of Biological Aging in Healthy Adults: CALERIE™ Trial Analysis
Authors: Waziry R , Corcoran DL , Huffman KM , Kobor MS , Kothari M , Kraus VB , Kraus WE , Lin DTS , Pieper CF , Ramaker ME , Bhapkar M , Das SK , Ferrucci L , Hastings WJ , Kebbe M , Parker DC , Racette SB , Shalev I , Schilling B , Belsky DW 
Published: September 2021

ABSTRACTCalorie restriction (CR) slows aging and increases healthy lifespan in model organisms. We tested if CR slowed biological aging in humans using DNA methylation analysis of blood samples from N=197 participants in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) randomized controlled trial. We quantified CR effects on biological aging by comparing change scores for six epigenetic-clock and Pace-of-Aging measures between n=128 CR-group and n=69 ad-libitum-control-group participants at 12- and 24-month follow-ups. CR effects were strongest for DunedinPACE Pace of Aging (12-month Cohen’s d=0.3; 24-month Cohen’s d=0.2, p<0.01 for both), followed by DunedinPoAm and the GrimAge epigenetic clock, although effects for these measures were not statistically different from zero (p>0.08). CR effects for other epigenetic clocks were in the opposite direction (all p>0.15). CALERIE intervention slowed Pace of Aging but showed minimal effect on epigenetic clocks hypothesized to reflect longer term accumulation of aging burden.
miRNAs Copy Number Variations repertoire as hallmark indicator of cancer species predisposition
Authors: Vischioni Chiara , Bove Fabio , Mandreoli Federica , Martoglia Riccardo , Pisi Valentino , Taccioli Cristian 
Published: September 2021

AbstractAging is one of the hallmarks of multiple human diseases, including cancer. However, the molecular mechanisms associated with high longevity and low cancer incidence percentages characterizing long-living organisms have not been fully understood yet. In this context, we hypothesized that variations in the number of copies (CNVs) of specific genes may protect some species from cancer onset. Based on the statistical comparison of gene copy numbers within the genomes of cancer -prone and -resistant organisms, we identified novel gene targets linked to the tumor predisposition of a species, such as CD52, SAT1 and SUMO protein family members. Furthermore, for the first time, we were able to discover that, considering the entire genome copy number landscape of a species, microRNAs (miRNAs) are among the most significant gene families enriched for cancer progression and predisposition. However, their roles in ageing and cancer resistance from a comparative perspective remains largely unknown. To this end, we identified through bioinformatics analysis, several alterations in miRNAs copy number patterns, represented by duplication of miR-221, miR-222, miR-21, miR-372, miR-30b, miR-30d and miR-31 among others. Therefore, our analysis provides the first evidence that an altered copy number miRNAs signature is able to statistically discriminate species more susceptible to cancer than those that are tumor resistant, helping researchers to discover new possible therapeutic targets involved in tumor predisposition.
Prevalence and risk factors for in-school transmission of SARS-CoV-2 in Massachusetts K-12 public schools, 2020-2021
Authors: Nelson Sandra B. , Dugdale Caitlin M. , Bilinski Alyssa , Cosar Duru , Pollock Nira R. , Ciaranello Andrea 
Published: September 2021

AbstractIntroductionThe SARS-CoV-2 secondary attack rate (SAR) in schools is low when mitigation measures are adopted, Data on the relative impact of such strategies are limited. We evaluated the SARS-CoV-2 SAR in Massachusetts schools during 2020-21 and factors associated with transmission risk.MethodsIn a convenience sample of 25 Massachusetts public K-12 school districts, de-identified information about SARS-CoV-2 cases and their school-based contacts was reported using a standardized contact-tracing tool. Index cases were included if they were in school while infectious. SAR was defined as the proportion of in-school contacts acquiring SARS-CoV-2 infection and designated as possible or probable in-school transmission by school-based teams. We compared exposure-specific SAR using unadjusted risk ratios (RR) with 95% confidence intervals (CI); p-values were calculated using Fishers exact tests.ResultsEight districts (70 schools with >33,000 enrolled students) participated. There were 435 index cases and 1,771 school-based contacts (Table 1). Most contacts (1327/1771 [75%]) underwent SARS-CoV-2 testing and 39/1327 (2.9%) contacts tested positive. Of 39 positive contacts, 10 (25.6%) had clear out-of-school exposures and were deemed not in-school transmissions, so were excluded from further calculations. Twenty-nine (74.4%) contacts were deemed possible or probable in-school transmissions, resulting in an in-school SAR of 2.2%. Of the 29 in-school transmissions, 6 (20.7%) were staff-to-staff, 7 (24.1%) were staff-to-student, 3 (10.3%) were student-to-staff, and 13 (44.8%) were student-to-student; 6 (20.7%) occurred from index cases attending work/school while symptomatic. The unadjusted SAR (Table 2) was significantly higher if the index case was a staff member versus a student (RR 2.18, 95% CI 1.06-4.49; p=0.030), if the index case was identified via in-school contact tracing versus via school-based asymptomatic testing (RR 8.44, 95% CI 1.98-36.06; p=0.001), if the exposure occurred at lunch versus elsewhere (RR 5.74, 95% CI 2.11-15.63; p<0.001; all lunch transmissions were staff-to-staff), and if both parties were unmasked versus both masked (RR 6.98, 95% CI 3.09-15.77; p<0.001). For students, SAR did not differ by grade level.ConclusionsSecondary attack rates for SARS-CoV-2 were low in public school settings with comprehensive mitigation measures in place before the emergence of the delta variant; lack of masking and staff-to-staff dining were associated with increased risk.
Initial emergency department vital signs may predict PICU admission in pediatric patients presenting with asthma exacerbation
Authors: Freedman Michael S , Forno Erick 
Published: September 2021

ABSTRACTObjectiveSevere asthma exacerbations account for a large share of asthma morbidity, mortality, and costs. Here, we aim to identify early predictive factors for pediatric intensive care unit (PICU) admission that could help improve outcomes.MethodsWe performed a retrospective observational study of 6,014 emergency department (ED) encounters at a large children’s hospital, including 95 (1.6%) resulting in PICU admission between 10/1/2015 and 8/31/2017 with ICD9/ICD10 codes for “asthma,” “bronchospasm,” or “wheezing”. Vital signs and demographic information were obtained from EHR data and analyzed for each encounter. Predictive factors were identified using adjusted regression models, and our primary outcome was PICU admission.ResultsHigher mean heartrates (HR) and respiratory rates (RR) and lower SpO2 within the first hour of ED presentation were independently associated with PICU admission. Odds of PICU admission increased 63% for each 10-beats/minute higher HR, 97% for each 10-breaths/minute higher RR, and 34% for each 5% lower SpO2. A binary predictive index using 1-hour vitals yielded OR 11.7 (95%CI 7.4-18.3) for PICU admission, area under the receiver operator characteristic curve (AUROC) 0.82 and overall accuracy of 81.5%. Results were essentially unchanged (AUROC 0.84) after adjusting for asthma severity and initial ED management. In combination with a secondary standardized clinical asthma distress score, positive predictive value increased by seven-fold (5.9% to 41%).ConclusionsA predictive index using HR, RR and SpO2 within the first hour of ED presentation accurately predicted PICU admission in this cohort. Automated vital signs trend analysis may help identify vulnerable patients quickly upon presentation.
The importance of sustained compliance with physical distancing during COVID-19 vaccination rollout
Authors: Teslya Alexandra , Rozhnova Ganna , Pham Thi Mui , van Wees Daphne A , Nunner Hendrik , Godijk Noortje G , Bootsma Martin , Kretzschmar Mirjam E 
Published: September 2021

Mass vaccination campaigns against SARS-CoV-2 are ongoing in many countries with increasing vaccination coverage enabling relaxation of lockdowns. Vaccination rollout is frequently supplemented with advisory from public health authorities for continuation of physical distancing measures. Compliance with these measures is waning while more transmissible virus variants such as Alpha (B.1.1.7) and Delta (B.1.617.2) have emerged. In this work, we considered a population where the waning of compliance depends on vaccine coverage. We used a SARS-CoV-2 transmission model which captures the feedback between compliance, infection incidence, and vaccination coverage to investigate factors that contribute to the increase of the prevalence of infection during the initial stages of the vaccination rollout as compared to no vaccination scenario. We analysed how the vaccine uptake rate affects cumulative numbers of new infections three and six months after the start of vaccination. Our results suggest that the combination of fast waning compliance in non-vaccinated population, low compliance in vaccinated population and more transmissible virus variants may result in a higher cumulative number of new infections than in a situation without vaccination. These adverse effects can be alleviated if vaccinated individuals do not revert to pre-pandemic contact rates, and if non-vaccinated individuals remain compliant with physical distancing measures. Both require convincing, clear and appropriately targeted communication strategies by public health authorities.Significance StatementSARS-CoV-2 vaccination campaigns are in progress in many countries around the world. As the vaccination coverage increases, the compliance with physical distancing measures aimed at reducing virus transmission may decline. Using a socio-epidemiological model we identify factors that are the drivers of increased transmission when SARS-CoV-2 prevalence is higher than the projected prevalence without vaccination. To maximize the benefits of vaccination campaigns, compliance in vaccinated and non-vaccinated groups should be targeted prioritizing one group over the other depending on the vaccination rate, the efficacy of vaccine in blocking the infection, and the circulating variant.