bluuebunny/crossref_metadata_2025 huggingface dataset:
Grey matter morphometric biomarkers for classifying early schizophrenia and PD psychosis: a multicentre study
Authors: Knolle Franziska , Arumugham Shyam S. , Barker Roger A. , Chee Michael W.L. , Justicia Azucena , Kamble Nitish , Lee Jimmy , Liu Siwei , Lenka Abhishek , Lewis Simon J.G. , Murray Graham K. , Pal Pramod Kumar , Saini Jitender , Szeto Jennifer , Yadav Ravi , Zhou Juan H. , Koch Kathrin
Published: May 2022

Psychotic symptoms occur in a majority of schizophrenia patients, and in approximately 50% of all Parkinson’s disease (PD) patients. Altered grey matter (GM) structure within several brain areas and networks may contribute to their pathogenesis. Little, however, is known about transdiagnostic similarities when psychotic symptoms occur in different disorders, such as schizophrenia and PD.

The present study investigated a large, multicenter sample containing 722 participants: 146 patients with first episode psychosis, FEP; 106 individuals at-risk mental state for developing psychosis, ARMS; 145 healthy controls matching FEP and ARMS, Con-Psy; 92 PD patients with psychotic symptoms, PDP; 145 PD patients without psychotic symptoms, PDN; 88 healthy controls matching PDN and PDP, Con-PD. We applied source-based morphometry in association with receiver operating curves (ROC) analyses to identify common GM structural covariance networks (SCN) and investigated their accuracy in identifying the different patient groups. We assessed group-specific homogeneity and variability across the different networks and potential associations with clinical symptoms.

SCN-extracted GM values differed significantly between FEP and Con-Psy, PDP and Con-PD as well as PDN and Con-PD, indicating significant overall grey matter reductions in PD and early schizophrenia. ROC analyses showed that SCN-based classification algorithms allow good classification (AUC∼0.80) of FEP and Con-Psy, and fair performance (AUC∼0.72) when differentiating PDP from Con-PD. Importantly, best performance was found in partly the same networks including the precuneus. Finally, reduced GM volume in SCN with increased variability was linked to increased psychotic symptoms in both FEP and PDP.

Alterations within selected SCNs may be related to the presence of psychotic symptoms in both early schizophrenia and PD psychosis, indicating some commonality of underlying mechanisms. Furthermore, results provide first evidence that GM volume within specific SCNs may serve as a biomarker for identifying FEP and PDP.
Accuracy and Glycemic Efficacy of Continuous Glucose Monitors in Critically Ill COVID-19 Patients: a Retrospective Study
Authors: Boeder Schafer , Kobayashi Emily , Ramesh Gautam , Serences Brittany , Kulasa Kristen , Majithia Amit R.
Published: May 2022

Background

Continuous Glucose Monitoring (CGM) is approved for insulin dosing decisions in the ambulatory setting, but not currently for inpatients. CGM has the capacity to reduce patient-provider contact in inpatients with coronavirus disease 2019 (COVID-19), thus potentially reducing in hospital virus transmission. However, there are sparse data on the accuracy and efficacy of CGM to titrate insulin doses in inpatients.

Methods

Under an emergency use protocol, CGM (Dexcom G6) was used alongside standard point-of-care (POC) glucose measurements in patients critically ill from complications of COVID-19 requiring intravenous (IV) insulin. Glycemic control during IV insulin therapy was retrospectively assessed comparing periods with and without adjunctive CGM use. Accuracy metrics were computed and Clarke Error Grid analysis performed comparing CGM glucose values with POC measurements.

Results

24 critically ill patients who met criteria for emergency use of CGM resulted in 47333 CGM and 5677 POC glucose values. During IV insulin therapy, individuals’ glycemic control improved when CGM was used (mean difference -30.2 mg/dL). Among 2194 matched CGM:POC glucose pairs a high degree of concordance was observed with a MARD of 14.8% and 99.5% of CGM:POC pairs falling in Zones A and B of the Clarke Error Grid.

Conclusions

CGM use in critically ill COVID-19 patients improved glycemic control during IV insulin therapy. CGM glucose data were highly concordant with POC glucose during IV insulin therapy in critically ill patients suggesting that CGM could substitute for POC measurements in inpatients thus reducing patient-provider contact and mitigating infection transmission.
Automated Prioritization of Sick Newborns for Whole Genome Sequencing Using Clinical Natural Language Processing and Machine Learning
Authors: Peterson Bennet , Hernandez Javier , Hobbs Charlotte , Jenkins Sabrina Malone , Moore Barry , Juarez Edwin , Zoucha Samuel , Kobayashi Erica Sanford , Bainbridge Matthew N. , Oriol Albert , Brunelli Luca , Kingsmore Stephen , Yandell Mark
Published: May 2022

Background

Rapidly and efficiently identifying critically ill infants for WGS is a costly and challenging task currently performed by scarce, highly trained experts, and is a major bottleneck for application of WGS in the NICU. Automated means to prioritize patients for WGS are thus badly needed.

Methods

Institutional databases of Electronic Health Records (EHRs) are logical starting points for identifying patients with undiagnosed Mendelian diseases. We have developed automated means to prioritize patients for Rapid and Whole Genome Sequencing (rWGS and WGS) directly from clinical notes. Our approach combines a Clinical Natural Language Processing (CNLP) workflow with a machine learning-based prioritization tool we call the Mendelian Phenotype Search Engine (MPSE).

Results

MPSE accurately and robustly identified NICU patients selected for WGS by clinical experts from Rady Children’s Hospital in San Diego (AUC 0.86) and the University of Utah (AUC 0.85). In addition to effectively identifying patients for WGS, MPSE scores also strongly prioritize diagnostic cases over non-diagnostic cases, with projected diagnostic yields exceeding 50% throughout the first and second quartiles of score-ranked patients.

Conclusions

Our results indicate that an entirely automated pipeline for selecting acutely ill infants in neonatal intensive care units (NICU) for WGS can meet or exceed diagnostic yields obtained through current selection procedures, which require time-consuming manual review of clinical notes and histories by specialized personnel.
Phase I study of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B
Authors: Orozco Natalia Martin , Vale Noah , Mihic Alan , Amor Talya , Reiter Lawrence , Arita Yuko , Samson Reuben , Hu Queenie , Gingras Anne-Claude , Sorenson Brad , Marcusson Eric G. , Patel Piyush
Published: May 2022

PTX-COVID19-B mRNA vaccine encodes for SARS-CoV-2 Spike protein G614 variant and lacks the proline-proline (986-987 position) mutation present in other COVID-19 vaccines. This Phase 1 observer-blinded, randomized, placebo-controlled, ascending dose study evaluated the safety, tolerability, and immunogenicity of two doses of PTX-COVID19-B vaccine in healthy seronegative adults. Participants received two intramuscular doses, 4 weeks apart, of 16-μg, 40-μg, or 100-μg PTX-COVID19-B. Adverse events were generally mild to moderate, self-resolving, and transient. The most common solicited local and systemic adverse event was pain at the injection site and headache, respectively. After the first immunization, all participants seroconverted, producing high titers of anti-receptor-binding-domain, anti-Spike, and neutralizing antibodies, including neutralizing antibodies against the ancestral viral strain and the Alpha, Beta, and Delta variants of concern, in a dose-dependent way, further increasing over 10-20 times after the second dose. All tested doses of PTX-COVID19-B were safe, well-tolerated, and provided a strong immunogenicity response. The 40-μg dose showed fewer adverse reactions than the 100-μg dose, supporting further investigation of the 40-μg dose.

Clinical Trial Registration

ClinicalTrials.gov identifier: NCT04765436 (https://clinicaltrials.gov/ct2/show/NCT04765436)
Factors influencing the sustainability of homestead vegetable production intervention in Rufiji, Tanzania: A cross-sectional mixed methods study
Authors: Mlalama Killian N , Matemu Athanasia , Kosia Ephraim , Canavan Chelsey R , Bellows Alexandra L , Blakstad Mia , Noor Ramadhani A , Kinabo Joyce , Fawzi Wafaie W , Masanja Honorati , Mosha Dominic
Published: May 2022

Background

There is growing evidence that home vegetable gardening interventions improve food security and nutrition outcomes at the family level. This study assessed factors influencing the sustainability of homestead vegetable production intervention in Rufiji district, Tanzania, one year after the cessation of external support.

Methods

This was a cross-sectional study using both quantitative and qualitative data collection methods. A total of 247 randomly selected women from households who participated in the homestead vegetable intervention were interviewed using a structured questionnaire. The study held four focus group discussions with women from households that participated in the intervention, and four In-Depth interviews with two extension workers, one community health worker, and one agriculture district officer. Multiple logistic regression for quantitative data and thematic analysis for qualitative data was conducted.

Results

About 20.24% (50/247) of households sustained homestead vegetable production for one year after the intervention phased out. Lack of seeds (adjusted OR=1.26: CI=0.39-0.89) and either manure or fertilizers (adjusted OR=1.69: CI =1.08-2.63) were significant factors influencing the sustainability of homesteads vegetable production. In the Focus Group discussions (FGDs) and In-Depth Interview (IDIs), all participating women and extension workers reported high cost of water, destruction from free-grazing animals, agriculture pests and diseases, poor soil fertility, shortage of seeds, and lack of capital affected homestead vegetable production sustainability.

Conclusion

Existing individual, community, and system challenges influence the sustainability of external-funded agriculture and nutrition interventions. The study findings underscore the importance of community authorities, scientists, and policymakers in having a well-thought sustainability plan in all promising external-funded interventions.
PCSK6 and Survival in Idiopathic Pulmonary Fibrosis
Authors: Oldham Justin M. , Allen Richard J. , Lorenzo-Salazar Jose M. , Molyneaux Philip L. , Ma Shwu-Fan , Joseph Chitra , Kim John S. , Guillen-Guio Beatriz , Hernández-Beeftink Tamara , Kropski Jonathan A. , Huang Yong , Lee Cathryn T. , Adegunsoye Ayodeji , Pugashetti Janelle Vu , Linderholm Angela L. , Vo Vivian , Strek Mary E. , Jou Jonathan , Muñoz-Barrera Adrian , Rubio-Rodriguez Luis A. , Hubbard Richard , Hirani Nik , Whyte Moira K.B. , Hart Simon , Nicholson Andrew G. , Lancaster Lisa , Parfrey Helen , Rassl Doris , Wallace William , Valenzi Eleanor , Zhang Yingze , Mychaleckyj Josyf , Stockwell Amy , Kaminski Naftali , Wolters Paul J. , Molina-Molina Maria , Fahy William A. , Martinez Fernando J. , Hall Ian P. , Tobin Martin D. , Maher Toby M. , Blackwell Timothy S. , Yaspan Brian L. , Jenkins R Gisli , Flores Carlos , Wain Louise V , Noth Imre
Published: May 2022

Rationale

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by limited treatment options and high mortality. Novel therapies and prognostic biomarkers are needed.

Objective

To identify and validate molecular determinants of IPF survival.

Methods

A staged genome-wide association study (GWAS) was performed using paired genomic and survival data. Stage I cases were drawn from centers across the US and Europe and stage II cases from Vanderbilt University. Cox proportional hazards regression was used to identify gene variants associated with differential transplant-free survival (TFS). Stage I variants with nominal significance (p<5×10−5) were advanced for stage II testing and meta-analyzed to identify those reaching genome-wide significance (p<5×10−8). Downstream analyses were performed for genes and proteins associated with variants reaching genome-wide significance.

Main Results

After quality controls, 1481 stage I cases and 397 stage II cases were included in the analysis. After filtering, 9,075,629 variants were tested in stage I, with 158 meeting advancement criteria. Four variants associated with TFS with consistent effect direction were identified in stage II, including one in an intron of proprotein convertase subtilisin/kexin type 6 (PCSK6) reaching genome-wide significance (HR 4.11; 95%CI 2.54-6.67; p=9.45×10−9). PCSK6 protein was highly expressed in IPF lung parenchyma and negatively correlated with survival. Peripheral blood PCSK6 gene expression and plasma concentration were associated with reduced transplant-free survival.

Conclusions

We identified four novel variants associated with IPF survival, including one in PCSK6 that reached genome-wide significance. Downstream analyses suggested that PCSK6 protein may serve as prognostic biomarker in IPF and potential therapeutic target.
HOXA Amplification Defines a Genetically Distinct Subset of Angiosarcomas
Authors: Xie Hongbo Michael , Bernt Kathrin M.
Published: May 2022

Angiosarcoma is a rare, devastating malignancy with few curative options for disseminated disease. We analyzed a recently published genomic data set of 48 angiosarcomas and noticed recurrent amplifications of HOXA cluster genes in 33% of patients. HOXA genes are master regulators of embryonic vascular development and adult neovascularization, which provides a molecular rationale to suspect that amplified HOXA genes act as oncogenes in angiosarcoma. HOXA amplifications typically affected multiple pro-angiogenic HOXA genes and co-occurred with amplifications of CD36 and KDR, whereas the overall mutation rate in these tumors was relatively low. HOXA amplifications were found most commonly in angiosarcomas located in the breast, and were rare in angiosarcomas arising in sun-exposed areas on the head, neck, face and scalp. Our data suggest that HOXA amplified angiosarcoma is a distinct molecular subgroup. Efforts to develop therapies targeting oncogenic HOX gene expression in AML and other sarcomas may have relevance for HOXA amplified angiosarcoma.
Time-specific effects of a multifaceted intervention on accelerometer-measured physical activity in primary school children: A cluster-randomized controlled trial
Authors: Liu Zheng , Yue Zhi-Han , Wen Li-Ming , Zhao Jinfeng , Zhou Shuang , Gao Ai-Yu , Zhang Fang , Wang Hai-Jun
Published: May 2022

Background

It is unclear whether intervention effects on school-aged children’s physical activity differ across specific periods of the week or day. This study aimed to assess the time-specific intervention effects on accelerometer-measured physical activity in primary school children.

Methods

This was a nested study in a cluster-randomized controlled trial conducted from September 2018 to June 2019 in China. The intervention group included 4 schools (119 children) and the control group included 4 schools (99 children) in Beijing. The obesity prevention intervention engaged schools and families to improve children’s physical activity. Outcome measures included accelerometer-assessed intensity and amounts of physical activity within specific periods of a week (weekday/weekend day) or a day (in-school/out-of-school periods). Linear mixed models were used to estimate intervention effects. Subgroup analyses were also conducted to examine potential moderators including sex, age, body mass index, physical activity, and accelerometer compliance.

Results

The intervention lead to an increase in time engaged in moderate-to-vigorous physical activity (MVPA) within in-school periods of a day (adjusted mean difference: 0.54 minutes/hour; 95% confidence interval: 0.13, 0.94, P = 0.012) but it did not improve physical activity within out-of-school periods (P > 0.05) compared with the control group. There was no difference in the effect size across most of the moderators except for age, as younger children appeared to benefit more from the intervention in the improvement of in-school MVPA (Pinteraction = 0.035). No between-group differences were observed in physical activity within the whole weekday or weekend day (P > 0.05).

Conclusion

The intervention effectively increased MVPA within in-school periods but did not improve out-of-school physical activity. Findings support the tailoring of intervention components to specific periods of a day to improve school-aged children’s whole pattern of physical activity.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT03665857
Large-Scale Longitudinal Comparison of Urine Cytological Classification Systems Reveals Potential Early Adoption of The Paris System Criteria
Authors: Levy Joshua J. , Liu Xiaoying , Marotti Jonathan D. , Kerr Darcy A. , Gutmann Edward J. , Glass Ryan E. , Dodge Caroline P. , Vaickus Louis J.
Published: May 2022

Urine cytology is used to screen for urothelial carcinoma in patients with hematuria or risk factors (e.g., smoking, industrial dye exposure) and is an essential clinical triage and longitudinal monitoring tool for patients with known bladder cancer. However, urine cytology is semi-subjective and thus susceptible to issues including specimen quality, inter-observer variability, and “hedging” towards equivocal (“atypical”) diagnoses. These factors limit the predictive value of urine cytology and increase reliance on invasive procedures (cystoscopy). The Paris System for Reporting Urine Cytology (TPS) was formulated to provide more quantitative/reproducible endpoints with well-defined criteria for urothelial atypia. TPS is often compared to other assessment techniques to justify its adoption. TPS results in decreased use of the atypical category and better reproducibility. Previous manuscripts comparing diagnoses pre- and post-TPS lacked a longitudinal component and thus failed to consider temporal differences between diagnoses made under prior systems and TPS. By aggregating across time, studies may underestimate the magnitude of differences between assessment methods. We conducted a large-scale longitudinal reassessment of urine cytology using TPS criteria from specimens collected from 2008 to 2018, prior to the mid-2018 adoption of TPS at an academic medical center. Findings indicate that differences in atypical assignment were largest at the start of the period and these differences progressively decreased towards insignificance just prior to TPS implementation. This finding suggests that cytopathologists had begun to utilize the quantitative TPS criteria prior to official adoption, which may more broadly inform adoption strategies, communication, and understanding for evolving classification systems in cytology.
The mortality risk factor of severe community-acquired pneumonia (SCAP) patients with Sepsis: a retrospective study
Authors: Geng Cong , Jin Jun , Yu Zhejun
Published: May 2022

Objectives

Sepsis is one of the most common comorbidities in severe community-acquired pneumonia (SCAP) patients. We aimed to investigate the characteristics and mortality risk factors of SCAP patients hospitalized with Sepsis.

Design

A retrospective, single-centre study.

Setting

This study was conducted at a tertiary hospital in Southern China.

Participants

A total of 119 patients with SCAP, aged 17 years or older, were treated in the Integrated intensive care unit from 1 January 2018 to 30 December 2020.

Interventions

none.

Outcome

180-day mortality was the primary outcome.

Results

119 patients were divided into the survivors (83 patients,69.75%), and the non-survivors (36 patients,30.25%). There are more pronounced inflammatory responses and respiratory problems at the beginning of the disease in non-survivors, requiring stronger respiratory and circulatory support. The CURB-65 score was a better predictor of mortality than the PSI and APACHE2 scores, AUCs of CURB-65: OR 0.744, p<0.005. For the entire treatment cycle, the non-survivors had a longer duration of persistent fever, required continuous and repeated airway intervention, and a longer duration of Vasopressor support (P<0.001). SCAP with bacterial infection as the onset, or secondary bacterial infection had a poor prognosis (P=0.018). The non-survivors had more use of different types of antimicrobials (P<0.05), because of Multidrug-resistant (MDR) organisms. And have faced more antifungal treatment failures (P=0.006). The mortality risk factors were comorbid with a duration of Vasopressors support, duration of persistent fever, age, numbers of antimicrobials for MDR organisms, CURB-65 score and duration of Neuromuscular Blocking Agents (NMBAs) (OR=1.234, OR=1.158, OR=1.084, OR=6.484, OR=3.386, OR=1.505, p<0.005, respectively).

Conclusion

Dynamic monitoring of the duration of patients’ abnormal indicators can help predict the prognosis. Age≥65.5 years, fever duration ≥9.5 days, number of antimicrobials for MDR organisms ≥2 types, longer NMBAs and Vasopressors use, and higher CURB-65 score were mortality risk factors in SCAP-Sepsis patients.

strengths and limitations of this study

We evaluated dynamic monitoring of the duration of patients’ abnormal indicators can help predict the prognosis. To the best of our knowledge, a very few studies had done a dynamic monitoring of the duration of patients’ abnormal indicators in the field of SCAP with Sepsis. The retrospective nature of the study was a limitation, statistical data including respiratory support in later treatment, can be further quantified.
Assessing the feasibility of sustaining SARS-CoV-2 local containment in China in the era of highly transmissible variants
Authors: Wang Yan , Sun Kaiyuan , Feng Zhaomin , Yi Lan , Wu Yanpeng , Liu Hengcong , Wang Quanyi , Ajelli Marco , Viboud Cécile , Yu Hongjie
Published: May 2022

We developed a spatially structured, fully stochastic, individual-based SARS-CoV-2 transmission model to evaluate the feasibility of sustaining SARS-CoV-2 local containment in mainland China considering currently dominant Omicron variants, China’s current immunization level, and non-pharmaceutical interventions (NPIs). We also built a statistical model to estimate the overall disease burden under various hypothetical mitigation scenarios. We found that due to high transmissibility, neither Omicron BA.1 or BA.2 could be contained by China’s pre-Omicron NPI strategies which were successful prior to the emergence of the Omicron variants. However, increased intervention intensity, such as enhanced population mobility restrictions and multi-round mass testing, could lead to containment success. We estimated that an acute Omicron epidemic wave in mainland China would result in significant number of deaths if China were to reopen under current vaccine coverage with no antiviral uptake, while increasing vaccination coverage and antiviral uptake could substantially reduce the disease burden. As China’s current vaccination has yet to reach high coverage in older populations, NPIs remain essential tools to maintain low levels of infection while building up protective population immunity, ensuring a smooth transition out of the pandemic phase while minimizing the overall disease burden.
Assessing the health risk of living near composting facilities on lung health, fungal and bacterial disease in cystic fibrosis: a UK CF Registry study
Authors: Khan Muhammad Saleem , Douglas Philippa , Hansell Anna L. , Simmonds Nicholas J. , Piel Frédéric B.
Published: May 2022

Aim

To explore the health risk of living near permitted composting sites (PCSs) on disease severity in children and adults with cystic fibrosis (CF) across the UK.

Methods

A semi-individual cross-sectional study was used to examine risk of disease severity in people with CF (pwCF) within and beyond 4 km of PCSs in the UK in 2016. All pwCF registered in the UK CF Registry were eligible for this study. Linear and Poisson regressions, adjusted for age, gender, genotype, BMI, Pseudomonas aeruginosa (P.aeruginosa) and deprivation, were used to quantify associations between distance to a PCS and percent predicted forced expiratory volume in one second (ppFEV1), pulmonary exacerbations (#IVdays), and fungal and bacterial infections.

Results

The mean age of the 9,361 pwCF (3,931 children and 5,430 adults) studied was 20.1 (SD=14.1) years; 53.3% were male; and 49.2% were homozygous F508del. Over 10% of pwCF (n=1,015) lived within 4 km of a PCS. We found no statistically significant difference in ppFEV1 and #IVdays/year in children. However, in adults, ppFEV1 was −1.07% lower (95% confidence interval (CI): −2.29%, 0.16 %) and #IVdays/year were 1.02 day higher (95%CI: 1.01, 1.04) within 4 km of a PCS. Furthermore, there were statistically significant differences in mean ppFEV1 in CF adults with Aspergillus fumigatus (54.5% vs 59.7%, p=0.001) and Candida spp. (54.8% vs 59.0%, p=0.001) residing within 4 km of a PCS. No associations were identified for allergic bronchopulmonary aspergillosis, P.aeruginosa or Staphylococcus aureus.

Conclusions

This novel national study provides evidence that adults with CF living near a PCS may experience small reductions in lung function, an increased risk of pulmonary exacerbations, and more frequent fungal infections. If confirmed by studies using refined exposure assessment methods accounting for bioaerosol dispersion, these results could have important implications for the living environment of pwCF.
Clinical characteristics of COVID-19 patients admitted to Intensive Care Unit in Panama during the first pandemic wave admissions in 2020
Authors: Vega Silvio , Blizniak Artur Gomez , Ballanis Simón Theoktisto , Cisneros Gabriel , Villalobos David , Armuelles Ana Kathleen , Moreno Luis , Fusumada Francis , Gonzalez Johanna , Romero Emilio , Torres-Atencio Ivonne , Cubilla-Batista Idalina , Goodridge Amador
Published: May 2022

The severe acute respiratory syndrome Coronavirus 2 (SARS COV-2) caused a global pandemic of COVID-19. Most of people affected are admitted to hospital with various grades of ADRS. A small proportion of these patients requires intensive care unit management and treatment. However not all of them survive. This study aims to describe the epidemiological and clinical characteristics of patients admitted to the intensive care units in Panama main hospital in the first six months of pandemic with available information. Special focus has been oriented to blood and respiratory biomarkers to correlate with survivors and non-survivors. Our results show that patients between 56-75 years old, with hypertension, obesity, and diabetes comorbid conditions are more likely to die in intensive care units. Regarding the PaFi ratio, we observed a greater proportion of non-survivor with values less than 200. The triglycerides, urea nitrogen, creatinine and procalcitonin levels resulted significantly higher in those non survivors. During clinical management, half of patient that were administered Tocilizumab did not survived. These results support the notion that age, comorbidities as well as therapeutic management of patient in intensive care units contribute to the final outcome. We recommend reinforcing patient care strategy, especially in those patients with clinical conditions that favor fatal outcomes.
High but Short-lived anti-SARS-CoV2 neutralizing, IgM, IgA, and IgG levels among mRNA-vaccinees compared to naturally-infected participants
Authors: Abou-Saleh Haissam , Abo-Halawa Bushra Y. , Younes Salma , Younes Nadin , Al-Sadeq Duaa W. , Shurrab Farah M. , Liu Na , Qotba Hamda , Al-Dewik Nader , Ismail Ahmad H. , Yassine Hadi M. , Abu-Raddad Laith J. , Nasrallah Gheyath K.
Published: May 2022

1.

Background

Waning of protection against emerging SARS-CoV-2 variants by pre-existing antibodies elicited due to current vaccination or natural infection is a global concern. Whether this is due to waning of immunity to SARS-COV-2 remains unclear.

Aim

We aimed to investigate dynamics of antibody isotype responses among vaccinated naïve (VN) and naturally infected (NI) individuals.

Methods

We followed up antibody levels in COVID-19 mRNA-vaccinated subjects without prior infection (VN, n=100) at two phases: phase-I (P-I) at ∼1.4 and phase-II (P-II) at ∼5.3 months. Antibody levels were compared to those of unvaccinated and naturally infected subjects (NI, n=40) at ∼1.7 (P-1) and 5.2 (P-II) months post-infection. Neutralizing antibodies (NTAb), anti-S-RBD-IgG, -IgM, and anti-S-IgA isotypes were measured.

Results

VN group produced significantly greater antibody responses (p<0.001) than NI group at P-I except for IgM. In VN group, a significant waning in antibody response was observed in all isotypes. There was about ∼ a 4-fold decline in NTAb levels (p<0.001), anti-S-RBD-IgG (∼5-folds, p<0.001), anti-S-RBD-IgM (∼6-folds, p<0.001), and anti-S1-IgA (2-folds, p<0.001). In NI group, a significant but less steady decline was notable in NTAb (∼1-folds, p<0.001), anti-S-RBD IgG (∼1-fold, p=0.005), and S-RBD-IgM (∼2-folds, p<0.001). Unlike VN group, NI group mounted a lasting anti-S1-IgA response with no significant decline. Anti-S1-IgA levels which were ∼3 folds higher in VN subjects compared to NI in P-1 (p<0.001), dropped to almost same levels, with no significant difference observed between the two groups in P-II.

Conclusion

While double dose mRNA vaccination boosted antibody levels, this “boost” was relatively short-lived in vaccinated individuals.
Association between environmental levels of PM2.5 and mortality from SARS-CoV-2 in inhabitants of Mexico City
Authors: Armando Alberto Moreno-Santillan , Rodolfo Rivas-Ruiz , Rocio Fuentes-Valdivieso , Ivonne Anali Roy-Garcia
Published: May 2022

Objective

To evaluate the association between exposure to environmental levels of PM2.5 and mortality from SARS-CoV-2 in inhabitants of Mexico City.

Material and methods

A secondary analysis with the total number of deaths from COVID-19 in residents of Mexico City as well as 25 municipalities in the interior of the Republic was carried out. Environmental levels of PM2.5 were between 2018 and 2021. Bivariate analysis and multivariate logistic regression were performed.

Results

A total of 1,083,175 cases of COVID-19 were included, with 57,384 deaths (5.3%), of which 30,561 were in residents with exposure to more than 20 μg/m3 of PM2.5 (OR 1.27, CI95%: 1.25 to 1.29). When performing the multivariate analysis, an OR of 1.39 (CI95%: 1.36 to 1.43) was observed.

Conclusions

Chronic exposure to elevated levels of PM2.5 is associated with increased death risk from COVID-19.
Identification of non-small cell lung cancer (NSCLC) patients who benefit from treatment beyond progression with pembrolizumab from individual lesion response dynamics
Authors: Qi Timothy , Cao Yanguang
Published: May 2022

Background

Pembrolizumab is the recommended first-line treatment for non-small cell lung cancer (NSCLC) with no driver alterations and PD-L1 Tumor Proportion Score (TPS) ≥ 50%. Salvage therapies for patients who develop resistance in this setting are limited. Several retrospective studies have highlighted a subset of patients who benefit from pembrolizumab treatment beyond progression (TBP), but these results have yet to be validated in a rigorous prospective study.

Methods

Due to the heterogeneity of within-patient responses to pembrolizumab, many patients can experience progressive disease while some of their lesions are still shrinking. We employed nonlinear mixed-effects modeling and virtual clinical trial simulations to evaluate the risk of unconditionally switching all progressors to salvage chemotherapy and to identify the subset of patients likely to benefit from pembrolizumab TBP. By using > 25,000 radiographic lesion diameter measurements from > 500 patients, we simulated individual lesion responses to pembrolizumab, chemotherapy, and pembrolizumab treatment failure followed by pembrolizumab TBP or salvage chemotherapy. We then assessed the benefit of pembrolizumab and chemotherapy in combination and explored a potential mechanism of intrapatient drug synergy called lesion-level independent action (LLIA).

Results

Switching all progressors to salvage chemotherapy was suboptimal. Pembrolizumab TBP could extend progression-free survival (PFS) and control tumor burden more in nontarget progressors with fewer lesions prior to treatment initiation. Assuming LLIA but not patient-level independent action (PLIA) for combination therapy yielded longer PFS.

Conclusions

Pembrolizumab TBP may benefit a subset of patients with PD-L1-high, driver alteration-free NSCLC who experience nontarget progression, but prospective studies are warranted.
Early detection of fraudulent COVID-19 products from Twitter chatter
Authors: Sarker Abeed , Lakamana Sahithi , Liao Ruqi , Abbas Aamir , Yang Yuan-Chi , Al-Garadi Mohammed Ali
Published: May 2022

Social media have served as lucrative platforms for misinformation and for promoting fraudulent products for the treatment, testing and prevention of COVID-19. This has resulted in the issuance of many warning letters by the United States Food and Drug Administration (FDA). While social media continue to serve as the primary platform for the promotion of such fraudulent products, they also present the opportunity to identify these products early by employing effective social media mining methods. In this study, we employ natural language processing and time series anomaly detection methods for automatically detecting fraudulent COVID-19 products early from Twitter. Our approach is based on the intuition that increases in the popularity of fraudulent products lead to corresponding anomalous increases in the volume of chatter regarding them. We utilized an anomaly detection method on streaming COVID-19-related Twitter data to detect potentially anomalous increases in mentions of fraudulent products. Our unsupervised approach detected 34/44 (77.3%) signals about fraudulent products earlier than the FDA letter issuance dates, and an additional 6/44 (13.6%) within a week following the corresponding FDA letters. Our proposed method is simple, effective and easy to deploy, and do not require high performance computing machinery unlike deep neural network-based methods.
The Application of Trimetazidine in Healthy Individuals: A Systematic Review
Authors: Bezuglov Eduard , Shoshorina Maria , Zholinsky Andrey , Waśkiewicz Zbigniew , Emanov Anton , Morgans Ryland , Bertholz Vladislav , Zelenskaya Vasilisa , Lazarev Artemii , Sokolskaya Maria , Talibov Oleg
Published: May 2022

Background

Currently, there is no evidence to support TMZ administration aiming to enhance any parameter of physical performance or post-exercise recovery in healthy individuals of the general population and athletes.

Objective

Considering the lack of empirical data, from a scientific and practical perspective it would be interesting to identify research with high methodological quality that examines the effects of trimetazidine (TMZ) on healthy individuals of the general population and athletes of varying age.

Methods

Data sources included English articles that were searched by keywords in the PubMed and Scopus databases and the Cochrane Library and published prior to November 2022. Thus, a systematic review of the scientific literature was performed utilizing databases with a traditional PRISMA methodology. An initial search by keyword found 2673 publications and the screening process selected 66 articles, of which two articles met the inclusion criteria.

Results

Two trials examining the effect of TMZ on healthy members of the general population that were published in 2017 and 2019 were analyzed. Athletes were not recruited for this type of research.

Conclusions

Currently there are no data reporting a positive effect of TMZ on physical performance, post-exercise recovery, or other health parameters in members of the general population, while its administration is associated with the development of relatively common adverse effects.
Sex-specific associations of childhood socioeconomic position and trajectories of metabolic traits across early life: prospective cohort study
Authors: O’Neill Kate N , Bell Joshua A , Smith George Davey , Fraser Abigail , Howe Laura D , Kearney Patricia M , Robinson Oliver , Tilling Kate , Willeit Peter , O’Keeffe Linda M
Published: May 2022

Background

Socioeconomic inequalities in cardiovascular disease risk begin early in life and are more pronounced in females compared with males in later life but the causal atherogenic traits that may explain this are not well understood. We explored sex-specific associations between indicators of childhood socioeconomic position (SEP) and changes in molecular measures of systemic metabolism across early life.

Methods

Data were from offspring of the Avon Longitudinal Study of Parents and Children (ALSPAC), born in 1991/1992. Maternal education was the primary indicator of SEP with paternal education and household social class used as secondary indicators; all measures were collected through questionnaires administered to mothers at 32-weeks’ gestation of the offspring pregnancy. Concentrations of 148 metabolic traits were measured using nuclear magnetic resonance spectroscopy performed on plasma samples at ages 7 years (y), 15y, 18y and 25y among offspring. The sex-specific slope index of inequality (SII) in trajectories of metabolic traits across these ages was estimated using multilevel models.

Results

Between 6,010-6,537 participants with 10,055-12,543 repeated measures of metabolic traits from 7y to 25y were included. Lower maternal education was associated with more adverse levels of several atherogenic lipids and other key metabolic traits among females at age 7y, but not males. For instance, the SII for very small very-low-density lipoprotein (VLDL) concentrations was 0.16 SD (95% CI: 0.01, 0.30) among females and -0.02 SD (95% CI: -0.16, 0.13) among males at 7y. Between 7y and 25y, inequalities widened among females and emerged among males particularly for VLDL particle concentrations, plasma apolipoprotein B concentrations and inflammatory glycoprotein acetyls. For instance, at 25y the SII for very small VLDL concentrations was 0.36 SD (95% CI: 0.20, 0.52) and 0.22 SD (95% CI: 0.04, 0.40) among females and males respectively. Findings for secondary SEP indicators were broadly similar although associations of paternal education with key metabolic traits were weak and less consistent among males at 25y compared with associations of maternal education.

Conclusion

Socioeconomic inequalities in causal atherogenic lipids and other key metabolic traits such as markers of inflammation begin in childhood and strengthen in adolescence among females but only emerge in adolescence among males, leading to wider socioeconomic inequalities among females compared with males by 25y. Prevention of socioeconomic inequalities in cardiovascular disease risk requires a life course approach that begins at the earliest opportunity in the life course especially among females.
Decision trees for COVID-19 prognosis learned from patient data: Desaturating the ER with Artificial Intelligence
Authors: Bernaola Nikolas , de Lima Guillermo , Riaño Miguel , Llanos Lucia , Heili-Frades Sarah , Sanchez Olga , Lara Antonio , Plaza Guillermo , Carballo Cesar , Gallego Paloma , Larrañaga Pedro , Bielza Concha
Published: May 2022

Objectives

To present a model that enhances the accuracy of clinicians when presented with a possibly critical Covid-19 patient.

Methods

A retrospective study was performed with information of 5,745 SARS-CoV2 infected patients admitted to the Emergency room of 4 public Hospitals in Madrid belonging to Quirón Salud Health Group (QS) from March 2020 to February 2021. Demographics, clinical variables on admission, laboratory markers and therapeutic interventions were extracted from Electronic Clinical Records. Traits related to mortality were found through difference in means testing and through feature selection by learning multiple classification trees with random initialization and selecting the ones that were used the most. We validated the model through cross-validation and tested generalization with an external dataset from 4 hospitals belonging to Sanitas Hospitals Health Group. The usefulness of two different models in real cases was tested by measuring the effect of exposure to the model decision on the accuracy of medical professionals.

Results

Of the 5,745 admitted patients, 1,173 died. Of the 110 variables in the dataset, 34 were found to be related with our definition of criticality (death in <72 hours) or all-cause mortality. The models had an accuracy of 85% and a sensitivity of 50% averaged through 5-fold cross validation. Similar results were found when validating with data from the 4 hospitals from Sanitas. The models were found to have 11% better accuracy than doctors at classifying critical cases and improved accuracy of doctors by 12% for non-critical patients, reducing the cost of mistakes made by 17%.
Remote self-report and speech-in-noise measures predict clinical audiometric thresholds
Authors: Motlagh Zadeh Lina , Brennan Veronica , Swanepoel De Wet , Lin Li , Moore David R.
Published: May 2022

Developments in smartphone technology and the COVID-19 pandemic have highlighted the feasibility and need for remote, but reliable hearing tests. Previous studies used remote testing but did not directly compare results in the same listeners with standard lab or clinic testing. This study investigated reliability of remote, self-administered digits-in-noise (remote-DIN) compared with lab-based, supervised (lab-DIN) testing. Predictive validity was further examined in relation to a commonly used self-report, Speech, Spatial, and Qualities of Hearing (SSQ-12), and lab-based, pure tone audiometry. DIN speech reception thresholds (SRTs) of adults (18-64 y/o) with normal-hearing (NH, N=16) and hearing loss (HL, N=18), were measured using English-language digits (0-9), binaurally presented as triplets in one of four speech-shaped noise maskers (broadband, low-pass filtered at 2, 4, 8 kHz) and two digit phases (diotic, antiphasic). High, significant intraclass correlation coefficients indicated strong internal consistency of remote-DIN SRTs, which also correlated significantly with lab-DIN SRTs. There was no significant mean difference between remote- and lab-DIN on any tests. NH listeners had significantly higher SSQ scores, and remote- and lab-DIN SRTs than listeners with HL. All versions of remote-DIN SRTs correlated significantly with pure-tone-average (PTA), with the 2-kHz filtered test the best predictor, explaining 50% of variance in PTA. SSQ total score also significantly and independently predicted PTA (17% of variance) and all test versions of the remote-DIN, except the antiphasic BB test. This study shows that remote SSQ-12 and remote-DIN are sensitive tools for capturing important aspects of auditory function.
Assessing the impacts of timing on the health benefits, cost-effectiveness and relative affordability of COVID-19 vaccination programmes in 27 African Countries
Authors: Liu Yang , Pearson Carl AB , Madriz Montero Andrés , Torres-Rueda Sergio , Asfaw Elias , Uzochukwu Benjamin , Drake Tom , Bergren Eleanor , Eggo Rosalind M , Ruiz Francis , Ndembi Nicaise , Nonvignon Justice , Jit Mark , Vassall Anna
Published: May 2022

Background

The COVID-19 vaccine supply shortage in 2021 constrained rollout efforts in Africa while populations experienced waves of epidemics. As supply picks up, a key question becomes if vaccination remains an impactful and cost-effective strategy given changes in the timing of implementation.

Methods

We assessed the impact of timing using an epidemiological and economic model. We fitted our mathematical epidemiological model to reported COVID-19 deaths in 27 African countries to estimate the existing immunity (resulting from infection) before substantial vaccine rollout. We then projected health outcomes for different programme start dates (2021-01-01 to 2021-12-01, n = 12) and roll-out rates (slow, medium, fast; 275, 826, and 2066 doses/ million population-day, respectively) for viral vector and mRNA vaccines. Rollout rates used were derived from observed uptake trajectories. We collected data on vaccine delivery costs by country income group. Lastly, we calculated incremental cost-effectiveness ratios and relative affordability.

Findings

Vaccination programmes with early start dates incur the most health benefits and are most cost-effective. While incurring the most health benefits, fast vaccine roll-outs are not always the most cost-effective. At a willingness-to-pay threshold of 0.5xGDP per capita, vaccine programmes starting in August 2021 using mRNA and viral vector vaccines were cost-effective in 6-10 and 17-18 of 27 countries, respectively.

Interpretation

African countries with large proportions of their populations unvaccinated by late 2021 may find vaccination programmes less cost-effective than they could have been earlier in 2021. Lower vaccine purchasing costs and/or the emergence of new variants may improve cost-effectiveness.

Funding

Bill and Melinda Gates Foundation, World Health Organization, National Institute of Health Research (UK), Health Data Research (UK)
Aggregated genomic data as cohort-specific allelic frequencies can boost variants and genes prioritization in non-solved cases of inherited retinal dystrophies
Authors: Iancu Ionut-Florin , Perea-Romero Irene , Núñez-Moreno Gonzalo , de la Fuente Lorena , Romero Raquel , Ávila-Fernandez Almudena , José Trujillo-Tiebas María , Riveiro-Álvarez Rosa , Almoguera Berta , Martín-Mérida Inmaculada , Del Pozo-Valero Marta , Damián-Verde Alejandra , Cortón Marta , Ayuso Carmen , Minguez Pablo
Published: May 2022

The introduction of NGS in genetic diagnosis has increased the repertoire of variants and genes involved and the amount of genomic information produced. We built an allelic-frequency (AF) database for a heterogeneous cohort of genetic diseases to explore the aggregated genomic information and boost diagnosis in inherited retinal dystrophies (IRD). We retrospectively selected 5683 index-cases with clinical exome sequencing tests available, 1766 with IRD and the rest, with diverse genetic diseases. We calculated subcohort’s IRD specific AF and compare it with suitable pseudocontrols. For non-solved IRD cases, we prioritized variants with a significant increment of frequencies, with 8 variants that may contribute to explain the phenotype, and 10/11 of uncertain significance that were reclassified as likely-pathogenic according to ACMG. Besides, we developed a method to highlight genes with more frequent pathogenic variants in IRD cases than in pseudocontrols weighted by the increment of benign variants in the same comparison. We identified 18 genes for further studies that provided new insights in five cases. This resource can also help to calculate the carrier-frequency in IRD genes. A cohort-specific AF database assist with variants and genes prioritization and operate as an engine that provides new hypothesis in non-solved cases, augmenting diagnosis rate.