bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible Role of P-selectin Adhesion in Long-COVID: A Case of Recovery After Long-COVID
Authors: Tarasev Michael , Gao Xiufeng , Ferranti Marta , Zaidi Aliya U. , Hines Patrick
Published: February 2023

Background

Long-term outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now recognized as an emerging public health challenge - a condition termed post-acute coronavirus 2019 syndrome (PACS) or Long-COVID. The pathophysiology of Long-COVID remains to be established, several mechanisms in study focus on the role of P-selectin, an inflammation-induced protein expressed by platelets and endothelial cells. Functional P-selectin activity, potentially implicated in COVID-19 and Long-COVID sequelae, was measured for a Long-COVID subject at 68 weeks from the SARS-CoV-2 infection after fully recover from the syndrome. It was compared with the results from the same subject at 20 weeks post-infection, when subject experienced severe Long-COVID symptoms.

Methods

Flow adhesion of whole blood or isolated white blood cells to P-selectin (FA-WB-Psel and FA-WBC-Psel) was measured using a standardized microfluidics clinical assay; impedance aggregometry with a collagen agonist was measured using model 590 Chrono-Log impedance aggregometer; standard laboratory assays were performed to evaluate changes in blood chemistries.

Results

After recovery from Long-COVID, RBC count and D-dimer remained elevated and other blood chemistry results remained within the normal range as compared to 20 weeks post infection when severe Long-COVID symptoms were present. Total iron and transferrin-iron saturation percentage values that were elevated when symptoms were present, declined to normal range. Whole blood aggregometry results indicate an absence of previously present platelet hyperactivity. FA-WB-PSel that was significantly elevated during Long-COVID (590 ± 260 cells/mm2) was significantly reduced after its symptoms’ resolution (98 ± 38 cells/mm2). However, supplementation of whole blood with crizanlizumab did not result in any measurable inhibition of cell adhesion to P-selectin, similarly with previously reported. Similar to what was observed for the subject when Long-COVID symptoms were present, crizanlizumab, even at a dose 10-fold lower than clinical, induced pronounced inhibition of FA-WBC-Psel when tested in buffer, but not in patient’s own plasma.

Conclusions

This report documents the changes in leukocyte adhesion properties for a patient at more than a year from the initial infection after the gradual resolution of Long-COVID symptoms, as compared to when Long-COVID symptoms were present. Recovery from Long-COVID may be associated with normalization of platelet activity, but not necessarily with complete alleviation of endothelial activation. It remains to be determined to what extent changes in leukocyte adhesion to P-selectin may represent a new risk factor for a mechanism driving Long-COVID syndrome.
Vaccine-induced correlate of protection against fatal COVID-19 in the old and frail during waves of neutralization resistant variants of concern
Authors: Vikström Linnea , Fjällström Peter , Gwon Yong-Dae , Sheward Daniel J. , Wigren-Byström Julia , Evander Magnus , Bladh Oscar , Widerström Michael , Molnar Christian , Rasmussen Gunlög , Bennet Louise , Åberg Mikael , Björk Jonas , Tevell Staffan , Thålin Charlotte , Blom Kim , Klingström Jonas , Murrell Benjamin , Ahlm Clas , Normark Johan , Johansson Anders F , Forsell Mattias NE
Published: February 2023

Background

To inform future preventive measures including repeated vaccinations, we have searched for a clinically useful immune correlate of protection against fatal Covid-19 among nursing homes residents.

Methods

We performed repeated capillary blood sampling with analysis of S-binding IgG in an open cohort study with inclusion of nursing home residents in Sweden. We analyzed immunological and registry data collected from September 2021 with end of follow-up 31 August 2022. The study period included implementation of the 3rd and 4th mRNA monovalent vaccine doses and Omicron virus waves.

Findings

A total of 3012 nursing home residents with median age 86 were enrolled. The 3rd mRNA dose elicited a 99-fold relative increase of S-binding IgG among 2606 blood-sampled individuals and corresponding increase of neutralizing antibodies. The 4th mRNA vaccine dose boosted the levels 3.8-fold. Half-life of S-binding IgG was 72 days. A total 528 residents acquired their first SARS-CoV-2 infection after the 3rd or the 4th vaccine dose and the 30-day mortality was 9.1%. We found no indication that levels of vaccine-induced antibodies protected against infection with Omicron VOCs. In contrast, the risk of death was inversely correlated to levels of S-directed IgG below the 20thpercentile. The risk plateaued at population average above lower 35th percentile of S-binding IgG.

Interpretation

In the absence of neutralizing antibodies that protection from infection, quantification of S-binding IgG post vaccination may be useful to identify the most vulnerable for fatal Covid-19 among the oldest and frailest. This information is of importance for future strategies to protect vulnerable populations against neutralization resistant variants of concern.

Funding

Swedish Research Council, SciLife, Knut and Alice Wallenberg Foundation and Vinnova.
Exploring the impact of parity and its interaction with history of preterm delivery on gestational duration
Authors: Ytterberg Karin , Jacobsson Bo , Flatley Christopher , Juodakis Julius , Nilsson Staffan , Sole-Navais Pol
Published: February 2023

Delivering preterm is the leading cause of death in neonates and children under five years of age. Both genetics and environmental factors play a role in timing of delivery, and these influences can be unique to a single pregnancy or shared across pregnancies of the same mother. The aim of this study was to understand how gestational duration is affected by parity and how parity modifies the association between history of preterm delivery and gestational duration. To investigate this, we analysed 1 118 318 spontaneous deliveries (1990 - 2012) from the Swedish Medical Birth Register, with access to pedigrees, using linear regressions and linear mixed models. We found that parity has a modest effect on the mean and a large effect on the variance of gestational duration. Interactions with a woman’s clinical and family history of preterm delivery revealed both pregnancy-specific and shared factors. For instance, the effect of a previous preterm delivery on gestational duration is present across pregnancies, but the magnitude of its effect is pregnancy specific. The access to pedigrees made it possible to apply linear mixed models, thus including all woman’s pregnancies in the model and accounting for unobserved mother-specific covariates. The linear mixed models highlighted a group effect bias when using linear regression to estimate the association between parity and gestational duration, likely caused by socioeconomic factors. Our study shed light on how parity affects gestational duration and modifies the effect of well-known risk factors of preterm delivery.
The Acceptability of Self-Collected Samples for STI Testing: A Qualitative Study Among Adults in Rakai, Uganda
Authors: Ogale Yasmin P. , Grabowski M. Kathryn , Nabakka Proscovia , Ddaaki William , Nakubulwa Rosette , Nakyanjo Neema , Nalugoda Fred , Kagaayi Joseph , Kigozi Godfrey , Denison Julie A. , Gaydos Charlotte , Kennedy Caitlin E.
Published: February 2023

Introduction

Self-collected samples (SCS) for sexually transmitted infection (STI) testing have been shown to be feasible and acceptable in high-resource settings. However, few studies have assessed the acceptability of SCS for STI testing in a general population in low-resource settings. This study explored the acceptability of SCS among adults in south-central Uganda.

Methods

Nested within the Rakai Community Cohort Study, we conducted semi-structured interviews with 36 symptomatic and asymptomatic adults who self-collected samples for STI testing. We analyzed the data using an adapted version of the Framework Method.

Results

Overall, participants did not find SCS physically uncomfortable. Reported acceptability did not meaningfully differ by gender or symptom status. Perceived advantages to SCS included increased privacy and confidentiality, gentleness, and efficiency. Disadvantages included the lack of provider involvement, fear of self-harm and the perception that SCS was unhygienic.Most participants preferred provider-collected samples to SCS. Nevertheless, almost all said they would recommend SCS and would do it again in the future.

Conclusion

Despite a preference for provider-collection, SCS are acceptable among adults in this setting and support expanded access to STI diagnostic services.

Key Questions

What is already known on this topic

Timely diagnosis is critical for STI control, with testing being the gold standard for diagnosis. Self-collected samples (SCS) for STI testing offer an opportunity to expand STI testing services and are well accepted in high-resource settings. However, patient acceptability of self-collected samples in low-resource settings is not well described.

What this study adds

We found that SCS was acceptable to both male and female participants in our population, regardless of whether they reported STI symptoms. Perceived advantages to SCS included: increased privacy and confidentiality, gentleness, and efficiency; disadvantages included lack of provider involvement, fear of self-harm and the perception that SCS was unhygienic. Overall, most participants preferred provider collection over SCS.

How this study might affect research, practice or policy

Patient education addressing perceived disadvantages may increase SCS acceptability and support the use of SCS as a means to identify cases and control STIs in low-resource settings.
On the ability to extract MLVA profiles ofVibrio choleraeisolates from WGS data generated with Oxford Nanopore Technologies
Authors: Ambroise Jérôme , Bearzatto Bertrand , Durant Jean-Francois , Irenge Leonid M. , Gala Jean-Luc
Published: February 2023

Multiple-Locus Variable Number of Tandem Repeats (VNTR) Analysis (MLVA) is widely used by laboratory-based surveillance networks to subtype pathogens causing foodborne and water-borne disease outbreaks. TheMLVATypeshiny application was previously designed to extract MLVA profiles ofVibrio choleraeisolates from WGS data, and provide backward compatibility with traditional MLVA typing methods. The previous development and validation work was done on short (pair-end 300 and 150 nt long) reads from Illumina MiSeq and Hiseq sequencing. In the initial phase of this work, theMLVATypeapplication was validated on long reads generated by Oxford Nanopore Technologies (ONT) sequencing platforms. The MLVA profiles ofV. choleraeisolates (n=9) from the Democratic Republic of the Congo were produced using theMLVATypeapplication on WGS data. The WGS-derived MLVA profiles were extracted from canu (v.2.2) assemblies obtained through MinION and GridION sequencing by ONT. The results were compared to those obtained from SPAdes assemblies (v3.13.0; k-mer 175) generated from short-read (pair-end 300-bp) data obtained by MiSeq sequencing, Illumina, taken as a reference. For each isolate, the MLVA profiles were concordant for all three sequencing methods, demonstrating that theMLVATypeapplication can accurately predict the MLVA profiles from assembled genomes generated with long-reads ONT sequencers.

In the final phase of this study, we conducted phylogenomic analysis on data generated by both sequencing technologies, highlighting the superior resolution of Illumina short-read sequencing compared to the ONT-based approach. However, there was a remarkable concordance between isolate clusters identified using ONT-based MLVA profiles and those derived from the short-read-based phylogenomic analysis. This striking agreement enabled us to identify specific benefits and drawbacks of both technologies.
Reducing Cross-Cultural Comparability Bias Obtained with Measurement Invariance Analysis by Means of Anchoring Vignettes in Heterogeneous Refugee Samples
Authors: Menold Natalja , Biddle Louise , von Hermanni Hagen , Kadel Jasmin , Bozorgmehr Kayvan
Published: February 2023

Background

Configural, metric, and scalar measurement invariance have been indicators of bias-free statistical cross-group comparisons, although they are difficult to verify in the data. Low comparability of translated questionnaires or the different use of response formats by respondents might lead to rejection of measurement invariance and point to comparability bias in studies that use different languages. Anchoring vignettes have been proposed as a method to control for the different use of response formats by respondents (RC-DIF) as implemented by means of rating scales. We evaluate the question whether the comparability bias obtained by means of measurement invariance analysis can be reduced by means of anchoring vignettes or by considering socio- demographic heterogeneity as an alternative approach.

Methods

We use the Health System Responsiveness (HSR) questionnaire in English and Arabic in a refugee population. We collected survey data in English (n = 183) and Arabic (n=121) in a random sample of refugees in the third largest German federal state. We conducted multiple-sample Confirmatory Factor Analyses (MGCFA) to analyse measurement invariance and compared the results when 1) using rescaled data on the basis of anchoring vignettes (non-parametric approach), 2) including information on DIF from the analyses with anchoring vignettes as covariates (parametric approach) and 3) including socio-demographic covariates.

Results

For the HSR, every level of measurement invariance between Arabic and English questionnaires was rejected. Implementing rescaling on the basis of anchoring vignettes provided superior results over the initial MGCFA analysis, since configural, metric and scalar invariance could not be rejected. When using solely socio-demographic covariates, scalar measurement invariance could not be rejected, but configural and metric invariance had to be rejected.

Conclusions

Surveys may consider anchoring vignettes as a method to obtain more satisfactory results of measurement invariance analyses; however, socio-demographic information cannot be included in the models as a standalone method. More research on the efficient implementation of anchoring vignettes and further development of methods to incorporate them when modelling measurement invariance is needed.
Identification of High Likelihood of Dementia in Population-Based Surveys using Unsupervised Clustering: a Longitudinal Analysis
Authors: Gharbi-Meliani Amin , Husson François , Vandendriessche Henri , Bayen Eleonore , Yaffe Kristine , Bachoud-Lévi Anne-Catherine , de Langavant Laurent Cleret
Published: February 2023

Background

Dementia is defined by cognitive decline that affects functional status. Longitudinal ageing surveys often lack a clinical diagnosis of dementia though measure cognitive and function over time. We used unsupervised machine learning and longitudinal data to identify transition to probable dementia.

Methods

Multiple Factor Analysis was applied to longitudinal function and cognitive data of 15,278 baseline participants (aged 50 years and more) from the Survey of Health, Ageing, and Retirement in Europe (SHARE) (waves 1, 2 and 4–7, between 2004 and 2017). Hierarchical Clustering on Principal Components discriminated three clusters at each wave. We estimated probable or “Likely Dementia” prevalence by sex and age, and assessed whether dementia risk factors increased the risk of being assigned probable dementia status using multistate models. Next, we compared the “Likely Dementia” cluster with self-reported dementia status and replicated our findings in the English Longitudinal Study of Ageing (ELSA) cohort (waves 1–9, between 2002 and 2019, 7,840 participants at baseline).

Findings

Our algorithm identified a higher number of probable dementia cases compared with self-reported cases and showed good discriminative power across all waves (AUC ranged from 0.754 [0.722–0.787] to 0.830 [0.800–0.861]). “Likely Dementia” status was more prevalent in older people, displayed a 2:1 female/male ratio and was associated with nine factors that increased risk of transition to dementia: low education, hearing loss, hypertension, drinking, smoking, depression, social isolation, physical inactivity, diabetes, and obesity. Results were replicated in ELSA cohort with good accuracy.

Interpretation

Machine learning clustering can be used to study dementia determinants and outcomes in longitudinal population ageing surveys in which dementia clinical diagnosis is lacking.

Funding

French Institute for Public Health Research (IReSP), French National Institute for Health and Medical Research (Inserm), NeurATRIS Grant (ANR-11-INBS-0011), and Front-Cog University Research School (ANR-17-EUR-0017).
Paediatric traumatic brain injury as a risk factor for psychosis and psychotic symptoms: a systematic review and meta-analysis
Authors: Yau King-Chi , Revill Grace , Blackman Graham , Shaikh Madiha , Bell Vaughan
Published: February 2023

Background

Psychosis is one of the most disabling psychiatric disorders. Paediatric traumatic brain injury (pTBI) has been cited as a developmental risk factor for psychosis, however this association has never been assessed meta-analytically.

Methods

A systematic review and meta-analysis of the association between pTBI and subsequent psychotic disorders/symptoms was performed. The study was pre-registered (CRD42022360772) adopting a random-effects model to estimate meta-analytic odds ratio (OR) and 95% confidence interval (CI) using the Paule–Mandel estimator. Subgroup (study location, study design, psychotic disorder vs subthreshold symptoms, assessment type, and adult vs adolescent onset) and meta-regression (quality of evidence) analyses were also performed. The robustness of findings was assessed through sensitivity analyses. The meta-analysis is available online as a computational notebook with an open dataset.

Results

We identified 10 relevant studies and eight were included in the meta-analysis. Based on a pooled sample size of 479,686, the pooled OR for the association between pTBI and psychosis outcomes was 1.80 (95% CI [1.11, 2.95]). There were no subgroup effects and no outliers. Both psychotic disorder and subthreshold symptoms were associated with pTBI. The overall association remained robust after removal of low-quality studies, however the OR reduced to 1.43 (95% CI [1.04, 1.98]). A leave-one-out sensitivity analysis showed the association was robust to removal of all but one study which changed the estimate to marginally non-significant.

Conclusions

We report cautious meta-analytic evidence for a positive association between pTBI and future psychosis. New evidence will be key in determining long-term reliability of this finding.
Chromatin accessibility associated with aquaculture relevant traits in tilapia
Authors: Mehta Tarang K. , Man Angela , Ciezarek Adam , Ranson Keith , Penman David , Di-Palma Federica , Haerty Wilfried
Published: February 2023

The Nile tilapia (Oreochromis niloticus) accounts for ∼9% of global freshwater finfish production however, extreme cold weather and decreasing freshwater resources has created the need to develop resilient strains. By determining the genetic bases of aquaculture relevant traits, we can genotype and breed desirable traits into farmed strains. We developed and optimised ATAC-seq fromO. niloticusgill tissues to identify regulatory regions accounting for gene expression associated with gill adaptations. We find that SNPs from 27 tilapia species are enriched in noncoding regions, with 95% of accessible gene promoter regions being SNP-containing. Regulatory variants of TF binding sites are likely driving gene expression differences associated with tilapia gill adaptations, and differentially segregate in freshwater and euryhaline tilapia species. The generation of novel open chromatin data integrated with gene expression and genetic variants revealed candidate genes, genetic relationships, and loci associated with aquaculture relevant traits like salinity and osmotic stress acclimation.
TRGdb: a universal resource for exploration of taxonomically restricted genes in bacteria
Authors: Zielezinski Andrzej , Dobrychlop Wojciech , Karlowski Wojciech M.
Published: February 2023

The TRGdb database is a resource dedicated to taxonomically restricted genes (TRGs) in bacteria. It provides a comprehensive collection of genes that are specific to different genera and species, according to the latest release of bacterial taxonomy. The user interface allows for easy browsing and searching as well as sequence similarity exploration. The website also provides information on each TRG protein sequence, including its level of disorder, complexity, and tendency to aggregate. TRGdb is a valuable resource for gaining a deeper understanding of the TRGs-associated, unique features and characteristics of bacterial organisms. The TRGdb resource is freely accessible throughwww.combio.pl/trgdb.
UV-B-induced dynamics of constitutive heterochromatin inArabidopsis thaliana
Authors: Johann to Berens Philippe , Golebiewska Kinga , Peter Jackson , Molinier Jean
Published: February 2023

Sunlight regulates transcriptional programs and triggers the shaping of the genome throughout plant development. Among the different sunlight wavelengths that reach the surface of the Earth, UV-B (280-315 nm) controls the expression of hundreds of genes for the photomorphogenic responses and also induces the formation of photodamage that interfere with genome integrity and transcriptional programs. The combination of cytogenetics and deep-learning-based analyses allowed determining the location of UV-B-induced photoproducts and quantifying the effects of UV-B irradiation on constitutive heterochromatin content in different Arabidopsis natural variants acclimated to various UV-B regimes. We identified that UV-B-induced photolesions are enriched within chromocenters. Furthermore, we uncovered that UV-B irradiation promotes constitutive heterochromatin dynamics that differs among the Arabidopsis ecotypes having divergent heterochromatin contents. Finally, we identified that the proper restoration of the chromocenter shape, upon DNA repair, relies on the UV-B photoreceptor, UV RESISTANCE LOCUS 8 (UVR8). These findings shed the light on the effect of UV-B exposure and perception in heterochromatin dynamics and structure inArabidopsis thaliana.

Statements and Declarations

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.
Cotranscriptional demethylation induces global loss of H3K4me2 from active genes inArabidopsis
Authors: Mori Shusei , Oya Satoyo , Takahashi Mayumi , Takashima Kazuya , Inagaki Soichi , Kakutani Tetsuji
Published: February 2023

Based on studies of animals and yeasts, methylation of histone H3 lysine 4 (H3K4me1/2/3, for mono-, di-, and tri-methylation, respectively) is regarded as the key epigenetic modification of transcriptionally active genes. In plants, however, H3K4me2 correlates negatively with transcription, and the regulatory mechanisms of this counterintuitive H3K4me2 distribution in plants remain largely unexplored. A previous genetic screen for factors regulating plant regeneration identified Arabidopsis LYSINE-SPECIFIC DEMETHYLASE 1-LIKE 3 (LDL3), which is a major H3K4me2 demethylase. Here, we show that LDL3-mediated H3K4me2 demethylation depends on the transcription elongation factor Paf1C and phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (RNAPII). In addition, LDL3 binds to phosphorylated RNAPII. These results suggest that LDL3 is recruited to transcribed genes by binding to elongating RNAPII and demethylates H3K4me2 cotranscriptionally. Importantly, the negative correlation between H3K4me2 and transcription is disrupted in theldl3mutant, demonstrating the genome-wide impacts of the transcription-driven LDL3 pathway to control H3K4me2 in plants. Our findings implicate H3K4me2 in plants as chromatin memory for transcriptionally repressive states, which ensures robust gene control.
Effects of hepatic mitochondrial pyruvate carrier deficiency on de novo lipogenesis and glycerol-mediated gluconeogenesis in mice
Authors: Yiew Nicole K.H. , Deja Stanislaw , Ferguson Daniel , Cho Kevin , Jarasvaraparn Chaowapong , Jacome-Sosa Miriam , Lutkewitte Andrew J. , Mukherjee Sandip , Fu Xiaorong , Singer Jason M. , Patti Gary J. , Burgess Shawn C. , Finck Brian N.
Published: February 2023

The liver coordinates the systemic response to nutrient deprivation and availability by producing glucose from gluconeogenesis during fasting and synthesizing lipids viade novolipogenesis (DNL) when carbohydrates are abundant. Mitochondrial pyruvate metabolism is thought to play important roles in both gluconeogenesis and DNL. We examined the effects of hepatocyte-specific mitochondrial pyruvate carrier (MPC) deletion on the fasting-refeeding response. Rates of DNL during refeeding were impaired by liver MPC deletion, but this did not reduce intrahepatic lipid content. During fasting, glycerol is converted to glucose by two pathways; a direct cytosolic pathway essentially reversing glycolysis and an indirect mitochondrial pathway requiring the MPC. MPC deletion reduced the incorporation of13C-glycerol into TCA cycle metabolites but not into newly synthesized glucose. However, suppression of glycerol metabolism did not affect glucose concentrations in fasted hepatocyte-specific MPC-deficient mice. Thus, glucose production by kidney and intestine may compensate for MPC deficiency in hepatocytes.
A novel order-level lineage of ammonia-oxidizingThaumarchaeotais widespread in marine and terrestrial environments
Authors: Zheng Yue , Wang Baozhan , Gao Ping , Yang Yiyan , Su Xiaoquan , Ning Daliang , Tao Qing , Zhao Feng , Wang Dazhi , Zhang Yao , Li Meng , Winkler Mari-K.H. , Ingalls Anitra E. , Zhou Jizhong , Zhang Chuanlun , Stahl David A. , Jiang Jiandong , Martens-Habbena Willm , Qin Wei
Published: February 2023

Ammonia-oxidizing archaea (AOA) are among the most ubiquitous and abundant groups of Archaea on Earth, widely distributed in marine, terrestrial, and geothermal ecosystems. However, the genomic diversity, biogeography, and evolutionary process of AOA populations in subsurface environments are vastly understudied compared to those of marine and soil AOA. We here report a novel AOA orderCandidatusNitrosomirales that forms a deeply branching basal sister lineage to the thermophilicCa.Nitrosocaldales. Metagenomic and 16S rRNA gene read mapping demonstrates the dominant presence ofNitrosomiralesAOA in various groundwater environments and their widespread distribution across a range of geothermal, terrestrial, and marine habitats. Notably, terrestrialNitrosomiralesAOA show the genetic capacity of using formate as an alternative source of reductant and appear to have acquired key metabolic genes and operons from other mesophilic populations via horizontal gene transfer, including the genes encoding urease, nitrite reductase, and V-type ATPase. Potential metabolic versatility and acquired functions may facilitate their radiation into a variety of subsurface, marine, and soil environments. Molecular thermometer-based evolutionary analysis suggests thatNitrosomiralesoriginated from thermophilic environments and transitioned into temperate habitats in parallel withNitrososphaeralesandNitrosopumilales. We also provide evidence that terrestrial-marine habitat transitions occurred within each one of the four AOA orders, which reveals a more complex evolutionary trajectory of major AOA lineages than previously proposed. Together, these findings establish a robust taxonomic and evolutionary framework of AOA and provide new insights into the ecology and evolution of this globally abundant functional guild.
Mental health symptoms in Latin America during the first year of COVID-19 pandemic: a meta-analysis of prevalence and potential moderator variables
Authors: Torrente F. , Ailán D. , Del Cerro E. , Del Negro J. , Gorodetzky B. , Slonimschik D. , Cetkovich-Bakmas M. , López P.
Published: February 2023

This meta-analysis examines the impacts of the COVID-19 pandemic on mental health in Latin America during its first year, using data from 71 studies with 231,441 participants. To address knowledge gaps in the existent literature we considered the type of study design, country of origin, effects of lockdown, and several potential moderating factors. We found prevalence rates of 31% for depression symptoms and 36% for anxiety symptoms. These estimates were higher than those observed in studies from the northern hemisphere. Longitudinal studies showed that depressive symptoms persisted over time, and lockdowns were associated with mildly increased anxiety levels. Female gender was associated with higher rates of depressive symptoms. Our analyses revealed high statistical heterogeneity, and moderating factors such as pandemic duration, COVID-19 cases and deaths, and lockdown stringency did not explain observed mental health symptoms. Methodological limitations include an overreliance on cross-sectional studies and a lack of pre-pandemic parameters that may lead to an overestimation of mental health symptom rates. Overall, this study provides valuable insights into mental health symptoms in Latin America during the first year of the COVID-19 pandemic, highlighting the need for improved epidemiological research and mental health support in the region.
A long-term ketogenic diet in young and aged rats has dissociable effects on prelimbic cortex and CA3 ensemble activity
Authors: Hernandez Abbi R. , Barrett Maya E. , Lubke Katelyn N. , Maurer Andrew P. , Burke Sara N.
Published: February 2023

Age-related cognitive decline has been linked to distinct patterns of cellular dysfunction in the prelimbic cortex (PL) and the CA3 subregion of the hippocampus. Because higher cognitive functions require both structures, selectively targeting a neurobiological change in one region, at the expense of the other, is not likely to restore normal behavior in older animals. One change with age that both the PL and CA3 share, however, is a reduced ability to utilize glucose, which can produce aberrant neural activity patterns. The current study used a ketogenic diet (KD) intervention, which reduces the brain’s reliance on glucose, and has been shown to improve cognition, as a metabolic treatment for restoring neural ensemble dynamics in aged rats. Expression of the immediate-early genesArcandHomer1a were used to quantify the neural ensembles that were active in the home cage prior to behavior, during a working memory/biconditional association task, and a continuous spatial alternation task. Aged rats on the control diet had increased activity in CA3 and less ensemble overlap in PL between different task conditions than did the young animals. In the PL, the KD was associated with increased activation of neurons in the superficial cortical layers. The KD did not lead to any significant changes in CA3 activity. These observations suggest that the KD does not restore neuron activation patterns in aged animals, but rather the availability of ketone bodies in the frontal cortices may permit the engagement of compensatory mechanisms that produce better cognitive outcomes.

Significance Statement

This study extends understanding of how a ketogenic diet (KD) intervention may improve cognitive function in older adults. Young and aged rats were given 3 months of a KD or a calorie-match control diet and then expression of the immediate-early genesArcandHomer1a were measured to examine neural ensemble dynamics during cognitive testing. The KD diet was associated with increased activation of neurons in the superficial layers of the PL, but there were no changes in CA3. These observations are significant because they suggest that compensatory mechanisms for improving cognition are engaged in the presence of elevated ketone bodies. This metabolic shift away from glycolysis can meet the energetic needs of the frontal cortices when glucose utilization is compromised.
Predicted loss of function alleles in Bassoon (BSN) are associated with obesity
Authors: Zhu Na , LeDuc Charles A. , Fennoy Ilene , Laferrère Blandine , Doege Claudia A. , Shen Yufeng , Chung Wendy K. , Leibel Rudolph L.
Published: February 2023

Bassoon (BSN) is a component of a hetero-dimeric presynaptic cytomatrix protein that orchestrates neurotransmitter release with Piccolo (PCLO) from glutamatergic neurons throughout the brain. Heterozygous missense variants inBSNhave previously been associated with neurodegenerative disorders in humans. We performed an exome-wide association analysis of ultra-rare variants in about 140,000 unrelated individuals from the UK Biobank to search for new genes associated with obesity. We found that rare heterozygous predicted loss of function (pLoF) variants inBSNare associated with higher BMI with log10-p value of 11.78 in the UK biobank cohort. The association was replicated in the All of Us whole genome sequencing data. Additionally, we have identified two individuals (one of whom has ade novovariant) with a heterozygous pLoF variant in a cohort of early onset or extreme obesity at Columbia University. Like the individuals identified in the UKBB and All of us Cohorts, these individuals have no history of neurobehavioral or cognitive disability. Heterozygosity for pLoFBSNvariants constitutes a new etiology for obesity.
The contribution of eye movements to memory retrieval depends on the visual input
Authors: Taub Keren , Yuval-Greenberg Shlomit
Published: February 2023

When attempting to recall previously seen visual information, people often move their eyes to the same locations where they initially viewed it. These eye-movements are thought to serve a role in enhancing memory retrieval, although the exact mechanism underlying this effect is yet unknown. To investigate this link between eye-movements and memory, we conducted an experiment with 80 adult participants. Participants were asked to perform a memory retrieval task, while viewing either the same visual context as during encoding or an altered one.

Results showed that the benefit of eye movements to memory retrieval was dependent on the visual input. This suggests that the contribution of eye-movements to memory may not be from the motor behavior itself, but from its visual consequences. Our findings thus challenge the hypothesis that eye movements act as a motor retrieval cue and support the view that their visual consequences act as a sensory one.

Statement of Relevance

An intriguing question in cognition is how humans encode memorized material and what helps them retrieve it. It is known that when an action or stimulus is repeated both when information is encoded and when it is retrieved, this can act as a ‘retrieval cue’ and enhance memory performance. It is also known that people tend to reenact the same eye movements during retrieval as they did during encoding, and this behavior is associated with higher memory performance. This has led to the hypothesis that eye movements act as a retrieval cue. However, we challenge this hypothesis by showing that the visualconsequencesof eye movements, rather than the motor action that accompanies them, is the key factor for memory enhancement. Understanding the factors that influence memory provides crucial insight into the relationship between external behaviors and internal memory processes, leading to significant implications for the educational and clinical settings.
Immune response to SARS-CoV-2 mRNA vaccination in multiple sclerosis patients after rituximab treatment interruption
Authors: Gröning Remigius , Dernstedt Andy , Ahlm Clas , Normark Johan , Sundström Peter , Forsell Mattias NE
Published: February 2023

Peripheral B cell depletion via anti-CD20 treatment is a highly effective disease-modifying treatment in multiple sclerosis (MS) patients. A drawback of anti-CD20 treatment is poor immune responses to vaccination. While this can be mitigated by treatment interruption of at least six months prior to vaccination, the timing to resume treatment while maintaining subsequent vaccine responses remains undetermined. We characterized SARS-CoV-2 S-directed antibody and B cell responses throughout three BNT162b2 doses in MS patients, where the first two doses were given during treatment interruption. The last anti-CD20 rituximab infusion was given 1.3 years (median) prior to the first vaccine dose and re-administered four weeks after the second vaccine dose. After two vaccine doses, antibody-mediated responses in SARS-CoV-2-naïve MS patients were comparable to vaccinated healthy controls, albeit with greater variation. We could demonstrate that the response to the second dose of vaccination was predictive of a boost effect after a third dose, even after re-initiation of rituximab. MS patients also exhibited lower frequencies of Decay Accelerating Factor-negative memory B cells, a suggested proxy for germinal centre activity, than healthy individuals. Our findings also offer a first indication on the potential importance of antigenic stimulation of CD27-IgD-double negative B cells and the possible long-term impairment of germinal centre activity in rituximab-treated MS patients.
Knowledge, Attitude and Practices Regarding Digital Well-Being Features and their Association with Screen Time and Addiction in Maharashtra, India
Authors: Ambike Amey , Rao Shirish , Paranjape Raghav , Adarkar Shilpa
Published: February 2023

Background & Objective

Digital Service Providers have come up with certain ‘Digital Well-Being Features’ as a step towards tackling harmful effects of screen overuse on physical and mental health. However, the awareness and use of the same remains scant. Our objective was to assess the knowledge, attitudes and practices regarding Digital Well-being features in the adult population of Maharashtra, India and the associations and correlations of the practice of using these features with screen time and degree of screen addiction.

Methods

A cross-sectional online questionnaire-based study was conducted among 335 participants who were selected using quota sampling and were administered a Smartphone Addiction Scale and a self-designed questionnaire.

Results

Knowledge attitudes were good and total of 65.4% participants were digital wellbeing feature users. Correlation of digital hygiene score and digital wellbeing score was found neither with addiction nor with the average screen time.

Interpretation & Conclusion

Knowledge, attitude and practices regarding Digital Well-Being features were adequate among the urban population of Maharashtra. However, their use was not found to be associated with reduced screen time or a low screen addiction score. With further development and standardization, these features can be a useful tool for prevention of screen overuse and addiction.
Social-spatial network structures among young urban and suburban persons who inject drugs in a large metropolitan area
Authors: Lin Qinyun , Rojas Aguilera Javier Andres , Williams Leslie D. , Mackesy-Amiti Mary Ellen , Latkin Carl , Pineros Juliet , Kolak Marynia , Boodram Basmattee
Published: February 2023

Background

It is estimated that there are 1.5% US adult population who inject drugs in 2018, with young adults aged 18-39 showing the highest prevalence. PWID are at a high risk of many blood-borne infections. Recent studies have highlight the importance of employing the syndemic approach to study opioid misuse, overdose, HCV and HIV, along with the social and environmental contexts where these interrelated epidemics occur in already marginalized communities. Social interactions and spatial contexts are important structural factors that are understudied.

Methods

Egocentric injection network and geographic activity spaces for young (aged 18-30) PWID and their injection, sexual, and social support network members (i.e., where reside, inject drugs, purchase drugs, and meet sex partners) were examined using baseline data from an ongoing longitudinal study (n=258). Participants were stratified based on the location of all place(s) of residence in the past year i.e., urban, suburban, and transient (both urban and suburban) to i) elucidate geospatial concentration of risk activities within multi-dimensional risk environments based on kernel density estimates; and ii) examine spatialized social networks for each residential group.

Results

Participants were mostly non-Hispanic white (59%); 42% were urban residents, 28% suburban, and 30% transient. We identified a spatial area with concentrated risky activities for each residence group on the West side of Chicago where a large outdoor drug market area is located. The urban group (80%) reported a smaller concentrated area (14 census tracts) compared to the transient (93%) and suburban (91%) with 30 and 51 tracts, respectively. Compared to other areas in Chicago, the identified area had significantly higher neighborhood disadvantages (e.g., higher poverty rate,p<0.001). Significant (p<0.01 for all) differences were observed in social network structures: suburban had the most homogenous network in terms of age and residence, transient participants had the largest network (degree) and more non-redundant connections.

Conclusion

We identified concentrated risk activity spaces among PWID from urban, suburban, and transient groups in a large outdoor urban drug market area, which highlights the need for considering the role of risk spaces and social networks in addressing the syndemics in PWID populations.
iCPET calculator: a web-based application to standardize the calculation of alpha distensibility in patients with pulmonary arterial hypertension
Authors: Elliott Jordan , Menakuru Nainika , Martin Kellan Juliet , Rahaghi Farbod Nicholas , Rischard Franz P. , Vanderpool Rebecca R.
Published: February 2023

Introduction

Pulmonary vascular distensibility associates with right ventricular function and clinical outcomes in patients with unexplained dyspnea and pulmonary hypertension. Alpha distensibility coefficient is determined from a non-linear fit to multipoint pressure-flow plots. The study aims were 1) to create and test a user-friendly tool to standardize analysis of exercise hemodynamics including distensibility and 2) to investigate changes in distensibility following treatment in patients with pulmonary arterial hypertension.

Methods

Participants with repeat exercise right heart catherization and PAH were identified from the University of Arizona PH Registry (n=29). Single-beat analysis was used to quantify right ventricular function including the coupling ratio and diastolic stiffness. Prototypes of theiCPET calculatorwere developed using Matlab, Python and RShiny to analyze exercise hemodynamics and alpha distensibility coefficient, α (%/mmHg) from multi-point pressure flow plots. Interclass coefficients were calculated for inter-platform and interobserver variability in alpha.

Results

No significant bias in the intra-platform (Matlab vs RShiny: ICC: 0.996) or inter-observer (ICC: 0.982) comparison of alpha values. Participants with PAH had a significant decrease in afterload at follow-up (p<0.05) but no significant change in alpha distensibility. At follow-up, participants with a resting mean PA pressure < 25 mmHg had no change in pressure, resistance or alpha distensibility. Alpha distensibility significantly correlated with PA compliance at both the index and follow-up visit.

Discussion

TheiCPET calculatorstandardizes alpha distensibility calculations. In this retrospective cohort, alpha distensibility did not change despite a decrease in pulmonary vascular afterload (PVR and mPAP) at follow-up after treatment with pulmonary vasodilators.
Optimising bi-level non-invasive ventilation in preterm neonates: a systematic review
Authors: Pickard Jack
Published: February 2023

Bi-level non-invasive ventilation (BiPAP) can be used as a step-up from continuous positive airway pressure (CPAP) in preterm neonates to reduce the amount of time spent mechanically ventilated. Prolonged mechanical ventilation is associated with increased morbidity and mortality. MEDLINE was searched using the terms CPAP and BiPAP. Four studies reported a significant reduction in the need for mechanical ventilation when applying BiPAP compared with CPAP. Two studies reported no significant benefit. Studies which used 15/5 cm H2O or 20/5 cm H2O were more successful than those that used 6/5 cm H2O or 8/5 cm H2O. There was no discernible pattern to the effectiveness of respiratory rate, synchronisation or inspiratory time. In conclusion, BiPAP should be delivered at 15-20/5 cm H2O or 20/5 cm H2O.

Key messages

BiPAP has greater efficacy than CPAP at reducing the need for mechanical ventilation in preterm neonates with respiratory distress

An inspiratory pressure of at least 15 cm H2O should be employed wherever possible

There is insufficient evidence to recommend any particular respiratory rate, inspiratory time or synchronisation mode over another

Structured clinical question

Is BiPAP (intervention) more effective than CPAP (control) at reducing the need for mechanical ventilation in preterm neonates, and if so, what are the most effective pressures, inspiratory time, respiratory rate and synchronization mode to use?

Search strategy

MEDLINE was searched via Pubmed using the terms ‘CPAP’ AND ‘BiPAP’. This yielded 223 results. Further references within these articles were considered. Studies were included if they compared the effect of BiPAP vs CPAP on the need for mechanical ventilation or tracheal intubation. A total of 18 relevant studies were identified, including 15 randomised controlled trials (RCT) and one meta-analysis. Eight studies were excluded because they were already reported in the meta-analysis. Two were excluded because they were retrospective. A further two were excluded due to a lack of statistical analysis in the reporting. [1, 2]. A total of six studies remained for consideration; see table.
Hippocampal Synaptic Alterations Associated with Tau Pathology in Primary Age-Related Tauopathy
Authors: Morris Meaghan , Coste Gabrielle I , Redding-Ochoa Javier , Guo Haidan , Graves Austin R , Troncoso Juan C , Huganir Richard L
Published: February 2023

Primary Age-Related Tauopathy (PART) is characterized by the aggregation of tau in the mesial temporal lobe in older individuals. High pathologic tau stage (Braak stage) or a high burden of hippocampal tau pathology have been associated with cognitive impairment in PART. However, the underlying mechanisms of cognitive impairment in PART are not well understood. Cognitive impairment in many neurodegenerative diseases correlates with synaptic loss, raising the question of whether synaptic loss occurs in PART. To address this, we investigated synaptic changes associated with tau Braak stage and a high tau pathology burden in PART using synaptophysin and phospho-tau immunofluorescence. We compared twelve cases of definite PART with six young controls and six Alzheimer’s disease cases. In this study, we identified loss of synaptophysin puncta and intensity in the CA2 region of the hippocampus in cases of PART with either a high stage (Braak IV) or a high burden of neuritic tau pathology. There was also loss of synaptophysin intensity in CA3 associated with a high stage or high burden of tau pathology. Loss of synaptophysin signal was present in AD, but the pattern was distinct from that seen in PART. These novel findings suggest the presence of synaptic loss in PART associated with either a high hippocampal tau burden or a Braak stage IV. These synaptic changes raise the possibility that synaptic loss in PART could contribute to cognitive impairment, though future studies including cognitive assessments are needed to address this question.