bluuebunny/crossref_metadata_2025_split huggingface dataset:
Entorhinal cortex glutamatergic and GABAergic projections bidirectionally control discrimination and generalization of hippocampal representations
Authors: Robert Vincent , O’Neil Keelin , Rashid Shannon K. , Johnson Cara D. , De La Torre Rodrigo G. , Zemelman Boris V. , Clopath Claudia , Basu Jayeeta 
Published: November 2023

AbstractDiscrimination and generalization are crucial brain-wide functions for memory and object recognition that utilize pattern separation and completion computations. Circuit mechanisms supporting these operations remain enigmatic. We show lateral entorhinal cortex glutamatergic (LECGLU) and GABAergic (LECGABA) projections are essential for object recognition memory. Silencing LECGLUduringin vivotwo-photon imaging increased the population of active CA3 pyramidal cells but decreased activity rates, suggesting a sparse coding function through local inhibition. Silencing LECGLUalso decreased place cell remapping between different environments validating this circuit drives pattern separation and context discrimination. Optogenetic circuit mapping confirmed that LECGLUdrives dominant feedforward inhibition to prevent CA3 somatic and dendritic spikes. However, conjunctively active LECGABAsuppresses this local inhibition to disinhibit CA3 pyramidal neuron soma and selectively boost integrative output of LEC and CA3 recurrent network. LECGABAthus promotes pattern completion and context generalization. Indeed, without this disinhibitory input, CA3 place maps show decreased similarity between contexts. Our findings provide circuit mechanisms whereby long-range glutamatergic and GABAergic cortico-hippocampal inputs bidirectionally modulate pattern separation and completion, providing neuronal representations with a dynamic range for context discrimination and generalization.
Nicotinamide Riboside Supplementation Ameliorates Mitochondrial Dysfunction and Neuronal Loss in POLG Mutant Midbrain Organoids
Authors: Yangzom Tsering , Chen Anbin , Sullivan Gareth John , Liang Kristina Xiao 
Published: November 2023

AbstractMitochondrial dysfunction is associated with many neurodegenerative disorders and is particularly prominent in conditions tied toPOLGmutations.POLGencodes DNA polymerase gamma vital for mitochondrial DNA replication. Employing 3D human pluripotent stem cell-derived midbrain organoids (hMOs), harbouringPOLGmutations, this study explores their differentiation, transcriptional alterations, and underlying pathways of neurodegeneration associated withPOLGmutations. The generated hMOs displayed midbrain specificity and, at three months, a reduced diameter, suggesting growth challenges fromPOLGmutations. A reduced presence of dopaminergic neurons, particularly in DA2 and ventral midbrain classes, was evident. Intriguingly, post-treatment with 1 mM Nicotinamide Riboside (NR), an NAD+precursor, the organoids demonstrated an increased count of DA and VMN neurons and an elevated gene expression, especially in processes crucial to mitochondrial and synaptic functions. Our findings spotlight NAD+supplementation has potential therapeutic value in addressing POLG-associated neuronal and mitochondrial deficits. Moreover, the unique insights garnered from single-cell RNA sequencing, and enrichment analyses further emphasize the significance of mitochondrial disturbances and potential interventions for POLG-related neurodegenerative conditions. In summary, we underscore the transformative potential of NAD+in managing neurodegenerative diseases associated withPOLGmutations. It also establishes the utility ofPOLGmutant hMOs as a potent research model.
Clock driven waves of Tbx6 expression prefigure somite boundaries
Authors: Venzin Olivier F. , Jollivet Chloé , Chiaruttini Nicolas , Rosspopoff Olga , Helsens Clément , Morelli Luis G. , Uriu Koichiro , Oates Andrew C. 
Published: November 2023

AbstractThe segmented body plan of vertebrates is established during embryogenesis by periodic and sequential formation of multi-cellular structures called somites. Somitogenesis is an example of patterning by a biological oscillator, the segmentation clock, which manifests as traveling waves of oscillating Hes/Her gene expression, reiterating during the formation of each1–3. How these waves are converted into the striped Mesp gene expression pattern that prefigures morphological somite boundaries4–8remains unclear. Here, we image this conversion in real-time at single-cell resolution in zebrafish, using light-sheet microscopy of a novel reporter of Tbx6, a key activator of Mesp expression. We observe cellular oscillations and kinematic waves of Tbx6 expression that are driven by Hes/Her genes. Tbx6 waves arrest precisely in boundary cells that eventually express Mesp, thereby prefiguring the Mesp pattern, whereas Hes/Her waves do not. Although Hes/Her oscillations began before somitogenesis9–11, the first Tbx6 wave defines the boundary cells of the anterior-most somite, forming the head-trunk interface. Our findings imply that Tbx6 acts as a genetic clutch, converting Her/Hes pacemaker waves into Mesp stripes. We propose that this clock design shields the pacemaker from external perturbations, allowing flexible and robust patterning, making it of interest for organoids and tissue-engineering.
Computationally Driven Discovery and Characterization of SIRT3 Activating Compounds that Fully Recover Catalytic Activity under NAD+Depletion
Authors: Guan Xiangying , Upadhyay Alok , Dumpati Rama Krishna , Munshi Sudipto , Roy Samir , Chall Santu , Rahnamoun Ali , Reverdy Celina , Errasti Gauthier , Delacroix Thomas , Ghosh Anisha , Chakrabarti Raj 
Published: November 2023

ABSTRACTMammalian sirtuins (SIRT1-SIRT7) are a family of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacylases that play critical roles in lifespan and age-related diseases. The physiological importance of sirtuins has stimulated intense interest in designing sirtuin activating compounds. However, except for allosteric activators of SIRT1-catalyzed reactions that are limited to specific substrates, methodologies for the rational design of sirtuin activating compounds -- including compounds that activate mitochondrial sirtuins implicated in the age-related decline of cellular metabolism -- have been lacking. Here, we use computational high-throughput screening methodologies and a biophysical model for activation of the major mitochondrial sirtuin SIRT3 to identify novel small molecule activators of the human SIRT3 enzyme from a 1.2 million compound library. Unlike previously reported SIRT3 activators like Honokiol, which only transiently upregulate SIRT3 under non-steady state conditions and reduce the steady state catalytic efficiency of the enzyme, several of the novel compounds identified here are potent SIRT3 activators in both the steady and non-steady states. Two such compounds can almost double the catalytic efficiency of the enzyme with respect to NAD+, which would be sufficient to almost entirely compensate for the loss in SIRT3 activity that occurs due to the reduction in mitochondrial coenzyme concentration associated with aging, and display AC50s (concentrations of half-maximal activation) as low as 100 nM. The current work thus reports first-in-class, non-allosteric steady state activators that activate SIRT3 through a novel, mechanism-based mode of activation and that may be developed further for therapeutic applications.
Importations of SARS-CoV-2 lineages decline after nonpharmaceutical interventions in phylogeographic analyses
Authors: Goliaei S. , Foroughmand-Araabi M.H. , Roddy A. , Weber A. , Översti S. , Kühnert D. , McHardy A.C. 
Published: November 2023

AbstractThe onset of the SARS-CoV-2 pandemic marked a period of substantial challenges as the virus and its variants rapidly spread, placing enormous strain on both society and healthcare systems. Prior to the widespread availability of vaccines, non-pharmaceutical interventions such as reducing contacts, antigenic testing, or travel restrictions were the primary means of reducing viral transmission and case numbers, and quantifying the success of these measures is therefore key for future pandemic preparedness. Using SARS-CoV-2 genomes collected in systematic surveillance, we studied lineage importations for the third, pandemic wave in Germany, employing a large-scale Bayesian phylogenetic and phylogeographic analysis coupled to a longitudinal assessment of lineage importation dynamics over multiple sampling strategies. We evaluated the effect of twelve major nationwide nonpharmaceutical interventions (NPIs) on lineage importations and dissemination within the country. All NPIs were followed by reduced lineage importations, with the most substantial decreases seen for the provision of free rapid tests, the strengthening of regulations on mask-wearing in public transport and stores, as well as on internal movements and gatherings. Most SARS-CoV-2 lineages first appeared in the three states with the largest populations and most cases, and from there spread within the country. Importations began to rise before and peaked shortly after the Christmas holidays. Analysis of SARS-CoV-2 data revealed the substantial effects of free rapid tests and obligatory medical/surgical mask-wearing, suggesting these as key for pandemic preparedness, given their relatively few, negative socioeconomic effects. The approach quantifies the relationships between environmental factors at the host population level to viral lineage dissemination from genomic surveillance data, facilitating similar analyses of rapidly evolving pathogens in the future.
Temporal relationships between food insecurity, water insecurity, and generalized anxiety among rural Kenyans: seeking to clarify a climate-related syndemic
Authors: Goodman Michael L. , Sharma Shreela , Woldu Dawit , McPherson Heidi , Ramphul Ryan , Gitari Stanley , Gatwiri Christine 
Published: November 2023

ABSTRACTBackgroundIncreased water and food insecurity are one mechanism through which climate change can undermine global mental health. Understanding correlations between mental health and resource insecurity is imperative to support local adaptive responses to climate change.ObjectiveWe investigate temporal relationships between food insecurity, water insecurity, and generalized anxiety within rural Kenyans (n=152 adults) during a period of erratic rainfall.MethodUsing refined existing scales of food and water insecurity and generalized anxiety, we assess temporal relationships between these factors using cross-lagged panel analysis of survey data collected in October 2021 and October 2022 among participants in a community empowerment program.ResultsFood and water insecurity demonstrated significant, positive, reciprocal cross-lagged correlations. Generalized anxiety demonstrated significant, positive, reciprocal cross-lagged correlations with water insecurity. Food insecurity was not correlated with generalized anxiety within or between panels.ConclusionsSupporting climate adaptation requires understanding temporal relationships between mental health and water and food security. Anxiety may reduce capacities to adapt to water insecurity, as well as be reduced by water insecurity. Food security may increase the capacity of households to adapt to water insecurity, though further research is required to establish causation and mechanisms for all observed temporal correlations in this study.
‘Admissions to paediatric medical wards with a primary mental health diagnosis: a systematic review of the literature’
Authors: Vázquez-Vázquez Adriana , Smith Abigail , Gibson Faith , Roberts Helen , Mathews Gabrielle , Ward Joseph , Viner Russell , Nicholls Dasha , Cornaglia Francesca , Roland Damian , Phillips Kirsty , Hudson Lee 
Published: November 2023

ABSTRACTObjectiveTo systematically review the literature describing children and young people (CYP) admissions to paediatric general wards because of primary mental health reasons, particularly in MH crisis.DesignPubMed, Embase, PsychINFO, Web of Science and Google Scholar were searched. We addressed five search questions to inform: trends and/or the number of admissions, the risk factors for adverse care, the experiences of CYP, families/carers and health care professionals (HCPs) and the evidence of interventions aimed at improving the care during admissions.Two reviewers independently assessed the relevance of abstracts identified, extracted data and undertook quality assessment. This review was registered with Prospero (CRD42022350655).ResultsThirty-two studies met the inclusion criteria. Eighteen addressed trends and or numbers/proportions of admissions, 12 provided data about the views/experiences of HCPs, two provided data about CYPs’ experiences and four explored improving care. We were unable to identify studies examining risk factors for harm during admissions, but studies did report the length of stay in general paediatric/adult settings while waiting for specialised care, which could be considered a risk factor while caring for this group.ConclusionsMH admissions to children’s wards are a long-standing issue and are increasing. CYP will continue to need to be admitted in crisis, with paediatric wards a common allocation whilst waiting for assessment. For services to be delivered effectively and for CYPs and their families/carers to feel supported and HCPs to feel confident, we need to facilitate more integrated physical and MH pathways of care.What is already known on this topic?-There is evidence that both the number of paediatric admissions and the severity of MH crisis in CYP have increased. Children’s wards are not designed to treat CYP with MH problems and HCPs haven’t had enough training.-There is no published systematic review on this topic.What this study adds?-This is the first systematic review on CYP admissions to paediatric wards with a primary MH indication.-Evidence suggested increased numbers of admissions to paediatric wards over time. HCPs reported concerns about skill sets to manage CYP with MH presentations and questioned the appropriateness of the acute ward for this care.-There is limited evidence on CYP experiences during admissions and on studies to improve care. We found no evidence of specific risk factors for adverse care for CYP and families/carers during admissions and no studies on families/carers’ experiences.
A mechanical model of ocular bulb vibrations and implications for acoustic tonometry
Authors: Tambroni Nicoletta , Tomassetti Giuseppe , Lombardi Silvia , Repetto Rodolfo 
Published: November 2023

AbstractIn this study, we propose a comprehensive mechanical model of ocular bulb vibrations and discuss its implications for acoustic tonometry. The model describes the eye wall as a spherical, pre-stressed elastic shell containing a viscoelastic material and accounts for the interaction between the elastic corneoscleral shell and the viscoelastic vitreous humor. We investigate the natural frequencies of the system and the corresponding vibration modes, expanding the solution in terms of scalar and vector spherical harmonics. Our findings reveal the significant role of intraocular pressure (IOP) and ocular rigidity in influencing vibration frequencies, while the vitreous rheological properties primarily affect damping. This study contributes to the understanding of the mechanical behavior of the eye under dynamic conditions, with potential implications for non-contact intraocular pressure measurement techniques such as acoustic tonometry. The model can also be relevant for other ocular pathological conditions, such as traumatic retinal detachment, which are believed to be influenced by the dynamic behavior of the eye.
Topic: Effect of Lockdown Of COVID-19 And The Impact On People Living In Enugu State, Nigeria
Authors: Ojielo Nwadiuto C , Onwuliri Daniel C , Onuh Augustine , Ilo Ada , Njeze Ngozi R 
Published: November 2023

AbstractIntroductionWhen the coronavirus (COVID-19) pandemic struck, countries employed diverse strategies in the control of the virus aimed at preventing, detecting, controlling and mitigating the impact of the pandemic. Initially, there was no known cure for this viral infection so this ‘stay-at-home’ necessitated the preventive measures to break the chain of transmission. This study aims to examine the different challenges people passed through as a result of this pandemic and the effect of the lockdown on people. This study will serve as the basis for future reference to know if this lockdown could be repeated in the face of another pandemic.MethodologyThe study was carried out in Enugu Metropolis, South East, Nigeria. This is a cross-sectional study among people living in Enugu State. Google forms were dispatched to adults from 18-65 years on social media or the internet. Data entry was to Excel, then to SPSS version 26 and analyzed with student’s t-test and Chi-square.ResultsFrom the study, 35% said there were financial losses, some complained of poor recreation, 52% of people said there was loss of learning opportunities for their children due to school shutdown 23% had a reduction in their income with 35% losing their job, 57.9% of people said the crime rate increased, 26.6% had a mental breakdown, 45.1% of people had relationship/spousal problems and 64.1% of people lost someone during the COVID-19 lockdown and There were also some benefits of the lockdown like 70% said there was reduction in RTA, air pollution, introduction to remote working popularly known as “working from home” and 32% of people claimed it caused family bonding. In all, 73% of people said they would not want or support a repeat lockdown.ConclusionThe impact of the lockdown on the residents of Enugu State was generally not a palatable experience. From this study, though some good things were achieved, it led to a number of irreversible crises. It also caused serious implications like a decline to access to healthcare, economic effects, political, social and cultural effects, educational impacts, an increase in crime rate, domestic violence, religious impact, and environmental effects. In future, a better method of approach is recommended.
A 4-year review of amniocentesis at a tertiary hospital in Ethiopia: an experience from a LMIC
Authors: Mekuria Haile G. , Suga Hilkiah K. , Bekele Gadise 
Published: November 2023

AbstractBackgroundAmniocentesis is a technique for withdrawing amniotic fluid from the uterine cavity using a needle via a trans-abdominal approach. It has multiple diagnostic and therapeutic uses such as prenatal genetic studies and amnioreduction for polyhydramnios. The commonest indications are advanced maternal age and increased risk on maternal serum screening. The objective of this study is to review the common indications, outcomes and complications of amniocentesis at a tertiary hospital in Ethiopia.MethodsA retrospective cross-sectional study was conducted at a tertiary hospital in Ethiopia. Data was collected from the Fetomaternal division’s log records and follow-up charts during the time period of 2019 to 2022. All records of patients who had amniocentesis done were included in the study. Socio-demographic information and obstetric history and variables related to the procedures were retrieved. Descriptive statistics was done using the software IBM Statistical Package for Social Sciences (SPSS) version 25.ResultsA total of 35 patients’ records were reviewed. The mean maternal age was 32 years (range, 19 – 43 years). The mean gestational age was 20.9 weeks (SD ± 2.2). The commonest indications for amniocentesis were previous history of Down syndrome (11%), advanced maternal age (9%) and QUAD 1:200 for Down syndrome (6%). Karyotype test was done in 29 of the 35 amniocentesis cases which was normal in 72% of the cases, 17% had Trisomy-21 and 11% had Trisomy-18. Fifty-two percent of the pregnancy had a live full term delivery and 25% of the cases terminated the pregnancy.ConclusionThe most common indications for amniocentesis in Ethiopia were abnormal ultrasound finding, advanced maternal age and abnormal QUAD test results. Around a quarter of the genetic tests which were done after the procedure had chromosomal abnormalities, from which, the majority were terminated. There was no complication related to the procedure.
Anemia during pregnancy and adverse maternal outcomes in Georgia – a birth registry-based cohort study
Authors: Skhvitaridze Natia , Gamkrelidze Amiran , Manjavidze Tinatin , Brenn Tormod , Anda Erik , Rylander Charlotta 
Published: November 2023

AbstractBackgroundAnemia in pregnancy is an important public health challenge; however, it has not been thoroughly studied in Georgia. We assessed the prevalence of anemia during pregnancy across Georgia and the association between anemia in the third trimester of pregnancy and adverse maternal outcomes.MethodsWe used data from the Georgian Birth Registry and included pregnant women who delivered between January 1, 2019, and August 31, 2022 (n=158,668). The prevalence of anemia (hemoglobin (Hb) < 110 g/L) at any time during pregnancy was calculated per region. Women in the third trimester were classified into three groups, based on their lowest measured Hb value: no (Hb ≥110 g/L, reference group); mild (Hb 100-109 g/L); and moderate to severe anemia (Hb <99 g/L). Adjusted odds ratios (aOR) with 95% confidence intervals (CIs) were calculated for the associations between anemia status and post-delivery intensive care unit (ICU) admission and preterm delivery.ResultsThe prevalence of anemia occurring at least once during pregnancy was 40.6%, with large regional differences in anemia prevalence (25.1%–47.0%). Of 105,811 pregnant women with Hb measurements in the third trimester, 71.0% had no anemia; 20.9%, mild anemia; and 8.1%, moderate or severe anemia. The odds of post-delivery ICU admission did not increase linearly with decreasing Hb value (Pfor trend .13), and the relationship was inverse for preterm delivery (Pfor trend .01).ConclusionsA considerable proportion of pregnant women in Georgia have anemia during pregnancy, and the prevalence and quality of reporting differ across regions. Anemia occurring in the third trimester did not substantially increase the odds of maternal ICU admission or preterm delivery. To accelerate national progress toward the Sustainable Development Goals and mitigate the consequences of anemia, equal countrywide access to high-quality antenatal care programs and complete registration of Hb values should be ensured.