Miracle-dz/UniFAR-FTUs huggingface dataset:
Aberrant fast spiking interneuronal activity precedes seizure transitions in humans

There is active debate regarding how GABAergic function changes during seizure initiation and propagation, and whether interneuronal activity drives or impedes the pathophysiology. Here, we track cell-type specific firing during spontaneous human seizures to identify neocortical mechanisms of inhibitory failure. Fast-spiking interneuron activity was maximal over 1 second before equivalent excitatory increases, and showed transitions to out-of-phase firing prior to local tissue becoming incorporated into the seizure-driving territory. Using computational modeling, we linked this observation to transient saturation block as a precursor to seizure invasion, as supported by multiple lines of evidence in the patient data. We propose that transient blocking of inhibitory firing due to selective fast-spiking interneuron saturation - resulting from intense excitatory synaptic drive - is a novel mechanism that contributes to inhibitory failure, allowing seizure propagation.
Correlation between autistic traits and brain functional connectivity in preschoolers with autism spectrum disorder: a resting state MEG study

Background. Neurophysiological studies recognized that Autism Spectrum Disorder (ASD) is associated with altered patterns of over- and under-connectivity. However, few results are available about network organization in children with ASD in the early phases of development and the correlation with the severity of core autistic features. Methods. The present study aimed at investigating the association between brain connectivity derived by MEG signals and severity of ASD traits measured with different diagnostic clinical scales, in a sample of 16 children with ASD aged 2 to 6 years. Results. A significant correlation emerged between connectivity strength in cortical brain areas implicated in several resting state networks and the severity of communication anomalies, social interaction problems, social affect problems, and repetitive behaviors. Seed analysis revealed that this pattern of correlation was mainly caused by global rather than local effects. Conclusions. The present results confirm that altered connectivity strength in several resting state networks is related to clinical features and may contribute to neurofunctional correlates of ASD. Future studies implementing the same method on a wider and stratified sample may further support functional connectivity as a possible biomarker of the condition.
Facial emotion recognition is associated with executive functions and depression scores, but not staging of dementia, in mild‐to‐moderate Alzheimer's disease

Abstract Background Although deficits in facial emotion recognition (FER) significantly affect interpersonal communication and social functioning, there is no consensus on how FER affects Alzheimer's disease (AD). In this study, we aimed to investigate the clinical and neuropsychological factors affecting the possible deficits in the FER abilities of patients with AD. Methods This cross‐sectional study included 37 patients with mild [clinical dementia rating (CDR) scale score = 1] or moderate (CDR = 2) AD, in whom vascular dementia and depression were excluded, and 24 cognitively normal (CDR = 0) subjects. FER ability was determined using the facial emotion identification test (FEIT) and facial emotion discrimination test (FEDT). All participants underwent mini‐mental state examination (MMSE), frontal assessment battery (FAB), and geriatric depression scale (GDS). The neuropsychiatric inventory‐clinician rating scale (NPI‐C), Katz index of independence in activities of daily living, and Lawton instrumental activities of daily living were also administered to patients with AD. Results The FEIT and FEDT total scores showed that patients with mild and moderate AD had significant FER deficits compared to healthy controls. However, no significant difference was observed between patients with mild and moderate AD in the FEIT and FEDT total scores. FEIT and FEDT scores were not correlated with the MMSE and NPI‐C total and subscales scores in patients with AD. Linear regression indicated that FEIT and FEDT total scores were significantly related to age and FAB scores. The GDS score negatively moderated the relationship between FAB and FEDT. Conclusions This study demonstrated a decreased FER ability in patients with AD. The critical point in FER deficits is the presence of dementia, not the dementia stage, in AD. It has been determined that executive functions and depression (even at a subsyndromal level), which have limited knowledge, are associated with FER abilities.
Features of virtual reality impact effectiveness of VR pain alleviation therapeutics in pediatric burn patients: A randomized clinical trial

Key features of virtual reality (VR) that impact the effectiveness of pain reduction remain unknown. We hypothesized that specific features of the VR experience significantly impact VR’s effectiveness in reducing pain during pediatric burn dressing care. Our randomized controlled trial included children 6 to 17 years (inclusive) who were treated in the outpatient clinic of an American Burn Association–verified pediatric burn center. Participants were randomly assigned (1:1:1) to active VR (playing the VR), passive VR (immersed in the same VR environment without interactions), or standard-of-care. On a scale from 0 to 100, participants rated overall pain (primary outcome) and features of the VR experience (game realism, fun, and engagement). Path analysis assessed the interrelationships among these VR key features and their impact on self-reported pain scores. From December 2016 to January 2019, a total of 412 patients were screened for eligibility, and 90 were randomly assigned (31 in the active VR group, 30 in the passive VR group, and 29 in the standard-of-care group). The current study only included those in the VR groups. The difference in median scores of VR features was not statistically significant between the active (realism, 77.5 [IQR: 50–100]; fun, 100 [IQR: 81–100]; engagement, 90 [IQR: 70–100]) and passive (realism, 72 [IQR: 29–99]; fun, 93.5 [IQR: 68–100]; engagement, 95 [IQR: 50–100]) VR distraction types. VR engagement had a significant direct (-0.39) and total (-0.44) effect on self-reported pain score (p<0.05). Key VR features significantly impact its effectiveness in pain reduction. The path model suggested an analgesic mechanism beyond distraction. Differences in VR feature scores partly explain active VR’s more significant analgesic effect than passive VR. Trial Registration: ClinicalTrials.gov Identifier: NCT04544631.
The influence of African easterly waves on Atlantic tropical cyclone activity

A high-resolution global atmospheric model is used to disentangle the relationship between African easterly waves (AEWs) and Atlantic tropical storms (TCs) from the large-scale environmental factors that may obscure their connection. Since the two most cited references on AEW interannual variability in relation to TC activity draw conflicting conclusions about the historical relationship, and the AEW counts in each study do not show agreement on historical variability, novel analysis procedures are developed to produce consistent AEW and TC count statistics for the historical record using reanalysis products. This reanalysis-derived historical record is used to legitimize the model for the study of AEWs, which is subsequently utilized to investigate the relationship between AEWs and TCs. The internal variability of the relationship between AEW and TC count, including the sensitivity to ENSO phase and annual trends, and the interplay between environmental factors, AEW activity, and TC activity are probed using three sets of simulations: 1) climatological simulations, consisting of three ensemble members forced with historical seasonally and annually varying SST; 2) simulations with interannually invariant forcing, including a control simulation with climatological mean SST and a perpetual La Niña simulation with composite SST from strong La Niña years; 3) perturbed simulations, in which the large-scale environment is drastically altered through the manipulation of African albedo. Since variability exists in AEW count that is unexplained by known indicators of large-scale environmental favorability, across all simulations and multiple timescales, it is unlikely that the ubiquitous covariance between AEW and TC count is simply a response to environmental factors. The statistically significant correlations between AEW and TC statistics suggest that AEW variability accounts for a portion of the observed variability in TC count not due to known environmental factors, since there is unexplained variance in AEW count, and both individual years and aggregated iii model runs with more (fewer) AEWs also tend to have more (fewer) TCs. It is argued that while half of the covariance between AEW and TC count interannually is mediated by the large-scale environment, the other half can be attributed to stochastic AEW variability.
Comparing glycemic traits in defining diabetes among rural Chinese older adults

Background We sought to identify the optimal cut-off of glycated hemoglobin (HbA1c) for defining diabetes and to assess the agreements of fasting plasma glucose (FPG), fasting serum glucose (FSG), and HbA1c in defining diabetes among rural older adults in China. Methods This population-based cross-sectional study included 3547 participants (age ≥61 years, 57.8% women) from the Multidomain Interventions to Delay Dementia and Disability in Rural China from 2018–2019; of these, 3122 had no previously diagnosed diabetes. We identified the optimal cut-off of HbA1c against FPG ≥7.0 mmol/L for defining diabetes by using receiver operating characteristic curve and Youden index. The agreements of FPG, FSG, and HbA1c in defining diabetes were assessed using kappa statistics. Results Among participants without previously diagnosed diabetes (n = 3122), the optimal HbA1c cut-off for defining diabetes was 6.5% (48 mmol/mol), with the sensitivity of 88.9%, specificity of 93.7%, and Youden index of 0.825. The correlation coefficients were 0.845 between FPG and FSG, 0.574 between FPG and HbA1c, and 0.529 between FSG and HbA1c in the total sample (n = 3547). The kappa statistic for defining diabetes was 0.962 between FSG and FPG, and 0.812 between HbA1c and FPG. Conclusions The optimal cut-off of HbA1c for diagnosing diabetes against FPG >7.0 mmol/L is ≥6.5% in Chinese rural-dwelling older adults. The agreement in defining diabetes using FPG, FSG, and HbA1c is nearly perfect. These results have relevant implications for diabetes research and clinical practice among older adults in China. Clinical trial registration The protocol of MIND-China was registered in the Chinese Clinical Trial Registry (ChiCTR, www.chictr.org.cn; registration no.: ChiCTR1800017758).
Marburg Virus Outbreak in Equatorial Guinea: Need for Speed

The co-existence of deadly viral pandemics can be considered a nightmare for public health authorities. The surge of a Marburg virus disease (MVD) outbreak in Africa at a time when the coronavirus-19 (COVID-19) pandemic is partially controlled with its limited resources is an urgent call for concern. Over the past decades, several bouts of MVD outbreaks have occurred in Africa with an alarming case fatality rate. Despite this, little has been done to end its recurrence, and affected countries essentially depend on preventative rather than curative measures of management. The recent outbreak of MVD declared by the health officials of Equatorial Guinea, causing several deaths in the context of the COVID-19 pandemic, signals the need for speed in the establishment and the implementation of appropriate health policies and health system strategies to contain, destroy, and prevent the spread of this deadly virus to other neighboring countries.
Updates on Neuronavigation: Emerging tools for tumor resection

Multiple studies have been conducted to properly elucidate the various tools available to help enhance the resection of tumor tissue, aneurysms, and arteriovenous malformations (AVM). Diffusion tensor imaging (DTI) tractography is useful in providing a map of the tumor borders, allowing the optimal preservation of function and structure of specific regions of the brain. During neurosurgery, especially craniotomies, the possibility of the brain shifting due to swelling or gravity is high. Thus, tools for intraoperative imaging such as high-frequency linear array ultrasound transducers and doppler ultrasonography are utilized for high resolution images and detecting frequency shifts. 4D-digital subtraction angiography (DSA) is another technique used to create spatial resolutions and 3D maps for aneurysms. These similar techniques can also be utilized to assess the integrity of white matter in AVM. By implementing effective evaluation strategies, healthcare professionals can make informed decisions regarding treatment options, preventive measures, and long-term care plans tailored to individual patients.
Kidins220 regulates the development of B cells bearing the λ light chain

The ratio between κ and λ light chain (LC)-expressing B cells varies considerably between species. We recently identified Kinase D-interacting substrate of 220 kDa (Kidins220) as an interaction partner of the BCR. In vivo ablation of Kidins220 in B cells resulted in a marked reduction of λLC-expressing B cells. Kidins220 knockout B cells fail to open and recombine the genes of the Igl locus, even in genetic scenarios where the Igk genes cannot be rearranged or where the κLC confers autoreactivity. Igk gene recombination and expression in Kidins220-deficient B cells is normal. Kidins220 regulates the development of λLC B cells by enhancing the survival of developing B cells and thereby extending the time-window in which the Igl locus opens and the genes are rearranged and transcribed. Further, our data suggest that Kidins220 guarantees optimal pre-BCR and BCR signaling to induce Igl locus opening and gene recombination during B cell development and receptor editing.
Analysis of translesion polymerases in colorectal cancer cells following cetuximab treatment: A network perspective

Abstract Introduction Adaptive mutagenesis observed in colorectal cancer (CRC) cells upon exposure to EGFR inhibitors contributes to the development of resistance and recurrence. Multiple investigations have indicated a parallel between cancer cells and bacteria in terms of exhibiting adaptive mutagenesis. This phenomenon entails a transient and coordinated escalation of error‐prone translesion synthesis polymerases (TLS polymerases), resulting in mutagenesis of a magnitude sufficient to drive the selection of resistant phenotypes. Methods In this study, we conducted a comprehensive pan‐transcriptome analysis of the regulatory framework within CRC cells, with the objective of identifying potential transcriptome modules encompassing certain translesion polymerases and the associated transcription factors (TFs) that govern them. Our sampling strategy involved the collection of transcriptomic data from tumors treated with cetuximab, an EGFR inhibitor, untreated CRC tumors, and colorectal‐derived cell lines, resulting in a diverse dataset. Subsequently, we identified co‐regulated modules using weighted correlation network analysis with a minKMEtostay threshold set at 0.5 to minimize false‐positive module identifications and mapped the modules to STRING annotations. Furthermore, we explored the putative TFs influencing these modules using KBoost, a kernel PCA regression model. Results Our analysis did not reveal a distinct transcriptional profile specific to cetuximab treatment. Moreover, we elucidated co‐expression modules housing genes, for example, POLK, POLI, POLQ, REV1, POLN, and POLM. Specifically, POLK, POLI, and POLQ were assigned to the “blue” module, which also encompassed critical DNA damage response enzymes, for example. BRCA1, BRCA2, MSH6, and MSH2. To delineate the transcriptional control of this module, we investigated associated TFs, highlighting the roles of prominent cancer‐associated TFs, such as CENPA, HNF1A, and E2F7. Conclusion We found that translesion polymerases are co‐regulated with DNA mismatch repair and cell cycle‐associated factors. We did not, however, identified any networks specific to cetuximab treatment indicating that the response to EGFR inhibitors relates to a general stress response mechanism.
The miR-146b-3p/TNFAIP2 axis regulates cell differentiation in acute myeloid leukaemia

Our purpose is to verify that miR-146b-3p targets the downstream transcript TNFAIP2 in order to reveal the machinery underlying the miR-146b-3p/TNFAIP2 axis regulating acute myeloid leukaemia (AML) differentiation. Bioinformatics analyses were performed using multiple databases and R packages. The CD11b+ and CD14+ cell frequencies were detected using flow cytometry and immunofluorescence staining. The TNFAIP2 protein expression was evaluated using western blotting, immunocytochemistry and immunofluorescence staining. The qRT-PCR was conducted to detect the expression of TNFAIP2 and miR-146b-3p. TNFAIP2 and its correlated genes were enriched in multiple cell differentiation pathways. TNFAIP2 was upregulated upon leukaemic cell differentiation. miR-146b-3p directly targeted TNFAIP2, resulting in a decrease in TNFAIP2 expression. Forced expression of TNFAIP2 or knockdown of miR-146b-3p significantly induced the differentiation of MOLM-13 cells. In this study, we demonstrated that TNFAIP2 is a critical driver in inducing differentiation and that the miR-146b-3p/TNFAIP2 axis involves in regulating cell differentiation in AML.
Abrupt Decline in Estimated Glomerular Filtration Rate after Initiating Sodium-Glucose Cotransporter 2 Inhibitors Predicts Clinical Outcomes: A Systematic Review and Meta-Analysis.

Background The initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) typically leads to a reversible initial dip in estimated glomerular filtration rate (eGFR). The implications of this phenomenon on clinical outcomes are not well-defined. Methods We searched MEDLINE, Embase, and Cochrane Library from inception to March 23, 2023 to identify randomized controlled trials and cohort studies comparing kidney and cardiovascular outcomes in patients with and without initial eGFR dip after initiating SGLT2i. Pooled estimates were calculated using random-effect meta-analysis. Results We included seven studies in our analysis, which revealed that an initial eGFR dip following the initiation of SGLT2i was associated with less annual eGFR decline (mean difference, 0.64; 95% confidence interval [CI], 0.437 to 0.843) regardless of baseline eGFR. The risk of major adverse kidney events was similar between the non-dipping and dipping groups but reduced in patients with a ≤10% eGFR dip (hazard ratio [HR], 0.915; 95% CI, 0.865 to 0.967). No significant differences were observed in the composite of hospitalized heart failure and cardiovascular death (HR, 0.824; 95% CI, 0.633 to 1.074), hospitalized heart failure (HR, 1.059; 95% CI, 0.574 to 1.952), or all-cause mortality (HR, 0.83; 95% CI, 0.589 to 1.170). The risk of serious adverse events (AEs), discontinuation of SGLT2i due to AEs, kidney-related AEs, and volume depletion were similar between the two groups. Patients with >10% eGFR dip had increased risk of hyperkalemia compared to the non-dipping group. Conclusion Initial eGFR dip after initiating SGLT2i might be associated with less annual eGFR decline. There were no significant disparities in the risks of adverse cardiovascular outcomes between the dipping and non-dipping groups.
Species-level resolution for the vaginal microbiota with short amplicons

ABSTRACT Specific bacterial species have been found to play important roles in human vagina. Achieving high species-level resolution is vital for analyzing vaginal microbiota data. However, contradictory conclusions were yielded from different methodological studies. More comprehensive evaluation is needed for determining an optimal pipeline for vaginal microbiota. Based on the sequences of vaginal bacterial species downloaded from NCBI, we conducted simulated amplification with various primer sets targeting different 16S regions as well as taxonomic classification on the amplicons applying different combinations of algorithms (BLAST+, VSEARCH, and Sklearn) and reference databases (Greengenes2, SILVA, and RDP). Vaginal swabs were collected from participants with different vaginal microecology to construct 16S full-length sequenced mock communities. Both computational and experimental amplifications were performed on the mock samples. Classification accuracy of each pipeline was determined. Microbial profiles were compared between the full-length and partial 16S sequencing samples. The optimal pipeline was further validated in a multicenter cohort against the PCR results of common STI pathogens. Pipeline V1–V3_Sklearn_Combined had the highest accuracy for classifying the amplicons generated from both the NCBI downloaded data (84.20% ± 2.39%) and the full-length sequencing data (95.65% ± 3.04%). Vaginal samples amplified and sequenced targeting the V1–V3 region but merely employing the forward reads (223 bp) and classified using the optimal pipeline, resembled the mock communities the most. The pipeline demonstrated high F1-scores for detecting STI pathogens within the validation cohort. We have determined an optimal pipeline to achieve high species-level resolution for vaginal microbiota with short amplicons, which will facilitate future studies. IMPORTANCE For vaginal microbiota studies, diverse 16S rRNA gene regions were applied for amplification and sequencing, which affect the comparability between different studies as well as the species-level resolution of taxonomic classification. We conducted comprehensive evaluation on the methods which influence the accuracy for the taxonomic classification and established an optimal pipeline to achieve high species-level resolution for vaginal microbiota with short amplicons, which will facilitate future studies.
Optimizing spaceborne LiDAR and very high resolution optical sensor parameters for biomass estimation at ICESat/GLAS footprint level using regression algorithms

Forests sequester large quantity of carbon in their woody biomass and hence accurate estimation of forest biomass is extremely crucial. The present study aims at combining information from spaceborne LiDAR (ICESat/GLAS) and high resolution optical data to estimate forest biomass. Estimation of aboveground biomass (AGB) at ICESat/GLAS footprint level was done by integrating data from multiple sensors using two regression algorithms, viz. random forest (RF) and support vector machine (SVM). The study used forest height and canopy return ratio (rCanopy) for determination of effective size of ICESat/GLAS footprints for field data collection. The forest height was predicted with root mean square error (RMSE) of 1.35 m. The study showed that six most important parameters derived from LiDAR, and passive optical data were able to explain 78.7% (adjusted) variation in the observed AGB with an RMSE of 13.9 Mg ha–1. It was also observed that 15 most important parameters were able to explain 83% (adjusted) variation in the observed AGB. It was found that SVM regression algorithm explained 88.7% of variation in AGB with an RMSE of 13.6 Mg ha–1 on the combined datasets while RF regression algorithm explained 83.5% of variation in AGB with an RMSE of 20.57 Mg ha–1. The study demonstrated that RF regression algorithm performs equally well on datasets irrespective of the correlation of underlying variables with the predicted variable whereas SVM regression was found to perform well on those datasets which had a subset of underlying variables that are correlated with the predicted variable. The study highlighted that sensor integration approach is more accurate than single sensor approach in predicting the AGB.