bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ketogenic diet reduces a neurobiological craving signature in alcohol use disorder
Authors: Wiers Corinde E. , Manza Peter , Wang Gene-Jack , Volkow Nora D. 
Published: September 2023

AbstractBackground and AimsIncreasing evidence suggests that a ketogenic (high-fat, low-carbohydrate) diet intervention reduces alcohol withdrawal severity and alcohol craving in individuals with alcohol use disorder (AUD) by shifting brain energetics from glucose to ketones. We hypothesized that the ketogenic diet would reduce a brain craving signature when individuals undergoing alcohol detoxification treatment were exposed to alcohol cues.MethodsWe performed a secondary analysis of functional magnetic resonance data of n=33 adults with an AUD were randomized to a ketogenic diet (n=19) or a standard American diet (n=14) and underwent three weeks of inpatient alcohol detoxification treatment. Once per week, participants performed an alcohol cue-reactivity paradigm with functional magnetic resonance imaging. We extracted brain responses to food and alcohol cues and quantified the degree to which each set of brain images shared a pattern of activation with a recently validated ‘Neurobiological Craving Signature’ (NCS). We then performed a group-by-time repeated measures ANOVA to test for differences in craving signature expression between the dietary groups over the three-week treatment period. We also correlated these expression patterns with self-reported wanting ratings for alcohol cues.ResultsFor alcohol relative to food cues, there was a main effect of group, such that the ketogenic diet group showed lower NCS expression across all three weeks of treatment. The main effect of time and the group-by-time interaction were not significant. Self-reported wanting for alcohol cues reduced with KD compared to SA but did not correlate with the NCS score.ConclusionsA ketogenic diet reduces self-reported alcohol wanting, and induced lower brain craving signatures to alcohol cues during inpatient treatment for AUD.
Developing and validating the Nepalese Abuse Assessment Screen (N-AAS) for identifying domestic violence among pregnant women in Nepal
Authors: Manandhar Pratibha , Chalise Pratibha , Rishal Poonam , Campbell Jacquelyn , Henriksen Lena , Infanti Jennifer J. , Joshi Sunil Kumar , Lukasse Mirjam , Pun Kunta Devi , Schei Berit , Swahnberg Katarina 
Published: September 2023

AbstractThis study culturally adapted and validated a Nepalese version of the Abuse Assessment Screen (AAS) tool for identifying domestic violence among pregnant women in Nepal, creating the Nepalese Abuse Assessment Screen (N-AAS). International and national topic experts reviewed the initial N-AAS version using the Delphi method, and pregnant women participated in cognitive interviews, providing feedback on the N-AAS as user experts. Subsequent pre-testing of a comprehensive questionnaire, which included the translated version of the N-AAS, occurred in two tertiary care hospitals using an electronic format known as Color-Coded Audio Computer-Assisted Self-Interview (C-ACASI). We assessed the content validity index, compared the concurrent validity of the N-AAS with the gold standard interview, estimated the prevalence of domestic violence from two hospitals, and calculated the Kappa coefficient. The reliability of the entire questionnaire was also evaluated through a test-retest analysis, with content validity rated as “good to excellent” by topic and user experts and high test-retest reliability (91.2–98.9%), indicating consistency across questionnaires completed at two different time points, with 12% of participants reporting any form of violence. The N-AAS demonstrated ≥91.7% specificity for all forms of abuse, accurately identifying non-abuse cases. In addition, moderate to excellent sensitivity was observed for emotional abuse (52.5%) and physical abuse since marriage (50%), while sensitivity for physical abuse in the past 12 months was 100%. Thus, the N-AAS demonstrated reliable test-retest results with a good Kappa coefficient and specificity, as well as showing excellent sensitivity for detecting recent physical abuse and moderate sensitivity for detecting emotional abuse and physical abuse since marriage. Because cultural context often leads women to normalize and tolerate abuse from spouses and family members and women are thus reluctant to report abuse, the results imply that the N-AAS can serve as a valuable screening tool for domestic abuse in antenatal care settings in Nepal.
Cladosporiumspecies detoxify multiple water micropollutants of emerging concern using diverse strategies
Authors: Leth Maria Louise , Tang Kai , Sørensen Trine , Andersen Aaron John , Hélix-Nielsen Claus , Andersen Birgitte , Frisvad Jens , Sondergaard Teis Esben , Andersen Henrik Rasmus , Hachem Maher Abou 
Published: September 2023

AbstractThe accumulation of micropollutants of emerging concern in aqueous systems raises safety concerns regarding biological systems and human health. Mycoremediation is a promising and green strategy to mitigate the micropollutant challenge. Hitherto, focus has mainly been on white-rot Basidiomycota and micropollutant transformation by ascomycetes remains underexplored. Here, we assayed 53 Ascomycota isolates from 10 genera for the removal of 22 micropollutants. Notably, 9 out of 22 micropollutants were removed from fungal culture supernatant at efficacies >45%. Temporal analysis of the nine top- performing strains, highlighted remarkable potency ofCladosporiumisolates in removal of multiple micropollutants. Importantly,Cladosporiumconsiderably reduced the toxicity of a micropollutant cocktail based on growth assays. Metabolomics analyses identified oxidation for 5-methyl-1H-benzotriazole and citalopram, whereas methylation and carboxylation were observed for 5-chlorobenzotriazole. No transformation products were detected for ciprofloxacin, sulfamethoxazole, and sertraline, hinting their extensive degradation. These findings suggest micropollutant transformation via diverse catalytic routes byCladosporium. Genome sequencing and proteomic analyses of the top-performing isolates were consistent with the observed transformations and tentatively identified the molecular apparatus, conferring micropollutant transformation. This unprecedented study brings novel insight into the micropollutant transformation and detoxification capabilities of the prevalentCladosporiumspecies, thereby revealing a considerable and hitherto underappreciated potential of this genus and potentially other ascomycetes in micropollutant transformation.ImportanceAt present, conventional wastewater treatment plants (WWTPs) are not designed for removing micropollutants, which are released into aqueous systems. This raises concerns due to the poor insight into micropollutant long-term interplay with biological systems. Innovating biotechnological solutions to tackle micropollutant require addressing the paucity of knowledge on microbial groups and molecular pathways, which mediate micropollutant transformation. Our study highlights the considerable potential of theCladosporiumgenus that remains underexplored in the arena of micropollutant transformation. We report the first genomes sequences for threeCladosporiumspecies:C. allicinum, C. inversicolor,andC. fusiforme, which sets the stage for further analyses of micropollutant transformation, but also offers an important resource on this ecologically significant, albeit under-studied genus and related Ascomycota.
Single-cell multi-omics map of human foetal blood in Down’s Syndrome
Authors: Marderstein Andrew R. , Zuani Marco De , Xue Haoliang , Bezney Jon , Wong Shuo , Coorens Tim H. H. , Montgomery Stephen B. , Cvejic Ana 
Published: September 2023

AbstractDown’s Syndrome (DS) predisposes individuals to haematological abnormalities, such as increased number of erythrocytes and leukaemia in a process that is initiated before birth and is not entirely understood. To understand dysregulated hematopoiesis in DS, we integrated single-cell transcriptomics of over 1.1 million cells with chromatin accessibility and spatial transcriptomics datasets using human foetal liver and bone marrow samples from three disomic and 15 trisomic foetuses. We found that differences in gene expression in DS were both cell type- and environment-dependent. Furthermore, we found multiple lines of evidence that DS haematopoietic stem cells (HSCs) are “primed” to differentiate. We subsequently established a DS-specific map of enhancer-gene relationships in disomic and trisomic HSCs using 10X Multiome data. By integrating this map with genetic variants associated with blood cell variation, we discovered that trisomy restructured enhancer-gene maps to dysregulate enhancer activity and gene expression critical to erythroid lineage differentiation. Further, as DS mutations display a signature of oxidative stress, we validated both increased mitochondrial mass and oxidative stress in DS, and observed that these mutations preferentially fell into regulatory regions of expressed genes in HSCs. Altogether, our single- cell, multi-omic resource provides a high-resolution molecular map of foetal haematopoiesis in Down’s Syndrome and indicates significant enhancer-gene restructuring giving rise to co- occurring haematological conditions.
HaloTag display enables quantitative single-particle characterization and functionalization of engineered extracellular vesicles
Authors: Mitrut Roxana E. , Stranford Devin M. , DiBiase Beth N. , Chan Jonathan M. , Bailey Matthew D. , Luo Minrui , Harper Clare S. , Meade Thomas J. , Wang Muzhou , Leonard Joshua N. 
Published: September 2023

ABSTRACTExtracellular vesicles (EVs) play key roles in diverse biological processes, transport biomolecules between cells, and have been engineered for therapeutic applications. A useful EV bioengineering strategy is to express engineered proteins on the EV surface to confer targeting, bioactivity, and other properties. Measuring how incorporation varies across a population of EVs is important for characterizing such materials and understanding their function, yet it remains challenging to quantitatively characterize the absolute number of engineered proteins incorporated at single-EV resolution. To address these needs, we developed a HaloTag-based characterization platform in which dyes or other synthetic species can be covalently and stoichiometrically attached to engineered proteins on the EV surface. To evaluate this system, we employed several orthogonal quantification methods, including flow cytometry and fluorescence microscopy, and found that HaloTag-mediated quantification is generally robust across EV analysis methods. We compared HaloTag-labeling to antibody-labeling of EVs using single vesicle flow cytometry, enabling us to measure the substantial degree to which antibody labeling can underestimate proteins present on an EV. Finally, we demonstrate the use of HaloTag to compare between protein designs for EV bioengineering. Overall, the HaloTag system is a useful EV characterization tool which complements and expands existing methods.
Gut microbial genomes with paired isolates from China signify probiotic and cardiometabolic effects
Authors: Huang Pan , Dong Quanbing , Wang Yifeng , Tian Yunfan , Wang Shunhe , Zhang Chengcheng , Yu Leilei , Tian Fengwei , Gao Xiaoxiang , Guo Hang , Yi Shanrong , Li Mingyang , Liu Yang , Zhang Qingsong , Lu Wenwei , Wang Gang , Yang Bo , Cui Shumao , Hua Dongxu , Wang Xiuchao , Jiao Yuwen , Liu Lu , Deng Qiufeng , Ma Beining , Wu Tingting , Zou Huayiyang ,   CGMR Consortium, Shi Jing , Zhang Haifeng , Fan Daming , Sheng Yanhui , Zhao Jianxin , Tang Liming , Zhang Hao , Sun Wei , Chen Wei , Kong Xiangqing , Chen Lianmin , Zhai Qixiao 
Published: September 2023

SUMMARYThe gut microbiome displays significant genetic differences between populations while systematic characterization of the genomic landscape of the gut microbiome in Asia populations remains limited. Here, we present the Chinese gut microbial reference (CGMR) set, comprising 101,060 high quality metagenomic assembled genomes (MAGs) of 3,707 non-redundant species paired with 1,376 live isolates from a national wide collection of 3,234 fecal samples across China. This improved reference set contains 987 novel species compared with existing resources worldwide. By associating MAGs with geographic and phenotypic characteristics, we observed regional-specific coexisting MAGs and MAGs with probiotic and cardiometabolic functionalities. We further conducted mice experiments to confirm the probiotic effects of twoFaecalibacterium intestinalisisolates in alleviating constipation, the cardiometabolic influences of threeBacteroides fragilis_Aisolates in obesity, and the functional potential of isolates from the two new species belonging to the generaParabacteroidesandLactobacillusin host lipids metabolism. Our study not only expands the current microbial genomes with paired isolates but also demonstrates their probiotic and cardiometabolic effects on hosts, contributing to the mechanistic understanding of host-microbe interactions and the translation of microbiome-based personalized therapies.
Comparing the Diagnostic Performance of qPCR, ddPCR, and NGS Liquid Biopsies for HPV-Associated Cancers
Authors: Naegele Saskia , Ruiz-Torres Daniel A. , Zhao Yan , Goss Deborah , Faden Daniel L. 
Published: September 2023

AbstractHPV-associated cancers, including oropharyngeal squamous cell carcinoma(HPV+OPSCC), cervical cancer(HPV+CC), and squamous cell carcinoma of the anus(HPV+SCCA), release circulating tumor HPV DNA(ctHPVDNA) into the blood. The diagnostic performance of ctHPVDNA detection depends on the approaches utilized and the individual assay metrics. A comparison of these approaches has not been systematically performed to inform expected performance, which in turn impacts clinical interpretation. A meta-analysis was performed using Ovid MEDLINE, Embase, and Web of Science Core Collection databases to assess the diagnostic accuracy of ctHPVDNA detection across cancer anatomic sites, detection platforms, and blood components. The population included HPV+OPSCC, HPV+CC, and HPV+SCCA patients with pre-treatment samples analyzed by quantitative PCR(qPCR), digital droplet PCR(ddPCR), or next generation sequencing(NGS). 36 studies involving 2,986 patients met the inclusion criteria. The sensitivity, specificity and quality of each study were assessed and pooled for each analysis.The sensitivity of ctHPVDNA detection was greatest with NGS, followed by ddPCR and lastly qPCR when pooling all studies, while specificity was similar(sensitivity: ddPCR>qPCR, p<0.001; NGS>ddPCR, p=0.014). ctHPVDNA from OPSCC was more easily detected compared to CC and SCCA, overall(p=0.044).In conclusion, detection platform, anatomic site of the cancer and blood component utilized impacts ctHPVDNA detection and must be considered when interpreting results. Plasma NGS-based testing should be considered the most sensitive approach for ctHPVDNA overall.
Assessment of Accuracy and Safety of LabTest Checker (LTC-AI)
Authors: Szumilas Dawid , Ochmann Anna , Zięba Katarzyna A. , Bartoszewicz Bartłomiej , Kubrak Anna , Makuch Sebastian , Agrawal Siddarth , Mazur Grzegorz , Chudek Jerzy 
Published: September 2023

AbstractBackgroundIn recent years, the implementation of artificial intelligence (AI) in healthcare is progressively transforming medical fields, with Clinical Decision Support Systems (CDSS) as a notable application. Laboratory tests are vital for accurate diagnoses, but their increasing reliance presents challenges. The need for effective strategies for managing laboratory test interpretation is evident from the millions of monthly searches on test results’ significance. The potential role of CDSS in laboratory diagnostics gains significance, however, more research needs to explore this area.ObjectiveThe primary objective of our study was to assess the accuracy and safety of LabTest Checker (LTC), a CDSS designed to support medical diagnoses by analyzing both laboratory test results and patients’ medical historiesMethodsThis cohort study embraced a prospective data collection approach. A total of 101 patients were enrolled, aged 18 and above, in stable condition, requiring comprehensive diagnosis. A panel of blood laboratory tests was conducted for each participant. Participants utilized LabTest Checker for test result interpretation. Accuracy and safety of the tool were assessed by comparing AI-generated suggestions to experienced doctor (consultant) recommendations, considered the gold standard.ResultsThe system achieved a 74.3% accuracy and 100% sensitivity for emergency safety and 92.3% sensitivity for urgent cases. It potentially reduced unnecessary medical visits by 41.6% and achieved an 82.9% accuracy in identifying underlying pathologies.ConclusionThis study underscores the transformative potential of AI-based CDSS in laboratory diagnostics, contributing to enhanced patient care, efficient healthcare systems, and improved medical outcomes. LabTest Checker’s performance evaluation highlights the advancements in AI’s role in laboratory medicine.
Dendrites support formation and reactivation of sequential memories through Hebbian plasticity
Authors: Quaresima Alessio , Fitz Hartmut , Duarte Renato , Hagoort Peter , Petersson Karl Magnus 
Published: September 2023

AbstractStorage and retrieval of sequences require memory that is sensitive to the temporal order of features. For example, in human language, words that are stored in long-term memory are retrieved based on the order of phonemes. It is currently unknown whether Hebbian learning supports the formation of memories that are structured in time. We investigated whether word-like memories can emerge in a network of neurons with dendritic structures. Dendrites provide neuronal processing memory on the order of 100 ms and have been implicated in structured memory formation. We compared a network of neurons with dendrites and two networks of point neurons that have previously been shown to acquire stable long-term memories and process sequential information. The networks were equipped with voltage-based, spike-timing dependent plasticity (STDP) and were homeostatically balanced with inhibitory STDP. In the learning phase, networks were exposed to phoneme sequences and word labels, which led to the formation of overlapping cell assemblies. In the retrieval phase, networks only received phoneme sequences as input, and we measured the firing activity of the corresponding word populations. The dendritic network correctly reactivated the word populations with a success rate of 80%, including words composed of the same phonemes in a different order. The networks of point neurons reactivated only words that contained phonemes that were unique to these words and confused words with shared phonemes (success rate below 20%). These results suggest that the slow timescale and non-linearity of dendritic depolarization allowed neurons to establish connections between neural groups that were sensitive to serial order. Inhibitory STDP prevented the potentiation of connections between unrelated neural populations during learning. During retrieval, it maintained the dendrites hyperpolarized and limited the reactivation of incorrect cell assemblies. Thus, the addition of dendrites enables the encoding of temporal relations into associative memories.
A synthetic Notch (synNotch) system linking intratumoral immune-cancer cell communication to a synthetic blood biomarker assay
Authors: Fu YangHao , Wang TianDuo , Ronald John A. 
Published: September 2023

ABSTRACTIntroductionCellular immunotherapy has greatly improved cancer treatment in recent years. For instance, chimeric antigen receptor (CAR) T-cell therapy has been proven highly effective in treating hematological malignancies, and many CAR cell designs are being explored for solid tumors. However, many questions remain why responses differ across patients and some tumor types are resistant. Improved and relatively inexpensive ways to monitor these cells could provide some answers. Clinically, blood tests are regularly used to monitor these therapies, but blood signals often do not reflect the activity of immune cells within the tumor(s). Here, using the synthetic Notch (synNotch) receptor that tethers antigen binding to customized transgene expression, we linked intratumoral immune-cancer cell communication to a simple secreted reporter blood test. Specifically, we engineered immune cells with a CD19-targeted synNotch receptor and demonstrate that binding to CD19 on cancer cells in vivo resulted in the production of secreted embryonic alkaline phosphatase (SEAP) at levels that are readily detected in the blood.Methods and ResultsJurkat T cells were engineered via sequential lentiviral transduction of two components: an anti-CD19 synNotch receptor and asynNotchresponse element encoding SEAP. Co-culture of engineered cells with CD19+, but not CD19-, Nalm6 cells, resulted in significantly elevated SEAP in media. Nod-scid-gamma (NSG) mice were subcutaneously injected with either CD19+or CD19-Nalm6 cells. Intratumoral injection of engineered T cells (1x107) resulted significantly elevated blood SEAP activity in mice bearing CD19+tumors (n=7), but not CD19-tumors (n=5).DiscussionOur synNotch reporter system allows for the monitoring of antigen-dependent intratumoral immune-cancer cell interactions through a simple and convenient blood test. Continued development of this system for different target antigens of interest should provide a broadly applicable platform for improved monitoring of many cell-based immunotherapies during their initial development and clinical translation, ultimately improving our understanding of design considerations and patient-specific responses.
Microdroplet-enabled high-throughput cultivation of vaginal bacteria using cervicovaginal fluids
Authors: Jackman Corine M. , Tan James Y. , Lin Xiaoxia Nina 
Published: September 2023

AbstractThe human vaginal microbiome (HVM) is closely associated with the health of the host. In particular, bacterial vaginosis, a condition where vaginal lactobacilli are reduced dramatically by an overgrowth of various other bacteria, has been linked to increased risk of sexually transmitted infectious diseases, including HIV, and preterm birth. Recent culture-independent studies leveraging next-generation sequencing technology have revealed that the HVM composition differs between women and changes over time. However, questions remain as to the underlying mechanisms and culture-dependent studies are needed for further elucidation of the HVM’s genotype-phenotype relationships and system-level propertiesin vivo. In this work, we have adapted a previously developed microdroplet-based high-throughput cultivation platform for the investigation of vaginal bacteria using the cervicovaginal fluid (CVF) as cultivation medium. Using undiluted CVF collected with Softdiscs discs, we observed the growth ofL. inersin microdroplets containing CVF pooled from samples with a high prevalence ofL. crispatus. Although demonstrated withL. iners, this work establishes a new framework for culturing microorganisms under clinically-relevant conditionsex vivousing minute volumes of host fluids; it can be further extended and adapted for addressing numerous questions about the HVM and other complex microbiomes.