bluuebunny/crossref_metadata_2025 huggingface dataset:
TREM2 Alteration Increases AD Biomarkers and is Associated with Key Genes with 5xFAD Mice Model Analysis on MODEL-AD Database
Authors: Budyak Elena I. , Kwon Jihoon , Messenger Evan J , Maharjan Surendra , Koothur Juan J
Published: August 2023

Alzheimer Disease is a multifactorial disorder characterized by cognitive decline and memory loss. A key gene associated with AD is the TREM2 gene which has been identified as a risk factor for AD. Studies show that TREM2 functions in microglia regulation that controls the amount of AB proteins by the mechanisms of clearance and degradation. However, the exact mechanism of how the TREM2 variations like TREM2 KO and TREM2 R47H contribute to the progression of Alzheimer is still debated. Moreover, research into the levels of gene expression and measurements of biomarkers that contribute to progression of AD is very limited. In this paper, we conduct a comprehensive analysis of the biomarker concentration and gene regulatory behavior in TREM2 KO and TREM2 R47H mutated mice models from the MODEL AD database in order to gain understanding of how these variations contribute to the formation of biomarkers and contribute to AD progression.

Our research indicates a correlation between the mutated mice model and the different biomarker concentrations in the brain like insoluble AB40 and 42 proteins, soluble AB40 and 42 proteins, and NFL, which shows that TREM2 gene may be associated with multiple biomarkers. Moreover, we identified some key genes that were associated with the downregulation of the TREM2 gene with the TREM2 KO mice model gene analysis. Finally, we took the confocal images of the TREM2 KO mice model to analyze the effect that the lack of TREM2 extracellular receptor has on the neuritic dystrophy in the brain. Overall, we analyzed the biomarker concentration, gene regulatory activity, and the neuritic effects of the TREM2 KO and TREM2 R47H mutated variants of the TREM2 gene.
Bayesian modeling disentangles language versus executive control disruption in stroke
Authors: Hartwigsen Gesa , Lim Jae-Sung , Bae Hee-Joon , Yu Kyung-Ho , Kuijf Hugo J. , Weaver Nick A. , Biesbroek J. Matthijs , Kopal Jakub , Bzdok Danilo
Published: August 2023

Stroke is the leading cause of long-term disability worldwide. Incurred brain damage disrupts cognition, often with persisting deficits in language and executive capacities. Despite their clinical relevance, the commonalities, and differences of language versus executive control impairments remain under-specified. We tailored a Bayesian hierarchical modeling solution in a largest-of-its-kind cohort (1080 stroke patients) to deconvolve language and executive control in the brain substrates of stroke insults. Four cognitive factors distinguished left- and right-hemispheric contributions to ischemic tissue lesion. One factor delineated language and general cognitive performance and was mainly associated with damage to left-hemispheric brain regions in the frontal and temporal cortex. A factor for executive control summarized control and visual-constructional abilities. This factor was strongly related to right-hemispheric brain damage of posterior regions in the occipital cortex. The interplay of language and executive control was reflected in two factors: executive speech functions and verbal memory. Impairments on both were mainly linked to left-hemispheric lesions. These findings shed light onto the causal implications of hemispheric specialization for cognition; and make steps towards subgroup-specific treatment protocols after stroke.
A genome-wide atlas of human cell morphology
Authors: Ramezani Meraj , Bauman Julia , Singh Avtar , Weisbart Erin , Yong John , Lozada Maria , Way Gregory P. , Kavari Sanam L. , Diaz Celeste , Haghighi Marzieh , Batista Thiago M. , Pérez-Schindler Joaquín , Claussnitzer Melina , Singh Shantanu , Cimini Beth A. , Blainey Paul C. , Carpenter Anne E. , Jan Calvin H. , Neal James T.
Published: August 2023

A key challenge of the modern genomics era is developing data-driven representations of gene function. Here, we present the first unbiased morphology-based genome-wide perturbation atlas in human cells, containing three genome-scale genotype-phenotype maps comprising >20,000 single-gene CRISPR-Cas9-based knockout experiments in >30 million cells. Our optical pooled cell profiling approach (PERISCOPE) combines a de-stainable high-dimensional phenotyping panel (based on Cell Painting1,2) with optical sequencing of molecular barcodes and a scalable open-source analysis pipeline to facilitate massively parallel screening of pooled perturbation libraries. This approach provides high-dimensional phenotypic profiles of individual cells, while simultaneously enabling interrogation of subcellular processes. Our atlas reconstructs known pathways and protein-protein interaction networks, identifies culture media-specific responses to gene knockout, and clusters thousands of human genes by phenotypic similarity. Using this atlas, we identify the poorly-characterized disease-associated transmembrane protein TMEM251/LYSET as a Golgi-resident protein essential for mannose-6-phosphate-dependent trafficking of lysosomal enzymes, showing the power of these representations. In sum, our atlas and screening technology represent a rich and accessible resource for connecting genes to cellular functions at scale.
An Atlas of the DevelopingDrosophilaVisual System Glia and Subcellular mRNA Localization of Transcripts in Single Cells
Authors: Ferreira Amanda A. G. , Desplan Claude
Published: August 2023

Glial cells are essential for proper nervous system development and function. To understand glial development and function, we comprehensively annotated glial cells in a single-cell mRNA-sequencing (scRNAseq) atlas of the developingDrosophilavisual system. This allowed us to study their developmental trajectories, from larval to adult stages, and to understand how specific types of glia diversify during development. For example, neuropil glia that are initially transcriptionally similar in larvae, split into ensheathing and astrocyte-like glia during pupal stages. Other glial types, such as chiasm glia change gradually during development without splitting into two cell types.

The analysis of scRNA-seq allowed us to discover that the transcriptome of glial cell bodies can be distinguished from that of their broken processes. The processes contain distinct enriched mRNAs that were validated in vivo. Therefore, we have identified most glial types in the developing optic lobe and devised a computational approach to identify mRNA species that are localized to cell bodies or cellular processes.
Machine learning models for prediction of xenobiotic chemicals with high propensity to transfer into human milk
Authors: Vijayaraghavan Sudharsan , Lakshminarayanan Akshaya , Bhargava Naman , Ravichandran Janani , Vivek-Ananth R.P. , Samal Areejit
Published: August 2023

Breast milk serves as a vital source of essential nutrients for infants. However, human milk contamination via transfer of environmental chemicals from maternal exposome is a significant concern for infant health. Machine learning based predictive toxicology models can be valuable in predicting chemicals with high propensity to transfer into human milk. To this end, we build such classification- and regression-based models by employing multiple machine learning algorithms and leveraging the largest curated dataset to date of 375 chemicals with known Milk to Plasma concentration (M/P) ratios. Our Support Vector Machine (SVM) based classifier outperforms other models in terms of different performance metrics, when evaluated on both (internal) test data and external test dataset. Specifically, the SVM based classifier on (internal) test data achieved a classification accuracy of 77.33%, specificity of 84%, sensitivity of 64%, and F-score of 65.31%. When evaluated on an external test dataset, our SVM based classifier is found to be generalizable with sensitivity of 77.78%. While we were able to build highly predictive classification models, our best regression models for predicting the M/P ratio of chemicals could achieve only moderate R2values on the (internal) test data. As noted in earlier literature, our study also highlights the challenges in developing accurate regression models for predicting the M/P ratio of xenobiotic chemicals. We have made our complete workflow, train and test datasets, and computer codes for the classification and regression models publicly available via a dedicated GitHub repository. Overall, this study attests the immense potential of predictive computational toxicology models in characterizing the myriad chemicals in the human exposome.
From forests to fields: investigatingCulicoides(Diptera: Ceratopogonidae) abundance and diversity in cattle pastures and adjacent woodlands
Authors: Steele Cassandra H. , McDermott Emily G.
Published: August 2023

CulicoidesLatreille (Diptera: Ceratopogonidae) biting midges are hematophagous flies that feed on wild and domestic ruminants, and transmit many arboviruses, including bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV) circulating in the United States (US). They occupy a range of aquatic and semiaquatic habitats, and disperse short distances from their development sites. In the southeastern US there are limited studies on the abundance and diversity ofCulicoidesin wooded and adjacent livestock pasture habitats. In thus study, we characterizedCulicoidesdiversity and abundance within these distinct habitat types by setting BG-Sentinel and CDC miniature suction traps baited with CO2or UV-light in wooded and pasture habitats at two locations on a university beef farm in Savoy, AR. Traps were set once per week for nine weeks in August-October of 2021-2022. Fifteen species were collected during this study. The two most abundant species wereCulicoides haematopotusMalloch andCulicoides stelliferCoquillett. There was a significant effect of site and location onC. haematopotuscollections, and a significant effect and interaction of site and trap onC. stellifercollections. In the woods, significantly moreC. stelliferwere collected from the CDC-UV trap, while in the pasture, significantly more were collected in the CDC-CO2trap. These data suggest thatC. stellifer, a putative vector of BTV and EHDV in the southeast, may be traveling into the pasture to host-seek, whileC. haematopotusremains primarily in the woods. This study reveals community differences between these habitat types and implications forCulicoidescontrol.
Highly accurate and robust protein sequence design with CarbonDesign
Authors: Ren Milong , Yu Chungong , Bu Dongbo , Zhang Haicang
Published: August 2023

Protein sequence design, the inverse problem of protein structure prediction, plays a crucial role in protein engineering. Although recent deep learning-based methods have shown promising advancements, achieving accurate and robust protein sequence design remains an ongoing challenge. Here, we present CarbonDesign, a new approach that draws inspiration from successful ingredients of AlphaFold for protein structure prediction and makes significant and novel developments tailored specifically for protein sequence design. At its core, CarbonDesign explores Inverseformer, a novel network architecture adapted from AlphaFold’s Evoformer, to learn representations from backbone structures and an amortized Markov Random Fields model for sequence decoding. Moreover, we incorporate other essential AlphaFold concepts into CarbonDesign: an end-to-end network recycling technique to leverage evolutionary constraints in protein language models and a multi-task learning technique to generate side chain structures corresponding to the designed sequences. Through rigorous evaluations on independent testing data sets, including the CAMEO and recent CASP15 data sets, as well as the predicted structures from AlphaFold, we show that CarbonDesign outperforms other published methods, achieving high accuracy in sequence generation. Moreover, it exhibits superior performance onde novobackbone structures obtained from recent diffusion generative models such as RFdiffusion and FrameDiff, highlighting its potential for enhancingde novoprotein design. Notably, CarbonDesign also supports zero-shot prediction of the functional effects of sequence variants, indicating its potential application in directed evolution-based design. In summary, our results illustrate CarbonDesign’s accurate and robust performance in protein sequence design, making it a promising tool for applications in bioengineering.
Gene-to-Gene Coordinated Regulation of Transcription and Alternative splicing by 3D Chromatin Remodeling upon NF-κB activation
Authors: Marie Paul , Ladet Julien , Bazire Matéo , Ameur Lamya Ben , Chahar Sanjay , Fontrodona Nicolas , Sexton Tom , Auboeuf Didier , Bourgeois Cyril F. , Mortreux Franck
Published: August 2023

The p65/RelA factor of NF-κB plays a pivotal role in coordinating gene expression in response to diverse stimuli, including viral infections. At the chromatin level, p65/RelA regulates gene transcription and alternative splicing (AS) through promoter enrichment and genomic exon occupancy, respectively. However, the mechanisms underlying the coordination of these processes across distinct genes remain elusive. In this study, we employed the HTLV-1 Tax oncoprotein, a potent activator of NF-κB, to investigate the integrative relationship between 3D chromatin architecture, NF-κB-regulated transcription and AS. Our analysis revealed that Tax induces a pronounced reorganization of the 3D genome, resulting in the formation of multigene complexes that comprise genes regulated either transcriptionally or through AS. Notably, we found that the Tax-induced gene-gene contact between the two master genesNFKBIAandRELAis associated with their differential regulation in gene expression and AS, respectively. Through dCas9-mediated approaches, we demonstrated thatNFKBIA-RELAinteraction is required for AS regulation and is caused by an intragenic enrichment of p65/RelA onRELA. Our findings shed light on new regulatory mechanisms upon HTLV-1 Tax and underscore the integral role of p65/RelA in coordinated regulation of NF-κB-responsive genes at both transcriptional and AS levels in the context of the 3D genome.
How heterogeneous wine lots result in a price discount relative to homogeneous lots
Authors: Breeden Joseph L.
Published: August 2023

Purpose

The purpose of this study is to determine whether the fine wine market is efficient between homogeneous lots and heterogeneous lots.

Design/methodology/approach

Auction price data for homogeneous (or solid) lots of fine wines was analyzed to create price prediction models. Those models were used to predict the expected auction price for the bottles within heterogeneous lots. Lastly, models were created to explain and predict the differences between expected and realized prices for heterogenous wine lots.

Findings

The results show that large inefficiencies exist. The more complex and expensive the heterogeneous lot, the greater the discount relative to what would have been realized if the bottles had been sold individually. This discount can exceed 50% of the expected auction price.

Practical implications

Heterogeneous lots may arise as a practical requirement from the auction house. Restaurant buyers probably have little interest in such lots because of the inclusion of wines the restaurant will be unable to sell. Collectors may be uniquely positioned to benefit from this price discount.

Originality/value

These results are unique in the literature, because the price dynamics of heterogeneous (or mixed) lots of fine wines have not previously been studied.
Exploratory study of an ally training program for mental health support
Authors: Wendeln Beatrice Meda , Sheehan Lindsay
Published: August 2023

Purpose

The purpose of this study was to evaluate the effects of an online mental health ally program on several measurements of readiness to help and stigma reduction. Allyship is one way to support people with mental health challenges beyond traditional care services.

Design/methodology/approach

The efficacy of the program was evaluated in pre and postintervention surveys (n = 26) including measures of self-care, help-seeking intentions, peer-support self-efficacy, advocacy, knowledge of resources and stigma. A within-subject, repeated measures design was conducted analyzing changes at completion. Twenty-six participants who completed the program (either with or without lived experience of mental illness) were included in the study. A subgroup of participants (n = 11) who reported lived experiences of mental illness were assigned additional measures of internalized stigma, stigma stress, stigma resistance and self-esteem.

Findings

Analysis of mean differences indicated a statistically significant change in scores pre and postcompletion. The program increased peer-support, help-seeking intentions and self-esteem, while reducing internalized stigma and stigma stress. Findings provide preliminary support for program effectiveness in training individuals to support others and themselves through mental health challenges.

Research limitations/implications

Trained allies might improve the lives of individuals with mental health challenges by reducing discrimination and improving social support. We discuss the implication of allies to complement the mental health system.

Originality/value

To the best of the authors’ knowledge, this is the first exploratory study on the efficacy of an online ally training program for individuals with mental illness. The NoStigmas Ally Program is a novel and original development in ally training.
Evaluating AI literacy proficiency among LIS researchers in ASEAN
Authors: A. Subaveerapandiyan , Paladhi Monali Mitra , Maruthaveeran Vijayalatchumy
Published: August 2023

Purpose

This paper aims to investigate AI literacy proficiency among LIS researchers in Association of Southeast Asian Nations (ASEAN) countries. This study also aims to assess current proficiency levels, identify challenges and gaps, explore recommendations for improving skills and examine how researchers stay updated on AI advancements.

Design/methodology/approach

A structured questionnaire was used to collect data, then analysed using appropriate statistical methods.

Findings

Most respondents showed proficiency in various aspects of AI literacy for LIS research. However, some aspects, such as understanding AI concepts, ethical considerations and programming skills, had lower proficiency levels. Factors influencing AI literacy included limited resources for enhancement, lack of awareness and insufficient AI-related courses in LIS education.

Originality/value

This study presents an original assessment of AI literacy proficiency among LIS researchers in ASEAN countries, shedding light on the current state of AI knowledge in the region’s library and information science field. The findings identify specific gaps and challenges, offering valuable insights for policymakers, educators and stakeholders seeking to enhance AI literacy skills in this context.
More effect of ephemeral plant species diversity on aboveground biomass than functional diversity and functional composition
Authors: Guo Hao , Zhou Xiaobing , Tao Ye , Yin Jinfei , Lin Yajun , Zang Yongxin , Zhang Yuanming
Published: August 2023

The quantification of plant diversity–productivity relationships is essential for accurate productivity assessments. Global change drivers are altering resource availability and biodiversity. However, the extent to which multiple attributes of diversity (species, functions) buffer community productivity in response to the resource availability changes and the potential driver mechanisms of the diversity‐productivity relationship still needs to be the consensus. We investigated the ephemeral plant diversity–productivity relationships of different attributes along a precipitation gradient in the Gurbantunggut Desert, China. To evaluate the potential mechanisms by which diversity and functional composition affect aboveground productivity (niche complementarity and selection effect). Our results showed that (1) the variance of species richness (SR), Rao's quadratic entropy (RaoQ), community‐weighted mean of height (CWMH), and community‐weighted mean of leaf phosphorus concentration (CWMP) was larger among sites (variation between different sites) than subplots (variation between different subplots). Among subplots, the variance of community‐weighted mean of specific leaf area (CWMSLA), community‐weighted mean of leaf carbon concentration (CWMC), and community‐weighted mean of leaf nitrogen concentration (CWMN) was larger than the sites. (2) SR, RaoQ, CWMC, CWMN, CWMH, pH, and mean annual precipitation (MAP) collectively influenced the accumulation of aboveground biomass (AGB). (3) Species diversity and MAP have strongly affected AGB and accounted for 50% and 42%. The study confirms that SR is the optimal predictor of biomass in ephemeral plants. Complementation effects may be the primary mechanism explaining the relationship between biodiversity and productivity in the Gurbantunggut Desert, and thus the effect of plant diversity cannot be downplayed.
Treatment pattern and changes in oral glucocorticoid dose after tocilizumab treatment in patients with adult Still's disease: An analysis of a Japanese claims database
Authors: Kaneko Yuko , Kameda Hideto , Ikeda Kei , Yamashita Katsuhisa , Ozaki Ryoto , Tanaka Yoshiya
Published: August 2023

Aim

Intravenous tocilizumab (TCZ‐IV) was approved for the treatment of adult Still's disease (ASD) in Japan in May 2019 based on its efficacy and safety in a phase III randomized controlled trial. This study determined treatment patterns in patients with ASD and assessed oral glucocorticoid (GC) dose changes after TCZ‐IV administration in Japanese clinical practice.

Methods

Patients in the Medical Data Vision database aged 16 years or older with one or more of International Classification of Diseases, 10th revision codes M061 (ASD) or M082 (systemic juvenile idiopathic arthritis) during January 2017–March 2021 (cohort 1) and those initiating TCZ‐IV during May 2019–March 2021 (cohort 2) were included.

Results

In cohort 1, the proportion of patients who were prescribed interleukin‐6 inhibitors (mainly TCZ‐IV) increased from 10.8% (January–April 2019 [before TCZ‐IV approval]; n = 2002) to 18.3% (January–March 2021 [after TCZ‐IV approval]; n = 2008). In cohort 2 (n = 193), 84.5% of patients were on oral GCs (≤5 mg/day: 23.8%) at index date (initial TCZ‐IV prescription date); 46/70 (65.7%) were on oral GC at 5 mg/day or higher 12 months after TCZ‐IV treatment (primary outcome). After 12 months of treatment, the TCZ‐IV retention rate was 73.6% and the TCZ‐IV administration interval was every 4 weeks and every 2 weeks in 31.9% and 27.7% of patients, respectively.

Conclusion

The use of interleukin‐6 inhibitors increased by 7.5% points in Japanese patients with ASD ~2 years after TCZ‐IV approval, suggesting that an unmet medical need existed. This study suggests the potential GC‐sparing effect of TCZ‐IV in patients with ASD in clinical practice.
A case of discordant histology and expression of programmed death ligand 1 between primary tumor and brain metastases in adenosquamous carcinoma of the lung
Authors: Takagi Hironori , Muto Satoshi , Enta Akio , Fukuhara Mitsuro , Asano Shigeyuki , Shio Yutaka , Suzuki Hiroyuki
Published: August 2023

A patient presented with vomiting and gait disturbance. Investigation revealed a single cerebellar tumor and another tumor in the upper lobe of the left lung. Based on the severe vomiting and gait disturbance, we removed the cerebellar tumor first, achieving resolution of symptoms. The cerebellar tumor was pathologically diagnosed as metastatic lung adenocarcinoma. No other metastases were identified, including in the mediastinal lymph nodes. We therefore resected the primary lung tumor. On final pathological analysis, the tumor in the upper lobe of the left lung was diagnosed as adenosquamous carcinoma with no lymph node metastasis. PD‐L1 expression was low in the primary lung adenosquamous carcinoma and high in the cerebellar metastasis. Furthermore, both tumors were KRASG12C‐positive. Tumor PD‐L1 expression is considered important for immune escape. In this case, adenocarcinoma cells in the primary adenosquamous carcinoma may have migrated to form a cerebellar metastasis. In advanced lung cancer, tumor growth may be observed in some lesions even when many other lesions are controlled by chemo‐ or immunotherapy. Biopsy to confirm histology and PD‐L1 expression is worth considering, depending on the location of the metastases and the invasiveness of the biopsy procedure.
Auditing with data and analytics: External reviewers' judgments of audit quality and effort
Authors: Emett Scott A. , Kaplan Steven E. , Mauldin Elaine G. , Pickerd Jeffrey S.
Published: August 2023

Audit firms hesitate to take full advantage of data and analytics (D&A) audit approaches because they lack certainty about how external reviewers evaluate those approaches. We propose that external reviewers use an effort heuristic when evaluating audit quality, judging less effortful audit procedures as lower quality, which could shape how external reviewers evaluate D&A audit procedures. We conduct two experiments in which experienced external reviewers evaluate one set of audit procedures (D&A or traditional) within an engagement review, while holding constant the procedures' level of assurance. Our first experiment provides evidence that external reviewers rely on an effort heuristic when evaluating D&A audit procedures—they perceive D&A audit procedures as lower in quality than traditional audit procedures because they perceive them to be less effortful. Our second experiment confirms these results and evaluates a theory‐based intervention that reduces reviewers' reliance on the effort heuristic, causing them to judge quality similarly across D&A and traditional audit procedures.
Assessing protected area effectiveness in western Tanzania: Insights from repeated line transect surveys
Authors: Kiffner Christian , Giliba Richard A. , Fust Pascal , Loos Jacqueline , Waltert Matthias
Published: August 2023

In many parts of East Africa, wildlife populations have declined over the past decades. Given these trends, site‐based studies are needed to assess how protected areas with differing management strategies enable the effective conservation of wildlife populations. In Tanzania, game reserves are managed for tourist hunting, while national parks are managed for non‐consumptive wildlife‐based tourism. To assess the relative performance of these management strategies, we here focus on two areas: Rukwa Game Reserve (RGR) and Katavi National Park (KNP). Based on systematically designed line distance surveys in 2004 and 2021, we compared densities and group sizes of large mammal populations (African elephant, giraffe, buffalo, zebra, topi, and hartebeest) over time. Contrary to published ecosystem‐wide declines observed in numerous species which considered earlier baselines, we did not detect significant population declines between 2004 and 2021. While these new results showing apparent stable populations do not invalidate earlier studies on wildlife declines, they could indicate a stabilisation phase after declines. This highlights the importance of considering appropriate temporal baselines and historical contexts when assessing conservation effectiveness.
Hsa_circ_0015382 is involved in the pathogenesis of preeclampsia by mediating THBS2 expression
Authors: Wang Yang , Liu Lingfang , Wang Jiayao , Gao Yan
Published: August 2023

Background

Preeclampsia (PE) is a hypertensive disorder of pregnancy that causes significant maternal and perinatal morbidity and mortality. Circular RNA (circRNA) hsa_circ_0015382 is associated with the pathogenesis of PE, but its underlying regulatory mechanism remains to be explored.

Methods

Relative RNA levels of hsa_circ_0015382, microRNA‐616‐3p and thrombospondin‐2 (THBS2) were detected by quantitative reverse transcription‐polymerase chain reaction. In vitro regulatory effects of hsa_circ_0015382 on the proliferation, migration, invasion and angiogenesis of trophoblasts were evaluated by CCK‐8, flow cytometry for cell cycle, EdU, transwell, wound healing and HUVEC tube formation assays, respectively. Targeting interaction was verified by dual‐luciferase reporter and RNA immunoprecipitation assays.

Results

Hsa_circ_0015382 was highly expressed in placental tissues from PE patients. Upregulation of hsa_circ_0015382 repressed trophoblast proliferation, migration, invasion and lowered trophoblast‐induced HUVEC tube formation. Hsa_circ_0015382 was validated as a miR‐616‐3p sponge and miR‐616‐3p targeted THBS2. Hsa_circ_0015382 could mediate trophoblast proliferation, migration, invasion and regulate trophoblast‐induced HUVEC tube formation by sponging miR‐616‐3p and regulating THBS2 expression.

Conclusion

Hsa_circ_0015382 is associated with the pathogenesis of PPE by regulating the miR‐616‐3p/THBS2 axis.

Highlights

Hsa_circ_0015382 is overexpressed in preeclampsia patients.

Hsa_circ_0015382 inhibits trophoblast proliferation, migration, invasion and decreases trophoblast‐induced HUVEC tube formation.

Hsa_circ_0015382 interacts with miR‐616‐3p to regulate THBS2 expression.
Rearview mirrors: Harvard Land Rover interviews and the ethnographic drive in midcentury Chiapas
Authors: Watson Matthew C.
Published: August 2023

In 1951, Mexico's Instituto Nacional Indigenista (INI) established a coordinating center for a pilot development project in San Cristóbal de las Casas, Chiapas. INI administrators sought to draw Tzotzil‐ and Tzeltal‐speaking indigenous communities that radiated around San Cristóbal into identification with the Mexican state and its political mythology of racial‐cultural mixture, or mestizaje. To do so, the INI built roads. State investment in the transportation infrastructure of indigenous Chiapas enabled the geographical mobility of scores of U.S. anthropologists and students who used these roads to access “closed corporate communities” such as Zinacantán during the late‐1950s and 1960s. Working from archived correspondence and field notes, this essay examines Harvard Chiapas Project founder Evon Vogt's early project interviews conducted on these roads in a Land Rover. Reading the Land Rover as a space‐making technology of ethnographic rapport, I ask how such vehicles have structured ethnographic forms of intimacy and attachment and whether they render the interview space a site of capitalist capture. I ultimately refract a surfaced critique of the interview form's capitalist coloniality through a weak‐theoretical evocation of the Land Rover's social, technological, and symbolic indeterminacy.
The League of Endarkenment: Hakim Bey and the Way of Disappearance into Nature
Authors: Adamo Ayesha
Published: August 2023

Among his later works, Peter Lamborn Wilson—known to many as Hakim Bey—began performing ritual art pieces in Upstate New York, which he referred to as acts of “Endarkenment.” This paper explores Endarkenment from the beginning of its organic growth in the fertile soil of The Temporary Autonomous Zone, to its blossoming as fully‐realized ritual art, nourished by Bey's intention of returning enchantment back to the land. Through parallels in the works of antiquity, Surrealism, Georges Bataille, Giordano Bruno, Djuna Barnes, and others, an adumbration of the body of Endarkenment comes into view at the very moment of its disappearance into Nature, giving an idea of what Endarkenment could be as a fully realized form of internal transformation.
Clinico‐histological and molecular features of hepatocellular carcinoma from nonalcoholic fatty liver disease
Authors: Fujiwara Naoto , Nakagawa Hayato
Published: August 2023

Patients with nonalcoholic fatty liver disease (NAFLD) continue to increase with the epidemics of obesity, and NAFLD is estimated to become the most prevalent etiology of hepatocellular carcinoma (HCC). Recently, NAFLD‐HCC has been recognized to have clinico‐histologically and molecularly distinct features from those from other etiologies, including a lower incidence rate of HCC and less therapeutic efficacy to immune checkpoint inhibitors (ICIs). Consistent with the clinical observations that up to 50% of NAFLD‐HCC occurs in the absence of cirrhosis, the imbalance of pro‐ and antitumorigenic hepatic stellate cells termed as myHSC and cyHSC can contribute to the creation of an HCC‐prone hepatic environment, independent of the absolute fibrosis abundance. Immune deregulations by accumulated metabolites in NAFLD‐affected livers, such as a fatty‐acid‐induced loss of cytotoxic CD4 T cells serving for immune surveillance and “auto‐aggressive” CXCR6+ CD8 T cells, may promote hepatocarcinogenesis and diminish therapeutic response to ICIs. Steatohepatitic HCC (SH‐HCC), characterized by the presence of fat accumulation in tumor cells, ballooned tumor cells, Mallory–Denk body, interstitial fibrosis, and intratumor immune cell infiltration, may represent a metabolic reprogramming for adapting to a lipid‐rich tumor microenvironment by downregulating CPT2 and leveraging its intermediates as an “oncometabolite.” Genome‐wide analyses suggested that SH‐HCC may be more responsive to ICIs given its mutual exclusiveness with β‐catenin mutation/activation that promotes immune evasion. Thus, further understanding of NAFLD‐specific hepatocarcinogenesis and HCC would enable us to improve the current daily practice and eventually the prognoses of patients with NAFLD.
Inflammation affects dynamic functional network connectivity pattern changes via plasma NFL in cognitive impairment patients
Authors: Yao Weina , Zhou Huijuan , Zhang Xiao , Chen Haifeng , Bai Feng ,   Alzheimer's Disease Neuroimaging Initiative
Published: August 2023

Background

Plasma neurofilament light chain (NFL) is a biomarker of inflammation and neurodegenerative diseases such as Alzheimer's disease (AD). However, the underlying neural mechanisms by which NFL affects cognitive function remain unclear. In this study, we investigated the effects of inflammation on cognitive integrity in patients with cognitive impairment through the functional interaction of plasma NFL with large‐scale brain networks.

Methods

This study included 29 cognitively normal, 55 LowNFL patients, and 55 HighNFL patients. Group independent component analysis (ICA) was applied to the resting‐state fMRI data, and 40 independent components (IC) were extracted for the whole brain. Next, the dynamic functional network connectivity (dFNC) of each subject was estimated using the sliding‐window method and k‐means clustering, and five dynamic functional states were identified. Finally, we applied mediation analysis to investigate the relationship between plasma NFL and dFNC indicators and cognitive scales.

Results

The present study explored the dynamics of whole‐brain FNC in controls and LowNFL and HighNFL patients and highlighted the temporal properties of dFNC states in relation to psychological scales. A potential mechanism for the association between dFNC indicators and NFL levels in cognitively impaired patients.

Conclusions

Our findings suggested the decreased ability of information processing and communication in the HighNFL group, which helps us to understand their abnormal cognitive functions clinically. Characteristic changes in the inflammation‐coupled dynamic brain network may provide alternative biomarkers for the assessment of disease severity in cognitive impairment patients.
Long‐term prognosis of vaccine‐induced contact allergy to aluminium: Third patch‐test with additional test preparations
Authors: Lidholm Anette Gente , Inerot Annica , Gillstedt Martin , Bergfors Elisabet , Trollfors Birger
Published: August 2023

Background

A high incidence of local itching subcutaneous nodules and aluminium allergy was observed in clinical trials of a new aluminium adsorbed pertussis vaccine in Gothenburg, Sweden, in the 1990s. A total of 495 children with itching nodules were patch tested with aluminium chloride hexahydrate 2% and an empty Finn Chamber®, 377 (76%) with positive reactions. When 241 of them were re‐tested some years later 186 (3 out of 4) had unexpectedly lost their patch test reactivity.

Aim

To investigate the long‐term prognosis of vaccine‐induced contact allergy to aluminium by a third patch test about 20 years after Patch test I.

Methods

Twenty individuals with positive and 11 with negative results in Patch test II were tested a third time with the same sensitisers as in in the first two tests. Three additional aluminium preparations were also tested.

Results

A total 15 out of 20 persons with positive results in the second test had lost their patch test reactivity. Two of 11 with negative tests had turned positive again. The addition of the preparations gave no conclusive results.

Conclusion

Contact allergy to aluminium caused by vaccination with aluminium‐adsorbed vaccines in childhood seems to fade away with time as measured by loss of patch test reactivity.
Evolving challenges with long‐term care of liver transplant recipients
Authors: Odenwald Matthew A. , Roth Hannah F. , Reticker Anesia , Segovia Maria , Pillai Anjana
Published: August 2023

The number of liver transplants (LT) performed worldwide continues to rise, and LT recipients are living longer post‐transplant. This has led to an increasing number of LT recipients requiring lifelong care. Optimal care post‐LT requires careful attention to both the allograft and systemic issues that are more common after organ transplantation. Common causes of allograft dysfunction include rejection, biliary complications, and primary disease recurrence. While immunosuppression prevents rejection and reduces incidences of some primary disease recurrence, it has detrimental systemic effects. Most commonly, these include increased incidences of metabolic syndrome, various malignancies, and infections. Therefore, it is of utmost importance to optimize immunosuppression regimens to prevent allograft dysfunction while also decreasing the risk of systemic complications. Institutional protocols to screen for systemic disease and heightened clinical suspicion also play an important role in providing optimal long‐term post‐LT care. In this review, we discuss these common complications of LT as well as unique considerations when caring for LT recipients in the years after transplant.
Intradermal substance P as a challenge agent in healthy individuals
Authors: ten Voorde Wouter , Akinseye Chika , Abdisalaam Ismahaan , Wind Selinde , Klarenbeek Naomi , Bergmans Menthe , van Doorn Martijn , Rissmann Robert , Kaur Rejbinder , Hotee Sarah , Foster Katie , Nair Arati , Fortunato Lea , Macphee Colin , Mole Sarah , Baumann Katrine , Brigandi Richard
Published: August 2023

Pharmacological challenge models are deployed to evaluate drug effects during clinical development. Intradermal injection of Substance P (SP) neuropeptide, a potential challenge agent for investigating local mediators, is associated with wheal and flare response mediated by the MRGPRX2 receptor. Although dose‐dependent data on SP effects exist, full characterization and information on potential carryover effect after repeated challenge are lacking. This open‐label, two‐part, prospective enabling study of SP intradermal challenge in healthy participants aimed to understand and distinguish between wheal and flare responses following various SP doses. Part 1 included one challenge visit to determine optimum SP dose range for evaluation in part 2, which determined variability in 20 participants and used intradermal microdialysis (IDM) for SP‐challenged skin sampling. At 5, 15, 50, and 150 pmol doses, respectively, posterior median area under the curve (AUC; AUC0–2h) was 4090.4, 5881.2, 8846.8, and 9212.8 mm2/min, for wheal response, and 12020.9, 38154.3, 65470.6, and 67404.4 mm2/min for flare response (SP‐challenge visit 2). When the challenge was repeated ~2 weeks later, no carryover effect was observed. IDM histamine levels were relatively low, resulting in low confidence in the data to define temporal characteristics for histamine release following SP challenge. No safety concerns were identified using SP. Wheal and flare responses following intradermal SP challenge were dose‐dependent and different. The results indicate that this challenge model is fit‐for‐purpose in future first‐in‐human studies and further assessment of novel drugs targeting dermal inflammatory disease responses, such as chronic spontaneous urticaria, chronic inducible urticaria, and pseudo‐allergic reactions.
Nonnative plant invasion increases urban vegetation structure and influences arthropod communities
Authors: Mitchell J. Christina , D'Amico Vincent , Trammell Tara L. E. , Frank Steven D.
Published: August 2023

Aim

Ecological theory and empirical evidence indicate that greater structural complexity and diversity in plant communities increases arthropod abundance and diversity. Nonnative plants are typically associated with low arthropod abundance and diversity due to lack of evolutionary history. However, nonnative plants increase the structural complexity of forests, as is common in urban forests. Therefore, urban forests are ideal ecosystems to determine whether structural complexity associated with nonnative plants will increase abundance and diversity of arthropods, as predicted by complexity literature, or whether structural complexity associated with nonnative plants will be depauperate of arthropods, as predicted by nonnative plant literature.

Location

We sampled 24 urban temperate deciduous and mixed forests in two cites, Raleigh, North Carolina and Newark, Delaware, in the eastern United States.

Methods

We quantified ground cover vegetation and shrub layer vegetation in each forest and created structural complexity metrics to represent total, nonnative and native understory vegetation structural complexity. We vacuum sampled arthropods from vegetation and quantified the abundance, biomass, richness and diversity of spiders and non‐spider arthropods.

Results

Nonnative plants increase understory vegetation complexity in urban forests. In Raleigh and Newark, we found support for the hypotheses that dense vegetation will increase arthropod abundance and biomass, and against the hypothesis that nonnative vegetation will decrease arthropods. Urban forest arthropod abundance and biomass, but not diversity, increased with greater nonnative and native structural complexity.

Main Conclusions

Invaded urban forests may provide adequate food in the form of arthropod biomass to transfer energy to the next trophic level, but likely fail to provide ecological services and functions offered by diverse species, like forest specialists. Urban land managers should survey urban forests for nonnative and native plant communities and prioritize replacing dense nonnative plants with native species when allocating vegetation maintenance resources.
Phenylacetylglutamine and trimethylamine N‐oxide: Two uremic players, different actions
Authors: Hobson Sam , Qureshi Abdul Rashid , Ripswedan Jonaz , Wennberg Lars , de Loor Henriette , Ebert Thomas , Söderberg Magnus , Evenepoel Pieter , Stenvinkel Peter , Kublickiene Karolina
Published: August 2023

Background

Chronic kidney disease (CKD) patients exhibit a heightened cardiovascular (CV) risk which may be partially explained by increased medial vascular calcification. Although gut‐derived uremic toxin trimethylamine N‐oxide (TMAO) is associated with calcium‐phosphate deposition, studies investigating phenylacetylglutamine's (PAG) pro‐calcifying potential are missing.

Methods

The effect of TMAO and PAG in vascular calcification was investigated using 120 kidney failure patients undergoing living‐donor kidney transplantation (LD‐KTx), in an observational, cross‐sectional manner. Uremic toxin concentrations were related to coronary artery calcification (CAC) score, epigastric artery calcification score, and markers of established non‐traditional risk factors that constitute to the ‘perfect storm’ that drives early vascular aging in this patient population. Vascular smooth muscle cells were incubated with TMAO or PAG to determine their calcifying effects in vitro and analyse associated pathways by which these toxins may promote vascular calcification.

Results

TMAO, but not PAG, was independently associated with CAC score after adjustment for CKD‐related risk factors in kidney failure patients. Neither toxin was associated with epigastric artery calcification score; however, PAG was independently, positively associated with 8‐hydroxydeoxyguanosine. Similarly, TMAO, but not PAG, promoted calcium‐phosphate deposition in vitro, while both uremic solutes induced oxidative stress.

Conclusions

In conclusion, our translational data confirm TMAO's pro‐calcifying effects, but both toxins induced free radical production detrimental to vascular maintenance. Our findings suggest these gut‐derived uremic toxins have different actions on the vessel wall and therapeutically targeting TMAO may help reduce CV‐related mortality in CKD.
Small lateral air pressure gradients generated by a large chamber system have a strong effect on CO2 transport in soil
Authors: Osterholt Laurin , Maier Martin , Schindler Dirk
Published: August 2023

Gas transport in soils is usually assumed to be purely diffusive, although several studies have shown that non‐diffusive processes can significantly enhance soil gas transport. These processes include barometric air pressure changes, wind‐induced pressure pumping and static air pressure fields generated by wind interacting with obstacles. The associated pressure gradients in the soil can cause advective gas fluxes that are much larger than diffusive fluxes. However, the contributions of the respective transport processes are difficult to separate. We developed a large chamber system to simulate pressure fields and investigate their influence on soil gas transport. The chamber consists of four subspaces in which pressure is regulated by fans that blow air in or out of the chamber. With this setup, we conducted experiments with oscillating and static pressure fields. CO2 concentrations were measured along two soil profiles beneath the chamber. We found a significant relationship between static lateral pressure gradients and the change in the CO2 profiles (R2 = 0.53; p‐value <2e‐16). Even small pressure gradients between −1 and 1 Pa relative to ambient pressure resulted in an increase or decrease in CO2 concentrations of 8% on average in the upper soil, indicating advective flow of air in the pore space. Positive pressure gradients resulted in decreasing, negative pressure gradients in increasing CO2 concentrations. The concentration changes were probably caused by an advective flow field in the soil beneath the chamber generated by the pressure gradients. No effect of oscillating pressure fields was observed in this study. The results indicate that static lateral pressure gradients have a substantial impact on soil gas transport and therefore are an important driver of gas exchange between soil and atmosphere. Lateral pressure gradients in a comparable range can be induced under windy conditions when wind interacts with terrain features. They can also be caused by chambers used for flux measurements at high wind speed or by fans used for head‐space mixing within the chambers, which yields biased flux estimates.