bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-ancestry meta-analysis and fine-mapping in Alzheimer’s disease
Authors: Lake Julie , Warly Solsberg Caroline , Kim Jonggeol Jeffrey , Acosta-Uribe Juliana , Makarious Mary B. , Li Zizheng , Levine Kristin , Heutink Peter , Alvarado Chelsea X. , Vitale Dan , Kang Sarang , Gim Jungsoo , Lee Kun Ho , Pina-Escudero Stefanie D. , Ferrucci Luigi , Singleton Andrew B. , Blauwendraat Cornelis , Nalls Mike A. , Yokoyama Jennifer S. , Leonard Hampton L. 
Published: May 2023

AbstractGenome-wide association studies (GWAS) of Alzheimer’s disease are predominantly carried out in European ancestry individuals despite the known variation in genetic architecture and disease prevalence across global populations. We leveraged published GWAS summary statistics from European, East Asian, and African American populations, and an additional GWAS from a Caribbean Hispanic population using previously reported genotype data to perform the largest multi-ancestry GWAS meta-analysis of Alzheimer’s disease and related dementias to date. This method allowed us to identify two independent novel disease-associated loci on chromosome 3. We also leveraged diverse haplotype structures to fine-map nine loci with a posterior probability >0.8 and globally assessed the heterogeneity of known risk factors across populations. Additionally, we compared the generalizability of multi-ancestry- and single-ancestry-derived polygenic risk scores in a three-way admixed Colombian population. Our findings highlight the importance of multi-ancestry representation in uncovering and understanding putative factors that contribute to risk of Alzheimer’s disease and related dementias.
Lipid profile after omega-3 supplementation in neonates with intrauterine growth retardation: a randomized controlled trial
Authors: Elsheikh Mai , El Amrousy Doaa , El-Mahdy Heba , Dawoud Heba , Harkan Ahmed , El-Barky Amany 
Published: May 2023

Abstract
Background
Neonates with intrauterine growth restriction (IUGR) have a high lipid profile that predisposes them to cardiovascular disease later in life. We aimed to evaluate the effect of omega 3 supplementation on serum leptin level, lipid profile, and growth in neonates with IUGR.

Methods
This clinical trial was conducted on 70 full-term neonates with IUGR. Neonates were randomly divided into two equal groups; the treatment group: received omega 3 supplement (40 mg/kg/day) for 2 weeks after the establishment of full feeding, and the control group, who were followed up to full feeding without any supplementation. Serum leptin level, total cholesterol (TC), high-density lipoprotein (HDL), triglycerides (TG), low-density lipoprotein (LDL), and anthropometric measurement were evaluated at admission and after 2 weeks of omega 3 supplementation in both groups.

Results
After treatment, HDL significantly increased, unlike TC, TG, LDL, LDL, and serum leptin levels, which significantly decreased in the treatment group compared to the control group after treatment. Interestingly, weight, length, and ponderal index greatly increased in omega 3-treated neonates compared to the control group.

Conclusion
Omega 3 supplementations lowered serum leptin level, TG, TC, LDL, and VLDL but increased HDL and growth in neonates with IUGR.

Clinical trial registration
The study was registered at clinicaltrials.gov (NCT05242107).

Impact

Neonates with intrauterine growth retardation (IUGR) were reported to have a high lipid profile that predisposes them to cardiovascular disease later in life. Leptin is a hormone that adjusts dietary intake and body mass and has a significant role in fetal development. Omega 3 is known to be essential for neonatal growth and brain development.

We aimed to evaluate the effect of omega 3 supplementation on serum leptin level, lipid profile, and growth in neonates with IUGR.

We found that omega 3 supplementations lowered serum leptin level and serum lipid profile but increased high density lipoprotein and growth in neonates with IUGR.
Initial evidence regarding the neurobiological basis of psychological symptoms in dementia caregivers
Authors: Smagula Stephen F. , Aizenstein Howard J. 
Published: May 2023

AbstractMood symptoms and disorders are common in dementia caregivers, who can be exposed to a myriad of potential stressors including their care recipient’s neuropsychiatric symptoms. Existing evidence indicates that the effects of potentially stressful exposures on mental health depend on the caregiver’s individual characteristics and responses. Specifically, prior studies indicate that risk factors measured on psychological (e.g., emotion-focused/behaviorally disengaged coping responses) and behavioral (e.g., sleep and activity restriction) levels of analysis may confer the effects of caregiving exposures on mental health. Theoretically, this process from caregiving stressors and other risk factors to mood symptoms is neurobiologically mediated. This article reviews recent studies that used brain imaging to identify neurobiological factors that are related to psychological outcomes in caregivers. Available observational data indicate that psychological outcomes in caregivers are related to differences in the structure/function of regions involved in socio-affective information processing (prefrontal), autobiographical memory (the posterior cingulate), and stress (amygdala). In addition, two small randomized controlled trials using repeated brain imaging showed that Mentalizing Imagery Therapy (a mindfulness program) increased prefrontal network connectivity and reduced mood symptoms. These studies raise the possibility that, in the future, brain imaging may be useful to detect the neurobiological basis of a given caregiver’s mood vulnerability and guide the selection of interventions that are known to modify it. However, there remains a need for evidence on whether brain imaging improves on simpler/inexpensive measurement modalities like self-report for identifying vulnerable caregivers and matching them with efficacious interventions. In addition, to target interventions, more evidence is needed regarding the effects that both risk factors and interventions have on mood neurobiology (e.g., how persistent emotion-focused coping, sleep disruption, and mindfulness affect brain function).
Tunnelling nanotubes between neuronal and microglial cells allow bi-directional transfer of α-Synuclein and mitochondria
Authors: Chakraborty Ranabir , Nonaka Takashi , Hasegawa Masato , Zurzolo Chiara 
Published: May 2023

AbstractTunnelling Nanotubes (TNTs) facilitate contact-mediated intercellular communication over long distances. Material transfer via TNTs can range from ions and intracellular organelles to protein aggregates and pathogens. Prion-like toxic protein aggregates accumulating in several neurodegenerative pathologies, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, have been shown to spread via TNTs not only between neurons, but also between neurons-astrocytes, and neurons-pericytes, indicating the importance of TNTs in mediating neuron–glia interactions. TNT-like structures were also reported between microglia, however, their roles in neuron-microglia interaction remain elusive. In this work, we quantitatively characterise microglial TNTs and their cytoskeletal composition, and demonstrate that TNTs form between human neuronal and microglial cells. We show thatα-Synuclein (α-Syn) aggregates increase the global TNT-mediated connectivity between cells, along with the number of TNT connections per cell pair. Homotypic TNTs formed between microglial cells, and heterotypic TNTs between neuronal and microglial cells are furthermore shown to be functional, allowing movement of bothα-Syn and mitochondria. Quantitative analysis shows thatα-Syn aggregates are transferred predominantly from neuronal to microglial cells, possibly as a mechanism to relieve the burden of accumulated aggregates. By contrast, microglia transfer mitochondria preferably toα-Syn burdened neuronal cells over the healthy ones, likely as a potential rescue mechanism. Besides describing novel TNT-mediated communication between neuronal and microglial cells, this work allows us to better understand the cellular mechanisms of spreading neurodegenerative diseases, shedding light on the role of microglia.
TIM-3 increases the abundance of type-2 dendritic cells during Leishmania donovani infection by enhancing IL-10 production via STAT3
Authors: Mishra Manish , Yadav Manisha , Kumar Sandeep , Kumar Raj , Sen Pradip 
Published: May 2023

AbstractThe outcome of the disease visceral leishmaniasis (VL), caused by Leishmania donovani (LD), largely relies on the relative dominance of host-protective type-1 T helper (Th1) cell response versus disease-promoting type-2 T helper (Th2) cell response. The Th1 and Th2 responses, in turn, are believed to be elicited by type-1 conventional dendritic cells (cDC1) and type-2 conventional DCs (cDC2), respectively. However, it is still unknown which DC subtype (cDC1 or cDC2) predominates during chronic LD infection and the molecular mechanism governing such occurrence. Here we report that in chronically infected mice, the splenic cDC1-cDC2 balance shifted toward the cDC2 subtype and that the receptor T cell immunoglobulin and mucin protein-3 (TIM-3) expressed by DCs played a key role in mediating this effect. Transfer of TIM-3-silenced DCs in fact prevented the predominance of the cDC2 subtype in mice with chronic LD infection. We also found that LD actually upregulated TIM-3 expression on DCs by triggering a TIM-3-mediated signaling pathway STAT3 (signal transducer and activator of transcription 3)→interleukin (IL)-10→c-Src→transcription factors Ets1, Ets2, USF1, and USF2. Notably, TIM-3 promoted STAT3 activation via a non-receptor tyrosine kinase Btk. Adoptive transfer experiments further demonstrated a critical role for STAT3-driven TIM-3 upregulation on DCs in increasing cDC2 abundance in chronically infected mice, which ultimately aided disease pathogenesis by augmenting Th2 responses. These findings document a new immunoregulatory mechanism contributing to disease pathology during LD infection and define TIM-3 as a key mediator of this process.
Butyrate limits inflammatory macrophage niche in NASH
Authors: Sarkar Ankita , Mitra Priya , Lahiri Abhishake , Das Tanusree , Sarkar Jit , Paul Sandip , Chakrabarti Partha 
Published: May 2023

AbstractImmune cell infiltrations with lobular inflammation in the background of steatosis and deregulated gut-liver axis are the cardinal features of non-alcoholic steatohepatitis (NASH). An array of gut microbiota-derived metabolites including short-chain fatty acids (SCFA) multifariously modulates NASH pathogenesis. However, the molecular basis for the favorable impact of sodium butyrate (NaBu), a gut microbiota-derived SCFA, on the immunometabolic homeostasis in NASH remains elusive. We show that NaBu imparts a robust anti-inflammatory effect in lipopolysaccharide (LPS) stimulated or classically activated M1 polarized macrophages and in the diet-induced murine NASH model. Moreover, it impedes monocyte-derived inflammatory macrophage recruitment in liver parenchyma and induces apoptosis of proinflammatory liver macrophages (LM) in NASH livers. Mechanistically, by histone deactylase (HDAC) inhibition NaBu enhanced acetylation of canonical NF-κB subunit p65 along with its differential recruitment to the proinflammatory gene promoters independent of its nuclear translocation. NaBu-treated macrophages thus exhibit transcriptomic signatures that corroborate with a M2-like prohealing phenotype. NaBu quelled LPS-mediated catabolism and phagocytosis of macrophages, exhibited a differential secretome which consequently resulted in skewing toward prohealing phenotype and induced death of proinflammatory macrophages to abrogate metaflammation in vitro and in vivo. Thus NaBu could be a potential therapeutic as well as preventive agent in mitigating NASH.
Single cell transcriptomics clarifies the basophil differentiation trajectory and identifies pre-basophils upstream of mature basophils
Authors: Miyake Kensuke , Ito Junya , Nakabayashi Jun , Shichino Shigeyuki , Ishiwata Kenji , Karasuyama Hajime 
Published: May 2023

AbstractBasophils are the rarest granulocytes and are recognized as critical cells for type 2 immune responses. However, their differentiation pathway remains to be fully elucidated. Here, we assess the ontogenetic trajectory of basophils by single-cell RNA sequence analysis. Combined with flow cytometric and functional analyses, we identify c-Kit-CLEC12Ahi pre-basophils located downstream of pre-basophil and mast cell progenitors (pre-BMPs) and upstream of CLEC12Alo mature basophils. The transcriptomic analysis predicts that the pre-basophil population includes previously-defined basophil progenitor (BaP)-like cells in terms of gene expression profile. Pre-basophils are highly proliferative and respond better to non-IgE stimuli but less to antigen plus IgE stimulation than do mature basophils. Although pre-basophils usually remain in the bone marrow, they emerge in helminth-infected tissues, probably through IL-3-mediated inhibition of their retention in the bone marrow. Thus, the present study identifies pre-basophils that bridge the gap between pre-BMPs and mature basophils during basophil ontogeny.
Acidic CO2-to-HCOOH electrolysis with industrial-level current on phase engineered tin sulfide
Authors: Shen Haifeng , Jin Huanyu , Li Haobo , Wang Herui , Duan Jingjing , Jiao Yan , Qiao Shi-Zhang 
Published: May 2023

AbstractAcidic CO2-to-HCOOH electrolysis represents a sustainable route for value-added CO2 transformations. However, competing hydrogen evolution reaction (HER) in acid remains a great challenge for selective CO2-to-HCOOH production, especially in industrial-level current densities. Main group metal sulfides derived S-doped metals have demonstrated enhanced CO2-to-HCOOH selectivity in alkaline and neutral media by suppressing HER and tuning CO2 reduction intermediates. Yet stabilizing these derived sulfur dopants on metal surfaces at large reductive potentials for industrial-level HCOOH production is still challenging in acidic medium. Herein, we report a phase-engineered tin sulfide pre-catalyst (π-SnS) with uniform rhombic dodecahedron structure that can derive metallic Sn catalyst with stabilized sulfur dopants for selective acidic CO2-to-HCOOH electrolysis at industrial-level current densities. In situ characterizations and theoretical calculations reveal the π-SnS has stronger intrinsic Sn-S binding strength than the conventional phase, facilitating the stabilization of residual sulfur species in the Sn subsurface. These dopants effectively modulate the CO2RR intermediates coverage in acidic medium by enhancing *OCHO intermediate adsorption and weakening *H binding. As a result, the derived catalyst (Sn(S)-H) demonstrates significantly high Faradaic efficiency (92.15 %) and carbon efficiency (36.43 %) to HCOOH at industrial current densities (up to −1 A cm−2) in acidic medium.
PI16+ reticular cells in human palatine tonsils govern T cell activity in distinct subepithelial niches
Authors: De Martin Angelina , Stanossek Yves , Lütge Mechthild , Cadosch Nadine , Onder Lucas , Cheng Hung-Wei , Brandstadter Joshua D. , Maillard Ivan , Stoeckli Sandro J. , Pikor Natalia B. , Ludewig Burkhard 
Published: May 2023

AbstractFibroblastic reticular cells (FRCs) direct the interaction and activation of immune cells in discrete microenvironments of lymphoid organs. Despite their important role in steering innate and adaptive immunity, the age- and inflammation-associated changes in the molecular identity and functional properties of human FRCs have remained largely unknown. Here, we show that human tonsillar FRCs undergo dynamic reprogramming during life and respond vigorously to inflammatory perturbation in comparison to other stromal cell types. The peptidase inhibitor 16 (PI16)-expressing reticular cell (PI16+ RC) subset of adult tonsils exhibited the strongest inflammation-associated structural remodeling. Interactome analysis combined with ex vivo and in vitro validation revealed that T cell activity within subepithelial niches is controlled by distinct molecular pathways during PI16+ RC–lymphocyte interaction. In sum, the topological and molecular definition of the human tonsillar stromal cell landscape reveals PI16+ RCs as a specialized FRC niche at the core of mucosal immune responses in the oropharynx.
A motor association area in the depths of the central sulcus
Authors: Jensen Michael A. , Huang Harvey , Valencia Gabriela Ojeda , Klassen Bryan T. , van den Boom Max A. , Kaufmann Timothy J. , Schalk Gerwin , Brunner Peter , Worrell Gregory A. , Hermes Dora , Miller Kai J. 
Published: May 2023

AbstractCells in the precentral gyrus directly send signals to the periphery to generate movement and are principally organized as a topological map of the body. We find that movement-induced electrophysiological responses from depth electrodes extend this map three-dimensionally throughout the gyrus. Unexpectedly, this organization is interrupted by a previously undescribed motor association area in the depths of the midlateral aspect of the central sulcus. This ‘Rolandic motor association’ (RMA) area is active during movements of different body parts from both sides of the body and may be important for coordinating complex behaviors.
Organic geochemical evidence of human-controlled fires at Acheulean site of Valdocarros II (Spain, 245 kya)
Authors: Stancampiano Lavinia M. , Rubio-Jara Susana , Panera Joaquín , Uribelarrea David , Pérez-González Alfredo , Magill Clayton R. 
Published: May 2023

AbstractAmong the outstanding questions about the emergence of human-controlled fire is the systematic recurrence between the geochemical remains of fire and its preservation in the archaeological record, as the use of fire is considered a technological landmark, especially for its importance in food cooking, defensive strategies, and heating. Here we report fossil lipid biomarkers associated with incomplete combustion of organic matter at the Valdocarros II site, one of the largest European Acheulean sites in Spain dated to marine isotopic stage (MIS) 8/7 (~ 245 kya) allowing a multiproxy analysis of human-controlled fire use. Our results reveal isolated cases of highly concentrated and diverse polycyclic aromatic hydrocarbons (PAHs) and alkylated PAHs (APAHs), along with diagnostic conifer-derived triterpenoids in two hearth-like archaeological structures. The presence of combustion byproducts suggests the presence of anthropogenic (controlled) fires at Valdocarros—one of the oldest evidence of fire use in Europe-in association with Acheulean tools and bones. Hominins possibly used fire for two main activities, as a means of defense against predators and cooking. Our results help to better delineate major gaps in our current knowledge of human-controlled fire in the context of the Middle-Pleistocene in Europe and suggest that human ancestors were able to control fire before at least 250 kya.
Applying appropriate frequency criteria to advance acoustic behavioural guidance systems for fish
Authors: Holgate A. , White P. R. , Leighton T. G. , Kemp P. S. 
Published: May 2023

AbstractDeterrents that use acoustics to guide fish away from dangerous areas depend on the elicitation of avoidance in the target species. Acoustic deterrents select the optimum frequency based on an assumption that highest avoidance is likely to occur at the greatest sensitivity. However, such an assumption may be unfounded. Using goldfish (Carassius auratus) as a suitable experimental model, this study tested this as a null hypothesis. Under laboratory conditions, the deterrence thresholds of individual goldfish exposed to 120 ms tones at six frequencies (250–2000 Hz) and four Sound Pressure Levels (SPL 115–145 dB) were quantified. The deterrence threshold defined as the SPL at which 25% of the tested population startled was calculated and compared to the hearing threshold obtained using Auditory Evoked Potential and particle acceleration threshold data. The optimum frequency to elicit a startle response was 250 Hz; different from the published hearing and particle acceleration sensitivities based on audiograms. The difference between the deterrence threshold and published hearing threshold data varied from 47.1 dB at 250 Hz to 76 dB at 600 Hz. This study demonstrates that information obtained from audiograms may poorly predict the most suitable frequencies at which avoidance behaviours are elicited in fish.
Geomorphological assessment of the preservation of archaeological tell sites
Authors: Forti Luca , Brandolini Filippo , Oselini Valentina , Peyronel Luca , Pezzotta Andrea , Vacca Agnese , Zerboni Andrea 
Published: May 2023

AbstractTells are multi-layered, archaeological mounds representing anthropogenic landforms common in arid regions. In such contexts, the preservation of the archaeological record is mined by ongoing climate changes, shift in land use, and intense human overgrazing. Such natural and human-driven factors tune the response of archaeological soils and sediments to erosion. Geomorphology offers a plethora of tools for mapping natural and anthropogenic landforms and evaluating their response to unremitting weathering, erosional and depositional processes. Here, we present a geomorphological investigation on two anthropogenic mounds in the Kurdistan Region of Iraq, with a special focus on the ongoing erosional processes mining their slope stability and threatening the preservation of the local archaeological landscape. Applying the revised universal soil loss equation model for soil loess derived from UAV imagery and implemented with geoarchaeological investigation, we assess the erosion rate along anthropogenic mounds and estimate the risk of losing archaeological deposits. We argue that a large-scale application of our approach in arid and semi-arid regions may improve our ability to (i) estimate the rate of soil and/or archaeological sediments loss, (ii) propose mitigation strategies to prevent the dismantling of the archaeological record, and (iii) schedule archaeological operations in areas of moderate to extreme erosion risk.
An organ-on-chip device with integrated charge sensors and recording microelectrodes
Authors: Aydogmus Hande , Hu Michel , Ivancevic Lovro , Frimat Jean-Philippe , van den Maagdenberg Arn M. J. M. , Sarro Pasqualina M. , Mastrangeli Massimo 
Published: May 2023

AbstractContinuous monitoring of tissue microphysiology is a key enabling feature of the organ-on-chip (OoC) approach for in vitro drug screening and disease modeling. Integrated sensing units are particularly convenient for microenvironmental monitoring. However, sensitive in vitro and real-time measurements are challenging due to the inherently small size of OoC devices, the characteristics of commonly used materials, and external hardware setups required to support the sensing units. Here we propose a silicon-polymer hybrid OoC device that encompasses transparency and biocompatibility of polymers at the sensing area, and has the inherently superior electrical characteristics and ability to house active electronics of silicon. This multi-modal device includes two sensing units. The first unit consists of a floating-gate field-effect transistor (FG-FET), which is used to monitor changes in pH in the sensing area. The threshold voltage of the FG-FET is regulated by a capacitively-coupled gate and by the changes in charge concentration in close proximity to the extension of the floating gate, which functions as the sensing electrode. The second unit uses the extension of the FG as microelectrode, in order to monitor the action potential of electrically active cells. The layout of the chip and its packaging are compatible with multi-electrode array measurement setups, which are commonly used in electrophysiology labs. The multi-functional sensing is demonstrated by monitoring the growth of induced pluripotent stem cell-derived cortical neurons. Our multi-modal sensor is a milestone in combined monitoring of different, physiologically-relevant parameters on the same device for future OoC platforms.