bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a novel fatty acid binding protein-5-CB2 receptor-dependent mechanism regulating anxiety behaviors in the prefrontal cortex
Authors: Uzuneser Taygun C , Szkudlarek Hanna J , Jones Matthew J , Nashed Mina G , Clement Timothy , Wang Hehe , Ojima Iwao , Rushlow Walter J , Laviolette Steven R 
Published: June 2022

AbstractThe endocannabinoid (eCB) system represents a promising neurobiological target for novel anxiolytic pharmacotherapies. Previous clinical and preclinical evidence has revealed that genetic and/or pharmacological manipulations altering eCB signaling modulate fear and anxiety behaviors. Water-insoluble eCB lipid anandamide requires chaperone proteins for its intracellular transport to degradation, a process that requires fatty acid-binding proteins (FABPs). Here, we investigated the effects of a novel FABP-5 inhibitor, SBFI-103, on fear and anxiety-related behaviors using rats. Acute intra-prelimbic cortex administration of SBFI-103 induced a dose-dependent anxiolytic response and reduced contextual fear expression. Surprisingly, both effects were reversed when a cannabinoid-2 receptor (CB2R) antagonist, AM630, was co-infused with SBFI-103. Co-infusion of the cannabinoid-1 receptor antagonist Rimonabant with SBFI-103 reversed the contextual fear response yet showed no reversal effect on anxiety. Furthermore, in vivo neuronal recordings revealed that intra-prelimbic region SBFI-103 infusion altered the activity of putative pyramidal neurons in the basolateral amygdala and ventral hippocampus, as well as oscillatory patterns within these regions in a CB2R-dependent fashion. Our findings identify a promising role for FABP5 inhibition as a potential target for anxiolytic pharmacotherapy. Furthermore, we identify a novel, CB2R-dependent FABP-5 signaling pathway in the PFC capable of strongly modulating anxiety-related behaviors and anxiety-related neuronal transmission patterns.
Effectiveness of Paxlovid in Reducing Severe Coronavirus Disease 2019 and Mortality in High-Risk Patients
Authors: Najjar-Debbiny Ronza , Gronich Naomi , Weber Gabriel , Khoury Johad , Amar Maisam , Stein Nili , Goldstein Lee Hilary , Saliba Walid 
Published: June 2022

AbstractBackgroundPaxlovid was granted an Emergency Use Authorization for the treatment of mild to moderate coronavirus disease 2019 (COVID-19), based on the interim analysis of the Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) trial. Paxlovid effectiveness needs to be assessed in a noncontrolled setting. In this study we used population-based real-world data to evaluate the effectiveness of Paxlovid.MethodsThe database of the largest healthcare provider in Israel was used to identify all adults aged 18 years or older with first-ever positive test for severe acute respiratory syndrome coronavirus 2 between January and February 2022, who were at high risk for severe COVID-19 and had no contraindications for Paxlovid use. Patients were included irrespective of their COVID-19 vaccination status. Cox hazard regression was used to estimate the 28-day hazard ratio (HR) for severe COVID-19 or mortality with Paxlovid examined as time-dependent variable.ResultsOverall, 180 351 eligible patients were included; of these, only 4737 (2.6%) were treated with Paxlovid, and 135 482 (75.1%) had adequate COVID-19 vaccination status. Both Paxlovid and adequate COVID-19 vaccination status were associated with significant decrease in the rate of severe COVID-19 or mortality with adjusted HRs of 0.54 (95% confidence interval [CI], .39–.75) and 0.20 (95% CI, .17–.22), respectively. Paxlovid appears to be more effective in older patients, immunosuppressed patients, and patients with underlying neurological or cardiovascular disease (interaction P &lt; .05 for all). No significant interaction was detected between Paxlovid treatment and COVID-19 vaccination status.ConclusionsThis study suggests that in the era of Omicron and in real-life settings, Paxlovid is highly effective in reducing the risk of severe COVID-19 or mortality.
AnthraxKP: a knowledge graph-based, Anthrax Knowledge Portal mined from biomedical literature
Authors: Feng Baiyang , Gao Jing 
Published: June 2022

AbstractAnthrax is a zoonotic infectious disease caused by Bacillus anthracis (anthrax bacterium) that affects not only domestic and wild animals worldwide but also human health. As the study develops in-depth, a large quantity of related biomedical publications emerge. Acquiring knowledge from the literature is essential for gaining insight into anthrax etiology, diagnosis, treatment and research. In this study, we used a set of text mining tools to identify nearly 14 000 entities of 29 categories, such as genes, diseases, chemicals, species, vaccines and proteins, from nearly 8000 anthrax biomedical literature and extracted 281 categories of association relationships among the entities. We curated Anthrax-related Entities Dictionary and Anthrax Ontology. We formed Anthrax Knowledge Graph (AnthraxKG) containing more than 6000 nodes, 6000 edges and 32 000 properties. An interactive visualized Anthrax Knowledge Portal(AnthraxKP) was also developed based on AnthraxKG by using Web technology. AnthraxKP in this study provides rich and authentic relevant knowledge in many forms, which can help researchers carry out research more efficiently.Database URL: AnthraxKP is permitted users to query and download data at http://139.224.212.120:18095/.
Impact of within-visit systolic blood pressure change patterns on blood pressure classification: the Cardiovascular Risk in Young Finns Study
Authors: Meng Yaxing , Magnussen Costan G , Wu Feitong , Juonala Markus , Buscot Marie-Jeanne , Pahkala Katja , Hutri-Kähönen Nina , Kähönen Mika , Laitinen Tomi , Viikari Jorma S A , Raitakari Olli T , Sharman James E 
Published: June 2022

Abstract

Aims
Most international guidelines recommend that repeat blood pressure (BP) readings are required for BP classification. Two international guidelines diverge from this by recommending that no further BP measurements are required if the first clinic BP is below a hypertension threshold. The extent to which within-visit BP variability patterns change over time, and whether this could impact BP classification is unknown. We sought to examine this.

Methods and results
Data were from the Cardiovascular Risk in Young Finns Study, a prospective cohort study. Up to 2799 participants were followed from childhood (9–15 years) to adulthood (18–49 years) over up to six visits. Patterns of within-visit systolic BP (SBP) variability were defined as no-change, decrease, increase between consecutive readings (with 5 mmHg change thresholds). Classification of SBP (normal, high-normal, hypertension) using the first reading was compared with repeat readings. On average, SBP decreased with subsequent measures, but with major individual variability (no-change: 56.9–62.7%; decrease: 24.1–31.6%; increase: 11.5–16.8%). Patterns of SBP variability were broadly similar from childhood to adulthood, with the highest prevalence of an increase among participants categorized with normal SBP (12.6–20.3%). The highest prevalence of SBP reclassification occurred among participants with hypertension (28.9–45.3% reclassified as normal or high-normal). The prevalence of reclassification increased with the magnitude of change between readings.

Conclusion
There is a major individual variation of within-visit SBP change in childhood and adulthood and can influence BP classification. This highlights the importance of consistency among guidelines recommending that repeat BP measurements are needed for BP classification.
Seismicity in a weak crust: the transtensional tectonics of the Brawley Seismic Zone section of the Pacific–North America Plate Boundary in Southern California, USA
Authors: Hauksson Egill , Stock Joann M , Husker Allen L 
Published: June 2022

SUMMARYThe Brawley Seismic Zone (BSZ) is a ∼58-km-long section of the Pacific–North America Plate boundary that connects the southernmost San Andreas Fault (SAF) and the Imperial Fault in southern California. We analyse the BSZ as two segments: a north segment, dominated by SAF tectonics, and a south segment that accommodates a higher level of seismicity. The south segment includes a ∼6 km wide right lateral step-over that includes the Salton Sea geothermal field (SSGF) and Holocene subaerial lava domes at the south end of the Salton Sea, called Salton Buttes. In general, the 40 yr (1981–2021) of BSZ seismicity is characterized by transitory sequences that often are accommodated simultaneously or in quick succession on intricate ladder-like faults. These sequences rarely reactivate faults associated with previous seismicity alignments but rather activate adjacent faults, sometimes located within less than 1 km. They can include several events of similar size as the mainshock, followed by bursts of aftershocks sometimes located away from the mainshock rupture. The seismicity rate and the spatial geometrical complexity varies between the BSZ-north and BSZ-south segments. The 24-km-long BSZ-north accommodates a ∼12-km-long linear trend of seismicity that extends from the SAF terminus into the Salton Sea, where moderate-sized northeast striking sequences form the rungs in a ladder-structure in a weak crust. The seismicity in this area is most likely influenced by the stress state of the SAF. In contrast, the 34 km long BSZ-south segment, which also has a weak crust, has accommodated larger sequences that illuminate irregular ladder-type faulting, with aftershocks defining linear distributions striking either north or northeast. The focal mechanisms exhibit a mostly strike-slip style of faulting with minor dip-slip faulting in the south Salton Sea area as well as the Mesquite basin to the south. The state of stress, as determined from focal mechanisms, consists of almost horizontal σ1, and σ3 with vertical σ2. The activation angle between the trend of σ1 and the preferred nodal plane of the largest nearby event decreases systematically from north to south along the long-axis of the BSZ. In the step-over zone, the Holocene volcanism and the frequent seismicity sequences suggest crustal extension as well as associated reduced crustal strength as compared to other parts of the BSZ. The presence of weak, thin, hot crust and distributed ladder-like or conjugate predominantly strike-slip faulting suggests that the whole BSZ acts as a several kilometre wide fault zone where no prominent principal slip surfaces are required to accommodate moderate-sized (M6+) earthquakes.
Modelling autosomal dominant optic atrophy associated with OPA1 variants in iPSC-derived retinal ganglion cells
Authors: Sladen Paul E , Jovanovic Katarina , Guarascio Rosellina , Ottaviani Daniele , Salsbury Grace , Novoselova Tatiana , Chapple J Paul , Yu-Wai-Man Patrick , Cheetham Michael E 
Published: June 2022

Abstract
Autosomal dominant optic atrophy (DOA) is the most common inherited optic neuropathy, characterized by the preferential loss of retinal ganglion cells (RGCs), resulting in optic nerve degeneration and progressive bilateral central vision loss. More than 60% of genetically confirmed patients with DOA carry variants in the nuclear OPA1 gene, which encodes for a ubiquitously expressed, mitochondrial GTPase protein. OPA1 has diverse functions within the mitochondrial network, facilitating inner membrane fusion and cristae modelling, regulating mitochondrial DNA maintenance and coordinating mitochondrial bioenergetics. There are currently no licensed disease-modifying therapies for DOA and the disease mechanisms driving RGC degeneration are poorly understood. Here, we describe the generation of isogenic, heterozygous OPA1 null induced pluripotent stem cell (iPSC) (OPA1+/−) through clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing of a control cell line, in conjunction with the generation of DOA patient-derived iPSC carrying OPA1 variants, namely, the c.2708_2711delTTAG variant (DOA iPSC), and previously reported missense variant iPSC line (c.1334G&gt;A, DOA plus [DOA]+ iPSC) and CRISPR/Cas9 corrected controls. A two-dimensional (2D) differentiation protocol was used to study the effect of OPA1 variants on iPSC-RGC differentiation and mitochondrial function. OPA1+/−, DOA and DOA+ iPSC showed no differentiation deficit compared to control iPSC lines, exhibiting comparable expression of all relevant markers at each stage of differentiation. OPA1+/− and OPA1 variant iPSC-RGCs exhibited impaired mitochondrial homeostasis, with reduced bioenergetic output and compromised mitochondrial DNA maintenance. These data highlight mitochondrial deficits associated with OPA1 dysfunction in human iPSC-RGCs, and establish a platform to study disease mechanisms that contribute to RGC loss in DOA, as well as potential therapeutic interventions.
The Water to Land Transition Submerged: Multifunctional Design of Pectoral Fins for Use in Swimming and in Association with Underwater Substrate
Authors: Hale Melina E , Galdston Seth , Arnold Benjamin W , Song Chris 
Published: June 2022

Abstract
Fins of fishes provide many examples of structures that are beautifully designed to power and control movement in water; however, some species also use their fins for substrate-associated behaviors where interactions with solid surfaces are key. Here, we examine how the pectoral fins of ray-finned fish with these multifunctional behavioral demands, in water and on solid surfaces, are structured and function. We subdivide fins used in swimming and substrate contact into two general morphological categories, regionalized vs. generalized fins. Regionalized fins have ventral rays that are free from connecting membrane or in which that membrane is reduced. Dorsally they maintain a more typical membranous fin. While all pectoral fins vary somewhat in their morphology from leading to trailing edge, generalized fins do not have the substantial membrane loss between rays that is seen in regionalized fins and the distal edge anatomy changes gradually along its margin. We add a new case study in regionalized fins with the dwarf hawkfish (Cirrhitichthys falco). Hawkfishes are most often found perching and moving on structures in their environments. During perching, the free ventral rays are in contact with the substrate and splayed. We found that unlike other fish with regionalized pectoral fins, hawkfish maintain use of the dorsal membranous region of its pectoral fin for rhythmic swimming. We found that typically hawkfish bend their ventral free rays under, toward the medial hemitrichs or hold them straight during substrate-associated postures. This appears also to be the case for the ventral free rays of other species with regionalized fins. Generalized fin use for substrate contact was reviewed in round gobies (Neogobius melanostomus). In addition, although their lobe fins are not representative of ray-finned fish anatomy, we explored fin contact on submerged substrates in the Senegal bichir (Polypterus senegalus), which has a generalized distal fin (no free fin rays or distinct membrane regions). Both groups use their pectoral fins for swimming. During substrate-based postures, unlike hawkfish, their distal rays generally bend outward toward the lateral hemitrichs and a large swath of the fin membrane can contact the surface. The alternative demands on multifunctional fins suggest specialization of the mechanosensory system. We review mechanosensation related to fin movement and surface contact. These alternative regionalized and generalized strategies for serving aquatic and substrate-based functions underwater provide opportunities to further investigate specializations, including sensory structures and systems, that accompany the evolution of substrate-based behaviors in vertebrates.
Spatio-temporal variability in drifting Fish Aggregating Device (dFAD) beaching events in the Seychelles Archipelago
Authors: MacMillan Isla , Attrill Martin J , Imzilen Taha , Lett Christophe , Walmsley Simon , Chu Clarus , Kaplan David M 
Published: June 2022

AbstractPurse-seine fisheries use drifting Fish Aggregating Devices (dFADs), human-made floating objects, to facilitate the capture of tropical tunas. Currently, the majority of dFADs are constructed primarily of highly durable non-biodegradable materials and there is no legal obligation to recover dFADs after deployment, leading to beaching events and potentially negative environmental impacts. We assessed beachings as a function of intra- and inter-annual trends, water depth, distance from land, seasonality, and benthic habitat within the local context of the Seychelles Archipelago using trajectories of dFADs deployed by French purse seiners over 2008–2020. Overall, 3842 beaching events associated with 2371 distinct dFAD tracking buoys were identified. Beachings occurred most frequently during the winter monsoon (December–March). Due to the shallow Mahé Plateau, beachings occurred in both nearshore (≤ 5 km from land) and offshore (&gt; 5 km) regions, predominantly in estimated depths less than 60 m. Despite representing &lt; 20% of overall mapped habitat, the benthic habitat “Coral/Algae” had the highest beaching rate (35.3% of beachings), and therefore, beachings pose a significant concern for conservation. Our results provide a detailed view of the spatio-temporal pattern of beachings in the Seychelles, supporting the development of mitigation and prevention methods to reduce marine debris and perturbations to the marine environment.
The role of immune cells in the liver tumor microenvironment: an involvement of gut microbiota-derived factors
Authors: Kamiya Tomonori , Ohtani Naoko 
Published: June 2022

AbstractAbstractMore than 500 species of microbiota reside in the human intestine and coexist with humans, their host. Gut microbial metabolites and components are absorbed from the intestine and influence cells in the liver, including hepatocytes and stromal cells, such as liver sinusoidal endothelial cells, hepatic stellate cells, Kupffer cells, natural killer (NK) cells, NK T cells and other immune cells. This gut-originated axis to the liver is called the “gut–liver axis”, which underscores the importance of the link between the gut and the liver. In this review, we discuss the gut microbial components and metabolites that affect cells in the liver, particularly in association with immune cells, and the related responses. We also highlight the mechanisms underlying gut microbiota-mediated liver carcinogenesis and discuss cancer prevention, including the recently clarified modulation of immune checkpoint inhibitor efficacy by the gut microbiota.
The Human Neck is Part of the Musculoskeletal Core: Cervical Muscles Help Stabilize the Pelvis During Running and Jumping
Authors: Boynton Alicia M , Carrier David R 
Published: June 2022

Synopsis
During locomotion, cervical muscles must be active to stabilize the head as the body accelerates and decelerates. We hypothesized that cervical muscles are also part of the linked chain of axial muscles that provide core stabilization against torques applied to the hip joint by the extrinsic muscles of the legs. To test whether specific cervical muscles play a role in postural stabilization of the head and/or core stabilization of the pelvic girdle, we used surface electromyography to measure changes in muscle activity in response to force manipulations during constant speed running and maximum effort counter-movement jumps. We found that doubling the mass of the head during both running and maximum effort jumping had little or no effect on (1) acceleration of the body and (2) cervical muscle activity. Application of horizontal forward and rearward directed forces at the pelvis during running tripled mean fore and aft accelerations, thereby increasing both the pitching moments on the head and flexion and extension torques applied to the hip. These manipulations primarily resulted in increases in cervical muscle activity that is appropriate for core stabilization of the pelvis. Additionally, when subjects jumped maximally with an applied downward directed force that reduced acceleration and therefore need for cervical muscles to stabilize the head, cervical muscle activity did not decrease. These results suggest that during locomotion, rather than acting to stabilize the head against the effects of inertia, the superficial muscles of the neck monitored in this study help to stabilize the pelvis against torques imposed by the extrinsic muscles of the legs at the hip joint. We suggest that a division of labor may exist between deep cervical muscles that presumably provide postural stabilization of the head versus superficial cervical muscles that provide core stabilization against torques applied to the pelvic and pectoral girdles by the extrinsic appendicular muscles.
Political Agency, Victimhood, and Gender in Contexts of Armed Conflict: Moving beyond Dichotomies
Authors: Kreft Anne-Kathrin , Schulz Philipp 
Published: June 2022

AbstractIn this article, we nuance the relationships between political agency, victimhood, and gender during armed conflicts. Dominant narratives often spotlight individuals as either passive victims or active agents. These representations are especially pronounced for sexual violence against women in conflict, where gendered conceptions of victimhood and agency remain particularly salient. Recent scholarship challenges this dichotomized way of thinking, showing how victimhood and agency sit alongside each other. We extend this growing body of scholarship by proposing a relational conception of agency that helps us better understand exactly how victimhood and agency intersect and can even be co-constitutive. Specifically, we propose that conceptualizing agency as relational—to others, to contextual structures, to own vulnerabilities and prior victimization—is particularly well suited to overcome inadequate dichotomizations, and to illuminate the spectrum of political agency, ranging from formalized politicized spaces to more mundane forms of agency within the quotidian. Drawing on qualitative fieldwork in Colombia and Uganda, we empirically tease out these complex intersections in a context of (gendered) vulnerability.
Cancer-associated mutations in SF3B1 disrupt the interaction between SF3B1 and DDX42
Authors: Zhao Bo , Li Zhuang , Qian Rui , Liu Gang , Fan Mingyue , Liang Zehua , Hu Xin , Wan Youzhong 
Published: June 2022

Abstract
While cancer-associated SF3B1 mutations causes alternative RNA splicing, the molecular mechanism underlying the alternative RNA splicing is not fully elucidated. Here, we analysed the proteins that interacted with the wild-type and K700E-mutated SF3B1 and found that the interactions of two RNA helicases, DDX42 and DDX46, with the mutated SF3B1 were reduced. Overexpression of DDX42 restored the decreased interaction between DDX42 and the K700E-mutated SF3B1, and suppressed some alternative RNA splicing associated with the SF3B1 mutation. Mutation that decreased the ATP hydrolysis activities of DDX42 abolished the suppressive effects of DDX42 on the alternative RNA splicing, suggesting that the ATP hydrolysis activity of DDX42 is involved in the mechanism of the altered RNA splicing associated with the SF3B1 mutation. Our study demonstrates an important function of the interaction between DDX42 and SF3B1 on regulating RNA splicing and revealed a potential role of DDX42 in the altered RNA splicing associated with the SF3B1 mutation.