bluuebunny/crossref_metadata_2025_split huggingface dataset:
A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility
Authors: Voloudakis Georgios , Vicari James M. , Venkatesh Sanan , Hoffman Gabriel E. , Dobrindt Kristina , Zhang Wen , Beckmann Noam D. , Higgins Christina A. , Argyriou Stathis , Jiang Shan , Hoagland Daisy , Gao Lina , Corvelo André , Cho Kelly , Lee Kyung Min , Bian Jiantao , Lee Jennifer S. , Iyengar Sudha K. , Luoh Shiuh-Wen , Akbarian Schahram , Striker Robert , Assimes Themistocles L. , Schadt Eric E. , Lynch Julie A. , Merad Miriam , tenOever Benjamin R. , Charney Alexander W. ,   Mount Sinai COVID-19 Biobank,   VA Million Veteran Program COVID-19 Science Initiative, Brennand Kristen J. , Fullard John F. , Roussos Panos 
Published: September 2022

AbstractRecent efforts have identified genetic loci that are associated with coronavirus disease 2019 (COVID-19) infection rates and disease outcome severity. Translating these genetic findings into druggable genes that reduce COVID-19 host susceptibility is a critical next step. Using a translational genomics approach that integrates COVID-19 genetic susceptibility variants, multi-tissue genetically regulated gene expression (GReX), and perturbagen signatures, we identified IL10RB as the top candidate gene target for COVID-19 host susceptibility. In a series of validation steps, we show that predicted GReX upregulation of IL10RB and higher IL10RB expression in COVID-19 patient blood is associated with worse COVID-19 outcomes and that in vitro IL10RB overexpression is associated with increased viral load and activation of disease-relevant molecular pathways.
Integrating rapid exome sequencing into NICU clinical care after a pilot research study
Authors: D’Gama Alissa M. , Del Rosario Maya C. , Bresnahan Mairead A. , Yu Timothy W. , Wojcik Monica H. , Agrawal Pankaj B. 
Published: September 2022

AbstractGenomic sequencing is a powerful diagnostic tool in critically ill infants, but performing exome or genome sequencing (ES/GS) in the context of a research study is different from implementing these tests clinically. We investigated the integration of rapid ES into routine clinical care after a pilot research study in a Level IV Neonatal Intensive Care Unit (NICU). We performed a retrospective cohort analysis of infants admitted with suspected genetic disorders to the NICU from December 1, 2018 to March 31, 2021 and compared results to those obtained from a previous research study cohort (March 1, 2017 to November 30, 2018). Clinical rapid ES was performed in 80/230 infants (35%) with a suspected genetic disorder and identified a genetic diagnosis in 22/80 infants (28%). The majority of diagnoses acutely impacted clinical management (14/22 (64%)). Compared to the previous research study, clinically integrated rapid ES had a significantly lower diagnostic yield and increased time from NICU admission and genetics consult to ES report, but identified four genetic diagnoses that may have been missed by the research study selection criteria. Compared to other genetic tests, rapid ES had similar or higher diagnostic yield and similar or decreased time to result. Overall, rapid ES was utilized in the NICU after the pilot research study, often as the first-tier sequencing test, and could identify the majority of disease-causing variants, shorten the diagnostic odyssey, and impact clinical care. Based on our experience, we have identified strategies to optimize the clinical implementation of rapid ES in the NICU.
Integration of body-mounted ultrasoft organic solar cell on cyborg insects with intact mobility
Authors: Kakei Yujiro , Katayama Shumpei , Lee Shinyoung , Takakuwa Masahito , Furusawa Kazuya , Umezu Shinjiro , Sato Hirotaka , Fukuda Kenjiro , Someya Takao 
Published: September 2022

AbstractCyborg insects have been proposed for applications such as urban search and rescue. Body-mounted energy-harvesting devices are critical for expanding the range of activity and functionality of cyborg insects. However, their power outputs are limited to less than 1 mW, which is considerably lower than those required for wireless locomotion control. The area and load of the energy harvesting device considerably impair the mobility of tiny robots. Here, we describe the integration of an ultrasoft organic solar cell module on cyborg insects that preserves their motion abilities. Our quantified system design strategy, developed using a combination of ultrathin film electronics and an adhesive–nonadhesive interleaving structure to perform basic insect motion, successfully achieved the fundamental locomotion of traversing and self-righting. The body-mounted ultrathin organic solar cell module achieves a power output of 17.2 mW. We demonstrate its feasibility by displaying the recharging wireless locomotion control of cyborg insects.
Massively parallel genomic perturbations with multi-target CRISPR interrogates Cas9 activity and DNA repair at endogenous sites
Authors: Zou Roger S. , Marin-Gonzalez Alberto , Liu Yang , Liu Hans B. , Shen Leo , Dveirin Rachel K. , Luo Jay X. J. , Kalhor Reza , Ha Taekjip 
Published: September 2022

AbstractHere we present an approach that combines a clustered regularly interspaced short palindromic repeats (CRISPR) system that simultaneously targets hundreds of epigenetically diverse endogenous genomic sites with high-throughput sequencing to measure Cas9 dynamics and cellular responses at scale. This massive multiplexing of CRISPR is enabled by means of multi-target guide RNAs (mgRNAs), degenerate guide RNAs that direct Cas9 to a pre-determined number of well-mapped sites. mgRNAs uncovered generalizable insights into Cas9 binding and cleavage, revealing rapid post-cleavage Cas9 departure and repair factor loading at protospacer adjacent motif-proximal genomic DNA. Moreover, by bypassing confounding effects from guide RNA sequence, mgRNAs unveiled that Cas9 binding is enhanced at chromatin-accessible regions, and cleavage by bound Cas9 is more efficient near transcribed regions. Combined with light-mediated activation and deactivation of Cas9 activity, mgRNAs further enabled high-throughput study of the cellular response to double-strand breaks with high temporal resolution, revealing the presence, extent (under 2 kb) and kinetics (~1 h) of reversible DNA damage-induced chromatin decompaction. Altogether, this work establishes mgRNAs as a generalizable platform for multiplexing CRISPR and advances our understanding of intracellular Cas9 activity and the DNA damage response at endogenous loci.
Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: a phase 1/2a trial
Authors: Baloh Robert H. , Johnson J. Patrick , Avalos Pablo , Allred Peggy , Svendsen Soshana , Gowing Genevieve , Roxas Kristina , Wu Amanda , Donahue Becky , Osborne Sheryl , Lawless George , Shelley Brandon , Wheeler Koral , Prina Carolyn , Fine Dana , Kendra-Romito Tami , Stokes Haniah , Manoukian Vicki , Muthukumaran Abirami , Garcia Leslie , Bañuelos Maria G. , Godoy Marlesa , Bresee Catherine , Yu Hong , Drazin Doniel , Ross Lindsey , Naruse Robert , Babu Harish , Macklin Eric A. , Vo Ashley , Elsayegh Ashraf , Tourtellotte Warren , Maya Marcel , Burford Matthew , Diaz Frank , Patil Chirag G. , Lewis Richard A. , Svendsen Clive N. 
Published: September 2022

AbstractAmyotrophic lateral sclerosis (ALS) involves progressive motor neuron loss, leading to paralysis and death typically within 3–5 years of diagnosis. Dysfunctional astrocytes may contribute to disease and glial cell line-derived neurotrophic factor (GDNF) can be protective. Here we show that human neural progenitor cells transduced with GDNF (CNS10-NPC-GDNF) differentiated to astrocytes protected spinal motor neurons and were safe in animal models. CNS10-NPC-GDNF were transplanted unilaterally into the lumbar spinal cord of 18 ALS participants in a phase 1/2a study (NCT02943850). The primary endpoint of safety at 1 year was met, with no negative effect of the transplant on motor function in the treated leg compared with the untreated leg. Tissue analysis of 13 participants who died of disease progression showed graft survival and GDNF production. Benign neuromas near delivery sites were common incidental findings at post-mortem. This study shows that one administration of engineered neural progenitors can provide new support cells and GDNF delivery to the ALS patient spinal cord for up to 42 months post-transplantation.
Association between Toxoplasma gondii infection and psychiatric disorders: a cross-sectional study in China
Authors: Liu Taixiu , Gao Peng , Bu Deyun , Liu Dong 
Published: September 2022

AbstractPsychiatric patients have become the focus of public attention, and current research suggests a possible link between Toxoplasma gondii (T. gondii) infection and mental illness. To understand the current situation of T. gondii infection in psychiatric patients in the study area, the relationship between T. gondii infection and mental diseases, and the influence of T. gondii infection on psychiatric patients, this study examined 3101 psychiatric inpatients from 2015 to 2020. All people included in the study were tested for anti-Toxoplasma IgM antibody and anti-Toxoplasma IgG antibody. Additionally, 4040 individuals from the general population were included as controls. The chi-square test and logistic regression analysis were carried out to determine the association between psychiatric disorders and T. gondii infection. The seroprevalence of anti-Toxoplasma IgM antibody was 0.23% (7/3101) in psychiatric inpatients and 0.11% (2/1846) in the general population, and there was no significant difference (p > 0.05). The seroprevalence rate of anti-Toxoplasma IgG antibodies was 3.03% (94/3101) in psychiatric inpatients and 1.05% (23/2194) in the general population, and there was a significant difference (p < 0.01). The seroprevalence of anti-Toxoplasma IgG antibody in psychiatric inpatients was significantly different between different age groups (p < 0.01). The positivity rate of anti-Toxoplasma IgG antibodies was 5.17% (3/58) in patients with mania, 3.24% (8/247) in patients with recurrent depressive disorder, 3.54% (13/367) in patients with depression, 3.22% (39/1213) in patients with schizophrenia, 2.41% (18/748) in patients with bipolar disorder and 2.25% (2/89) in patients with dissociative disorder. Compared to the general population, patients with mania (OR = 5.149 95% CI 1.501–17.659 p = 0.009), schizophrenia (OR = 3.136 95% CI 1.864–5.275 p = 0.000), depression (OR = 3.466 95% CI 1.740–6.906 p = 0.000), recurrent depressive disorder (OR = 3.160 95% CI 1.398–7.142 p = 0.006) and bipolar disorder (OR = 2.327 95% CI 1.249–4.337 p = 0.008) were found to be significantly associated with the seroprevalence of anti-Toxoplasma IgG antibody. This study suggests that the seroprevalence of T. gondii infection in psychiatric patients was higher and that age was an influencing factor of T. gondii infection in psychiatric patients. T. gondii infection was associated with mania, schizophrenia, depression, recurrent depressive disorder and bipolar disorder.
Whole structural reconstruction and quantification of epidermal innervation through the suction blister method and skin-clearing technique
Authors: Kim Dai Hyun , Lee Se Jeong , Kim June Hoan , Park Sung Jin , Seo Soo Hong , Ahn Hyo Hyun , Sun Woong , Kim Byung-Jo , Rhyu Im Joo 
Published: September 2022

AbstractThree-dimensional (3-D) analysis of intraepidermal nerve fibers (IENFs) is conducted to advance assessment methods for peripheral neuropathies and pruritic skin disorders. The skin-clearing technique was proven to be a reliable method for 3-D imaging of IENFs. Nonetheless, it still requires further improvement in the imaging process. The aim of this study was to standardize the 3-D evaluation method of IENFs and to suggest promising 3-D biomarkers for clinical application. A total of nine healthy individuals were prospectively enrolled. The newly adopted suction blister method was combined with the tissue-clearing technique. The detailed structure of the IENFs was reconstructed and quantified using the neuron tracing software. The suction blister method showed improved linear integrity of IENFs compared with those obtained from the previously used salt-split skin test. The 3-D parameters most significantly related to natural aging were the convex hull two-dimensional perimeter and the total length (both p = 0.020). The meaningful correlations were followed by total volume (p = 0.025), ends (p = 0.026), convex hull 3-D surface, and complexity (both p = 0.030). Thus, the 3-D parameters could be utilized as possible biomarkers to identify ambiguous pathologies of peripheral neuropathies and pruritic skin disorders.
Assessing mammal trapping standards in wild boar drop-net capture
Authors: Conejero Carles , López-Olvera Jorge Ramón , González-Crespo Carlos , Ráez-Bravo Arián , Castillo-Contreras Raquel , Tampach Stefania , Velarde Roser , Mentaberre Gregorio 
Published: September 2022

AbstractApplying contemporary trapping standards when managing wildlife should no longer be an option, but a duty. Increasing wild boar populations originate a growing number of conflicts and hunting is the only cost-effective management option in most cases. However, new scenarios where hunting is unfeasible emerge and trapping necessities cope with lacking regulatory frameworks and technical guidelines. In this research, we evaluated drop nets, a capture method not considered by the international trapping standards, to capture Eurasian wild boar (Sus scrofa), a wildlife species not included in the list of mammal species under the scope of the Agreement on International Humane Trapping Standards (AIHTS). Less than 20% of the captured wild boars presented moderate or severe injuries attributable to the capture method, hence fulfilling the acceptance thresholds of the outdated AIHTS. Based on the new standards thresholds of acceptance, the humaneness of drop-nets in our study ranged 66–78%, under the 85% required. The capture success and selectivity were 100%, as ensured by operator-driven triggering, which should be considered the main strengths of this method, together with the minimization of animal suffering owing the short duration of the stressful situation. Additionally, in spite of the socially adverse environment, with people contrary to wild boar removal, no disturbances against the capture system or operations occurred. This is the first assessment of a drop-net capture method according to internationally accepted mammal trapping standards, with unconclusive results. However, there is a need for adapted procedures and thresholds of acceptance aimed at not-mechanical traps in general, and specifically at drop-nets. Compared to other live-capture methods, drop-nets minimize the duration of the stressful situation —at the expense of a strong adrenergic acute response—, maximize the probabilities of capturing entire sounders of prosocial species, which may be also considered as more humane, and has the ability to coordinate higher values of capture success, absolute selectivity and adaptability to difficult environments.
Oleanolic acid stimulation of cell migration involves a biphasic signaling mechanism
Authors: Stelling-Férez Javier , Gabaldón José Antonio , Nicolás Francisco José 
Published: September 2022

AbstractCell migration is a critical process for wound healing, a physiological phenomenon needed for proper skin restoration after injury. Wound healing can be compromised under pathological conditions. Natural bioactive terpenoids have shown promising therapeutic properties in wound healing. Oleanolic acid (OA), a triterpenoid, enhances in vitro and in vivo cell migration. However, the underlying signaling mechanisms and pathways triggered by OA are poorly understood. We have previously shown that OA activates epidermal growth factor receptor (EGFR) and downstream effectors such as mitogen-activated protein (MAP) kinase cascade and c-Jun N-terminal kinase (JNK), leading to c-Jun transcription factor phosphorylation, all of which are involved in migration. We performed protein expression or migration front protein subcellular localization assays, which showed that OA induces c-Jun activation and its nuclear translocation, which precisely overlaps at wound-edge cells. Furthermore, c-Jun phosphorylation was independent of EGFR activation. Additionally, OA promoted actin cytoskeleton and focal adhesion (FA) dynamization. In fact, OA induced the recruitment of regulator proteins to FAs to dynamize these structures during migration. Moreover, OA changed paxillin distribution and activated focal adhesion kinase (FAK) at focal adhesions (FAs). The molecular implications of these observations are discussed.
Sleep targets highly connected global and local nodes to aid consolidation of learned graph networks
Authors: Feld G. B. , Bernard M. , Rawson A. B. , Spiers H. J. 
Published: September 2022

AbstractMuch of our long-term knowledge is organised in complex networks. Sleep is thought to be critical for abstracting knowledge and enhancing important item memory for long-term retention. Thus, sleep should aid the development of memory for networks and the abstraction of their structure for efficient storage. However, this remains unknown because past sleep studies have focused on discrete items. Here we explored the impact of sleep (night-sleep/day-wake within-subject paradigm with 25 male participants) on memory for graph-networks where some items were important due to dense local connections (degree centrality) or, independently, important due to greater global connections (closeness/betweenness centrality). A network of 27 planets (nodes) sparsely interconnected by 36 teleporters (edges) was learned via discrete associations without explicit indication of any network structure. Despite equivalent exposure to all connections in the network, we found that memory for the links between items with high local connectivity or high global connectivity were better retained after sleep. These results highlight that sleep has the capacity for strengthening both global and local structure from the world and abstracting over multiple experiences to efficiently form internal networks of knowledge.
Reduced variability of bursting activity during working memory
Authors: Lundqvist Mikael , Rose Jonas , Brincat Scott L. , Warden Melissa R. , Buschman Timothy J. , Herman Pawel , Miller Earl K. 
Published: September 2022

AbstractWorking memories have long been thought to be maintained by persistent spiking. However, mounting evidence from multiple-electrode recording (and single-trial analyses) shows that the underlying spiking is better characterized by intermittent bursts of activity. A counterargument suggested this intermittent activity is at odds with observations that spike-time variability reduces during task performance. However, this counterargument rests on assumptions, such as randomness in the timing of the bursts, which may not be correct. Thus, we analyzed spiking and LFPs from monkeys’ prefrontal cortex (PFC) to determine if task-related reductions in variability can co-exist with intermittent spiking. We found that it does because both spiking and associated gamma bursts were task-modulated, not random. In fact, the task-related reduction in spike variability could largely be explained by a related reduction in gamma burst variability. Our results provide further support for the intermittent activity models of working memory as well as novel mechanistic insights into how spike variability is reduced during cognitive tasks.
Roadmap for achieving net-zero emissions in global food systems by 2050
Authors: Costa Ciniro , Wollenberg Eva , Benitez Mauricio , Newman Richard , Gardner Nick , Bellone Federico 
Published: September 2022

AbstractFood systems (FSs) emit ~ 20 GtCO2e/y (~ 35% of global greenhouse gas emissions). This level tends to raise given the expected increases in food demands, which may threaten global climate targets. Through a rapid assessment, evaluating 60+ scenarios based on existing low-emission and carbon sequestration practices, we estimate that intensifying FSs could reduce its emissions from 21.4 to − 2.0 GtCO2e/y and address increasing food demands without relying on carbon offsets (e.g., related to afforestation and reforestation programs). However, given historical trends and regional contexts, a more diverse portfolio of practices, including diet shifts and new-horizon technologies, will be needed to increase the feasibility of achieving net-zero FSs. One likely pathway consists of implementing practices that shift food production to the 30th-percentile of least emission-intensive FSs (~ 45% emissions reduction), sequester carbon at 50% of its potential (~ 5 GtCO2e/y) and adopt diet shifts and new-horizon technologies (~ 6 GtCO2e/y). For a successful transition to happen, the global FSs would, in the next decade (2020s), need to implement cost-effective mitigation practices and technologies, supported by improvements in countries’ governance and technical assistance, innovative financial mechanisms and research focused on making affordable technologies in the following two decades (2030–2050). This work provides options and a vision to guide global FSs to achieving net-zero by 2050.
The effect of COVID-19 on employees' mental health
Authors: Rodoplu Şahin Didem , Aslan Mustafa , Demirkaya Harun , Ateşoğlu Hülya 
Published: September 2022

AbstractLong lockdowns, food shortages, and the inability to receive basic primary healthcare have aggravated the effects of pandemics. However, most studies have focused on the health problems of the infected people or the measures employed to keep the disease under control. This cross-sectional study focused primarily on the mental health issues of employees. By employing a convenient sampling method, we reached 237 respondents (135 with coronavirus history) to assess the impact of the pandemic on employees. Multivariate causal relationships were assessed with Structural Equation Modeling (SEM). The predictors included internal entrapment (INT) and difficulty identifying feelings (DIF), which are significant predictors of depression (DEPR). DIF was found to be a significant predictor of INT and EXT feelings, while FEAR was found to be a significant predictor of INT, DIF, and DEPR. Quality of life (QoL) was found to be a significant predictor of DIF and DDF, DEPR, EXT and INT, and FEAR. The results also showed that DIF mainly manifested its effect on depression through INT. The DEPR level of employees working only from home was higher than that of other employees. The depression levels of women, young employees, and those whose QoL was adversely affected by the coronavirus were higher than the rest.