bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic epidemiology of Escherichia coli: antimicrobial resistance through a One Health lens in sympatric humans, livestock and peri-domestic wildlife in Nairobi, Kenya
Authors: Muloi Dishon M. , Hassell James M. , Wee Bryan A. , Ward Melissa J. , Bettridge Judy M. , Kivali Velma , Kiyong’a Alice , Ndinda Christine , Gitahi Nduhiu , Ouko Tom , Imboma Titus , Akoko James , Murungi Maurice K. , Njoroge Samuel M. , Muinde Patrick , Alumasa Lorren , Kaitho Titus , Amanya Fredrick , Ogendo Allan , van Bunnik Bram A. D. , Kiiru John , Robinson Timothy P. , Kang’ethe Erastus K. , Kariuki Samuel , Pedersen Amy B. , Fèvre Eric M. , Woolhouse Mark E. J. 
Published: December 2022

Abstract

Background
Livestock systems have been proposed as a reservoir for antimicrobial-resistant (AMR) bacteria and AMR genetic determinants that may infect or colonise humans, yet quantitative evidence regarding their epidemiological role remains lacking. Here, we used a combination of genomics, epidemiology and ecology to investigate patterns of AMR gene carriage in Escherichia coli, regarded as a sentinel organism.

Methods
We conducted a structured epidemiological survey of 99 households across Nairobi, Kenya, and whole genome sequenced E. coli isolates from 311 human, 606 livestock and 399 wildlife faecal samples. We used statistical models to investigate the prevalence of AMR carriage and characterise AMR gene diversity and structure of AMR genes in different host populations across the city. We also investigated household-level risk factors for the exchange of AMR genes between sympatric humans and livestock.

Results
We detected 56 unique acquired genes along with 13 point mutations present in variable proportions in human and animal isolates, known to confer resistance to nine antibiotic classes. We find that AMR gene community composition is not associated with host species, but AMR genes were frequently co-located, potentially enabling the acquisition and dispersal of multi-drug resistance in a single step. We find that whilst keeping livestock had no influence on human AMR gene carriage, the potential for AMR transmission across human-livestock interfaces is greatest when manure is poorly disposed of and in larger households.

Conclusions
Findings of widespread carriage of AMR bacteria in human and animal populations, including in long-distance wildlife species, in community settings highlight the value of evidence-based surveillance to address antimicrobial resistance on a global scale. Our genomic analysis provided an in-depth understanding of AMR determinants at the interfaces of One Health sectors that will inform AMR prevention and control.
Links between electroconvulsive therapy responsive and cognitive impairment multimodal brain networks in late-life major depressive disorder
Authors: Qi Shile , Calhoun Vince D. , Zhang Daoqiang , Miller Jeremy , Deng Zhi-De , Narr Katherine L. , Sheline Yvette , McClintock Shawn M. , Jiang Rongtao , Yang Xiao , Upston Joel , Jones Tom , Sui Jing , Abbott Christopher C. 
Published: December 2022

Abstract
Background
Although electroconvulsive therapy (ECT) is an effective treatment for depression, ECT cognitive impairment remains a major concern. The neurobiological underpinnings and mechanisms underlying ECT antidepressant and cognitive impairment effects remain unknown. This investigation aims to identify ECT antidepressant-response and cognitive-impairment multimodal brain networks and assesses whether they are associated with the ECT-induced electric field (E-field) with an optimal pulse amplitude estimation.

Methods
A single site clinical trial focused on amplitude (600, 700, and 800 mA) included longitudinal multimodal imaging and clinical and cognitive assessments completed before and immediately after the ECT series (n = 54) for late-life depression. Another two independent validation cohorts (n = 84, n = 260) were included. Symptom and cognition were used as references to supervise fMRI and sMRI fusion to identify ECT antidepressant-response and cognitive-impairment multimodal brain networks. Correlations between ECT-induced E-field within these two networks and clinical and cognitive outcomes were calculated. An optimal pulse amplitude was estimated based on E-field within antidepressant-response and cognitive-impairment networks.

Results
Decreased function in the superior orbitofrontal cortex and caudate accompanied with increased volume in medial temporal cortex showed covarying functional and structural alterations in both antidepressant-response and cognitive-impairment networks. Volume increases in the hippocampal complex and thalamus were antidepressant-response specific, and functional decreases in the amygdala and hippocampal complex were cognitive-impairment specific, which were validated in two independent datasets. The E-field within these two networks showed an inverse relationship with HDRS reduction and cognitive impairment. The optimal E-filed range as [92.7–113.9] V/m was estimated to maximize antidepressant outcomes without compromising cognitive safety.

Conclusions
The large degree of overlap between antidepressant-response and cognitive-impairment networks challenges parameter development focused on precise E-field dosing with new electrode placements. The determination of the optimal individualized ECT amplitude within the antidepressant and cognitive networks may improve the treatment benefit–risk ratio.

Trial registration
ClinicalTrials.gov Identifier: NCT02999269.
Advanced one-pot deconstruction and valorization of lignocellulosic biomass into triacetic acid lactone using Rhodosporidium toruloides
Authors: Otoupal Peter B. , Geiselman Gina M. , Oka Asun M. , Barcelos Carolina A. , Choudhary Hemant , Dinh Duy , Zhong Wenqing , Hwang HeeJin , Keasling Jay D. , Mukhopadhyay Aindrila , Sundstrom Eric , Haushalter Robert W. , Sun Ning , Simmons Blake A. , Gladden John M. 
Published: December 2022

Abstract
Background
Rhodosporidium toruloides is capable of co-utilization of complex carbon sources and robust growth from lignocellulosic hydrolysates. This oleaginous yeast is therefore an attractive host for heterologous production of valuable bioproducts at high titers from low-cost, deconstructed biomass in an economically and environmentally sustainable manner. Here we demonstrate this by engineering R. toruloides to produce the polyketide triacetic acid lactone (TAL) directly from unfiltered hydrolysate deconstructed from biomass with minimal unit process operations.

Results
Introduction of the 2-pyrone synthase gene into R. toruloides enabled the organism to produce 2.4 g/L TAL from simple media or 2.0 g/L from hydrolysate produced from sorghum biomass. Both of these titers are on par with titers from other better-studied microbial hosts after they had been heavily engineered. We next demonstrate that filtered hydrolysates produced from ensiled sorghum are superior to those derived from dried sorghum for TAL production, likely due to the substantial organic acids produced during ensiling. We also demonstrate that the organic acids found in ensiled biomass can be used for direct synthesis of ionic liquids within the biomass pretreatment process, enabling consolidation of unit operations of in-situ ionic liquid synthesis, pretreatment, saccharification, and fermentation into a one-pot, separations-free process. Finally, we demonstrate this consolidation in a 2 L bioreactor using unfiltered hydrolysate, producing 3.9 g/L TAL.

Conclusion
Many steps involved in deconstructing biomass into fermentable substrate can be combined into a distinct operation, and directly fed to cultures of engineered R. toruloides cultures for subsequent valorization into gram per liter titers of TAL in a cost-effective manner.
CT-based radiogenomic analysis dissects intratumor heterogeneity and predicts prognosis of colorectal cancer: a multi-institutional retrospective study
Authors: Zhong Min-Er , Duan Xin , Ni-jia-ti Ma-yi-di-li , Qi Haoning , Xu Dongwei , Cai Du , Li Chenghang , Huang Zeping , Zhu Qiqi , Gao Feng , Wu Xiaojian 
Published: December 2022

AbstractBackgroundThis study aimed to develop a radiogenomic prognostic prediction model for colorectal cancer (CRC) by investigating the biological and clinical relevance of intratumoural heterogeneity.MethodsThis retrospective multi-cohort study was conducted in three steps. First, we identified genomic subclones using unsupervised deconvolution analysis. Second, we established radiogenomic signatures to link radiomic features with prognostic subclone compositions in an independent radiogenomic dataset containing matched imaging and gene expression data. Finally, the prognostic value of the identified radiogenomic signatures was validated using two testing datasets containing imaging and survival information collected from separate medical centres.ResultsThis multi-institutional retrospective study included 1601 patients (714 females and 887 males; mean age, 65 years ± 14 [standard deviation]) with CRC from 5 datasets. Molecular heterogeneity was identified using unsupervised deconvolution analysis of gene expression data. The relative prevalence of the two subclones associated with cell cycle and extracellular matrix pathways identified patients with significantly different survival outcomes. A radiogenomic signature-based predictive model significantly stratified patients into high- and low-risk groups with disparate disease-free survival (HR = 1.74, P = 0.003). Radiogenomic signatures were revealed as an independent predictive factor for CRC by multivariable analysis (HR = 1.59, 95% CI:1.03–2.45, P = 0.034). Functional analysis demonstrated that the 11 radiogenomic signatures were predominantly associated with extracellular matrix and immune-related pathways.ConclusionsThe identified radiogenomic signatures might be a surrogate for genomic signatures and could complement the current prognostic strategies.
MyD88-TLR4-dependent choroid plexus activation precedes perilesional inflammation and secondary brain edema in a mouse model of intracerebral hemorrhage
Authors: Akeret Kevin , Buzzi Raphael M. , Thomson Bart R. , Schwendinger Nina , Klohs Jan , Schulthess-Lutz Nadja , Baselgia Livio , Hansen Kerstin , Regli Luca , Vallelian Florence , Hugelshofer Michael , Schaer Dominik J. 
Published: December 2022

Abstract
Background
The functional neurological outcome of patients with intracerebral hemorrhage (ICH) strongly relates to the degree of secondary brain injury (ICH-SBI) evolving within days after the initial bleeding. Different mechanisms including the incitement of inflammatory pathways, dysfunction of the blood–brain barrier (BBB), activation of resident microglia, and an influx of blood-borne immune cells, have been hypothesized to contribute to ICH-SBI. Yet, the spatiotemporal interplay of specific inflammatory processes within different brain compartments has not been sufficiently characterized, limiting potential therapeutic interventions to prevent and treat ICH-SBI.

Methods
We used a whole-blood injection model in mice, to systematically characterized the spatial and temporal dynamics of inflammatory processes after ICH using 7-Tesla magnetic resonance imaging (MRI), spatial RNA sequencing (spRNAseq), functional BBB assessment, and immunofluorescence average-intensity-mapping.

Results
We identified a pronounced early response of the choroid plexus (CP) peaking at 12–24 h that was characterized by inflammatory cytokine expression, epithelial and endothelial expression of leukocyte adhesion molecules, and the accumulation of leukocytes. In contrast, we observed a delayed secondary reaction pattern at the injection site (striatum) peaking at 96 h, defined by gene expression corresponding to perilesional leukocyte infiltration and correlating to the delayed signal alteration seen on MRI. Pathway analysis revealed a dependence of the early inflammatory reaction in the CP on toll-like receptor 4 (TLR4) signaling via myeloid differentiation factor 88 (MyD88). TLR4 and MyD88 knockout mice corroborated this observation, lacking the early upregulation of adhesion molecules and leukocyte infiltration within the CP 24 h after whole-blood injection.

Conclusions
We report a biphasic brain reaction pattern after ICH with a MyD88-TLR4-dependent early inflammatory response of the CP, preceding inflammation, edema and leukocyte infiltration at the lesion site. Pharmacological targeting of the early CP activation might harbor the potential to modulate the development of ICH-SBI.
Profiling genome-wide recombination in Epstein Barr virus reveals type-specific patterns and associations with endemic-Burkitt lymphoma
Authors: Agwati Eddy O. , Oduor Cliff I. , Ayieko Cyrus , Ong’echa John Michael , Moormann Ann M. , Bailey Jeffrey A. 
Published: December 2022

Abstract
Background
Endemic Burkitt lymphoma (eBL) is potentiated through the interplay of Epstein Barr virus (EBV) and holoendemic Plasmodium falciparum malaria. To better understand EBV’s biology and role in eBL, we characterized genome-wide recombination sites and patterns as a source of genetic diversity in EBV genomes in our well-defined population of eBL cases and controls from Western Kenya.

Methods
EBV genomes representing 54 eBL cases and 32 healthy children from the same geographic region in Western Kenya that we previously sequenced were analyzed. Whole-genome multiple sequence alignment, recombination analyses, and phylogenetic inference were made using multiple alignment with fast Fourier transform, recombination detection program 4, and molecular evolutionary genetics analysis.

Results
We identified 28 different recombination events and 71 (82.6%) of the 86 EBV genomes analyzed contained evidence of one or more recombinant segments. Associated recombination breakpoints were found to occur in a total of 42 different genes, with only 7 (16.67%) being latent genes. Recombination events were major drivers of clustering within genome-wide phylogenetic trees. The occurrence of recombination segments was comparable between genomes from male and female participants and across age groups. More recombinant segments were found in EBV type 1 genomes (p = 6.4e − 06) and the genomes from the eBLs (p = 0.037). Two recombination events were enriched in the eBLs; event 47 (OR = 4.07, p = 0.038) and event 50 (OR = 14.24, p = 0.012).

Conclusions
EBV genomes have extensive evidence of recombination likely acquired progressively and cumulatively over time. Recombination patterns display a heterogeneous occurrence rate across the genome with enrichment in lytic genes. Overall, recombination appears to be a major evolutionary force impacting EBV diversity and genome structure with evidence of the association of specific recombinants with eBL.
Anterosuperior approach versus deltopectoral approach for reverse total shoulder arthroplasty: a systematic review and meta-analysis
Authors: Seok Hyun-Gyu , Park Jeong Jin , Park Sam-Guk 
Published: December 2022

Abstract
Background
Surgical approach is an important factor that may affect the outcomes of reverse total shoulder arthroplasty (RTSA). The most common approaches for RTSA are anterosuperior (AS) and deltopectoral (DP). However, controversy exists on which surgical approach is better. This meta-analysis aimed to compare both approaches in terms of radiological and clinical outcomes and complications.

Methods
We searched PubMed, Embase, and Cochrane Library databases for studies that compared the postoperative outcomes of the AS and DP approaches for RTSA. After screening and quality assessment of the articles, we obtained two randomized controlled trials and four retrospective comparative studies. We analyzed the radiologic outcomes, functional outcomes, and complications between the two approaches. The standardized mean difference and odds ratio were used to analyze the differences in outcomes between the two surgical approaches. Statistical significance was set at P < 0.05.

Results
The incidence rate of glenoid implant loosening was significantly (P = 0.04) lower in the AS group than that in the DP group. In terms of forward flexion after surgery, the DP approach produced significantly (P = 0.03) better outcomes compared with the AS approach. There were no significant differences in radiological outcomes or other complication rates between the two approaches.

Conclusion
As a result of this meta-analysis, one of the two approaches did not bring a better result than the other. One has strength for better forward flexion and the other for a lower glenoid loosening rate. With this in mind, it is recommended to use the approach that the surgeon is most familiar with.
Desferrioxamine alleviates UHMWPE particle-induced osteoclastic osteolysis by inhibiting caspase-1-dependent pyroptosis in osteocytes
Authors: Zhao Shenli , Ge Chen , Li Yao , Chang Leilei , Dan Zhou , Tu Yihui , Deng Lianfu , Kang Hui , Li Changwei 
Published: December 2022

Abstract
Background
Cell death and inflammation are the two important triggers of wear particle-induced osteolysis. Particles, including cobalt-chromium-molybdenum and tricalcium phosphate, have been reported to induce pyroptosis in macrophages and osteocytes. Although macrophage pyroptosis facilitates osteoclastic bone resorption and osteolysis, whether osteocyte pyroptosis is involved in osteoclastic osteolysis still needs further investigation. Desferrioxamine (DFO), an FDA-approved medication and a powerful iron chelator, has been proven to reduce ultrahigh-molecular-weight polyethylene (UHMWPE) particle-induced osteolysis. However, whether DFO can ameliorate UHMWPE particle-induced osteolysis by decreasing pyroptosis in osteocytes is unknown.

Results
A mouse calvarial osteolysis model and the mouse osteocyte cell line MLO-Y4 was used, and we found that pyroptosis in osteocytes was significantly induced by UHMWPE particles. Furthermore, our findings uncovered a role of caspase-1-dependent pyroptosis in osteocytes in facilitating osteoclastic osteolysis induced by UHMWPE particles. In addition, we found that DFO could alleviate UHMWPE particle-induced pyroptosis in osteocytes in vivo and in vitro.

Conclusions
We uncovered a role of caspase-1-dependent pyroptosis in osteocytes in facilitating osteoclastic osteolysis induced by UHMWPE particles. Furthermore, we found that DFO alleviated UHMWPE particle-induced osteoclastic osteolysis partly by inhibiting pyroptosis in osteocytes.

Graphical Abstract
Schematic of DFO reducing UHMWPE particle-induced osteolysis by inhibiting osteocytic pyroptosis. Wear particles, such as polymers, generated from prosthetic implant materials activate canonical inflammasomes and promote the cleavage and activation of caspase-1. This is followed by caspase-1-dependent IL-β maturation and GSDMD cleavage. The N-terminal fragment of GSDMD binds to phospholipids on the cell membrane and forms holes in the membrane, resulting in the release of mature IL-β and inflammatory intracellular contents. This further facilitates osteoclastic differentiation of BMMs, resulting in excessive bone resorption and ultimately leading to prosthetic osteolysis. DFO reduces UHMWPE particle-induced osteolysis by inhibiting osteocytic pyroptosis.
The A-to-I editing of KPC1 promotes intrahepatic cholangiocarcinoma by attenuating proteasomal processing of NF-κB1 p105 to p50
Authors: Gao Chengming , Zhou Guangming , Shi Jie , Shi Peipei , Jin Liang , Li Yuanfeng , Wang Xiaowen , Liao Song , Yan Han , Wu Junjie , Lu Yiming , Zhai Yun , Zhang Jinxu , Zhang Haitao , Zhang Hongxing , Yang Chenning , Cao Pengbo , Cheng Shuqun , Zhou Gangqiao 
Published: December 2022

Abstract
Background
Aberrant RNA editing of adenosine-to-inosine (A-to-I) has been linked to multiple human cancers, but its role in intrahepatic cholangiocarcinoma (iCCA) remains unknown. We conducted an exome-wide investigation to search for dysregulated RNA editing that drive iCCA pathogenesis.

Methods
An integrative whole-exome and transcriptome sequencing analysis was performed to elucidate the RNA editing landscape in iCCAs. Putative RNA editing sites were validated by Sanger sequencing. In vitro and in vivo experiments were used to assess the effects of an exemplary target gene Kip1 ubiquitination-promoting complex 1 (KPC1) and its editing on iCCA cells growth and metastasis. Crosstalk between KPC1 RNA editing and NF-κB signaling was analyzed by molecular methods.

Results
Through integrative omics analyses, we revealed an adenosine deaminases acting on RNA 1A (ADAR1)-mediated over-editing pattern in iCCAs. ADAR1 is frequently amplified and overexpressed in iCCAs and plays oncogenic roles. Notably, we identified a novel ADAR1-mediated A-to-I editing of KPC1 transcript, which results in substitution of methionine with valine at residue 8 (p.M8V). KPC1 p.M8V editing confers loss-of-function phenotypes through blunting the tumor-suppressive role of wild-type KPC1. Mechanistically, KPC1 p.M8V weakens the affinity of KPC1 to its substrate NF-κB1 p105, thereby reducing the ubiquitinating and proteasomal processing of p105 to p50, which in turn enhances the activity of oncogenic NF-κB signaling.

Conclusions
Our findings established that amplification-driven ADAR1 overexpression results in overediting of KPC1 p.M8V in iCCAs, leading to progression via activation of the NF-κB signaling pathway, and suggested ADAR1-KPC1-NF-κB axis as a potential therapeutic target for iCCA.
Genetic diversity of Echinococcus granulosus sensu lato from animals and humans in Bosnia and Herzegovina
Authors: Hodžić Adnan , Alić Amer , Spahić Amir , Harl Josef , Beck Relja 
Published: December 2022

Abstract
Background
Cystic echinococcosis (CE) is recognized as one of the most prevalent zoonotic diseases in Bosnia and Herzegovina. However, no systemic investigation of the genetic diversity of Echinococcus granulosus sensu lato circulating among animals and humans in the country has been performed to date.

Methods
In this preliminary study, we analysed one cyst each from 36 sheep, 27 cattle, 27 pigs, 11 wild boars and 16 human patients for amplification and partial sequencing of the adenosine triphosphate 6 (atp6) and cytochrome c oxidase 1 (cox1) genes. The host species, fertility rate and organ cyst location were recorded for each subject involved in the study.

Results
Overall, the atp6 gene was successfully amplified and sequenced from 110 samples, while 96 of the PCRs for cox1 were positive. Three zoonotic genotypes of E. granulosus sensu stricto (G1 and G3) and Echinococcus canadensis (G7) were identified in our isolates based on analyses of the atp6 gene. These genotypes were represented by 11 different genetic variants (haplotypes), six of which were identified for the first time in the present study.

Conclusions
This study demonstrates, for the first time, that CE in Bosnia and Herzegovina is predominantly caused by E. granulosus sensu stricto and E. canadensis clusters, which exhibited a lower genetic diversity compared to isolates from other European countries. Further molecular studies employing other mitochondrial and nuclear genes are required to better understand the transmission cycles of E. granulosus sensu stricto among intermediate and definitive hosts in the country.

Graphical Abstract