bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investment Tribunals as Courts of Appeal? Determining State Responsibility for Substantive Denial of Justice
Authors: Prislan Vid 
Published: October 2023

Abstract
The contribution looks into the circumstances under which states can held be responsible for the content of judgments rendered by their courts pursuant to the denial of justice standard. The standard has received increased attention in the context of investor-state arbitration, where it has become widely used as a measure for determining the propriety of judicial conduct. Although ostensibly claimed to concern solely the propriety of judicial procedure, in the practice of investment tribunals, the standard has no less frequently been applied to measure the substantive adequacy of domestic courts’ judgments. The contribution examines this emerging practice by mapping the jurisprudence and evaluating the nature of arbitral tribunals’ scrutiny. It also sets out certain normative considerations that should guide the tribunals’ assessment of whether or not a particular judicial outcome is an adequate one from the standpoint of international standards of administration of justice. The contribution advances three arguments: first, that judicial decisions, as the final product of the domestic adjudicative process, can properly be the object of scrutiny by arbitral tribunals; second, that the task of arbitral tribunals must be limited to determining whether the particular decision is supported by adequate reasoning, and does not extend to inquiring whether the substantive outcome – i.e. the judicial decision on its merits – is also reasonable as such; and third, that the substantive review performed under the denial of justice standard necessarily requires the application of deferential standards of review.
Expression of taste sentinels, T1R, T2R, and PLCβ2, on the passageway for olfactory signals in zebrafish
Authors: Birdal Günes , D’Gama Percival P , Jurisch-Yaksi Nathalie , Korsching Sigrun I 
Published: October 2023

Abstract
The senses of taste and smell detect overlapping sets of chemical compounds in fish, e.g. amino acids are detected by both senses. However, so far taste and smell organs appeared morphologically to be very distinct, with a specialized olfactory epithelium for detection of odors and taste buds located in the oral cavity and lip for detection of tastants. Here, we report dense clusters of cells expressing T1R and T2R receptors as well as their signal transduction molecule PLCβ2 in nostrils of zebrafish, i.e. on the entrance funnel through which odor molecules must pass to be detected by olfactory sensory neurons. Quantitative evaluation shows the density of these chemosensory cells in the nostrils to be as high or higher than that in the established taste organs oral cavity and lower lip. Hydrodynamic flow is maximal at the nostril rim enabling high throughput chemosensation in this organ. Taken together, our results suggest a sentinel function for these chemosensory cells in the nostril.
Priorities and Progress in Gram-positive Bacterial Infection Research by the Antibacterial Resistance Leadership Group: A Narrative Review
Authors: Doernberg Sarah B , Arias Cesar A , Altman Deena R , Babiker Ahmed , Boucher Helen W , Creech C Buddy , Cosgrove Sara E , Evans Scott R , Fowler Vance G , Fritz Stephanie A , Hamasaki Toshimitsu , Kelly Brendan J , Leal Sixto M , Liu Catherine , Lodise Thomas P , Miller Loren G , Munita Jose M , Murray Barbara E , Pettigrew Melinda M , Ruffin Felicia , Scheetz Marc H , Shopsin Bo , Tran Truc T , Turner Nicholas A , Williams Derek J , Zaharoff Smitha , Holland Thomas L ,   for the Antibacterial Resistance Leadership Group, Patel Robin , King Heather , Kinamon Tori , Dai Weixiao , Geres Holly , Deckard Nancie , Schuler Carl , Bunn Ivra , Sharma Shrabani , Wickward Cathy , Waller Jason , Wilson Holly , Mehigan Maureen , Ghazaryan Varduhi , Raterman Erica , Samuel Tamika , Lee Marina 
Published: October 2023

AbstractThe Antibacterial Resistance Leadership Group (ARLG) has prioritized infections caused by gram-positive bacteria as one of its core areas of emphasis. The ARLG Gram-positive Committee has focused on studies responding to 3 main identified research priorities: (1) investigation of strategies or therapies for infections predominantly caused by gram-positive bacteria, (2) evaluation of the efficacy of novel agents for infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci, and (3) optimization of dosing and duration of antimicrobial agents for gram-positive infections. Herein, we summarize ARLG accomplishments in gram-positive bacterial infection research, including studies aiming to (1) inform optimal vancomycin dosing, (2) determine the role of dalbavancin in MRSA bloodstream infection, (3) characterize enterococcal bloodstream infections, (4) demonstrate the benefits of short-course therapy for pediatric community-acquired pneumonia, (5) develop quality of life measures for use in clinical trials, and (6) advance understanding of the microbiome. Future studies will incorporate innovative methodologies with a focus on interventional clinical trials that have the potential to change clinical practice for difficult-to-treat infections, such as MRSA bloodstream infections.
Prdm16 mutation determines sex-specific cardiac metabolism and identifies two novel cardiac metabolic regulators
Authors: Kühnisch Jirko , Theisen Simon , Dartsch Josephine , Fritsche-Guenther Raphaela , Kirchner Marieluise , Obermayer Benedikt , Bauer Anna , Kahlert Anne-Karin , Rothe Michael , Beule Dieter , Heuser Arnd , Mertins Philipp , Kirwan Jennifer A , Berndt Nikolaus , MacRae Calum A , Hubner Norbert , Klaassen Sabine 
Published: October 2023

Abstract

Aims
Mutation of the PRDM16 gene causes human dilated and non-compaction cardiomyopathy. The PRDM16 protein is a transcriptional regulator that affects cardiac development via Tbx5 and Hand1, thus regulating myocardial structure. The biallelic inactivation of Prdm16 induces severe cardiac dysfunction with post-natal lethality and hypertrophy in mice. The early pathological events that occur upon Prdm16 inactivation have not been explored.

Methods and results
This study performed in-depth pathophysiological and molecular analyses of male and female Prdm16csp1/wt mice that carry systemic, monoallelic Prdm16 gene inactivation. We systematically assessed early molecular changes through transcriptomics, proteomics, and metabolomics. Kinetic modelling of cardiac metabolism was performed in silico with CARDIOKIN. Prdm16csp1/wt mice are viable up to 8 months, develop hypoplastic hearts, and diminished systolic performance that is more pronounced in female mice. Prdm16csp1/wt cardiac tissue of both sexes showed reductions in metabolites associated with amino acid as well as glycerol metabolism, glycolysis, and the tricarboxylic acid cycle. Prdm16csp1/wt cardiac tissue revealed diminished glutathione (GSH) and increased inosine monophosphate (IMP) levels indicating oxidative stress and a dysregulated energetics, respectively. An accumulation of triacylglycerides exclusively in male Prdm16csp1/wt hearts suggests a sex-specific metabolic adaptation. Metabolic modelling using CARDIOKIN identified a reduction in fatty acid utilization in males as well as lower glucose utilization in female Prdm16csp1/wt cardiac tissue. On the level of transcripts and protein expression, Prdm16csp1/wt hearts demonstrate an up-regulation of pyridine nucleotide-disulphide oxidoreductase domain 2 (Pyroxd2) and the transcriptional regulator pre-B-cell leukaemia transcription factor interacting protein 1 (Pbxip1). The strongest concordant transcriptional up-regulation was detected for Prdm16 itself, probably through an autoregulatory mechanism.

Conclusions
Monoallelic, global Prdm16 mutation diminishes cardiac performance in Prdm16csp1/wt mice. Metabolic alterations and transcriptional dysregulation in Prdm16csp1/wt affect cardiac tissue. Female Prdm16csp1/wt mice develop a more pronounced phenotype, indicating sexual dimorphism at this early pathological window. This study suggests that metabolic dysregulation is an early event in the PRDM16 associated cardiac pathology.
Host–pathogen coevolution promotes the evolution of general, broad-spectrum resistance and reduces foreign pathogen spillover risk
Authors: Hulse Samuel V , Antonovics Janis , Hood Michael E , Bruns Emily L 
Published: October 2023

Abstract
Genetic variation for disease resistance within host populations can strongly impact the spread of endemic pathogens. In plants, recent work has shown that within-population variation in resistance can also affect the transmission of foreign spillover pathogens if that resistance is general. However, most hosts also possess specific resistance mechanisms that provide strong defenses against coevolved endemic pathogens. Here we use a modeling approach to ask how antagonistic coevolution between hosts and their endemic pathogen at the specific resistance locus can affect the frequency of general resistance, and therefore a host’s vulnerability to foreign pathogens. We develop a two-locus model with variable recombination that incorporates both general resistance (effective against all pathogens) and specific resistance (effective against endemic pathogens only). With coevolution, when pathogens can evolve to evade specific resistance, we find that the regions where general resistance can evolve are greatly expanded, decreasing the risk of foreign pathogen invasion. Furthermore, coevolution greatly expands the conditions that maintain polymorphisms at both resistance loci, thereby driving greater genetic diversity within host populations. This genetic diversity often leads to positive correlations between host resistance to foreign and endemic pathogens, similar to those observed in natural populations. However, if resistance loci become linked, the resistance correlations can shift to negative. If we include a third linkage-modifying locus in our model, we find that selection often favors complete linkage. Our model demonstrates how coevolutionary dynamics with an endemic pathogen can mold the resistance structure of host populations in ways that affect its susceptibility to foreign pathogen spillovers, and that the nature of these outcomes depends on resistance costs, as well as the degree of linkage between resistance genes.
Activity of novel β-lactam/β-lactamase inhibitor combinations against serine carbapenemase-producing carbapenem-resistant Pseudomonas aeruginosa
Authors: Lee Su Young , Gill Christian M , Nicolau David P ,   ERACE-PA Global Study Group, Aktas Elif , Alfouzan Wadha , Bourassa Lori , Brink Adrian , Burnham Carey-Ann D , Canton Rafael , Carmeli Yehuda , Falcone Marco , Kiffer Carlos , Marchese Anna , Martinez Octavio , Pournaras Spyros , Satlin Michael , Seifert Harald , Thabit Abrar K , Thomson Kenneth S , Villegas Maria Virginia , Wille Julia , Rezende Thais Teles Freitas , Cekin Zuhal , Malkocoglu Gulsah , Gijón Desirae , Tarakmeh Layla Abdullah , Chu Chun Yat , Opperman Christoffel Johannes , Tootla Hafsah Deepa , Moodley Clinton , Coetzee Jennifer , Vourli Sophia , Dimopoulos George , Attallah Dalya M , Tiseo Giusy , Leonildi Alessandro , Giordano Cesira , Barnini Simona , Menichetti Francesco , Di Pilato Vincenzo , Codda Giulia , Vena Antonio , Giacobbe Daniele Roberto , Westblade Lars , Cardona Armando , Curtis Lauren , Fang Ferric , Thomson Gina 
Published: October 2023

Abstract

Background
Antimicrobial resistance in Pseudomonas aeruginosa is complex and multifaceted. While the novel β-lactamase inhibitors (BLIs) avibactam, relebactam and vaborbactam inhibit serine-based β-lactamases, the comparative potency of the novel β-lactam (BL)/BLI combinations against serine carbapenemase-producing P. aeruginosa is unknown.

Objectives
To compare the in vitro activity of ceftazidime/avibactam, ceftazidime, imipenem/relebactam, imipenem, meropenem/vaborbactam and meropenem against serine β-lactamase-producing P. aeruginosa.

Methods
Carbapenem-resistant P. aeruginosa were collated through the Enhancing Rational Antimicrobials against Carbapenem-resistant P. aeruginosa (ERACE-PA) Global Surveillance. Isolates positive for serine-based carbapenemases were assessed. MICs were determined by broth microdilution to each novel BL/BLI and BL alone.

Results
GES was the most common carbapenemase identified (n = 59) followed by KPC (n = 8). Ceftazidime/avibactam had MIC50/MIC90 values of 4/8 mg/L and 91% of isolates were susceptible. Conversely, ceftazidime alone was active against only 3% of isolates. The MIC50/MIC90 of imipenem/relebactam were 16/&gt;16 mg/L and 13% of all isolates were defined as susceptible. Of the KPC-producing isolates, 38% were susceptible to imipenem/relebactam, compared with 0% to imipenem. The meropenem/vaborbactam MIC50/MIC90 were &gt;16/&gt;16 mg/L, and 6% of isolates were susceptible, which was similar to meropenem alone (MIC50/90, &gt;8/&gt;8 mg/L; 3% susceptible) suggesting the addition of vaborbactam cannot overcome co-expressed, non-enzymatic resistance mechanisms.

Conclusions
Among the novel BL/BLIs, ceftazidime/avibactam displayed better in vitro activity and thus is a rational treatment option for serine carbapenemase-harbouring P. aeruginosa. While imipenem/relebactam displayed some activity, particularly against isolates with blaKPC, meropenem/vaborbactam exhibited poor activity, with MICs similar to meropenem alone.
Ownership networks and labor income
Authors: Huneeus Federico , Larrain Borja , Larrain Mauricio , Prem Mounu 
Published: October 2023

Abstract
We document a novel relationship between networks of firms linked through ownership (i.e., business groups) and labor income using matched employer–employee data for Chile. Business group affiliation is associated with higher wages, even after controlling for firm size and individual worker effects. The group premium is stronger for top workers; hence, group firms have higher wage dispersion. The premium remains present when comparing group firms and matched stand-alone firms, and in within-firm comparisons using transitions in and out of groups. Our results are consistent with workers reaching higher productivity and wages by leveraging their skills on the group’s organizational structure (JEL G32, J31).
The emerging roles of nitric oxide and its associated scavengers—phytoglobins—in plant symbiotic interactions
Authors: Pathak Pradeep Kumar , Yadav Nidhi , Kaladhar Vemula Chandra , Jaiswal Rekha , Kumari Aprajita , Igamberdiev Abir U , Loake Gary J , Gupta Kapuganti Jagadis 
Published: October 2023

Abstract
A key feature in the establishment of symbiosis between plants and microbes is the maintenance of the balance between the production of the small redox-related molecule, nitric oxide (NO), and its cognate scavenging pathways. During the establishment of symbiosis, a transition from a normoxic to a microoxic environment often takes place, triggering the production of NO from nitrite via a reductive production pathway. Plant hemoglobins [phytoglobins (Phytogbs)] are a central tenant of NO scavenging, with NO homeostasis maintained via the Phytogb–NO cycle. While the first plant hemoglobin (leghemoglobin), associated with the symbiotic relationship between leguminous plants and bacterial Rhizobium species, was discovered in 1939, most other plant hemoglobins, identified only in the 1990s, were considered as non-symbiotic. From recent studies, it is becoming evident that the role of Phytogbs1 in the establishment and maintenance of plant–bacterial and plant–fungal symbiosis is also essential in roots. Consequently, the division of plant hemoglobins into symbiotic and non-symbiotic groups becomes less justified. While the main function of Phytogbs1 is related to the regulation of NO levels, participation of these proteins in the establishment of symbiotic relationships between plants and microorganisms represents another important dimension among the other processes in which these key redox-regulatory proteins play a central role.
Identification and quantification of small exon-containing isoforms in long-read RNA sequencing data
Authors: Liu Zhen , Zhu Chenchen , Steinmetz Lars M , Wei Wu 
Published: October 2023

Abstract
Small exons are pervasive in transcriptomes across organisms, and their quantification in RNA isoforms is crucial for understanding gene functions. Although long-read RNA-seq based on Oxford Nanopore Technologies (ONT) offers the advantage of covering transcripts in full length, its lower base accuracy poses challenges for identifying individual exons, particularly microexons (≤ 30 nucleotides). Here, we systematically assess small exons quantification in synthetic and human ONT RNA-seq datasets. We demonstrate that reads containing small exons are often not properly aligned, affecting the quantification of relevant transcripts. Thus, we develop a local-realignment method for misaligned exons (MisER), which remaps reads with misaligned exons to the transcript references. Using synthetic and simulated datasets, we demonstrate the high sensitivity and specificity of MisER for the quantification of transcripts containing small exons. Moreover, MisER enabled us to identify small exons with a higher percent spliced-in index (PSI) in neural, particularly neural-regulated microexons, when comparing 14 neural to 16 non-neural tissues in humans. Our work introduces an improved quantification method for long-read RNA-seq and especially facilitates studies using ONT long-reads to elucidate the regulation of genes involving small exons.
MINRbase: a comprehensive database of nuclear- and mitochondrial-ribosomal-RNA-derived fragments (rRFs)
Authors: Pliatsika Venetia , Cherlin Tess , Loher Phillipe , Vlantis Panagiotis , Nagarkar Parth , Nersisyan Stepan , Rigoutsos Isidore 
Published: October 2023

Abstract
We describe the Mitochondrial and Nuclear rRNA fragment database (MINRbase), a knowledge repository aimed at facilitating the study of ribosomal RNA-derived fragments (rRFs). MINRbase provides interactive access to the profiles of 130 238 expressed rRFs arising from the four human nuclear rRNAs (18S, 5.8S, 28S, 5S), two mitochondrial rRNAs (12S, 16S) or four spacers of 45S pre-rRNA. We compiled these profiles by analyzing 11 632 datasets, including the GEUVADIS and The Cancer Genome Atlas (TCGA) repositories. MINRbase offers a user-friendly interface that lets researchers issue complex queries based on one or more criteria, such as parental rRNA identity, nucleotide sequence, rRF minimum abundance and metadata keywords (e.g. tissue type, disease). A ‘summary’ page for each rRF provides a granular breakdown of its expression by tissue type, disease, sex, ancestry and other variables; it also allows users to create publication-ready plots at the click of a button. MINRbase has already allowed us to generate support for three novel observations: the internal spacers of 45S are prolific producers of abundant rRFs; many abundant rRFs straddle the known boundaries of rRNAs; rRF production is regimented and depends on ‘personal attributes’ (sex, ancestry) and ‘context’ (tissue type, tissue state, disease). MINRbase is available at https://cm.jefferson.edu/MINRbase/.
Ubiquitin signaling and the proteasome drive human DNA–protein crosslink repair
Authors: Essawy Maram , Chesner Lisa , Alshareef Duha , Ji Shaofei , Tretyakova Natalia , Campbell Colin 
Published: October 2023

Abstract
DNA–protein crosslinks (DPCs) are large cytotoxic DNA lesions that form following exposure to chemotherapeutic drugs and environmental chemicals. Nucleotide excision repair (NER) and homologous recombination (HR) promote survival following exposure to DPC-inducing agents. However, it is not known how cells recognize DPC lesions, or what mechanisms selectively target DPC lesions to these respective repair pathways. To address these questions, we examined DPC recognition and repair by transfecting a synthetic DPC lesion comprised of the human oxoguanine glycosylase (OGG1) protein crosslinked to double-stranded M13MP18 into human cells. In wild-type cells, this lesion is efficiently repaired, whereas cells deficient in NER can only repair this lesion if an un-damaged homologous donor is co-transfected. Transfected DPC is subject to rapid K63 polyubiquitination. In NER proficient cells, the DPC is subject to K48 polyubiquitination, and is removed via a proteasome-dependent mechanism. In NER-deficient cells, the DNA–conjugated protein is not subject to K48 polyubiquitination. Instead, the K63 tag remains attached, and is only lost when a homologous donor molecule is present. Taken together, these results support a model in which selective addition of polyubiquitin chains to DNA-crosslinked protein leads to selective recruitment of the proteasome and the cellular NER and recombinational DNA repair machinery.
Anisodine hydrobromide injection in the treatment of acute ischemic stroke: A protocol for systematic review and meta-analysis
Authors: Liu Yunlu , Wang Yang , Wan Feng 
Published: October 2023

Background:
Acute ischemic stroke (AIS) is a common disease of the central nervous system, with high mortality, and disability rates. Anisodine hydrobromide (Ani) injection has been used clinically for the treatment of AIS in China. However, no systematic review and meta-analysis have provided rigorous evidence for the clinical use of Ani injection in the treatment of AIS. This study aims to assess the efficacy and safety of Ani injection in the treatment of AIS.

Methods:
Following databases will be searched to identify eligible articles: CNKI, VIP, Wanfang, Chinese Biomedical Literature Database, EMBASE, PubMed, Cochrane, and Web of Science. All databases will be searched from their inception to May, 2023. RevMan software will be used for data analysis.

Results:
The results from meta-synthesis and descriptive analysis of National Institute of Health Stroke Scale, modified Rankin scale, Barthel Index, CT parameters, clinical efficacy rate, and adverse reactions of included articles will provide latest evidence.

Conclusion:
Findings of this study will provide a solid evidence-based basis for the rational and precise application of Ani injection for the treatment of AIS.