bluuebunny/crossref_metadata_2025_split huggingface dataset:
Site-selective arene C–H functionalization by cooperative metal catalysis
Authors: Nakao Yoshiaki 
Published: March 2024

Abstract
Efforts made over the past 3 decades have led to the development of various organic transformations that directly convert unfunctionalized C–H bonds into functional groups by metal catalysis. However, many of these transformations are restricted to specific reaction sites controlled by directing groups, which bring the metal centers into proximity with the C–H bonds being functionalized. These directing groups are typically tailored for specific C–H functionalization reactions, necessitating additional steps for their installation and removal, thereby limiting overall utility and efficiency. There is a strong desire to achieve site-selectivity control using catalysts with compounds bearing common functional groups. We have investigated catalytic Lewis-pair formations to electronically activate substrates and control the site selectivity of metal-catalyzed arene C–H functionalization. In this account, we present C–C and C–B bond-forming reactions through cooperative transition metal/Lewis acid (LA) catalysis. Common LA catalysts derived from Zn, B, and Al have been demonstrated as highly efficient co-catalysts for Ni- and Ir-catalyzed arene C–H functionalization. Steric repulsion between the LA and Ni or Ir catalysts facilitates para-selective C–H functionalization, while ligands bearing LA moieties effectively control meta-selectivity.
Incremental cost analysis model of distribution network based on economic dispatch of distributed new-energy storage system
Authors: Zhou Zhuan , Bian Jiayu , Yu Zhiyong 
Published: March 2024

Abstract
With the implementation of China’s carbon-peaking and carbon-neutrality strategy, new energy will achieve leapfrog growth. Due to the good economics of distributed new-energy generation, it can not only save users’ own investment, but also help to achieve local consumption of new energy. However, it will also bring about a series of incremental costs to the power grid. This paper first enumerates the concept, development status and scheduling mode of a distributed new-energy storage system. Based on the above, it establishes a new-energy power generation model and an energy storage system charging and discharging model, and proposes a global optimization scheduling model for a distributed new-energy storage system, considering the time-of-use electricity price and taking the lowest total operating cost of the distributed new-energy power generation system as the objective function. Finally, it proposes a distribution network incremental cost analysis model based on the penetration of distributed new energy. The calculation results show that the incremental cost of grid-connected distributed new energy is 1.0849, 1.2585 and 1.3473 yuan/kWh, respectively, which indicates that the global dispatching model can optimize the power consumption structure of a distributed power generation system, and has the function of peak shaving and valley filling, but the incremental cost of the distribution network will also increase.
Plasma homocysteine level, estradiol level, and brain atrophy: a Mendelian randomization study
Authors: Gao Wen , Zhu Wei-Wen , Yu Ya-Huan , Wang Juan 
Published: March 2024

Abstract

Objectives
Observational studies link elevated plasma homocysteine (Hcy) with vascular disease. Our aim was to assess the gender difference in the association between the plasma tHcy level and brain atrophy and identify the possible influencer. We employed Mendelian randomization (MR) to explore the causal relationship between plasma tHcy level, estradiol level, and brain atrophy.

Methods
A total of 687 patients with brain atrophy were included, and gender-specific subgroup analyses in association between tHcy and brain atrophy are conducted. From genome-wide association studies, we selected genetic variants (P &lt; 5 × 10−8) for the plasma tHcy level and estradiol level. We investigated the degree of brain atrophy (including gray matter volume and total brain volume) in the UK biobank (n = 7,916). The inverse variance–weighted and several sensitivity MR regression analyses were carried out.

Results
The plasma tHcy level was significantly associated with brain atrophy for females, but not for males. An MR study showed that there was little evidence of the causal link between elevated plasma tHcy and brain atrophy. On the other hand, we found evidence to support causality for genetically decreased estradiol with higher risk of brain atrophy. Furthermore, genetic predisposition to elevated plasma tHcy was associated with a lower estradiol level.

Conclusions
The influence of estradiol on the association between tHcy and brain atrophy deserves further investigation.
Nuclear Medicine Imaging Tools in Fever of Unknown Origin: Time for a Revisit and Appropriate Use Criteria
Authors: Wright William F , Kandiah Sheetal , Brady Rebecca , Shulkin Barry L , Palestro Christopher J , Jain Sanjay K 
Published: March 2024

Abstract
Fever of unknown origin (FUO) is a clinical conundrum for patients and clinicians alike, and imaging studies are often performed as part of the diagnostic workup of these patients. Recently, the Society of Nuclear Medicine and Molecular Imaging convened and approved a guideline on the use of nuclear medicine tools for FUO. The guidelines support the use of 2-18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in adults and children with FUO. 18F-FDG PET/CT allows detection and localization of foci of hypermetabolic lesions with high sensitivity because of the 18F-FDG uptake in glycolytically active cells that may represent inflammation, infection, or neoplasia. Clinicians should consider and insurers should cover 18F-FDG PET/CT when evaluating patients with FUO, particularly when other clinical clues and preliminary studies are unrevealing.
Evaluating the effect of inequalities in oral anti-coagulant prescribing on outcomes in people with atrial fibrillation
Authors: Mulholland Ryan J , Manca Francesco , Ciminata Giorgio , Quinn Terry J , Trotter Robert , Pollock Kevin G , Lister Steven , Geue Claudia 
Published: March 2024

Abstract

Aims
Whilst anti-coagulation is typically recommended for thromboprophylaxis in atrial fibrillation (AF), it is often never prescribed or prematurely discontinued. The aim of this study was to evaluate the effect of inequalities in anti-coagulant prescribing by assessing stroke/systemic embolism (SSE) and bleeding risk in people with AF who continue anti-coagulation compared with those who stop transiently, permanently, or never start.

Methods and results
This retrospective cohort study utilized linked Scottish healthcare data to identify adults diagnosed with AF between January 2010 and April 2016, with a CHA2DS2-VASC score of ≥2. They were sub-categorized based on anti-coagulant exposure: never started, continuous, discontinuous, and cessation. Inverse probability of treatment weighting-adjusted Cox regression and competing risk regression was utilized to compare SSE and bleeding risks between cohorts during 5-year follow-up. Of an overall cohort of 47 427 people, 26 277 (55.41%) were never anti-coagulated, 7934 (16.72%) received continuous anti-coagulation, 9107 (19.2%) temporarily discontinued, and 4109 (8.66%) permanently discontinued. Lower socio-economic status, elevated frailty score, and age ≥ 75 were associated with a reduced likelihood of initiation and continuation of anti-coagulation. Stroke/systemic embolism risk was significantly greater in those with discontinuous anti-coagulation, compared with continuous [subhazard ratio (SHR): 2.65; 2.39–2.94]. In the context of a major bleeding event, there was no significant difference in bleeding risk between the cessation and continuous cohorts (SHR 0.94; 0.42–2.14).

Conclusion
Our data suggest significant inequalities in anti-coagulation prescribing, with substantial opportunity to improve initiation and continuation. Decision-making should be patient-centred and must recognize that discontinuation or cessation is associated with considerable thromboembolic risk not offset by mitigated bleeding risk.
The interkingdom horizontal gene transfer in 44 early diverging fungi boosted their metabolic, adaptive, and immune capabilities
Authors: Ciach Michał Aleksander , Pawłowska Julia , Górecki Paweł , Muszewska Anna 
Published: March 2024

Abstract
Numerous studies have been devoted to individual cases of horizontally acquired genes in fungi. It has been shown that such genes expand the hosts’ metabolic capabilities and contribute to their adaptations as parasites or symbionts. Some studies have provided an extensive characterization of the horizontal gene transfer (HGT) in Dikarya. However, in the early diverging fungi (EDF), a similar characterization is still missing. In order to fill this gap, we have designed a computational pipeline to obtain a statistical sample of reliable HGT events with a low false discovery rate. We have analyzed 44 EDF proteomes and identified 829 xenologs in fungi ranging from Chytridiomycota to Mucoromycota. We have identified several patterns and statistical properties of EDF HGT. We show that HGT is driven by bursts of gene exchange and duplication, resulting in highly divergent numbers and molecular properties of xenologs between fungal lineages. Ancestrally aquatic fungi are generally more likely to acquire foreign genetic material than terrestrial ones. Endosymbiotic bacteria can be a source of useful xenologs, as exemplified by NOD-like receptors transferred to Mortierellomycota. Closely related fungi have similar rates of intronization of xenologs. Posttransfer gene fusions and losses of protein domains are common and may influence the encoded proteins’ functions. We argue that there is no universal approach for HGT identification and inter- and intra-kingdom transfers require tailored identification methods. Our results help to better understand how and to what extent HGT has shaped the metabolic, adaptive, and immune capabilities of fungi.
Glycosylation as a tracer of off-target Cre-lox activation in development
Authors: Glendenning Leandre M , Reynero Kalob M , Cobb Brian A 
Published: March 2024

Abstract
The Cre-lox system is one of the most widely used methods for lineage-specific and inducible genome editing in vivo. However, incomplete penetrance and off-target effects due to transient promoter expression in a stem or pluripotent precursor cell can be problematic and difficult to detect, especially if the target gene is not normally present in the fully differentiated but off-target cells. Yet, the loss of the target gene through the transient expression of Cre may impact the differentiation of those cells by virtue of transient expression in a precursor population. In these situations, off-target effects in an unknown precursor cell can, at best, complicate conclusions drawn from the model, and at worst, invalidate all data generated from that knockout strain. Thus, identifying Cre-driver promoter expression along entire cell lineages is crucial to improve rigor and reproducibility. As an example, transient expression in an early precursor cell has been documented in a variety of Cre strains such as the Tie2-based Cre-driver system that is used as an “endothelial cell-specific” model 1. Yet, Tie2 is now known to be transiently expressed in a stem cell upstream of both hematopoietic and endothelial cell lineages. Here, we use the Tie2 Cre-driver strain to demonstrate that due to its ubiquitous nature, plasma membrane glycans are a useful marker of both penetrance and specificity of a Cre-based knockout.
Bacterial diversity and chemical ecology of natural product–producing bacteria from Great Salt Lake sediment
Authors: Bring Horvath Elijah R , Brazelton William J , Kim Min Cheol , Cullum Reiko , Mulvey Matthew A , Fenical William , Winter Jaclyn M 
Published: March 2024

Abstract
Great Salt Lake (GSL), located northwest of Salt Lake City, UT, is the largest terminal lake in the USA. While the average salinity of seawater is ~3.3%, the salinity in GSL ranges between 5% and 28%. In addition to being a hypersaline environment, GSL also contains toxic concentrations of heavy metals, such as arsenic, mercury, and lead. The extreme environment of GSL makes it an intriguing subject of study, both for its unique microbiome and its potential to harbor novel natural product–producing bacteria, which could be used as resources for the discovery of biologically active compounds. Though work has been done to survey and catalog bacteria found in GSL, the Lake’s microbiome is largely unexplored, and little to no work has been done to characterize the natural product potential of GSL microbes. Here, we investigate the bacterial diversity of two important regions within GSL, describe the first genomic characterization of Actinomycetota isolated from GSL sediment, including the identification of two new Actinomycetota species, and provide the first survey of the natural product potential of GSL bacteria.
Genomics to detect transmission of livestock-associated methicillin-resistant Staphylococcus aureus from UK pigs in abattoirs during slaughter
Authors: Anjum Muna F , Duggett Nicholas , Sheldon Ewart , Sharma Meenaxi , Smith Richard P , Teale Chris J 
Published: March 2024

Abstract

Background
Livestock-associated MRSA (LA-MRSA) transmission/cross-contamination can occur at abattoir through colonized pigs, increasing occupational hazards and health concerns for workers. To assess this risk we used genomics to identify LA-MRSA lineages present in batches of pigs sent to slaughter and distribution of clones.

Methods
WGS was performed on 85 LA-MRSA previously isolated from six abattoirs from 105 batches of pigs sent from 100 UK farms. spa typing and MLST were performed on all isolates. A mashtree tree was constructed to compare genomes of the LA-MRSA with 1281 global isolates from livestock and humans. A phylogenetic tree and pairwise SNP distance matrices were built from whole genomes of 109 isolates closest to those from abattoirs to compare evolutionary relationships and identify clones.

Results
All abattoir isolates belonged to CC398 and were mainly of spa type t011, although other spa types were present. Phylogenetic analysis confirmed the abattoir isolates were most closely related to each other and to pig LA-MRSA from across Europe, indicating a common evolutionary origin with related lineages colonizing UK pigs.
Comparison of genomes using SNPs suggested between one and four clones were transferring between pigs from different batches. Transmission likely occurred on farm premises, during transportation, and/or within abattoirs through contact with contaminated surfaces in lairage or post-stunning.

Conclusions
Genomics forensically identified related isolates/clones circulating in pigs at slaughter, showing contamination occurs often. Results suggest that further genomic tracking will identify hotspots, and improvements in measures such as biosecurity and disinfection will help reduce risk for workers.
14-Year Epidemiologic study of Pseudomonas aeruginosa bloodstream infection incidence and resistance in the Veterans Health Administration system, 2009–2022
Authors: Hojat Leila S , Wilson Brigid M , Satlin Michael J , Perez Federico , Mojica Maria F , Singer Mendel E , Bonomo Robert A , Epstein Lauren H 
Published: March 2024

Abstract

Background
Multidrug resistant Pseudomonas aeruginosa (PA) represents a serious threat to hospitalized patients. Characterizing the incidence of PA infection and degree of resistance can inform empiric treatment and preventative measures.

Objectives
We sought to describe trends in incidence and resistance characteristics of PA bloodstream infections (BSI) observed within the Veterans Health Administration (VHA) system and identify factors contributing to higher observed mortality within this population.

Methods
We characterized demographic and clinical features of unique patients among the VHA population presenting with their first episode of PA-BSI between 2009 and 2022 and summarized trends related to mortality and resistance phenotype based on year and geographical location. We additionally used logistic regression analysis to identify predictors of 30-day mortality among this cohort.

Results
We identified 8039 PA-BSIs during the study period, 32.7% of which were hospital onset. Annual PA-BSI cases decreased by 35.8%, and resistance among all antimicrobial classes decreased during the study period, while the proportion of patients receiving early active treatment based on susceptibility testing results increased. Average 30-day mortality rate was 23.3%. Higher Charlson Comorbidity Index, higher mAPACHE score, VHA facility complexity 1b and hospital-onset cases were associated with higher mortality, and early active treatment was associated with lower mortality.

Conclusions
PA-BSI resistance decreased across the VHA system during the study period. Further investigation of antimicrobial stewardship measures possibly contributing to the observed decreased resistance in this cohort and identification of measures to improve on the high mortality associated with PA-BSI in the VHA population is warranted.
Identification of an novel genetic variant associated with osteoporosis: insights from the Taiwan Biobank Study
Authors: Liaw Yi-Ching , Matsuda Koichi , Liaw Yung-Po 
Published: March 2024

Abstract

Purpose
The purpose of this study was to identify new independent significant SNPs associated with osteoporosis using data from the Taiwan Biobank (TWBB).

Material and Methods
The dataset was divided into discovery (60%) and replication (40%) subsets. Following data quality control, genome-wide association study (GWAS) analysis was performed, adjusting for sex, age, and the top 5 principal components, employing the Scalable and Accurate Implementation of the Generalized mixed model approach. This was followed by a meta-analysis of TWBB1 and TWBB2. The Functional Mapping and Annotation (FUMA) platform was used to identify osteoporosis-associated loci. Manhattan and quantile–quantile plots were generated using the FUMA platform to visualize the results. Independent significant SNPs were selected based on genome-wide significance (P &lt; 5 × 10−8) and independence from each other (r2 &lt; 0.6) within a 1 Mb window. Positional, eQTL(expression quantitative trait locus), and Chromatin interaction mapping were used to map SNPs to genes.

Results
A total of 29 084 individuals (3154 osteoporosis cases and 25 930 controls) were used for GWAS analysis (TWBB1 data), and 18 918 individuals (1917 cases and 17 001 controls) were utilized for replication studies (TWBB2 data). We identified a new independent significant SNP for osteoporosis in TWBB1, with the lead SNP rs76140829 (minor allele frequency = 0.055, P-value = 1.15 × 10−08). Replication of the association was performed in TWBB2, yielding a P-value of 6.56 × 10−3. The meta-analysis of TWBB1 and TWBB2 data demonstrated a highly significant association for SNP rs76140829 (P-value = 7.52 × 10−10). In the positional mapping of rs76140829, 6 genes (HABP2, RP11-481H12.1, RNU7-165P, RP11-139 K1.2, RP11-57H14.3, and RP11-214 N15.5) were identified through chromatin interaction mapping in mesenchymal stem cells.

Conclusions
Our GWAS analysis using the Taiwan Biobank dataset unveils rs76140829 in the VTI1A gene as a key risk variant associated with osteoporosis. This finding expands our understanding of the genetic basis of osteoporosis and highlights the potential regulatory role of this SNP in mesenchymal stem cells.
Mouse mandibular–derived osteoclast progenitors have differences in intrinsic properties compared with femoral–derived progenitors
Authors: Clark Rachel , Park Soo Y , Bradley Elizabeth W , Mansky Kim , Tasca Amy 
Published: March 2024

Abstract
Craniofacial osteoclasts are essential for site–specific processes such as alveolar bone resorption, tooth eruption, and orthodontic tooth movement. Much of the current understanding of osteoclast development and function comes from studies using long bone–derived cells. Minimal investigation has been done to explore skeletal site differences. The overall goal of this study was to determine if mandibular– and femoral–derived osteoclasts represent distinct populations. To test this hypothesis, bone marrow cells were initially analyzed from the mandible and femur of 2–month–old mice. It was shown that mandibular–derived osteoclasts have enhanced size (mm2) compared with femoral–derived osteoclasts. Since bone marrow macrophages are a heterogenous population, we additionally selected for monocytes and demonstrated that mandibular–derived monocytes also form osteoclasts with increased size compared with femoral–derived monocytes. Osteoclast precursor populations from both skeletal sites were analyzed by flow cytometry. A newly described Ly6CHigh+ population as well as the Ly6Cint population was increased in the mandibular–derived cells. The difference in differentiation potential between monocyte cultures suggests that the increase in the Ly6CHigh+ population may explain the enhanced differentiation potential in mandibular–derived cells. Monocyte genes such as Pu.1, C/ebp-a, and Prdm1 are increased in expression in mandibular–derived monocytes compared with femoral–derived monocytes. As expected with enhanced differentiation, osteoclast genes including Nfatc1, Dc-stamp, Ctsk, and Rank are upregulated in mandibular–derived osteoclast precursors. Future studies will determine how changes in the environment of the mandible lead to changes in percentages of osteoclast progenitors and their differentiation potential.
Round-up of English patent litigation 2023
Authors: Cook Trevor 
Published: March 2024

Abstract
2023 saw 15 decisions, concerning 22 patents, in inter partes proceedings in which patent infringement and/or validity was in issue. 6 patents were held to be valid and infringed, 9 not to be infringed and 9 to be invalid, all but 3 on the ground of obviousness. 2023 also saw 6 Court of Appeal decisions in such proceedings, in 3 of which the trial judge was reversed on validity - in two cases in favour of the patentee.
Publish and perish: mental health among communication and media scholars
Authors: Hanitzsch Thomas , Markiewitz Antonia , Bødker Henrik 
Published: March 2024

Abstract
Studies point to a significantly higher prevalence of mental health issues among academics compared to most other working populations. However, we know relatively little about the situation within the field of media and communication studies. Based on an international survey of 1028 researchers within this field, we found mental health issues to be widespread. Early career researchers, women, and those in nonpermanent positions were significantly more strongly affected by these issues than scholars in later career stages, men, and those in permanent employment. Academics in our field worry most about structural aspects of their work, most notably about publication pressure and future career prospects. We argue that while our findings are somewhat aligned with results from or across other fields, they are still worrisome. We thus argue for the need to start a conversation about how to reduce the mental burden, especially for young and early career researchers.