bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of subcutaneous versus intravenous ceftriaxone administration in older patients: A retrospective study
Authors: Pardo Inès , Pierre‐Jean Morgane , Bouzillé Guillaume , Fauchon Heloïse , Corvol Aline , Prud'homm Joaquim , Somme Dominique 
Published: February 2024

AbstractBackgroundAntibiotics play a central role in infection management. In older patients, antibiotics are frequently administered subcutaneously. Ceftriaxone pharmacokinetics after subcutaneous administration is well documented, but little data are available on its safety.MethodsWe compared the occurrence of adverse events associated with ceftriaxone administered subcutaneously versus intravenously in ≥75‐year‐old patients. We used data from a single‐center, retrospective, clinical‐administrative database to compare the occurrence of adverse events at day 14 and outcome at day 21 in older patients who received ceftriaxone via the subcutaneous route or the intravenous route at Rennes University Hospital, France, from May 2020 to February 2023.ResultsThe subcutaneous and intravenous groups included 402 and 3387 patients, respectively. Patients in the subcutaneous group were older and more likely to receive palliative care. At least one adverse event was reported for 18% and 40% of patients in the subcutaneous and intravenous group, respectively (RR = 2.21). Mortality at day 21 was higher in the subcutaneous route group, which could be linked to between‐group differences in clinical and demographic features.ConclusionsIn ≥75‐year‐old patients, ceftriaxone administered by the subcutaneous route is associated with less‐adverse events than by the intravenous route. The subcutaneous route, which is easier to use, has a place in infection management in geriatric settings.
Bioinformatics analysis identifies potential autophagy key genes and immune infiltration in preeclampsia
Authors: Sun Lu , He Yanhong , Chen Jie , Yang Xiaofeng , Ding Yuzhen , Shi Meiting , He Andong , Zhang Ping , Huang Zhengrui , Li Ruiman 
Published: February 2024

AbstractBackgroundPreeclampsia (PE) is a disease that seriously threatens maternal and fetal health. Appropriate autophagy can shield the placenta from oxidative stress, but its role in PE is unclear.ObjectiveTo identify potential autophagy‐related genes in PE.MethodsMicroarray datasets from the Gene Expression Omnibus database, compassing the test dataset GSE10588, along with validation datasets GSE4707 and GSE60438 GPL10558, were utilized. Differentially expressed genes (DEGs) were identified using the limma R package, intersected with autophagy‐related genes. Hub genes were obtained using the Cytoscape software and analyzed via gene set enrichment analysis (GSEA). The diagnostic capability of hub genes was evaluated using receiver operating characteristic (ROC) curve analysis. Analysis of immune cell infiltration was conducted using single‐sample gene set enrichment analysis (ssGSEA) and CIBERSORT methods. Placental tissues were collected from 10 normal pregnant women and 10 preeclamptic pregnant women, and the expression of hub genes was validated through immunohistochemistry and western blot analysis.ResultsAnalysis of the microarray data identified 2224 DEGs, among which 26 were autophagy‐related DEGs identified through intersection with autophagy genes. Ten hub genes were identified. Immune cell infiltration analysis suggested the potential involvement of T regulatory cells (Tregs), natural killer cells, neutrophils, and T follicular helper cells in the pathogenesis of PE. ROC curve analysis indicated promising diagnostic capabilities for EGFR and TP53. Additionally, levels of EGFR and TP53 were significantly higher in placental tissue from PE pregnancies compared to normal pregnancies.ConclusionEGFR and TP53 may play a role in PE by influencing autophagy.
Melatonin is a potential novel analgesic agent for osteoarthritis: Evidence from cohort studies in humans and preclinical research in rats
Authors: Li Hui , Zhou Bin , Wu Jing , Zhang Yuqing , Zhang Weiya , Doherty Michael , Deng Xinjia , Wang Ning , Xie Dongxing , Wang Yilun , Xie Hui , Li Changjun , Wei Jie , Lei Guanghua , Zeng Chao 
Published: February 2024

AbstractMelatonin exhibits potential for pain relief and long‐term safety profile. We examined the analgesic effects of oral melatonin on osteoarthritis (OA) and investigated the underlying mechanism. Using data from a UK primary care database, we conducted a cohort study in individuals with OA to compare the number of oral analgesic prescriptions and the risk of knee/hip replacement between melatonin initiators and hypnotic benzodiazepines (i.e., active comparator) initiators using quantile regression models and Cox‐proportional hazard models, respectively. To elucidate causation, we examined the effects of melatonin on pain behaviors and explored several metabolites that may serve as potential regulatory agents of melatonin in the monoiodoacetate rat model of OA. Using data from another community‐based cohort study, that is, the Xiangya OA Study, we verified the association between the key serum metabolite and incident symptomatic knee OA. Compared with the hypnotic benzodiazepines cohort (n = 8135), the melatonin cohort (n = 813) had significantly fewer subsequent prescriptions of oral analgesics (50th percentile: 5 vs. 7, 75th percentile: 19 vs. 29, and 99th percentile: 140 vs. 162) and experienced a lower risk of knee/hip replacement (hazard ratio = 0.47, 95% Cl: 0.30–0.73) during the follow‐up period. In rats, oral melatonin alleviated pain behaviors and increased serum levels of glycine. There was an inverse association between baseline serum glycine levels and the risk of incident symptomatic knee OA in humans (n = 760). In conclusion, our findings indicate that oral melatonin shows significant potential to be a novel treatment for OA pain. The potential role of glycine in its analgesic mechanism warrants further investigation.
Detection of nephrocalcinosis using ultrasonography, micro‐computed tomography, and histopathology in cats
Authors: Tang Pak‐Kan , Geddes Rebecca F. , Chang Yu‐Mei , Jepson Rosanne E. , van den Broek Dirk Hendrik Nicolaas , Lötter Nicola , Elliott Jonathan 
Published: February 2024

AbstractBackgroundIdentification of nephrocalcinosis in cats with chronic kidney disease (CKD) is of clinical interest but the ability of ultrasonography to detect nephrocalcinosis is uncertain.ObjectivesTo compare ultrasonography, micro‐computed tomography (μCT) and histopathology for identification of nephrocalcinosis.AnimalsTwelve kidneys from 7 euthyroid client‐owned cats with CKD.MethodsDescriptive study. Renal ultrasonography was performed ante‐mortem for nephrocalcinosis detection. Kidneys were grouped based on nephrocalcinosis: present, suspected, or absent. When cats died, necropsy was performed. Renal tissue was evaluated using μCT for macroscopic nephrocalcinosis, and nephrocalcinosis volume‐to‐kidney tissue ratio (macro‐VN:KT) and sagittal nephrocalcinosis area‐to‐kidney tissue ratio (macro‐AN:KT) were calculated. Each kidney subsequently was bisected longitudinally, formalin‐fixed, and paraffin‐embedded for microscopic nephrocalcinosis assessment using von Kossa and Alizarin red staining with AN:KT (VK‐micro‐AN:KT and AR‐micro‐AN:KT) quantified using ImageJ. Data are presented as median (range). Relationships between macroscopic and microscopic AN:KT were assessed using Spearman's correlation.ResultsNephrocalcinosis by ultrasonography was considered to be absent in 3, suspected in 3, and present in 5 kidneys; 1 kidney had nephrolithiasis with nephrocalcinosis. The macro‐VN:KT was 0.001%, 0.001%, and 0.019%, and the macro‐AN:KT was 0.08%, 0.30%, and 1.47%, respectively. Histologically, VK‐micro‐AN:KT was 0.21%, 2.85%, and 4.56%, and AR‐micro‐AN:KT was 1.73%, 5.82%, and 8.90% for kidneys where ultrasonographic macro‐nephrocalcinosis was absent, suspected, or present, respectively. A strong correlation was identified between macroscopic (macro‐AN:KT) and microscopic (VK‐micro‐AN:KT) nephrocalcinosis (rs = 0.76; P = .01).Conclusions and Clinical ImportanceUltrasonographically diagnosed nephrocalcinosis correlates well with macroscopic and microscopic nephrocalcinosis at necropsy despite their separation in time.
GhRCD1 promotes cotton tolerance to cadmium by regulating the GhbHLH12–GhMYB44–GhHMA1 transcriptional cascade
Authors: Wei Xi , Geng Menghan , Yuan Jiachen , Zhan Jingjing , Liu Lisen , Chen Yanli , Wang Ye , Qin Wenqiang , Duan Hongying , Zhao Hang , Li Fuguang , Ge Xiaoyang 
Published: February 2024

SummaryHeavy metal pollution poses a significant risk to human health and wreaks havoc on agricultural productivity. Phytoremediation, a plant‐based, environmentally benign, and cost‐effective method, is employed to remove heavy metals from contaminated soil, particularly in agricultural or heavy metal‐sensitive lands. However, the phytoremediation capacity of various plant species and germplasm resources display significant genetic diversity, and the mechanisms underlying these differences remain hitherto obscure. Given its potential benefits, genetic improvement of plants is essential for enhancing their uptake of heavy metals, tolerance to harmful levels, as well as overall growth and development in contaminated soil. In this study, we uncover a molecular cascade that regulates cadmium (Cd2+) tolerance in cotton, involving GhRCD1, GhbHLH12, GhMYB44, and GhHMA1. We identified a Cd2+‐sensitive cotton T‐DNA insertion mutant with disrupted GhRCD1 expression. Genetic knockout of GhRCD1 by CRISPR/Cas9 technology resulted in reduced Cd2+ tolerance in cotton seedlings, while GhRCD1 overexpression enhanced Cd2+ tolerance. Through molecular interaction studies, we demonstrated that, in response to Cd2+ presence, GhRCD1 directly interacts with GhbHLH12. This interaction activates GhMYB44, which subsequently activates a heavy metal transporter, GhHMA1, by directly binding to a G‐box cis‐element in its promoter. These findings provide critical insights into a novel GhRCD1–GhbHLH12–GhMYB44–GhHMA1 regulatory module responsible for Cd2+ tolerance in cotton. Furthermore, our study paves the way for the development of elite Cd2+‐tolerant cultivars by elucidating the molecular mechanisms governing the genetic control of Cd2+ tolerance in cotton.
Integrating climate change into legislative drafting: An analysis of regulatory impact assessment obligations and practices in the EU and Finland
Authors: Leskinen Paula , Belinskij Antti , Saarela Sanna‐Riikka 
Published: February 2024

AbstractDiverse aspects of climate change must be considered when drafting legislation to successfully address mitigation and adaptation objectives. In this article, we examine the legal requirements to conduct regulatory climate impact assessment (climate RIA) and analyse to what extent these have been implemented in the European Union (EU) and Finland. Our particular interest is Article 6(4) of the European Climate Law, a provision obligating the European Commission to assess the consistency of draft measures or proposals with the Union's climate objectives. Our results demonstrate that climate RIA has not been applied methodically in the EU or Finland and that where it has been conducted, it has mainly addressed impacts of the legislative proposals on greenhouse gas emissions and neglected impacts on climate change adaptation and carbon sinks. These results indicate that the obligations have been inadequately implemented. While an explicit requirement to conduct climate RIA heightens acknowledgement of climate impacts in legislative drafting, guidance in fulfilling the requirement in practice is equally essential.
Testing and Expanding the Concept of Traditional and Contemporary Localism in Rural Local Food Systems with Ozark Wild Harvesters☆
Authors: Massengale Sarah Hultine , Hendrickson Mary 
Published: February 2024

AbstractWhile research shows the potential benefits of local food systems to improve community economy and quality of life, there is a critique that these studies overlook how informal, non‐market food access practices contribute to local food systems, especially in rural places. McEntee promoted the concepts of traditional and contemporary localism in his work with rural food systems, arguing that the motivations of participants define the categories. Using narrative research with wild harvesters in the Ozark Highlands, we propose that while McEntee's definitions are useful for expanding the conversation about why people may choose local food or not, more efforts should focus on valuing and welcoming the broader intersection of priorities and strategies that people use to engage in local food systems in their communities. Promoting a wider portfolio of local food access strategies is important to communicate that there are a variety of ways to participate in localized food systems, some in regular market transactions and some in informal non‐market ways, and that all are potentially valuable in building sustainable food systems in rural areas.
Effect of optimal nitrogen application and mid‐season drainage on rice root activity and reductive substances in straw‐incorporated paddy
Authors: Li Wangmei , Zhang Donghui , He Wenhai , Fan Mingsheng , Chen Haiqing 
Published: February 2024

AbstractThe straw incorporation in paddy fields exacerbates the reductive toxicity caused by flooding during the rice tillering stage in cold regions. Mid‐drainage can alleviate reductive toxicity, while nitrogen fertilizer (NF) application can enhance the drought resistance of rice. However, there is still a lack of convincing evidence about the types of reductive toxicity and appropriate draining thresholds with straw incorporation. A field experiment was conducted in northeast China to investigate the reductive toxicity of paddy fields caused by flooding and straw incorporation. Primarily, the study aimed to investigate the reduction of toxicity caused by straw incorporation. Additionally, the investigation verified the role of varying NF (0, 50, 100, 150 kg N ha−1) in conjunction with mid‐season drainage (−15 cm) to mitigate soil reductive toxicity while preserving root activity. Before mid‐season drainage, the contents of soil total amount of reductive matter, active reductive matter, Fe2+, and Mn2+ were 5.1–5.9 cmol kg−1, 3.2–3.9 cmol kg−1, 399.4–410.1 mg kg−1 and 290.3–340.1 mg kg−1, respectively. Mid‐season drainage of 15 cm depth decreased the total amount of reductive matter, active reductive matter and Fe2+ content by 51.8%, 56.0% and 29.6%, respectively. However, upon rewetting, the content of reductive substances reverted to pre‐drainage levels. Drainage led to a reduction in soil organic acid content by 56.6–78.8% and an increase in rice root activity by 160–290%. While increased NF application correlated with higher rice root activity, a significant yield increase was only observed within the range of 0–100 kg ha−1. In summary, an alternate wetting and drying threshold of −15 cm in combination with 100 kg ha−1 of NF rate significantly increased root activity and reduced reductive toxicity of the tillage layer without decreased rice yield. The reductive substance content rebounded to the pre‐drainage level after reflooding in the subsequent growth stage. Therefore, to minimize the reductive toxicity and methane emission caused by straw incorporation, rice fields can be drained to a depth of 15 cm during mid‐season drainage. Additionally, the fields should be drained several times in the following growth stage.
Sensing and regulation of C and N metabolism – novel features and mechanisms of the TOR and SnRK1 signaling pathways
Authors: Artins Anthony , Martins Marina C. M. , Meyer Christian , Fernie Alisdair R. , Caldana Camila 
Published: February 2024

SUMMARYCarbon (C) and nitrogen (N) metabolisms are tightly integrated to allow proper plant growth and development. Photosynthesis is dependent on N invested in chlorophylls, enzymes, and structural components of the photosynthetic machinery, while N uptake and assimilation rely on ATP, reducing equivalents, and C‐skeletons provided by photosynthesis. The direct connection between N availability and photosynthetic efficiency allows the synthesis of precursors for all metabolites and building blocks in plants. Thus, the capacity to sense and respond to sudden changes in C and N availability is crucial for plant survival and is mediated by complex yet efficient signaling pathways such as TARGET OF RAPAMYCIN (TOR) and SUCROSE‐NON‐FERMENTING‐1‐RELATED PROTEIN KINASE 1 (SnRK1). In this review, we present recent advances in mechanisms involved in sensing C and N status as well as identifying current gaps in our understanding. We finally attempt to provide new perspectives and hypotheses on the interconnection of diverse signaling pathways that will allow us to understand the integration and orchestration of the major players governing the regulation of the CN balance.
Computed tomography of a canine omental torsion secondary to a chronic abdominal gossypiboma and concurrent incidental broad ligament torsion
Authors: Ball Emily , Larkin Amy , Hung Germaine 
Published: February 2024

AbstractA 5‐year‐old female spayed Dogue de Bordeaux was referred for concerns of an abdominal mass and peritoneal effusion. Abdominal radiographs identified a mid‐ventral abdominal soft tissue opaque mass containing a radiopaque marker consistent with a gossypiboma. Contrast‐enhanced abdominal CT identified two whirl signs associated with the abdominal gossypiboma. Exploratory laparotomy confirmed an omental torsion with encapsulated gossypiboma and concurrent incidental torsion of the remnant of the right broad ligament. Based on a literature review, omental torsions are an unreported complication of gossypibomas in canids.
Inhibition of AMPK activation in
Echinococcus granulosus
sensu stricto limits the parasite’s glucose metabolism and survival
Authors: Yan Mingzhi , Liu Hui , Su Yansen , Bi Xiaojuan , Yang Ning , Lin Renyong , Lü Guodong 
Published: February 2024

ABSTRACT

Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by larvae of the
Echinococcus granulosus sensu lato
(s.l.) cluster. There is an urgent need to develop new drug targets and drug molecules to treat CE. Adenosine monophosphate (AMP)-activated protein kinase (AMPK), a serine/threonine protein kinase consisting of α, β, and γ subunits, plays a key role in the regulation of energy metabolism. However, the role of AMPK in regulating glucose metabolism in
E. granulosus
s.l. and its effects on parasite viability is unknown. In this study, we found that targeted knockdown of EgAMPKα or a small-molecule AMPK inhibitor inhibited the viability of
E. granulosus sensu stricto
(s.s.) and disrupted the ultrastructure. The results of
in vivo
experiments showed that the AMPK inhibitor had a significant therapeutic effect on
E. granulosus
s.s.-infected mice and resulted in the loss of cellular structures of the germinal layer. In addition, the inhibition of the EgAMPK/EgGLUT1 pathway limited glucose uptake and glucose metabolism functions in
E. granulosus
s.s.. Overall, our results suggest that EgAMPK can be a potential drug target for CE and that inhibition of EgAMPK activation is an effective strategy for the treatment of disease.
Klebsiella pneumoniae
K2 capsular polysaccharide degradation by a bacteriophage depolymerase does not require trimer formation
Authors: Ye Ting-Juan , Fung Kit-Man , Lee I-Ming , Ko Tzu-Ping , Lin Chia-Yi , Wong Chia-Ling , Tu I-Fan , Huang Tzu-Yin , Yang Feng-Ling , Chang Yu-Pei , Wang Jin-Town , Lin Tzu-Lung , Huang Kai-Fa , Wu Shih-Hsiung 
Published: February 2024

ABSTRACT

K2-capsular
Klebsiella pneumoniae
is a hypervirulent pathogen that causes fatal infections. Here, we describe a phage tailspike protein, named K2-2, that specifically depolymerizes the K2 capsular polysaccharide (CPS) of
K. pneumoniae
into tetrasaccharide repeating units. Nearly half of the products contained
O
-acetylation, which was thought crucial to the immunogenicity of CPS. The product-bound structures of this trimeric enzyme revealed intersubunit carbohydrate-binding grooves, each accommodating three tetrasaccharide units of K2 CPS. The catalytic residues and the key interactions responsible for K2 CPS recognition were identified and verified by site-directed mutagenesis. Further biophysical and functional characterization, along with the structure of a tetrameric form of K2-2, demonstrated that the formation of intersubunit catalytic center does not require trimerization, which could be nearly completely disrupted by a single-residue mutation in the C-terminal domain. Our findings regarding the assembly and catalysis of K2-2 provide cues for the development of glycoconjugate vaccines against
K. pneumoniae
infection.

IMPORTANCE

Generating fragments of capsular polysaccharides from pathogenic bacteria with crucial antigenic determinants for vaccine development continues to pose challenges. The significance of the C-terminal region of phage tailspike protein (TSP) in relation to its folding and trimer formation remains largely unexplored. The polysaccharide depolymerase described here demonstrates the ability to depolymerize the K2 CPS of
K. pneumoniae
into tetrasaccharide fragments while retaining the vital
O
-acetylation modification crucial for immunogenicity. By carefully characterizing the enzyme, elucidating its three-dimensional structures, conducting site-directed mutagenesis, and assessing the antimicrobial efficacy of the mutant enzymes against K2
K. pneumoniae
, we offer valuable insights into the mechanism by which this enzyme recognizes and depolymerizes the K2 CPS. Our findings, particularly the discovery that trimer formation is not required for depolymerizing activity, challenge the current understanding of trimer-dependent TSP activity and highlight the catalytic mechanism of the TSP with an intersubunit catalytic center.