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This research analyzes how foreign organizational practices diffuse among indigenous enterprises in a developing economy. It highlights the collective knowledge-building process as central for understanding diffusion. Based on a longitudinal case study of a cluster of dairy producers in Nicaragua, a representative low-income country, it looks at cross-border diffusion in conditions that differ significantly from advanced economies. The current literature that highlights institutional pressures driving global spread of practices has limits for capturing a significant dynamic caused by increased integration of markets and production. By focusing on production organization and practices in a late developing context, this paper explains the intertwined process of spreading new standards and changing existing local practices by elaborating the relationship among building collective capabilities, learning, and standards diffusion. This study enriches current views on institutional effects and adds to the practice-based literature, as well as to the work on developing economy firms in organizational research.

Flaviviruses are a group of viruses transmitted mainly by mosquitoes and ticks, causing severe diseases in humans. Examples include dengue, Zika, West Nile virus, and yellow fever. They primarily affect individuals in tropical and subtropical regions, causing public health problems such as epidemic outbreaks and significant economic burdens due to hospitalizations and treatments. They share antigens, leading to cross-reactivity where antibodies generated against one flavivirus can react with others, complicating the accurate diagnosis of individual infections and making the development of treatments or vaccines more challenging. The role of T cells in the immune response to flaviviruses is a complex topic debated by scientists. On one hand, T cells help control infection by eliminating infected cells and protecting against disease. However, there is evidence that an excessive or dysregulated T cell response can cause tissue damage and worsen the disease, as seen in severe dengue cases. This duality underscores the complexity of the immune response to flavivirus infections, posing a significant challenge for researchers. Gaining a deeper understanding of the immune response at the cellular level, particularly the role of T follicular helper cells, can reveal new avenues of investigation that could lead to novel strategies for disease management. This review explores the dynamics of T cell responses, focusing on circulatory T follicular helper cells (cTFH), to enhance our understanding of flavivirus immunity and inform future interventions.

Opuntia ficus-indica (cactus pear) emerged as a promising crop for sustainable bioenergy production on marginal agricultural land, mitigating competition with food crops and lowering the risk of other indirect land use changes. In this study, the bioenergy potential is investigated of cactus pear residues within a smallholder farming context of Nopaltepec, a rural municipality in Central Mexico. Nopaltepec is a native environment of cactus pear and shows an annual production volume of 30 Gg of fresh matter. A bottom-up approach employing semi-structured interviews (n = 16) was utilized to assess the feasibility of transforming the pruning residues of cactus pear into a viable bioenergy source. The results indicate a substantial bioenergy potential, with 27 Mg of fresh matter biomass (equivalent to 9720 m3 biogas) per hectare obtainable annually without compromising fruit yields. Moreover, the digestate produced through anaerobic digestion can be recycled as biofertilizer, offering economic and ecological advantages to smallholders. Notably, farmers expressed keen interest in integrating this technology into their agricultural systems. This research underscores the potential of cactus pear residues for developing a decentralized bioenergy sector and provides valuable ideas for future bottom-up assessments in rural communities like Nopaltepec.

Lower activity of the histaminergic system is associated with neurological disorders, including Alzheimer’s disease (AD). Thus, the enhancement of histaminergic neurotransmission by inhibition of histamine N-methyl transferase (HNMT), which degrades histamine, appears as an important approach. For this purpose, rigid and flexible molecular docking studies of 185 FDA-approved drugs with the HNMT enzyme were carried out to select two compounds to perform molecular dynamics (MD) simulations to evaluate the binding free energies and stability of the enzyme–drug complexes. Finally, an HNMT inhibition assay was performed to corroborate their effect towards HNMT. Molecular docking studies with HNMT allowed the selection of dihydroergotamine and vilazodone since these molecules showed the lowest Gibbs free energy values. Analysis of the binding mode of vilazodone showed interactions with the binding pocket of HNMT with Glu28, Gln143, and Asn283. In contrast, dihydroergotamine binds to the HNMT active site in a different location, apparently because it is overall the more rigid ligand compared to flexible vilazodone. HNMT inhibitory activity for dihydroergotamine and vilazodone was corroborated (IC50 = 72.89 μM and 45.01 μM, respectively) by in vitro assays. Drug repurposing of HNMT was achieved by employing computational studies.

Periodontitis affects billions of people worldwide. To address relationships of periodontal niche cell types and microbes in periodontitis, we generated an integrated single-cell RNA sequencing (scRNAseq) atlas of human periodontium (34-sample, 105918-cell), including sulcular and junctional keratinocytes (SK/JKs). SK/JKs displayed altered differentiation states and were enriched for effector cytokines in periodontitis. Single-cell metagenomics revealed 37 bacterial species with cell-specific tropism. Fluorescence in situ hybridization detected intracellular 16   S and mRNA signals of multiple species and correlated with SK/JK proinflammatory phenotypes in situ. Cell-cell communication analysis predicted keratinocyte-specific innate and adaptive immune interactions. Highly multiplexed immunofluorescence (33-antibody) revealed peri-epithelial immune foci, with innate cells often spatially constrained around JKs. Spatial phenotyping revealed immunosuppressed JK-microniches and SK-localized tertiary lymphoid structures in periodontitis. Here, we demonstrate impacts on and predicted interactomics of SK and JK cells in health and periodontitis, which requires further investigation to support precision periodontal interventions in states of chronic inflammation. Here, Easter et al. generate a single-cell atlas of human periodontium including sulcular and junctional keratinocytes. Cell-cell communication analysis is used to predict keratinocyte-specific immune cell interactions.

The aim of this study was to analyze the diagnostic performance of Leucine-Rich Alpha-2-Glycoprotein (LRG1) in pediatric acute appendicitis (PAA). We conducted a systematic review of the literature in the main databases of medical bibliography. Two independent reviewers selected the articles and extracted relevant data. Methodological quality was assessed using the QUADAS2 index. A synthesis of the results, standardization of the metrics and 4 random-effect meta-analyses were performed. Eight studies with data from 712 participants (305 patients with confirmed diagnosis of PAA and 407 controls) were included in this review. The random-effect meta-analysis of serum LRG1 (PAA vs control) resulted in a significant mean difference (95% CI) of 46.76 μg/mL (29.26–64.26). The random-effect meta-analysis for unadjusted urinary LRG1 (PAA vs control) resulted in a significant mean difference (95% CI) of 0.61 μg/mL (0.30–0.93). The random-effect meta-analysis (PAA vs control) for urinary LRG1 adjusted for urinary creatinine resulted in a significant mean difference (95% CI) of 0.89 g/mol (0.11–1.66).     Conlusion : Urinary LRG1 emerges as a potential non-invasive biomarker for the diagnosis of PAA. On the other hand, due to the high between-study heterogeneity, the results on serum LRG1 should be interpreted with caution. The only study that analyzed salivary LRG1 showed promising results. Further prospective studies are needed to confirm these findings. What is Known: • Pediatric acute appendicitis continues to be a pathology with a high rate of diagnostic error. • Invasive tests, although useful, are a source of stress for patients and their parents. What is New: • LRG1 emerges as a promising urinary and salivary biomarker for the noninvasive diagnosis of pediatric acute appendicitis.

ObjectivesSjögren’s syndrome (SS) is an autoimmune sialadenitis with unknown aetiology. Although extensive research implicated an abnormal immune response associated with lymphocytes, an initiating event mediated by salivary gland epithelial cell (SGEC) abnormalities causing activation is poorly characterised. Transcriptome studies have suggested alternations in lysosomal function are associated with SS, but a cause and effect linkage has not been established. In this study, we demonstrated that altered lysosome activity in SGECs by expression of lysosome-associated membrane protein 3 (LAMP3) can initiate an autoimmune response with autoantibody production and salivary dysfunction similar to SS.MethodsRetroductal cannulation of the submandibular salivary glands with an adeno-associated virus serotype 2 vector encoding LAMP3 was used to establish a model system. Pilocarpine-stimulated salivary flow and the presence of autoantibodies were assessed at several time points post-cannulation. Salivary glands from the mice were evaluated using RNAseq and histologically.ResultsFollowing LAMP3 expression, saliva flow was significantly decreased and serum anti-Ro/SSA and La/SSB antibodies could be detected in the treated mice. Mechanistically, LAMP3 expression increased apoptosis in SGECs and decreased protein expression related to saliva secretion. Analysis of RNAseq data suggested altered lysosomal function in the transduced SGECs, and that the cellular changes can chemoattract immune cells into the salivary glands. Immune cells were activated via toll-like receptors by damage-associated molecular patterns released from LAMP3-expressing SGECs.ConclusionsThese results show a critical role for lysosomal trafficking in the development of SS and establish a causal relationship between LAMP3 misexpression and the development of SS.

Background Whole transcriptome RNA variant analyses have shown that adenosine deaminases acting on RNA ( ADAR ) enzymes modify a large proportion of cellular RNAs, contributing to transcriptome diversity and cancer evolution. Despite the advances in the understanding of ADAR function in breast cancer, ADAR RNA editing functional consequences are not fully addressed. Results We characterized A to G(I) mRNA editing in 81 breast cell lines, showing increased editing at 3′UTR and exonic regions in breast cancer cells compared to immortalized non-malignant cell lines. In addition, tumors from the BRCA TCGA cohort show a 24% increase in editing over normal breast samples when looking at 571 well-characterized UTRs targeted by ADAR1 . Basal-like subtype breast cancer patients with high level of ADAR1 mRNA expression shows a worse clinical outcome and increased editing in their 3′UTRs. Interestingly, editing was particularly increased in the 3′UTRs of ATM , GINS4 and POLH transcripts in tumors, which correlated with their mRNA expression. We confirmed the role of ADAR1 in this regulation using a shRNA in a breast cancer cell line (ZR-75-1). Conclusions Altogether, these results revealed a significant association between the mRNA editing in genes related to cancer-relevant pathways and clinical outcomes, suggesting an important role of ADAR1 expression and function in breast cancer.

Background The study evaluates the impact of the time between commencing non-invasive ventilation (NIV) support and initiation of venovenous extracorporeal membrane oxygenation (VV-ECMO) in a cohort of critically ill patients with coronavirus disease 2019 (COVID-19) associated acute respiratory distress syndrome (ARDS). Methods Prospective observational study design in an intensive Care Unit (ICU) of a tertiary hospital in Barcelona (Spain). All patients requiring VV-ECMO support due to COVID-19 associated ARDS between March 2020 and January 2022 were analysed. Survival outcome was determined at 90 days after VV-ECMO initiation. Demographic data, comorbidities at ICU admission, RESP (respiratory ECMO survival prediction) score, antiviral and immunomodulatory treatments received, inflammatory biomarkers, the need for vasopressors, the thromboprophylaxis regimen received, and respiratory parameters including the length of intubation previous to ECMO and the length of each NIV support (high-flow nasal cannula, continuous positive airway pressure and bi-level positive airway pressure), were also collated in order to assess risk factors for day-90 mortality. The effect of the time lapse between NIV support and VV-ECMO on survival was evaluated using logistic regression and adjusting the association with all factors that were significant in the univariate analysis. Results Seventy-two patients finally received VV-ECMO support. At 90 days after commencing VV-ECMO 35 patients (48%) had died and 37 patients (52%) were alive. Multivariable analysis showed that at VV-ECMO initiation, age ( p  = 0.02), lactate ( p  = 0.001), and days from initiation of NIV support to starting VV-ECMO ( p  = 0.04) were all associated with day-90 mortality. Conclusions In our small cohort of VV-ECMO patients with COVID-19 associated ARDS, the time spent between initiation of NIV support and VV-ECMO (together with age and lactate) appeared to be a better predictor of mortality than the time between intubation and VV-ECMO.

Obesity is an inflammatory state associated with delayed lactogenesis stage II and altered mammary gland morphology. Serotonin mediates inflammation and mammary gland involution. The objective of this study was to determine if a genetic deficiency of tryptophan hydroxylase 1, the rate-limiting enzyme in peripheral serotonin synthesis, would result in an improved ability to lactate in dams fed a high fat diet. Twenty-six female mice were fed a high (HFD) or low fat (LFD) diet throughout pregnancy and lactation. Fourteen mice were genetically deficient for Tph1 (Tph1-/-), and twelve were wild type. Milk yield, pup mortality, and dam weights were recorded and milk samples were collected. On day 10 of lactation, dams were sacrificed and mammary glands were harvested for RT-PCR and histological evaluation. HFD dams weighed more than LFD dams at the onset of lactation. WT HFD dams were unable to lactate on day 1 of lactation and exhibited increased pup mortality relative to all other treatments, including Tph1-/- HFD dams. mRNA expression of immune markers C-X-C motif chemokine 5 and tumor necrosis factor alpha were elevated in WT HFD mammary glands. Mammary gland histology showed a reduced number of alveoli in WT compared to Tph1-/- dams, regardless of diet, and the alveoli of HFD dams were smaller than those of LFD dams. Finally, fatty acid profile in milk was dynamic in both early and peak lactation, with reduced de novo synthesis of fatty acids on day 10 of lactation in the HFD groups. Administration of a HFD to C57BL/6 dams produced an obese phenotype in the mammary gland, which was alleviated by a genetic deficiency of Tph1. Serotonin may modulate the effects of obesity on the mammary gland, potentially contributing to the delayed onset of lactogenesis seen in obese women.