Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional, transcriptomic, and lipidomic studies of the choC gene encoding a phospholipid methyltransferase in Aspergillus fumigatus

ABSTRACT Phosphatidylcholines (PCs) are a class of cell membrane phospholipids playing important roles in cellular integrity and signaling. In eukaryotes, PCs are biosynthesized via the Kennedy cytidine nucleotide and the Bremer-Greenberg pathways. The Aspergillus choC gene is predicted to encode a phospholipid methyltransferase, the key enzyme in the latter pathway. In this study, we have characterized choC in the opportunistic human pathogenic fungus Aspergillus fumigatus and show that ChoC plays a vital role in the endogenous biosynthesis of PC, which is necessary for proper vegetative growth, development, cell viability, and cell wall integrity of the fungus. Transcriptomic analyses have revealed that the deletion (Δ) of choC leads to the differential expression of diverse genes related to PC biosynthetic pathways, G protein signaling pathways, cell cycle, and autophagy. Importantly, the ΔchoC mutant averted cell death and regained cellular proliferation by regulating the expression of different PC synthesis genes after 4 days of incubation. Lipidomic analyses have demonstrated that ΔchoC directly leads to decreased PC synthesis, thereby affecting the length and unsaturation of PC fatty acid chains. In addition, ΔchoC leads to disturbed metabolism of other lipids, such as reduced phosphatidylethanolamine and neutral lipid triacylglycerol, but increased diacylglycerol amounts. Murine infection studies showed that invasive pathogenicity of the ΔchoC spores was significantly weakened coupled with a drastic reduction of their ability to colonize in kidneys. In summary, ChoC plays central roles in PC biosynthesis, lipid metabolism, cell membrane/wall integrity, endoplasmic reticulum function, and pathogenicity in A. fumigatus, implying that ChoC can be a novel target for antifungal therapy. IMPORTANCE This study explored the phospholipid metabolic pathway in A. fumigatus and its relationship with fungal growth, metabolism, and pathogenicity. ChoC, based on its critical roles in many aspects of the fungus and relatively conserved characteristics in filamentous fungi with low similarity with mammalian ones, can be a novel target of new antifungal drugs. This study explored the phospholipid metabolic pathway in A. fumigatus and its relationship with fungal growth, metabolism, and pathogenicity. ChoC, based on its critical roles in many aspects of the fungus and relatively conserved characteristics in filamentous fungi with low similarity with mammalian ones, can be a novel target of new antifungal drugs.
Results of video-assisted thoracoscopic surgery versus thoracotomy for lung cancer in a mixed practice medium-volume hospital: a propensity-matched study

Abstract OBJECTIVES The aim of this study was to compare the short- and long-term results of video-assisted thoracoscopic surgery (VATS) and thoracotomy for non-small-cell lung cancer in a medium-volume centre, where cardiothoracic surgeons perform both cardiac and general thoracic surgery. The primary outcome of interest was 5-year overall survival and disease-specific survival. Secondary outcomes were short-term postoperative complications, length of hospital stay and lymph node yield. METHODS This was a retrospective cohort study including 670 lung cancer patients undergoing VATS (n = 207) or open surgery (n = 463) with a curative intent in Oulu University Hospital between the years 2000–2020. Propensity score matching was implemented with surgical technique as the dependent and age, sex, Charlson comorbidity index, pulmonary function, pathological stage, histological type and the year of the operation as covariates resulting in 127 pairs. RESULTS In the propensity-matched cohort, 5-year overall survival was 64.3% after VATS and 63.2% after thoracotomy (P = 0.969). Five-year disease-specific survival was 71.6% vs 76.2% (P = 0.559). There were no differences in overall (34.6% vs 44.9%, p = 0.096) or major postoperative complications (8.7% vs 14.2%, P = 0.167) between the study groups. The average length of hospital stay was shorter (5.8 vs 6.6 days, P = 0.012) and the median lymph node yield was lower (4.0 vs 7.0, P < 0.001) in the VATS group compared to the thoracotomy group. CONCLUSIONS According to this study, the long-term results of lung cancer surgery in a mixed practice are comparable between VATS and open surgery.
Morphometric Analysis of Siswan Drainage Basin, Punjab (India) using Geographical Information System

In present study the morphometric analysis Siswan Nadi watershed is carried using GIS technique. Detailed drainage map is prepared from SOI toposheets. This drainage map is used for the morphometric analysis the watershed. Geographical Information System (GIS) has proved to be an efficient tool in delineation of drainage pattern and water resources management and its planning. GIS technique is adopted for the identification and analysis of morphological features and their properties of the Siswan River Basin area of Punjab, India. The basin morphometric parameters such as linear and aerial aspects of the river basin were determined and computed. It is 5 th order drainage basin and drainage pattern mainly in subdendritic to dendritic type with moderate drainage texture. High bifurcation ratio of the watershed indicates its strong structural control on the drainage. It is observed that the drainage density value is high which indicates the basin is highly impermeable subsoil and sparse vegetative cover. The circularity ratio value reveals that the basin is strongly elongated and highly permeable homogenous geologic materials. This study would help the local people to utilize the resources for sustainable development of the basin area.
The two synthetic cannabinoid compounds 4′‐F‐CBD and HU‐910 efficiently restrain inflammatory responses of brain microglia and astrocytes

To study the anti‐inflammatory potential of the two synthetic cannabinoids 4′‐F‐CBD and HU‐910, we used post‐natal brain cultures of mouse microglial cells and astrocytes activated by reference inflammogens. We found that 4′‐F‐CBD and HU‐910 efficiently curtailed the release of TNF‐α, IL‐6, and IL‐1β in microglia and astrocytes activated by the bacterial Toll‐Like Receptor (TLR)4 ligand LPS. Upon LPS challenge, 4′‐F‐CBD and HU‐910 also prevented the activation of phenotypic activation markers specific to microglia and astrocytes, that is, Iba‐1 and GFAP, respectively. In microglial cells, the two test compounds also efficiently restrained LPS‐stimulated release of glutamate, a non‐cytokine inflammation marker for these cells. The immunosuppressive effects of the two cannabinoid compounds were concentration‐dependent and observable between 1 and 10 μM. These effects were not dependent on cannabinoid or cannabinoid‐like receptors. Both 4′‐F‐CBD and HU‐910 were also capable of restraining the inflammogenic activity of Pam3CSK4, a lipopeptide that activates TLR2, and of BzATP, a prototypic agonist of P2X7 purinergic receptors, suggesting that these two cannabinoids could exert immunosuppressive effects against a variety of inflammatory stimuli. Using LPS‐stimulated microglia and astrocytes, we established that the immunosuppressive action of 4′‐F‐CBD and HU‐910 resulted from the inhibition of ROS produced by NADPH oxidase and subsequent repression of NF‐κB‐dependent signaling events. Our results suggest that 4′‐F‐CBD and HU‐910 may have therapeutic utility in pathological conditions where neuroinflammatory processes are prominent.
Experiences and perspectives of healthcare professionals, patients and caregivers toward the serious illness conversation guide: protocol for a qualitative meta-synthesis

Introduction Exploring the experiences and perspectives of healthcare professionals, patients and caregivers toward serious illness conversations based on the Serious Illness Care Program is vital for improving communication with patients who are seriously ill, as has been shown in previous studies. However, few studies have carried out a systematic review to examine common themes, strengthen conclusions and identify gaps in the literature, the findings of which could help steer further research, policies and practice to improve more timely and person-centred conversations about the values and priorities of patients with serious illnesses. The objective of this qualitative meta-synthesis is to explore how healthcare professionals, patients and caregivers described their own experiences of the processes of serious illness communication through a secondary analysis of published qualitative data. Methods and analysis Meta-aggregation will be used to conduct a systematic review of qualitative studies. We conducted an initial search on 10 October 2023; papers published in English will be searched using electronic databases, including PubMed (MEDLINE), Web of Science, Embase, Ovid and CINAHL. Studies that satisfy the eligibility criteria will be evaluated for methodological quality using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Qualitative Research. The meta-aggregative review will consist of the following: (1) extraction of findings of all included studies; (2) categorisation of the findings, with at least two findings per category; and (3) synthesis of one or more findings from at least two categories. Study eligibility screening, data extraction, analysis and JBI Critical Appraisal Checklist and Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research assessments will be undertaken independently by two authors. Ethics and dissemination Secondary data analysis of published literature does not require ethical approval. The results will be disseminated in peer-reviewed journals and presented in conference papers and elsewhere. PROSPERO registration number CRD42022330859.
Constraints on upper plate deformation in the Nicaraguan subduction zone from earthquake relocation and directivity analysis

In the Nicaraguan segment of the Central American subduction zone, bookshelf faulting has been proposed as the dominant style of Caribbean plate deformation in response to oblique subduction of the Cocos plate. A key element of this model is left‐lateral motion on arc‐normal strike‐slip faults. On 3 August 2005, a Mw 6.3 earthquake and its extensive foreshock and aftershock sequence occurred near Ometepe Island in Lake Nicaragua. To determine the fault plane that ruptured in the main shock, we relocated main shock, foreshock, and aftershock hypocenters and analyzed main shock source directivity using waveforms from the TUCAN Broadband Seismic Experiment. The relocation analysis was carried out by applying the hypoDD double‐difference method to P and S onset times and differential traveltimes for event pairs determined by waveform cross correlation. The relocated hypocenters define a roughly vertical plane of seismicity with an N60°E strike. This plane aligns with one of the two nodal planes of the main shock source mechanism. The directivity analysis was based on waveforms from 16 TUCAN stations and indicates that rupture on the N60°E striking main shock nodal plane provides the best fit to the data. The relocation and directivity analyses identify the N60°E vertical nodal plane as the main shock fault plane, consistent with the style of faulting required by the bookshelf model. Relocated hypocenters also define a second fault plane that lies to the south of the main shock fault plane with a strike of N350°E–N355°E. This fault plane became seismically active 5 h after the main shock, suggesting the influence of stresses transferred from the main shock fault plane. The August 2005 earthquake sequence was preceded by a small eruption of a nearby volcano, Concepción, on 28 July 2005. However, the local seismicity does not provide evidence for earthquake triggering of the eruption or eruption triggering of the main shock through crustal stress transfer.
Emerging innovations and advancements in the treatment of extremity and truncal soft tissue sarcomas

In this special edition update on soft tissue sarcomas (STS), we cover classifications, emerging technologies, prognostic tools, radiation schemas, and treatment disparities in extremity and truncal STS. We discuss the importance of enhancing local control and reducing complications, including the role of innovative imaging, surgical guidance, and hypofractionated radiation. We review advancements in systemic and immunotherapeutic treatments and introduce disparities seen in this vulnerable population that must be considered to improve overall patient care.
A Global Overview of Missed Nursing Care During the COVID-19 Pandemic: A Systematic Review

The coronavirus disease 2019 (COVID-19) pandemic has placed unparalleled pressure on many countries’ healthcare systems, impacting the delivery of health and nursing care services. Despite the growing number of missed care studies during the pandemic, a broader perspective is essential when designing theory-driven strategies to improve nursing care delivery. This review aimed to synthesize evidence of missed nursing care during the COVID-19 pandemic in acute care settings through a systematic review and narrative synthesis. An electronic search of articles published since the emergence of the pandemic was conducted using 5 databases (Scopus, PubMed, Web of Science, CINAHL, and PsycINFO). A total of 470 articles were identified during the initial search, and 10 articles were included in the review. The sample sizes of the studies ranged from 37 to 536 nurses. Results of the content analysis were grouped into 5 categories: (1) prevalence of missed care, (2) frequency of missed care, (3) reasons for missed care, (4) nurses’ and organizational variables contributing to missed care, and (5) work environment elements contributing to missed care. The review’s findings revealed a shift in the nature of missed nursing care during the pandemic, with an emphasis on nursing care tasks vital for the recovery of patients with COVID-19. Despite the unique circumstances brought about by the pandemic, an inadequate nursing workforce continued to be identified as the primary reason for missed care, consistent with the pre-pandemic period.
Formulation and evaluation of atovaquone-loaded macrophage-derived exosomes against Toxoplasma gondii: in vitro and in vivo assessment

ABSTRACT This study aimed to prepare and assess atovaquone (ATQ)-loaded exosomes (EXO-ATQ) against Toxoplasma gondii to improve their therapeutic activities on acute and chronic phases of murine toxoplasmosis. Exosomes were isolated from a mouse macrophage cell line (J774A.1). The isolated exosomes were loaded with ATQ (EXO-ATQ), applying the co-incubation method. In vitro efficacy of EXO-ATQ against T. gondii infection was assessed in Vero cell culture. An in vivo experiment was carried out in BALB/c mice infected with RH (acute strain) and Tehran (chronic strain) of T. gondii, followed by treatment with EXO-ATQ. Their survival time and parasite load were compared with that in the suspension of ATQ (S-ATQ) as a positive control group. The in vitro study showed that exosomes improved the efficacy of ATQ, and EXO-ATQ significantly reduced intracellular proliferation of T. gondii tachyzoites compared to S-ATQ (P ≤ 0.05). In acute experimental toxoplasmosis, the mice treated with EXO-ATQ showed a significant reduction in tachyzoites count of the peritoneal cavity and a longer survival time (P ≤ 0.05). Furthermore, EXO-ATQ administration significantly decreased the mean number (97.3% cyst reduction) and the average size of the brain cysts of chronically infected mice with T. gondii, Tehran strain (P ≤ 0.05). Besides, the decrease in cyst numbers was confirmed by the down-regulation of BAG1 using a real-time PCR assay. Our results implied that exosomes have the potential to be used as an efficient drug delivery system, and the loading of ATQ into the exosomes ameliorates the effect of ATQ against T. gondii. This study suggests a new strategy for improving the effectiveness of ATQ against acute and chronic phases of T. gondii. IMPORTANCE This study is the first of its kind that suggests exosomes as a nano-carrier loaded with atovaquone (ATQ), which could be considered as a new strategy for improving the effectiveness of ATQ against acute and chronic phases of Toxoplasma gondii. This study is the first of its kind that suggests exosomes as a nano-carrier loaded with atovaquone (ATQ), which could be considered as a new strategy for improving the effectiveness of ATQ against acute and chronic phases of Toxoplasma gondii.
Olympia Interstadial: vegetation, landscape history, and paleoclimatic implications of a mid-Wisconsinan (MIS3) nonglacial sequence from southwest British Columbia, Canada

Lithostratigraphic, 14C, and palynologic analyses of peat and silty peat at three nearby sites reveal a 25 000 year vegetation and climate history of the Olympia Interstade for the Fraser Lowland, British Columbia, 300 km within the southern limit of the Cordilleran Ice Sheet. At Lynn Valley, Polypodiaceae fern spores and nonarboreal pollen dominate >47.8 14C ka BP, reflecting unstable and cold landscapes. A Pinus–Poaceae zone follows, representing pine parkland and cool dry climate. Fluctuating values of Picea and Tsuga mertensiana pollen at Lynn and Seymour valleys and Port Moody characterize most of the Olympia Interstade during local peat deposition in Cyperaceae and Myrica wetlands until about 26.7 14C ka BP under a cool and moist climate. A brief Pinus – Tsuga heterophylla zone at Lynn Valley 44–39 14C ka BP suggests a climatic optimum. A Poaceae–Artemisia assemblage and deposition of silty sand after 26.7 14C ka BP reflect cooling and drying after which a unique Lycopodium assemblage at Lynn Valley.
Image‐guided core‐needle or surgical biopsy for neuroblastoma diagnosis in children: A systematic review and meta‐analysis from the International Society of Pediatric Surgical Oncology (IPSO)

Image‐guided core‐needle biopsy (IGCNB) is a widely used and valuable clinical tool for tissue diagnosis of pediatric neuroblastoma. However, open surgical biopsy remains common practice even if children undergo more invasive and painful procedures. This review aims to determine the diagnostic accuracy and safety of IGCNBs in pediatric patients with neuroblastoma.
Digestibility and nitrogen balance of goats on high and low protein rations supplemented with a commercial tannin feed-additive

ABSTRACT Despite the increasing importance of goat production in response to high demand for their products and their relative robustness to environmental stressors, and in contrast to other ruminant species, little data is available on how tannin extract feeding affects their feed intake, nutrient digestion and nitrogen (N) metabolism. Therefore, a trial in Oman investigated the respective variables by using a commercial tannin feed additive. In a 4 (treatments) x 3 (periods) x 2 (animals) Youden square, two weaned Batinah bucks each were fed a high or low protein diet of Rhodes grass hay and crushed barley grain, with or without the addition of a chestnut and quebracho tannin extract at 2 g/kg metabolic weight. Feed offered, feed refused and faeces and urine excreted were quantified to determine diet digestibility, total N excretion, N retention and rumen microbial protein synthesis (MPS). Due to their young age and low live weight, feed intake of goats was relatively low. Crude protein level and tannin addition had no statistically significant effect on dry matter (DM) and N intake, DM digestibility, N excretion in faeces and urine, as well as MPS. In consequence, no benefit of tannin feeding could be confirmed for the goats’ N retention, irrespective of diet composition. These results indicate, on one hand, an effective neutralisation of the tested tannin extract along the gastrointestinal tract of goats, but on the other hand, that stimulation of MPS or N retention by tannins cannot be evidenced when diet components are present that simultaneously release energy and protein, as is the case with barley.
Targeting the lipid kinase PIKfyve upregulates surface expression of MHC class I to augment cancer immunotherapy

Significance Immunotherapies have shown clinical success in certain indications, but many patients fail to respond to treatment and exhibit resistance. Despite tremendous efforts to solve this clinical challenge, developing therapeutic strategies to improve response to immunotherapies remains a pressing clinical problem. The lack of a thorough understanding of the molecular processes that cancer cells adopt to downregulate MHC-I (major histocompatibility complex class I) to evade antitumor immunity has hindered the development of a rational combination treatment for overcoming resistance to immunotherapies. This study identifies therapeutic targeting of PIKfyve as a strategy to upregulate surface expression of MHC-I in cancer cells and thus enhance response to immunotherapies across various cancer types, including those such as pancreatic cancer that are often unresponsive to immunotherapies.
Association between chronotype and metabolic-associated fatty liver disease in employed adults: A longitudinal study in Southwestern China

ABSTRACT The circadian system is an essential physiological regulator of mammals, and sleep chronotype may be associated with the risk of metabolic disorders. However, evidence regarding the role of sleep chronotype in the development of metabolic-associated fatty liver disease (MAFLD) is scarce, particularly in employed adults. We conducted a longitudinal study of 1,309 employed adults in Southwestern China with a five-year follow-up from 2017 to 2021. MAFLD was assessed by the presence of hepatic steatosis using abdominal ultrasonography, overweight/obese status, diabetes mellitus, metabolic dysregulation, or elevation of high-sensitivity C-reactive protein. Chronotype was assessed by the Morning and Evening Questionnaire-5 (MEQ-5). The logistic random effects model was applied to analyze the 5-year panel data to estimate the association between chronotype and MAFLD, and the potential effect modification of demographics on such association. The MAFLD prevalence of participants was 38.6% at baseline and showed an increasing trend during follow-up (p for trends < 0.05). Compared with morning chronotype, evening chronotype was positively associated with MAFLD (OR = 2.19, 95%CI: [1.09, 4.40]) after controlled for covariates. Age, sex, ethnicity, and educational level did not modify the association between chronotype and MAFLD. These findings suggest that improving circadian rhythms could reduce the risk of MAFLD and chronic disease burden among employed adults.