Miracle-dz/UniFAR-FTUs huggingface dataset:
B Cell Activation and Plasma Cell Differentiation Are Promoted by IFN-λ in Systemic Lupus Erythematosus

Type I IFN is essential for viral clearance but also contributes to the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE), via aberrant nucleic acid–sensing pathways, leading to autoantibody production. Type III IFN (IFN-λ) is now appreciated to have a nonredundant role in viral infection, but few studies have addressed the effects of IFN-λ on immune cells given the more restricted expression of its receptor primarily to the epithelium. In this study, we demonstrate that B cells display a prominent IFN gene expression profile in patients with lupus. Serum levels of IFN-λ are elevated in SLE and positively correlate with B cell subsets associated with autoimmune plasma cell development, including CD11c+T-bet+CD21− B cells. Although B cell subsets express all IFN receptors, IFNLR1 strongly correlates with the CD11c+CD21− B cell expansion, suggesting that IFN-λ may be an unappreciated driver of the SLE IFN signature and B cell abnormalities. We show that IFN-λ potentiates gene transcription in human B cells typically attributed to type I IFN as well as expansion of T-bet–expressing B cells after BCR and TLR7/8 stimulation. Further, IFN-λ promotes TLR7/8-mediated plasmablast differentiation and increased IgM production. CD11c+ B cells demonstrate IFN-λ hyperresponsive signaling compared with other B cell subsets, suggesting that IFN-λ accelerates plasma cell differentiation through this putative extrafollicular pathway. In summary, our data support type III IFN-λ as a cytokine promoting the Ab-secreting cell pool in human viral and autoimmune disease. Key Points A type I IFN transcriptional profile is upregulated in SLE B cells. Human B cells express type I IFN genes in response to IFN-λ (type III IFN). IFN-λ may enhance TLR7-mediated B cell activation and PC differentiation in SLE.
Commentary - Association of metformin use among diabetics and the incidence of primary open-angle glaucoma – The Chennai Eye Disease Incidence Study

Glaucoma is one of the leading causes of blindness worldwide, with primary open-angle glaucoma (POAG) being the most common subtype. Progression of POAG is influenced by risk factors such as increased intraocular pressure (IOP), ancestry, family history, and age. Diabetes mellitus (DM) has emerged as a major global health problem in the recent past. DM is considered a risk factor for the development and progression of glaucoma. [1] Recent studies have shown that the diabetic population has a greater risk of developing POAG. Patients with DM have an increased corneal thickness, increased corneal stiffness, altered corneal hysteresis, and compromised vascular autoregulation at the level of optic nerve head. All these factors contribute to the progression of glaucoma. [1] Certain mechanisms are postulated to be common to the pathogenesis of glaucoma and diabetic retinopathy (DR) in patients with DM. Hyperglycemia in DM causes increased glycation of lipids, abnormalities in lipid metabolism, vascular dysregulation, upregulation of nitric oxide levels, and increased oxidative stress. These factors lead to promotion of cellular apoptosis and loss of retinal ganglion cells (RGCs), contributing to development and progression of glaucoma. The proposed mechanisms common to the development of glaucoma and DR also include an increase in inflammatory cytokines, increased protein kinase C levels, increased glial cell dysfunction, and retrograde axonal transport. Moreover, overexpression of matrix metalloprotease-9 has also been postulated to be associated with structural optic nerve head changes in patients with DM. [1] An increase in RGC apoptosis and retinal nerve fiber loss are the key structural findings seen in glaucoma as well as DR. Studies have shown that the loss of RGCs in glaucoma is specific to the magnocellular and parvocellular pathways, which is also seen in DR.[1,2] As such, the strong association between DM and glaucoma is now well documented in the literature.
Regulatory role of folic acid in biomass production and physiological activities of Coriandrum sativum L. under irrigation regimes

Abstract Water deficiency represents the major cause that affects agricultural output globally. A water-saving strategy was introduced by using water deficit conditions and growth regulators. Foliar application of folic acid (FA) has been found suitable not only for drought stress alleviation in Coriandrum. sativum but also beneficial for improvement in growth and yield under water deficit circumstances. The current study examined the potential roles of FA under drought to improve C. sativum growth. The C. sativum variety was subjected to three levels of irrigation regimes (IR100, IR75, and IR50) with or without the foliar application of FA concentrations. The results showed that the application of 50 mM FA was very effective in improving the plant height, number of secondary branches, number of umbels, and leaf area index in comparison to FA water deficit treated plants alone under IR75 and IR50. Similarly, physiological and gaseous exchange parameters also upgraded that improved the economic yield (81 and 163%), fresh biomass (28 and 131%), dry biomass (63 and 66%), and harvest index (10 and 58%) of C. sativum plants under irrigation regimes IR75 and IR50 compared to their non-treated FA plants. All the observed growth parameters showed a positive correlation with each other vs. LAI except a weight of 1,000. Overall, this study indicated that foliar-applied 50 mM FA may be used as an alternate strategy to improve C. sativum performance in biomass production and can play a key part in solving difficulties caused by drought stress on plant development. Novelity statement Folic acid is a convenient, affordable growth regulator to increase the efficiency of plants and preserve their nutrients. As far as abiotic stress alleviation is concerned, we have not found sufficient literature explaining the possible role of folic acid in the reduction of water-deficit stress in plants. The role of folic acid in the orchestration of metabolic activities in Coriandrum sativum L. under water deficit conditions has never been documented. This study will open new avenues discussing the role of FA in the enhancement of crop production in drought conditions.
Short-chain fatty acids produced by Ruminococcaceae mediates α-Linolenic acid promote intestinal stem cells proliferation.

SCOPE The proliferation and differentiation of intestinal stem cells (ISCs) are the basis of intestinal renewal and regeneration, and gut microbiota plays an important role in it. Dietary nutrition has the effect of regulating the activity of ISCs, however, the regulation effect of α-linolenic acid (ALA) has seldom been reported. METHODS AND RESULTS After intervening mice with different doses of ALA for 30 days, we found that ALA (0.5 g/kg) promoted small intestinal and villus growth by activating the Wnt/β-catenin signaling pathway to stimulate the proliferation of ISCs. Furthermore, ALA administration increased the abundance of the Ruminococcaceae and Prevotellaceae, and promoted the produce of short-chain fatty acids (SCFAs). Subsequent fecal transplantation and antibiotic experiments demonstrated that ALA on the proliferation of ISCs are gut microbiota dependent, among them the functional microorganism may be derived from Ruminococcaceae. Administration of isobutyrate showed a similar effect to ALA in terms of promoting ISCs proliferation. Furthermore, ALA mitigated 5-fluorouracil-induced intestinal mucosal damage by promoting ISCs proliferation. CONCLUSION These results indicate that SCFAs produced by Ruminococcaceae mediates ALA promote ISCs proliferation by activating Wnt/β-catenin signaling pathway, and suggest the possibility of ALA as a prebiotic agent for the prevention and treatment of intestinal mucositis. This article is protected by copyright. All rights reserved.
Knowledge and Beliefs of Cancer Risk Factors and Early Cancer Symptoms in Lebanon: A Cross-sectional Survey Among Adults in the Community

Background Lebanon has an increasing cancer burden. Sufficient knowledge of cancer risk factors and early cancer symptoms can help lower cancer burden by facilitating primary prevention and early diagnosis. This study (i) assessed Lebanese adults’ knowledge and beliefs of cancer risk factors and early cancer symptoms, (ii) analyzed whether knowledge was correlated with personal behavior, and (iii) assessed the presence of barriers that keep knowledge from turning into healthcare seeking behavior. Methods We performed a cross-sectional survey in the Lebanese adult population, consisting of a questionnaire administered during face-to-face interviews on a community-based non-probability sample (n = 726) that was frequency matched to national government estimates on age, level of education and gender. Results Recognition was high for carcinogens and protective factors (75%), but low for neutral factors (22%) which were often seen as carcinogenic. A quarter of participants (27.8%) could not name any early warning signs. For some risk factors, high knowledge scores were correlated with low-risk behavior, but this was not the case for cigarette smoking. The most frequent barriers for not seeking timely care were financial (57.0%) fear of finding illness (53.7%), and having other things to worry about (42.4%). Conclusion This study revealed important knowledge gaps which are likely to hamper primary prevention and early diagnosis. However, we also showed that high knowledge of risk was not always correlated with low-risk behavior. This, together with the barriers we found that kept people from seeking timely health care, emphasizes that efforts to lower cancer burden should not only focus on increasing knowledge.
Beneficial worm allies warn plants of parasite attack below‐ground and reduce above‐ground herbivore preference and performance

Antagonistic interactions among different functional guilds of nematodes have been recognized for quite some time, but the underlying explanatory mechanisms are unclear. We investigated responses of tomato (Solanum lycopersicum) to two functional guilds of nematodes—plant parasite (Meloidogyne javanica) and entomopathogens (Heterorhabditis bacteriophora, Steinernema feltiae below‐ground, and S. carpocapsae)—as well as a leaf mining insect (Tuta absoluta) above‐ground. Our results indicate that entomopathogenic nematodes (EPNs): (1) reduced root knot nematode (RKN) infestation below‐ground, (2) reduced herbivore (T. absoluta) host preference and performance above‐ground, and (3) induced overlapping plant defence responses by rapidly activating polyphenol oxidase and guaiacol peroxidase activity in roots, but simultaneously suppressing this activity in above‐ground tissues. Concurrently, we investigated potential plant signalling mechanisms underlying these interactions using transcriptome analyses. We found that both entomopathogens and plant parasites triggered immune responses in plant roots with shared gene expression. Secondary metabolite transcripts induced in response to the two nematode functional guilds were generally overlapping and showed an analogous profile of regulation. Likewise, we show that EPNs modulate plant defence against RKN invasion, in part, by suppressing active expression of antioxidant enzymes. Inoculations of roots with EPN triggered an immune response in tomato via upregulated phenylpropanoid metabolism and synthesis of protease inhibitors in plant tissues, which may explain decreased egg laying and developmental performance exhibited by herbivores on EPN‐inoculated plants. Furthermore, changes induced in the volatile organic compound‐related transcriptome indicated that M. javanica and/or S. carpocapsae inoculation of plants triggered both direct and indirect defences. Our results support the hypothesis that plants “mistake” subterranean EPNs for parasites, and these otherwise beneficial worms activate a battery of plant defences associated with systemic acquired resistance and/or induced systemic resistance with concomitant antagonistic effects on temporally co‐occurring subterranean plant pathogenic nematodes and terrestrial herbivores.
Comparison of anatomical and functional outcomes of vitrectomy with internal limiting membrane peeling in recalcitrant diabetic macular edema with and without traction in Indian patients

Purpose: To study and compare the outcomes of pars plana vitrectomy (PPV) with the internal limiting membrane (ILM) peeling in the eyes with recalcitrant diabetic macular edema (DME) with and without vitreomacular traction. Methods: A comparative prospective interventional study was undertaken in which group 1 included 45 eyes of 45 patients with DME with vitreomacular tractional component and group 2 included 45 eyes of 45 patients with recalcitrant DME without a tractional component. Both groups underwent standard PPV with ILM peeling. All the patients were followed up for a minimum of 6 months. The parameters evaluated were changes in the best-corrected visual acuity (BCVA), central macular thickness (CMT), multifocal electroretinogram (mfERG) parameters, and occurrence of any intraoperative/postoperative surgical complication. Results: The mean CMT improved significantly from 540.6 and 490.2 μm at the baseline to 292.5 and 270.6 μm at 6 months in groups 1 and 2, respectively (P < 0.001). The mean BCVA logMAR improved from 0.78 ± 0.21 to 0.62 ± 0.22 in group 1 and 0.84 ± 0.19 to 0.65 ± 0.21 in group 2 at 6 months follow-up which was not statistically significant. The improvement in the mfERG was seen in group 2 as a significant increase in P1 wave amplitude in ring 2 (2–5°) (P < 0.004) and a significant decrease in P 1 wave implicit time in ring 1 (central 2°) (P < 0.001). None of the eyes suffered from the loss of BCVA or any major surgical complication in either group. Conclusion: PPV in recalcitrant DME provides good anatomical outcomes and the results are comparable in DME with and without a tractional component.
Impact of systemic parameters before commencing anti-vascular endothelial growth factor therapy for diabetic macular edema – Pan-Indian survey of retina specialists

Purpose: Intravitreal anti-vascular endothelial growth factor (VEGF) injection therapy has emerged as the mainstay of treatment in the management of diabetic macular edema (DME) today. Various systemic risk factors have to be considered before initiating anti-VEGF therapy. The aim of our study was to form a consensus on various systemic factors to consider before starting anti-VEGF therapy for DME. Methods: A questionnaire was created and sent across to various retina specialists across India. A Google™ form with various questions pertaining to what systemic parameters would one consider before giving anti-VEGF therapy for DME was sent to each of them by email/WhatsApp™/direct telephonic interview. Results: Of the 650 retina specialists contacted, 322 responded to the questionnaire. There was no difference in responses between private and institutional practitioners. The majority would consider RBS (85%), HbA1c (61%), blood pressure (63%), and renal function (57%) as a routine before administering the anti-VEGF injection, while the majority would not consider hemoglobin (63%) or lipid profile (55%) of the patient as a routine practice prior to administering the injection. Conclusion: In our study, most VR specialists prefer to consider RBS, HbA1c, BP, and renal profile (creatinine) routinely prior to anti-VEGF injection. We suggest that it is important to consider blood pressure control, glycemic control, HbA1c, Hb, lipid profile, and renal profile (UACR, eGFR, and creatinine) prior to anti-VEGF therapy in all diabetic patients and to discuss the need for statins in patients with dyslipidemias with the physician.
Exploring the Intersection Between Academic and Professional Practice During the COVID-19 Pandemic: Undergraduate and Graduate Nursing Students’ Experiences

Background The coronavirus disease-2019 (COVID-19) pandemic has implications for students who are also nurses. Purpose and Methods This qualitative descriptive study used a practice development approach to explore the intersection between academic and professional work experiences for undergraduate Post-Diploma Registered Practical Nurses bridging to Registered Nurse Bachelor of Science in Nursing students and Master of Nursing graduate nursing students during the first wave of the COVID-19 pandemic. The study incorporated critical aesthetic reflections that focused on the personal and aesthetic ways of knowing, as a data collection approach and knowledge dissemination strategy. Results Analysis of the narrative component of participants’ reflections revealed the following themes: sensing a “call to duty,” experiencing a myriad of emotions, shifting societal and individual perceptions of nursing, and learning in an uncertain environment. Conclusions The results of the study can inform educational strategies and academic policies to support this unique nursing population, who are frontline practitioners as well as student learners.
Bowel Obstruction After Sacrocolpopexy: A Case Series

Objectives Bowel obstruction after sacrocolpopexy (SC) can cause significant morbidity. The aim of this study was to delineate clinical and surgical factors associated with bowel obstruction after SC and to describe its presentation, management, and sequelae. Methods We performed a retrospective case series of patients who underwent open, laparoscopic, or robotic SC within a large health maintenance organization and a single academic medical center between January 1, 2009, and December 31, 2019. Results Of 3,231 patients who underwent SC, 32 (1.0%) experienced a bowel obstruction. Sacrocolpopexy was performed laparoscopically or robotically in 19 (59.4%) and abdominally in 13 (40.6%). The mean time to bowel obstruction was 1.9 years (SD, 2.5; range, 3 days to 8.8 years). In patients who experienced bowel obstruction, medical management was undertaken in 19 (61.3%) cases. Eight of the 13 (61.5%) surgically managed cases underwent bowel resection, and 3 cases (23.1%) reported partial mesh excision. Recurrent obstruction was seen in 2 (10.5%) of the medically managed and 2 (15.4%) of the surgically managed cases. Conclusions Bowel obstruction is a rare complication of SC and our rate of at least 1.0% corroborates those in the literature. Obstruction occurs from days to years after SC. Nonsurgical management was effective in most cases, with low rates of recurrent obstruction. In surgically managed cases, the majority included bowel resection or mesh excision; however, mesh excision was not associated with a subsequent identifiable procedural intervention for recurrent prolapse. These data inform patient counseling and surgical planning before SC and aid in diagnosis and management of bowel obstruction after SC.
Antifungal and synergistic activities of some selected essential oils on the growth of significant indoor fungi of the genus Aspergillus

Abstract The study aimed to assess the antifungal activity of twenty–five essential oils (EOs) and the potential synergistic activity of the most effective EOs against significant indoor fungi of the genus Aspergillus [A. fumigatus (KBio–122), A. flavus (KBio–134), A. terreus (KBio–145) and A. niger (KBio–202)]. The chemical composition of all EOs was evaluated by the gas chromatography coupled with mass spectrometry (GC/MS) and gas chromatography with flame ionization detector (GC–FID) analysis. The antifungal susceptibility of EOs was evaluated by using the broth microdilution method. The most effective EOs were selected to determine the minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) at a concentration range from 256 to 0.125 μg/mL. For the synergistic activities, the most effective EOs were tested using the chessboard pattern. The most sensitive strain to treatments with essential oils alone and in the combination of EOs was A. flavus (KBio–134). The chessboard assay showed that combinations of lemongrass and thyme EOs proved the most potent synergistic antifungal activity (FICI = 0.1875) against A. fumigatus (KBio–122). The synergy displayed by a combination of some EOs may be used to control fungal growth or increasing resistance to available synthetic antifungals, consequently permitting the reduction of their most active doses.
Long non‐coding RNA NEAT1 and its targets (microRNA‐21 and microRNA‐125a) in rheumatoid arthritis: Altered expression and potential to monitor disease activity and treatment outcome

The present study aimed to explore the association of long non‐coding RNA nuclear‐enriched abundant transcript 1 (lnc‐NEAT1) with inflammation, disease activity, treatment outcome, and its targets (microRNA [miR]‐21 and miR‐125a) in patients with rheumatoid arthritis (RA).
Replication stress response defects are associated with response to immune checkpoint blockade in nonhypermutated cancers

Description Endogenous and induced replication stress response defects promote tumor immunogenicity via generation of cytosolic single-stranded DNA. Predicting ICB response Immune checkpoint blockade (ICB) benefits a subset of patients with cancer, but predicting who will respond is difficult, especially for nonhypermutated cancers. Here, McGrail and colleagues found that a replication stress response (RSR) defect gene signature was associated with ICB response in 12 cohorts of patients with nonhypermutated cancers. They showed that alterations of RSR affected response to ICB in mouse models of breast and renal cell cancer, with RSR deficiency resulting in the accumulation of immunostimulatory cytosolic single-stranded DNA and improved ICB response. These findings indicate a way to predict response to ICB in nonhypermutated cancers and suggest that induction of RSR defects might allow more patients to benefit from ICB. Treatment with immune checkpoint blockade (ICB) has resulted in durable responses for a subset of patients with cancer, with predictive biomarkers for ICB response originally identified largely in the context of hypermutated cancers. Although recent clinical data have demonstrated clinical responses to ICB in certain patients with nonhypermutated cancers, previously established ICB response biomarkers have failed to accurately identify which of these patients may benefit from ICB. Here, we demonstrated that a replication stress response (RSR) defect gene expression signature, but not other proposed biomarkers, is associated with ICB response in 12 independent cohorts of patients with nonhypermutated cancer across seven tumor types, including those of the breast, prostate, kidney, and brain. Induction or suppression of RSR deficiencies was sufficient to modulate response to ICB in preclinical models of breast and renal cancers. Mechanistically, we found that despite robust activation of checkpoint kinase 1 signaling in RSR-deficient cancer cells, aberrant replication origin firing caused exhaustion of replication protein A, resulting in accumulation of immunostimulatory cytosolic DNA. We further found that deficient RSR coincided with increased intratumoral dendritic cells in both mouse cancer models and human tumors. Together, this work demonstrates that the RSR defect gene signature can accurately identify patients who may benefit from ICB across numerous nonhypermutated tumor types, and pharmacological induction of RSR defects may further expand the benefits of ICB to more patients.