Miracle-dz/UniFAR-FTUs huggingface dataset:
Case Report: Effective Treatment for Acute Chlorpyrifos Poisoning Complicated by a Non-ST-Segment Elevation Myocardial Infarction

Background: Acute myocardial infarction (AMI) is a rare complication of acute organophosphorus pesticide poisoning. Although chlorpyrifos has been widely used as an organophosphate insecticide, a few cases of AMI complicated by chlorpyrifos poisoning have been reported thus far. Hence, a suitable treatment strategy remains to be explored. Case Presentation: Based on the clinical manifestations, medical history, results of an auxiliary examination, and serum biomarkers, a 65-year-old male farmer with complaints of nausea, vomiting, chest tightness, and pain was clearly diagnosed as having a severe chlorpyrifos self-poisoning with acute non-ST-segment elevation MI. Because the patient and his family confirmedly refused a coronary intervention, conservative treatment was used instead. It should be noted that there were some conflicts of the management for chlorpyrifos poisoning and AMI. Although rapid atropinization would contribute to the relief of muscarinic symptoms, it would also lead to an increased heart rate and myocardial oxygen consumption in AMI. Furthermore, the reduction of platelet aggregation, which is necessary for coronary recanalization of an AMI patient, is known to aggravate the gastrointestinal injury caused by poisoning. In this case, these conflicts were properly addressed, which led to an excellent effect and prognosis of the patient. Conclusions: To our knowledge, this is the first case report of acute chlorpyrifos poisoning with AMI. It is emphasized that patients with chest pain or coronary heart disease should be treated with atropine more cautiously because of the possible AMI. Moreover, proper resolution of conflicts in the management for chlorpyrifos poisoning and AMI played contributing roles in patient improvement.
Combined Effects of Vitamin D Status, Renal Function and Age on Serum Parathyroid Hormone Levels

Background Vitamin D status and renal function are well-known independent predictors of serum parathyroid hormone (PTH) levels. We aimed to describe the combined effects of 25-hydroxy vitamin D (25(OH)D), glomerular filtration rate (GFR) and age on serum PTH levels across the whole clinical spectrum. Methods We retrieved from our endocrinology center database all PTH measurement between 2012 and 2020 for which a simultaneous measurement of serum 25(OH)D, calcium and creatinine was available. Age, sex and diagnosis were available for all subjects. Intact PTH was measured using the same electrochemiluminescence assay. Results There were 6,444 adults and 701 children without a diagnosis of hyper- or hypoparathyroidism or abnormal serum calcium levels. In adults with 25(OH)D≥12 ng/mL multiple regression models showed that serum PTH was negatively correlated with both 25(OH)D and GFR. Regression (-0.68 and -1.59 vs. -0.45 and -0.22 respectively), partial correlation (-0.16 and -0.35 vs. -0.12 and -0.10 respectively) and determination coefficients (0.14 vs. 0.031) were higher in CKD than in normal renal function. In subjects with 25(OH)D<12 ng/mL, GFR was the only significant predictor in those with CKD (β-coefficient=-2.5, r=-0.55) and 25(OH)D was the only significant predictor in those with normal renal function (β-coefficient=-2.05, r=-0.11). Increasing age was associated with higher PTH levels only in those with normal renal function and 25(OH)D≥12 ng/mL. Conclusions We showed that declining vitamin D and renal function have additive effects on serum PTH in subjects without vitamin D deficiency. In vitamin D deficient subjects this dependency is stronger but is not additive anymore.
Hepatosplenic Protective Actions of Spirulina platensis and Matcha Green Tea Against Schistosoma mansoni Infection in Mice via Antioxidative and Anti-inflammatory Mechanisms

Schistosomiasis, a major parasitic illness, has high morbidity and negative financial effects in subtropical and tropical countries, including Egypt. The present study investigated the therapeutic effects of Spirulina platensis (SP) and matcha green tea (MGT) in Schistosoma mansoni-infected mice combined with tracing their possible antioxidant and anti-inflammatory impacts and their protective potency. A total of 60 Swiss albino mice were randomly allocated into six groups (n = 10): control group (CNT, received normal saline); SP–MGT group [received oral SP (3 g/kg bodyweight/day) plus MGT (3 g/kg bodyweight/day)]; S. mansoni group (infected with S. mansoni cercariae, 100 ± 10/mouse, using the tail immersion method); SP-infected group (infected with S. mansoni and received oral SP); MGT-infected group (received oral MGT after S. mansoni infection); and SP–MGT-infected group (received combined treatment of SP and MGT after S. mansoni infection). Treatment with SP and MGT started 4 weeks after S. mansoni infection and ended 10 weeks after. SP and MGT treatment (SP-infected and MGT-infected groups) and the combined treatment (SP–MGT-infected group) minimized the hepatic damage induced by S. mansoni; circulating alanine aminotransferase and aspartate transaminase decreased, and total protein, albumin, and globulin serum levels increased. The serum level of malondialdehyde significantly declined, and catalase, glutathione peroxidase, superoxide dismutase, and total antioxidant capacity increased in SP-infected, MGT-infected, and SP–MGT-infected groups compared with the infected group. Co-administration of SP and MGT reduced serum cytokine levels (tumor necrosis factor-alpha, interferon-gamma, and interleukin-13) and increased interleukin-10 levels after S. mansoni infection compared with the infected group. Moreover, treatment with SP and/or MGT decreased the number of granulomas in hepatic and splenic tissues compared with the infected group. Collectively, our results suggest that combined SP and MGT treatment is effective for S. mansoni infection. Liver and spleen tissue alterations were improved, the antioxidant systems were stimulated, and the inflammatory response was suppressed. Further research is recommended to investigate the mechanisms of the combined SP and MGT treatment effects to facilitate the development of novel therapies against this disease.
Elucidating Mitochondrial DNA Markers of Ogura-Based CMS Lines in Indian Cauliflowers (Brassica oleracea var. botrytis L.) and Their Floral Abnormalities Due to Diversity in Cytonuclear Interactions

Mitochondrial markers can be used to differentiate diverse mitotypes as well as cytoplasms in angiosperms. In cauliflower, cultivation of hybrids is pivotal in remunerative agriculture and cytoplasmic male sterile lines constitute an important component of the hybrid breeding. In diversifying the source of male sterility, it is essential to appropriately differentiate among the available male sterile cytoplasms in cauliflower. PCR polymorphism at the key mitochondrial genes associated with male sterility will be instrumental in analyzing, molecular characterization, and development of mitotype-specific markers for differentiation of different cytoplasmic sources. Presence of auto- and alloplasmic cytonuclear combinations result in complex floral abnormalities. In this context, the present investigation highlighted the utility of organelle genome-based markers in distinguishing cytoplasm types in Indian cauliflowers and unveils the epistatic effects of the cytonuclear interactions influencing floral phenotypes. In PCR-based analysis using a set of primers targeted to orf-138, 76 Indian cauliflower lines depicted the presence of Ogura cytoplasm albeit the amplicons generated exhibited polymorphism within the ofr-138 sequence. The polymorphic fragments were found to be spanning over 200–280 bp and 410–470 bp genomic regions of BnTR4 and orf125, respectively. Sequence analysis revealed that such cytoplasmic genetic variations could be attributed to single nucleotide polymorphisms and insertion or deletions of 31/51 nucleotides. The cytoplasmic effects on varying nuclear-genetic backgrounds rendered an array of floral abnormalities like reduction in flower size, fused flowers, splitted style with the exposed ovule, absence of nonfunctional stamens, and petaloid stamens. These floral malformations caused dysplasia of flower structure affecting female fertility with inefficient nectar production. The finding provides an important reference to ameliorate understanding of mechanism of cytonuclear interactions in floral organ development in Brassicas. The study paves the way for unraveling developmental biology of CMS phenotypes in eukaryotic organisms and intergenomic conflict in plant speciation.
Heat Treatment of Milk: A Rapid Review of the Impacts on Postprandial Protein and Lipid Kinetics in Human Adults

Background: Most milk consumed by humans undergoes heat treatment to ensure microbiological safety and extend shelf life. Although heat treatment impacts the structure and physiochemical properties of milk, effects on nutrient absorption in humans are unclear. Therefore, a rapid review was performed to identify studies conducted on healthy human adult subjects that have assessed the impacts of heat treatment of milk on protein and fat digestion and metabolism in the postprandial period (up to 24 h). Methods: Relevant databases (Medline, EMBASE, Cochrane, Scopus) were systematically screened for intervention studies on healthy adult men and women that assessed the impact of consuming heat-treated milk on the postprandial kinetics or appearance in peripheral circulation or urine of ingested proteins and/or lipids. The risk-of-bias assessment tool 2 was used for quality assessment. Results: Of 511 unique database records, 4 studies were included encompassing 6 study treatments (n = 57 participants, 20–68 years). Three studies evaluated pasteurization, two evaluated ultra-high temperature (UHT) treatment, and one evaluated oven-heated milk. Protein and lipid appearances in peripheral blood were reported in two sets of two studies. None of the studies used the same heat treatments and outcome measures, limiting generalization of effects. Protein appearance (ng/mL or area under the curve) (as plasma amino acids - lysine) was reduced when milk was oven-heated for 5 h in one study (n = 7 participants), while the other study reported a reduced retention of dietary N with UHT milk (n = 25 participants). Overall plasma triacylglycerol responses were unaffected by milk heat treatments reported, but plasma fatty acid composition differed. The studies observed higher plasma myristic and palmitic acid abundance with successive heat treatment at 2 h (n = 11 participants; pasteurized) and 4 h (n = 14 participants; UHT) after ingestion; other differences were inconsistent. All studies had moderate-high risk of bias, which should be taken into consideration when interpreting findings. Discussion: This review identified few studies reporting the effects of milk heat treatment on postprandial nutrient responses in adults. Although the findings suggest that milk heat treatment likely affects postprandial protein and lipid dynamics, generalization of the findings is limited as treatments, outcomes, and methods differed across studies. Because of the study variability, and the acute post-prandial nature of the studies, it is also difficult to draw conclusions regarding potential long-term health outcomes. However, the possibility that altered digestive kinetics may influence postprandial protein retention and anabolic use of dietary N suggests heat treatment of milk may impact outcomes such as long-term maintenance of muscle mass.
Increased Resting-State Interhemispheric Functional Connectivity of Posterior Superior Temporal Gyrus and Posterior Cingulate Cortex in Congenital Amusia

Interhemispheric connectivity of the two cerebral hemispheres is crucial for a broad repertoire of cognitive functions including music and language. Congenital amusia has been reported as a neurodevelopment disorder characterized by impaired music perception and production. However, little is known about the characteristics of the interhemispheric functional connectivity (FC) in amusia. In the present study, we used a newly developed voxel-mirrored homotopic connectivity (VMHC) method to investigate the interhemispheric FC of the whole brain in amusia at resting-state. Thirty amusics and 29 matched participants underwent a resting-state functional magnetic resonance imaging (fMRI) scanning. An automated VMHC approach was used to analyze the fMRI data. Compared to the control group, amusics showed increased VMHC within the posterior part of the default mode network (DMN) mainly in the posterior superior temporal gyrus (pSTG) and posterior cingulate cortex (PCC). Correlation analyses revealed negative correlations between the VMHC value in pSTG/PCC and the music perception ability among amusics. Further ROC analyses showed that the VMHC value of pSTG/PCC showed a good sensibility/specificity to differentiate the amusics from the controls. These findings provide a new perspective for understanding the neural basis of congenital amusia and imply the immature state of DMN may be a credible neural marker of amusia.
Velvet Antler Ameliorates Cardiac Function by Restoring Sarcoplasmic Reticulum Ca2+-ATPase Activity in Rats With Heart Failure After Myocardial Infarction

Objective: Velvet antler (VA; cornu cervi pantotrichum), a well-known traditional Chinese medicine, has been shown to exert cardioprotective effects. The purpose of this study was to investigate the effect of VA on heart failure (HF) caused by ischemia-reperfusion, and explore its possible mechanism from the regulation of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2 alpha (SERCA2a). Methods: A rat model of HF was established by ligating the left anterior descending coronary artery of male Sprague–Dawley rats (n = 88). One week after surgery, VA (200, 400, or 800 mg/[kg day−1]) or enalapril (1 mg/[kg day−1]) was administered daily for the next 4 weeks. Heart function was detected by echocardiography and histopathological analysis. The serum BNP level was measured by ELISA, and the expression of SERCA2a, PLB, PLB-Ser16, and PKA was determined by western blotting. SERCA2a and PLB mRNA levels were determined by real-time quantitative PCR. Results: Compared with the sham group, cardiac function in the HF group, including the serum BNP level, heart mass index, myocardial collagen deposition, and left ventricular ejection fraction, was markedly reduced; however, these changes could be reversed by VA treatment. In addition, VA (200 mg/[kg·d−1]) inhibited the decrease of SERCA2a and PLB mRNA levels and SERCA2a, PLB, PLB-Ser16, and PKA protein expression and restored the activity of SERCA2a and PKA. Enalapril affected only PLB protein expression. Conclusion: VA can improve myocardial fibrosis and ventricular remodeling in rats, thereby helping to restore cardiac function. The underlying mechanism may be related to the upregulation of the expression and activation of PKA and PLB and the restoration of the expression and activity of SERCA2a.
TolCV1 Has Multifaceted Roles During Vibrio vulnificus Infection

RtxA1 is a major cytotoxin of Vibrio vulnificus (V. vulnificus) causing fatal septicemia and necrotic wound infections. Our previous work has shown that RpoS regulates the expression and secretion of V. vulnificus RtxA1 toxin. This study was conducted to further investigate the potential mechanisms of RpoS on RtxA1 secretion. First, V. vulnificus TolCV1 and TolCV2 proteins, two Escherichia coli TolC homologs, were measured at various time points by Western blotting. The expression of TolCV1 was increased time-dependently, whereas that of TolCV2 was decreased. Expression of both TolCV1 and TolCV2 was significantly downregulated in an rpoS deletion mutation. Subsequently, we explored the roles of TolCV1 and TolCV2 in V. vulnificus pathogenesis. Western blot analysis showed that RtxA1 toxin was exported by TolCV1, not TolCV2, which was consistent with the cytotoxicity results. Furthermore, the expression of TolCV1 and TolCV2 was increased after treatment of the host signal bile salt and the growth of tolCV1 mutant was totally abolished in the presence of bile salt. A tolCV1 mutation resulted in significant reduction of V. vulnificus induced-virulence in mice. Taken together, TolCV1 plays key roles in RtxA1 secretion, bile salt resistance, and mice lethality of V. vulnificus, suggesting that TolCV1 could be an attractive target for the design of new medicines to treat V. vulnificus infections.
Delirium: A Marker of Vulnerability in Older People

Delirium is an acute neuropsychiatric syndrome and one of the most common presenting symptoms of acute medical illnesses in older people. Delirium can be triggered by a single cause, but in most cases, it is multifactorial as it depends on the interaction between predisposing and precipitating factors. Delirium is highly prevalent in older patients across various settings of care and correlates with an increased risk of adverse clinical outcomes. Several pathophysiological mechanisms may contribute to its onset, including neurotransmitter imbalance, neuroinflammation, altered brain metabolism, and impaired neuronal network connectivity. Several screening and diagnostic tools for delirium exist, but they are unfortunately underutilized. Additionally, the diagnosis of delirium superimposed on dementia poses a formidable challenge – especially if dementia is severe. Non-pharmacological approaches for the prevention and multidomain interventions for the treatment of delirium are recommended, given that there is currently no robust evidence of drugs that can prevent or resolve delirium. This article aims to review the current understanding about delirium in older people. To achieve this goal, we will describe the epidemiology and outcomes of the syndrome, the pathophysiological mechanisms that are supposed to be involved, the most commonly used tools for screening and diagnosis, and prevention strategies and treatments recommended. This review is intended as a brief guide for clinicians in hospital wards to improve their knowledge and practice. At the end of the article, we propose an approach to improve the quality of care provided to older patients throughout a systematic detection of delirium.
Natural Killer Cells and Regulatory T Cells Cross Talk in Hepatocellular Carcinoma: Exploring Therapeutic Options for the Next Decade

Despite major advances in immunotherapy, hepatocellular carcinoma (HCC) remains a challenging target. Natural Killer (NK) cells are crucial components of the anti-HCC immune response, which can be manipulated for immunotherapeutic benefit as primary targets, modulators of the tumour microenvironment and in synchronising with tumour antigen specific effector CD8 cells for tumour clearance. Regulatory T cells shape the anti-tumour response from effector T cells via multiple suppressive mechanisms. Future research is needed to address the development of novel NK cell-targeted immunotherapy and on restraining Treg frequency and function in HCC. We have now entered a new era of anti-cancer treatment using checkpoint inhibitor (CPI)-based strategies. Combining GMP-NK cell immunotherapy to enhance the frequency of NK cells with CPI targeting both NK and CD8 T cells to release co-inhibitory receptors and enhance the cells anti-tumour immunity of HCC would be an attractive therapeutic option in the treatment of HCC. These therapeutic approaches should now be complemented by the application of genomic, proteomic and metabolomic approaches to understanding the microenvironment of HCC which, together with deep immune profiling of peripheral blood and HCC tissue before and during treatment, will provide the much-needed personalised medicine approach required to improve clinical outcomes for patients with HCC.
Cognitive Control, Cognitive Biases and Emotion Regulation in Depression: A New Proposal for an Integrative Interplay Model

Research traditions on cognition and depression focus on relatively unconnected aspects of cognitive functioning. On one hand, the neuropsychological perspective has concentrated on cognitive control difficulties as a prominent feature of this condition. On the other hand, the clinical psychology perspective has focused on cognitive biases and repetitive negative patterns of thinking (i.e., rumination) for emotional information. A review of the literature from both fields reveals that difficulties are more evident for mood-congruent materials, suggesting that cognitive control difficulties interact with cognitive biases to hinder cognitive switching, working memory updating, and inhibition of irrelevant information. Connecting research from these two traditions, we propose a novel integrative cognitive model of depression in which the interplay between mood-congruent cognitive control difficulties, cognitive biases, and rumination may ultimately lead to ineffective emotion-regulation strategies to downregulate negative mood and upregulate positive mood.
Characterization of T-Cell Responses to SMX and SMX-NO in Co-Trimoxazole Hypersensitivity Patients Expressing HLA-B*13:01

HLA-B*13:01-positive patients in Thailand can develop frequent co-trimoxazole hypersensitivity reactions. This study aimed to characterize drug-specific T cells from three co-trimoxazole hypersensitive patients presenting with either Stevens-Johnson syndrome or drug reaction with eosinophilia and systemic symptoms. Two of the patients carried the HLA allele of interest, namely HLA-B*13:01. Sulfamethoxazole and nitroso sulfamethoxazole specific T cell clones were generated from T cell lines of co-trimoxazole hypersensitive HLA-B*13:01-positive patients. Clones were characterized for antigen specificity and cross-reactivity with structurally related compounds by measuring proliferation and cytokine release. Surface marker expression was characterized via flow cytometry. Mechanistic studies were conducted to assess pathways of T cell activation in response to antigen stimulation. Peripheral blood mononuclear cells from all patients were stimulated to proliferate and secrete IFN-γ with nitroso sulfamethoxazole. All sulfamethoxazole and nitroso sulfamethoxazole specific T cell clones expressed the CD4+ phenotype and strongly secreted IL-13 as well as IFN-γ, granzyme B and IL-22. No secretion of IL-17 was observed. A number of nitroso sulfamethoxazole-specific clones cross-reacted with nitroso dapsone but not sulfamethoxazole whereas sulfamethoxazole specific clones cross-reacted with nitroso sulfamethoxazole only. The nitroso sulfamethoxazole specific clones were activated in both antigen processing-dependent and -independent manner, while sulfamethoxazole activated T cell responses via direct HLA binding. Furthermore, activation of nitroso sulfamethoxazole-specific, but not sulfamethoxazole-specific, clones was blocked with glutathione. Sulfamethoxazole and nitroso sulfamethoxazole specific T cell clones from hypersensitive patients were CD4+ which suggests that HLA-B*13:01 is not directly involved in the iatrogenic disease observed in co-trimoxazole hypersensitivity patients.