Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunohistochemical Analysis of Toll-Like Receptors, MyD88, and TRIF in Human Papillary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma

Purpose We hypothesized that innate immune response pathways might be involved in thyroid carcinogenesis. To investigate this hypothesis, we aimed at analyzing the expression of several receptors and molecules in the innate immune system in papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC) tissues. Methods Of the surgically resected specimens, 11 ATC tissues, 25 PTC tissues, and 8 nodular hyperplasia (NH) tissues were selected and examined for the expression of toll-like receptor (TLR) 2, TLR3, TLR4, TLR5, TLR7, TLR9, the myeloid differentiation primary response gene 88 (MyD88), and toll-interleukin-1 receptor domain-containing adaptor inducing INF-β (TRIF) by immunohistochemistry (IHC). Results Several TLRs were expressed in each tissue. TLR3 was strongly expressed in all tissues. In contrast, TLR4 was not detected in any tissues. While TLR5 was moderately expressed in NH but significantly reduced in PTC and ATC, TLR9 was absent in NH tissue but moderately expressed in both PTC and ATC. On MyD88 expression, no significant difference was found between PTC and ATC. TRIF was significantly upregulated in PTC and ATC compared to NH. Surprisingly, PTC and ATC tissues exhibited similar expression patterns of TLRs, MyD88, and TRIF. Conclusion These data suggest the involvement of the innate immune system in both PTC and ATC. Specifically, TLR3-mediated TRIF activation was confirmed in PTC and ATC. This provides new insight into thyroid carcinogenesis.
Systemic Thrombolysis for Treatment of Postpartum Saddle Embolism Complicated by Postpartum Hemorrhage: A Case Report and Brief Literature Review

Venous thromboembolic events (VTE), specifically pulmonary embolisms, account for a significant portion of maternal morbidity and mortality. Due to the procoagulant physiological changes that occur, pregnancy and the postpartum period are known risk factors for thromboembolic events. The risk is greatest during the first-week postpartum and remains elevated for up to six weeks as compared to the general population. Treatment guidelines regarding the use of thrombolytics for massive pulmonary embolism occurring in pregnancy and the postpartum are not well established. In nonpregnant populations, thrombolytic agents are well known to decrease the mortality in the setting of a massive pulmonary embolism. However, in the absence of management guidelines, thrombolysis in pregnancy remains guided by case reports and case series. We present a case of a massive pulmonary embolism (PE) causing hemodynamic instability during the postpartum period treated with tissue plasminogen activator (tPA). The case was complicated by delayed postpartum hemorrhage successfully managed with the uterotonic methylergometrine. The patient was started on oral anticoagulation and continued for six months without recurrent VTE. Our case demonstrates a rare occurrence of a saddle embolism after a vaginal delivery within the first postpartum week which was successfully managed with the use of systemic thrombolysis and minimal intervention to manage the iatrogenic delayed postpartum hemorrhage. To the authors' knowledge, no other similar case report exists. This case highlights the need to develop guidelines for the use of thrombolysis in mothers who present with massive pulmonary embolus and a noninvasive means to manage adverse bleeding events in the puerperium.
Ketone bodies – causes and effects of their increased presence in cows’ body fluids: A review

Ketosis is the most common metabolic disease in high-performance dairy cows during the first 6-8 weeks of lactation. Its main symptoms include an excessive amount of so-called ketone bodies in a cow’s body fluids. Ketone bodies consist of β-hydroxybutyric acid (βHBA), acetoacetic acid, and acetone. βHBA is the main component with its share of the total volume of ketone bodies in the blood of about 70%. Clinical symptoms of ketosis in cows include loss of appetite, preference for forage to concentrated feed, and acetone odor in their mouth and urine. Those symptoms are accompanied by a production drop, an increase of concurrent illness (mastitis, metritis, and displaced abomasum), and poor reproductive performance. One of the ketosis characteristic effects is an increase in the level of fat in milk (>5%), while protein levels decrease (<2.9%). In the case of subclinical ketosis (SCK), the fat–protein ratio in milk is increased to above 1.4:1. The current consensus for SCK is to consider a cutoff point of βHBA to be at least 1.2 mmol/L in blood plasma. Ketosis prevention is based on keeping perinatal cows in good condition, that is, with around 3.5 points in the five-point body condition scoring, carefully balancing food doses during the first 2 months of lactation with the correct energy–protein ratio. Glucose precursor products should be administered orally, in particular to at-risk herds. Ketosis occurs in 7-14% on average of the total number of cows in a herd. In general, data on the prevalence of SCK vary considerably, depending on their source. Moreover, the problem is mostly observed in poorly-fed animals with high milk production potential. The objectives of this review are to reveal the current situation of ketosis prevalence, the possibility of diagnosis, consequences in dairy cows and to provide some recommendations for ketosis treatment and prevention.
Microshear Bond Strength of Resin Composite to Pretreated Dentin with Silver Diamine Fluoride/Potassium Iodide: An In Vitro Study

The aim of this in vitro study was to evaluate the microshear bond strength of total etch adhesives to pretreated dentin with silver diamine fluoride (SDF) or silver diamine fluoride/potassium iodide (SDF/KI) and to evaluate the mode of bond failure under scanning electron microscope (SEM). Forty five dentin specimens were prepared from extracted human permanent premolars and divided into three groups (n = 15) based on the dentin surface treatment as follows: Control group (A) : total etch bonding system ;group (B) SDF pretreatment of etched dentin followed by bonding system and group (C) SDF/KI pretreatment of etched dentin followed by bonding system . Resin composite cylinder was built on the dentin slabs to a height of 4 mm and dentincomposite cross section is approximately 0.8 mm. The prepared specimens were subjected to microshear bond strength analysis, and evaluation of the mode of failure of fractured surface was observed under SEM. Statistical Analysis: One-way ANOVA followed by Tukey’s post hoc multiple comparison tests. Group C was found to have the highest mean value of microshear bond strength followed by a mean value of group A then group, B mean value. The difference between all group was nonsignificant as shown by the non-significant one-way ANOVA Tukey and post-hoc (P>0.05). The predominant mode of failure was adhesive followed by cohesive in resin and mixed. Dentin Pretreatment with SDF or SDF/KI then dentin surface washing showed non-significant effect on the microshear bond strength of resin composite to dentin.
Structural and chemical heterogeneity of Proterozoic organic microfossils of the ca. 1 Ga old Angmaat Formation, Baffin Island, Canada

Organic microfossils in Meso‐ and Neoproterozoic rocks are of key importance to track the emergence and evolution of eukaryotic life. An increasing number of studies combine Raman spectroscopy with synchrotron‐based methods to characterize these microfossils. A recurring observation is that Raman spectra of organic microfossils show negligible variation on a sample scale and that variation between different samples can be explained by differences in thermal maturation or in the biologic origin of organic precursor material. There is a paucity of work, however, that explores the extent to which the petrographic framework and diagenetic processes might influence the chemical structure of organic materials. We present a detailed Raman spectroscopy‐based study of a complex organic microfossil assemblage in the ca. 1 Ga old Angmaat Formation, Baffin Island, Canada. This formation contains abundant early diagenetic chert that preserves silicified microbial mats with numerous, readily identifiable organic microfossils. Individual chert beds show petrographic differences with discrete episodes of cementation and recrystallization. Raman spectroscopy reveals measurable variation of organic maturity between samples and between neighboring organic microfossils of the same taxonomy and taphonomic state. Scanning transmission X‐ray microscopy performed on taphonomically similar coccoidal microfossils from the same thin section shows distinct chemical compositions, with varying ratios of aromatic compounds to ketones and phenols. Such observations imply that geochemical variation of organic matter is not necessarily coupled to thermal alteration or organic precursor material. Variation of the Raman signal across single samples is most likely linked to the diagenetic state of analyzed materials and implies an association between organic preservation and access to diagenetic fluids. Variation in the maturity of individual microfossils may be a natural outcome of local diagenetic processes and potentially exceeds differences derived from precursor organic material. These observations stress the importance of detailed in situ characterization by Raman spectroscopy to identify target specimens for further chemical analysis.
Current vaccine approaches and emerging strategies against herpes simplex virus (HSV)

ABSTRACT Introduction Vaccine development for the disease caused by the herpes simplex virus (HSV) has been challenging over the years and is always in dire need of novel approaches for prevention and cure. To date, the HSV disease remains incurable and challenging to prevent. The disease is extremely widespread due to its high infection rate, resulting in millions of infection cases worldwide. Areas covered This review first explains the diverse forms of HSV-related disease presentations and reports past vaccine history for the disease. Next, this review examines current and novel HSV vaccine approaches being studied and tested for efficacy and safety as well as vaccines in clinical trial phases I to III. Modern approaches to vaccine design using bioinformatics are described. Finally, we discuss measures to enhance new vaccine development pipelines for HSV. Expert opinion Modernized approaches using in silico analysis and bioinformatics are emerging methods that exhibit potential for producing vaccines with enhanced targets and formulations. Although not yet fully established for HSV disease, we describe current studies using these approaches for HSV vaccine design to shed light on these methods. In addition, we provide up-to-date requirements of immunogenicity, adjuvant selection, and routes of administration.
Characterization of E93 in neometabolous thrips Frankliniella occidentalis and Haplothrips brevitubus

Insect metamorphosis into an adult occurs after the juvenile hormone (JH) titer decreases at the end of the juvenile stage. This generally coincides with decreased transcript levels of JH-response transcription factors Krüppel homolog 1 (Kr-h1) and broad (br), and increased transcript levels of the adult specifier E93. Thrips (Thysanoptera) develop through inactive and non-feeding stages referred to as “propupa” and “pupa”, and this type of distinctive metamorphosis is called neometaboly. To understand the mechanisms of hormonal regulation in thrips metamorphosis, we previously analyzed the transcript levels of Kr-h1 and br in two thrips species, Frankliniella occidentalis (Thripidae) and Haplothrips brevitubus (Phlaeothripidae). In both species, the transcript levels of Kr-h1 and br decreased in the “propupal” and “pupal” stages, and their transcription was upregulated by exogenous JH mimic treatment. Here we analyzed the developmental profiles of E93 in these two thrips species. Quantitative RT-PCR revealed that E93 expression started to increase at the end of the larval stage in F. occidentalis and in the “propupal” stage of H. brevitubus, as Kr-h1 and br mRNA levels decreased. Treatment with an exogenous JH mimic at the onset of metamorphosis prevented pupal-adult transition and caused repression of E93. These results indicated that E93 is involved in adult differentiation after JH titer decreases at the end of the larval stage of thrips. By comparing the expression profiles of Kr-h1, br, and E93 among insect species, we propose that the “propupal” and “pupal” stages of thrips have some similarities with the holometabolous prepupal and pupal stages, respectively.
Intradermal lipopolysaccharide challenge as an acute in vivo inflammatory model in healthy volunteers

Whereas intravenous administration of Toll‐like receptor 4 ligand lipopolysaccharide (LPS) to human volunteers is frequently used in clinical pharmacology studies, systemic use of LPS has practical limitations. We aimed to characterize the intradermal LPS response in healthy volunteers, and as such qualify the method as local inflammation model for clinical pharmacology studies.
An Analysis of Frequency of Continuous Blood Pressure Variation and Haemodynamic Responses during Haemodialysis

Background: Higher beat-to-beat blood pressure (BP) variation during haemodialysis (HD) has been shown to be associated with elevated cardiac damage markers and white matter ischaemic changes in the brain suggesting relevance to end-organ perfusion. We aimed to characterize individual patterns of BP variation and associated haemodynamic responses to HD. Methods: Fifty participants underwent continuous non-invasive haemodynamic monitoring during HD and BP variation were assessed using extrema point (EP) frequency analysis. Participants were divided into those with a greater proportion of low frequency (LF, n = 21) and high frequency (HF, n = 22) of BP variation. Clinical and haemodynamic data were compared between groups. Results: Median EP frequencies for mean arterial pressure (MAP) of mid-week HD sessions were 0.54 Hz (interquartile range 0.18) and correlated with dialysis vintage (r = 0.32, p = 0.039), NT pro-BNP levels (r = 0.32, p = 0.038), and average real variability (ARV) of systolic BP (r = 0.33, p = 0.029), ARV of diastolic BP (r = 0.46, p = 0.002), and ARV of MAP (r = 0.57, p < 0.001). In the LF group, MAP positively correlated with cardiac power index (CPI) in each hour of dialysis, but not with total peripheral resistance index (TPRI). In contrast, in the HF group, MAP correlated with TPRI in each hour of dialysis but only with CPI in the first hour. Conclusions: EP frequency analysis of continuous BP monitoring during dialysis allows assessment of BP variation and categorization of individuals into low- or high-frequency groups, which were characterized by different haemodynamic responses to dialysis. This may assist in improved individualization of dialysis therapy.
Trends in urine biomarker discovery for urothelial bladder cancer: DNA, RNA, or protein?

Urothelial bladder cancer is a complex disease displaying a landscape of heterogenous molecular subtypes, mutation profiles and clinical presentations. Diagnosis and surveillance rely on flexible cystoscopy which has high accuracy, albeit accompanied by a high-cost burden for healthcare providers and discomfort for patients. Advances in “omic” technologies and computational biology have provided insights into the molecular pathogenesis of bladder cancer and provided powerful tools to identify markers for disease detection, risk stratification, and predicting responses to therapy. To date, numerous attempts have been made to discover and validate diagnostic biomarkers that could be deployed as an adjunct to the cystoscopic diagnosis and long-term surveillance of bladder cancer. We report a comprehensive literature analysis using PubMed to assess the changing trends in investigating DNA, RNA, or proteins as diagnostic urinary biomarkers over a period of 5 decades: 1970–2020. A gradual shift has been observed in research away from protein biomarkers to nucleic acids including different classes of RNA, and DNA methylation and mutation markers. Until 2000, publications involving protein biomarker discovery constituted 87% of the total number of research articles with DNA comprising 6% and RNA 7%. Since 2000 the proportion of protein biomarker articles has fallen to 40%, and DNA and RNA studies increased to 32% and 28%, respectively. Clearly research focus, perhaps driven by technological innovation, has shifted from proteins to nucleic acids. We optimistically hypothesise that, following thorough validation, a clinically useful detection test for bladder cancer based on a panel of DNA or RNA markers could become reality within 5–10 years.
Hepatocellular carcinoma: a clinical and pathological overview

Summary HCC incidence rates have been rising in the past 3 decades and by 2025 > 1 million individuals will be affected annually. High-throughput sequencing technologies led to the identification of several molecular HCC subclasses that can be broadly grouped into 2 major subgroups, each characterized by specific morphological and phenotypical features. It is likely that this increasing knowledge and a more appropriate characterization of HCC at the pathological level will impact HCC patient management.
Systematic review of human post‐mortem immunohistochemical studies and bioinformatics analyses unveil the complexity of astrocyte reaction in Alzheimer's disease

Reactive astrocytes in Alzheimer's disease (AD) have traditionally been demonstrated by increased glial fibrillary acidic protein (GFAP) immunoreactivity; however, astrocyte reaction is a complex and heterogeneous phenomenon involving multiple astrocyte functions beyond cytoskeletal remodelling. To better understand astrocyte reaction in AD, we conducted a systematic review of astrocyte immunohistochemical studies in post‐mortem AD brains followed by bioinformatics analyses on the extracted reactive astrocyte markers.
Serum glycine levels are associated with cortical bone properties and fractures risk in men.

CONTEXT In a recent study a pattern of 27 metabolites, including serum glycine, associated with bone mineral density (BMD). OBJECTIVE To investigate associations for serum and urinary glycine levels with BMD, bone microstructure and fracture risk in men. METHODS In the population based MrOS Sweden study (men, 69-81 years) serum glycine and BMD were measured at baseline (n=965) and 5-year follow up (n=546). Cortical and trabecular bone parameters of the distal tibia were measured at follow-up using high resolution peripheral quantitative computed tomography. Urinary (n=2,682) glycine was analyzed at baseline. X-ray validated fractures (n=594) were ascertained during a median follow-up of 9.6 years. Associations were evaluated using linear regression (bone parameters) or Cox regression (fractures). RESULTS Circulating glycine levels were inversely associated with femoral neck (FN)-BMD. A meta-analysis (n=7,543) combining MrOS Sweden data with data from three other cohorts confirmed a robust inverse association between serum glycine levels and FN-BMD (p=7.7 x 10 -9). Serum glycine was inversely associated with the bone strength parameter failure load in the distal tibia (p=0.002), mainly as a consequence of an inverse association with cortical cross-sectional area and a direct association with cortical porosity. Both serum and urinary glycine levels predicted major osteoporotic fractures (serum, HR per SD increase = 1.20, 95% CI 1.03-1.40; urine HR=1.13, 95% CI 1.02-1.24). These fracture associations were only marginally reduced in models adjusted for FRAX with BMD. CONCLUSIONS Serum and urinary glycine are indirectly associated with FN-BMD and cortical bone strength, and directly associated with fracture risk in men.
Therapeutic Potential of Endothelial Progenitor Cells in Pulmonary Diseases.

Compromised alveolar development and pulmonary vascular remodeling are hallmarks of pediatric lung diseases such as bronchopulmonary dysplasia (BPD) and alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). Although advances in surfactant therapy, corticosteroids, and anti-inflammatory drugs have improved clinical management of preterm infants, still those who suffer with severe vascular complications lack viable treatment options. Paucity of the alveolar capillary network in ACDMPV causes respiratory distress and leads to mortality in a vast majority of ACDMPV infants. The discovery of endothelial progenitor cells (EPCs) in 1997 brought forth the paradigm of postnatal vasculogenesis and hope for promoting vascularization in fragile patient populations, such as those with BPD and ACDMPV. The identification of diverse EPC populations, both hematopoietic and nonhematopoietic in origin, provided a need to identify progenitor cell selective markers which are linked to progenitor properties needed to develop cell-based therapies. Focusing to the future potential of EPCs for regenerative medicine, this review will discuss various aspects of EPC biology, beginning with the identification of hematopoietic, nonhematopoietic, and tissue-resident EPC populations. We will review knowledge related to cell surface markers, signature gene expression, key transcriptional regulators, and will explore the translational potential of EPCs for cell-based therapy for BPD and ACDMPV. The ability to produce pulmonary EPCs from patient-derived induced pluripotent stem cells (iPSCs) in vitro, holds promise for restoring vascular growth and function in the lungs of patients with pediatric pulmonary disorders.
RNA‐dependent RNA polymerase 1 delays the accumulation of viroids in infected plants

Abstract RNA‐dependent RNA polymerase 1 (RDR1) is essential for plant antiviral defence, but its role in plant defence against viroid infection remains unknown. The present study aimed to identify the function and mechanism of RDR1 in plant resistance to viroid infection. Overexpression of Nicotiana tabacum RDR1 (NtRDR1) delayed the accumulation of potato spindle tuber viroid (PSTVd) genomic RNA and PSTVd‐derived small RNA (sRNA) in Nicotiana benthamiana plants at the early invasion stage, but not in the late stage of infection. Conversely, virus‐induced gene silencing of tomato RDR1 (SlRDR1a) increased the susceptibility to PSTVd infection (increased viroid accumulation). Salicylic acid (SA) pretreatment induced SlRDR1a expression and enhanced the defence against PSTVd infection in tomato plants. Our study demonstrated that RDR1 is involved in SA‐mediated defence and restricts the early systemic invasion by PSTVd in plants. The decreased PSTVd accumulation in N. benthamiana was not caused by efficient accumulation of PSTVd sRNAs. These results deepen our understanding of the mechanism of RDR1 in plant defence responses to viroid attack.