: Julia Creek dunnarts are an endangered species of carnivorous marsupials and the focus of multiple conservation strategies involving significant resources such as captive breeding programs. Despite the relevance for conservation, no study to date has focused on evaluating geriatric diseases in dunnarts. This study describes the pathology findings in a group of one wild and 35 captive-born, mostly geriatric Julia Creek dunnarts that failed to produce offspring over multiple breeding periods. A total of 20 females and 16 males were submitted for a postmortem examination, with ages ranging from 9-42 and 12-42 months for females and males, respectively. Of these, 10 had unremarkable findings. The most common condition in females was cystic glandular hyperplasia (n=8), typical of hormonal dysregulation profiles in senescence, particularly hyperestrogenism. Rarely, cutaneous disease represented by unidentified dermal round cell infiltrates was observed in females (n=2). Primary reproductive hormonal dysregulation was also suspected in males diagnosed with testicular degeneration, aspermatogenesis and/or atrophy (n=3). Cutaneous round cell infiltrates, possibly compatible with epitheliotropic lymphomas were seen in males (n=3), and 2/3 affected males also had concurrent testicular degeneration or atrophy, indicating male sex could be a predictor for lymphoid neoplasia in aged dunnarts especially in individuals with concurrent testosterone-luteinizing hormone dysregulation as it occurs in gonadectomized animals. The role of an underlying viral etiology is also explored. This study is the first to describe major spontaneous diseases in endangered aged Julia Creek dunnarts, providing an important understanding of senescence and geriatric diseases within a conservation context.

The importance of Muscovy ducks in industrial poultry production is growing; however, little is known about the physiology of their reproductive cycles. This study investigated the influence of male biostimulation on female ducks before the commencement of the laying phase. A total of 15 female Muscovites were kept in contact with a male duck until the point of laying, while 15 other females were kept without any contact with a male conspecific. Before reaching egg-laying maturity, the cloacae of 29 adult ducks were subjected to daily clinical assessments. The evaluations yielded four unique categories of outcomes, determined by assessing factors such as the degree of redness and protrusion of the mucous membrane, moisture level, and swelling of the cloacal sphincter muscle. In terms of biostimulation, the findings demonstrated that, on average, ducks in contact with males laid the first egg 16 days earlier than isolated ducks. Furthermore, there was no significant difference observed in the mean initial egg weight between both groups (p = 0.841). The changes in the cloacal morphology indicated significant morphological changes 25–26 days before laying. Efforts to improve Muscovy production and develop biotechnological techniques to modify the reproductive cycle will benefit from these advancements.

Background: Permanent tracheostomy because of total laryngectomy surgery entails great conse-quences for the patient regarding respiratory physiopathology such as the filtering, humidifying, and heating function of the air by the nose is lost. The use of special stomal filters can determine adequate protection of the trachea-broncho-pulmonary system with a reduction in respiratory pathologies. In fact, in most cases laryngectomee patients are first cigarette smokers who for this reason already have also respiratory diseases such as chronic obstructive pulmonary disease (COPD). Despite the availability of tracheal filters, multiple times, as reported in the literature, the patient tends to limit their use due to reported breathing difficulties, especially in conditions of intense breathing. Methods: The objective of this clinical study was to evaluate the most suitable stomal filter for the laryngectomee patient during physical activity. The filters studied were an INHEALTH device (Blom-Singer SpeakFree HME); two ATOS devices (Provox® Life™ Energy HME and Provox® Life™ Home HME); and an FAHL device (Laryvox HME Sport). Results: For this purpose, the performances of 31 laryngectomee patients, subjected to medi-um-high physical effort, were analyzed through a standardized pneumological test, the Six Minute Walking Test (6MWT) which involves a sustained walk lasting six minutes, with evaluation , every 60 seconds, heart rate, oxygen saturation and meters travelled; furthermore, it examines two sub-jective indices, namely, the basal and final dyspnea index and the initial and final muscular fatigue index.

Background/Objectives: Endocrine disruptors are ubiquitous agents in the environment and are present in everyday consumer products. These agents can interfere with the endocrine system, and subsequently the reproductive system, especially in pregnancy. Increasing research has been conducted to discover and describe the health effects of these agents on humans, including pregnant women, their fetuses, and the placenta. This review discusses prenatal exposure to various endocrine disruptors focusing on Bisphenols, Phthalates, Organophosphates, and Perfluoroalkyl substances, and their effects on pregnancy and fetal development. Methods: We reviewed the literature via PubMed and EBSCO databases and included the most relevant studies. Results: Our findings reveal that several negative health outcomes were linked to endocrine disruptors. However, despite the seriousness of this topic and the abundance of research on these agents, it remains challenging to draw strong conclusions about their effects from the available studies. This does not allow for strong, universal guidelines and might result in poor patient counseling and heterogeneous approaches to regulating endocrine disruptors. Conclusion: The urgency of the matter calls for urgent efforts, as more studies are needed in this realm, to protect pregnant patients ultimately and in the long term, society.

Carboxymethyl cellulose (CMC) can act as a nonpermeating cryoprotectant, reducing the toxicity of glycerol. The dog spermatozoa were diluted and frozen in freezing extender supplemented with 0 (control), 0.1, 0.25, 0.5, or 0.75 % (w/v) CMC. Post-thaw, the sperm kinematic parameters (CASA), viability (SYBR-14/PI), and acrosome integrity (FITC-PSA) were evaluated. The expression of genes related to apoptosis (BCL2, BAX, and ANAXA), motility (BACTIN), cold shock proteins (YBX3), and ROS (CAT, ROMO1, and SMOX) was evaluated using qPCR. The total motility was higher in the 0.1 % CMC group compared to the other groups (p<0.05). In addition, the expression of the antiapoptotic gene BCL2 was upregulated in 0.1 % CMC group compared to the control, whereas the gene expression of BAX and SMOX exhibited lower levels in 0.1 and 0.25 % CMC groups than the control group (p<0.05). The expression of YBX3 genes was significantly decreased with 0.25 % CMC supplementation. No significant differences were found in viability, acrosome integrity, or the relative expression of ANAXA, BACTIN, CAT, and ROMO1 genes between the groups. In conclusion, the addition of CMC to a freezing extender improved sperm motility and alleviated cryostress by regulating the gene expression of BCL2, BAX, SMOX, and YBX3.

Obsessive–compulsive disorder (OCD) is believed to follow a waxing and waning course, often according to environmental stressors. During the COVID-19 pandemic, pre-existing OCD symptoms were reported to increase and to change from checking to washing behaviors, while new-onset symptoms were predominantly of the hoarding type. In the present study, we followed the evolution of OCD symptoms, anxiety, depression, and insight of illness in forty-six OCD patients throughout the pandemic. Clinical measures were collected at four different time points before and during the COVID-19 pandemic in Italy. Within-subject comparisons were used to compare clinical scale scores across time, and correlations were examined between patients' baseline characteristics and changes in clinical scores. We found that all clinical measures increased during the first Italian lockdown, with respect to the pre-pandemic values. Anxiety decreased during the temporary elimination of restriction provisions, whereas severity of OCD symptoms and insight returned to pre-pandemic values during the second mandatory lockdown. These results were observed only in two sub-groups of patients: those taking benzodiazepines and those with shorter illness duration. Our findings suggest the need of additional clinical attention to these specific sub-groups of OCD patients in case of particularly distressing circumstances, while pointing to a possible adaptive role of their OCD symptoms when the environment requires a higher care of hygiene and extraordinary supply of essential resources.

The nuclear hormone family of receptors regulates gene expression. The androgen receptor (AR) shuttles upon ligand binding and homodimerization from the cytosol into the nucleus to activate gene expression. Thyroid hormone receptors(TR), retinoic acid receptors (RAR), and the vitamin D receptor (VDR) are present in the nucleus bound to chromatin as a heterodimer with the retinoid X receptors (RXR) and repress gene expression. Ligand binding leads to transcription activation. The hormonal ligands for these receptors play crucial roles to ensure the proper conduct of very many tissues and exert effects on prostate cancer (PCa) cells. Androgens support PCa proliferation and deprivation alone or with chemotherapy is the standard therapy for PCa. RAR activation and 3,5,3'-triiodo-L-thyronine (T3) stimulation of TR support the growth of PCa cells. Ligand stimulation of VDR drives growth arrest, differentiation, and apoptosis of PCa cells. Often these receptors are explored as separate avenues to find treatments for PCa and other cancers. However, there is accumulating evidence to support receptor interactions and crosstalk of regulatory events whereby a better understanding might lead to new combinatorial treatments.

Immunohistochemistry (IHC) helps identify different types of tissues and provides important information about the pattern, shape, and structure of cells in a tissue sample. It is a very useful tool and widely used to uncover histology and pathology diagnosis uses. The IHC is a very useful tool to conduct research in the developmental biology area. Some insects, like butterflies, bees, beetles, ants, wasps, and moths, undergo a unique life cycle called complete metamorphosis, which has four distinct stages: egg, larva, pupa, and adult. Larvae are often wingless and have different habits and forms than adults, which are better suited for growth and development. During the metamorphosis, how does the insect legs change is a really an interesting issue.To better understand insect development, agriculture pest control, and insect pathogen interaction, here we use an insect Bombyx mori (domestic silk moth) as a model to detail how to conduct the IHC assays, such as HE staining, TUNEL to see the cell apoptosis, pH3 and BrdU staining to check cell division. The reagents can be easily found, and this step-by-step protocol is easily reproduced.

Introduction Sepsis-associated encephalopathy (SAE) is common in sepsis and is linked to high mortality and impaired neurologic outcome. Brain ultrasonography (US), including transcranial Doppler (TCD) and transcranial color-coded duplex sonography (TCCS), is a non-invasive tool for cerebral monitoring and might be useful in sepsis. The aims of this review are: 1) to explore whether brain perfusion is altered in sepsis, 2) to determine the role of brain US in guiding resuscitation, and 3) its ability to predict neurological outcomes in septic patients. Materials and methods This scoping review adhered to the PRISMA-ScR protocol and JBI methodology. A comprehensive literature search was conducted across MEDLINE, Scopus, and Web of Science. The review included studies on adults with sepsis or septic shock in the ICU. Randomised controlled trials, clinical trials, observational studies and systematic reviews were included. All the data related to the review's key questions were extracted and charted independently by two authors. Results 625 articles were screened, and 34 were ultimately included after application of exclusion criteria. 85% of the studies were observational 15% were systematic reviews with or without meta-analysis. The studies primarily focused on cerebral blood flow (CBF) alterations in sepsis, reporting variable results. Findings showed variable cerebral autoregulation (CAR) impairment, with higher incidence in the early stages of sepsis and associations with poor neurological outcomes. However, while alterations in CAR and CBF are common in septic patients, their impact on neurological outcomes and mortality is not clear. Regarding resuscitation, only a paucity of studies were found and no conclusions can be drawn. Conclusions The current body of evidence has a poor grade, but it is possible to say that brain US can identify cerebral perfusions alterations. Its usage during resuscitation is feasible and warrants further investigations. Use of brain US during resuscitation and for prediction of outcome is not currently supported by evidence. Further studies on brain perfusion, acquisition of 2D images of parenchyma (TCCS) and application of a multimodal brain monitoring might be useful in these contexts.

Cancer develops from abnormal cell growth in the body, causing significant mortalities every year. To date, potent therapeutic approaches have been developed to eradicate tumor cells, but intolerable toxicity and drug resistance can occur in treated patients, limiting the efficiency of existing treatment strategies. Therefore, searching for novel genes critical for cancer progression and therapeutic response is urgently needed for successful cancer therapy. Recent advances in bioinformatic and proteomic techniques have allowed the identification of a novel category of peptides encoded by non-canonical open reading frames (ncORFs) from historically non-coding genomic regions. Surprisingly, many of the ncORFs express functional microproteins that play a vital role in human cancers. In this review, we provide a comprehensive description of different ncORF types with coding capacity and technological methods in discovering ncORFs among human genomes. We also summarize the diagnostic and prognostic value of these ncORF as well as their carcinogenic role in cancer progression and underestimated potential as therapeutic targets.

Background: People with Down syndrome (DS) have a trisomy of chromosome 21 and marked deficits in verbal memory but relatively preserved visuospatial perception. Verbal memories are related to semantic knowledge. Little is known about the organization of semantic knowledge in people with DS, which was the aim of this study. Aims: The extent of false memory in people with DS was examined. Possible differences in the number of false memories induced by nominal and verbal themes were examined. Methods and Procedures: In the study phase, ten word lists with semantically related associates were presented. In the recognition phase, participants made judgments on whether each word had been represented previously as semantically related lures, old words, and semantically unrelated new words. Outcomes and Results: Differences in the processing of nominal and verbal theme-related lures were observed among people with DS. When processing nominal theme-related lures, people with DS showed delayed false positives. When processing verbal theme-related lures, people with DS showed no differences compared to controls. Similar patterns have been observed in people with DS when processing nominal theme-related associates and verbal theme-related associates. People with DS have delayed recognition of associates. When processing unrelated words, they showed significantly higher false positives than controls for both nominal and verbal eliciting themes. Further analyses of the themes revealed differences in false positives across syntactic categories among groups. Conclusions and Implications: People with DS showed a delayed recognition of associates and deviance in recognizing unrelated words in the nominal and verbal theme categories. People with DS were delayed in terms of nouns, but deviated with verbs in associated and unrelated words. Additionally, people with DS showed distinct patterns in processing five nominal lures and three verbal lures, suggesting that they formed false memories differently based on distinct syntactic categories. Thus, it was concluded that people with DS develop a deviant semantic structure. Category-based interventions for people with DS should be implemented in order to improve their semantic knowledge through lexical connections.

Goldenhar Syndrome (GS), also known as oculoauriculovertebral spectrum (OVAS), is a rare congenital condition characterized by impaired development of structures such as ears, eyes, nose, palate, lip, mandible, maxilla, and teeth. The etiopathogenesis is multifactorial and dependent on genetic and environmental factors, yet the syndrome has many unknowns. We report a case of a 31-year-old male diagnosed clinically with GS as an infant with an absent left ear, hearing loss, absent left lung lobe, reduced growth of left upper limb, decreased size of left face, absent left kidney, and a missing left thumb, who was seen in the genetic clinic for prenatal genetic counseling. A microarray comparative genome hybridization (aCGH) was performed for copy number abnormalities and targeted NGS panels were performed for hereditary hearing loss and limb/digital malformations. aCGH revealed a 471kb loss at 16p12.2 and a mosaic 7.3Mb gain at 19p12q12. Metaphase FISH confirmed the orientation of 19p12q12 gain as small supernumerary ring chromosome 19. NGS revealed multiple variants (MYH14 c.4001C&gt;T, PDE1C c.8C&gt;T, ADGRV1 c.15502A&gt;G, CDH23 c.8772C&gt;A, MYO3A c.484G&gt;A, ADAMTS10 c.506G&gt;A, CHUK c.1294C&gt;T, CSPP1 c.1972A&gt;G, and TCTN2 c.160G&gt;A). Due to the heterogeneous clinical manifestation and genetic heterogeneity of GS, a comprehensive genetic testing strategy is needed for timely diagnosis and better patient care.

SET protein carries out multiple functions including those for protein phosphatase 2A (PP2A) inhibition, histone modification, DNA repair and gene regulation. SET overexpression has been detected in brain neurons of Alzheimer's disease patients, follicle theca cells of Polycystic Ovary Syndrome (PCOS) patients, and ovarian cancer cells, indicating that SET may play a pathological role for these disorders. SET transcript 2, produced by a specific promoter, represents a major transcript variant in different cell types. In this study, we characterized the transcriptional activation of human SET transcript 2 promoter in HeLa cells. Promoter deletion experiments and co-transfection assays indicated that ZFX, the Zinc finger and X-linked transcription factor, was able to transactivate the SET promoter. A proximal promoter region containing four ZFX-binding sites was found to be critical for the ZFX-mediated transactivation. Mutagenesis study indicated that the site located closest to the transcription start site accounted for most of the ZFX-mediated transactivity. Manipulation of ZFX levels by overexpression or siRNA knockdown confirmed the significance and specificity of the ZFX-mediated SET promoter activation. Chromatin immunoprecipitation results verified the binding of ZFX to its cognate site in the SET promoter. These findings have led to identification of ZFX as an upstream factor regulating SET gene expression. More studies are required to define the in vivo significance of this mechanism, and specifically, its implication for several benign and malignant diseases related to SET dysregulation.

In the world's first pig-to-human cardiac xenotransplant, the elevated levels of porcine cytomeg-alovirus (PCMV) are considered key factors contributing to patient mortality. This has renewed attention to PCMV, a virus widely prevalent in pigs. Currently, there are no effective drugs or vaccines targeting PCMV, and its high detection difficulty poses challenges for prevention and control research. In this study, antiviral small hairpin RNA (shRNA) was selected and inserted into the Rosa26 and miR-17-92 loci of pigs via a CRISPR/Cas9-mediated knock-in strategy. Further in vitro viral challenge experiments demonstrated that these genetically edited pig cells could effec-tively limit PCMV replication. Through this process, we constructed a PCMV-infected cell model, validated partial viral interference sites, enhanced gene knock-in efficiency, performed gene editing at two different gene loci, and ultimately demonstrated that RNA interference (RNAi) technology combined with CRISPR/Cas9 has the potential to generate pig cells with enhanced antiviral infec-tion capabilities. This opens up possibilities for the future production of pig populations with anti-viral functionalities.

Uterine tube extracellular matrix is a key component that regulates tubal tissue physiology, and it has a region-specific structural distribution, which are directly associated to their functions. Considering this, application of biological matrices in culture systems is an interesting strategy to develop biomimetic tubal microenvironments and enhance their complexity. However, there are no established protocols to produce tubal biological matrices that consider the organ morphophysiology for such applications. Therefore, this study aimed to establish region-specific protocols to obtain decellularized scaffolds derived from porcine infundibulum, ampulla, and isthmus to provide suitable sources of biomaterials for tissue-engineering approaches. Porcine uterine tubes were decellularized in solutions of 0.1% SDS and 0.5% Triton X-100. Decellularization efficiency was evaluated by DAPI staining and DNA quantification. We analyzed ECM composition and structure by optical and scanning electronic microscopy, FTIR and Raman spectroscopy. DNA and DAPI assays validated the decellularization, presenting significative reduction of cellular content. Structural and spectroscopy analyses revealed that produced scaffolds remained well structured and with ECM composition preserved. YS and HEK293 cells were used to attest cytocompatibility, allowing cell survival and successful interaction with the scaffolds. These results suggest that such matrices are applicable for future biotechnological approaches in the reproductive field.

Metals play vital roles in biological systems, with iron/heme being essential for cellular and metabolic functions necessary for survival and/or virulence in many bacterial pathogens. Given the rise of bacterial resistance to current antibiotics, there is an urgent need for the development of non-toxic and novel antibiotics that do not contribute to resistance to other antibiotics. Gallium, which mimics iron, has emerged as a promising antimicrobial agent, offering a novel approach to combat bacterial infections. Gallium does not have any known functions in biological systems. Gallium exerts its effects primarily by replacing iron in redox enzymes, effectively inhibiting bacterial growth by targeting multiple iron/heme-dependent biological processes and suppressing the development of drug resistance. The aim of this review is to highlight recent findings on the mechanisms of action of gallium and provide further insights into the development of gallium-based compounds. Understanding the mechanisms underlying gallium’s biological activities will enhance its therapeutic application across various medical fields, offering promising avenues for the treatment of infectious diseases, cancer, and inflammatory conditions.

(1) Background: The aim of this investigation is to determine the effect of archwires’ deflection on the temperature transitions driving the austenite to martensite transformation (and vice versa) and the force released by NiTi and CuNiTi orthodontic wires. (2) Methods: Round cross-section archwires have been investigated. The calorimetric approach has been used for measuring transition temperatures occurring in the unstressed (e.g. undeflected) state of the wires. Static Thermo-mechanical analysis in a temperature controlled wet environment has been performed in the range of temperature between 5°C and 55°C for measuring temperature transitions occurring in highly deflected archwires in conjunction with the force released by these wires. (3) Results: Plateau forces investigated in Part I and those reported in the literature describes the wire’s behaviour only at deflection levels close to the end point of the force plateau extension detected at 37°C. Upon heating or cooling, the austenite finish (Af) transition temperature and the martensite start (Ms) temperature largely depends on the deflection level for both NiTi and CuNiTi. (4) Conclusions: The plateau force levels at 37°C, broadly reported in the literature, only represent the lower boundary force that a superelastic wire releases at 37°C above its elastic limit. For both NiTi and CuNiTi, plateau force levels at 37°C can be predicted by the static TMA profile matching the end point of the force plateau extension. Transition temperatures in largely deflected wires are significantly higher than those determined through the calorimetric approach.

The intestinal microbiota, comprised of bacteria, archaea, and phages, inhabits the gastrointestinal tract of the organism. Male reproductive sterility is currently a prominent topic in medical research. Increasing research suggests that gut microbiota dysbiosis can result in various reproductive health problems. This article specifically investigates the impact of gut microbiota dysbiosis on male reproductive infertility development. Gut microbiota imbalances can disrupt the immune system and immune cell metabolism, affecting testicular growth and sperm production. This dysfunction can compromise the levels of hormones produced and secreted by the endocrine glands, affecting male reproductive health. Furthermore, imbalance of the gut microbiota can disrupt the gut-brain-reproductive axis, resulting in male reproductive infertility. This article will explore how the imbalance of the gut microbiota impacts male reproductive infertility through immune regulation, endocrine regulation, and interactions of the gut-brain-reproductive axis, concluding with recommendations for prevention and treatment.

Both bacteria product flagellin and macrophages are implicated in HIV infection/disease progression. However, the impact of their interaction on HIV infection and the associated mechanisms remain to be determined. We thus examined the effect of the flagellins on HIV infection of primary human macrophages. We observed that the pretreatment of macrophages with the flagellins from the different bacteria significantly inhibited HIV infection. The mechanistic investigation showed that the flagellin treatment of macrophages downregulated the major HIV entry receptors (CD4 and CCR5) and upregulated the CC chemokines (MIP-1α, MIP-1β, and RANTES), the ligands of CCR5. These effects of the flagellin could be compromised by a toll like receptor 5 (TLR5) antagonist. Given the important role of flagellin as a vaccine adjuvant in TLR5 activation-mediated immune regulation and in HIV infection of macrophages, future investigations are necessary to determine the in vivo impact of flagellin-TLR5 interaction on macrophage-mediated innate immunity against HIV infection and the effectiveness of flagellin adjuvant-based vaccines studies.

The mortality of birds resulting from collisions and electrocutions with overhead lines, such as power lines, and phone line among others, has been implicated in the decline of various avian species globally. Specifically, overhead line collisions pose a significant threat to the conserva-tion of the Canarian houbara bustard (Chlamydotis undulata fuertaventurae), an endangered sub-species endemic to the Canary Islands. This study centres on the postmortem findings of Canarian houbara bustards that have collided with overhead lines, providing insights into the post-collision outcomes for these birds. A com-plete standardized necropsy of nine Canarian houbara bustards revealed that polytrauma was the cause of death in all cases. The most notable gross lesions associated with trauma included bone fractures, soft tissue lacerations, haemorrhages, luxations, and hemocoelom, with certain body regions being more frequently affected. Histopathology, immunohistochemistry, and en-tomology analysis confirmed that numerous birds survived the initial trauma, exhibiting varia-ble survival intervals before succumbing to their injuries. We concluded that when a houbara bustard collide with an overhead line it frequently survives the initial trauma. The histopathology, immunohistochemistry, or entomologic analysis may be helpful to approximate the timing interval between trauma and death.

Sinonasal carcinomas are aggressive neoplasms that present a high morbidity and mortality rate with unfavorable prognosis. This group of tumors exhibits morphological and genetic diversity. Genetic and epigenetic alterations in these neoplasms are currently targets for diagnosis and treatment. The most common type of cancer originated in the sinonasal tract are sinonasal squa-mous cell carcinomas (SNSCC), which presents different histological patterns and variable his-tological aggressiveness. A significant number of alterations have been reported in sinonasal tu-mors, including deficiencies in the SwItch/Sucrose non-fermentable (SWI/SNF) chromatin remod-eling complex. In the sinonasal tract, deficiencies of the subunits SMARCB1/INI1, SMAR-CA4/BRG1 and SMARCA2 have been noted in carcinomas, adenocarcinomas, and soft tissue tu-mors with distinctive high-grade morphology and fatal prognosis. Objective: To identify the status of the SWI/SNF complex using immunohistochemistry in sinonasal squamous cell carci-nomas and its association with morphology and survival. Methods: A total of 1582 SNSCC cases were analyzed, selecting those with high-grade malignancy morphology, which were then evalu-ated immunohistochemically for SMARCB1 and SMARCA4 proteins. Their expression was compared with the biological behavior and survival of the patients. Results: Among the SNSCC, 47% corresponded to the non-keratinizing squamous cell carcinoma (NKSCC) type with high-grade characteristics, 40% were keratinizing squamous cell carcinomas (KSCC), 9% were SMARCB1-deficient carcinomas, and 4% were SMARCA4-deficient carcinomas. Mosaic expres-sion for SMARCB1 (NKSCC 33%, KSCC 21.9%) and SMARCA4 (NKSCC 14.6%, KSCC 12.2%) was identified, showing an impact on tumor size and progression. Conclusions: We identified that the mosaic expression of INI1 in NKSCC exhibited a worse prognosis compared to intact carcinomas and was similar to SMARCB1-deficent carcinoma.

Fungi are rich sources of secondary metabolites of agrochemical, pharmaceutical and food importances, such as mycotoxins, antibiotics and antitumor agents. Secondary metabolites play vital roles in fungal pathogenesis, growth and development, oxidative status modulation, and adaptation/resistance to various environmental stresses. LaeA contains an S-adenosylmethionine binding site and displays methyltransferase activity. The members of velvet proteins include VeA, VelB, VelC, VelD and VosA, for each member with a velvet domain. LaeA and velvet proteins can form multimeric complexes such as VosA-VelB and VelB-VeA-LaeA. They belong to global regulators and are mainly impacted by light. One of their most important functions is to regulate gene expression that are responsible for secondary metabolite biosynthesis. The aim of this mini-review is to represent the newest cognition on the biosynthetic regulation of mycotoxins and other fungal secondary metabolites by LaeA and velvet proteins. In most cases, LaeA and velvet proteins positively regulated production of fungal secondary metabolites. The regulated fungal species mainly belong to the toxigenic fungi from the genera of Alternaria, Aspergillus, Botrytis, Fusarium, Magnaporthe, Monascus, and Penicillium for the production of mycotoxins. We can control secondary metabolite production to inhibit the production of harmful mycotoxins while promoting the production of useful metabolites by global regulation of LaeA and velvet proteins in fungi. Furthermore, the regulation by LaeA and velvet proteins should be a practical strategy in activating silent biosynthetic gene clusters (BGCs) in fungi to obtain previously undiscovered metabolites.

Survival of Medulloblastoma (MB) depends on various factors, including the gene expression profiles of MB tumor tissues. In this study, we identified 967 MB survival related genes (SRBs) using the gene expression dataset of Cavalli et al. (2017) and the Cox proportional hazards regression model. Notably, the SRGs were over-represented on chromosomes 6 and 17, known for the abnormalities monosomy 6 and isochromosome 17 in MB. The most significant SRG was HMGA1 (high mobility group AT-hook 1), which is a known oncogene and a histone H1 competitor. High expression of HMGA1 was associated with worse survival, primarily in the Group 3γ subtype. The high expression of HMGA1 was unrelated to any known somatic copy number alteration. Most SRGs on chromosome 17p were associated with low expression in Group 4β, the MB subtype with 93% deletion of 17p and 98% copy gain of 17q. Pathway analysis showed that both chromosomes 6 and 17 included SRGs related to telomere maintenance and provide a rationale for testing telomerase inhibitors in Group 3 MBs. We conclude that HMGA1, along with other SRGs on chromosome 6 and 17 warrant further investigation as potential therapeutic targets in selected subgroups or subtypes of MB.

Intrahepatic cholangiocarcinoma (ICCA) is a malignant epithelial neoplasm characterized by biliary differentiation within the liver. ICCA is molecularly heterogeneous and exhibits a broad spectrum of histopathological features. It is a highly aggressive carcinoma with high mortality and poor survival rates. ICCAs are classified into two main subtypes: small duct type and large duct types. These two tumor types have different cell origins and clinicopathological features. ICCAs are characterized by numerous molecular alterations, including mutations in KRAS, TP53, IDH1/2, ARID1A, BAP1, BRAF, SAMD4, and EGFR, and FGFR2 fusion. Two main molecular subtypes–inflammation and proliferation–have been proposed. Recent advances in high-throughput assays using next-generation sequencing have improved our understanding of ICCA pathogenesis and molecular genetics. The diagnosis of ICCA poses a significant challenge for pathologists because of its varied morphologies and phenotypes. Accurate diagnosis of ICCA is essential for effective patient management and prognostic determination. This article provides an updated overview of ICCA pathology, focusing particularly on molecular features, histological subtypes, and diagnostic approaches.

Background and Objectives: Renal cell carcinomas and upper tract urothelial carcinomas are types of malignancies that originate in the kidneys. Each of these examples shows an increasing trend in the frequency and the mortality rate. This study aims to comprehensively define carcinomas by analysing clinical, paraclinical, and histological aspects to predict aggressiveness and mortality. Materials and Methods: We conducted a retrospective investigation on a group of patients suspected with kidney cancers. Results: We identified 188 cases. We observed a higher mortality rate and older age in individuals with urothelial carcinomas. Anemia, acute kidney injury, hematuria and perineural invasion were the main risk factors that predicted their mortality. Tumour size in renal cell carcinomas correlates with the presence of necrosis and sarcomatoid areas. Factors that indicate a higher rate of death are older age, exceeding of the renal capsule, the lesion that includes the entire kidney, lymphovascular invasion, acute kidney injury, and anemia. Conclusions: Even if they originate at the renal level, and the clinical-paraclinical picture is similar, the histopathological characteristics make the difference. In addition, to these are added the previously mentioned common parameters that can represent important prognostic factors. In conclusion, the characteristics commonly identified in one type of cancer may act as risk factors for the other tumor. The detected data include threshold values and risk factors, making a significant contribution to the existing literature.

(1) Background: Double-strand breaks (DSBs) in a single nucleus are usually measured using the sperm chromatin structure assay (SCSA), sperm chromatin dispersion (SCD) test, and comet assay (CA). We developed mono-dimensional single-cell pulsed-field gel electrophoresis (1D-SCPFGE) and angle-modulated two-dimensional single-cell pulsed-field gel electrophoresis (2D-SCPFGE) to observe DNA fragmentation in separated motile sperm. (2) Methods: We set up comparative standards, calibration curves, the required sensitivity, and eligibility criteria for test sperm to validate their measurement principles. (3) Results: We revealed that the conventional methods overlooked the interference of nucleoproteins in their measurements. In-gel proteolysis improves the measurement accuracies of 1D- and 2D-SCPFGE. We recommend using naked DNA for comparative standards and test specimens. Moreover, we have observed several dysfunctions that may induce DNA damage in the separated motile sperm. Overall, our discussion highlights the need to revisit the conventional univariable analyses based on the SCSA, SCD test, and CA. (4) Conclusions: Human infertility is a complex syndrome, and the aim of quality control in intracytoplasmic sperm injection is to identify the underlying dysfunctions remaining in the separated motile sperm that render them ineligible for injection. Well-designed, multivariable analyses with special consideration to confounding factors are necessary in future cohort studies.

The classification of kidney tumors has undergone a remarkable evolution since the early 19th century, reflecting advances in medical science and technology. This historical overview traces the development of renal tumor classification, beginning with early clinical observations and macroscopic descriptions to the integration of molecular diagnostics in contemporary classifications. The establishment of international organizations like the World Health Organization (WHO) facilitated collaboration and standardization in tumor classification, leading to refined classifications and standardized nomenclature. Advancements in histological and molecular studies, particularly genetic analyses, revolutionized the understanding of renal cell carcinomas, enabling precise categorization based on molecular characteristics. The journey from rudimentary classifications to sophisticated systems based on detailed histological, immunohistochemical, and molecular criteria underscores the continuous evolution of kidney tumor classification. This article provides a comprehensive overview of this evolution, highlighting the contributions of scholars and the impact of technological advancements on our understanding and management of kidney tumors.

Lung cancer is the leading cause of cancer death worldwide therefore studies about the etiological factors and carcinogenesis are important.The aim of the study is to detect the presence and types of Human papilloma virus (HPV) in lung cancer and non-tumoral lung and Epidermal Growth Factor Receptor (EGFR) mutation prevalance in lung cancer with Polymerase Chain Reaction (PCR) method.Fifty patients who were histopathologically diagnosed lung cancer and 7 patients with non-neoplastic lung disease were enrolled in the study. HPV positivity was detected in 75.4% of the patients. The rate of high-risk HPV positivity was 100% in adenocarcinomas, 64.5% in squamous cell carcinomas, and 57% in non-neoplastic lung. HPV 51 was the most frequent type followed by HPV 16 (43.9%). There was no statistically significant relationship between HPV infection and age, gender and smoking history and EGFR mutation. The prevalence of HPV positivity is variable in lung cancer in different studies and this may be due to many factors including HPV detection methods, number of patients, geographic regions. New studies about the role of HPV infection need to be performed in order to obtain information about the use of prophylactic and theurepatic agents in lung cancer.

Follicular helper CD4+ T cells (TFH) are a major cellular pool for the maintenance of HIV reservoir. Therefore, the delineation of the follicular (F)/germinal center (GC) immune landscape will significantly advance our understanding of HIV pathogenesis. We have applied multiplex confocal imaging, in combination with relevant computational tools, to investigate, F/GC in situ immune dynamics in viremic (vir-HIV), antiretroviral treated (cART HIV) People Living With HIV (PLWH) and compare them to reactive, non-infected controls. Lymph nodes (LNs) from viremic and cART PLWH could be further grouped based on their TFH cell densities in high-TFH and low-TFH subgroups. These subgroups were also characterized by different in situ distribution of PD1hi TFH cells. The significantly accumulated follicular, compared to extrafollicular, FOXP3hi CD4+ T cells found in the low-TFH cART-HIV group were characterized by a less scattered in situ distribution and strongly correlated with the cell density of CD8+ T cells in this group. An inverse correlation between plasma viral load and LN GrzBhiCD8+ T and CD16hiCD15lo cells was found. Our data reveal the complex GC immune landscaping in HIV infection and suggest that follicular FOXP3hi CD4+ T cells could be negative regulators of TFH cell prevalence in cART-HIV.

Rice, as a staple crop feeding billions, faces constant threats from various diseases jeopardizing global food security. Precise understanding of disease resistance mechanisms is crucial for developing resilient rice varieties. Traditional genetic mapping methods, such as QTL mapping, provide valuable insights into the genetic basis of diseases. However, the complex nature of rice diseases demands a holistic approach to gain accurate knowledge of it. Omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, enable a comprehensive analysis of biological molecules, uncovering intricate molecular interactions within the rice plant. Integration of various mapping techniques using multi-omics data has revolutionized our understanding of rice disease resistance. By overlaying genetic maps with high-throughput omics datasets, researchers can pinpoint specific genes, proteins, or metabolites associated with disease resistance. This integration enhances the precision of disease-related biomarkers with better understanding of their functional roles in disease resistance. Improvement of rice breeding for disease resistance through this integration represents a significant stride in agricultural science because better understanding of the molecular intricacies and interactions underlying disease resistance architecture leads to more precise and efficient development of resilient and productive rice varieties. In this review, we explore how the integration of mapping and omics data can give a transformative impact on rice breeding for enhancing disease resistance.

Extensive genome structure variation, such as copy number variations (CNVs) and presence/absence variations, is the basis for the remarkable maize genetic diversity; however, the effect of CNVs on maize herbivory defense remains largely underexplored. Here, we report that the naturally occurring duplication of the maize 9-lipoxygenase gene, ZmLOX5, leads to increased resistance of maize to herbivory by fall armyworms (FAW). Previously, we showed that ZmLOX5-derived oxylipins are required for defense against chewing insect herbivores and identified several inbred lines, including Yu796, that contained duplicated CNVs of ZmLOX5, referred to as Yu796-2×LOX5. To test whether introgression of the Yu796-2×LOX5 locus into the herbivore-susceptible B73 background that contains a single ZmLOX5 gene is a feasible approach to increase resistance, we generated a series of near-isogenic lines that contained either 2, 1 or 0 copies of the Yu796-2×LOX5 locus in the B73 background by six back crosses (BC6). Droplet digital PCR (ddPCR) confirmed the successful introgression of the Yu796-2×LOX5 locus in B73. The resulting B73-2×LOX5 inbred line displayed increased resistance against FAW associated with increased expression of ZmLOX5, increased wound-induced production of its primary oxylipin product, the α-ketol, 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid (9,10-KODA), and the downstream defense hormones regulated by this molecule, 12-oxo-phytodienoic acid (12-OPDA) and abscisic acid (ABA). Surprisingly, wound-induced JA-Ile production was not increased in B73-2×LOX5, resulting from the increased JA catabolism. Furthermore, B73-2×LOX5 displayed enhanced drought tolerance likely due to increased ABA and 12-OPDA content. Taken together, this study revealed that the duplicated CNV of ZmLOX5 quantitively contributes to maize antiherbivore defense and presents proof-of-concept evidence that the introgression of naturally occurring duplicated CNVs of a defensive gene into the productive, but susceptible, crop varieties is a feasible breeding approach for enhancing plant resistance to herbivory and tolerance to abiotic stress.

The age-related loss of muscle mass and strength is referred to as “sarcopenia”. The combined effect of sarcopenia and osteoporosis is a devastating threat to the old adult, accounting for reduced mobility, risk for falls and subsequent fractures. In previous studies, we observed a high degree of inter-individual variability of paraspinal muscle fatty infiltration, one most relevant index of muscle wasting. This aspect solicited us to develop a computerized method to quantitatively characterize muscle fatty infiltration in aging and diseases. Magnetic resonance images of paraspinal muscles from 58 women of different age (age range 23-85 years) and physio-pathological status (healthy young, pre-menopause, post-menopause, and os-teoporosis), were used to set up the method. It is based on fractal analysis of lean muscle area (contractile muscle) to estimate muscle fatty infiltration. In particular, lacunarity was computed by parameter β from our hyperbola model function, used to fit the GBA (gliding box algorithm) curvilinear plot. Succolarity was estimated by parameter µ, for the four main directions, through an algorithm implemented on purpose. Results show that fractal lacunarity, by quantifying muscle fatty infiltration, can discriminate be-tween osteoporosis and healthy aging while succolarity can separate the other three groups showing similar lacunarity. Therefore, fractal features of contractile muscle, by measuring fatty infiltration, can represent good indices of sarcopenia in aging and disease.

We have designed cell penetrating peptides that target the leucine zipper transcription factors ATF5, CE-BPB and CEBPD and that promote apoptotic death of a wide range of cancer cell types, but not normal cells, in vitro and in vivo. While such peptides have the potential for clinical application, their mechanisms of action are not fully understood. Here, we show that one such peptide, Dpep, compromises glucose uptake and glycolysis in a cell-context-dependent manner (in about 2/3 of cancer lines assessed). These actions are dependent on induction of tumor suppressor TXNIP (thioredoxin interacting protein) mRNA and protein. Knockdown studies show that TXNIP significantly contributes to apoptotic death in those cancer cells in which it is induced by Dpep. The metabolic actions of Dpep on glycolysis led us to explore combinations of Dpep with clinically approved drugs metformin and atovaquone that inhibit oxidative phosphorylation and that are in trials for cancer treatment. Dpep showed additive to synergistic activities in all lines tested. In summary, we find that Dpep induces TXNIP in a cell-context-dependent manner that in turn sup-presses glucose uptake and glycolysis and contributes to apoptotic death of a range of cancer cells.

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation is analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors -of both primitive endocardial tubes- committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant nov-elty, our results revealed that miR-1 increases Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression, during early differentiation of cardiac sinoatrial region. Further-more, we observed in this developmental context that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacts with HDAC4 and Calmodulin, as well as with Erk2/MAPK1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in early differenti-ation of cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

Visual exploration of complex data helps interpretation, especially in the case of omics data analysis in life sciences and clinical research. Generating and analysing omics data requires bioinformatic skills, while they are interpreted by domain experts, for whom parsing large and complex data structures may be challenging. However, outcomes of visual analytics are often difficult to quantify, which emphasises precision and reproducibility, especially for research on human diseases. Here, we propose a workflow combining a reproducible computational environment with a dedicated visualisation functionality for systems biology diagrams. By linking the Galaxy with the MINERVA Platform, we visualise and explore COVID-19 transcriptomic data to demonstrate the utility of our workflow. Visualised data recapitulate findings of the original publication and offer new insights about the COVID-19 pathology. Our results offer a blueprint for quick prototyping of computational workflows that facilitate communication and exploration of complex data in biomedical research.

Introduction. Autopsy is a medical procedure that consists of the corpse’s examination to determine the cause of death and obtain information on pathological conditions or injuries present in the body. In recent years there has been a reduction in hospital autopsies and an increase in forensic autopsies. Material and methods. A retrospective observational study was conducted on the reports of all the 645 hospital autopsies performed at Polyclinic of Bari from 2006 to 2021.Results. Group A, 2006-2009, 174 cases were studied: 58% male, 58% adults, 55% neonatology, pulmonary disease was the cause of death in 23%, and 55% of discrepancy between clinical and autopsy diagnosis. Group B, 2010-2013, comprised 119 cases: 52% male, 46% infants, 48% neonatology, pulmonary disease was the cause of death in 25%, and 56% of discrepancy between clinical and autopsy diagnosis. Group C, 2014-2017, comprised 168 cases: gender equality, 37% infants, 25% gynecology, pulmonary disease was the cause of death in 24%, and 58% of discrepancy between clinical and autopsy diagnosis. Group D, 2018-2021 comprised 184 cases: 56% male, 38% adult, 32% gynecology, pulmonary disease was the cause of death in 27%, and 58% discrepancy between clinical and autopsy diagnosis.Conclusion. The study of hospital autopsies at the Polyclinic of Bari shows that the discrepancy between clinical and autopsy diagnosis is around 56.75%. Thus, the hospital autopsy is helpful in the modern age, especially for diagnosing fetal and neonatal diseases.

Breast cancer poses a global health challenge, yet the influence of ethnicity on the tumor microenvironment (TME) remains understudied. In this investigation, we examined immune cell infiltration in 230 breast cancer samples, emphasizing diverse ethnic populations. Leveraging tissue microarrays (TMAs) and core samples, we applied multiplex immunofluorescence (mIF) to dissect immune cell subtypes across TME regions. Our analysis revealed distinct immune cell distribution patterns, particularly enriched in aggressive molecular subtypes triple-negative and HER2-positive tumors. We observed significant correlations between immune cell abundance and key clinicopathological parameters, including tumor size, lymph node involvement, and patient overall survival. Notably, immune cell location within different TME regions showed varying correlations with clinicopathologic parameters. Additionally, ethnicities exhibited diverse distributions of cells, with certain ethnicities showing higher abundance compared to others. In TMA samples, patients of Chinese and Caribbean origin displayed significantly lower numbers of B cells, TAMs, and FOXP3-positive cells. These findings highlight the intricate interplay between immune cells and breast cancer progression, with implications for personalized treatment strategies. Moving forward, integrating advanced imaging techniques, and exploring immune cell heterogeneity in diverse ethnic cohorts can uncover novel immune signatures and guide tailored immunotherapeutic interventions, ultimately improving breast cancer management.

In late December 2019 a novel RNA beta-coronavirus was recognized as the causative agent of previously pneumonia cases of unknown origin. The virus was successively named Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) as well as the respiratory illness that it causes Coronavirus disease 19 (COVID-19) (1, 2). The global spread of SARS-CoV-2 and the thousands of deaths caused by COVID-19 led the World Health Organization (WHO) to declare a pandemic on 11 March 2020. To date, the world has paid a high toll in this pandemic in terms of human lives lost, economic repercussions and increased poverty. Indeed, even if most patients with COVID-19 are asymptomatic or experience mild self-limiting disease, 14% of them progress to severe disease and 5% to critical illness with complications, such as interstitial pneumonia, respiratory failure with acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndromes (MODS) (3). It is accepted that SARS-CoV-2 primarily affects the respiratory system, although other organs are also involved (4). The virus enters host cells by attaching its Spike like surface projections to the angiotensin-converting enzyme-2 (ACE2) receptor which is mainly expressed on alveolar epithelial cells and in nearly all human organs in varying degrees. Thus, although the central target of SARS-CoV-2 infection is the lung, the wide distribution of ACE2 receptors in other organs may lead to cardiovascular, gastrointestinal, kidney, liver, central nervous system and ocular damages that have to be closely monitored during the disease (5, 6). The virus then activates the innate and adaptive immune system resulting in a large number of cytokines release, known as “cytokine storm”, that is directly correlated with tissue injury and unfavourable prognosis of severe lung disease (7). In particular, interleukin (IL)-6 seems to plays an important role in driving this cytokine release so that its increased levels have been recognized as a hallmark inflammatory signature in sera of COVID-19 patients (8). IL-6 is a polyfunctional cytokine with both anti-inflammatory and pro-inflammatory properties which exerts its several functions through two main signal transduction pathways (9). In the classical signal transduction pathway, IL-6 binds to IL-6-trans membrane receptor (IL-6R) to form a complex that, then, binds to the trans membrane glycoprotein gp130, inducing its homo-dimerization and initiating intracellular signal transduction. This kind of signaling is limited to cells (hepatocytes, macrophages, neutrophils, T cells, etc.) that express IL-6R on their cell surface (10). Nevertheless, cells do not express IL- 6R, as stromal and epithelial cells, are able to still respond to IL-6 because the soluble form of the receptor (sIL-6R) binds to IL-6 in circle and then anchors to membrane gp130 receptor, initiating the trans-signaling pathway. For this reason, sIL-6R is able to increase the function of IL-6 and is considered the agonist form of its receptor. When the level of IL-6 increases, its effects are widely expressed because gp130 molecules are ubiquitous and, therefore, also present in cells without IL-6R in the membrane form. On the contrary, a soluble form of the glycoprotein 130 (sgp130) can complex with sIL-6R to prevent the sIL-6R from binding to the membrane-bound gp130. In this case sgp130 is able to decrease the function of IL-6 and is considered the antagonist form of IL-6 receptor system (11). Based on the central role of IL-6 in the inflammatory pathology of COVID-19 and the consistent association between elevated levels of the cytokine and severe disease outcomes found in the first phase of infection, we sought to analysis IL-6 and its soluble receptor complex behavior during the different waves of COVID-19 pandemic, in order to evaluate the possible differences which occur among them and to hypothesize if they might be used as prognostic markers of disease severity.

The artificial intelligence (AI) refers to the science and engineering of creating intelligent machines for imitating and expanding human intelligence. Given the ongoing evolution of the multidisciplinary integration trend in modern medicine, numerous studies have investigated the power of AI to address orthopaedic-specific problems. One particular area of investigation focuses on the shoulder pathology, which is a range of disorders or abnormalities of shoulder joint, causing pain, inflammation, stiffness, weakness, and reduced range of motion. There has not yet been a comprehensive review of the recent advancements in this field. Therefore, the purpose of this review is to evaluate the current AI applications in the shoulder pathology. This review mainly summarizes several crucial stages of the clinical practice, including predictive models and prognosis, diagnosis, treatment, and physical therapy. In addition, the challenges and future development of AI are also discussed.

The global incidence of cutaneous squamous cell carcinoma (cSCC), a prevalent and aggressive skin cancer, has risen significantly, posing a substantial public health challenge. This study investigates the tumor microenvironment (TME) of cSCC by focusing on the spatial distribution patterns of immune and vascular markers (CD31, CD20, CD4, and CD8) using fractal dimension (FD) analysis. Our analysis encompassed 141 cases, including 100 invasive cSCC and 41 specimens with pre-invasive lesions exclusively, and the rest being peripheral pre-invasive lesions from the invasive cSCC class. The FD values for each marker were computed and compared between pre-invasive and invasive lesion classes. The results revealed significant differences in FD values between the two classes for CD20 and CD31 markers, suggesting distinct alterations in B cell distribution and angiogenic activity during cSCC progression. However, CD4 and CD8 markers did not exhibit significant changes individually. Still, the CD4/CD8 ratio showed a significant difference, indicating a potential shift in the immune landscape as lesions progress from pre-invasive to invasive stages. These findings underscore the complexity and heterogeneity of the TME in cSCC and highlight the potential of FD analysis as a quantitative tool for characterizing tumor progression. Further research is needed to elucidate the implications of these differences in the clinical management of cSCC.

Background: Peritoneal sclerosis (PS) and its most severe form, encapsulating PS (EPS), are rare entities that can occur in various procedures (liver transplantation, intraperitoneal chemotherapy), secondary to medications ( beta-blockers); however, PS or EPS typically occur in patients undergoing peritoneal dialysis as a form of renal function substitution. Medical or surgical treatments can be applied, but morbidity and mortality have high rates . This condition typically presents clinically as an intestinal obstruction caused by the inclusion of the intestinal loops in the peritoneal fibrous membrane. Methods: Herein we present data from a single tertiary surgery center that has dedicated teams for patients receiving dialysis. In 12 years we analyzed a group of 63 patients admitted for catheter replacement/removal or for acute surgical pathology. In 5 cases (7,9%) we diagnosed EPS . Two patients with EPS presented with atypical abdominal pathologies requiring emergency surgery: one case of hemoperitoneum caused by a ruptured ovarian cyst and one case of uterine fibroids and metrorrhagia. Results: The definitive diagnoses were established intraoperatively and by analyzing the morpho-pathological changes of the peritoneum. The possible intraoperative challenges included laborious dissection, difficulties in restoring the correct anatomical landmarks, increased duration of the surgical intervention and a high rate of incidents and accidents Conclusions: The aim of the present study was to emphasize the possibility of other surgical pathologies overlapping with EPS, increasing the complexity of the surgical intervention. Also, we sought to determine whether there is a correlation between the morpho-pathological results of these patients who underwent emergency surgery and the common EPS morpho-pathological changes.

Soil-borne Trichoderma spp. have been extensively studied for their biocontrol activities against pathogens and growth promotion ability with plants. However, the beneficial effect of Trichoderma on inducing resistance against insect herbivores has been considered only recently. Among diverse Trichoderma species, consistent with previous reports, we showed that root colonization by T. virens triggered induced systemic resistance (ISR) to leaf-infecting fungal pathogens. Whether T. virens induces ISR to insect pests has not been tested before. In this study, we investigated whether T. virens affects jasmonic acid (JA) biosynthesis and defense against fall armyworm (FAW) and western corn rootworm (WCR). Unexpectedly, the results showed that T. virens colonization of maize seedlings grown in autoclaved soil suppressed wound-induced production of JA, resulting in reduced resistance to FAW. Similarly, the bacterial endophyte Pseudomonas chlororaphis 30-84 suppressed systemic resistance to FAW due to reduced JA. Further comparative analyses of the systemic effects of these endophytes when applied into sterile or non-sterile field soil showed that both T. virens and P. chlororaphis 30-84 triggered ISR against hemibiotrophic fungal pathogen Colletotrichum graminicola in both soil conditions, but only suppressed resistance to FAW in sterile soil. In contrast to the effect on FAW defense, T. virens colonization of maize roots suppressed WCR larvae survival and weight gain. This is the first report suggesting the potential role of T. virens as a biocontrol agent against WCR.

A Challenging task in routine practice is finding distinction between benign and malignant paragangliomas and pheochromocytomas. The aim of this study is a comparative analysis of angiogenesis by assessing intratumoral microvascular density (MVD) with immunohistochemical (IHC) markers (CD31, CD34, CD105, ERG), and S100 immunoreactivity, Ki67 proliferative index, SDHB expressiveness, tumor size with one the most utilized score Pheochromocytoma of Adrenal Gland Scales Score (PASS), using tissue microarray (TMA) with 115 tumor samples, 61 benign (PASS&lt;4) and 54 potentially malignant (PASS ≥4). We found no notable difference between intratumoral MVD and potentially malignant behavior. Group of potentially malignant tumors are significantly larger in size, have lower intratumoral MVD, and decreased number of S100 labeled sustentacular cells. Both groups have low proliferative activity (mean Ki67 is 1,02 and 1,22 respectively). Most tumors maintains SDHB expression, only 6 cases (5,2%) showed a loss of expression (4 of them in PASS&lt;4 group and 2 in PASS≥4). PASS score is easy available for assessment, and complemented with markers of biological behavior completes risk stratification algorithm. Size is directly related with PASS score and malignancy. Intratumoral MVD is extensively developed but it is not crucial in evaluating the malignant potential.

(1) Background: A wide literature based on loading and unloading bending tests has been carried out over the half past century for assessing the force released by superelastic wires. The aim of this investigation is not only to characterize a broadly described superelastic NiTi and a novel CuNiTi archwire, but also to provide novel insights into the load vs deflection profiles. A harmonic scenario for superelastic wires will be shown as temperature is kept constant at 37°C. However, a completely different picture will be highlighted as a temporary heating step up to 50°C is introduced within the force vs deflection profiles. (2) Methods: A variety of NiTi and a novel CuNiTi round and rectangular cross-section archwires have been investigated. Static 3-point bending tests up to a deflection level of 3.0 mm have been carried out for detecting the unloading force plateau levels occurring at 37°C. A hold deflection step of 5 min at deflection levels occurring along the unloading plateau extension is introduced. The effect of a temporary heating up to 50°C on the force plateau level released by the investigated wires is analyzed. (3) Results: Mechanical profiles suggest that the plateau force levels detected at 37°C are consistent with those broadly reported in the literature, but they only represent a single block puzzle of the force scenario that a superelastic wire releases during the orthodontic treatment. (4) Conclusions: Once a superelastic wire is bent and clinically applied, the effect of a temporary heating up to 50°C (e.g. hot food or drink ingestion) produces a significant plateau force increase whose magnitude depends on the deflection level. The highest force increase of about 50% and 40% have been detected at deflection levels located at the beginning of the unloading plateau extension for NiTi and CuNiTi wires, respectively.

Objectives: To assess the short-term impact of a single global stretching session on plantar pressures and lumbar range of motion (RoM) over one week in sedentary university students. Design: A randomised controlled trial with two parallel groups. Participants: Sixty-four university students were randomly assigned to a stretching group or control group. The stretching group received a single session of global stretching and the control group remained seated for the same length of time as the stretching session. Main outcome measures: Lumbar RoM and plantar pressures were assessed before, immediately after, 48 hours after, and 7 days after intervention. Results: Group-by-time interaction was significant for lumbar lateral flexion (p = 0.044), right maximal pressure (p = 0.003), left maximal pressure (p = 0.008), right mean pressure (p = 0.025), left mean pressure (p = 0.002), and maximal pressure minus mean pressure in right foot (p = 0.007). The model with plantar pressures showed a significant difference for group-by-time interaction (p = 0.010).Conclusion: Global stretching seems to counteract the ill-effects of prolonged sitting up to seven days with respect to plantar pressure in standing without improving lumbar ROM

Mutations affecting codon 172 of the isocitrate dehydrogenase 2 (IDH2) gene define a subgroup of sinonasal undifferentiated carcinomas (SNUCs) with a relatively favorable prognosis and a globally hypermethylated phenotype. They are also recurrent (along with IDH1 mutations) in gliomas, acute myeloid leukemia, and intrahepatic cholangiocarcinoma. Commonly reported mutations, all associated with aberrant IDH2 enzymatic activity, include R172S, R172T, R172G, and R172M. We present a case of SNUC with a never-before-described IDH2 mutation, R172A. Our report compares the methylation pattern of our sample to other cases from the GEO database. Hierarchical clustering suggests a strong association between our sample and other IDH-mutant SNUCs and a clear distinction between sino-nasal normal tissues and tumors. Principal component analysis (PCA), using 100 principal components explaining 94.5% of the variance, shows the position of our sample within 1.02 standard deviation of the other IDH-mutant SNUCs. Molecular modeling analysis of the IDH2 R172A versus other R172 variants provides a structural explanation to how they affect the protein active site. Our findings thus suggest that the R172A mutation in IDH2 confers a gain of function similar to other R172 mutations in IDH2, resulting in a similar hypermethylated profile.

Background: Ovarian, cervical, and endometrial cancers stand as fatal health killers for women's mental and physical health, especially affecting female reproductive systems. Exploiting weakly supervised learning and explainable AI techniques are crucial for fast, accurate, and robust automatic marker detection, efficient prevention, and primary treatment of gynecological tumors. Methods: With respect to the PRIMSA methodology, weakly supervised learning schemes and deep learning-based schemes are investigated in the cross-subject fields of clinical diagnostic imaging and explainable AI technology. Related methods, opening research problems, and challenging subjects are explored in the screening and treatment of gynecological tumors and performing cancer image diagnosis in the latest study. Results: Keynote approaches combining ultrasound medicine, explainable AI, and clinical imaging technology are summarized. In combination with learning-based methods with medical imaging, prospective insights are put forward for refreshed concepts on treatments in the area of gynecological oncology, with a feasible range of applications for their corresponding AI techniques. Conclusions: Explainable AI and deep learning-based approaches are capable of performing accurate classification between benign and malignant tumors, yielding a pathway to care for women's health, improving the survival rate of patients, pacing with disease prediction, and matching the strategic goal of "Healthy China 2030".

In recent experimental studies, we reported the aggravating effects of Asian sand dust (ASD) on male reproductive function in mice. However, the effects of fetal ASD exposure on male reproductive function have not been investigated. The present study investigated the effects of fetal ASD exposure on reproductive function in male offspring. Using pregnant CD-1 mice, ASD was administered intratracheally on days 7 and 14 of gestation, and the reproductive function of male offspring was determined at 5, 10, and 15 weeks after birth. The secondary sex ratio was significantly lower in the fetal ASD-exposed mice than in the controls. Histologic examination showed partial vacuolation of seminiferous tubules in immature mice. Moreover, daily sperm production (DSP) was significantly less in the fetal ASD-exposed mice than in the controls. DSP in the fetal ASD-exposed mice was approximately 10% less than the controls at both 5 and 10 weeks. However, both the histologic changes and the DSP decrease were reversed as the mice matured. These findings suggest that ASD exposure affects both the fetal development and the reproductive function of male offspring. In the future, it will be necessary to clarify the onset mechanisms of ASD-induced male fetus death and male reproductive disorders.

The aim of this article is to identify the best available evidences analyzing liver samples, normall and pathological. In the study were used liver samples, collected during necropsy, from healthy patients and from patients diagnosed with cirrhosis .This mentioned, are known as routinally practice for hepatitis C diagnosis, which conduct to hepatic cirrhosis. Were made permanent preparations and used Hematoxylin–Eosin staining and other special stainings for structural observations at optical microscope using lens with differents magnifications, such us x10 and x40.

Background and Objectives: ARNE score was developed for the prediction of difficult airway for both general and ENT surgery with a universal cut-off value. We tested the accuracy of this score in the case of laryngeal surgery and provided an insight of its combination with flexible laryngoscopy. Materials and Methods: This prospective pilot clinical study included 100 patients who were being scheduled for microscopic laryngeal surgery. We have calculated ARNE score for every patient and flexible laryngoscopy was provided preoperative. Difficult intubation was assessed according to intubation difficulty score (IDS). Results: A total of 33% patients had difficult intubation according to IDS. ARNE score showed to be accurate for prediction of difficult intubation in laryngology with P&lt;0.0001 and AUC 0.784. Flexible laryngoscopy showed to be an independent parameter with P&lt;0.0001 and AUC 0.766. We have defined a new cut-off value of 15.50 for laryngology, according to AUC curve. After the patients were divided in two groups, according to the new cut-off value and provided cut-off value, AUC improved to 0.707 from 0.619 respectively. Flexible laryngoscopy improved the prediction model of ARNE score to AUC 0.882 and of new cut-off value to AUC 0.833. Conclusions: It is recommended to use flexible laryngoscopy together with ARNE score in difficult airway prediction in patients with laryngeal pathology. Also, universally recommended cut-off value of 11 can not be effectively used in laryngology and a new cut-off value of 15.50 is recommended.

Mitochondria are dynamic organelles ubiquitously present in nucleated eukaryotic cells, subserving multiple metabolic functions, including cellular ATP generation by oxidative phosphorylation (OXPHOS). The OXPHOS machinery comprises five transmembrane respiratory chain enzyme complexes (RC). Defective OXPHOS gives rise to mitochondrial diseases (mtD). The incredible phenotypic and genetic diversity of mtD can be attributed at least in part to the RC dual genetic control (nuclear DNA [nDNA] and mitochondrial DNA [mtDNA]) and the complex interaction between the two genomes. Despite the increasing use of next-generation-sequencing (NGS) and various -omics platforms in unraveling novel mtD genes and pathomechanisms, current clinical practice for investigating mtD essentially involves a multipronged approach including clinical assessment, metabolic screening, imaging, pathological, biochemical and functional testing to guide molecular genetic analysis. This review addresses the broad muscle pathology landscape including genotype-phenotype correlations in adult and paediatric mtD, the role of immunodiagnostics in understanding some of the pathomechanisms underpinning the canonical features of mtD, and recent diagnostic advances in the field.

With its unique properties and potential applications, nanoparticle-based delivery platforms for vac-cines have gained significant attention in recent years. Nanoparticles have the advantages of enhancing immunogenicity, targeting delivery and improving stability, providing a new solution for drug and vaccine delivery. And in some clinical studies, a variety of nanoparticle delivery platforms have been gradually applied to a wide range of vaccine applications. Current research priorities are exploring various types of nanoparticles as vaccine delivery system to enhance vaccine stability and immunogen-icity. Lipid nanoparticles have shown promising potential in preclinical and clinical studies to efficiently deliver antigens to immune cells. Moreover, lipid nanoparticles (LNPs) and other nanoparticles as nu-cleic acids especially mRNA delivery system, have shown vast potential for vaccine development. In this review, we present various vaccine platforms with an emphasis on nanoparticles for mRNA nano-vaccine delivery vehicles. We introduce several novel nanoparticles delivery platforms for mRNA vac-cine such as lipid, polymer, protein-based nanoparticle and so on. In addition, we overview the an-ti-tumor immunity of nanovaccine against different tumors in cancer immunotherapy. Finally, we give an outlook future perspectives and remaining challenges for this promising technolo-gy-nanoparticle-based delivery platforms for vaccines.

Purpose: Arab Americans are one of the largest ethnic groups in the United States. The mental health of Arab Americans and opinions on mental health, however, remain understudied despite higher rates of mental illness and lower rates of treatment. Unique cultural conceptualizations of mental illness may generate stigma, contributing to disparities in treatment. This study aimed to assess the attitudes and perspectives of Arab Americans regarding mental illness in order to address barriers to treatment. Methods:Using an anonymous bilingual Qualtrics survey, we assessed Arab and non-Arab participants (n = 294; ages 18+) on their conceptualizations of the causes of mental illness and on their stigma towards mental illness and mental health treatments. Comparisons were performed between Arabs and non-Arabs, as well as among Arabs. Results:Compared to non-Arabs, Arabs reported higher average mental illness stigma and were more likely to rate psychiatric medications as addictive and unhelpful. Among Arabs, being Christian, male, and older (>29 years old) were each associated with higher stigma. Arabs were less likely than non-Arabs to believe in a biological explanation for mental illness. Conclusion: Our results demonstrate higher levels of stigma towards mental illness among Arab Americans, especially Christian, male, and older Arabs, potentially related to a weaker belief in a biomedical model for mental illness. These are among the first findings describing mental illness stigma and beliefs about mental health in an Arab American community and may inform future interventions providing culturally competent care to Arab Americans.

Coccidioidomycosis (Valley Fever) is a disease caused by inhalation of Coccidioides spp. This neglected tropical disease of the Americas has substantial public health impact despite its geographic restriction to desert areas of the southwestern U.S., Mexico, Central and South America. The incidence of this infection in California and Arizona has been increasing over the past fifteen years. The burden of disease in outside the U.S. remains poorly understood. Several large cities are within the endemic region in the U.S. Coccidioidomycosis accounts for 25,000 hospital admissions per year in California. While most cases of coccidioidomycosis resolve spontaneously, up to 40% are severe enough to require anti-fungal treatment, and a significant number disseminate beyond the lungs. Disseminated infection, especially involving the meninges, is fatal without appropriate treatment. Infection with Coccidioides spp. is protective against a second infection, so vaccination seems biologically plausible. This review of efforts to develop a vaccine against coccidioidomycosis focuses on vaccine approaches and the difficulties in identifying protein antigen/adjuvant combinations that protect in experimental mouse models. Although the quest for a vaccine has not yet resulted in a clinically useful product, scientific efforts of vaccine development pave the way for future success.

Diagnosing melanocytic lesions is among the most challenging problems in the practice of pathology. The difficulty of physically masking melanin pigment and the similarity of its color to commonly used chromogens often complicate examination of the cytomorphology and immunohistochemical staining results for tumor cells. Melanin bleach can be very helpful for histopathological diagnosis of heavily pigmented melanocytic lesions. Although various depigmentation methods have been reported, no standardized methods have been developed. This study developed a fully automated platform that incorporates hydrogen peroxide-based melanin depigmentation in an automated immunohistochemical analysis. The utility of the method was tested in one cell block of malignant melanoma cells in pleural effusion, ten ocular melanoma tissue samples, and ten cutaneous melanoma tissue samples. Our results demonstrated that the proposed method, which can be performed in only 3 hours, effectively preserves cell cytomorphology and immunoreactivity. The method is particularly effective for removing melanin pigment to facilitate histopathological examination of cytomorphology and for obtaining an unmasked tissue section for immunohistochemical analysis.

The effects of toxic air in the form of air pollution are known to harm women’s health. New data has shown that air pollution has effects on maternal anemia. Yet the effects of particulate matter 2.5 (PM_2.5) on hemoglobin among reproductive maternal (15-49 years) has been understudied. In this population-based study, we study the region-specific associations between prevalence of hemoglobin among reproductive women and PM_2.5 in 43 countries of Africa from 2000-2019. Using generalized linear regression models, we found that after adjusting for key covariates, PM_2.5 had a slight negative association with hemoglobin among reproductive women. Other studies are needed in other low-income settings to expand our findings.

(1) Background: With the rising incidence of life expectancy, obesity, and tumours, understanding the incretory influence of adipose tissue in tumorigenesis becomes increasingly important. As the adipokines leptin and adiponectin are released by fat tissue, we aimed to analyse the expression of their respective receptors in tumours for which an association with obesity is epidemiologically hypothesized; (2) Methods: The expression of leptinR and adipoR1 were analysed in cohorts of renal cell cancer (n = 391), cervical cancer (n = 155), vulvar cancer (n = 107), and endometrial cancer (n = 90) by immunohistochemistry and correlated with clinicopathological parameters including survival times; (3) Results: Expression of leptinR was high in renal cell cancer (62.2% of cases), vulvar carcinoma (50%) and endometrial cancer (80.5% of tissue-samples). High expression was associated with favourable clinicopathological markers and longer overall survival times in renal cell cancer and vulvar cancer. AdipoR1 was only weakly expressed in all four tumor entities and did not show significant associations with clinicopathological parameters or prognosis; (4) Conclusion: High leptinR is a promising biomarker for favourable tumour outcome in renal cell carcinoma and vulvar carcinoma.

In some species of salmon, reproductive maturity triggers the development of massive pathology resulting from reproductive effort, leading to rapid post-reproductive death. Such reproductive death, which occurs in many semelparous organisms (with a single bout of reproduction), can be prevented by blocking reproductive maturation, and this can increase lifespan dramatically. Reproductive death is often viewed as distinct from senescence in iteroparous organisms (with multiple bouts of reproduction) such as humans. Here we review the evidence that reproductive death occurs in C. elegans and discuss what this means for its use as a model organism to study aging. Inhibiting insulin/IGF-1 signaling and germline removal suppresses reproductive death and greatly extends lifespan in C. elegans, but can also extend lifespan to a small extent in iteroparous organisms. We argue that mechanisms of senescence operative in reproductive death exist in a less catastrophic form in iteroparous organisms, particularly those involving costly resource reallocation, and exhibiting endocrine-regulated plasticity. Thus, mechanisms of senescence in semelparous organisms (including plants) and iteroparous ones form an etiological continuum. Therefore understanding mechanisms of reproductive death in C. elegans can teach us about some mechanisms of senescence that are operative in iteroparous organisms.

For the first time, mathematical models were obtained for evaluating biomedical images using fuzzy set methods on the basis of expert knowledge bases, which made it possible to carry out complex qualitative diagnostics and increase the reliability and efficiency of diagnosis, to form a methodology for analyzing biomedical images based on the fuzzy set apparatus, which allowed to more fully assess the level of the disease for glaucoma. Aspects of practical implementation of the optical-electronic system of biomedical information processing are considered. An algorithm and an optical-electronic system of biomedical image analysis are proposed, which are used to increase the informativeness and reliability of diagnosing eye pathologies, in particular, glaucoma.

The purpose of this review is to elucidate the actual threat of the most prevalent mycotoxins in agricultural commodities and human/animal food/feed for appearance of foodborne ailments and diseases. The underestimated hazard of joint mycotoxin uptake of animals or humans is critically discussed with regards to synergistic or additive interaction between some target mycotoxins. The real toxicity of target mycotoxin combinations as it happens in practice is evaluated and possible lower limit values or control measures are suggested in such cases. Some critical points in adequate risk assessment, hygiene control and regulation of mycotoxns are discussed. The efficiency of current mycotoxin regulations and control measures is evaluated in regards to human/animal health hazard. The risk assessment in the case of multiple mycotoxin exposure of humans/animals via the food/feed or agricultural commodities is evaluated and some suggestions are proposed in such cases. Appropriate control measures and food safety issues throughout the food supply chain are proposed in order to prevent target foodborne diseases. Some preventive measures and possible veterinary hygiene control or risk assessment are proposed in some practical cases of foodborne diseases for preventing mycotoxin contamination of animal products designed for human consumption and to avoid possible public health issues.

Selenoproteins are a group of proteins containing selenium in the form of selenocysteine (Sec, U) as the 21st amino acid coded in the genetic code. Their synthesis is dependent on dietary selenium uptake and a common set of cofactors. Selenoproteins accomplish diverse roles in the body and cell processes by acting, for example, as antioxidants, modulators of the immune function, detoxification agents for heavy metals, and other xenobiotics, key compounds in thyroid hormone metabolism. Although the functions of all this protein family are still unknown, several disorders in their structure, activity or expression have been described by researchers. They concluded that selenium or cofactors deficiency, on one hand, or the polymorphism in selenoproteins genes and synthesis, on the other hand, are involved in a large variety of pathological conditions, including type 2 diabetes, cardiovascular, muscular, oncological, hepatic, endocrine, immuno-inflammatory, neurodegenerative diseases. This review is focused on specific roles in medicine only of selenoproteins that are each named after an alphabet letter, less known than the rest of them, regarding their implications in patho-logical processes of several prevalent diseases and also in disease prevention.

Abstract: Autoimmune encephalitis is a complex and multifaceted pathology that involves the immune-mediated inflammation of the brain. It is characterized by the body's immune system mistakenly attacking the brain tissue, leading to a cascade of inflammatory processes. What makes autoimmune encephalitis vast is the wide range of causes, mechanisms, clinical presentations, and diagnostic challenges associated with the condition. The clinical presentations of autoimmune encephalitis are broad and can mimic other neurological disorders, making it a challenging differential diagnosis. This diverse clinical presentation can overlap with other conditions, making it crucial for healthcare professionals to maintain a high level of suspicion for autoimmune encephalitis when evaluating patients. The diagnostic challenges associated with autoimmune encephalitis further contribute to its vastness. Due to the variable nature of the condition, there is no definitive diagnostic test that can confirm autoimmune encephalitis in all cases. In this context, personalized patient management is crucial for achieving favorable outcomes. Each patient's treatment plan should be tailored to their specific clinical presentation, underlying cause, and immune response. Our objective is to raise awareness about the frequent yet under-diagnosed nature of autoimmune encephalitis by sharing five cases we encountered, along with a brief literature review.

Mucosal healing (MH) is the main treatment target in ulcerative colitis and Crohn’s disease, and it is defined by a combination of complete endoscopic and histologic remission. Indeed, the complete resolution of mucosal inflammation should be confirmed at histology. Neutrophil infiltration represents the unique histological marker in discriminating the active vs quiescent phase of disease, also including crypt injuries (cryptitis and crypt abscesses), erosions and ulcerations. Basal plasmacytosis do not qualify by itself the remission in inflammatory bowel diseases (IBD), but it represents a diagnostic clue, mostly at onset. Several histological scoring systems have been developed to evaluate therapeutic efficacy, even though they often resulted tricky and subjective. Moreover, these scores listed a heterogeneous group of histological features as parameters. The recently proposed simplified histological score on MH was based on neutrophils and their distribution in the gut mucosa was also considered, aiming to provide a simple, time-sparing and reproducible tool to be applied to the routinary diagnostic practice. The artificial intelligence could be a promising tool both in evaluating and standardizing the histological assessment of disease activity in IBD. Moreover, novel molecules involved in the inflammatory dynamics in the gut could be employed in supporting the diagnostic practice in IBD.

Deep learning techniques, such as convolutional neural networks (CNN), generative adversarial networks (GAN), and graph neural networks (GNN), have over the past decade changed the ac-curacy of prediction in many diverse fields. In recent years, the application of deep learning tech-niques in computer vision tasks in pathology demonstrated extraordinary potential in assisting clinicians, automating diagnosis, and reducing costs for patients. Formerly unknown pathologi-cal evidence, such as morphological features related to specific biomarkers, copy number varia-tions, and other molecular features, were also able to be captured by deep learning models. In this paper, we review popular deep learning methods and some recent publications about their appli-cations in pathology.

Abstract: Ovarian cancer (OC) ranks as the fifth most common cancer among women in the United States and globally, posing a significant health threat. Reactive oxygen species (ROS) have emerged as critical factors in the pathophysiology of this malignancy. ROS, characterized by their instability due to an unpaired electron, are involved in essential cellular functions and play a crucial role in the immune response under normal physiological conditions. However, an imbalance in ROS homeostasis, leading to excessive ROS production, results in oxidative stress (OS), which can cause indiscriminate damage to cellular structures and contribute to the pathogenesis of specific diseases, including OC. OC is primarily classified based on the originating cell type into epithelial, stromal, and germinal tumors, with epithelial tumors being the most prevalent. Despite advancements in medical technology, early detection of OC remains challenging, often leading to delayed treatment initiation. Current therapeutic approaches include surgical excision of tumor tissue, radiotherapy and chemotherapy. While these treatments are effective in early-stage OC, high mortality rates and frequent relapse underscore the urgent need for novel diagnostic and therapeutic strategies. This review aims to elucidate the role of ROS in OC, emphasizing the potential for developing innovative diagnostic tools and treatments that target ROS-mediated pathways. Given the critical impact of early detection and effective treatment, advancing our understanding of ROS in the context of OC could significantly enhance patient outcomes.

Family Parvoviridae consists of small, non-enveloped viruses with linear, single-stranded DNA genomes of approximately 4-6 kilobases, subdivided into 3 subfamilies: Parvovirinae, Densovirinae and Hamaparvovirinae. Parvoviruses of aquatic animals infect crustaceans, mollusks, and finfish. In this review, these parvoviruses, which are highly host-specific and are associated with mass morbidity and mortality in both farmed and wild aquatic animals are described. They include Cherax quadricarinatus densovirus (CqDV) in freshwater crayfish; Sea star-associated densovirus (SSaDV) in sunflower sea star on the Northeastern Pacific Coast; Clinch densovirus 1 in freshwater mussels in the Clinch River, Virginia, and Tennessee, USA, in subfamily Densovirinae; Hepatopancreatic parvovirus (HPV) and Infectious hypodermal and hematopoietic necrosis virus (IHHNV) in farmed shrimp worldwide; Syngnathid ichthamaparvovirus 1 in gulf pipefish in the Gulf of Mexico and parts of South America; and Tilapia parvovirus (TiPV) in farmed tilapia in China and Thailand, in the subfamily Hamaparvovirinae. In addition, virus megataxonomy has enabled the inclusion of novel parvoviruses detected in both diseased and healthy animals using metagenomic sequencing for virus discovery, such as the novel zander parvovirus from zander in Hungary, novel salmon parvovirus from sockeye salmon smolts in British Columbia-Canada, and Spawner-isolated mortality virus (SMV) from shrimp broodstock in Australia.

The objectives of this study was to assess the impact of a reproductive approach in high-yielding nulliparous and parous Holstein cows on the interestrus interval, estrus detection rates, conception rates, and pregnancy rates. The strategy involved giving GnRH on day 5 following artificial insemination (AI). For nulliparous cows, there appears to be no noticeable effect of GnRH therapy on the interestrus interval. In both groups, nearly all of the cows exhibited an 18–25-day cycle interval (P < 0.05). In the 18–25 day cycle period, the untreated multiparous cows exhibited the highest proportion (P < 0.05), while the treated group demonstrated the highest proportion (P < 0.05) in the 26–35 day cycle interval. The study found that the conception rate was higher in repeat breeder nulliparous and 3+ lactation treated Holstein cows compared with untreated ones. However, the cumulative heat detection rate, pregnancy rate and conception rates were similar in both groups (P > 0.05). Also, this study found that in the hottest months of the year, this therapeutic approach can't counteract the negative effect of heat stress in high-yielding dairy cows. Thus, it is not advised of using the hormonal method to create supplementary corpus luteum across the herd.

Abstract: The use of IVF and related procedures has offered opportunities for couples to conceive who otherwise would remain childless. This technology is often viewed as the only option but is very expensive and not highly effective. ln an effort to improve access to care, governments are attempting to provide funding. In Ireland for example the Health Service Executive (HSE) has recently made IVF funding available through Regional Fertility Hubs. for couples who qualify. However, this policy has threatened a less invasive approach available in Ireland that can help many couples before IVF is employed. We propose that a newly emerging “medical treatment process” called Restorative Reproductive Medicine (RRM), combined with methods or apps that track biomarkers of the menstrual cycle as a prerequisite option for appropriate patients. To illustrate the effectiveness, we compared live birth rates from an established Irish RRM clinic that uses the ChartNeo app to HFEA (Human Fertilization and Embryology Authority) data, both from 2019. RRM treatment had a live birth rate of 40.4% compared to 24.4% per treatment cycle for IVF (P>0.0001). RRM twin pregnancy rate was 2.5% compared to 7% for IVF. RRM babies were usually full term and normal birth weight. Therefore, RRM is less expensive, less invasive, and more effective than IVF for most patients. This merits further evaluation and support by the HSE and other global authorities guiding health policy.

Introduction: Gastric cancer (GC) is one of the most common cancers in the world. It is a very aggressive and heterogeneous tumor. GC does not cause symptoms, so it is often diagnosed in an advanced stage and associated with poor prognosis. Despite new treatment options, it still remains a therapeutic problem. An important element determining the method of treatment of locally advanced gastric cancer (LAGC) is the assessment of lymph node metastases in preoperative and postoperative imaging and/or histopathological examination.Aim: The assessment of lymphovascular invasion (LVI) in histopathological examination in patients with LAGC after gastrectomy. The groups of patients were divided into patients who received preoperative chemotherapy, patients without preoperative chemotherapy, and all patients. Additionally, we assessed the correlation between the presence of LVI and the number of lymph nodes collected during gastrectomy.Material and method: We collected patients with histologically confirmed GC after gastrectomy. The collected samples were divided into three subgroups: patients with neoadjuvant chemotherapy (NAC), patients without NAC, and all patients. Histopathological examination assessed the presence of LVI infiltration. We then assessed the correlation between the presence of LVI and the presence of lymph node metastasis in GC. Additionally, we assessed the correlation between LVI and the number of lymph nodes evaluated in patients in each group. The statistical analyses were performed using Statistica v13.3 and Microsoft Excel 2021. The significance limit was set at p<0.05.Results:The presence of LVI strongly correlated with node involvement, and the result was statistically significant in all patients and the group of patients treated with NAC. The difference was not statistically significant in the group not treated by NAC. Additionally, we did not observe a correlation between the presence of LVI and the number of metastatic lymph nodes in GC.Summary and Conclusions: The presence of LVI in a patient with GC indicates a high probability of lymph node metastasis, which should translate into therapeutic procedures. Assessment of LVI may help identify potential patients with lymph node metastases, particularly in patients undergoing endoscopic resection without planned lymphadenectomy. It is advisable to expand research on a larger scale in order to establish clear standards in this area.

The detection of Fasciola eggs in ruminant fecal samples typically occurs around 15 weeks post-infection during patent infections. The recent introduction of coproantigen ELISA (cELISA) diagnostics, which capture antigenic enzymes in fecal material, holds promise for monitoring Fasciola fecal egg count (FFEC) to implement control programs, particularly targeted treatments. This study compared two study groups, those with positive FFEC (FFEC+ve) and negative FFEC (FFEC-ve), to assess the sensitivity of Flukefinder sedimentation and a cELISA kit. This study reports that the coproantigen ELISA detection limit was 4.5 eggs per gram (epg) for a 100% positivity rate. Additionally, a moderate, statistically significant positive correlation (r²=0.716, p-value < 0.01) and an odds ratio of 1.96 (p-value < 0.01) were observed between FFEC and Fasciola coproantigen from cELISA. This implies that for every single unit increase in FFEC, there is a 96% likelihood of obtaining a higher optical density (OD) reading from the cELISA test. The results suggest that cELISA can complement fecal sedimentation tests, serving as a valuable tool for detecting cattle with high FFEC. This capability facilitates targeted treatment strategies, thereby aiding in the control and prevention of the spread of fasciolosis within the studied area.

Here, we present a staged approach for an innovative repurposing of a portable infant humidicrib into a live cell growth, observation, and imaging system. Furthmore, humidicrib can support different variations of “umbilical” bioreactors, and can be used to conduct electrophysiology experiments and in situ immunohistochemistry. Modifications incorporate a closed loop carbon dioxide (CO₂) concentration control system with umbilical CO₂ and heating support for tailored bioreactors. The repurposing cost is inexpensive and allows for the continued observation and imaging of cells. This prototype unit has been used to continuously observe and image live primary neurons for up to 21 days. This demonstrates the repurposed units’ suitability for use in tissue culture based research, particularly where modifications to microscopes are required or where sensitive manipulation outside of a standard incubator is needed.

The study aimed to manage and to analyse the results of the laboratory tests, routinally practice for hepatitis C diagnosis, using blood tests. Comparison of ELISA method results (Enzyme-Linked Immunosorbent Assay) and chemiluminescence methods results. Statistical analysis of this study results, was performed using the laboratory informatic system. The results of the study are substantial and intricate reffering to comparision between two methods concretlly ELISA method (Enzyme-Linked Immunosorbent Assay) and chemiluminescence methods and their results. For this purpose, the results of preliminary EСL screening method of patients at risk for HCV who took part in the study, are presented in specific tables. More than good to mention that the correlations of results were used in order to identify a possible relationships between indicators of ELISA method and ECL index. In addition, correlations antibodies detected in electrochemiluminescence, ECL and Enzyme-Linked Immunosorbent Assay ELISA are pointed out. EСL and ELISA method results, are relevant for screening and for diagnostic confirmation in HCV risk patients. Unfortunately in the present study, were impossible to conclude about false-negative results. Good to know our opinion that RT-PCR technique, it is considered proper for the diagnosis of HCV.

Rosette caused by rose rosette virus (RRV) is the most devastating malady of rose in the United States. Because of the recent discovery of the virus and the completion of Koch’s postulates all assumptions about the disease are based on visual observations of material that may or may have not been infected by the virus. This study addresses several aspects of virus and disease epidemiology. Twenty rose genotypes were screened for mite and/or virus resistance. Phyllocoptes fructiphilus the only known vector of RRV, was able to establish, lay eggs and develop to nymphs and adults in all genotypes. ‘Stormy Weather’ shows resistance to the virus as assessed by both mite and cleft-grafting transmission experiments. The acquisition/latent and inoculation access periods were studied revealing long acquisition/latent periods but rapid inoculation time frames. The outputs of this study will assist in the better management of the vector and the disease. The resistant genotype identified could be used in areas with high disease pressure to minimize spread and for identification of the mechanisms behind resistance or as breeding material to incorporate virus resistance to new cultivars. The short inoculation access period indicates that chemical control for the vector may be a challenging undertaking.

Vitamin D and iron deficiencies are the most prevalent micronutrient deficiencies among women of reproductive age (WRA) in Morocco. Recent studies suggest that Vitamin D deficiency (VDD) may reduce iron bioavailability necessary for erythropoiesis, potentially leading to iron deficiency (ID) and anemia. This study investigates the association between vitamin D status, iron levels, and anemia risk among Moroccan WRA aged 18-49 years. A cross-sectional study was conducted with 463 participants. Serum levels of 25(OH)D, blood count parameters, iron, ferritin, C-reactive protein, and creatinine were measured. Lifestyle factors, including dietary intake, sun exposure, and physical activity, were evaluated using validated questionnaires, and anthropometric data were collected. Linear and logistic regression models assessed the relationships between variables, while Receiver Operating Characteristic (ROC) curve analysis evaluated the predictive accuracy of VDD for ID and anemia. VDD (25(OH)D &lt; 20 ng/ml) was significantly associated with lower levels of hemoglobin, hematocrit, red blood cells, and ferritin (all p &lt; 0.01), suggesting a role of vitamin D in erythropoiesis and iron storage. Multivariate logistic regression showed that VDD increased the risk of anemia (OR: 7.17, 95% CI: 3.19-19.28, p &lt; 0.001), ID (OR: 2.20, 95% CI: 1.32-3.77, p = 0.007), and IDA (OR: 4.10, 95% CI: 1.73-12.08, p = 0.004). Dietary iron intake was inadequate among all participants, with minimal protective effect against anemia and ID (β(SE): -0.08(0.03), p = 0.030 and β(SE): -0.05(0.02), p=0.037 respectively). ROC analysis demonstrated moderate discriminative power for VDD in diagnosing IDA and anemia (AUC: 0.643 and 0.603) but reduced accuracy for ID (AUC: 0.575). This study identifies VDD as a significant risk factor for impaired iron status and anemia among Moroccan WRA, underscoring the need for targeted nutritional interventions and further research to explore effective prevention strategies.

Background: Histone deacetylases (HDACs) are implicated in carcinogenesis, and HDAC inhibitors (HDACis) are explored as a therapeutic tool in several tumors. The aim of this study was to evaluate the clinical significance of HDAC -2, -4, and -5 expression in epithelial ovarian carcinoma (EOC). Methods: HDAC-2, -4, and -5 immunohistochemical expression was examined in 92 EOC tissue specimens and was correlated with clinicopathological characteristics. Results: HDAC-2 was the most frequently (94.4%) expressed isoform, being marginally higher in serous tumors compared with other types (p=0,08). HDAC-5 was the less frequently expressed (28.1%), being positively associated with HDAC-4. HDAC-4 positivity was associated with lower FIGO-stage (p=0,045) and T-category (p=0.,043) and the absence of lymph node (p=0,05) or distant metastasis (p=0,09) in serous carcinomas. HDAC-2 positivity was correlated with absence of lymph node metastasis in serous tumors (p=0,045). On the contrary, HDAC-5 nuclear positivity was correlated with lymph node metastasis in the entire cohort (p=0,048). HDAC-4 positivity was marginally associated with favorable prognosis in serous carcinomas in univariate survival analysis (p=0,086), a correlation which was not significant in multivariate analysis. Conclusion: These findings suggest a differential expression of HDAC-2, -4 and -5, providing evidence for a potential role in the pathobiology of EOC.

There is evidence that kidney involvement is frequently observed in COVID-19 patients, and can manifest as mild proteinuria to advancing acute kidney injury (AKI). One of the mechanisms is microvascular and macrovascular thrombosis caused by the hypercoagulation phase of the disease. Thromboelastography (TEG) is a valuable examination to detect significant hemostatic abnormalities, including the hypercoagulable state. This study analyzed the coagulation profiles, including TEG parameters, in COVID-19 patients who developed AKI compared to those who did not during their intensive care unit (ICU) stay, to identify predictors of AKI. Our single-center cohort retrospective study involved adult patients of COVID-19 in the ICU of Sardjito Hospital in Yogyakarta, Indonesia between May and September 2021. Patients were divided into two groups of AKI and non-AKI based on 2012 KDIGO definition and the elaboration by Indonesian Society of Nephrology. Variables showing a significant difference in the two groups were then analyzed using univariate and multivariate binary logistic regression. A total of 60 COVID-19 patients were included in the study, and 35% of them developed AKI. Compared to non-AKI patients, those with AKI exhibited a greater prevalence of diabetes mellitus (66.7% versus 35.9%, P = 0.023), higher D-Dimer levels (970 versus 685 ng/mL, P = 0.045), and higher values in TEG parameters of maximum amplitude/MA (74.6 versus 65.9 mm, P = 0.001) and coagulation index/CI (2.3 versus 1.0, P = 0.033). TEG parameter of MA emerged as the sole significant predictor for the development of AKI (OR, 6.33; 95% CI, 1.56 to 25.64). Our study validated the kidney involvement of COVID-19 infection, and showed that diabetes mellitus, high D-Dimer levels, and hypercoagulability serve as prominent risk factors in the development of AKI. Furthermore, TEG parameter of MA exceeding 70 mm is the single independent significant predictor of AKI.

Global coverage and scale up of interventions to reduce newborn mortality remains low, though progress has been achieved in improving newborn survival in many low-income settings. An important factor in the success of newborn health interventions, and moving to scale, is appropriate design of community-based programs and strategies for local implementation. We report the results of formative research undertaken to inform the design of a newborn health intervention in Cambodia. Information was gathered on newborn care practices over a period of three months using multiple qualitative methods of data collection in the primary health facility and home setting. Analysis of the data indicated important gaps, both at home and facility level, between recommended newborn care practices and those typical in the study area. The results of this formative research have informed strategies for behavior change and improving referral of sick infants in the subsequent implementation study. Collection and dissemination of data on newborn care practices from settings such as these can contribute to efforts to advance survival, growth and development of newborns for intervention research, and for future newborn health programming.

Leafhopper Yamatotettix flavovittatus Matsumura is a phloem feeder that causes significant damage to sugarcane and also transmits sugarcane white leaf (SCWL) disease. Understanding the settling preference, feeding behavior, honeydew production and biophysical factors affecting Y. flavovittatus leafhopper infestation in sugarcane cultivation is crucial for effective pest management strategies. This study investigated these aspects across nine sugarcane cultivars. Significant variability was observed among cultivars in terms of settling behavior, with KK3 and LK92-11 showing the highest number of settled leafhopper adults. Similarly, honeydew production varied significantly among cultivars, with KK3 and LK92-11 exhibiting the highest production. Employing the electrical penetration graph (EPG) technique provided insights into distinct probing behaviors across cultivars, highlighting correlations between settling preference, honeydew production, and specific EPG waveforms. Principal component analysis (PCA) categorized cultivars into four groups based on settling preference, honeydew production, feeding behavior, and biophysical factors. Strong correlations were found between settling preference, honeydew production, and various EPG waveforms, while negative correlations were observed with the number of silica cells and rows per unit area, indicating their potential role in deterring leafhopper settlement. We concluded that TPJ04-768 and K84-200 are promising for resistance to leafhoppers and exploited in sugarcane breeding programs for resistance to insects.

Tumid Lupus Erythematosus has been the subject of heated debate as to its correct nosographic classification. In particular, its definition has changed over time, depending on the different studies performed. In this review we address the initial definition of TLE, the changes that have taken place in the understanding and placement within the classification of Lupus Erythematosus (LE), and focus on clinical, histopathological, immunophenotypical and differential diagnosis aspects.

Over the past 10 years, developments in precision oncology have led to a rise in the demand for predictive tools that assist the screening and stratification of patients for treatment. The possibility digitizing tissue slide images has led to the creation of artificial intelligence (AI) and machine learning algorithms in digital pathology, which could ultimately improve patient care. In this context, we assessed a variety of AI-based computational models for digital pathology. In this review, we described the latest AI applications in oncology, current challenges and future prospects.

Lynch syndrome (LS) is an inherited cancer predisposition disorder associated with an elevated risk of various epithelial cancers. Despite sharing the same pathogenic variant (PV), Lynch syn-drome variant heterozygotes (LSVH) exhibit considerable phenotypic variability in cancer risk. The role of Human Leukocyte Antigen (HLA) in modifying cancer risk prompted our investiga-tion into whether HLA variations act as genetic modifiers influencing age at cancer diagnosis in a unique cohort of LSVH carrying a PV in the hMLH1 gene in South Africa. Within our extensive LS cohort, 426 individuals carried the same hMLH1 PV (MLH1:c.1528C>T). We selected 100 indi-viduals with the greatest diversity in age at cancer diagnosis and the oldest unaffected individu-als for high-throughput HLA genotyping of 12 HLA class I and II loci using next-generation se-quencing. Statistical analyses employed Kaplan-Meier survival analyses with Logrank tests and Cox proportional hazards. Following the robust application of statistical correction methods, six HLA alleles (3.2%) were significantly associated with a young age at cancer diagnosis. Notably, HLA-B*15:17 and HLA-DPB1*55:01 correlated significantly with very young colorectal cancer (CRC) diagnosis (Mean age: 21y [17-25]; HR = 71.59; q

Ferritin is an indirect marker for total body iron stores. Comparison of the ferritin concentrations in the meconium with the concentrations of proteins regulating iron metabolism could aid better understanding of principles behind the adjustment between the fetal iron pool and newborn body size. Ferritin, transferrin, haptoglobin, ceruloplasmin, lactoferrin, myeloperoxidase, neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin concentrations were measured by ELISA in meconium samples from 122 neonates. The neonates were classified according to the meconium ferritin tertiles and the values were collated with the meconium concentrations of other proteins and newborn body weight and length measurements. Increasing ferritin concentrations in meconium in consecutive tertiles (p < 0.05) were parallel to increased NGAL concentrations (p < 0.05). The interrelationships between the meconium concentrations of transferrin, haptoglobin and NGAL as well as between myeloperoxidase, calprotectin and lactoferrin are maintained in all subsequent tertiles of ferritin concentrations, (p < 0.05). In contrast to ferritin, increasing meconium NGAL concentrations in consecutive tertiles were linked to increased concentrations of transferrin, haptoglobin, lactoferrin and myeloperoxidase (p < 0.05) and of calprotectin, ferritin and ceruloplasmin (p < 0.1). Meconium ceruloplasmin concentrations correlate exclusively with neutrophil granule proteins, i.e. myeloperoxidase, NGAL, lactoferrin and calprotectin (p < 0.05). Meconium ferritin concentrations negatively correlates with birth weight (r= -0.20) and length (r= -0.31) of neonates, whereas NGAL concentrations just with birth length (r= -0.26). The remaining proteins did not show such relationships with the size of the newborn. High meconium concentrations of both ferritin and NGAL may specifically characterize neonates of smaller size. High meconium concentrations of both ferritin and NGAL may specifically characterize neonates with lower body measurements. Correlations between meconium transferrin, haptoglobin and NGAL may confirm the interrelationships of these proteins for proper iron control and transport in the intrauterine environment. Meconium ceruloplasmin concentrations may reflect the control of neutrophil activity in utero.

TRPS1 (Tricho-rhino-phalangeal syndrome 1), is a GATA transcriptional activator gene encoding for a protein used as a sensitive immunohistochemical marker of breast carcinomas. In dermatopathology, TRPS1 is used as a marker of mammary Paget’s disease, and is also expressed by a variety of primary cutaneous tumors, mostly of adnexal origin. So far, limited data exist on the expression of TRPS1 in metastatic skin tumors. We studied the immunohistochemical expression of TRPS1 in 72 cutaneous metastatic tumors from the breast (n: 19) and other origins (n: 53) in order to assess its diagnostic usefulness. The intensity of TRPS1 immunostaining was expressed as a histoscore: product of percentage of positive cells (scored semi-quantitatively 0-4) and staining intensity (scored 0-3). In normal skin, nuclear TRPS1 expression was observed in cells of adnexal structures (pilosebaceous follicles and sweat glands). Eighteen (18/19, 94.7%) metastatic breast carcinomas showed diffuse and strong TRPS1 positivity (histoscore 12). Lower reactivity was found in some other metastases, including from the lung (11/22), the female genital tract (3/4), the kidney (2/4), whereas most (20/22) metastases from the digestive system and peritoneum, along with a case of metastatic prostate carcinoma, were negative. These results suggest that a high histoscore for TRPS1 is in favor of the mammary origin of a metastatic cutaneous carcinoma. Although TRPS1 is not absolutely specific or sensitive of a particular primary, we believe it can be added to a panel of other markers when investigating the origin of a cutaneous metastasis, namely when this is the first manifestation of the neoplastic disease.

Porcine parvovirus 8 (PPV8), a novel virus in the Parvoviridae family, was first identified in 2022 in lung samples of domestic pigs from China. Retrospective analyses showed that it had been circulating in China since 1998, but no other countries had reported its presence so far. A recent study conducted in South America did not detect any PPV8-positive samples in that region. Here we report the detection of PPV8 in Hungarian and Slovakian pig farms and the estimated prevalence of the virus in Hungary. Altogether 2230 serum, 233 oral fluid, and 115 processing fluid samples were systematically collected from 23 Hungarian and 2 Slovakian pig farms between 2020 and 2023. A real-time quantitative PCR method was developed to detect the viral genome. Our results revealed the presence of PPV8 on 65% of the Hungarian farms and on both Slovakian farms included in our study, marking its first detection in Europe. Oral fluid samples showed the highest positivity rates, reaching up to 100% in some herds. The viral genome was successfully detected in serum and processing fluid samples too, but with significantly lower prevalence rates of 4% and 5%, respectively. Genetic analysis of 11 partial VP2 sequences demonstrated high similarity to the original Chinese strain but with unique amino acid mutations, suggesting possible local evolution of the virus. Our study presents the first scientific evidence of PPV8 infection outside of China and offers a comprehensive assessment of its prevalence in the Hungarian pig population. Further research is required to understand its potential impact on swine health.

MicroRNAs are small non-coding RNAs, which contribute to the regulation of many physiolog-ical and pathological processes. Conventionally, miRNAs perform their activity in the cyto-plasm, where they regulate gene expression by interacting in a sequence-specific manner with mature messenger RNAs. Recent studies point to the presence of mature miRNAs in the nucleus. This review summarizes current findings regarding the molecular activities of nuclear miRNAs. These molecules can regulate gene expression at the transcriptional level by directly binding DNA on the promoter or the enhancer of regulated genes. MiRNAs recruit to these regions dif-ferent protein complexes, resulting both in activation or repression of transcription, through a number of molecular mechanisms. Haematopoiesis is presented as a paradigmatic biological process whereby nuclear miRNAs possess a relevant regulatory role. Nuclear miRNAs may af-fect gene expression also acting on nuclear mRNA processing and on the biogenesis of miRNA themselves by regulating pri-miRNA maturation. Overall, nuclear miRNAs are biologically ac-tive molecules that can be critical for the fine tuning of gene expression and deserve further studies in a number of physiological and pathological conditions

This aim of this study was to investigate the relationships between lifestyle factors, insulin resistance, and male fertility in 73 men with and without insulin resistance. The participants were divided based on insulin resistance status. Their physical activity, diet, perceived stress, sleep quality, libido level, and the duration of sexual abstinence were assessed on the basis of a number of parameters, including indices proposed by the authors. The results highlighted associations between a number of parameters, i.e., micronutrient and vitamin intake, diet quality, body composition, insulin resistance, and the duration of sexual abstinence, and semen quality, as measured by sperm motility. Significantly, the presence or absence of insulin resistance was linked to male fertility. A multivariate model was developed, incorporating parameters such as the Matsuda index, vitamin intake, and sexual abstinence duration, to predict motility scores. The study underscores the negative impact of modern civilization’s lifestyle choices on male fertility. Notably, vitamin and mineral consumption, especially from antioxidant-rich diets like the Mediterranean diet, emerged as key modifiable factors affecting fertility. Routine diagnostics for insulin resistance in fertility-related interventions is recommended. The study also highlights the importance of considering sexual abstinence duration during semen collection for accurate diagnostic results. Future research should focus on validating the proposed multivariate model and exploring the effects of lifestyle modifications, particularly vitamin supplementation, on fertility outcomes in men, especially in the context of insulin resistance.

The mutation in NF2 is the most common alteration associated with meningioma oncogenesis, and it is related to the loss of a suppressing protein called merlin. At the same time, alterations in energy production are visible in cancer cells where increased demand for energy is observed. Fatty acid oxidation could be one of the ways cancer cells obtain energy. This metabolic pathway uses the acylcarnitine shuttle system, which is responsible for the acylation of fatty acids and their transport through mitochondria. Therefore, this study aimed to profile acylcarnitines with short-, medium- and long-acyl chain length in meningiomas to assess their changes in tumors with different NF2 mutation statuses. For the analysis, solid-phase microextraction (SPME) coupled with liquid chromatography high resolution mass spectrometry (LC-HRMS) was used. The presented sampling method enables low invasive and easy collection of the analytes from the studied lesions, which can be crucial for future analysis of potential biomarkers in the surgery room. It was observed that higher levels of these analytes characterized meningiomas with NF2 mutation. Moreover, increased energy consumption and elevated levels of acylcarnitines show that these analytes can be considered as a marker of increased fatty acid oxidation in NF2 mutated cells.

Thymomas (TH) are a unique group of heterogeneous tumors of the thymic epithelium. In particular, the subtypes B2 and B3 tend to be aggressive and metastatic. Radical tumor resection remains the only curative option for localized tumors, while more advanced TH require multimodal treatment. Deep sequencing analyses have failed to identify known oncogenic driver mutations in TH, with the notable exception of the GTF2I mutation, which occurs predominantly in type A and AB TH. However, there are multiple alternative non-mutational mechanisms (e.g., perturbed thymic developmental programs, metabolism, non-coding RNA networks) that control cellular behavior and tumorigenesis through deregulation of critical molecular pathways. Here, we attempted to show how the results of studies investigating such alternative mechanisms could be integrated into a current model of TH biology. This model could be used to focus ongoing research and therapeutic strategies.

Epidemic diseases that arise from infectious RNA viruses, particularly influenza viruses, pose a constant threat to the global economy and public health. Viral evolution has undermined the efficacy of acquired immunity from vaccines and the antiviral effects of FDA-approved drugs. As such, there is an urgent need to develop new antiviral lead agents. Natural compounds, owing to their historical validation of application and safety, have become a promising solution. In this light, a novel marine bacterium, Pseudomonas sp. M20A4R8, has been found to exhibit significant antiviral activity [half maximal inhibitory concentration (IC50) = 1.3 µg/mL, selectivity index (SI) = 919.4] against influenza virus A/Puerto Rico/8/34, surpassing the activity of chloroquine. The antiviral response by M20A4R8 extract was induced during post-entry stages of the influenza virus, indicating suitability for post-application after the establishment of viral infection. Furthermore, post-treatment with M20A4R8 extract protected the host from virus-induced apoptosis, suggesting its potential use in acute respiratory disease complexes resulting from immune effectors' overstimulation and autophagy-mediated self-apoptosis. The extract demonstrated an outstanding therapeutic index against influenza virus A/Wisconsin/15/2009 (IC50 = 8.1 µg/mL, SI = 146.2) and B/Florida/78/2015 Victoria lineage (IC50 = 3.5 µg/mL, SI = 343.8), indicating a broad anti-influenza virus activity with guaranteed safety and effectiveness. This study provides a new perspective on mechanisms for preventing a broad spectrum of viral infections through antiviral agents from novel and natural origins. Future studies on a single or combined compound from the extract hold promise, encouraging its use in preclinical challenge tests with various influenza virus strains.

Distinguishing the level of pathology in the lungs through the sound of a cough is a complicated process that includes many factors. This paper explores the challenges of diagnosing lung pathology based solely on cough sounds. It emphasizes that while cough type can offer initial clues, it is just one piece of a complex diagnostic puzzle. For example, the differentiation of dry, productive, barking, hacking, and wheezing coughs provides initial insights into potential pathologies, which can range from respiratory infections to chronic diseases. The examination of cough characteristics, such as frequency, strength, and persistence, aids in identifying the severity of underlying conditions. Moreover, associated respiratory and systemic symptoms further contribute to the diagnostic landscape, with manifestations such as dyspnea, wheezing, chest pain, and hemoptysis offering valuable clinical information. Diagnostic tests, such as imaging studies and laboratory analyses, play a pivotal role in confirming diagnoses. However, challenges in diagnosis based solely on cough sounds require a more holistic approach, taking into consideration the complexity of lung pathologies. The paper concludes that accurately diagnosing lung pathologies based on cough sounds alone is difficult and requires careful consideration of multiple factors and stresses on contextualizing cough characteristics with other clinical features and diagnostic tests for an accurate assessment and comprehensive treatment planning.

Global climate change, particularly rising sea surface temperatures, profoundly impacts coral ecosystems, disrupting reproduction synchrony, symbiotic relationships with algae from the Symbiodiniceae family, and causing widespread bleaching and mortality among coral populations.  Oculina patagonica, a temperate scleractinian coral dominant in Mediterranean coastal waters, tolerates an annual temperature range of 10- 31°C. Moreover, in the past three decades, sea surface temperatures have rapidly risen in the Eastern Mediterranean Sea. O. patagonica offers insight into evolutionary adaptation to rapid environmental changes. This study investigated the effects of temperature changes on O. patagonica reproductive development, synchrony, and thermal sensitivity. Monthly monitoring of O. patagonica colonies for a year reveals no disruption in gonad development compared to previous studies, suggesting an unaffected sexual reproduction capacity. Thermal performance

As environmental and health concerns increase, the trend of sustainable agriculture moves toward using biological agents. About 60% of all biological fungicides have Trichoderma species as the active ingredient, with T. harzianum as the most common species in these products. However, the name T. harzianum has often been incorrectly used in culture collections, databases, and the scientific literature due to the division of the Harzianum Complex Clade (HCC) into more than 95 cryptic species with only one being named T. harzianum. In this study, 49 strains previously identified as T. harzianum in three surveys of Trichoderma species from soils in South and Central America were re-identified using phylogenetic analyses based on tef1α, rpb2, and ITS loci and were combined with the corresponding species in two other studies, where the species were correctly identified. Based on the results of the five surveys of the total 148 strains in HCC, 11 species were identified and T. afroharzianum, T. lentiforme, T. endophyticum followed by T. azedevio and T. harzianum were detected as the dominant species of the HCC in South and Central America. This is the first report of identifying dominant Trichoderma species within the HCC in South and Central American soil based on multiple studies, which will be useful in selecting strains within the complex clade for formulation of biocontrol and biofertilizer products in the continent.

(1) Background: The diagnosis of lumbosacral radiculopathy involves anamnesis, assessment of sensitivity and strength, diagnostic imaging—usually magnetic resonance imaging (MRI)—and electrodiagnostic testing (EDX), typically electromyography (EMG) and electroneurography (ENG). MRI evaluates the structures supporting the spinal cord, while EDX evaluates root functionality. The present study aimed to analyze the concordance of MRI and EDX findings in patients with clinically suspected radiculopathy. Additionally, we investigated the comparison between these two reference tests and various clinical variables and questionnaires. (2) Methods: We designed a prospective epidemiological study of consecutive cases with an observational, descriptive, cross-sectional, and double-blind nature following the STROBE guidelines, encompassing 142 patients with clinical suspicion of lumbosacral radiculopathy. (3) Results: Of the sample, 58.5% tested positive for radiculopathy using EDX as the reference test, while 45.8% tested positive using MRI. The comparison between MRI and EDX in the diagnosis of radiculopathy in patients with clinical suspicion was not significant; the overall agreement was 40.8%. Only the years with symptoms were comparatively significant between the positive and negative radiculopathy groups as determined by EDX. (4) Conclusion: The comparison between lumbar radiculopathy diagnoses in patients with clinically suspected pathology using MRI and EDX as diagnostic modalities did not yield statistically significant findings. MRI and EDX are complementary tests assessing different aspects in patients with suspected radiculopathy; degeneration of the structures supporting the spinal cord does not necessarily imply root dysfunction.

Pueraria mirifica (PM), a plant whose dried and powdered tuberous roots are now widely used in rejuvenating preparations to promote youthfulness in both men and women, may have major estrogenic influence. In this study, we investigated modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized animals at doses of 0.03%, 0.3%, and 3% in a phytoestrogen-low diet for 2 weeks caused significant increase in uterus weight. Secondly, a 4 week PM application to non-operated rats at a dose of 3% after 7,12-dimethylbenz[a]anthracene (DMBA) initiation resulted in significant elevation of cell proliferation in the mammary glands. In a third experiment, postpubertal administration of 0.3% (200 mg/kg body weight (b.w.)/day) PM to 5-week-old non-operated animals for 36 weeks following initiation of mammary and endometrial carcinogenesis with DMBA and N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG), respectively, resulted in significant increase of mammary adenocarcinoma incidence. A significant increase of endometrial atypical hyperplasia multiplicity was also observed. Furthermore, PM at doses of 0.3% and, more pronouncedly, of 1% induced dilatation, hemorrhage and inflammation of the uterine wall. In conclusion, postpubertal long-term PM administration to Donryu rats exerts estrogenic effects in the mammary gland and uterus, and at a dose of 200 mg/kg b.w./day was found to promote mammary carcinogenesis initiated by DMBA.

We conducted a pilot study to analyze the differential methylation status of 20 primary acinar adenocarcinomas of the lungs. These adenocarcinomas had to be wild type in mutation analysis and had either high (TPS&gt;50%; n=10) or low (TPS&lt;1%; n=10) PD-L1 status to be integrated into our study. To examine the methylation of 866,895 specific sites, we utilized the Illumina Infinium EPIC bead chip array. Both hypermethylation and hypomethylation play significant roles in tumor development, progression, and metastasis. They also impact the formation of the tumor microenvironment, which plays a decisive role in tumor differentiation, epigenetics, dissemination, and immune evasion. The gained methylation patterns were correlated with PD-L1 expression. Our analysis has identified distinct methylation patterns in lung adenocarcinomas with high and low PD-L1 expression. After analyzing the correlation between methylation results of genes and promoters with their pathobiology, we found that tumors with high expression of PD-L1 tend to exhibit oncogenic effects through hypermethylation. On the other hand, tumors with low PD-L1 expression show loss of their suppressor functions through hypomethylation. The suppressor functions of hypermethylated genes and promoters are ineffective compared to simultaneously activated dominant oncogenic mechanisms. The tumor microenvironment supports tumor growth in both groups.

The enhancement of early diagnosis of lung cancer is mandatory to improve prognosis. We observed the increase cancer stem cells (CSC) and circulating tumor cells (CTC) in blood of mice on d3 after Lewis lung carcinoma (LLC) cell implantation before disease symptom. Besides we have developed an approach to reprogramming immune cells by inhibiting the MAPK/ERK pathway through MEKi and the PD-1/PD-L1 immune checkpoint signaling pathway. We hypothesized that reprogramming of spleen CD8+ T-cells could also create a population of immune cells with high antitumor activity. We reprogrammed CD8+ T-cells derived from the spleen of C57BL/6 mice (rsCD8+T-cells). The rsCD8+T-cells were able to migrate to lung and were more resistant after the exhaustion in vitro in comparison with naïve sCD8+T-cells. In the orthotopic LLC model, the rsCD8+T-cells therapy increased the amount of proliferating CD8+ and CD4+ T-cells in blood and lung from mice. The amount of CSC decreased in the blood and lung of mice treated with rsCD8+ T-cells. A morphological study revealed a decrease in the number of metastases in lung tissue. The antitumor effects of rsCD8+T-cells are based on the activation of the host immune response by increasing the populations of CD8+ and CD4+ T-cells and apoptosis of CSCs.

Rapid microscopic analysis of tissue is an essential diagnostic tool in oncological surgery. The gold standard for intraoperative histological tissue evaluation are frozen sections. However, frozen sections are prone to a variety of artefacts and require skilled staff and specialized lab equipment. A potential method for rapid intraoperative tissue evaluation that does not require fixation, freezing nor sectioning of the tissue, is ex vivo fluorescence confocal microscopy (FCM). The visualization of the structurally important extracellular matrix (ECM) in conventional ex vivo FCM lags behind the standards of conventional histology. The objective of this study was to find a stain that will improve the depiction of the ECM to resemble FFPE H&amp;E sections as closely as possible.

The occurrence of ovarian dysfunction is often due to the imbalance between the formation of reactive oxygen species (ROS) and the (in)effectiveness of the antioxidative defense mechanisms. Primary sources of ROS are the respiratory electron transfer and the activity of NADPH oxidases (NOX), while Superoxide dismutases (SOD) are the main key reg-ulators that control the levels of ROS and reactive nitrogen species intra- and extracel-lularly. Because of their central role, SODs are the subject of research on human ovarian dysfunction, but the sample acquisition is low. The high degree of cellular and molecular similarity between Drosophila melanogaster ovaries and human ovaries provides this model organism with the best conditions for analyzing the role of ROS during ovarian function. In this study, we clarify the localization of the ROS producing enzyme dNox within ovaries of Drosophila melanogaster and by a tissue specific knockdown, we show that dNox derived ROS are involved in the chorion hardening process. Furthermore, we analyze the dSod3 localization and show that reduced activity of dSod3 impacts egg laying behavior, but not the chorion hardening process.

Lung cancer remains the main cause of global cancer-related deaths. Currently low-dose computed tomography (LD-CT) shows a 20% reduction of mortality. However, its clinical suitability is hindered by cost, radiation, and some false positives. Thus, the discovery non-invasive and less-expensive biomarker is urgent needed. In this scenario, proteins released in biological fluids could be considered interesting biomarkers for their role in cancer development. We conducted a pioneering case-control pilot study aimed at assessing the usefulness of Raf Kinase Inhibitory Protein (RKIP) and its phosphorylated form (pRKIP) as potential early-stage lung cancer biomarkers. Urine and Blood samples of two consecutive and independent cohorts of lung cancer patients and healthy controls were screened by means of a novel experimental ELISA assay designed to evaluate both forms of the biomarker. Although urinary levels of RKIP were not statistically different between the lung cancer group and high-risk healthy group, serum ones instead increased significantly in early stage LC patients and permitted to discriminate LC patients from both low-risk (HS) and high-risk healthy subjects (HR-HS) with an overall 93% accuracy (AUC 0.93) when LC was compared to HS and 74% (AUC 0.73) when it was compared to high-risk group. Of note, the analysis of RKIP/pRKIP ratio also showed a high accuracy (90% - AUC 0.95) in discriminating LC patients from HS and more importantly, it allowed to identify LC patients compared to HR-HS, with a higher accuracy (79% - AUC 0.79) than RKIP alone. We hypothesize that serum RKIP levels may be correlated to the activation of the immune systems against the tumor during the first phases of its development. Our study identified a preliminary, non-invasive, RKIP and pRKIP profile able to discriminate with high specificity and sensitivity the early-stage lung cancer patients from high-risk Healthy Subjects. These results, although preliminary, suggest the utility of measuring RKIP/pRKIP as potential new screening test for lung cancer and provide the basis for future validation studies.

Broflanilide is a novel active ingredient from a unique insecticide class (IRAC Group 30) and was investigated as a control option against modern insecticide resistant strains of the common bed bug, Cimex lectularius. The susceptibility of technical grade broflanilide and efficacy of a broflanilide-based aerosol formulation (Earth Corp., Japan) were evaluated against five C. lectularius strains (MONH, SYD, DARL, PARRA, RIPPO). Results demonstrated that bed bugs had high susceptibility to broflanilide (RR50: SYD=1.22-fold, DARL=1.03-fold, PARRA=3.65-fold, RIPPO=2.77-fold), compared to the susceptible MONH strain. The aerosol showed high efficacy to adult bed bugs (97.5–100 % mortality to five strains after 24 hrs post-spray) and produced a notable decrease in egg hatch rates (MONH=9.7–23.4 %, PARRA=14.9–22.6 %). The aerosol also demonstrated high residual activity with 97.5–100% mortality in all five bed bug strains within 7 days exposure. The impact of different surface types upon aerosol residual efficacy was limited, although residues on a non-porous surface (tile) killed bed bugs slightly quicker than that on a porous surface (filter paper). The aerosol provided long residual activity to bed bugs, as 6-month-old residues were as equally efficacious to that of fresh residues. Bed bugs did not avoid surfaces treated with the aerosol. The high efficacy (including ovicidal efficacy), long residual activity, and non-avoidance of bed bugs on treated surfaces, demonstrated that broflanilide is highly suitable for modern bed bug management.