Miracle-dz/UniFAR-FTUs huggingface dataset:
NTRK gene aberrations in triple‐negative breast cancer: detection challenges using IHC, FISH, RT‐PCR, and NGS

Triple‐negative breast cancer (TNBC) is usually an aggressive disease with a poor prognosis and limited treatment options. The neurotrophic tyrosine receptor kinase (NTRK) gene fusions are cancer type‐agnostic emerging biomarkers approved by the Food and Drug Administration (FDA), USA, for the selection of patients for targeted therapy. The main aim of our study was to investigate the frequency of NTRK aberrations, i.e. fusions, gene copy number gain, and amplification, in a series of TNBC using different methods. A total of 83 TNBCs were analyzed using pan‐TRK immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), real‐time polymerase chain reaction (RT‐PCR), and RNA‐based next‐generation sequencing (NGS). Of 83 cases, 16 showed pan‐TRK positivity although no cases had NTRK‐fusions. Indeed, FISH showed four cases carrying an atypical NTRK1 pattern consisting of one fusion signal and one/more single green signals, but all cases were negative for fusion by NGS and RT‐PCR testing. In addition, FISH analysis showed six cases with NTRK1 amplification, one case with NTRK2 copy number gain, and five cases with NTRK3 copy number gain, all negative for pan‐TRK IHC. Our data demonstrate that IHC has a high false‐positive rate for the detection of fusions and molecular testing is mandatory; there is no need to perform additional molecular tests in cases negativity for NTRK by IHC. In conclusion, the NTRK genes are not involved in fusions in TNBC, but both copy number gain and amplification are frequent events, suggesting a possible predictive role for other NTRK aberrations.
Exercise preconditioning attenuates cerebral ischemia‐induced neuronal apoptosis, Th17/Treg imbalance, and inflammation in rats by inhibiting the JAK2/STAT3 pathway

Exercise preconditioning (EP) is essential for preventing ischemic stroke. Recent studies have shown that EP exerts neuroprotective effects in the cerebral ischemia‐reperfusion injury model. Nonetheless, there have been few reports on the relationship between EP and the Th17/Treg balance. Moreover, it is unclear whether the JAK2/STAT3 pathway is responsible for the neuroprotective effect of EP. Therefore, we aimed to explore the impact of EP, other than the anti‐inflammatory and antiapoptotic functions, on the Th17/Treg balance via the JAK2/STAT3 pathway in a middle cerebral artery occlusion (MCAO)‐induced model.
Renal involvement in monogenic autoinflammatory diseases: A narrative review

Autoinflammatory diseases (AIDs) are mostly caused by dysfunctions in single genes encoding for proteins with a prominent role in the regulation of innate immunity, such as complement factors, inflammasome components, tumour necrosis factor (TNF)‐α, and proteins belonging to type I‐interferon (IFN) signalling pathways. Due to the deposition of amyloid A (AA) fibrils in the glomeruli, unprovoked inflammation in AIDs frequently affects renal health. In fact, secondary AA amyloidosis is the most common form of amyloidosis in children. It is caused by the extracellular deposition of fibrillar low‐molecular weight protein subunits resulting from the degradation and accumulation of serum amyloid A (SAA) in numerous tissues and organs, primarily the kidneys. The molecular mechanisms underlying AA amyloidosis in AIDs are the elevated levels of SAA, produced by the liver in response to pro‐inflammatory cytokines, and a genetic predisposition due to specific SAA isoforms. Despite the prevalence of amyloid kidney disease, non‐amyloid kidney diseases may also be responsible for chronic renal damage in children with AIDs, albeit with distinct characteristics. Glomerular damage can result in various forms of glomerulonephritis with distinct histologic characteristics and a different underlying pathophysiology. This review aims to describe the potential renal implications in patients with inflammasomopathies, type‐I interferonopathies, and other rare AIDs in an effort to improve the clinical course and quality of life in paediatric patients with renal involvement.
The correlation between hemostatic blood parameters and sepsis in patients with gunshot wounds referred to a training and research hospital

ABSTRACT BACKGROUND: War injuries are different among the causes of trauma compared to cases in normal life. Patients with multi-trauma due to war injury are prone to develop infective complications such as sepsis or septic shock. Septic complications are one of the leading causes of late death in multi-trauma patients. Prompt, appropriate, and effective management of sepsis has been shown to prevent multiorgan dysfunction and improve mortality and clinical outcomes. However, there is no ideal biomarker to predict sepsis. The aim of this study was to determine whether there is a correlation between hemostatic blood parameters and sepsis in patients with gunshot wounds (GSW). METHODS: This descriptive study was conducted as a retrospective analysis of patients who were referred to the adult emergency department of a training and research hospital between October 1, 2016, and December 31, 2017, with a diagnosis of GSW and who developed sepsis (n=56) and did not develop sepsis (n=56) during follow-up. Demographic data such as age, sex, and blood parameters obtained from the hospital information system in the emergency department were recorded for each case. The statistical difference in hemostatic blood parameters between the two groups with and without sepsis was evaluated with Statistical Package for the Social Sciences 20.0 program. RESULTS: The mean age of the patients was 26.9±6.67. All of the patients were male. Of the patients who developed sepsis, 57% (n=32) were injured with improvised explosive devices (IEDs), 30% (n=17) were injured with firearms and when the anatomical injury sites were analyzed, 64% (n=36) had multiple injuries. In patients who did not develop sepsis, 48% (n=27) had IED, 43% (n=24) had GSW and 48% (n=27) had multiple injuries and 32% (n=18) had extremity injuries. Among the hemostatic blood parameters, platelet count (PLT), PTZ, INR, and Ca values showed a statistically significant difference between patients with and without sepsis, and when analyzed with the receiver operating characteristics curve, PTZ and INR showed the best diagnostic performance compared to the tested values. CONCLUSION: Increased PTZ and INR values and decreased Ca and PLT values in patients with GSW may alert clinicians to sepsis and direct them to initiate or change antibiotic therapy.
SOME RESULTS IN BE-ALGEBRAS

In this paper we use the regular congruence relation I to construct a quotient BE-algebra X=I from a self distributive BE-algebra X. Then we study the notion of homomorphisms on BE-algebras and the properties are studied. Finally we stated and proved the rst, second and third isomorphism theorems in self distributive BE-algebras. together with its properties in set theory and the implicational functor in logical systems. They are closely related to partially ordered commutative monoids as well as various logical algebras. Their names are originated form the combinators B, C, K and I in combinatory logic. It is known that the class of BCK-algebras is a proper subclass of the class of BCI-algebras. Recently, H. S. Kim and Y. H. Kim dened a BE-algebra (8). S. S. Ahn and K. S. So dened notion of ideals in BE-algebras, and then stated and proved several characterizations of such ideals (2). Quotient algebras are a basic tool for exploring the structures of BE-algebras. There are close contacts among ideals, homomorphism and quotient algebras. In this paper, construction of a regular congruence relation and an obstinate ideal of a BE-algebra also a quotient algebra is presented. Then we introduced the concept BE-homomorphism on BE-algebras and study the rst, second and third isomor- phism theorems in BE-algebras. We state and prove some theorem.
Challenges Experienced by Nurses in Providing Pediatric Palliative Care: An Interpretive Phenomenological Analysis

Objectives: Pediatric leukemia is the most common cancer among children younger than 14 years of age. Children with leukemia require palliative care as additional support from the health care team. Providing palliative care to children is challenging. Thus, this study explored the challenges experienced by nurses in providing pediatric palliative care to children with leukemia. Methods: Semi-structured face-to-face interviews were conducted on a purposive sample of 11 nurses in the hematology-oncology units of a tertiary care hospital in Oman. Results: Interviews were transcribed and analyzed using interpretive phenomenological analysis, which revealed three main themes and seven subthemes related to challenges in providing pediatric palliative care: Personal challenges: Nurses were unable to neutralize their emotions, which burdened them emotionally; due to multitasking, nurses were unable to manage their tasks within the expected time frame; nurses were stressful when they participated in explaining the diagnosis to the parents; and nurses felt powerless when the health condition of some children deteriorated. Educational challenges: Nurses felt unprepared to meet the physical/psychosocial aspects of caring for children with leukemia. Organizational challenges: Nurses stated that families and nurses required rooms to pray, rest, and read Quran, and they needed a private place to speak to families; and nurses mentioned that there are limited number of psychologists to meet the psychological and social needs of children and their families. Conclusion: Prioritizing and implementing strategies for a supportive workplace, guided clinical practice, and maximizing nurses’ satisfaction are crucial.
Blocking coprophagy increases the levels of inflammation and depression in healthy mice as well as mice receiving fecal microbiota transplantation from disease model mice donors

Rodents have been extensively used as animal models in microbiome studies. However, all rodents have a habitual nature called coprophagy, a phenomenon that they self‐reinoculate feces into their gastrointestinal tract. Recent studies have shown that blocking coprophagy can alter rodents' diversity of gut microbiota, metabolism, neurochemistry, and cognitive behavior. However, whether rodents' coprophagy behavior affects the levels of inflammation and depression is unclear. In order to address this problem, we first blocked coprophagy in healthy mice. It displayed an increase in the levels of depression, verified by depressive‐like behaviors and mood‐related indicators, and inflammation, verified by the increased levels of the pro‐inflammatory cytokine, in coprophagy‐blocked mice. Furthermore, we transplanted fecal microbiota from chronic restraint stress (CRS) depression model mice and lipopolysaccharide (LPS) inflammation model mice to healthy recipient mice, respectively. It showed that the disease‐like phenotypes in the coprophagy‐blocked group were worse than those in the coprophagy‐unblocked group, including severer depressive symptoms and higher levels of pro‐inflammatory cytokines (IL‐1β, IL‐6, TNF‐α and IFN‐γ) in serum, prefrontal cortex (PFC), and hippocampus (HIP). These findings showed that blocking coprophagy in mice not only increased the levels of inflammation and depression in healthy mice but also aggravated inflammation and depression induced by fecal microbiota from disease donors. The discovery may provide a vital reference for future research involving FMT in rodents.
Immune-related adverse events and immune checkpoint inhibitors: a focus on neurotoxicity and clinical management

ABSTRACT Introduction Immune checkpoint inhibitors (ICIs) represent an innovative therapeutic approach of oncologic diseases. In Europe, this therapeutic class currently includes eight agents: ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, cemiplimab, durvalumab and dostarlimab. Despite their proved clinical benefits, they can induce immune-related adverse events (irADRs), that can also involve the nervous system. Areas covered Despite their rarity, neurological irADRs related to ICI-treatments can lead to serious and dangerous complications, highlighting the importance of a strict monitoring of patients. This review aims to summarize the safety profile of ICIs, focusing on their possible neurotoxicity and their management. Expert opinion Considering the clinical relevance of ICIs-induced irADRs and that the underlying mechanisms are still not completely understood, the use of ICIs requires extensive safety monitoring. Before to prescribe immunotherapy, oncologists should identify possible individual risk factors that may favor the onset of irADRs. Oncologists and general practitioners should inform and educate patients about the specific toxicities of immunological checkpoint inhibitors, including nervous ones. They should be carefully monitored at least 6 months after the end of treatment. ICIs-related nervous toxicities require a multidisciplinary management, in which neurologists and clinical pharmacologists should participate.
Highly differentiated genomic properties underpin the different cell walls of Poaceae and eudicots

Abstract Plant cell walls of Poaceae and eudicots differ substantially, both in the content and composition of their components. However, the genomic and genetic basis underlying these differences is not fully resolved. In this research, we analyzed multiple genomic properties of 150 cell wall gene families across 169 angiosperm genomes. The properties analyzed include gene presence/absence, copy number, synteny, occurrence of tandem gene clusters, and phylogenetic gene diversity. Results revealed a profound genomic differentiation of cell wall genes between Poaceae and eudicots, often associated with the cell wall diversity between these plant groups. For example, overall patterns of gene copy number variation and synteny were clearly divergent between Poaceae and eudicot species. Moreover, differential Poaceae–eudicot copy number and genomic contexts were observed for all the genes within the BEL1-like HOMEODOMAIN 6 regulatory pathway, which respectively induces and represses secondary cell wall synthesis in Poaceae and eudicots. Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. All these patterns are discussed in detail in this study, along with their evolutionary and biological relevance for cell wall (genomic) diversification between Poaceae and eudicots.
Trophozoite fitness dictates the intestinal epithelial cell response to Giardia intestinalis infection

Giardia intestinalis is a non-invasive, protozoan parasite infecting the upper small intestine of most mammals. Symptomatic infections cause the diarrhoeal disease giardiasis in humans and animals, but at least half of the infections are asymptomatic. However, the molecular underpinnings of these different outcomes of the infection are still poorly defined. Here, we studied the early transcriptional response to G. intestinalis trophozoites, the disease-causing life-cycle stage, in human enteroid-derived, 2-dimensional intestinal epithelial cell (IEC) monolayers. Trophozoites preconditioned in media that maximise parasite fitness triggered only neglectable inflammatory transcription in the IECs during the first hours of co-incubation. By sharp contrast, “non-fit” or lysed trophozoites induced a vigorous IEC transcriptional response, including high up-regulation of many inflammatory cytokines and chemokines. Furthermore, “fit” trophozoites could even suppress the stimulatory effect of lysed trophozoites in mixed infections, suggesting active G. intestinalis suppression of the IEC response. By dual-species RNA-sequencing, we defined the IEC and G. intestinalis gene expression programs associated with these differential outcomes of the infection. Taken together, our results inform on how G. intestinalis infection can lead to such highly variable effects on the host, and pinpoints trophozoite fitness as a key determinant of the IEC response to this common parasite.
Adverse Effects of Virtual and Augmented Reality Interventions in Psychiatry: Systematic Review

Background Virtual reality (VR) and augmented reality (AR) are emerging treatment modalities in psychiatry, which are capable of producing clinical outcomes broadly comparable to those achieved with standard psychotherapies. Objective Because the side effect profile associated with the clinical use of VR and AR remains largely unknown, we systematically reviewed available evidence of their adverse effects. Methods A systematic review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework across 3 mental health databases (PubMed, PsycINFO, and Embase) to identify VR and AR interventions targeting mental health diagnoses. Results Of 73 studies meeting the inclusion criteria, 7 reported worsening clinical symptoms or an increased fall risk. Another 21 studies reported “no adverse effects” but failed to identify obvious adverse effects, mainly cybersickness, documented in their results. More concerningly, 45 of the 73 studies made no mention of adverse effects whatsoever. Conclusions An appropriate screening tool would help ensure that VR adverse effects are correctly identified and reported.
Effect of promethazine on biofilms of gram-positive cocci associated with infectious endocarditis

Abstract This study evaluated the antimicrobial activity of promethazine against Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus mutans and its effect on the antimicrobial susceptibility of biofilms grown in vitro and ex vivo on porcine heart valves. Promethazine was evaluated alone and in combination with vancomycin and oxacillin against Staphylococcus spp. and vancomycin and ceftriaxone against S. mutans in planktonic form and biofilms grown in vitro and ex vivo. Promethazine minimum inhibitory concentration range was 24.4-95.31 μg/mL and minimum biofilm eradication concentration range was 781.25-3.125 μg/mL. Promethazine interacted synergistically with vancomycin, oxacillin and ceftriaxone against biofilms in vitro. Promethazine alone reduced (p < 0.05) the CFU-counts of biofilms grown on heart valves for Staphylococcus spp. , but not for S. mutans, and increased (p < 0.05) the activity of vancomycin, oxacillin and ceftriaxone against biofilms of Gram-positive cocci grown ex vivo. These findings bring perspectives for repurposing promethazine as adjuvant in the treatment of infective endocarditis.
Evolution of chorus emissions into plasmaspheric hiss observed by Van Allen Probes

The two classes of whistler mode waves (chorus and hiss) play different roles in the dynamics of radiation belt energetic electrons. Chorus can efficiently accelerate energetic electrons, and hiss is responsible for the loss of energetic electrons. Previous studies have proposed that chorus is the source of plasmaspheric hiss, but this still requires an observational confirmation because the previously observed chorus and hiss emissions were not in the same frequency range in the same time. Here we report simultaneous observations form Van Allen Probes that chorus and hiss emissions occurred in the same range ∼300–1500 Hz with the peak wave power density about 10−5 nT2/Hz during a weak storm on 3 July 2014. Chorus emissions propagate in a broad region outside the plasmapause. Meanwhile, hiss emissions are confined inside the plasmasphere, with a higher intensity and a broader area at a lower frequency. A sum of bi‐Maxwellian distribution is used to model the observed anisotropic electron distributions and to evaluate the instability of waves. A three‐dimensional ray tracing simulation shows that a portion of chorus emission outside the plasmasphere can propagate into the plasmasphere and evolve into plasmaspheric hiss. Moreover, hiss waves below 1 kHz are more intense and propagate over a broader area than those above 1 kHz, consistent with the observation. The current results can explain distributions of the observed hiss emission and provide a further support for the mechanism of evolution of chorus into hiss emissions.
Relative contributions of fasting and postprandial glucose increments, glycemic variability, and non‐glycemic factors to HbA1c in individuals with type 1 diabetes

Evidence for contribution of basal and postprandial glucose increment, and glycemic variability to glycated hemoglobin (HbA1c) among adults with type 1 diabetes (T1D) is limited. This study aimed to capture glycemic fluctuation patterns and quantify contributions of these factors to HbA1c levels among adults with T1D.
The human microbiome links to prostate cancer risk and treatment (Review)

Prostate cancer (Pca) is the second most common cancer type worldwide. Microorganisms colonized in different body parts may affect the development/progression and treatment of Pca through direct or indirect interactions. The composition of microorganisms in different colonization sites and their effects on Pca may differ. In recent years, several studies have focused on the differences in the microbiota of patients with Pca, and dysbiosis may affect the inflammatory status, hormone levels and microbial metabolites leading to Pca progression. However, little is known about the interaction between Pca treatment and microorganisms; for example, how androgen deprivation therapy and androgen receptor axis-targeting therapeutics for Pca affect microbiota composition and metabolism, and how the microbiota affects treatment response in patients with Pca remain to be understood. The present review explored the current studies on the relevance of microbiota to Pca progression and treatment to provide direction for future microbiome-Pca research. Due to the complexity of the potential interconnections between Pca and the microbiota, further investigation is critical.