Miracle-dz/UniFAR-FTUs huggingface dataset:
Outcomes of rituximab‐BEAM versus BEAM conditioning regimen in patients with diffuse large B cell lymphoma undergoing autologous transplantation

Although rituximab‐based high‐dose therapy is frequently used in diffuse large B cell lymphoma (DLBCL) patients undergoing autologous hematopoietic cell transplantation (auto‐HCT), data supporting the benefits are not available. Herein, we report the impact of rituximab‐based conditioning on auto‐HCT outcomes in patients who have DLBCL.
Streptococcus thermophilus alters the expression of genes associated with innate and adaptive immunity in human peripheral blood mononuclear cells

Consumption of probiotics contributes to a healthy microbiome of the GIT leading to many health benefits. They also contribute to the modulation of the immune system and are becoming popular for the treatment of a number of immune and inflammatory diseases. The main objective of this study was to evaluate anti-inflammatory and modulatory properties of Streptococcus thermophilus. We used peripheral blood mononuclear cells from healthy donors and assessed modifications in the mRNA expression of their genes related to innate and adaptive immune system. Our results showed strong immune modulatory effects of S. thermophilus 285 to human peripheral blood mononuclear cells with an array of anti-inflammatory properties. S. thermophilus 285 reduced mRNA expression in a number of inflammatory immune mediators and markers, and upregulated a few of immune markers. S. thermophilus is used in the dairy industry, survives during cold storage, tolerates well upon ingesting, and their consumption may have beneficial effects with potential implications in inflammatory and autoimmune disorders.
Predictors of Postoperative Seizure Outcome in Low Grade Glioma: From Volumetric Analysis to Molecular Stratification

The importance of the extent of resection (EOR) has been widely demonstrated as the main predictor for survival, nevertheless its effect on tumor related epilepsy is less investigated. A total of 155 patients were enrolled after a first-line surgery for supratentorial Diffuse Low Grade Gliomas (DLGGs). Postoperative seizure outcome was analyzed stratifying the results by tumor volumetric data and molecular markers according to 2016 WHO classification. Receiver operating characteristic (ROC) curves were computed to asses EOR, residual tumor volume, and ΔT2T1 MRI index (expressing the tumor growing pattern) corresponding to optimal seizure outcome. A total of 70.97% of patients were seizure-free 18 months after surgery. Better seizure outcome was observed in IDH1/2 mutated and 1p/19q codeleted subgroup. At multivariate analysis, age (p = 0.014), EOR (p = 0.030), ΔT2T1 MRI index (p = 0.016) resulted as independent predictors of postoperative seizure control. Optimal parameters to improve postoperative seizure outcome were EOR ≥ 85%, ΔT2T1 MRI index ≤ 18 cm3, residual tumor volume ≤ 15 cm3. This study confirms the role of EOR and tumor growing pattern on postoperative seizure outcome independently from the molecular class. Higher ΔT2T1 MRI index, representing the infiltrative component of the tumor, is associated with worse seizure outcome and strengthens the evidence of common pathogenic mechanisms underlying tumor growth and postoperative seizure outcome.
Consensus recommendations for a standardized brain tumor imaging protocol for clinical trials in brain metastases (BTIP-BM).

A recent meeting was held on March 22, 2019, among the U.S. Food and Drug Administration (FDA), clinical scientists, pharmaceutical and biotech companies, clinical trials cooperative groups, and patient advocacy groups to discuss challenges and potential solutions for increasing development of therapeutics for central nervous system (CNS) metastases. A key issue identified at this meeting was the need for consistent tumor measurement for reliable tumor response assessment, including the first step of standardized image acquisition with an MRI protocol that could be implemented in multicenter studies aimed at testing new therapeutics. This document builds upon previous consensus recommendations for a standardized brain tumor imaging protocol (BTIP) in high-grade gliomas and defines a protocol for brain metastases (BTIP-BM) that addresses unique challenges associated with assessment of CNS metastases. The "minimum standard" recommended pulse sequences include: 1) parameter matched pre- and post-contrast inversion-recovery (IR)-prepared, isotropic 3D T1-weighted gradient echo (IR-GRE); 2) axial 2D T2-weighted turbo spin echo acquired after gadolinium-based contrast agent (GBCA) injection and before post-contrast 3D T1-weighted images; 3) axial 2D or 3D T2-weighted FLAIR; 4) axial 2D, 3-directional diffusion-weighted images; and 5) post-contrast 2D T1-weighted spin echo images for increased lesion conspicuity. Recommended sequence parameters are provided for both 1.5T and 3T MR systems. An "ideal" protocol is also provided, which replaces IR-GRE with 3D TSE T1-weighted imaging pre- and post-gadolinium, is best performed at 3T, and for which DSC perfusion is included. Recommended DSC perfusion parameters are given.
Minimally invasive surgery under local anaesthesia for chronic rhinosinusitis with nasal polyps: our experience in older adults

Abstract Objective This paper aims to report our experience with a minimally invasive surgical procedure for the treatment of chronic rhinosinusitis with nasal polyps, performed in a day-surgery setting under local anaesthesia. Methods A retrospective study of 30 patients with chronic rhinosinusitis with nasal polyps was conducted. Sino-Nasal Outcome Test 22 and modified Lund–Kennedy scores were collected. Intra- and post-operative pain was evaluated using a 10-point visual analogue scale. Results The mean Sino-Nasal Outcome Test 22 score decreased from 41.8 ± 15.8 pre-operatively to 13.3 ± 9.5 post-operatively (p < 0.001). Accordingly, the mean endoscopic score decreased from 6.8 ± 1.8 to 0.2 ± 0.7 (p < 0.001). The mean intra-operative pain score was 2.9 ± 3.2, and 29 patients (96.7 per cent) reported no pain in the post-operative period (visual analogue scale score = 0). Conclusion Our study confirms that minimally invasive surgery represents a safe, repeatable procedure that results in remarkable subjective and objective improvement, without intra- and post-operative pain or discomfort.
Deficiency of Interleukin-36 Receptor Protected Cardiomyocytes from Ischemia-Reperfusion Injury in Cardiopulmonary Bypass

Background Interleukin-36 has been demonstrated to be involved in inflammatory responses. Inflammatory responses due to ischemia-reperfusion injury following cardiopulmonary bypass (CPB) can cause heart dysfunction or damage. Material/Methods The CPB models were constructed in IL-36R−/−, IL-36RN−/−, and wild-type SD rats. Ultrasonic cardiography and ELISA were used to evaluate the cardiac function and measuring myocardial biomarker levels in different groups. TUNEL assay was used to evaluate apoptosis. Western blot assays and RT-PCR were performed to measure the expression of chemokines and secondary inflammatory cytokines in the heart. Oxidative stress in tissue and cultured cells was assessed using a DCFH-DA fluorescence probe and quantification of superoxide dismutase activity. Results Improved systolic function and decreased serum levels of myocardial damage biomarkers were found in IL-36R−/− rats compared to WT rats, while worse cardiac function and cardiomyocyte IR injury were observed in IL-36RN−/− rats compared to WT rats. TUNEL staining and Western blot analyses found that cardiomyocyte apoptosis and inflammation were significantly lower in the hearts of IL-36R−/− rats compared with that of WT rats. Oxidative stress was significantly lower in IL-36R−/− rats compared to WT rats. iNOS expression was significantly reduced, while eNOS expression was increased in the hearts of IL-36R−/− rats. Silencing of IL-36R expression in vitro activated SIRT1/FOXO1/p53 signaling in cardiomyocytes. Conclusions IL-36R deficiency in cardiomyocytes repressed infiltration of bone marrow-derived inflammatory cells and oxidative stress dependent on SIRT1-FOXO1 signaling, thus protecting cardiomyocytes and improving cardiac function in CPB model rats.
Vaccarin hastens wound healing by promoting angiogenesis via activation of MAPK/ERK and PI3K/AKT signaling pathways in vivo 1

Abstract Purpose To explore the potential role and unclear molecular mechanisms of vaccarin in wound healing. Methods Rats’ skin excision model to study the effects of vaccarin on wound healing in vivo . Hematoxylin and eosin staining was performed to evaluate Histopathologic characteristics. Immunohistochemistry was employed to assess the effects of vaccarin in accelerating angiogenesis. Western blot was used to evaluate relative protein expressed levels. Results Vaccarin could significantly promote wound healing and endothelial cells and fibroblasts proliferation in the wound site. Immunohistochemistry and Western blot studies showed that the nodal proteins and receptor (bFGFR) related to angiogenesis signaling pathway were activated, and the microvascular density in the wound site was markedly higher than that in the control group. Conclusions The present study was the first to demonstrate that vaccarin is able to induce angiogenesis and accelerate wound healing in vivo by increasing expressions of p-Akt, p-Erk and p-bFGFR. This process is mediated by MAPK/ERK and PI3K/AKT signaling pathways.
A male germ cell assay and supporting somatic cells: its application for the detection of phase specificity of genotoxins in vitro

ABSTRACT Male germ stem cells are responsible for transmission of genetic information to the next generation. Some chemicals exert a negative impact on male germ cells, either directly, or indirectly affecting them through their action on somatic cells. Ultimately, these effects might inhibit fertility, and may exhibit negative consequences on future offspring. Genotoxic anticancer agents may interact with DNA in germ cells potentially leading to a heritable germline mutation. Experimental information in support of this theory has not always been reproducible and suitable in vivo studies remain limited. Thus, alternative male germ cell tests, which are now able to detect phase specificity of such agents, might be used by regulatory agencies to help evaluate the potential risk of mutation. However, there is an urgent need for such approaches for identification of male reproductive genotoxins since this area has until recently been dependent on in vivo studies. Many factors drive alternative approaches, including the (1) commitment to the principles of the 3R’s (Replacement, Reduction, and Refinement), (2) time-consuming nature and high cost of animal experiments, and (3) new opportunities presented by new molecular analytical assays. There is as yet currently no apparent appropriate model of full mammalian spermatogenesis in vitro, under the REACH initiative, where new tests introduced to assess genotoxicity and mutagenicity need to avoid unnecessary testing on animals. Accordingly, a battery of tests used in conjunction with the high throughput STAPUT gravity sedimentation was recently developed for purification of male germ cells to investigate genotoxicity for phase specificity in germ cells. This system might be valuable for the examination of phases previously only available in mammals with large-scale studies of germ cell genotoxicity in vivo. The aim of this review was to focus on this alternative approach and its applications as well as on chemicals of known in vivo phase specificities used during this test system development.
Treatment Efficacy of Internet Gaming Disorder With Attention Deficit Hyperactivity Disorder and Emotional Dysregulaton

Abstract Background Recent youth with Attention Deficit Hyperactivity Disorder (ADHD) noticed emotional dysregulation if they had Internet Gaming Disorder (IGD). This study aims to understand the treatment efficacy of IGD with ADHD and emotional dysregulaton. Method A total of 101 ADHD youths were recruited. We used the Chen Internet Addiction Scale and IGD criteria of the diagnotsic statistical manual (DSM)-5 to confirm IGD. The Swanson, Nolan, and Pelham questionnaire Version IV was used for symptoms of ADHD and oppositional defiant disorder. Disruptive mood dysregulation disorder was assessed by psychiatrist. Results There is a new phenomenon that emotional dysregulation has been frequently noticed in severely gaming-addicted ADHD youth. Treatment efficacy of IGD is good when the underlying symptom of ADHD is controlled. Symptom scores of disruptive mood dysregulation (DMDD) were significantly reduced by 71.9%, 74.8%, and 84.4% at week 2, 3, and 4, respectively (P ≤ .001) after adjusting baseline symptom severity. Conclusion IGD may strongly arouse emotional dysregulation. Future DSM criteria could consider these gaming-addicted youth as a specific subclass of ADHD.
Dynamic changes of periostin and collagen I in the sclera during progressive myopia in guinea pigs.

PURPOSE To investigate periostin and collagen I expression during a scleral remodeling in myopic eyes and to determine their role in collagen remodeling of the myopic sclera. METHODS Fifty one-week-old guinea pigs were divided into the control and form-deprivation myopia (FDM) groups. The eyes of animals in the form-deprivation myopia group were covered for 2, 4, and 8 weeks, or were covered for 4 weeks and then uncovered for 2 weeks. The diopters and axial lengths in the eyes in each group of guinea pigs were measured. Immunohistochemistry and reverse transcription polymerase chain reaction were used to detect the relative protein and mRNA expressions of periostin and collagen I in the scleral tissues of guinea pig. RESULTS Before masking, guinea pigs in the control and form-deprivation myopia groups were hypermetropic and did not differ significantly (p>0.05). Hypermetropic refraction in the control group gradually decreased. In guinea pigs from the form-deprivation myopia group, the refractive power gradually changed from +2.14 ± 0.33 D to -7.22 ± 0.51 D, and the axial length gradually changed from 5.92 ± 0.37 mm to 8.05 ± 0.34 mm from before until the end of masking. Before covering, no significant difference was observed in the relative collagen I and periostin mRNA and protein expression levels in the sclera of the guinea pig control and form-deprivation myopia groups (p>0.05). The relative collagen I and periostin protein and mRNA expression levels in the sclera of guinea pigs in the form-deprivation myopia group at 2, 4, and 8 weeks, and after covering the eyes for 4 weeks followed by uncovering for 2 weeks, were significantly lower than those in the control group (p<0.05). The collagen I and periostin mRNA expression levels were positively correlated with protein expression levels in the sclera of guinea pigs (protein: r=0.936, p<0.05; mRNA: r=0.909, p<0.05). CONCLUSIONS Periostin was expressed in the myopic sclera of guinea pigs, and changes in periostin and collagen I expression were highly consistent. Periostin and collagen I may be involved in the regulation of scleral remodeling in myopia.
Wearable Device to Monitor Back Movements Using an Inductive Textile Sensor

Low back pain (LBP) is the most common work-related musculoskeletal disorder among healthcare workers and is directly related to long hours of working in twisted/bent postures or with awkward trunk movements. It has already been established that providing relevant feedback helps individuals to maintain better body posture during the activities of daily living. With the goal of preventing LBP through objective monitoring of back posture, this paper proposes a wireless, comfortable, and compact textile-based wearable platform to track trunk movements when the user bends forward. The smart garment developed for this purpose was prototyped with an inductive sensor formed by sewing a copper wire into an elastic fabric in a zigzag pattern. The results of an extensive simulation study showed that this unique design increases the inductance value of the sensor, and, consequently, improves its resolution. Furthermore, experimental evaluation on a healthy participant confirmed that the proposed wearable system with the suggested sensor design can easily detect forward bending movements. The evaluation scenario was then extended to also include twisting and lateral bending of the trunk, and it was observed that the proposed design can successfully discriminate such movements from forward bending of the trunk. Results of the magnetic interference test showed that, most notably, moving a cellphone towards the unworn prototype affects sensor readings, however, manipulating a cellphone, when wearing the prototype, did not affect the capability of the sensor in detecting forward bends. The proposed platform is a promising step toward developing wearable systems to monitor back posture in order to prevent or treat LBP.
Complete sporogony of the blood parasite Haemoproteus nucleocondensus in common biting midges: why is its transmission interrupted in Europe?

Abstract Haemoproteus species (Haemoproteidae) are widespread blood parasites and are transmitted by Culicoides biting midges and Hippoboscidae louse flies. Although these pathogens may cause morbidity or mortality, the vectors and patterns of transmission remain unknown for the great majority of avian haemoproteids. Haemoproteus nucleocondensus has been frequently reported in Europe in great reed warblers Acrocephalus arundinaceus after their arrival from African wintering grounds, but this infection has not been found in juveniles at the breeding sites. The factors that prevent its transmission remain unclear. This study was designed to test whether the sporogony of H. nucleocondensus (lineage hGRW8) can be completed in Culicoides impunctatus, one of the most abundant European biting midge species. Wild-caught females were infected with H. nucleocondensus from great reed warblers. Microscopic examination and PCR-based methods were used to detect sporogonic stages and to confirm species identity. This study showed that H. nucleocondensus completes sporogony in C. impunctatus, suggesting that there are no obstacles to its transmission from the point of view of vector availability and average temperature in Northern Europe. We discuss other ecological factors which should be considered to explain why the transmission of H. nucleocondensus and some other Southern origin haemosporidians are interrupted in North Europe.
Motivation and difficulties to reduce or quit smoking.

OBJECTIVE To understand what factors motivate people to reduce or stop tobacco use and what difficulties they face in this process. METHOD Qualitative, empirical and interpretative research that used a focal group technique for data collection and Discourse Analysis as a theoretical reference for analysis. RESULTS The responses centered on the following aspects: motivation for reduction or cessation of smoking, family and community support received during treatment, benefits from cessation of tobacco, difficulties encountered and strategies for overcoming triggers. FINAL CONSIDERATIONS The results showed that the users expressed their desire for cessation of tobacco use and that to achieve this goal, family and group support, professional help and changing habits are key factors for this process.
The DOF Transcription Factors in Seed and Seedling Development

The DOF (DNA binding with one finger) family of plant-specific transcription factors (TF) was first identified in maize in 1995. Since then, DOF proteins have been shown to be present in the whole plant kingdom, including the unicellular alga Chlamydomonas reinhardtii. The DOF TF family is characterised by a highly conserved DNA binding domain (DOF domain), consisting of a CX2C-X21-CX2C motif, which is able to form a zinc finger structure. Early in the study of DOF proteins, their relevance for seed biology became clear. Indeed, the PROLAMIN BINDING FACTOR (PBF), one of the first DOF proteins characterised, controls the endosperm-specific expression of the zein genes in maize. Subsequently, several DOF proteins from both monocots and dicots have been shown to be primarily involved in seed development, dormancy and germination, as well as in seedling development and other light-mediated processes. In the last two decades, the molecular network underlying these processes have been outlined, and the main molecular players and their interactions have been identified. In this review, we will focus on the DOF TFs involved in these molecular networks, and on their interaction with other proteins.
Nucleolar localization of RAG1 modulates V(D)J recombination activity

Significance Vertebrate immune systems can respond to many infections and insults. This ability relies on a diverse binding repertoire of antigen receptors. Antigen receptor diversity is created through a process called V(D)J recombination in which arrayed gene segments are shuffled to form functional receptors. This process introduces breaks in chromosomal DNA catalyzed by the RAG1-RAG2 protein complex and requires strict regulation to guard genome integrity. Here we demonstrate a mode of RAG1 regulation by nucleolar sequestration. RAG1’s nucleolar localization is dynamically regulated and is disrupted during a B cell’s transition to a prorecombination state, leading to increased recombination. V(D)J recombination assembles and diversifies Ig and T cell receptor genes in developing B and T lymphocytes. The reaction is initiated by the RAG1-RAG2 protein complex which binds and cleaves at discrete gene segments in the antigen receptor loci. To identify mechanisms that regulate V(D)J recombination, we used proximity-dependent biotin identification to analyze the interactomes of full-length and truncated forms of RAG1 in pre-B cells. This revealed an association of RAG1 with numerous nucleolar proteins in a manner dependent on amino acids 216 to 383 and allowed identification of a motif required for nucleolar localization. Experiments in transformed pre-B cell lines and cultured primary pre-B cells reveal a strong correlation between disruption of nucleoli, reduced association of RAG1 with a nucleolar marker, and increased V(D)J recombination activity. Mutation of the RAG1 nucleolar localization motif boosts recombination while removal of the first 215 amino acids of RAG1, required for efficient egress from nucleoli, reduces recombination activity. Our findings indicate that nucleolar sequestration of RAG1 is a negative regulatory mechanism in V(D)J recombination and identify regions of the RAG1 N-terminal region that control nucleolar association and egress.