Miracle-dz/UniFAR-FTUs huggingface dataset:
Populational and individual information based PET image denoising using conditional unsupervised learning

Our study aims to improve the signal-to-noise ratio of positron emission tomography (PET) imaging using conditional unsupervised learning. The proposed method does not require low- and high-quality pairs for network training which can be easily applied to existing PET/computed tomography (CT) and PET/magnetic resonance (MR) datasets. This method consists of two steps: populational training and individual fine-tuning. As for populational training, a network was first pre-trained by a group of patients’ noisy PET images and the corresponding anatomical prior images from CT or MR. As for individual fine-tuning, a new network with initial parameters inherited from the pre-trained network was fine-tuned by the test patient's noisy PET image and the corresponding anatomical prior image. Only the last few layers were fine-tuned to take advantage of the populational information and the pre-training efforts. Both networks shared the same structure and took the CT or MR images as the network input so that the network output was conditioned on the patient’s anatomic prior information. The noisy PET images were used as the training and fine-tuning labels. The proposed method was evaluated on a 68Ga-PPRGD2 PET/CT dataset and a 18F-FDG PET/MR dataset. For the PET/CT dataset, with the original noisy PET image as the baseline, the proposed method has a significantly higher contrast-to noise ratio (CNR) improvement (71.85% ± 27.05%) than Gaussian (12.66% ± 6.19%, P = 0.002), nonlocal mean method (22.60% ± 13.11%, P = 0.002) and conditional deep image prior method (52.94% ± 21.79%, P = 0.0039). For the PET/MR dataset, compared to Gaussian (18.73% ± 9.98%, P < 0.0001), NLM (26.01% ± 19.40%, P < 0.0001) and CDIP (47.48% ± 25.36%, P < 0.0001), the CNR improvement ratio of the proposed method (58.07% ± 28.45%) is the highest. In addition, the denoised images using both datasets also showed that the proposed method can accurately restore tumor structures while also smoothing out the noise.
Molecular Genetics in Epstein–Barr Virus-Associated Malignancies

Global genomic studies have detected the role of genomic alterations in the pathogenesis of Epstein–Barr virus (EBV)-associated tumors. EBV oncoproteins cause a vital shift of EBV from an infectious virus to an oncogenic form during the latent and lytic phase within the lymphoid B cells and epithelial cells. This epigenetic alteration modulates the virus and host genomes and inactivates and disrupts numerous tumor suppressors and signaling pathways. Genomic profiling has played the main role in identifying EBV cancer pathogenesis and its related targeted therapies. This article reviews the role of genetic changes in EBV-associated lymphomas and carcinomas. This includes the prolific molecular genesis, key diagnostic tools, and target-specific drugs that have been in recent clinical use.
Molecular Insight into the Regulation of Vimentin by Cysteine Modifications and Zinc Binding

The intermediate filament protein vimentin is involved in essential cellular processes, including cell division and stress responses, as well as in the pathophysiology of cancer, pathogen infection, and autoimmunity. The vimentin network undergoes marked reorganizations in response to oxidative stress, in which modifications of vimentin single cysteine residue, Cys328, play an important role, and is modulated by zinc availability. However, the molecular basis for this regulation is not fully understood. Here, we show that Cys328 displays a low pKa, supporting its reactivity, and is readily alkylated and oxidized in vitro. Moreover, combined oxidation and crosslinking assays and molecular dynamics simulations support that zinc ions interact with Cys328 in its thiolate form, whereas Glu329 and Asp331 stabilize zinc coordination. Vimentin oxidation can induce disulfide crosslinking, implying the close proximity of Cys328 from neighboring dimers in certain vimentin conformations, supported by our computational models. Notably, micromolar zinc concentrations prevent Cys328 alkylation, lipoxidation, and disulfide formation. Moreover, zinc selectively protects vimentin from crosslinking using short-spacer cysteine-reactive but not amine-reactive agents. These effects are not mimicked by magnesium, consistent with a lower number of magnesium ions hosted at the cysteine region, according to molecular dynamics simulations. Importantly, the region surrounding Cys328 is involved in interaction with several drugs targeting vimentin and is conserved in type III intermediate filaments, which include glial fibrillary acidic protein and desmin. Altogether, our results identify this region as a hot spot for zinc binding, which modulates Cys328 reactivity. Moreover, they provide a molecular standpoint for vimentin regulation through the interplay between cysteine modifications and zinc availability.
Nutritional Value of Moringa oleifera Lam. Leaf Powder Extracts and Their Neuroprotective Effects via Antioxidative and Mitochondrial Regulation

Age-related neurodegenerative disorders are an increasing public health problem. Oxidative stress is one of the major causes. Medicinal plant-based functional foods can be effective for these diseases. The aim of this work is to investigate the neuroprotective role of methanol extracts of Moringa oleifera leaf powder on antioxidant/oxidant imbalance and mitochondrial regulation in a H2O2-induced oxidative stress model in human neuroblastoma cells. On nutritional analysis, results showed that moringa contained 28.50% carbohydrates, 25.02% proteins, 10.42% fat, 11.83% dietary fiber, 1.108 mg β-carotene, 326.4 µg/100 g vitamin B1 and 15.2 mg/100 g vitamin C. In-vitro assays revealed that moringa methanol extracts had more phenolic content and higher antioxidant activity than acetone extracts. Moreover, pretreatments with methanol extracts showed a protective effect against H2O2-induced oxidative damage through increasing cell viability and reducing free radicals. Furthermore, the extract decreased lipid peroxidation and enhanced glutathione levels and antioxidant enzyme activity. Finally, moringa also prevented mitochondrial dysfunction by regulating calcium levels and increasing mitochondrial membrane potential. The most active concentration was 25 µg/mL. In summary, the nutritional and functional properties of Moringa oleifera as a neuroprotective agent could be beneficial to protect against oxidative stress and provide necessary nutrients for a healthy diet.
Integration of Ultra-Low Volume Pneumatic Microfluidics with a Three-Dimensional Electrode Network for On-Chip Biochemical Sensing

This paper reports a novel miniaturized pseudo reference electrode (RE) design for biasing Ion Sensitive Field Effect Transistors (ISFETs). It eliminates the need for post-CMOS processing and can scale up in numbers with the CMOS scaling. The presented design employs silane-mediated transfer of patterned gold electrode lines onto PDMS microfluidics such that the gold conformally coats the inside of microfluidic channel. Access to this electrode network is made possible by using “through-PDMS-vias” (TPV), which consist of high metal-coated SU-8 pillars manufactured by a novel process that employs a patterned positive resist layer as SU-8 adhesion depressor. When integrated with pneumatic valves, TPV and pseudo-RE network were able to bias 1.5 nanoliters (nL) of isolated electrolyte volumes. We present a detailed characterization of our pseudo-RE design demonstrating ISFET operation and its DC characterization. The stability of pseudo-RE is investigated by measuring open circuit potential (OCP) against a commercial Ag/AgCl reference electrode.
The Influence of Long-Term Treatment with Asenapine on Liver Cytochrome P450 Expression and Activity in the Rat. The Involvement of Different Mechanisms

Therapy of schizophrenia requires long-term treatment with a relevant antipsychotic drug to achieve a therapeutic effect. The aim of the present study was to investigate the influence of prolonged treatment with the atypical neuroleptic asenapine on the expression and activity of rat cytochrome P450 (CYP) in the liver. The experiment was carried out on male Wistar rats. Asenapine (0.3 mg/kg s.c.) was administered for two weeks. The levels of CYP mRNA protein and activity were determined in the liver and hormone concentrations were measured in the pituitary gland and blood serum. Asenapine significantly decreased the activity of CYP1A (caffeine 8-hydroxylation and 3-N-demethylation), CYP2B, CYP2C11 and CYP3A (testosterone hydroxylation at positions 16β; 2α and 16α; 2β and 6β, respectively). The neuroleptic did not affect the activity of CYP2A (testosterone 7α-hydroxylation), CYP2C6 (warfarin 7-hydroxylation) and CYP2E1 (chlorzoxazone 6-hydroxylation). The mRNA and protein levels of CYP1A2, CYP2B1, CYP2C11 and CYP3A1 were decreased, while those of CYP2B2 and CYP3A2 were not changed. Simultaneously, pituitary level of growth hormone-releasing hormone and serum concentrations of growth hormone and corticosterone were reduced, while that of triiodothyronine was enhanced. In conclusion, chronic treatment with asenapine down-regulates liver cytochrome P450 enzymes, which involves neuroendocrine mechanisms. Thus, chronic asenapine treatment may slow the metabolism of CYP1A, CYP2B, CYP2C11 and CYP3A substrates (steroids and drugs). Since asenapine is metabolized by CYP1A and CYP3A, the neuroleptic may inhibit its own metabolism, therefore, the plasma concentration of asenapine in patients after prolonged treatment may be higher than expected based on a single dose.
Extensive Limb Lengthening for Achondroplasia and Hypochondroplasia

Extensive limb lengthening (ELL) was completed in 75 patients: 66 achondroplasia and 9 hypochondroplasia. The average lengthening was 27 cm for achondroplasia (12–40 cm) and 17 cm for hypochondroplasia (range 10–25 cm). There were 48 females and 27 males. Lengthening was done either by 2-segment (14 patients; both tibias and/or both femurs) or by 4-segment lengthenings (64 patients; both femurs and tibias at the same time). Most patients also had bilateral humeral lengthening. Patients had 2 or 3 lower limb lengthenings and one humeral lengthening. Lengthenings were either juvenile-onset (31), adolescent-onset (38) or adult-onset (6). The average age at final follow-up was 26 years old (range 17–43 years). There were few permanent sequelae of complications. The most serious was one paraparesis. All patients returned to activities of normal living and only one was made worse by the surgery (paraparesis). This is the first study to show that ELL can lead to an increase of height into the normal height range. Previous studies showed mean increases of height of up to 20 cm, while this study consistently showed an average increase of 30 cm (range 15–40 cm) for juvenile-onset and mean increase of 26 cm (range 15–30 cm) for adolescent-onset. This results in low normal height at skeletal maturity for males and females. The adult-onset had a mean increase of 16.8 (range 12–22 cm). This long-term follow-up study shows that ELL can be done safely even with large lengthenings and that 4-segment lengthening may offer advantages over 2-segment lengthening. While all but the more recent cases were performed using external fixation, implantable limb lengthening promises to be an excellent alternative and perhaps an improvement.
MHC Class I Deficiency in Solid Tumors and Therapeutic Strategies to Overcome It

It is now well accepted that the immune system can control cancer growth. However, tumors escape immune-mediated control through multiple mechanisms and the downregulation or loss of major histocompatibility class (MHC)-I molecules is a common immune escape mechanism in many cancers. MHC-I molecules present antigenic peptides to cytotoxic T cells, and MHC-I loss can render tumor cells invisible to the immune system. In this review, we examine the dysregulation of MHC-I expression in cancer, explore the nature of MHC-I-bound antigenic peptides recognized by immune cells, and discuss therapeutic strategies that can be used to overcome MHC-I deficiency in solid tumors, with a focus on the role of natural killer (NK) cells and CD4 T cells.
Walking Cadence during Moderate-Intensity Physical Activity in Pregnant Women

Evidence has established that a cadence of 100 steps/min is indicative of the moderate intensity threshold of 3 metabolic equivalents (METs), but this has only been described in non-pregnant individuals. As metabolic alterations are well established during pregnancy, the purpose of this study was to determine if the walking cadence equivalent to 3 METs in pregnant women is similar to non-pregnant populations. Pregnant females (n = 29; age = 30.3 ± 3.2 years, gestational age = 23.9 ± 6.6 weeks) in their second or third trimester (>12 weeks gestation) completed three stages of treadmill walking for 5 min at different standardized walking speeds: 2.5, 3.0, and 3.5 miles per hour (mph). Oxygen consumption (VO2) and heart rate (HR) were measured each minute and METs were calculated for each stage. Real-time continuous monitoring of walking cadence was evaluated by an OptoGait gait analysis system. Following the three standardized speed stages, participants completed an additional stage walking at a speed that elicited 100 steps/min; VO2 and HR were also collected. A one-sample t-test was used to compare MET values at each stage to the heuristic 3 MET cutoff, and Pearson correlation coefficient was calculated to evaluate the relationship between cadence and METs. Mean cadence increased linearly across the three stages (2.5 mph = 103.7 ± 4.5, 3.0 mph = 112.5 ± 5.3, and 3.5 mph = 120.4 ± 6.2 steps/min), as did METs (2.5 mph = 2.7 ± 1.7, 3.0 mph = 3.2 ± 0.8, and 3.5 mph = 4.3 ± 1.8 METs) regardless of trimester. The average treadmill speed at which women walked at 100 steps/min was 2.4 ± 0.4 mph which elicited an oxygen consumption of 9.5 mL•kg−1•min−1, or 2.7 ± 0.7 METs. There was no significant difference between METs at 3.0 mph and the conventional 3 MET cut point for moderate-intensity PA (p < 0.05). There was a moderate and significant relationship between METs and cadence (2nd trimester: r = 0.51; 3rd trimester: r = 0.42). Current data indicate for the first time that the traditionally used 3 MET cutoff for moderate-intensity activity is appropriate for pregnant women despite metabolic alterations associated with pregnancy. This may have important implications for exercise prescription in pregnant populations.
The Immune Microenvironment of Malignant Pleural Mesothelioma: A Literature Review

Simple Summary Malignant pleural mesothelioma is a rare and aggressive tumour, associated with asbestos exposure. Current therapeutic approaches for malignant mesothelioma are mainly based on systemic chemotherapy with a median overall survival of less than two years. In the setting of immunotherapy development, there is a need to better understand the immune microenvironment of malignant pleural mesothelioma. In this review, we aim to synthetize the recent advances in knowledge on the immune microenvironment of malignant pleural mesothelioma. This literature review shows that the immune microenvironment of malignant pleural mesothelioma is highly heterogeneous and can be considered as mainly immunotolerant or immunosuppressive. Better understanding of this immune microenvironment is particularly relevant to target molecular vulnerabilities and develop new treatment strategies. Abstract Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour with a poor prognosis, associated with asbestos exposure. Nowadays, treatment is based on chemotherapy with a median overall survival of less than two years. This review highlights the main characteristics of the immune microenvironment in MPM with special emphasis on recent biological advances. The MPM microenvironment is highly infiltrated by tumour-associated macrophages, mainly M2-macrophages. In line with infiltration by M2-macrophages, which contribute to immune suppression, other effectors of innate immune response are deficient in MPM, such as dendritic cells or natural killer cells. On the other hand, tumour infiltrating lymphocytes (TILs) are also found in MPM, but CD4+ and CD8+ TILs might have decreased cytotoxic effects through T-regulators and high expression of immune checkpoints. Taken together, the immune microenvironment is particularly heterogeneous and can be considered as mainly immunotolerant or immunosuppressive. Therefore, identifying molecular vulnerabilities is particularly relevant to the improvement of patient outcomes and the assessment of promising treatment approaches.
The Impact of Healthy Lifestyles on Late Sequelae in Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors. A Systematic Review by the Fondazione Italiana Linfomi

Simple Summary With the presented study, Fondazione Italiana Linfomi (FIL) researchers want to fill a gap in the literature regarding long-lived lymphoma patients (beyond 5 years after diagnosis). These patients can develop a series of late sequelae that affect their quality of life and overall survival, especially cardiotoxicity and secondary malignancies. In this context, although part of the risk is closely related to the chemotherapy and radiotherapy, some risk factors can be modified through tertiary prevention. There are currently no specific indications for tertiary prevention in the subset of long-term lymphoma survivors. This systematic review conducted by the FIL researchers is aimed at understanding whether there is evidence that correcting unhealthy lifestyles can reduce the onset of late sequelae. Abstract Background: In recent years, the scientific community has been paying ever more attention to the promotion of lifestyles aimed at the prevention of late toxicities related to anti-cancer treatments. Methods: Fondazione Italiana Linfomi (FIL) researchers conducted a systematic review in order to evaluate the evidence in favor of the promotion of lifestyles aimed at the prevention of the main sequelae of long-term classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) in survivors treated at adulthood with first-line or second-line therapy, including autologous stem cell transplants (ASCTs). Pubmed, Embase and Cochrane Library were searched up to December 2020. Results: Seven studies were ultimately included in this systematic review; some of them were eligible for multiple PICOS. The majority of the studies emerged from data extraction regarding cHL; less evidence resulted for DLBCL survivors. Five studies in favor of physical activity provided consistent data for a reduction of the cardiovascular risk in cHL and also in survivors who underwent ASCT. A beneficial effect of physical activity in reducing chronic fatigue was found. Being overweight was associated with a higher risk of coronary heart disease in cHL survivors in one of the two eligible studies. Studies aiming to evaluate the impact of the Mediterranean diet on late toxicities and secondary cancers were lacking. Tailored survivorship care plans (SCP) seemed to represent an optimal tool to guide the follow-up and promote healthier lifestyles in the one eligible study. Thus, promotion of healthy lifestyles and empowering of lymphoma survivors should be implemented through structured models. The study also brought to light numerous areas of future clinical research.
Sevoflurane Modulates AKT Isoforms in Triple Negative Breast Cancer Cells. An Experimental Study

(1) Background: Triple negative breast cancer (TNBC) is a highly aggressive tumor, associated with high rates of early distant recurrence and short survival times, and treatment may require surgery, and thus anesthesia. The effects of anesthetic drugs on cancer progression are under scrutiny, but published data are controversial, and the involved mechanisms unclear. Anesthetic agents have been shown to modulate several molecular cascades, including PI3K/AKT/mTOR. AKT isoforms are frequently amplified in various malignant tumors and associated with malignant cell survival, proliferation and invasion. Their activation is often observed in human cancers and is associated with decreased survival rate. Certain anesthetics are known to affect hypoxia cell signaling mechanisms by upregulating hypoxia-inducible factors (HIFs). (2) Methods: MCF-10A and MDA-MB 231 cells were cultivated and CellTiter-Blue® Cell Viability assay, 2D and 3D matrigel assay, immunofluorescence assays and gene expressions assay were performed after exposure to different sevoflurane concentrations. (3) Results: Sevoflurane exposure of TNBC cells results in morphological and behavioral changes. Sevoflurane differently influences the AKT isoforms expression in a time-dependent manner, with an important early AKT3 upregulation. The most significant effects occur at 72 h after 2 mM sevoflurane treatment and consist in increased viability, proliferation and aggressiveness and increased vimentin and HIF expression. (4) Conclusions: Sevoflurane exposure during surgery may contribute to cancer recurrence via AKT3 induced epithelial–mesenchymal transition (EMT) and by all three AKT isoforms enhanced cancer cell survival and proliferation.
Mitogenomes Reveal Two Major Influxes of Papuan Ancestry across Wallacea Following the Last Glacial Maximum and Austronesian Contact

The tropical archipelago of Wallacea contains thousands of individual islands interspersed between mainland Asia and Near Oceania, and marks the location of a series of ancient oceanic voyages leading to the peopling of Sahul—i.e., the former continent that joined Australia and New Guinea at a time of lowered sea level—by 50,000 years ago. Despite the apparent deep antiquity of human presence in Wallacea, prior population history research in this region has been hampered by patchy archaeological and genetic records and is largely concentrated upon more recent history that follows the arrival of Austronesian seafarers ~3000–4000 years ago (3–4 ka). To shed light on the deeper history of Wallacea and its connections with New Guinea and Australia, we performed phylogeographic analyses on 656 whole mitogenomes from these three regions, including 186 new samples from eight Wallacean islands and three West Papuan populations. Our results point to a surprisingly dynamic population history in Wallacea, marked by two periods of extensive demographic change concentrated around the Last Glacial Maximum ~15 ka and post-Austronesian contact ~3 ka. These changes appear to have greatly diminished genetic signals informative about the original peopling of Sahul, and have important implications for our current understanding of the population history of the region.