Miracle-dz/UniFAR-FTUs huggingface dataset:
Geometric and Hydraulic Void Constrictions in Granular Media

AbstractConstrictions in the void space between soil particles govern hydraulic conductivity, internal stability, and filtration performance of sands and gravels. Various analytical, numerical, and image-based methods have been proposed to measure void constrictions based solely on analysis of particle and void geometry. These geometric constrictions are increasingly being used in models to predict hydraulic conductivity or filtration performance. However, both of these phenomena depend not only on the void geometry, but also on the directions and magnitudes of fluid velocities within the void space. This paper presents computational fluid dynamics (CFD) simulations performed on microcomputed tomography (microCT) images of voids in real sands, as well as idealized materials generated by discrete element modeling (DEM). Laminar flow conditions are considered and an alternative definition of a void constriction is presented, the hydraulic constriction, which is based on fluid velocities rather than void geo.
Quality of Life in Systemic Lupus Erythematosus and Other Chronic Diseases: Highlighting the Amplified Impact of Depressive Episodes

Background: Extensive research has explored SLE’s impact on health-related quality of life (H-QoL), especially its connection with mental wellbeing. Recent evidence indicates that depressive syndromes significantly affect H-QoL in SLE. This study aims to quantify SLE’s impact on H-QoL, accounting for comorbid depressive episodes through case-control studies. Methods: A case-control study was conducted with SLE patients (meeting the ACR/EULAR 2019 criteria of age ≥ 18). The control group was chosen from a community database. H-QoL was measured with the SF-12 questionnaire, and PHQ-9 was used to assess depressive episodes. Results: SLE significantly worsened H-QoL with an attributable burden of 5.37 ± 4.46. When compared to other chronic diseases, only multiple sclerosis had a worse impact on H-QoL. Major depressive episodes had a significant impact on SLE patients’ H-QoL, with an attributable burden of 9.43 ± 5.10, similar to its impact on solid cancers but greater than its impact on other diseases. Conclusions: SLE has a comparable impact on QoL to serious chronic disorders. Concomitant depressive episodes notably worsened SLE patients’ QoL, exceeding other conditions, similar to solid tumors. This underscores the significance of addressing mood disorders in SLE patients. Given the influence of mood disorders on SLE outcomes, early identification and treatment are crucial.
Gemtuzumab Ozogamicin in Acute Myeloid Leukemia: Efficacy, Toxicity, and Resistance Mechanisms—A Systematic Review

Acute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with chromosomal rearrangements and multiple gene mutations and the impairment of normal hematopoiesis. Current efforts to improve AML outcomes have focused on developing targeted therapies that may allow for improved antileukemic effects while reducing toxicity significantly. Gemtuzumab ozogamicin (GO) is one of the most thoroughly studied molecularly targeted therapies in adults. GO is a monoclonal antibody against CD33 IgG4 linked to the cytotoxic drug calicheamicin DMH. The use of GO as a chemotherapeutic agent is not generalized for all patients who suffer from AML, particularly for those whose health prevents them from using intensive conventional chemotherapy, in which case it can be used on its own, and those who have suffered a first relapse, where its combination with other chemotherapeutic agents is possible. This systematic review aimed to comprehensively evaluate GO, focusing on its molecular structure, mode of action, pharmacokinetics, recommended dosage, resistance mechanisms, and associated toxicities to provide valuable information on the potential benefits and risks associated with its clinical use. A systematic review of eight scientific articles from 2018 to 2023 was conducted using PRISMA analysis. The results showed that GO treatment activates proapoptotic pathways and induces double-strand breaks, initiating DNA repair mechanisms. Cells defective in DNA repair pathways are susceptible to GO cytotoxicity. GO has recommended doses for newly diagnosed CD33+ AML in combination or as a single agent. Depending on the treatment regimen and patient status, GO doses vary for induction, consolidation, and continuation cycles. Multidrug resistance (MDR) involving P-glycoprotein (P-gp) is associated with GO resistance. The overexpression of P-gp reduces GO cytotoxicity; inhibitors of P-gp can restore sensitivity. Mitochondrial pathway activation and survival signaling pathways are linked to GO resistance. Other resistance mechanisms include altered pharmacokinetics, reduced binding ability, and anti-apoptotic mechanisms. GO has limited extramedullary toxicity compared to other AML treatments and may cause hepatic veno-occlusive disease (HVOD). The incidence of hepatic HVOD after GO therapy is higher in patients with high tumor burden. Hematological side effects and hepatotoxicity are prominent, with thrombocytopenia and neutropenia observed. In conclusion, GO’s reintroduction in 2017 followed a thorough FDA review considering its altered dose, dosing schedule, and target population. The drug’s mechanism involves CD33 targeting and calicheamicin-induced DNA damage, leading to apoptosis and resistance mechanisms, including MDR and survival signaling, which impact treatment outcomes. Despite limited extramedullary toxicity, GO is associated with hematological side effects and hepatotoxicity.
Garrè Sclerosing Osteomyelitis of the Clavicle: Clinical Results after Clavicular Resection

(1) Background: Chronic non-bacterial osteomyelitis (CNO), also known as sclerosing osteomyelitis of Garrè, is a rare inflammatory bone disease with a specific clinical picture, uncertain pathogenesis, and no consensus on an effective treatment. Most frequently affecting other long bones, CNO may rarely involve the clavicle. The aim of this study was to present the results of a series of patients affected by CNO of the clavicle treated with total and partial clavicula resection. In addition, a literature review of different types of treatment of CNO was performed. (2) Methods: We retrospectively reviewed three patients with Sclerosing Osteomyelitis of Garre’ of the clavicle treated with partial resection of the clavicle (one) and with total clavicular resection (two). (3) Results: Patients (two female and one male) were an average age of 35.7 years at the time of the operation. At the 4-year follow-up, the mean active ROM was: 143° forward flexion, 133° abduction, 42° external rotation with an internal rotation of two patients at the interscapular level and one patient at the lumbosacral junction. The mean ASES score was 92/100 (range 87–100). In the literature review, after screening the abstracts and full texts for eligibility, 34 studies met the inclusion criteria. Conclusions: Partial or total clavicular resection resulted an effective treatment of CNO of the clavicle. The procedure seems to be particularly indicated after the failure of more conservative treatments.
The Role of microRNAs Related to Apoptosis for N-Methyl-d-Aspartic Acid-Induced Neuronal Cell Death in the Murine Retina

Glaucoma is one of the leading causes of acquired blindness and characterized by retinal ganglion cell (RGC) death. MicroRNAs are small noncoding RNAs that degrade their target mRNAs. Apoptosis is one of the common mechanisms leading to neuronal death in many neurodegenerative diseases, including glaucoma. In the present study, we identified microRNAs that modulate RGC death caused by the intravitreal injection of N-methyl-d-aspartic acid (NMDA). We found an upregulation of miR-29b and downregulation of miR-124 in the retina of the NMDA-injected eyes. The intravitreal injection of an miR-29b inhibitor 18 h before NMDA injection reduced RGC death and the downregulation of myeloid cell leukemia 1 (MCL-1), an anti-apoptotic factor, induced by intravitreal NMDA. The intravitreal injection of an miR-124 mimic 18 h before NMDA injection also reduced RGC death and the upregulation of B-cell/chronic lymphocytic leukemia lymphoma 2 (bcl-2)-associated X protein (Bax) and bcl-2 interacting protein (Bim), pro-apoptotic factors, induced by intravitreal NMDA. These data suggest that expressional changes in microRNA are involved in the excitotoxicity of RGCs, and that complement and/or inhibition of microRNA may be a potential therapeutic approach for the diseases related to the excitotoxicity of RGCs, such as glaucoma and retinal central artery occlusion.
Feeling better? – Identification, interventions, and remission among women with early postpartum depressive symptoms in Sweden: a nested cohort study

Background Postpartum depression affects around 12% of mothers in developed countries, with consequences for the whole family. Many women with depressive symptoms remain undetected and untreated. The aim of this study was to investigate to what extent women with depressive symptoms at 6 weeks postpartum are identified by the healthcare system, the interventions they received, and remission rates at 6 months postpartum. Methods Postpartum women scoring 12–30 on the Edinburgh Postnatal Depression Scale (EPDS) at 6 weeks after delivery (n = 697) were identified from the longitudinal cohort study “Biology, Affect, Stress, Imaging and Cognition” (BASIC) in Uppsala, Sweden. A total of 593 women were included. Background and remission information at 6 months was collected from the BASIC dataset. Medical records were examined to identify interventions received. Results Most women (n = 349, 58.7%) were not identified by the healthcare system as having depressive symptoms and 89% lacked any record of interventions. Remission rates at 6 months postpartum were 69% in this group. Among women identified by the healthcare system, 90% received interventions and about 50% were in remission at 6 months postpartum. The EPDS reduction during the study period was largest in the group identified by the child health services (CHS, −5.15) compared to the non-identified (−4.24, p < 0.001). Conclusions Despite screening guidelines, many women with depressive symptoms had no documentation of screening or interventions by the healthcare system. Furthermore, a significant proportion did not achieve remission despite interventions. Being identified by CHS was associated with the largest reduction of symptoms. Research is needed to understand gaps in the healthcare processes, to better identify peripartum depression.
ANÁLISIS DE LA EFICIENCIA DE SISTEMAS AGROPECUARIOS EN AMÉRICA LATINA Y EL CARIBE MEDIANTE LA INCORPORACIÓN DE ASPECTOS AMBIENTALES Analysis of the Efficiency of Farming Systems in Latin America and the Caribbean Considering Environmental Issues

This paper provides a survey about environmental efficiency (EE) measure issue. The paper mainly focuses on nonparametrical methods, particularly on DEA (Data Envelopment Analysis) methods. First, the necessity of assessing the EE is considered due to its being required for sustainable systems, especially because this sustainability is threatened by negative factors from the technological progress. On the other hand, the assessment of environmental efficiency is also related to productivity. Afterwards, the paper deals with different ways for including environmental variables, which offer several perspectives for measuring efficiency with frontier methods. Finally, some studies, wherein the described methods are applied, are reported in regard to both, the exclusive scope of Latin America and the Caribbean Sea, and also to the contrast of these countries with other countries around the world. As conclusion, more attention to the environmental aspects is highly recommended in the efficiency analysis studies. It will provide an important support for the mitigation of the damaging expected effects of the climate change.
Development of Stable Infectious cDNA Clones of Tomato Black Ring Virus Tagged with Green Fluorescent Protein

Tomato black ring virus (TBRV) is a member of the Nepovirus genus in the Secoviridae family, which infects a wide range of important crop species worldwide. In this work, we constructed four cDNA infectious clones of the TBRV tagged with the green fluorescent protein (TBRV-GFP), which varied in (i) the length of the sequences flanking the GFP insert, (ii) the position of the GFP insert within the RNA2 polyprotein, and (iii) the addition of a self-cutting 2A protein. The presence of the GFP coding sequence in infected plants was verified by RT-PCR, while the infectivity and stability of the constructs were verified by mechanical inoculation of the host plants. The systemic spread of TBRV-GFP within plants was observed under UV light at a macroscopic level, monitoring GFP-derived fluorescence in leaves, and at a microscopic level using confocal microscopy. The obtained clones are a valuable tool for future studies of TBRV-host interactions, virus biology, and the long-term monitoring of its distribution in infected plants.
Reliable method for predicting the binding affinity of RNA-small molecule interactions using machine learning

Abstract Ribonucleic acids (RNAs) play important roles in cellular regulation. Consequently, dysregulation of both coding and non-coding RNAs has been implicated in several disease conditions in the human body. In this regard, a growing interest has been observed to probe into the potential of RNAs to act as drug targets in disease conditions. To accelerate this search for disease-associated novel RNA targets and their small molecular inhibitors, machine learning models for binding affinity prediction were developed specific to six RNA subtypes namely, aptamers, miRNAs, repeats, ribosomal RNAs, riboswitches and viral RNAs. We found that differences in RNA sequence composition, flexibility and polar nature of RNA-binding ligands are important for predicting the binding affinity. Our method showed an average Pearson correlation (r) of 0.83 and a mean absolute error of 0.66 upon evaluation using the jack-knife test, indicating their reliability despite the low amount of data available for several RNA subtypes. Further, the models were validated with external blind test datasets, which outperform other existing quantitative structure-activity relationship (QSAR) models. We have developed a web server to host the models, RNA-Small molecule binding Affinity Predictor, which is freely available at: https://web.iitm. ac.in/bioinfo2/RSAPred/.
TR-57 Treatment of SUM159 Cells Induces Mitochondrial Dysfunction without Affecting Membrane Potential

Recent works identified ClpXP, mitochondrial caseinolytic protease, as the only target of imipridones, a new class of antitumor agents. Our study of the mechanism of imipridone derivative TR-57 action in SUM159 human breast cancer cells demonstrated mitochondrial fragmentation, degradation of mitochondrial mtDNA and mitochondrial dysfunction due to inhibition of Complex I and Complex II activity. Complete inhibition of oxidative phosphorylation accompanied 90, 94, 88 and 87% decreases in the content of Complex I, II, III and IV proteins, respectively. The content of the FOF1-ATPase subunits decreased sharply by approximately 35% after 24 h and remained unchanged up to 72 h of incubation with TR-57. At the same time, a disappearance of the ATPIF1, the natural inhibitor of mitochondrial FOF1-ATPase, was observed after 24 h exposure to TR-57. ATPase inhibitor oligomycin did not affect the mitochondrial membrane potential in intact SUM159, whereas it caused a 65% decrease in TR-57-treated cells. SUM159 cells incubated with TR57 up to 72 h retained the level of proteins facilitating the ATP transfer across the mitochondrial membranes: VDAC1 expression was not affected, while expression of ANT-1/2 and APC2 increased by 20% and 40%, respectively. Thus, our results suggest that although TR-57 treatment leads to complete inhibition of respiratory chain activity of SUM159 cells, hydrolysis of cytoplasmic ATP by reversal activity of FOF1-ATPase supports mitochondrial polarization.
How Does Trauma Make You Sick? The Role of Attachment in Explaining Somatic Symptoms of Survivors of Childhood Trauma

Exposure to traumatic events during childhood is common, and the consequences for physical and mental health can be severe. Adverse childhood experiences (ACEs) such as physical abuse, sexual abuse, emotional abuse, and neglect appear to contribute to the onset and severity of a variety of somatic inflictions, including obesity, diabetes, cancer, and heart disease. The aim of this scoping review was to try to gain insight into how this might occur. Given the evidence of indirect (i.e., through unhealthy behaviours such as excessive drinking or poor eating habits) and direct (i.e., through its impact on the endocrine, immune, and cardiovascular systems as well as on the brain) effects of attachment on health, we examined the possibility that insecure attachment might contribute to the development of somatic symptoms in adult survivors of childhood trauma. Eleven studies met our inclusion criteria. Findings from this review suggest that insecure and disorganized attachment orientations are related to DNA damage, metabolic syndrome and obesity, physical pain, functional neurological disorder, and somatization in adults exposed to childhood trauma. We discuss the implications of this for the conceptualization and treatment of trauma and stress disorders.
The Role of Vortioxetine in the Treatment of Depressive Symptoms in General Hospital Psychiatry: A Case-Series and PRISMA-Compliant Systematic Review of the Literature

Depressive symptoms are a customary finding in hospitalized patients, particularly those who are undergoing long hospitalizations, underwent major surgical procedures or suffer from high levels of multimorbidity and frailty. The patients included in this case series shared high degrees of frailty-complexity and were evaluated within the ordinary consultation and liaison psychiatry service of the University Hospital in Pisa, Italy, from September 2021 to June 2023. Patients were administered at least one follow-up evaluation after a week and before discharge. To relate this case series to the extant literature, a comprehensive systematic review of vortioxetine safety and efficacy was performed. None of the six patients included developed serious safety issues, but one patient complained of mild-to-moderate nausea for some days after the vortioxetine introduction. Five out of six patients exhibited at least a slight clinical benefit as measured by the clinical global impression scale. Of the 858 entries screened via Scopus and Medline/PubMed, a total of 134 papers were included in our review. The present case series provides preliminary evidence for vortioxetine’s safety in this healthcare domain. The literature reviewed in this paper seems to endorse a promising safety profile and a very peculiar efficacy niche for vortioxetine in consultation and liaison psychiatry.
Effects of Supplementing Zinc Magnesium Aspartate on Sleep Quality and Submaximal Weightlifting Performance, following Two Consecutive Nights of Partial Sleep Deprivation

Purpose: We examined whether supplementation of zinc magnesium aspartate (ZMA), while partially sleep deprived, was beneficial to sleep quality and subsequent morning (07:00 h) submaximal weightlifting. Methods: Using a double-blinded, randomized counterbalanced design, sixteen trained males were recruited and completed six sessions: (i) one repetition max (1 RM) for bench press and back squat; (ii) two familiarisation sessions; (iii) three conditions with 4 h sleep and either: ZMA, placebo (PLA), or NoPill control (NoPill). Submaximal exercise session consisted of three repetitions at 40, 60 and 80% of 1 RM for bench press and back squat. Average power (AP), average velocity (AV), peak velocity (PV), displacement (D) and time-to-peak velocity (tPV) were recorded using MuscleLab linear encoders. Data were analysed using a general linear model with repeated measures and linear correlation. Results: No significant main effect for condition was found for performance values or subjective ratings of fatigue. Main effect for “load” on the bar was found, where AP and tPV values increased with load (p < 0.05). No significant relationship between dose of zinc or magnesium ingested and change in performance for 80% 1 RM power-outputs was found. Conclusion: Supplementation of ZMA for two nights of partial sleep deprivation had no effect on sleep or subsequent morning performance.
Methodology for the Detection of Contaminated Training Datasets for Machine Learning-Based Network Intrusion-Detection Systems

With the significant increase in cyber-attacks and attempts to gain unauthorised access to systems and information, Network Intrusion-Detection Systems (NIDSs) have become essential detection tools. Anomaly-based systems use machine learning techniques to distinguish between normal and anomalous traffic. They do this by using training datasets that have been previously gathered and labelled, allowing them to learn to detect anomalies in future data. However, such datasets can be accidentally or deliberately contaminated, compromising the performance of NIDS. This has been the case of the UGR’16 dataset, in which, during the labelling process, botnet-type attacks were not identified in the subset intended for training. This paper addresses the mislabelling problem of real network traffic datasets by introducing a novel methodology that (i) allows analysing the quality of a network traffic dataset by identifying possible hidden or unidentified anomalies and (ii) selects the ideal subset of data to optimise the performance of the anomaly detection model even in the presence of hidden attacks erroneously labelled as normal network traffic. To this end, a two-step process that makes incremental use of the training dataset is proposed. Experiments conducted on the contaminated UGR’16 dataset in conjunction with the state-of-the-art NIDS, Kitsune, conclude with the feasibility of the approach to reveal observations of hidden botnet-based attacks on this dataset.