Miracle-dz/UniFAR-FTUs huggingface dataset:
Parasagittal Approach of Epidural Steroid Injection as a Treatment for Chronic Low Back Pain: A Systematic Review and Meta-Analysis

Background: Epidural steroid injection (ESI) has proven benefits in controlling chronic low back pain and can be performed via the midline interlaminar (MIL) or transforaminal (TF) approach. A modified interlaminar approach, the parasagittal interlaminar (PIL), has surfaced as a more reliable, safe, and suitable approach to minimize complications related to MIL and TF. Objective: To conduct a systematic review and meta-analysis to assess and compare the effectiveness and safety of PIL with both MIL and TF approaches in adult patients with a history of chronic low back pain. Methods: A literature search was conducted using major electronic databases, such as PubMed, EMBASE, and Cochrane. Selected studies included patients with unilateral radicular symptoms, secondary to lumbar intervertebral disc hernias or degenerative lumbar disc disease, that, additionally, received ESIs via PIL or either MIL or TF under fluoroscopic guidance. Randomized and observational studies with pain relief score and/or functional disability assessment and at least a 2-week follow-up were included. Results: The search led to the initial identification of 174 studies. Following the screening, eight studies were included in the qualitative analysis and seven randomized controlled trials (RCTs) were included in the statistical analysis. PIL showed statistically significantly more pain relief and functional improvement than MIL at 1-, 3-, and 6-month post-procedure. Compared to TF, PIL showed statistically significantly more pain relief at 3- and 6-month after the procedure. Additionally, PIL showed benefits in terms of lower mean fluoroscopy time, less radiation exposure, zero adverse events in all the included studies, no cases of intravascular spread compared with the TF approach, and a higher anterior epidural spread (AES) of PIL compared with TF. Conclusions: Our systematic review and meta-analysis suggest that the PIL approach is an effective and safe alternative to the MIL and TF approaches in patients presenting with chronic low back pain when epidural injections are indicated, demonstrating a higher level of pain relief and a stronger improvement in functionality post-procedure.
Biogeographical Regionalization of Wine Yeast Communities in Greece and Environmental Drivers of Species Distribution at a Local Scale

Recent research has expanded our understanding on vineyard-associated fungal community assembly, suggesting non-random distribution and implicating regional differences in the wine terroir effect. Here, we focused on the culturable fraction of the fungal community that resides on grapes and determine wine quality, the so-called wine yeast populations. We aimed to analyze local-scale yeast community assemblages and to test whether the hypothesis of biogeographical patterns also applies to wine yeasts in particular. Surveying 34 vineyards across four main viticultural zones in Greece showed significant trends in vineyard-specific patterns. At a local scale, viticultural regions were also linked to distinct yeast community compositions. Importantly, major yeast populations directly related to wine fermentation contributed significantly to the delimitation of regions, highlighting their potential influence on the regionality of wine characteristics. In terms of the microbial terroir influence, yeast communities within an area were temporarily stable, which is critical for the regional character of the wine. Community structure could be explained only partially by environmental features. Maximum temperature, elevation, and net precipitation were the highest correlated variables with the yeast community biogeographic patterns. Finally, we also showed that certain environmental factors may drive the population size of specific yeast populations. The present results indicate that the wine yeast community has a geographical character at local scale, which is an important feature of the microbial terroir concept and thus for the wine industry.
CDK10 in Gastrointestinal Cancers: Dual Roles as a Tumor Suppressor and Oncogene

Cyclin-dependent kinase 10 (CDK10) is a CDC2-related serine/threonine kinase involved in cellular processes including cell proliferation, transcription regulation and cell cycle regulation. CDK10 has been identified as both a candidate tumor suppressor in hepatocellular carcinoma, biliary tract cancers and gastric cancer, and a candidate oncogene in colorectal cancer (CRC). CDK10 has been shown to be specifically involved in modulating cancer cell proliferation, motility and chemosensitivity. Specifically, in CRC, it may represent a viable biomarker and target for chemoresistance. The development of therapeutics targeting CDK10 has been hindered by lack a specific small molecule inhibitor for CDK10 kinase activity, due to a lack of a high throughput screening assay. Recently, a novel CDK10 kinase activity assay has been developed, which will aid in the development of small molecule inhibitors targeting CDK10 activity. Discovery of a small molecular inhibitor for CDK10 would facilitate further exploration of its biological functions and affirm its candidacy as a therapeutic target, specifically for CRC.
Inhibition of AKT Signaling Alters βIV Spectrin Distribution at the AIS and Increases Neuronal Excitability

The axon initial segment (AIS) is a highly regulated subcellular domain required for neuronal firing. Changes in the AIS protein composition and distribution are a form of structural plasticity, which powerfully regulates neuronal activity and may underlie several neuropsychiatric and neurodegenerative disorders. Despite its physiological and pathophysiological relevance, the signaling pathways mediating AIS protein distribution are still poorly studied. Here, we used confocal imaging and whole-cell patch clamp electrophysiology in primary hippocampal neurons to study how AIS protein composition and neuronal firing varied in response to selected kinase inhibitors targeting the AKT/GSK3 pathway, which has previously been shown to phosphorylate AIS proteins. Image-based features representing the cellular pattern distribution of the voltage-gated Na+ (Nav) channel, ankyrin G, βIV spectrin, and the cell-adhesion molecule neurofascin were analyzed, revealing βIV spectrin as the most sensitive AIS protein to AKT/GSK3 pathway inhibition. Within this pathway, inhibition of AKT by triciribine has the greatest effect on βIV spectrin localization to the AIS and its subcellular distribution within neurons, a phenotype that Support Vector Machine classification was able to accurately distinguish from control. Treatment with triciribine also resulted in increased excitability in primary hippocampal neurons. Thus, perturbations to signaling mechanisms within the AKT pathway contribute to changes in βIV spectrin distribution and neuronal firing that may be associated with neuropsychiatric and neurodegenerative disorders.
Up State of the SARS-COV-2 Spike Homotrimer Favors an Increased Virulence for New Variants

The COVID-19 pandemic has spread worldwide. However, as soon as the first vaccines—the only scientifically verified and efficient therapeutic option thus far—were released, mutations combined into variants of SARS-CoV-2 that are more transmissible and virulent emerged, raising doubts about their efficiency. This study aims to explain possible molecular mechanisms responsible for the increased transmissibility and the increased rate of hospitalizations related to the new variants. A combination of theoretical methods was employed. Constant-pH Monte Carlo simulations were carried out to quantify the stability of several spike trimeric structures at different conformational states and the free energy of interactions between the receptor-binding domain (RBD) and angiotensin-converting enzyme II (ACE2) for the most worrying variants. Electrostatic epitopes were mapped using the PROCEEDpKa method. These analyses showed that the increased virulence is more likely to be due to the improved stability to the S trimer in the opened state, in which the virus can interact with the cellular receptor, ACE2, rather than due to alterations in the complexation RBD-ACE2, since the difference observed in the free energy values was small (although more attractive in general). Conversely, the South African/Beta variant (B.1.351), compared with the SARS-CoV-2 wild type (wt), is much more stable in the opened state with one or two RBDs in the up position than in the closed state with three RBDs in the down position favoring the infection. Such results contribute to understanding the natural history of disease and indicate possible strategies for developing new therapeutic molecules and adjusting the vaccine doses for higher B-cell antibody production.
Segregation Analysis of Genotyped and Family-Phased, Long Range MHC Classical Class I and Class II Haplotypes in 5 Families With Type 1 Diabetes Proband in the United Arab Emirates

The classical Human Leucocyte Antigen (HLA) class II haplotypes of the Major Histocompatibility Complex (MHC) that are associated with type 1 diabetes (T1D) were identified in five families from the United Arab Emirates (UAE). Segregation analyses were performed on these 5 families with the disease, 3 with one child and 2 with 2 children diagnosed with T1D. Three HLA-DR4 haplotypes were identified: HLA- DRB1∗04:01:01-DQB1∗03:02:01:01; HLA- DRB1∗04:02:01- DQB1∗03:02:01; and HLA -DRB1∗04:05:01-DQB1∗02:02:01:02. All have previously been identified to be associated with T1D in studies of the Arabian population. In the 10 parents from the 5 families, 9 had at least one HLA-DR4 and HLA-DR3 haplotype which potentially increases the risk of T1D. Of these 9 parents, 3 were heterozygous for HLA-DR4/HLA-DR3 and one was homozygous for HLA-DR3. Two haplotypes that were identified here extend to the HLA class I region were previously designated AH8.2 (HLA -A∗26-B∗08-DRB1∗03) and AH50.2 (HLA -C∗06-B∗50-DRB1∗03:01-DQ∗02) and associated with diabetes in neighboring North Indian populations. This study provides examples of MHC haplotype analysis in pedigrees to improve our understanding of the genetics of T1D in the understudied population of the UAE.
Hepcidin Downregulation Correlates With Disease Aggressiveness And Immune Infiltration in Liver Cancers

Background Hepcidin is a polypeptide hormone mainly produced by hepatocytes to modulate systemic iron balance. A drastic downregulation of the hepcidin gene was found in liver cancers. However, there is a paucity of information about the clinical significance of hepcidin gene downregulation in liver cancers. Methods Hepcidin expression profiles were assessed using multiple public datasets via several bioinformatics platforms. Clinical and pathological information was utilized to stratify patients for comparison. Patient survival outcomes were evaluated using the Kaplan-Meier plotter, a meta-analysis tool. Tumor immune infiltration was analyzed using the single sample gene set enrichment analysis (ssGSEA) approach on the Cancer Genome Atlas (TCGA) dataset. Hepcidin antagonist Fursultiamine was used to treat liver cancer HepG2 and Huh7 cells together with Sorafenib. Results Hepcidin gene was predominantly expressed in benign liver tissues but drastically decreased in liver cancer tissues. Hepcidin reduction in liver cancers correlated with risk factors like non-alcoholic fatty liver disease (NAFLD) and liver fibrosis, as well as cancer grade and tumor stage. Hepcidin downregulation was associated with a rapid cancer progression and worse disease-specific survival, especially in patients of the White race without alcohol consumption history. Hepcidin expression in liver cancer tissues positively correlated with the bone morphogenetic protein-6 (BPM6)/interleukin-6 (IL6) cytokines and cytotoxic immune infiltration. Blocking hepcidin action with its antagonist Fursultiamine moderately reduced Sorafenib-induced apoptotic cell death in HepG2 and Huh7 cells. Conclusion Hepcidin downregulation in liver cancers correlated with liver cancer risk factors, cancer aggressiveness, cytotoxic immune cell infiltration, and patient survival outcomes. BMP6/IL6 pathway insufficiency is a potential cause of hepcidin downregulation in liver cancers.
Behavioral and Thermoregulatory Responses to Changes in Ambient Temperature and Wheel Running Availability in Octodon degus

Octodon degus is primarily a diurnal species, however, in laboratory conditions, it can switch from diurnal to nocturnal in response to wheel running availability. It has been proposed that this activity inversion obeys thermoregulatory constraints induced by vigorous physical exercise. Thus, its activity shifts to the night as the ambient temperature is lower.Here, we investigate the relationship between thermoregulation and the activity phase-inversion in response to wheel-running in this species. We measured behavioral activity and body temperature rhythms in diurnal naïve animals under 12 h light: 12 h dark cycles at four different ambient temperatures (spanning from ~26°C to 32°C), and following access to running wheels while maintained under high ambient temperature.Our results show that naïve degus do not shift their diurnal activity and body temperature rhythms to a nocturnal phase when subjected to sequential increases in ambient temperature. However, when they were provided with wheels under constant high-temperature conditions, all animals inverted their diurnal phase preference becoming nocturnal. Both, negative masking by light and entrainment to the dark phase appeared involved in the nocturnalism of these animals. Analysis of the thermoregulatory response to wheel running revealed some differences between masked and entrained nocturnal chronotypes.These data highlight the importance of the coupling between wheel running availability and ambient temperature in the nocturnalism of the degus. The results support the view that an innate “protective” pre-program mechanism (associating darkness and lower ambient temperature) may change the timing of behavioral activity in this species to reduce the potential risk of hyperthermia.
The Diabetic Cardiomyopathy: The Contributing Pathophysiological Mechanisms

Individuals with diabetes mellitus (DM) disclose a higher incidence and a poorer prognosis of heart failure (HF) than non-diabetic people, even in the absence of other HF risk factors. The adverse impact of diabetes on HF likely reflects an underlying “diabetic cardiomyopathy” (DM–CMP), which may by exacerbated by left ventricular hypertrophy and coronary artery disease (CAD). The pathogenesis of DM-CMP has been a hot topic of research since its first description and is still under active investigation, as a complex interplay among multiple mechanisms may play a role at systemic, myocardial, and cellular/molecular levels. Among these, metabolic abnormalities such as lipotoxicity and glucotoxicity, mitochondrial damage and dysfunction, oxidative stress, abnormal calcium signaling, inflammation, epigenetic factors, and others. These disturbances predispose the diabetic heart to extracellular remodeling and hypertrophy, thus leading to left ventricular diastolic and systolic dysfunction. This Review aims to outline the major pathophysiological changes and the underlying mechanisms leading to myocardial remodeling and cardiac functional derangement in DM-CMP.
The PERSonalized Glucose Optimization Through Nutritional Intervention (PERSON) Study: Rationale, Design and Preliminary Screening Results

Background: It is well-established that the etiology of type 2 diabetes differs between individuals. Insulin resistance (IR) may develop in different tissues, but the severity of IR may differ in key metabolic organs such as the liver and skeletal muscle. Recent evidence suggests that these distinct tissue-specific IR phenotypes may also respond differentially to dietary macronutrient composition with respect to improvements in glucose metabolism. Objective: The main objective of the PERSON study is to investigate the effects of an optimal vs. suboptimal dietary macronutrient intervention according to tissue-specific IR phenotype on glucose metabolism and other health outcomes. Methods: In total, 240 overweight/obese (BMI 25 – 40 kg/m2) men and women (age 40 – 75 years) with either skeletal muscle insulin resistance (MIR) or liver insulin resistance (LIR) will participate in a two-center, randomized, double-blind, parallel, 12-week dietary intervention study. At screening, participants undergo a 7-point oral glucose tolerance test (OGTT) to determine the hepatic insulin resistance index (HIRI) and muscle insulin sensitivity index (MISI), classifying each participant as either “No MIR/LIR,” “MIR,” “LIR,” or “combined MIR/LIR. ” Individuals with MIR or LIR are randomized to follow one of two isocaloric diets varying in macronutrient content and quality, that is hypothesized to be either an optimal or suboptimal diet, depending on their tissue-specific IR phenotype (MIR/LIR). Extensive measurements in a controlled laboratory setting as well as phenotyping in daily life are performed before and after the intervention. The primary study outcome is the difference in change in disposition index, which is the product of insulin sensitivity and first-phase insulin secretion, between participants who received their hypothesized optimal or suboptimal diet. Discussion: The PERSON study is one of the first randomized clinical trials in the field of precision nutrition to test effects of a more personalized dietary intervention based on IR phenotype. The results of the PERSON study will contribute knowledge on the effectiveness of targeted nutritional strategies to the emerging field of precision nutrition, and improve our understanding of the complex pathophysiology of whole body and tissue-specific IR. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03708419, clinicaltrials.gov as NCT03708419.
Comparison of Upper Neck Loading in Young Adult and Elderly Volunteers During Low Speed Frontal Impacts

Cervical pain and injuries are a major health problem globally. Existing neck injury criteria are based on experimental studies that included sled tests performed with volunteers, post-mortem human surrogates and animals. However, none of these studies have addressed the differences between young adults and elderly volunteers to date. Thus, this work analyzed the estimated axial and shear forces, and the bending moment at the craniocervical junction of nine young volunteers (18–30 years old) and four elderly volunteers (>65 years old) in a low-speed frontal deceleration. Since the calculation of these loads required the use of the mass and moment of inertia of the volunteers' heads, this study proposed new methods to estimate the inertial properties of the head of the volunteers based on external measurements that reduced the error of previously published methods. The estimated mean peak axial force (Fz) was −164.38 ± 35.04 N in the young group and −170.62 ± 49.82 N in the elderly group. The average maximum shear force (Fx) was −224.42 ± 54.39 N and −232.41 ± 19.23 N in the young and elderly group, respectively. Last, the estimated peak bending moment (My) was 13.63 ± 1.09 Nm in the young group and 14.81 ± 1.36 Nm in the elderly group. The neck loads experienced by the elderly group were within the highest values in the present study. Nevertheless, for the group of volunteers included in this study, no substantial differences with age were observed.
Playing Entropy Mastermind can Foster Children’s Information-Theoretical Intuitions

Conceptual descriptions and measures of information and entropy were established in the twentieth century with the emergence of a science of communication and information. Today these concepts have come to pervade modern science and society, and are increasingly being recommended as topics for science and mathematics education. We introduce a set of playful activities aimed at fostering intuitions about entropy and describe a primary school intervention that was conducted according to this plan. Fourth grade schoolchildren (8–10 years) played a version of Entropy Mastermind with jars and colored marbles, in which a hidden code to be deciphered was generated at random from an urn with a known, visually presented probability distribution of marble colors. Children prepared urns according to specified recipes, drew marbles from the urns, generated codes and guessed codes. Despite not being formally instructed in probability or entropy, children were able to estimate and compare the difficulty of different probability distributions used for generating possible codes.
Application of a quaternary ammonium agent on surgical face masks before use for pre-decontamination of nosocomial infection-related bioaerosols

ABSTRACT Surgical face masks are commonly used by the general public in indoor environments. However, masks could be contaminated, resulting in secondary microbial infections when they act as touchable fomites. Therefore, we evaluated the ability and durability of a covalently bound antimicrobial surfactant coated onto mask surfaces before use to reduce the bacterial burden upon exposure to aerosols. With regard to bacteria that settled onto the mask surface, this antimicrobial product provided >99.3% efficiency for all three tested bacterial species. In addition, the antimicrobial ability of the coated mask maintained efficacy at least one week after coating. For bioaerosols that came into contact with the mask (103 CFU/m3), the antimicrobial agent reduced the average colony rates by 91.8%, but the rates decreased with increased bioaerosol concentrations. Moreover, regardless of whether the coated mask was processed with the bioaerosol penetration test or the National Institute for Occupational Safety and Health-certified sodium chloride aerosol test, the filtration performance of the surgical mask was not significantly altered. These results demonstrate that this antimicrobial product has a durable inhibitory activity for the reduction of bacterial burdens on masks. Copyright © 2016 American Association for Aerosol Research
Large Animal Models of Vascularized Composite Allotransplantation: A Review of Immune Strategies to Improve Allograft Outcomes

Over the past twenty years, significant technical strides have been made in the area of vascularized composite tissue allotransplantation (VCA). As in solid organ transplantation, the allogeneic immune response remains a significant barrier to long-term VCA survival and function. Strategies to overcome acute and chronic rejection, minimize immunosuppression and prolong VCA survival have important clinical implications. Historically, large animals have provided a valuable model for testing the clinical translatability of immune modulating approaches in transplantation, including tolerance induction, co-stimulation blockade, cellular therapies, and ex vivo perfusion. Recently, significant advancements have been made in these arenas utilizing large animal VCA models. In this comprehensive review, we highlight recent immune strategies undertaken to improve VCA outcomes with a focus on relevant preclinical large animal models.