Miracle-dz/UniFAR-FTUs huggingface dataset:
Utility of the SARC-F Questionnaire for Sarcopenia Screening in Patients with Chronic Liver Disease: A Multicenter Cross-Sectional Study in Japan

Diagnosing sarcopenia is challenging. This multicenter cross-sectional study aimed to evaluate the utility of the SARC-F score system for identifying sarcopenia in patients with chronic liver disease (CLD). We enrolled 717 patients from five participating centers who completed the SARC-F between November 2019 and March 2021. Sarcopenia was diagnosed based on the Japan Society of Hepatology Working Group on Sarcopenia in Liver Disease Consensus. Muscle strength was estimated using a grip dynamometer, and muscle mass was assessed using computed tomography or bioelectrical impedance analysis. The association between SARC-F and sarcopenia was analyzed using a logistic regression model. The optimal SARC-F cutoff value for identifying sarcopenia was determined using receiver operating characteristic (ROC) curve analysis. Of the 676 eligible patients, 15% were diagnosed with sarcopenia. The SARC-F distribution was 0 points in 63% of patients, 1 point in 17%, 2 points in 7%, 3 points in 4%, and ≥4 points in 8%. The SARC-F items of “Strength” (odds ratio (OR), 1.98; 95% confidence interval (CI), 1.03–3.80) and “Falls” (OR, 2.44; 95% CI, 1.48–4.03) were significantly associated with sarcopenia. The SARC-F value of 1 point showed a higher discriminative ability for identifying sarcopenia than the 4 points that are conventionally used (p < 0.001), with an area under the ROC curve of 0.68, sensitivity of 0.65, specificity of 0.68, positive predictive value of 0.27, and negative predictive value of 0.92. SARC-F is useful for identifying patients with CLD who are at risk of sarcopenia.
Inflammatory Response in COVID-19 Patients Resulting from the Interaction of the Inflammasome and SARS-CoV-2

The outbreak of the coronavirus disease 2019 (COVID-19) began at the end of 2019. COVID-19 is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with COVID-19 may exhibit poor clinical outcomes. Some patients with severe COVID-19 experience cytokine release syndrome (CRS) or a cytokine storm—elevated levels of hyperactivated immune cells—and circulating pro-inflammatory cytokines, including interleukin (IL)-1β and IL-18. This severe inflammatory response can lead to organ damage/failure and even death. The inflammasome is an intracellular immune complex that is responsible for the secretion of IL-1β and IL-18 in various human diseases. Recently, there has been a growing number of studies revealing a link between the inflammasome and COVID-19. Therefore, this article summarizes the current literature regarding the inflammasome complex and COVID-19.
Noscapine Prevents Rotenone-Induced Neurotoxicity: Involvement of Oxidative Stress, Neuroinflammation and Autophagy Pathways

Parkinson’s disease is characterized by the loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) and the resultant loss of dopamine in the striatum. Various studies have shown that oxidative stress and neuroinflammation plays a major role in PD progression. In addition, the autophagy lysosome pathway (ALP) plays an important role in the degradation of aggregated proteins, abnormal cytoplasmic organelles and proteins for intracellular homeostasis. Dysfunction of ALP results in the accumulation of α-synuclein and the loss of dopaminergic neurons in PD. Thus, modulating ALP is becoming an appealing therapeutic intervention. In our current study, we wanted to evaluate the neuroprotective potency of noscapine in a rotenone-induced PD rat model. Rats were administered rotenone injections (2.5 mg/kg, i.p.,) daily followed by noscapine (10 mg/kg, i.p.,) for four weeks. Noscapine, an iso-qinulinin alkaloid found naturally in the Papaveraceae family, has traditionally been used in the treatment of cancer, stroke and fibrosis. However, the neuroprotective potency of noscapine has not been analyzed. Our study showed that administration of noscapine decreased the upregulation of pro-inflammatory factors, oxidative stress, and α-synuclein expression with a significant increase in antioxidant enzymes. In addition, noscapine prevented rotenone-induced activation of microglia and astrocytes. These neuroprotective mechanisms resulted in a decrease in dopaminergic neuron loss in SNpc and neuronal fibers in the striatum. Further, noscapine administration enhanced the mTOR-mediated p70S6K pathway as well as inhibited apoptosis. In addition to these mechanisms, noscapine prevented a rotenone-mediated increase in lysosomal degradation, resulting in a decrease in α-synuclein aggregation. However, further studies are needed to further develop noscapine as a potential therapeutic candidate for PD treatment.
Oesophageal pH-Impedance for the Diagnosis of Gastro-Oesophageal Reflux Disease: Validation of General Population Reference Values in Children with Chronic Neurological Impairments

Diagnosis of gastro-oesophageal reflux disease (GORD) in children with chronic neurological impairment (NI) remains a clinical challenge. The study aimed to validate the relevance of the reference values used to assess gastro-oesophageal reflux (GOR) in children with NI and to determine the optimal cut-off level of the pH-impedance parameter with the best predictive value for outcomes associated with endoscopic assessments of the oesophagus. Sixty-seven children (32 male, 35 female; age: interquartile range, 5 years 6 months–14 years 10 months; median, 11 years 3 months) with NI were prospectively recruited for the study. The exclusion criteria were previous fundoplication and lack of consent for the study. All patients underwent evaluations for GOR disease, including pH-impedance and gastroscopy. Based on endoscopy, oesophagitis was diagnosed in 22/67 children (32.8%); 9/67 (13.4%) were classified as having Hetzel–Dent grade III or IV. GOR was present in 18/67 children (26.9%), as determined by pH-impedance. Patients with endoscopic lesions had a significantly higher number of total reflux (p = 0.0404) and acidic episodes (p = 0.0219). The total number of reflux episodes, with a cut-off level of 44 episodes, was the pH-impedance parameter most strongly predictive of the presence of lesions in gastroscopy (specificity: 50%, sensitivity: 73%). These findings suggest that endoscopic lesions may be present in children with chronic NI with a low number of GOR episodes, as recorded by pH-impedance. The use of standardised reference norms determined for the general population may underestimate GOR episodes in this group of patients.
A novel combined resilience and advance care planning intervention for adolescents and young adults with advanced cancer: A feasibility and acceptability cohort study

Few evidence‐based psychosocial programs have been tested among adolescents and young adults (AYAs) with advanced cancer (AC), and early advance care planning (ACP) in this population is rare. The authors aimed to determine the feasibility and acceptability of 1) delivering an established resilience‐coaching program, and 2) integrating ACP into that program, among AYAs with AC.
Novel Insight in Idiopathic Normal Pressure Hydrocephalus (iNPH) Biomarker Discovery in CSF

Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible neurological disease, causing motor and cognitive dysfunction and dementia. iNPH and Alzheimer’s disease (AD) share similar molecular characteristics, including amyloid deposition, t-tau and p-tau dysregulation; however, the disease is under-diagnosed and under-treated. The aim was to identify a panel of sphingolipids and proteins in CSF to diagnose iNPH at onset compared to aged subjects with cognitive integrity (C) and AD patients by adopting multiple reaction monitoring mass spectrometry (MRM-MS) for sphingolipid quantitative assessment and advanced high-resolution liquid chromatography–tandem mass spectrometry (LC–MS/MS) for proteomic analysis. The results indicated that iNPH are characterized by an increase in very long chains Cer C22:0, Cer C24:0 and Cer C24:1 and of acute-phase proteins, immunoglobulins and complement component fragments. Proteins involved in synaptic signaling, axogenesis, including BACE1, APP, SEZ6L and SEZ6L2; secretory proteins (CHGA, SCG3 and VGF); glycosylation proteins (POMGNT1 and DAG1); and proteins involved in lipid metabolism (APOH and LCAT) were statistically lower in iNPH. In conclusion, at the disease onset, several factors contribute to maintaining cell homeostasis, and the protective role of very long chains sphingolipids counteract overexpression of amyloidogenic and neurotoxic proteins. Monitoring specific very long chain Cers will improve the early diagnosis and can promote patient follow-up.
Dendritic Cells and CCR7 Expression: An Important Factor for Autoimmune Diseases, Chronic Inflammation, and Cancer

Chemotactic cytokines—chemokines—control immune cell migration in the process of initiation and resolution of inflammatory conditions as part of the body’s defense system. Many chemokines also participate in pathological processes leading up to and exacerbating the inflammatory state characterizing chronic inflammatory diseases. In this review, we discuss the role of dendritic cells (DCs) and the central chemokine receptor CCR7 in the initiation and sustainment of selected chronic inflammatory diseases: multiple sclerosis (MS), rheumatoid arthritis (RA), and psoriasis. We revisit the binary role that CCR7 plays in combatting and progressing cancer, and we discuss how CCR7 and DCs can be harnessed for the treatment of cancer. To provide the necessary background, we review the differential roles of the natural ligands of CCR7, CCL19, and CCL21 and how they direct the mobilization of activated DCs to lymphoid organs and control the formation of associated lymphoid tissues (ALTs). We provide an overview of DC subsets and, briefly, elaborate on the different T-cell effector types generated upon DC–T cell priming. In the conclusion, we promote CCR7 as a possible target of future drugs with an antagonistic effect to reduce inflammation in chronic inflammatory diseases and an agonistic effect for boosting the reactivation of the immune system against cancer in cell-based and/or immune checkpoint inhibitor (ICI)-based anti-cancer therapy.
Assessing Parent Behaviours in Parent–Child Interactions with Deaf and Hard of Hearing Infants Aged 0–3 Years: A Systematic Review

Background: Despite early identification and advancements in cochlear implant and hearing aid technology, delays in language skills in deaf children continue to exist. Good-quality parent–child interaction (PCI) is a key predictor for the successful development of deaf children’s signed and/or spoken language. Though professionals have standard assessments to monitor child language, a clinical tool to observe the quality of parental interaction is yet to be developed. Aims and methods: This systematic review with narrative synthesis aims to uncover which parent behaviours are assessed in PCI studies with deaf infants aged 0–3 years, how these behaviours are assessed, and which are correlated with higher scores in child language. Results: Sixty-one papers were included, spanning 40 years of research. Research included in the review assessed parents’ skills in gaining attention, joint engagement, emotional sensitivity, and language input. PCI was mostly assessed using coding systems and frame-by-frame video analysis. Some of the parent behaviours mentioned previously are associated with more words produced by deaf children. Conclusion: The results of the review provide the evidence base required to develop the content of a future clinical assessment tool for parent–child interaction in deafness.
Antimicrobial Peptide Modifications against Clinically Isolated Antibiotic-Resistant Salmonella

Antimicrobial peptides are promising molecules to address the global antibiotic resistance problem, however, optimization to achieve favorable potency and safety is required. Here, a peptide-template modification approach was employed to design physicochemical variants based on net charge, hydrophobicity, enantiomer, and terminal group. All variants of the scorpion venom peptide BmKn-2 with amphipathic α-helical cationic structure exhibited an increased antibacterial potency when evaluated against multidrug-resistant Salmonella isolates at a MIC range of 4–8 µM. They revealed antibiofilm activity in a dose-dependent manner. Sheep red blood cells were used to evaluate hemolytic and cell selectivity properties. Peptide Kn2-5R-NH2, dKn2-5R-NH2, and 2F-Kn2-5R-NH2 (variants with +6 charges carrying amidated C-terminus) showed stronger antibacterial activity than Kn2-5R (a variant with +5 charges bearing free-carboxyl group at C-terminus). Peptide dKn2-5R-NH2 (d-enantiomer) exhibited slightly weaker antibacterial activity with much less hemolytic activity (higher hemolytic concentration 50) than Kn2-5R-NH2 (l-enantiomer). Furthermore, peptide Kn2-5R with the least hydrophobicity had the lowest hemolytic activity and showed the highest specificity to Salmonella (the highest selectivity index). This study also explained the relationship of peptide physicochemical properties and bioactivities that would fulfill and accelerate progress in peptide antibiotic research and development.
A Proteomic Analysis of Discolored Tooth Surfaces after the Use of 0.12% Chlorhexidine (CHX) Mouthwash and CHX Provided with an Anti-Discoloration System (ADS)

Chlorhexidine (CHX) is considered the gold standard for the chemical control of bacterial plaque and is often used after surgical treatment. However, CHX employment over an extended time is responsible for side effects such as the appearance of pigmentations on the teeth and tongue; the discoloration effects are less pronounced when using a CHX-based mouthwash with added an anti-discoloration system (ADS). The aim of this study was to evaluate, using one- and two-dimensional gel electrophoresis combined with mass spectrometry, the possible proteomic changes induced by CHX and CHX+ADS in the supragingival dental sites susceptible to a discoloration effect. The tooth surface collected material (TSCM) was obtained by curettage after resective bone surgery from three groups of patients following a supportive therapy protocol in which a mechanical control was combined with placebo rinses or CHX or a CHX+ADS mouthwash. The proteomic analysis was performed before surgery (basal conditions) and four weeks after surgery when CHX was used (or not) as chemical plaque control. Changes in the TSCM proteome were only revealed following CHX treatment: glycolytic enzymes, molecular chaperones and elongation factors were identified as more expressed. These changes were not detected after CHX+ADS treatment. An ADS could directly limit TSCM forming and also the CHX antiseptic effect reduces its ability to alter bacterial cell permeability. However, Maillard’s reaction produces high molecular weight molecules that change the surface properties and could facilitate bacterial adhesion.
Health Risk Assessment of Heavy Metals Contamination in Edible Fish Species from the Barekese Reservoir in Kumasi, Ghana

Heavy metals pollution and it resultant accumulation to toxic levels in the Barekese Reservoir may threaten human health through the consumption of fish from the Reservoir. The presence and concentrations of arsenic and some other heavy metals (Hg, Pb, Ni, Cr, and Cd) were determined in muscle tissues of widely distributed and highly consumed fish species from the Barekese reservoir using Atomic Absorption Spectrophotometry. A total of 45 fish samples comprising three species (Oreochromis niloticus, Tilapia zilli and Heterotis niloticus) were analyzed for their metals levels. Heavy metals concentrations (mg/kg, w.w) recorded showed varying trends of detection among muscle tissues of selected fish species. However, Hg, Ni, Cr and Cd were detected in muscle tissues of all fish species examined in the study. Indices for non-carcinogenic and carcinogenic risks were estimated for children and adult upon their consumption of fish from the Reservoir. Results of the study indicated a significant levels of exposure to Hg, Ni, Cr and Cd through the consumption of fish species from the Reservoir. Health risk assessment also revealed that children are at a relatively higher non-carcinogenic risk through the consumption of metals in Heterotis niloticus whiles the consumption of Cr from all examined fish species from the Reservoir could pose cancer risk health effects to humans with adults being at a higher risk. The present study therefore concludes that anthropogenic activities along the Offin River and within the Reservoir’s catchments are deteriorating the quality of fish from the Reservoir and could pose a significant adverse health risk to consumers.
Structure and Thermodynamics of Silicon Oxycarbide Polymer-Derived Ceramics with and without Mixed-Bonding †

Silicon oxycarbides synthesized through a conventional polymeric route show characteristic nanodomains that consist of sp2 hybridized carbon, tetrahedrally coordinated SiO4, and tetrahedrally coordinated silicon with carbon substitution for oxygen, called “mixed bonds. ” Here we synthesize two preceramic polymers possessing both phenyl substituents as unique organic groups. In one precursor, the phenyl group is directly bonded to silicon, resulting in a SiOC polymer-derived ceramic (PDC) with mixed bonding. In the other precursor, the phenyl group is bonded to the silicon through Si-O-C bridges, which results in a SiOC PDC without mixed bonding. Radial breathing-like mode bands in the Raman spectra reveal that SiOC PDCs contain carbon nanoscrolls with spiral-like rolled-up geometry and open edges at the ends of their structure. Calorimetric measurements of the heat of dissolution in a molten salt solvent show that the SiOC PDCs with mixed bonding have negative enthalpies of formation with respect to crystalline components (silicon carbide, cristobalite, and graphite) and are more thermodynamically stable than those without. The heats of formation from crystalline SiO2, SiC, and C of SiOC PDCs without mixed bonding are close to zero and depend on the pyrolysis temperature. Solid state MAS NMR confirms the presence or absence of mixed bonding and further shows that, without mixed bonding, terminal hydroxyls are bound to some of the Si-O tetrahedra. This study indicates that mixed bonding, along with additional factors, such as the presence of terminal hydroxyl groups, contributes to the thermodynamic stability of SiOC PDCs.
Daytime Dependence of the Activity of the Rat Brain Pyruvate Dehydrogenase Corresponds to the Mitochondrial Sirtuin 3 Level and Acetylation of Brain Proteins, All Regulated by Thiamine Administration Decreasing Phosphorylation of PDHA Ser293

Coupling glycolysis and mitochondrial tricarboxylic acid cycle, pyruvate dehydrogenase (PDH) complex (PDHC) is highly responsive to cellular demands through multiple mechanisms, including PDH phosphorylation. PDHC also produces acetyl-CoA for protein acetylation involved in circadian regulation of metabolism. Thiamine (vitamin B1) diphosphate (ThDP) is known to activate PDH as both coenzyme and inhibitor of the PDH inactivating kinases. Molecular mechanisms integrating the function of thiamine-dependent PDHC into general redox metabolism, underlie physiological fitness of a cell or an organism. Here, we characterize the daytime- and thiamine-dependent changes in the rat brain PDHC function, expression and phosphorylation, assessing their impact on protein acetylation and metabolic regulation. Morning administration of thiamine significantly downregulates both the PDH phosphorylation at Ser293 and SIRT3 protein level, the effects not observed upon the evening administration. This action of thiamine nullifies the daytime-dependent changes in the brain PDHC activity and mitochondrial acetylation, inducing diurnal difference in the cytosolic acetylation and acetylation of total brain proteins. Screening the daytime dependence of central metabolic enzymes and proteins of thiol/disulfide metabolism reveals that thiamine also cancels daily changes in the malate dehydrogenase activity, opposite to those of the PDHC activity. Correlation analysis indicates that thiamine abrogates the strong positive correlation between the total acetylation of the brain proteins and PDHC function. Simultaneously, thiamine heightens interplay between the expression of PDHC components and total acetylation or SIRT2 protein level. These thiamine effects on the brain acetylation system change metabolic impact of acetylation. The changes are exemplified by the thiamine enhancement of the SIRT2 correlations with metabolic enzymes and proteins of thiol-disulfide metabolism. Thus, we show the daytime- and thiamine-dependent changes in the function and phosphorylation of brain PDHC, contributing to regulation of the brain acetylation system and redox metabolism. The daytime-dependent action of thiamine on PDHC and SIRT3 may be of therapeutic significance in correcting perturbed diurnal regulation.
Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder whose aetiology is still unknown. Most hypotheses point out the gut-brain axis as a key factor for IBS. The axis is composed of different anatomic and functional structures intercommunicated through neurotransmitters. However, the implications of key neurotransmitters such as norepinephrine, serotonin, glutamate, GABA or acetylcholine in IBS are poorly studied. The aim of this review is to evaluate the current evidence about neurotransmitter dysfunction in IBS and explore the potential therapeutic approaches. IBS patients with altered colorectal motility show augmented norepinephrine and acetylcholine levels in plasma and an increased sensitivity of central serotonin receptors. A decrease of colonic mucosal serotonin transporter and a downregulation of α2 adrenoceptors are also correlated with visceral hypersensitivity and an increase of 5-hydroxyindole acetic acid levels, enhanced expression of high affinity choline transporter and lower levels of GABA. Given these neurotransmitter dysfunctions, novel pharmacological approaches such as 5-HT3 receptor antagonists and 5-HT4 receptor agonists are being explored for IBS management, for their antiemetic and prokinetic effects. GABA-analogous medications are being considered to reduce visceral pain. Moreover, agonists and antagonists of muscarinic receptors are under clinical trials. Targeting neurotransmitter dysfunction could provide promising new approaches for IBS management.