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This study investigates the perception and production of a specific type of metaphoric gesture that mimics melody in speech, also called pitch gesture, in the learning of L2 suprasegmental features. In a between-subjects design, a total of 106 participants with no previous knowledge of Chinese were asked to observe (Experiment 1) and produce (Experiment 2) pitch gestures during a short multimodal training session on Chinese tones and words. In both experiments they were tested on (a) tone identification and (b) word learning. Results showed the positive effect of a training session with pitch gesture observation compared to a training session without it (Experiment 1) and the benefits of producing gestures compared to only observing them and repeating the words aloud (Experiment 2). A comparison of the results of the two experiments revealed that there was no significant difference between the simple observation of pitch gestures and the production of speech accompanied by pitch gestures in facilitating lexical tone identification and word learning. Thus, both perception and production tasks with pitch gestures can be regarded as beneficial learning strategies for the initial stages of tones acquisition in the Chinese as a Second Language classroom.

This review explores recent advancements in gene therapy as a potential treatment for neurodegenerative diseases, focusing on intervention mechanisms, administration routes, and associated limitations. Following the PRISMA procedure guidelines, we systematically analyzed studies published since 2020 using the PICO framework to derive reliable conclusions. The efficacy of various gene therapies was evaluated for Parkinson’s disease (n = 12), spinal muscular atrophy (n = 8), Huntington’s disease (n = 3), Alzheimer’s disease (n = 3), and amyotrophic lateral sclerosis (n = 6). For each condition, we assessed the therapeutic approach, curative or disease-modifying potential, delivery methods, advantages, drawbacks, and side effects. Results indicate that gene therapies targeting specific genes are particularly effective in monogenic disorders, with promising clinical outcomes expected in the near future. In contrast, in polygenic diseases, therapies primarily aim to promote cell survival. A major challenge remains: the translation of animal model success to human clinical application. Additionally, while intracerebral delivery methods enhance therapeutic efficacy, they are highly invasive. Despite these hurdles, gene therapy represents a promising frontier in the treatment of neurodegenerative diseases, underscoring the need for continued research to refine and personalize treatments for each condition.

Purpose To identify 5-year survival prognostic variables in patients with colorectal cancer (CRC) and to propose a survival prognostic score that also takes into account changes over time in the patient’s health-related quality of life (HRQoL) status. Methods Prospective observational cohort study of CRC patients. We collected data from their diagnosis, intervention, and at 1, 2, 3, and 5 years following the index intervention, also collecting HRQoL data using the EuroQol-5D-5L (EQ-5D-5L), European Organization for Research and Treatment of Cancer’s Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30), and Hospital Anxiety and Depression Scale (HADS) questionnaires. Multivariate Cox proportional models were used. Results We found predictors of mortality over the 5-year follow-up to be being older; being male; having a higher TNM stage; having a higher lymph node ratio; having a result of CRC surgery classified as R1 or R2; invasion of neighboring organs; having a higher score on the Charlson comorbidity index; having an ASA IV; and having worse scores, worse quality of life, on the EORTC and EQ-5D questionnaires, as compared to those with higher scores in each of those questionnaires respectively. Conclusions These results allow preventive and controlling measures to be established on long-term follow-up of these patients, based on a few easily measurable variables. Implications for cancer survivors Patients with colorectal cancer should be monitored more closely depending on the severity of their disease and comorbidities as well as the perceived health-related quality of life, and preventive measures should be established to prevent adverse outcomes and therefore to ensure that better treatment is received. Trial registration ClinicalTrials.gov identifier: NCT02488161.

Objectives: Gastric cancer is one of the leading causes of cancer-related mortality. Sarcopenia, characterized by reduced skeletal muscle mass, strength, and physical performance, is associated with poorer outcomes in gastrointestinal cancers. This study aimed to evaluate the prevalence of sarcopenia, including the Total Psoas Area Index (TPAI), and its association with tumor stage, postoperative complications, and survival in patients with gastric adenocarcinoma. Methods: A retrospective study was conducted, including 79 patients who underwent surgery for gastric adenocarcinoma. Sarcopenia was assessed using a combination of CT-derived muscle mass (TPAI), muscle strength (dynamometry), and functional status (SARC-F). Patients were divided into sarcopenic (SG) and non-sarcopenic (NSG) groups. Clinical and survival data were compared between groups. Results: Sarcopenia was identified in 36.7% of patients. Early-stage disease (I–II) was less frequent in the SG (20.7%) compared to the NSG (44%), whereas stage IV tumors were more common in the SG (20.7% vs. 6%). Sarcopenic patients had a lower body mass index and underwent fewer laparoscopic procedures (44.8% vs. 68%, p = 0.03). Postoperative complications, such as pneumonia and ileus, were more frequent in the SG. Overall survival was significantly lower in the SG (17 vs. 21 months, respectively, p = 0.042), with a reduction in disease-free survival as well. Postoperative TPAI values remained lower in the SG. Conclusions: Sarcopenia, as defined by combined assessment including TPAI, was associated with advanced tumor stage, increased postoperative risk, and reduced survival in patients with gastric cancer. Preoperative assessment of muscle mass may help identify high-risk patients and optimize clinical management.

The digestion of A1 β-casein present in conventional milk releases β-casomorphin-7 (βCM-7), a bioactive peptide with potential implications for gastrointestinal and neurological health. A scoping review was performed to respond to the following research question: What are the health effects of consuming milk containing the A1 β-casein variant compared to the exclusive consumption of the A2 variant in humans? The evidence collected in this review of human studies with different populations (i.e., children, middle-aged adults, athletes) suggests that the consumption of milk containing A1 β-casein may negatively influence gut health by altering microbial composition, reducing intestinal motility, and increasing colonic fermentation, leading to elevated gas production and altered short-chain fatty acid (SCFA) profiles. The release of βCM-7 upon digestion can also compromise intestinal-barrier integrity, which may exacerbate symptoms of lactose intolerance, irritable bowel syndrome (IBS), or other allergy-related sensitivities. Its ability to cross the blood–brain barrier raises concerns about potential neurological effects. In contrast, milk containing exclusively A2 β-casein is associated with improved gastrointestinal outcomes, including the enhanced abundance of beneficial bacteria such as Bifidobacterium spp. and reduced inflammatory markers.

Phosphorus is an essential mineral involved in bone mineralization, energy metabolism, and cellular signaling, whose serum concentration is tightly regulated by an endocrine network including fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), vitamin D and Klotho. Disruption of this balance, particularly in chronic kidney disease (CKD), leads to hyperphosphatemia, which is strongly associated with bone fragility, vascular calcification, and increased mortality. In CKD, impaired phosphorus homeostasis triggers endocrine dysregulation characterized by elevated PTH and FGF23 levels, Klotho deficiency, and altered vitamin D metabolism, resulting in major skeletal and vascular consequences. Experimental and clinical evidence indicates that phosphorus overload contributes directly to skeletal deterioration and early vascular remodeling, even prior to clinically detectable renal impairment. Moreover, high dietary phosphorus intake under conditions of normal renal function reproduces several molecular and structural alterations typically observed in CKD, supporting a pathogenic role for chronic phosphorus excess. The dietary source of phosphorus has gained increasing relevance, as inorganic phosphate additives exhibit high intestinal bioavailability and impose a greater systemic phosphorus burden. Current management strategies rely on dietary restriction, phosphate binders, modulation of intestinal phosphorus transport and optimization of mineral-regulating hormones, although evidence for improved clinical outcomes remains limited. A deeper understanding of the molecular mechanisms linking phosphorus overload to bone and vascular pathology may facilitate the development of more effective preventive and therapeutic strategies.

Background Childhood maltreatment significantly increases the risk of early substance use and psychiatric disorders; however, the sex differences in this relationship and the varying effects of different types of maltreatment in youths remain largely unexplored. Therefore, this study aimed to explore sex differences in the relationship between various maltreatment subtypes and the onset of early substance use. It also sought to examine how other indirect forms of mistreatment, such as household dysfunction, affect the age at which substance use begins. Methods This multicenter study involved 187 children and adolescents (58% female) aged 7 to 17, with 62% meeting the criteria for a psychiatric disorder. We examined how maltreatment, including both direct (abuse and neglect) and indirect (household dysfunction), was related to the development of substance use. To explore sex differences in the effects of maltreatment subtypes, we conducted sex-stratified correlation analyses. We used linear regression to assess how household dysfunction independently contributes to early substance use while controlling for direct maltreatment, age at assesment, socioeconomic status, psychiatric history and pubertal stage. Additionally, it was analyzed whether this early initiation of drugs is associated with worse mental health. Results Female participants exposed to maltreatment began substance use earlier (average age 13 compared to 14 for males), with strong associations identified for physical abuse and household dysfunction. Household dysfunction was a significant predictor of nearly two years earlier substance use in girls (B = −1.904, 95% CI: −3.027 to −0.782, p  = 0.001). Furthermore, early substance use in females was associated with higher internalizing/externalizing symptoms and poorer functioning, while males showed no significant associations. Conclusions Maltreatment and family dysfunction disproportionately impact females, accelerating the onset of substance use and exacerbating mental health issues. Customized interventions that address family dynamics and trauma are essential for effective prevention. Clinical trial number Not applicable.

This study examined the expression of the renin-angiotensin system (RAS) and inflammatory markers in cardiovascular complications associated with long-term type 1 diabetes (T1D) using a rat model. After 24 weeks of streptozotocin-induced T1D, the animals exhibited metabolic alterations indicative of both cardiac and renal dysfunction. Tissue-specific dysregulation of RAS components and pro-inflammatory markers were observed in the heart, aorta, and perivascular adipose tissue (PVAT). In the heart, there was a significant upregulation of both classical (AT1R, 1.00 (0.22) vs. 1.70 (0.45) R.U.) and counter-regulatory RAS components (ACE2, 1.00 (0.43) vs. 1.96 (0.67) R.U.; p < 0.001) and MasR (1.00 (0.56) vs. 1.33 (0.29) R.U.; p = 0.004). The aorta displayed increased expression of classical RAS components alongside a significant reduction in ACE2 expression (1.00 (0.74) vs. 0.51 (0.48) R.U.; p < 0.032). Notably, PVAT showed a significant overexpression of classical RAS components (ACE 1.00 (0.22) vs. 4.08 (1.32) R.U.; p < 0.001, AT1R 1.00 (0.59) vs. 7.22 (4.14) R.U.; p < 0.001) and MasR (1.00 (0.70) vs. 4.52 (1.91) R.U.; p < 0.001), accompanied by increased expression of TNFα and ADAM17. These findings suggest that long-term T1D induces tissue-specific activation patterns of the RAS and inflammatory pathways within the cardiovascular system, which may contribute to the progression of diabetic cardiovascular complications. Therapeutic targeting of RAS components may represent a viable strategy for mitigating cardiovascular damage in T1D.

Background: The increasing prevalence of processed foods has significantly elevated dietary phosphorus intake globally, posing a risk to skeletal health. Elevated serum phosphate promotes parathyroid hormone (PTH) release, leading to bone resorption and decreased bone formation. Objective: This study investigated the influence of chronically elevated phosphorus intake on bone structure in rats with normal renal function, focusing on the Receptor Activator of Nuclear factor Kappa-B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway and its related components, leucine rich repeat containing G protein-coupled receptor 4 (LGR4), and R-spondins (RSPOs). Methods: Rats were fed a high-phosphorus diet, followed by assessment of the bone microstructure and of the expression of key signalling molecules. Results: Elevated phosphorus intake induced significant bone deterioration, particularly in the trabecular bone compartment, associated with alterations in the RANK/RANKL/OPG pathway and in the LGR4 and RSPO1 and RSPO4 signalling components in bone. Moreover, we also observed changes in RANKL, RSPO1 and RSPO4 serum levels in the rats that had received a high-phosphorus diet. Conclusions: These findings highlight the detrimental impact of excessive dietary phosphorus on skeletal health, even without renal impairment, and suggest that components of this pathway, particularly RSPO1 and RSPO4, could serve as potential biomarkers of bone deterioration. The widespread consumption of phosphorus-rich processed foods underscores the importance of nutritional education to mitigate these skeletal risks in industrialized populations.

A room temperature benzene and formaldehyde gas sensor system with an ionogel as sensing material is presented. The sensing layer is fabricated employing poly( N -isopropylacrylamide) polymerized in the presence of 1-ethyl-3-methylimidazolium ethyl sulfate ionic liquid onto gold interdigitated electrodes. When the ionogel is exposed to increasing formaldehyde concentrations employing N 2 as a carrier gas, a more stable response is observed in comparison to the bare ionic liquid, but no difference in sensitivity occurs. On the other hand, when air is used as carrier gas the sensitivity of the system towards formaldehyde is decreased by one order of magnitude. At room temperature, the proposed sensor exhibited in air higher sensitivities to benzene, at concentrations ranging between 4 and 20 ppm resulting, in a limit of detection of 47 ppb, which is below the standard permitted concentrations. The selectivity of the IL towards HCHO and C 6 H 6 is demonstrated by the absence of response when another IL is employed. Humidity from the ambient air slightly affects the resistance of the system proving the protective role of the polymeric matrix. Furthermore, the gas sensor system showed fast response/recovery times considering the thickness of the material, suggesting that ionogel materials can be used as novel and highly efficient volatile organic compounds sensors operating at room temperature. Graphical abstract