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Utilization of Immersive Virtual Reality in Cognitive Stimulation Therapy (IVR-CST) for elderly with mild cognitive impairment: A randomized controlled pilot study protocol

Objectives Mild cognitive impairment (MCI) affects about 11.4% of the elderly population in Hong Kong. This study mainly investigates the feasibility and efficacy of immersive virtual reality-based cognitive stimulation therapy (IVR-CST) on MCI, and the use of eye-tracking technology in studying treatment outcome. Hypothesis to be tested 1) Whether IVR-CST is a feasible intervention for the elderly with MCI. 2) Whether IVR-CST is efficacious (and more efficacious than conventional CST) in improving cognition. 3) Whether changes in eye movements across therapy and treatment outcome are associated. Design and subjects An open-label, two-armed, assessor-blinded, randomized controlled trial will be conducted. Sixty-six elderly individuals with MCI will be recruited and randomly allocated to either the IVR-CST or the conventional CST group. Their cognition will be measured before and immediately after therapy and 4 weeks post-therapy. Interventions A 14-session IVR-CST or conventional CST, with content adapted from the Chinese-translated manual of CST, will be carried out twice per week in groups of three to four individuals. Outcome measures and data analysis The Hong Kong Montreal Cognitive Assessment and measures on executive functions/working memory will serve as primary outcomes. The within-subject (before and after therapy) and between-subject (IVR-CST vs. conventional CST) differences will be examined. Besides, eye movements during therapy in the IVR-CST group will be collected and its correlation with primary outcomes will be studied. Expected results Positive changes in cognition are expected after therapy in both treatment groups, which may be maintained four weeks post-therapy. Trial registration ClinicalTrials.gov ID: NCT06838494

Dehydroxy-Perfluoro-tert-butylation of alcohols with PhSO2C(CF3)3 and insights into the structure of the [C(CF3)3]− anion

Kras and ciliary gene mutations cooperatively lead to pancreatic tumorigenesis only when induced during embryogenesis

Development of the MSKP index: Risk model of musculoskeletal pain in Colombian adolescents

Objective This study aimed to develop a model to evaluate the risk of musculoskeletal pain (MSKP) in adolescents and identify the associated factors. Methods A total of 680 adolescents were surveyed, with assessments of chronic neck, back, and shoulder pain, and related factors such as mobile dependence, physical activity, sleep quality, and sociodemographics. A multivariate logistic regression model was employed, with feature selection through correlation analysis and Lasso regression, to identify significant predictors and establish a risk scale. The model’s performance was evaluated using the area under the ROC curve. Results The prevalence of positive MSKP cases was 22.6% [95% CI: 19.7% – 25.9%]. Despite the self-reporting nature of the input data, the model achieved an AUC-ROC of 0.82, demonstrating good discriminatory ability. Key predictors include sleep disturbances, high mobile dependency, engagement in household chores, age 16–18, and urban residence. Girls exhibited a higher propensity for MSKP. Engagement in football was the only feature associated with a reduction of positive MSKP probability. A risk model is proposed to group the students into tertiles with low (2.3%), medium (17.4%) and high (44.7%) prevalence of MSKP. Conclusions The MSKP Index effectively stratifies adolescent risk based on key factors, with significant associations between MSKP and sleep problems, mobile dependency, age, and gender. Regular physical activity, especially soccer, emerges as a protective factor, supporting targeted prevention strategies.

Scaling and mechanical optimality of bristled wings in microinsects

It is crucial for both animal evolution and engineering to optimize the relative size of structures. Animal wings are no exception, every structural design having its limits in terms of achievable size and performance. For instance, many microinsects have bristled wings, which are more efficient at small scales than the membranous wings common in larger insects. However, the limitations and the optimal characteristics of bristled wings remain largely underinvestigated. We collected morphological and kinematic data on a variety of beetles ranging between 0.3 and 5 mm in wing length. This was followed by a theoretical analysis to explain from the mechanical standpoint the morphological traits and allometric scalings observed in the data. We derived functional dependencies for parameters such as the number of bristles, bristle length and diameter, size of the wing blade, etc., from considerations of wing inertia minimization under the aerodynamic and structural stiffness constraints. The solution of the optimization problem reveals scaling relationships aligning with empirical trends, which suggests that the reduction of wing membrane during miniaturization can be explained by mechanical optimality. Thus, scaling of the number of bristles and the average gap width between bristles follows directly from the aerodynamic condition of maintaining low permeability, while the bristle diameter and length are determined mainly by the structural stiffness requirement. Similar mechanical arguments are likely applicable to other miniature animals that propel through fluids.

Heme allocation in eukaryotic cells relies on mitochondrial heme export through FLVCR1b to cytosolic GAPDH

Abstract Heme is an iron-containing cofactor generated in mitochondria that must leave this organelle to reach protein targets in other cell compartments. Because mitochondrial heme binding by cytosolic GAPDH enables its distribution in cells, we sought to uncover how heme reaches GAPDH. Experiments utilizing two human cell lines and a GAPDH reporter protein whose heme binding can be followed by fluorescence reveal that the mitochondrial protein FLVCR1b provides heme to GAPDH in concert with a rise and fall in their association. An absence of FLVCR1b diminishes GAPDH association with mitochondria and prevents GAPDH and cell hemeproteins from receiving heme. GAPDH heme procurement also requires the TANGO2 protein, which interacts with FLVCR1b to presumably support heme export. In isolated mitochondria, GAPDH associates with FLVCR1b to trigger heme release and delivery to client hemeproteins. Identifying FLVCR1b as the source of mitochondrial heme for GAPDH reveals a path by which this essential cofactor can reach multiple protein targets within eukaryotic cells.

Comparison of the number of peripapillary perforating scleral vessels between glaucomatous eyes and healthy eyes

Editorial Note: Somatization symptomology and its association with stress in patients with irritable bowel syndrome

Laser-emitting aqueous bioreactors for ultrasensitive bioactivity analysis

Water droplets, acting as natural bioreactors and optical whispering-gallery-mode (WGM) resonators, hold the potential for laser-assisted analysis. However, water/aqueous droplet lasers can only survive in air with a limited lifespan (<100 s) due to rapid evaporation, restricting their applications in bioreactions. To address this challenge, we introduce laser-emitting aqueous bioreactors (LEABs) in fluorocarbon oils. These LEABs enable stable laser emission and extend a droplet lifespan over 1,000-fold. LEABs enable the encapsulation of bioactive materials for long-term analysis with unique lasing characteristic fingerprints. The reactions within LEAB can interact with the most resonating light, enhancing detection sensitivity by over 100-fold compared to conventional WGM sensors. By integrating LEABs with microfluidic droplet technology, we demonstrated their application in monitoring enzyme activity and cellular metabolism at single-cell and multicellular levels. Furthermore, we showed the laser threshold-gated screening of single yeast. This platform can bridge the gap between laser technology and biochemical applications, broadening the scope of laser-based analysis.

Experimental confirmation of secondary flows within granular media

Assessing the impact of interregional mobility on COVID19 spread in Spain using transfer entropy

Correction: Quantum spin models for numerosity perception

The <i>Medicago truncatula</i> lncRNA <i>ENOD40</i> is a mediator of <i>microRNA169</i> -controlled <i>NF-YA</i> activity in nodule initiation

The hallmark of the legume lncRNA EARLY NODULIN40 ( ENOD40 ), involved in rhizobium-induced nodulation, is the presence of a highly conserved stretch of 24 nucleotides, designated box2, preceded by a small open-reading-frame (sORF) coding for a peptide of 12 to 13 amino acids. Although there is a well-established link between ENOD40 and nodulation, it is not fully clear by which mechanism ENOD40 functions in this process. Here, we show that a region harboring box2 can complement nodule formation in an ENOD40 knock-out mutant ( enod40-1-2/1 ). The sequence of box2 bears the characteristics of a miR169 target mimic. We show that the artificial target mimic MIM169defg can indeed complement the reduced capability of nodule formation in enod40-1-2/1 , and that box2 exhibits target mimic activity in a transient luciferase assay. In addition, the introduction of a miR169 -resistant form of MtNF-YA1 also elevates the capacity to form nodules in enod40-1-2/1. We conclude that ENOD40 effectuates nodule initiation by posttranscriptional upregulation of the miR169 target NF-YA1 , which encodes an essential transcription factor in this step of the nodulation process.

Up-recycling of waste wood into value-added room temperature phosphorescent materials

Author Correction: P53 represses pyrimidine catabolic gene dihydropyrimidine dehydrogenase (DPYD) expression in response to thymidylate synthase (TS) targeting

Piezo1 regulates autophagy in HT22 hippocampal neurons through the Ca2+/Calpain and Calcineurin/TFEB signaling pathways

Objective To investigate the functional and molecular mechanisms by which Piezo1regulates HT-22 hippocampal neuronal autophagy, and to explore whether Piezo1 regulates hippocampal neuronal autophagy via the Ca2+/Calpain, CaMKKβ, or Calcineurin pathways. Methods The impacts of Piezo1 inhibition, activation and gene knockdown on the autophagy of HT22 neurons was investigated by Western blotting, PCR and immunofluorescence. The changes of intracellular calcium (Ca2+) concentration were also observed. To pinpoint the specific downstream Ca2+ signaling pathway by which Piezo1 modulates autophagy, the calcium chelator BAPTA-AM, the Calpain inhibitor PD151746, and the CaMKKβ inhibitor STO609 were employed either alone or in combination. Results Enhanced autophagy was observed when Piezo1 was activated using the agonist Yoda1, manifesting as increased release of autophagic vacuoles, enhanced LC3 II/LC3 I ratio, decreased p62 protein level, and elevated nuclear translocation and expression of the TFEB protein. ATG7 knockdown by ATG7 shRNA mitigated the effects of Yoda1 on LC3 II/LC3 I ratio and p62 protein levels. The Piezo1 inhibitor GsMTx4 partially reversed the autophagy caused by starvation in HT22 neurons while Yoda1 still activated autophagy in the presence of BDNF. Following Piezo1 knockdown, neuronal autophagy was decreased. Piezo1-induced autophagy was accompanied with an increased cytoplasmic concentration of Ca2+. The calcium chelator BAPTA-AM partly reversed Piezo1 activation-induced autophagy, which was also mitigated by blocking calcineurin/TFEB signaling or Calpain signaling. Conclusion Piezo1 modulates the autophagy of HT-22 neurons by activating Ca2+/Calpain and Calcineurin/TFEB pathways.

Post-functionalization of polyethers by photoinduced C–H amidation via polar-radical relay

Implantable electrical stimulation device enhances pelvic floor tissue repair and reduces collagen over-degradation in rats with stress urinary incontinence

The efficacy of virtual reality in adults during puncture biopsy: A systematic review and meta-analysis of randomized controlled trials

Background Virtual reality, as a nascent technology, possesses the potential to enhance patient comfort by mitigating pain and anxiety during medical procedures. This study aimed to evaluate the efficacy of virtual reality intervention in managing pain for adults undergoing puncture biopsy procedures. Methods From the outset of the development of databases until October 8, 2024, a comprehensive search of the published literature was performed across eight electronic databases. The collected data was consolidated and subjected to meta-analysis by using RevMan 5.4. The quality of the inclusion of randomized controlled trials in terms of methodological quality was assessed by the Cochrane Risk of Bias Assessment Tool. Additionally, strength and certainty of the evidence was assessed by the GRADE system. Results The study was conducted on data from a sample of 445 patients from six randomized controlled trials. The pooled analysis revealed that the virtual reality group demonstrated an analgesic effect (MD = −1.61, 95% CI: −2.54 to −0.68; p = 0.0007; I2 = 90%). Moreover, the virtual reality intervention was found to reduce patient anxiety during puncture biopsy procedures (MD = −9.49, 95% CI −14.47 to −4.50; p = 0.0002; I2 = 88%). In addition, three studies that could not be included in the meta-analysis also reported a positive impact of increasing patient satisfaction with the operation. Conclusions Virtual reality can be used as an analgesic method in adult puncture biopsies and as a reliable alternative therapy in clinical settings, providing a valuable non-pharmacologic approach to pain management. Nevertheless, the level of evidence is relatively low, thus further high-quality studies are required to substantiate our conclusion. Systematic review registration PROSPERO database, CRD4202459303.

Hippocampal mismatch signals are based on episodic memories and not schematic knowledge

Prediction errors drive learning by signaling mismatches between expectations and reality, but the neural systems supporting these computations remain debated. The hippocampus is implicated in mismatch detection, yet it is not known whether it signals mismatches with episodic memories or generalized knowledge. Across three functional Magnetic Resonance Imaging (fMRI) experiments, we show that the hippocampus selectively responds to mismatches with episodic memories of specific events. In contrast, schematic mismatches engage Semantic Control and Multiple Demand Networks, as well as subcortical regions linked to prediction error signaling. Episodic mismatches also recruit the Default Mode Network. These findings challenge accounts that propose the hippocampus is a domain-general mismatch detector. Instead, the findings support a more specialized role for the hippocampus in learning that is underpinned by its well-established importance in processing episodic memories.