γδ T-Cell Immunophenotype for the Study of Human Aging.

Flow cytometry serves as a crucial tool in immunology, allowing for the detailed analysis of immune cell populations. γδ T cells, a subset of T cells, play pivotal roles in immune surveillance and immune aging. Assessing the phenotype and functional capabilities of γδ T cells isolated from whole blood or tissue within the context of human aging yields invaluable insights into the dynamic changes affecting immune function, tissue homeostasis, susceptibility to infections, and inflammatory responses.

Inducible tolerance to low Ca:Mg in serpentine ecotype of Erythranthe guttata.

In serpentine soils, the low level of calcium relative to magnesium (Ca:Mg) is detrimental to the growth of most plant species. Ecotypic variation in Erythranthe guttata allows for some populations to maintain high photosynthetic rates and biomass despite low Ca:Mg. In this study, the mechanism of tolerance was investigated by treating hydroponically grown plants with either high (1.0) or low (0.02) Ca:Mg growth solutions and assaying excised leaf discs for rates of photosynthesis and disc expansion, and for starch, Ca2+ and Mg2+ ion concentrations. Low Ca:Mg in the assay solutions reduced both photosynthesis and leaf disc expansion after one week of treatment. However, serpentine tissues show stable photosynthetic rates after one week and a recovery in leaf tissue expansion after two weeks exposure to low Ca:Mg conditions. Values for non-serpentine tissues continued to decline. Increased growth of low Ca:Mg treated discs supplied with exogenous sucrose suggests that growth in serpentine-exposed tissues is limited by availability of carbon products from photosynthesis. Serpentine leaves had higher vacuole Mg concentrations than non-serpentine leaves after three weeks of treatment with low Ca:Mg. The combination of elevated starch concentrations, reduced growth and lower vacuolar Mg concentrations in leaves of non-serpentine plants grown in low Ca:Mg indicate an inefficient use of carbon resources and starch degradation as an observed response to Mg toxicity. Together, these results suggest that serpentine E. guttata exhibits an inducible tolerance to low Ca:Mg through gradual compartmentalization of magnesium to maintain the production and metabolism of photosynthates necessary for growth.

Potential vs challenges of expanding the protein universe with genetic code expansion in eukaryotic cells.

Following decades of innovation and perfecting, genetic code expansion has become a powerful tool for in vivo protein modification. Some of the major hurdles that had to be overcome include suboptimal performance of GCE-specific translational components in host systems, competing cellular processes, unspecific modification of the host proteome and limited availability of codons for reassignment. Although strategies have been developed to overcome challenges, there is critical need for further improvement. Here we discuss the current state-of-the-art in genetic code expansion technology and the issues that still need to be addressed to unleash the full potential of this method in eukaryotic cells.

Land use, land cover changes and expansion of artificial reservoirs in Eastern Thailand: implications for agriculture and vegetation drought reduction.

Eastern Thailand and Rayong province face perennial drought and water scarcity due to natural characteristics of climate and geology. Therefore, increasing water surface by man-made reservoirs is one of the priorities in the regional development plan to provide water adequately for industrial purposes, domestic consumption, and agriculture. The large reservoir constructions may induce land use, land cover changes (LULCC), yet it also is expected to alleviate the drought harshness in the region. By delineating Landsat satellite images and spatial analysis, this study revealed the LULCC in Rayong from 1990 to 2020. The most prominent LULCC was surface water expansion, about 10.9% per year, yet the increase was the most substantial in the first decade rather than the last two decades. Vegetation expansion was observed, contributing to an increase in forests/plantations and intensified agriculture by 39.19% and 25.54%, respectively. The LULCC corresponded to a 3.64% increase in ecosystem service values (ESV), implying positive benefits from the LULCC. Vegetation drought conditions monitored by the vegetation health index (VHI) exhibited an improvement trend, especially in the eastern basins. The development of artificial reservoirs was proven to stimulate the expansion of intensive agriculture and vegetation drought mitigation with spatial heterogeneity, spreading mainly across areas of the basins rather than remote areas. The research findings inform the efficiency of the reservoirs and irrigation systems regarding the beneficial effects on drought mitigation and water scarcity for agricultural cultivation. They also provide spatial information on areas still hindered by water problems that should be addressed in future strategies.

Achieving ZT > 1 in Cu and Ga Co-doped Ag6Ge10P12 with Superior Mechanical Performance and Its Fundamental Physical Properties toward Practical Thermoelectric Device Applications.

Recently, phosphorus-based compounds have emerged as potential candidates for thermoelectric materials. One of the key challenges facing this field is to achieve ZT > 1, which is the benchmark for thermoelectric device applications. In this study, it is demonstrated that the thermoelectric performance of environmentally friendly Ag6Ge10P12 is enhanced by co-doping Cu and Ga. The mechanical properties, coefficient of linear thermal expansion, work function, and compatibility factor are comprehensively clarified to provide guidelines for reliable device applications. The peak and average dimensionless figures of merit of Ag5.85Cu0.15Ge9.875Ga0.125P12 reach 1.04 at 723 K and 0.63 at 300-723 K, respectively, which are the highest values for phosphorus-based thermoelectric materials. The Young's modulus, Vickers microhardness, fracture toughness, and compressive strength of Ag5.85Cu0.15Ge9.875Ga0.125P12 are 132 GPa, 589, 1.23 MPa m1/2, and 219 MPa, respectively, which are superior to those of typical state-of-the-art thermoelectric materials. The remarkable thermoelectric and mechanical performance of Ag5.85Cu0.15Ge9.875Ga0.125P12 mean that it is a promising candidate for medium-temperature thermoelectric conversion. Ti, V, Rh, and Pt are suitable for electrodes without exfoliation under thermal expansion and with ohmic contacts to Ag5.85Cu0.15Ge9.875Ga0.125P12 in terms of the coefficient of linear thermal expansion and work function. Considering that the compatibility factor of Ag5.85Cu0.15Ge9.875Ga0.125P12 is approximately 2.8, half-Heusler, skutterudite, and magnesium silicide-stannide compounds are suitable n-type thermoelectric counterpart materials in thermoelectric devices. These insights will lead to the development of phosphorus-based thermoelectric materials toward practical thermoelectric device applications.

Piezo1 Promotes Osteogenesis Through CaMKII Signalling in a Rat Maxillary Expansion Model.

OBJECTIVES: Rapid maxillary expansion (RME) is a widely used technique to treat maxillary transverse deficiency. Piezo1 is a cation channel that is activated by mechanical force and regulates bone formation. This study aims to elucidate the role of Piezo1 in bone remodelling during the RME process. MATERIALS AND METHODS: In this study, the periosteal-derived stem cells (PDSCs) were cultured and stretched by the Flexcell system. The effects of Piezo1 on osteogenesis were assessed via RNA sequencing, real-time quantitative PCR, and western blot analyses. Moreover, for in vivo analyses, the rat RME model was established. The function of Piezo1 in mid-palatal suture bone remodelling was evaluated using micro-CT, haematoxylin-eosin (HE) staining, and immunohistochemistry analyses. RESULTS: It was revealed that under tension force, the osteogenic factors (Runt-related transcription factor 2, Osterix, and Alkaline Phosphatase) and Ca2+/calmodulin -dependent protein kinase (CaMKII) were significantly enhanced in PDSCs over time. Furthermore, these were also upregulated in the RME model with the expansion of the mid-palatal suture. However, Piezo1 inhibition by Grammostola spatulata mechanotoxin 4 downregulated the levels of these factors in the RME model. CONCLUSIONS: This study indicated that Piezo1 is associated with the osteogenesis of PDSCs and bone remodelling in the RME process. CaMKII might also participate in this process.

Disambiguating Clinical Abbreviations by One-to-All Classification: Algorithm Development and Validation Study.

Background: Electronic medical records store extensive patient data and serve as a comprehensive repository, including textual medical records like surgical and imaging reports. Their utility in clinical decision support systems is substantial, but the widespread use of ambiguous and unstandardized abbreviations in clinical documents poses challenges for natural language processing in clinical decision support systems. Efficient abbreviation disambiguation methods are needed for effective information extraction. Objective: This study aims to enhance the one-to-all (OTA) framework for clinical abbreviation expansion, which uses a single model to predict multiple abbreviation meanings. The objective is to improve OTA by developing context-candidate pairs and optimizing word embeddings in Bidirectional Encoder Representations From Transformers (BERT), evaluating the model's efficacy in expanding clinical abbreviations using real data. Methods: Three datasets were used: Medical Subject Headings Word Sense Disambiguation, University of Minnesota, and Chia-Yi Christian Hospital from Ditmanson Medical Foundation Chia-Yi Christian Hospital. Texts containing polysemous abbreviations were preprocessed and formatted for BERT. The study involved fine-tuning pretrained models, ClinicalBERT and BlueBERT, generating dataset pairs for training and testing based on Huang et al's method. Results: BlueBERT achieved macro- and microaccuracies of 95.41% and 95.16%, respectively, on the Medical Subject Headings Word Sense Disambiguation dataset. It improved macroaccuracy by 0.54%-1.53% compared to two baselines, long short-term memory and deepBioWSD with random embedding. On the University of Minnesota dataset, BlueBERT recorded macro- and microaccuracies of 98.40% and 98.22%, respectively. Against the baselines of Word2Vec + support vector machine and BioWordVec + support vector machine, BlueBERT demonstrated a macroaccuracy improvement of 2.61%-4.13%. Conclusions: This research preliminarily validated the effectiveness of the OTA method for abbreviation disambiguation in medical texts, demonstrating the potential to enhance both clinical staff efficiency and research effectiveness.

Effects of recalling place memory on promoting cooperative behaviors in local communities.

AIMS: The present study aimed to develop a theoretical model that explores the influence of recalling place memory on cooperative behaviors in local communities. METHODS: Five hundred ninety-five Japanese residents (mean age = 49.75 years) participated in an online survey, in which they received one of the three interventions: (1) positive memory; (2) neutral memory and (3) negative memory. Participants were instructed to recall their place memories within their living areas and provide ratings for their place attachment, emotional valence, perceived self-interest, and willingness to engage in cooperative behaviors. RESULTS: The results revealed that individuals who recalled positive-valenced place memories exhibited a higher willingness to engage in cooperative behaviors. Additionally, this study reveals the previously unreported mediating role of place attachment and perceived self-interest in promoting cooperative behaviors. CONCLUSION: The findings hold significance in elucidating the relationship between place memory and cooperative behaviors, offering novel insights for community management.

A Dual Purpose Non-Canonical Amino Acid for the Expanded Genetic Code: Combining Metal-Binding and Click Chemistry.

A rationally designed dual purpose non-canonical amino acid (Trz) has been synthesised and successfully incorporated into a protein scaffold via genetic code expansion. Trz contains a 5-pyridyl-1,2,4-triazine system, which allows for inverse electron-demand Diels-Alder (IEDDA) reactions to occur on the triazine ring and for metal ions to be chelated both before and after the click reaction. Trz was successfully incorporated into a protein scaffold and the IEDDA utility of Trz demonstrated through the site-specific labelling of the purified protein with a bicyclononyne. Additionally, Trz was shown to successfully coordinate a cyclometallated iridium(III) centre, providing access to a bioorthogonal luminogenic probe. The luminescent properties of the Ir(III)-bound protein blue-shift upon IEDDA click reaction with bicyclononyne, providing a unique method for monitoring the extent and location of the labelling reaction. In summary, Trz is a new dual purpose non-canonical amino acid, which has great potential for myriad bioapplications where metal-based functionality is required, for example in imaging, catalysis, or photo-dynamic therapy, in conjunction with a bioorthogonal reactive handle to impart additional functionalities, such as dual modality imaging or therapeutic payloads.

Effect of treatment of transverse maxillary deficiency using rapid palatal expansion on oral health-related quality of life in children: complementary results for a controlled clinical trial.

OBJECTIVE: To evaluate the effect of rapid palatal expansion (RPE) using Haas-type expanders on children's oral health-related quality of life (OHRQOL) and compare said effect with that previously reported for the use of Hyrax-type expanders. MATERIALS AND METHODS: Forty participants aged 8-10 years with transverse maxillary deficiency were treated using Haas appliances. OHRQOL was measured using the CPQ8 - 10 before RPE, during RPE (T1), at the end of RPE (T2), and 1 month after appliance removal (T3). Generalized mixed models were fitted to assess the effect of the Haas-type expander compared to previously collected data (a nontreated and a Hyrax-type expander-treated group). RESULTS: RPE with Haas-type appliances had a negative impact on overall OHRQOL at T1 and T2 (P = 0.001), and a positive impact at T3 (P = 0.001). The Haas-type expander had a significantly greater negative impact on OHRQOL than the Hyrax-type appliance during RPE. At T1, overall scores using the Haas-type expander were 1.08 times the scores using the Hyrax-type expander (i.e., 8% increase; 95% CI, 1.01-1.17; P = 0.033). Patients using the Haas appliance had 1.24 times the scores of those using Hyrax-type devices for the oral symptoms domain at T1 (i.e., 24% increase; 95% CI, 1.06-1.46; P = 0.009). CONCLUSIONS: Correction of the transverse maxillary deficiency by RPE using the Haas appliance in children 8-10 years improves OHRQOL. The Haas- and Hyrax-type devices temporarily worsen OHRQOL during treatment, however, the negative impact is less with the Hyrax-type expander than with the Haas-type expander, because it causes fewer negative oral symptoms. CLINICAL RELEVANCE: From a patient-centered perspective, the use of the Hyrax over the Haas appliance may be suggested as it causes less negative oral symptoms during use.

District mental health program: Then and now.

District Mental Health Program (DMHP) is part of the broader National Mental Health Program (NMHP) launched in 1982. In India, DMHP has evolved over the years, moving from a pilot project to an integrated component of the NMHP. Efforts have been made to expand services, protect the rights of individuals with mental illness, and integrate mental healthcare into the primary healthcare system. Recent updates and efforts taken by the Government of India and state governments (60% and 40% budget share respectively) have improved the quality of services provided under DMHP. With the increasing use of the internet and mobile technology, DMHP has spread its arena of services more deeply and widely in the last few years reaching up to 738 districts in the country. However, there is still work to be done to address many challenges associated with mental health in India though the recent developments seem promising as a substantial number of patients are now having access to the programme. This narrative review is the summary of information available to date on the evolution of implementation and expansion of DMHP over the years and provides a gist of the positive aspects as well as limitations of the DMHP witnessed in recent years.

The impact of different activation protocols of rapid maxillary expansion on external root resorption: a systematic review and meta-analysis.

This comprehensive meta-analysis investigated the effects of Rapid Maxillary Expansion (RME) on external root resorption, which is a prevalent orthodontic treatment intended to correct transverse maxillary deficiency and constricted dental arches. By conducting a systematic literature search across prominent electronic databases, including the Cochrane Library, EMBASE, LILACS, MEDLINE, PubMed, and Web of Science, the study compiled evidence until April 2023. A spectrum of search terms was utilized to capture diverse aspects of root resorption, RME, palatal expansion methods, and tooth erosion. Registered with INPLASY (202430057), the meta-analysis meticulously screened 11 studies that fulfilled stringent inclusion criteria. The quality of these studies was assessed using the Cochrane Bias Risk Assessment Tool for Randomized Controlled Trials (RCTs) and the Methodological Index for Non-Randomized Studies (MINORS) for other research designs. The collective analyses disclosed a substantial impact of RME on external root resorption, indicating that the treatment may induce pronounced root erosion. Subgroup analyses further elucidated distinct patterns in root resorption among various types of RME, underscoring the variability in treatment outcomes and the need for personalized care. Consequently, the meta-analysis unequivocally confirmed that external root resorption may be a concerning consequence of RME treatment, necessitating thorough monitoring and management strategies to mitigate potential adverse effects on dental health.

Effect of rapid maxillary expansion on intracranial pressure.

Objective: The aim of this study was to evaluate the effects of rapid maxillary expansion on the optic nerve sheath diameter and to examine its possible effects on intracranial pressure. Design: 20 patients with bilateral crossbite were selected. Hyrax Expander was applied and activated twice daily until the overcorrection was achieved. The optic nerve sheath diameter (ONSD) was measured via ultrasonography before the first activation (T0), then repeated after 1 (T1) and 10 min (T2). At the end of the expansion, ONSD was measured (T3) again, then the screw was activated for the last time, and measurements were repeated after 1 (T4) and 10 min (T5). The Friedman test was performed to compare the changes, and The Wilcoxon Signed-Rank test was done to determine the significant intergroup changes (p < 0.05). Results: The ONSD increased significantly 1 min after the activations (T0-T1 and T3-T4) (P < 0.05). The ONSD values measured 10 min after the activations also increased significantly compared to the baseline values (T0-T2 and T3-T5) (P < 0.05). Conclusion: The activation of maxillary expansion appliances increased the optic nerve sheath diameter in adolescents. Therefore, orthodontists should be careful with patients at risk of intracranial hypertension.

Hematoma expansion prediction in intracerebral hemorrhage patients by using synthesized CT images in an end-to-end deep learning framework.

Spontaneous intracerebral hemorrhage (ICH) is a type of stroke less prevalent than ischemic stroke but associated with high mortality rates. Hematoma expansion (HE) is an increase in the bleeding that affects 30%-38% of hemorrhagic stroke patients. It is observed within 24 h of onset and associated with patient worsening. Clinically it is relevant to detect the patients that will develop HE from their initial computed tomography (CT) scans which could improve patient management and treatment decisions. However, this is a significant challenge due to the predictive nature of the task and its low prevalence, which hinders the availability of large datasets with the required longitudinal information. In this work, we present an end-to-end deep learning framework capable of predicting which cases will exhibit HE using only the initial basal image. We introduce a deep learning framework based on the 2D EfficientNet B0 model to predict the occurrence of HE using initial non-contrasted CT scans and their corresponding lesion annotation as priors. We used an in-house acquired dataset of 122 ICH patients, including 35 HE cases, containing longitudinal CT scans with manual lesion annotations in both basal and follow-up (obtained within 24 h after the basal scan). Experiments were conducted using a 5-fold cross-validation strategy. We addressed the limited data problem by incorporating synthetic images into the training process. To the best of our knowledge, our approach is novel in the field of HE prediction, being the first to use image synthesis to enhance results. We studied different scenarios such as training only with the original scans, using standard image augmentation techniques, and using synthetic image generation. The best performance was achieved by adding five generated versions of each image, along with standard data augmentation, during the training process. This significantly improved (p=0.0003) the performance obtained with our baseline model using directly the original CT scans from an Accuracy of 0.56 to 0.84, F1-Score of 0.53 to 0.82, Sensitivity of 0.51 to 0.77, and Specificity of 0.60 to 0.91, respectively. The proposed approach shows promising results in predicting HE, especially with the inclusion of synthetically generated images. The obtained results highlight the significance of this research direction, which has the potential to improve the clinical management of patients with hemorrhagic stroke. The code is available at: https://github.com/NIC-VICOROB/HE-prediction-SynthCT.

C9orf72 repeat expansions in Wakayama: One potential cause of amyotrophic lateral sclerosis in the Kii Peninsula, Japan.

A cluster of cases of amyotrophic lateral sclerosis (ALS) exists in the southern part of the Kii Peninsula in Japan. Although both genetic and environmental factors are thought to be causative, the critical cause of this cluster has not been identified. C9orf72 is the most common genetic factor in both familial and sporadic C9orf72-related ALS in people of European ancestry, but it is rare among Japanese populations. However, a previous report revealed that the frequency of C9orf72-related ALS was significantly higher in the cluster area. We evaluated the proportion of C9orf72 hexanucleotide repeat expansions in 99 cases of ALS diagnosed in Wakayama Prefecture, including the cluster area, by using repeat-primed polymerase chain reaction and fluorescence fragment length analysis. We found that 2 of the 99 patients (0 % of those with familial ALS and 2.4 % of those with sporadic ALS) had hexanucleotide repeat expansions in C9orf72, and long-read sequencing revealed that these expansions were causative. No expansions were observed among 90 patients with Parkinson's disease or among 90 healthy controls. Haplotype analysis with long-read sequencing data revealed that the two patients with repeat expansions shared the common haplotype with that previously reported in Finnish patients with C9orf72-related ALS, which suggests a founder effect. C9orf72 was thought to be a rare causative gene in Japan, but this study revealed that it may be relatively common in Wakayama Prefecture.

Genomes of the Caribbean reef-building corals Colpophyllia natans, Dendrogyra cylindrus, and Siderastrea siderea.

Corals populations worldwide are declining rapidly due to elevated ocean temperatures and other human impacts. The Caribbean harbors a high number of threatened, endangered, and critically endangered coral species compared to reefs of the larger Indo-Pacific. The reef corals of the Caribbean are also long diverged from their Pacific counterparts and may have evolved different survival strategies. Most genomic resources have been developed for Pacific coral species which may impede our ability to study the changes in genetic composition of Caribbean reef communities in response to global change. To help fill the gap in genomic resources, we used PacBio HiFi sequencing to generate the first genome assemblies for three Caribbean, reef-building corals, Colpophyllia natans, Dendrogyra cylindrus, and Siderastrea siderea. We also explore the genomic novelties that shape scleractinian genomes. Notably, we find abundant gene duplications of all classes (e.g., tandem and segmental), especially in S. siderea. This species has one of the largest genomes of any scleractinian coral (822Mb) which seems to be driven by repetitive content and gene family expansion and diversification. As the genome size of S. siderea was double the size expected of stony corals, we also evaluated the possibility of an ancient whole genome duplication using Ks tests and found no evidence of such an event in the species. By presenting these genome assemblies, we hope to develop a better understanding of coral evolution as a whole and to enable researchers to further investigate the population genetics and diversity of these three species.

A robust evaluation of TDP-43, poly GP, cellular pathology and behavior in a AAV-C9ORF72 (G4C2)66 mouse model.

The G4C2 hexanucleotide repeat expansion in C9ORF72 is the major genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). Despite considerable efforts, the development of mouse models of C9-ALS/FTD useful for therapeutic development has proven challenging due to the intricate interplay of genetic and molecular factors underlying this neurodegenerative disorder, in addition to species differences. This study presents a robust investigation of the cellular pathophysiology and behavioral outcomes in a previously described AAV mouse model of C9-ALS expressing 66 G4C2 hexanucleotide repeats. Despite displaying key molecular ALS pathological markers including RNA foci, dipeptide repeat (DPR) protein aggregation, p62 positive stress granule formation as well as mild gliosis, the AAV-(G4C2)66 mouse model in this study exhibits negligible neuronal loss, no motor deficits, and functionally unimpaired TAR DNA-binding protein-43 (TDP-43). While our findings indicate and support that this is a robust and pharmacologically tractable model for investigating the molecular mechanisms and cellular consequences of (G4C2) repeat driven DPR pathology, it is not suitable for investigating the development of disease associated neurodegeneration, TDP-43 dysfunction, gliosis, and motor performance. Our findings underscore the complexity of ALS pathogenesis involving genetic mutations and protein dysregulation and highlight the need for more comprehensive model systems that reliably replicate the multifaceted cellular and behavioral aspects of C9-ALS.

Preparation irinotecan hydrochloride loaded PEGylated liposomes using novel method supercritical fluid and condition optimized by Box-Behnken design.

A semi-synthetic camptothecin derivative known as irinotecan hydrochloride is frequently used to treat colorectal cancer, including colorectal adenocarcinoma and lung cancers involving small cells. Irinotecan has a very short half-life; therefore, continuous infusions are required to keep the drug's blood levels at therapeutic levels, which could produce cumulative toxicities. Effective delivery techniques, including liposomes, have been developed to address these shortcomings. In this study, a continuous supercritical fluid approach dubbed Expansion Supercritical Fluid into an aqueous solution, in which the pressure decreases rapidly but remains over the critical pressure, is proposed to manufacture polyethylene glycolylated (PEGylated) liposomes carrying irinotecan hydrochloride. To accomplish this, PEGylated liposomes were created using a Box-Behnken design, and the operating parameters (flow rate, temperature, and pressure drop) were optimized. Encapsulation efficiency, mean size, and prepared liposome count were 94.6%, 55 nm, and 758 under ideal circumstances. Additionally, the stability of the PEGylated liposome was investigated during 8 weeks, and also PEGylated liposome-loaded irinotecan release profile was compared to conventional liposomes and free irinotecan, and a constant drug release was seen after the first burst release from liposomes.