Next-generation integrated sequencing identifies poor prognostic factors in patients with MYD88-mutated chronic lymphocytic leukemia in Taiwan.

INTRODUCTION: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the western countries and is very rare in Asia. METHODS: Peripheral blood or bone marrow mononuclear cells obtained at initial diagnosis from 215 patients with CLL were analyzed by using next-generation sequencing to investigate the ethnic differences in genetic abnormalities. RESULTS: Whole-genome sequencing and whole-exome sequencing analyses on 30 cases showed that 9 genes, including IGLL5, MYD88, TCHH, DSCAM, AXDND1, BICRA, KMT2D, MYT1L, RBM43 were more frequently mutated in our Taiwanese cohort compared with those of the western cohorts. IGLL5, MYD88, and KMT2D genes were further analyzed by targeted sequencing in another 185 CLL patients, unravelling frequencies of 29.3%, 20.9%, and 15.0%, respectively. The most frequent positional mutation of MYD88 was V217F (26/45, 57.8%), followed by L265P (9/45, 20.0%). MYD88 mutations were significantly associated with IGLL5 mutations (P = 0.0004), mutated IGHV (P < 0.0001) and 13q deletion (P = 0.0164). CLL patients with co-occurrence of MYD88 mutations with KMT2D or/and IGLL5 mutations were associated with a significantly inferior survival compared to those with MYD88 mutation alone (not reached vs. 131.8 months, P = 0.007). In multivariate analysis, MYD88 mutation without KMT2D or IGLL5 mutations was an independently favorable predictor. CONCLUSIONS: IGLL5, MYD88, and KMT2D mutations were enriched in Taiwanese CLL, and co-occurrence of MYD88 mutations with KMT2D or/and IGLL5 mutations was associated with a poorer prognosis.

Feedback matters: EEG correlates of empathy involved in the naturalistic communication of emotions.

Empathy involves the processing of complex information related to dynamic interactions between the empathizer and target. One neural signature of empathy is the suppression of electroencephalographic mu rhythm (8-13 Hz) over the sensorimotor region. It is important to consider that few researchers have studied the effects of empathizer feedback on empathy and its underlying neural mechanism, and most previous research has lacked ecological validity due to standardized emotional stimuli and constraints on the experiment environment. Our objective in this study was to investigate the means by which empathizer feedback influences one's own empathy in naturalistic social situations. Our results revealed that empathizer feedback decreases empathic accuracy but does not affect the emotional contagion nor the emotional intensity of the empathizer. We also found that the ability to accurately infer sadness is hindered by empathizer feedback. Empathizers presented lower alpha activity in the sensorimotor cortical areas only while receiving sad narratives and not providing feedback. This study contributes to the emerging research on the influence of empathizer feedback in naturalistic social settings.

Morphological changes of cerebral gray matter in spinocerebellar ataxia type 3 using fractal dimension analysis.

Spinocerebellar ataxia type 3 (SCA3), or Machado-Joseph disease, presents as a cerebellar cognitive affective syndrome (CCAS) and represents the predominant SCA genotype in Taiwan. Beyond cerebellar involvement, SCA3 patients exhibit cerebral atrophy. While prior neurodegenerative disease studies relied on voxel-based morphometry (VBM) for brain atrophy assessment, its qualitative nature limits individual and region-specific evaluations. To address this, we employed fractal dimension (FD) analysis to quantify cortical complexity changes in SCA3 patients. We examined 50 SCA3 patients and 50 age- and sex-matched healthy controls (HC), dividing MRI cerebral gray matter (GM) into 68 auto-anatomical subregions. Using three-dimensional FD analysis, we identified GM atrophy manifestations in SCA3 patients. Results revealed lateral atrophy symptoms in the left frontal, parietal, and occipital lobes, and fewer symptoms in the right hemisphere's parietal and occipital lobes. Focal areas of atrophy included regions previously identified in SCA3 studies, alongside additional regions with decreased FD values. Bilateral postcentral gyrus and inferior parietal gyrus exhibited pronounced atrophy, correlating with Scale for the Assessment and Rating of Ataxia (SARA) scores and disease duration. Notably, the most notable focal areas were the bilateral postcentral gyrus and the left superior temporal gyrus, serving as imaging biomarkers for SCA3. Our study enhances understanding of regional brain atrophy in SCA3, corroborating known clinical features while offering new insights into disease progression.

Analysis of the difference between Alzheimer's disease, mild cognitive impairment and normal people by using fractal dimensions and small-world network.

This research examined the distinctions in brain network characteristics among individuals with Alzheimer's disease (AD), mild cognitive impairment (MCI), and a control group. Magnetic resonance imaging (MRI) and mini-mental state examination (MMSE) data were retrieved from the Alzheimer's Disease Neuroimaging Initiative (ANDI) database, comprising 40 subjects in each group. Correlation maps for evaluating brain network connectivity were generated using fractal dimension (FD) analysis, a method capable of quantifying morphological changes in cortical and cerebral regions. Employing graph theory, each parcellated brain region was represented as a node, and edges between nodes were utilized to compute small-world network properties for each group. In the comparison between control and AD demonstrated the significantly lower FD values (P<0.05) in temporal lobe, motor cortex, part of occipital and parietal, hippocampus, amygdala, and entorhinal cortex, which present the atrophy. Similarly, comparing control group to MCIs, regions closely associated with memory, such as the hippocampus, showed significantly lower FD values. Furthermore, both AD and MCI groups displayed diminished connectivity and decreased network efficiency. In conclusion, fractal dimension (FD) analysis illustrate the progression of structural declination from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Additionally, structural small-world network analysis presents itself as a potential method for assessing network efficiency and the progression of AD. Moving forward, further clinical assessments are warranted to validate the findings observed in this study.

Features and allele frequency of JAK2 Exon 12-mutated polycythemia vera in comparison with JAK2V617F-mutated disease.

BACKGROUND AND AIM: JAK2 exon 12 mutation status and the clinical characteristics of patients with polycythemia vera (PV) in Asia remain to be defined. METHOD: We analyzed the clinical, molecular, and genetic features and outcomes of patients with PV harboring exon 12 mutation and compared them with the JAK2V617F-mutated patients in Taiwan. JAK2V617F with allele burden was measured by pyrosequencing and/or RT/qPCR. The allele frequency of exon 12 mutation was analyzed by next-generation sequencing in JAK2V617F-negative patients. RESULTS: A total of 532 patients diagnosed with PV were enrolled. The JAK2V617F mutation was present in 94.9% and exon 12 mutations in 5.1%. At diagnosis, patients with exon 12 mutation had higher hemoglobin (p = 0.012), and hematocrit levels (p = 0.003), and lower platelet (p < 0.001), and leukocyte counts (p < 0.001) compared to patients with JAK2V617F mutations. Patients harboring the JAK2V617F mutation had a higher incidence of high allele burden (p < 0.001), disease risk (p= 0.014), and bleeding events (p= 0.013) compared to patients with PV with exon 12 mutations. These patients showed similar outcomes (overall survival, leukemia-free, myelofibrosis and thrombosis-free survival) to those with JAK2V617F mutations. An allele frequency ≥ 52.5% conferred an inferior overall survival compared to ≤ 52.5% in both exon 12-mutated (p = 0.029) and JAK2V617F patients with PV (p = 0.038). CONCLUSION: Taiwanese patients with PV showed differences in blood count, risk group, and bleeding events between exon 12 and JAK2V617F patients. Higher mutant allele burden had a negative impact on overall survival for both mutation types.

Tet1-mediated activation of the Ampk signaling by Trpv1 DNA hydroxymethylation exerts neuroprotective effects in a rat model of Parkinson's disease.

Epigenetic regulation plays a role in Parkinson's disease (PD), and ten-eleven translocation methylcytosine dioxygenase 1 (TET1) catalyzes the first step in DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine. We investigated whether TET1 binds to the promoter of the transient receptor potential cation channel subfamily V member 1 (TRPV1) and regulates its expression, thereby controlling oxidative stress in PD. TRPV1 was identified as an oxidative stress-associated gene in the GSE20186 dataset including substantia nigra from 14 patients with PD and 14 healthy controls and the Genecards database. Lentiviral vectors were used to manipulate Trpv1 expression in rats, followed by 6-hydroxydopamine hydrochloride (6-OHDA) injection for modeling. Behavioral tests, immunofluorescence, Nissl staining, western blot assays, DHE fluorescent probe, biochemical analysis, and ELISA were conducted to assess oxidative stress and neurotoxicity. Trpv1 expression was significantly reduced in the brain tissues of 6-OHDA-treated Parkinsonian rats. Trpv1 alleviated behavioral dysfunction, oxidative stress, and dopamine neuron loss in rats. TET1 mediated TRPV1 hydroxymethylation to promote its expression, and Trpv1 inhibition reversed the mitigating effect of Tet1 on oxidative stress and behavioral dysfunction in PD. TRPV1 activated the AMPK signaling by promoting AMPK phosphorylation to alleviate neurotoxicity and oxidative stress in SH-SY5Y cells. Tet1-mediated Trpv1 hydroxymethylation modification promotes the Ampk signaling activation, thereby eliciting neuroprotection in 6-OHDA-treated Parkinsonian rats. These findings provide experimental evidence that targeting the TET1/TRPV1 axis may be neuroprotective for PD by acting on the AMPK signaling.

Remote Control: Electrochemically Driving EGaIn@Fe Liquid Metal for Application of Soft Robotics.

This study introduces magnetized EGaIn@Fe, an innovative material synthesized by incorporating iron powder into the eutectic gallium-indium alloy (EGaIn). Unlike traditional methods requiring electrolyte environments for electrical control, EGaIn@Fe can be manipulated using external magnetic fields, expanding control from 2D to 3D spaces. The material exhibits both active and passive splitting capabilities under magnetic and electrical control, demonstrating exceptional deformability, precision, and flexibility. EGaIn@Fe shows significant promise in applications such as microfluidic channels, circuit repair, and soft robotics. Specifically, 5 wt.% EGaIn@Fe is optimal for microfluidic tasks and circuit repairs in confined spaces, while higher concentrations (10 and 15 wt.%) enhance 3D control and reduce material usage. Additionally, 20 wt.% EGaIn@Fe displays octopus-like movements for navigating impassable channels. EGaIn@Fe can enhance fluid manipulation in microfluidics, bridge gaps in circuit repairs, and enable flexible actuators in soft robotics, driving advancements in adaptive materials and technologies.

Non-invasive glucose extraction by a single polarization rotator system in patients with diabetes.

This study utilizes a Mueller matrix-based system to extract accurate glucose levels from human fingertips, addressing challenges in skin complexity. Integration of domain knowledge and data science aims to enhance prediction accuracy using a Random Forest model. The primary goal is to improve glucose level predictions by selecting effective features based on the Pearson product-moment correlation coefficient (PPMCC). The interpolation compensates for delayed glucose concentration. This study integrates domain knowledge and data science, combining a Mueller matrix-based system and a random forest model. It is noted that 16 effective features were identified from 27 test points collected from a healthy volunteer in the laboratory. These features were divided into training and prediction sets in a ratio of 8:2. As a result, the regression coefficient, R2, was 0.8907 and the mean absolute relative difference (MARD) was 6.8%, respectively. This significantly improves prediction accuracy, demonstrating the model's robustness and reliability in accurately forecasting outcomes based on the identified features. In addition, in the Institutional Review Board (IRB) tests at NCKU's hospital, all data passed the same preprocessing and model. The measurement results from an individual diabetic patient demonstrate high accuracy for blood glucose concentrations below 150 mg/dL, with acceptable deviation at higher levels and no severe error zones. Over a three-month period, data from the participating diabetic patient showed a MARD of 4.44% with the R2 of 0.836, and the other patient recorded a MARD of 7.79% with the R2 of 0.855. The study shows the proposed approach accurately extracts glucose levels. Integrating domain knowledge, data science, and effective strategies significantly improves prediction accuracy.

Recent progress in one-pot enzymatic synthesis and regeneration of high-value cofactors.

One-pot enzymatic synthesis is flourishing in synthetic chemistry, heralding a sustainable and green era. Recent advancements enable the creation of complex enzymatic prosthetic groups and regeneration of enzymatic cofactors such as S-adenosylmethionine. The next frontier is to develop the effective and innovative cofactors for essential micronutrients, metabolic modulators, and biomedicines.

Vitamin B12 as a source of variability in isotope effects for chloroform biotransformation by Dehalobacter.

Carbon and chlorine isotope effects for biotransformation of chloroform by different microbes show significant variability. Reductive dehalogenases (RDase) enzymes contain different cobamides, affecting substrate preferences, growth yields, and dechlorination rates and extent. We investigate the role of cobamide type on carbon and chlorine isotopic signals observed during reductive dechlorination of chloroform by the RDase CfrA. Microcosm experiments with two subcultures of a Dehalobacter-containing culture expressing CfrA-one with exogenous cobamide (Vitamin B12, B12+) and one without (to drive native cobamide production)-resulted in a markedly smaller carbon isotope enrichment factor (εC, bulk) for B12- (-22.1 ± 1.9‰) compared to B12+ (-26.8 ± 3.2‰). Both cultures exhibited significant chlorine isotope fractionation, and although a lower εCl, bulk was observed for B12- (-6.17 ± 0.72‰) compared to B12+ (-6.86 ± 0.77‰) cultures, these values are not statistically different. Importantly, dual-isotope plots produced identical slopes of ΛCl/C (ΛCl/C, B12+ = 3.41 ± 0.15, ΛCl/C, B12- = 3.39 ± 0.15), suggesting the same reaction mechanism is involved in both experiments, independent of the lower cobamide bases. A nonisotopically fractionating masking effect may explain the smaller fractionations observed for the B12- containing culture.

High-Performance Semiconducting Carbon Nanotube Transistors Using Naphthalene Diimide-Based Polymers with Biaxially Extended Conjugated Side Chains.

Polymer-wrapped single-walled carbon nanotubes (SWNTs) are a potential method for obtaining high-purity semiconducting (sc) SWNT solutions. Conjugated polymers (CPs) can selectively sort sc-SWNTs with different chiralities, and the structure of the polymer side chains influences this sorting capability. While extensive research has been conducted on modifying the physical, optical, and electrical properties of CPs through side-chain modifications, the impact of these modifications on the sorting efficiency of sc-SWNTs remains underexplored. This study investigates the introduction of various conjugated side chains into naphthalene diimide-based CPs to create a biaxially extended conjugation pattern. The CP with a branched conjugated side chain (P3) exhibits reduced aggregation, resulting in improved wrapping ability and the formation of larger bundles of high-purity sc-SWNTs. Grazing incidence X-ray diffraction analysis confirms that the potential interaction between sc-SWNTs and CPs occurs through π-π stacking. The field-effect transistor device fabricated with P3/sc-SWNTs demonstrates exceptional performance, with a significantly enhanced hole mobility of 4.72 cm2 V-1 s-1 and high endurance/bias stability. These findings suggest that biaxially extended side-chain modification is a promising strategy for improving the sorting efficiency and performance of sc-SWNTs by using CPs. This achievement can facilitate the development of more efficient and stable electronic devices.

Manufacturing CD20/CD19-targeted iCasp9 regulatable CAR-TSCM cells using a Quantum pBac-based CAR-T engineering system.

CD19-targeted chimeric antigen receptor (CAR) T cell therapies have driven a paradigm shift in the treatment of relapsed/refractory B-cell malignancies. However, >50% of CD19-CAR-T-treated patients experience progressive disease mainly due to antigen escape and low persistence. Clinical prognosis is heavily influenced by CAR-T cell function and systemic cytokine toxicities. Furthermore, it remains a challenge to efficiently, cost-effectively, and consistently manufacture clinically relevant numbers of virally engineered CAR-T cells. Using a highly efficient piggyBac transposon-based vector, Quantum pBac™ (qPB), we developed a virus-free cell-engineering system for development and production of multiplex CAR-T therapies. Here, we demonstrate in vitro and in vivo that consistent, robust and functional CD20/CD19 dual-targeted CAR-T stem cell memory (CAR-TSCM) cells can be efficiently produced for clinical application using qPB™. In particular, we showed that qPB™-manufactured CAR-T cells from cancer patients expanded efficiently, rapidly eradicated tumors, and can be safely controlled via an iCasp9 suicide gene-inducing drug. Therefore, the simplicity of manufacturing multiplex CAR-T cells using the qPB™ system has the potential to improve efficacy and broaden the accessibility of CAR-T therapies.

Efficacy of Aromatherapy Against Behavioral and Psychological Disturbances in People With Dementia: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Behavioral and psychological symptoms of dementia (BPSD) are common in people with dementia. Aromatherapy may reduce the frequency and severity of BPSD. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of aromatherapy in relieving BPSD and improving functional ability in people with dementia. DESIGN: Systematic review and meta-analysis. SETTING AND PARTICIPANTS: Patients with dementia receiving aromatherapy. METHODS: A literature search was conducted using PubMed, Embase, and Cochrane Library for RCTs published before March 2024 comparing aromatherapy with control treatments in patients with dementia. RESULTS: There were 15 trials involving 821 patients. Overall, significant reduction in BPSD was observed after 1 month of aromatherapy treatment. Among 15 trials, 9 reported the Cohen-Mansfield Agitation Inventory (CMAI) score, and 7 evaluated the Neuropsychiatric Inventory (NPI) score. The meta-analysis showed significant improvement in CMAI score [weighted mean difference (WMD) -6.31, 95% CI -9.52 to -3.11] and NPI score (WMD -8.07, 95% CI -13.53 to -2.61) in patients receiving 3 to 4 weeks of aromatherapy compared with the control group. Four of the 15 trials reported improvement in depressive mood and 3 trials reported no significant improvement in functional ability. CONCLUSIONS AND IMPLICATIONS: In conclusion, aromatherapy is a safe and viable nonpharmacologic treatment to improve BPSD in people with dementia and its combination with massage showed higher efficacy.

Prior Bariatric Surgery Predicts Lower Life-Threatening Morbidity in Patients Admitted for Acute Allergic Reaction and Anaphylaxis: a Propensity Score-Matched Analysis of the U.S. Nationwide Inpatient Sample, 2005-2018.

PURPOSE: Acute allergic reactions may occur in susceptible individuals following exposure to various allergens. Obesity is linked to allergic reactions, and weight loss from bariatric surgery may attenuate the severity of certain conditions such as airway hyperresponsiveness in asthma. This retrospective observational study investigates associations between prior bariatric surgery and lower risk for life-threatening conditions in patients hospitalized with acute allergic reactions and anaphylaxis. MATERIALS AND METHODS: Adults ≥ 18 years old diagnosed with morbid obesity and admitted to US hospitals with acute allergic reactions/anaphylaxis were included. All data were extracted from the US Nationwide Inpatient Sample (NIS) database 2005-2018. Patients without information on in-hospital mortality, discharge destination, hospital costs, and length of stay (LOS) were excluded. Patients were divided into two groups based on prior bariatric surgery or not. All diagnoses were verified through ICD-9 and ICD-10 codes. Between-group differences and associations between variables were evaluated using logistic regression analysis. RESULTS: After matching, patients with prior bariatric surgery had significantly lower proportions of any life-threatening morbidity (37.2% vs. 47.4%), respiratory distress or failure (11.2% vs. 17.0%), pneumonia or severe infection (7.4% vs. 10.2%), sepsis/septic shock (15.2% vs. 20.9%), intubation and mechanical ventilation (11.2% vs. 14.6%), prolonged LOS (10.3% vs. 20.6%) and unfavorable discharge (6.9% vs. 12.5%) than those without prior bariatric surgery. CONCLUSION: Prior bariatric surgery predicts a lower risk of life-threatening morbidity and prolonged LOS among adults hospitalized for acute allergic reaction and anaphylaxis. Future prospective studies are warranted to confirm the present findings and reveal underlying mechanisms.

Reactions Driven by Primitive Nonbiological Polyesters.

ConspectusAll life on Earth is composed of cells, which are built from and run by biological reactions and structures. These reactions and structures are generally the result of action by cellular biomolecules, which are indispensable for the function and survival of all living organisms. Specifically, biological catalysis, namely by protein enzymes, but also by other biomolecules including nucleic acids, is an essential component of life. How the biomolecules themselves that perform biological catalysis came to exist in the first place is a major unanswered question that plagues researchers to this day, which is generally the focus of the origins of life (OoL) research field. Based on current knowledge, it is generally postulated that early Earth was full of a myriad of different chemicals, and that these chemicals reacted in specific ways that led to the emergence of biochemistry, cells, and later, life. In particular, a significant part of OoL research focuses on the synthesis, evolution, and function of biomolecules potentially present under early Earth conditions, as a way to understand their eventual transition into modern life. However, this narrative overlooks possibilities that other molecules contributed to the OoL, as while biomolecules that led to life were certainly present on early Earth, at the same time, other molecules that may not have strict, direct biological lineage were also widely and abundantly present. For example, hydroxy acids, although playing a role in metabolism or as parts of certain biological structures, are not generally considered to be as essential to modern biology as amino acids (a chemically similar monomer), and thus research in the OoL field tends to perhaps focus more on amino acids than hydroxy acids. However, their likely abundance on early Earth coupled with their ability to spontaneously condense into polymers (i.e., polyesters) make hydroxy acids, and their subsequent products, functions, and reactions, a reasonable target of investigation for prebiotic chemists. Whether "non-biological" hydroxy acids or polyesters can contribute to the emergence of life on early Earth is an inquiry that deserves attention within the OoL community, as this knowledge can also contribute to our understanding of the plausibility of extraterrestrial life that does not exactly use the biochemical set found in terrestrial organisms. While some demonstrations have been made with respect to compartment assembly, compartmentalization, and growth of primitive polyester-based systems, whether these "non-biological" polymers can contribute any catalytic function and/or drive primitive reactions is still an important step toward the development of early life. Here, we review research both from the OoL field as well as from industry and applied sciences regarding potential catalysis or reaction driven by "non-biological" polyesters in various forms: as linear polymers, as hyperbranched polyesters, and as membraneless microdroplets.

Specific and efficient knockdown of intracellular miRNA using partially neutralized phosphate-methylated DNA oligonucleic acid-loaded mesoporous silica nanoparticles.

Antisense oligonucleotides (ASOs) are molecules used to regulate RNA expression by targeting specific RNA sequences. One specific type of ASO, known as neutralized DNA (nDNA), contains site-specific methyl phosphotriester (MPTE) linkages on the phosphate backbone, changing the negatively charged DNA phosphodiester into a neutralized MPTE with designed locations. While nDNA has previously been employed as a sensitive nucleotide sequencing probe for the PCR, the potential of nDNA in intracellular RNA regulation and gene therapy remains underexplored. Our study aims to evaluate the regulatory capacity of nDNA as an ASO probe in cellular gene expression. We demonstrated that by tuning MPTE locations, partially and intermediately methylated nDNA loaded onto mesoporous silica nanoparticles (MSNs) can effectively knock down the intracellular miRNA, subsequently resulting in downstream mRNA regulation in colorectal cancer cell HCT116. Additionally, the nDNA ASO-loaded MSNs exhibit superior efficacy in reducing miR-21 levels over 72 hours compared to the efficacy of canonical DNA ASO-loaded MSNs. The reduction in the miR-21 level subsequently resulted in the enhanced mRNA levels of tumour-suppressing genes PTEN and PDCD4. Our findings underscore the potential of nDNA in gene therapies, especially in cancer treatment via a fine-tuned methylation location.

The lower incidence of endometrial cancer after sodium-glucose cotransporter 2 inhibitors administration in type 2 diabetes mellitus population: a nationwide cohort study.

The Sodium-glucose co-transporter 2 (SGLT2) inhibitor is an anti-glycemic agent that frequently used in type 2 diabetes mellitus (T2DM) with antioxidant effects. Endometrial cancer (EC) is a common gynecological malignancy that correlates with oxidative stress. The aim in the present study is to survey the potential association between the SGLT2 inhibitor administration and the incidence of EC by the application of the National Health Insurance Research Database (NHIRD) of Taiwan. A retrospective cohort study was directed and the T2DM participants were divided into the SGLT2 inhibitors users and non-SGLT2 inhibitors users. After matching, a total of 163,668 and 327,336 participants were included into the SGLT2 inhibitors and control groups, respectively. The primary outcome is regarded as the development of EC according to the diagnostic, image, and procedure codes. Cox proportional hazard regression was employed to generate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of EC between the two groups. There were 422 and 876 EC events observed in the SGLT2 inhibitors and control groups, respectively. The SGLT2 inhibitors group demonstrated a significantly lower incidence of EC formation compared to the control groups (aHR: 0.87, 95% CI: 0.76-0.99). In the subgroup analysis, the correlation between SGLT2 inhibitor administration and lower rate of EC existed in the T2DM individuals with aged under 60. Moreover, the association between SGLT2 inhibitor administration and lower EC incidence only presented in the T2DM population with SGLT2 inhibitor administration under one year (aHR: 0.58, 95% CI: 0.45-0.73). In conclusion, the administration of SGLT2 inhibitors correlates to lower incidence of EC in T2DM population.

Impact of CD44 genetic variants on clinicopathological characteristics of uterine cervical cancer patients.

CD44 genetic variants have been found to be related to various cancers. However, to date, no study has demonstrated the involvement of CD44 polymorphisms in uterine cervical cancer in Taiwanese women. Therefore, we conducted a retrospective study, consecutively recruiting 113 patients with invasive cancer, 92 patients with high-grade cervical intraepithelial neoplasias, and 302 control women to assess the relationships among CD44 polymorphisms, cervical carcinogenesis, and patient survival. Real-time polymerase chain reaction was used to determine the genotypic distributions of six polymorphisms: rs1425802, rs187115, rs713330, rs11821102, rs10836347, and rs13347. The results revealed that women with the mutant homozygous genotype CC exhibited a higher risk of invasive cancer compared to those with the wild homozygous genotype TT [p=0.035; hazard ratio (HR)=10.29, 95% confidence interval (95% CI)=1.18-89.40] and TT/TC [p=0.032; HR=10.66, 95% CI=1.23-92.11] in the CD44 polymorphism rs713330. No significant association was found between CD44 genetic variants and clinicopathological parameters. Among the clinicopathological parameters, only positive pelvic lymph node metastasis (p=0.002; HR=8.57, 95% CI=2.14-34.38) and the AG/GG genotype compared to AA (p=0.014; HR=3.30, 95% CI=1.28-8.49) in CD44 polymorphism rs187115 predicted a higher risk of poor five-year survival, according to multivariate analysis. In conclusion, an important and novel finding revealed that Taiwanese women with the AG/GG genotype in CD44 polymorphism rs187115 exhibited a higher risk of poor five-year survival.

Programmable DNA Nanomachine Integrated with Electrochemically Controlled Atom Transfer Radical Polymerization for Antibody Detection at Picomolar Level.

The quantitative detection of antibodies is crucial for the diagnosis of infectious and autoimmune diseases, while the traditional methods experience high background signal noise and restricted signal gain. In this work, we have developed a highly efficient electrochemical biosensor by constructing a programmable DNA nanomachine integrated with electrochemically controlled atom transfer radical polymerization (eATRP). The sensor works by binding the target antidigoxin antibody (anti-Dig) to the epitope of the recognization probe, which then initiates the cascaded strand displacement reaction on a magnetic bead, leading to the capture of cupric oxide (CuO) nanoparticles through magnetic separation. After CuO was dissolved, the eATRP initiators were attached to the electrode based on the CuΙ-catalyzed azide-alkyne cycloaddition. The subsequent eATRP reaction results in the formation of long electroactive polymers (poly-FcMMA), producing an amplified current response for sensitive detection of anti-Dig. This method achieved a detection limit at clinically relevant picomolar concentration in human serum, offering a sensitive, convenient, and cost-effective tool for detecting various biomarkers in a wide range of applications.

A single-center, assessor-blinded, randomized controlled clinical trial to test the safety and efficacy of a novel brain-computer interface controlled functional electrical stimulation (BCI-FES) intervention for gait rehabilitation in the chronic stroke population.

BACKGROUND: In the United States, there are over seven million stroke survivors, with many facing gait impairments due to foot drop. This restricts their community ambulation and hinders functional independence, leading to several long-term health complications. Despite the best available physical therapy, gait function is incompletely recovered, and this occurs mainly during the acute phase post-stroke. Therapeutic options are limited currently. Novel therapies based on neurobiological principles have the potential to lead to long-term functional improvements. The Brain-Computer Interface (BCI) controlled Functional Electrical Stimulation (FES) system is one such strategy. It is based on Hebbian principles and has shown promise in early feasibility studies. The current study describes the BCI-FES clinical trial, which examines the safety and efficacy of this system, compared to conventional physical therapy (PT), to improve gait velocity for those with chronic gait impairment post-stroke. The trial also aims to find other secondary factors that may impact or accompany these improvements and establish the potential of Hebbian-based rehabilitation therapies. METHODS: This Phase II clinical trial is a two-arm, randomized, controlled, longitudinal study with 66 stroke participants in the chronic (> 6 months) stage of gait impairment. The participants undergo either BCI-FES paired with PT or dose-matched PT sessions (three times weekly for four weeks). The primary outcome is gait velocity (10-meter walk test), and secondary outcomes include gait endurance, range of motion, strength, sensation, quality of life, and neurophysiological biomarkers. These measures are acquired longitudinally. DISCUSSION: BCI-FES holds promise for gait velocity improvements in stroke patients. This clinical trial will evaluate the safety and efficacy of BCI-FES therapy when compared to dose-matched conventional therapy. The success of this trial will inform the potential utility of a Phase III efficacy trial. TRIAL REGISTRATION: The trial was registered as "BCI-FES Therapy for Stroke Rehabilitation" on February 19, 2020, at clinicaltrials.gov with the identifier NCT04279067.