Towards single electron transistor-based photon detection with microplasma-enabled graphene quantum dots.

Single-electron transistors (SETs) represent a new generation of electronic devices with high charge sensitivity, high switching speed, and low power consumption. Here a simple and controlled fabrication of graphene quantum dot (GQD)-based SETs for photon detectors has been demonstrated. The plasma-synthesized GQDs exhibit stable photoluminescence and are successfully used as the Coulomb islands between heteroepitaxial spherical-gold/platinum (HS-Au/Pt) nanogap electrodes. The as-fabricated GQD-SETs enable photon detection with 410 nm excitation owing to the ability of GQDs to generate photoluminescence emission.

Adapting Strategy Training for Adults With Acquired Brain Injury: A Feasibility Study in a Chinese Population.

IMPORTANCE: Before introducing strategy training into a cross-cultural (Chinese) context, it is necessary to evaluate its feasibility. OBJECTIVE: To examine the feasibility of applying strategy training to improve participation outcomes of rehabilitation patients in Taiwan and evaluate the potential intervention effects. DESIGN: A single-group, repeated-measures study. SETTING: Rehabilitation outpatient settings. PARTICIPANTS: A convenience sample of adults (N = 20) with a primary diagnosis of acquired brain injury (ABI) and with cognitive impairment received the intervention and were assessed before and after it. INTERVENTION: The participation-focused strategy training intervention, a modified version of the strategy training intervention, was provided to participants in 1-2 sessions weekly for a total of 10-20 intervention sessions. OUTCOMES AND MEASURES: Feasibility indicators, Participation Measure-3 Domains, 4 Dimensions (PM-3D4D), and Canadian Occupational Performance Measure (COPM). RESULTS: Eighteen participants completed 100% of the scheduled intervention sessions. Participants had very good engagement in the intervention sessions with sufficient comprehension. Participants reported moderate to high satisfaction. Positive score changes were observed for the PM-3D4D (d = 0.46-1.25) and COPM scales (d = 1.82 and 2.12). CONCLUSIONS AND RELEVANCE: This study demonstrated the feasibility of delivering participation-focused strategy training in Taiwan to people with cognitive impairment after ABI. The preliminary evidence also showed that participants who received the strategy training intervention had positive changes in participation outcomes and in performance of their self-identified goals. On the basis of this study's findings, a larger clinical trial is warranted to evaluate the efficacy of the strategy training intervention. WHAT THIS ARTICLE ADDS: Participation-focused strategy training is feasible and acceptable for Taiwanese community-dwelling adults with cognitive impairment after ABI. However, because strategy training is quite different from traditional rehabilitation delivered in Taiwan, additional instructions and discussion among the therapist, client, and caregiver may be needed before the intervention is provided.

DNA damage induces targeted, genome-wide variation of poly(A) sites in budding yeast.

Systemic response to DNA damage and other stresses is a complex process that includes changes in the regulation and activity of nearly all stages of gene expression. One gene regulatory mechanism used by eukaryotes is selection among alternative transcript isoforms that differ in polyadenylation [poly(A)] sites, resulting in changes either to the coding sequence or to portions of the 3' UTR that govern translation, stability, and localization. To determine the extent to which this means of regulation is used in response to DNA damage, we conducted a global analysis of poly(A) site usage in Saccharomyces cerevisiae after exposure to the UV mimetic, 4-nitroquinoline 1-oxide (4NQO). Two thousand thirty-one genes were found to have significant variation in poly(A) site distributions following 4NQO treatment, with a strong bias toward loss of short transcripts, including many with poly(A) sites located within the protein coding sequence (CDS). We further explored one possible mechanism that could contribute to the widespread differences in mRNA isoforms. The change in poly(A) site profile was associated with an inhibition of cleavage and polyadenylation in cell extract and a decrease in the levels of several key subunits in the mRNA 3'-end processing complex. Sequence analysis identified differences in the cis-acting elements that flank putatively suppressed and enhanced poly(A) sites, suggesting a mechanism that could discriminate between variable and constitutive poly(A) sites. Our analysis indicates that variation in mRNA length is an important part of the regulatory response to DNA damage.

Performance of ChatGPT on Stage 1 of the Taiwanese medical licensing exam.

Introduction: Since its release by OpenAI in November 2022, numerous studies have subjected ChatGPT to various tests to evaluate its performance in medical exams. The objective of this study is to evaluate ChatGPT's accuracy and logical reasoning across all 10 subjects featured in Stage 1 of Senior Professional and Technical Examinations for Medical Doctors (SPTEMD) in Taiwan, with questions that encompass both Chinese and English. Methods: In this study, we tested ChatGPT-4 to complete SPTEMD Stage 1. The model was presented with multiple-choice questions extracted from three separate tests conducted in February 2022, July 2022, and February 2023. These questions encompass 10 subjects, namely biochemistry and molecular biology, anatomy, embryology and developmental biology, histology, physiology, microbiology and immunology, parasitology, pharmacology, pathology, and public health. Subsequently, we analyzed the model's accuracy for each subject. Result: In all three tests, ChatGPT achieved scores surpassing the 60% passing threshold, resulting in an overall average score of 87.8%. Notably, its best performance was in biochemistry, where it garnered an average score of 93.8%. Conversely, the performance of the generative pre-trained transformer (GPT)-4 assistant on anatomy, parasitology, and embryology was not as good. In addition, its scores were highly variable in embryology and parasitology. Conclusion: ChatGPT has the potential to facilitate not only exam preparation but also improve the accessibility of medical education and support continuous education for medical professionals. In conclusion, this study has demonstrated ChatGPT's potential competence across various subjects within the SPTEMD Stage 1 and suggests that it could be a helpful tool for learning and exam preparation for medical students and professionals.

Assessing AI efficacy in medical knowledge tests: A study using Taiwan's internal medicine exam questions from 2020 to 2023.

Background: The aim of this study is to evaluate the ability of generative artificial intelligence (AI) models to handle specialized medical knowledge and problem-solving in a formal examination context. Methods: This research utilized internal medicine exam questions provided by the Taiwan Internal Medicine Society from 2020 to 2023, testing three AI models: GPT-4o, Claude_3.5 Sonnet, and Gemini Advanced models. Rejected queries for Gemini Advanced were translated into French for resubmission. Performance was assessed using IBM SPSS Statistics 26, with accuracy percentages calculated and statistical analyses such as Pearson correlation and analysis of variance (ANOVA) performed to gauge AI efficacy. Results: GPT-4o's top annual score was 86.25 in 2022, with an average of 81.97. Claude_3.5 Sonnet reached a peak score of 88.13 in 2021 and 2022, averaging 84.85, while Gemini Advanced lagged with an average score of 69.84. In specific specialties, Claude_3.5 Sonnet scored highest in Psychiatry (100%) and Nephrology (97.26%), with GPT-4o performing similarly well in Hematology & oncology (97.10%) and Nephrology (94.52%). Gemini's best scores were in Psychiatry (86.96%) and Hematology & Oncology (82.76%). Gemini Advanced models struggled with Neurology, scoring below 60%. Additionally, all models performed better on text-based questions than on image-based ones, without significant differences. Claude 3 Opus scored highest on COVID-19-related questions at 89.29%, followed by GPT-4o at 75.00% and Gemini Advanced at 67.86%. Conclusions: AI models showed varied proficiency across medical specialties and question types. GPT-4o demonstrated higher image-based correction rates. Claude_3.5 Sonnet generally and consistently outperformed others, highlighting significant potential for AI in assisting medical education.

Using a 3D-Printed Hand Orthosis to Improve Three-Jaw Chuck Hand Function in Individuals With Cervical Spinal Cord Injury: A Feasibility Study.

Individuals with cervical spinal cord injury (C-SCI) often use a tenodesis grip to compensate for their hand function deficits. Although clinical evidence confirms that assistive devices can help achieve hand function improvements, the currently available devices have some limitations in terms of their price and accessibility and the difference in the user's muscle strength. Therefore, in this study, we developed a 3D-printed wrist-driven orthosis to improve the gripping effect and tested the feasibility of this device by assessing its functional outcomes. A total of eight participants with hand function impairment due to a C-SCI were enrolled, and a wrist-driven orthosis with a triple four-bar linkage was designed. The hand function of the participants was assessed before and after they wore the orthosis, and the outcomes were assessed using a pinch force test, a dexterity test (Box and block test, BBT), and a Spinal Cord Independence Measure Version III questionnaire. In the results, before the participants wore the device, the pinch force was 0.26 lb. However, after they wore the device, it increased by 1.45 lb. The hand dexterity also increased by 37%. After 2 weeks, the pinch force increased by 1.6 lb and the hand dexterity increased by 78%. However, no significant difference was observed in the self-care ability. The results showed that this 3D-printed device with a triple four-bar linkage for individual with C-SCI improved pinch strength and hand dexterity in these patients, but did not improve their self-care ability. It may help patient in the early stages of C-SCI to learn and use the tenodesis grip easily. However, the usability of the device in daily life needs further research.

Machine Learning and Radiomics of Bone Scintigraphy: Their Role in Predicting Recurrence of Localized or Locally Advanced Prostate Cancer.

BACKGROUND: Machine-learning (ML) and radiomics features have been utilized for survival outcome analysis in various cancers. This study aims to investigate the application of ML based on patients' clinical features and radiomics features derived from bone scintigraphy (BS) and to evaluate recurrence-free survival in local or locally advanced prostate cancer (PCa) patients after the initial treatment. METHODS: A total of 354 patients who met the eligibility criteria were analyzed and used to train the model. Clinical information and radiomics features of BS were obtained. Survival-related clinical features and radiomics features were included in the ML model training. Using the pyradiomics software, 128 radiomics features from each BS image's region of interest, validated by experts, were extracted. Four textural matrices were also calculated: GLCM, NGLDM, GLRLM, and GLSZM. Five training models (Logistic Regression, Naive Bayes, Random Forest, Support Vector Classification, and XGBoost) were applied using K-fold cross-validation. Recurrence was defined as either a rise in PSA levels, radiographic progression, or death. To assess the classifier's effectiveness, the ROC curve area and confusion matrix were employed. RESULTS: Of the 354 patients, 101 patients were categorized into the recurrence group with more advanced disease status compared to the non-recurrence group. Key clinical features including tumor stage, radical prostatectomy, initial PSA, Gleason Score primary pattern, and radiotherapy were used for model training. Random Forest (RF) was the best-performing model, with a sensitivity of 0.81, specificity of 0.87, and accuracy of 0.85. The ROC curve analysis showed that predictions from RF outperformed predictions from other ML models with a final AUC of 0.94 and a p-value of <0.001. The other models had accuracy ranges from 0.52 to 0.78 and AUC ranges from 0.67 to 0.84. CONCLUSIONS: The study showed that ML based on clinical features and radiomics features of BS improves the prediction of PCa recurrence after initial treatment. These findings highlight the added value of ML techniques for risk classification in PCa based on clinical features and radiomics features of BS.

Direct and specific binding of the UL16 tegument protein of herpes simplex virus to the cytoplasmic tail of glycoprotein E.

The UL16 tegument protein of herpes simplex virus (HSV) is conserved throughout all of the herpesvirus families. Previous studies have shown that the binding of HSV to heparan sulfate molecules on the host cell triggers the release of UL16 from the capsid, but the mechanism by which the signal is sent from the virion surface into the tegument is unknown. Here, we report that a glutathione S-transferase chimera bearing the cytoplasmic tail of viral glycoprotein E (gE) is capable of binding to UL16 in lysates of eukaryotic cells or purified from bacteria. Moreover, mass spectrometry studies of native-UL16 complexes purified from infected cells also revealed the presence of gE. Proof that UL16-gE can interact within cells required the fortuitous discovery of a mutant possessing only the first 155 residues of UL16. Confocal microscopy of cotransfected cells revealed that this mutant colocalized with gE in the cytoplasm, whereas it was found throughout the cytoplasm and nucleus when expressed alone. In contrast, the full-length UL16 molecule was very poorly capable of finding gE. Moreover, membrane flotation assays showed that UL16(1-155) was able to float to the top of sucrose step gradients when coexpressed with gE, whereas full-length UL16 was not. Thus, the discovery of the UL16(1-155) mutant confirmed the specific in vitro interaction with gE and provides evidence that a binding domain at the N terminus of UL16 may be controlled by a regulatory domain within the C terminus. These findings suggest the possibility that the UL16-gE interaction may play roles in the tegument signaling mechanism, virus budding, and the gE-mediated mechanism of cell-to-cell spread.

Plasma Nanoengineering of Bioresource-Derived Graphene Quantum Dots as Ultrasensitive Environmental Nanoprobes.

Environmental contamination and energy shortage are among the most critical global issues that require urgent solutions to ensure sustainable ecological balance. Rapid and ultrasensitive monitoring of water quality against pollutant contaminations using a low-cost, easy-to-operate, and environmentally friendly technology is a promising yet not commonly available solution. Here, we demonstrate the effective use of plasma-converted natural bioresources for environmental monitoring. The energy-efficient microplasmas operated at ambient conditions are used to convert diverse bioresources, including fructose, chitosan, citric acid, lignin, cellulose, and starch, into heteroatom-doped graphene quantum dots (GQDs) with controlled structures and functionalities for applications as fluorescence-based environmental nanoprobes. The simple structure of citric acid enables the production of monodispersed 3.6 nm averaged-size GQDs with excitation-independent emissions, while the saccharides including fructose, chitosan, lignin, cellulose, and starch allow the synthesis of GQDs with excitation-dependent emissions due to broader size distribution. Moreover, the presence of heteroatoms such as N and/or S in the chemical structures of chitosan and lignin coupled with the highly reactive species generated by the plasma facilitates the one-step synthesis of N, S-codoped GQDs, which offer selective detection of toxic environmental contaminants with a low limit of detection of 7.4 nM. Our work provides an insight into the rapid and green fabrication of GQDs with tunable emissions from natural resources in a scalable and sustainable manner, which is expected to generate impact in the environmental safety, energy conversion and storage, nanocatalysis, and nanomedicine fields.

Interaction domains of the UL16 and UL21 tegument proteins of herpes simplex virus.

The UL16 protein of herpes simplex virus is capsid associated and was previously identified as a binding partner of the membrane-associated UL11 tegument protein (J. S. Loomis, R. J. Courtney, and J. W. Wills, J. Virol. 77:11417-11424, 2003). In those studies, a less-prominent, approximately 65-kDa binding partner of unknown identity was also observed. Mass spectrometry studies have now revealed this species to be UL21, a tegument protein that has been implicated in the transport of capsids in the cytoplasm. The validity of the mass spectrometry results was tested in a variety of coimmunoprecipitation and glutathione S-transferase pull-down experiments. The data revealed that UL21 and UL16 can form a complex in the absence of other viral proteins, even when the assays used proteins purified from Escherichia coli. Moreover, UL11 was able to pull down UL21 only when UL16 was present, suggesting that all three proteins can form a complex. Deletion analyses revealed that the second half of UL21 (residues 268 to 535) is sufficient for the UL16 interaction and packaging into virions; however, attempts to map a subdomain of UL16 were largely unsuccessful, with only the first 40 (of 373) residues being found to be dispensable. Nevertheless, it is clear that UL16 must have two distinct binding sites, because covalent modification of its free cysteines with N-ethylmaleimide blocked binding to UL11 but not UL21. These findings should prove useful for elucidating the molecular machinery used to transmit a signal into a virion when it attaches to cells, a recently discovered mechanism in which UL16 is a central player.

Analysis of the interaction between the UL11 and UL16 tegument proteins of herpes simplex virus.

The UL11 and UL16 tegument proteins of herpes simplex virus are conserved throughout the herpesvirus family. Previous studies have shown that these proteins interact, perhaps to link UL16-bound nucleocapsids to UL11, which resides on the cytoplasmic face of the trans-Golgi network, where maturation budding occurs. Little is known about the interaction except that it requires the leucine-isoleucine (LI) and acidic cluster motifs in UL11 and that no other viral proteins are involved. In particular, the important question of whether these two proteins bind to each other directly has not been addressed. Accordingly, UL11 and UL16 were expressed in bacteria, and the purified proteins were found to retain the ability to interact in a manner that was dependent upon the LI and acidic cluster. In an attempt to map the UL11-binding site contained in UL16, a large number of deletion mutants were constructed. The first 40 (nonconserved) amino acids were found to be dispensable, but all the other constructs failed to bind UL11 or had poor expression in transfected cells, suggesting that UL16 is very sensitive to alterations and probably lacks a multidomain structure. As an alternative strategy for identifying residues that are important for the interaction, the cysteines of UL16 were investigated, because many of these are highly conserved. Approximately half of the 20 cysteines in UL16 have been shown to be covalently modified by N-ethylmaleimide, and this treatment was found to block the interaction with UL11. Moreover, individual serine replacements of six of the most conserved cysteine residues were made, and four of these disrupted the interaction with UL11 without affecting protein stability. However, the UL11-UL16 interaction does not involve the formation of interspecies disulfide bonds, because binding occurred even when all the cysteines in UL11 were eliminated. Thus, UL16 directly interacts with UL11 and does so in a manner that requires free cysteines.

Impregnation of Graphene Quantum Dots into a Metal-Organic Framework to Render Increased Electrical Conductivity and Activity for Electrochemical Sensing.

Graphene quantum dots (GQD) with an average size of 3.1 nm were incorporated into a mesoporous porphyrinic zirconium-based metal-organic framework (MOF) by direct impregnation to render the donor-acceptor charge transfer from GQDs to porphyrinic linkers. The hybrid material still possesses around half porosity of the pristine MOF and shows a 100-fold higher electrical conductivity compared to that of the parent MOF. By utilizing the porphyrinic linkers as catalytically active units, the GQD-MOF material exhibits a better electrochemical sensing activity toward nitrite in aqueous solutions compared to both the pristine MOF and GQD.

Novel interactions at the essential N-terminus of poly(A) polymerase that could regulate poly(A) addition in Saccharomyces cerevisiae.

Addition of poly(A) to the 3' ends of cleaved pre-mRNA is essential for mRNA maturation and is catalyzed by Pap1 in yeast. We have previously shown that a non-viable Pap1 mutant lacking the first 18 amino acids is fully active for polyadenylation of oligoA, but defective for pre-mRNA polyadenylation, suggesting that interactions at the N-terminus are important for enzyme function in the processing complex. We have now identified proteins that interact specifically with this region. Cft1 and Pta1 are subunits of the cleavage/polyadenylation factor, in which Pap1 resides, and Nab6 and Sub1 are nucleic-acid binding proteins with known links to 3' end processing. Our results suggest a novel mechanism for controlling Pap1 activity, and possible models invoking these newly-discovered interactions are discussed.

Sequences in the UL11 tegument protein of herpes simplex virus that control association with detergent-resistant membranes.

The product of the UL11 gene of HSV-1 is a small, membrane-bound tegument protein with features that are conserved among all herpesviruses. For all viruses examined, mutants lacking this protein (or its homolog) have budding defects and accumulate capsids in the cytoplasm of the infected cell. UL11 binds to the cytoplasmic faces of host membranes via N-terminal myristate and nearby palmitate moieties. These fatty-acid modifications are typical of proteins that localize to detergent-resistant membranes (DRMs), and the experiments described here revealed that a small amount (approximately 10%) of UL11 retains the ability to float in sucrose gradients following treatment of cells with Triton X-100. However, mutants lacking sequences previously shown to be involved in the trafficking of UL11 from the plasma membrane (LI and acidic cluster motifs) were found to have a dramatically increased association with DRMs. These findings emphasize the dynamic properties of this poorly-understood but conserved tegument protein.