Rice LIKE EARLY STARVATION1 cooperates with FLOURY ENDOSPERM6 to modulate starch biosynthesis and endosperm development.

In cereal grains, starch is synthesized by the concerted actions of multiple enzymes on the surface of starch granules within the amyloplast. However, little is known about how starch-synthesizing enzymes access starch granules, especially for amylopectin biosynthesis. Here, we show that the rice (Oryza sativa) floury endosperm9 (flo9) mutant is defective in amylopectin biosynthesis, leading to grains exhibiting a floury endosperm with a hollow core. Molecular cloning revealed that FLO9 encodes a plant-specific protein homologous to Arabidopsis (Arabidopsis thaliana) LIKE EARLY STARVATION1 (LESV). Unlike Arabidopsis LESV, which is involved in starch metabolism in leaves, OsLESV is required for starch granule initiation in the endosperm. OsLESV can directly bind to starch by its C-terminal tryptophan (Trp)-rich region. Cellular and biochemical evidence suggests that OsLESV interacts with the starch-binding protein FLO6, and loss-of-function mutations of either gene impair ISOAMYLASE1 (ISA1) targeting to starch granules. Genetically, OsLESV acts synergistically with FLO6 to regulate starch biosynthesis and endosperm development. Together, our results identify OsLESV-FLO6 as a non-enzymatic molecular module responsible for ISA1 localization on starch granules, and present a target gene for use in biotechnology to control starch content and composition in rice endosperm.

Dominance of felsic continental crust on Earth after 3 billion years ago is recorded by vanadium isotopes.

The transition from mafic to felsic upper continental crust (UCC) is crucial to habitability of Earth, and may be related to the onset of plate tectonics. Thus, defining when this crustal transition occurred has great significance for the evolution of Earth and its inhabitants. We demonstrate that V isotope ratios (reported as δ51V) provide insights into this transition because they correlate positively with SiO2 and negatively with MgO contents during igneous differentiation in both subduction zones and intraplate settings. Because δ51V is not affected by chemical weathering and fluid-rock interactions, δ51V of the fine-grained matrix of Archean to Paleozoic (3 to 0.3 Ga) glacial diamictite composites, which sample the UCC at the time of glaciation, reflect the chemical composition of the UCC through time. The δ51V values of glacial diamictites systematically increase with time, indicating a dominantly mafic UCC at ~3 Ga; the UCC was dominated by felsic rocks only after 3 Ga, coinciding with widespread continental emergence and many independent estimates for the onset of plate tectonics.

Microglial Reactivity Correlates with Presynaptic Loss Independent of ß-Amyloid and Tau.

OBJECTIVE: Triggering receptor expressed on myeloid cells-2 (TREM2) and progranulin (PGRN) are critical regulators of microglia activation and can be detected in cerebrospinal fluid (CSF). However, whether microglial reactivity is detrimental or neuroprotective for Alzheimer disease (AD) is still debatable. METHODS: We identified 663 participants with baseline ß-amyloid (Aß) positron emission tomography (PET) and CSF biomarker data, including phosphorylated tau181 (p-Tau181), soluble TREM2 (sTREM2), PGRN, and growth-associated protein-43 (GAP-43). Among them, 254 participants had concurrent longitudinal CSF biomarkers. We used multivariate regression analysis to study the associations of CSF microglial biomarkers with Aß PET, CSF p-Tau181, and CSF GAP-43 cross-sectionally and longitudinally. A Chinese aging cohort's independent CSF samples (n = 65) were analyzed as a validation. RESULTS: Higher baseline levels of CSF microglial biomarkers were related to faster rates of CSF sTREM2 increase and CSF PGRN decrease. Elevated CSF p-Tau181 was associated with higher levels of CSF microglial biomarkers and faster rates of CSF sTREM2 increase and CSF PGRN decrease. In both cohorts, higher Aß burden was associated with attenuated CSF p-Tau181 effects on CSF microglial biomarker increases. Independent of Aß PET and CSF p-Tau181 pathologies, higher levels of CSF sTREM2 but not CSF PGRN were related to elevated CSF GAP-43 levels and faster rates of CSF GAP-43 increase. INTERPRETATION: These findings suggest that higher Aß burden may attenuate the p-Tau-associated microglial responses, and TREM2-related microglial reactivity may independently correlate with GAP-43-related presynaptic loss. This study highlights the two-edged role of microglial reactivity in AD and other neurodegenerative diseases. ANN NEUROL 2024;95:917-928.

Restriction on molecular fluxionality by substitution: A case study for the 1,10-dicyanobullvalene.

We show herein that 1,10-dicyano substitution restricts the paragon fluxionality of bullvalene to just 14 isomers which isomerize along a single cycle. The restricted fluxionality of 1,10-dicyanobullvalene (DCB) is investigated by means of: (i) Bonding analyses of the isomer structures using the adaptive natural density partitioning (AdNDP). (ii) Quantum dynamical simulations of the isomerizations along the cyclic intrinsic reaction coordinate of the potential energy surface (PES). The PES possesses 14 equivalent potential wells supporting 14 isomers which are separated by 14 equivalent potential barriers supporting 14 transition states. Accordingly, at low temperatures, DCB appears as a hindered molecular rotor, without any delocalization of the wavefunction in the 14 potential wells, without any nuclear spin isomers, and with completely negligible tunneling. These results are compared and found to differ from those for molecular boron rotors. (iii) Born-Oppenheimer molecular dynamics (BOMD) simulations of thermally activated isomerizations. (iv) Calculations of the rate constants in the frame of transition state theory (TST) with reasonable agreement achieved with the BOMD results. (v) Simulations of the equilibration dynamics using rate equations for the isomerizations with TST rate coefficients. Accordingly, in the long-time limit, isomerizations of the 14 isomers, each with Cs symmetry, approach the "14 Cs → C7v" thermally averaged structure. This is a superposition of the 14 equally populated isomer structures with an overall C7v symmetry. By extrapolation, the results for DCB yield working hypotheses for so far un-explored properties e.g. for the equilibration dynamics of C10H10.

Artificial intelligence in the risk prediction models of cardiovascular disease and development of an independent validation screening tool: a systematic review.

BACKGROUND: A comprehensive overview of artificial intelligence (AI) for cardiovascular disease (CVD) prediction and a screening tool of AI models (AI-Ms) for independent external validation are lacking. This systematic review aims to identify, describe, and appraise AI-Ms of CVD prediction in the general and special populations and develop a new independent validation score (IVS) for AI-Ms replicability evaluation. METHODS: PubMed, Web of Science, Embase, and IEEE library were searched up to July 2021. Data extraction and analysis were performed for the populations, distribution, predictors, algorithms, etc. The risk of bias was evaluated with the prediction risk of bias assessment tool (PROBAST). Subsequently, we designed IVS for model replicability evaluation with five steps in five items, including transparency of algorithms, performance of models, feasibility of reproduction, risk of reproduction, and clinical implication, respectively. The review is registered in PROSPERO (No. CRD42021271789). RESULTS: In 20,887 screened references, 79 articles (82.5% in 2017-2021) were included, which contained 114 datasets (67 in Europe and North America, but 0 in Africa). We identified 486 AI-Ms, of which the majority were in development (n = 380), but none of them had undergone independent external validation. A total of 66 idiographic algorithms were found; however, 36.4% were used only once and only 39.4% over three times. A large number of different predictors (range 5-52,000, median 21) and large-span sample size (range 80-3,660,000, median 4466) were observed. All models were at high risk of bias according to PROBAST, primarily due to the incorrect use of statistical methods. IVS analysis confirmed only 10 models as "recommended"; however, 281 and 187 were "not recommended" and "warning," respectively. CONCLUSION: AI has led the digital revolution in the field of CVD prediction, but is still in the early stage of development as the defects of research design, report, and evaluation systems. The IVS we developed may contribute to independent external validation and the development of this field.

Intermolecular Interactions, Morphology, and Photovoltaic Patterns in p-i-n Heterojunction Solar Cells With Fluorine-Substituted Organic Photovoltaic Materials.

During the layer-by-layer (LBL) processing of polymer solar cells (PSCs), the swelling and molecule interdiffusion are essential for achieving precise, controllable vertical morphology, and thus efficient PSCs. However, the influencing mechanism of material properties on morphology and correlated device performance has not been paid much attention. Herein, a series of fluorinated/non-fluorinated polymer donors (PBDB-T and PBDB-TF) and non-fullerene acceptors (ITIC, IT-2F, and IT-4F) are employed to investigate the performance of LBL devices. The impacts of fluorine substitution on the repulsion and miscibility between the donor and acceptor, as well as the molecular arrangement of the donor/acceptor and the vertical distribution of the LBL devices are systematically explored by the measurement of donor/acceptor Flory-Huggins interaction parameters, spectroscopic ellipsometry, and neutron reflectivity, respectively. With efficient charge transfer due to the ideal vertical and horizon morphology properties, devices based on PBDB-TF/IT-4F exhibit the highest fill factors (FFs) as well as champion power conversion efficiencies (PCEs). With this guidance, high-performance LBL devices with PCE of 17.2%, 18.5%, and 19.1% are obtained by the fluorinated blend of PBDB-TF/Y6, PBDB-TF/L8-BO, and D18/L8-BO respectively.

[18F]-D3FSP ß-amyloid PET imaging in older adults and alzheimer's disease.

PURPOSE: [18F]-D3FSP is a new ß-amyloid (Aß) PET imaging tracer designed to decrease nonspecific signals in the brain by reducing the formation of the N-demethylated product. However, its optimal reference region for calculating the standardized uptake value ratio (SUVR) and its relation to the well-established biomarkers of Alzheimer's disease (AD) are still unclear. METHODS: We recruited 203 participants from the Greater Bay Area Healthy Aging Brain Study (GHABS) to undergo [18F]-D3FSP Aß PET imaging. We analyzed plasma Aß42/Aß40, p-Tau181, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) using the Simoa platform. We compared the standardized uptake value (SUV) of five reference regions (cerebellum, cerebellum cortex, brainstem/PONs, white matter, composite of the four regions above) and AD typical cortical region (COMPOSITE) SUVR among different clinical groups. The association of D3FSP SUVR with plasma biomarkers, imaging biomarkers, and cognition was also investigated. RESULTS: Brainstem/PONs SUV showed the lowest fluctuation across diagnostic groups, and COMPOSITE D3FSP SUVR had an enormous effect distinguishing cognitively impaired (CI) individuals from cognitively unimpaired (CU) individuals. COMPOSITE SUVR (Referred to brainstem/PONs) was positively correlated with p-Tau181 (p < 0.001), GFAP (p < 0.001), NfL (p = 0.014) in plasma and temporal-metaROI tau deposition (p < 0.001), and negatively related to plasma Aß42/Aß40 (p < 0.001), temporal-metaROI cortical thickness (p < 0.01), residual hippocampal volume (p < 0.001) and cognition (p < 0.001). The voxel-wise analysis replicated these findings. CONCLUSION: This study suggests brainstem/PONs as an optimal reference region for calculating D3FSP SUVR to quantify cortical Aß plaques in the brain. [18F]-D3FSP could distinguish CI from CU and strongly correlates with well-established plasma biomarkers, tau PET, neurodegeneration, and cognitive decline. However, future head-to-head comparisons of [18F]-D3FSP PET images with other validated Aß PET tracers or postmortem results are crucial.

The development of probiotics and prebiotics therapy to ulcerative colitis: a therapy that has gained considerable momentum.

Ulcerative colitis (UC) is increasingly common, and it is gradually become a kind of global epidemic. UC is a type of inflammatory bowel disease (IBD), and it is a lifetime recurrent disease. UC as a common disease has become a financial burden for many people and has the potential to develop into cancer if not prevented or treated. There are multiple factors such as genetic factors, host immune system disorders, and environmental factors to cause UC. A growing body of research have suggested that intestinal microbiota as an environmental factor play an important role in the occurrence and development of UC. Meanwhile, evidence to date suggests that manipulating the gut microbiome may represent effective treatment for the prevention or management of UC. In addition, the main clinical drugs to treat UC are amino salicylate and corticosteroid. These clinical drugs always have some side effects and low success rate when treating patients with UC. Therefore, there is an urgent need for safe and efficient methods to treat UC. Based on this, probiotics and prebiotics may be a valuable treatment for UC. In order to promote the wide clinical application of probiotics and prebiotics in the treatment of UC. This review aims to summarize the recent literature as an aid to better understanding how the probiotics and prebiotics contributes to UC while evaluating and prospecting the therapeutic effect of the probiotics and prebiotics in the treatment of UC based on previous publications.

Low prevalence of mcr-1 in Escherichia coli from food-producing animals and food products in China.

BACKGROUND: mcr-1-positive Escherichia coli has emerged as a significant threat to human health, veterinary health, and food safety in recent years. After the prohibition of colistin as a feed additive in animal husbandry in China, a noticeable reduction in both colistin resistance and the prevalence of mcr-1 was observed in E. coli from animals and humans. OBJECTIVES: To assess the prevalence of the colistin resistance gene mcr-1 and characterize its genetic context in E. coli strains derived from fecal and meat samples from food-producing animals in China. METHODS: A total of 1,353 fecal samples and 836 food samples were collected between 2019 and 2020 in China. E. coli isolates were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and their susceptibility to colistin were determined using the broth microdilution method. The colistin-resistant E. coli isolates were screened for the presence of mcr by PCR analysis and sequencing. The minimal inhibitory concentrations (MICs) of 15 antimicrobial agents against the mcr-1-positive strains were further tested using the agar dilution method, conjugation assays were performed, and whole genome sequencing was performed using Illumina HiSeq. RESULTS: In total, 1,403 E. coli strains were isolated. Thirteen isolates from chicken meat (n = 7), chickens (n = 3), and pigs (n = 3) were resistant to colistin with MIC values of 4 to 16 mg/L, and carried mcr-1. All mcr-1-positive strains, except for isolate AH20PE105, contained multiple resistance genes and exhibited multidrug-resistant phenotypes. They belonged to 10 sequence types (STs), including a novel ST (ST14521). mcr-1 was located on IncI2 (n = 9), IncX4 (n = 2), and IncHI2 (n = 2) plasmids, which were highly similar to other mcr-1-carrying plasmids sharing the same incompatibility type. Seven mcr-1-carrying plasmids could be successfully conjugally transferred to E. coli C600. CONCLUSIONS: While the low prevalence of mcr-1 (0.93%) identified in this study may not immediately seem alarming, the very emergence of this gene merits attention given its implications for colistin resistance and public health. Hence, ongoing surveillance of mcr-1 in E. coli remains crucial.

Pitfalls in Developing Machine Learning Models for Predicting Cardiovascular Diseases: Challenge and Solutions.

UNSTRUCTURED: In recent years, there has been an explosive development of artificial intelligence (AI), which has been widely applied in the healthcare field. As a typical AI technology, machine learning (ML) models have emerged as great potential in predicting cardiovascular diseases (CVDs) by leveraging large amounts of medical data for training and optimization, which are expected to play a crucial role in reducing the incidence and mortality rates of CVDs. Although the field has become a research hotspot, there are still many pitfalls that researchers need to pay close attention to. These pitfalls may affect the predictive performance, credibility, reliability, reproducibility of the studied models, ultimately reducing the value of the research and affecting the prospects for clinical application. Therefore, identifying and avoiding these pitfalls is a crucial task before implementing the research. However, there is currently a lack of comprehensive summary on this topic. This viewpoint aims to analyze the existing problems in terms of data quality, dataset characteristics, model design and statistical methods as well as clinic implication, and provide possible solutions to these problems, like gathering objective data, improving training, repeating measurements, increasing sample size, preventing overfitting using statistical methods, utilizing specific AI algorithms to address targeted issues, standardizing outcomes and evaluation criteria, as well as enhancing fairness and replicability, with the goal of offering reference and assistance to researchers, algorithm developers, policy makers, and clinical practitioners.

Climates and associated factors for evidence-based practice implementation among nurses: a cross-sectional study.

BACKGROUND: The organizational climate that fosters and supports the implementation of evidence is a key factor influencing the effective implementation of evidence-based practice (EBP). Nurses, being the largest group of medical staff, play a crucial role in EBP implementation. The perception of the climate for EBP implementation among nurses in their organizations is unknown, especially among Chinese nurses. AIMS: To clarify the implementation climate of EBP among Chinese nurses and identify the factors associated with the implementation and development of evidence-based nursing practices. METHODS: This study employed a descriptive cross-sectional study design. From March 2023 to April 2023, a sample of nurses (n = 1260) from two Tertiary care hospitals in central China were selected and surveyed by self-designed social-demographic questionnaire and Implementation Climate Scale. Multiple linear stepwise regression analysis was conducted to determine the predictors of implementation climate. RESULTS: The nurses achieved a mean ICS score of 59.10 ± 11.22, with mean scores exceeding 3 points for each sub-dimension and item. In the results of multiple linear regression, income satisfaction, implementation of evidence-based nursing practice project(s) within the unit, experience of evidence-based nursing practice during working life, and specific training or courses in evidence-based nursing practice were predictors of ICS. Of these, income satisfaction was the most significant predictor. These factors could explain 17.5% of the total variance in implementation climate. CONCLUSION: The climate for implementing EBP in Chinese nursing organizations was relatively strong. Nursing managers can enhance the climate for implementing EBP in their organizations by actively improving salary and enhancing EBP-related trainings and practices. RELEVANCE TO CLINICAL PRACTICE: Understanding nurses' perceptions of the EBP implementation climate in their organizations can help to identify specific barriers and facilitators to the development of EBP and facilitate its successful implementation. PATIENT OR PUBLIC CONTRIBUTION: Clinical nurses were involved in data collection and completed the questionnaires on EBP implementation climate.

SlBEL11 regulates flavonoid biosynthesis, thus fine-tuning auxin efflux to prevent premature fruit drop in tomato.

Auxin regulates flower and fruit abscission, but how developmental signals mediate auxin transport in abscission remains unclear. Here, we reveal the role of the transcription factor BEL1-LIKE HOMEODOMAIN11 (SlBEL11) in regulating auxin transport during abscission in tomato (Solanum lycopersicum). SlBEL11 is highly expressed in the fruit abscission zone, and its expression increases during fruit development. Knockdown of SlBEL11 expression by RNA interference (RNAi) caused premature fruit drop at the breaker (Br) and 3 d post-breaker (Br+3) stages of fruit development. Transcriptome and metabolome analysis of SlBEL11-RNAi lines revealed impaired flavonoid biosynthesis and decreased levels of most flavonoids, especially quercetin, which functions as an auxin transport inhibitor. This suggested that SlBEL11 prevents premature fruit abscission by modulating auxin efflux from fruits, which is crucial for the formation of an auxin response gradient. Indeed, quercetin treatment suppressed premature fruit drop in SlBEL11-RNAi plants. DNA affinity purification sequencing (DAP-seq) analysis indicated that SlBEL11 induced expression of the transcription factor gene SlMYB111 by directly binding to its promoter. Chromatin immunoprecipitation-quantitative polymerase chain reaction and electrophoretic mobility shift assay showed that S. lycopersicum MYELOBLASTOSIS VIRAL ONCOGENE HOMOLOG111 (SlMYB111) induces the expression of the core flavonoid biosynthesis genes SlCHS1, SlCHI, SlF3H, and SlFLS by directly binding to their promoters. Our findings suggest that the SlBEL11-SlMYB111 module modulates flavonoid biosynthesis to fine-tune auxin efflux from fruits and thus maintain an auxin response gradient in the pedicel, thereby preventing premature fruit drop.

Electrochemical Ni-Catalyzed Decarboxylative C(sp3 )-N Cross-Electrophile Coupling.

A new electrochemical transformation is presented that enables chemists to couple simple alkyl carboxylic acid derivatives with an electrophilic amine reagent to construct C(sp3 )-N bond. The success of this reaction hinges on the merging of cooperative electrochemical reduction with nickel catalysis. The chemistry exhibits a high degree of practicality, showcasing its wide applicability with 1°, 2°, 3° carboxylic acids and remarkable compatibility with diverse functional groups, even in the realm of late-stage functionalization. Furthermore, extensive mechanistic studies have unveiled the engagement of alkyl radicals and iminyl radicals; and elucidated the multifaceted roles played by i Pr2 O, Ni catalyst, and electricity.

Loss of polarity protein Par3 in the intestinal epithelium promotes colitis-associated colorectal cancer progression by damaging tight junction assembly.

Partitioning defective 3 (Par3) is a polarity protein critical in establishing epithelial cell polarity and tight junctions (TJs). Impaired intestinal epithelial barrier integrity is closely associated with colitis-associated colorectal cancer (CRC) progression. According to the GEO and TCGA database analyses, we first observed that the expression of Par3 was reduced in CRC patients. To understand how Par3 is related to CRC, we investigated the role of Par3 in the development of CRC using an in vivo genetic approach. Our results show that the intestinal epithelium-specific PAR3 deletion mice demonstrated a more severe CRC phenotype in the context of azoxymethane/dextran sodium sulfate (AOM/DSS) treatment, with a corresponding increase in tumor number and inflammatory cytokines profile. Mechanistically, loss of Par3 disrupts the TJs of the intestinal epithelium and increases mucosal barrier permeability. The interaction of Par3 with ZO-1 prevents intramolecular interactions within ZO-1 protein and facilitates the binding of occludin to ZO-1, hence preserving TJs integrity. Our results suggest that Par3 deficiency permits pathogenic bacteria and their endotoxins to penetrate the intestinal submucosa and activate TLR4/MyD88/NF-κB signaling, promoting inflammation-driven CRC development and that Par3 may be a novel potential molecular marker for the diagnosis of early-stage CRC.

The HD-Zip transcription factor SlHB15A regulates abscission by modulating jasmonoyl-isoleucine biosynthesis.

Plant organ abscission, a process that is important for development and reproductive success, is inhibited by the phytohormone auxin and promoted by another phytohormone, jasmonic acid (JA). However, the molecular mechanisms underlying the antagonistic effects of auxin and JA in organ abscission are unknown. We identified a tomato (Solanum lycopersicum) class III homeodomain-leucine zipper transcription factor, HOMEOBOX15A (SlHB15A), which was highly expressed in the flower pedicel abscission zone and induced by auxin. Knocking out SlHB15A using clustered regularly interspaced short palindromic repeats-associated protein 9 technology significantly accelerated abscission. In contrast, overexpression of microRNA166-resistant SlHB15A (mSlHB15A) delayed abscission. RNA sequencing and reverse transcription-quantitative PCR analyses showed that knocking out SlHB15A altered the expression of genes related to JA biosynthesis and signaling. Furthermore, functional analysis indicated that SlHB15A regulates abscission by depressing JA-isoleucine (JA-Ile) levels through inhabiting the expression of JASMONATE-RESISTANT1 (SlJAR1), a gene involved in JA-Ile biosynthesis, which could induce abscission-dependent and abscission-independent ethylene signaling. SlHB15A bound directly to the SlJAR1 promoter to silence SlJAR1, thus delaying abscission. We also found that flower removal enhanced JA-Ile content and that application of JA-Ile severely impaired the inhibitory effects of auxin on abscission. These results indicated that SlHB15A mediates the antagonistic effect of auxin and JA-Ile during tomato pedicel abscission, while auxin inhibits abscission through the SlHB15A-SlJAR1 module.

Association of Presynaptic Loss with Alzheimer's Disease and Cognitive Decline.

OBJECTIVE: Increased presynaptic dysfunction measured by cerebrospinal fluid (CSF) growth-associated protein-43 (GAP43) may be observed in Alzheimer's disease (AD), but how CSF GAP43 increases relate to AD-core pathologies, neurodegeneration, and cognitive decline in AD requires further investigation. METHODS: We analyzed 731 older adults with baseline ß-amyloid (Aß) positron emission tomography (PET), CSF GAP43, CSF phosphorylated tau181 (p-Tau181 ), and 18 F-fluorodeoxyglucose PET, and longitudinal residual hippocampal volume and cognitive assessments. Among them, 377 individuals had longitudinal 18 F-fluorodeoxyglucose PET, and 326 individuals had simultaneous longitudinal CSF GAP43, Aß PET, and CSF p-Tau181 data. We compared baseline and slopes of CSF GAP43 among different stages of AD, as well as their associations with Aß PET, CSF p-Tau181 , residual hippocampal volume, 18 F-fluorodeoxyglucose PET, and cognition cross-sectionally and longitudinally. RESULTS: Regardless of Aß positivity and clinical diagnosis, CSF p-Tau181 -positive individuals showed higher CSF GAP43 concentrations (p < 0.001) and faster rates of CSF GAP43 increases (p < 0.001) compared with the CSF p-Tau181 -negative individuals. Moreover, higher CSF GAP43 concentrations and faster rates of CSF GAP43 increases were strongly related to CSF p-Tau181 independent of Aß PET. They were related to more rapid hippocampal atrophy, hypometabolism, and cognitive decline (p < 0.001), and predicted the progression from MCI to dementia (area under the curve for baseline 0.704; area under the curve for slope 0.717) over a median 4 years of follow up. INTERPRETATION: Tau aggregations rather than Aß plaques primarily drive presynaptic dysfunction measured by CSF GAP43, which may lead to sequential neurodegeneration and cognitive impairment in AD or neurodegenerative diseases. ANN NEUROL 2022;92:1001-1015.

Spatiotemporal mode-locking of an all-fiber laser based on InP quantum dot saturable absorber.

Passive mode-locking based on saturable absorbers (SAs) is an effective way to generate ultrafast pulses, while the spatiotemporal mode-locking (STML) based on SAs are rarely studied. We construct an all-fiber laser with InP quantum dots (QDs) SA, and realize multi-mode Q-switching (MMQS) and STML. In addition, by adjusting the polarization controller (PC) in the laser cavity, we obtain two different single-pulse STML states. The narrowest pulse widths of the two states are 57 ps and 32 ps, respectively, and the pulse width can be tuned continuously with increasing the pump power. By decoupling the effects of the PC and the SA in our experiment, we find that the polarization plays a key role in the selection of transverse modes. The effect of independent polarization on spatiotemporal mode-locked pulses has not been investigated before. To further analyze and understand the experimental results, we numerically solve the nonlinear Schrodinger equation, and compare the numerical simulation with the experimental results. In addition to passively adjusting cavity loss, the InP QD SA can balance the large walk off between different transverse modes, due to the spatial and spectral filtering effects. Our work has important implications for the design and application of all-fiber STML lasers.

Integrated efficient radiative transfer model named Dayu for simulating the imager measurements in cloudy atmospheres.

Rapid radiative transfer models are crucial to remote sensing and data assimilation. An integrated efficient radiative transfer model named Dayu, which is an updated version of the Efficient Radiative Transfer Model (ERTM) is developed to simulate the imager measurements in cloudy atmospheres. In Dayu model, the Optimized alternate Mapping Correlated K-Distribution model (OMCKD) which is predominant in dealing with the overlap of multiple gaseous lines is employed to efficiently calculate the gaseous absorption. The cloud and aerosol optical properties are pre-calculated and parameterized by the particle effective radius or length. Specifically, the ice crystal model is assumed as a solid hexagonal column, of which the parameters are determined based on massive aircraft observations. For the radiative transfer solver, the original 4-stream Discrete ordinate aDding Approximation (4-DDA) is extended to 2N-DDA (2N is the number of streams) which can calculate not only the azimuthally dependent radiance in the solar spectrum (including solar and infrared spectra overlap) but also the azimuthally averaged radiance in the thermal infrared spectrum through a unified adding method. Then the accuracy and efficiency of Dayu model are evaluated by comparing it with the benchmark model, i.e., Line-By-Line Radiative Transfer Model (LBLRTM) and DIScrete Ordinate Radiative Transfer (DISORT). Under the standard atmospheric profile, the maximum relative biases between Dayu model with 8-DDA / 16-DDA and the benchmark model (OMCKD with 64-stream DISORT) are 7.63% / 2.62% at solar channels but decreased to 2.66% / 1.39% at spectra-overlapping channel (3.7 µm). The computational efficiency of Dayu model with 8-DDA / 16-DDA is approximately three / two orders of magnitude higher than that of the benchmark model. At thermal infrared channels, the brightness temperature (BT) differences between Dayu model with 4-DDA and the benchmark model (LBLRTM with 64-stream DISORT) are bounded by 0.65K. Compared to the benchmark model, Dayu model with 4-DDA improves the computational efficiency by five orders of magnitude. In the application to the practical Typhoon Lekima case, the simulated reflectances and BTs by Dayu model have a high consistency with the imager measurements, demonstrating the superior performance of Dayu model in satellite simulation.

Neoadjuvant Modified FOLFOXIRI With Selective Radiotherapy in Locally Advanced Rectal Cancer: Long-term Outcomes of Phase II Study and Propensity-Score-Matched Comparison With Chemoradiotherapy.

BACKGROUND: Neoadjuvant modified FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) chemotherapy with selective radiotherapy did not compromise pathologic complete response and tumor downstaging in locally advanced rectal cancer. OBJECTIVE: The study aimed to analyze disease-free survival and local recurrence of neoadjuvant chemotherapy with modified FOLFOXIRI (mFOLFOXIRI). DESIGN: This was a prospective single-arm phase II study. A propensity score-adjusted method was implemented to compare outcomes against historical controls of chemoradiotherapy. SETTINGS: The study was conducted at single institutions. PATIENTS: One hundred 6 patients with stage II and III rectal cancers were included. INTERVENTION: All patients received neoadjuvant mFOLFOXIRI chemotherapy before total mesorectal excision. Patients with mesorectal fascia-positive or ycT4a/b after reevaluation with MRI received radiation before surgery. Otherwise, immediate total mesorectal excision would be performed. MAIN OUTCOME AND MEASURES: The primary end point was tumor downstaging (ypStage 0-I) rate, which was reported previously. Disease-free survival and local recurrence rate were the main outcomes for the current study. RESULTS: After a median follow-up of 43.3 months, the 2-year disease-free survival rate was 85.6% and the 3-year disease-free survival rate was 78.9%. The local recurrence rate was 7.8% after surgery. After propensity score matching, 73 patients were available for comparison in each group. The pathologic complete response rate was 23.3% and 13.7% ( p = 0.14), the proportion of ypStage 0-I was 45.2% vs 39.7% ( p = 0.5), the 3-year disease-free survival was 87.6% vs 75.8% (HR = 0.46; 95% CI, 0.22-0.95, p = 0.037). The local recurrence rate in the mFOLFOXIRI group was 5.5% and in the chemoradiotherapy group was 4.1% ( p = 0.70). Patients receiving mFOLFOXIRI had a lower incidence of anastomotic fistula compared with the chemoradiotherapy group (5.5% vs 17.8%, p = 0.02). LIMITATIONS: This was a single-arm, nonrandomized phase II study. CONCLUSIONS: Neoadjuvant mFOLFOXIRI with selective radiotherapy was feasible and safe, and it improved 3-year disease-free survival compared with propensity score-matched historical controls who received chemoradiotherapy. See Video Abstract at http://links.lww.com/DCR/B989 .Trial registration: NCT02217020. FOLFOXIRI MODIFICADO NEOADYUVANTE CON RADIOTERAPIA SELECTIVA EN CNCER DE RECTO LOCALMENTE AVANZADO RESULTADOS A LARGO PLAZO DEL ESTUDIO DE FASE II Y COMPARACIN EMPAREJADA POR PUNTUACIN DE PROPENSIN CON QUIMIORRADIOTERAPIA: ANTECEDENTES:La quimioterapia neoadyuvante con FOLFOXIRI modificado (ácido folínico, 5-fluoruracilo, oxaliplatino e irinotecan) con radioterapia selectiva no comprometió la respuesta patológica completa ni la reducción del estadio del tumor en el cáncer de recto localmente avanzado.OBJETIVO:El estudio tuvo como objetivo analizar la sobrevida libre de enfermedad y la recurrencia local de la quimioterapia neoadyuvante con FOLFOXIRI modificado (mFOLFOXIRI).DISEÑO:Este fue un estudio prospectivo de fase II de un solo brazo. Se implementó un método ajustado por puntaje de propensión para comparar los resultados con los controles históricos de quimiorradioterapia.ESCENARIO:El estudio se realizó en instituciones individuales.PACIENTES:Se incluyeron 106 pacientes con cáncer de recto en estadio II y III.INTERVENCIÓN:Todos los pacientes recibieron quimioterapia neoadyuvante con mFOLFOXIRI antes de la escisión total del mesorrecto. Los pacientes con fascia mesorrectal positiva o ycT4a/b después de la reevaluación con MRI recibirían radiación antes de la cirugía. En caso contrario, se realizaría una escisión mesorrectal total inmediata.PRINCIPALES RESULTADOS Y MEDIDAS:El criterio principal de valoración fue la tasa de disminución del estadio del tumor (ypEstadio 0-I), que se informó anteriormente. La sobrevida libre de enfermedad y la tasa de recurrencia local son los principales resultados del estudio actual.RESULTADOS:Después de una mediana de seguimiento de 43,3 meses, las tasas de sobrevida libre de enfermedad a 2 y 3 años fueron del 85,6 % y 78,9 %, respectivamente. La tasa de recidiva local fue del 7,8% tras la cirugía. Después del emparejamiento por puntaje de propensión, 73 pacientes estaban disponibles para la comparación en cada grupo. La tasa de respuesta patológica completa fue de 23,3 % y de 13,7 % (p = 0,14), la proporción de ypEstadio 0-I fue del 45,2 % frente al 39,7 % (p = 0,5), la SLE a los 3 años fue del 87,6 % frente al 75,8 % (HR = 0,46, IC del 95 % 0,22-0,95, p = 0,037) y la tasa de recurrencia local fue del 5,5 % y del 4,1 % (p = 0,70) en el grupo de mFOLFOXIRI frente al grupo de quimiorradioterapia, respectivamente. Los pacientes que recibieron mFOLFOXIRI tuvieron una menor incidencia de fístula anastomótica en comparación con el grupo de quimiorradioterapia (5,5 % frente a 17,8 %, p = 0,02).LIMITACIONES:Este fue un estudio de fase II no aleatorizado de un solo brazo.CONCLUSIONES:El mFOLFOXIRI neoadyuvante con radioterapia selectiva fue factible y seguro, y mejoró la SSE a los 3 años en comparación con los controles históricos emparejados por puntaje de propensión que recibieron quimiorradioterapia. Consulte Video Resumen en http://links.lww.com/DCR/B989 . (Traducción-Dr. Felipe Bellolio ).

Development and validation of LightGBM algorithm for optimizing of Helicobacter pylori antibody during the minimum living guarantee crowd based gastric cancer screening program in Taizhou, China.

Gastric cancer continues to be a significant health concern in China, with a high incidence rate. To mitigate its impact, early detection and treatment is key. However, conducting large-scale endoscopic gastric cancer screening is not feasible in China. Instead, a more appropriate approach would be to initially screen high-risk groups and follow up with endoscopic testing as needed. We conducted a study on 25,622 asymptomatic participants aged 45-70 years from a free gastric cancer screening program in the Taizhou city government's Minimum Living Guarantee Crowd (MLGC) initiative. Participants completed questionnaires, blood tests, and underwent gastrin-17 (G-17), pepsinogen I and II (PGI and PGII), and H. pylori IgG antibody (IgG) assessments. Using the light gradient boosting machine (lightGBM) algorithm, we developed a predictive model for gastric cancer risk. In the full model, F1 score was 2.66%, precision was 1.36%, and recall was 58.14%. In the high-risk model, F1 score was 2.51%, precision was 1.27%, and recall was 94.55%. Excluding IgG, the F1 score was 2.73%, precision was 1.40%, and recall was 68.62%. We conclude that H. pylori IgG appears to be able to be excluded from the prediction model without significantly affecting its performance, which is important from a health economic point of view. It suggests that screening indicators can be optimized, and expenditures reduced. These findings can have important implications for policymakers, as we can focus resources on other important aspects of gastric cancer prevention and control.