bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelo Autorregressivo de Integração Adaptativa
Authors: Ronald Arthur , Salles Rebecca , Belloze Kele , Pastore Dayse , Ogasawara Eduardo
Published: January 2020

Diversas técnicas de preprocessamento combinadas a modelos de series temporais vêm sendo utilizadas para previsão de séries temporais nãoestacionárias. O estudo das propriedades matemáticas e estatísticas dos dados e das técnicas de preprocessamento pode auxiliar no ajustamento de modelos de aprendizado de máquina. Tal estudo, entretanto, muitas vezes não é facilmente obtido. Modelos lineares, por sua vez, possibilitam a interpretação de tais propriedades. Este artigo introduz e analisa, por meio de prova de conceito, um novo modelo linear aplicado a séries estacionárias construídas com base em normalização adaptativa. O modelo viabiliza o uso de modelos autorregressivos em cenários de janelas deslizantes que preservam as propriedades da série original, e permitem acompanhar a sua inércia. O modelo foi capaz de apresentar desempenho de previsão superior a outros modelos lineares consolidados na literatura, principalmente em horizontes de curto-prazo.
A Science Gateway to Support Research in Spectral Graph Theory
Authors: Oliveira Daniel , Abreu Carlos Magno , Ogasawara Eduardo , Bezerra Eduardo , de Lima Leonardo
Published: January 2020

Describing classes of graphs that optimize a function of the eigenvalues subject to some constraints is one of the topics addressed by Spectral Graph Theory (SGT). In this paper, we propose RioGraphX, a science gateway developed on top of Apache Spark, which aims to obtain all graphs that optimize a given mathematical function of the eigenvalues of a graph. Initial experiments involving small graphs have pointed out optimal graphs in a reasonable computational time, and also have shown that leveraging parallel processing is a promising approach to handle larger graphs.
Processamento Eficiente de Consultas Analíticas Estendidas com Predicado de Similaridade em Spark
Authors: da Rocha Guilherme Muzzi , Ciferri Cristina Dutra de Aguiar
Published: January 2020

Um data warehousing de imagens estende um data warehousing convencional para também manipular imagens representadas por vetores de características e atributos para pesquisa por similaridade. Um desafio que surge é o processamento de consultas analíticas estendidas com predicado de similaridade, desde que essas consultas possuem alto custo computacional. Neste artigo, é proposto o método BrOmnImg, o qual soluciona eficientemente esse desafio usando o framework Spark. Comparado com o método mais próximo, BrOmnImg proveu ganhos de desempenho de até 65,49%.
Data Warehouse Educacional: Uma visão sobre a Evasão no Ensino Superior
Authors: Santos G. A. S. , Bordignon A. L. , Haddad D. B. , Brandão D. N. , Tarrataca L. , Belloze K. T.
Published: January 2020

A evasão mostra-se como um dos principais desafios das instituições de ensino. Nesse sentido, este trabalho apresenta a implementação de um Data Warehouse para análise de dados e auxílio à tomada de decisão em uma instituição de ensino superior do Brasil. O Data Warehouse apresentado permite visões integradas que auxiliam em análises de: 1) distribuição do coeficiente de desempenho dos alunos; 2) identificação dos perfis dos estudantes e 3) um dashboard sobre o rendimento dos alunos por localidade. Essas análises têm como propósito auxiliar a gestão acadêmica na identificação de padrões que acarretam na evasão e, desta forma, promover direcionamentos para medidas preventivas e, principalmente, expandir o uso deste banco de dados analítico para desenvolver novas soluções, como por exemplo, modelos preditivos.
Desenvolvimento de Modelos de Armazenamento em Sensores com Reutilização de Código
Authors: Ordakowski Alexandre R. , Carrero Marcos A. , Musicante Martin A. , dos Santos Aldri L. , Hara Carmem S.
Published: January 2020

Sensores são componentes essenciais da Internet das Coisas (IoT). Em consonância com a tendência de armazenar dados próximos `as fontes de dados, preconizada pela computação de borda e de névoa, alguns sensores podem desempenhar o papel de repositório dos dados capturados. Dado o crescimento da quantidade de dispositivos e de aplicações para IoT, há a necessidade de investigar e desenvolver novos modelos de armazenamento para sensores. No entanto, poucos trabalhos propõem uma abordagem que trate da modelagem e implementação de sistemas de armazenamento e consulta dos dados da rede de uma maneira sistemática. Este artigo investiga a aplicação de um modelo de componentes para a geração de código para os dispositivos sensores, com a elaboração do framework RCBM-S (RCBM for Sensor devices). No RCBM-S a orquestração dos componentes é baseada em máquinas de estados. Um estudo de caso mostra a reutilização de código promovida pelo RCBM-S para códigos em nesC para o sistema TinyOS.
Differentially Private Group-by Data Releasing Algorithm
Authors: Chaves Iago , Machado Javam
Published: January 2020

Privacy concerns are growing fast because of data protection regulations around the world. Many works have built private algorithms avoiding sensitive information leakage through data publication. Differential privacy, based on formal definitions, is a strong guarantee for individual privacy and the cutting edge for designing private algorithms. This work proposes a differentially private group-by algorithm for data publication under the exponential mechanism. Our method publishes data groups according to a specified attribute while maintaining the desired privacy level and trustworthy utility results.
Agregação Não Supervisionada de Rankings para Redução de Cold-Start em Recuperação Multimodal de Imagens
Authors: da Silva Wanderson Bezerra , Calumby Rodrigo Tripodi
Published: January 2020

Em sistemas de recuperação de imagens por conteúdo, a técnica de realimentação de relevância visa permitir ao usuário exprimir a sua necessidade de busca sem conhecer propriedades de baixo nível das imagens. Para o bom funcionamento desta técnica, o conjunto de resultados anterior à primeira interação do usuário deve apresentar resultados relevantes. Para atenuar o problema de cold-start e aprimorar o conjunto inicial de resultados, neste trabalho realizou-se uma avaliação experimental de métodos de agregação de rankings para combinar resultados obtidos a partir de diferentes critérios de ranqueamento de imagens. Resultados considerando diferentes modalidades de características indicam eficácia promissora em relação aos baselines.
Proficiency Testing of Standardized Samples Shows High Interlaboratory Agreement for Clinical Next-Generation Sequencing–Based Hematologic Malignancy Assays With Survey Material–Specific Differences in Variant Frequencies
Authors: Keegan Alissa , Bridge Julia A. , Lindeman Neal I. , Long Thomas A. , Merker Jason D. , Moncur Joel T. , Montgomery Nathan D. , Nagarajan Rakesh , Rothberg Paul G. , Routbort Mark J. , Vasalos Patricia , Xian Rena , Kim Annette S.
Published: January 2020

Context.—

As laboratories increasingly turn from single-analyte testing in hematologic malignancies to next-generation sequencing–based panel testing, there is a corresponding need for proficiency testing to ensure adequate performance of these next-generation sequencing assays for optimal patient care.

Objective.—

To report the performance of laboratories on proficiency testing from the first 4 College of American Pathologists Next-Generation Sequencing Hematologic Malignancy surveys.

Design.—

College of American Pathologists proficiency testing results for 36 different engineered variants and/or allele fractions as well as a sample with no pathogenic variants were analyzed for accuracy and associated assay performance characteristics.

Results.—

The overall sensitivity observed for all variants was 93.5% (2190 of 2341) with 99.8% specificity (22 800 of 22 840). The false-negative rate was 6.5% (151 of 2341), and the largest single cause of these errors was difficulty in identifying variants in the sequence of CEBPA that is rich in cytosines and guanines. False-positive results (0.18%; 40 of 22 840) were most likely the result of preanalytic or postanalytic errors. Interestingly, the variant allele fractions were almost uniformly lower than the engineered fraction (as measured by digital polymerase chain reaction). Extensive troubleshooting identified a multifactorial cause for the low variant allele fractions, a result of an interaction between the linearized nature of the plasmid and the Illumina TruSeq chemistry.

Conclusions.—

Laboratories demonstrated an overall accuracy of 99.2% (24 990 of 25 181) with 99.8% specificity and 93.5% sensitivity when examining 36 clinically relevant somatic single-nucleotide variants with a variant allele fraction of 10% or greater. The data also highlight an issue with artificial linearized plasmids as survey material for next-generation sequencing.
De la question littéraire à l’oeuvre : aspects métapoétiques de l’oeuvre romanesque de Boubacar Boris Diop
Authors: Uwe Christian
Published: January 2020

L’oeuvre littéraire de Boubacar Boris Diop comporte une importante dimension métapoétique qui interroge constamment l’ensemble du processus d’écriture. Dès le premier roman, Le temps de Tamango, une mise en abyme de l’écriture est prise à la fois dans les plis de sa propre élaboration et dans le dialogue avec un autre texte – Tamango de Mérimée. Après cette oeuvre inaugurale, dans la facture de laquelle Mongo Beti a vu une admirable « expérimentation esthétique », les romans suivants n’ont cessé de revenir à la question, classique et inépuisable, du sens, et non pas seulement des moyens, de l’écriture littéraire. D’un roman à l’autre, le lecteur reconnaît quelques préoccupations récurrentes, dont le rapport entre la fiction et la réalité (plus particulièrement l’histoire politique) et l’effet de la littérature sur ses acteurs. À travers ces aspects, Boubacar Boris Diop semble explorer la crise du littéraire sur fond de crise politique à l’ère des indépendances. Cependant, cette interrogation n’est pas celle d’un sociologue, mais celle d’un créateur de fiction. Le titre de cette contribution peut ainsi se lire de deux manières qui se complètent. C’est, d’une part, la trace du mouvement subtil qui va de la question littéraire, en tant que périmètre d’un problème relatif à la production écrite, à l’oeuvre en tant que résultat et reflet de cette production. D’autre part, c’est aussi l’étude de la façon dont cette question littéraire, déplacée au sein même de l’oeuvre par le truchement de la mise en abyme, s’y révèle à la fois problématique et féconde, permettant d’approcher, de façon plus large, la place de la littérature dans les sociétés africaines postcoloniales.
celsr1a is essential for tissue homeostasis and onset of aging phenotypes in the zebrafish
Authors: Li Chunmei , Barton Carrie , Henke Katrin , Daane Jake , Treaster Stephen , Caetano-Lopes Joana , Tanguay Robyn L , Harris Matthew P
Published: January 2020

The use of genetics has been invaluable in defining the complex mechanisms of aging and longevity. Zebrafish, while a prominent model for vertebrate development, have not been used systematically to address questions of how and why we age. In a mutagenesis screen focusing on late developmental phenotypes, we identified a new mutant that displays aging phenotypes at young adult stages. We find that the phenotypes are due to loss-of-function in the non-classical cadherin celsr1a. The premature aging is not associated with increased cellular senescence or telomere length but is a result of a failure to maintain progenitor cell populations. We show that celsr1a is essential for maintenance of stem cell progenitors in late stages. Caloric restriction can ameliorate celsr1a aging phenotypes. These data suggest that celsr1a function helps to mediate stem cell maintenance during maturation and homeostasis of tissues and thus regulates the onset or expressivity of aging phenotypes.
Distinct inactive conformations of the dopamine D2 and D3 receptors correspond to different extents of inverse agonism
Authors: Lane J Robert , Abramyan Ara M , Adhikari Pramisha , Keen Alastair C , Lee Kuo-Hao , Sanchez Julie , Verma Ravi Kumar , Lim Herman D , Yano Hideaki , Javitch Jonathan A , Shi Lei
Published: January 2020

By analyzing and simulating inactive conformations of the highly homologous dopamine D2 and D3 receptors (D2R and D3R), we find that eticlopride binds D2R in a pose very similar to that in the D3R/eticlopride structure but incompatible with the D2R/risperidone structure. In addition, risperidone occupies a sub-pocket near the Na+ binding site, whereas eticlopride does not. Based on these findings and our experimental results, we propose that the divergent receptor conformations stabilized by Na+-sensitive eticlopride and Na+-insensitive risperidone correspond to different degrees of inverse agonism. Moreover, our simulations reveal that the extracellular loops are highly dynamic, with spontaneous transitions of extracellular loop 2 from the helical conformation in the D2R/risperidone structure to an extended conformation similar to that in the D3R/eticlopride structure. Our results reveal previously unappreciated diversity and dynamics in the inactive conformations of D2R. These findings are critical for rational drug discovery, as limiting a virtual screen to a single conformation will miss relevant ligands.
Comparison of Glasgow Blatchford Score and AIMS65 in Predicting Mortality in Patients with Upper Gastrointestinal Bleeding
Authors: Hajavi Nasser , Isazadehfar Khatereh , Hosseyni Mohammad Hosseyn , Habibzadeh Afshin , Yousefi Ardabili Elham
Published: January 2020

Introduction: Upper gastrointestinal bleeding (UGIB) is the most common cause of emergency admission in gastrointestinal disease. UGIB could accompany with adverse events if not treated timely. Different scoring systems have been suggested for diagnosing these patients, In this study we aimed to compare the predictive value of two scoring systems AIMS65 and Glasgow Blatchfors scale (GBS) in patients with UGIB. Methods: In this cross-sectional study, 153 patients (71.9% male with mean age of 56.72±21.64 years) with acute UGIB between April 2017 and September 2018 were included. Demographic findings, past medical history, laboratory findings, AMIS65 and GBS score, as well as, need for urgent endoscopy, transfusion and mortality were recorded. Both methods value in predicting the outcomes were measured using ROC curves. Results and Conclusion: Urgent endoscopy was performed in 44.4%. The most common finding was peptic ulcer with mostly clean base type. Rebleeding occurred in 15%, need for transfusion was in 44.4% and mortality rate was 5.2%. AIMS65 compared to GBS was superior in predicting mortality (AUC of 0.947 vs. 0.80) but was inferior compared to GBS in predicting need for transfusion (0.849 vs. 0.947). None of the systems could predict the need for urgent endoscopy. AIMS65 with cut off 2 and 0 and GBS with cut off of 12 and 8 could predict mortality and need for transfusion. GBS seems a better system in predicting the need for blood transfusion, while AIMS65 is better system for predicting in-hospital mortality in patients with UGIB.
Survey of Relation between Midcycle Progesterone Level with IUI Cycles Success Rate
Authors: Ghasemzadeh Alieh , Mostafavi Gilda , Nouri Mohammad , Chaichi Parastoo , Farzadi Laya , Hakimi Parvin
Published: January 2020

Introduction: Assisted reproductive technology is used routinely for treatment of infertile spouses. Previous studies reported conflicting results regarding effect of progesterone rise at the HCG injection day. The aim of current study is to evaluate the effects of mid cycle progesterone levels in IUI cycles. Methods: In this analytical cross-sectional study, the outcome of treatment in 200 IUI cycles were evaluated. Patients’ demographic findings, progesterone level at the day of HCG injection, number of follicles >16 mm, endometrial thickness and clinical pregnancy rate were recorded. For better evaluation, progesterone levels were divided to <0.5, 0.5-1.5 and >1.5 ng/dl. Results: Patients’ mean age was 29.70±4.38 years. The progesterone levels of <0.5, 0.5-1.5 and >1.5 ng/dl was detected in 24.5%, 56% and 19.5% of patients, respectively. The rate of clinical pregnancy was 27.5%. Cases with positive pregnancy had significantly lower progesterone levels (0.88±0.31 vs.1.11±0.80, p=0.04). The highest pregnancy rate was in progesterone levels 0.5-1.5 compared to levels <0.5 and >1.5 ng/dl (42% vs. 12.2% vs. 5.2%, p<0.001). There was no significant correlation between progesterone levels with endometrial thickness (r=-0.130, p=0.06) and number of follicles >16 mm(r=0.02, p=0.77). Conclusion: The results of current study showed that the increase in progesterone levels at the day of HCG injection accompanies with lower pregnancy rate. However, this increase has no correlation with number of mature follicles and endometrial thickness.
Bacterial inoculations can perturb the growth trajectory of diatoms with an existing microbiome
Authors: Baker Lydia J. , Kemp Paul F.
Published: January 2020

Inoculation of axenic diatom monocultures with individual bacterial strains has been used effectively to examine the relationship between bacteria and a diatom host. Both beneficial and harmful effects on diatom fitness have been observed. Yet, diatoms commonly host a consortium of bacteria that could influence their response to perturbation by bacterial inoculations. In this study, diatom cultures with an existing microbiome were inoculated with individual bacterial strains. Strains of two genera of bacteria commonly found associated with diatoms (Alteromonas and Marinobacter) were isolated from a culture of the diatom Chaetoceros sp. KBDT20. To evaluate whether bacterial inoculations can impact the growth, peak abundance, or decline of diatoms with an intact microbiome, individual bacterial strains were inoculated into batch cultures of the original host as well as two non-origin diatom hosts (Chaetoceros sp. KBDT32 and Amphiprora sp. KBDT35). Inoculations were repeated under vitamin-replete and vitamin-deficient conditions to assess whether vitamin concentration modulates the impact of bacterial inoculations on the host. The origin Chaetoceros culture was largely unperturbed by bacterial inoculations. In contrast, non-origin hosts experienced long-term impacts on their growth trajectory, and those impacts were found to be dependent on the concentration of vitamins in the growth medium. For the non-origin Chaetoceros, all positive impacts were observed in vitamin-replete conditions and all negative impacts were observed in vitamin-deficient conditions. Amphiprora was only impacted by inoculation with Marinobacter strains in vitamin-deficient conditions, and the effect was negative. Neither individual bacterial strains nor genera resulted in exclusively beneficial nor detrimental impacts, and the magnitude of effect varied among bacterial strains. This study demonstrates that bacterial inoculations can have long-lasting impacts on the growth trajectory of diatoms with an existing microbiome, that this impact can differ even between congeneric diatoms, and that the impact can be significantly modulated by vitamin concentration.
Effects of precipitation changes on soil bacterial community composition and diversity in the Junggar desert of Xinjiang, China
Authors: Wu Ke , Xu Wenxuan , Yang Weikang
Published: January 2020

Variation in precipitation can markedly affect the structure and function of soil microbial communities, especially in arid areas which are limited by water resources. Therefore, it is critical to understand how soil bacterial community composition and diversity will respond to variation in precipitation. In this study, we examined the soil bacterial community structure and diversity between five precipitation treatments (60% decrease, 30% decrease, control, 30% increase and 60% increase in precipitation) in the same arid site, in the Junggar desert of Xinjiang, northern China. The dominant bacterial phyla, present at similar frequencies in plots with different precipitation levels, were Actinobacteria, Proteobacteria, Bacteroidetes, Acidobacteria and Chloroflexi. The Shannon-Wiener and Chao1 indices of soil bacterialα-diversity were both positively correlated with plant diversity. Our results indicated that (1) extreme drought significantly decreased bacterial abundance and diversity compared with increased precipitation; (2) variation in precipitation did not change the dominant components of the bacterial communities; and (3) soil pH and total nitrogen concentration were the key factors affecting soil bacterial composition in the Junggar desert.
Biased Language in Simulated Handoffs and Clinician Recall and Attitudes
Authors: Wesevich Austin , Langan Erica , Fridman Ilona , Patel-Nguyen Sonya , Peek Monica E. , Parente Victoria
Published: December 2024

Importance

Poor-quality handoffs can lead to medical errors when transitioning patient care. Biased language within handoffs may contribute to errors and lead to disparities in health care delivery.

Objective

To compare clinical information recall accuracy and attitudes toward patients among trainees in paired cases of biased vs neutral language in simulated handoffs.

Design, Setting, and Participants

Surveys administered from April 29 to June 15 and from July 20 to October 10, 2023, included 3 simulated verbal handoffs, randomized between biased and neutral, and measured clinical information recall, attitudes toward patients, and key takeaways after each handoff. Participants included residents in internal medicine, pediatrics, and internal medicine–pediatrics and senior medical students at 2 academic medical centers in different geographic regions of the US. Data were analyzed from November 2023 to June 2024.

Exposures

Each participant received 3 handoffs that were based on real handoffs about Black patients at 1 academic center. These handoffs were each randomized to either a biased or neutral version. Biased handoffs had 1 of 3 types of bias: stereotype, blame, or doubt. The order of handoff presentation was also randomized. Internal medicine and pediatrics residents received slightly different surveys, tailored for their specialty. Internal medicine–pediatrics residents received the pediatric survey. Medical students were randomly assigned the survey type.

Main Outcomes and Measures

Each handoff was followed by a clinical information recall question, an adapted version of the Provider Attitudes Toward Sickle Cell Patients Scale (PASS), and 3 free-response takeaways.

Results

Of 748 trainees contacted, 169 participants (142 residents and 27 medical students) completed the survey (23% overall response rate), distributed across institutions, residency programs, and years of training (95 female [56%]; mean [SD] age, 28.6 [2.3] years). Participants who received handoffs with blame-based bias had less accurate information recall than those who received neutral handoffs (77% vs 93%; P = .005). Those who reported bias as a key takeaway of the handoff had lower clinical information recall accuracy than those who did not (85% vs 93%; P = .01). Participants had less positive attitudes toward patients per PASS scores after receiving biased compared with neutral handoffs (mean scores, 22.9 [3.3] vs 25.2 [2.7]; P < .001). More positive attitudes toward patients were associated with higher clinical information recall accuracy (odds ratio, 1.12; 95% CI, 1.02-1.22).

Conclusions and Relevance

In this survey study of residents and medical students, biased handoffs impeded accurate transfer of key clinical information and decreased empathy, potentially endangering patients and worsening health disparities. Handoff standardization is critical to addressing racial bias and improving patient safety.
Frequency Stability
Authors: Howe David A.
Published: December 2024

Radio navigation, digital signal processing, photonics, high‐speed communications, and numerous other important systems require a high degree of frequency stability in a variety of oscillators used to “clock” or time the electronic circuits. This chapter reviews definitions of frequency stability and methods of measuring the frequency stability of oscillators. Physical interpretations of common noise processes are discussed. The equipment and setup for stability measurements are outlined. Examples and typical stability results are presented.
A new double observer‐based census framework to improve abundance estimations in mountain ungulates and other gregarious species with a reduced effort
Authors: Panaccio Matteo , Brambilla Alice , Bassano Bruno , Smith Tessa , von Hardenberg Achaz
Published: December 2024

Estimating animal abundance has a key role to play in ecology and conservation, but survey methods are always challenged by imperfect detection. Among the techniques applied to deal with this issue, Double Observer (DO) is increasing in popularity due to its cost‐effectiveness. However, the effort of using DO for surveying large territories can be significant. A DO‐based survey method that allows accurate abundance estimations with reduced effort would increase the applicability of the method. This would have positive effects on the conservation of species which are challenging to survey such as mountain ungulates.

We used computer simulations based on real data and a field test to assess the reliability of the DO and of a new proposed survey procedure, the Double Observer Adjusted Survey (DOAS). DOAS is based on total block counts adjusted with some DO surveys conducted in a proportion of the total area only. Such DO surveys are then used to estimate detection probability with a mark‐recapture‐derived approach.

We found that full DO is much more accurate than simple block counts for abundance estimations. DOAS is a less demanding alternative to full DO and can produce comparable abundance estimates, at the cost of a slightly lower precision. However, in the DOAS overall detectability has to be estimated within a sufficient number of sites (around a quarter of the total) to obtain a higher precision and avoid large overestimations.

Practical implications. DO methods could increase the reliability of abundance estimations in mountain ungulates and other gregarious species. Full DO in particular could allow researchers to obtain unbiased estimations with high precision and its usage is therefore suggested instead of block counts in wildlife monitoring. Given the high costs of full DO, the DOAS procedure could be a viable and cost‐effective survey strategy to improve abundance estimates when resources are scarce.
Retinal thinning differentiates treatment effects in relapsing multiple sclerosis below the clinical threshold
Authors: Bsteh Gabriel , Hegen Harald , Krajnc Nik , Föttinger Fabian , Altmann Patrick , Auer Michael , Berek Klaus , Kornek Barbara , Leutmezer Fritz , Macher Stefan , Monschein Tobias , Ponleitner Markus , Rommer Paulus , Schmied Christiane , Zebenholzer Karin , Zulehner Gudrun , Zrzavy Tobias , Deisenhammer Florian , Di Pauli Franziska , Pemp Berthold , Berger Thomas
Published: December 2024

Objective

To investigate retinal layer thinning as a biomarker of disease‐modifying treatment (DMT) effects in relapsing multiple sclerosis (RMS).

Methods

From an ongoing prospective observational study, we included patients with RMS, who (i) had an optical coherence tomography (OCT) scan within 6 to 12 months after DMT start (rebaseline) and ≥1 follow‐up OCT ≥12 months after rebaseline and (ii) adhered to DMT during follow‐up. Differences between DMT in thinning of peripapillary‐retinal‐nerve‐fiber‐layer (pRNFL) and macular ganglion cell‐plus‐inner plexiform‐layer (GCIPL) were analyzed using mixed‐effects linear regression. Eyes suffering optic neuritis during follow‐up were excluded.

Results

We included 291 RMS patients (mean age 30.8 years [SD 7.9], 72.9% female, median disease duration 9 months [range 6–94], median rebaseline‐to‐last‐follow‐up‐interval 32 months [12–82]).

Mean annualized rates of retinal layer thinning (%/year) in reference to DMF (n = 84, GCIPL 0.28, pRNFL 0.53) were similar under TERI (n = 18, GCIPL 0.34, pRNFL 0.59), GLAT (n = 24, GCIPL 0.32, pRNFL 0.56), and IFNb (n = 13, GCIPL 0.33, pRNFL 0.60) were slightly lower under S1PM (n = 27, GCIPL 0.19, pRNFL 0.42) and CLA (n = 23, GCIPL 0.20, pRNFL 0.42), and were significantly lower under NTZ (n = 47, GCIPL 0.09, pRNFL 0.24; both p < 0.001) and antiCD20 (n = 55, GCIPL 0.10, pRNFL 0.23; both p < 0.001). In patients achieving NEDA‐2, observed thinning rates were lower overall, but still significantly lower under NTZ and antiCD20.

Interpretation

Applying a rebaselining concept, retinal layer thinning differentiates DMT effects even in clinically stable patients and, thus, might be a useful biomarker to monitor DMT efficacy on subclinical neuroaxonal degeneration—at least on a group level.
Theoretical Design and Synthesis of Metal–Inorganic Frameworks Using Host Atom‐Centered Building Blocks for Efficient Catalysis with Diverse Reactive Sites
Authors: He Chao , Dong Xingxing , Zhang Junqiu , Xu Shaogang , Huang Xiang , Wang Hui , He Changchun , Liang Xiaowei , Xie Maohai , Xu Hu
Published: December 2024

The modular assembly of organic molecules commonly guides the design of metal–organic frameworks (MOFs), yet the systematic exploration of inorganic building blocks remains limited. Given the promising applications in catalytic reactions and topological materials, the study of metal–inorganic frameworks (MIFs)—which fundamentally differ from the well‐established MOFs—has become urgent. This study introduces a strategy for designing MIFs using host atom‐centered building blocks, applied to the platinum–Phosphorus (Pt–P) system. By combining experimental observations with theoretical calculations, a Pt18P18 framework utilizing PtP3 building blocks, demonstrating significant energetic benefits is proposed. PtP3 units are employed to characterize Pt3P6 clusters within the pores, leading to a “compass” model that aligns with experimental findings. To address computational challenges associated with the large periodicity of the superstructure, a robust machine learning force field is developed. The analysis, combining surface nucleation studies, first‐principles calculations, and machine learning techniques, provides a comprehensive understanding of MIF structure. This validated Pt–P MIF exhibits exceptional catalytic properties with diverse reaction sites, significantly outperforming Pt(111) in the hydrogen evolution reaction. The findings not only present additional candidates for practical applications of metal phosphides but also highlight the vast potential of MIFs, paving the way for the discovery of numerous promising materials.
Anion‐Selective Ion Conductor Boosting Highly Flexible All‐In‐One Electrochromic Fabrics
Authors: Li Wanzhong , Li Ang , Wang Yuhao , Ding Mingyu , Liu Jingbing , Wang Hao , Zheng Zilong , Zhang Qianqian
Published: December 2024

Flexible all‐in‐one electrochromic fabrics (AECF) have attracted attention for application in wearable intelligent electronics. However, undifferentiated and disordered ion transport within the AECFs usually cause a slow transfer kinetics of reactive ions and thus restrict their electrochromic performance. Here, a new strategy is proposed to optimize active ion transport based on a well‐designed anion‐selective ion conductor (ASIC) for boosting the anionic AECF. The ASIC is developed by the interaction difference between ions and electronegative functional groups in the fabric substrate. Benefiting from cation immobilization and free anion transport, the ASIC exhibits both high anion transference number (0.75) and ionic conductivity (2.41 × 10−3 S cm−1) at room temperature. Such optimization of anion transport dynamics enhances the efficiency of the electrochromic redox reaction in the polyaniline‐based anionic AECF, contributing to a significant improvement of the overall electrochromic performance. Based on the switchable earth yellow and dark green discoloration, the AECF is further integrated into a camouflage uniform, achieving dynamic environment adaptation in deserts or forests. This work is anticipated to provide some fresh ideas for developing functional ion conductors of electrochromic fabrics toward applications in wearable intelligent electronics.
Glutathione Induced In Situ Activation of Dual‐Locked Cuproptosis Nanoamplifier with Glycolysis Metabolism Inhibition to Boost Cancer Immunotherapy
Authors: Wu Xiaomei , Zhang Shuo , Feng Mei , Sun Haoya , Lan Xiaopeng , Liang Wenlong , Liu Chunzhao , Li Yongxin
Published: December 2024

Interference with glycolysis metabolism not only promotes the efficient sensitization of cuproptosis, but also amplifies cytotoxic T cell functions and proliferations, thus contributing to relieve immunosuppressive tumor microenvironment. However, the synergistic mechanism and the design of multicomponent nanoformulations involving these three pathways have not yet been explored. a copper‐coordinated nanoassembly (designated as Cu‐GM) is reported here that integrates a lactate dehydrogenase inhibitor, galloflavin (GF), with an immune checkpoint inhibitor, myricetin (MY), to boost cancer cuproptosis‐immunotherapy. These results suggest that Cu‐GM can be activated by the endogenous overexpressed glutathione to release Cu+, leading to the abnormal aggregation of lipoylated proteins and iron‐sulfur cluster proteins loss, which triggers proteotoxic stress and cell cuproptosis. Meanwhile, the released GF not only inhibits the glycolysis to amplify cuproptosis efficacy but also achieves effective lactate depletion, thus alleviating immunosuppressive effects of lactate. Notably, the killed tumor cells can induce immunogenic cell death to evoke the anti‐tumor immunity, which further augmented by the MY‐mediated immune checkpoint blockade. Taken together, the first anticancer synergy of glycolysis metabolism, cuproptosis, and immunotherapy is presented, showcasing remarkable in vivo antitumor effects and encouraging further exploration of a rational multimodal treatment approach.
Matrix Viscoelasticity Controls Differentiation of Human Blood Vessel Organoids into Arterioles and Promotes Neovascularization in Myocardial Infarction
Authors: Sun Dayu , Zhang Kunyu , Zheng Feiyang , Yang Guanyuan , Yang Mingcan , Xu Youqian , Qin Yinhua , Lin Mingxin , Li Yanzhao , Tan Ju , Li Qiyu , Qu Xiaohang , Li Gang , Bian Liming , Zhu Chuhong
Published: December 2024

Stem cell‐derived blood vessel organoids are embedded in extracellular matrices to stimulate vessel sprouting. Although vascular organoids in 3D collagen I‐Matrigel gels are currently available, they are primarily capillaries composed of endothelial cells (ECs), pericytes, and mesenchymal stem‐like cells, which necessitate mature arteriole differentiation for neovascularization. In this context, the hypothesis that matrix viscoelasticity regulates vascular development is investigated in 3D cultures by encapsulating blood vessel organoids within viscoelastic gelatin/β‐CD assembly dynamic hydrogels or methacryloyl gelatin non‐dynamic hydrogels. The vascular organoids within the dynamic hydrogel demonstrate enhanced angiogenesis and differentiation into arterioles containing smooth muscle cells. The dynamic hydrogel mechanical microenvironment promotes vascular patterning and arteriolar differentiation by elevating notch receptor 3 signaling in mesenchymal stem cells and downregulating platelet‐derived growth factor B expression in ECs. Transplantation of vascular organoids in vivo, along with the dynamic hydrogel, leads to the reassembly of arterioles and restoration of cardiac function in infarcted hearts. These findings indicate that the viscoelastic properties of the matrix play a crucial role in controlling the vascular organization and differentiation processes, suggesting an exciting potential for its application in regenerative medicine.
Polyphenol Mediated Assembly: Tailored Nano‐Dredger Unblocks Axonal Autophagosomes Retrograde Transport Traffic Jam for Accelerated Alzheimer's Waste Clearance
Authors: Meng Ran , Li Yixian , Yang Xiyu , Cheng Yunlong , Xu Minjun , Zhou LingLing , Wu Chengqin , Yu Shuai , Huang Wenyi , Wang Tianying , Zhang Qizhi
Published: December 2024

Clear‐cut evidence has linked defective autophagy to Alzheimer's disease (AD). Recent studies underscore a unique hurdle in AD neuronal autophagy: impaired retrograde axonal transport of autophagosomes, potent enough to induce autophagic stress and neurodegeneration. Nonetheless, pertinent therapy is unavailable. Here, a novel combinational therapy composed of siROCK2 and lithospermic acid B (LA) is introduced, tailored to dredge blocked axonal autophagy by multi‐mitigating microtubule disruption, ATP depletion, oxidative stress, and autophagy initiation impediments in AD. Leveraging the recent discovery of multi‐interactions between polyphenol LA and siRNA, ε‐Poly‐L‐lysine, and anionic lipid nanovacuoles, LA and siROCK2 are successfully co‐loaded into a fresh nano‐drug delivery system, LIP@PL‐LA/siRC, via a ratio‐flexible and straightforward fabrication process. Further modification with the TPL peptide onto LIP@PL‐LA/siRC creates a brain‐neuron targeted, biocompatible, and pluripotent nanomedicine, named “Nano‐dredger” (T‐LIP@PL‐LA/siRC). Nano‐dredger efficiently accelerates axonal retrograde transport and lysosomal degradation of autophagosomes, thereby facilitating the clearance of neurotoxic proteins, improving neuronal complexity, and alleviating memory defects in 3×Tg‐AD transgenic mice. This study provides a fresh and flexible polyphenol/siRNA co‐delivery paradigm and furnishes conceptual proof that dredging axonal autophagy represents a promising AD therapeutic avenue.
Single‐Nucleus and Spatial Transcriptome Profiling Delineates the Multicellular Ecosystem in Hepatocellular Carcinoma After Hepatic Arterial Infusion Chemotherapy
Authors: Huang YeXing , Du ZeFeng , Lai ZhiCheng , Wen DongSheng , Huang LiChang , He MinKe , Wu ZiChao , Li HuiFang , OuYang HanYue , Wu WenChao , Kan Anna , Shi Ming
Published: December 2024

Hepatic arterial infusion chemotherapy (HAIC) has emerged as a promising treatment strategy for hepatocellular carcinoma (HCC), but a detailed understanding of the multicellular ecosystem after HAIC treatment is lacking. Here, we collected tumor samples from treatment‐naïve primary and post‐HAIC HCC, and integrated single‐nucleus RNA sequencing with spatial transcriptomics to characterize the tumor ecosystem in the post‐HAIC HCC. Increased fractions and enhanced cellular communication of CD4+ T, CD20+ B, and dendritic cell subtypes were identified in post‐HAIC tumors. Moreover, it is substantiated that HAIC promoted tertiary lymphoid structures (TLS) formation, and addressed the roles of TLSs as spatial niches of cellular communication. Specifically, intermediate exhausted CD8+ T cells expressing Granzyme‐K and PD‐1 (PD‐1+CD8+ Tex‐int) expanded following HAIC and exhibited a functionally antitumor phenotype. PD‐1+CD8+ Tex‐int accumulated in the TLS vicinity and disseminated throughout the tumor microenvironment, demonstrating potential as an effective biomarker for HAIC‐based treatment in HCC. This study provides valuable resources and biological insights in the cellular underpinnings of HAIC treatment.
Consumption of Endogenous Caspase‐3 Activates Molecular Theranostic Nanoplatform against Inflammation‐Induced Profibrotic Positive Feedback in Pulmonary Fibrosis
Authors: Li Qiu‐Ling , Chang Xin , Han Yu‐Mo , Guo Zi‐Chao , Liu Yi‐Na , Guo Bin , Liu Chang , Yang Bin‐Rong , Fan Zhong‐Kai , Jiang Hu‐Lin , Chang Xin
Published: December 2024

The limited and backward diagnostic approaches elicit high mortality associated with pulmonary fibrosis (PF) because they fail to identify injury phase of PF. Developing a precisely theranostic nanoplatform presents a promising shortcut to reverse PF. Herein, a specific molecular nanotheranostic (Casp‐GNMT), which is triggered by endogenous cysteinyl aspartate specific proteinase‐3 (caspase‐3), boosts antifibrotic efficacy through bioimaging synergistic with chemotherapy at molecular level, facilitating by ionizable lipid and reactive oxygen species sensitive lipid for precise and manageable therapy. The activation of molecular imaging probe (pCY‐pairs) by consumption of endogenous caspase‐3 initiates fluorescence resonance energy transfer‐guided theranostic pattern, aiming to restore mitochondrial dysfunction‐induced oxidative stress and inflammatory responses in alveolar epithelial cells II (AECs II). This process sequentially resists the expression of interleukin‐1β and vascular endothelial growth factor receptor through combined with nintedanib, further suppressing abnormal injury of AECs II and persistent migration and proliferation of inflammatory cells. Especially, the homeostasis of injured AECs II diminishes excessive accumulation of transforming growth factor‐β to restrain myofibroblasts proliferation and collagen deposition, thereby amplifying the possibility of reversing PF. This theranostic nanoplatform is proposed to provide a prompt and exact approach to enhance diagnostic authenticity and treating efficiency through harnessing endogenous indicator for PF reversal.
Reversible Carrier Modulation in InP Nanolasers by Ionic Liquid Gating with Low Energy Consumption
Authors: Wu Chia‐Hung , Chen Chi‐Wen , Shen Hung‐Jung , Chuang Hsiang‐Yu , Tan Hark Hoe , Jagadish Chennupati , Lu Tien‐Chang , Ishii Satoshi , Chen Kuo‐Ping
Published: December 2024

Nanoscale light sources are demanded vigorously due to rapid development in photonic integrated circuits (PICs). III‐V semiconductor nanowire (NW) lasers have manifested themselves as indispensable components in this field, associated with their extremely compact footprint and ultra‐high optical gain within the 1D cavity. In this study, the carrier concentrations of indium phosphide (InP) NWs are actively controlled to modify their emissive properties at room temperature. The InP NW lasers can achieve repetitive switching between photoluminescence (PL) and lasing with an extinction ratio of 22‐fold by applying a gate voltage of 3 V using ionic liquid (IL) as a dielectric layer. IL brings forth ultra‐high capacitance due to the nanometer‐wide electric double layer (EDL) between interfaces, mapping out gating efficiency of ≈100‐fold compared to the conventional bottom gate configurations. This IL‐embedded nanolaser device can be a promising platform for the advanced integrated nanophotonic system.
Pulse Dynamics in Reduced Graphene Oxide Electrolyte‐Gated Transistors: Charge Memory Effects and Mechanisms Governing the Ion‐To‐Electron Transduction
Authors: Selmi Guilherme Segolin , Lourenço Neto Eduardo Rodrigues , Lelis Gabrielle Coelho , Okazaki Anderson Kenji , Riul Antonio , Braunger Maria Luisa , de Oliveira Rafael Furlan
Published: December 2024

Electrolyte‐gated transistors (EGTs) are widely employed in bioelectronics due to their ability to bridge ionic and electronic phenomena in a single device. Among potential materials, reduced graphene oxide (rGO) has gained significant attention due to its ambipolar current response, quantum capacitance, and tunable conductivity. However, the rGO EGT dynamic behavior remains significantly unexplored. Here, the time‐dependent response of rGO EGTs is systematically investigated under gate voltage pulsing across different time scales (10 ms to 40 s) and amplitudes (up to |±0.8 V|). Significant charge memory is observed, particularly for long (40 s) pulses at 0.8 V, with effects also evident for shorter (1 s) and weaker stimuli (0.6 V). Multiple low‐level (0.1 V) fast pulsing (100 ms) further demonstrate charge retention post‐stimulation. All these characteristics are attributed to a complex interplay between ion entrapment within the rGO film, electrical double‐layer formation, and charge transfer processes. The stability of rGO EGTs under prolonged bias stress is also examined, aiming to contribute to the development of more robust devices. These findings revealed the complex role of electrolyte ions and electronic carriers governing the ion‐to‐electron transduction and charge memory effects in rGO EGTs, contributing to the advancement of the next‐generation bioelectronic devices.
A Homozygous MYH1 Variant Underlies Autosomal Recessive Isolated Recurrent Rhabdomyolysis
Authors: Uctepe Eyyup , Mancılar Hanifenur , Esen Fatma Nisa , Unverengil Gokcen Gundogdu , Vona Barbara , Yesilyurt Ahmet
Published: December 2024

Rhabdomyolysis is a severe condition involving the breakdown of skeletal muscle fibers, leading to the release of muscle components into the bloodstream, which can lead to potential complications such as acute kidney injury and electrolyte imbalances. The etiology of rhabdomyolysis is multifactorial, encompassing traumatic, exertional, metabolic, infectious, toxic, and genetic causes. Genetic causes, including variants in LPIN1, RYR1, and CACNA1S, are increasingly recognized as significant contributors to recurrent rhabdomyolysis. MYH1 has recently been identified as a candidate gene for recurrent rhabdomyolysis with limited evidence originating from a single patient. In this report, we describe a 35‐year‐old male, born to consanguineous parents, who presented with recurrent rhabdomyolysis attacks, beginning at age 28, characterized by muscle pain, weakness, and episodes of acute kidney injury requiring dialysis. During attacks, the patient exhibited remarkably elevated markers of muscle breakdown and mildly elevated creatine kinase levels between episodes. A muscle biopsy revealed non‐specific myopathic changes. Exome sequencing analysis was carried out and revealed a novel homozygous variant (NM_005963.4: c.1825G>A [p.Val609Met]) in MYH1 segregating in a manner compatible with an autosomal recessive pattern. In summary, this case provides confirmatory support for the role of pathogenic MYH1 variants in the pathogenesis of recurrent rhabdomyolysis and emphasizes the importance of comprehensive genetic testing in patients with unexplained recurrent episodes of muscle breakdown. Further cases are necessary to fully elucidate the genotypic and phenotypic spectrum of MYH1‐related muscle disorders.
C−H Methylthiolation/d3‐Methylthiolation of Pyrazole Skeleton via Interrupted Pummerer Reaction
Authors: Shi Haofeng , Sun Fengxia , Wu Jialiang , He Jiaxin , Sun Yuli , Du Yunfei
Published: December 2024

The reaction of a series of pyrazole derivatives with DMSO/ ‐DMSO‐d6 and thionyl chloride conveniently afforded the 4‐thiolated pyrazole products under metal‐free conditions. This C−H functionalization/elelctrophilic thiolation process is postulated to involve the in situ generation of the electrophilic hypochlorothioite via interrupted Pummerer reaction, followed with the electrophilic methylthiolation of pyrazole skeleton.
An Unconventional Redox‐Neutral Regioselective Iodoamination of Allenamides
Authors: Tian Zhe , Zeng Zhaoxuan , Xie Hongqiang , Liu Qing , Yan Fachao , Liu Hui
Published: December 2024

A novel unconventional redox‐neutral regioselective iodoamination of allenamides was developed. In the absence of metal catalyst, base and oxidant, the selective iodoamination of allenamides was achieved by using iodide salt in combination with morpholine/imidazole. The Iodide‐substituted Z‐enamides were synthesized under mild reaction conditions, and the products were stable and highly amenable to further modification.