bluuebunny/crossref_metadata_2025 huggingface dataset:
Monocyte-derived transcriptomes explain the ineffectiveness of abatacept in rheumatoid arthritis
Authors: Iwasaki Takeshi , Watanabe Ryu , Ito Hiromu , Fujii Takayuki , Ohmura Koichiro , Yoshitomi Hiroyuki , Murata Koichi , Murakami Kosaku , Onishi Akira , Tanaka Masao , Matsuda Shuichi , Matsuda Fumihiko , Morinobu Akio , Hashimoto Motomu
Published: January 2024

Background

The biological mechanisms underlying the differential response to abatacept in patients with rheumatoid arthritis (RA) are unknown. Here, we aimed to identify cellular, transcriptomic, and proteomic features that predict resistance to abatacept in patients with RA.

Methods

Blood samples were collected from 22 RA patients treated with abatacept at baseline and after 3 months of treatment. Response to treatment was defined by the European League Against Rheumatism (EULAR) response criteria at 3 months, and seven patients were classified as responders and the others as non-responders. We quantified gene expression levels by RNA sequencing, 67 plasma protein levels, and the expression of surface molecules (CD3, 19, and 56) by flow cytometry. In addition, three gene expression data sets, comprising a total of 27 responders and 50 non-responders, were used to replicate the results.

Results

Among the clinical characteristics, the number of monocytes was significantly higher in the non-responders before treatment. Cell type enrichment analysis showed that differentially expressed genes (DEGs) between responders and non-responders were enriched in monocytes. Gene set enrichment analysis, together with single-cell analysis and deconvolution analysis, identified that Toll-like receptor 5 (TLR5) and interleukin-17 receptor A (IL17RA) pathway in monocytes was upregulated in non-responders. Hepatocyte growth factor (HGF) correlated with this signature showed higher concentrations in non-responders before treatment. The DEGs in the replication set were also enriched for the genes expressed in monocytes, not for the TLR5 and IL17RA pathway but for the oxidative phosphorylation (OXPHOS) pathway.

Conclusions

Monocyte-derived transcriptomic features before treatment underlie the differences in abatacept efficacy in patients with RA. The pathway activated in monocytes was the TLR5 and IL17RA-HGF signature in the current study, while it was the OXPHOS pathway in the replication set. Elevated levels of HGF before treatment may serve as a potential biomarker for predicting poor responses to abatacept. These findings provide insights into the biological mechanisms of abatacept resistance, contributing valuable evidence for stratifying patients with RA.
Clinical characteristics of hypertrophic cranial pachymeningitis in granulomatosis with polyangiitis: a retrospective single-center study in China
Authors: Chen Yiran , Gou Lijuan , Wang Li , Qian Min , Wu Qingjun , Zheng Wenjie , Li Mengtao , Zeng Xiaofeng , Zhang Fengchun
Published: January 2024

Background

Hypertrophic cranial pachymeningitis (HCP) is uncommon but a poorly understood complication of granulomatosis with polyangiitis (GPA).

Objectives

We conducted this retrospective study to elucidate the clinical characteristics and factors independently associated with granulomatosis with polyangiitis (GPA) complicated by hypertrophic cranial pachymeningitis (HCP) in China.

Methods

We collected the medical records of 78 patients diagnosed with GPA who were admitted to the inpatient department of Peking Union Medical College Hospital between January 2003 and September 2021. Clinical features, laboratory and radiological findings, and Birmingham Vasculitis Activity Scores (excluding meningitis score) were recorded. A binary logistic regression analysis was performed to analyze factors independently associated with GPA-related HCP.

Results

Headache (100%) and cranial nerve palsy (61.5%) were common manifestations of HCP. Compared to 52 GPA patients without HCP, 26 patients with HCP required more time from initial symptoms to diagnosis, with a lower ratio of pulmonary and renal involvement, a higher ratio of myeloperoxidase–antineutrophil cytoplasmic antibody (MPO-ANCA) positivity, conductive or sensorineural hearing loss, mastoiditis, and decreased vision or sudden visual loss. Binary logistic regression analysis indicated that proteinase 3–antineutrophil cytoplasmic antibody (PR3-ANCA) negativity (OR 10.698, p = 0.001), conductive or sensorineural hearing loss (OR 10.855, p = 0.005), and decreased vision or sudden visual loss (OR 8.647, p = 0.015) were significantly associated with GPA-related HCP. Of the 26 patients, 18 received methylprednisolone pulse treatment, and 18 received intrathecal injections of dexamethasone and methotrexate.

Conclusions

HCP was a severe manifestation of GPA in our study. Independent factors associated with the occurrence of HCP in patients with GPA included PR3-ANCA negativity, conductive or sensorineural hearing loss, and decreased vision or sudden visual loss. Furthermore, GPA-related HCP was associated with higher disease activity, requiring more intensive treatments.
Evaluating the reliability of the athlete sleep behavior questionnaire (ASBQ): a meta-analysis of Cronbach’s alpha and intraclass correlation coefficient
Authors: Trabelsi Khaled , Saif Zahra , Driller Matthew W , Vitiello Michael V. , Jahrami Haitham
Published: January 2024

Background

The Athlete Sleep Behavior Questionnaire (ASBQ) was designed to identify maladaptive sleep practices among athletes. The aim of this meta-analysis was to evaluate the internal consistency and the test-retest reliability coefficients of the ASBQ.

Methods

A systematic search across 10 databases from inception of the ASBQ to August 2023 was performed. Publications that reported estimates of internal consistency and/or test-retest reliability of the ASBQ were included. A random-effects model was employed to estimate the overall reliability measures of the ASBQ.

Results

Meta-analytic results demonstrated a good level of internal consistency within the ASBQ, evidenced by a Cronbach’s alpha of 0.73 (95% CI: 0.63 to 0.80). This suggests a modest correlation among the questionnaire items, supporting its reliability as an effective measure of sleep behavior. In terms of test-retest reliability, our meta-analysis revealed a very good degree of consistency (ICC = 0.88; 95% CI: 0.87 to 0.89), suggesting that the ASBQ can serve as an instrument for monitoring and evaluating changes in athletes’ sleep behavior over time. No evidence of publication bias was identified.

Conclusion

While the ASBQ demonstrates a moderate level of internal consistency, its test-retest reliability suggests that it can serve as an instrument for longitudinal assessments of athletes’ sleep behavior. Future studies focusing on refining the ASBQ to optimize its internal consistency and validate its applicability across diverse athletic populations are warranted.
Identification of transcriptional networks controlling leaf sheath growth in Sorghum bicolor
Authors: De Riseis Samuel , Harmon Frank G.
Published: January 2024

Objectives

The objective of this data set was to identify transcriptional networks that control elongation of seedling leaf sheaths in the C4 grass Sorghum bicolor. One motivation was that leaf sheaths are a primary constituent of stems in grass seedlings; therefore, genes that control growth of this organ are important contributors to successful transition from the seedling stage to the mature plant stage and, ultimately, crop success. Since diurnal rhythms contribute to regulation of signaling networks responsible for growth, a time course representing the late afternoon and early evening was anticipated to pinpoint important control genes for stem growth. Ultimately, the expected outcome was discovery of transcript networks that integrate internal and external signals to fine tune leaf sheath growth and, consequently, plant height.

Data description

The data set is RNAseq profiling of upper leaf sheaths collected from wild type Sorghum bicolor (BTx623 line) plants at four-hour intervals from 12.5 h after dawn to 20 h after dawn. Global transcript levels in leaves were determined by deep sequencing of mRNA from four individual seedlings at each time point. This data set contains sequences representing the spectrum of mRNAs from individual genes. This data set enables detection of significant changes in gene-level expression caused by the progression of the day from late afternoon to the middle of the night. This data set is useful to identify gene expression networks regulating growth in the leaf sheath, an organ that is a major contributor to the sorghum seedling stem and defines seedling height.
Unraveling the intercellular communication disruption and key pathways in Alzheimer’s disease: an integrative study of single-nucleus transcriptomes and genetic association
Authors: Liu Andi , Fernandes Brisa S. , Citu Citu , Zhao Zhongming
Published: January 2024

Background

Recently, single-nucleus RNA-seq (snRNA-seq) analyses have revealed important cellular and functional features of Alzheimer's disease (AD), a prevalent neurodegenerative disease. However, our knowledge regarding intercellular communication mediated by dysregulated ligand-receptor (LR) interactions remains very limited in AD brains.

Methods

We systematically assessed the intercellular communication networks by using a discovery snRNA-seq dataset comprising 69,499 nuclei from 48 human postmortem prefrontal cortex (PFC) samples. We replicated the findings using an independent snRNA-seq dataset of 56,440 nuclei from 18 PFC samples. By integrating genetic signals from AD genome-wide association studies (GWAS) summary statistics and whole genome sequencing (WGS) data, we prioritized AD-associated Gene Ontology (GO) terms containing dysregulated LR interactions. We further explored drug repurposing for the prioritized LR pairs using the Therapeutic Targets Database.

Results

We identified 190 dysregulated LR interactions across six major cell types in AD PFC, of which 107 pairs were replicated. Among the replicated LR signals, we found globally downregulated communications in the astrocytes-to-neurons signaling axis, characterized, for instance, by the downregulation ofAPOE-related and Calmodulin (CALM)-related LR interactions and their potential regulatory connections to target genes. Pathway analyses revealed 44 GO terms significantly linked to AD, highlighting Biological Processes such as ‘amyloid precursor protein processing’ and ‘ion transmembrane transport,’ among others. We prioritized several drug repurposing candidates, such as cromoglicate, targeting the identified dysregulated LR pairs.

Conclusions

Our integrative analysis identified key dysregulated LR interactions in a cell type-specific manner and the associated GO terms in AD, offering novel insights into potential therapeutic targets involved in disrupted cell–cell communication in AD.
Metabolic switching, growth kinetics and cell yields in the scalable manufacture of stem cell-derived insulin-producing cells
Authors: Iworima Diepiriye G. , Baker Robert K. , Ellis Cara , Sherwood Chris , Zhan Lisa , Rezania Alireza , Piret James M. , Kieffer Timothy J.
Published: January 2024

Background

Diabetes is a disease affecting over 500 million people globally due to insulin insufficiency or insensitivity. For individuals with type 1 diabetes, pancreatic islet transplantation can help regulate their blood glucose levels. However, the scarcity of cadaveric donor islets limits the number of people that could receive this therapy. To address this issue, human pluripotent stem cells offer a potentially unlimited source for generating insulin-producing cells through directed differentiation. Several protocols have been developed to make stem cell-derived insulin-producing cells. However, there is a lack of knowledge regarding the bioprocess parameters associated with these differentiation protocols and how they can be utilized to increase the cell yield.

Methods

We investigated various bioprocess parameters and quality target product profiles that may influence the differentiation pipeline using a seven-stage protocol in a scalable manner with CellSTACKs and vertical wheel bioreactors (PBS-Minis).

Results

Cells maintained > 80% viability through all stages of differentiation and appropriately expressed stage-specific markers. During the initial four stages leading up to the development of pancreatic progenitors, there was an increase in cell numbers. Following pancreatic progenitor stage, there was a gradual decrease in the percentage of proliferative cells, as determined by Ki67 positivity, and a significant loss of cells during the period of endocrine differentiation. By minimizing the occurrence of aggregate fusion, we were able to enhance cell yield during the later stages of differentiation. We suggest that glucose utilization and lactate production are cell quality attributes that should be considered during the characterization of insulin-producing cells derived from stem cells. Our findings also revealed a gradual metabolic shift from glycolysis, during the initial four stages of pancreatic progenitor formation, to oxidative phosphorylation later on during endocrine differentiation. Furthermore, the resulting insulin-producing cells exhibited a response to several secretagogues, including high glucose.

Conclusion

This study demonstrates process parameters such as glucose consumption and lactate production rates that may be used to facilitate the scalable manufacture of stem cell-derived insulin-producing cells.
Pan PPAR agonist stimulation of induced MSCs produces extracellular vesicles with enhanced renoprotective effect for acute kidney injury
Authors: Kim Hongduk , Lee Seul Ki , Hong Sungok , Park Tae Sub , Kim Jimin , Kim Soo , Kim Tae Min
Published: January 2024

Background

Acute kidney injury (AKI) has a complex pathophysiology and imposes serious health concerns worldwide. Extracellular vesicles (EVs) derived from induced mesenchymal stem cells (iMSCs) have been recognized as novel cell-free therapeutics for various inflammatory and degenerative disorders. In this study, we investigated whether iMSCs stimulated with a pan-peroxisome proliferator-activated receptor (PPAR) agonist could enhance the therapeutic efficacy of EVs against AKI.

Methods

Human iMSCs were primed with or without lanifibranor, a PPAR agonist for 24 h, and EVs were collected after an additional 24 h. The basic characteristics of EVs were evaluated using cryo-transmission electron microscopy imaging, immunoblot detection of EV markers, nanoparticle tracking analysis, and localization in AKI kidneys. In vitro, the potential of the EVs to promote the growth and survival of HK-2 cells undergoing cisplatin-induced apoptosis and anti-inflammatory effects in M1-polarized THP-1 was compared. Subsequently, AKI was induced in BALB/c mice using cisplatin. After 8 and 24 h of cisplatin treatment, iMSC-EVs or pan-PPAR-iMSC-EVs were injected intravascularly. At 96 h after cisplatin administration, the renoprotective effects of iMSC-EVs or pan-PPAR-iMSC-EVs in inhibiting inflammation and apoptosis were compared using serum biochemistry, histology, immunohistochemistry, and gene expression analysis by qPCR.

Results

Both EV types expressed EV markers and had typical EV morphology, and their localization in the renal tissue was confirmed. The proliferation and survival of HK-2 cells were higher in pan-PPAR-iMSC-EVs than those in iMSC-EVs. In M1-polarized THP-1 cells, the reduction in the mRNA expression of inflammatory cytokines was more significant in pan-PPAR-iMSC-EVs than that in iMSC-EVs. In the mouse model of cisplatin-induced AKI, pan-PPAR-iMSC-EVs markedly enhanced renoprotective effects compared to iMSC-EVs. Specifically, pan-PPAR-iMSC-EVs reduced tissue inflammation, immune cell infiltration, and apoptosis. Pan-PPAR-iMSC-EVs also increased renal capillary density.

Conclusion

Priming iMSCs with a PPAR agonist significantly improved the therapeutic potential of EVs by reducing inflammation and apoptosis. The reported strategy may contribute to the development of a novel cell-free option for AKI treatment.

Trial registration: Not applicable.
Exosome-mediated repair of spinal cord injury: a promising therapeutic strategy
Authors: Yu Tong , Yang Li-Li , Zhou Ying , Wu Min-Fei , Jiao Jian-Hang
Published: January 2024

Spinal cord injury (SCI) is a catastrophic injury to the central nervous system (CNS) that can lead to sensory and motor dysfunction, which seriously affects patients' quality of life and imposes a major economic burden on society. The pathological process of SCI is divided into primary and secondary injury, and secondary injury is a cascade of amplified responses triggered by the primary injury. Due to the complexity of the pathological mechanisms of SCI, there is no clear and effective treatment strategy in clinical practice. Exosomes, which are extracellular vesicles of endoplasmic origin with a diameter of 30–150 nm, play a critical role in intercellular communication and have become an ideal vehicle for drug delivery. A growing body of evidence suggests that exosomes have great potential for repairing SCI. In this review, we introduce exosome preparation, functions, and administration routes. In addition, we summarize the effect and mechanism by which various exosomes repair SCI and review the efficacy of exosomes in combination with other strategies to repair SCI. Finally, the challenges and prospects of the use of exosomes to repair SCI are described.
Switching of hypertrophic signalling towards enhanced cardiomyocyte identity and maturity by a GATA4-targeted compound
Authors: Pohjolainen Lotta , Kinnunen Sini M. , Auno Samuli , Kiriazis Alexandros , Pohjavaara Saana , Kari-Koskinen Julia , Zore Matej , Jumppanen Mikael , Yli-Kauhaluoma Jari , Talman Virpi , Ruskoaho Heikki , Välimäki Mika J.
Published: January 2024

Background

The prevalence of heart failure is constantly increasing, and the prognosis of patients remains poor. New treatment strategies to preserve cardiac function and limit cardiac hypertrophy are therefore urgently needed. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly used as an experimental platform for cardiac in vitro studies. However, in contrast to adult cardiomyocytes, hiPSC-CMs display immature morphology, contractility, gene expression and metabolism and hence express a naive phenotype that resembles more of a foetal cardiomyocyte.

Methods

A library of 14 novel compounds was synthesized in-house and screened for GATA4-NKX2-5 reporter activity and cellular toxicity. The most potent compound, 3i-1262, along with previously reported GATA4-acting compounds, were selected to investigate their effects on hypertrophy induced by endothelin-1 or mechanical stretch. Morphological changes and protein expression were characterized using immunofluorescence staining and high-content analysis. Changes in gene expression were studied using qPCR and RNA sequencing.

Results

The prototype compound 3i-1262 inhibited GATA4-NKX2-5 synergy in a luciferase reporter assay. Additionally, the isoxazole compound 3i-1262 inhibited the hypertrophy biomarker B-type natriuretic peptide (BNP) by reducing BNP promoter activity and proBNP expression in neonatal rat ventricular myocytes and hiPSC-CMs, respectively. Treatment with 3i-1262 increased metabolic activity and cardiac troponin T expression in hiPSC-CMs without affecting GATA4 protein levels. RNA sequencing analysis revealed that 3i-1262 induces gene expression related to metabolic activity and cell cycle exit, indicating a change in the identity and maturity status of hiPSC-CMs. The biological processes that were enriched in upregulated genes in response to 3i-1262 were downregulated in response to mechanical stretch, and conversely, the downregulated processes in response to 3i-1262 were upregulated in response to mechanical stretch.

Conclusions

There is currently a lack of systematic understanding of the molecular modulation and control of hiPSC-CM maturation. In this study, we demonstrated that the GATA4-interfering compound 3i-1262 reorganizes the cardiac transcription factor network and converts hypertrophic signalling towards enhanced cardiomyocyte identity and maturity. This conceptually unique approach provides a novel structural scaffold for further development as a modality to promote cardiomyocyte specification and maturity.
Nodal solutions for Neumann systems with gradient dependence
Authors: Saoudi Kamel , Alzahrani Eadah , Repovš Dušan D.
Published: January 2024

We consider the following convective Neumann systems: $$ ( \mathrm{S} ) \quad \textstyle\begin{cases} -\Delta _{p_{1}}u_{1}+ \frac{ \vert \nabla u_{1} \vert ^{p_{1}}}{u_{1}+\delta _{1} }=f_{1}(x,u_{1},u_{2}, \nabla u_{1},\nabla u_{2}) & \text{in } \Omega , \\ -\Delta _{p_{2}}u_{2}+ \frac{ \vert \nabla u_{2} \vert ^{p_{2}}}{u_{2}+\delta _{2} }=f_{2}(x,u_{1},u_{2}, \nabla u_{1},\nabla u_{2}) & \text{in } \Omega , \\ \vert \nabla u_{1} \vert ^{p_{1}-2}\frac{\partial u_{1}}{\partial \eta }=0= \vert \nabla u_{2} \vert ^{p_{2}-2}\frac{\partial u_{2}}{\partial \eta } & \text{on } \partial \Omega ,\end{cases} $$
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Timed-release encryption anonymous interaction protocol based on smart contract
Authors: Yuan Ke , Wang Zilin , Chen Keyan , Zhou Bingcai , Li Zheng , Jia Chunfu
Published: January 2024

Timed-release encryption (TRE) is a cryptographic primitive that can control the decryption time and has significant application value in time-sensitive scenarios. To solve the reliability issue of nodes in existing TRE anonymous interaction schemes, we propose a blockchain-based TRE protocol for anonymous query time trapdoors. In our protocol, the recipient divides the encrypted trapdoor request information intonciphertext fragments using secret sharing technology near the decryption time, and employs the idea of onion routing to perform layer-by-layer encryption, creating onion-type data transmitted through middlemen selected from the smart contract. After receiving the ciphertext fragments, the time server integrates them to obtain the trapdoor request information and returns the corresponding time trapdoor to the recipient. This allows the recipient to query any time trapdoor anonymously. Our protocol provides a normative design for the smart contract and specific constraints on the participants’ behavior. Compared with the related anonymous query trapdoor schemes, our protocol improves the probability of successful queries. Security analysis shows that our protocol can resist release-ahead attack, interruption attack, eavesdropping attack, and replacement attack. Performance analysis shows that our protocol outperforms related protocols regarding anonymity, efficiency, and flexibility, achieving highly efficient anonymous interactions. Finally, we conducted an experiment in the EthereumRinkebytest network. For the settings of ciphertext fragment number$$n=3$$n=3and ciphertext fragment threshold$$t=2$$t=2, the gas consumption for a user to execute the contract was $5.66, which was higher than the contract cost of related schemes, but the contract execution cost was within an acceptable range.
Enhancing trust transfer in supply chain finance: a blockchain-based transitive trust model
Authors: Shu Chang , Chen Yuling , Tan Chaoyue , Luo Yun , Dou Hui
Published: January 2024

Artificial intelligence and blockchain technology have become indispensable in the era of the digital economy, particularly in the field of financial financing. However, when it comes to supply chain finance (SCF), existing models primarily focus on risk identification and credit evaluation, neglecting the critical aspects of trust transfer continuity and reliability within the chain. To address this issue, this paper proposes a blockchain-based transitive trust model for SCF, which ensures seamless trust transfer from core enterprises to bottom suppliers during financing enterprise credit evaluation. The model utilizes multi-layer metrics to calculate the comprehensive trust value of underlying suppliers, serving as the basis for credit delivery. Additionally, the model stores transitive signature receivable warrants on the blockchain and utilizes splittable delivery of warrants to underlying suppliers. The model’s rationality and correctness are verified through experimental analysis, with results demonstrating that the transitive trust model enhances Small and Medium-Sized Enterprises’ (SMEs) trust at the bottom of the supply chain, thus alleviating financing difficulties for SMEs.
“Cigarettes play the equalizer”: discrimination experiences and readiness to quit cigarette smoking among African Americans experiencing homelessness: a qualitative analysis
Authors: Jones-Patten Alexandria , Shin Sanghyuk S. , Nyamathi Adeline , Bounds Dawn
Published: January 2024

Background

Approximately 70–80% of people experiencing homelessness in the United States use tobacco. Smoking cessation programs specifically for this population have been found to be less effective for African American participants. The purpose of this study was to explore discrimination experiences and their impact on smoking habits and readiness to quit cigarette smoking while experiencing homelessness.

Methods

In the qualitative phase of this mixed methods study, five focus groups were conducted for African Americans residing in a homeless shelter in Skid Row, Los Angeles, CA. Using a semi-structured interview guide, we asked participants about discrimination experiences, how smoking habits were impacted by these experiences, and tools needed to successfully abstain from cigarette smoking. Qualitative descriptive content analysis was used to explore discrimination experiences and its association with readiness to quit cigarette smoking.

Results

Of the 17 participants, 14 (82.4%) were male, and the average age was 46.8 years. Using a qualitative In Vivo coding method, three themes were revealed: “Experiencing Discrimination while Black”, “The Psychosocial Fabric—Why Quitting Cigarette Smoking is a Challenge”, and “The Lesser of Two Evils—Choosing to Smoke over More Harmful Options.” Participants discussed working in the blue-collar workforce while Black, identifying as a double minority, smoking to cope with stress, early exposure to cigarettes, smoking being a central part of one’s belonging to a group, and the legality of cigarette smoking.

Discussion

Our findings show that African Americans experiencing homelessness (1) may experience discrimination in multiple settings, regardless of housing status, (2) could have grown up around cigarette smoking and remain surrounded by it while experiencing homelessness, and (3) may experience a calming effect with smoking, which slows some from reacting negatively to adverse situations.

Conclusion

Barriers to successfully abstaining from smoking are multifactorial among African Americans experiencing homelessness and should be addressed individually. Future research should explore the cultural tailoring of interventions that support cessation efforts unique to minoritized populations to improve smoking cessation programs offered to this population.
A literature review and meta-analysis of the optimal factors study of repetitive transcranial magnetic stimulation in post-infarction aphasia
Authors: Tan Yang , Zhang Lin-Ming , Liang Xing-ling , Xiong Guei-fei , Xing Xuan-lin , Zhang Qiu-juan , Zhang Bing-ran , Yang Zi-bin , Liu Ming-wei
Published: January 2024

Background

The existing literature indicates that repetitive transcranial magnetic stimulation (rTMS) can potentially enhance the prognosis of poststroke aphasia (PSA). Nevertheless, these investigations did not identify the most effective parameters or settings for achieving optimal treatment outcomes. This study involved a meta-analysis aimed to identify the optimal variables for rTMS in treating post-infarction aphasia to guide the use of rTMS in rehabilitating PSA.

Methods

PubMed, Embase, and Cochrane Library databases were searched from inception to May 2023, and articles were reviewed manually using subject words and free words and supplemented with references from the included literature to obtain additional relevant literature. The search terms included “poststroke aphasia” and “repetitive transcranial magnetic stimulation (rTMS)” repetitive transcranial magnetic stimulation. Additionally, a review of the reference lists of previously published systematic reviews identified through the Cochrane Database of Systematic Reviews (search terms: poststroke aphasia, rTMS; restrictions: none) and PubMed (search terms: poststroke aphasia, rTMSs; restrictions: systematic review or meta-analysis) was performed. Information from studies involving different doses of rTMS in PSA was independently screened and extracted by 2 researchers.

Results

This meta-analysis included 387 participants with PSA across 18 randomized controlled trials. The results showed that the total pulse had a trend toward a significant correlation with the treatment effect (P = 0.088), while all other variables did not correlate significantly. When rTMS was not grouped by stimulus parameter and location, our nonlinear results showed that when the total pulses were 40,000 (standardized mean difference (SMD):1.86, 95% credible interval (CrI) 0.50 to 3.33), the pulse/session was 1000 (SMD:1.05, 95% CrI 0.55–1.57), and an RMT of 80% (SMD:1.08, 95% CrI 0.60–1.57) had the best treatment effect. When rTMS was grouped by stimulus parameters and location, our nonlinear results showed that when the total low-frequency (LF)-rTMS-right inferior frontal gyrus (RIFG) pulse was 40,000 (SMD:1.76, 95% CrI:0.36–3.29), the pulse/session was 1000 (SMD:1.06, 95% CrI:0.54–1.59). Optimal results were obtained with an RMT of 80% (SMD:1.14, 95% CrI 0.54 − 1.76).

Conclusions

The optimal treatment effects of rTMS for PSA may be obtained with a total pulse of 40,000, a pulse/session of 1000, and an RMT of 80%. Further rigorous randomized controlled studies are required to substantiate the validity of these results.
Use of machine learning techniques for identifying ischemic stroke instead of the rule-based methods: a nationwide population-based study
Authors: Lim Hyunsun , Park Youngmin , Hong Jung Hwa , Yoo Ki-Bong , Seo Kwon-Duk
Published: January 2024

Background

Many studies have evaluated stroke using claims data; most of these studies have defined ischemic stroke using an operational definition following the rule-based method. Rule-based methods tend to overestimate the number of patients with ischemic stroke.

Objectives

We aimed to identify an appropriate algorithm for identifying stroke by applying machine learning (ML) techniques to analyze the claims data.

Methods

We obtained the data from the Korean National Health Insurance Service database, which is linked to the Ilsan Hospital database (n = 30,897). The performance of prediction models (extreme gradient boosting [XGBoost] or gated recurrent unit [GRU]) was evaluated using the area under the receiver operating characteristic curve (AUROC), the area under precision–recall curve (AUPRC), and calibration curve.

Results

In total, 30,897 patients were enrolled in this study, 3145 of whom (10.18%) had ischemic stroke. XGBoost, a tree-based ML technique, had the AUROC was 94.46% and AUPRC was 92.80%. GRU showed the highest accuracy (99.81%), precision (99.92%) and recall (99.69%).

Conclusions

We proposed recurrent neural network-based deep learning techniques to improve stroke phenotyping. This can be expected to produce rapid and more accurate results than the rule-based methods.
May I come in? A probe into the contributions of self-esteem, teacher support, and critical thinking to anxiety and shyness in language classes
Authors: Li Lei , Heydarnejad Tahereh
Published: January 2024

Many students feel uncomfortable when obliged to communicate in English. Students’ fear of speaking English is influenced by psychological reasons such as the fear of failing, being misunderstood, and making grammatical errors. Students’ active participation in English class discussions might be hindered by shyness, nervousness, lack of confidence, and motivation. Helping these reserved students gain self-assurance and perfect their spoken English is a top priority for all English language instructors. In the classroom, teachers may use some simple methods to encourage their reserved students to open up and speak English with more ease and confidence. The existing literature on students’ shyness shows that the gap in this realm is great and a critical look is needed. To this end, the current research intended to gauge the effects of self-esteem, teacher support, and critical thinking on anxiety and shyness in language classes. 385 language learners attending English language institutions took part in this research. They were at intermediate and upper intermediate levels. The findings of both confirmatory factor analysis (CFA) and structural equation modeling (SEM) point to the fact that improving students’ self-esteem, teacher support, and critical thinking may have a moderating effect on students ‘anxiety and shyness in language learning. The implications of this inquiry may be advantageous for language learners, language instructors, as well as policymakers.
Pharmacokinetics and pharmacodynamics of perfluoropropane after intra-venous bolus injection of perflutren lipid microsphere injection (DEFINITY®) in healthy Chinese volunteers
Authors: Li Pengfei , Du Ping , Peng Jun , Zhao Zhixia , Li Huiling , Yu Weiyue , Wang Shumin , Liu Lihong
Published: January 2024

Background and objective

Definity is an ultrasound contrast agent consisting of phospholipids-encapsulated perfluoropropane (PFP), also known as perflutren, microspheres, which is initially designed to enhance echocardiographic ultrasound images. With no pharmacologic action, Definity can increase the backscatter of ultrasound resulting enhanced ultrasound signals. The objective of this study was to determine the pharmacokinetics (PKs), Pharmacodynamics (PDs) and safety of Definity in healthy male and female Chinese volunteers.

Methods

A simple GC-MS method was developed and applied to simultaneously quantify PFP both in human whole blood and in expired air using Perfluorobutane (PFB) as internal standard. Meanwhile, the blood microbubble Doppler intensities were continuously monitored as companion PDs by a Doppler ultrasonography system using a non-imaging method.

Results

After intravenous infusion of 10 µL/kg of PFP within 30 seconds, the mean AUClast of the pharmacokinetic analysis set was 0.000653 (uL/mL)*min, the average AUC∞ was 0.001051 (uL/mL)*min. The main coefficient of variation of parameters were within 30%. In this trial, the blood drug concentration of female subjects was lower than that of males. Female Cmax, AUClast and AUC∞ were lower than males’, Tmax and t1/2 was close to males’, Vss and CL were slightly higher than males’. The concentration of PFP in the expired air of the subject reached the maximum value 1–2 min after administration and the PFP accumulation curve in the expired air began to become flat at 9.5–11 min after administration. The PFP in the expired air at the last sampling point of most subjects was still measurable. The results of the analysis showed that female subjects had slightly more and faster PFP excretion via the lungs than males. The change of blood drug concentration in this trial was related to the change process of Doppler signal intensity. The trend of the two was close, but the peak time of blood drug concentration was slightly delayed compared with the peak time of the Doppler signal intensity. The results showed that female tmax−pd, t10 was earlier than male, and women have lower AUCpd than men.

Conclusion

The pharmacokinetics and pharmacodynamics of Definity in blood and expired air were systematically evaluated for the first time in this study. The PK/PD analysis results of this trial showed that the change of blood concentration was related to the change process of Doppler signal intensity, the trend of the two was close and expired air are the main excretion pathways of Definity. Definity was well tolerated by all subjects in the trial.

Trial registration

This study was registered on 08 December 2017 at the Chinese Clinical Trial Registry (CTR20171087).
Automatic damage identification of Sanskrit palm leaf manuscripts with SegFormer
Authors: Wang Yue , Wen Ming , Zhou Xiao , Gao Feng , Tian Shuai , Jue Dan , Lu Hongmei , Zhang Zhimin
Published: January 2024

Palm leaf manuscripts (PLMs) are of great importance in recording Buddhist Scriptures, medicine, history, philosophy, etc. Some damages occur during the use, spread, and preservation procedure. The comprehensive investigation of Sanskrit PLMs is a prerequisite for further conservation and restoration. However, current damage identification and investigation are carried out manually. They require strong professional skills and are extraordinarily time-consuming. In this study, PLM-SegFormer is developed to provide an automated damage segmentation for Sanskrit PLMs based on the SegFormer architecture. Firstly, a digital image dataset of Sanskrit PLMs (the PLM dataset) was obtained from the Potala Palace in Tibet. Then, the hyperparameters for pre-processing, model training, prediction, and post-processing phases were fully optimized to make the SegFormer model more suitable for the PLM damage segmentation task. The optimized segmentation model reaches 70.1% mHit and 51.2% mIoU. The proposed framework automates the damage segmentation of 10,064 folios of PLMs within 12 h. The PLM-SegFormer framework will facilitate the preservation state survey and record of the Palm-leaf manuscript and be of great value to the subsequent preservation and restoration. The source code is available at https://github.com/Ryan21wy/PLM_SegFormer.
Plant disease detection and classification techniques: a comparative study of the performances
Authors: Demilie Wubetu Barud
Published: January 2024

One of the essential components of human civilization is agriculture. It helps the economy in addition to supplying food. Plant leaves or crops are vulnerable to different diseases during agricultural cultivation. The diseases halt the growth of their respective species. Early and precise detection and classification of the diseases may reduce the chance of additional damage to the plants. The detection and classification of these diseases have become serious problems. Farmers’ typical way of predicting and classifying plant leaf diseases can be boring and erroneous. Problems may arise when attempting to predict the types of diseases manually. The inability to detect and classify plant diseases quickly may result in the destruction of crop plants, resulting in a significant decrease in products. Farmers that use computerized image processing methods in their fields can reduce losses and increase productivity. Numerous techniques have been adopted and applied in the detection and classification of plant diseases based on images of infected leaves or crops. Researchers have made significant progress in the detection and classification of diseases in the past by exploring various techniques. However, improvements are required as a result of reviews, new advancements, and discussions. The use of technology can significantly increase crop production all around the world. Previous research has determined the robustness of deep learning (DL) and machine learning (ML) techniques such as k-means clustering (KMC), naive Bayes (NB), feed-forward neural network (FFNN), support vector machine (SVM), k-nearest neighbor (KNN) classifier, fuzzy logic (FL), genetic algorithm (GA), artificial neural network (ANN), convolutional neural network (CNN), and so on. Here, from the DL and ML techniques that have been included in this particular study, CNNs are often the favored choice for image detection and classification due to their inherent capacity to autonomously acquire pertinent image features and grasp spatial hierarchies. Nevertheless, the selection between conventional ML and DL hinges upon the particular problem, the accessibility of data, and the computational capabilities accessible. Accordingly, in numerous advanced image detection and classification tasks, DL, mainly through CNNs, is preferred when ample data and computational resources are available and show good detection and classification effects on their datasets, but not on other datasets. Finally, in this paper, the author aims to keep future researchers up-to-date with the performances, evaluation metrics, and results of previously used techniques to detect and classify different forms of plant leaf or crop diseases using various image-processing techniques in the artificial intelligence (AI) field.
Can we explain the post-2015 absence of the Chandler wobble?
Authors: Yamaguchi Ryuji , Furuya Masato
Published: January 2024

Recent polar motion data do not show a 6-year beat and indicate the absence of the Chandler wobble (CW), whereas we could observe the 6-year beat even in the 1920-40 s when the CW amplitude was known to be smallest. As a free mode, the CW needs excitation one or more sources that were debated decades ago but are now attributed to the atmosphere, ocean, and possibly land water. Here, we show that the anomaly started in 2015, after which two independent estimates of the atmospheric CW excitation became persistently smaller than before. However, the estimates of the oceanic and land–water contributions are too large, suggesting improved estimates are needed. Taking advantage of the recent CW anomaly, we show that the quality factor of CW is not as high as 100 as previously preferred. Although the CW excitation processes have been assumed random, a termination of near-resonant processes would rather be consistent with the present findings.

Graphical Abstract
Enzyme engineering for functional lipids synthesis: recent advance and perspective
Authors: Guan Ailin , Hou Yue , Yang Run , Qin Jiufu
Published: January 2024

Functional lipids, primarily derived through the modification of natural lipids by various processes, are widely acknowledged for their potential to impart health benefits. In contrast to chemical methods for lipid modification, enzymatic catalysis offers distinct advantages, including high selectivity, mild operating conditions, and reduced byproduct formation. Nevertheless, enzymes face challenges in industrial applications, such as low activity, stability, and undesired selectivity. To address these challenges, protein engineering techniques have been implemented to enhance enzyme performance in functional lipid synthesis. This article aims to review recent advances in protein engineering, encompassing approaches from directed evolution to rational design, with the goal of improving the properties of lipid-modifying enzymes. Furthermore, the article explores the future prospects and challenges associated with enzyme-catalyzed functional lipid synthesis.
Nitric oxide mediates red light-induced perylenequinone production in Shiraia mycelium culture
Authors: Wang Wen Juan , Li Xin Ping , Shen Wen Hao , Huang Qun Yan , Cong Rui Peng , Zheng Li Ping , Wang Jian Wen
Published: January 2024

Perylenequinones (PQs) from bambusicolous Shiraia fungi serve as excellent photosensitizers for photodynamic therapy. However, the lower yield of PQ production in mycelium cultures is an important bottleneck for their clinical application. Light has long been recognized as a pivotal regulatory signal for fungal secondary metabolite biosynthesis. In this study, we explored the role of nitric oxide (NO) in the growth and PQ biosynthesis in mycelium cultures of Shiraia sp. S9 exposed to red light. The continuous irradiation with red light (627 nm, 200 lx) suppressed fungal conidiation, promoted hyphal branching, and elicited a notable increase in PQ accumulation. Red light exposure induced NO generation, peaking to 81.7 μmol/g FW on day 8 of the culture, with the involvement of nitric oxide synthase (NOS)- or nitrate reductase (NR)-dependent pathways. The application of a NO donor sodium nitroprusside (SNP) restored conidiation of Shiraia sp. S9 under red light and stimulated PQ production, which was mitigated upon the introduction of NO scavenger carboxy-PTIO or soluble guanylate cyclase inhibitor NS-2028. These results showed that red light-induced NO, as a signaling molecule, was involved in the regulation of growth and PQ production in Shiraia sp. S9 through the NO-cGMP-PKG signaling pathway. While mycelial H2O2 content exhibited no significant alternations, a transient increase of intracellular Ca2+ and extracellular ATP (eATP) content was detected upon exposure to red light. The generation of NO was found to be interdependent on cytosolic Ca2+ and eATP concentration. These signal molecules cooperated synergistically to enhance membrane permeability and elevate the transcript levels of PQ biosynthetic genes in Shiraia sp. S9. Notably, the combined treatment of red light with 5 μM SNP yielded a synergistic effect, resulting in a substantially higher level of hypocrellin A (HA, 254 mg/L), about 3.0-fold over the dark control. Our findings provide valuable insights into the regulation of NO on fungal secondary metabolite biosynthesis and present a promising strategy involving the combined elicitation with SNP for enhanced production of photoactive PQs and other valuable secondary metabolites in fungi.

Graphical Abstract