bluuebunny/crossref_metadata_2025_split huggingface dataset:
The therapeutic potential of curculigoside in poststroke depression: a focus on hippocampal neurogenesis and mitochondrial function
Authors: Zeng Ning-Xi , Chen Xin , Yang Xiao-Yan , Chen De-sheng , Shen Mei 
Published: July 2024

Abstract

Objectives
To investigate the effects and mechanism of curculigoside against poststroke depression (PSD).

Methods
In vivo, a PSD rat model was created by combining bilateral common carotid artery occlusion and chronic unpredictable mild stress stimulations. After 4-week modeling and intragastrically administration of curculigoside, the effects of curculigoside on behavior, hippocampal neurogenesis, and hippocampal mitochondrial oxidative phosphorylation (OxPhos) were investigated. In vitro, PSD-like primary neural stem cells (NSCs) model was established by oxygen-glucose deprivation/recovery (OGD/R) combing high-corticosterone (CORT) concentration, followed by treatment with curculigoside. The investigation subsequently examined the impact of curculigoside on mitochondrial OxPhos, proliferation, and differentiation of NSCs under OGD/R + CORT conditions.

Key findings
In vivo, PSD rats showed significantly depressive behaviors, dysfunctional neurogenesis in hippocampus, as well as decreased hippocampus adenosine triphosphate (ATP) levels, reduced electron transport chain complexes activity, and downregulates mitochondrial transcription factor A (TFAM) and PPAR-gamma coactivator 1 alpha (PGC-1α) expression in hippocampus. In vitro, OGD/R +CORT significantly injured the proliferation and differentiation, as well as impaired the mitochondrial OxPhos in NSCs. Curculigoside treatment was effective in improving these abnormal changes.

Conclusion
Curculigoside may repair hippocampal neurogenesis in PSD rats by enhancing hippocampal mitochondrial OxPhos, and has shown a great potential for anti-PSD.
A prediction method for the individual serum concentration and therapeutic effect for optimizing adalimumab therapy in inflammatory bowel disease
Authors: Kimura Koji , Yoshida Atsushi 
Published: July 2024

Abstract

Objectives
Adalimumab (ADM) therapy is effective for inflammatory bowel disease (IBD), but a significant number of IBD patients lose response to ADM. Thus, it is crucial to devise methods to enhance ADM’s effectiveness. This study introduces a strategy to predict individual serum concentrations and therapeutic effects to optimize ADM therapy for IBD during the induction phase.

Methods
We predicted the individual serum concentration and therapeutic effect of ADM during the induction phase based on pharmacokinetic and pharmacodynamic (PK/PD) parameters calculated using the empirical Bayesian method. We then examined whether the predicted therapeutic effect, defined as clinical remission or treatment failure, matched the observed effect.

Results
Data were obtained from 11 IBD patients. The therapeutic effect during maintenance therapy was successfully predicted at 40 of 47 time points. Moreover, the predicted effects at each patient’s final time point matched the observed effects in 9 of the 11 patients.

Conclusion
This is the inaugural report predicting the individual serum concentration and therapeutic effect of ADM using the Bayesian method and PK/PD modelling during the induction phase. This strategy may aid in optimizing ADM therapy for IBD.
Estimating spatially varying health effects of wildland fire smoke using mobile health data
Authors: Wu Lili , Gao Chenyin , Yang Shu , Reich Brian J , Rappold Ana G 
Published: July 2024

Abstract
Wildland fire smoke exposures are an increasing threat to public health, highlighting the need for studying the effects of protective behaviours on reducing health outcomes. Emerging smartphone applications provide unprecedented opportunities to deliver health risk communication messages to a large number of individuals in real-time and subsequently study the effectiveness, but also pose methodological challenges. Smoke Sense, a citizen science project, provides an interactive smartphone app platform for participants to engage with information about air quality, and ways to record their own health symptoms and actions taken to reduce smoke exposure. We propose a doubly robust estimator of the structural nested mean model that accounts for spatially and time-varying effects via a local estimating equation approach with geographical kernel weighting. Moreover, our analytical framework also handles informative missingness by inverse probability weighting of estimating functions. We evaluate the method using extensive simulation studies and apply it to Smoke Sense data to increase the knowledge base about the relationship between health preventive measures and health-related outcomes. Our results show that the protective behaviours’ effects vary over space and time and find that protective behaviours have more significant effects on reducing health symptoms in the Southwest than the Northwest region of the U.S.
Thermodynamics of Alfvénic slow solar wind produced by Alfvénic turbulence
Authors: Lee Hwanhee , Seough Jungjoon , Li Bo , Kim Yeon-Han , Cho Kyung-Suk 
Published: July 2024

ABSTRACT
Alfvén-wave turbulence is known as a plasma heating mechanism associated with the acceleration of fast solar wind, found emanating from open magnetic fields adjacent to coronal holes. In this study, we expand the scope of this mechanism to investigate the thermodynamics of Alfvénic slow solar wind, a phenomenon originating from open fields near a streamer, as observed in recent inner heliospheric missions. We demonstrate a one-dimensional two-fluid model that incorporates three components: (1) low-frequency Alfvén-wave turbulence, serving as the primary dissipation mechanism, (2) a curved magnetic field that reproduces the streamer’s boundary, and (3) the kinetic instabilities to address proton temperature anisotropy. Our findings suggest that this dissipation mechanism can be applied in common to both fast and Alfvénic slow solar winds. We identify the proton-cyclotron instability near the Sun and the oblique and parallel firehose instabilities occurring close to 1 au as crucial factors governing temperature anisotropy. This study contributes to our understanding of the complex thermodynamics of solar winds and provides valuable insights for future space missions.
Re-engineered guide RNA enables DNA loops and contacts modulating repression in E. coli
Authors: Yang Yunshi , Rocamonde-Lago Iris , Shen Boxuan , Berzina Ieva , Zipf Johanna , Högberg Björn 
Published: July 2024

Abstract
RNA serves as information media as well as molecular scaffold in nature and synthetic systems. The single guide RNA (sgRNA) widely applied in CRISPR techniques exemplifies both functions, with a guide region bearing DNA base-pairing information, and a structural motif for Cas9 protein scaffolding. The scaffold region has been modified by fusing RNA aptamers to the tetra-stem loop. The guide region is typically not regarded as a pluggable module as it encodes the essential function of DNA sequence recognition. Here, we investigate a chimera of two sgRNAs, with distinct guide sequences joined by an RNA linker (dgRNA), regarding its DNA binding function and loop induction capability. First, we studied the sequence bi-specificity of the dgRNA and discovered that the RNA linker allows distal parts of double-stranded DNA to be brought into proximity. To test the activity of the dgRNA in organisms, we used the LacZ gene as a reporter and recapitulated the loop-mediated gene inhibition by LacI in E. coli. We found that the dgRNA can be applied to target distal genomic regions with comparable levels of inhibition. The capability of dgRNA to induce DNA contacts solely requires dCas9 and RNA, making it a minimal system to remodel chromosomal conformation in various organisms.
A new approach to RNA synthesis: immobilization of stably and functionally co-tethered promoter DNA and T7 RNA polymerase
Authors: MalagodaPathiranage Kithmie , Banerjee Ruptanu , Martin Craig T 
Published: July 2024

Abstract
Current approaches to RNA synthesis/manufacturing require substantial (and incomplete) purification post-synthesis. We have previously demonstrated the synthesis of RNA from a complex in which T7 RNA polymerase is tethered to promoter DNA. In the current work, we extend this approach to demonstrate an extremely stable system of functional co-tethered complex to a solid support. Using the system attached to magnetic beads, we carry out more than 20 rounds of synthesis using the initial polymerase-DNA construct. We further demonstrate the wide utility of this system in the synthesis of short RNA, a CRISPR guide RNA, and a protein-coding mRNA. In all cases, the generation of self-templated double stranded RNA (dsRNA) impurities are greatly reduced, by both the tethering itself and by the salt-tolerance that local co-tethering provides. Transfection of the mRNA into HEK293T cells shows a correlation between added salt in the transcription reaction (which inhibits RNA rebinding that generates RNA-templated extensions) and significantly increased expression and reduced innate immune stimulation by the mRNA reaction product. These results point in the direction of streamlined processes for synthesis/manufacturing of high-quality RNA of any length, and at greatly reduced costs.
SigAlign: an alignment algorithm guided by explicit similarity criteria
Authors: Bahk Kunhyung , Sung Joohon 
Published: July 2024

Abstract
In biological sequence alignment, prevailing heuristic aligners achieve high-throughput by several approximation techniques, but at the cost of sacrificing the clarity of output criteria and creating complex parameter spaces. To surmount these challenges, we introduce ‘SigAlign’, a novel alignment algorithm that employs two explicit cutoffs for the results: minimum length and maximum penalty per length, alongside three affine gap penalties. Comparative analyses of SigAlign against leading database search tools (BLASTn, MMseqs2) and read mappers (BWA-MEM, bowtie2, HISAT2, minimap2) highlight its performance in read mapping and database searches. Our research demonstrates that SigAlign not only provides high sensitivity with a non-heuristic approach, but also surpasses the throughput of existing heuristic aligners, particularly for high-accuracy reads or genomes with few repetitive regions. As an open-source library, SigAlign is poised to become a foundational component to provide a transparent and customizable alignment process to new analytical algorithms, tools and pipelines in bioinformatics.
Single-mode termination of phage transcriptions, disclosing bacterial adaptation for facilitated reinitiations
Authors: Song Eunho , Han Sun , Uhm Heesoo , Kang Changwon , Hohng Sungchul 
Published: July 2024

Abstract
Bacterial and bacteriophage RNA polymerases (RNAPs) have divergently evolved and share the RNA hairpin-dependent intrinsic termination of transcription. Here, we examined phage T7, T3 and SP6 RNAP terminations utilizing the single-molecule fluorescence assays we had developed for bacterial terminations. We discovered the phage termination mode or outcome is virtually single with decomposing termination. Therein, RNAP is displaced forward along DNA and departs both RNA and DNA for one-step decomposition, three-dimensional diffusion and reinitiation at any promoter. This phage displacement-mediated decomposing termination is much slower than readthrough and appears homologous with the bacterial one. However, the phage sole mode of termination contrasts with the bacterial dual mode, where both decomposing and recycling terminations occur compatibly at any single hairpin- or Rho-dependent terminator. In the bacterial recycling termination, RNA is sheared from RNA·DNA hybrid, and RNAP remains bound to DNA for one-dimensional diffusion, which enables facilitated recycling for reinitiation at the nearest promoter located downstream or upstream in the sense or antisense orientation. Aligning with proximity of most terminators to adjacent promoters in bacterial genomes, the shearing-mediated recycling termination could be bacterial adaptation for the facilitated reinitiations repeated at a promoter for accelerated expression and coupled at adjoining promoters for coordinated regulation.
The RNA helicase DDX39 contributes to the nuclear export of spliceosomal U snRNA by loading of PHAX onto RNA
Authors: Taniguchi Ichiro , Hirose Tetsuro , Ohno Mutsuhito 
Published: July 2024

Abstract
RNA helicases are involved in RNA metabolism in an ATP-dependent manner. Although many RNA helicases unwind the RNA structure and/or remove proteins from the RNA, some can load their interacting proteins onto RNAs. Here, we developed an in vitro strategy to identify the ATP-dependent factors involved in spliceosomal uridine-rich small nuclear RNA (U snRNA) export. We identified the RNA helicase UAP56/DDX39B, a component of the mRNA export complex named the transcription-export (TREX) complex, and its closely related RNA helicase URH49/DDX39A as the factors that stimulated RNA binding of PHAX, an adapter protein for U snRNA export. ALYREF, another TREX component, acted as a bridge between PHAX and UAP56/DDX39B. We also showed that UAP56/DDX39B and ALYREF participate in U snRNA export through a mechanism distinct from that of mRNA export. This study describes a novel aspect of the TREX components for U snRNP biogenesis and highlights the loading activity of RNA helicases.
mRNA-specific readthrough of nonsense codons by antisense oligonucleotides (R-ASOs)
Authors: Susorov Denis , Echeverria Dimas , Khvorova Anastasia , Korostelev Andrei A 
Published: July 2024

AbstractNonsense mutations account for &gt;10% of human genetic disorders, including cystic fibrosis, Alagille syndrome, and Duchenne muscular dystrophy. A nonsense mutation results in the expression of a truncated protein, and therapeutic strategies aim to restore full-length protein expression. Most strategies under development, including small-molecule aminoglycosides, suppressor tRNAs, or the targeted degradation of termination factors, lack mRNA target selectivity and may poorly differentiate between nonsense and normal stop codons, resulting in off-target translation errors. Here, we demonstrate that antisense oligonucleotides can stimulate readthrough of disease-causing nonsense codons, resulting in high yields of full-length protein in mammalian cellular lysate. Readthrough efficiency depends on the sequence context near the stop codon and on the precise targeting position of an oligonucleotide, whose interaction with mRNA inhibits peptide release to promote readthrough. Readthrough-inducing antisense oligonucleotides (R-ASOs) enhance the potency of non-specific readthrough agents, including aminoglycoside G418 and suppressor tRNA, enabling a path toward target-specific readthrough of nonsense mutations in CFTR, JAG1, DMD, BRCA1 and other mutant genes. Finally, through systematic chemical engineering, we identify heavily modified fully functional R-ASO variants, enabling future therapeutic development.
Intraoperative mapping of epileptogenic foci and tumor infiltration in neuro-oncology patients with epilepsy
Authors: Sun Dongqing , Schaft Eline V , van Stempvoort Bibi M , Gebbink Tineke A , van ‘t Klooster Maryse , van Eijsden Pieter , van der Salm Sandra M A , Willem Dankbaar Jan , Zijlmans Maeike , Robe Pierre A 
Published: July 2024

Abstract

Background
Epileptogenesis and glioma growth have a bidirectional relationship. We hypothesized people with gliomas can benefit from the removal of epileptic tissue and that tumor-related epileptic activity may signify tumor infiltration in peritumoral regions. We investigated whether intraoperative electrocorticography (ioECoG) could improve seizure outcomes in oncological glioma surgery, and vice versa, what epileptic activity (EA) tells about tumor infiltration.

Methods
We prospectively included patients who underwent (awake) ioECoG-assisted diffuse-glioma resection through the oncological trajectory. The IoECoG-tailoring strategy relied on ictal and interictal EA (spikes and sharp waves). Brain tissue, where EA was recorded, was assigned for histopathological examination separate from the rest of the tumor. Weibull regression was performed to assess how residual EA and extent of resection (EOR) related to the time-to-seizure recurrence, and we investigated which type of EA predicted tumor infiltration.

Results
Fifty-two patients were included. Residual spikes after resection were associated with seizure recurrence in patients with isocitrate dehydrogenase (IDH) mutant astrocytoma or oligodendroglioma (HR = 7.6[1.4–40.0], P-value = .01), independent from the EOR. This was not observed in IDH-wildtype tumors. All tissue samples resected based on interictal spikes were infiltrated by tumor, even if the MRI did not show abnormalities.

Conclusions
Complete resection of epileptogenic foci in ioECoG may promote seizure control in IDH-mutant gliomas. The cohort size of IDH-wildtype tumors was too limited to draw definitive conclusions. Interictal spikes may indicate tumor infiltration even when this area appears normal on MRI. Integrating electrophysiology guidance into oncological tumor surgery could contribute to improved seizure outcomes and precise guidance for radical tumor resection.
Comparison of subjectively and objectively measured sleep–wake patterns among patients with primary brain tumors
Authors: Kim Youngdeok , Kenyon Jonathan , Kim Jisu , Willis Kelcie D , Lanoye Autumn , Loughan Ashlee R 
Published: July 2024

Abstract

Background
The sleep diary and wrist-worn actigraphy are widely used to assess sleep disturbances in patients with primary brain tumors (PwPBT) in both clinical and research settings. However, their comparability has not been systematically examined. This study aimed to compare the sleep–wake patterns measured using the subjectively measured Consensus Sleep Diary (CSD) and the objectively measured ActiGraph (AG) actigraphy among PwPBT.

Methods
Sleep–wake patterns were assessed through CSD and AG over 14 consecutive nights across 2 occasions among 30 PwPBT. AG data were processed with AG proprietary and open-source GGIR (GGIR-based approach without the aid of sleep log algorithms), both with and without the assistance of CSD. Thirteen sleep parameters covering sleep–wake times, sleep disruptions, sleep durations, and sleep efficiency were compared using equivalency testing, mean absolute percent error (MAPE), and intra-class correlation. The estimated sleep parameters were correlated with perceived sleep quality and compared across the different sleep measures.

Results
Significant between-measure equivalency was claimed for sleep–wake time parameters (P ≤ .05), with acceptable MAPEs (&lt;10%). Sleep disruption parameters such as wake-after-sleep-onset were not statistically equivalent, with a large MAPE (≥10%) between the measures. Sleep efficiency was equivalent, though varied depending on how sleep efficiency was calculated. For most sleep parameters, ICCs were low and unacceptable (&lt;0.50) suggesting incomparability between the measures. Lastly, CSD-derived sleep parameters exhibited a stronger correlation with perceived sleep quality compared to actigraphy measures.

Conclusions
The findings suggest the incomparability of sleep parameters estimated from different measures. Both subjective and objective measures are recommended to better describe sleep health among PwPBT.
Investigating thermal properties of 2D non-layered material using a NEMS-based 2-DOF approach towards ultrahigh-performance bolometer
Authors: Wang Luming , Wu Song , Zhang Zejuan , Zhu Jiankai , Zou Luwei , Xu Bo , Wu Jiaqi , Zhu Junzhi , Xiao Fei , Jiao Chenyin , Pei Shenghai , Qin Jiaze , Zhou Yu , Xia Juan , Wang Zenghui 
Published: July 2024

ABSTRACT
Two-dimensional (2D) non-layered materials in many aspects differ from their layered counterparts, and the exploration of their physical properties has produced many intriguing findings. However, due to challenges in applying existing experimental techniques to such nanoscale samples, their thermal properties have remained largely uncharacterized, hindering further exploration and device application using this promising material system. Here, we demonstrate an experimental study of thermal conduction in β-In2S3, a typical non-layered 2D material, using a resonant nanoelectromechanical systems (NEMS) platform. We devise a new two-degrees-of-freedom technique, more responsive and sensitive than Raman spectroscopy, to simultaneously determine both the thermal conductivity to be 3.7 W m−1 K−1 and its interfacial thermal conductance with SiO2 as 6.4 MW m−2 K−1. Leveraging such unique thermal properties, we further demonstrate a record-high power-to-frequency responsivity of −447 ppm/μW in β-In2S3 NEMS sensors, the best among drumhead NEMS-based bolometers. Our findings offer an effective approach for studying thermal properties and exploring potential thermal applications of 2D non-layered materials.
Perceptions of Smoking Stigma Among African Americans: A Qualitative Study
Authors: Crittendon Denine R , Brecher Alison C , Okere Samantha , Hass Richard , Frasso Rosemary , Brawer Rickie , Zeigler-Johnson Charnita 
Published: July 2024

Abstract

Introduction
African Americans/Blacks (AAB) are at increased risk for morbidity and mortality from smoking-related diseases including lung cancer (LC). Smoking stigma is believed to be a primary barrier to health care-seeking for people who smoke. Previous studies illustrate that perceptions of smoking vary across populations. However, little is known about the prevalence of smoking stigmas among AAB. The purpose of this study was to increase understanding of the perception of cigarette smoking by AAB.

Aims and Methods
We conducted free-listing interviews in which individuals listed all-thoughts and feelings regarding smoking and health-related questions with a convenience sample of eligible AAB adults (n = 58) in the Philadelphia region. Additionally, we collected participant self-reported demographic data. Data were cleaned and the salience of each term was computed using Anthropac. Graphical methods were then used to determine salient responses across groups stratified by gender, age, education, and smoking status.

Results
The sample had a median age of 51 years and was 67.2% female. Most participants had completed college (58.6%) and had never smoked (74.1%). Regarding their perceptions of people who smoke cigarettes, results showed that “smelly,” “health hazard,” and “judgment” were the most salient terms among all-participants. Overall, “smelly” and “unhealthy” were salient for both males and females. However, “dental,” “dirty,” “addictive,” and “habit” were also salient among males. Phrases such as “unhealthy” and “addictive” were primarily salient for older participants (&gt;51 years) versus “smelly” for younger participants. The term “smelly” was salient among all-education levels. However, “unhealthy” was also salient among those with less than a 4-year college degree. Moreover, the terms “smelly” and “annoying” were most common among people who smoke as opposed to “health hazard” among people who don’t smoke.

Conclusions
We observed that the most stigmatizing language was primarily associated with perceptions of negative social interactions, social judgment, and health-related concerns. Future studies are needed to explore how smoking-related stigmas impact patient adherence to smoking cessation programs and LC screening protocols.

Implications
Little is known about the prevalence of smoking stigmas among AAB. This study explores the AAB perspective of cigarette smoking and related stigmas. Among AAB, smoking is represented by stigmatizing language across gender, age groups, and smoking history. It is primarily associated with negative social interactions, social judgement, and health-related concerns indicating that smoking stigma is a concern for AAB individuals who smoke. Further research is warranted.