bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ictal EEG Source Imaging With Supplemental Electrodes
Authors: Loube Deanne Kennedy , Tan Yee-Leng , Yoshii-Contreras June , Kleen Jonathan , Rao Vikram R. , Chang Edward F. , Knowlton Robert C. 
Published: October 2023

Introduction:
Noninvasive brain imaging tests play a major role in guiding decision-making and the usage of invasive, costly intracranial electroencephalogram (ICEEG) in the presurgical epilepsy evaluation. This study prospectively examined the concordance in localization between ictal EEG source imaging (ESI) and ICEEG as a reference standard.

Methods:
Between August 2014 and April 2019, patients during video monitoring with scalp EEG were screened for those with intractable focal epilepsy believed to be amenable to surgical treatment. Additional 10-10 electrodes (total = 31–38 per patient, “31+”) were placed over suspected regions of seizure onset in 104 patients. Of 42 patients requiring ICEEG, 30 (mean age 30, range 19–59) had sufficiently localized subsequent intracranial studies to allow comparison of localization between tests. ESI was performed using realistic forward boundary element models used in dipole and distributed source analyses.

Results:
At least partial sublobar concordance between ESI and ICEEG solutions was obtained in 97% of cases, with 73% achieving complete agreement. Median Euclidean distances between ESI and ICEEG solutions ranged from 25 to 30 mm (dipole) and 23 to 38 mm (distributed source). The latter was significantly more accurate with 31+ compared with 21 electrodes (P < 0.01). A difference of ≤25 mm was present in two thirds of the cases. No significant difference was found between dipole and distributed source analyses.

Conclusions:
A practical method of ictal ESI (nonuniform placement of 31–38 electrodes) yields high accuracy for seizure localization in epilepsy surgery candidates. These results support routine clinical application of ESI in the presurgical evaluation.
TENDINopathy Severity assessment – Achilles (TENDINS-A): Evaluation of reliability and validity in accordance with COSMIN recommendations
Authors: Murphy Myles C , McCleary Fergus , Hince Dana , Chimenti Ruth L , Chivers Paola T , Vosseller J. Turner , Nimphius Sophia , Mkumbuzi Nonhlanhla , Malliaras Peter , Maffuli Nicola , De Vos Robert-Jan , Rio Ebonie 
Published: October 2023

ABSTRACTObjectivesEvaluate the construct validity (structural validity and hypothesis-testing), reliability (test-retest reliability, measurement error and internal consistency) and minimal detectable change (MDC) of the 13-item TENDINopathy Severity assessment–Achilles (TENDINS-A).MethodsParticipants with Achilles pain completed an online survey: demographics, TENDINS-A, Foot and Ankle Outcome Score (FAOS) and Victorian Institute of Sport Assessment-Achilles (VISA-A). Exploratory factor analysis (EFA) assessed dimensionality. Confirmatory Factor Analysis (CFA) assessed structural validity [root-mean-squared error of approximation (RMSEA); Comparative Fit Index (CFI); Tucker-Lewis Index (TLI); Standardised Root Measure Square (SRMS)]. Correlations between TENDINS-A and the FAOS/ VISA-A assessed hypothesis-testing. Intraclass correlation (ICC) assessed test-retest reliability. Cronbach’s α assessed internal consistency. Standard error of the measurement (SEM) assessed measurement error. A distribution-based approach assessed MDC.ResultsSeventy-nine participants (51% female) with a mean (SD) age=42.6 (13.0)years, height=175.0 (11.7)cm and body mass=82.0 (19.1)kg were included. EFA identified three meaningful factors, proposed to be pain, symptoms and function. The best model identified using CFA had adequate structural validity (CFI= 0.959, TLI= 0.947, RMSEA= 0.101, SRMS=0.068) excluded three items from the original TENDINS-A, included three factors (Pain, Symptoms, and Function). TENDINS-A exhibited moderate positive correlation with FAOS (rho=0.598,p<0.001), moderate, negative correlation with VISA-A (r=-0.639,p<0.001). Reliability of the TENDINS-A is excellent (ICC=0.930; Cronbach’s α=0.808; SEM=6.54 units) and has an MDC of 12 units.ConclusionsOur evaluation of the revised 10-item TENDINS-A has determined it has adequate validity and reliability. Thus, the TENDINS-A can be recommended for immediate use, being the preferred tool over other PROMs to assess disability in Achilles tendinopathy.
A phase I/II clinical trial of intradermal, controllable self-replicating RNA vaccine EXG-5003 against SARS-CoV-2
Authors: Koseki Takenao , Teramachi Mayumi , Koga Minako , Ko Minoru S.H. , Amano Tomokazu , Yu Hong , Amano Misa , Leyder Erica , Badiola Maria , Ray Priyanka , Kim Jiyoung , Ko Akihiro C. , Achour Achouak , Weng Nan-ping , Imai Takumi , Yoshida Hisako , Taniuchi Satsuki , Shintani Ayumi , Fujigaki Hidetsugu , Kondo Masashi , Doi Yohei 
Published: October 2023

AbstractmRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have played a key role in reducing morbidity and mortality from coronavirus disease 2019 (COVID-19). We conducted a double-blind, placebo-controlled phase I/II trial to evaluate the safety, tolerability, and immunogenicity of EXG-5003, a two-dose, controllable self-replicating RNA vaccine against SARS-CoV-2. EXG-5003 encodes the receptor binding domain (RBD) of SARS-CoV-2 and was administered intradermally without lipid nanoparticles (LNP). The participants were followed for 12 months. Forty healthy participants were enrolled in Cohort 1 (5 µg per dose, n = 16; placebo, n = 4) and Cohort 2 (25 µg per dose, n = 16; placebo, n = 4). No safety concerns were observed with EXG-5003 administration. SARS-CoV-2 RBD antibody titers and neutralizing antibody titers were not elevated in either cohort. Elicitation of antigen-specific cellular immunity was observed in the EXG-5003 recipients in Cohort 2. At the 12-month follow-up, participants who had received an approved mRNA vaccine (BNT162b2 or mRNA-1273) >1 month after receiving the second dose of EXG-5003 showed higher cellular responses compared to equivalently vaccinated participants in the placebo group. The findings suggest a priming effect by EXG-5003 on the long-term cellular immunity of approved SARS-CoV-2 mRNA vaccines.
Foveolar drusen decrease fixation stability in pre-symptomatic AMD
Authors: Murari J. , Gautier J. , Daout J. , Krafft L. , Senée P. , Mecê P. , Grieve K. , Seiple W. , Sheynikhovich D. , Meimon S. , Paques M. , Arleo A. 
Published: October 2023

AbstractPurposeThis study aims at linking subtle changes of fixational eye movements (FEM) in controls and in patients with foveal drusen using adaptive optics retinal imaging in order to find anatomo-functional markers for pre-symptomatic Age-related Macular Degeneration (AMD).MethodsWe recruited 7 young controls, 4 older controls and 16 presymptomatic AMD patients with foveal drusen from the Silversight Cohort. A high speed research-grade adaptive optics flood illumination ophthalmoscope (AO-FIO) was used for monocular retinal tracking of fixational eye movements. The system allows for sub-arcminute resolution, high-speed and distortion-free imaging of the foveal area. Foveal drusen position and size were documented using gaze-dependent imaging on a clinical-grade AO-FIO.ResultsFEM were measured with high precision (RMS-S2S=0.0015° on human eyes) and small foveal drusen (median=60µm) were detected with high contrast imaging. Microsaccade amplitude, drift diffusion coefficient and ISOline Area (ISOA) were significantly larger for patients with foveal drusen compared with controls. Among the drusen participants, microsaccade amplitude was correlated to drusen eccentricity from the center of the fovea.ConclusionsA novel high-speed high-precision retinal tracking technique allowed for the characterization of FEM at the microscopic level. Foveal drusen altered fixation stability, resulting in compensatory FEM changes. Particularly, drusen at the foveolar level seemed to have a stronger impact on microsaccade amplitudes and ISOA. The unexpected anatomo-functional link between small foveal drusen and fixation stability opens up a new perspective of detecting oculomotor signatures of eye diseases at the presymptomatic stage.
Telomeres control human telomerase (hTERT) expression through non-telomeric TRF2
Authors: Sengupta Antara , Vinayagamurthy Soujanya , Soni Drishti , Deb Rajlekha , Mukherjee Ananda Kishore , Dutta Subhajit , Jaiswal Jushta , Yadav Mukta , Sharma Shalu , Bagri Sulochana , Roy Shuvra Shekhar , Poonia Priya , Singh Ankita , Khanna Divya , Bhatt Amit Kumar , Sharma Akshay , Saurav Suman , Motiani Rajender K , Chowdhury Shantanu 
Published: October 2023

AbstractThe function of the human telomerase reverse transcriptase (hTERT) in the synthesis and maintenance of chromosome ends, or telomeres, is widely understood. Whether and how telomeres, on the other hand, influencehTERTregulation is relatively less studied. We foundhTERTwas transcriptionally up/downregulated depending on telomere length (TL). This resulted from TL-dependent binding of TRF2 between telomeres and thehTERTpromoter.hTERTpromoter-bound TRF2 was non-telomeric and did not involve the looping of telomeres to thehTERTpromoter. Cell lines from different tissue types (fibrosarcoma (HT1080), colon cancer (HCT116), and breast cancer (MDA-MB-231), engineered for either telomere elongation/shortening gave increase/decrease inhTERT, respectively. Mechanistically, we showhTERTpromoter-bound non-telomeric TRF2 recruits the canonical PRC2-complex inducing repressor histone H3K27-trimethylation in a TL-dependent fashion. This was further supported by TL-dependent promoter activity from an exogenously insertedhTERTreporter. Increase in TL over days followed by gradual decline, resulted in activation followed by repression ofhTERTin a concerted manner, further implicating TL as a key factor forhTERTregulation. Notably on reprogramming primary fibroblasts to induced pluripotent stem cells (iPSCs), TRF2 loss from thehTERTpromoter was evident along with telomere elongation andhTERTupregulation. Conversely, on telomere shortening in iPSCs,hTERTpromoter-bound TRF2 was restored with marked reduction inhTERTfurther supporting the causal role of TL inhTERTtranscription. Mechanisms of tight control ofhTERTby TL shown here are likely to have major implications in telomere-related physiologies, particularly, cancer, ageing and pluripotency.TeaserTelomere length controlshTERTexpression by modulating TRF2 distribution and PRC2-mediated repression, highlighting a self-regulatory mechanism in cancer.
SHIFTR enables the unbiased and multiplexed identification of proteins bound to specific RNA regions in live cells
Authors: Aydin Jens , Gabel Alexander , Zielinski Sebastian , Ganskih Sabina , Schmidt Nora , Hartigan Christina R. , Schenone Monica , Carr Steven A. , Munschauer Mathias 
Published: October 2023

ABSTRACTRNA-protein interactions determine the cellular fate of RNA and are central to regulating gene expression outcomes in health and disease. To date, no method exists that is able to identify proteins that interact with specific regions within endogenous RNAs in live cells. Here, we develop SHIFTR (Selective RNaseH-mediated interactome framing for target RNA regions), an efficient and scalable approach to identify proteins bound to selected regions within endogenous RNAs using mass spectrometry. Compared to state-of-the-art techniques, SHIFTR is superior in accuracy, captures close to zero background interactions and requires orders of magnitude lower input material. We establish SHIFTR workflows for targeting RNA classes of different length and abundance, including short and long non-coding RNAs, as well as mRNAs and demonstrate that SHIFTR is compatible with sequentially mapping interactomes for multiple target RNAs in a single experiment. Using SHIFTR, we comprehensively identify interactions ofcis-regulatory elements located at the 5ʹ and 3ʹ- terminal regions of the authentic SARS-CoV-2 RNA genome in infected cells and accurately recover known and novel interactions linked to the function of these viral RNA elements. SHIFTR enables the systematic mapping of region-resolved RNA interactomes for any RNA in any cell type and has the potential to revolutionize our understanding of transcriptomes and their regulation.
ABTrans: A Transformer-based model for predicting interaction between anti-Aß antibodies and peptides
Authors: Su Yuhong , Zhang Lingfeng , Wang Yangjing , Ma Buyong 
Published: October 2023

AbstractUnderstanding the recognition of antibodies and Aβ peptide is crucial for the development of more effective therapeutic agents. Here we studied the interaction between anti-Aβ antibodies and different peptides by building a deep learning model, using the dodecapeptide sequences elucidated from phage display and known anti-Aβ antibody sequences collected from public sources. Our multi-classification model, ABTrans was trained to determine the four levels of binding ability between anti-Aβ antibody and dodecapeptide: not binding, weak binding, medium binding, and strong binding. The accuracy of our model reached 0.8278. Using the ABTrans, we examined the cross-reaction of anti-Aβ antibodies with other human amyloidogenic proteins, and we found that Aducanumab and Donanemab have the least cross-reactions with other human amyloidogenic proteins. We also systematically screened all human proteins interaction with eleven selected anti-Aβ antibodies to identify possible peptide fragments that could be an off-target candidate.Key PointsABTrans is a Transformer-based model that was developed for the first time to predict the interaction between anti-Aß antibodies and peptides.ABTrans was trained using a dataset with 1.5 million peptides and 110 anti-Aβ antibodies.ABTrans achieved an accuracy of 0.8278 and is capable of determining the four levels of binding ability between antibody and Aß: not binding, weak binding, medium binding, and strong binding.ABTrans has potential applications in predicting off-target and cross-reactivity effects of antibodies and in designing new anti-Aß antibodies.
Urea excreted by tropical frogs is explained by their body mass and the mass of insects consumed
Authors: Dev Akash M , Sreedharan Gayathri , Panwar Yashwant Singh , Vasudevan Karthikeyan 
Published: October 2023

ABSTRACTFrog insect interactions are prominent and they result in services that are crucial in the ecosystem. The primary nitrogenous waste that frogs produce is urea. However, the role of biotic variables on urea excretion, has not been fully investigated. Frogs comprising of sixPolypedates maculatusand sevenMinervarya agricolawere maintained in controlled condition after tagging them with passive integrated transponders. Thirteen experiments were performed to test whether, frog species or frogs’ body mass or insect body mass, or a combination of these explained the amount of urea excreted by the frogs. We found that body mass of the frogs and the amount of insect biomass consumed explained the amount of urea excreted in the two species. In the light of these findings, we discuss the role of frogs in converting insect biomass into urea in the ecosystem.
Hindlimb Unloading Induces Bone Microarchitectural and Transcriptomic Changes in Murine Long Bones in an Age-Dependent Manner
Authors: Meas Steven J. , Daire Gabriella M. , Friedman Michael A. , DeNapoli Rachel , Ghosh Preetam , Farr Joshua N. , Donahue Henry J. 
Published: October 2023

ABSTRACTAge and disuse-related bone loss both result in decreases in bone mineral density, cortical thickness, and trabecular thickness and connectivity. Disuse induces physiological changes in bone like those seen with aging.Bone microarchitecture and biomechanical properties were compared between 6- and 22-month-old C57BL/6J male control mice and 6-month-old mice that were hindlimb unloaded (HLU) for 3 weeks. Epiphyseal trabecular bone was the compartment most affected by HLU and demonstrated an intermediate bone phenotype between age-matched controls and aged controls.RNA extracted from whole-bone marrow-flushed tibiae was sequenced and analyzed. Differential gene expression analysis additionally included 4-month-old male mice unloaded for 3 weeks compared to age-matched controls. Gene ontology analysis demonstrated that there were age-dependent differences in differentially expressed genes. Genes related to downregulation of cellular processes were most affected in 4-month-old mice after disuse whereas those related to mitochondrial function were most affected in 6- month-old mice. Cell-cycle transition was downregulated with aging.A publicly available dataset (GSE169292) from 3-month female C57BL/6N mice unloaded for 7 days was included in ingenuity pathway analysis with the other datasets. IPA was used to identify the leading canonical pathways and upstream regulators in each HLU age group. IPA identified “Senescence Pathway” as the second leading canonical pathway enriched in mice exposed to HLU. HLU induced activation of the senescence pathway in 3- month and 4-month-old mice but inhibited it in 6-month-old mice.In conclusion, we demonstrate that hindlimb unloading and aging initiate similar changes in bone microarchitecture and gene expression. However, aging is responsible for more significant transcriptome and tissue-level changes compared to hindlimb unloading.HighlightsEpiphyseal trabecular bone is most susceptible to hindlimb unloading.Hindlimb unloaded limbs resemble an intermediate phenotype between age-matched and aged controls.Hindlimb unloading induces gene expression changes that are age dependent and may lead to inflammation and/or mitochondrial dysfunction depending on context.Younger mice (3-4 months) activate the senescence pathway upon hindlimb unloading, whereas skeletally mature (6 months) mice inhibit it.
Saltational episodes of reticulate evolution in theDrosophila saltansspecies group
Authors: Prediger Carolina , Ferreira Erina A. , Zorzato Samara Videira , Hua-Van Aurélie , Klasson Lisa , Miller Wolfgang J. , Yassin Amir , Madi-Ravazzi Lilian 
Published: October 2023

AbstractPhylogenomics reveals reticulate evolution to be widespread across taxa, but whether reticulation is due to low statistical power or it is a true evolutionary pattern remains a field of investigation. Here, we investigate the phylogeny and quantify reticulation in theDrosophila saltansspecies group, a Neotropical clade of the subgenusSophophoracomprising 23 species whose relationships have long been problematic. Phylogenetic analyses revealed conflicting topologies between the X chromosome, autosomes and the mitochondria. We extended the ABBA-BABA test of asymmetry in phylogenetic discordance to cases where no “true” species tree could be inferred, and applied our new test (called 2A2B) to whole genome data and to individual loci. We used four strategies, two of which consisted of windows from pseudo-reference genomes aligned to either an outgroup or ingroup species, and two based on our new assemblies using either conserved genes or ≥50 kb-long syntenic blocks with conserved collinearity across NeotropicalSophophora. Evidence for reticulation varied among the strategies, being lowest in the synteny-based approach, where it did not exceed ∼7% of the blocks in the most conflicting species quartets. High incidences of low phylogenetic resolution (polytomy) were restricted to three nodes on the tree, that coincided with major paleogeographical events in South America. Our results identify possible technical biases in quantifying reticulate evolution and indicate that episodic rapid radiations have played a major role in the evolution of a largely understudied Neotropical clade.
An osmolarity dependent mechanism partially ameliorates retinal cysts and rescues cone function in a mouse model of X-linked Retinoschisis
Authors: Gehrke Ella J. , Thompson Jacob , Kalmanek Emily , Stanley Sarah , Bhattarai Sajag , Lobeck Brianna , Mayer Sara , Mahoney Angela , Hassan Salma , Hsu Ying , Drack Arlene V. 
Published: October 2023

AbstractIntroductionX-linked retinoschisis (XLRS) is a vitreoretinal dystrophy caused byRS1gene mutations which disrupt retinoschisin protein function. A vital protein for maintaining retinal architecture, the absence of functional retinoschisin leads to the development of intraretinal cysts. The preliminary goal of this study was to investigate a low dose gene therapy inRs1knockout (Rs1-KO) mice; however, our experiments revealed an unexpected therapeutic effect of a hypertonic buffer, which led to further exploration of this effect.Methods10Rs1-KO mice were subretinally injected with an AAV2/4 vector containing theRS1gene driven by anEf1αpromoter. 16Rs1-KO mice were subretinally injected with a hypertonic buffer (180 mM NaCl 0.001% F68/PBS (pH 7.4)) or an isotonic buffer (155.2 mM NaCl 0.001% F68/PBS, pH 7.0) as a sham control. Endpoints included electroretinogram (ERG), optical coherence tomography (OCT), and a visually guided swim assay (VGSA). An immunohistochemistry assay was used to quantify cone density in buffer injected and treatment-naïve eyes.ResultsUnexpectedly, hypertonic buffer-injected eyes had significantly reduced cyst severity at 1 month post-injection (MPI) (p=<0.0001), significantly higher amplitudes in cone-dominant ERGs persisting to 5 months post-injection (5 Hz flicker; p=0.0018; 3.0 Flash; p=0.0060) and demonstrated improved navigational vision in the light compared to untreatedRs1-KO eyes (p<0.0001). To investigate the role of tonicity on this effect, an isotonic buffer-injected cohort was created (155.2 mM NaCl 0.001% F68/PBS, pH 7.0) (n=6). Surprisingly, hypertonic buffer-injected eyes exhibited a greater reduction in cyst severity and demonstrated improved cone-dominant ERG metrics over isotonic buffer-injected eyes. Using an immunohistochemistry assay, we demonstrated greater cone density in hypertonic buffer-injected eyes than untreated controls (p=0.0147), suggesting a possible cone preservation mechanism. Moreover, our findings reveal a negative correlation between the peak severity of cysts and long-term cone-dominant ERG metrics, implying that effectively managing cysts could yield enduring benefits for cone function.Discussion/ConclusionThis study presents evidence that cyst resolution can be triggered through an osmosis-dependent pathway, and cyst resolution can have long term effects on cone signaling and survival, offering potential insights for the development of novel treatments for patients with XLRS.