bluuebunny/crossref_metadata_2025_split huggingface dataset:
Choroid plexus mis-splicing and altered cerebrospinal fluid composition in myotonic dystrophy type 1
Authors: Nutter Curtis A , Kidd Benjamin M , Carter Helmut A , Hamel Johanna I , Mackie Philip M , Kumbkarni Nayha , Davenport Mackenzie L , Tuyn Dana M , Gopinath Adithya , Creigh Peter D , Sznajder Łukasz J , Wang Eric T , Ranum Laura P W , Khoshbouei Habibeh , Day John W , Sampson Jacinda B , Prokop Stefan , Swanson Maurice S 
Published: May 2023

Abstract
Myotonic dystrophy type 1 is a dominantly inherited multisystemic disease caused by CTG tandem repeat expansions in the DMPK 3′ untranslated region. These expanded repeats are transcribed and produce toxic CUG RNAs that sequester and inhibit activities of the MBNL family of developmental RNA processing factors. Although myotonic dystrophy is classified as a muscular dystrophy, the brain is also severely affected by an unusual cohort of symptoms, including hypersomnia, executive dysfunction, as well as early onsets of tau/MAPT pathology and cerebral atrophy. To address the molecular and cellular events that lead to these pathological outcomes, we recently generated a mouse Dmpk CTG expansion knock-in model and identified choroid plexus epithelial cells as particularly affected by the expression of toxic CUG expansion RNAs.
To determine if toxic CUG RNAs perturb choroid plexus functions, alternative splicing analysis was performed on lateral and hindbrain choroid plexi from Dmpk CTG knock-in mice. Choroid plexus transcriptome-wide changes were evaluated in Mbnl2 knockout mice, a developmental-onset model of myotonic dystrophy brain dysfunction. To determine if transcriptome changes also occurred in the human disease, we obtained post-mortem choroid plexus for RNA-seq from neurologically unaffected (two females, three males; ages 50–70 years) and myotonic dystrophy type 1 (one female, three males; ages 50–70 years) donors. To test that choroid plexus transcriptome alterations resulted in altered CSF composition, we obtained CSF via lumbar puncture from patients with myotonic dystrophy type 1 (five females, five males; ages 35–55 years) and non-myotonic dystrophy patients (three females, four males; ages 26–51 years), and western blot and osmolarity analyses were used to test CSF alterations predicted by choroid plexus transcriptome analysis.
We determined that CUG RNA induced toxicity was more robust in the lateral choroid plexus of Dmpk CTG knock-in mice due to comparatively higher Dmpk and lower Mbnl RNA levels. Impaired transitions to adult splicing patterns during choroid plexus development were identified in Mbnl2 knockout mice, including mis-splicing previously found in Dmpk CTG knock-in mice. Whole transcriptome analysis of myotonic dystrophy type 1 choroid plexus revealed disease-associated RNA expression and mis-splicing events. Based on these RNA changes, predicted alterations in ion homeostasis, secretory output and CSF composition were confirmed by analysis of myotonic dystrophy type 1 CSF. Our results implicate choroid plexus spliceopathy and concomitant alterations in CSF homeostasis as an unappreciated contributor to myotonic dystrophy type 1 CNS pathogenesis.
TERT and BRAF V600E mutations in thyroid cancer of World Trade Center Responders
Authors: van Gerwen Maaike , Cerutti Janete Maria , Mendes Thais Biude , Brody Rachel , Genden Eric , Riggins Gregory J , Taioli Emanuela 
Published: May 2023

Abstract
The 2-fold excess thyroid cancer risk reported in multiple World Trade Center (WTC) disaster exposed cohorts cannot entirely be explained by surveillance and physician bias thus highlighting the need to investigate the potential consequences of the dust exposure, containing carcinogenic and endocrine disruptive elements, on the thyroid. This study investigated the presence of TERT promoter and BRAF V600E mutations in 20 WTC-exposed versus 23 matched non-exposed thyroid cancers as potential mechanism explaining the excess risk. Although no significant difference in BRAF V600E mutation was found, TERT promoter mutations were significantly more prevalent in WTC thyroid cancer versus non-exposed thyroid cancers (P = 0.021). The odds of a TERT promoter mutation was significantly higher in the WTC versus the non-WTC thyroid cancers after adjustment [ORadj: 7.11 (95% CI: 1.21–41.83)]. These results may indicate that exposure to the mixture of pollutants present in the WTC dust resulted in an excess thyroid cancer risk and potentially more aggressive thyroid cancer, warranting investigating WTC responders on thyroid-associated symptoms during their health checkups. Future studies should include long-term follow-up to provide important insights in whether thyroid-specific survival is negatively affected by WTC dust exposure and whether this is because of the presence of one or more driver mutations.
Inter-individual variability during neurodevelopment: an investigation of linear and nonlinear resting-state EEG features in an age-homogenous group of infants
Authors: Davoudi Saeideh , Schwartz Tyler , Labbe Aurélie , Trainor Laurel , Lippé Sarah 
Published: May 2023

Abstract
Electroencephalography measures are of interest in developmental neuroscience as potentially reliable clinical markers of brain function. Features extracted from electroencephalography are most often averaged across individuals in a population with a particular condition and compared statistically to the mean of a typically developing group, or a group with a different condition, to define whether a feature is representative of the populations as a whole. However, there can be large variability within a population, and electroencephalography features often change dramatically with age, making comparisons difficult. Combined with often low numbers of trials and low signal-to-noise ratios in pediatric populations, establishing biomarkers can be difficult in practice. One approach is to identify electroencephalography features that are less variable between individuals and are relatively stable in a healthy population during development. To identify such features in resting-state electroencephalography, which can be readily measured in many populations, we introduce an innovative application of statistical measures of variance for the analysis of resting-state electroencephalography data. Using these statistical measures, we quantified electroencephalography features commonly used to measure brain development—including power, connectivity, phase-amplitude coupling, entropy, and fractal dimension—according to their intersubject variability. Results from 51 6-month-old infants revealed that the complexity measures, including fractal dimension and entropy, followed by connectivity were the least variable features across participants. This stability was found to be greatest in the right parietotemporal region for both complexity feature, but no significant region of interest was found for connectivity feature. This study deepens our understanding of physiological patterns of electroencephalography data in developing brains, provides an example of how statistical measures can be used to analyze variability in resting-state electroencephalography in a homogeneous group of healthy infants, contributes to the establishment of robust electroencephalography biomarkers of neurodevelopment through the application of variance analyses, and reveals that nonlinear measures may be most relevant biomarkers of neurodevelopment.
Long-term outcome of thoracoscopic ablation and radiofrequency catheter ablation for persistent atrial fibrillation as a de novo procedure
Authors: Kim Juwon , Kim Ju Youn , Jeong Dong Seop , Chung Tae-Wan , Park Seung-Jung , Park Kyoung-Min , Kim June Soo , Lee Joo Myung , On Young Keun 
Published: May 2023

Abstract

Aims
Limited data are available regarding the efficacy of thoracoscopic ablation as the first procedure for persistent atrial fibrillation (AF). We sought to compare the long-term efficacy of thoracoscopic ablation vs. radiofrequency (RF) catheter ablation as the first procedure for persistent AF.

Methods and results
Between February 2011 and December 2020, 575 patients who underwent ablation for persistent AF were studied. Among them, thoracoscopic ablation was performed in 281 patients, RF catheter ablation in 228, and hybrid ablation in 66. Rhythm, clinical, and safety outcomes during 7-year follow-up were compared. The patients who underwent thoracoscopic ablation were older, had a higher prevalence of stroke, and had a larger left atrial volume than those who underwent RF catheter ablation. In the propensity score-matched population (n = 306), incidences of atrial tachyarrhythmia recurrence were 51.4% in the thoracoscopic ablation group and 62.5% in the RF catheter ablation group [adjusted hazard ratio (HR) 0.869, 95% confidence interval (CI) 0.618–1.223, P = 0.420]. Stroke and total procedural adverse events were not significantly different between thoracoscopic and RF catheter ablation (2.7 vs. 2.5%, P = 0.603, and 7.1 vs. 4.8%, P = 0.374, respectively). The hybrid ablation group showed similar rhythm outcomes compared with both the thoracoscopic and the RF catheter ablation groups. At the redo procedure, pulmonary vein gaps were more frequently observed in the RF catheter ablation group (32.6%) than in the thoracoscopic ablation group (7.9%) and in the hybrid ablation group (8.8%) (P &lt; 0.001).

Conclusion
As a first procedure in persistent AF, thoracoscopic ablation and RF catheter ablation showed comparable efficacy, clinical, and safety outcomes during long-term follow-up.
Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients without previous oral anticoagulants or stable under warfarin: a nationwide cohort study
Authors: Liu Shin-Huei , Chao Tze-Fan , Chan Yi-Hsin , Liao Jo-Nan , Chen Tzeng-Ji , Lip Gregory Y H , Chen Shih-Ann 
Published: May 2023

Abstract

Aims
Investigations on non-VKA oral anticoagulants (NOACs) for atrial fibrillation (AF) patients without taking any oral anticoagulants (OACs) or staying well on warfarin were limited. We aimed to investigate the associations between stroke prevention strategies and clinical outcomes among AF patients who were previously well without taking any OACs or stayed well on warfarin for years.

Methods and results
The retrospective analysis included a total of 54 803 AF patients who did not experience an ischaemic stroke or intra-cranial haemorrhage (ICH) for years after AF was diagnosed. Among these patients, 32 917 patients who did not receive OACs were defined as the ‘original non-OAC cohort’ (group 1), and 8007 patients who continuously received warfarin were defined as the ‘original warfarin cohort’ (group 2). In group 1, compared to non-OAC, warfarin showed no significant difference in ischaemic stroke (aHR 0.979, 95%CI 0.863–1.110, P = 0.137) while those initiated NOACs were associated with lower risk (aHR 0.867, 95%CI 0.786–0.956, P = 0.043). When compared to warfarin, the composite of ‘ischaemic stroke or ICH’ and ‘ischaemic stroke or major bleeding’ was significantly lower in the NOAC initiator with an aHR of 0.927 (95%CI 0.865–0.994; P = 0.042) and 0.912 (95%CI 0.837–0.994; P &lt; 0.001), respectively. In group 2, when compared to warfarin, those shifted to NOACs were associated with a lower risk of ischaemic stroke (aHR 0.886, 95%CI 0.790–0.993, P = 0.002) and major bleeding (aHR 0.849, 95%CI 0.756–0.953, P &lt; 0.001).

Conclusions
The NOACs should be considered for AF patients who were previously well without taking OACs and those who were free of ischaemic stroke and ICH under warfarin for years.
Tolerance-conferring defensive symbionts and the evolution of parasite virulence
Authors: Smith Cameron A , Ashby Ben 
Published: May 2023

Abstract
Defensive symbionts in the host microbiome can confer protection from infection or reduce the harms of being infected by a parasite. Defensive symbionts are therefore promising agents of biocontrol that could be used to control or ameliorate the impact of infectious diseases. Previous theory has shown how symbionts can evolve along the parasitism–mutualism continuum to confer greater or lesser protection to their hosts and in turn how hosts may coevolve with their symbionts to potentially form a mutualistic relationship. However, the consequences of introducing a defensive symbiont for parasite evolution and how the symbiont may coevolve with the parasite have received relatively little theoretical attention. Here, we investigate the ecological and evolutionary implications of introducing a tolerance-conferring defensive symbiont into an established host–parasite system. We show that while the defensive symbiont may initially have a positive impact on the host population, parasite and symbiont evolution tend to have a net negative effect on the host population in the long term. This is because the introduction of the defensive symbiont always selects for an increase in parasite virulence and may cause diversification into high- and low-virulence strains. Even if the symbiont experiences selection for greater host protection, this simply increases selection for virulence in the parasite, resulting in a net negative effect on the host population. Our results therefore suggest that tolerance-conferring defensive symbionts may be poor biocontrol agents for population-level infectious disease control.
Post-injury Inhibition of Endothelin-1 Dependent Renal Vasoregulation Mitigates Rhabdomyolysis-Induced Acute Kidney Injury
Authors: Afolabi Jeremiah M , Kanthakumar Praghalathan , Williams Jada D , Kumar Ravi , Soni Hitesh , Adebiyi Adebowale 
Published: May 2023

Abstract
In patients with rhabdomyolysis, the overwhelming release of myoglobin into the circulation is the primary cause of kidney injury. Myoglobin causes direct kidney injury as well as severe renal vasoconstriction. An increase in renal vascular resistance (RVR) results in renal blood flow (RBF) and glomerular filtration rate (GFR) reduction, tubular injury, and acute kidney injury (AKI). The mechanisms that underlie rhabdomyolysis-induced AKI are not fully understood but may involve the local production of vasoactive mediators in the kidney. Studies have shown that myoglobin stimulates endothelin-1 (ET-1) production in glomerular mesangial cells. Circulating ET-1 is also increased in rats subjected to glycerol-induced rhabdomyolysis. However, the upstream mechanisms of ET-1 production and downstream effectors of ET-1 actions in rhabdomyolysis-induced AKI remain unclear. Vasoactive ET-1 is generated by ET converting enzyme 1 (ECE-1)-induced proteolytic processing of inactive big ET to biologically active peptides. The downstream ion channel effectors of ET-1-induced vasoregulation include the transient receptor potential cation channel, subfamily C member 3 (TRPC3). This study demonstrates that glycerol-induced rhabdomyolysis in Wistar rats promotes ECE-1-dependent ET-1 production, RVR increase, GFR decrease, and AKI. Rhabdomyolysis-induced increases in RVR and AKI in the rats were attenuated by post-injury pharmacological inhibition of ECE-1, ET receptors, and TRPC3 channels. CRISPR/Cas9-mediated knockout of TRPC3 channels attenuated ET-1-induced renal vascular reactivity and rhabdomyolysis-induced AKI. These findings suggest that ECE-1-driven ET-1 production and downstream activation of TRPC3-dependent renal vasoconstriction contribute to rhabdomyolysis-induced AKI. Hence, post-injury inhibition of ET-1-mediated renal vasoregulation may provide therapeutic targets for rhabdomyolysis-induced AKI.
3-D imaging of the Balmuccia peridotite body (Ivrea–Verbano zone, NW-Italy) using controlled source seismic data
Authors: Ryberg Trond , Haberland Christian , Wawerzinek Britta , Stiller Manfred , Bauer Klaus , Zanetti Alberto , Ziberna Luca , Hetényi György , Müntener Othmar , Weber Michael M , Krawczyk Charlotte M 
Published: May 2023

SUMMARY
We provide new results from a controlled-source seismic experiment on the deepest part of the Val Sesia crust–mantle section of the Ivrea–Verbano zone (IVZ) in the Italian Alps. The IVZ is a tilted, almost complete section through the continental crust and exposes gabbros and peridotites in the structurally deepest level, coinciding with high-resolution gravity anomalies imaging the Ivrea geophysical body. The seismic experiment SEIZE (SEismic imaging of the Ivrea ZonE) was conducted along two crossing profiles: an NNE-SSW profile of ∼11 km length and an E-W profile of ∼16 km length. 432 vibration points were recorded with 110 receivers resulting in 24 392 traveltime picks. Inversion methods using Markov chain Monte Carlo techniques have been used to derive an isotropic 3-D P-wave velocity model based on first break traveltimes (refracted phases) from controlled source seismic data. Resulting seismic P-wave velocities (Vp ) range from 4.5 to 7.5 km s−1, with an expected general trend of increasing velocities with depth. A sharp velocity change from low Vp in the West to high Vp in the East marks the Insubric Zone (ISZ), the Europe–Adria plate boundary. The most prominent feature of the 3-D tomography model is a high-velocity body (Vp increases from 6 to 7.5 km s−1) that broadens downwards. Its pointy shape peaks the surface East of Balmuccia at a location coincident with the exposed Balmuccia peridotite. Considering rock physics, high-resolution gravity and other geophysical data, we interpret this high-velocity body as dominantly composed of peridotite. The dimension of this seismically imaged peridotite material is far bigger than interpreted from geological cross-sections and requires a revision of previous models. The interpretation of ultramafic bodies in the IVZ as fragments of mantle peridotites interfingered in the crust during pre-Permian accretion is not supported by the new data. Instead, we revive a model that the contact between the Balmuccia peridotite and the Permian mafic magmas might represent a fossil continental crust–mantle transition zone.
Elucidating the toxic effect and disease mechanisms associated with Lyso-Gb3 in Fabry disease
Authors: Nikolaenko Valeria , Warnock David G , Mills Kevin , Heywood Wendy E 
Published: May 2023

Abstract
Fabry disease stems from a deficiency of alpha-galactosidase and results in the accumulation of globotriaosylceramide (Gb3). However, the production of its deacylated form globotriaosylsphingosine (lyso-Gb3) is also observed and its plasma levels have closer association with disease severity. Studies have shown that lyso-Gb3 directly affects podocytes and causes sensitisation of peripheral nociceptive neurons. However, little is understood of the mechanisms of this cytotoxicity. To study the effect on neuronal cells, we incubated SH-Sy5y cells with lyso-Gb3 at low (20 ng/mL) and high (200 ng/mL) levels, to mimic mild and classical FD serum levels. We used glucosylsphingosine as a positive control to determine specific effects of lyso-Gb3. Proteomic analyses revealed that cellular systems affected by lyso-Gb3 included cell signalling particularly protein ubiquitination and protein translation. To confirm ER/proteasome perturbations, we performed an immune enrichment of ubiquitinated proteins and demonstrated specific increased protein ubiquitination at both doses. The most ubiquitinated proteins observed included the chaperone/heat shock proteins, cytoskeletal proteins and synthesis/translation proteins. To detect proteins that interact directly with lyso-Gb3, we immobilised lyso-lipids, then incubated them with neuronal cellular extracts and identified bound proteins using mass spectrometry. Proteins that specifically bound were chaperones and included HSP90, HSP60 and the TRiC complex. In conclusion, lyso-Gb3 exposure affects pathways involved in protein translation and folding. This response is observed as increased ubiquitination and changes in signalling proteins which may explain the multiple biological processes, particularly cellular remodelling, often associated with FD.
Typical meteorological year data analysis for optimal usage of energy systems at six selected locations in Nigeria
Authors: Kilanko Oluwaseu , Oyedepo Sunday O , Dirisu Joseph O , Leramo Richard O , Babalola Philip , Aworinde Abraham K , Udo Mfon , Okonkwo Alexander M , Akomolafe Marvelous I 
Published: May 2023

ABSTRACT
In this study, the typical meteorological year (TMY) data for six locations representing the six geopolitical zones in Nigeria were generated and analyzed using the Sandia method. The analysis shows that seasonal variations exist in all the selected locations indicating two distinct seasons: the dry and wet seasons with varying lengths from north to south of the country. Due to its high global radiation levels (21–25 MJ/m2/d), the North is a desirable location for solar-thermal systems. In addition, the high monthly mean temperature variations (~18°C), low relative humidity (RHM) (15%) and constant wind speeds (4 m/s) experienced in the first 3 months of the year aid the installation of wind energy systems and the application of evaporative cooling techniques that reduce the thermal load and energy consumption of buildings. On the other side, the high RHM (80%) and mediocre radiation values derived almost throughout the year in the Southwest, Southeast and South–south regions discourages the extensive application of evaporative cooling and solar energy-based systems in such locations, but the moderate wind speeds (2.9 m/s) and monthly mean temperature variations associated with these regions between the first 3 months of the year allow for the application of natural ventilation and some passive cooling systems so as to reduce the thermal load of buildings in the regions. The information presented in this work can serve as a guide for design and selection of energy systems and application of energy-related projects in Nigeria.
Proof of the Strong Ivić Conjecture for the Cubic Moment of Maass-Form L-Functions
Authors: Qi Zhi 
Published: May 2023

Abstract
In this paper, we prove the following asymptotic formula for the spectral cubic moment of central $L$-values: $$\begin{align*}& \sum_{t_f \leqslant T} \frac{2 L \big( \tfrac 1 2, f \big)^3} {L(1, \textrm{Sym}^2 f)} + \frac{2} {\pi} \int_{ 0}^{T} \frac{\left| \zeta \big(\tfrac 1 2 + it \big) \right|^{6}} { | \zeta (1 + 2 it ) |^2 } \textrm{d} t = T^2 P_3 (\log T) + O (T^{1+{\varepsilon}}), \end{align*}$$where $f$ ranges in an orthonormal basis of (even) Hecke–Maass cusp forms and $P_3$ is a certain polynomial of degree $3$. It improves on the error term $O (T^{8/7+{\varepsilon} })$ in a paper of Ivić and hence confirms his strong conjecture for the cubic moment. This is the 1st time that the (strong) moment conjecture is fully proven in a cubic case. Moreover, we establish the short-interval variant of the above asymptotic formula on intervals of length as short as $T^{{\varepsilon} }$.
Fluorescent and Bioluminescent Reporter Mouse-Adapted Ebola Viruses Maintain Pathogenicity and Can Be Visualized in Vivo
Authors: Davies Katherine A , Welch Stephen R , Jain Shilpi , Sorvillo Teresa E , Coleman-McCray JoAnn D , Montgomery Joel M , Spiropoulou Christina F , Albariño César , Spengler Jessica R 
Published: May 2023

Abstract
Ebola virus (EBOV) causes lethal disease in humans but not in mice. Here, we generated recombinant mouse-adapted (MA) EBOVs, including 1 based on the previously reported serially adapted strain (rMA-EBOV), along with single-reporter rMA-EBOVs expressing either fluorescent (ZsGreen1 [ZsG]) or bioluminescent (nano-luciferase [nLuc]) reporters, and dual-reporter rMA-EBOVs expressing both ZsG and nLuc. No detriment to viral growth in vitro was seen with inclusion of MA-associated mutations or reporter proteins. In CD-1 mice, infection with MA-EBOV, rMA-EBOV, and single-reporter rMA-EBOVs conferred 100% lethality; infection with dual-reporter rMA-EBOV resulted in 73% lethality. Bioluminescent signal from rMA-EBOV expressing nLuc was detected in vivo and ex vivo using the IVIS Spectrum CT. Fluorescent signal from rMA-EBOV expressing ZsG was detected in situ using handheld blue-light transillumination and ex vivo through epi-illumination with the IVIS Spectrum CT. These data support the use of reporter MA-EBOV for studies of Ebola virus in animal disease models.