bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of triglyceride-glucose index with clinical outcomes in patients with acute ischemic stroke receiving intravenous thrombolysis
Authors: Toh Emma M. S. , Lim Amanda Y. L. , Ming Chua , Yeo Leonard L. L. , Sia Ching-Hui , Tan Bryce W. Q. , Leow Aloysius S. T. , Ho Jamie S. Y. , Chan Bernard P. L. , Sharma Vijay Kumar , Tan Benjamin Y. Q. 
Published: January 2022

AbstractIntravenous tissue plasminogen activator (tPA) remains the cornerstone of recanalization therapy for acute ischemic stroke (AIS), albeit with varying degrees of response. The triglyceride-glucose (TyG) index is a novel marker of insulin resistance, but association with outcomes among AIS patients who have received tPA has not been well elucidated. We studied 698 patients with AIS who received tPA from 2006 to 2018 in a comprehensive stroke centre. TyG index was calculated using the formula: ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. TyG index was significantly lower in patients that survived at 90-days than those who died (8.61 [Interquartile Range: 8.27–8.99] vs 8.76 [interquartile range: 8.39–9.40], p = 0.007). In multivariate analysis, TyG index was significantly associated with 90-day mortality (OR: 2.12, 95% CI: 1.39–3.23, p = 0.001), poor functional outcome (OR: 1.41 95% CI: 1.05–1.90, p = 0.022), and negatively associated with early neurological improvement (ENI) (OR: 0.68, 95% CI: 0.52–0.89, p = 0.004). There was no association between TyG index and symptomatic intracranial hemorrhage. ‘High TyG’ (defined by TyG index ≥ 9.15) was associated with mortality, poor functional outcomes and no ENI. In conclusion, the TyG index, a measure of insulin resistance, was significantly associated with poorer clinical outcomes in AIS patients who received tPA.
Weekly treatment with SAMiRNA targeting the androgen receptor ameliorates androgenetic alopecia
Authors: Yun Sung-Il , Lee Sang-Kyu , Goh Eun-Ah , Kwon Oh Seung , Choi Woorim , Kim Jangseon , Lee Mi Sun , Choi Soon Ja , Lim Seung Sik , Moon Tae Kee , Kim Sin Hae , Kyong Keeyeol , Nam Gaewon , Park Han-Oh 
Published: January 2022

AbstractAndrogenetic alopecia (AGA) is the most common type of hair loss in men and women. Dihydrotestosterone (DHT) and androgen receptor (AR) levels are increased in patients with AGA, and DHT-AR signaling correlates strongly with AGA pathogenesis. In this study, treatment with self-assembled micelle inhibitory RNA (SAMiRNA) nanoparticle-type siRNA selectively suppressed AR expression in vitro. Clinical studies with application of SAMiRNA to the scalp and massaging to deliver it to the hair follicle confirmed its efficacy in AGA. For identification of a potent SAMiRNA for AR silencing, 547 SAMiRNA candidates were synthesized and screened. SAMiRNA-AR68 (AR68) was the most potent and could be efficiently delivered to human follicle dermal papilla cells (HFDPCs) and hair follicles, and this treatment decreased the AR mRNA and protein levels. We confirmed that 10 µM AR68 elicits no innate immune response in human PBMCs and no cytotoxicity up to 20 µM with HFDP and HaCaT cells. Clinical studies were performed in a randomized and double-blind manner with two different doses and frequencies. In the low-dose (0.5 mg/ml) clinical study, AR68 was applied three times per week for 24 weeks, and through quantitative analysis using a phototrichogram, we confirmed increases in total hair counts. In the 24-week long high-dose (5 mg/ml) clinical study, AR68 showed average additional hair growth of 1.3-1.9 hairs/cm2 per month, which is comparable to finasteride. No side effects were observed. Therefore, SAMiRNA targeting AR mRNA is a potential novel topical treatment for AGA.
Casein kinases are required for the stability of the glucose-sensing receptor Rgt2 in yeast
Authors: Kim Jeong-Ho , Bloor Daniel , Rodriguez Rebeca , Mohler Emma , Mailloux Levi , Melton Sarah , Jung Dajeong 
Published: January 2022

AbstractIn yeast, glucose induction of HXT (glucose transporter gene) expression is achieved via the Rgt2 and Snf3 glucose sensing receptor (GSR)-mediated signal transduction pathway. The membrane-associated casein kinases Yck1 and Yck2 (Ycks) are involved in this pathway, but their exact role remains unclear. Previous work suggests that the Ycks are activated by the glucose-bound GSRs and transmit the glucose signal from the plasma membrane to the nucleus. However, here we provide evidence that the YCks are constitutively active and required for the stability of the Rgt2 receptor. Cell surface levels of Rgt2 are significantly decreased in a yck1Δyck2ts mutant, but this is not due to endocytosis-mediated vacuolar degradation of the receptor. Similar observations are made in an akr1Δ mutant, where the Ycks are no longer associated with the membrane, and in a sod1Δ mutant in which the kinases are unstable. Of note, in an akr1Δ mutant, both the Ycks and Rgt2 are mislocalized to the cytoplasm, where Rgt2 is stable and functions as an effective receptor for glucose signaling. We also demonstrate that Rgt2 is phosphorylated on the putative Yck consensus phosphorylation sites in its C-terminal domain (CTD) in a Yck-dependent manner and that this glucose-induced modification is critical for its stability and function. Thus, these results indicate a role for the Ycks in stabilizing Rgt2 and suggest that Rgt2 may use glucose binding as a molecular switch not to activate the Ycks but to promote Yck-dependent interaction and phosphorylation of the CTD that increases its stability.
Reading on a smartphone affects sigh generation, brain activity, and comprehension
Authors: Honma Motoyasu , Masaoka Yuri , Iizuka Natsuko , Wada Sayaka , Kamimura Sawa , Yoshikawa Akira , Moriya Rika , Kamijo Shotaro , Izumizaki Masahiko 
Published: January 2022

AbstractElectronic devices have become an indispensable part of our daily lives, while their negative aspects have been reported. One disadvantage is that reading comprehension is reduced when reading from an electronic device; the cause of this deficit in performance is unclear. In this study, we investigated the cause for comprehension decline when reading on a smartphone by simultaneously measuring respiration and brain activity during reading in 34 healthy individuals. We found that, compared to reading on a paper medium, reading on a smartphone elicits fewer sighs, promotes brain overactivity in the prefrontal cortex, and results in reduced comprehension. Furthermore, reading on a smartphone affected sigh frequency but not normal breathing, suggesting that normal breathing and sigh generation are mediated by pathways differentially influenced by the visual environment. A path analysis suggests that the interactive relationship between sigh inhibition and overactivity in the prefrontal cortex causes comprehension decline. These findings provide new insight into the respiration-mediated mechanisms of cognitive function.
Weaning differentially affects the maturation of piglet peripheral blood and jejunal Peyer’s patches
Authors: Correa Federico , Luise Diana , Bosi Paolo , Trevisi Paolo 
Published: January 2022

AbstractThe study aimed to assess how the post-weaning condition changes piglet peripheral blood (PB) and jejunal Peyer’s patches (JPPs) as compared to the suckling period, and how these changes are associated with intestinal microbiota evolution. Sixteen pigs were slaughtered and sampled for PB, JPPs and jejunal content (JC) at weaning (26 days) or at 12 days fed on a pre-starter diet. The PB and JPP transcriptomes were analysed using mRNA-seq. The Gene Set Enrichment Analysis was used to demonstrate enriched gene clusters, depending on sampling time. Jejunal microbiota was profiled using 16S rRNA gene sequencing. Post-weaning JPPs were enriched for processes related to the activation of IFN-γ and major histocompatibility complex (MHC) class I antigen processing which clustered with the reduced abundance of the Weisella genus and Faecalibacterium prausnitzii in JC. The post-weaning microbiome differed from that seen in just-weaned pigs. For just-weaned PB, the enrichment of genes related to hemoglobin and the iron metabolism indicated the greater presence of reticulocytes and immature erythrocytes. The JPP genes involved in the I MHC and IFN-γ activations were markers of the post-weaning phase. Several genes attributable to reticulocyte and erythrocyte maturation could be interesting for testing the iron nutrition of piglets.
Exogenous polyserine and polyleucine are toxic to recipient cells
Authors: Owada Ryuji , Mitsui Shinichi , Nakamura Kazuhiro 
Published: January 2022

AbstractRepeat-associated non-AUG (RAN) translation of mRNAs/transcripts responsible for polyglutamine (polyQ) diseases may generate peptides containing different mono amino acid tracts such as polyserine (polyS) and polyleucine (polyL). The propagation of aggregated polyQ from one cell to another is also an intriguing feature of polyQ proteins. However, whether the RAN translation-related polyS and polyL have the ability to propagate remains unclear, and if they do, whether the exogenous polyS and polyL exert toxicity on the recipient cells is also not known yet. In the present study, we found that aggregated polyS and polyL peptides spontaneously enter neuron-like cells and astrocytes in vitro. Aggregated polyS led to the degeneration of the differentiated neuron-like cultured cells. Likewise, the two types of aggregates taken up by astrocytes induced aberrant differentiation and cell death in vitro. Furthermore, injection of each of the two types of aggregates into the ventricles of adult mice resulted in their behavioral changes. The polyS-injected mice showed extensive vacuolar degeneration in the brain. Thus, the RAN translation-related proteins containing polyS and polyL have the potential to propagate and the proteins generated by all polyQ diseases might exert universal toxicity in the recipient cells.
Phasor map analysis to investigate Hutchinson–Gilford progeria cell under polarization-resolved optical scanning microscopy
Authors: Mohebi Ali , Le Gratiet Aymeric , Trianni Alberta , Callegari Fabio , Bianchini Paolo , Diaspro Alberto 
Published: January 2022

AbstractPolarized light scanning microscopy is a non-invasive and contrast-enhancing technique to investigate anisotropic specimens and chiral organizations. However, such arrangements suffer from insensitivity to confined blend of structures at sub-diffraction level. Here for the first time, we present that the pixel-by-pixel polarization modulation converted to an image phasor approach issues an insightful view of cells to distinguish anomalous subcellular organizations. To this target, we propose an innovative robust way for identifying changes in the chromatin compaction and distortion of nucleus morphology induced by the activation of the lamin-A gene from Hutchinson–Gilford progeria syndrome that induces a strong polarization response. The phasor mapping is evaluated based on the modulation and phase image acquired from a scanning microscope compared to a confocal fluorescence modality of normal cell opposed to the progeria. The method is validated by characterizing polarization response of starch crystalline granules. Additionally, we show that the conversion of the polarization-resolved images into the phasor could further utilized for segmenting specific structures presenting various optical properties under the polarized light. In summary, image phasor analysis offers a distinctly sensitive fast and easy representation of the polarimetric contrast that can pave the way for remote diagnosis of pathological tissues in real-time.
TdfH selectively binds metal-loaded tetrameric calprotectin for zinc import
Authors: Bera Aloke K. , Wu Runrun , Harrison Simone , Cornelissen Cynthia Nau , Chazin Walter J. , Noinaj Nicholas 
Published: January 2022

AbstractTo combat nutritional immunity, N. gonorrhoeae has evolved systems to hijack zinc and other metals directly from host metal-binding proteins such as calprotectin (CP). Here, we report the 6.1 Å cryoEM structure of the gonococcal surface receptor TdfH in complex with a zinc-bound CP tetramer. We further show that TdfH can also interact with CP in the presence of copper and manganese, but not with cobalt.
Three-dimensional imaging of convective cells in the photosphere of Betelgeuse
Authors: López Ariste A. , Georgiev S. , Mathias Ph. , Lèbre A. , Wavasseur M. , Josselin E. , Konstantinova-Antova R. , Roudier Th. 
Published: January 2022

Aims. Understanding convection in red supergiants and the mechanisms that trigger the mass loss from these evolved stars are the general goals of most observations of Betelgeuse and its inner circumstellar environment.
Methods. Linear spectropolarimetry of the atomic lines of the spectrum of Betelgeuse reveals information about the three-dimensional (3D) distribution of brightness in its atmosphere. We model the distribution of plasma and its velocities and use inversion algorithms to fit the observed linear polarization.
Results. We obtain the first 3D images of the photosphere of Betelgeuse. Within the limits of the used approximations, we recover vertical convective flows and measure the velocity of the rising plasma at different heights in the photosphere. In several cases, we find this velocity to be constant with height, indicating the presence of forces other than gravity acting on the plasma and counteracting it. In some cases, these forces are sufficient to maintain plasma rising at 60 km s−1 to heights where this velocity is comparable to the escape velocity.
Conclusions. Forces are present in the photosphere of Betelgeuse that allow plasma to reach velocities close to the escape velocity. These mechanisms may suffice to trigger mass loss and sustain the observed large stellar winds of these evolved stars.
Panzytopenie und B-Symptomatik – unerwartetes Souvenir?
Authors: Gebel Benjamin , Rupp Jan , Kramme Evelyn 
Published: January 2022

Zusammenfassung
Anamnese und klinischer Befund Die Vorstellung des 79-jährigen Patienten erfolgte bei rezidivierenden Fieberepisoden, Gewichtsverlust, Nachtschweiß, deutlicher Abnahme der Belastbarkeit sowie flächigen Hämatomen an den Extremitäten.
Untersuchungen In der durchgeführten Laboruntersuchung zeigte sich eine Panzytopenie bei eingeschränkter Nierenfunktion sowie erhöhtem CRP. Sonografisch konnte eine Splenomegalie nachgewiesen werden. Es erfolgte eine Knochenmarkspunktion.
Diagnose In der Knochenmarkbiopsie konnte histologisch die Diagnose einer viszeralen Leishmaniasis gestellt werden, welche mittels PCR aus dem peripheren Blut bestätigt wurde.
Therapie und Verlauf Unter der Therapie mit liposomalem Amphotericin B kam es zu einer deutlichen Besserung der Panzytopenie sowie einem Abfall des CRP. Die Nierenfunktion erholte sich nach initialer Verschlechterung nur langsam. Fieber trat nicht mehr auf.
Folgerung Bei Vorliegen einer Panzytopenie mit entsprechender klinischer Symptomatik sollte bei möglicher Exposition auch bei vermeintlich immunkompetenten Patienten an eine viszerale Leishmaniasis gedacht werden.
Windenergieanlagen und Infraschall: Keine Evidenz für gesundheitliche Beeinträchtigungen – eine physikalische, medizinische und gesellschaftliche Einordnung
Authors: Koch Susanne , Holzheu Stefan , Hundhausen Martin 
Published: January 2022

ZusammenfassungAufgrund der Diskussion über gesundheitliche Folgen von Schallemissionen und Infraschall von Windenergieanlagen, fassen wir hier im Rahmen eines narrativen Reviews die Studienlage zusammen und stellen die physikalischen Fakten vor. Infraschall unterschiedlichster Quellen umgibt uns täglich, wobei Windenergieanlagen keine besonders hohen Emissionen verursachen. Epidemiologische Studien zeigen keinen Zusammenhang zwischen Windenergieanlagen und der Inzidenz von Diabetes mellitus, Herzinfarkten, Schlaganfällen und Bluthochdruck; nur eine häufigere Verschreibung von Schlafmitteln war nachweisbar. Allerdings zeigen objektiv erhobene Schlafparameter keine Assoziation zu Windenergieanlagen. Gesundheitliche Klagen treten vermehrt auf, wenn Anti-Windkraft-Gruppen aktiv sind, was dafürspricht, dass psychogene Einflüsse und Nocebo-Effekte eine wichtige Rolle spielen. Bei fehlender wissenschaftlicher Evidenz für gesundheitliche Beeinträchtigungen durch Windenergieanlagen ist ein Ausbremsen des Ausbaus erneuerbarer Energien nicht zu rechtfertigen.
The First 4 Years – Outcome of Children Identified by Newborn
Screening for CF in Germany
Authors: Schütz Katharina , Kontsendorn Julia , Janzen Nils , Fuge Jan , Grewendorf Simon , Klemann Christian , Happle Christine , Junge Sibylle , Rudolf Isa , Dopfer Christian , Sedlacek Ludwig , Renz Diane , Hansen Gesine , Dittrich Anna-Maria 
Published: January 2022

Abstract
Background Newborn screening (NBS) has been shown to improve cystic
fibrosis (CF) disease course and has been widely implemented worldwide. This
monocentric study compared children diagnosed by NBS vs. a cohort preceding the
implementation of NBS in Germany in 2016 to evaluate ascribed benefits of
NBS.
Methods We compared all children with confirmed CF diagnosis
(n=19, “NBS group”) out of all children presenting with
positive NBS at our center after implementation of NBS (n=100) to
children diagnosed with CF at our center within 4 years before NBS
implementation (n=29, “pre-NBS group”) for outcomes of
anthropometry, gastrointestinal and pulmonary disease manifestations and
respiratory microbiology.
Results Children diagnosed by NBS had a lower incidence of initial
difficulty to thrive (15 vs. 41%) and showed higher mean z-scores for
Body-Mass-Index (BMI), weight and length at diagnosis and during study period.
Children in the pre-NBS group displayed higher proportions of oxygen-dependent
pulmonary exacerbations (10 vs. 0%). They show a significantly lower
amount of normal bacterial flora (p=0.005) along with a significantly
higher number of throat swab cultures positive for Pseudomonas aeruginosa
(p=0.0154) in the first year of life. Yet, pulmonary imaging did not
reveal less pulmonary morbidity in the NBS group.
Conclusions Our results confirm that NBS for CF leads to earlier diagnosis
and improves nutritional outcomes in early childhood. Although trajectories of
structural lung damage at early age were unaffected by NBS, NBS positive CF
patients at preschool age displayed less pulmonary exacerbations and
pathological bacteria in throat swabs.
Impact of expert center endoscopic assessment of confirmed low grade dysplasia in Barrett’s esophagus diagnosed in community hospitals
Authors: Nieuwenhuis Esther A. , van Munster Sanne N. , Curvers Wouter L. , Weusten Bas L. A. M. , Alvarez Herrero Lorenza , Bogte Auke , Alkhalaf Alaa , Schenk B. Ed , Koch Arjun D. , Spaander Manon C. W. , Tang Thjon J. , Nagengast Wouter B. , Westerhof Jessie , Houben Martin H. M. G. , Bergman Jacques J.G.H.M. , Schoon Erik J. , Pouw Roos E. ,   on behalf of the Dutch Barrett Expert Centers
Published: January 2022

Background The optimal management for patients with low grade dysplasia (LGD) in Barrett’s esophagus (BE) is unclear. According to the Dutch national guideline, all patients with LGD with histological confirmation of the diagnosis by an expert pathologist (i. e. “confirmed LGD”), are referred for a dedicated re-staging endoscopy at an expert center. We aimed to assess the diagnostic value of re-staging endoscopy by an expert endoscopist for patients with confirmed LGD.
Methods This retrospective cohort study included all patients with flat BE diagnosed in a community hospital who had confirmed LGD and were referred to one of the nine Barrett Expert Centers (BECs) in the Netherlands. The primary outcome was the proportion of patients with prevalent high grade dysplasia (HGD) or cancer during re-staging in a BEC.
Results Of the 248 patients with confirmed LGD, re-staging in the BEC revealed HGD or cancer in 23 % (57/248). In 79 % (45/57), HGD or cancer in a newly detected visible lesion was diagnosed. Of the remaining patients, re-staging in the BEC showed a second diagnosis of confirmed LGD in 68 % (168/248), while the remaining 9 % (23/248) had nondysplastic BE.
Conclusion One quarter of patients with apparent flat BE with confirmed LGD diagnosed in a community hospital had prevalent HGD or cancer after re-staging at an expert center. This endorses the advice to refer patients with confirmed LGD, including in the absence of visible lesions, to an expert center for re-staging endoscopy.
Psychiatric Manifestations in Patients with Biopterin Defects
Authors: Parfyonov Maksim , Friedlander Robin , Banno Brian , Elbe Dean , Horvath Gabriella 
Published: January 2022

AbstractPsychiatric manifestations in patients with tetrahydrobiopterin (BH4) defects are common, and may occur even with treatment of the underlying disorder. The neurobiological background of these conditions has been linked to abnormalities of neurotransmitters, such as dopamine, serotonin, norepinephrine, and gamma-aminobutyric acid. Here, we review the psychiatric profile of all patients with BH4 defects followed in the pediatric and adult metabolic clinics at our center. Three patients with autosomal recessive (AR) guanosine triphosphate cyclohydrolase (GTPCH) deficiency and three patients with 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency were reviewed.All patients had behavioral disturbances and two had significant psychiatric comorbidities. These included attention deficit/hyperactivity disorder, anxiety, depression, aggression, or oppositional defiant disorder. One patient with PTPS deficiency had a severe psychiatric presentation, requiring inpatient admission and temporary placement into foster care for intensive behavioral therapy. Another with AR GTPCH deficiency was diagnosed with aggressive behavioral dysregulation requiring intensive psychiatric treatment. Management of the psychiatric manifestations of BH4 defects can be challenging, due to lack of information and studies of interactions between psychiatric medications on the deficient neurotransmitters and their receptors in these conditions. Further studies are needed to establish safety and efficacy of these treatments.
Probability weighting and insurance demand in a unified framework
Authors: Jaspersen Johannes G. , Peter Richard , Ragin Marc A. 
Published: January 2022

AbstractWe provide a comprehensive analysis of the impact of probability weighting on optimal insurance demand in a unified framework. We identify decreasing relative overweighting as a new local condition on the probability weighting function that is useful for comparative static analysis. We discuss the effects of probability weighting on coinsurance, deductible choice, insurance demand for low-probability, high-impact risks versus high-probability, low-impact risks, and insurance demand in the presence of nonperformance risk. Probability weighting can make better or worse predictions than expected utility depending on the insurance demand problem at hand.
ASK1 signaling regulates phase-specific glial interactions during neuroinflammation
Authors: Guo Xiaoli , Kimura Atsuko , Namekata Kazuhiko , Harada Chikako , Arai Nobutaka , Takeda Kohsuke , Ichijo Hidenori , Harada Takayuki 
Published: January 2022

Significance
Neuroinflammation is associated with many neurodegenerative diseases such as Alzheimer’s disease and multiple sclerosis (MS). Thus, decreasing neuroinflammation may be a promising treatment for these diseases. Apoptosis signal-related kinase 1 (ASK1) has been shown to cause neuroinflammation in neurodegenerative disease models, but its mechanism of action has been unclear. Here, we generated conditional knockout mice that lack ASK1 in T cells, dendritic cells, microglia/macrophages, microglia, or astrocytes, to assess the roles of ASK1 during experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We propose that ASK1 is required in microglia and astrocytes to cause and maintain neuroinflammation by a feedback loop between these two cell types.