bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective Characterization of Progressive Supranuclear Palsy in a Multi-Ethnic Asian Cohort
Authors: Lim Shen-Yang , Dy Closas Alfand Marl F. , Tan Ai Huey , Lim Jia Lun , Tan Yi Jayne , Vijayanathan Yuganthini , Tay Yi Wen , Abdul Khalid Raihanah binti , Ng Wai Keong , Kanesalingam Ruban , Martinez-Martin Pablo , Foo Jia Nee , Lim Weng Khong , Lyn Ng Adeline Su , Tan Eng-King 
Published: October 2022

ABSTRACTBackgroundProgressive supranuclear palsy (PSP) is a rare, disabling, neurodegenerative disease. There are limited studies on the spectrum of PSP predominance-types and their clinico-demographic features among Asian patients. We prospectively characterized the clinical features, disease severity, and caregiver burden in a multi-ethnic Asian PSP cohort.MethodsConsecutively-recruited patients with PSP (n=104, 64.4% male; 67.3% Chinese, 21.2% Indians, 9.6% Malays) were extensively phenotyped by a movement disorders neurologist using the MDS-PSP clinical diagnostic criteria and PSP-Clinical Deficits Scale (PSP-CDS). Caregiver burden was measured using the modified Zarit Burden Interview (ZBI). Investigations were reviewed to help rule out potential PSP mimics.ResultsThere were 104 patients, consisting of 48.1% Richardson syndrome (PSP-RS), 37.5% parkinsonian phenotype (PSP-P), and 10.6% progressive gait freezing phenotype (PSP-PGF). Mean age at motor onset was 66.3±7.7 years, with no significant differences between the PSP phenotypes. Interestingly, REM-sleep behaviour disorder (RBD) symptoms and visual hallucinations (considered rare in PSP) were reported in 23.5% and 22.8% of patients, respectively, and a family history of possible neurodegenerative or movement disorder in 20.4%. PSP-CDS scores were highest (worst) in PSP-RS; and correlated moderately with disease duration (rs=0.45, P<0.001) and weakly with caregiver burden (rs=0.22, P=0.029) in the overall cohort. Three of 48 (6.3%) patients who had whole-exome sequencing harboured pathogenic/likely pathogenic GBA variants.ConclusionsThis prospective characterization of a relatively large cohort of Asian PSP patients depicts significant heterogeneity in clinical features and disease burden. Unexpectedly high rates of RBD symptoms, visual hallucinations, and familial involvement warrant further study.
Teaching medical students about Kawasaki Disease: The development and evaluation of a digital educational resource
Authors: Song Jong Eun , Tombs Michal 
Published: October 2022

AbstractIntroductionThe use of digital educational resources has gained widespread popularity across all disciplines in medical education; paediatrics being no exception. This paper focuses on the development and in particular, the evaluation, of an e-learning resource on Kawasaki Disease which was primarily developed as a revision aid for undergraduate medical students.MethodsThis digital resource was created using Xerte Online toolkit and was guided by the instructional model ADDIE. The design and development of the resource was based on Mayer’s 12 Multimedia Principles, while Zaharias and Poylymenakou’s usability evaluation method informed the preliminary evaluation.FindingsFeedback from the preliminary evaluation, which was based on the instructional design parameters of ‘navigation’, ‘visual design’ and ‘intrinsic motivation to learn’, was overwhelmingly positive. However, in light of this being a small-scale evaluation conducted on just seven undergraduate students, a protocol was developed for a more in-depth and robust evaluation.Conclusions and further developmentThe evaluation of digital educational resources remains a fundamental and essential component in creating meaningful and effective e-learning material. In line with literature on evaluation of digital educational resources in medical education, the evaluation protocol set out in this paper considers three aspects; evaluating the ability of the resource to meet its intended outcomes; evaluating the ability of the resource to meet learners’ needs; and evaluating the educational context.
The capacity for adaptation to climate warming in an annual plant (Brassica rapa)
Authors: So Cameron P. , Grieshop Karl , Weis Arthur E. 
Published: October 2022

ABSTRACTThe persistence of a declining population in the face of environmental change may depend on how fast natural selection restores fitness, a process called “evolutionary rescue”. In turn, evolutionary rescue depends on a population’s adaptive potential. Fisher’s theorem states that a population’s adaptive potential equals the additive genetic variance for fitness (VA(W)) divided by mean fitness . Both the numerator and denominator of this rate can differ across environments even when holding allele frequencies constant. However, little is known about how these rates change in wild populations during adaptation, including changes in additive and dominance variance. We assessed the change in adaptive potential and dominance variance in fitness (VD(W)) for a Québec population of wild mustard (Brassica rapa) under climate warming. We also assessed adaptive constraints that could arise from negative genetic correlations across environments. We grew a pedigreed population of 7000 plants under ambient and heated (+4°C) temperatures and estimated the change in , VA(W), VD(W), and the cross-environment genetic correlations (rA). As predicted, estimates of VA(W) and adaptive potentials were higher under heated conditions but non-significantly so. This is perhaps because, surprisingly, plants exposed to a warmer climate exhibited greater . Nevertheless, increased fitness in the warmer environment suggests a plasticity-based short-term potential for adaptation, and that weak but non-significant genetic correlations across environments will enable slow on-going adaptation to warming. Overall, this population of B. rapa harbours existing genetic architecture to persist under warmer temperatures through pre-adaptation but not through evolutionary rescue.
Arena3Dweb: Interactive 3D visualization of multilayered networks supporting multiple directional information channels, clustering analysis and application integration
Authors: Kokoli Maria , Karatzas Evangelos , Baltoumas Fotis A. , Schneider Reinhard , Pafilis Evangelos , Paragkamian Savvas , Doncheva Nadezhda T. , Jensen Lars Juhl , Pavlopoulos Georgios A. 
Published: October 2022

ABSTRACTArena3Dwebis an interactive web tool that visualizes multi-layered networks in 3D space. In this update, Arena3Dwebsupports directed networks as well as up to nine different types of connections between pairs of nodes with the use of Bézier curves. It comes with different color schemes (light/gray/dark mode), custom channel coloring, four node clustering algorithms which one can run on-the-fly, visualization in VR mode and predefined layer layouts (zig-zag, star and cube). This update also includes enhanced navigation controls (mouse orbit controls, layer dragging and layer/node selection), while its newly developed API allows integration with external applications as well as saving and loading of sessions in JSON format. Finally, a dedicated Cytoscape app has been developed, through which users can automatically send their 2D networks from Cytoscape to Arena3Dwebfor 3D multi-layer visualization. Arena3Dwebis accessible athttp://arena3d.pavlopouloslab.infoorhttp://arena3d.org
An in silico evaluation of anthraquinone derivatives as potential inhibitors of DNA gyrase B of Mycobacterium tuberculosis
Authors: Amorim Juliana C. , Cabrera Bermeo Andrea E. , Vásquez Urgilés Viviana E. , Martínez León Maritza R. , Carpio Arévalo Juan M. 
Published: October 2022

AbstractThe World Health Organization reported that tuberculosis remains on the list of the top ten threats to public health worldwide. Among the main causes is the limited effectiveness of treatments due to the emergence of a diverse spectrum of resistant strains of Mycobacterium tuberculosis, the causative agent of the disease. One of the main drug targets studied to combat M. tuberculosis is DNA gyrase, the only enzyme responsible for regulating DNA topology in this specie and considered essential in all bacteria. In this context, the present work tested the ability of 2,824 anthraquinones retrieved from the PubChem database to act as competitive inhibitors through interaction with ATP-binding pocket of DNA gyrase B of M. tuberculosis. Virtual screening results based on molecular docking identified 7122772 (N-(2-hydroxyethyl)-9,10-dioxoanthracene-2-sulfonamide) as the best-scored ligand. From this anthraquinone, a new derivative was designed harbouring an aminotriazole moiety, which exhibited higher binding energy calculated by molecular docking scoring and free energy calculation from molecular dynamics simulations. In addition, in these last analyses, this ligand showed to be stable in complex with the enzyme and further predictions indicated an acceptable pharmacokinetic profile. Taken together, the presented results show a new anthraquinone synthetically accessible and with promising potential to inhibit the GyrB of M. tuberculosis.
Bigger is better: Thicker maize brace roots are advantageous for both strength and nitrogen uptake
Authors: Rasmussen Amanda , Erndwein Lindsay , Stager Adam , Reneau Jonathan , Sparks Erin E. 
Published: October 2022

AbstractPlant root systems provide critical functions to enable plant survival. From anchoring the plant in the soil to finding and acquiring water and nutrients, these organs are essential for plant productivity. Despite a variety of root functions, research typically focuses on defining only one function. In this study, we explore a trade-off hypothesis, that the optimization of one root function (i.e. anchorage) may negatively impact another root function (i.e. nitrogen uptake). Previous work has demonstrated that larger roots are stronger, but may also have a diminished capacity for nutrient acquisition due to a reduced surface area to volume ratio. Using maize brace roots that had entered the soil, we show here that larger roots are both stronger and take up more nitrogen. Despite this general relationship, there are subtle trade-offs between mechanics and uptake that occur when assessing individual genotypes. These trade-offs represent an opportunity to optimize one root function without compromising other root functions. Together these data demonstrate that our original trade-off hypothesis was incorrect for maize brace roots, and that larger roots are both stronger and take up more nitrogen.
Top-heavy trophic structure within benthic viral dark matter
Authors: Cissell Ethan C. , McCoy Sophie J. 
Published: October 2022

ABSTRACTViruses exert considerable influence on microbial population dynamics and community structure, with cascading effects on ecosystem-scale biogeochemical cycling and functional trajectories. Creating broadly generalizable theory on viral trophic ecology requires further inquiry into historically unexplored microbial systems that currently lack empirically demonstrated patterns in viral infectivity, such as structurally complex benthic communities. This becomes increasingly relevant considering recently proposed revisions to the fundamental mechanisms that modulate the strength and direction viral trophic linkages. Here, we employed deep longitudinal multiomic sequencing to characterize the viral assemblage (includingssDNA,dsDNA, anddsRNA viruses) and profile lineage-specific host-virus interactions within benthic cyanobacterial mats sampled from Bonaire, Caribbean Netherlands, over a complete diel time-series, and reconstruct patterns in intra-mat trophic structure. We recovered 11,020 unique viral populations spanning at least 10 viral families across the orders Caudovirales, Petitvirales, and Mindivirales, with evidence for extensive genomic novelty from reference and environmental viral sequences. Analysis of coverage ratios of viral sequences and computationally predicted hosts spanning 15 phyla and 21 classes revealed virus:host abundance and activity ratios consistently exceeding 1:1, with overall power-law scaling indicating an increasingly top-heavy intra-mat trophic structure with significant top-down pressure. Diel activity of cyanophages showed clear temporal patterns that seem to follow host physiological condition. These data generate important hypotheses concerning taxon-dependent variation in the relative contribution of top-down vs. bottom-up forcing in driving mat community dynamics, and establish a useful database of viral sequences from this previously unexplored system toward the generation of generalizable trans-system theory on viral trophic ecology.SIGNIFICANCE STATEMENTRecent advances in viral ecological theory suggest a better understanding of system-specific viral ecology is needed from diverse environments to create generalizable theory that accurately predicts patterns of trophic interaction strengths across systems, especially in the Anthropocene. This study characterized viral-host trophic structure within coral reef benthic cyanobacterial mats - a globally proliferating cause and consequence of coral reef degradation - using paired multiomic sequencing. Recovered viral sequences displayed remarkable genomic novelty from other well-characterized viruses and spanned diverse viral taxa. Unexpectedly, lineage-resolved trophic linkages displayed a strongly active top-heavy trophic structure, suggesting extensive top-down forcing. These results highlight the context-dependence of viral trophic interaction strengths and suggest that viruses strongly influence reef cyanobacterial mat and reef ecosystem functional trajectories.
Dynein-mediated trafficking and degradation of nephrin in diabetic podocytopathy
Authors: Sun Hua , Weidner Jillian , Allamargot Chantal , Piper Robert , Misurac Jason , Nester Carla 
Published: October 2022

AbstractDiabetic nephropathy (DN) is characterized by increased endocytosis and degradation of nephrin, a protein that comprises the molecular sieve of the glomerular filtration barrier, but the key trafficking mechanism that connects the initial endocytic events and the homeostasis of nephrin is unknown. Our work implicates cytoplasmic dynein, a transport complex that is upregulated in DN, plays a critical role in triaging the endocytosed nephrin between recycling and proteolytic pathways. Using Nephroseq platform, our transcription analysis in public DN databases revealed dynein overexpression in human DN and diabetic mouse kidney, correlated with the severity of hyperglycemia and nephropathy. The increased expression of dynein subunits was confirmed in high glucose-treated podocytes and in glomeruli isolated from streptozotocin (STZ)-induced diabetic mice. Using live cell imaging, we illustrated that dynein-mediated post-endocytic sorting of nephrin was upregulated, resulting in accelerated nephrin degradation and disrupted nephrin recycling. In diabetic podocytopathy, Dynll1 is one of the most upregulated dynein components that was recruited to endocytosed nephrin. This was corroborated by observing enhanced Dynll1-nephrin colocalization in podocytes of diabetic patients, as well as dynein-mediated trafficking and degradation of nephrin in STZ-induced diabetic mice. Knockdown of Dynll1 attenuated lysosomal degradation of nephrin and promoted its recycling, suggesting the essential role of Dynll1 in dynein-mediated mistrafficking. Defining the role of dynein-mediated mistrafficking of nephrin in diabetes will not only fill the knowledge gap about the early events of DN, but also inspire novel therapeutics that target a broad spectrum of molecular events involved in the dynein-mediated trafficking.Translational StatementDiabetic nephropathy (DN), the leading cause of end stage kidney disease in the United States, is characterized by a podocytopathy with mistrafficking and depletion of the slit diaphragm protein nephrin, which in turn compromises the podocytes’ function in maintaining the glomerular filtration barrier. There is a critical need to define the trafficking mechanisms underlying the depletion of nephrin. Our work implicates cytoplasmic dynein, a trafficking complex that connects diabetes-triggered endocytosis with proteolytic pathways. Delineation of the dynein-driven pathogenesis of diabetic podocytopathy will inspire new therapies that potentially target a broad spectrum of molecules involved in dynein-mediated trafficking and degradation pathways.
Magnitude, Associated Factors and Immediate Outcomes of Non-Reassuring Fetal Heart Rate Status Among Laboring Mothers at South Gondar Zone Public Hospitals, North, West Ethiopia, 2022; Cross Sectional Study
Authors: Belete Ewunetu , Bazezew Yibelu , Desta Melaku , Misganaw Dawit , Tefera Mitiku 
Published: October 2022

AbstractBackgroundNon-reassuring fetal heart rate status (NRFHRS) is an abnormal fetal heart rate monitoring which necessitates immediate intervention. It is one of the common reducible causes of perinatal morbidity and mortality in developing countries. Despite there is limited data on the magnitude, associated factors and its outcomes in Ethiopia.ObjectiveTo assess the magnitude, associated factors and immediate outcomes of non-reassuring fetal heart rate status among laboring mothers at South Gondar zone public hospitals, northwest Ethiopia 2022.MethodsAn institutional-based cross-sectional study was conducted from June 1-30, 2022. A total of 586 laboring mothers were included. The participants were selected through systematic sampling method. Bivariable and multivariable logistic regression analysis were carried out. OR with 95% CI was used and statistically significant variables were declared if p < 0.05 in multivariable analysis.ResultThe magnitude of NRFHRS was 21.16% (95%, CI: 17.9-24.7) with a response rate of 97.34%. Primigravida [AOR= 1.86, 95% CI: 1.03-3.37], anemia [AOR= 4.59, 95% CI: 1.87-11.30], referred [AOR= 1.95, 95% CI: 1.07-3.55], induction of labor [AOR= 3.78, 95% CI: 1.20-11.9], meconium-stained amniotic fluid [AOR= 14.13, 95% CI: 7.53-26.50], prolonged rupture of membrane [AOR= 11.70), 95% CI: 5.40-25.34] and low birth weight [AOR=5.08, 95% CI: 2.20-11.74] were significantly associated with NRFHRS. 4.8% of fetus was still birth.ConclusionIn this study the magnitude of NRFHRS was high compared to studies in Africa. Being primigravida, anemic, referred, induction of labor, meconium-stained amniotic fluid, prolonged rupture of membrane and low birth weight were significantly associated with NRFHRS. Assigning adequate number of midwifes for good labor follow-up, properly counsel on nutrition and iron and folic acid and give due attention on labor follow-up would minimize NRFHRS.
Engineering Highly Thermostable Cas12b via De Novo Structural Analyses for One-Pot Detection of Nucleic Acids
Authors: Nguyen Long T. , Rananaware Santosh R. , Yang Lilia G. , Macaluso Nicolas C. , Ocana-Ortiz Julio E. , Meister Katelyn S. , Pizzano Brianna L.M. , Sandoval Luke Samuel W. , Hautamaki Raymond C. , Fang Zoe R. , Joseph Sara M. , Shoemaker Grace M. , Carman Dylan R. , Chang Liwei , Rakestraw Noah R. , Zachary Jon F. , Guerra Sebastian , Perez Alberto , Jain Piyush K. 
Published: October 2022

AbstractClustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based diagnostics have elevated nucleic acid detection in terms of sensitivity, specificity, and rapidity in recent years. CRISPR-Cas systems can be combined with a pre-amplification step in a one-pot reaction to simplify workflow and reduce carryover contamination. Here, we report an engineered Cas12b system from Brevibacillus (eBrCas12b) with improved thermostability that falls within the optimal range (60-65°C) of the Reverse Transcription-Loop-Mediated Isothermal Amplification (RT-LAMP). Using de novo structural analyses via DeepDDG and HotSpot Wizard based on Alpha Fold and SWISS-MODEL predicted structures, mutations were introduced into the REC and RuvC domains of wild-type BrCas12b to tighten the hydrophobic cores of the protein, thereby enhancing its stability at high temperatures. We expressed, purified, and systematically characterized 49 BrCas12b variants with an emphasis on functionality and thermostability. The assay utilizing eBrCas12b, which we coined SPLENDID (Single-pot LAMP-mediated engineered BrCas12b for nucleic acid detection of infectious diseases), exhibits robust trans-cleavage activity up to 67°C in a one-pot setting—4°C and 7°C higher than wild-type BrCas12b and AapCas12b, respectively. We further validated SPLENDID clinically in 40 Hepatitis C (HCV) positive and 40 negative serum samples. A specificity of 97.5%, an accuracy of 90.0%, and a sensitivity of 82.5% were achieved. Results can be obtained via one-pot testing in as little as 20 minutes. With the extraction process, the entire assay can be performed in under an hour. Therefore, we believe that SPLENDID has the potential to become a widely universal platform for the detection of infectious diseases.
Glucoregulatory Reprogramming in Male Mice Offspring Induced by Maternal Transfer of Indoor Flame Retardant Endocrine Disruptors
Authors: Kozlova Elena V. , Chinthirla Bhuvaneswari D. , Bishay Anthony E. , Pérez Pedro A. , Denys Maximillian E. , Krum Julia M. , DiPatrizio Nicholas V. , Currás-Collazo Margarita C. 
Published: October 2022

AbstractPolybrominated diphenyl ethers (PBDEs) are commercially used as indoor flame retardants that penetrate biota and bioaccumulate in human tissues, including breast milk. PBDEs have been associated with endocrine disruption, diabetes and metabolic syndrome (MetS) in humans and animals. However, their sex-specific diabetogenic effects are not completely understood. Our past works show diabetogenic effects of the commercial penta-mixture of PBDEs, DE-71, in perinatally exposed C57Bl/6 female mice. As a comparison, in the current study, the effects of DE-71 on glucose homeostasis in male offspring were examined. C57BL/6 dams were exposed to DE-71 at 0.1 mg/kg/d (L-DE-71), 0.4 mg/kg/d (H-DE-71) or received corn oil vehicle (VEH/CON) for a total of 10 wks, including gestation and lactation. Male offspring were examined in adulthood and DE-71 exposure produced hypoglycemia upon extended fasting. In vivo glucose challenge testing showed marked intolerance (H-DE-71) and incomplete clearance (L- and H-DE-71). Moreover, L-DE-71-exposed mice showed altered glucose responses to insulin, especially incomplete glucose clearance and/or utilization. In addition, L-DE-71 produced elevated levels of plasma glucagon and the incretin GLP-1 but no changes were detected on insulin. These alterations, which represent relevant criteria used clinically to diagnose diabetes, were accompanied with reduced hepatic glutamate dehydrogenase enzymatic activity, elevated adrenal epinephrine and decreased thermogenic brown adipose tissue mass, which may indicate several organ system targets of PBDEs. Liver levels of several endocannabinoid species were not altered by perinatal exposure to DE-71 in males. Our findings demonstrate that chronic low exposure to PBDEs in mothers can reprogram glucose homeostasis and glucoregulatory hormones in male offspring. Previous findings using female offspring showed altered glucose homeostasis that aligned with a contrasting diabetogenic phenotype. We summarize the results of the current work generated in males in light of previous findings on females. Taken together, these findings, combined with our prior results, offer a comprehensive account of sex-dependent effects of maternally transferred environmentally relevant PBDEs on glucose homeostasis and glucoregulatory endocrine dysregulation.