bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiplex CRISPR/Cas9-mediated knockout of the phytoene desaturase gene in Coffea canephora
Authors: Casarin Tatiane , Freitas Natália Chagas , Pinto Renan Terassi , Breitler Jean‑Christophe , Rodrigues Leonardo Augusto Zebral , Marraccini Pierre , Etienne Hervé , Diniz Leandro Eugenio Cardamone , Andrade Alan Carvalho , Paiva Luciano Vilela 
Published: October 2022

AbstractCoffea canephora (2n = 2x = 22 chromosomes) is a species with extensive genetic diversity and desirable agronomic traits for coffee breeding programs. However, obtaining a new coffee cultivar through conventional breeding techniques may require more than 30 years of crossing cycles and selection, which hampers the effort of keeping up with market demands and rapidly proposing more resilient to climate change varieties. Although, the application of modern biotechnology tools such as precision genetic engineering technologies may enable a faster cultivar development process. Therefore, we aimed to validate the CRISPR/Cas9 system to generate mutations on a selected genotype of C. canephora, the clone 14. Embryogenic calli and a multiplex binary vector containing two sgRNAs targeting different exons of the CcPDS gene were used. The sgRNAs were under the C. canephora U6 promoter regulation. The target gene encodes phytoene desaturase, an enzyme essential for photosynthesis involved in β-carotene biosynthesis. Somatic seedlings and embryos with albino, variegated and green phenotypes regenerated after Agrobacterium tumefaciens-mediated genetic transformation were analyzed by verifying the insertion of the Cas9 gene and later by sequencing the sgRNAs target regions in the genome of Robusta modified seedlings. Among them, 77% had the expected mutations, and of which, 50% of them had at least one target with a homozygous mutation. The genotype, temperature of co-cultivation with the bacteria, and light intensity used for subsequent embryo regeneration appeared to strongly influence the successful regeneration of plants with a mutated CcPDS gene in the Coffea genus.
A performance comparison between fluorescent immunoassay and immunochromatography for rapid dengue detection in clinical specimens
Authors: Ruchusatsawat Kriangsak , Benjamungkalarak Tanawat , Phunikom Naruphong , Vateh Husneeyah , Kowitdamrong Ekasit , Wongpiyabovorn Jongkonnee , Boonyasuppayakorn Siwaporn 
Published: October 2022

AbstractDengue virus (DENV 1–4) infection has been a global health threat where no specific treatment is currently available. Therefore, a rapid and accurate diagnosis is critical for an appropriate management as it could reduce the burden of severe clinical manifestation. Currently, dengue immunochromatography (IC) is commonly used to primarily differentiate acute febrile illnesses. Fluorescent immunoassay (FIA) utilized a highly sensitive detection system and claimed 70–100% sensitivity and 83.5–91.7% specificity for dengue infection in a preliminary report. This report recruited samples with acute febrile illnesses sent for dengue screening and tested IC and FIA in parallel. The performance of both tests was verified by a definitive diagnosis retrieved from combinatorial reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) for IgM and IgG confirmation tests. Results showed that the viral nonstructural protein (NS1) performance of FIA was slightly higher than IC with the sensitivity, specificity, PPV, NPV, agreement, kappa, and its standard error at 79.11, 92.28, 86.81, 87.31, 352 (87.13%), 0.725 ± 0.035, respectively; whereas those of the IC were at 76.58, 92.28, 86.43, 85.98, 348 (86.14%), 0.703 ± 0.037, respectively. Moreover, the IgM and IgG performance of FIA had higher specificity, PPV, and agreement than the IgM IC performance, suggesting that the FIA was more specific but less sensitive for antibody detection. No correlation was observed in IgM and IgG levels of ELISA and FIA assays. In conclusion, the FIA and IC were highly sensitive, specific, and substantially agreed in NS1 detection but moderately agreed in IgM and IgG detection.
Identification of in vivo roles of ErbB4-JMa and its direct nuclear signaling using a novel isoform-specific knock out mouse
Authors: Doherty Robert , MacLeod Brenna L. , Nelson Megan M. , Ibrahim Mostafa M. H. , Borges Beatriz C. , Jaradat Nada W. , Finneran Matthew C. , Giger Roman J. , Corfas Gabriel 
Published: October 2022

AbstractLike all receptor tyrosine kinases (RTKs), ErbB4 signals through a canonical signaling involving phosphorylation cascades. However, ErbB4 can also signal through a non-canonical mechanism whereby the intracellular domain is released into the cytoplasm by regulated intramembrane proteolysis (RIP) and translocates to the nucleus where it regulates transcription. These different signaling mechanisms depend on the generation of alternative spliced isoforms, a RIP cleavable ErbB4-JMa and an uncleavable ErbB4-JMb. Non-canonical signaling by ErbB4-JMa has been implicated in the regulation of brain, heart, mammary gland, lung, and immune cell development. However, most studies on non-canonical ErbB4 signaling have been performed in vitro due to the lack of an adequate mouse model. We created an ErbB4-JMa specific knock out mouse and demonstrate that RIP-dependent, non-canonical signaling by ErbB4-JMa is required for the regulation of GFAP expression during cortical development. We also show that ErbB4-JMa signaling is not required for the development of the heart, mammary glands, sensory ganglia. Furthermore, we identify genes whose expression during cortical development is regulated by ErbB4, and show that the expression of three of them,CRYM,PRSS12andDBi, depend on ErbB4-JMa whereasWDFY1relies on ErbB4-JMb. Thus, we provide the first animal model to directly study the roles of ErbB4-JMa and non-canonical ErbB4 signaling in vivo.
Prognostic factors for the treatment of meniscus horizontal tear
Authors: Lee Joon Kyu , Lee Myung Chul , Kim Joong Il , Lim Subin 
Published: October 2022

AbstractMeniscus horizontal tears are usually degenerative. It could be asymptomatic and unrelated to knee symptoms. Therefore, there are controversies regarding treatment choices. The aim of this study was to evaluate factors that affect the results of non-surgical and surgical treatments for meniscus horizontal tears. We retrospectively studied 159 patients with meniscus horizontal tears with a minimum 2-year follow-up period. Patients were treated non-surgically or arthroscopically. The treatment results were dichotomized into success and failure. The factors considered were age, sex, joint line tenderness, mechanical symptoms, widest tear gap width on sagittal MRI, cartilage lesion grade, discoid meniscus, tear site, and joint alignment. Joint alignment and cartilage lesion grade were the factors that significantly influenced non-surgical treatment results. The widest tear gap width and cartilage lesion grade significantly affected arthroscopic surgery results. The mechanical symptoms did not show any significant relationship with either treatment result. In treating patients with meniscus horizontal tears, patients with varus alignment and advanced cartilage lesions should be informed of possible poor outcomes with non-surgical treatment. If the patient has a wide tear gap or minimal cartilage lesion, arthroscopic surgery would be a good treatment choice. The mechanical symptom was not an adequate factor for arthroscopic surgery.
Antimicrobial and antioxidant activities of Streptomyces species from soils of three different cold sites in the Fez-Meknes region Morocco
Authors: Rammali Said , Hilali Lahoucine , Dari Khadija , Bencharki Bouchaib , Rahim Abdellatif , Timinouni Mohammed , Gaboune Fatima , El Aalaoui Mohamed , khattabi Abdelkrim 
Published: October 2022

AbstractThe increasing demand for new bioactive compounds to combat the evolution of multi-drug resistance (MDR) requires research on microorganisms in different environments in order to identify new potent molecules. In this study, initial screening regarding the antimicrobial activity of 44 Actinomycetes isolates isolated from three soil samples from three different extremely cold sites in Morocco was carried out. Primary and secondary screening were performed against Candida albicans ATCC 60,193, Escherichia coli ATCC 25,922, Staphylococcus aureus ATCC 25,923, Bacillus cereus ATCC 14,579, other clinical MDR bacteria, and thirteen phytopathogenic fungi. Based on the results obtained, 11 active isolates were selected for further study. The 11microbial isolates were identified based on morphological and biochemical characters and their molecular identification was performed using 16S rRNA sequence homology. The UV–visible analysis of dichloromethane extracts of the five Streptomyces sp. Strains that showed high antimicrobial and antioxidant (ABTS 35.8% and DPPH 25.6%) activities revealed the absence of polyene molecules. GC–MS analysis of the dichloromethane extract of E23-4 as the most active strain revealed the presence of 21 volatile compounds including Pyrrolopyrazine (98%) and Benzeneacetic acid (90%). In conclusion, we studied the isolation of new Streptomyces strains to produce new compounds with antimicrobial and antioxidant activities in a cold and microbiologically unexplored region of Morocco. Furthermore, this study has demonstrated a significant (P < 0.0001) positive correlation between total phenolic and flavonoid contents and antioxidant capacity, paving the way for the further characterization of these Streptomyces sp. isolates for their optimal use for anticancer, antioxidant, and antimicrobial purposes.
Isolation and characterization of an anti-proliferative polysaccharide from the North American fungus Echinodontium tinctorium
Authors: Zeb Mehreen , Li Wai Ming , Heiss Christian , Black Ian , Tackaberry Linda E. , Massicotte Hugues B. , Egger Keith N. , Reimer Kerry , Azadi Parastoo , Lee Chow H. 
Published: October 2022

AbstractA novel polysaccharide EtGIPL1a was purified from fruiting bodies of Echinodontium tinctorium, a fungus unique to western North America. EtGIPL1a has an estimated weight average molecular weight of 275 kDa and is composed of glucose (54.3%), galactose (19.6%), mannose (11.1%), fucose (10.3%), glucuronic acid (4%), and rhamnose (0.6%). It has multiple glycosidic linkages, with 3-Glcp (28.9%), 6-Glcp (18.3%), 3,6-Glcp (13%), 4-GlcpA (9.2%), 6-Galp (3.9%), 2,6-Galp (2.6%), 3-Fucp (2.5%), 6-Manp (2.4%) being the most prominent, and unsubstituted glucose (15.3%), mannose (1.3%) and fucose (0.9%) as major terminal sugars. EtGIPL1a has a backbone containing mostly 3-substituted β-glucopyranose with 4-substituted glucopyranosyluronic acid. EtGIPL1a showed anti-proliferative activity against multiple cancer cell lines, with IC50 ranging from 50.6 to 1446 nM. Flow cytometry analyses confirmed that apoptosis induction is one mechanism for its anti-proliferative activity. EtGIPL1a should be further investigated for its potential anti-cancer activity in animal models, and for its possible utility in differentiation cancer therapy.
Arsenic removal performance and mechanism from water on iron hydroxide nanopetalines
Authors: Wang Yulong , Zhang Lin , Guo Chen , Gao Yali , Pan Shanshan , Liu Yanhong , Li Xuhui , Wang Yangyang 
Published: October 2022

AbstractHuman health has been seriously endangered by arsenic pollution in drinking water. In this paper, iron hydroxide nanopetalines were synthesized through a precipitation method using KBH4 and their performance and mechanism of As(V) and As(III) removal were investigated. The prepared material was characterized by SEM–EDX, XRD, BET, zeta potential and FTIR analyses. Batch experiments indicated that the iron hydroxide nanopetalines exhibited more excellent performance for As(V) and As(III) removal than ferrihydrite. The adsorption processes were very fast in the first stage, followed a relatively slower adsorption rate and reached equilibria after 24 h, and the reaction could be fitted best by the pseudo-second order model, followed by the Elovich model. The adsorption isotherm data followed to the Freundlich model, and the maximal adsorption capacities of As(V) and As(III) calculated by the Langmuir model were 217.76 and 91.74 mg/g at pH 4.0, respectively, whereas these values were 187.84 and 147.06 mg/g at pH 8.0, respectively. Thermodynamic studies indicated that the adsorption process was endothermic and spontaneous. The removal efficiencies of As(V) and As(III) were significantly affected by the solution pH and presence of PO43– and citrate. The reusability experiments showed that more than 67% of the removal efficiency of As(V) could be easily recovered after four cycles. The SEM and XRD analyses indicated that the surface morphology and crystal structure before and after arsenic removal were stable. Based on the analyses of FTIR, XRD and XPS, the predominant adsorption mechanism was the formation of inner-sphere surface complexes by the surface hydroxyl exchange reactions of Fe–OH groups with arsenic species. This research provides a new strategy for the development of arsenic immobilization materials and the results confirm that iron hydroxide nanopetalines could be considered as a promising material for removing arsenic from As-contaminated water for their highly efficient performance and stability.
Association of functional competencies with vaccination among older adults: a JAGES cross-sectional study
Authors: Iwai-Saito Kousuke , Sato Koryu , Kondo Katsunori 
Published: October 2022

AbstractIt is unknown whether higher functions in sublevels of competence other than instrumental activities of daily living (IADL) are associated with vaccinations. This study examined whether higher functions, including intellectual activity (IA) and social role (SR), were associated with vaccinations among 26,177 older adults. Older adults with incapable activities in IA and SR had increased risks for non-receipt of influenza vaccinations (IA: for one incapable task/activity: incident rate ratio (IRR) = 1.05, 95% confidence interval (CI) = 1.02–1.09; SR: for two incapable tasks: IRR = 1.12, 95% CI = 1.08–1.16). Those with incapable activities in IADL and IA had increased risks for non-receipt of pneumococcal vaccination (IADL: for two incapable tasks: IRR = 1.13, 95% CI = 1.05–1.23; IA: for two incapable tasks: IRR = 1.10, 95% CI = 1.08–1.12). Those with incapable activities in IADL, IA, and SR had increased risks for non-receipt of both of the two vaccinations (IADL: for two incapable tasks: IRR = 1.17, 95% CI = 1.03–1.33; IA: for two incapable tasks: IRR = 1.18, 95% CI = 1.11–1.25; SR: for two incapable tasks: IRR = 1.13, 95% CI = 1.07–1.20). Having a family physician mitigated associations for non-receipt, regardless of competency. Our results suggest—maintaining the higher functions are important for older adults to undergo recommended vaccinations as scheduled; also, having a family physician to promote vaccinations is beneficial even for older adults with limited functions.
Effect of prior Zika and dengue virus exposure on the severity of a subsequent dengue infection in adults
Authors: Valencia Braulio M. , Sigera Ponsuge C. , Weeratunga Praveen , Tedla Nicodemus , Fernando Deepika , Rajapakse Senaka , Lloyd Andrew R. , Rodrigo Chaturaka 
Published: October 2022

AbstractGiven the structural similarity between Zika and dengue viruses, prior infection from one virus is hypothesized to modulate the severity of a subsequent infection from the other virus. A previous paediatric cohort study observed that a prior Zika infection may increase the risk of a subsequent symptomatic or severe dengue infection. The Colombo Dengue study is a prospective hospital-based cohort study in Sri Lanka that recruits symptomatic adult dengue patients within the first three days of fever. Anti-Dengue Envelope and anti-Zika NS1 IgG antibodies were tested by ELISA (Euroimmun, Lubeck, Germany) in all recruited patients. Associations between pre-morbid seroprevalence for either or both infections and adverse clinical outcomes of the current dengue infection were explored. A total of 507 dengue infected patients were assessed of whom 342 (68%) and 132 (26%) patients had anti-dengue IgG and anti-Zika IgG respectively. People with combined prior dengue and zika exposure as well as prior dengue exposure alone, were at increased risk of plasma leakage, compensated and uncompensated shock, and severe dengue (p < 0·05), compared to people without prior exposure to either infection. The effect of prior Zika exposure alone could not be established due to the small the number of primary dengue infections with prior Zika exposure.
Rapid differentiation of hiPSCs into functional oligodendrocytes using an OLIG2 synthetic modified messenger RNA
Authors: Xu Jian , Yang Zhihua , Wang Rui , He Fumei , Yan Rong , Zhang Yidi , Yu Liying , Deng Wenbin , Nie Yichu 
Published: October 2022

AbstractTranscription factors (TFs) have been introduced to drive the highly efficient differentiation of human-induced pluripotent stem cells (hiPSCs) into lineage-specific oligodendrocytes (OLs). However, effective strategies currently rely mainly on genome-integrating viruses. Here we show that a synthetic modified messenger RNA (smRNA)-based reprogramming method that leads to the generation of transgene-free OLs has been developed. An smRNA encoding a modified form of OLIG2, in which the serine 147 phosphorylation site is replaced with alanine, OLIG2S147A, is designed to reprogram hiPSCs into OLs. We demonstrate that repeated administration of the smRNA encoding OLIG2S147A lead to higher and more stable protein expression. Using the single-mutant OLIG2 smRNA morphogen, we establish a 6-day smRNA transfection protocol, and glial induction lead to rapid NG2+ OL progenitor cell (OPC) generation (>70% purity) from hiPSC. The smRNA-induced NG2+ OPCs can mature into functional OLs in vitro and promote remyelination in vivo. Taken together, we present a safe and efficient smRNA-driven strategy for hiPSC differentiation into OLs, which may be utilized for therapeutic OPC/OL transplantation in patients with neurodegenerative disease.
Binary combinatorial scanning reveals potent poly-alanine-substituted inhibitors of protein-protein interactions
Authors: Ye Xiyun , Lee Yen-Chun , Gates Zachary P. , Ling Yingjie , Mortensen Jennifer C. , Yang Fan-Shen , Lin Yu-Shan , Pentelute Bradley L. 
Published: October 2022

AbstractEstablishing structure–activity relationships is crucial to understand and optimize the activity of peptide-based inhibitors of protein–protein interactions. Single alanine substitutions provide limited information on the residues that tolerate simultaneous modifications with retention of biological activity. To guide optimization of peptide binders, we use combinatorial peptide libraries of over 4,000 variants—in which each position is varied with either the wild-type residue or alanine—with a label-free affinity selection platform to study protein–ligand interactions. Applying this platform to a peptide binder to the oncogenic protein MDM2, several multi-alanine-substituted analogs with picomolar binding affinity were discovered. We reveal a non-additive substitution pattern in the selected sequences. The alanine substitution tolerances for peptide ligands of the 12ca5 antibody and 14-3-3 regulatory protein are also characterized, demonstrating the general applicability of this new platform. We envision that binary combinatorial alanine scanning will be a powerful tool for investigating structure–activity relationships.
A novel technique using chronic infusion of small extracellular vesicles from gestational diabetes mellitus causes glucose intolerance in pregnant mice
Authors: James-Allan Laura B , Rosario Frederick J , Madi Lana , Barner Kelsey , Nair Soumyalekshmi , Lai Andrew , Carrion Flavio , Powell Theresa L , Salomon Carlos , Jansson Thomas 
Published: October 2022

AbstractSmall extracellular vesicles (sEVs) play a central role in cell-to-cell communication in normal physiology and in disease, including gestational diabetes mellitus (GDM). The goal of the present study was to test the hypothesis that chronic administration of sEVs isolated from GDM causes glucose intolerance in healthy pregnant mice. Small EVs were isolated from plasma between 24 and 28 weeks gestation from healthy pregnant women (controls) and GDM, and infused intravenously for 4 days in late pregnant mice using a mini-osmotic pump. Subsequently in vivo glucose tolerance was assessed, and muscle and adipose tissue insulin sensitivity and islet glucose stimulated insulin secretion (GSIS) were determined in vitro. Mice infused with sEVs from GDM developed glucose intolerance. Administration of sEVs from controls, but not sEVs from GDM women, stimulated islet GSIS and increased fasting insulin levels in pregnant mice. Neither infusion of sEVs from controls nor from GDM women affected muscle insulin sensitivity, placental insulin or mTOR signaling, placental and fetal weight. Moreover, these results were not associated with immunomodulatory effects as human sEVs did not activate mouse T cells in vitro. We suggest that circulating sEVs regulate maternal glucose homeostasis in pregnancy and may contribute to the attenuated islet insulin secretion and more pronounced glucose intolerance in GDM as compared with healthy pregnancy.
Multifrequency Narrowband Chirp Evoked Cervical Vestibular Myogenic Potentials: Evaluation of Responses in Normal-Hearing Young Adults
Authors: Lodha Vidhi , Neupane Anuj Kumar 
Published: October 2022

Purpose:
The study aimed to explore the various parameters of multifrequency narrowband Claus Elberling chirp (NB CE-chirp) evoked cervical vestibular evoked myogenic potentials (cVEMPs) in normal-hearing healthy young adults. The study also attempted to define the optimal frequency tuning characteristic of NB CE-chirp evoked cVEMPs.

Method:
cVEMP was performed on 26 young healthy adults using four different NB CE-chirps centered at 500, 1000, 2000, and 4000 Hz. The neck torsion method was applied for electrode placement. To have the acute recording, visual feedback of sternocleidomastoid muscle contraction was provided, and electromyography (EMG) scaling was done.

Results:
cVEMPs were present for 100% across all frequencies except at 4000 Hz. Amplitudes between each pair of frequencies were significantly different for EMG scaled and unscaled conditions. Frequency tuning was observed at 500 Hz regardless of scaling done. Positive peak 1 of cVEMP (P1) latencies showed no differences between frequencies while both negative peak 1 of cVEMP and the complex of positive peak 1 and negative peak 1 of cVEMP (P1N1) interpeak latency values decreased with increasing frequency. Interaural amplitude asymmetry ratio showed no difference between scaled and unscaled amplitudes. Intraclass correlation revealed a range of test–retest reliability across frequencies. EMG unscaled amplitude were having relatively lower test–retest reliability consistently across frequencies

Conclusions:
Differences in amplitudes between frequencies with a maximum at 500 Hz can be attributed to the low frequency centered saccular response. No differences in P1 were observed. Yet, N1 latency and P1N1 interpeak latency difference gradually shortened with the decrement in the stimulus duration as the stimulation frequency increased. The lower reliability of EMG unscaled amplitude across frequencies supports the need to use EMG scaling to avoid confounding variables related to muscle contraction.