bluuebunny/crossref_metadata_2025 huggingface dataset:
Att studera gymnasieelevers prestationsemotioner genom berättelser
Authors: Löfgren Håkan , Faleström Caroline , Råbesjö Linda , Stafstedt Britta , Strömberg Lars , Finnberg Patrik , Selberg Josefin , Hallqvist Anders , Grönlund Agneta
Published: September 2023

Följande ULF-projekt (Utveckling, lärande, forskning) är ett samarbete mellan en kommunal gymnasieskola i en mellanstor stad samt Linköpings Universitet. Syftet är att öka förståelsen för hur gymnasieelever upplever prestationssituationer. Genom en narrativ ansats har 261 elevberättelser analyserats och kategoriserats. De känslor som kan knytas till erfarenheter av att bli bedömda kallas i studien för prestationsemotioner. En prestation kan definieras som en aktivitet som mäts mot någon form av standard och prestationsemotioner är emotioner som kopplas till en sådan aktivitet. Vanligt förekommande positiva prestationsemotioner är stolthet, nöje, hopp, tacksamhet, avslappning, belåtenhet och lättnad. Negativa prestationsemotioner är oro, ångest, stress, skam, tristess, hopplöshet eller besvikelse (Pekrun, 2007; 2014). I studien finns en rad positiva och negativa emotioner som eleverna tillskriver sina prestationer, samt att elevernas känslor ofta förändras i samband med viktiga prestationer. Eleverna gör känsloresor som verkar ha betydelse för deras vilja och förmåga att prestera i framtiden. En mer utförlig resultatredovisning görs i en annan artikel i Venue. Utöver dessa resultat har projektet skapat ett kollegialt lärande som lyfter och bidrar till en mer hållbar bedömningspraktik.
Enhancing individual animal resilience to environmental disturbances to address low productivity in dairy cattle performing in sub-Saharan Africa
Authors: Oloo Richard D. , Ojango Julie M. K. , Ekine-Dzivenu Chinyere C. , Gebreyohanes Gebregziabher , Mrode Raphael , Mwai Okeyo A. , Chagunda Mizeck G. G.
Published: September 2023

The current review examines potential solutions to enhance the sustainability and productivity of the dairy sector in sub-Saharan Africa (SSA) with an emphasis on breeding for resilience. Additionally, the paper explores various indicators for measuring resilience and provides insights into the data that can be utilized to quantify resilience in SSA’s dairy production systems. Dairy production contributes significantly to food and nutritional security and employment in SSA. However, besides the general lack of enabling policy and institutional environments, production is negatively affected by environmental challenges such as high temperatures and heat stress, diseases and parasites, unreliable rainfall patterns, shortages of feeds and forages and undue preference for taurine cattle breeds regardless of their poor adaptability to prevailing local conditions. Fostering the resilience capacity of dairy animals is imperative to combat climate-related adversities and maintain productivity. This can only be achieved if reliable and practical methods for quantifying and analyzing resilience in SSA are described and undertaken. This study has reviewed variance of deviations, root mean square of deviations, autocorrelation of deviations, skewness of deviations, slope of the reaction norm and its absolute value as possible indicators of resilience in SSA. While previous research has reported genetic variation and favorable correlations of these indicators with health, fitness, and fertility traits, their potential in SSA environments requires further investigation. Besides, labor- and cost-effective phenotypic data collection is essential for characterization of resilience using these indicators. Through this study, we propose frequently collected data on milk production traits, body fat-related traits, and activity patterns as suitable in the sub-Saharan Africa context. The African Asian Dairy Genetic Gains Project by the International Livestock Research Institute (ILRI) offers a valuable opportunity to collate data from diverse dairy systems in SSA for testing the potential of these indicators. Insights from this study are helpful in improving resilience of dairy animals in SSA, which would contribute to poverty alleviation, animal welfare improvement, and better preparedness in lieu of climate change in SSA.
Insights into the time course of evidentiality processing in Turkish heritage speakers using a self-paced reading task
Authors: Tokaç-Scheffer Suzan D. , Arslan Seçkin , Nickels Lyndsey
Published: September 2023

Introduction

Studies with heritage language speakers (HLS) have often used offline measurements, investigating the post-interpretive effects which emerge after processing has been completed. Relatively few studies have investigated heritage language processing using time-sensitive methods that allow the collection of evidence regarding real-time language processing rather than post-interpretive judgments. Using a self-paced-reading paradigm, we aimed to expand our understanding of HLS language processing by investigating evidentiality-the linguistic marking of information source, which is grammatically expressed in Turkish, but not in English.

Method

Participants were 54 bilingual speakers of Turkish and English: 24 HLS (English onset: 0-5 yrs) and 30 emigrant Turkish speakers (ES) who grew up in Turkey before emigrating to Australia (English onset = 6-17 yrs). Participants read sentences with evidential-marked verb forms that either matched or mismatched to the information source context. Word-by-word reading times and end-of-sentence acceptability judgment speed and accuracy were measured.

Results

The results showed that although the HLS' responses were slower and less accurate than the ES in both reading times and end-of-sentence acceptability judgments, they showed similarities in online processing patterns. Both groups were faster at reading the mismatching sentences compared to the matching sentences; however, this pattern emerged during the time course of reading first for the indirect condition for the ES, and only later for the direct condition and for the HLS for both evidential conditions. Only HLS read faster in the target region with the direct evidential that is shown to be acquired earlier in childhood, than they did for the indirect evidential which is mastered later. In contrast, the end-of-sentence judgment data showed that while the ES group responded faster to matching direct sentences than matching indirect, this effect was missing for the HLS. Nevertheless, there were similar patterns for accuracy across evidential conditions: both groups were more accurate with the direct evidential.

Discussion

Overall, the use of the self-paced-reading paradigm allowed insights into HLS' evidentiality processing above and beyond their generally slower and less accurate processing compared to the reference group. This study provides further evidence for differences in the patterns observed using online vs. post interpretive measures in HLS, reinforcing the importance of combining these methodologies for further understanding of HLS competence and performance.
Neutrophil autophagy induced by monosodium urate crystals facilitates neutrophil extracellular traps formation and inflammation remission in gouty arthritis
Authors: Huang Shanshan , Wang Yaohui , Lin Shibo , Guan Wei , Liang Hui , Shen Jiajia
Published: September 2023

Neutrophil extracellular traps (NETs) are composed of chromatin filaments coated with granular and cytosolic proteins, which contribute to the pathogenesis and progression of immune-related diseases. NETs are frequently observed in gouty arthritis, but the related mechanisms remain poorly understood. The aim of our study was to systematically elucidate the molecular mechanisms of self-remitting effects in gouty arthritis, and the causative relationship between neutrophil autophagy and NETs. The air pouch and paw edema model were used to simulate gouty arthritis in mice. Neutrophil infiltration and the formation of NETs were found in gouty arthritis. Interestingly, monosodium urate (MSU) crystals could induce the formation of NETs, degrade inflammatory factors, and alleviate the inflammatory response in gouty arthritis. In addition, MSU crystals resulted in profound molecular alterations in neutrophils using RNA-seq analysis, including autophagy activation. MSU crystals could activate neutrophil autophagy in vitro, and autophagy activators and inhibitors could regulate the formation of NETs. Furthermore, we explored the mechanism of autophagy-induced NETs. Autophagy related protein 7 (ATG7) produced by neutrophils stimulated with MSU crystals worked synergistically with p53 to enter the nucleus, promoting peptidyl arginine deiminase 4 (PAD4) expression, and inducing the formation of NETs. Finally, we substantiated that neutrophil autophagy regulates the severity of gouty arthritis via the formation of NETs in PAD4 -/- mice. Our results indicated that the autophagy of neutrophils regulates the formation of NETs and degrades inflammatory factors. Regulating autophagy and interfering with the formation of NETs represents a potential therapeutic approach against gouty arthritis during clinical practice.
Lack of associations of microRNAs with severe NAFLD in people living with HIV: discovery case-control study
Authors: Frías Mario , Corona-Mata Diana , Moyano Jose M. , Camacho-Espejo Angela , López-López Pedro , Caballero-Gómez Javier , Ruiz-Cáceres Inmaculada , Casares-Jiménez Marı́a , Pérez-Valero Ignacio , Rivero-Juárez Antonio , Rivero Antonio
Published: September 2023

Background & objective

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in people living with HIV (PLWH) and the expression of some microRNAs could be useful as biomarkers for the diagnosis of NAFLD. The aim of this study was to identify patterns of differential expression of microRNAs in PLWH and assess their diagnostic value for NALFD.

Methods

A discovery case-control study with PLWH was carried out. The expression of miRNAs was determined using HTG EdgeSeq technology. Cases were defined as patients with severe NAFLD and controls as patients without NAFLD, characterized using the controlled attenuation parameter (CAP). Cases and controls were matched 1:1 for age, sex, BMI, CD4+ lymphocyte count, active HCV infection, and ART regimen.

Results

Serum 2,083 simultaneous microRNA transcripts were analyzed using HTG technology and compared between cases and controls. Forty-five patients, 23 cases, and 22 controls were included in the study. In the analysis of the expression pattern of the 2,083 microRNAs, no differential expression patterns were found between both groups of patients included in the study.

Conclusion

Analysis of the microRNA transcriptome profile of nonobese PLWH with severe NAFLD did not appear to differ from that of patients without NAFLD. Thus, microRNA might not serve as a proper biomarker for predicting severe NALFD in this population.
Lifestyle factors, serum parameters, metabolic comorbidities, and the risk of kidney stones: a Mendelian randomization study
Authors: Liu Minghui , Wu Jian , Gao Meng , Li Yongchao , Xia Weiping , Zhang Youjie , Chen Jinbo , Chen Zhiyong , Zhu Zewu , Chen Hequn
Published: September 2023

Background and objective

The early identification of modifiable risk factors is important for preventing kidney stones but determining causal associations can be difficult with epidemiological data. We aimed to genetically assess the causality between modifiable factors (lifestyle factors, serum parameters, and metabolic comorbidities) and the risk of kidney stones. Additionally, we aimed to explore the causal impact of education on kidney stones and its potential mediating pathways.

Methods

We conducted a two-sample Mendelian randomization (MR) study to explore the causal association between 44 modifiable risk factors and kidney stones. The FinnGen dataset initially explored the causal relationship of risk factors with kidney stones and the UK Biobank dataset was used as the validation set. Then, a meta-analysis was conducted by combining discovery and validation datasets. We used two-step MR to assess potential mediators and their mediation proportions between education and kidney stones.

Results

The combined results indicated that previous exposures may increase the risk of kidney stones, including sedentary behavior, urinary sodium, the urinary sodium/potassium ratio, the urinary sodium/creatinine ratio, serum calcium, 25-hydroxyvitamin D (25OHD), the estimated creatinine-based glomerular filtration rate (eGFRcrea), GFR estimated by serum cystatin C (eGFRcys), body mass index (BMI), waist circumference, type 2 diabetes mellitus (T2DM), fasting insulin, glycated hemoglobin, and hypertension. Coffee intake, plasma caffeine levels, educational attainment, and the urinary potassium/creatinine ratio may decrease the risk of kidney stones. Ranked by mediation proportion, the effect of education on the risk of kidney stones was mediated by five modifiable risk factors, including sedentary behavior (mediation proportion, 25.7%), smoking initiation (10.2%), BMI (8.2%), T2DM (5.8%), and waist circumference (3.2%).

Conclusion

This study provides MR evidence supporting causal associations of many modifiable risk factors with kidney stones. Sedentary lifestyles, obesity, smoking, and T2DM are mediating factors in the causal relationship between educational attainment and kidney stones. Our results suggest more attention should be paid to these modifiable factors to prevent kidney stones.
Difference analysis method of grid connection influence between CRE and DRE based on bus state trajectory
Authors: Xu Chao , He Sijing , Wang Lu , Yu Haifeng
Published: September 2023

This paper presents a method to investigate the impact of centralized and distributed renewable energy on the power grid system, aiming to discern their differences. First, we derived the coupling relationship between renewable energy permeability and access point voltage under a simplified model. Second, we proposed a holomorphic embedding model designed for non-global variation, enabling the construction of the bus state trajectory index. This index is employed to analyze the influence of centralized and distributed renewable energy access on power grid stability and voltage under low-permeability conditions. Furthermore, under high permeability, we determined the limit permeability of centralized and distributed renewable energy. Last, we provided renewable energy configuration recommendations to enhance the system’s receptive capacity.
Mitochondrial dysfunctions in T cells: focus on inflammatory bowel disease
Authors: Lee Hoyul , Jeon Jae-Han , Kim Eun Soo
Published: September 2023

Mitochondria has emerged as a critical ruler of metabolic reprogramming in immune responses and inflammation. In the context of colitogenic T cells and IBD, there has been increasing research interest in the metabolic pathways of glycolysis, pyruvate oxidation, and glutaminolysis. These pathways have been shown to play a crucial role in the metabolic reprogramming of colitogenic T cells, leading to increased inflammatory cytokine production and tissue damage. In addition to metabolic reprogramming, mitochondrial dysfunction has also been implicated in the pathogenesis of IBD. Studies have shown that colitogenic T cells exhibit impaired mitochondrial respiration, elevated levels of mROS, alterations in calcium homeostasis, impaired mitochondrial biogenesis, and aberrant mitochondria-associated membrane formation. Here, we discuss our current knowledge of the metabolic reprogramming and mitochondrial dysfunctions in colitogenic T cells, as well as the potential therapeutic applications for treating IBD with evidence from animal experiments.
Human inborn errors of immunity associated with IRF4
Authors: Thouenon Romane , Kracker Sven
Published: September 2023

The transcription factor interferon regulatory factor 4 (IRF4) belongs to the IRF family and has several important functions for the adaptive immune response. Mutations affecting IRF family members IRF1, IRF3, IRF7, IRF8, or IRF9 have been described in patients presenting with inborn errors of immunity (IEI) highlighting the importance of these factors for the cellular host defense against mycobacterial and/or viral infections. IRF4 deficiency and haploinsufficiency have been associated with IEI. More recently, two novel IRF4 disease-causing mechanisms have been described due to the characterization of IEI patients presenting with cellular immunodeficiency associated with agammaglobulinemia. Here, we review the phenotypes and physiopathological mechanisms underlying IEI of IRF family members and, in particular, IRF4.
Characterization of pre-existing anti-PEG and anti-AGAL antibodies towards PRX-102 in patients with Fabry disease
Authors: Lenders Malte , Feidicker Lina Marleen , Brand Stefan-Martin , Brand Eva
Published: September 2023

Polyethylene glycol (PEG)ylated drugs are used for medical treatment, since PEGylation either decreases drug clearance or/and shields the protein from undesirable immunogenicity. PEGylation was implemented in a new enzyme replacement therapy for Fabry disease (FD), pegunigalsidase-alfa (PRX-102). However, exposure to PEG via life-style products and vaccination can result in the formation of anti-PEG antibodies. We demonstrate the de novo formation of functional anti-PEG antibodies in a healthy male after the second mRNA-based vaccination against SARS-CoV-2. Consequently, we analyzed the frequency and inhibitory function of anti-PEG and anti-α-Galactosidase A (AGAL) antibodies in 102 FD patients (46.9% males). We identified 29 out of 87 (33.3%) patients with low anti-PEG titers. Sera from patients without anti-AGAL antibodies [n=70] showed a higher rescued AGAL activity of agalsidase-beta and PRX-102 [both p<0.0001] compared to those with anti-AGAL antibodies [n=15]. Sera from anti-AGAL antibody-negative and -positive patients had less inhibitory effects on PRX-102 (rescued activity: 89 ± 6% versus 85 ± 7% and 49 ± 26% versus 25 ± 32%; both p<0.0001). Enzyme stability assays demonstrated that AUCs in anti-AGAL-negative sera (n=20) were 7.6-fold higher for PRX-102, while AUCs of both enzymes in anti-AGAL-positive sera (n=6) were decreased. However, AUC for PRX-102 was 33% of non-anti-AGAL-positive sera treated PRX-102 and 5-fold higher compared to agalsidase-beta. Anti-PEG antibodies had no significant effects on serum half-life of PRX-102, probably due to low titers. Conceivably, therapy efficacy may be superior under next-generation PRX-102 therapy compared to current enzyme replacement therapies in terms of reduced inhibitory effects of anti-AGAL and minor inhibitory effects of anti-PEG antibodies.
Functional evaluation of constructed pseudo-endogenous microRNA-targeted myocardial ultrasound nanobubble
Authors: Ainiwan Ailifeire , Wei Yuanyuan , Dou Jing , Tang Lingpeng , Mu Yuming , Guan Lina
Published: September 2023

Background

Stem cell transplantation is one of the treatment methods for acute myocardial infarction (AMI). MicroRNA-1 contributes to the study of the essential mechanisms of stem cell transplantation for treating AMI by targeted regulating the myocardial microenvironment after stem cell transplantation at the post-transcriptional level. Thus, microRNA-1 participates in regulating the myocardial microenvironment after stem cell transplantation, a promising strategy for the Stem cell transplantation treatment of AMI. However, the naked microRNA-1 synthesized is extremely unstable and non-targeting, which can be rapidly degraded by circulating RNase. Herein, to safely and effectively targeted transport the naked microRNA-1 synthesized into myocardial tissue, we will construct pseudo-endogenous microRNA-targeted myocardial ultrasound nanobubble pAd-AAV-9/miRNA-1 NB and evaluate its characteristics, targeting, and function.

Methods

The pAd-AAV-9/miRNA-1 gene complex was linked to nanobubble NBs by the “avidin-biotin bridging” method to prepare cardiomyocyte-targeted nanobubble pAd-AAV-9/miRNA-1 NB. The shape, particle size, dispersion, and stability of nanobubbles and the connection of pAd-AAV-9/miRNA-1 gene complex to nanobubble NB were observed. The virus loading efficiency was determined, and the myocardium-targeting imaging ability was evaluated using contrast-enhanced ultrasound imaging in vivo. The miRNA-1 expression level in myocardial tissue and other vital organs ex vivo of SD rats was considered by Q-PCR. Also, the cytotoxic effects were assessed.

Results

The particle size of NBs was 504.02 ± 36.94 nm, and that of pAd-AAV-9/miRNA-1 NB was 568.00 ± 37.39 nm. The particle size and concentration of pAd-AAV-9/miRNA-1 NBs did not change significantly within 1 h at room temperature (p > 0.05). pAd-AAV-9/miRNA-1 NB had the highest viral load rate of 86.3 ± 2.2% (p < 0.05), and the optimum viral load was 5 μL (p < 0.05). pAd-AAV-9/miRNA-1 NB had good contrast-enhanced ultrasound imaging in vivo. Quantitative analysis of miRNA-1 expression levels in vital organs ex vivo of SD rats by Q-PCR showed that pAd-AAV-9/miRNA-1 NB targeted the myocardial tissue. Q-PCR indicated that the expression level of miRNA-1 in the myocardium of the pAd-AAV-9/miRNA-1 NB + UTMD group was significantly higher than that of the pAd-AAV-9/miRNA-1 NB group (p < 0.05). pAd-AAV-9/miRNA-1 NB had no cytotoxic effect on cardiomyocytes (p > 0.05).

Conclusion

The pAd-AAV-9/miRNA-1 NB constructed in this study could carry naked miRNA-1 synthesized in vitro for targeted transport into myocardial tissue successfully and had sound contrast-enhanced imaging effects in vivo.
A comparison of clinical outcomes among people living with HIV of different age groups attending queen Elizabeth central hospital outpatient ART Clinic in Malawi
Authors: Chakakala-Chaziya Jessica , Patson Noel , Samuel Vincent , Mbotwa John , Buonsenso Danilo , Chisale Master , Phiri Eddie , O’Hare Bernadette
Published: September 2023

Introduction

Adherence to Antiretroviral Treatment (ART) in children and adolescents living with HIV in low-resource settings is not extensively studied in large cohort studies including both adults and pediatric patients. We compared rates of virological suppression, adherence and defaulting among children, adolescents and adults attending a family ART clinic at Queen Elizabeth Central Hospital; a tertiary hospital situated in the southern region of Malawi.

Methods

The study was longitudinal and made use of routinely collected data for all 27,229 clinic attendees. Clinical information obtained at routine clinical visits entered electronically since 2008 was extracted in February 2017. This data was used to ascertain differences across the different age groups. Logistic regression and Cox regression models were fitted to compare rates of Virological Suppression (VS), adherence, and defaulting, respectively.

Results

Younger and older adolescents (ages 10–14 years and 15–19 years respectively) were less likely to achieve VS compared to adults in the final model AOR 0.4 (0.2–0.9, 95% CI) and AOR 0.2 (0.1–0.4, 95% CI) respectively. Young children (ages 0–4 years), older children (ages 5–9 years) and younger adolescents were less adherent to ART compared to adults AOR 0.1 (0.1–0.2, 95% CI), AOR 0.2 (0.1–0.3, 95% CI), and AOR 0.4 (0.3–0.5, 95% CI) respectively. Young adults and younger children had an increased likelihood of defaulting compared to adults.

Conclusion

Poor performance on ART of children and adolescents highlights unaddressed challenges to adherence. Ongoing research to explore these potential barriers and possible interventions needs to be carried out. The adherence assessment methods used and strategies for improving it among children and adolescents need to be revised at the clinic.
Liquid biopsy for early detection of hepatocellular carcinoma
Authors: Manea Ioana , Iacob Razvan , Iacob Speranta , Cerban Razvan , Dima Simona , Oniscu Gabriel , Popescu Irinel , Gheorghe Liliana
Published: September 2023

Hepatocellular carcinoma (HCC) is a highly prevalent and lethal cancer globally. Over 90% of HCC cases arise in the context of liver cirrhosis, and the severity of the underlying liver disease or advanced tumor stage at diagnosis significantly limits treatment options. Early diagnosis is crucial, and all guidelines stress the importance of screening protocols for HCC early detection as a public health objective. As serum biomarkers are not optimal for early diagnosis, liquid biopsy has emerged as a promising tool for diagnosis, prognostication, and patients’ stratification for personalized therapy in various solid tumors, including HCC. While circulating tumor cells (CTCs) are better suited for personalized therapy and prognosis, cell-free DNA (cfDNA) and extracellular vesicle-based technologies show potential for early diagnosis, HCC screening, and surveillance protocols. Evaluating the added value of liquid biopsy genetic and epigenetic biomarkers for HCC screening is a key goal in translational research. Somatic mutations commonly found in HCC can be investigated in cfDNA and plasma exosomes as genetic biomarkers. Unique methylation patterns in cfDNA or cfDNA fragmentome features have been suggested as innovative tools for early HCC detection. Likewise, extracellular vesicle cargo biomarkers such as miRNAs and long non-coding RNAs may serve as potential biomarkers for early HCC detection. This review will explore recent findings on the utility of liquid biopsy for early HCC diagnosis. Combining liquid biopsy methods with traditional serological biomarkers could improve the overall diagnostic accuracy for early HCC detection.
Herpetic anterior uveitis following COVID-19 vaccines: a case series
Authors: Ott Muriel , Nagamany Thanoosha , Zandi Souska , Pichi Francesco , Agarwal Aniruddha , Carreño Ester , Gupta Vishali , Grewal Dilraj S. , Cunningham Emmett T. , Munk Marion R.
Published: September 2023

Purpose

To report a case series of herpetic uveitis following COVID-19 vaccinations.

Methods

Demographic, clinical and treatment-related data of herpetic anterior uveitis cases was collected at five tertiary eye hospitals between January 2021 and June 2022. A retrospective database review at one of the centers comparing the number of cases of herpetic eye disease before and after the introduction of COVID-19 vaccination was performed as well.

Results

Twenty-four patients (9 female, 15 male) with a mean age of 54 years (range 28–83 years) were diagnosed with herpetic uveitis, reporting an onset of symptoms 3–42 days after the first, second or third dose of COVID-19 vaccination. Median time between vaccination and onset of herpetic eye disease was 10 days (mean 12.7 ± 10.15 days) days. The administered vaccines were BNT162b2, mRNA-1273, BBIBP-CorV and Ad26.COV2.S. The cases included 11 HSV, 10 VZV and 1 CMV anterior uveitis, 2 were not further specified. There was an equal number of first episodes (n = 12, 50%) and recurrent episodes (n = 12, 50%). Response to established regimens was generally good. The retrospective database review revealed the exact same incidence of herpetic uveitis during the pandemic and ongoing vaccination compared to prior SARS-CoV-2.

Conclusion

This report includes 24 cases of herpetic anterior uveitis in a temporal relationship to various COVID-19 vaccines. This study supports the potential risk of herpetic eye disease following COVID-19 vaccines, but proof of a direct, causal relationship is missing.
Auction market placement and a rest stop during transportation affect the respiratory bacterial microbiota of beef cattle
Authors: Uddin Muhammed Salah , Schwartzkopf-Genswein Karen S. , Waldner Matthew , Meléndez Daniela M. , Niu Yan D. , Alexander Trevor W.
Published: September 2023

Background

Bovine respiratory disease (BRD) is a significant health problem in beef cattle production, resulting in considerable economic losses due to mortalities, cost of treatment, and reduced feed efficiency. The onset of BRD is multifactorial, with numerous stressors being implicated, including transportation from farms to feedlots. In relation to animal welfare, regulations or practices may require mandatory rest times during transportation. Despite this, there is limited information on how transportation and rest stops affect the respiratory microbiota.

Results

This study evaluated the effect of cattle source (ranch-direct or auction market-derived) and rest stop duration (0 or 8 h of rest) on the upper respiratory tract microbiota and its relationship to stress response indicators (blood cortisol and haptoglobin) of recently weaned cattle transported for 36 h. The community structure of bacteria was altered by feedlot placement. When cattle were off-loaded for a rest, several key bacterial genera associated with BRD (Mannheimia, Histophilus, Pasteurella) were increased for most sampling times after feedlot placement for the ranch-direct cattle group, compared to animals given no rest stop. Similarly, more sampling time points had elevated levels of BRD-associated genera when auction market cattle were compared to ranch-direct. When evaluated across time and treatments several genera including Mannheimia, Moraxella, Streptococcus and Corynebacterium were positively correlated with blood cortisol concentrations.

Conclusion

This is the first study to assess the effect of rest during transportation and cattle source on the respiratory microbiota in weaned beef calves. The results suggest that rest stops and auction market placement may be risk factors for BRD, based solely on increased abundance of BRD-associated genera in the upper respiratory tract. However, it was not possible to link these microbiota to disease outcome, due to low incidence of BRD in the study populations. Larger scale studies are needed to further define how transportation variables impact cattle health.
Variation of endosymbiont and citrus tristeza virus (CTV) titers in the Huanglongbing insect vector, Diaphorina citri, on CTV-infected plants
Authors: Cui Xiaoqing , Liu Yangyang , Zhang Jingtian , Hu Panpan , Zheng Zheng , Deng Xiaoling , Xu Meirong
Published: September 2023

“Candidatus Liberibacter asiaticus” (CLas) is a notorious agent that causes Citrus Huanglongbing (HLB), which is transmitted by Diaphorina citri (D. citri). We recently found that the acquisition and transmission of CLas by D. citri was facilitated by Citrus tristeza virus (CTV), a widely distributed virus in the field. In this study, we further studied whether different CTV strains manipulate the host preference of D. citri, and whether endosymbionts variation is related to CTV strains in D. citri. The results showed that the non-viruliferous D. citri preferred to select the shoots infected with CTV, without strain differences was observed in the selection. However, the viruliferous D. citri prefered to select the mixed strain that is similar to the field’s. Furthermore, D. citri effectively acquired the CTV within 2–12 h depending on the strains of the virus. The persistence period of CTV in D. citri was longer than 24 days, without reduction of the CTV titers being observed. These results provide a foundation for understanding the transmission mode of D. citri on CTV. During the process of CTV acquisition and persistence, the titers of main endosymbionts in D. citri showed similar variation trend, but their relative titers were different at different time points. The titers of the “Candidatus Profftella armatura” and CTV tended to be positively correlated, and the titers of Wolbachia and “Candidatus Carsonella ruddii” were mostly negatively related with titers of CT31. These results showed the relationship among D. citri, endosymbionts, and CTV and provided useful information for further research on the interactions between D. citri and CLas, which may benefit the development of approaches for the prevention of CLas transmission and control of citrus HLB.
Evaluation of probiotic growth stimulation using prebiotic ingredients to optimize compounds for in ovo delivery
Authors: Akhavan Niloofar , Hrynkiewicz Katarzyna , Thiem Dominika , Randazzo Cinzia , Walsh Ann M. , Guinan Kieran J. , O’Sullivan John T. , Stadnicka Katarzyna
Published: September 2023

The use of probiotics, prebiotics and synbiotics in poultry diets beneficially stimulates the gut microbiome thus promoting the health and welfare of the animals. In this study, we analyzed 7 poultry probiotics (Lactobacillus plantarum – B1 and B4, Lactobacillus rhamnosus – B3, Bifidobacterium lactis – B2, Carnobacterium divergens – B5, Propionibacterium thoenii – B6, Clostridium butyricum – B7) and 12 prebiotics, differing in chemical composition and source of origin (fungi, algae, animal, etc.). The main goal of our research was to select the most promising candidates to develop synbiotic combinations. We determined the growth kinetics of all probiotics in the presence of prebiotics in a series of in vitro studies to select optimal combinations. Five out of seven investigated probiotics were significantly stimulated by astragalus polysaccharide, and this prebiotic was characterized in our work as the most effective. Moreover, in the case of three probiotics, B2, B3 and B4, significant growth stimulation has been found when beta-glucan, vegetable protein hydrolysate and liquid seaweed extract were supplied. Strain B1 (L. plantarum) was stimulated by 6 out of 12 prebiotics. The growth of B4 (L. plantarum) and B2 (B. lactis) was enhanced by prebiotics after 2 h of incubation. A high growth rate of 3.13% was observed in the case of L. plantarum (B4) and a 3.37% higher rate for B. lactis (B3), compared to the growth of probiotics in the control medium with glucose but no prebiotics. The best candidates for synbiotic combinations based on this in vitro work are the strains belonging to L. plantarum (B4), L. rhamnosus (B3) and B. lactis (B2), consistent with prebiotics such as astragalus polysaccharides and vegetable protein hydrolysate. These combinations will be subject to future in vivo poultry trials involving the in ovo microbiome modulation.
Cervical dystonia and no oculomotor apraxia as new manifestation of ataxia-telangiectasia-like disorder 1 – case report and review of the literature
Authors: Bajek Agnieszka , Przewodowska Dominika , Koziorowski Dariusz , Jędrzejowska Maria , Szlufik Stanisław
Published: September 2023

Ataxia-telangiectasia-like disorder 1 (ATLD1) is a rare neurodegenerative disorder associated with early onset ataxia and oculomotor apraxia. The genetic determination of ATLD1 is a mutation in the MRE11 gene (meiotic recombination 11 gene), which causes DNA-double strand break repair deficits. Clinical features of patients with ATLD1 resemble those of ataxia telangiectasia (AT), with slower progression and milder presentation. Main symptoms include progressive cerebellar ataxia, oculomotor apraxia, cellular hypersensitivity to ionizing radiations. Facial dyskinesia, dystonia, dysarthria have also been reported. Here we present a 45-year old woman with cervical and facial dystonia, dysarthria and ataxia, who turned out to be the first case of ATLD without oculomotor apraxia, and with dystonia as a main manifestation of the disease. She had presented those non-specific symptoms for years, before whole exome sequencing confirmed the diagnosis.
The retrograde IFT dynein is required for normal function of diverse mechanosensory cilia in Drosophila
Authors: Sharma Yashoda , Jacobs Julie S. , Sivan-Loukianova Elena , Lee Eugene , Kernan Maurice J. , Eberl Daniel F.
Published: September 2023

Introduction

Cilia biogenesis relies on intraflagellar transport (IFT), a conserved transport mechanism which functions bi-directionally to bring protein complexes to the growing ciliary tip and recycle signaling and transport proteins between the cilium and cell body. In Drosophila, anterograde IFT is critical for assembly of sensory cilia in the neurons of both chordotonal (ch) organs, which have relatively long ciliary axonemes, and external sensory (es) organs, which have short axonemal segments with microtubules in distal sensory segments forming non-axonemal bundles. We previously isolated the beethoven (btv) mutant in a mutagenesis screen for auditory mutants. Although many btv mutant flies are deaf, some retain a small residual auditory function as determined both by behavior and by auditory electrophysiology.

Results

Here we molecularly characterize the btv gene and demonstrate that it encodes the IFT-associated dynein-2 heavy chain Dync2h1. We also describe morphological changes in Johnston’s organ as flies age to 30 days, and we find that morphological and electrophysiological phenotypes in this ch organ of btv mutants become more severe with age. We show that NompB protein, encoding the conserved IFT88 protein, an IFT complex B component, fails to be cleared from chordotonal cilia in btv mutants, instead accumulating in the distorted cilia. In macrochaete bristles, a class of es organ, btv mutants show a 50% reduction in mechanoreceptor potentials.

Discussion

Thus, the btv-encoded Dync2h1 functions as the retrograde IFT motor in the assembly of long ciliary axonemes in ch organs and is also important for normal function of the short ciliary axonemes in es organs.
Effects of anthocyanin supplementation in diet on glycemic and related cardiovascular biomarkers in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials
Authors: Mao Ting , Akshit F. N. U. , Mohan Maneesha S.
Published: September 2023

Purpose

This study is the first systematic review and meta-analysis based on RCTs on the effects of anthocyanins on patients with type 2 diabetes mellitus (T2DM) and the effect on T2DM-related cardiovascular disease.

Methods

RCTs published in English from five electronic databases were evaluated for glycated hemoglobin (HbA1c), fasting blood glucose (FBG), 2-h postprandial blood glucose, fasting insulin, model assessment for insulin resistance, triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, systolic blood pressure, and diastolic blood pressure. The quality of the studies was rated (Cochrane Risk of Bias tool) and weighted mean differences were calculated (DerSimonian-Laird model with random effects). Leave-one-out sensitivity, subgroup, and publication bias analyses were conducted. The strength of the evidence was rated according to the GRADE guidelines.

Results

In all, 13 RCTs were analyzed out of the 239 identified studies, with a duration longer than 4 weeks (703 participants with T2DM). Our findings indicate that a median dose of 320 mg/day anthocyanins, either from fruit extracts or pure supplements, for a median intervention length of 8 weeks significantly reduced HbA1c [Weighted Mean Difference (WMD) −0.31, p = 0.00], FBG (WMD −0.63, p = 0.00), 2-h postprandial glucose (WMD −1.60, p = 0.00), TG (WMD −0.45, p = 0.01), and LDL (WMD −0.26 p = 0.02). However, the effects of anthocyanins on fasting insulin, HOMA-IR, TC, HDL cholesterol, systolic blood pressure, and diastolic blood pressure in patients with T2DM were not statistically significant. Anthocyanins from fruit extracts or powder exhibited a higher reduction of HbA1c compared to pure anthocyanin supplements.

Conclusion

The significant improvements in glycemic parameters and lipid profile, suggest the benefits of anthocyanins, especially from fruit extract or powder, in the management of T2DM, and their ability to delay the onset of lipid disorder-related diseases such as cardiovascular disease associated with T2DM. The mechanism behind this reduction in glycemic markers could be attributed to the antioxidant and anti-inflammatory activity of anthocyanins. Further research with well-designed RCTs is required to determine the optimal dosage of anthocyanins for the treatment of T2DM and to comprehend the consequences.
Serum autoantibody profiling of oral squamous cell carcinoma patients reveals NUBP2 as a potential diagnostic marker
Authors: Abdulla Riaz , Devasia Puthenpurackal Jofy , Pinto Sneha M. , Rekha Punchappady Devasya , Subbannayya Yashwanth
Published: September 2023

Introduction

Oral Squamous Cell Carcinoma (OSCC), a common malignancy of the head and neck region, is frequently diagnosed at advanced stages, necessitating the development of efficient diagnostic methods. Profiling autoantibodies generated against tumor-associated antigens have lately demonstrated a promising role in diagnosis, predicting disease course, and response to therapeutics and relapse.

Methods

In the current study, we, for the first time, aimed to identify and evaluate the diagnostic value of autoantibodies in serum samples of patients with OSCC using autoantibody profiling by an immunome protein array. The utility of anti-NUBP2 antibody and tissue positivity in OSCC was further evaluated.

Results and discussion

We identified a total of 53 autoantibodies with significant differential levels between OSCC and control groups, including 25 that were increased in OSCC and 28 that were decreased. These included autoantibodies against Thymidine kinase 1 (TK1), nucleotide-binding protein 2 (NUBP2), and protein pyrroline-5-carboxylate reductase 1 (PYCR1), among others. Immunohistochemical validation indicated positive staining of NUBP2 in a large majority of cases (72%). Further, analysis of OSCC data available in TCGA revealed higher NUBP2 expression correlated with better disease-free patient survival. In conclusion, the differential serum autoantibodies identified in the current study, including those for NUBP2, could be used as potential biomarkers for early diagnosis or as screening biomarkers for OSCC pending investigation in a larger cohort.
Nrf2 signaling pathway: current status and potential therapeutic targetable role in human cancers
Authors: Lin Li , Wu Qing , Lu Feifei , Lei Jiaming , Zhou Yanhong , Liu Yifei , Zhu Ni , Yu You , Ning Zhifeng , She Tonghui , Hu Meichun
Published: September 2023

Cancer is a borderless global health challenge that continues to threaten human health. Studies have found that oxidative stress (OS) is often associated with the etiology of many diseases, especially the aging process and cancer. Involved in the OS reaction as a key transcription factor, Nrf2 is a pivotal regulator of cellular redox state and detoxification. Nrf2 can prevent oxidative damage by regulating gene expression with antioxidant response elements (ARE) to promote the antioxidant response process. OS is generated with an imbalance in the redox state and promotes the accumulation of mutations and genome instability, thus associated with the establishment and development of different cancers. Nrf2 activation regulates a plethora of processes inducing cellular proliferation, differentiation and death, and is strongly associated with OS-mediated cancer. What’s more, Nrf2 activation is also involved in anti-inflammatory effects and metabolic disorders, neurodegenerative diseases, and multidrug resistance. Nrf2 is highly expressed in multiple human body parts of digestive system, respiratory system, reproductive system and nervous system. In oncology research, Nrf2 has emerged as a promising therapeutic target. Therefore, certain natural compounds and drugs can exert anti-cancer effects through the Nrf2 signaling pathway, and blocking the Nrf2 signaling pathway can reduce some types of tumor recurrence rates and increase sensitivity to chemotherapy. However, Nrf2’s dual role and controversial impact in cancer are inevitable consideration factors when treating Nrf2 as a therapeutic target. In this review, we summarized the current state of biological characteristics of Nrf2 and its dual role and development mechanism in different tumor cells, discussed Keap1/Nrf2/ARE signaling pathway and its downstream genes, elaborated the expression of related signaling pathways such as AMPK/mTOR and NF-κB. Besides, the main mechanism of Nrf2 as a cancer therapeutic target and the therapeutic strategies using Nrf2 inhibitors or activators, as well as the possible positive and negative effects of Nrf2 activation were also reviewed. It can be concluded that Nrf2 is related to OS and serves as an important factor in cancer formation and development, thus provides a basis for targeted therapy in human cancers.
Identification of alternative splicing associated with clinical features: from pan-cancers to genitourinary tumors
Authors: Duan Chen , Zhang Yangjun , Li Lu , Liu Kai , Yao Xiangyang , Wu Xiaoliang , Li Bo , Mao Xiongmin , Wu Huahui , Liu Haoran , Zeng Jin , Li Sheng , Gong Yan , Hu Zhiquan , Xu Hua
Published: September 2023

Background

Alternative splicing events (ASEs) are vital causes of tumor heterogeneity in genitourinary tumors and many other cancers. However, the clinicopathological relevance of ASEs in cancers has not yet been comprehensively characterized.

Methods

By analyzing splicing data from the TCGA SpliceSeq database and phenotype data for all TCGA samples from the UCSC Xena database, we identified differential clinical feature-related ASEs in 33 tumors. CIBERSORT immune cell infiltration data from the TIMER2.0 database were used for differential clinical feature-related immune cell infiltration analysis. Gene function enrichment analysis was used to analyze the gene function of ASEs related to different clinical features in tumors. To reveal the regulatory mechanisms of ASEs, we integrated race-related ASEs and splicing quantitative trait loci (sQTLs) data in kidney renal clear cell carcinoma (KIRC) to comprehensively assess the impact of SNPs on ASEs. In addition, we predicted regulatory RNA binding proteins in bladder urothelial carcinoma (BLCA) based on the enrichment of motifs around alternative exons for ASEs.

Results

Alternative splicing differences were systematically analyzed between different groups of 58 clinical features in 33 cancers, and 30 clinical features in 24 cancer types were identified to be associated with more than 50 ASEs individually. The types of immune cell infiltration were found to be significantly different between subgroups of primary diagnosis and disease type. After integrating ASEs with sQTLs data, we found that 63 (58.9%) of the race-related ASEs were significantly SNP-correlated ASEs in KIRC. Gene function enrichment analyses showed that metastasis-related ASEs in KIRC mainly enriched Rho GTPase signaling pathways. Among those ASEs associated with metastasis, alternative splicing of GIT2 and TUBB3 might play key roles in tumor metastasis in KIRC patients. Finally, we identified several RNA binding proteins such as PCBP2, SNRNP70, and HuR, which might contribute to splicing differences between different groups of neoplasm grade in BLCA.

Conclusion

We demonstrated the significant clinical relevance of ASEs in multiple cancer types. Furthermore, we identified and validated alternative splicing of TUBB3 and RNA binding proteins such as PCBP2 as critical regulators in the progression of urogenital cancers.