bluuebunny/crossref_metadata_2025 huggingface dataset:
The Human, Non-human Affective Entanglements: A Posthuman Perspective of an ESOL Classroom
Authors: Karthika V. K.
Published: May 2024

In the age of Anthropocene, we problematize the multitudes of affordances of humanism that we are ultimately entwined by and within. Education is a discipline that always placed predominance to the human centredness ignoring several non-human and non-living objects that also form a part of teaching and learning. However, the humanistic notions of hierarchies have undergone radical changes. The locus in a classroom is no longer regulated by teachers and in a multicultural, multilingual classroom, the interaction between teacher, learners, materials and methods are evolving continually redefining the power relations. This essay highlights how every assemblage (an assemblage being a random clubbing of several human and non-human elements) is unique and in a state of flux to act and react with various human and non-human elements within/outside classroom territories. Designed as an autoethnographic study, by analysing the major tenets of posthumanism and by connecting them with English language education, this article argues for a posthuman turn in English language teaching and learning by examining the research diary entries of the author to identify how the entanglement of affect, rhizome and assemblage results in deterritorialization. Episodes and anecdotes from an ESOL (English for Speakers of Other Languages) teaching context in England serve as primary data. This autoethnographic study reveals the agential assemblages in the classrooms which problematize the singular agency of the teacher as the reservoir of knowledge and discusses how the power structure in the classroom is altered when learners and their affective assemblages influence the teacher and the very practice of teaching.
Random forest-based mineral prospectivity modelling over the Southern Kibi–Winneba belt of Ghana using geophysical and remote sensing techniques
Authors: Forson Eric Dominic , Amponsah Prince Ofori , Wemegah David Dotse , Ahwireng Michael Darko
Published: May 2024

This study determines which predictors derived from geophysics or remote sensing data best generate a mineral prospectivity model (MPM) over Ghana's southern Kibi-Winneba belt in a scenario-based modeling case using Random Forest (RF) algorithm. Ten geophysically-derived predictors and six-remote sensing derived predictors were used as inputs in the first and second scenarios respectively. In the third case, the sixteen predictors derived from these afore-mentioned geoscientific datasets were used as inputs. Thus, three binary RF-based MPM were generated, and compared accordingly. The predictive performance in all three scenario-based RF-derived MPM produced was determined using the area under the receiver operating characteristic curve (AUC). AUC scores of 0.840, 0.785 and 0.809 respectively, were obtained for the first, second and third scenarios. The AUC scores obtained further indicates that, MPM developed based on using only the geophysics-sourced layers as inputs performed better in comparison with the MPMs generated in second and third scenarios.
Correlation of serum interleukin-8 levels and prostate volume to the degree of lower urinary tract symptoms in patients with benign prostate enlargement: a cross-sectional study
Authors: Bahrun Uleng , Atmanto Yohanes Kusumo Adi Arji , Nurulita Asvin , Mangarengi Fitriani , Palinrungi Muhammad Asykar , Bahar Burhanuddin
Published: May 2024

Background

Benign prostatic enlargement (BPE) and lower urinary tract symptoms (LUTS) are pro-inflammatory cytokine interleukin-8 (IL-8)-associated which causes epithelial hyperplasia of the prostate transitional zone. This study aimed to determine the correlation between the levels of IL-8 serum and the prostate volume with the degree of LUTS severity in patients with BPE.

Methods

Determination of the correlation between serum IL-8 levels and prostate volume with the LUTS severity degree was conducted using a cross-sectional approach. The International Prostate Symptom Score was used to measure the LUTS severity degree, the enzyme-linked immunosorbent assay (ELISA) technique was used to measure the serum IL-8 level, and the transabdominal ultrasonography (TAUS) was used to measure the prostate volume. The sample used in this study was 32 patients with BPE grouped by the degree of LUTS severity of the patients. The correlation between variables was then analyzed using the Pearson correlation test.

Results

The prostate volume was higher in severe LUTS degree (38.19 cc) than in the mild LUTS degree (13.05 cc). The levels of serum IL-8 were higher in the severe LUTS degree (21.65 pg/mL) than in the mild LUTS degree (8.44 pg/m). Both the levels of serum IL-8 and the degree of LUTS did not have a significant correlation with the volume of prostate (p > 0.05). On the other side, the prostate volume and the degree of LUTS severity had a significant positive correlation (p = 0.001, R = 0.913).

Conclusion

The prostate volume and the levels of serum IL-8 are higher in the severe LUTS degree. There is a trend of increasing prostate volume with the severity of LUTS symptoms and higher serum IL-8 levels. The severity of prostate enlargement can be assessed by measuring the levels of IL-8 in the serum.
Whole genome sequence analysis of shallot virus X from India reveals it to be a natural recombinant with positive selection pressure
Authors: Singh Jyoti , Teotia Sachin , Singh Ajay Kumar , Arya Meenakshi , Rout Ajaya Kumar , Behera Bijay Kumar , Majumder Shahana
Published: May 2024

Background

Shallots are infected by various viruses like Onion yellow dwarf virus (OYDV), Leek yellow stripe virus (LYSV), Shallot latent virus (SLV) and Shallot virus X (ShVX). In India, they have been found to be persistently infected by ShVX. ShVX also infects onion and garlic in combination with other carlaviruses and potyviruses. ShVX is a member of genus Allexivirus of family Alphaflexiviridae. ShVX has a monopartite genome, which is represented by positive sense single-stranded RNA. Globally, only six complete and 3 nearly complete genome sequences of ShV X are reported to date. This number is insufficient to measure a taxon’s true molecular diversity. Moreover, the complete genome sequence of ShVX from Asia has not been reported as yet. Therefore, this study was undertaken to generate a complete genome sequence of ShVX from India.

Results

Shallot virus X (ShVX) is one of the significant threats to Allium crop production. In this study, we report the first complete genome sequence of the ShVX from India through Next-generation sequencing (NGS). The complete genome of the ShVX (Accession No. OK104171), from this study comprised 8911 nucleotides. In-silico analysis of the sequence revealed variability between this isolate and isolates from other countries. The dissimilarities are spread all over the genome specifically some non-coding intergenic regions. Statistical analysis of individual genes for site-specific selection indicates a positive selection in NABP region. The presence of a recombination event was detected in coat protein region. The sequence similarity percentage and phylogenetic analysis indicate ShVX Indian isolate is a distinctly different isolate. Recombination and site-specific selection may have a function in the evolution of this isolate. This is the first detailed study of the ShVX complete genome sequence from Southeast Asia.

Conclusion

This study presents the first report of the entire genome sequence of an Indian isolate of ShVX along with an in-depth exploration of its evolutionary traits. The findings highlight the Indian variant as a naturally occurring recombinant, emphasizing the substantial role of recombination in the evolution of this viral species. This insight into the molecular diversity of strains within a specific geographical region holds immense significance for comprehending and forecasting potential epidemics. Consequently, the insights garnered from this research hold practical value for shaping ShVX management strategies and providing a foundation for forthcoming studies delving into its evolutionary trajectory.
Refraction and ocular biometric parameters in 3-to 6-year-old preschool children : a large-scale population-based study in Chengdu, China
Authors: Mu Jingyu , Zhang Zengrui , Wu Xiaoxiao , Chen Siyu , Geng Haoming , Duan Junguo
Published: May 2024

Purpose

To understand the ocular biometric parameters characteristics and refractive errors in 3-to 6-year-old preschool children in Chengdu, China, and to investigate the prevalence of refractive errors.

Method

A school-based cross-sectional study was conducted in Chengdu from 2020 to2022 with a total of 666 kindergartens. All children were measured by non-cycloplegic autorefraction and uncorrected visual acuity (UCVA) and ocular biometric parameters. Finally, univariate linear regression models were used to analyze the relationship between ocular biometric parameters and refraction.

Results

A total of 108,578 preschool children aged 3–6 underwent examinations, revealing a myopia prevalence of 6.1%. The mean axial length (AL), keratometry (K), corneal radius (CR), axial length/corneal radius (AL/CR) Ratio, central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), and vitreous chamber depth (VCD) were 22.35 ± 0.69 mm, 43.35 ± 1.58 D, 7.80 ± 0.28 mm, 2.87 ± 0.08, 533.31 ± 32.51 μm, 2.70 ± 0.28 mm, 3.91 ± 0.27 mm, and 15.20 ± 0.68 mm, respectively. With increasing age, AL, CR, AL/CR ratio, CCT, ACD, LT, and VCD also increased. Regardless of age, males consistently exhibited longer AL, flatter corneal curvature, shallower ACD, thicker CCT, thinner LT, and longer VCD compared to females. AL, K, CR, LT, and VCD all showed significant linear relationships with SE (all P < 0.001) in univariate linear regression analysis after adjusting for gender and age.

Conclusion

The prevalence of myopia among preschool children aged 3–6 in Chengdu is relatively low. Ocular biometric parameters affecting refractive errors include AL, K, CR, LT, and VCD. The preschool period serves as a critical phase for myopia prevention and control.
Benchmarking the university campus food environment and exploring student perspectives about food insecurity and healthy eating: a case study from Australia
Authors: Keat Jemma , Dharmayani Putu Novi Arfirsta , Mihrshahi Seema
Published: May 2024

Objective

To benchmark the university food environment and explore students’ experiences with food insecurity and healthy eating in order to inform interventions to improve access and affordability of healthy foods for university students.

Design

A food environment audit was conducted on the university campus using the Uni-Food tool from April to May 2022 and was comprised of three main components, university systems and governance, campus facilities and environment, and food retail outlets. A qualitative study design was also used to conduct focus groups and semi-structured interviews with students to explore key themes regarding their experiences with food insecurity and healthy eating.

Setting

Macquarie University, Australia.

Participants

For the food environment audit 24 retail outlets on campus and for the qualitative component 29 domestic and international students enrolled at Macquarie University.

Results

The university only scored 27% in total for all components in the food environment audit. The results showed the need for better governance and leadership of the food environment. The qualitative component suggested that the main barriers to accessing healthy foods were related to availability, pricing, and knowledge of healthy foods. Future intervention ideas included free fruits and vegetables, food relief, discounts, improved self-catering facilities, education, and increased healthy food outlets.

Conclusions

Improving governance measures related to healthy eating on campus are a core priority to strengthen the food environment and students identified pricing and availability as key issues. These findings will inform effective and feasible interventions to improve food security and healthy eating on campus.
Exploring the Quality of Life (QOL) of medical students in Karachi, Pakistan
Authors: Bilawal Makhdoom , Shafique Ramna , Ansari Rafay Shahab , Bashir Muhammad Arsalan , Nadeem Muhammad Amaan , Qayyum Sardar Noman , Shah Hussain Haider , Tehseen Annoushay , Alnemr Lujain , Noori Samim
Published: May 2024

Background

The pursuit of medical and dental education is challenging and can affect the overall quality of life of medical students. Assessing the quality of life of medical students is the first step in the preparation of efficient future health care professionals. This study used the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) to evaluate the quality of life of medical and dental students in Karachi, Pakistan.

Objectives

The study objectives include: assessing the QoL of medical and dental students and their general health satisfaction and self-satisfaction.

Materials and methods

This cross-sectional study was conducted among 344 medical and dental students from different medical and dental schools in Karachi, Pakistan. The World Health Organization Quality of Life Brief Version (WHOQOL-BREF) questionnaire was used to assess QOL, which included 26 items covering four domains: physical, psychological, social, and environmental. All scores for the domains ranged from 4 to 20. Scoring was done according to the WHOQOL-BREF procedure manual. The questionnaire was disseminated to medical students using Google Forms. SPSS software was used to analyze the data. Cronbach’s alpha and the Kaiser-Meyer-Olkin (KMO) test were used to evaluate the reliability and sampling adequacy of the data for factor analysis. Descriptive statistics were computed for each variable and QoL domain, including frequencies, percentages, averages, and standard deviations. Domain scores were compared using a t-test and one-way ANOVA, with p-values less than 0.05, indicating statistical significance.

Results

Among the 344 medical students, 56.7% (n = 195) were female and 43.3% (n = 149) were male. The WHOQOL-BREF demonstrated excellent reliability, with a Cronbach’s alpha of 0.918. Most medical students rated their overall QOL (62.2%) and health satisfaction (46.8%) as good, and were able to get around well (71.3%). No significant sex differences were found across the various QOL domains. Marital status significantly affected QOL scores (p < 0.005). Single students had significantly higher QOL scores than married/separated/divorced students did. Overall, the environmental domain had the highest mean score (26.81 ± 6.17), while social relationships had the lowest mean score (9.68 ± 2.93).

Conclusion

The findings of this study provide valuable insights into the QoL of medical and dental students. Most participants reported moderate satisfaction with their physical health and lower satisfaction with the psychological, social, and environmental components of QoL. Marital status was found to significantly impact the QoL as compared to single students with greater QoL. These findings can help form targeted interventions to enhance medical students’ quality of life and prepare efficient future healthcare professionals.
Association between Mir-17-92 gene promoter polymorphisms and depression in a Chinese population
Authors: Liang Peng , Yang Xue , Long Rui , Li Yue , Wang Ziling , Yang Pingliang , Liang Yundan
Published: May 2024

Background

Depression is a common chronic debilitating disease with a heavy social burden. single nucleotide polymorphisms (SNPs) can affect the function of microRNAs (miRNAs), which is in turn associated with neurological diseases. However, the association between SNPs located in the promoter region of miR-17-92 and the risk of depression remains unclear. Therefore, we investigated the association between rs982873, rs9588884 and rs1813389 polymorphisms in the promoter region of miR-17-92 and the incidence of depression in a Chinese population.

Methods

we used GWAS (Genome-wide association study) and NCBI (National Center for Biotechnology Information) to screen three SNPs in the miR-17-92 cluster binding sites. A case-control study (including 555 cases and 541 controls) was conducted to investigate the relationship between the SNPs and risk of depression in different regions of China. The gene sequencing ii was used to genotype the collected blood samples.

Results

the following genotypes were significantly associated with a reduced risk of depression: rs982873 TC (TC vs. TT: OR = 0.72, 95% CI, 0.54–0.96, P = 0.024; TC/CC vs. TT: OR = 0.74, 95% Cl, 0.56–0.96, P = 0.025); CG genotype of rs9588884 (CG vs. CC: OR = 0.74, 95% CI, 0.55–0.98, P = 0.033; CG/GG vs. CC: OR = 0.75, 95% Cl, 0.57–0.98, P = 0.036); and AG genotype of rs1813389 (AG vs. AA: OR = 0.75, 95% CI, 0.57-1.00, P = 0.049; AG/GG vs. AA: OR = 0.76, 95% Cl, 0.59-1.00, P = 0.047). Stratified analysis showed that there was no significant correlation between the three SNPS and variables such as family history of suicidal tendency (P > 0.05).

Conclusions

our findings suggest that rs982873, rs9588884, and rs1813389 polymorphisms may be associated with protective factors for depression.
Objective monitoring tools for improved management of childhood asthma
Authors: Au-Doung Phillip L.W. , Chan Jason C.H. , Kui Oliver Y.H. , Ho Marco K.Y. , Cheung Yin Ting , Lam Jenny K.W. , Chan Hak-Kim , Brannan John , Chan Kate C.C. , Li Albert M. , Leung Sharon S.Y.
Published: May 2024

Asthma is a common chronic disease amongst children. Epidemiological studies showed that the mortality rate of asthma in children is still high worldwide. Asthma control is therefore essential to minimize asthma exacerbations, which can be fatal if the condition is poorly controlled. Frequent monitoring could help to detect asthma progression and ensure treatment effectiveness. Although subjective asthma monitoring tools are available, the results vary as they rely on patients’ self-perception. Emerging evidence suggests several objective tools could have the potential for monitoring purposes. However, there is no consensus to standardise the use of objective monitoring tools. In this review, we start with the prevalence and severity of childhood asthma worldwide. Then, we detail the latest available objective monitoring tools, focusing on their effectiveness in paediatric asthma management. Publications of spirometry, fractional exhaled nitric oxide (FeNO), hyperresponsiveness tests and electronic monitoring devices (EMDs) between 2016 and 2023 were included. The potential advantages and limitations of each tool were also discussed. Overall, this review provides a summary for researchers dedicated to further improving objective paediatric asthma monitoring and provides insights for clinicians to incorporate different objective monitoring tools in clinical practices.
Insulin sensitivity estimates and their longitudinal association with coronary artery disease in type 1 diabetes. Does it matter?
Authors: Mutter Stefan , Parente Erika B. , Januszewski Andrzej S. , Simonsen Johan R. , Harjutsalo Valma , Groop Per-Henrik , Jenkins Alicia J. , Thorn Lena M. ,   the FinnDiane Study Group
Published: May 2024

Background

Insulin resistance and chronic kidney disease are both associated with increased coronary artery disease risk. Many formulae estimating glucose disposal rate in type 1 diabetes infer insulin sensitivity from clinical data. We compare associations and performance relative to traditional risk factors and kidney disease severity between three formulae estimating the glucose disposal rate and coronary artery disease in people with type 1 diabetes.

Methods

The baseline glucose disposal rate was estimated by three (Williams, Duca, and Januszewski) formulae in FinnDiane Study participants and related to subsequent incidence of coronary artery disease, by baseline kidney status.

Results

In 3517 adults with type 1 diabetes, during median (IQR) 19.3 (14.6, 21.4) years, 539 (15.3%) experienced a coronary artery disease event, with higher rates with worsening baseline kidney status. Correlations between the three formulae estimating the glucose disposal rate were weak, but the lowest quartile of each formula was associated with higher incidence of coronary artery disease. Importantly, only the glucose disposal rate estimation by Williams showed a linear association with coronary artery disease risk in all analyses. Of the three formulae, Williams was the strongest predictor of coronary artery disease. Only age and diabetes duration were stronger predictors. The strength of associations between estimated glucose disposal rate and CAD incidence varied by formula and kidney status.

Conclusions

In type 1 diabetes, estimated glucose disposal rates are associated with subsequent coronary artery disease, modulated by kidney disease severity. Future research is merited regarding the clinical usefulness of estimating the glucose disposal rate as a coronary artery disease risk factor and potential therapeutic target.
Engineering PD-1-targeted small protein variants for in vitro diagnostics and in vivo PET imaging
Authors: Mierzwicka Joanna Maria , Petroková Hana , Kafková Leona Rašková , Kosztyu Petr , Černý Jiří , Kuchař Milan , Petřík Miloš , Bendová Kateřina , Krasulová Kristýna , Groza Yaroslava , Vaňková Lucie , Bharadwaj Shiv , Panova Natalya , Křupka Michal , Škarda Jozef , Raška Milan , Malý Petr
Published: May 2024

Background

Programmed cell death 1 (PD-1) belongs to immune checkpoint proteins ensuring negative regulation of the immune response. In non-small cell lung cancer (NSCLC), the sensitivity to treatment with anti-PD-1 therapeutics, and its efficacy, mostly correlated with the increase of tumor infiltrating PD-1+ lymphocytes. Due to solid tumor heterogeneity of PD-1+ populations, novel low molecular weight anti-PD-1 high-affinity diagnostic probes can increase the reliability of expression profiling of PD-1+ tumor infiltrating lymphocytes (TILs) in tumor tissue biopsies and in vivo mapping efficiency using immune-PET imaging.

Methods

We designed a 13 kDa β-sheet Myomedin scaffold combinatorial library by randomization of 12 mutable residues, and in combination with ribosome display, we identified anti-PD-1 Myomedin variants (MBA ligands) that specifically bound to human and murine PD-1-transfected HEK293T cells and human SUP-T1 cells spontaneously overexpressing cell surface PD-1.

Results

Binding affinity to cell-surface expressed human and murine PD-1 on transfected HEK293T cells was measured by fluorescence with LigandTracer and resulted in the selection of most promising variants MBA066 (hPD-1 KD = 6.9 nM; mPD-1 KD = 40.5 nM), MBA197 (hPD-1 KD = 29.7 nM; mPD-1 KD = 21.4 nM) and MBA414 (hPD-1 KD = 8.6 nM; mPD-1 KD = 2.4 nM). The potential of MBA proteins for imaging of PD-1+ populations in vivo was demonstrated using deferoxamine-conjugated MBA labeled with 68Galium isotope. Radiochemical purity of 68Ga-MBA proteins reached values 94.7–99.3% and in vitro stability in human serum after 120 min was in the range 94.6–98.2%. The distribution of 68Ga-MBA proteins in mice was monitored using whole-body positron emission tomography combined with computerized tomography (PET/CT) imaging up to 90 min post-injection and post mortem examined in 12 mouse organs. The specificity of MBA proteins was proven by co-staining frozen sections of human tonsils and NSCLC tissue biopsies with anti-PD-1 antibody, and demonstrated their potential for mapping PD-1+ populations in solid tumors.

Conclusions

Using directed evolution, we developed a unique set of small binding proteins that can improve PD-1 diagnostics in vitro as well as in vivo using PET/CT imaging.

Graphical Abstract
The putative proton-coupled organic cation antiporter is involved in uptake of triptans into human brain capillary endothelial cells
Authors: Svane Nana , Pedersen Alberte Bay Villekjær , Rodenberg Anne , Ozgür Burak , Saaby Lasse , Bundgaard Christoffer , Kristensen Mie , Tfelt-Hansen Peer , Brodin Birger
Published: May 2024

Background

Triptans are anti-migraine drugs with a potential central site of action. However, it is not known to what extent triptans cross the blood–brain barrier (BBB). The aim of this study was therefore to determine if triptans pass the brain capillary endothelium and investigate the possible underlying mechanisms with focus on the involvement of the putative proton-coupled organic cation (H+/OC) antiporter. Additionally, we evaluated whether triptans interacted with the efflux transporter, P-glycoprotein (P-gp).

Methods

We investigated the cellular uptake characteristics of the prototypical H+/OC antiporter substrates, pyrilamine and oxycodone, and seven different triptans in the human brain microvascular endothelial cell line, hCMEC/D3. Triptan interactions with P-gp were studied using the IPEC-J2 MDR1 cell line. Lastly, in vivo neuropharmacokinetic assessment of the unbound brain-to-plasma disposition of eletriptan was conducted in wild type and mdr1a/1b knockout mice.

Results

We demonstrated that most triptans were able to inhibit uptake of the H+/OC antiporter substrate, pyrilamine, with eletriptan emerging as the strongest inhibitor. Eletriptan, almotriptan, and sumatriptan exhibited a pH-dependent uptake into hCMEC/D3 cells. Eletriptan demonstrated saturable uptake kinetics with an apparent Km of 89 ± 38 µM and a Jmax of 2.2 ± 0.7 nmol·min−1·mg protein−1 (n = 3). Bidirectional transport experiments across IPEC-J2 MDR1 monolayers showed that eletriptan is transported by P-gp, thus indicating that eletriptan is both a substrate of the H+/OC antiporter and P-gp. This was further confirmed in vivo, where the unbound brain-to-unbound plasma concentration ratio (Kp,uu) was 0.04 in wild type mice while the ratio rose to 1.32 in mdr1a/1b knockout mice.

Conclusions

We have demonstrated that the triptan family of compounds possesses affinity for the H+/OC antiporter proposing that the putative H+/OC antiporter plays a role in the BBB transport of triptans, particularly eletriptan. Our in vivo studies indicate that eletriptan is subjected to simultaneous brain uptake and efflux, possibly facilitated by the putative H+/OC antiporter and P-gp, respectively. Our findings offer novel insights into the potential central site of action involved in migraine treatment with triptans and highlight the significance of potential transporter related drug-drug interactions.

Graphical Abstract
A case of hyalinizing trabecular tumor of the thyroid: diagnostic significance of PAX8-GLIS3 fusion
Authors: Hayashi Shuto , Bandoh Nobuyuki , Baba Shogo , Hayashi Misaki , Goto Takashi , Takahara Miki , Kato Yasutaka , Aimono Eriko , Nishihara Hiroshi
Published: May 2024

Background

Hyalinizing trabecular tumor (HTT) is an uncommon follicular cell-derived thyroid tumor classified as a low-risk neoplasm by the World Health Organization Classification of Tumors of Endocrine Organs, 5th edition. The PAX8-GLIS3 gene fusion is reportedly a pathognomonic genetic alteration of HTT.

Case presentation

A 43-year-old Japanese female was incidentally discovered to have an 8-mm, well-defined, hypoechoic mass in the left lobe of the thyroid gland by ultrasound examination. Contrast-enhanced computed tomography scan revealed a solid mass exhibiting slight homogeneous enhancement in the lower pole of the thyroid gland. The mass was diagnosed as atypia of undetermined significance by fine-needle aspiration cytology. The patient underwent left hemithyroidectomy with routine central compartment dissection. Histologic findings revealed tumor cells with elongated nuclei and intranuclear pseudoinclusions arranged with trabeculae architecture or small nests in hyalinized stroma. Weak membranous and cytoplasmic staining was found by MIB1 (Ki-67) immunostaining. The final diagnosis was HTT of the thyroid gland. Next-generation sequencing genetic analysis of a surgical specimen revealed no pathologic mutations, including BRAF, H/K/NRAS, or RET-PTC fusions. The PAX8-GLIS3 fusion was detected by RT-PCR.

Conclusions

A rare case of HTT was demonstrated through imaging, cytologic, histologic and molecular investigations. PAX8-GLIS3 fusion detected by RT-PCR and Sanger sequencing was confirmed to be a genetic hallmark of HTT.
Ficolin 3 promotes ferroptosis in HCC by downregulating IR/SREBP axis-mediated MUFA synthesis
Authors: Yuan Yanmei , Xu Junting , Jiang Quanxin , Yang Chuanxin , Wang Ning , Liu Xiaolong , Piao Hai-long , Lu Sijia , Zhang Xianjing , Han Liu , Liu Zhiyan , Cai Jiabin , Liu Fang , Chen Suzhen , Liu Junli
Published: May 2024

Background

Targeting ferroptosis has been identified as a promising approach for the development of cancer therapies. Monounsaturated fatty acid (MUFA) is a type of lipid that plays a crucial role in inhibiting ferroptosis. Ficolin 3 (FCN3) is a component of the complement system, serving as a recognition molecule against pathogens in the lectin pathway. Recent studies have reported that FCN3 demonstrates inhibitory effects on the progression of certain tumors. However, whether FCN3 can modulate lipid metabolism and ferroptosis remains largely unknown.

Methods

Cell viability, BODIPY-C11 staining, and MDA assay were carried out to detect ferroptosis. Primary hepatocellular carcinoma (HCC) and xenograft models were utilized to investigate the effect of FCN3 on the development of HCC in vivo. A metabonomic analysis was conducted to assess alterations in intracellular and HCC intrahepatic lipid levels.

Results

Our study elucidates a substantial decrease in the expression of FCN3, a component of the complement system, leads to MUFA accumulation in human HCC specimens and thereby significantly promotes ferroptosis resistance. Overexpression of FCN3 efficiently sensitizes HCC cells to ferroptosis, resulting in the inhibition of the oncogenesis and progression of both primary HCC and subcutaneous HCC xenograft. Mechanistically, FCN3 directly binds to the insulin receptor β (IR-β) and its pro-form (pro-IR), inhibiting pro-IR cleavage and IR-β phosphorylation, ultimately resulting in IR-β inactivation. This inactivation of IR-β suppresses the expression of sterol regulatory element binding protein-1c (SREBP1c), which subsequently suppresses the transcription of genes related to de novo lipogenesis (DNL) and lipid desaturation, and consequently downregulates intracellular MUFA levels.

Conclusions

These findings uncover a novel regulatory mechanism by which FCN3 enhances the sensitivity of HCC cells to ferroptosis, indicating that targeting FCN3-induced ferroptosis is a promising strategy for HCC treatment.
Refraining from closed reduction of displaced distal radius fractures in the emergency department—in short: the RECORDED trial
Authors: Derksen B. M. , Jawahier P. A. , Wijers O. , Knops S. P. , de Vries M. R. , van Hooff C. C. Drijfhout , Verhofstad M. H. J. , Schep N. W. L.
Published: May 2024

Background

With roughly 45,000 adult patients each year, distal radius fractures are one of the most common fractures in the emergency department. Approximately 60% of all these fractures are displaced and require surgery. The current guidelines advise to perform closed reduction of these fractures awaiting surgery, as it may lead to post-reduction pain relief and release tension of the surrounding neurovascular structures. Recent studies have shown that successful reduction does not warrant conservative treatment, while patients find it painful or even traumatizing. The aim of this study is to determine whether closed reduction can be safely abandoned in these patients.

Methods

In this multicenter randomized clinical trial, we will randomize between closed reduction followed by plaster casting and only plaster casting. Patients aged 18 to 75 years, presenting at the emergency department with a displaced distal radial fracture and requiring surgery according to the attending surgeon, are eligible for inclusion. Primary outcome is pain assessed with daily VAS scores from the visit to the emergency department until surgery. Secondary outcomes are function assessed by PRWHE, length of stay at the emergency department, length of surgery, return to work, patient satisfaction, and complications. A total of 134 patients will be included in this study with follow-up of 1 year.

Discussion

If our study shows that patients who did not receive closed reduction experience no significant drawbacks, we might be able to reorganize the initial care for distal radial fractures in the emergency department. If surgery is warranted, the patient can be sent home with a plaster cast to await the call for admission, decreasing the time spend in the emergency room drastically.

Trial registration

This trial was registered on January 27, 2023.
Discovery of novel cholesteryl ester transfer protein (CETP) inhibitors by a multi-stage virtual screening
Authors: Liu Yanfeng , Deng Liangying , Ding Feng , Wang Qiang , Zhang Shuran , Mi Nana , Zhang Wenhui , Zeng Bailin , Tong Huangjin , Wu Lixing
Published: May 2024

Cholesteryl ester transfer protein (CETP) is a promising therapeutic target for cardiovascular diseases. It effectively lowers the low-density lipoprotein cholesterol levels and increases the high-density lipoprotein cholesterol levels in the human plasma. This study identified novel and highly potent CETP inhibitors using virtual screening techniques. Molecular docking and molecular dynamics (MD) simulations revealed the binding patterns of these inhibitors, with the top 50 compounds selected according to their predicted binding affinity. Protein–ligand interaction analyses were performed, leading to the selection of 26 compounds for further evaluation. A CETP inhibition assay confirmed the inhibitory activities of the selected compounds. The results of the MD simulations revealed the structural stability of the protein–ligand complexes, with the binding site remaining significantly unchanged, indicating that the five compounds (AK-968/40709303, AG-690/11820117, AO-081/41378586, AK-968/12713193, and AN-465/14952302) identified have the potential as active CETP inhibitors and are promising leads for drug development.

Graphical Abstract
Molecular weight control of poly-γ-glutamic acid reveals novel insights into extracellular polymeric substance synthesis in Bacillus licheniformis
Authors: Wei Xiaoyu , Yang Lijie , Chen Zhen , Xia Wenhao , Chen Yongbin , Cao Mingfeng , He Ning
Published: May 2024

Background

The structural diversity of extracellular polymeric substances produced by microorganisms is attracting particular attention. Poly-gamma-glutamic acid (γ-PGA) is a widely studied extracellular polymeric substance from Bacillus species. The function of γ-PGA varies with its molecular weight (Mw).

Results

Herein, different endogenous promoters in Bacillus licheniformis were selected to regulate the expression levels of pgdS, resulting in the formation of γ-PGA with Mw values ranging from 1.61 × 103 to 2.03 × 104 kDa. The yields of γ-PGA and exopolysaccharides (EPS) both increased in the pgdS engineered strain with the lowest Mw and viscosity, in which the EPS content was almost tenfold higher than that of the wild-type strain. Subsequently, the compositions of EPS from the pgdS engineered strain also changed. Metabolomics and RT-qPCR further revealed that improving the transportation efficiency of EPS and the regulation of carbon flow of monosaccharide synthesis could affect the EPS yield.

Conclusions

Here, we present a novel insight that increased pgdS expression led to the degradation of γ-PGA Mw and changes in EPS composition, thereby stimulating EPS and γ-PGA production. The results indicated a close relationship between γ-PGA and EPS in B. licheniformis and provided an effective strategy for the controlled synthesis of extracellular polymeric substances.
Enhanced upgrading of lignocellulosic substrates by coculture of Saccharomyces cerevisiae and Acinetobacter baylyi ADP1
Authors: Liu Changshuo , Choi Bohyun , Efimova Elena , Nygård Yvonne , Santala Suvi
Published: May 2024

Background

Lignocellulosic biomass as feedstock has a huge potential for biochemical production. Still, efficient utilization of hydrolysates derived from lignocellulose is challenged by their complex and heterogeneous composition and the presence of inhibitory compounds, such as furan aldehydes. Using microbial consortia where two specialized microbes complement each other could serve as a potential approach to improve the efficiency of lignocellulosic biomass upgrading.

Results

This study describes the simultaneous inhibitor detoxification and production of lactic acid and wax esters from a synthetic lignocellulosic hydrolysate by a defined coculture of engineered Saccharomyces cerevisiae and Acinetobacter baylyi ADP1. A. baylyi ADP1 showed efficient bioconversion of furan aldehydes present in the hydrolysate, namely furfural and 5-hydroxymethylfurfural, and did not compete for substrates with S. cerevisiae, highlighting its potential as a coculture partner. Furthermore, the remaining carbon sources and byproducts of S. cerevisiae were directed to wax ester production by A. baylyi ADP1. The lactic acid productivity of S. cerevisiae was improved approximately 1.5-fold (to 0.41 ± 0.08 g/L/h) in the coculture with A. baylyi ADP1, compared to a monoculture of S. cerevisiae.

Conclusion

The coculture of yeast and bacterium was shown to improve the consumption of lignocellulosic substrates and the productivity of lactic acid from a synthetic lignocellulosic hydrolysate. The high detoxification capacity and the ability to produce high-value products by A. baylyi ADP1 demonstrates the strain to be a potential candidate for coculture to increase production efficiency and economics of S. cerevisiae fermentations.
Taurine-mediated gene transcription and cell membrane permeability reinforced co-production of bioethanol and Monascus azaphilone pigments for a newly isolated Monascus purpureus
Authors: Yi Xia , Han Jianqi , Xu Xiaoyan , Wang Yilong , Zhang Meng , Zhu Jie , He Yucai
Published: May 2024

Background

Taurine, a semi-essential micronutrient, could be utilized as a sulfur source for some bacteria; however, little is known about its effect on the accumulation of fermentation products. Here, it investigated the effect of taurine on co-production of bioethanol and Monascus azaphilone pigments (MonAzPs) for a fungus.

Results

A newly isolated fungus of 98.92% identity with Monascus purpureus co-produced 23.43 g/L bioethanol and 66.12, 78.01 and 62.37 U/mL red, yellow and orange MonAzPs for 3 d in synthetic medium (SM). Taurine enhanced bioethanol titer, ethanol productivity and ethanol yield at the maximum by 1.56, 1.58 and 1.60 times than those of the control in corn stover hydrolysates (CSH), and red, yellow and orange MonAzPs were raised by 1.24, 1.26 and 1.29 times, respectively. Taurine was consumed extremely small quantities for M. purpureus and its promotional effect was not universal for the other two biorefinery fermenting strains. Taurine intensified the gene transcription of glycolysis (glucokinase, phosphoglycerate mutase, enolase and alcohol dehydrogenase) and MonAzPs biosynthesis (serine hydrolases, C-11-ketoreductase, FAD-dependent monooxygenase, 4-O-acyltransferase, deacetylase, NAD(P)H-dependent oxidoredutase, FAD-dependent oxidoredutase, enoyl reductase and fatty acid synthase) through de novo RNA-Seq assays. Furthermore, taurine improved cell membrane permeability through changing cell membrane structure by microscopic imaging assays.

Conclusions

Taurine reinforced co-production of bioethanol and MonAzPs by increasing gene transcription level and cell membrane permeability for M. purpureus. This work would offer an innovative, efficient and taurine-based co-production system for mass accumulation of the value-added biofuels and biochemicals from lignocellulosic biomass.
Impact of infrasound exposure and streptozotocin-induced glucose intolerance on bone composition in Wistar rats
Authors: Zagalo Luísa , Pereira Gonçalo , Casal Diogo , Gonçalves Luísa L. , Zagalo Carlos , Oliveira Maria João , Oliveira Pedro , Brito José A. A.
Published: May 2024

The elemental composition of chemical elements can vary between healthy and diseased tissues, providing essential insights into metabolic processes in physiological and diseased states. This study aimed to evaluate the calcium (Ca) and phosphorus (P) levels in the bones of rats with/without streptozotocin-induced diabetes and/or exposure to infrasound. X-ray fluorescence spectroscopy was used to determine the concentrations of Ca and P in Wistar rat tibiae samples.

The results showed a significant decrease in bone P concentration in streptozotocin-induced diabetic rats compared to untreated animals. Similarly, the Ca/P ratio was higher in the streptozotocin-induced diabetic group. No significant differences were observed in bone Ca concentration between the studied groups or between animals exposed and not exposed to infrasound.

Moreover, streptozotocin-induced diabetic rats had lower bone P concentration but unaltered bone Ca concentration compared to untreated rats. Infrasound exposure did not impact bone Ca or P levels. The reduced bone P concentration may be associated with an increased risk of bone fractures in diabetes.
Combined in vivo MRI assessment of locus coeruleus and nucleus basalis of Meynert integrity in amnestic Alzheimer’s disease, suspected-LATE and frontotemporal dementia
Authors: Lagarde Julien , Olivieri Pauline , Tonietto Matteo , Noiray Camille , Lehericy Stéphane , Valabrègue Romain , Caillé Fabien , Gervais Philippe , Moussion Martin , Bottlaender Michel , Sarazin Marie
Published: May 2024

Background

The locus coeruleus (LC) and the nucleus basalis of Meynert (NBM) are altered in early stages of Alzheimer’s disease (AD). Little is known about LC and NBM alteration in limbic-predominant age-related TDP-43 encephalopathy (LATE) and frontotemporal dementia (FTD). The aim of the present study is to investigate in vivo LC and NBM integrity in patients with suspected-LATE, early-amnestic AD and FTD in comparison with controls.

Methods

Seventy-two participants (23 early amnestic-AD patients, 17 suspected-LATE, 17 FTD patients, defined by a clinical-biological diagnosis reinforced by amyloid and tau PET imaging, and 15 controls) underwent neuropsychological assessment and 3T brain MRI. We analyzed the locus coeruleus signal intensity (LC-I) and the NBM volume as well as their relation with cognition and with medial temporal/cortical atrophy.

Results

We found significantly lower LC-I and NBM volume in amnestic-AD and suspected-LATE in comparison with controls. In FTD, we also observed lower NBM volume but a slightly less marked alteration of the LC-I, independently of the temporal or frontal phenotype. NBM volume was correlated with the global cognitive efficiency in AD patients. Strong correlations were found between NBM volume and that of medial temporal structures, particularly the amygdala in both AD and FTD patients.

Conclusions

The alteration of LC and NBM in amnestic-AD, presumed-LATE and FTD suggests a common vulnerability of these structures to different proteinopathies. Targeting the noradrenergic and cholinergic systems could be effective therapeutic strategies in LATE and FTD.
Monocytes prevent apoptosis of iPSCs and promote differentiation of kidney organoids
Authors: Pecksen Ekaterina , Tkachuk Sergey , Schröder Cristoph , Vives Enrich Marc , Neog Anindita , Johnson Cory P. , Lachmann Niko , Haller Hermann , Kiyan Yulia
Published: May 2024

Background

Induced pluripotent stem cells (iPSCs)-derived kidney organoids are a promising model for studying disease mechanisms and renal development. Despite several protocols having been developed, further improvements are needed to overcome existing limitations and enable a wider application of this model. One of the approaches to improve the differentiation of renal organoids in vitro is to include in the system cell types important for kidney organogenesis in vivo, such as macrophages. Another approach could be to improve cell survival. Mesodermal lineage differentiation is the common initial step of the reported protocols. The glycogen synthase kinase-3 (GSK-3) activity inhibitor, CHIR99021 (CHIR), is applied to induce mesodermal differentiation. It has been reported that CHIR simultaneously induces iPSCs apoptosis that can compromise cell differentiation. We thought to interfere with CHIR-induced apoptosis of iPSCs using rapamycin.

Methods

Differentiation of kidney organoids from human iPSCs was performed. Cell survival and autophagy were analyzed using Cell counting kit 8 (CCK8) kit and Autophagy detection kit. Cells were treated with rapamycin or co-cultured with human monocytes isolated from peripheral blood or iPSCs-macrophages using a transwell co-culture system. Monocyte-derived extracellular vesicles (EVs) were isolated using polyethylene glycol precipitation. Expression of apoptotic markers cleaved Caspase 3, Poly [ADP-ribose] polymerase 1 (PARP-1) and markers of differentiation T-Box Transcription Factor 6 (TBX6), odd-skipped related 1 (OSR1), Nephrin, E-Cadherin, Paired box gene 2 (Pax2) and GATA Binding Protein 3 (Gata3) was assessed by RT-PCR and western blotting. Organoids were imaged by 3D-confocal microscopy.

Results

We observed that CHIR induced apoptosis of iPSCs during the initial stage of renal organoid differentiation. Underlying mechanisms implied the accumulation of reactive oxygen species and decreased autophagy. Activation of autophagy by rapamacin and by an indirect co-culture of differentiating iPSCs with iPSCs-macrophages and human peripheral blood monocytes prevented apoptosis induced by CHIR. Furthermore, monocytes (but not rapamycin) strongly promoted expression of renal differentiation markers and organoids development via released extracellular vesicles.

Conclusion

Our data suggest that co-culturing of iPSCs with human monocytes strongly improves differentiation of kidney organoids. An underlying mechanism of monocytic action implies, but not limited to, an increased autophagy in CHIR-treated iPSCs. Our findings enhance the utility of kidney organoid models.
Exploring different stroke populations’ information needs: a cross-sectional study in England
Authors: Harfoush Allam , Chatterjee Kausik , Deery Elizabeth , Hamdallah Hanady
Published: May 2024

Background

While tailored information might have the potential to motivate stroke survivors to make essential lifestyle changes and improve long-term outcomes, how this varies among different stroke populations is not yet fully understood.

Method

From November 2022 to May 2023, stroke survivors in the UK, who were clinically stable, participated in a community-based, descriptive cross-sectional study. Participants rated several information themes on a Likert scale from one to five, indicating the relevance of each information group to them. Data were analysed using Wilcoxon and chi-squared tests on SPSS. Descriptive statistics were employed for examining the preferred information delivery method, timing, personnel, and frequency.

Results

Seventy survivors, with an average age of 67 ± 19 (61% males), were recruited. Survivors emphasised the importance of symptoms, risk factors, and recovery information during hospital stay, while medication and lifestyle change information were more significant in the community. Subgroup analysis revealed distinct patterns: First-time stroke survivors highlighted the importance of social and financial support (acute phase median Likert score 3, chronic phase median Likert score 4; p < 0.01), while those with prior strokes emphasised information on driving and working after stroke (acute phase median Likert score 4, chronic phase median Likert score 3; p < 0.05). Survivors recruited after six months of stroke prioritised knowledge of carer support in the community (acute phase median Likert score 3.5, chronic phase median Likert score 4; p < 0.01).

Conclusion

Survivors’ information needs differ depending on factors such as the recovery phase, type of stroke, time since diagnosis, and the presence of a previous stroke. Considering these factors is essential when developing or providing information to stroke survivors.