bluuebunny/crossref_metadata_2025_split huggingface dataset:
SGLT2 inhibition, circulating metabolites, and atrial fibrillation: a Mendelian randomization study
Authors: Li Jiang , Yu Yuefeng , Sun Ying , Yu Bowei , Tan Xiao , Wang Bin , Lu Yingli , Wang Ningjian 
Published: October 2023

Abstract
Background
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown promise in reducing the risk of atrial fibrillation (AF). However, the results are controversial and the underlying metabolic mechanism remains unclear. Emerging evidence implied that SGLT2 inhibitors have extra beneficial metabolic effects on circulating metabolites beyond glucose control, which might play a role in reducing the risk of AF. Hence, our study aimed to investigate the effect of circulating metabolites mediating SGLT2 inhibition in AF by Mendelian randomization (MR).

Methods
A two-sample and two-step MR study was conducted to evaluate the association of SGLT2 inhibition with AF and the mediation effects of circulating metabolites linking SGLT2 inhibition with AF. Genetic instruments for SGLT2 inhibition were identified as genetic variants, which were both associated with the expression of SLC5A2 gene and glycated hemoglobin level (HbA1c). Positive control analysis on type 2 diabetes mellitus (T2DM) was conducted to validate the selection of genetic instruments.

Results
Genetically predicted SGLT2 inhibition (per 1 SD decrement in HbA1c) was associated with reduced risk of T2DM (odds ratio [OR] = 0.63 [95% CI 0.45, 0.88], P = 0.006) and AF (0.51 [0.27, 0.97], P = 0.039). Among 168 circulating metabolites, two metabolites were both associated with SGLT2 inhibition and AF. The effect of SGLT2 inhibition on AF through the total concentration of lipoprotein particles (0.88 [0.81, 0.96], P = 0.004) and the concentration of HDL particles (0.89 [0.82, 0.97], P = 0.005), with a mediated proportion of 8.03% (95% CI [1.20%, 14.34%], P = 0.010) and 7.59% ([1.09%, 13.34%], P = 0.011) of the total effect, respectively.

Conclusions
This study supported the association of SGLT2 inhibition with a reduced risk of AF. The total concentration of lipoprotein particles and particularly the concentration of HDL particles might mediate this association. Further mechanistic and clinical studies research are needed to understand the mediation effects of circulating metabolites especially blood lipids in the association between SGLT2 inhibition and AF.
Two-step conversion of polyethylene into recombinant proteins using a microbial platform
Authors: Connor Alexander , Lamb Jessica V. , Delferro Massimiliano , Koffas Mattheos , Zha R. Helen 
Published: October 2023

Abstract
Background
The increasing prevalence of plastic waste combined with the inefficiencies of mechanical recycling has inspired interest in processes that can convert these waste streams into value-added biomaterials. To date, the microbial conversion of plastic substrates into biomaterials has been predominantly limited to polyhydroxyalkanoates production. Expanding the capabilities of these microbial conversion platforms to include a greater diversity of products generated from plastic waste streams can serve to promote the adoption of these technologies at a larger scale and encourage a more sustainable materials economy.

Results
Herein, we report the development of a new strain of Pseudomonas bacteria capable of converting depolymerized polyethylene into high value bespoke recombinant protein products. Using hexadecane, a proxy for depolymerized polyethylene, as a sole carbon nutrient source, we optimized media compositions that facilitate robust biomass growth above 1 × 109 cfu/ml, with results suggesting the benefits of lower hydrocarbon concentrations and the use of NH4Cl as a nitrogen source. We genomically integrated recombinant genes for green fluorescent protein and spider dragline-inspired silk protein, and we showed their expression in Pseudomonas aeruginosa, reaching titers of approximately 10 mg/L when hexadecane was used as the sole carbon source. Lastly, we demonstrated that chemically depolymerized polyethylene, comprised of a mixture of branched and unbranched alkanes, could be converted into silk protein by Pseudomonas aeruginosa at titers of 11.3 ± 1.1 mg/L.

Conclusion
This work demonstrates a microbial platform for the conversion of a both alkanes and plastic-derived substrates to recombinant, protein-based materials. The findings in this work can serve as a basis for future endeavors seeking to upcycle recalcitrant plastic wastes into value-added recombinant proteins.
KHDRBS3 accelerates glycolysis and promotes malignancy of hepatocellular carcinoma via upregulating 14-3-3ζ
Authors: Zhao Mingda , Zhang Yibing , Li Longfei , Liu Xiaobin , Zhou Wenping , Wang Chunhui , Tang Yufu 
Published: October 2023

Abstract
Background
Primary hepatocellular carcinoma (HCC) is a malignancy with high morbidity and mortality. KH domain-containing, RNA-binding signal transduction-associated protein 3 (KHDRBS3) is an RNA-binding protein that is aberrantly expressed in multiple tumors; however, its expression and biological function in HCC have not been reported.

Methods
KHDRBS3 knockdown and overexpression were performed using the lentiviral vector system to investigate the effects of KHDRBS3 on cell proliferation, apoptosis, chemoresistance, and glycolysis. Murine xenograft tumor models were constructed to study the role of KHDRBS3 on tumor growth in vivo. Furthermore, RNA-Pull Down and RNA immunoprecipitation were utilized to explore the interaction between KHDRBS3 and 14-3-3ζ, a phosphopeptide-binding molecule encoded by YWHAZ.

Results
KHDRBS3 was highly expressed in human HCC tissues and predicted the poor prognosis of patients with HCC. Knockdown of KHDRBS3 exhibited a carcinostatic effect in HCC and impeded proliferation and tumor growth, reduced glycolysis, enhanced cell sensitivity to doxorubicin, and induced apoptosis. On the contrary, forced expression of KHDRBS3 expedited the malignant biological behaviors of HCC cells. The expression of KHDRBS3 was positively correlated with the expression of 14-3-3ζ. RNA immunoprecipitation and RNA pull-down assays demonstrated that KHDRBS3 bound to YWHAZ. We further confirmed that 14-3-3ζ silencing significantly reversed the promotion of proliferation and glycolysis and the inhibition of apoptosis caused by KHDRBS3 overexpression.

Conclusions
Our findings suggest that KHDRBS3 promotes glycolysis and malignant progression of HCC through upregulating 14-3-3ζ expression, providing a possible target for HCC therapy.
Implication of agricultural practices in the micro-geographic heterogeneity of malaria transmission in Bouna, Côte d’Ivoire
Authors: Beke Obo Armel-Hermann , Assi Serge-Brice , Kokrasset Akedjro Paul Harvey , Dibo Kacou Jean Denis , Tanoh Méa Antoine , Danho Mathias , Remoué Franck , Koudou Guibehi Benjamin , Poinsignon Anne 
Published: October 2023

Abstract
Background
Wetlands and irrigated agricultural crops create potential breeding sites for Anopheles mosquitoes, leading to a heterogeneity in malaria transmission. In agricultural areas, heterogeneity of malaria transmission is often associated with the presence of hotspots consisting of localized clusters of higher transmission intensity. This study aims to identify micro-geographic hotspots of malaria transmission in an agricultural setting using a multidisciplinary approach.

Methods
Two cross-sectional surveys were conducted at the end of the dry season and at the peak of the rainy season in rural and urban sites in Bouna, northeastern Côte d'Ivoire. A total of 296 individuals from 148 farming households were randomly selected and sociological, geographical, entomological, and clinical data as well as blood samples were collected during each visit. Parasitological data and Anopheles exposure (measured using entomological and immunological methods) were compared with demographic, agricultural, and geographic data to identify drivers of malaria transmission. Heat maps combining these data were used to identify households with ongoing malaria transmission throughout the year.

Results
In rural areas, Plasmodium prevalence was consistent between the dry and the rainy seasons, with roughly half of the population infected. In urban areas, malaria transmission indicators were lower, with a parasite prevalence of less than 20%, which remained comparable between the dry and the rainy season. The presence of irrigated crops and proximity to wetlands were associated with increased Anopheles exposure. By mapping Plasmodium infection and Anopheles exposure, two different types of hotspots of malaria transmission were identified: micro-geographical scale and local scale hotspots.

Conclusions
The presence of wetlands in urban areas and irrigated agriculture in rural areas resulted in heterogeneity in malaria transmission on a micro-geographical scale. These specific households present particular risk of malaria transmission and could fuel malaria transmission in surrounding households. The identification of micro-geographical areas using heat maps combining several epidemiological parameters can help to identify hotspots of malaria transmission. The implementation of malaria control measures, such as seasonal chemoprophylaxis or vector control, in these areas could help to reduce the incidence of malaria and facilitate its elimination.
Occupation-related factors affecting the health of migrants working during the COVID-19 pandemic – a qualitative study in Norway
Authors: Benavente Pierina , Ronda Elena , Diaz Esperanza 
Published: October 2023

Abstract
Background
The effects of the COVID-19 pandemic were more pronounced among migrants than in the majority population and went beyond those directly caused by the virus. Evidence suggests that this overburden is due to complex interactions between individual and structural factors. Some groups of working migrants were in vulnerable positions, overrepresented in essential jobs, under precarious work conditions, and ineligible for social benefits or special COVID-19 economic assistance. This study aimed to explore the experience of migrants working in Norway during the COVID-19 pandemic to gather an in-depth understanding of the pandemic´s impact on their health and well-being, focusing on occupation-related factors.

Methods
In-depth personal interviews with 20 working migrants from different job sectors in Bergen and Oslo were conducted. Recruitment was performed using a purposive sampling method. Thematic analysis was used.

Results
At the workplace level, factors such as pressure to be vaccinated, increased in occupational hazards, and increased structural discrimination negatively impacted migrants’ health. Other factors at the host country context, such as changes in social networks in and out of the workplace and changes in the labour market, also had a negative effect. However, the good Norwegian welfare system positively impacted migrants’ well-being, as they felt financially protected by the system. Increased structural discrimination was the only factor clearly identified as migrant-specific by the participants, but according to them, other factors, such as changes in social networks in and out of the workplace and social benefits in Norway, seemed to have a differential impact on migrants.

Conclusions
Occupational-related factors affected the health and well-being of working migrants during the pandemic. The pressure to get vaccinated and increased structural discrimination in the workplace need to be addressed by Norwegian authorities as it could have legal implications. Further research using intersectional approaches will help identify which factors, besides discrimination, had a differential impact on migrants. This knowledge is crucial to designing policies towards zero discrimination at workplaces and opening dialogue arenas for acknowledging diversity at work.
Accuracy and adequacy of photoprotection in pediatric systemic lupus erythematosus patients, and the effect of education on photoprotection: a prospective study
Authors: Suebsarakam Porntipa , Mairiang Dara 
Published: October 2023

Abstract
Background
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is associated with multiple organ involvement and leads to significant morbidity and mortality. One of the important environmental factors that influences the exacerbation of preexisting SLE is ultraviolet (UV) radiation, so photoprotection is essential. The aims of this study were to evaluate the accuracy and adequacy of photoprotection in pediatric SLE patients, and to investigate the effect of education on photoprotection.

Methods
SLE patients aged ≤ 18 years who attended pediatric outpatient clinics were prospectively enrolled. The accuracy and adequacy of photoprotection were assessed by the questionnaire, and compared between baseline and the ≥ 3-month follow-up timepoint. Comprehensive written and verbal photoprotection education was provided to all patients and parents/caregivers after the first assessment.

Results
One hundred patients were included (mean age 13.6 ± 2.5, 92% female). At the first assessment, 79% of patients used sunscreen with a sunburn protection factor ≥ 30 (77%) and protection grade of ultraviolet A +  +  + (63%). Fifty-two percent of patients applied sunscreen every day. A minority of patients applied an adequate amount of sunscreen (32%), used water-resistant sunscreen (34%), used lip balm with sunscreen (23%) and reapplied sunscreen when sweating (13%). The most commonly missed areas when applying sunscreen were the ears and dorsum of the feet. The least often practiced sun protection behavior was wearing sunglasses. The most often reported activities during the peak UV index, were playing with friends and walking to the cafeterias. At the second assessment, the majority of photoprotection practices were improved in all aspects except using water-resistant sunscreen, reapplying sunscreen when sweating, applying sunscreen on the ears and dorsum of feet, and wearing sunglasses. The main reason for not using sunscreen switched from thinking it was unnecessary at the first assessment to disliking its texture at the second assessment.

Conclusions
Education on photoprotection was effective in improving photoprotection practices. The photoprotection practices that need to be specifically emphasized are applying an adequate amount of sunscreen and using lip balm with sunscreen. The photoprotection which were least practiced at both the first and seconds assessments were reapplying sunscreen when sweating, applying sunscreen on the ears and dorsum of the feet, and wearing sunglasses.
Attachment in close relationships and glycemic outcomes in children with type 1 diabetes
Authors: Klemenčič Simona , Lipovšek Jasna Klara , Turin Anja , Dovč Klemen , Bratina Nataša , Shmueli-Goetz Yael , Trebušak Podkrajšek Katarina , Repič Lampret Barbka , Jenko Bizjan Barbara , Karakatič Sašo , Battelino Tadej , Drobnič Radobuljac Maja 
Published: October 2023

Abstract
Background
Our aim was to determine whether child attachment to parents, parent attachment style, and morning cortisol levels were related to diabetes outcomes measured by average glycated hemoglobin (HbA1c), HbA1c variability over 4 years and time in range (TIR) in children with type 1 diabetes (T1D).

Research design and methods
101 children with T1D and one of their parents were assessed at baseline for child attachment (Child Attachment Interview; CAI) and parent attachment (Relationship Structures Questionnaire; ECR-RS). Serum samples were collected for cortisol measurements before the interviews. HbA1c levels were measured during a 4-year follow-up period at regular 3-monthly visits, and data for TIR were exported from blood glucose measuring devices. Multivariate linear regression models were constructed to identify independent predictors of glycemic outcomes.

Results
More girls than boys exhibited secure attachment to their mothers. The results of the regression models showed that securely attached girls (CAI) had higher average HbA1c than did insecurely attached girls (B = −0.64, p = 0.03). In boys, the more insecure the parent's attachment style, the worse the child's glycemic outcome: the higher the average Hb1Ac (B = 0.51, p = 0.005), the higher the HbA1c variability (B = 0.017, p = 0.011), and the lower the TIR (B = −8.543, p = 0.002).

Conclusions
Attachment in close relationships is associated with glycemic outcomes in children with T1D, and we observed significant differences between sexes. A sex- and attachment-specific approach is recommended when treating children with less favorable glycemic outcomes. Special attention and tailored support should be offered to securely attached girls in transferring responsibility for diabetes care and at least to male children of insecurely attached parents to prevent suboptimal glycemic control. Further studies in larger samples and more daily cortisol measurements may help us better understand the links between stress response, attachment and T1D.
α-Synuclein propagation leads to synaptic abnormalities in the cortex through microglial synapse phagocytosis
Authors: Pérez-Acuña Dayana , Shin Soo Jean , Rhee Ka Hyun , Kim Sang Jeong , Lee Seung-Jae 
Published: October 2023

AbstractThe major neuropathologic feature of Parkinson’s disease is the presence of widespread intracellular inclusions of α-synuclein known as Lewy bodies. Evidence suggests that these misfolded protein inclusions spread through the brain with disease progression. Changes in synaptic function precede neurodegeneration, and this extracellular α-synuclein can affect synaptic transmission. However, whether and how the spreading of α-synuclein aggregates modulates synaptic function before neuronal loss remains unknown. In the present study, we investigated the effect of intrastriatal injection of α-synuclein preformed fibrils (PFFs) on synaptic activity in the somatosensory cortex using a combination of whole-cell patch-clamp electrophysiology, histology, and Golgi-Cox staining. Intrastriatal PFF injection was followed by formation of phosphorylated α-synuclein inclusions in layer 5 of the somatosensory cortex, leading to a decrease in synapse density, dendritic spines, and spontaneous excitatory post-synaptic currents, without apparent neuronal loss. Additionally, three-dimensional reconstruction of microglia using confocal imaging showed an increase in the engulfment of synapses. Collectively, our data indicate that propagation of α-synuclein through neural networks causes abnormalities in synaptic structure and dynamics prior to neuronal loss.
Differential expression of zinc finger CCHC-type superfamily proteins in thyroid carcinoma and their associations with tumor immunity
Authors: Yin Yin , Chen Jing , Chen Qian , He Hongyan , Zhu Nannan , Xia Pengcheng , Yu Chunli , Meng Lingyun 
Published: October 2023

Abstract
Background
The zinc-finger CCHC-type (ZCCHC) superfamily proteins are characterized by the shared sequence CX2-CX4-HX4-C and thought to own high affinity to single-stranded nucleic acids, particularly RNAs. In humans, a total of 24 ZCCHC proteins have been annotated in the HUGO Gene Nomenclature Committee (HGNC, https://www.genenames.org/) database with most of these members involved in multiple steps of RNA metabolism. Many studies have indicated that the ZCCHC genes play a regulatory role in the development and progression of solid tumors. To date, the expression pattern and prognostic value of ZCCHC factors in thyroid carcinomas have not been reported.

Methods
Bioinformatics analyses on the functions of ZCCHC factors in thyroid carcinoma (THCA) patients were performed based on various databases, i.e., TCGA, GEPIA, Kaplan-Meier Plotter, and TIMER.

Results
Compared with normal tissues, the expression of ZCCHC12 mRNA was significantly increased in THCA tissues. And it was associated with the overall survival of THCA patients, based on the Kaplan-Meier Plotter database. Furthermore, the expression levels of all ZCCHCs were correlated with tumor stages, implying its high relevance to THCA, specifically its immunity.

Conclusion
The ZCCHC genes, represented by ZCCHC12, are differentially expressed in THCA staging. These genes are associated with immune infiltration of THCA and identified as the potential therapeutic targets for immunotherapy in THCA patients, which are possible novel biomarkers for the treatment of THCA.
Single-cell metabolic profiling reveals subgroups of primary human hepatocytes with heterogeneous responses to drug challenge
Authors: Sanchez-Quant Eva , Richter Maria Lucia , Colomé-Tatché Maria , Martinez-Jimenez Celia Pilar 
Published: October 2023

Abstract
Background
Xenobiotics are primarily metabolized by hepatocytes in the liver, and primary human hepatocytes are the gold standard model for the assessment of drug efficacy, safety, and toxicity in the early phases of drug development. Recent advances in single-cell genomics demonstrate liver zonation and ploidy as main drivers of cellular heterogeneity. However, little is known about the impact of hepatocyte specialization on liver function upon metabolic challenge, including hepatic metabolism, detoxification, and protein synthesis.

Results
Here, we investigate the metabolic capacity of individual human hepatocytes in vitro. We assess how chronic accumulation of lipids enhances cellular heterogeneity and impairs the metabolisms of drugs. Using a phenotyping five-probe cocktail, we identify four functional subgroups of hepatocytes responding differently to drug challenge and fatty acid accumulation. These four subgroups display differential gene expression profiles upon cocktail treatment and xenobiotic metabolism-related specialization. Notably, intracellular fat accumulation leads to increased transcriptional variability and diminishes the drug-related metabolic capacity of hepatocytes.

Conclusions
Our results demonstrate that, upon a metabolic challenge such as exposure to drugs or intracellular fat accumulation, hepatocyte subgroups display different and heterogeneous transcriptional responses.