bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential roles of the interactions between gut microbiota and metabolites in LPS-induced intrauterine inflammation (IUI) and associated preterm birth (PTB)
Authors: Jia Bei , Tang Lijun , Liu Huibing , Chen Wenqian , Chen Qian , Zhong Mei , Yin Ailan 
Published: January 2024

Abstract
Background
Prenatal exposure to intrauterine inflammation (IUI) is a crucial event in preterm birth (PTB) pathophysiology, increasing the incidence of neurodevelopmental disorders. Gut microbiota and metabolite profile alterations have been reported to be involved in PTB pathophysiology.

Method and results
In this study, IUI-exposed PTB mouse model was established and verified by PTB rate and other perinatal adverse reactions; LPS-indued IUI significantly increased the rates of PTB, apoptosis and inflammation in placenta tissue samples. LPS-induced IUI caused no significant differences in species richness and evenness but significantly altered the species abundance distribution. Non-targeted metabolomics analysis indicated that the metabolite profile of the preterm mice was altered, and differential metabolites were associated with signaling pathways including pyruvate metabolism. Furthermore, a significant positive correlation between Parasutterella excrementihominis and S4572761 (Nb-p-coumaroyltryptamine) and Mreference-1264 (pyruvic acid), respectively, was observed. Lastly, pyruvic acid treatment partially improved LPS-induced IUI phenotypes and decreased PTB rates and decreased the apoptosis and inflammation in placenta tissue samples.

Conclusion
This study revealed an association among gut microbiota dysbiosis, metabolite profile alterations, and LPS-induced IUI and PTB in mice models. Our investigation revealed the possible involvement of gut microbiota in the pathophysiology of LPS-induced IUI and PTB, which might be mediated by metabolites such as pyruvic acid. Future studies should be conducted to verify the findings through larger sample-sized animal studies and clinical investigations.
The SOX4/EZH2/SLC7A11 signaling axis mediates ferroptosis in calcium oxalate crystal deposition-induced kidney injury
Authors: Yan Xinzhou , Xia Yuqi , Li Bojun , Ye Zehua , Li Lei , Yuan Tianhui , Song Baofeng , Yu Weimin , Rao Ting , Ning Jinzhuo , Lin Fangyou , Mei Shuqin , Mao Zhiguo , Zhou Xiangjun , Li Wei , Cheng Fan 
Published: January 2024

AbstractEpigenetic regulation is reported to play a significant role in the pathogenesis of various kidney diseases, including renal cell carcinoma, acute kidney injury, renal fibrosis, diabetic nephropathy, and lupus nephritis. However, the role of epigenetic regulation in calcium oxalate (CaOx) crystal deposition-induced kidney injury remains unclear. Our study demonstrated that the upregulation of enhancer of zeste homolog 2 (EZH2)-mediated ferroptosis facilitates CaOx-induced kidney injury. CaOx crystal deposition promoted ferroptosis in vivo and in vitro. Usage of liproxstatin-1 (Lip-1), a ferroptosis inhibitor, mitigated CaOx-induced kidney damage. Single-nucleus RNA-sequencing, RNA-sequencing, immunohistochemical and western blotting analyses revealed that EZH2 was upregulated in kidney stone patients, kidney stone mice, and oxalate-stimulated HK-2 cells. Experiments involving in vivo EZH2 knockout, in vitro EZH2 knockdown, and in vivo GSK-126 (an EZH2 inhibitor) treatment confirmed the protective effects of EZH2 inhibition on kidney injury and ferroptosis. Mechanistically, the results of RNA-sequencing and chromatin immunoprecipitation assays demonstrated that EZH2 regulates ferroptosis by suppressing solute carrier family 7, member 11 (SLC7A11) expression through trimethylation of histone H3 lysine 27 (H3K27me3) modification. Additionally, SOX4 regulated ferroptosis by directly modulating EZH2 expression. Thus, this study demonstrated that SOX4 facilitates ferroptosis in CaOx-induced kidney injury through EZH2/H3K27me3-mediated suppression of SLC7A11.
Graphical Abstract
Bladder cancer risk stratification with the Oncuria 10-plex bead-based urinalysis assay using three different Luminex xMAP instrumentation platforms
Authors: Furuya Hideki , Sakatani Toru , Tanaka Sunao , Murakami Kaoru , Waldron Richard T. , Hogrefe Wayne , Rosser Charles J. 
Published: January 2024

Abstract
Background
No single marker of bladder cancer (BC) exists in urine samples with sufficient accuracy for disease diagnosis and treatment monitoring. The multiplex Oncuria BC assay noninvasively quantifies the concentration of 10 protein analytes in voided urine samples to quickly generate a unique molecular profile with proven BC diagnostic and treatment-tracking utility. Test adoption by diagnostic and research laboratories mandates reliably reproducible assay performance across a variety of instrumentation platforms used in different laboratories.

Methods
We compared the performance of the clinically validated Oncuria BC multiplex immunoassay when data output was generated on three different analyzer systems. Voided urine samples from 36 subjects (18 with BC and 18 Controls) were reacted with Oncuria test reagents in three 96-well microtiter plates on Day 1, and consecutively evaluated on the LED/image-based MagPix, and laser/flow-based Luminex 200 and FlexMap 3D (all xMAP instruments from Luminex Corp., Austin, TX) on Day 2. The BC assay uses magnetic bead-based fluorescence technology (xMAP, Multi-analyte profiling; Luminex) to simultaneously quantify 10 protein analytes in urine specimens [i.e., angiogenin (ANG), apolipoprotein E (ApoE), carbonic anhydrase IX (CA9), CXCL8/interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-10 (MMP-10), serpin A1/alpha-1 anti-trypsin (A1AT), serpin E1/plasminogen activator inhibitor-1 (PAI-1), CD138/syndecan-1 (SDC1), and vascular endothelial growth factor-A (VEGF-A)]. All three analyzers quantify fluorescence signals generated by the Oncuria assay.

Results
All three platforms categorized all 10 analytes in identical samples at nearly identical concentrations, with variance across systems typically < 5%. While the most contemporary instrument, the FlexMap 3D, output higher raw fluorescence values than the two comparator systems, standard curve slopes and analyte concentrations determined in urine samples were concordant across all three units. Forty-four percent of BC samples registered ≥ 1 analyte above the highest standard concentration, i.e., A1AT (n = 7/18), IL-8 (n = 5), and/or ANG (n = 2), while only one control sample registered an analyte (A1AT) above the highest standard concentration.

Conclusion
Multiplex BC assays generate detailed molecular signatures useful for identifying BC, predicting treatment responsiveness, and tracking disease progression and recurrence. The similar performance of the Oncuria assay across three different analyzer systems supports test adaptation by clinical and research laboratories using existing xMAP platforms.
Trial Registration: This study was registered at ClinicalTrials.gov as NCT04564781, NCT03193528, NCT03193541, and NCT03193515.
Prospective study to characterize adalimumab exposure in pediatric patients with rheumatic diseases
Authors: Welzel Tatjana , Golhen Klervi , Atkinson Andrew , Gotta Verena , Ternant David , Kuemmerle-Deschner Jasmin B. , Michler Christine , Koch Gilbert , van den Anker Johannes N. , Pfister Marc , Woerner Andreas 
Published: January 2024

Abstract
Background
In pediatric rheumatic diseases (PRD), adalimumab is dosed using fixed weight-based bands irrespective of methotrexate co-treatment, disease activity (DA) or other factors that might influence adalimumab pharmacokinetics (PK). In rheumatoid arthritis (RA) adalimumab exposure between 2–8 mg/L is associated with clinical response. PRD data on adalimumab is scarce. Therefore, this study aimed to analyze adalimumab PK and its variability in PRD treated with/without methotrexate.

Methods
A two-center prospective study in PRD patients aged 2–18 years treated with adalimumab and methotrexate (GA-M) or adalimumab alone (GA) for ≥ 12 weeks was performed. Adalimumab concentrations were collected 1–9 (maximum concentration; Cmax), and 10–14 days (minimum concentration; Cmin) during ≥ 12 weeks following adalimumab start. Concentrations were analyzed with enzyme-linked immunosorbent assay (lower limit of quantification: 0.5 mg/L). Log-normalized Cmin were compared between GA-M and GA using a standard t-test.

Results
Twenty-eight patients (14 per group), diagnosed with juvenile idiopathic arthritis (71.4%), non-infectious uveitis (25%) or chronic recurrent multifocal osteomyelitis (3.6%) completed the study. GA-M included more females (71.4%; GA 35.7%, p = 0.13). At first study visit, children in GA-M had a slightly longer exposure to adalimumab (17.8 months [IQR 9.6, 21.6]) compared to GA (15.8 months [IQR 8.5, 30.8], p = 0.8). Adalimumab dosing was similar between both groups (median dose 40 mg every 14 days) and observed DA was low. Children in GA-M had a 27% higher median overall exposure compared to GA, although median Cmin adalimumab values were statistically not different (p = 0.3). Cmin values ≥ 8 mg/L (upper limit RA) were more frequently observed in GA-M versus GA (79% versus 64%). Overall, a wide range of Cmin values was observed in PRD (0.5 to 26 mg/L).

Conclusion
This study revealed a high heterogeneity in adalimumab exposure in PRD. Adalimumab exposure tended to be higher with methotrexate co-treatment compared to adalimumab monotherapy although differences were not statistically significant. Most children showed adalimumab exposure exceeding those reported for RA with clinical response, particularly with methotrexate co-treatment. This highlights the need of further investigations to establish model-based personalized treatment strategies in PRD to avoid under- and overexposure.

Trial registration
NCT04042792, registered 02.08.2019.
Pediatrics severe low back pain by disc herniation: an uncommon entity
Authors: Tiendrebeogo/Zabsonre Wendlassida Joelle Stéphanie , Zabsonre Denlewende Sylvain , Kabore Fulgence , Sanou Abdoulaye , Haro Yakouba , Zoungrana Inoussa , Ouedraogo Dieu-Donné 
Published: January 2024

Abstract
Background
Common severe back pain due to disc herniation is rare in the paediatric population which involves children under eighteen years of age. Paediatric lumbar disc herniation (LDH) cannot be considered the same disease as in adults, as it has potentially different natural and clinical backgrounds. The treatment of pediatric LDH is the other particularity of this condition. Indeed, in children, delaying surgery for a conservative treatment is justified. We report 3 cases treated in 8 years.

Case presentation
Three patients, two of whom were 14 years of age and one 17 years of age, were admitted for L5 or S1 lumbosciatica. A CT scan showed a lumbar disc herniation L5S1 associated with bi-isthmic lysis (and a transitional abnormality in 1 case or spina bifida occulta in 1 other case). The last patient had an magnetic resonance imaging (MRI) that showed a herniated L4L5 disc. The diagnosis of low back pain disc herniation was retained in two patients and that of disabling low back disc in one patient. Percutaneous discolysis in the two hyperalgesic cases and epidural corticosteroid infiltration in the disabling case were effective on lumbosciatica.

Conclusion
Paediatric common lomw back pain caused by a disc herniation with a hyperalgic or disabling character posed a therapeutic problem which were solved by the invasive approaches that must be given priority nowadays with children.
Helicobacter pylori infection and Parkinson’s Disease: etiology, pathogenesis and levodopa bioavailability
Authors: Wei Bang-rong , Zhao Yu-jia , Cheng Yu-feng , Huang Chun , Zhang Feng 
Published: January 2024

AbstractParkinson’s disease (PD), a neurodegenerative disorder with an unknown etiology, is primarily characterized by the degeneration of dopamine (DA) neurons. The prevalence of PD has experienced a significant surge in recent years. The unidentified etiology poses limitations to the development of effective therapeutic interventions for this condition. Helicobacter pylori (H. pylori) infection has affected approximately half of the global population. Mounting evidences suggest that H. pylori infection plays an important role in PD through various mechanisms. The autotoxin produced by H. pylori induces pro-inflammatory cytokines release, thereby facilitating the occurrence of central inflammation that leads to neuronal damage. Simultaneously, H. pylori disrupts the equilibrium of gastrointestinal microbiota with an overgrowth of bacteria in the small intestinal known as small intestinal bacterial overgrowth (SIBO). This dysbiosis of the gut flora influences the central nervous system (CNS) through microbiome-gut-brain axis. Moreover, SIBO hampers levodopa absorption and affects its therapeutic efficacy in the treatment of PD. Also, H. pylori promotes the production of defensins to regulate the permeability of the blood-brain barrier, facilitating the entry of harmful factors into the CNS. In addition, H. pylori has been found to induce gastroparesis, resulting in a prolonged transit time for levodopa to reach the small intestine. H. pylori may exploit levodopa to facilitate its own growth and proliferation, or it can inflict damage to the gastrointestinal mucosa, leading to gastrointestinal ulcers and impeding levodopa absorption. Here, this review focused on the role of H. pylori infection in PD from etiology, pathogenesis to levodopa bioavailability.
Dysregulation of mitochondrial dynamics mediated aortic perivascular adipose tissue-associated vascular reactivity impairment under excessive fructose intake
Authors: Wu Kay L. H. , Wu Chih-Wei , Chen Lee-Wei , Chang Hsiao-Huang , Cheng Ching-Li , Wu Cai-Yi , Lee Yu-Chi , Chen I-Chun , Hung Chun-Ying , Liu Wen-Chung 
Published: January 2024

AbstractExcessive fructose intake presents the major risk factor for metabolic cardiovascular disease. Perivascular adipose tissue (PVAT) is a metabolic tissue and possesses a paracrine function in regulating aortic reactivity. However, whether and how PVAT alters vascular function under fructose overconsumption remains largely unknown. In this study, male Sprague-Dawley rats (8 weeks old) were fed a 60% high fructose diet (HFD) for 12 weeks. Fasting blood sugar, insulin, and triglycerides were significantly increased by HFD intake. Plasma adiponectin was significantly enhanced in the HFD group. The expression of uncoupling protein 1 (UCP1) and mitochondrial mass were reduced in the aortic PVAT of the HFD group. Concurrently, the expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and mitochondrial transcription factor A (TFAM) were suppressed. Furthermore, decreased fusion proteins (OPA1, MFN1, and MFN2) were accompanied by increased fission proteins (FIS1 and phospho-DRP1). Notably, the upregulated α-smooth muscle actin (α-SMA) and osteocalcin in the PVAT were concurrent with the impaired reactivity of aortic contraction and relaxation. Coenzyme Q10 (Q, 10 mg/100 mL, 4 weeks) effectively reversed the aforementioned events induced by HFD. Together, these results suggested that the dysregulation of mitochondrial dynamics mediated HFD-triggered PVAT whitening to impair aortic reactivity. Fortunately, coenzyme Q10 treatment reversed HFD-induced PVAT whitening and aortic reactivity.
Preliminary exploration of herbal tea products based on traditional knowledge and hypotheses concerning herbal tea selection: a case study in Southwest Guizhou, China
Authors: Long Xiaofeng , Ranjitkar Sailesh , Waldstein Anna , Wu Huan , Li Qingqing , Geng Yanfei 
Published: January 2024

Abstract
Background
Herbal tea usually refers to “beverage plants that do not belong to the genus Camellia”, and it holds a significant historical legacy as a traditional beverage among specific regions and ethnic groups. In light of this, our research aims to investigate and analyze the traditional knowledge pertaining to herbal tea plants used by local people in the Qianxinan Buyi and Miao Autonomous Prefecture, Guizhou Province. We also initiated preliminary efforts to create tea products from herbal tea leaves using various processing techniques. Additionally, we attempted to test hypotheses to elucidate how local people select herbal tea plants.

Methods
Data related to the use of herbal tea plants in this study were collected through semi-structured interviews and participatory observations in four villages in Qianxinan. Quantitative indicators, including the relative frequency of citation (RFC) and the relative importance (RI) value, were calculated, and the availability of plants was also evaluated. General linear model was performed to examine the relationship between the frequency of citation and resource availability, as well as the correlation between the relative frequency of citation and the relative importance, to test both the resource availability hypothesis and the versatility hypothesis. Centella asiatica tea was processed using techniques from green tea, black tea and white tea, with a preliminary sensory evaluation conducted.

Results
A total of 114 plant species were documented as being used for herbal teas by local residents, representing 60 families and 104 genera. Of these, 61% of herbal tea plants were found growing in the wild, and 11 species were exotic plants. The family with the highest number of species was Asteraceae (20 species). The study identified 33 major medicinal functions of herbal tea, with clearing heat-toxin and diuresis being the most common functions. General linear model revealed a strong correlation (correlation coefficient of 0.72, p < 0.001) between the frequency of citation and plant availability, as well as a significant correlation (correlation coefficient of 0.63, p < 0.001) between RFC and RI. Under different processing conditions, the characteristics of Centella asiatica tea exhibited variations and were found to be suitable for consumption.

Conclusion
The consumption of herbal tea serves as a preventive measure against common ailments for local residents. The resource availability hypothesis, diversification hypothesis and the versatility hypothesis were shown to provide some insight into “how and why local communities select plants for use.” Exotic herbal tea plants in the study area also possess valuable therapeutic properties. The processing and production of Centella asiatica herbal tea products hold promising prospects.
Stereotactic body radiotherapy for early-stage lung cancer: a systematic review on the choice of photon energy and linac flattened/unflattened beams
Authors: Gill Ashlesha , Hirst Andrew L , Rowshanfarzad Pejman , Gill Suki , Bucknell Nicholas , Dass Joshua , Sabet Mahsheed 
Published: January 2024

AbstractSBRT is an effective local treatment for patients with early-stage non-small cell lung cancer (NSCLC). This treatment is currently used in patients who have poor lung function or who decline surgery. As SBRT usually has small PTV margins, reducing the beam-on-time (BOT) is beneficial for accurate dose delivery by minimising intrafraction motion as well as improved patient comfort. Removal of the linear accelerator flattening filter can provide a higher dose rate which results in a faster treatment. In addition, the choice of photon energy can also affect the dose distribution to the target and the organs-at-risk (OAR). In this systematic review, studies analysing the choice of various photon beam energies, with a flattening filter or flattening filter free (FFF), were compared for their overall dosimetric benefit in the SBRT treatment for early-stage NSCLC. It was found that FFF treatment delivers a comparatively more conformal dose distribution, as well as a better homogeneity index and conformity index, and typically reduces BOT by between 30 and 50%. The trade-off may be a minor increase in monitor units for FFF treatment found in some studies but not others. Target conformity and OAR sparing, particularly lung doses appear better with 6MV FFF, but 10MV FFF was marginally more advantageous for skin sparing and BOT reduction. The favourable beam modality for clinical use would depend on the individual case, for which tumour size and depth, radiotherapy technique, as well as fractionation scheme need to be taken into account.
Social skills interventions for Thai adolescents with Autism Spectrum Disorder (ASD): a qualitative study of the perceptions and experiences of Thai adolescents, their caregivers and healthcare professionals
Authors: Tawankanjanachot Nadlada , Truesdale Maria , Orachon Pornpun , Kidd Lisa 
Published: January 2024

Abstract
Background
Social skills interventions (SSIs) are effective for enhancing social skills and decreasing mental health problems in adolescents with autism spectrum disorder (ASD). However, these interventions have been designed and their effectiveness has been established in Western countries. Lack of culturally acceptable SSIs for Asian nations is a possible barrier to implementing effective and tailored interventions that address the unique requirements of ASD individuals across countries and cultures. This study aims to explore the needs and preferences of adolescents with ASD, their caregivers, and healthcare professionals (HPs) in Thailand regarding the components, delivery formats, and cultural adaptation required for an outpatient-based social skills intervention.

Methods
Qualitative data was collected via three focus groups of HPs (n = 20) and 24 paired interviews with adolescents with ASD and their caregivers from a child psychiatric hospital in Thailand. Purposive sampling was employed, and thematic analysis was used to analyse the data.

Results
Nine themes emerged from the data generated by HPs, and seven from adolescents with ASD and their caregivers. SSIs for Thai adolescents with ASD and their caregivers should emphasise specific social skills training and assess the abilities of adolescents as required. Incorporating various learning strategies is important. Parental involvement is essential and provides knowledge of an adolescent’s symptoms and coaching skills, which are best used to support their adolescents. Cultural considerations include the need for social knowledge of Thai culture, promoting assertiveness and praising parents’ abilities, implementing a programme in time to not interrupt academic achievement, and renaming a programme from social skills intervention to social communication intervention. Barriers to implementing a programme included HPs’ need for specialised training and education and decreased workload. Also, the caregivers’ and adolescents’ stigma reduced attendance in a programme. Increased extra compensation and relocation days off are provided as policy support for staff who deliver the intervention.

Conclusion
The results suggest that SSIs for Thai adolescents with ASD should be tailored to meet the needs for specific knowledge, skills, and parental collaboration as coaches for their adolescents. Additionally, it should incorporate Thai culture. It is necessary to consider staff knowledge, workload, and stigma in order to reduce barriers to implementation in practice.