bluuebunny/crossref_metadata_2025_split huggingface dataset:
PBTK model-based analysis of CYP3A4 induction and the toxicokinetics of the pyrrolizidine alkaloid retrorsine in man
Authors: Lehmann Anja , Geburek Ina , Hessel-Pras Stefanie , Enge Anne-Margarethe , Mielke Hans , Müller-Graf Christine , Kloft Charlotte , Hethey Christoph 
Published: March 2024

AbstractCytochrome P450 (CYP)3A4 induction by drugs and pesticides plays a critical role in the enhancement of pyrrolizidine alkaloid (PA) toxicity as it leads to increased formation of hepatotoxic dehydro-PA metabolites. Addressing the need for a quantitative analysis of this interaction, we developed a physiologically-based toxicokinetic (PBTK) model. Specifically, the model describes the impact of the well-characterized CYP3A4 inducer rifampicin on the kinetics of retrorsine, which is a prototypic PA and contaminant in herbal teas. Based on consumption data, the kinetics after daily intake of retrorsine were simulated with concomitant rifampicin treatment. Strongest impact on retrorsine kinetics (plasma AUC$$_{24}$$

24

and $$C_{{\text {max}}}$$

C
max

reduced to 67% and 74% compared to the rifampicin-free reference) was predicted directly after withdrawal of rifampicin. At this time point, the competitive inhibitory effect of rifampicin stopped, while CYP3A4 induction was still near its maximum. Due to the impacted metabolism kinetics, the cumulative formation of intestinal retrorsine CYP3A4 metabolites increased to 254% (from 10 to 25 nmol), while the cumulative formation of hepatic CYP3A4 metabolites was not affected (57 nmol). Return to baseline PA toxicokinetics was predicted 14 days after stop of a 14-day rifampicin treatment. In conclusion, the PBTK model showed to be a promising tool to assess the dynamic interplay of enzyme induction and toxification pathways.
Biocatalytic transesterification of salmon oil in ionic liquid media to obtain concentrates of omega-3 polyunsaturated fatty acids
Authors: Fuster Marta G. , Moulefera Imane , Montalbán Mercedes G. , Víllora Gloria 
Published: March 2024

AbstractIn this study, a biphasic system combining oil and ionic liquid was utilized for lipase-catalyzed transesterification of salmon oil and alcohol to concentrate n-3 PUFAs, notably EPA and DHA. Various process variables, such as enzyme type, quantity, alcohol chain length, temperature, reactant proportions, and ionic liquid selection, were systematically assessed to optimize the process and enhance the yield of these valuable fatty acids. It was found that the Novozym 435 and Lipolase 100L Type EX emerged as the most effective enzymes. The impact of varying alcohol chain lengths (C1–C8) was examined, revealing that the Novozym 435 enzyme displayed its peak synthetic activity with 2-propanol. The results revealed a substantial increase in the overall activity during the transesterification reaction when employing ILs featuring hydrophobic cations and anions with low nucleophilicity. Specifically, the [omim+][NTf2−] ionic liquid exhibited the highest level of activity. This research holds promise for more efficiently and sustainably obtaining concentrated n-3 PUFAs from fish oil while reducing environmental impact relative to other existing concentration processes.
[3H]-NFPS binding to the glycine transporter 1 in the hemi-parkinsonian rat brain
Authors: Frouni Imane , Kim Esther , Shaqfah Judy , Bédard Dominique , Kwan Cynthia , Belliveau Sébastien , Huot Philippe 
Published: March 2024

AbstractL-3,4-dihydroxyphenylalanine (L-DOPA) is the main treatment for Parkinson’s disease (PD) but with long term administration, motor complications such as dyskinesia are induced. Glycine transporter 1 (GlyT1) inhibition was shown to produce an anti-dyskinetic effect in parkinsonian rats and primates, coupled with an improvement in the anti-parkinsonian action of L-DOPA. The expression of GlyT1 in the brain in the dyskinetic state remains to be investigated. Here, we quantified the levels of GlyT1 across different brain regions using [3H]-NFPS in the presence of Org-25,935. Brain sections were chosen from sham-lesioned rats, L-DOPA-naïve 6-hydroxydopamine (6-OHDA)-lesioned rats and 6-OHDA-lesioned rats exhibiting mild or severe abnormal involuntary movements (AIMs). [3H]-NFPS binding decreased in the ipsilateral and contralateral thalamus, by 28% and 41%, in 6-OHDA-lesioned rats with severe AIMs compared to sham-lesioned animals (P < 0.01 and 0.001). [3H]-NFPS binding increased by 21% in the ipsilateral substantia nigra of 6-OHDA-lesioned rats with severe AIMs compared to 6-OHDA-lesioned rats with mild AIMs (P < 0.05). [3H]-NFPS binding was lower by 19% in the contralateral primary motor cortex and by 20% in the contralateral subthalamic nucleus of 6-OHDA-lesioned rats with mild AIMs animals compared to rats with severe AIMs (both P < 0.05). The severity of AIMs scores positively correlated with [3H]-NFPS binding in the ipsilateral substantia nigra (P < 0.05), ipsilateral entopeduncular nucleus (P < 0.05) and contralateral primary motor cortex (P < 0.05). These data provide an anatomical basis to explain the efficacy of GlyT1 inhibitors in dyskinesia in PD.
Exploring the Unknown: Evaluating ChatGPT's Performance in Uncovering Novel Aspects of Plastic Surgery and Identifying Areas for Future Innovation
Authors: Lim Bryan , Seth Ishith , Xie Yi , Kenney Peter Sinkjaer , Cuomo Roberto , Rozen Warren M. 
Published: March 2024

Abstract
Background
Artificial intelligence (AI) has emerged as a powerful tool in various medical fields, including plastic surgery. This study aims to evaluate the performance of ChatGPT, an AI language model, in elucidating historical aspects of plastic surgery and identifying potential avenues for innovation.

Methods
A comprehensive analysis of ChatGPT's responses to a diverse range of plastic surgery-related inquiries was performed. The quality of the AI-generated responses was assessed based on their relevance, accuracy, and novelty. Additionally, the study examined the AI's ability to recognize gaps in existing knowledge and propose innovative solutions. ChatGPT’s responses were analysed by specialist plastic surgeons with extensive research experience, and quantitatively analysed with a Likert scale.

Results
ChatGPT demonstrated a high degree of proficiency in addressing a wide array of plastic surgery-related topics. The AI-generated responses were found to be relevant and accurate in most cases. However, it demonstrated convergent thinking and failed to generate genuinely novel ideas to revolutionize plastic surgery. Instead, it suggested currently popular trends that demonstrate great potential for further advancements. Some of the references presented were also erroneous as they cannot be validated against the existing literature.

Conclusion
Although ChatGPT requires major improvements, this study highlights its potential as an effective tool for uncovering novel aspects of plastic surgery and identifying areas for future innovation. By leveraging the capabilities of AI language models, plastic surgeons may drive advancements in the field. Further studies are needed to cautiously explore the integration of AI-driven insights into clinical practice and to evaluate their impact on patient outcomes.

Level of Evidence V
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266
Extreme dry advection dominates the record-breaking Yangtze River heatwave in midsummer of 2022
Authors: Hu Shuai , Zhou Tianjun , Peng Dongdong , Jiang Wanyi , Lu Bo , Wu Bo , Chen Xiaolong , Zhang Lixia , Zhang Wenxia 
Published: March 2024

AbstractThe Yangtze River Valley (YRV) experienced an unprecedented heatwave in midsummer of 2022. Still, the detailed physical processes involved in the influence of abnormal large-scale atmospheric circulation on the heatwave remain unexplored. Here, we show that the positive meridional gradient of anomalous atmospheric moisture at the middle-lower troposphere and associated extreme dry air advection over the YRV are vital prerequisites for forming the 2022 YRV heatwave. The 2022 YRV heatwave is dominated by interannual variability, contributing 72.7% to the total temperature anomalies. Diagnosis of the surface heat budget equation indicates that the surface cloud radiative forcing is the most critical process in driving the 2022 YRV heatwave, which is dominated by the positive surface short-wave cloud radiative forcing associated with the suppressed precipitation and the middle-low clouds. The suppressed precipitation is induced by the vertical dynamical processes of anomalous moisture advection caused by the abnormal descending flows over the YRV, which are driven by the negative advection of anomalous latent heat energy by climatological meridional wind (anomalous dry air advection) according to the atmospheric moist static energy equation. Simulations from the Lagrangian model FLEXPART further indicate that the moisture anomaly over the north of YRV mainly originated from the surface evaporation in the YRV, implying that there is a positive land-air feedback during the life cycle of the YRV heatwave. Our study enriches the mechanism understanding of the 2022 YRV heatwave from the perspective of surface energy budget and land-air feedback.
Enhanced spring warming of the Tibetan Plateau amplifies summer heat stress in Eastern Europe
Authors: Yang Xiaoye , Shen Cheng , Zhang Guwei , Chen Deliang 
Published: March 2024

AbstractThe Tibetan Plateau (TP), often referred to as the “Roof of the World”, has experienced rapid warming in recent decades. This warming has had significant impacts on downstream regions, while its effects on upstream regions are less well-defined. This study explores the relationship between TP warming and the occurrence of summer heat stress days in Europe, with a particular focus on Eastern Europe (EEU). Our analysis reveals a robust correlation between TP warming in both the summer and the preceding spring, and the frequency of heat stress days in EEU, demonstrating a significant interannual connection. During the spring, pronounced warming in the southern TP generates a strong local Rossby wave source, triggering a substantial divergence anomaly that amplifies the warming effect. This mechanism weakens the subtropical jet and strengthens the polar jet during the summer, setting the stage for anticyclonic anomalies over EEU. Furthermore, anomalies induced by TP warming, characterized by local upward movement and divergence at upper levels, intensify convergence and sinking airflow in the upstream region, leading to increased adiabatic heating in EEU. The dynamic response of the summer circulation anomaly, exemplified by the anticyclone anomaly over EEU, to prior TP warming is further corroborated through numerical simulations.
A systematic review of Sandifer syndrome in children with severe gastroesophageal reflux
Authors: Kato Daiki , Uchida Hiroo , Amano Hizuru , Yokota Kazuki , Shirota Chiyoe , Tainaka Takahisa , Sumida Wataru , Makita Satoshi , Yasui Akihiro , Gohda Yousuke , Maeda Takuya , Hinoki Akinari 
Published: March 2024

Abstract
Purpose
Sandifer syndrome (SS), which combines gastroesophageal reflux (GER) and a neurological or psychiatric disorder, is an uncommon condition that often takes a long time to diagnosis. We aimed to systematically review available papers regarding SS.

Methods
After presenting our two cases of SS, we systematically reviewed articles published in MEDILINE/PubMed, Cochrane Library, and Web of Science.

Results
The meta-analysis included 54 reported cases and 2 of our own cases. Our results showed that all cases achieved symptom improvement with appropriate treatment for GER. Notably, 19 of the 56 cases exhibited anatomical anomalies, such as hiatal hernia and malrotation. Significantly more patients with than without anatomical anomalies required surgery (p < 0.001). However, 23 of the 29 patients without anatomical anomalies (79%) achieved symptom improvement without surgery. Patients who did not undergo surgery had a median (interquartile range) duration to symptom resolution of 1 (1–1) month.

Conclusion
The primary care providers should keep SS in the differential diagnosis of patients presenting with abnormal posturing and no apparent neuromuscular disorders. Fundoplication may be effective especially for patients with anatomical anomalies or those whose symptoms do not improve after more than 1 month with nonsurgical treatment.
Insulin and glycolysis dependency of cardioprotection by nicotinamide riboside
Authors: Xiao Y. , Wang Q. , Zhang H. , Nederlof R. , Bakker D. , Siadari B. A. , Wesselink M. W. , Preckel B. , Weber N. C. , Hollmann M. W. , Schomakers B. V. , van Weeghel M. , Zuurbier C. J. 
Published: March 2024

AbstractDecreased nicotinamide adenine dinucleotide (NAD+) levels contribute to various pathologies such as ageing, diabetes, heart failure and ischemia–reperfusion injury (IRI). Nicotinamide riboside (NR) has emerged as a promising therapeutic NAD+ precursor due to efficient NAD+ elevation and was recently shown to be the only agent able to reduce cardiac IRI in models employing clinically relevant anesthesia. However, through which metabolic pathway(s) NR mediates IRI protection remains unknown. Furthermore, the influence of insulin, a known modulator of cardioprotective efficacy, on the protective effects of NR has not been investigated. Here, we used the isolated mouse heart allowing cardiac metabolic control to investigate: (1) whether NR can protect the isolated heart against IRI, (2) the metabolic pathways underlying NR-mediated protection, and (3) whether insulin abrogates NR protection. NR protection against cardiac IRI and effects on metabolic pathways employing metabolomics for determination of changes in metabolic intermediates, and 13C-glucose fluxomics for determination of metabolic pathway activities (glycolysis, pentose phosphate pathway (PPP) and mitochondrial/tricarboxylic acid cycle (TCA cycle) activities), were examined in isolated C57BL/6N mouse hearts perfused with either (a) glucose + fatty acids (FA) (“mild glycolysis group”), (b) lactate + pyruvate + FA (“no glycolysis group”), or (c) glucose + FA + insulin (“high glycolysis group”). NR increased cardiac NAD+ in all three metabolic groups. In glucose + FA perfused hearts, NR reduced IR injury, increased glycolytic intermediate phosphoenolpyruvate (PEP), TCA intermediate succinate and PPP intermediates ribose-5P (R5P) / sedoheptulose-7P (S7P), and was associated with activated glycolysis, without changes in TCA cycle or PPP activities. In the “no glycolysis” hearts, NR protection was lost, whereas NR still increased S7P. In the insulin hearts, glycolysis was largely accelerated, and NR protection abrogated. NR still increased PPP intermediates, with now high 13C-labeling of S7P, but NR was unable to increase metabolic pathway activities, including glycolysis. Protection by NR against IRI is only present in hearts with low glycolysis, and is associated with activation of glycolysis. When activation of glycolysis was prevented, through either examining “no glycolysis” hearts or “high glycolysis” hearts, NR protection was abolished. The data suggest that NR’s acute cardioprotective effects are mediated through glycolysis activation and are lost in the presence of insulin because of already elevated glycolysis.
Association between physical fitness and perceived work ability among Finnish population: a cross-sectional study
Authors: Pohjola Valtteri , Sarttila Katariina , Kuusela Markus , Nikander Riku , Lundqvist Annamari , Lahti Jouni 
Published: March 2024

Abstract
Objective
This cross-sectional study aims to examine association between different components of physical fitness and perceived work ability among working age population.

Methods
The population-based study sample included 2050 participants aged 18–74 from the Finnish national Health 2011 study. Physical fitness was assessed by the single leg stand test, the modified push-up test, the vertical jump test and the six-minute walk test, and perceived work ability was assessed via interview. Logistic regression was used for examining the associations between physical fitness and work ability.

Results
After adjusting for potential confounders (age, sex, marital status, educational level, work characteristics, total physical activity, daily smoking, BMI and number of diseases), odds ratios indicated that good work ability was more likely among those who had better balance in single leg stand test (OR = 1.54; 95% CI 1.07–2.24), and who belonged in the high fitness thirds in six-minute walking test (OR = 2.08; 95% CI 1.24–3.49) and in vertical jump test (OR = 2.51; 95% CI 1.23–5.12) compared to lowest third. Moreover, moderate (OR = 1.76; 95% CI 1.02–3.05) to high fitness (OR = 2.87; 95% CI 1.40–5.92) in modified push-up test increased the likelihood of good work ability compared to lowest third.

Conclusion
These study results indicate that good musculoskeletal as well as cardiorespiratory fitness are associated with better perceived work ability. Promoting physical fitness in individual and societal level may be potential targets for maintaining good work ability in working age population.
COVID-19-associated secondary sclerosing cholangitis with liver transplantation
Authors: Fischer Anne Kristin , Stippel Dirk , Canbay Ali , Nierhoff Dirk , Thomas Michael , Best Jan , Büttner Reinhard , Drebber Uta 
Published: March 2024

AbstractWe report on two cases of orthotopic liver transplantation (OLTX) due to SARS-Cov2-associated secondary sclerosing cholangitis (SSC) following long-term artificial respiration and extra-corporal membrane oxygenation in intensive care. Under these conditions, SSC is a rapidly progredient biliary disease featuring degenerative cholangiopathy, loss of bile ducts, ductular and parenchymal cholestasis, biliary fibrosis, and finally cirrhosis. Reduced perfusion and oxygenation of the peribiliary plexus, severe concurrent infections, and secondary medico-toxic effects appear to play a crucial role in the pathogenesis of the disease. A direct cytopathic effect of SARS-Cov2 on endothelial cells followed by thrombosis and fibrosing obliteration in all parts of the vascular bed of the liver may enhance the virus-associated liver disease and particularly SSC.
Osteopontin promotes tumor growth and metastasis and GPX4-mediated anti-lipid peroxidation in triple-negative breast cancer by activating the PI3k/Akt/mTOR pathway
Authors: Guo Man , Liu Mengyue , Li Weihan , Wang Cao , Zhang Lu , Zhang Hao 
Published: March 2024

Abstract
Purpose
Triple-negative breast cancer (TNBC) features high aggressiveness, metastasis rate, drug resistance as well as poor prognosis. Osteopontin (OPN) is a key protein in the process of osteogenesis and has emerged as a new tumor marker in recent years.

Methods
Cell viability was tested with the CCK-8 kit. Transwell and wound healing were adopted to test cell invasive and migratory abilities. Tumor sphere formation was detected by tumor sphere formation assay. Human umbilical vein endothelial cell (HUVEC) tube formation assay was used to measure the angiogenesis of tumor cells. Western blot was applied for the estimation of the expression of cancer stem cell markers, angiogenesis-, signaling pathway-related proteins as well as OPN. Bioinformatics tools predicted OPN expression in breast cancer tissues. The levels of oxidative stress-related markers were assessed with ELISA. Following the overexpression of OPN in MD-MB-436 cells and the addition of the PI3K/AKT/mTOR pathway inhibitor LY294002, the aforementioned functional experiments were implemented again to investigate the mechanism. Finally, in vivo experiments of tumor-bearing mice were performed for further verification.

Results
The proliferative, invasive, migratory and tumor sphere formation capabilities as well as angiogenesis of TNBC cells were conspicuously increased in contrast to non-TNBC cell lines. OPN expression in TNBC tissues and cells was dramatically enhanced. OPN upregulation significantly elevated cell proliferative, invasive and migratory capabilities as well as tumor sphere formation and angiogenesis. The mechanism might be achieved by activating PI3K/AKT/mTOR signaling to regulate glutathione peroxidase 4 (GPX4)-mediated anti-lipid peroxidation.

Conclusion
OPN promoted tumor sphere formation and angiogenesis in TNBC by activating the PI3K/AKT/mTOR pathway to regulate GPX4-mediated anti-lipid peroxidation levels.
Phlebotomine sand fly (Diptera: Phlebotominae) diversity in the foci of cutaneous leishmaniasis in the Surxondaryo Region of Uzbekistan: 50 years on
Authors: Usarov Gofur X. , Turitsin Vladimir S. , Sattarova Xulkar G. , Sádlová Jovana , Mustanov Javokhir Abdusamat ugli , Saura Andreu , Yurchenko Vyacheslav 
Published: March 2024

AbstractIn Uzbekistan, the number of reported leishmaniasis cases is rising at the alarming rate. In this work, we studied the phlebotomine sand fly (Diptera: Phlebotominae) diversity in the foci of cutaneous leishmaniasis in the Surxondaryo Region of Uzbekistan and compared it with the data obtained for the same area 50 years ago, when infection prevalence was reportedly low. We found that the implicated vector for zoonotic leishmaniasis, P. papatasi, remained eudominant; the proportion of implicated anthroponotic leishmaniasis vector, P. sergenti, rose significantly from averaged 5.4 to 41.4%; Phlebotomus alexandri, a suspected visceral leishmaniasis vector, was eudominant at two sites, and a second suspected vector for this disease, P. longiductus, was newly recorded in the region. We conclude that the increase in the documented cases of cutaneous leishmaniasis in the Surxondaryo Region of Uzbekistan may be connected to the changes in fauna of sand flies vectoring Leishmania spp.
The crucial prognostic signaling pathways of pancreatic ductal adenocarcinoma were identified by single-cell and bulk RNA sequencing data
Authors: Wang Wenwen , Chen Guo , Zhang Wenli , Zhang Xihua , Huang Manli , Li Chen , Wang Ling , Lu Zifan , Xia Jielai 
Published: March 2024

AbstractPancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with poor prognosis and high mortality. Although a large number of studies have explored its potential prognostic markers using traditional RNA sequencing (RNA-Seq) data, they have not achieved good prediction effect. In order to explore the possible prognostic signaling pathways leading to the difference in prognosis, we identified differentially expressed genes from one scRNA-seq cohort and four GEO cohorts, respectively. Then Cox and Lasso regression analysis showed that 12 genes were independent prognostic factors for PDAC. AUC and calibration curve analysis showed that the prognostic model had good discrimination and calibration. Compared with the low-risk group, the high-risk group had a higher proportion of gene mutations than the low-risk group. Immune infiltration analysis revealed differences in macrophages and monocytes between the two groups. Prognosis related genes were mainly distributed in fibroblasts, macrophages and type 2 ducts. The results of cell communication analysis showed that there was a strong communication between cancer-associated fibroblasts (CAF) and type 2 ductal cells, and collagen formation was the main interaction pathway.