bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disc degeneration influences the strain magnitude and stress distribution within the adjacent trabecular bone
Authors: Raftery Kay A. , Kargarzadeh Alireza , Tavana Saman , Newell Nicolas 
Published: December 2024

IntroductionUp to one in five will suffer from osteoporotic vertebral fracture within their lifetime. Accurate fracture prediction poses challenges using bone mineral density (BMD) measures. Trabecular bone strains may be influenced by the underlying intervertebral disc (IVD). Understanding how disc degeneration alters load distribution to the vertebra may demonstrate that supplementing fracture risk tools with IVD metrics could improve predictions. The aim of this study was to assess the influence of IVD degeneration on the stress and strain magnitude and distribution in the trabecular bone of adjacent vertebrae.MethodsTen human cadaveric lumbar bi-segment specimens (20 IVDs, 9 degenerated, 11 non-degenerated) were µCT-imaged under 1000N. Digital volume correlation was used to quantify axial, principal, maximum shear, and von Mises strain in the superior and inferior regions of the vertebra. Volumetric BMD from quantitative-CT was used to calculate Young’s modulus, which was then registered with the von Mises strain field to calculate internal von Mises stress.ResultsTwo bi-segments fractured during mechanical testing, resulting in N = 8 endplate regions per group. Trabecular bone adjacent to degenerated IVDs presented higher maximum principal and shear strains in the anterior region, relative to non-degenerated (peak ε1: 6,020 ± 1,633 µε versus 3,737 ± 1,548 µε, p &lt; 0.01; peak γmax: 6,202 ± 1948 µε versus 3,938 ± 2086 µε, p &lt; 0.01). Von Mises stress distribution was significantly skewed towards the anterior region in the degenerated group only (28.3% ± 10.4%, p &lt; 0.05). Reduced disc height correlated with increased central-region axial compressive strain, decreased central-region BMD, and increased anterior region von Mises stress (all p &lt; 0.05).DiscussionDisc degeneration may encourage high strains to be experienced within the anterior region of the adjacent bone, owing to changes in load distribution. This study demonstrates the potential of utilising IVD metrics in fracture risk assessment, to inform clinical decision making and preventative treatment.
Congenital hyperinsulinism in the Ukraine: a 10-year national study
Authors: Globa Evgenia , Christesen Henrik Thybo , Mortensen Michael Bau , Houghton Jayne A. L. , Nielsen Anne Lerberg , Detlefsen Sönke , Flanagan Sarah E. 
Published: December 2024

IntroductionCongenital Hyperinsulinism (CHI) has not been previously studied in Ukraine. We therefore aimed to elucidate the genetics, clinical phenotype, histological subtype, treatment and long-term outcomes of Ukrainian patients with CHI.MethodsForty-one patients with CHI were recruited to the Ukrainian national registry between the years 2014-2023. Genetic testing (n=40), 18F-fluorodihydroxyphenylalanin and 68Ga-DOTANOC PET/CT imaging followed by surgical treatment and subsequent histological analysis (n=19) was performed through international collaboration.ResultsPathogenic variants were identified in 19/22 (86.3%) individuals with persistent CHI (p-CHI) and 8/18 (44.4%) with early remission CHI (er-CHI). Pathogenic variants in the K-ATP channel genes were the only identified genetic cause of p-CHI (ABCC8 (n=17) and KCNJ11 (n=2)) with greater genetic heterogeneity observed in those with er-CHI (ABCC8 (n=3), KMT2D (Kabuki Syndrome, n=1), Beckwith-Wiedemann syndrome (n=2) and INSR (Donohue syndrome (n=2)). Histological analysis performed on 19 children with persistent CHI confirmed focal disease in 14 (73.7%), diffuse disease in two (10.5%) and atypical histology in three (15.8%). After surgery, complete recovery was observed in all 14 with focal disease, while relapse occurred in three patients with diffuse or atypical histology.ConclusionA genetic diagnosis was achieved for 67.5% (27/40) of the cohort with a higher pick-up rate observed in those with p-CHI. The genetics and imaging studies enabled subtype-targeted treatment with surgical cure achieved in all individuals with focal disease.
Hepatocyte nuclear factor 4-α is necessary for high fat diet-induced pancreatic β-cell mass expansion and metabolic compensations
Authors: de Ramos Francieli Caroline , Barth Robson , Santos Marcos Rizzon , Almeida Milena dos Santos , Ferreira Sandra Mara , Rafacho Alex , Boschero Antônio Carlos , Santos Gustavo Jorge dos 
Published: December 2024

AimsThis study investigates the role of Hepatocyte Nuclear Factor 4α (HNF4α) in the adaptation of pancreatic β-cells to an HFD-induced obesogenic environment, focusing on β cell mass expansion and metabolic adaptations.Main methodsWe utilized an HNF4α knockout (KO) mouse model, with CRE-recombinase enzyme activation confirmed through tamoxifen administration. KO and Control (CTL) mice were fed an HFD for 20 weeks. We monitored body weight, food intake, glucose tolerance, insulin sensitivity, and insulinemia. Also, to assess structural and metabolic changes, histological analyses of pancreatic islets and liver tissue were conducted.Key findingsKO mice displayed lower fasting blood glucose levels compared to CTL mice after tamoxifen administration, indicating impaired glucose-regulated insulin secretion. HFD-fed KO mice consumed less food but exhibited greater weight gain and perigonadal fat accumulation, reflecting higher energy efficiency. Histological analysis revealed more pronounced liver steatosis and fibrosis in KO mice on HFD. Glucose intolerance and insulin resistance were exacerbated in KO mice, highlighting their inability to adapt to increased metabolic demand. Structural analysis showed that KO mice failed to exhibit HFD-induced β cell mass expansion, resulting in reduced islet diameter and number, confirming the critical role of HNF4α in β cell adaptation.SignificanceThis study demonstrates that HNF4α is essential for the proper metabolic and structural adaptation of pancreatic β-cells in response to an obesogenic environment. The lack of HNF4α impairs β cell functionality, leading to increased susceptibility to glucose intolerance and insulin resistance. These findings underscore the importance of HNF4α in maintaining glucose homeostasis and highlight its potential as a therapeutic target for diabetes management in obesity.
Development of a recombinant human IgG1 monoclonal antibody against the TRBV5-1 segment of the T cell receptor for the treatment of mature T cell neoplasms
Authors: Pitaro Michele , Antonini Giovanni , Arcovito Alessandro , Buccisano Francesco , De Lauro Alfredo , Irno Consalvo Maria , Gallo Valentina , Giacon Noah , Mangiatordi Giuseppe Felice , Pacelli Maddalena , Pitaro Maria Teresa , Polticelli Fabio , Sorrenti Matteo , Venditti Adriano 
Published: December 2024

BackgroundMature T-cell neoplasms arise from the neoplastic transformation of a single T lymphocyte, and all cells in a neoplastic clone share the same V segment in the beta chain of the T-cell receptor (TCR). These segments may represent an innovative target for the development of targeted therapies.MethodsA specific V segment of the TCR beta chain (TRBV5-1) was analyzed using bioinformatic tools, identifying three potential antigenic peptides. One of these peptides, selected for synthesis, was used to screen a library of human single-chain variable fragments (scFv) through phage display. One fragment demonstrated high affinity and specificity for the antigen and was used to produce a human monoclonal antibody of the IgG1 class.ResultsSurface plasmon resonance (SPR) studies confirmed the high affinity of the monoclonal antibody for the antigen in the nanomolar range. Flow cytometry analysis on patients’ samples demonstrated that the antibody, conjugated with a fluorochrome, selectively binds to tumor T lymphocytes expressing TRBV5-1, without binding to other lymphocytes or blood cell components.ConclusionsThe development of fully human IgG1 monoclonal antibodies targeting specific V segments of the TCR beta chain represents a potential therapeutic option for patients with mature T-cell neoplasms.
Association between diabetes mellitus and trochanteric bone mineral density in individuals with osteoporotic fractures: a retrospective study
Authors: Guo Shao-han , Xu Jian , Xu Min-zhe , Li Chong , Gong Ya-qin , Lu Ke 
Published: December 2024

BackgroundThe relationship between diabetes mellitus (DM) and bone mineral density (BMD) in patients with osteoporotic fractures (OPFs) remains complex and heterogeneous, specifically between the genders. This study aimed to explore the association between diabetes status and trochanteric BMD in a cohort of patients with OPFs and elucidate the differences between male and female patients.MethodsThis retrospective analysis was performed on 710 admitted patients aged 50 years or older with OPFs. In this study, the exposure variable was diabetes status. Trochanteric BMD comprised the dependent variable. While controlling for covariance influences, generalized estimating equations (GEE) were applied to examine the independent link between diabetes status and trochanteric BMD in OPFs patients. Moreover, a subgroup analysis was also conducted to validate the result’s stability.ResultsA substantial positive association was noted between diabetes status and trochanteric BMD in diabetic patients, as determined by the fully adjusted model (β = 0.017, 95% CI 0.001 to 0.033, p = 0.035). Furthermore, the sex-specific analysis showed a significant positive relationship between diabetes status and trochanteric BMD in male patients (β = 0.040, 95% CI 0.006 to 0.075, p = 0.022), whereas no significant relationship was observed in female patients (β = 0.010, 95% CI −0.008 to 0.028, p = 0.256).ConclusionThis study highlighted the significant sex differences in the impact of diabetes on trochanteric BMD among patients with OPFs. The male diabetic patients had higher trochanteric BMD than their non-diabetic counterparts; however, this association was not evident in female patients. Further research is necessary to understand the underlying mechanisms that contribute to these sex-specific differences and to evaluate the clinical implications of managing fracture risk in diabetic patients.
Breast pericytes: a newly identified driver of tumor cell proliferation
Authors: Del Toro Katelyn , Licon-Munoz Yamhilette , Crabtree William , Oper Tristan , Robbins Christine , Hines William C. 
Published: December 2024

IntroductionEffective treatment of breast cancer remains a formidable challenge, partly due to our limited understanding of the complex microenvironmental factors that contribute to disease pathology. Among these factors are tissue-resident perivascular cells, which play crucial roles in shaping vascular basement membranes, maintaining vessel integrity, and communicating with adjacent endothelial cells. Despite their essential functions, perivascular cells have been relatively overlooked. Identifying them by immunostaining has been challenging due to their low abundance, inherent heterogeneity, and shared marker expression with other cell types. These challenges have hindered efforts to purify pericytes and generate primary cell models for studying their biology.MethodsUsing a recently developed FACS method, we successfully identified and purified each cell type from breast tissues, allowing us to deep-sequence their transcriptomes and generate primary cell models of each cell type—including pericytes. Here, we used these data to analyze cell-type-specific gene expression in tumors, which revealed a strong association between pericyte-specific genes and breast cancer patient mortality. To explore this association, we defined the heterogeneity of breast pericytes using single-cell RNA sequencing and identified a broad marker for visualizing perivascular cells in breast tumors.ResultsRemarkably, we discovered perivascular cells dissociated from vessels and emerged as a dominant mesenchymal cell type in a subset of breast tumors that contrasted with their normal perivascular location. Moreover, when we purified pericytes from the breast and cultured them alongside breast tumor cells, we discovered that they induced rapid tumor cell growth significantly greater than isogenic fibroblast controls.DiscussionThese findings identify perivascular cells as a key microenvironmental factor in breast cancer, highlighting the critical need for further research to explore their biology and identify specific stimulatory mechanisms that could be targeted therapeutically.
Cost-effectiveness analysis of anlotinib plus chemotherapy with or without benmelstobart versus chemotherapy alone for extensive-stage small-cell lung cancer in China
Authors: You Caicong , Zhang Jiahao , Lei Jianying , Fu Wu , Zheng Bin , Liu Maobai , Li Na 
Published: December 2024

ObjectivesThe ETER701 trial demonstrated that benmelstobart combined with anlotinib and etoposide-carboplatin (EC) significantly extends survival in patients with extensive-stage small cell lung cancer (ES-SCLC), setting a new record for median overall survival. In contrast, anlotinib plus EC only significantly prolongs progression-free survival. However, there is currently no evidence evaluating the cost-effectiveness of these regimens as first-line treatments. Therefore, this study assesses the cost-effectiveness of these three first-line treatment options from the perspective of the Chinese healthcare system.MethodsA time-varying Markov model was constructed to simulate the disease progression of a 62-year-old patient with ES-SCLC, assessing direct medical costs, health benefits, and incremental cost-effectiveness ratios (ICER). Both flexible and standard parametric models were included to fit and extrapolate survival data. The probabilities, costs, and health utilities required for the model were sourced from literature, databases, and expert consultations. Additionally, sensitivity and scenario analyses were conducted to explore the impact of various parameters on model uncertainty.ResultsCompared to EC alone, the combination of benmelstobart, anlotinib, and EC added $80,879.12 in cost for 0.7288 quality-adjusted life years (QALYs), an ICER of $110,970.19/QALY. Anlotinib plus EC added $4,107.86for 0.1951 QALYs, an ICER of $21,056.19/QALY. At a $37,598/QALY threshold, the cost-effectiveness probability for benmelstobart combination is 0%, and for anlotinib combination is 80.42%. A 73.79% price cut for benmelstobart is needed for cost-effectiveness.ConclusionsIn China, benmelstobart combined with anlotinib and EC is not a cost-effective first-line treatment for ES-SCLC; however, reducing the price of benmelstobart by 73.79% could make this regimen cost-effective. In contrast, anlotinib combined with EC may represent a more cost-effective first-line treatment option.
A Screen of Traditional Chinese Medicinal Plant Extracts Reveals 17 Species with Antimicrobial Properties
Authors: Ellward Garrett L. , Binda Macie E. , Dzurny Dominika I. , Bucher Michael J. , Dees Wren R. , Czyż Daniel M. 
Published: December 2024

Background/Objectives: Antimicrobial resistance (AMR) is a growing threat that undermines the effectiveness of global healthcare. The Centers for Disease Control and Prevention and the World Health Organization have identified numerous microbial organisms, particularly members of the ESKAPEE pathogens, as critical threats to global health and economic security. Many clinical isolates of these pathogens have become completely resistant to current antibiotics, making treatment nearly impossible. Herbal remedies, such as those found in Traditional Chinese Medicine (TCM), have been practiced for thousands of years and successfully used to treat a wide range of ailments, including infectious diseases. Surprisingly, despite this extensive knowledge of folk medicine, no plant-derived antibacterial drugs are currently approved for clinical use. As such, the objective of this study is to evaluate the antimicrobial properties of extracts derived from TCM plants. Methods: This study explores a comprehensive library comprising 664 extracts from 132 distinct TCM plant species for antimicrobial properties against gram-negative (Escherichia coli) and gram-positive (Micrococcus luteus) bacteria using liquid and solid in vitro assays. Results: Intriguingly, our results reveal 17 plant species with potent antimicrobial properties effective primarily against gram-positive organisms, including Streptococcus aureus and epidermidis. A literature search revealed that nearly 100 purified compounds from the identified TCM plants were previously isolated and confirmed for their antimicrobial properties, collectively inhibiting 45 different bacterial species. Conclusions: Our results indicate that phytobiotics from the identified plants could serve as potential candidates for novel antimicrobials.
Synergistic Effect of Lactobacillus Mixtures and Lagerstroemia speciosa Leaf Extract in Reducing Obesity in High-Fat Diet-Fed Mice
Authors: Lee Kippeum , Kim Hyeon-Ji , Kim Joo Yun , Shim Jae Jung , Lee Jae Hwan 
Published: December 2024

In this study, we describe the anti-obesity effects of a novel combination of Lactobacillus mixture (Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032) and leaf extract of Lagerstroemia speciosa (L. speciosa) in mice. The administration of the probiotic mixture of HY7601 and KY1032 in combination with the leaf extract of L. speciosa significantly attenuated fat tissue formation and body weight gain in mice fed a high-fat diet. The white adipose fat mass, comprising the inguinal and epididymal fat pads, was most effectively reduced when the probiotic mixture and L. speciosa leaf extract was orally administered to the mice in combination. This combination also reduced the mRNA expression of adipogenic genes (those encoding CCAAT/enhancer-binding protein alpha, peroxisome proliferator-activated receptor gamma, and fatty acid-binding protein 4) in inguinal and epididymal white adipose tissue depots and the liver. Finally, the combination of reduced blood glucose concentrations regulated the insulin resistance of high-fat diet-fed obese mice. These findings provide insight into the mechanisms underlying the effect of this combination and suggest that using Lactobacillus mixture (HY7601 and KY1032) is as safe as microbial monotherapy, but more effective at preventing obesity.
CRISPR-Cas-Based Pen-Side Diagnostic Tests for Anaplasma marginale and Babesia bigemina
Authors: Muriuki Robert , Ndichu Maingi , Githigia Samuel , Svitek Nicholas 
Published: December 2024

Anaplasma marginale and Babesia bigemina are tick-borne pathogens, posing significant threats to the health and productivity of cattle in tropical and subtropical regions worldwide. Currently, detection of Babesia bigemina and Anaplasma marginale in infected animals relies primarily on microscopic examination of Giemsa-stained blood or organ smears, which has limited sensitivity. Molecular methods offer higher sensitivity but are costly and impractical in resource-limited settings. Following the development of a pen-side test for detecting Theileria parva infections in cattle, we have created two additional CRISPR-Cas12a assays targeting Anaplasma marginale and Babesia bigemina. The assays target the major surface protein 5 (MSP5) for A. marginale and rhoptry-associated protein 1a (RAP1a) for B. bigemina. These additional tests involve a 20 min recombinase polymerase amplification (RPA) reaction followed by a 60 min CRISPR-Cas12a detection with a lateral strip readout. Results demonstrate high specificity, with no cross-reactivity against other tick-borne parasites, and a limit of detection down to 102 DNA copies/µL of each target marker. The findings pave the way for sensitive and user-friendly pen-side tests to diagnose A. marginale and B. bigemina infections.
Antifungal Properties of Bioactive Compounds Isolated from Fucus vesiculosus Supercritical Carbon Dioxide Extract
Authors: Tyśkiewicz Katarzyna , Rüttler Felix , Tyśkiewicz Renata , Nowak Artur , Gruba Marcin , Wziątek Anita , Dębczak Agnieszka , Sandomierski Michał , Vetter Walter 
Published: December 2024

The exploration of natural antifungal substances from algal origins is significant due to the increasing resistance of pathogens to conventional antifungal agents and the growing consumer demand for natural products. This manuscript represents the inaugural investigation into the antifungal attributes of bioactive compounds extracted from Fucus vesiculosus via supercritical carbon dioxide (scCO2) extraction utilizing contemporary countercurrent chromatography (CCC). In aligning with the prospective utilization of this extract within the agricultural sector, this study also serves as the preliminary report demonstrating the capability of Fucus vesiculosus scCO2 extract to enhance the activity of plant resistance enzymes. The fractions obtained through CCC were subjected to evaluation for their efficacy in inhibiting the macrospores of Fusarium culmorum. The CCC methodology facilitated the successful separation of fatty acids (reaching up to 82.0 wt.% in a given fraction) and fucosterol (attaining up to 79.4 wt.% in another fraction). All CCC fractions at the concentration of 1.0% were found to inhibit 100% of Fusarium culmorum growth. Moreover, Fucus vesiculosus scCO2 extract was able to activate plant resistance enzymes (Catalase, Ascorbic Peroxidase, Guaiacol Peroxidase, Phenylalanine Ammonia-Lyase, and Phenylalanine Ammonia-Lyase Activity).
Dynamically Cyclic Fe
2+
/Fe
3+
Active Sites as Electron and Proton-Feeding Centers Boosting CO
2
Photoreduction Powered by Benzyl Alcohol Oxidation
Authors: Lei Ben , Zhou Gaofeng , Gong Zhongyou , Liu Chao , Zhou Ying , Guro Vitaliy P. , Sun Yanjuan , Sheng Jianping , Dong Fan 
Published: December 2024

Solar-driven CO
2
photoreduction holds promise for sustainable fuel and chemical productions, but the complex proton-coupled multi-electron transfer processes and sluggish oxidation half-reaction kinetics substantially hinder its efficiency. Here, we devised a rational catalyst design to address these challenges by fabricating ferrocene carboxylic acid-functionalized Cs
3
Sb
2
Br
9
nanocrystals (CSB-Fc NCs), which facilitate simultaneous benzyl alcohol oxidation and CO
2
reduction reactions under visible-light irradiation. The synchronized proton-coupled electron transfer processes between the reduction and oxidation half-reactions on CSB-Fc NCs resulted in a 5-fold increase in the CO
2
reduction rate (45.56 μmol g
−1
h
−1
, 97.9% CO selectivity) and a 5.8-fold enhancement in benzyl alcohol conversion (97.7% selectivity for benzaldehyde) compared to the CSB. In situ Raman and ultraviolet-visible diffuse reflectance spectra revealed that the dynamic Fe
2+
/Fe
3+
redox loop within the Fc unit serves as the actual active site, facilitating the activation of substrate molecules. More importantly, in situ attenuated total reflection Fourier transform infrared spectroscopy and gas chromatography–mass spectrometry spectroscopy, with isotope labeling of Deuteron-benzyl alcohol and
13
CO
2
, confirmed that proton transfer from the hydroxyl group generates reactive protons at the Fe
2+
/Fe
3+
site, enabling efficient CO
2
photoreduction through subsequent protonation steps. This work offers a cost-effective and efficient approach for synergetic CO
2
photoreduction driven by organic synthesis, advancing solar energy utilization.