bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dermal stiffness governs the topography of the epidermis and the underlying basement membrane in young and old human skin
Authors: Roig‐Rosello Eva , Dayan Guila , Bovio Simone , Manissier Patricia , Errazuriz Elisabeth , Rousselle Patricia 
Published: March 2024

AbstractThe epidermis is a stratified epithelium that forms the outer layer of the skin. It is composed primarily of keratinocytes and is constantly renewed by the proliferation of stem cells and their progeny that undergo terminal differentiation as they leave the basal layer and migrate to the skin surface. Basal keratinocytes rest on a basement membrane composed of an extracellular matrix that controls their fate via integrin‐mediated focal adhesions and hemidesmosomes which are critical elements of the epidermal barrier and promote its regenerative capabilities. The distribution of basal cells with optimal activity provides the basement membrane with its characteristic undulating shape; this configuration disappears with age, leading to epidermal weakness. In this study, we present an in‐depth imaging analysis of basal keratinocyte anchorage in samples of human skin from participants across the age spectrum. Our findings reveal that skin aging is associated with the depletion of hemidesmosomes that provide crucial support for stem cell maintenance; their depletion correlates with the loss of the characteristic basement membrane structure. Atomic force microscopy studies of skin and in vitro experiments revealed that the increase in tissue stiffness observed with aging triggers mechanical signals that alter the basement membrane structure and reduce the extent of basal keratinocyte anchorage, forcing them to differentiate. Genomic analysis revealed that epidermal aging was associated with mechanical induction of the transcription factor Krüppel‐like factor 4. The altered mechanical properties of tissue being a new hallmark of aging, our work opens new avenues for the development of skin rejuvenation strategies.
High burden of clonal mast cell disorders and hereditary α‐tryptasemia in patients who need Hymenoptera venom immunotherapy
Authors: Korošec Peter , Sturm Gunter J. , Lyons Jonathan J. , Marolt Tinkara Pirc , Svetina Manca , Košnik Mitja , Zidarn Mihaela , Kačar Mark , Frelih Nina , Lalek Nika , Luzar Ajda Demšar , Zver Samo , Škerget Matevž , Czarnobilska Ewa , Dyga Wojciech , Grle Sanja Popović , Samarzija Miroslav , Arzt‐Gradwohl Lisa , Čerpes Urban , Porebski Grzegorz , Pevec Branko , Schadelbauer Eva , Kopač Peter , Šelb Julij , Rijavec Matija 
Published: March 2024

AbstractBackgroundIn patients who require venom immunotherapy (VIT), there is a need to identify underlying mast cell (MC) disorders since these may affect the risk and severity of future sting reactions and the long‐term effectiveness of VIT.Methods1319 individuals with Hymenoptera venom allergy (HVA) who needed VIT from referral centers in Slovenia, Austria, Croatia, and Poland underwent examination for KIT p.D816V in peripheral blood leukocytes (PBL) using a highly sensitive PCR test and tryptase genotyping by digital droplet PCR. We also included 183 control individuals with large local reactions (LLRs) to Hymenoptera stings and with asymptomatic sensitization to Hymenoptera venoms.Results285 of 1319 individuals recommended for VIT (21.6%) were positive for KIT p.D816V in PBL, preferably those who present with severe reaction (33.9% [n = 207 of 610] with Ring‐Messmer grade 3–4 vs. 11% [n = 78 of 709] with Grade 1–2; p < .0001), whereas only 1.3% (n = 2 of 152) of controls with LLR and none with asymptomatic sensitization (n = 31) had KIT p.D816V. KIT p.D816V allelic burden was higher in those with severe reaction (median 0.018% [n = 207] in Grade 3–4 vs. 0.001% [n = 78] in Grade 1–2; p < .0001), and the majority had normal baseline serum tryptase levels (69% [n = 196 of 285]). All KIT p.D816V‐positive individuals (n = 41) who underwent bone marrow (BM) biopsy were found to have underlying clonal diseases, principally BM mastocytosis. HαT was also associated with severe HVA and symptoms (p < .01), and remarkably, 31.0% (n = 31 of 100) were found to have concomitant KIT p.D816V. Concomitant HαT and KIT p.D816V showed an additive effect, and having both was associated with the highest risk for severe HVA, even higher than having either HαT or KIT p.D816V alone (OR = 3.8; p < .01).ConclusionsBy employing prospective universal tryptase genotyping and examination for KIT p.D816V in PBL in large HVA populations, we have demonstrated a high burden of clonal MC disorders and HαT in patients who require VIT.
RNA‐sequencing of paired tape‐strips and skin biopsies in atopic dermatitis reveals key differences
Authors: Fritz Blaine , Halling Anne‐Sofie , Cort Isabel Díaz‐Pinés , Christensen Maria Oberländer , Rønnstad Amalie Thorsti Møller , Olesen Caroline Meyer , Knudgaard Mette Hjorslev , Zachariae Claus , Heegaard Steffen , Thyssen Jacob P. , Bjarnsholt Thomas 
Published: March 2024

AbstractBackgroundSkin tape‐strips and biopsies are widely used methods for investigating the skin in atopic dermatitis (AD). Biopsies are more commonly used but can cause scarring and pain, whereas tape‐strips are noninvasive but sample less tissue. The study evaluated the performance of skin tape‐strips and biopsies for studying AD.MethodsWhole‐transcriptome RNA‐sequencing was performed on paired tape‐strips and biopsies collected from lesional and non‐lesional skin from AD patients (n = 7) and non‐AD controls (n = 5). RNA yield, mapping efficiency, and differentially expressed genes (DEGs) for the two methods (tape‐strip/biopsy) and presence of AD (AD/non‐AD) were compared.ResultsTape‐strips demonstrated a lower RNA yield (22 vs. 4596 ng) and mapping efficiency to known genes (28% vs. 93%) than biopsies. Gene‐expression profiles of paired tape‐strips and biopsies demonstrated a medium correlation (R2 = 0.431). Tape‐strips and biopsies demonstrated systematic differences in measured expression levels of 6483 genes across both AD and non‐AD samples. Tape‐strips preferentially detected many itch (CCL3/CCL4/OSM) and immune‐response (CXCL8/IL4/IL5/IL22) genes as well as markers of epidermal dendritic cells (CD1a/CD207), while certain cytokines (IL18/IL37), skin‐barrier genes (KRT2/FLG2), and dermal fibroblasts markers (COL1A/COL3A) were preferentially detected by biopsies. Tape‐strips identified more DEGs between AD and non‐AD (3157 DEGs) then biopsies (44 DEGs). Tape‐strips also detected higher levels of bacterial mRNA than biopsies.ConclusionsThis study concludes that tape‐strips and biopsies each demonstrate respective advantages for measuring gene‐expression changes in AD. Thus, the specific skin layers and genes of interest should be considered before selecting either method.
Factors affecting the use of a three‐dimensional model during robot‐assisted partial nephrectomy
Authors: Yamazaki Masahiro , Takayama Tatsuya , Sugihara Toru , Kikuchi Tomohiro , Kamimura Tomoki , Kamei Jun , Ando Satoshi , Terauchi Fumihito , Morita Tatsuo , Fujimura Tetsuya 
Published: March 2024

AbstractIntroductionThis study aimed to identify cases that require a three‐dimensional‐printed kidney model in robot‐assisted partial nephrectomy.MethodsWe enrolled 93 patients undergoing robot‐assisted partial nephrectomy for renal tumors at a single institution between November 2018 and May 2021. The endpoints were how often and how long the surgeon consulted the three‐dimensional‐printed model, determined using intraoperative video. Multivariate analyses of the endpoints were adjusted by preoperative patient and kidney characteristics, including renal vascular complexity that was defined as the number of vascular branches penetrating the surface tangential to the ventral side of the kidney.ResultsOf the 93 cases, the median frequency and duration of intraoperative three‐dimensional‐printed model consultation were four times and 39 s, respectively. The multivariate linear regression analyses showed that the frequency of intraoperative three‐dimensional‐printed model consultation by the surgeon was significantly related to the complexity of the arterial structure (≥4 branches), presence of hilar tumor, and high Mayo Adhesive Probability score; the regression coefficients were 1.81, 2.79, and 1.34, respectively. All p‐values were ≤.03. The duration of the three‐dimensional‐printed model consultation was significantly related to the complexity of the arterial structure (≥4 branches) and the presence of hilar tumor; the regression coefficients were 21.6, and 29.0 s, respectively. All p‐values were <.01.ConclusionDuring robot‐assisted partial nephrectomy, a three‐dimensional‐printed model would be helpful in cases with a complex arterial structure or hilar tumor.
Functional specialisation and coordination of myonuclei
Authors: Korb Amaury , Tajbakhsh Shahragim , Comai Glenda E. 
Published: March 2024

ABSTRACTMyofibres serve as the functional unit for locomotion, with the sarcomere as fundamental subunit. Running the entire length of this structure are hundreds of myonuclei, located at the periphery of the myofibre, juxtaposed to the plasma membrane. Myonuclear specialisation and clustering at the centre and ends of the fibre are known to be essential for muscle contraction, yet the molecular basis of this regionalisation has remained unclear. While the ‘myonuclear domain hypothesis’ helped explain how myonuclei can independently govern large cytoplasmic territories, novel technologies have provided granularity on the diverse transcriptional programs running simultaneously within the syncytia and added a new perspective on how myonuclei communicate. Building upon this, we explore the critical cellular and molecular sources of transcriptional and functional heterogeneity within myofibres, discussing the impact of intrinsic and extrinsic factors on myonuclear programs. This knowledge provides new insights for understanding muscle development, repair, and disease, but also opens avenues for the development of novel and precise therapeutic approaches.
LncRNA CTBP1‐AS inhibits TP63‐mediated activation of S100A14 during prostate cancer progression
Authors: Wu Guangzheng , Dong Zhenkun , Dong Yuhang , Chen Yinmei , Zhu Huan , Ding Dexin , Cui Yan , Wang Yiwen , Xu Yangyang , Chen Hui 
Published: March 2024

AbstractLong noncoding RNAs (lncRNAs) have emerged as important molecules and potential new targets for human cancers. This study investigates the function of lncRNA CTBP1 antisense RNA (CTBP1‐AS) in prostate cancer (PCa) and explores the entailed molecular mechanism. Aberrantly expressed genes potentially correlated with PCa progression were probed using integrated bioinformatics analyses. A cohort of 68 patients with PCa was included, and their tumor and para‐cancerous tissues were collected. CTBP1‐AS was highly expressed in PCa tissues and cells and associated with poor patient prognosis. By contrast, tumor protein p63 (TP63) and S100 calcium binding protein A14 (S100A14) were poorly expressed in the PCa tissues and cells. CTBP1‐AS did not affect TP63 expression; however it blocked the TP63‐mediated transcriptional activation of S100A14, thereby reducing its expression. CTBP1‐AS silencing suppressed proliferation, apoptosis resistance, migration, invasion, and tumorigenicity of PCa cell lines, while its overexpression led to inverse results. The malignant phenotype of cells was further weakened by TP63 overexpression but restored following artificial S100A14 silencing. In conclusion, this study demonstrates that CTBP1‐AS plays an oncogenic role in PCa by blocking TP63‐mediated transcriptional activation of S100A14. This may provide insight into the management of PCa.
ctDNA predicts clinical T1a to pathological T3a upstaging after partial nephrectomy
Authors: Park Jee Soo , Kim Hongkyung , Jang Won Sik , Kim Jongchan , Ham Won Sik , Lee Seung‐Tae 
Published: March 2024

AbstractMost patients diagnosed with clear cell renal cell carcinoma (ccRCC) are also detected with small and organ‐confined tumors, and the majority of these are classified as clinical tumor stage 1a (cT1a). A considerable proportion of patients with cT1 RCC shows tumor upstaging to pathological stage 3a (pT3a), and these patients have worse oncological outcomes. The role of circulating tumor DNA (ctDNA) in RCC has been limited to monitoring treatment response and resistance. Therefore, the present study aimed to evaluate the potential of ctDNA in predicting pT3a upstaging in cT1a ccRCC. We sequenced plasma samples preoperatively collected from 48 patients who had undergone partial nephrectomy for cT1a ccRCC using data from a prospective cohort RCC. The ctDNA were profiled and compared with clinicopathological ccRCC features to predict pT3a upstaging. Associations between ctDNA, tumor complexity, and pT3a upstaging were evaluated. Tumor complexity was assessed using the anatomical classification system. Univariate analysis used chi‐squared and Student's t‐tests; multivariate analysis considered significant factors from univariate analyses. Of the 48 patients with cT1a ccRCC, 12 (25%) were upstaged to pT3a, with ctDNA detected in 10 (20.8%), predominantly in patients with renal sinus fat invasion (SFI; n = 8). Among the pT3a group, ctDNA was detected in 75%, contrasting with only 2.8% in patients with pT1a (1/36). Detection of ctDNA was the only significant preoperative predictor of pT3a upstaging, especially in SFI. This study is the first to suggest ctDNA as a preoperative predictor of pT3a RCC upstaging from cT1a based on preoperative radiological images.
Asiatic acid inhibits rheumatoid arthritis fibroblast‐like synoviocyte growth through the Nrf2/HO‐1/NF‐κB signaling pathway
Authors: Zhang Li , Liu Zhi‐ning , Han Xi‐yuan , Liu Xin , Li Yang 
Published: March 2024

AbstractAsiatic acid (AA) is generally recognized in the treatment of various diseases and has significant advantages in the treatment of various inflammatory diseases. The treatment of rheumatoid arthritis (RA) with AA is a completely new entry point. RA is a complex autoimmune inflammatory disease, and despite the involvement of different immune and nonimmune cells in the pathogenesis of RA, fibroblast‐like synoviocytes (FLS) play a crucial role in the progression of the disease. si‐Nrf2 was transfected in RA‐FLS and the cells were treated with AA. MTT assay and colony formation assay were used to detect the effect of AA on the viability and formation of clones of RA‐FLS, respectively. Moreover, the apoptosis of RA‐FLS was observed by Hoechst 33342 staining and flow cytometry. Western blot was applied to measure the expression of the Nrf2/HO‐1/NF‐κB signaling pathway‐related proteins. Compared with the control group, RA‐FLS proliferation, and clone formation were significantly inhibited by the increase of AA concentration, and further experiments showed that AA‐induced apoptosis of RA‐FLS. In addition, AA activated the Nrf2/HO‐1 pathway to inhibit NF‐κB protein expression. However, the knockdown of Nrf2 significantly offsets the effects of AA on the proliferation, apoptosis, and Nrf2/HO‐1/NF‐κB signaling pathway of RA‐FLS cells. AA can treat RA by inhibiting the proliferation and inducing the apoptosis of RA‐FLS. The mechanism may be related to the activation of the Nrf2/HO‐1/NF‐κB pathway.
Serum exosomal miR‐3662 down‐regulates the expression of RBMS3 to promote malignant progression and gemcitabine resistance of breast cancer cells
Authors: Li Xiang , Chu Xu , Wang Hao , Xiang Ling , Yue Xuandi 
Published: March 2024

AbstractBreast cancer (BC) is a prevalent malignancy among women worldwide. As an anticancer drug of pyrimidine nucleoside analogs, gemcitabine can be used to treat BC, but its clinical application is restricted due to drug resistance. This study investigated the effect of serum exosomal microRNA‐3662 (miR‐3662) on gemcitabine resistance in BC cells by targeting RNA‐Binding Motif Single‐Stranded Interacting Protein 3 (RBMS3) and related molecular mechanisms. We performed the bioinformatics analyses on the differential miRNAs in BC and predicted the downstream regulators. Quantitative real‐time polymerase chain reaction was conducted to determine miR‐3662 and RBMS3 expression, while dual luciferase was conducted to confirme the regulatory relationship between them. Flow cytometry, cell counting kit‐8, and transwell assays were applied to assess apoptosis, cell viability, invasion, and migration. The expression of marker proteins (TSG101, CD63, and CD81) in patients' serum exosomes was evaluated through western blot, and exosomes were observed using transmission electron microscopy. miR‐3662 expression was significantly upregulated in BC, and miR‐3662 knockdown significantly reduced BC cell viability and gemcitabine resistance. As the downstream gene of miR‐3662, RBMS3 was significantly downregulated in BC, and dual luciferase assay verified the binding of RBMS3‐3′UTR to miR‐3662. Rescue experiments revealed that silencing RBMS3 reversed the inhibitory effect of miR‐3662 knockdown on BC cells. Besides, we also found that miR‐3662 expression was significantly low in serum exosome samples from BC patients and could be transmitted to tumor cells. miR‐3662 was upregulated in serum exosomes and promoted BC cell progression and gemcitabine resistance by targeting RBMS3.
Educational identity processes in adolescence: An analysis of longitudinal evidence and the role of educational systems
Authors: Negru‐Subtirica Oana 
Published: March 2024

AbstractEducational identity has been studied increasingly in the past decades since school is a structured context that shapes adolescent identity formation. Across the academic years, adolescents learn to position themselves in terms of their education and schooling, perceiving these entities as more or less relevant for their self‐formation. In this article, I analyze educational identity in the context of personal identity formation in adolescence through longitudinal studies from Japan, the Netherlands, and Romania that used the identity process approach. I also examine the role educational systems play in educational identity trajectories, outlining the limits of personal intentionality when adolescents make educational choices. In addition, I address the relations of educational identity development with two important outcomes of education: academic achievement and vocational development. I conclude that educational identity formation reflects the freedom or coercion that country‐specific educational systems teach adolescents through educational tracking and the timing of educational transitions.
Fracture resistance of hybrid ceramic abutments with different restoration lengths: A pilot study
Authors: D'haese Rani , Vervack Valentin , Tytgat Manon , Vandeweghe Stefan 
Published: March 2024

AbstractAimIn this pilot study, the fracture resistance of hybrid abutments with different restoration lengths was investigated.Materials and MethodsSixteen monolithic zirconia restorations of an upper right incisor were designed to fit a titanium base abutment. Eight central incisors had a crown length of 8 mm (T1) and the other half a length of 12 mm (T2). All crowns were cemented on the titanium base using a resin cement. After cementation, the samples were placed in a thermocycler for 5000 cycles. Fracture strength was measured using a universal test machine. Deformations and fractures of the samples were investigated.ResultsThe mean fracture resistance of T1 was 515 N (SD 96 N, 339–650) and 305 N (SD 57 N, 234–408) for T2 (p < 0.001). Both groups showed deformation of the titanium base, with no significant difference between both groups (p = 0.200). A difference in fracture type (p = 0.013) was observed, with significantly more screw fractures occurring in group T1 (p = 0.026).ConclusionWithin the limitations of this study, hybrid restorations with standard titanium base abutments can withstand forces that have been associated with chewing, irrespective of the crown length. However, the shorter crowns demonstrated more fatal fractures.
Quantifying assumptions underlying peak oxygen consumption equations across the body mass spectrum
Authors: Busque Vincent , Christle Jeffrey W. , Moneghetti Kegan J. , Cauwenberghs Nicholas , Kouznetsova Tatiana , Blumberg Yair , Wheeler Matthew T. , Ashley Euan , Haddad Francois , Myers Jonathan 
Published: March 2024

SummaryThe goal of this study is to quantify the assumptions associated with the Wasserman‐Hansen (WH) and Fitness Registry and the Importance of Exercise: A National Database (FRIEND) predictive peak oxygen consumption (pVO2) equations across body mass index (BMI). Assumptions in pVO2 for both equations were first determined using a simulation and then evaluated using exercise data from the Stanford Exercise Testing registry. We calculated percent‐predicted VO2 (ppVO2) values for both equations and compared them using the Bland–Altman method. Assumptions associated with pVO2 across BMI categories were quantified by comparing the slopes of age‐adjusted VO2 ratios (pVO2/pre‐exercise VO2) and ppVO2 values for different BMI categories. The simulation revealed lower predicted fitness among adults with obesity using the FRIEND equation compared to the WH equations. In the clinical cohort, we evaluated 2471 patients (56.9% male, 22% with BMI >30 kg/m2, pVO2 26.8 mlO2/kg/min). The Bland–Altman plot revealed an average relative difference of −1.7% (95% CI: −2.1 to −1.2%) between WH and FRIEND ppVO2 values with greater differences among those with obesity. Analysis of the VO2 ratio to ppVO2 slopes across the BMI spectrum confirmed the assumption of lower fitness in those with obesity, and this trend was more pronounced using the FRIEND equation. Peak VO2 estimations between the WH and FRIEND equations differed significantly among individuals with obesity. The FRIEND equation resulted in a greater attributable reduction in pVO2 associated with obesity relative to the WH equations. The outlined relationships between BMI and predicted VO2 may better inform the clinical interpretation of ppVO2 values during cardiopulmonary exercise test evaluations.
Free‐ranging livestock reduces the habitat suitability of subalpine pheasants during breeding season in Southwest China
Authors: Shang Xiao‐Tong , Fan Fan , Shen Xiao‐Li , Zheng Yong , Zhao Lian‐Jun , Sun Hong‐Ou , Li Sheng , Zhang Li 
Published: March 2024

AbstractFree‐ranging livestock pose a threat to forest biodiversity, exerting a profound influence on the survival of several endangered species. The mountains of Southwest China represent a biodiversity hotspot enriched with pheasant species of global significance; however, the influence of free‐ranging livestock on the survival and population of forest pheasants remains unclear. We examined the impact of livestock on the habitat suitability of subalpine pheasants and the associated mechanism during the breeding season in Southwest China (forest with and without grazing) over 2 years (2018–2019). Artificial nest experiments monitored by infrared‐triggered cameras showed that the nest failure rate was 2.18 folds higher in livestock‐active areas, where livestock directly accounted for 26.09% of all nest predation events, compared with other areas. Small animal trapping and vegetation quadrat surveys showed a 46% lower abundance of ground invertebrates, a critical food resource for breeding pheasants and their chicks, in grazing areas than in grazing‐free areas. Thus, livestock grazing markedly reduces the habitat suitability of subalpine pheasants during the breeding season. These results highlight the impacts of grazing on endangered pheasant species and the underlying mechanisms, necessitating centralized livestock management in these protected areas from April to July, coupled with livelihood transformation initiatives.