bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered tumor microenvironment heterogeneity of penile cancer during progression from non‐lymphatic to lymphatic metastasis
Authors: Xu Da‐Ming , Zhuang Xiao‐Yu , Ma Hua‐Li , Li Zai‐Shang , Wei Li‐Chao , Luo Jun‐Hang , Han Hui 
Published: July 2024

AbstractBackgroundLymphatic metastasis is the major challenge in the treatment of penile cancer. The prognosis of individuals with lymphatic metastasis is extremely poor. Therefore, early identification of disease progression and lymphatic metastasis is an urgent task for researchers in penile cancer worldwide.MethodsIn this study, using single‐cell RNA sequencing, an immune landscape was established for the cancer ecosystem based on 46,861 cells from six patients with penile cancer (four with lymphatic metastasis [stage IV] and two without lymphatic metastasis [stage I]). Using bulk RNA sequencing, the discrepancy between the cancers and their respective metastatic lymph nodes was depicted based on seven patients with penile cancer.ResultsThe interaction between epithelial cells, fibroblasts, and endothelial cells, and the functional cooperation among invasion, epithelial‐mesenchymal transition, and angiogenesis were found to be important landscapes in the penile cancer ecosystem, playing important roles in progression of cancer and lymph node metastasis.ConclusionsThis study is the first to investigate the altered tumor microenvironment heterogeneity of penile cancer as it evolves from non‐lymphatic to lymphatic metastasis and provides insights into the mechanisms underlying malignant progression, the premetastatic niche, and lymphatic metastasis in penile cancer.
RGS1 and CREB5 are direct and common transcriptional targets of ZNF384‐fusion proteins
Authors: Yamada Chiharu , Okada Kentaro , Odaira Koya , Tokoro Mahiru , Iwamoto Eisuke , Sanada Masashi , Noura Mina , Okamoto Syuichi , Yasuda Takahiko , Tsuzuki Shinobu , Kiyoi Hitoshi , Hayakawa Fumihiko 
Published: July 2024

AbstractBackgroundZNF384‐fusion (Z‐fusion) genes were recently identified in B‐cell acute lymphoblastic leukemia (B‐ALL) and are frequent in Japanese adult patients. The frequency is about 20% in those with Philadelphia chromosome‐negative B‐ALL. ZNF384 is a transcription factor and Z‐fusion proteins have increased transcriptional activity; however, the detailed mechanisms of leukemogenesis of Z‐fusion proteins have yet to be clarified.MethodsWe established three transfectants of cell lines expressing different types of Z‐fusion proteins, and analyzed their gene expression profile (GEP) by RNA‐seq. We also analyzed the GEP of clinical ALL samples using our previous RNA‐seq data of 323 Japanese ALL patients. We selected upregulated genes in both Z‐fusion gene‐expressing transfectants and Z‐fusion gene‐positive ALL samples, and investigated the binding of Z‐fusion proteins to regulatory regions of the candidate genes by ChIP‐qPCR.ResultsWe selected six commonly upregulated genes. After the investigation by ChIP‐qPCR, we finally identified CREB5 and RGS1 as direct and common target genes. RGS1 is an inhibitor of CXCL12‐CXCR4 signaling that is required for the homing of hematopoietic progenitor cells to the bone marrow microenvironment and development of B cells. Consistent with this, Z‐fusion gene transfectants showed impaired migration toward CXCL12.ConclusionsWe identified CREB5 and RGS1 as direct and common transcriptional targets of Z‐fusion proteins. The present results provide novel insight into the aberrant transcriptional regulation by Z‐fusion proteins.
Targeting polo‐like kinase 1 to treat kidney diseases
Authors: Kulkarni Hrushikesh , Dagar Neha , Gaikwad Anil Bhanudas 
Published: July 2024

AbstractGlobally, ∼850 million individuals suffer from some form of kidney disease. This staggering figure underscores the importance of continued research and innovation in the field of nephrology to develop effective treatments and improve overall global kidney health. In current research, the polo‐like kinase (Plk) family has emerged as a group of highly conserved enzyme kinases vital for proper cell cycle regulation. Plks are defined by their N‐terminal kinase domain and C‐terminal polo‐box domain, which regulate their catalytic activity, subcellular localization, and substrate recognition. Among the Plk family members, Plk1 has garnered significant attention due to its pivotal role in regulating multiple mitotic processes, particularly in the kidneys. It is a crucial serine–threonine (Ser‐Thr) kinase involved in cell division and genomic stability. In this review, we delve into the types and functions of Plks, focusing on Plk1's significance in processes such as cell proliferation, spindle assembly, and DNA damage repair. The review also underscores Plk1's vital contributions to maintaining kidney homeostasis, elucidating its involvement in nuclear envelope breakdown, anaphase‐promoting complex/cyclosome activation, and the regulation of mRNA translation machinery. Furthermore, the review discusses how Plk1 contributes to the development and progression of kidney diseases, emphasizing its overexpression in conditions such as acute kidney injury, chronic kidney disease, and so forth. It also highlights the importance of exploring Plk1 modulators as targeted therapies for kidney diseases in future. This review will help in understanding the role of Plk1 in kidney disease development, paving the way for the discovery and development of novel therapeutic approaches to manage kidney diseases effectively.
Nitrate Reduction Catalyzed by Bimetallic Silver‐Copper Macroporous Foams
Authors: Sun Jing , Zhou Yulin , Loyaux‐Lawniczak Stéphanie , Kéranguéven Gwenaelle , Boudon Corinne , Bonnefont Antoine , Ruhlmann Laurent , Badets Vasilica 
Published: July 2024

AbstractIn this work we describe the use of bimetallic silver‐copper macroporous foams for electrochemical nitrate reduction in acidic conditions (pH 2, 0.1 M NaClO4). By carefully selecting the composition of the electrodeposition bath, we have successfully prepared foams with atomic percentage varying from Ag dominant to Cu dominant. Also, we have succeeded to obtain morphologies that vary between the one specific to pure Ag foam to the one specific to pure Cu foam. We have shown that these foams contain a pure silver phase and also a silver‐copper alloy. The electrochemical active surface area of the foams depends both on the morphology as well as on the atomic composition. These materials were used for the first time as catalysts for nitrate electrochemical reaction (NO3RR). Both liquid and gaseous products were quantified with several analytical techniques. It was shown that bimetallic foams present superior faradaic efficiency (FE) towards liquid products in comparisons with pure silver and copper foams, suggesting a synergetic contribution from both metals. The Ag94Cu6 (AgCu10) foam shows a FE as high as 92 % towards liquid products and the lowest FE (3 %) towards the undesired product, i. e. nitrous acid. Also, this material shows a better stability than pure copper materials in the presence of nitrate in acidic conditions.
Energy‐Transfer Enabled Divergent Synthesis of Polycyclic γ‐Sultines
Authors: Zhou Pan , Zhang Yongxin , Ma Xinyue , Yang Xiaoxiao , Fang Xing , Lu Xi , Shu Chao 
Published: July 2024

AbstractA visible‐light‐initiated energy‐transfer enabled radical cyclization for the divergent synthesis of polycyclic γ‐sultine derivatives has been developed. The reaction provides an alternative and expeditious access to benzofused γ‐sultine frameworks, the analogues of γ‐lactones and γ‐sultones, and features good functional group compatibility, mild reaction conditions and excellent diastereoselectivity. The robustness and application potential of this method have also been successfully displayed by two gram‐scale reactions and the synthesis of polycyclic sultones. Mechanistic studies indicated the transformations through a possible energy‐transfer enabled intramolecular radical homolytic substitution or hydrogen atom transfer process mainly.
Impact of a High‐Fat Meal on the Pharmacokinetics of Sotorasib, a KRAS G12C Inhibitor
Authors: Cardona Panli , Dutta Sandeep , Houk Brett 
Published: July 2024

AbstractSotorasib is a small molecule drug that specifically and irreversibly inhibits the KRAS p.G12C mutant protein. This analysis investigated the impact of a high‐calorie high‐fat meal on the pharmacokinetics, safety, and tolerability of sotorasib in both healthy volunteers and patients with KRAS G12C advanced solid tumors. Each subject received a single oral dose of 360 or 960 mg of sotorasib under fasted conditions or with a high‐fat meal (fed conditions). The geometric least squares means (GLSM) ratios (fed/fasted) for 360 mg of sotorasib Cmax and AUCinf were 1.03 and 1.38, respectively, in healthy volunteers (N = 14). The GLSM ratios (fed/fasted) for Cmax and AUC0‐24h were 1.38 and 1.75, respectively, with 360 mg of sotorasib in cancer patients (N = 2). The GLSM ratios (fed/fasted) for Cmax and AUC0‐24h were 0.660 and 1.25, respectively, with 960 mg of sotorasib in cancer patients (N = 8). Sotorasib was well tolerated in fast and fed conditions. The impact of a high‐fat meal on sotorasib exposure is less than a 2‐fold increase or decrease in Cmax and AUCs.
Adhesion of Candida albicans on PTFE membranes used in guided bone regeneration
Authors: Al‐Asfour Adel , Karched Maribasappa , Qasim Syed Saad Bin , Zafiropoulos Gregor‐Georg 
Published: July 2024

AbstractObjectivesGuided bone regeneration (GBR) is a core procedure used to regenerate bone defects. The aim of the study was to investigate the adherence of Candida albicans on six commercially available polytetrafluoroethylene (PTFE) membranes used in GBR procedures and the subsequent clinical consequences.Materials and MethodsSix commercially available PTFE membranes were tested. Two of the membranes had a textured surface and the other four a plane, nontextured one. C. albicans (ATCC 24433) was cultured for 24 h, and its cell surface hydrophobicity was assessed using a modified method. C. albicans adhesion to membrane discs was studied by scanning electron microscopy (SEM) and real‐time polymerase chain reaction (PCR).ResultsC. albicans was found to be hydrophobic (77.25%). SEM analysis showed that C. albicans adherence to all membranes examined was characterized by patchy, scattered, and small clustered patterns except for one nontextured membrane with a most rough surface in which a thick biofilm was observed. Real‐time PCR quantification revealed significantly greater adhesion of C. albicans cells to PTFE membranes than the control membrane (p ≤ .001) with the membranes having a textured surface exhibiting the highest count of 2680 × 104 cells/ml compared to the count of 707 × 104 cells/mL on those with a nontextured one (p ≤ .001). One membrane with nontextured surface, but with most rough surface was found to exhibit the highest count of 3010 × 104 cells/ml (p ≤ .05).ConclusionThe results of this study indicate that C. albicans adhesion on membranes' surfaces depends on the degree of surface roughness and/or on the presence of a texture. Textured PTFE membranes and/or membranes high roughness showed significantly more adhered C. albicans cells. These findings can impact the surgeon's choice of GBR membrane and postoperative maintenance.
Simulating the Entire Clinical Process for an Implant‐Supported Fixed Prosthesis: In Vitro Study on the Vertical Implications of Implant‐Abutment Connections and Rotational Freedom
Authors: Zipprich Holger , Ecker Stefanie , Gutmann Pauline , Seidel Kathrin , Weigl Paul , Schlee Markus , Brandt Silvia 
Published: July 2024

ABSTRACTObjectivesThe aim of this in vitro study was to investigate whether and to what extent different scenarios of rotational freedom in different IAC designs affect the vertical dimension of a three‐part fixed partial denture (FPD). At the same time, the experimental setup should simulate all clinical and laboratory steps of the implementation of such an FPD as accurately as possible.Material and MethodsTwenty identical pairs of jaw models were fabricated from aluminum, each lower‐jaw model holding two implants with conical or flat IACs. Three impressions of each model were taken to fabricate stone casts and three‐unit FPDs. Three assembly scenarios were compared for the vertical position stability they offered for these FPDs, differing by how the sequential implant components (impression posts > laboratory analogs > abutments 1 > abutments 2) were aligned with the positional index of the IAC. In this way, a total of 60 stone casts and FPDs were fabricated and statistically analyzed for changes in vertical dimension (p < 0.05).ResultsRegardless of whether a conical/flat IAC was used (p > 0.05), significantly greater mean changes in vertical dimension were consistently (all comparisons p < 0.0001) found in a “worst‐case scenario” of component alignment alternating between the left‐ and right‐limit stop of the positional index (0.286/0.350 mm) than in a “random scenario” of 10 dentists and 10 technicians with varying levels of experience freely selecting the alignment (0.003/0.014 mm) or in a “best‐case scenario” of all components being aligned with the right‐limit stop (−0.019/0.005 mm).ConclusionsThe likelihood of integrating a superstructure correctly in terms of vertical dimension appears to vary considerably more with assembly strategies than with IAC designs. Specifically, our findings warrant a recommendation that all implant components should be aligned with the right‐limit stop of the positioning index.
Tailored Postsynthetic Nitration of a Hypercrosslinked Polymer for Single‐Step Ethylene Purification from a Ternary C2 Gas Mixture
Authors: Lee Su Min , Yun Hongryeol , Kang Minjung , Kim Hyojin , Kang Dong Won , Hong Chang Seop 
Published: July 2024

AbstractPurifying C2H4 from a ternary C2H2/C2H4/C2H6 mixture poses a substantial industrial challenge due to their close physical and chemical properties. In this study, we introduce an innovative design approach to regulate and optimize the nitration degree of a hypercrosslinked polymer to achieve targeted separation performance. We synthesized a porous organic polymer (HCP) using the solvent knitting method and carried out its postsynthetic nitration, resulting in HCP‐NO2‐1 and HCP‐NO2‐2 with different nitration degrees. Notably, the adsorption capacity shifted from C2H6 > C2H4 ≈ C2H2 for HCP to C2H2 > C2H6 > C2H4 for HCP‐NO2‐1 and to C2H2 > C2H4 ≈ C2H6 for HCP‐NO2‐2, demonstrating the controllable nature of the separation process via the polar nitro group insertion. Remarkably, HCP‐NO2‐1 exhibited a desirable, selective separation of C2H4 from the C2H6/C2H4/C2H2 mixture thanks to an exquisite combination of the acidic proton‐polar nitro group and nonpolar C−H⋅⋅⋅π interactions. Separation capability was further corroborated by computational simulations and breakthrough tests. This work marks a significant advancement as the first successful postsynthetic functionalization strategy for C2H4 purification from a ternary gas mixture among porous organic polymers.
IL‐6 and hsCRP predict cardiovascular mortality in patients with heart failure with preserved ejection fraction
Authors: Berger Martin , März Winfried , Niessner Alexander , Delgado Graciela , Kleber Marcus , Scharnagl Hubert , Marx Nikolaus , Schuett Katharina 
Published: July 2024

AbstractAimsInflammation accompanies heart failure (HF) and elevated levels of inflammatory biomarkers are linked to new onset of HF. However, whether the prognostic relevance of inflammatory biomarkers is different in HF with reduced (HFrEF) and preserved ejection fraction (HFpEF) is unclear. The aim of the current study is to explore the role of inflammation on the mortality risk in patients with HF.MethodsWe analysed interleukin‐6 and hsCRP levels by ELISA and immunonephelometry, respectively, in HFpEF and HFrEF patients referred for coronary angiography and assessed the prognostic value in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study.ResultsHF was present in 1086 patients (N = 506 HFpEF; N = 580 HFrEF; mean age 65 ± 10 years; 28% female). Increasing IL‐6 levels were significantly associated with increased CV mortality in HFpEF [1.5 (95% CI: 1.1–2.2), P = 0.018] but not HFrEF [HR 1.3 (95% CI: 1.0–1.7), P = 0.06] patients. High‐sensitive CRP followed a similar pattern but failed to reach statistical significance after full‐adjustment (HFpEF: HR 1.4 95%C I: 1.0–2.0; P = 0.065; HFrEF HR: 1.0 95% CI: 0.7–1.3; P = 0.800). Interaction analysis in patients stratified by IL‐6 and N terminal pro brain natriuretic peptide (NT‐proBNP) above and below the median revealed a stepwise increase in CV‐mortality in HFpEF (P = 0.036) but not HFrEF patients (P = 0.220). To investigate the relationship between IL‐6 and NT‐proBNP, we assessed the genetic IL6‐Receptor variant p.Asp358Ala (rs2228145) which is linked to impaired IL‐6 receptor signalling. Homozygous carriers with HFpEF but not HFrEF exhibited significantly lower NT‐pro‐BNP levels compared with wildtype carriers (HFpEF 779 pg/mL ± 787 vs. 1180 pg/ mL ± 1532; P = 0.008; HFrEF 2289 pg/ mL ± 3439 vs. 2326 pg/ mL ± 3386; P = 0.94), raising the hypothesis that IL‐6 signalling may play a pathophysiological role in HFpEF.ConclusionsThese data suggest a predictive value of elevated IL‐6 for CV‐mortality in HFpEF but not in HFrEF patients.
Pulmonary congestion assessed by lung ultrasound in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation: Prevalence and prognostic implications
Authors: Lillo Rosa , Cangemi Stefano , Graziani Francesca , Locorotondo Gabriella , Pedicino Daniela , Aurigemma Cristina , Romagnoli Enrico , Malara Silvia , Meucci Maria Chiara , Iannaccone Giulia , Bianchini Francesco , Nesta Marialisa , Bruno Piergiorgio , Lombardo Antonella , Trani Carlo , Burzotta Francesco 
Published: July 2024

AbstractAimsLung ultrasound (LUS) is a sensitive tool to assess pulmonary congestion (PC). Few data are available on LUS‐PC evaluation in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). The aim of this study was to assess the prevalence and prognostic impact of LUS‐PC in patients with severe AS before and after TAVI.Methods and resultsWe designed a single‐centre prospective study in patients referred for TAVI for severe AS (ClinicalTrials.gov identification number: NCT05024942). All patients underwent echocardiography and LUS (according to a simplified 8‐zone scanning protocol) the day before and within 72 h after the procedure. The primary endpoint was the composite of all‐cause mortality, hospitalization for heart failure and urgent medical visits for worsening dyspnoea at 12‐month follow‐up. A total of 127 patients were enrolled (mean age 81.1 ± 5.8 years; 54.3% female). Pre‐TAVI LUS‐PC was documented in 65 patients (51%). After TAVI, the prevalence of LUS‐PC significantly decreased as compared to pre‐TAVI evaluation, being documented in only 28 patients (22% vs. 51%, p < 0.001) with a median B‐lines score of 4 (interquartile range [IQR] 0–11) versus 11 (IQR 6–19) pre‐TAVI (p < 0.001). During a median follow‐up of 12 (12–17) months, 25 patients (19.6%) met the composite endpoint. On multivariable Cox regression analysis, pre‐TAVI LUS‐PC was independently associated with cardiovascular events (hazard ratio 2.764, 95% confidence interval 1.114–6.857; p = 0.028).ConclusionsLung ultrasonography reveals a high prevalence of PC in patients with severe AS undergoing TAVI, which is significantly reduced by the procedure. Pre‐TAVI PC, measured by LUS, is an independent predictor of 1‐year clinical outcome.
Multicenter retrospective study of patients with PCDH19‐related epilepsy: The first Hungarian cohort
Authors: Kovacs Monika , Fogarasi Andras , Hegyi Marta , Siegler Zsuzsanna , Kelemen Anna , Mellar Monika , Orbok Anna , Simon Gabor , Farkas Kristof , Bessenyei Monika , Hollody Katalin 
Published: July 2024

AbstractObjectivePCDH19‐related epilepsy occurs predominantly in girls and is caused by pathogenic variant of the protocadherin‐19 gene. The initial seizures usually develop in association with fever, begin on average at 15 months of age, and often occur in clusters. Autistic symptoms, intellectual disability, and sleep disturbance are often associated.MethodsIn our retrospective, multicenter study, we reviewed clinical data of nine children with epilepsy genetically confirmed to be associated with PCDH19.ResultsIn the Hungarian patient population aged 0–18 years, the prevalence of PCDH19‐related epilepsy was found to be lower (1/100000 live births in females) than the reported international data (4–5/100000 live births in females). Four of our nine patients had positive family history of epilepsy (cousins, sister, and mother). We assessed brain anomalies in three patients (in one patient focal cortical dysplasia and left anterior cingulate dysgenesis, and in two children right or left hippocampal sclerosis) and in another three cases incidentally identified benign alterations on brain MRI were found. The first seizure presented as a cluster in seven out of nine children. In seven out of nine cases occurred status epilepticus. Six out of nine children had autistic symptoms and only one child had normal intellectual development. Seven of our patients were seizure free with combined antiseizure medication (ASM). The most effective ASMs were levetiracetam, valproate, and clobazam.SignificanceThe prevalence of PCDH19‐related epilepsy is presumably underestimated because of the lack of widely performed molecular genetic evaluations. Molecular genetic testing including PCDH19 pathogenic variants is recommended for female patients with an onset of seizures before the age of 3 years.
The effect of myo‐inositol supplementation on AMPK/PI3K/AKT pathway and insulin resistance in patients with NAFLD
Authors: Aghajani Taha , Arefhosseini Sara , Ebrahimi‐Mameghani Mehrangiz , Safaralizadeh Reza 
Published: July 2024

AbstractInsulin resistance (IR) is the pivotal pathological hit in non‐alcoholic fatty liver disease (NAFLD). There is specific attention to combination/conjugated therapies for NAFLD management. As myo‐inositol (MI) has been shown to improve IR in animal and human trials, this study aimed to investigate the influence of MI supplementation on glycemic response and IR through AMPK/PI3K/AKT signaling pathway in obese patients with NAFLD. This double‐blinded placebo‐controlled randomized clinical trial was conducted on 48 obese (BMI = 30–40 kg/m2) patients with NAFLD who were randomly assigned to receiving either MI (4 g/day) or placebo (maltodextrin 4 g/day) group for 8 weeks. Before and after the trial, weight, height, serum glycemic parameters (inc. fasting glucose and insulin) as well as IR indices were assessed. Moreover, the mRNA expression levels of AMPK, AKT, and PDK‐1 in peripheral blood mononuclear cells (PBMCs) were determined. MI supplementation resulted in significant increases in the fold changes of AMPK, AKT, and PDK‐1 genes (p = .019, p = .049, and p = .029, respectively). Indeed, IR improved in terms of all IR indices in MI group (p < .05) after adjusting for the confounders, apart from quantitative insulin sensitivity check index (QUICKI). The results showed that MI supplementation not only upregulated AMPK, AKT, and PDK‐1 mRNA in PBMCs but also improved IR in obese patients with NAFLD.