bluuebunny/crossref_metadata_2025_split huggingface dataset:
Possible effects of plasminogen activator inhibitor‐1 on promoting angiogenesis through matrix metalloproteinase 9 in advanced mycosis fungoides
Authors: Fujimura Taku , Ohuchi Kentaro , Ikawa Tetsuya , Kambayashi Yumi , Amagai Ryo , Furudate Sadanori , Asano Yoshihide 
Published: January 2024

AbstractMycosis fungoides (MF) progresses slowly before advancing to skin tumors followed by lymph node and visceral involvement. Among MF progression, stage IIB is an initial time point of tumor formation in MF. Since MF in tumor stage possess abundant blood vessels, it is important to evaluate the pro‐angiogenic factors before and after MF in stage IIB. In this report, we investigated pro‐angiogenic soluble factors in MF patients, as well as its pro‐angiogenetic effects on tumor cells and stroma cells. We first evaluated the serum levels of pro‐angiogenic factors in 9 MF patients without tumor formation and 8 MF patients with tumor formation. Among them, the serum MMP‐9 and plasminogen activator inhibitors 1 (PAI‐1) was significantly increased in MF with tumor formation compared in MF without tumor formation, leading to favorable formation of human dermal microvascular endothelial cells tube networks. Moreover, PAI‐1 stimulation significantly increased the mRNA expression and protein production MMP‐9 on monocytes derived M2 macrophages and HUT‐78. Furthermore, since MMP‐9 production from tumor cells as well as stromal cells is suppressed by bexarotene, we evaluate the baseline serum pro‐angiogenic factors including MMP‐9 in 16 patients with advanced cutaneous T cell lymphoma treated with bexarotene. The serum levels of MMP‐2 and MMP‐9 was significantly increased in bexarotene non‐responded patients compared to responded patients. Our present study suggested the significance of MMP‐9 and PAI‐1 for the progression of MF stage toward to the tumor stage, and could be a therapeutic target in future.
A Delphi study to determine the epidemiology and clinical management of patients treated with HDMTX who develop methotrexate (MTX) delayed elimination in France, Germany, Italy, and the UK
Authors: Bielack Stefan , Fox Christopher P. , Hoang‐Xuan Khê , Giró‐Perafita Ariadna , Rizzari Carmelo 
Published: January 2024

AbstractIntroductionHigh‐dose methotrexate (HDMTX) is administered for the treatment of some malignancies. Serious complications after the administration of HDMTX are rare, but occasionally MTX may precipitate in the renal tubes causing a delayed elimination leading to renal, multiorgan toxicities and to life‐threatening complications. This study aims to estimate the incidence and clinical management of delayed MTX elimination in France, Germany, Italy, and the UK.MethodsTwelve haemato‐oncology and pediatric oncology clinical experts from leading European hospitals participated in the study. A two‐round Delphi methodology was used to gather data on different variables relevant to evaluate the HDMTX induced‐toxicity impact. For quantitative data, median and interquartile ranges were calculated. Data on prevalence was calculated considering the number of patients in each hospital and the population they cover, and then, extrapolated to the country population.ResultsThe total number of patients treated annually with HDMTX in France, Germany, Italy, and the UK is estimated in 7155. Of these, 16% are estimated to develop delayed MTX elimination and around 9% may develop HDMTX‐induced acute kidney injury (AKI). Leucovorin, hyperhydration and urine alkalinization are applied to prevent MTX toxicity and precipitation whilst glucarpidase, hemofiltration and hemodialysis are being used for persisting toxic MTX serum levels. Grade 3 systemic toxicities are common in these patients, hematologic and gastrointestinal being the most common ones.ConclusionsThis report provides expert clinical practice experience and opinion of the incidence and management of HDMTX‐delayed elimination in France, Germany, Italy and the UK, thereby contributing to the evidence available on this relevant medical condition which can be life‐threatening.
A systematic methodology for epicardial and epiaortic echocardiography in swine research models
Authors: Galbas Michelle C. , Meissner Florian , Asmussen Alexander , Straky Hendrik C. , Schimmel Marius , Reuter Johanna , Grundmann Sebastian , Czerny Martin , Bothe Wolfgang 
Published: January 2024

AbstractBackgroundPerioperative echocardiography is of paramount importance during cardiac surgery. Nonetheless, in the experimental large‐animal setting, it might be challenging obtaining optimal imaging when using conventional imaging acquisition techniques, such as transthoracic and transesophageal screenings. Open‐chest surgery allows epicardial echocardiographic assessment with direct contact between probe and heart, thus providing superior quality. Standard protocols regarding the use of epicardial ultrasound in swine for research purposes are lacking.MethodsEpicardial echocardiography was performed in 10 female German Landrace pigs undergoing cardiac surgery. A structured and comprehensive protocol for epicardial echocardiography was elaborated including apical, ventricular long and short axis, as well as epiaortic planes. All experiments were approved by the local board for animal welfare and conducted in accordance with the German animal protection law (TierSchG) and the ARRIVE guidelines.ConclusionsSystematic protocols using epicardial echocardiography may serve as an additional tool to assess cardiac dimensions and function in experimental scenarios with swine models.
Advances in DNA walking nanomachine‐based biosensors
Authors: Shen Bo , Li Li , Guo Minghui , Li Xinyu , Fan Yunpeng , Li Xinmin , Chen Rui , Ding Shijia , Cheng Wei 
Published: January 2024

AbstractThe field of DNA nanotechnology has evolved beyond the realm of controllable movements and randomly shaped nanostructures, now encompassing a diverse array of nanomachines, each with unique nanostructures and biofunctional attributes. These DNA nanostructures boast exceptional characteristics such as programmability, integrability, biocompatibility, and universality. Among this variety, DNA walking nanomachines have emerged as one of the most prominent nanomotors, distinguished by their ingenious design and comprehensive functionality. In recent times, these DNA walkers have witnessed remarkable advancements in areas ranging from nanostructural designs to biological applications, including the creation of sophisticated biosensors capable of efficiently detecting tumor‐related biomarkers and bioactive substances. This review delves into the operational mechanisms of DNA walking nanomachines, which are driven by processes such as protease and DNAzyme action as well as strand displacement and photoactivated reactions. It further provides a comprehensive overview of DNA walking nanomachines with different dimensional (1D, 2D, and 3D) walking tracks. A subsequent section introduces the biosensing applications of DNA walking nanomachines including electrochemical, optical, and other biosensors. The review concludes with a forward‐looking perspective on the novel advancements and challenges in developing DNA walking nanomachine‐based biosensors.
Robust aortic media adhesion using hydrophobically modified Alaska pollock gelatin‐based adhesive for aortic dissections
Authors: Ito Temmei , Mizuta Ryo , Ito Shima , Taguchi Tetsushi 
Published: January 2024

AbstractType‐A aortic dissection is an acute injury involving the delamination of the aorta at the parts of the aortic media. Aldehyde crosslinker‐containing glues have been used to adhere to the media of the dissected aorta before joining an artificial graft. These glues effectively adhere to the aortic media; however, they show low biocompatibility due to the release of aldehyde compounds. In this study, we report innovative adhesives based on hydrophobically modified Alaska pollock gelatin (hm‐ApGltn) with different alkyl or cholesteryl (Chol) groups that adhere to the media of the dissected aorta by combining hm‐ApGltns with a biocompatible crosslinker, pentaerythritol poly(ethylene glycol) ether tetrasuccinimidyl glutarate. The modification of alkyl or Chol groups contributed to enhanced adhesion strength between porcine aortic media. The adhesion strength increased with increasing modification ratios of alkyl groups from propanoyl to dodecanoyl groups and then decreased at a modification ratio of ~20 mol %. Porcine aortic media adhered using 7.5Chol‐ApGltn adhesive showed stretchability even when expanded and shrunk vertically by 25% at least five times. Hm‐ApGltn adhesives subcutaneously injected into the backs of mice showed no severe inflammation and were degraded during the implantation period. These results indicated that hm‐ApGltn adhesives have potential applications in type‐A aortic dissection.
Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses
Authors: van de Wakker Simonides Immanuel , Bauzá‐Martinez Julia , Ríos Arceo Carla , Manjikian Herak , Snijders Blok Christian Jamie Bernard , Roefs Marieke Theodora , Willms Eduard , Maas Renee Goverdina Catharina , Pronker Matti Feije , de Jong Olivier Gerrit , Wu Wei , Görgens André , El Andaloussi Samir , Sluijter Joost Petrus Gerardus , Vader Pieter 
Published: January 2024

AbstractCardiac progenitor cell (CPC)‐derived small extracellular vesicles (sEVs) exhibit great potential to stimulate cardiac repair. However, the multifaceted nature of sEV heterogeneity presents a challenge in understanding the distinct mechanisms underlying their regenerative abilities. Here, a dual‐step multimodal flowthrough and size‐exclusion chromatography method was applied to isolate and separate CPC‐derived sEV subpopulations to study the functional differences related to cardiac repair responses. Three distinct sEV subpopulations were identified with unique protein profiles. Functional cell assays for cardiac repair‐related processes demonstrated that the middle‐sized and smallest‐sized sEV subpopulations exhibited the highest pro‐angiogenic and anti‐fibrotic activities. Proteasome activity was uniquely seen in the smallest‐sized subpopulation. The largest‐sized subpopulation showed no effect in any of the functional assays. This research uncovers the existence of sEV subpopulations, each characterized by a distinct composition and biological function. Enhancing our understanding of sEV heterogeneity will provide valuable insights into sEV mechanisms of action, ultimately accelerating the translation of sEV therapeutics.
MRI Assessment of Cerebral White Matter Microvascular Hemodynamics Across the Adult Lifespan
Authors: Damestani Nikou L. , Jacoby John , Michel Christa B. , Rashid Barnaly , Salat David H. , Juttukonda Meher R. 
Published: January 2024

BackgroundChanges in cerebral hemodynamics with aging are important for understanding age‐related variation in neuronal health. While many prior studies have focused on gray matter, less is known regarding white matter due in part to measurement challenges related to the lower vascular density in white matter.PurposeTo investigate the impact of age and sex on white matter hemodynamics in a Human Connectome Project in Aging (HCP‐A) cohort using tract‐based spatial statistics (TBSS).Study TypeRetrospective cross‐sectional.PopulationSix hundred seventy‐eight typically aging individuals (381 female), aged 36–100 years.Field Strength/SequenceMulti‐delay pseudo‐continuous arterial spin labeling (ASL) and diffusion‐weighted pulsed‐gradient spin‐echo echo planar imaging sequences at 3.0 T.AssessmentA skeleton of mean fractional anisotropy (FA) was produced using TBSS. This skeleton was used to project ASL‐derived cerebral blood flow (CBF) and arterial transit time (ATT) measures onto white matter tracts.Statistical TestsGeneral linear models were applied to white matter FA, CBF, and ATT maps, while covarying for age and sex. Threshold‐free cluster enhancement multiple comparisons correction was performed for the effects of age and sex, thresholded at PFWE < 0.05. CBF, ATT, and FA were compared between sex for each tract using analysis of covariance, with multiple comparisons correction for the number of tracts at PFDR < 0.05.ResultsSignificantly lower white matter CBF and significantly prolonged white matter ATTs were associated with older age. These effects were widespread across tracts for ATT. Significant (PFDR < 0.05) sex differences in ATT were observed across all tracts, and significant sex differences in CBF were observed in all tracts except the bilateral uncinate fasciculus. Females demonstrated significantly higher CBF compared to males across the lifespan. Few tracts demonstrated significant sex differences in FA.Data ConclusionThis study identified significant sex‐ and age‐associated differences in white matter hemodynamics across tracts.Evidence Level3Technical EfficacyStage 3
Association between chronic viral infection‐related hospitalization and risk of cardiovascular disease: A population‐based cohort study
Authors: Yang Luoyao , Lu Zhen , Bian Junye , Li Feng , Zou Huachun 
Published: January 2024

AbstractChronic viral infection induces immunosenescence and systemic low‐grade inflammation, leading to worsened long‐term outcomes. We sought to explore the short‐ and long‐term effects of chronic viral infection on cardiovascular disease (CVD). Based on UK Biobank data, exposed group was identified as individuals who had chronic virus infection‐related hospitalization (IRH). Unexposed group was randomly selected, matched by 5‐year age interval, sex, and Charlson comorbidity index at a ratio up to 1:10. Restricted cubic splines were used to model time‐varying effects of IRH in nonproportional Cox models. A cut‐off value of 5 years was recorded and used in piecewise Cox proportional hazards models as we estimated short‐ and long‐term effects of IRH on CVD. A total of 2826 exposed participants and 28 212 matched unexposed participants were included. Chronic viral IRH was associated with increased risk of CVD (0–5 years: hazard ratio, 1.57 [95% confidence interval: 1.32, 1.87] and 5+ years: 1.31 [1.06, 1.61]). Elevated risk of stroke was only observed within the initial 5‐year follow‐up (0–5 years: 1.91 [1.30, 2.81]). The short‐ and long‐term associations were observed in herpes or hepatitis virus IRH with risk of CVD (all p < 0.05). Subgroup analysis revealed long‐term association between chronic viral IRH and CVD among female (5+ years: 1.68 [1.27, 2.22]) but not among male. The association between chronic viral infection and elevated CVD risk appeared to be stronger among individuals who did not take cholesterol‐lowering medication, antithrombotic medication, or certain antihypertensive medications (all p for interaction < 0.05). The risk of CVD event remained persistently higher within and over 5 years following chronic viral IRH, especially in individuals infected with herpes and hepatitis virus.
Saliva‐based Proteinase K method: A rapid and reliable diagnostic tool for the detection of SARS‐COV‐2 in children
Authors: Kim Min Jung , Park Pil‐gu , Hwang Su Jin , Bang Seung Jun , Jung Jae Hwa , Kown Eun Bin , Sul Eun Kyung , Song Kyung Chul , Choi Joon‐sik , Han Kyeo Re , Lee Hye Young , Kim Dong Hyun , Lee Jae Myun 
Published: January 2024

AbstractEarly and accurate detection of viruses in children might help prevent transmission and severe diseases. In this study, the severe acute respiratory syndrome coronavirus 2 (SARS‐COV‐2) detection in children was evaluated using saliva specimens with a Proteinase K (PTK)‐based RNA preparation, as saliva collection is a simple and noninvasive procedure, even in young children, with fewer concerns about sample contamination. The saliva‐based PTK and the conventional paired nasopharyngeal aspiration (NPA)‐based detection methods were compared between COVID‐19‐positive and ‐negative children. In addition, the detection rate for SARS‐COV‐2 and the difference between admission and discharge by the saliva‐based PTK method was tested in COVID‐19 patients. The diagnostic accuracy of the saliva‐based PTK method was 98.8% compared to NP swab‐based reverse transcriptase polymerase chain reaction. Saliva samples showed high sensitivity (94.1%) and specificity (100%) when using the PTK method. Furthermore, the saliva‐based PTK method significantly reduced the test processing time by 2 h. Notably, Ct values at discharge increased in saliva samples compared with those at admission, which might indicate patients' clinical conditions or virus activity. In conclusion, the saliva‐based PTK implemented in this study streamlines RNA extraction, making the process faster, safer, and more cost‐effective, demonstrating that this method is a rapid and reliable diagnostic tool for SARS‐CoV‐2 detection in children.
Coinfections with additional oncoviruses in HPV+ individuals: Status, function and potential clinical implications
Authors: Dai Lu , Wilson Lillie G. , Nakagawa Mayumi , Qin Zhiqiang 
Published: January 2024

AbstractOncovirus infections account for an estimated 12%−20% of human cancers worldwide. High‐risk human papillomavirus (HPV) infection is the etiological agent of some malignancies such as cervical, oropharyngeal, anal, penile, vaginal, and vulvar cancers. However, HPV infection is not the only cause of these cancers or may not be sufficient to initiate cancer development. Actually, certain other risk factors including additional oncoviruses coinfections have been reported to increase the risk of patients exposed to HPV for developing different HPV‐related cancers. In the current review, we summarize recent findings about coinfections with different oncoviruses in HPV+ patients from both clinical and mechanistic studies. We believe such efforts may lead to an interesting direction for improving our understanding and developing new treatments for virus‐induced cancers.
Rainstorm variability is mainly influenced by the southwest monsoon in the Hanjiang River basin of China during 1985–2020
Authors: Jing Yuanyuan , Shi Peijun , Zhang Gangfeng , Sun Shao 
Published: January 2024

AbstractThe extreme precipitation in China is greatly influenced by the East Asian summer monsoon, which can be divided into two components: the southeast monsoon (SEM) and the southwest monsoon (SWM). The Hanjiang River basin (HJB), a representative monsoon‐influenced basin in China, is alternately influenced by the southwest monsoon and southeast monsoon throughout the year. However, the specific relationship between rainstorms and monsoons, and the relative contribution of different monsoons, remains unclear in the HJB. Using multiple datasets, this study analysed the variability of various rainstorm types in the HJB during 1985–2020, investigated their relationships with different monsoon indicators and assessed the contribution of monsoons on the rainstorm variance. The results reveal a nonsignificant increasing trend in rainstorms within the basin, the severe convective rainstorm days accounted for a high proportion of the total rainstorm days, and the spatiotemporal characteristics of different rainstorm types are different. The rainstorm indicators are significantly correlated with the monsoon within the HJB and are positively correlated with the SWM, particularly its intensity. The SEM exhibits a weak correlation with rainstorms and has limited explanation for the variance in rainstorms. The intensity of SWM within the HJB shows a significant positive correlation with all rainstorm indicators. It is also detected as the most important indicator for explaining the interannual variation in rainstorms, explaining 41.97% and 39.45% of the variance in daily rainstorm frequency and totals, which comprises more than half of the total explanatory portion. The explanation of circulation factors for the variance in daily rainstorms is higher than that for severe convective rainstorms. In addition to monsoons, the Pacific Decadal Oscillation and the Southern Oscillation Index also have a great contribution to the rainstorm variability in the HJB.
Never Ending Stories? Hebrew Writers' Creative Journey in the Second Half of Life
Authors: Aharoni Lir Shlomit , Ayalon Liat 
Published: January 2024

ABSTRACTThis qualitative study explored the relationship between creativity, time, age, and the literary world among 16 award‐winning Israeli writers in the second half of their lives. Based on data collected through in‐depth interviews with the participants, the findings indicate that the writers' creativity in the second half of life was linked to Preservation, Growth, and Decline, leading to four interrelated dimensions: (a) preserving youth through creativity, (b) enhancing creativity over time, (c) navigating creativity, acclaim, and ageism, and (d) managing creativity amidst a changing world. The study found that the writers' creativity was enhanced over time, as they gained experience and developed their skills. However, some writers experienced a decline in stamina or their ability to write long novels. The study also found that the writers' experiences of acceptance from the literary world and the audience changed over time. Some writers continued to receive acclaim and attention, while others experienced ageism and a decline in the audience's interest in their work.
Estimating the burden of skin diseases using patient‐reported daily time trade‐off as a measure of disease impact and unmet needs
Authors: Andersen Yuki M. F. , Zachariae Claus , Thomsen Simon Francis , Thyssen Jacob Pontoppidan , Egeberg Alexander 
Published: January 2024

AbstractBackgroundDermatological diseases may cause significantly impaired quality of life, however patient reported outcomes are often disease specific, and not comparable across diseases.ObjectivesTo examine daily time trade‐off (dTTO), as a measure of disease burden.MethodsAn epidemiological study based on patient data from Danish Skin Cohort (prospective cohort of Danish dermatology patients) was conducted. Data were linked with routinely collected data from Statistics Denmark. We included adults with either alopecia areata (AA), atopic dermatitis (AD), hidradenitis suppurative (HS), psoriasis, or rosacea. All patients with a diagnostic code listed above were invited to participate. The primary outcome was defined as a dTTO of more than 30 minutes daily.ResultsA total of 680, 1605, 611, 1664, and 1698 adults with AA, AD, HS, psoriasis, and rosacea, respectively, were included. In multiple regression models, patients with AA were most likely to have a dTTO of more than 30 minutes, followed by patients with HS, AD, psoriasis and rosacea. A total of 33.7% (AA), 29.3% (HS), 14.6% (AD), 11.1% (psoriasis), and 9.0% (rosacea) of patients were willing to spend two hours or more per day. The dTTO correlated with disease severity and DLQI across disease groups.ConclusionsPatients with AA, followed by HS were willing to spend most time on treatment, possibly reflecting unmet needs in these patient groups. Daily TTO correlated with perceived disease severity in all groups and may be a useful measure of dermatological disease burden.