bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plum blossom low molecular weight polypeptide protects HaCaT cells against UVB‐induced oxidative damage in vitro and underlying mechanism
Authors: Chen Zhixiong , Cao Ping , Zhu Tingheng , Yan Cui , Zheng Zhongbo , Yao Hong 
Published: January 2024

AbstractBackgroundIncreasing amounts of ultraviolet radiation occur as ozone depletion causes the earth's ozone layer to be destroyed, making antioxidant efficacy a research hotspot. Previous studies on plum blossom have mostly focused on Volatile Oils, Flavonoids, Phenylpropanoids, and other compounds, whereas few studies have focused on low molecular weight polypeptide (LMWP) of plum blossom. This research provides a reference for the deep processing and utilization of plum blossom.Objectives(a) Plum blossom low molecular weight polypeptides protect HaCaT cells against UVB‐induced oxidative damage in vitro and the underlying mechanism. (b) Improve the theoretical basis for the intense processing and utilization of plum blossom.MethodsThe safe concentration of LMWP and the survival rate of HaCaT cells were determined using the CCK‐8 experiment. The fluorescence intensity of reactive oxygen species (ROS) was identified using the dichlorofluorescin diacetate (DCFH‐DA) method; Superoxide dismutase (SOD) and malondialdehyde (MDA) concentrations were measured in ruptured cells; Western blot analysis was used to examine the expression levels of three proteins: nuclear factor E2‐related factor 2 (Nrf2), heme oxygenase 1 (HO‐1), and benzoquinone oxidoreductase 1 (NQO‐1).ResultsIt was noted that a certain concentration of LMWP could promote cell proliferation. In oxidatively damaged HaCaT cells, SOD levels and survival rates were markedly reduced, but ROS and MDA levels were elevated. However, after treatment with LMWP, the survival rate of the cells and SOD levels were markedly increased, and the levels of ROS and MDA were markedly decreased. As shown by Western blotting, the model group exhibited lower levels of Nrf2, HO‐1, and NQO‐1 expression than the control group, whereas LMWP‐treated cells had significantly higher levels of Nrf2, HO‐1, and NQO‐1 expression than their model‐treated counterparts.ConclusionsLMMP can effectively protect HaCaT cells against oxidative damage in vitro induced by UVB, and the underlying mechanism is linked to the activation of the transcription factor Nrf2.
Lip color diversity: An intricate study
Authors: Vergnaud Héloïse , Charton Zoé , Blumenthal David , Couturaud Virginie , Le Fur Marie , Loescher Eléonore , Caisey Laurence , Gazano Germaine 
Published: January 2024

AbstractBackgroundLip investigations and characterizations in the literature are less prevalent than for skin, particularly on the topic of color diversity. However, as the consumer demand increases for a nude lip makeup result, that is, shades close to the bare lip color, the identification and modification of lip color is essential for the cosmetic industry.ObjectiveThe objective was to highlight lip color diversity among three ethnicities (Caucasian, African and Hispanic), through the use of a spectral color measurement device especially adapted to the lip area, and to consider lip color ethnic specificities and overlaps.Materials and MethodsThe inferior natural lip color was measured with a full‐face hyperspectral imaging system, SpectraFace (Newtone Technologies, Lyon, France), on 410 healthy women aged 19 to 68 (Caucasian French, Caucasian American, African American, and Hispanic American women). A hierarchical ascending classification, was deployed to determine clusters based on the lip colorimetric parameters along two strategies to identify the best statistical analysis to preserve the lip color diversity.ResultsLip color is a continuous color space, with great intra‐ethnic and inter‐ethnic diversity, especially for African American women in terms of chroma and lightness. Among the two strategies of data analysis, our two‐step statistical clustering analysis yielded 11 groups (i.e., 11 lip tones), revealing an accurate representation of the scope of diversity, but also of the overlaps.ConclusionThe 11 lip tones/colors could potentially serve as target shades for the development of a more diverse and inclusive range of lip cosmetics, such as nude lipsticks.
Figurate erythema in 11 Eastern European sphynx cats
Authors: Mendoza‐Kuznetsova Ekaterina , Lokianskiene Viktorija , Matise‐VanHoutan Ilze , Fiskovich Olesya , Olivry Thierry 
Published: January 2024

AbstractBackgroundIn humans, figurate erythema (FE) represents a heterogenous group of dermatoses with circular or serpiginous erythematous skin lesions; FE has not been reported in cats.ObjectivesTo report clinical and histological characteristics and outcomes of FE in sphynx cats from Baltic sea‐bordering countries.AnimalsEleven client‐owned sphynx cats with FE.Materials and MethodsWe recruited cases meeting the following criteria: (i) a sphynx breed, (ii) FE with or without scaling, (iii) a chronic, waxing‐and‐waning course lasting longer than a month and (iv) an absence of other skin diseases.ResultsOf 11 cats, there were seven Donskoys, one Peterbald, one Ukrainian Levkoy and two presumed Canadian sphynxes; all except one were males, and the age of onset was <12 months in eight cats. Skin lesions lasted between 1.2 and 56 months, and they consisted of erythematous plaques with a linear‐to‐serpiginous, annular, gyrate or iris configuration predominating on the trunk and extremities. Scaling was often seen trailing the edge of the centrifugally expanding erythema. All cats were otherwise asymptomatic or mildly pruritic. Dermatophytosis was ruled out by special stains and/or fungal cultures in eight cats. Microscopic lesions revealed focal, mild‐to‐moderate epidermal hyperplasia and hyperkeratosis, minimal‐to‐mild dysplasia and subepidermal collagen smudging. Special stains were negative for dermatophytes. The clinical remission of FE was not achieved with diet changes or medical interventions; yet, a spontaneous, transient, partial or complete improvement occurred in most cats.Conclusion and Clinical RelevanceThis is the first report of FE in sphynx cats from Eastern Europe.
Prenatal maternal glucocorticoid exposure modifies sperm miRNA profiles across multiple generations in the guinea‐pig
Authors: Hamada Hirotaka , Casciaro Christopher , Moisiadis Vasilis G. , Constantinof Andrea , Kostaki Alisa , Matthews Stephen G. 
Published: January 2024

AbstractMaternal stress and glucocorticoid exposure during pregnancy have multigenerational effects on neuroendocrine function and behaviours in offspring. Importantly, effects are transmitted through the paternal lineage. Altered phenotypes are associated with profound differences in transcription and DNA methylation in the brain. In the present study, we hypothesized that maternal prenatal synthetic glucocorticoid (sGC) exposure in the F0 pregnancy will result in differences in miRNA levels in testes germ cells and sperm across multiple generations, and that these changes will associate with modified microRNA (miRNA) profiles and gene expression in the prefrontal cortex (PFC) of subsequent generations. Pregnant guinea‐pigs (F0) were treated with multiple courses of the sGC betamethasone (Beta) (1 mg kg–1; gestational days 40, 41, 50, 51, 60 and 61) in late gestation. miRNA levels were assessed in testes germ cells and in F2 PFC using the GeneChip miRNA 4.0 Array and candidate miRNA measured in epididymal sperm by quantitative real‐time PCR. Maternal Beta exposure did not alter miRNA levels in germ cells derived from the testes of adult male offspring. However, there were significant differences in the levels of four candidate miRNAs in the sperm of F1 and F2 adult males. There were no changes in miRNA levels in the PFC of juvenile F2 female offspring. The present study has identified that maternal Beta exposure leads to altered miRNA levels in sperm that are apparent for at least two generations. The fact that differences were confined to epididymal sperm suggests that the intergenerational effects of Beta may target the epididymis.
imageKey points
Paternal glucocorticoid exposure prior to conception leads to profound epigenetic changes in the brain and somatic tissues in offspring, and microRNAs (miRNAs) in sperm may mediate these changes.
We show that there were significant differences in the miRNA profile of epididymal sperm in two generations following prenatal glucocorticoid exposure that were not observed in germ cells derived from the testes.
The epididymis is a probable target for intergenerational programming.
The effects of prenatal glucocorticoid treatment may span multiple generations.
Challenging the gold standard: the limitations of molecular assays for detection ofMycobacterium tuberculosisheteroresistance
Authors: Danchuk Sarah N , Solomon Ori E , Kohl Thomas Andreas , Dreyer Viola , Barilar Ivan , Utpatel Christian , Niemann Stefan , Soolingen Dick van , Anthony Richard , van Ingen Jakko , Michael Joy S , Behr Marcel A 
Published: January 2024

ObjectivesHeteroresistant infections are defined as infections in which a mixture of drug-resistant and drug-susceptible populations are present. InMycobacterium tuberculosis(M. tb), heteroresistance poses a challenge in diagnosis and has been linked with poor treatment outcomes. We compared the analytical sensitivity of molecular methods, such as GeneXpert and whole genome sequencing (WGS) in detecting heteroresistance when compared with the ‘gold standard’ phenotypic assay: the agar proportion method (APM).MethodsUsing two rounds of proficiency surveys with defined monoresistant BCG strains and mixtures of susceptible/resistantM. tb, we determined the limit of detection (LOD) of known resistance associated mutations.ResultsThe LOD for rifampin-R (RIF-R) detection was 1% using APM, 60% using GeneXpert MTB/RIF, 10% using GeneXpert MTB/RIF Ultra and 10% using WGS. While WGS could detect mutations beyond those associated with RIF resistance, the LOD for these other mutations was also 10%. Additionally, we observed instances where laboratories did not report resistance in the majority population, yet the mutations were present in the raw sequence data.ConclusionThe gold standard APM detects minority resistant populations at a lower proportion than molecular tests.Mycobacterium bovisBCG strains with defined resistance and extracted DNA fromM. tbprovided concordant results and can serve in quality control of laboratories offering molecular testing for resistance. Further research is required to determine whether the higher LOD of molecular tests is associated with negative treatment outcomes.
Anti-inflammatory effects of sericin and swimming exercise in treating experimental Achilles tendinopathy in rat
Authors: Gundogdu Koksal , Kılıc Erkek Ozgen , Gundogdu Gulsah , Sayin Dilek , Abban Mete Gulcin 
Published: January 2024

The aim of this study was to assess the effectiveness of combining sericin with swimming exercise as a treatment for type-I collagenase-induced Achilles tendinopathy (AT) in rats, with a focus on inflammatory cytokines. An experimental AT model was established using type-I collagenase in male Sprague–Dawley rats, categorized into five groups: Group 1 (Control + Saline), Group 2 (AT), Group 3 (AT + exercise), Group 4 (AT + sericin), and Group 5 (AT + sericin + exercise). Intratendinous sericin administration (0.8 g/kg/mL) took place from days 3 to 6, coupled with 30 min daily swimming exercise sessions (5 days/week, 4 weeks). Serum samples were analyzed using ELISA for tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-10 (IL-10), and total antioxidant-oxidant status (TAS-TOS), alongside histopathological and immunohistochemical assessments of Achilles tendon samples. Elevated TNF-α and IL-1β and decreased IL-10 levels were evident in Group 2; Of these, TNF-α and IL-1β were effectively reduced and IL-10 increased across all treatment groups, particularly groups 4 and 5. Serum TAS was notably lower in Group 2 and significantly increased in Group 5 compared to Group 2. Histopathologically, Group 2 displayed severe degeneration, irregular fibers, and round cell nuclei, while Group 5 exhibited decreased degeneration and spindle-shaped fibers. The Bonar score increased in Group 2 and decreased in groups 4 and 5. Collagen type-I alpha-1 (Col1A1) expression was notably lower in Group 2 ( P = 0.001) and significantly increased in groups 4 and 5 compared to Group 2 ( P = 0.011 and 0.028, respectively). This study underscores the potential of sericin and swimming exercises in mitigating inflammation and oxidative stress linked to AT pathogenesis, presenting a promising combined therapeutic strategy.
Tumor Cell–Intrinsic p38 MAPK Signaling Promotes IL1α-Mediated Stromal Inflammation and Therapeutic Resistance in Pancreatic Cancer
Authors: Singh Samara P. , Dosch Austin R. , Mehra Siddharth , De Castro Silva Iago , Bianchi Anna , Garrido Vanessa T. , Zhou Zhiqun , Adams Andrew , Amirian Haleh , Box Edmond W. , Sun Xiaodian , Ban Yuguang , Datta Jashodeep , Nagathihalli Nagaraj S. , Merchant Nipun B. 
Published: January 2024

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a KRAS-driven inflammatory program and a desmoplastic stroma, which contribute to the profoundly chemoresistant phenotype. The tumor stroma contains an abundance of cancer-associated fibroblasts (CAF), which engage in extensive paracrine cross-talk with tumor cells to perpetuate protumorigenic inflammation. IL1α, a pleiotropic, tumor cell–derived cytokine, plays a critical role in shaping the stromal landscape. To provide insights into the molecular mechanisms regulating IL1A expression in PDAC, we performed transcriptional profiling of The Cancer Genome Atlas datasets and pharmacologic screening in PDAC cells and identified p38α MAPK as a key positive regulator of IL1A expression. Both genetic and pharmacologic inhibition of p38 MAPK significantly diminished IL1α production in vitro. Chromatin- and coimmunoprecipitation analyses revealed that p38 MAPK coordinates the transcription factors Sp1 and the p65 subunit of NFκB to drive IL1A overexpression. Single-cell RNA sequencing of a highly desmoplastic murine PDAC model, Ptf1aCre/+; LSL-KrasG12D/+; Tgfbr2flox/flox (PKT), confirmed that p38 MAPK inhibition significantly decreases tumor cell–derived Il1a and attenuates the inflammatory CAF phenotype in a paracrine IL1α-dependent manner. Furthermore, p38 MAPK inhibition favorably modulated intratumoral immunosuppressive myeloid populations and augmented chemotherapeutic efficacy to substantially reduce tumor burden and improve overall survival in PKT mice. These findings illustrate a cellular mechanism of tumor cell–intrinsic p38-p65/Sp1-IL1α signaling that is responsible for sustaining stromal inflammation and CAF activation, offering an attractive therapeutic approach to enhance chemosensitivity in PDAC.

Significance:
Inhibition of p38 MAPK suppresses tumor cell–derived IL1α and attenuates the inflammatory stroma and immunosuppressive tumor microenvironment to overcome chemotherapeutic resistance in pancreatic cancer.
Associations between Plasma Tocopherols and Lung Cancer Risk: Results from the Southern Community Cohort Study
Authors: Yoon Hyung-Suk , Wu Jie , Shidal Chris , Sun Yan , Franke Adrian A. , Yang Jae Jeong , Braithwaite Dejana , Courtney Regina , Cai Hui , Blot William J. , Shu Xiao-Ou , Zheng Wei , Cai Qiuyin 
Published: January 2024

Abstract

Background:
Despite the various anticancer activities of tocopherols, little is known about tocopherols associated with lung cancer risk among low-income African Americans (AA) and European Americans (EA) who are disproportionately affected by the disease.

Methods:
We conducted a nested case–control study that included 209 incident lung cancer cases and 406 matched controls within the Southern Community Cohort Study. Using biospecimens collected at cohort enrollment, plasma levels of α-, β/γ-, δ-, and total-tocopherols were measured by high-performance liquid chromatography with photodiode array detection. Conditional logistic regression was used to estimate ORs and 95% confidence intervals (CI) for lung cancer risk after adjusting for potential confounders. Stratified analyses were also conducted.

Results:
Plasma levels of total-tocopherols were inversely associated with lung cancer risk overall [OR (95% CI) for the highest vs. lowest tertile = 0.51 (0.30–0.90)]. The inverse association remained significant among EAs [0.20 (0.06–0.65)], men [0.43 (0.21–0.90)], current smokers [0.49 (0.26–0.93)], and cases diagnosed within 2 years of blood draw [0.36 (0.15–0.86)], though we did not find a significant risk reduction among AAs [0.75 (0.39–1.45)]. Notably, we found significant interactions between α-tocopherol and race after controlling the FDR to correct for multiple comparisons (Pinteraction = 0.02).

Conclusions:
Our results indicate that plasma total-tocopherols are inversely associated with lung cancer risk, but the association may differ across specific isomeric forms of tocopherols, race, or other individuals’ characteristics. Further large-scale studies are warranted to confirm our findings.

Impact:
Recommendations on tocopherols for lung cancer prevention should take isomers, race, and smoking behaviors into consideration.
Semi-Supervised, Attention-Based Deep Learning for Predicting TMPRSS2:ERG Fusion Status in Prostate Cancer Using Whole Slide Images
Authors: Omar Mohamed , Xu Zhuoran , Rand Sophie B. , Alexanderani Mohammad K. , Salles Daniela C. , Valencia Itzel , Schaeffer Edward M. , Robinson Brian D. , Lotan Tamara L. , Loda Massimo , Marchionni Luigi 
Published: January 2024

Abstract
Prostate cancer harbors several genetic alterations, the most prevalent of which is TMPRSS2:ERG gene fusion, affecting nearly half of all cases. Capitalizing on the increasing availability of whole-slide images (WSI), this study introduces a deep learning (DL) model designed to detect TMPRSS2:ERG fusion from H&E-stained WSIs of radical prostatectomy specimens. Leveraging the TCGA prostate adenocarcinoma cohort, which comprises 436 WSIs from 393 patients, we developed a robust DL model, trained across 10 different splits, each consisting of distinct training, validation, and testing sets. The model's best performance achieved an AUC of 0.84 during training, and 0.72 on the TCGA test set. This model was subsequently validated on an independent cohort comprising 314 WSIs from a different institution, in which it has a robust performance at predicting TMPRSS2:ERG fusion with an AUC of 0.73. Importantly, the model identifies highly-attended tissue regions associated with TMPRSS2:ERG fusion, characterized by higher neoplastic cell content and altered immune and stromal profiles compared with fusion-negative cases. Multivariate survival analysis revealed that these morphologic features correlate with poorer survival outcomes, independent of Gleason grade and tumor stage. This study underscores the potential of DL in deducing genetic alterations from routine slides and identifying their underlying morphologic features, which might harbor prognostic information.

Implications:
Our study illuminates the potential of deep learning in effectively inferring key prostate cancer genetic alterations from the tissue morphology depicted in routinely available histology slides, offering a cost-effective method that could revolutionize diagnostic strategies in oncology.
Conduction System Stimulation to Avoid Left Ventricle Dysfunction
Authors: González-Matos Carlos E. , Rodríguez-Queralto Oriol , Záraket Fátima , Jiménez Jesús , Casteigt Benjamín , Vallès Ermengol 
Published: January 2024

BACKGROUND:
Right ventricular apical pacing (RVAP) can produce left ventricle dysfunction. Conduction system pacing (CSP) has been used successfully to reverse left ventricle dysfunction in patients with left bundle branch block. To date, data about CSP prevention of left ventricle dysfunction in patients with preserved left ventricular ejection fraction (LVEF) are scarce and limited mostly to nonrandomized studies. Our aim is to demonstrate that CSP can preserve normal ventricular function compared with RVAP in the setting of a high burden of ventricular pacing.

METHODS:
Consecutive patients with a high-degree atrioventricular block and preserved or mildly deteriorated LVEF (>40%) were included in this prospective, randomized, parallel, controlled study, comparing conventional RVAP versus CSP.

RESULTS:

Seventy-five patients were randomized, with no differences between basal characteristics in both groups. The stimulated QRS duration was significantly longer in the RVAP group compared with the CSP group (160.4±18.1 versus 124.2±20.2 ms;
p
<0.01). Seventy patients were included in the intention-to-treat analyses. LVEF showed a significant decrease in the RVAP group at 6 months compared with the CSP group (mean difference, −5.8% [95% CI, −9.6% to −2%];
P
<0.01). Left ventricular end-diastolic diameter showed an increase in the RVAP group compared with the CSP group (mean difference, 3.2 [95% CI, 0.1–6.2] mm;
P
=0.04). Heart failure–related admissions were higher in the RVAP group (22.6% versus 5.1%;
P
=0.03).

CONCLUSIONS:
Conduction system stimulation prevents LVEF deterioration and heart failure–related admissions in patients with normal or mildly deteriorated LVEF requiring a high burden of ventricular pacing. These results are only short term and need to be confirmed by further larger studies.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT06026683.
Development of an Optimal Postprocessing Model Using the Microgenetic Algorithm to Improve Precipitation Forecasting in South Korea
Authors: Kim Junsu , Kim Yeon-Hee , Bok Hyejeong , Jang Sungbin , Cho Eunju , Kim Seungbum 
Published: January 2024

Abstract
We developed an advanced postprocessing model for precipitation forecasting using a microgenetic algorithm (MGA). The algorithm determines the optimal combination of three general circulation models: the Korean Integrated Model, the Unified Model, and the Integrated Forecast System model. To measure model accuracy, including the critical success index (CSI), probability of detection (POD), and frequency bias index, the MGA calculates optimal weights for individual models based on a fitness function that considers various indices. Our optimized multimodel yielded up to 13% and 10% improvement in CSI and POD performance compared to each individual model, respectively. Notably, when applied to an operational definition that considers precipitation thresholds from three models and averages the precipitation amount from the satisfactory models, our optimized multimodel outperformed the current operational model used by the Korea Meteorological Administration by up to 1.0% and 6.8% in terms of CSI and false alarm ratio performance, respectively. This study highlights the effectiveness of a weighted combination of global models to enhance the forecasting accuracy for regional precipitation. By utilizing the MGA for the fine-tuning of model weights, we achieved superior precipitation prediction compared to that of individual models and existing standard postprocessing operations. This approach can significantly improve the accuracy of precipitation forecasts.

Significance Statement
We developed an optimized multimodel for predicting precipitation occurrence using advanced techniques. By integrating various weather models with their optimized weights, our approach outperforms the method of using an arithmetic average of all models. This study underscores the potential to enhance regional precipitation forecasts, thereby facilitating more precise weather predictions for the public.