bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokines in predicting JAK inhibitors clinical efficacy for COVID-19
Authors: Novikov A. A. , Aleksandrova E. N. , Bajmakanova G. E. , Lukina G. V. , Bodunova N. A. , Vechorko V. I. , Averkov O. V. , Shcherbo S. N. , Savina M. I. , Turkina T. I. , Khatkov I. E. 
Published: November 2023

Janus kinases inhibitors (JAKi) have an immunosuppressive effect due to the normalization of levels of proinflammatory cytokines, are used in the treatment of cytokine storm in COVID-19. This fact makes it necessary to search a predictor of an efficacy of this small-molecules. The aim of the study. To evaluate the possibility of using cytokines in predicting the efficacy of JAKi in COVID-19. Materials and methods. We examined 86 patients with COVID-19: 50 men and 36 women. The age was 57,0; (50,0–65,0) years. The SARS-CoV-2 presence was confirmed by PCR. The control group consisted of 30 healthy donors matched by sex and age. The criterion for the efficacy of JAKi was recovery, in efficacy – switching to another drug, or death. The serum concentration of IL-1β, –6, –8, –17, TNF-α and GM–CSF by ELISA was estimates using Invitrogen test-systems (USA), according to the manufacturer’s instructions. Results. In COVID-19 patients who received baricitinib (BTC), compared with healthy individuals, basal (before JAKi starting) IL-6, TNF-α serum concentrations were increased; tofacitinib (TFT) – IL-6, ruxilitinib (RLT) – IL-6 and TNF-α. A decrease of IL-1β and GM–CSF serum concentration was noted before the start of TFT and RLT. Basal concentrations of IL-6 and TNF-α are most statistically strongly associated with the diagnosis COVID-19. After 5 days of treatment with BTC, there was an increase in IL-8 level compared to the basal, a decrease in the GM–CSF concentration and a slight increase IL-6 concentration relative to healthy donors (p < 0.05 in all cases). Basal concentration of IL-17 (more than 13.9 pg/ml) indicated the possibility of successful RLT treatment (area under the ROC-curve = 0.99; AP = 99 %; DS = 80 %; OP+ = 5.0; OP– = 0.2; CI: 0.9–1.0). Conclusions. Basal serum concentration of cytokines may predict JAKi efficacy in COVID-19 patients.
Capillary pruning couples tissue perfusion and oxygenation with cardiomyocyte maturation in the postnatal mouse heart
Authors: Santamaría Ricardo , Cruz-Caballero Javier , Gkontra Polyxeni , Jiménez-Montiel Alberto , Clemente Cristina , López Juan A. , Villalba-Orero María , Vázquez Jesús , Hutloff Andreas , Lara-Pezzi Enrique , Arroyo Alicia G. 
Published: November 2023

Introduction: Removal of poorly perfused capillaries by pruning contributes to remodeling the microvasculature to optimize oxygen and nutrient delivery. Blood flow drives this process by promoting the intravascular migration of endothelial cells in developing networks, such as in the yolk sac, zebrafish brain or postnatal mouse retina.Methods: In this study, we have implemented innovative tools to recognize capillary pruning in the complex 3D coronary microvasculature of the postnatal mouse heart. We have also experimentally tested the impact of decreasing pruning on the structure and function of this network by altering blood flow with two different vasodilators: losartan and prazosin.Results: Although both drugs reduced capillary pruning, a combination of experiments based on ex vivo imaging, proteomics, electron microscopy and in vivo functional approaches showed that losartan treatment resulted in an inefficient coronary network, reduced myocardial oxygenation and metabolic changes that delayed the arrest of cardiomyocyte proliferation, in contrast to the effects of prazosin, probably due to its concomitant promotion of capillary expansion.Discussion: Our work demonstrates that capillary pruning contributes to proper maturation and function of the heart and that manipulation of blood flow may be a novel strategy to refine the microvasculature and improve tissue perfusion after damage.
The influence of fluid inclusions, organics, and calcite fabric on trace element distributions in stalagmites
Authors: Kost O. , Sliwinski J. , Gies N. , Lueder M. , Stoll H. 
Published: November 2023

Trace elements and calcite fabrics in stalagmites are increasingly employed as indicators of past environmental conditions. The drivers of trace element concentrations and fabrics reflect a complex interplay of factors during crystal growth, and accurate interpretation of geochemical proxies requires a clear understanding of the incorporation of the proxy signal in the stalagmite. We employ a series of non-destructive techniques to compare the spatial distribution of water, organic components, and trace elements and in relationship with calcite fabrics, and evaluate if these distributions are consistent with recent hypotheses about controlling factors on crystal fabrics, fluid inclusions, and element incorporation. We use for the first time Fourier Transformation Infrared Focal-Plane Array (FTIR-FPA) imaging to show the distribution of molecular water (3,400 cm−1 absorbance) and organic matter (2,983 cm−1) in calcite. To test if entrapped water in speleothem calcite affects the abundance or distribution of trace elements, the element distribution (Na, Mg, Sr, U, Al, Y, and Zn) is mapped by Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS). Transmitted Light Microscope imaging constrains crystal fabrics. We find that stalagmite areas with strong Organic Matter fluorescence via Confocal Laser Scanning Microscopy coincide with areas of high Fourier Transformation Infrared absorbance at 2,983 cm−1, suggesting common co-location of multiple organic matter types in the stalagmite. While microscopic fluid inclusions visible in transmitted light are also detected by FTIR 3400 cm−1 absorbance, the FTIR additionally detects submicroscopic fluid inclusions, but not evident in transmitted light microscopy. In most samples, Na concentration is elevated in regions of high fluid inclusion density, suggesting that a significant portion of Na may be hosted in entrapped water rather than in the calcite. Only samples with 100-fold higher Y, feature Na concentrations which appear dominated by coupled Y-Na substitution and little influenced by fluid inclusion hosted Na. Our analysis provides new evidence of the influence of fluid inclusions on trace element content of stalagmites and illustrates the utility of several non-destructive imaging techniques to improve interpretations of proxy signals based on trace elements.
Unraveling the associations and causalities between glucose metabolism and multiple sleep traits
Authors: Yi Minhan , Fei Quanming , Chen Ziliang , Zhao Wangcheng , Liu Kun , Jian Shijie , Liu Bin , He Meng , Su Xiaoli , Zhang Yuan 
Published: November 2023

PurposeThe aim of our study is to estimate the associations and causalities of glucose metabolism traits of fasting blood glucose (FBG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), and 2-h glucose post-challenge (2hGlu) with sleep traits consisting of excessive daytime sleepiness (EDS), insomnia, and sleep duration.MethodsWe employed standard quantitative analysis procedures to assess the associations between sleep traits and glucose metabolism. Moreover, we acquired published genome-wide association studies (GWAS) summary statistics for these traits and conducted Mendelian randomization (MR) analyses to estimate their causal directions and effects. Inverse variance weighting (IVW) was employed as the primary approach, followed by sensitivity analyses.ResultsA total of 116 studies with over 840,000 participants were included in the quantitative analysis. Our results revealed that participants with abnormal glucose metabolism had higher risks for EDS (OR [95% CI] = 1.37 [1.10,1.69]), insomnia (OR [95% CI] = 1.65 [1.24,2.20]), and both short and long sleep duration (OR [95% CI] = 1.35 [1.12,1.63]; OR [95% CI] = 1.38 [1.13,1.67] respectively). In addition, individuals with these sleep traits exhibited alterations in several glycemic traits compared with non-affected controls. In MR analysis, the primary analysis demonstrated causal effects of 2hGlu on risks of EDS (OR [95% CI] = 1.022 [1.002,1.042]) and insomnia (OR [95% CI] = 1.020[1.001,1.039]). Furthermore, FINS was associated with short sleep duration (OR [95% CI] = 1.043 [1.018,1.068]), which reversely presented a causal influence on HbA1c (β [95% CI] = 0.131 [0.022,0.239]). These results were confirmed by sensitivity analysis.ConclusionOur results suggested mutual risk and causal associations between the sleep traits and glycemic traits, shedding new light on clinical strategies for preventing sleep disorders and regulating glucose metabolism. Future studies targeting these associations may hold a promising prospect for public health.
Comparative transcriptome analysis reveals deep molecular landscapes in stony coral Montipora clade
Authors: Han Tingyu , Liao Xin , Guo Zhuojun , Chen J.-Y. , He Chunpeng , Lu Zuhong 
Published: November 2023

Introduction: Coral reefs, among the most invaluable ecosystems in the world, face escalating threats from climate change and anthropogenic activities. To decipher the genetic underpinnings of coral adaptation and resilience, we undertook comprehensive transcriptome profiling of two emblematic coral species, Montipora foliosa and Montipora capricornis, leveraging PacBio Iso-Seq technology. These species were strategically selected for their ecological significance and their taxonomic proximity within the Anthozoa class.Methods: Our study encompassed the generation of pristine transcriptomes, followed by thorough functional annotation via diverse databases. Subsequently, we quantified transcript abundance and scrutinized gene expression patterns, revealing notable distinctions between the two species.Results: Intriguingly, shared orthologous genes were identified across a spectrum of coral species, highlighting a substantial genetic conservation within scleractinian corals. Importantly, a subset of genes, integral to biomineralization processes, emerged as exclusive to scleractinian corals, shedding light on their intricate evolutionary history. Furthermore, we discerned pronounced upregulation of genes linked to immunity, stress response, and oxidative-reduction processes in M. foliosa relative to M. capricornis. These findings hint at the presence of more robust mechanisms in M. foliosa for maintaining internal equilibrium and effectively navigating external challenges, underpinning its potential ecological advantage. Beyond elucidating genetic adaptation in corals, our research underscores the urgency of preserving genetic diversity within coral populations.Discussion: These insights hold promise for informed conservation strategies aimed at safeguarding these imperiled ecosystems, bearing ecological and economic significance. In synthesis, our study seamlessly integrates genomic inquiry with ecological relevance, bridging the gap between molecular insights and the imperative to conserve coral reefs in the face of mounting threats.
Optimization study of finite element simulation based on multi-layer structure and anisotropic CFRP
Authors: Yu-xin Qin , Xin-meng Xiong , Wen-li Zhang 
Published: November 2023

Introduction: Current research has mostly simplified CFRP components as isotropic media or homogenized them as anisotropic media, which fails to present the actual acoustic propagation behavior inside the CFRP components and restricts the accuracy of decoupling sound line tracking results and defect feature information.Method: Based on clarifying the influence of fiber direction on the spatial distribution of CFRP elastic properties, this paper proposes an acoustic modeling method for CFRP multi-directional plates considering the coupling effect of multi-layer structure and elastic anisotropy.Results: There are two main innovations: 1. The model is optimized using the Voigt representation method, which can quantitatively characterize the elastic anisotropy of any homogeneous material with a 6 × 6 elastic stiffness matrix containing 21 independent elastic constants. In this paper, the elastic stiffness matrix only includes five independent elastic constants; 2. Finite element simulation is used to analyze the propagation rules of ultrasonic waves inside CFRP and compare the detection methods with or without sound coupling layer.Discussion: The acoustic characteristics of the sound coupling layer are changed to find the optimal coupling method, reduce the refraction of ultrasonic waves in the specimen layer, and make the sound line path more accurate.
Risk factors for patients hospitalized with recurrent colon diverticular bleeding: a single center experience
Authors: You Hye-Su , Kim Dong Hyun , Cho Seo-Yeon , Park Seon-Young , Park Chang Hwan , Kim Hyun-Soo , Choi Sung Kyu 
Published: November 2023

Background/aimsColonic diverticular bleeding (CDB) is a common cause of acute lower gastrointestinal bleeding. Patients with CDB are at increased risk for recurrence. Here, we aimed to evaluate the clinical course of patients with CDB and identify risk factors for recurrent CDB (rCDB).MethodsWe included patients who were hospitalized at a single tertiary center for management of CDB between January 2005 and March 2020. A Cox proportional hazards regression analysis was performed to evaluate the risk factors of patients with rCDB as follows: model 1 adjusted by age, Charlson comorbidity index (CCI), and presence of bilateral colon diverticula; model 2 adjusted by age, CCI, and presence of left side colon diverticula; model 3 adjusted by age, CCI, and presence of sigmoid colon diverticula.ResultsAmong 219 patients (mean age, 68.0 years; 55 females), 56 and 163 had definite and presumptive CDB, respectively. During the median period of 506 days, 62 patients (28.3%) experienced rCDB. CCI score ≥ 4 was independently associated with rCDB in models 1, 2 and 3 (all p &lt; 0.05). Age ≥ 75 years was independently associated with rCDB in models 1 and 2 (both p &lt; 0.05). The presence of bilateral colon and sigmoid colon diverticula were independently associated with rCDB in models 1 and 3, respectively (both p &lt; 0.05).ConclusionrCDB frequently occurred at any time in patients with previous CDB. High CCI scores and distribution of colon diverticula were associated with rCDB. Clinicians should consider a possible rCDB for a patient considering age, comorbidity, and distribution of colon diverticula.
Expression profiles of α-synuclein in cortical lesions of patients with FCD IIb and TSC, and FCD rats
Authors: Zhang Li , Huang Jun , Dai Lu , Zhu Gang , Yang Xiao-Lin , He Zeng , Li Yu-Hong , Yang Hui , Zhang Chun-Qing , Shen Kai-Feng , Liang Ping 
Published: November 2023

BackgroundFocal cortical dysplasia (FCD) IIb and tuberous sclerosis complex (TSC) are common causes of drug-resistant epilepsy in children. However, the etiologies related to the development of FCD IIb and TSC are not fully understood. α-synuclein (α-syn) is a member of synucleins family that plays crucial roles in modulating synaptic transmission in central nervous system. Here, we explored the expression profiles and potential pathogenic functions of α-syn in cortical lesions of epileptic patients with FCD IIb and TSC.MethodsSurgical specimens from epileptic patients with FCD IIb and TSC, as well as FCD rats generated by in utero X-ray-radiation were adopted in this study and studied with immunohistochemistry, immunofluorescence, western blotting, and co-immunoprecipitation etc. molecular biological techniques.ResultOur results showed that α-syn expression was reduced in FCD IIb and TSC lesions. Specifically, α-syn protein was intensely expressed in dysplastic neurons (DNs) and balloon cells (BCs) in FCD IIb lesions, whereas was barely detected in DNs and giant cells (GCs) of TSC lesions. Additionally, p-α-syn, the aggregated form of α-syn, was detected in DNs, BCs, GCs, and glia-like cells of FCD IIb and TSC lesions. We previous showed that the function of N-methyl-D-aspartate receptor (NMDAR) was enhanced in FCD rats generated by X-ray-radiation. Here, we found the interaction between α-syn and NMDAR subunits NMDAR2A, NMDAR2B were augmented in cortical lesions of FCD patients and FCD rats.ConclusionThese results suggested a potential role of α-syn in the pathogenesis of FCD IIb and TSC by interfering with NMDAR.
Immune responses and clinical outcomes following the third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in advanced breast cancer patients receiving targeted therapies: a prospective study
Authors: Nelli Fabrizio , Fabbri Agnese , Botticelli Andrea , Giannarelli Diana , Marrucci Eleonora , Fiore Cristina , Virtuoso Antonella , Berrios Julio Rodrigo Giron , Scagnoli Simone , Pisegna Simona , Cirillo Alessio , Panichi Valentina , Massari Annalisa , Silvestri Maria Assunta , Ruggeri Enzo Maria 
Published: November 2023

PurposeMetastatic breast cancer patients are the most prevalent oncology population with advanced disease facing COVID-19 pandemic. Immune responses after mRNA-based vaccination during treatment with CDK4/6 inhibitors or HER2-directed agents remain unclear. We conducted a prospective analysis to elucidate changes in antibody titers and lymphocyte counts following full course of mRNA-BNT162b2 (tozinameran) vaccination in recipients undergoing these targeted therapies.MethodsPatients who had received a booster dosing and had been treated for at least 6 months were eligible. Antibody titers against SARS-CoV-2 spike protein were measured at four subsequent time points. Immunophenotyping of circulating lymphocytes was performed before the third dose of tozinameran and four weeks later to quantify the absolute counts of CD3+CD4+ T-helper cells, CD3+CD8+ T-cytotoxic cells, CD19+ B cells, and CD56+CD16+ NK cells. We also assessed the incidence of breakthrough infections and investigated whether immune changes affect time-to-treatment failure (TTF) after booster vaccination.ResultsThe current analysis included 69 patients, of whom 38 (55%) and 31 (45%) were being treated with CDK4/6 inhibitors and HER2-targeted therapies, respectively. All participants received a third dose of tozinameran between September 23 and October 7, 2021. Multivariate analysis revealed that CDK4/6 inhibition predicted a significantly impaired humoral response after the booster dose. This detrimental effect was also evident for T-helper cell counts before the third immunization, but it disappeared in the subsequent evaluation. After a median follow-up of 22.3 months, we observed 19 (26%) cases of COVID-19 outbreaks, all experiencing favorable clinical outcomes. Univariate analysis showed a significant association between the onset of SARS-CoV-2 infections and the use of CDK4/6 inhibitors, as well as with an impaired antibody and T-helper cell response. Only the last two covariates remained independent predictors after multivariate testing. Dynamic variations in antibody titers and T-helper cell counts did not affect TTF in multivariate regression analysis.ConclusionsOur results confirm that the immune response to tozinameran is impaired by CDK4/6 inhibitors, increasing the odds of breakthrough infections despite the third vaccine dose. Current evidence recommends maintaining efforts to provide booster immunizations to the most vulnerable cancer patients, including those with advanced breast cancer undergoing CDK4/6 inhibition.
Dynamic changes in physical function during intensive chemotherapy affect transplant outcomes in older adults with AML
Authors: Min Gi-June , Cho Byung-Sik , Kwag Daehun , Park Sung-Soo , Park Silvia , Yoon Jae-Ho , Lee Sung-Eun , Eom Ki-Seong , Kim Yoo-Jin , Lee Seok , Min Chang-Ki , Cho Seok-Goo , Lee Jong Wook , Kim Hee-Je 
Published: November 2023

IntroductionIntensive chemotherapy (IC) can affect all geriatric assessment (GA) domains in older adults with acute myeloid leukemia (AML), but data on the effects of these changes on transplant outcomes are lacking.MethodsTherefore, we prospectively assessed the prognostic role of GA domains at diagnosis and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 51 patients with AML aged ≥60 years who achieved complete remission after IC. We performed both baseline and pre-allo-HSCT GA; moreover, physical function, including a short physical performance battery (SPPB), cognitive function, psychological function, nutritional status, and social support were examined.ResultsAll GA domains showed dynamic changes between the two time points. The directions of change were statistically significant for social support, self-reported physical and psychological functions, and distress, but not for nutritional status, cognitive function, or physical function. Among all GA domains at each time point, only poor physical function and its submaneuvers at diagnosis but not at allo-HSCT were significantly associated with inferior survival. In particular, since the direction of change varied between patients, we found that patients whose physical function improved before allo-HSCT were more likely to survive longer than those with persistently impaired SPPB (55.6% vs. 28.6%, p=0.268). Finally, persistent impairment in SPPB (28.6% vs. 65.9%, p=0.006), tandem stand (0% vs. 63.3%, p=0.012), sit-and-stand (41.2% vs. 70.6%, p=0.009), and gait speed (38.5% vs. 68.4%, p=0.027) further strongly predicted inferior survival.DiscussionThis study showed that IC courses can induce dynamic changes in different directions in the GA domains of each patient and that changes in objectively measured physical function can predict transplant outcomes.
Efficacy of adjunctive topical liposomal clarithromycin on systemic Glucantime in Old World cutaneous leishmaniasis: a pilot clinical study
Authors: Hakamifard Atousa , Radmehr Reza , Sokhanvari Fatemeh , Sherkat Fatemeh , Hariri Amirali , Varshosaz Jaleh , Shahmoradi Zabihollah , Feizi Awat , Abtahi-Naeini Bahareh , Pourmahdi-Boroujeni Mahsa 
Published: November 2023

Aim: This study aimed to investigate the effects of topical liposomal clarithromycin in combination with meglumine antimoniate (Glucantime®) on cutaneous leishmaniasis (CL) lesions.Methods: This pilot, randomized, double-blinded clinical trial was conducted on patients with CL lesions. Patients were randomly assigned to two groups: the first group received liposomal clarithromycin in combination with Glucantime for 28 days, while the second group received Glucantime and a placebo. Afterward, patients were followed up at 1.5, 3, and 6 months after treatment initiation and were evaluated for recovery time, induration, and size of the lesions.Results: Sixty patients with CL lesions were divided into two separate groups with 30 members each and were examined. Within-group analysis revealed that recovery time in the clarithromycin group was 26.65 ± 5.12 days, while in the placebo group, it was 32.84 ± 24.43, which was statistically insignificant (p = 0.18). Lesion size comparison in the first and last follow-ups reduced in both groups: 7.73 ± 4.31 to 0.48 ± 0.50 in the clarithromycin group (p = 0.006) and 5.47 ± 5.83 to 0.76 ± 0.88 in the placebo group (p = 0.03). Moreover, the size of lesions in the intervention group was significantly reduced compared to that in the placebo group (p = 0.02). Recognizable induration reduction was observed in the clarithromycin group (2.60 ± 0.77 to 1.0 ± 0.00). No adverse effects attributable to clarithromycin were reported.Conclusion: The administration of liposomal clarithromycin in combination with systemic Glucantime had a significant beneficial effect on reducing lesion size in leishmaniasis. Further studies on larger populations are recommended.Systematic Review Registration: https://www.irct.ir/trial/46611.