bluuebunny/crossref_metadata_2025_split huggingface dataset:
First Morning Pregnanetriol and 17-Hydroxyprogesterone Correlated Significantly in 21-Hydroxylase Deficiency
Authors: Itonaga Tomoyo , Izawa Masako , Hamajima Takashi , Hasegawa Yukihiro 
Published: January 2022

BackgroundBiochemically monitoring 21-hydroxylase deficiency (21-OHD) is challenging. Serum/blood 17-hydroxyprogesterone (17OHP) measurements are normally used for this purpose. Urinary pregnanetriol (PT), a urinary metabolite of 17OHP, may also be used. Based on auxological data, we previously reported that the optimal first morning PT value fell in the range of 2.2–3.3 mg/gCr (95% confidence interval of the mean) and 0.59-6.0 mg/gCr (10th – 90th percentile) for monitoring 21-OHD treatment. No report thus far has directly compared the first morning urinary PT value with the 17OHP value at various times during the day.ObjectiveTo explore the correlation between the first morning urinary PT value before glucocorticoid administration and the serum/blood 17OHP value at three time points, namely, before and two and four hours after glucocorticoid administration.DesignThis was a prospective study done at two children’s hospitals.MethodsIn total, 25 patients with 21-OHD aged 3-25 years were recruited. Their urinary PT levels and 17OHP levels were measured for three days within a total period of one week. The first morning PT value was collected on all three days. Dried blood spots and serum were used to measure 17OHP.ResultsThe range for the first morning PT value for all the samples (n=69) was 0.10-56.1 mg/gCr. A significant, positive correlation was found between the first morning PT and 17OHP values before medication (r=0.87, p&lt;0.01), and weaker correlation was observed between the first morning PT and 17OHP values after medication.ConclusionsThe first morning PT correlated more significantly with 17OHP before the morning medication. Measuring the first morning PT value may be more practical and useful for monitoring 21-OHD biochemically.
Prevalence of Vancomycin Resistant Enterococcus in Wastewater Treatment Plants and Their Recipients for Reuse Using PCR and MALDI-ToF MS
Authors: Adegoke Anthony A. , Madu Chibuzor E. , Reddy Poovendhree , Stenström Thor A. , Okoh Anthony I. 
Published: January 2022

The World Health Organization in 2017 listed vancomycin-resistant enterococci (VRE) among those with high priority for research. This study determined the efficiency of two wastewater treatment plants (WWTPs) in removing both vancomycin-resistant enterococci (VRE) and vancomycin-sensitive enterococci (VSE) from wastewater and the effect of their effluents on the receiving water bodies being reused. VRE and total enterococci (TE) respectively were isolated using Slanetz and Bartley agar with and without vancomycin from wastewater and river samples. Isolate speciation was confirmed by PCR and Matrix-Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) mass spectrometry (MS). Molecular methods were used for confirmation of presumptive VRE and for detection of van genes. Resistance to antibiotics was determined by the disk diffusion method. The TE and VRE counts of the two WWTPs influents ranged from 6.1 to 7.2 log10 CFU/100 ml and 4.3 to 6.7 log10 CFU/100 ml respectively while the effluent counts ranged from 0 to 4.4 log10 CFU/100 ml and 0 to 3.4 log10 CFU/100 ml for the chlorinated effluents. The TE and VRE counts of the recipient river samples were higher than the effluents. Exactly 186 (80.1%) isolates tallied with PCR as Enterococcus while 22 (9.5%) were positive by PCR but negative with MALDI-TOF. Enterococcus faecium and E. faecalis were the most abundant species. The isolates showed 34–100% resistance to quinopristin-dalfopristin, streptomycin, doxycycline, tetracycline, ciprofloxacin and cefixime. VanA (73.8%) were dominant among the isolates. The two WWTPs were efficient in reducing the VRE counts. Thus, the VRE in the river is most likely due to contamination from other sources and it may result in threat to human health when reused.
Is There a Crucial Link Between Vitamin D Status and Inflammatory Response in Patients With COVID-19?
Authors: Saponaro Federica , Franzini Maria , Okoye Chukwuma , Antognoli Rachele , Campi Beatrice , Scalese Marco , Neri Tommaso , Carrozzi Laura , Monzani Fabio , Zucchi Riccardo , Celi Alessandro , Paolicchi Aldo , Saba Alessandro 
Published: January 2022

BackgroundHypovitaminosis D has been suggested to play a possible role in coronavirus disease 2019 (COVID-19) infection.MethodsThe aim of this study is to analyze the relationship between vitamin D status and a biochemical panel of inflammatory markers in a cohort of patients with COVID-19. A secondary endpoint was to evaluate the correlation between 25OHD levels and the severity of the disease. Ninety-three consecutive patients with COVID-19-related pneumonia were evaluated from March to May 2020 in two hospital units in Pisa, in whom biochemical inflammatory markers, 25OHD levels, P/F ratio at nadir during hospitalization, and complete clinical data were available.ResultsSixty-five percent of patients presented hypovitaminosis D (25OHD ≤ 20 ng/ml) and showed significantly higher IL-6 [20.8 (10.9–45.6) vs. 12.9 (8.7–21.1) pg/ml, p = 0.02], CRP [10.7 (4.2–19.2) vs. 5.9 (1.6–8.1) mg/dl, p = 0.003], TNF-α [8.9 (6.0–14.8) vs. 4.4 (1.5–10.6) pg/ml, p = 0.01], D-dimer [0.53 (0.25–0.72) vs. 0.22 (0.17–0.35) mg/l, p = 0.002], and IL-10 [3.7 (1.8–6.9) vs. 2.3 (0.5–5.8) pg/ml, p = 0.03]. A significant inverse correlation was found between 25OHD and all these markers, even adjusted for age and sex. Hypovitaminosis D was prevalent in patients with severe ARDS, compared with the other groups (75% vs. 68% vs. 55%, p &lt; 0.001), and 25OHD levels were lower in non-survivor patients.ConclusionsThe relationship between 25OHD levels and inflammatory markers suggests that vitamin D status needs to be taken into account in the management of these patients. If vitamin D is a marker of poor prognosis or a possible risk factor with beneficial effects from supplementation, this still needs to be elucidated.
The PDE4 Inhibitor Tanimilast Blunts Proinflammatory Dendritic Cell Activation by SARS-CoV-2 ssRNAs
Authors: Nguyen Hoang Oanh , Schioppa Tiziana , Tiberio Laura , Facchinetti Fabrizio , Villetti Gino , Civelli Maurizio , Del Prete Annalisa , Sozio Francesca , Gaudenzi Carolina , Passari Mauro , Barbazza Ilaria , Sozzani Silvano , Salvi Valentina , Bosisio Daniela 
Published: January 2022

Phosphodiesterase 4 (PDE4) inhibitors are immunomodulatory drugs approved to treat diseases associated with chronic inflammatory conditions, such as COPD, psoriasis and atopic dermatitis. Tanimilast (international non-proprietary name of CHF6001) is a novel, potent and selective inhaled PDE4 inhibitor in advanced clinical development for the treatment of COPD. To begin testing its potential in limiting hyperinflammation and immune dysregulation associated to SARS-CoV-2 infection, we took advantage of anin vitromodel of dendritic cell (DC) activation by SARS-CoV-2 genomic ssRNA (SCV2-RNA). In this context, Tanimilast decreased the release of pro-inflammatory cytokines (TNF-α and IL-6), chemokines (CCL3, CXCL9, and CXCL10) and of Th1-polarizing cytokines (IL-12, type I IFNs). In contrast to β-methasone, a reference steroid anti-inflammatory drug, Tanimilast did not impair the acquisition of the maturation markers CD83, CD86 and MHC-II, nor that of the lymph node homing receptor CCR7. Consistent with this, Tanimilast did not reduce the capability of SCV2-RNA-stimulated DCs to activate CD4+T cells but skewed their polarization towards a Th2 phenotype. Both Tanimilast and β-methasone blocked the increase of MHC-I molecules in SCV2-RNA-activated DCs and restrained the proliferation and activation of cytotoxic CD8+T cells. Our results indicate that Tanimilast can modulate the SCV2-RNA-induced pro-inflammatory and Th1-polarizing potential of DCs, crucial regulators of both the inflammatory and immune response. Given also the remarkable safety demonstrated by Tanimilast, up to now, in clinical studies, we propose this inhaled PDE4 inhibitor as a promising immunomodulatory drug in the scenario of COVID-19.
Clinical and Echographic Features of Morning Glory Disc Anomaly in Children: A Retrospective Study of 249 Chinese Patients
Authors: Zou Yihua , She Kaiqin , Hu Yiqian , Ren Jianing , Fei Ping , Xu Yu , Peng Jie , Zhao Peiquan 
Published: January 2022

PurposeTo report the clinical and echographic features, the prevalence of retinal detachment (RD), and associated visual acuity in a cohort of pediatric patients with morning glory disc anomaly (MGDA).MethodsThis was a retrospective review of 249 pediatric patients with MGDA (271 eyes) seen at the Dept. of Ophthalmology, Xinhua Hospital. Their medical records were reviewed for demographic data and ocular and systemic findings. The maximal depth and width of the cavity were measured using standardized echographic images. The ratios of cavitary depth to axial length, cavitary depth to maximal cavitary width, and the product of cavitary depth and width were calculated and used to indicate the relative size of the excavation. The clinical and echographic findings were correlated with visual acuity and the occurrence of RD of the patient.ResultsThe relative size of the excavation and the presence of RD were positively associated with increased risk of poor vision (p &lt; 0.05). The presence of persistent fetal vasculature was not associated with the risk of RD and poor vision. The ratio of cavitary depth to axial length more than or equal to 0.25 conferred an increased risk of RD (OR, 2.101; 95% CI, 1.469–3.003).ConclusionsClinical and echographic features of MGDA may be used in predicting the risk of RD. Measuring the relative size of excavation via echography may guide the follow-ups and assist in the early diagnosis of RD.
Sex Differences in Kidney Transplantation: Austria and the United States, 1978–2018
Authors: Hödlmoser Sebastian , Gehrig Teresa , Antlanger Marlies , Kurnikowski Amelie , Lewandowski Michał , Krenn Simon , Zee Jarcy , Pecoits-Filho Roberto , Kramar Reinhard , Carrero Juan Jesus , Jager Kitty J. , Tong Allison , Port Friedrich K. , Posch Martin , Winkelmayer Wolfgang C. , Schernhammer Eva , Hecking Manfred , Ristl Robin 
Published: January 2022

BackgroundSystematic analyses about sex differences in wait-listing and kidney transplantation after dialysis initiation are scarce. We aimed at identifying sex-specific disparities along the path of kidney disease treatment, comparing two countries with distinctive health care systems, the US and Austria, over time.MethodsWe analyzed subjects who initiated dialysis from 1979–2018, in observational cohort studies from the US and Austria. We used Cox regression to model male-to-female cause-specific hazard ratios (csHRs, 95% confidence intervals) for transitions along the consecutive states dialysis initiation, wait-listing, kidney transplantation and death, adjusted for age and stratified by country and decade of dialysis initiation.ResultsAmong 3,053,206 US and 36,608 Austrian patients starting dialysis, men had higher chances to enter the wait-list, which however decreased over time [male-to-female csHRs for wait-listing, 1978–1987: US 1.94 (1.71, 2.20), AUT 1.61 (1.20, 2.17); 2008–2018: US 1.35 (1.32, 1.38), AUT 1.11 (0.94, 1.32)]. Once wait-listed, the advantage of the men became smaller, but persisted in the US [male-to-female csHR for transplantation after wait-listing, 2008–2018: 1.08 (1.05, 1.11)]. The greatest disparity between men and women occurred in older age groups in both countries [male-to-female csHR for wait-listing after dialysis, adjusted to 75% age quantile, 2008–2018: US 1.83 (1.74, 1.92), AUT 1.48 (1.02, 2.13)]. Male-to-female csHRs for death were close to one, but higher after transplantation than after dialysis.ConclusionsWe found evidence for sex disparities in both countries. Historically, men in the US and Austria had 90%, respectively, 60% higher chances of being wait-listed for kidney transplantation, although these gaps decreased over time. Efforts should be continued to render kidney transplantation equally accessible for both sexes, especially for older women.
Towards Elucidating Structure–Spectra Relationships in Rhamnogalacturonan II: Computational Protocols for Accurate 13C and 1H Shifts for Apiose and Its Borate Esters
Authors: Bharadwaj Vivek S. , Westawker Luke P. , Crowley Michael F. 
Published: January 2022

Apiose is a naturally occurring, uncommon branched-chain pentose found in plant cell walls as part of the complex polysaccharide Rhamnogalacturonan II (RG-II). The structural elucidation of the three-dimensional structure of RG-II by nuclear magnetic resonance (NMR) spectroscopy is significantly complicated by the ability of apiose to cross-linkviaborate ester linkages to form RG-II dimers. Here, we developed a computational approach to gain insight into the structure–spectra relationships of apio–borate complexes in an effort to complement experimental assignments of NMR signals in RG-II. Our protocol involved structure optimizations using density functional theory (DFT) followed by isotropic magnetic shielding constant calculations using the gauge-invariant atomic orbital (GIAO) approach to predict chemical shifts. We evaluated the accuracy of 23 different functional–basis set (FBS) combinations with and without implicit solvation for predicting the experimental1H and13C shifts of a methyl apioside and its three borate derivatives. The computed NMR predictions were evaluated on the basis of the overall shift accuracy, relative shift ordering, and the ability to distinguish between dimers and monomers. We demonstrate that the consideration of implicit solvation during geometry optimizations in addition to the magnetic shielding constant calculations greatly increases the accuracy of NMR chemical shift predictions and can correctly reproduce the ordering of the13C shifts and yield predictions that are, on average, within 1.50 ppm for13C and 0.12 ppm for1H shifts for apio–borate compounds.
Immune Response on Optimal Timing and Fractionation Dose for Hypofractionated Radiotherapy in Non–Small-Cell Lung Cancer
Authors: Zhao Xianlan , Li Jixi , Zheng Linpeng , Yang Qiao , Chen Xu , Chen Xiewan , Yu Yongxin , Li Feng , Cui Jianxiong , Sun Jianguo 
Published: January 2022

Background: The intervention timing of immune checkpoint inhibitors (ICIs) and radiotherapy fractionations are critical factors in clinical efficacy. This study aims to explore dynamic changes of the tumor immune microenvironment (TIME) after hypofractionated radiotherapy (HFRT) at different timepoints and fractionation doses in non–small-cell lung cancer (NSCLC).Methods: In the implanted mouse model, the experimental groups received HFRT 3.7 Gy × 4 F, 4.6 Gy × 3 F, 6.2 Gy × 2 F, and 10 Gy × 1 F, respectively, with the same biological equivalent dose (BED) of 20Gy. Tumor volume and survival time were compared with those of the control group. Flow cytometry was performed to detect immune cells and their PD-1/PD-L1 expressions using tail-tip blood at different timepoints and tumor tissues at 48 h after radiotherapy. In NSCLC patients, immune cells, PD-1/PD-L1, and cytokines were detected in peripheral blood for 4 consecutive days after different fractionation radiotherapy with the same BED of 40Gy.Results: Tumor volumes were significantly reduced in all experimental groups compared with the control group, and the survival time in 6.2 Gy × 2 F (p &lt; 0.05) was significantly prolonged. In tail-tip blood of mice, CD8+ T counts increased from 48 h to 3 weeks in 4.6 Gy × 3 F and 6.2 Gy × 2 F, and CD8+ PD-1 shortly increased from 48 h to 2 weeks in 6.2 Gy × 2 F and 10 Gy × 1 F (p &lt; 0.05). Dentritic cells (DCs) were recruited from 2 to 3 weeks (p &lt; 0.01). As for NSCLC patients, CD8+ T counts and PD-1 expression increased from 24 h in 6.2 Gy × 4 F, and CD8+ T counts increased at 96 h in 10 Gy × 2 F (p &lt; 0.05) in peripheral blood. DC cells were tentatively recruited at 48 h and enhanced PD-L1 expression from 24 h in both 6.2 Gy × 4 F and 10 Gy × 2 F (p &lt; 0.05). Besides, serum IL-10 increased from 24 h in 6.2 Gy × 4 F (p &lt; 0.05). Conversely, serum IL-4 decreased at 24 and 96 h in 10 Gy × 2 F (p &lt; 0.05).Conclusion: HFRT induces the increase in CD8+ T cells and positive immune cytokine response in specific periods and fractionation doses. It was the optimal time window from 48 h to 2 weeks for the immune response, especially in 6.2 Gy fractionation. The best immune response was 96 h later in 10 Gy fractionation, delivering twice instead of a single dose. During this time window, the intervention of immunotherapy may achieve a better effect.
PaDef (Persea americana var. drymifolia), a Plant Antimicrobial Peptide, Triggers Apoptosis, and Induces Global Epigenetic Modifications on Histone 3 in an Acute Lymphoid Leukemia Cell Line
Authors: Jiménez-Alcántar Paola , López-Gómez Rodolfo , López-Meza Joel E. , Ochoa-Zarzosa Alejandra 
Published: January 2022

In recent years, it has been recognized that epigenetic alterations play an important role in the development and maintenance of cancer, including leukemias. Furthermore, it is known that these alterations are involved in the emergence of resistance to conventional chemotherapeutics. Consequently, molecules with an anticancer activity whose activity is ruled by epigenetic modifications are attractive to search for new therapies against cancer. The plant antimicrobial peptides have been widely evaluated as molecules with anticancer activity; however, the analysis of the epigenetic regulation induced by these molecules associated with this activity is scarce and still is an unexplored field. In this work, we show that the PaDef defensin, a plant antimicrobial peptide from Mexican avocado fruit (Persea americana var. drymifolia) is cytotoxic for Jurkat cell line from acute lymphoid leukemia cells, through an apoptotic process. PaDef inhibited cell viability in a concentration-dependent manner, with an IC50 = 47.3 μM. Treatment of Jurkat cells with PaDef (IC50) induced cell death by apoptosis dependent on caspases 8 and 9; besides, it was related to an increase in the production of reactive oxygen species and the loss of mitochondrial membrane potential. Interestingly, the inhibition of caspase activation by inhibitors of caspases 8 and 9 does not revert the reduction in viability, suggesting that other mechanisms, in addition to caspase activity, could be participating in the PaDef cytotoxic effect. Also, the modifications in the histone 3 tails induced by PaDef in Jurkat cells were evaluated, specifically acetylation and methylation. PaDef increased global histone 3 acetylation and lysine 9 specific marks (2-fold and up to 4-fold, respectively). These effects correlated with the reduction of the Histone Deacetylase activity (HDAC, ∼50%). Based on methylation marks, PaDef treatment increased lysine 9 di- and tri-methylation tags (2-fold in both cases). The epigenetic modulation induced by PaDef on Jurkat cells could be related to the chromatin compaction-decompaction promoting gene expression or repression; however, further studies are necessary to correlate these marks with the transcription of specific genes. Therefore, the study of new molecules that may have anticancer activity through epigenetic modulation is interesting.
Comparison of Minimally Invasive Versus Abdominal Radical Hysterectomy for Early-Stage Cervical Cancer: An Updated Meta-Analysis
Authors: Zhang Mengting , Dai Wei , Si Yuexiu , Shi Yetan , Li Xiangyuan , Jiang Ke , Shen Jingyi , Ying Liying 
Published: January 2022

BackgroundAlthough minimally invasive surgery (MIS) was commonly used to treat patients with early-stage cervical cancer, its efficacy remained controversial.MethodsWe systematically searched PubMed, Web of Science, and Cochrane Library databases until March 2021 to compare the prognosis of early-stage cervical cancer patients who underwent MIS (laparoscopic or robot-assisted radical hysterectomy) or ARH. The primary outcomes included rates of 3- and 5-year disease-free survival (DFS) and overall survival (OS). The study protocol was registered in PROSPERO: CRD42021258116.ResultsThis meta-analysis included 48 studies involving 23346 patients (11220, MIS group; 12126, ARH group). The MIS group had a poorer medium-term (3-year) DFS (HR=1.08, 95% CI: 1.01-1.16, p=0.031) than the ARH group, without significant difference in medium-term OS as well as long-term (5-year) DFS and OS. Subgroup analysis of 3-year prognosis revealed that although patients in Western countries who underwent MIS had shorter DFS than those who underwent ARH (HR=1.10, p=0.024), no difference was observed in DFS among those in Asian countries. Moreover, MIS was linked to poorer 3-year DFS in patients with stage I cervical cancer (HR=1.07, p=0.020). Notably, subgroup analysis of 5-year prognosis revealed that patients with tumor size ≥2 cm undergoing MIS exhibited a shorter DFS than those who underwent ARH (HR=1.65, p=0.041).ConclusionPatients with early-stage cervical cancer undergoing MIS may have a poorer prognosis than those undergoing ARH. Therefore, applying MIS in early-stage cervical cancer patients should be conducted with caution.Systematic Review RegistrationThe study protocol was registered in PROSPERO: CRD42021258116.
One Cycle of Concurrent Chemotherapy vs. Two Cycles of Concurrent Chemotherapy With Radiation Therapy in Patients With Limited-Stage Small Cell Lung Cancer
Authors: Yu Hao , Zhang Jiaqi , Zhang Zhen , Wang Youyou , Xu Guangying , Xu Liming , Liu Ningbo , Zhao Lujun , Wang Ping 
Published: January 2022

BackgroundThe optimal number of concurrent chemotherapy cycles during thoracic radiotherapy (RT) in patients with limited stage-small cell lung cancer (LS-SCLC) is not well defined. The purpose of this study was to evaluate the impact of the number of concurrent chemotherapy cycles on prognosis of LS-SCLC.Material and MethodsPatients with LS-SCLC treated with concurrent chemo-radiotherapy from May 2008 to December 2020 in our hospital were retrospectively analyzed. The prescribed radiation dose was 60Gy administrated with conventional RT in 30 fractions within 6 weeks. The prognostic role of cycle number of chemotherapy administrated concurrently with RT were analyzed. All patients were followed up at one month after the treatment, then once every three months until two years after the treatment, and every six months thereafter. Propensity score matching (PSM) was performed to reduce confounding factors. The primary endpoint was overall survival (OS). Survival analysis was performed with Kaplan-Meier and multivariate analysis was performed with Cox regression model.ResultsAmong the 370 patients who received radical radiotherapy, 206 patients received concurrent chemo-radiotherapy and were included for the analysis. Multivariate analysis showed that stage and PCI were independent prognostic factors for OS. The median OS in patients who received one cycle and two cycles of chemotherapy concurrently with RT were 32.9 months and 31.6 months, respectively (P = 0.241). And the median PFS were 20.6 months and 18.4 months, respectively (P = 0.764). After PSM, no statistical differences in OS and PFS were observed between patients who received one cycle and those who received two cycles of concurrent chemotherapy.ConclusionTwo cycles of concurrent chemotherapy during RT were not necessarily superior compared to one cycle in LS-SCLC. The optimal cycle number of concurrent chemotherapy during RT needs to be further studied.