bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Performance of BAL Metagenomic Next-Generation Sequence and Serum (1,3)-β-D-Glucan for Differential Diagnosis of Pneumocystis jirovecii Pneumonia and Pneumocystis jirovecii Colonisation
Authors: Liu Li , Yuan Mingjuan , Shi Yi , Su Xin 
Published: December 2021

BackgroundDifferentiating Pneumocystis jirovecii infection from colonisation is crucial for appropriate therapy administration. In this study, we evaluated the performance of bronchoalveolar lavage fluid (BAL) metagenomic next-generation sequencing (mNGS) and serum 1,3-β-D-glucan (BDG) tests in differentiating colonisation and infection with P. jirovecii.MethodsFrom January 2018 to March 2021, 47 patients were enrolled in this study at the Hunan Provincial People’s Hospital. The final diagnosis was used as a reference, and cases were classified into the P. jirovecii pneumonia (PJP) group or the P. jirovecii colonisation (PJC) group. Clinical data were recorded. The performances of mNGS and BDG were compared.ResultThe fungal load significantly differed between patients with PJP and PJC, with median reads of 3,215.79 ± 1,797 vs. 5.61 ± 0.88 in the PJP and PJC groups, respectively (P &lt; 0.0001). BDG also significantly differed between the two groups, with a median titre of 233.60 ± 39.65 pg/ml in the PJP group and 68.48 ± 19.21 pg/ml in the PJC group (P = 0.0006). The area under the curve was 0.973 (95%CI: 0.868–1.007) for mNGS of the BAL and 0.879 (95%CI: 0.769–0.989) for the serum BDG. The optimal threshold value for discriminating P. jirovecii infection from colonisation appeared to be 14 reads (sensitivity, 83.3%; specificity, 95.7%; positive likelihood ratio, 19.2) and BDG = 88.6 pg/ml (sensitivity, 79.2%; specificity, 92.9%; positive likelihood ratio, 18.2). No correlation between mNGS reads and the BDG titre was found in mNGS-positive patients (r2 = 0.0076, P = 0.583). The levels of lactate dehydrogenase and C-reactive protein were significantly higher in the PJP group than in the PJC group.ConclusionBAL mNGS and serum BDG are useful adjunct tests that can assist with differentiating between colonisation and infection of P. jirovecii.
Gut Microbiota and Serum Metabolic Signatures of High-Fat-Induced Bone Loss in Mice
Authors: Lu Lingyun , Tang Mengjia , Li Jiao , Xie Ying , Li Yujue , Xie Jinwei , Zhou Li , Liu Yi , Yu Xijie 
Published: December 2021

BackgroundAccumulating evidence indicates that high-fat diet (HFD) is a controllable risk factor for osteoporosis, but the underlying mechanism remains to be elucidated. As a primary biological barrier for nutrient entry into the human body, the composition and function of gut microbiota (GM) can be altered rapidly by HFD, which may trigger abnormal bone metabolism. In the current study, we analyzed the signatures of GM and serum metabolomics in HFD-induced bone loss and explored the potential correlations of GM and serum metabolites on HFD-related bone loss.MethodsWe conducted a mouse model with HFD-induced bone loss through a 12-week diet intervention. Micro-CT, Osmium-μCT, and histological analyses were used to observe bone microstructure and bone marrow adipose tissue. Quantitative Real-Time PCR was applied to analyze gene expression related to osteogenesis, adipogenesis, and osteoclastogenesis. Enzyme-linked immunosorbent assay was used to measure the biochemical markers of bone turnover. 16s rDNA sequencing was employed to analyze the abundance of GM, and UHPLC-MS/MS was used to identify serum metabolites. Correlation analysis was performed to explore the relationships among bone phenotypes, GM, and the metabolome.ResultsHFD induced bone loss accompanied by bone marrow adipose tissue expansion and bone formation inhibition. In the HFD group, the relative abundance of Firmicutes was increased significantly, while Bacteroidetes, Actinobacteria, Epsilonbacteraeota, and Patescibacteria were decreased compared with the ND group. Association analysis showed that thirty-two bacterial genera were significantly related to bone volume per tissue volume (BV/TV). One hundred and forty-five serum metabolites were identified as differential metabolites associated with HFD intervention, which were significantly enriched in five pathways, such as purine metabolism, regulation of lipolysis in adipocyte and cGMP-PKG signaling pathway. Sixty-four diffiential metabolites were matched to the MS2 spectra; and ten of them were positively correlated with BV/TV and five were negatively correlated with BV/TV.ConclusionsThese findings indicated that the alternations of GM and serum metabolites were related to HFD-induced bone loss, which might provide new insights into explain the occurrence and development of HFD-related osteoporosis. The regulatory effects of GM and metabolites associated with HFD on bone homeostasis required further exploration.
Inhibition of SOS Response by Nitric Oxide Donors in Escherichia coli Blocks Toxin Production and Hypermutation
Authors: Crane John K. , Burke Sarah R. , Alvarado Cassandra L. 
Published: December 2021

BackgroundPrevious reports have differed as to whether nitric oxide inhibits or stimulates the SOS response, a bacterial stress response that is often triggered by DNA damage. The SOS response is an important regulator of production of Shiga toxins (Stx) in Shiga-toxigenic E. coli (STEC). In addition, the SOS response is accompanied by hypermutation, which can lead to de novo emergence of antibiotic resistance. We studied these effects in vitro as well as in vivo.ResultsNitric oxide donors inhibited induction of the SOS response by classical inducers such as mitomycin C, ciprofloxacin, and zidovudine, as measured by assays for E. coli RecA. Nitric oxide donors also inhibited Stx toxin protein production as well as stx2 RNA in vitro and in vivo. In vivo experiments were performed with ligated ileal segments in the rabbit using a 20 h infection. The NO donor S-nitroso-acetylpenicillamine (SNAP) reduced hypermutation in vitro and in vivo, as measured by emergence of rifampin resistance. SNAP blocked the ability of the RecA protein to bind to single-stranded DNA in an electrophoretic mobility shift assay (EMSA) in vitro, an early event in the SOS response. The inhibitory effects of SNAP were additive with those of zinc acetate.ConclusionsNitric oxide donors blocked the initiation step of the SOS response. Downstream effects of this blockade included inhibition of Stx production and of hypermutation. Infection of rabbit loops with STEC resulted in a downregulation, rather than stimulation, of nitric oxide host defenses at 20 h of infection.
Serum Free Fatty Acids Independently Predict Adverse Outcomes in Acute Heart Failure Patients
Authors: Yu Yi , Jin Chunna , Zhao Chengchen , Zhu Shiyu , Meng Simin , Ma Hong , Wang Jian'an , Xiang Meixiang 
Published: December 2021

Background: Perturbation of energy metabolism exacerbates cardiac dysfunction, serving as a potential therapeutic target in congestive heart failure. Although circulating free fatty acids (FFAs) are linked to insulin resistance and risk of coronary heart disease, it still remains unclear whether circulating FFAs are associated with the prognosis of patients with acute heart failure (AHF).Methods: This single-center, observational cohort study enrolled 183 AHF patients (de novo heart failure or decompensated chronic heart failure) in the Second Affiliated Hospital, Zhejiang University School of Medicine. All-cause mortality and heart failure (HF) rehospitalization within 1 year after discharge were investigated. Serum FFAs were modeled as quartiles as well as a continuous variable (per SD of FFAs). The restricted cubic splines and cox proportional hazards models were applied to evaluate the association between the serum FFAs level and all-cause mortality or HF rehospitalization.Results: During a 1-year follow-up, a total of 71 (38.8%) patients had all-cause mortality or HF rehospitalization. The levels of serum FFAs positively contributed to the risk of death or HF rehospitalization, which was not associated with the status of insulin resistance. When modeled with restricted cubic splines, the serum FFAs increased linearly for the incidence of death or HF rehospitalization. In a multivariable analysis adjusting for sex, age, body-mass index, coronary artery disease, diabetes mellitus, hypertension, left ventricular ejection fraction and N-terminal pro-brain natriuretic peptid, each SD (303.07 μmol/L) higher FFAs were associated with 26% higher risk of death or HF rehospitalization (95% confidence interval, 2–55%). Each increasing quartile of FFAs was associated with differentially elevated hazard ratios for death or HF rehospitalization of 1 (reference), 1.71 (95% confidence interval, [0.81, 3.62]), 1.41 (95% confidence interval, [0.64, 3.09]), and 3.18 (95% confidence interval, [1.53, 6.63]), respectively.Conclusion: Serum FFA levels at admission among patients with AHF were associated with an increased risk of adverse outcomes. Additional studies are needed to determine the causal-effect relationship between FFAs and acute cardiac dysfunction and whether FFAs could be a potential target for AHF management.
Cardiac Magnetic Resonance Radiomics Reveal Differential Impact of Sex, Age, and Vascular Risk Factors on Cardiac Structure and Myocardial Tissue
Authors: Raisi-Estabragh Zahra , Jaggi Akshay , Gkontra Polyxeni , McCracken Celeste , Aung Nay , Munroe Patricia B. , Neubauer Stefan , Harvey Nicholas C. , Lekadir Karim , Petersen Steffen E. 
Published: December 2021

Background: Cardiovascular magnetic resonance (CMR) radiomics analysis provides multiple quantifiers of ventricular shape and myocardial texture, which may be used for detailed cardiovascular phenotyping.Objectives: We studied variation in CMR radiomics phenotypes by age and sex in healthy UK Biobank participants. Then, we examined independent associations of classical vascular risk factors (VRFs: smoking, diabetes, hypertension, high cholesterol) with CMR radiomics features, considering potential sex and age differential relationships.Design: Image acquisition was with 1.5 Tesla scanners (MAGNETOM Aera, Siemens). Three regions of interest were segmented from short axis stack images using an automated pipeline: right ventricle, left ventricle, myocardium. We extracted 237 radiomics features from each study using Pyradiomics. In a healthy subset of participants (n = 14,902) without cardiovascular disease or VRFs, we estimated independent associations of age and sex with each radiomics feature using linear regression models adjusted for body size. We then created a sample comprising individuals with at least one VRF matched to an equal number of healthy participants (n = 27,400). We linearly modelled each radiomics feature against age, sex, body size, and all the VRFs. Bonferroni adjustment for multiple testing was applied to all p-values. To aid interpretation, we organised the results into six feature clusters.Results: Amongst the healthy subset, men had larger ventricles with dimmer and less texturally complex myocardium than women. Increasing age was associated with smaller ventricles and greater variation in myocardial intensities. Broadly, all the VRFs were associated with dimmer, less varied signal intensities, greater uniformity of local intensity levels, and greater relative presence of low signal intensity areas within the myocardium. Diabetes and high cholesterol were also associated with smaller ventricular size, this association was of greater magnitude in men than women. The pattern of alteration of radiomics features with the VRFs was broadly consistent in men and women. However, the associations between intensity based radiomics features with both diabetes and hypertension were more prominent in women than men.Conclusions: We demonstrate novel independent associations of sex, age, and major VRFs with CMR radiomics phenotypes. Further studies into the nature and clinical significance of these phenotypes are needed.
Mechanical Properties of Frozen Glacial Tills due to Short Periods of Thawing
Authors: Fu Yanju , Jiang Yao , Wang Jiao , Liu Ziming , Lu Xingsheng 
Published: December 2021

Due to the warming climate, glacier retreat has left massive glacial tills in steep gullies; ice in the soil is prone to change phase resulting in the decrease of the ice strength and bonding of soil particles; collapse of thawing tills can lead to debris flows with disastrous consequences for geotechnical infrastructures. To improve our understanding of the mechanics of thawing glacial tills, we conducted unconsolidated–undrained direct shear tests on glacial tills from Tianmo gully on the southeastern Tibetan Plateau. Control specimens were not subjected to freeze–thaw action. A total of 648 specimens with three different dry densities, three initial water contents, and 18 thawing times were tested. Peak shear strength, peak stress to displacement ratio (0.857), and cohesion were the highest in frozen specimens. After a thawing time of 0.25 h, there was a marked decline in shear strength; maximum friction was 2.58, which was far below the value of cohesive strength. For thawing times of 0.25–4 h, peak strength varied little with thawing time, but cohesion decreased and internal friction angle increased with increasing thawing time. Our results indicate that thawing of the solid ice in the till during the initial phase of till thawing is the key control of peak till strength; the effect of ice on cohesion is greater during the initial phase of thawing and in loose tills. Moreover, frequent sediment recharge of gullies may be explained by the decrease of cohesion with increasing thawing time caused by short-term destruction of ice bonding.
Growth in Children With Noonan Syndrome and Effects of Growth Hormone Treatment on Adult Height
Authors: Libraro Annachiara , D’Ascanio Vito , Cappa Marco , Chiarito Mariangela , Digilio Maria Cristina , Einaudi Silvia , Grandone Anna , Maghnie Mohamad , Mazzanti Laura , Mussa Alessandro , Patti Giuseppa , Scarano Emanuela , Spinuzza Antonietta , Vannelli Silvia , Wasniewska Malgorzata Gabriela , Ferrero Giovanni Battista , Faienza Maria Felicia 
Published: December 2021

ObjectivesGrowth impairment is a common manifestation in Noonan syndrome (NS). Recombinant human GH (rhGH) treatment has been shown to increase growth and adult height (AH) in a few studies. We aimed to evaluate the growth trajectory towards the AH, and the effects of rhGH treatment in a large cohort of NS children.MethodsRetrospective, multicenter, cohort study including subjects with genetic diagnosis of NS. A total of 228 NS patients, 154 with PTPN11 mutations, 94 who reached AH, were recruited. Auxological data were collected at 2, 5, and 10 years, at pubertal onset, at AH. Sixty-eight NS subjects affected with GH deficiency (GHD) were treated with rhGH at a mean dose of 0.24 mg/kg per week until AH achievement.ResultsANOVA analysis showed a significant difference between birth length and height standard deviation scores (HSDS) at the different key ages (p&lt;0.001), while no significant differences were found between HSDS measurements at 2, 5, and 10 years, at pubertal onset, and at AH. HSDS increased from −3.10 ± 0.84 to −2.31 ± 0.99 during rhGH treatment, with a total height gain of 0.79 ± 0.74, and no significant difference between untreated and treated NS at AH.ConclusionsrhGH treatment at the standard dose used for children with GH idiopathic deficiency is effective in improving growth and AH in NS with GHD. Further studies are needed to assess genotype-specific response to rhGH treatment in the different pathogenic variants of PTPN11 gene and in the less common genotypes.
Head-to-Head Comparison of 68Ga-PSMA-11 and 131I in the Follow-Up of Well-Differentiated Metastatic Thyroid Cancer: A New Potential Theragnostic Agent
Authors: Pitalua-Cortes Quetzali , García-Perez Francisco Osvaldo , Vargas-Ahumada Joel , Gonzalez-Rueda Sofia , Gomez-Argumosa Edgar , Ignacio-Alvarez Eleazar , Soldevilla-Gallardo Irma , Torres-Agredo Liliana 
Published: December 2021

IntroductionThyroid cancer is the main endocrine neoplasia worldwide, for which 131I therapy is the cornerstone treatment. One of the main problems of follow up in patients with this type of cancer, is the need for thyroglobulin stimulation, not to mention the poor availability of 123I or 124I, to perform studies with a higher degree of sensitivity. Prostatic Specific Membrane Antigen (PSMA) PET/CT has demonstrated to be quite useful in a diversified number of neoplasms, on behalf of its capacity of evaluating the extent of type II carboxypeptidase expression in vascular endothelium. The end point of this article is to assess whether this novel image method possesses applicability in thyroid neoplasms follow up, for diagnostic and potentially therapeutic purposes.MethodsWe retrospectively evaluated well differentiated metastatic thyroid cancer patients, who underwent a post therapeutic 131I dose whole body scan (WBS) and complementary SPECT/CT, as well as 68Ga-PSMA–11 PET/CT.ResultsTen patients with differentiated thyroid cancer were included, of whom 80% were women and 20% men, mean age was 58 years old (± 11.6). Sixty-four metastatic lesions were analyzed, 67.19% had papillary histology and 32.81% were follicular type, the most affected site of metastases was bone in 57.81%, followed by lung 17.19%, lymph nodes 7.81%, postoperative thyroid bed 4.69%, brain 4.69% and others 7.81%. 68Ga PSMA-11 PET/CT detected 64/64 lesions, all of them also identified by computed tomography (CT), whereas 131I SPECT/CT detected 55/64 lesions. Discrepant lesions were localized in lung 44.4%, brain 22.2%, postoperative thyroid bed 11.1%, lymph nodes 11.1% and bone 11.1%. The degree of correspondence among observers was outstanding for both radiotracers, but close upon perfect for PSMA-11 (κ = 0.98; 95% CI, 0.80 – 0.91), as opposed to 131 I (κ = 0.86; 95% CI, 0.71 – 0.76).Conclusions68Ga-PSMA PET/CT showed an utterly superior capability for metastatic lesion detection when compared to 131I SPECT/CT. These findings suggest that PSMA PET/CT could possibly and precociously identify radioiodine refractoriness. PSMA uptake values not only expedite diagnosis, but also award it the ability to be used for therapeutic intents.
Endoscopic Lateral Neck Dissection: A New Frontier in Endoscopic Thyroid Surgery
Authors: Zhang Zeyu , Sun Botao , Ouyang Hui , Cong Rong , Xia Fada , Li Xinying 
Published: December 2021

BackgroundEndoscopic thyroidectomy and robotic thyroidectomy are effective and safe surgical options for thyroid surgery, with excellent cosmetic outcomes. However, in regard to lateral neck dissection (LND), much effort is required to alleviate cervical disfigurement derived from a long incision. Technologic innovations have allowed for endoscopic LND, without the need for extended cervical incisions and providing access to remote sites, including axillary, chest–breast, face-lift, transoral, and hybrid approaches.MethodsA comprehensive review of published literature was performed using the search terms “lateral neck dissection”, “thyroid”, and “endoscopy OR endoscopic OR endoscope OR robotic” in PubMed.ResultsThis review provides an overview of the current knowledge regarding endoscopic LND, and it specifically addresses the following points: 1) the surgical procedure, 2) the indications and contraindications, 3) the complications and surgical outcomes, and 4) the technical advantages and limitations. Robotic LND, totally endoscopic LND, and endoscope-assisted LND are separately discussed.ConclusionsEndoscopic LND is a feasible and safe technique in terms of complete resection of the selected neck levels, complications, and cosmetic outcomes. However, it is recommended to strictly select criteria when expanding the population of eligible patients. A formal indication for endoscopic LND has not yet been established. Thus, a well-designed, multicenter study with a large cohort is necessary to confirm the feasibility, long-term outcomes, oncological safety, and influence of endoscopic LND on patient quality of life (QoL).
Neutronics Perturbation Calculation Method Study of Solid Breeder Tritium Breeding Blanket for TBR Enhancement
Authors: Qu Shen , Cao Qixiang , Zhao Fengchao , Wang Xueren , Duan Xuru , Wang Xiaoyu 
Published: December 2021

Tritium breeding blanket (TBB) is an essential component in a fusion reactor, which has functions of tritium breeding, energy generation, and neutron shielding. Tritium breeding ratio (TBR) is a key parameter to evaluate whether the TBB could produce enough tritium to achieve the tritium self-sufficiency (TBR &gt;1) for fusion reactor. Current codes or software are hard to meet the requirements of high efficiency, high resolution, and high automation for neutronic optimization of TBB. In this article, the application of the density perturbation calculation on a solid breeder TBB was first performed. Then, the method of the geometry perturbation calculation based on the virtual density theory was studied. Results and comparison analysis indicate that the 1st + 2nd-order neutronic perturbation calculations (including the density perturbation and the geometry perturbation) results are consistent with the transport results under a perturbation of −15% to +15%. It is proven to be valid to use the perturbation calculation for rapid TBR enhancement study of the solid breeder TBB.
miR-214-5p Regulating Differentiation of Intramuscular Preadipocytes in Goats via Targeting KLF12
Authors: Du Yu , Wang Yong , Li Yanyan , Emu Quzhe , Zhu Jiangjiang , Lin Yaqiu 
Published: December 2021

Intramuscular fat (i.m.) is an adipose tissue that is deposited between muscle bundles. An important type of post-transcriptional regulatory factor, miRNAs, has been observed as an important regulator that can regulate gene expression and cell differentiation through specific binding with target genes, which is the pivotal way determining intramuscular fat deposition. Thus, this study intends to use RT-PCR, cell culture, liposome transfection, real-time fluorescent quantitative PCR (qPCR), dual luciferase reporter systems, and other biological methods clarifying the possible mechanisms on goat intramuscular preadipocyte differentiation that is regulated by miR-214-5p. Ultimately, our results showed that the expression level of miR-214-5p peaked at 48 h after the goat intramuscular preadipocytes were induced for adipogenesis. Furthermore, after inhibition of the expression of miR-214-5p, the accumulation of lipid droplets and adipocyte differentiation in goat intramuscular adipocytes were promoted by the way of up-regulation of the expression level of lipoprotein lipase (LPL) (p &lt; 0.05) and peroxisome proliferator-activated receptor gamma (PPARγ) (p &lt; 0.01) but inhibited the expression of hormone-sensitive lipase (HSL) (p &lt; 0.01). Subsequently, our study confirmed that Krüppel-like factor 12 (KLF12) was the target gene of miR-214-5p. Inhibition of the expression of KLF12 promoted adipocyte differentiation and lipid accumulation by upregulation of the expression of LPL and CCAAT/enhancer binding protein (C/EBPα) (p &lt; 0.01). Overall, these results indicated that miR-214-5p and its target gene KLF12 were negative regulators in progression of goat preadipocyte differentiation. Our research results provided an experimental basis for finally revealing the mechanism of miR-214-5p in adipocytes.