bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis, radiolabeling, and evaluation of 68Ga-labeled aminoquinoxaline derivative as a potent PFKFB3-targeted PET tracer
Authors: Chen Feng , Wu Yi , Ma Yixuan , Yin Honghai , Su Feijing , Huang Rui , Wu Xiaoai , Liu Qian 
Published: March 2023

Glycolysis, as a multi-step oxidation process, plays important roles in the energy supply for living cells, including malignant tumor cells. Recent studies have revealed that 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (named PFKFB3), a bifunctional enzyme in glycolysis, is upregulated in a variety of malignant solid tumors and has been regarded as a potential biomarker for the diagnosis and treatment of tumor patients. Based on the structure of selective PFKFB3 inhibitors, we designed and synthesized a radio-metal radiolabeled small molecule, 68Ga-5, which also showed potent selectivity in enzymatic and biochemical tests (with an IC50 value of 12.5 nM). According to further in vitro and in vivo evaluations, 68Ga-5 showed promising properties as a PET ligand, and selective accumulation in PFKFB3-positive tumors was observed in PET images (with max SUV values of 0.60). Our results indicated that radio-metal radiolabeled aminoquinoxaline derivative, as represented by 68Ga-5, held the potential to be developed as selective PFKFB3-targeted PET tracers, and further investigation and optimization would also be required for this scaffold.
Anti-viral drug discovery against monkeypox and smallpox infection by natural curcumin derivatives: A Computational drug design approach
Authors: Akash Shopnil , Hossain Arafat , Hossain Md. Sarowar , Rahman Md. Mominur , Ahmed Mohammad Z. , Ali Nemat , Valis Martin , Kuca Kamil , Sharma Rohit 
Published: March 2023

BackgroundIn the last couple of years, viral infections have been leading the globe, considered one of the most widespread and extremely damaging health problems and one of the leading causes of mortality in the modern period. Although several viral infections are discovered, such as SARS CoV-2, Langya Henipavirus, there have only been a limited number of discoveries of possible antiviral drug, and vaccine that have even received authorization for the protection of human health. Recently, another virial infection is infecting worldwide (Monkeypox, and Smallpox), which concerns pharmacists, biochemists, doctors, and healthcare providers about another epidemic. Also, currently no specific treatment is available against Monkeypox. This research gap encouraged us to develop a new molecule to fight against monkeypox and smallpox disease. So, firstly, fifty different curcumin derivatives were collected from natural sources, which are available in the PubChem database, to determine antiviral capabilities against Monkeypox and Smallpox.Material and methodPreliminarily, the molecular docking experiment of fifty different curcumin derivatives were conducted, and the majority of the substances produced the expected binding affinities. Then, twelve curcumin derivatives were picked up for further analysis based on the maximum docking score. After that, the density functional theory (DFT) was used to determine chemical characterizations such as the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), softness, and hardness, etc.ResultsThe mentioned derivatives demonstrated docking scores greater than 6.80 kcal/mol, and the most significant binding affinity was at -8.90 kcal/mol, even though 12 molecules had higher binding scores (-8.00 kcal/mol to -8.9 kcal/mol), and better than the standard medications. The molecular dynamic simulation is described by root mean square deviation (RMSD) and root-mean-square fluctuation (RMSF), demonstrating that all the compounds might be stable in the physiological system.ConclusionIn conclusion, each derivative of curcumin has outstanding absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics. Hence, we recommended the aforementioned curcumin derivatives as potential antiviral agents for the treatment of Monkeypox and Smallpox virus, and more in vivo investigations are warranted to substantiate our findings.
Bipolar anodal septal pacing with direct LBB capture preserves physiological ventricular activation better than unipolar left bundle branch pacing
Authors: Curila Karol , Jurak Pavel , Prinzen Frits , Jastrzebski Marek , Waldauf Petr , Halamek Josef , Tothova Marketa , Znojilova Lucie , Smisek Radovan , Kach Jakub , Poviser Lukas , Linkova Hana , Plesinger Filip , Moskal Pawel , Viscor Ivo , Vondra Vlastimil , Leinveber Pavel , Osmancik Pavel 
Published: March 2023

BackgroundLeft bundle branch pacing (LBBP) produces delayed, unphysiological activation of the right ventricle. Using ultra-high-frequency electrocardiography (UHF-ECG), we explored how bipolar anodal septal pacing with direct LBB capture (aLBBP) affects the resultant ventricular depolarization pattern.MethodsIn patients with bradycardia, His bundle pacing (HBP), unipolar nonselective LBBP (nsLBBP), aLBBP, and right ventricular septal pacing (RVSP) were performed. Timing of local ventricular activation, in leads V1–V8, was displayed using UHF-ECG, and electrical dyssynchrony (e-DYS) was calculated as the difference between the first and last activation. Durations of local depolarizations were determined as the width of the UHF-QRS complex at 50% of its amplitude.ResultsaLBBP was feasible in 63 of 75 consecutive patients with successful nsLBBP. aLBBP significantly improved ventricular dyssynchrony (mean −9 ms; 95% CI (−12;−6) vs. −24 ms (−27;−21), ), p &lt; 0.001) and shortened local depolarization durations in V1–V4 (mean differences −7 ms to −5 ms (−11;−1), p &lt; 0.05) compared to nsLBBP. aLBBP resulted in e-DYS −9 ms (−12; −6) vs. e-DYS 10 ms (7;14), p &lt; 0.001 during HBP. Local depolarization durations in V1–V2 during aLBBP were longer than HBP (differences 5-9 ms (1;14), p &lt; 0.05, with local depolarization duration in V1 during aLBBP being the same as during RVSP (difference 2 ms (−2;6), p = 0.52).ConclusionAlthough aLBBP improved ventricular synchrony and depolarization duration of the septum and RV compared to unipolar nsLBBP, the resultant ventricular depolarization was still less physiological than during HBP.
Anatomic distribution of lower extremity deep venous thrombosis is associated with an increased risk of pulmonary embolism: A 10-year retrospective analysis
Authors: Zhang Jianjun , Chen Yan , Wang Zhicong , Chen Xi , Liu Yuehong , Liu Mozhen 
Published: March 2023

AimsTo investigate the potential relationship between anatomic distribution of lower extremity deep venous thrombosis (LEDVT) and pulmonary embolism (PE).MethodsA retrospective case-control study was performed in patients diagnosed with LEDVT, which were confirmed by bilateral lower extremity compression ultrasonography (CUS) examination. According to the ultrasound reports, thrombus sidedness was categorized as unilateral and bilateral lower extremity, thrombus location was classified into distal and proximal LEDVT. Anatomic distributions of LEDVT were further subdivided depending on the combination of thrombus sidedness and location. Patients with PE were identified using the International Classification of Diseases-10 (ICD-10) codes (I26.0 and I26.9), and divided into PE group and Non-PE group. Univariate and multivariate logistic regression analyses were used to assess the association between anatomic distribution of LEDVT and PE. Sensitivity analyses were also conducted.ResultsA total of 2,363 consecutive patients with LEDVT were included, of whom 66.10% and 33.90% were unilateral and bilateral LEDVT, as well as 71.39% and 28.61% were isolated distal and proximal LEDVT, respectively. After the diagnosis of LEDVT, 185 patients (7.83%) developed PE. The proportions of PE ranged between the lowest (4.07%) in unilateral-distal LEDVT and highest (14.55%) in bilateral-proximal LEDVT. Multivariate logistic regression analysis showed that bilateral LEDVT (odds ratios [OR] = 2.455, 95% confidence interval [CI]: 1.803–3.344, P &lt; 0.001) and proximal LEDVT (OR = 1.530, 95% CI: 1.105–2.118, P = 0.010) were risk factors for developing PE. Moreover, unilateral-proximal (OR = 2.129, 95% CI: 1.365–3.320, P = 0.00), bilateral-distal (OR = 3.193, 95% CI: 2.146–4.752, P &lt; 0.001) and bilateral-proximal LEDVT(OR = 3.425, 95% CI: 2.093–5.603, P &lt; 0.001) were significantly associated with an increased risk of PE. Sensitivity analyses also confirmed the robustness of these associations.ConclusionPatients with unilateral-proximal, bilateral-distal or bilateral-proximal are more likely to suffer from PE than those with unilateral-distal LEDVT.
Metabolomics analysis reveals serum biomarkers in patients with diabetic sarcopenia
Authors: Tan Yuwei , Liu Xiaosong , Yang Yinping , Li Baoying , Yu Fei , Zhao Wenqian , Fu Chunli , Yu Xin , Han Zhenxia , Cheng Mei 
Published: March 2023

IntroductionDiabetic sarcopenia (DS) is characterized by muscle atrophy, slower nerve conduction, reduced maximum tension generated by skeletal muscle contraction, and slower contraction rate. Hence, DS can cause limb movement degeneration, slow movement, reduced balance, reduced metabolic rate, falls, fractures, etc. Moreover, the relevant early biological metabolites and their pathophysiological mechanism have yet to be characterized.MethodThe current cross-sectional study employed serum metabolomics analysis to screen potential noninvasive biomarkers in patients with diabetic sarcopenia. A total of 280 diabetic patients were enrolled in the study (n = 39 sarcopenia [DS], n = 241 without sarcopenia [DM]). Ten patients were randomly selected from both groups. Non-targeted metabolomic analysis was performed by ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.ResultsA total of 632 differential metabolites were identified, including 82 that were significantly differentially abundant (P &lt; 0.05, VIP &gt; 1, FC &gt; 1.2 or FC &lt; 0.8). Compared with the DM group, the contents of pentadecanoic acid, 5'-methylthioadenosine (5'-MTA), N,N-dimethylarginine (asymmetric dimethylarginine, ADMA), and glutamine in the DS group were significantly increased, while that of isoxanthohumol was decreased.DiscussionBased on receiver operating characteristic curve analysis, pentadecanoic acid, 5'-MTA, ADMA, and glutamine may serve as potential biomarkers of DS. Moreover, ATP-binding cassette (ABC) transporters and the mammalian target of the rapamycin signaling pathway were found to potentially have important regulatory roles in the occurrence and development of DS (P &lt; 0.05). Collectively, the differential metabolites identified in this study provide new insights into the underlying pathophysiology of DS and serve as a basis for therapeutic interventions.
Pure androgen-secreting adrenal tumor (PASAT): A rare case report of bilateral PASATs and a systematic review
Authors: Liao Zhangcheng , Gao Yuting , Zhao Yang , Wang Zhan , Wang Xu , Zhou Jiaquan , Zhang Yushi 
Published: March 2023

BackgroundAdult pure androgen–secreting adrenal tumors (PASATs) are extremely rare, and their characteristics are largely unknown.MethodsA rare case of adult bilateral PASATs was reported, and a systematic literature review of adult PASATs was conducted to summarize the characteristics of PASATs.ResultsIn total, 48 studies, including 40 case reports and 8 articles, were identified in this review. Analysis based on data of 42 patients (including current case and 41 patients from 40 case reports) showed that average age was 40.48 ± 15.80 years (range of 18-76). The incidence of adult PASAT peaked at 21-30 years old, while that of malignant PASAT peaked at 41-50 years old. Most PASAT patients were female (40/42, 95.23%), and hirsutism was the most common symptom (37/39, 94.87%). Testosterone (T) was the most commonly elevated androgen (36/42, 85.71%), and 26 of 32 tested patients presented increased dehydroepiandrosterone sulfate (DS) levels. In malignancy cases, disease duration was significantly decreased (1.96 vs. 4.51 years, P=0.025), and tumor diameter was significantly increased (8.9 vs. 4.9 cm, p=0.011). Moreover, the androgen levels, namely, T/upper normal range limit (UNRL) (11.94 vs. 4.943, P=0.770) and DS/UNRL (16.5 vs. 5.28, P=0.625), were higher in patients with malignancy. In total, 5 out of 7 patients showed an increase in DS or T in the human chorionic gonadotropin (HCG) stimulation test. Overall, 41 out of 42 patients (including current case) underwent adrenal surgery, and recurrence, metastasis, or death was reported in 5 out of 11 malignant patients even with adjuvant or rescue mitotane chemotherapy.ConclusionAdult PASAT, which is predominant in women, is characterized by virilism and menstrual dysfunction, especially hirsutism. Elevated T and DS may contribute to the diagnosis of adult PASAT, and HCG stimulation test might also be of help in diagnosis. Patients with malignant PASAT have a shorter disease duration, larger tumor sizes and relatively higher androgen levels. Surgery is recommended for all local PASATs, and Malignancy of PASAT should be fully considered due to the high risk of malignancy, poor prognosis and limited effective approaches.
Characterization of the inflammatory proteome of synovial fluid from patients with psoriatic arthritis: Potential treatment targets
Authors: Barbarroja Nuria , López-Montilla Maria Dolores , Cuesta-López Laura , Pérez-Sánchez Carlos , Ruiz-Ponce Miriam , López-Medina Clementina , Ladehesa-Pineda Maria Lourdes , López-Pedrera Chary , Escudero-Contreras Alejandro , Collantes-Estévez Eduardo , Arias-de la Rosa Iván 
Published: March 2023

Objectives1) To characterize the inflammatory proteome of synovial fluid (SF) from patients with Psoriatic Arthritis (PsA) using a high-quality throughput proteomic platform, and 2) to evaluate its potential to stratify patients according to clinical features.MethodsInflammatory proteome profile of SF from thirteen PsA patients with active knee arthritis were analyzed using proximity extension assay (PEA) technology (Olink Target 96 Inflammation panel). Four patients with OA were included as control group.ResultsSeventy-nine inflammation-related proteins were detected in SF from PsA patients (SF-PsA). Unsupervised analyzes of the molecular proteome profile in SF-PsA identified two specific phenotypes characterized by higher or lower levels of inflammation-related proteins. Clinically, SF-PsA with higher levels of inflammatory proteins also showed increased systemic inflammation and altered glucose and lipid metabolisms. Besides, SF from PsA patients showed 39 out of 79 proteins significantly altered compared to SF-OA specifically related to cell migration and inflammatory response. Among these, molecules such as TNFα, IL-17A, IL-6, IL-10, IL-8, ENRAGE, CCL20, TNFSF-14, OSM, IFNγ, MCP-3, CXCL-11, MCP4, CASP-8, CXCL-6, CD-6, ADA, CXCL-10, TNFβ and IL-7 showed the most significantly change.ConclusionThis is the first study that characterizes the inflammatory landscape of synovial fluid of PsA patients by analyzing a panel of 92 inflammatory proteins using PEA technology. Novel SF proteins have been described as potential pathogenic molecules involved in the pathogenesis of PsA. Despite the flare, inflammatory proteome could distinguish two different phenotypes related to systemic inflammation and lipid and glucose alterations.
An ELISA-based assay for determining haemagglutinin potency in egg, cell, or recombinant protein derived influenza vaccines
Authors: Bodle Jesse , Vandenberg Kirsten , Laurie Karen , Barr Ian G. , Zhang Ying , Rockman Steven 
Published: March 2023

BackgroundThe current compendial assay for haemagglutinin antigen potency in influenza vaccine is the single radial immunodiffusion (SRID) which is time consuming and can lead to delays in release of vaccine. We previously described an alternate capture and detection enzyme linked immunoassay (ELISA) that utilizes sub-type specific, sub-clade cross-reactive monoclonal antibodies (mAbs) that are haemagglutination inhibiting (HAI) and correlate with SRID. The aim of this study is to determine the applicability of ELISA across current platforms for quantitation of seasonal quadrivalent vaccine.MethodsA single mAb capture and detection ELISA was employed to quantitate hemagglutinin (HA) derived from different vaccine platforms and host organisms and compared to SRID and a polyclonal antibody based ELISA.ResultsWe selected mAbs that displayed appropriate characteristics for a stability indicating potency assay which reacted to avian, insect and mammalian derived HA. Qualification of the homologous mAb assay against egg and cell derived HA demonstrated performance similar to that of the SRID however, superiority in sensitivity and specificity against strains from both influenza B/Victoria and B/Yamagata lineages. Analysis of drifted strains across multiple seasons demonstrated continued utility of this approach, reducing the need to develop reagents each season. With modification of the assay, we were able to accurately measure HA from different platforms and process stages using a single calibrated reference standard. We demonstrated the accuracy of ELISA when testing vaccine formulations containing selected adjuvants at standard and higher concentrations. Accelerated stability analysis indicated a strong correlation in the rate of degradation between the homologous mAb ELISA and SRID but not with ELISA utilizing polyclonal antisera. Further, we demonstrated specificity was restricted to the trimeric and oligomeric forms of HA but not monomeric HA.ConclusionWe believe this homologous mAb ELISA is a suitable replacement for the SRID compendial assay for HA antigen quantitation and stability assessment. Identification of suitable mAbs that are applicable across multiple vaccine platforms with extended sub-type reactivity across a number of influenza seasons, indicate that this assay has broad applicability, leading to earlier availability of seasonal and pandemic vaccines without frequent replacement of polyclonal antisera that is required with SRID.
Quantitative liver SPECT/CT is a novel tool to assess liver function, prognosis, and response to treatment in cirrhosis
Authors: Kaur Amritjyot , Verma Nipun , Singh Baljinder , Kumar Ajay , Kumari Sunita , De Arka , Sharma Ratti Ram , Singh Virendra 
Published: March 2023

BackgroundFunctional liver reserve is an important determinant of survival in cirrhosis. The traditional indocyanine green test (ICG) is cumbersome. Hence, we developed and validated a novel liver imaging, a hybrid of SPECT and CT (Q-SPECT/CT), for evaluating disease severity, outcomes, and response to treatment in decompensated cirrhosis (DC).MethodsWe recruited a cohort of DC patients at a tertiary institute between 2016–2019. First, we standardized the Q-SPECT/CT across a predefined range of volumes through phantom experiments. Then we performed clinical and laboratory evaluations, ICG test (retention at 15 min), and Q-SPECT/CT at baseline and 12 months of granulocyte colony-stimulating factor (G-CSF) and standard medical treatment (SMT).ResultsIn 109 DC patients, 87.1% males, aged 51 ± 10 years, MELD: 14 (7–21), the percent quantitative liver uptake (%QLU) on Q-SPECT/CT exhibited a strong correlation with CTP (r = −0.728, p &lt; 0.001), MELD (r = −0.743; p &lt; 0.001) and ICG-R-15 (r = −0.720, p &lt; 0.001) at baseline. %QLU had the maximum discrimination (AUC: 0.890–0.920), sensitivity (88.9–90.3%), specificity (81.2–90.7%), and accuracy (85.8–89.4%) than liver volumes on Q-SPECT/CT or ICG test for classifying patients in CTP/MELD based prognostic categories. A significant increase in %QLU (26.09 ± 10.06 to 31.2 ± 12.19, p = 0.001) and improvement in CTP/MELD correlated with better survival of G-CSF treated DC patients (p &lt; 0.05). SMT did not show any improvement in Q-SPECT/CT or clinical severity scores (p &gt; 0.05). %QLU &gt; 25 (adj.H.R.: 0.234, p = 0.003) and G-CSF treatment (adj.H.R.: 0.414, p = 0.009) were independent predictors of better 12-months survival in DC.ConclusionQ-SPECT/CT (%QLU) is a novel non-invasive, diagnostic, prognostic, and theragnostic marker of liver reserve and its functions in cirrhosis patients.Clinical trial registrationClinicaltrials.gov, NCT02451033 and NCT03415698.
Seropositive for hepatitis B and C viruses is associated with the risk of decreased bone mineral density in adults: An analysis of studies from the NHANES database
Authors: Tao Jiasheng , Yan Zijian , Huang Wenmian , Feng Tao 
Published: March 2023

BackgroundSome studies had reported that patients with viral hepatitis are at increased risk of reduced bone mineral density and even osteoporosis. However, the interaction between reduced bone mineral density (BMD) and viral hepatitis remains inconclusive. Therefore, our study collected hepatitis test results and bone mineral density from respondents in the NHANES database. The aim of this study was to investigate whether there is an association between hepatitis and a decrease in bone mineral density.MethodsThe respondents with both hepatitis- and BMD-related indicators from the NHANES database in the United States from 2005–2010, 2013–2014, to 2017–2020 were collected for this study. BMD were compared between respondents who were positive and negative for respondents related to hepatitis B and C. BMD was measured using dual-energy X-ray absorptiometry of the femur and lumbar spine. Finally, multiple regression analysis was performed between hepatitis B surface antigen (HBsAg) and hepatitis C RNA (HCV-RNA) and BMD in the respondents.ResultsA total of 15,642 respondents were included in the hepatitis B surface antigen-related survey. Of these, 1,217 respondents were positive for hepatitis B surface antigen. A total of 5111 hepatitis C RNA-related responders were included. Hepatitis C RNA-positive had 268 respondents. According to the results of the multiple regression analysis, the femoral BMD was significantly lower in HBsAg (+) respondents compared to HBsAg (–) respondents: −0.018 (−0.026, −0.009) (P &lt; 0.01). Moreover, spinal BMD was significantly lower in HBsAg (+) respondents compared to HBsAg (–) respondents: −0.020 (−0.030, −0.010) (P &lt; 0.01). According to the results of multiple regression analysis for hepatitis C RNA, HCV-RNA (+) respondents had significantly lower BMD compared to HCV-RNA (–) respondents: −0.043 (−0.059, −0.026) (P &lt; 0.01).ConclusionDuring the analysis of respondents in the NHANES database in the United States, positive tests for hepatitis B surface antigen and hepatitis C RNA were found to be associated with a reduction in BMD. Positive serology for these hepatitis indicators may increase the risk of reduced BMD. Of course, this conclusion still needs to be further confirmed by more large clinical trials.