bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Efficacy of Li-ESWT Combined With VED in Diabetic ED Patients Unresponsive to PDE5is: A Single-Center, Randomized Clinical Trial
Authors: Tao Rongzhen , Chen Jianhuai , Wang Dujian , Li Yunpeng , Xiang Jun , Xiong Lei , Ji Junbiao , Wu Jie , Zhou Shuang , Jia Chunping , Lv Jianlin , Yang Jie , Tang Qinglai 
Published: June 2022

IntroductionPhosphodiesterase type 5-inhibitors (PDE5is) are the first-line treatment for patients with diabetes mellitus-induced erectile dysfunction (DMED), however, some patients are non-responser to PDE5is. We performed a perspective, randomized, comparative study to explore the efficacy of low intensity extracorporeal shock wave treatment (Li-ESWT) combined with vacuum erectile device (VED) in the treatment of DMED patients who were unresponsive to PDE5is.MethodsOne hundred and five eligible patients were randomly divided into three groups: group A (VED), group B (Li-ESWT) and group C (VED plus Li-ESWT). Follow-up was conducted at 4 weeks, 8 weeks and 12 weeks after the end of treatment. The erectile function was estimated by the international index of erectile function-erectile function domain (IIEF-EF), erection hardness score (EHS), sexual encounter profile questions 2 and 3 (SEP2 and SEP3) and global assessment question 1 and 2 (GAQ1 and GAQ2) before and after treatment. The changes of five points in IIEF-EF were calculated as the minimal clinical important difference (MCID), which was considered as the main index of efficacy.ResultsThe MCID was achieved in 14.7%, 14.7% and 17.6% patients in group A at the follow up on 4 weeks, 8 weeks and 12 weeks, respectively (36.4%, 39.4% and 36.4% in group B; 36.4%, 51.5%, and 66.7% in group C). There were significant differences in the percentage of MCID cases between group A and group C at the follow up on 12 weeks (P&lt;0.001), as well as that between group B and group C (P=0.014). Additionally, comparison in MCID within group C showed that there were significant differences between 4 weeks and 12 weeks follow-up (P=0.014).ConclusionOur findings indicated the combined therapy Li-ESWT and VED was more beneficial to shift turn PDE5is non-responders to responders for moderate patients with DMED than VED or Li-ESWT monotherapy. Moreover, this study provided evidence that patients with DMED who failed after taking oral PDE5is could attempt to opt for an alternative physicotherapy (Li-ESWT or VED) prior to more invasive alternatives.
Long-Term Effects of Biochar Application With Reduced Chemical Fertilizer on Paddy Soil Properties and japonica Rice Production System
Authors: Gu Wenqi , Wang Yuning , Feng Zhibo , Wu Di , Zhang Honggui , Yuan Hechong , Sun Yuanyuan , Xiu Liqun , Chen Wenfu , Zhang Weiming 
Published: June 2022

To clarify the effects of co-application of rice-straw biochar and different chemical fertilizer doses on paddy soil properties and japonica rice production in Northeast China, a located-field experiment was adopted for 5 years. The treatments included fertilization (F, no biochar, control) and rice-straw biochar (7.5 t ha−1) combined with different chemical fertilizer doses (100, 80, and 60% that of F) set as CF, CF1, and CF2, respectively. The results showed that the co-application of biochar and chemical fertilizers after 5 years reduced soil bulk density, increased soil total and capillary porosity, changed the soil solid–liquid–gas ratio (increased the liquid and air ratios and decreased the solid ratio), and increased soil macroaggregates (&gt;0.25 mm) and aggregate stability, which enhanced the soil’s physical properties. Furthermore, the co-application improved soil pH and soil enzyme activity (urease, sucrase, and catalase) and had a significant effect on promoting SOM. The soil total N, P, and K of CF and CF1, were 23.48, %, 47.28%, and 26.59% and 9.47%, 43.98%, and 27.87% higher than those of the control, respectively. The soil available nutrients (N, P, and K) increased in the co-application treatment, shown as the nitrogen was promoted higher in the early growth of rice, while phosphorus and potassium were exhibited greater in the late growth. With the soil amendment, the co-application increased the rice plant height and dry matter accumulation, and the CF and CF1 increased yields by 5.78 and 2.41%, respectively, by increasing the rice effective panicles, grains per panicle, and seed-setting rate. The co-application of biochar and chemical fertilizers could significantly amend soil properties and reduce chemical fertilizer use to ensure rice–grain output, which has an important significance for enhancing sustainable soil and crop productivity.
Evaluation of Association Studies and Meta-Analyses of eNOS Polymorphisms in Type 2 Diabetes Mellitus Risk
Authors: Wang Di , Liu Liangshu , Zhang Chengyu , Lu Wensheng , Wu Feifei , He Xiaofeng 
Published: June 2022

Background: Numerous studies reported the associations between endothelial nitric oxide synthase (eNOS) polymorphisms (4b/a VNTR (rs869109213), G894T (rs1799983) and T786C (rs2070744)) and type 2 diabetes mellitus (T2DM) risk. However, the conclusions were incongruent. Moreover, since no published meta-analyses were performed, a key issue regarding false-positive results needs to be addressed. Furthermore, four new articles have been published on these issues. Therefore, an updated meta-analysis was conducted to further explore these associations.Objectives: To investigate the association between eNOS 4b/a, G894T and T786C polymorphisms and T2DM risk.Methods: Studies were searched by using the PubMed, China National Knowledge Infrastructure (CNKI), Medline, Embase, International Statistical Institute (ISI) and the China Wanfang databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the associations using five genetic models. Furthermore, the false-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and the Venice criteria were employed to assess the credibility of statistically significant associations.Results: Overall, the eNOS 4b/a polymorphism was associated with a significantly decreased T2DM risk in Asians (bb vs. aa: OR = 0.44, 95% CI = 0.23–0.84; ab + bb vs. aa: OR = 0.45, 95% CI = 0.24–0.86; bb vs. aa + ab: OR = 0.73, 95% CI = 0.59–0.91; b vs. a: OR = 0.71, 95% CI = 0.57–0.88); the eNOS G894T polymorphism was associated with a significantly increased T2DM risk in Asians (GT vs. GG: OR = 1.52, 95% CI = 1.15–2.01; GT + TT vs. GG: OR = 1.52, 95% CI = 1.15–2.01; T vs. G: OR = 1.39, 95% CI = 1.09–1.76); the eNOS T786C polymorphism was associated with a significantly increased T2DM risk in Indian (TC vs. TT: OR = 1.93, 95% CI = 1.27–2.94; TC + CC vs. TT: OR = 2.06, 95%CI = 1.26–3.36; C vs. T: OR = 1.90, 95%CI = 1.17–3.08). However, when a sensitivity analysis was performed after excluding low quality and Hardy–Weinberg Disequilibrium (HWD) studies, no significant association was found for the eNOS G894T polymorphism. After credibility assessment, we identified “less-credible positive results” for the statistically significant associations in the current meta-analysis.Conclusion: In conclusion, this article suggests that all substantial relationships between eNOS 4b/a, G894T, and T786C polymorphisms and T2DM risk are most likely due to false positive results rather than real connections or biological variables.
Immune- and Stemness-Related Genes Revealed by Comprehensive Analysis and Validation for Cancer Immunity and Prognosis and Its Nomogram in Lung Adenocarcinoma
Authors: Chen Mengqing , Wang Xue , Wang Wenjun , Gui Xuemei , Li Zhan 
Published: June 2022

ObjectiveLung adenocarcinoma (LUAD) is a familiar lung cancer with a very poor prognosis. This study investigated the immune- and stemness-related genes to develop model related with cancer immunity and prognosis in LUAD.MethodThe Cancer Genome Atlas (TCGA) was utilized for obtaining original transcriptome data and clinical information. Differential expression, prognostic value, and correlation with clinic parameter of mRNA stemness index (mRNAsi) were conducted in LUAD. Significant mRNAsi-related module and hub genes were screened using weighted gene coexpression network analysis (WGCNA). Meanwhile, immune-related differential genes (IRGs) were screened in LUAD. Stem cell index and immune-related differential genes (SC-IRGs) were screened and further developed to construct prognosis-related model and nomogram. Comprehensive analysis of hub genes and subgroups, involving enrichment in the subgroup [gene set enrichment analysis (GSEA)], gene mutation, genetic correlation, gene expression, immune, tumor mutation burden (TMB), and drug sensitivity, used bioinformatics and reverse transcription polymerase chain reaction (RT-PCR) for verification. ResultsThrough difference analysis, mRNAsi of LUAD group was markedly higher than that of normal group. Clinical parameters (age, gender, and T staging) were ascertained to be highly relevant to mRNAsi. MEturquoise and MEblue were found to be the most significant modules (including positive and negative correlations) related to mRNAsi via WGCNA. The functions and pathways of the two mRNAsi-related modules were mainly enriched in tumorigenesis, development, and metastasis. Combining stem cell index–related differential genes and immune-related differential genes, 30 prognosis-related SC-IRGs were screened via Cox regression analysis. Then, 16 prognosis-related SC-IRGs were screened to construct a LASSO regression model at last. In addition, the model was successfully validated by using TCGA-LUAD and GSE68465, whereas c-index and the calibration curves were utilized to demonstrate the clinical value of our nomogram. Following the validation of the model, GSEA, immune cell correlation, TMB, clinical relevance, etc., have found significant difference in high- and low-risk groups, and 16-gene expression of the SC-IRG model also was tested by RT-PCR. ADRB2, ANGPTL4, BDNF, CBLC, CX3CR1, and IL3RA were found markedly different expression between the tumor and normal group.ConclusionThe SC-IRG model and the prognostic nomogram could accurately predict LUAD survival. Our study used mRNAsi combined with immunity that may lay a foundation for the future research studies in LUAD.
Immune Responses Against SARS-CoV-2 WT and Delta Variant in Elderly BNT162b2 Vaccinees
Authors: Jäger Michael , Sonnleitner Sissy Therese , Dichtl Stefanie , Lafon Eliott , Diem Gabriel , Walder Gernot , Lass-Flörl Cornelia , Wilflingseder Doris , Posch Wilfried 
Published: June 2022

BackgroundResidents of nursing homes are one of the most vulnerable groups during the severe acute syndrome coronavirus 2 (SARS-CoV-2) pandemic. The aim of this study was to characterize cellular and humoral immune responses in &gt;70-year-old participants before vaccination, after first and second vaccination with BNT162b2, in contrast to second-dose-vaccinated participants younger than 60 years.MethodsPeripheral blood mononuclear cells of 45 elderly and 40 younger vaccinees were analyzed by IFNγ ELISpot, specific immunoglobulin G antibody titers against SARS-CoV-2 spike protein, and neutralization abilities against SARS-CoV-2 wild-type (WT) and Delta variant (B.1.617.2).ResultsOur results clearly demonstrate a significantly increased T cell response, IgG titers, and neutralization activities against SARS-CoV-2 WT and Delta between first and second vaccination with BNT162b2 in elderly vaccinees, thereby highlighting the importance of the second booster. Interestingly, similar cellular and humoral immune responses against SARS-CoV-2 WT and Delta were found after the second vaccine dose in the young and elderly groups.ConclusionsOur data demonstrate a full picture of cellular and humoral immune responses of BNT162b2-vaccinees in two age cohorts. In all vaccines, SARS-CoV-2 WT-specific antibodies with similar neutralizing activity were detected in all vaccinees. After the second vaccination, neutralization titers against SARS-CoV-2 Delta were impaired in both age groups compared with SARS-CoV-2 WT, thereby emphasizing the need for an additional booster to overcome rising variants of SARS-CoV-2.
Nationwide Effectiveness of First and Second SARS-CoV2 Booster Vaccines During the Delta and Omicron Pandemic Waves in Hungary (HUN-VE 2 Study)
Authors: Kiss Zoltán , Wittmann István , Polivka Lőrinc , Surján György , Surján Orsolya , Barcza Zsófia , Molnár Gergő Attila , Nagy Dávid , Müller Veronika , Bogos Krisztina , Nagy Péter , Kenessey István , Wéber András , Pálosi Mihály , Szlávik János , Schaff Zsuzsa , Szekanecz Zoltán , Müller Cecília , Kásler Miklós , Vokó Zoltán 
Published: June 2022

BackgroundIn Hungary, the pandemic waves in late 2021 and early 2022 were dominated by the Delta and Omicron SARS-CoV-2 variants, respectively. Booster vaccines were offered with one or two doses for the vulnerable population during these periods.Methods and FindingsThe nationwide HUN-VE 2 study examined the effectiveness of primary immunization, single booster, and double booster vaccination in the prevention of Covid-19 related mortality during the Delta and Omicron waves, compared to an unvaccinated control population without prior SARS-CoV-2 infection during the same study periods. The risk of Covid-19 related death was 55% lower during the Omicron vs. Delta wave in the whole study population (n=9,569,648 and n=9,581,927, respectively; rate ratio [RR]: 0.45, 95% confidence interval [CI]: 0.44–0.48). During the Delta wave, the risk of Covid-19 related death was 74% lower in the primary immunized population (RR: 0.26; 95% CI: 0.25–0.28) and 96% lower in the booster immunized population (RR: 0.04; 95% CI: 0.04–0.05), vs. the unvaccinated control group. During the Omicron wave, the risk of Covid-19 related death was 40% lower in the primary immunized population (RR: 0.60; 95% CI: 0.55–0.65) and 82% lower in the booster immunized population (RR: 0.18; 95% CI: 0.16–0.2) vs. the unvaccinated control group. The double booster immunized population had a 93% lower risk of Covid-19 related death compared to those with only one booster dose (RR: 0.07; 95% CI. 0.01–0.46). The benefit of the second booster was slightly more pronounced in older age groups.ConclusionsThe HUN-VE 2 study demonstrated the significantly lower risk of Covid-19 related mortality associated with the Omicron vs. Delta variant and confirmed the benefit of single and double booster vaccination against Covid-19 related death. Furthermore, the results showed the additional benefit of a second booster dose in terms of SARS-CoV-2 infection and Covid-19 related mortality.
Cognitive Trajectories in Community-Dwelling Older Adults and Incident Dementia, Disability and Death: A 10-Year Longitudinal Study
Authors: Wu Zimu , Woods Robyn L. , Chong Trevor T. J. , Orchard Suzanne G. , Shah Raj C. , Wolfe Rory , Storey Elsdon , Sheets Kerry M. , Murray Anne M. , McNeil John J. , Ryan Joanne 
Published: June 2022

ObjectiveThe inter-individual variability in cognitive changes may be early indicators of major health events. We aimed to determine whether late-life cognitive trajectories were associated with incident dementia, persistent physical disability and all-cause mortality.MethodsData came from a cohort of older community-dwelling individuals aged 70 years or above in Australia and the United States. Global cognition, verbal fluency, episodic memory and psychomotor speed were assessed regularly at up to seven waves between 2010 and 2017. Dementia, disability in activities of daily living, and death were adjudicated between 2017 and 2020. Latent classes of cognitive trajectories over seven years were determined using group-based trajectory modeling. Multivariable logistic regression was used for the prospective associations between cognitive trajectories and these outcomes.ResultsCognitive trajectories were defined for 16,174 participants (mean age: 78.9 years; 56.7% female) who were alive and without incident dementia or disability by 2017, among which 14,655 participants were included in the association analysis. Between three and five trajectory classes were identified depending on the cognitive test. Cognitive trajectories were strongly associated with the risk of dementia. For example, compared to those in the highest-functioning trajectory, the worst performers of episodic memory had a 37-fold increased risk of dementia (95% CI: 17.23–82.64). The lowest trajectories of both global cognition and episodic memory also predicted increased mortality risk (OR: 1.80, 95% CI: 1.28–2.52; OR: 1.61, 95% CI: 1.09–2.36, respectively), while only slow psychomotor speed was marginally associated with physical disability (OR: 2.39, 95% CI: 0.99–5.77).ConclusionsIn older individuals, cognitive trajectories appear to be early indicators of clinically relevant health outcomes. Systematic cognitive assessments as part of routine geriatric evaluation may facilitate early identification and interventions for those individuals at highest risk.
Effectiveness and Safety of JAK Inhibitors in Autoinflammatory Diseases: A Systematic Review
Authors: Boyadzhieva Zhivana , Ruffer Nikolas , Burmester Gerd , Pankow Anne , Krusche Martin 
Published: June 2022

IntroductionAutoinflammatory diseases (AID) are rare diseases presenting with episodes of sterile inflammation. These involve multiple organs and can cause both acute organ damage and serious long-term effects, like amyloidosis. Disease-specific anti-inflammatory therapeutic strategies are established for some AID. However, their clinical course frequently includes relapsing, uncontrolled conditions. Therefore, new therapeutic approaches are needed. Janus Kinase inhibitors (JAKi) block key cytokines of AID pathogenesis and can be a potential option.MethodsA systematic review of the literature in accordance with the PRISMA guidelines was conducted. Three databases (MEDLINE, Embase and Cochrane Central Register of Controlled Trials) were searched for publications regarding the use of JAKi for AID. Data from the included publications was extracted and a narrative synthesis was performed. Criteria for defining treatment response were defined and applied.ResultsWe report data from 38 publications with a total of 101 patients describing the effects of JAKi in AID. Data on Type I Interferonopathies, Adult-Onset Still's Disease (AOSD), Systemic Juvenile Idiopathic Arthritis (sJIA), Familial Mediterranean Fever (FMF), and Behçet's Syndrome (BS) was identified. From a total of 52 patients with type I interferonopathies, in seven patients (7/52, 13.5%) a complete response was achieved, most (35/52, 67.3%) showed a partial response and a minority (10/52, 19.2%) showed no treatment response. For AOSD, a complete or a partial response was achieved by eleven (11/26, 42.3%) patients each. Two sJIA patients achieved complete response (2/4, 50%) and in two cases (2/4, 50%) a partial response was reported. Half of FMF patients showed a complete response and the other half had a partial one (3/6, 50.0%). Amongst BS patients most achieved a partial response (8/13, 61.5%). Five patients showed no response to therapy (5/13, 38.5%). Overall, the most frequent AEs were upper respiratory tract infections (17), pneumonia (10), BK virus viremia (10) and viruria (4), herpes zoster infection (5), viral gastroenteritis (2) and other infections (4).ConclusionThe results from this systematic review show that JAKi can be beneficial in certain AID. The risk of AEs, especially viral infections, should be considered. To accurately assess the risk benefit ratio of JAKi for AID, clinical trials should be conducted.
Unique Reciprocal Association Seen Between Latent Tuberculosis Infection and Diabetes Is Due to Immunoendocrine Modulation (DM-LTB-1)
Authors: Aravindhan Vivekanandhan , Bobhate Anup , Sathishkumar Kuppan , Patil Aruna , Kumpatla Satyavani , Viswanathan Vijay 
Published: June 2022

AimThe prevalence of latent tuberculosis infection (LTBI) among diabetes patients is poorly studied. In the present study, the prevalence of LTBI among pre-diabetes and diabetes patients was studied, along with immunoendocrine biomarkers (n = 804).MethodsLTBI was screened by Quantiferon TB gold in Normal glucose tolerance [(NGT); n = 170, [Pre-diabetes (PDM; n = 209), Newly diagnosed diabetes (NDM; n = 165) and Known diabetes (KDM; n = 260) subjects. CRP, TNF-α, IL-6, IL-1β, IFN-β, IL-12, IFN-γ, IL-2, insulin, leptin, and adiponectin levels in serum and IFN-γ levels in quantiferon supernatants were quantified by ELISA. The expression of T-bet was quantified using qRT-PCR. Serum TBARS and nitrite levels were quantified by colorimetry.ResultsThe LTBI prevalence was 32% in NGT, 23% in PDM, 24% in NDM, and 32% in KDM groups, with an adjusted OR of 0.61 (p &lt; 0.05). Downregulation of CRP, TNF-α, and nitrites and upregulation of adiponectin could be responsible for LTBI mediated protection against insulin resistance (IR), while the high levels of IL-1β, IL-12, and leptin could be responsible for IR mediated anti-TB immunity. The defective antigen-specific IFN-γ response, as seen in the KDM group, could be responsible for the low detection rate of LTBI and high probability of endogenous reactivation.ConclusionThere appears to be a biphasic relationship between diabetes-latent tuberculosis: At the early stages of diabetes it is reciprocal, while at a late stage it is synergistic, this important phenomenon obviously needs further research.
Associations of Circulating Insulin-Growth Factor-1 With Cognitive Functions and Quality of Life Domains in Ambulatory Young Adults With Cerebral Palsy: A Pilot Study
Authors: Ng Ted Kheng Siang , Heyn Patricia C. , Tagawa Alex , Coughlan Christina , Carollo James J. 
Published: June 2022

ObjectiveAdults with cerebral palsy (CP) often have impaired cognitive functions. CP also has deteriorations in multiple quality-of-life (QoL) domains. The bio-psycho-social health psychology model posits that biological factor interacts with social and psychological functions. However, the biological determinant of psycho-social and functional outcomes in CP has been scarcely examined. Circulating Insulin-like growth factor-1 (IGF-1) is associated with cognitive deficits in older adults, we thus aimed to examine the associations of circulating IGF-1 with: (1) objectively measured cognitive functions, (2) self-reported cognitive functions, and (3) QoL measures in adults diagnosed with CP.MethodsSeventy-two adults with CP and varying degrees of cognitive functions were recruited from an accredited clinical motion analysis laboratory at a regional Children's Hospital. Circulating IGF-1 was measured using post-fasting serum. The Wechsler Adult Intelligence Scale (WAIS) tests were administered to assess multiple cognitive functions, whereas the Patient-Reported Outcomes Measurement Information System (PROMIS) was used to measure multiple domains of self-reported health, including cognitive complaints and eight QoL domains.ResultsSixty-eight participants had complete data [mean age = 25 (SD = 5.3), female = 52.8%]. Controlling for covariates, circulating IGF-1 was associated with multiple cognitive domains, including positively with declarative memory and executive function and inversely with visual-spatial and motor skills, and processing speed, while no association with subjective memory complaint was detected. Circulating IGF-1 was also inversely associated with four QoL domains, including depressive symptoms, executive function, physical function, and social roles and activities.ConclusionsIn CP, circulating IGF-1 might be a useful biological determinant of objective cognitive functions and several quality-of-life domains commonly impaired in CP.