bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetic retinopathy predicts cardiovascular disease independently of subclinical atherosclerosis in individuals with type 2 diabetes: A prospective cohort study
Authors: Castelblanco Esmeralda , Granado-Casas Minerva , Hernández Marta , Pinyol Montserrat , Correig Eudald , Julve Josep , Rojo-López Marina Idalia , Alonso Núria , Avogaro Angelo , Ortega Emilio , Mauricio Didac 
Published: November 2022

BackgroundDiabetic retinopathy (DR) and preclinical atherosclerosis are associated with higher cardiovascular risk. However, no studies have investigated the predictive role of DR and preclinical atherosclerosis jointly on cardiovascular events in subjects with type 2 diabetes (T2D). We aimed to assess the contribution of DR and subclinical atherosclerosis on the risk of adverse cardiovascular events in subjects with T2D without previous cardiovascular disease (CVD).MethodsWe included two prospective cohorts of subjects with T2D from the same geographical area. Assessment of subclinical atherosclerosis was performed by carotid ultrasound. An ophthalmologist classified DR according to standard criteria. Cardiovascular outcomes considered for analysis were the following: ischemic heart disease, stroke, heart failure, peripheral artery disease, revascularization procedures, and cardiovascular mortality. Bivariable and multivariable predictive models were performed.ResultsFrom a total of 374 subjects with T2D 44 developed cardiovascular events during the 7.1 years of follow-up. Diabetes duration, total cholesterol, and glycated hemoglobin (HbA1c) at baseline were higher in subjects who developed cardiovascular outcomes (p &lt; 0.001, p = 0.026, and p = 0.040, respectively). Compared with subjects without events, those developing cardiovascular events had higher prevalence of retinopathy (65.9% vs. 38.8%, p = 0.001; respectively) and more than mild retinopathy (43.2% vs. 31.8%, p = 0.002; respectively). Furthermore, all-cause mortality was higher in subjects with MACE than those without events (13.6% vs. 3.3%, p = 0.009; respectively). The multivariable analyses showed that HbA1c and the presence of DR at baseline were predictive of cardiovascular outcomes (p = 0.045 and p = 0.023, respectively). However, the burden of subclinical atherosclerosis was not (p = 0.783 and p = 0.071, respectively).ConclusionDR is a strong predictor of cardiovascular events in T2D individuals at primary CVD prevention, even after accounting for the presence of preclinical carotid atherosclerosis. These results may help to individualize CVD prevention strategies in T2D.
NW-dipping versus SE-dipping causative faults of the 1783 M7.1 Southern Calabria (Italy) earthquake: The contribution from the analysis of the coseismic hydrological changes
Authors: Cucci Luigi 
Published: November 2022

The 1783 Mw7.1 Southern Calabria (Italy) earthquake originated a remarkable number of observations of hydrological changes (variations of flow in springs and streams, liquefaction, changes in water temperature) that occurred in different localities. To provide further constraints on the mechanism and the geometry of the causative fault of the event, I compared the distribution of the hydrological changes with the coseismic strain produced by eight seismogenic sources proposed for the earthquake. The most important outcomes of the study can be summarized as follows: a) the group of potential sources that display the best agreement between expected deformation and hydrological signature consists of NW-dipping systems of three to four surface-rupturing almost pure normal fault segments (Cittanova fault system), capable of generating earthquakes of magnitude Mw6.9–7.1; b) the distribution of the observed coseismic hydrological anomalies does not support the role of the SE-dipping faults as potential sources of the 1783 earthquake; c) the pattern of deformation associated with the best fit source strengthens the hypothesis that the 20 km-long surface ruptures testified soon after the 1783 event reflect primary faulting; d) a minimum magnitude Mw6.9–7.0 is required to obtain the pattern and the extent of distribution of the coseismic hydrological changes observed in the field; e) the location of the hydrological variations that were observed only along the western side of southern Calabria suggests that the Cittanova fault system acts as a hydrological barrier that hampers the groundwater circulation toward the East.
A 5-year follow-up study on the efficacy and safety of ultrasound-guided laser ablation in elderly patients with papillary thyroid microcarcinoma: A retrospective, single-center study from China
Authors: Juan Zhang , Yongping Liang , Han Xiaochen , Wang Zhiwu , Liu Jingping , Zhao Yongfeng , Liu Wengang , Zhou Ping 
Published: November 2022

ObjectiveThe aim of this study is to evaluate the long-term efficacy and safety of ultrasound-guided percutaneous laser ablation (PLA) for the treatment of elderly patients with papillary thyroid microcarcinoma (PTMC).MethodsFrom September 2015 to April 2017, 38 elderly patients with PTMC confirmed through fine-needle aspiration biopsy (FNAB) were treated with PLA. Before the treatment, the location and volume of the nodule together with the patients’ symptoms were evaluated. Twenty-four hours after the treatment, contrast-enhanced ultrasound (CEUS) was performed to evaluate the completeness of the ablation. To evaluate the volume of the ablation area and recurrence or metastasis, ultrasound examination was performed at 1, 3, 6, and 12 months after the treatment and every 6 months thereafter. FNAB was performed for any suspicious recurrence or metastasis lesions.ResultThe ablation of all the 38 patients was all achieved completely as confirmed by CEUS. No obvious complications were found. The success rate of single ablation was 100%. The average follow-up time was 64.58 ± 5.29 months (60–78 months). By the time of the last follow-up, 31 (81.58%) ablation lesions disappeared completely and seven (18.42%) ablation lesions showed scar-like changes. The volume of nodules was 40.69 ± 16.45 mm3 before operation, which decreased to 0.22 ± 0.76 mm3 by the end of 42 months, and all nodules disappeared 4 years after ablation (P &lt; 0.01). At 6, 12, 18, 24, 30, 36, and 42 months after ablation, the average volume reduction rates (VRRs) were 12.09%, 31.21%, 50.9%, 72.06%, 84.79%, 95.65%, and 100%, respectively. Of all the patients enrolled, one patient (2.6%) had local recurrence and was treated with PLA again. No regrowth of treated nodule or lymph node metastasis and distant metastases was detected.ConclusionUltrasound-guided PLA is effective and safe for the treatment of elderly patients with PTMC who are ineligible for surgery.
A multi-center study on glucometabolic response to bariatric surgery for different subtypes of obesity
Authors: Liu Yao , Sheng Chunjun , Feng Wenhuan , Sun Fang , Zhang Jingjing , Chen Ying , Su Lili , Liu Jia , Du Lei , Jia Xuyang , You Hui , Huang Xiu , Wu Shandong , Lin Ziwei , Qu Shen 
Published: November 2022

ObjectivesTo assess the benefit of a bariatric surgery in four artificial intelligence-identified metabolic (AIM) subtypes of obesity with respect to the improvement of glucometabolism and the remission of diabetes and hyperinsulinemia.MethodsThis multicenter retrospective study prospectively collected data from five hospitals in China from 2010 to 2021. At baseline 1008 patients who underwent a bariatric surgery were enrolled (median age 31 years; median BMI 38.1kg/m2; 57.40% women) and grouped into the four AIM subtypes. Baseline and follow-up data (506 and 359 patients at 3- and 12-month post-surgery) were collected for longitudinal effect analysis.ResultsOut of the four AIM subgroups, hypometabolic obesity (LMO) group was characterized by decompensated insulin secretion and high incidence of diabetes (99.2%) pre-surgery. After surgery, 62.1% of LMO patients with diabetes achieved remission, lower than the other three subgroups. Still, the bariatric surgery significantly reduced their blood glucose (median HbA1c decreased by 27.2%). The hypermetabolic obesity-hyperinsulinemia (HMO-I) group was characterized by severe insulin resistance and high incidence of hyperinsulinemia (87.8%) pre-surgery, which had been greatly alleviated post-surgery. For both metabolic healthy obesity (MHO) and hypermetabolic obesity-hyperuricemia (HMO-U) groups who showed a relatively healthy glucometabolism pre-surgery, rate of glucometabolic comorbidities improved moderately post-surgery.ConclusionIn terms of glucometabolism, the four AIM subtypes of patients benefited differently from a bariatric surgery, which significantly relieved hyperglycemia and hyperinsulinemia for the LMO and HMO-I patients, respectively. The AIM-based subtypes may help better inform clinical decisions on bariatric surgery and patient counseling pertaining to post-surgery outcomes.
The application of biochar mitigated the negative effects of freeze-thaw on soil and nutrient loss in the restored soil of the alpine mining area
Authors: Li Fayong , Wang Desheng , You Yongjun , Li Guoyu , Eltohamy Kamel Mohamed , Khan Sangar , Riaz Luqman 
Published: November 2022

Mining operations accelerate ecological damage in alpine mountain locations by contributing to soil erosion and nutrient loss in the freeze-thaw (FT) climate. However, limited studies have been conducted to reduce the soil erosion and nutrient loss in FT climate. This study’s goal was to determine how biochar effected soil erosion in the restored soil of the alpine mining region under FT circumstances. Rainfall simulation and FT cycles (FTCs; three and 5) were used to investigate the effects of 500 and 1,000 kg hm−2biochar application rates (BARs) on runoff, soil loss, and runoff loss of ammonia nitrogen (AN), nitrate nitrogen (NN), total phosphorus (TP), and dissolved phosphorus (DP). Soil residual AN, NN, and DP concentrations after FTCs were also evaluated. Biochar application significantly reduced the runoff, soil loss rate, AN and NN loss rates, but increased the runoff NN concentration and decreased the total AN and NN loss under FTCs condition. Reductions in AN (37.2%–52.2%) and NN (14.3%–27.1%) runoff loss can be differentially attributed to the adsorption effect of biochar and decrease in total runoff. The runoff P concentrations, rates, and magnitudes for soils subjected to FTCs significantly decreased with biochar addition, owing to the particulate P loss decrease in soil and increased adsorption effect of soil DP. Biochar addition increased soil residual AN, NN, and DP concentrations. However, the increase in FTCs weakened the inhibitory effects of biochar on soil erosion. This study suggested the important role of biochar application for the recovery of low-nutrient eroded soils in alpine mining areas.
Runnels mitigate marsh drowning in microtidal salt marshes
Authors: Watson Elizabeth B. , Ferguson Wenley , Champlin Lena K. , White Jennifer D. , Ernst Nick , Sylla Habibata A. , Wilburn Brittany P. , Wigand Cathleen 
Published: November 2022

As a symptom of accelerated sea level rise and historic impacts to tidal hydrology from agricultural and mosquito control activities, coastal marshes in the Northeastern U.S. are experiencing conversion to open water through edge loss, widening and headward erosion of tidal channels, and the formation and expansion of interior ponds. These interior ponds often form in high elevation marsh, confounding the notion applied in predictive modeling that salt marshes convert to open water when elevation falls below a critical surface inundation threshold. The installation of tidal channel extension features, or runnels, is a technique that has been implemented to reduce water levels and permit vegetation reestablishment in drowning coastal marshes, although there are limited data available to recommend its advisability. We report on 5 years of vegetation and hydrologic monitoring of two locations where a total of 600-m of shallow (0.15–0.30-m in diameter and depth) runnels were installed in 2015 and 2016 to enhance drainage, in the Pettaquamscutt River Estuary, in southern Rhode Island, United States. Results from this Before-After Control-Impact (BACI) designed study found that runnel installation successfully promoted plant recolonization, although runnels did not consistently promote increases in high marsh species presence or diversity. Runnels reduced the groundwater table (by 0.07–0.12 m), and at one location, the groundwater table experienced a 2-fold increase in the fraction of the in-channel tidal range that was observed in the marsh water table. We suggest that restoration of tidal hydrology through runnel installation holds promise as a tool to encourage revegetation and extend the lifespan of drowning coastal marshes where interior ponds are expanding. In addition, our study highlights the importance of considering the rising groundwater table as an important factor in marsh drowning due to expanding interior ponds found on the marsh platform.
An enigmatic beetle with affinity to Lamingtoniidae in mid-Cretaceous amber from northern Myanmar (Coleoptera: Cucujoidea)
Authors: Li Yan-Da , Leschen Richard A. B. , Liu Zhen-Hua , Huang Di-Ying , Cai Chen-Yang 
Published: November 2022

An enigmatic cucujiform beetle, Alloterocucus atratus Li, Leschen, Liu, and Cai gen. et sp. nov., is reported from mid-Cretaceous Burmese amber. The character combination of the new fossil is not completely consistent with any of the known cucujoid or erotyloid families. Based on our phylogenetic analyses, Alloterocucus is assigned to Cucujoidea and may be allied to Lamingtoniidae, which contains a single Australasian genus in the extant fauna. Alloterocucus shares with Lamingtoniidae a similar habitus and a series of characters, including the absence of postocular constriction, 3-segmented antennal club, externally open procoxal cavities, laterally open mesocoxal cavities, exposed pro- and mesotrochantins, and the absence of epipleural fovea and pronotal setose cavities, but differs from extant Lamingtoniidae in its apically truncate terminal maxillary palpomeres, 5-5-4 tarsi in male and absence of distinct dorsal punctation.Zoobank registration[https://zoobank.org/], identifier [111CE15E-5B49-4154-9E4A-7B3A738C6D2A].
Mechanisms underlying the therapeutic effects of 4-octyl itaconate in treating sepsis based on network pharmacology and molecular docking
Authors: Chen Maolin , Su Wenxing , Chen Fangling , Lai Tianlun , Liu Yilun , Yu Daojiang 
Published: November 2022

Objective: Through network pharmacology and molecular docking technology, the hub genes, biological functions, and signaling pathways of 4-Octyl itaconate (4-OI) against sepsis were revealed.Methods: Pathological targets of sepsis were screened using GeneCards and GEO databases. Similarly, the pharmacological targets of 4-OI were obtained through Swiss TargetPrediction (STP), Similarity ensemble approach (SEA), and TargetNet databases. Then, all the potential targets of 4-OI anti-sepsis were screened by the online platform Draw Venn diagram, and the hub genes were screened by Cytoscape software. The identified hub genes were analyzed by GO and KEGG enrichment analysis, protein interaction (PPI) network, and molecular and docking technology to verify the reliability of hub gene prediction, further confirming the target and mechanism of 4-OI in the treatment of sepsis.Results: After the target screening of 4-OI and sepsis, 264 pharmacological targets, 1953 pathological targets, and 72 genes related to 4-OI anti-sepsis were obtained, and eight hub genes were screened, namely MMP9, MMP2, SIRT1, PPARA, PTPRC, NOS3, TLR2, and HSP90AA1. The enrichment analysis results indicated that 4-OI might be involved in regulating inflammatory imbalance, immunosuppression, and oxidative stress in developing sepsis. 4-OI protects multiple organ dysfunction in sepsis by acting on hub genes, and MMP9 is a reliable gene for the prognosis and diagnosis of sepsis. The molecular docking results showed that 4-OI binds well to the hub target of sepsis.Conclusion: 4-OI plays an antiseptic role by regulating MMP9, MMP2, SIRT1, PPARA, PTPRC, NOS3, TLR2 and HSP90AA1. These Hub genes may provide new insights into follow-up research on the target of sepsis treatment.
Expanding spectrum, intrafamilial diversity, and therapeutic challenges from 15 patients with heterozygous CARD11-associated diseases: A single center experience
Authors: Urdinez Luciano , Erra Lorenzo , Palma Alejandro M. , Mercogliano María F. , Fernandez Julieta Belén , Prieto Emma , Goris Verónica , Bernasconi Andrea , Sanz Marianela , Villa Mariana , Bouso Carolina , Caputi Lucia , Quesada Belen , Solis Daniel , Aguirre Bruzzo Anabel , Katsicas Maria Martha , Galluzzo Laura , Weyersberg Christian , Bocian Marcela , Bujan Maria Marta , Oleastro Matías , Almejun María B. , Danielian Silvia 
Published: November 2022

CARD11-associated diseases are monogenic inborn errors of immunity involving immunodeficiency, predisposition to malignancy and immune dysregulation such as lymphoproliferation, inflammation, atopic and autoimmune manifestations. Defects in CARD11 can present as mutations that confer a complete or a partial loss of function (LOF) or contrarily, a gain of function (GOF) of the affected gene product. We report clinical characteristics, immunophenotypes and genotypes of 15 patients from our center presenting with CARD11-associated diseases. Index cases are pediatric patients followed in our immunology division who had access to next generation sequencing studies. Variant significance was defined by functional analysis in cultured cells transfected with a wild type and/or with mutated hCARD11 constructs. Cytoplasmic aggregation of CARD11 products was evaluated by immunofluorescence. Nine index patients with 9 unique heterozygous CARD11 variants were identified. At the time of the identification, 7 variants previously unreported required functional validation. Altogether, four variants showed a GOF effect as well a spontaneous aggregation in the cytoplasm, leading to B cell expansion with NF-κB and T cell anergy (BENTA) diagnosis. Additional four variants showing a LOF activity were considered as causative of CARD11-associated atopy with dominant interference of NF-kB signaling (CADINS). The remaining variant exhibited a neutral functional assay excluding its carrier from further analysis. Family segregation studies expanded to 15 individuals the number of patients presenting CARD11-associated disease. A thorough clinical, immunophenotypical, and therapeutic management evaluation was performed on these patients (5 BENTA and 10 CADINS). A remarkable variability of disease expression was clearly noted among BENTA as well as in CADINS patients, even within multiplex families. Identification of novel CARD11 variants required functional studies to validate their pathogenic activity. In our cohort BENTA phenotype exhibited a more severe and expanded clinical spectrum than previously reported, e.g., severe hematological and extra hematological autoimmunity and 3 fatal outcomes. The growing number of patients with dysmorphic facial features strengthen the inclusion of extra-immune characteristics as part of the CADINS spectrum. CARD11-associated diseases represent a challenging group of disorders from the diagnostic and therapeutic standpoint, especially BENTA cases that can undergo a more severe progression than previously described.
Association between immune-mediated adverse events and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab and tremelimumab
Authors: Dey Agnish , Austin Matthew , Kluger Harriet M. , Trunova Nataliya , Mann Helen , Shire Norah , Morgan Claire , Zhou Diansong , Mugundu Ganesh M. 
Published: November 2022

PurposeImmune-mediated adverse events (imAEs) may be associated with response to immune checkpoint inhibitors. We assessed the relationship between imAE development and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab (anti-programmed cell death ligand-1 [PD-L1]) alone or in combination with tremelimumab (anti-cytotoxic T-lymphocyte-associated protein 4).MethodsThe analysis used individual patient-level data from 307 and 310 patients in the monotherapy and combination arms of MYSTIC, respectively. We evaluated the association between treatment efficacy and development of imAEs using univariate and multivariate survival analyses. Using machine learning, we built a predictive model utilizing baseline clinical and laboratory features to identify patients at risk of developing imAEs and further evaluated patient survival based on a threshold index extracted from the model.ResultsPatients who developed any grade of imAE had improved overall survival versus patients without (hazard ratio [HR] 0.51; 95% confidence interval [CI]: 0.41–0.62). imAE development was associated with improved overall survival (HR 0.54; 95% CI 0.44–0.66) in a multivariate Cox proportional hazard model considering patient demographic features and baseline characteristics. Higher odds of imAE development were observed (odds ratio 3.023; 95% CI: 1.56–5.83) in responders versus non-responders in patients treated with immunotherapy. Based on baseline characteristics, the random forest classification algorithm was used to formulate a predictive model to identify patients at increased risk of developing imAEs during treatment.ConclusionPost-hoc exploratory analysis found that the efficacy of immunotherapy was improved in patients who developed on-treatment imAEs. This was independent of severity of imAEs or the need for steroid treatment, which is important in allowing patients to remain on treatment and derive optimal clinical benefit. Further research is warranted to establish the correlation between incidence of imAEs and efficacy in this patient population.
Activation of distinct antiviral T-cell immunity: A comparison of bi- and trispecific T-cell engager antibodies with a chimeric antigen receptor targeting HBV envelope proteins
Authors: Debelec-Butuner Bilge , Quitt Oliver , Schreiber Sophia , Momburg Frank , Wisskirchen Karin , Protzer Ulrike 
Published: November 2022

Despite the availability of an effective prophylactic vaccine, 820,000 people die annually of hepatitis B virus (HBV)-related liver disease according to WHO. Since current antiviral therapies do not provide a curative treatment for the 296 million HBV carriers around the globe, novel strategies to cure HBV are urgently needed. A promising approach is the redirection of T cells towards HBV-infected hepatocytes employing chimeric antigen receptors or T-cell engager antibodies. We recently described the effective redirection of T cells employing a second-generation chimeric antigen receptor directed against the envelope protein of hepatitis B virus on the surface of infected cells (S-CAR) as well as bispecific antibodies that engage CD3 or CD28 on T cells employing the identical HBV envelope protein (HBVenv) binder. In this study, we added a trispecific antibody comprising all three moieties to the tool-box. Cytotoxic and non-cytolytic antiviral activities of these bi- and trispecific T-cell engager antibodies were assessed in co-cultures of human PBMC with HBV-positive hepatoma cells, and compared to that of S-CAR-grafted T cells. Activation of T cells via the S-CAR or by either a combination of the CD3- and CD28-targeting bispecific antibodies or the trispecific antibody allowed for specific elimination of HBV-positive target cells. While S-CAR-grafted effector T cells displayed faster killing kinetics, combinatory treatment with the bispecific antibodies or single treatment with the trispecific antibody was associated with a more pronounced cytokine release. Clearance of viral antigens and elimination of the HBV persistence form, the covalently closed circular (ccc) DNA, through cytolytic as well as cytokine-mediated activity was observed in all three settings with the combination of bispecific antibodies showing the strongest non-cytolytic, cytokine-mediated antiviral effect. Taken together, we demonstrate that bi- and trispecific T-cell engager antibodies can serve as a potent, off-the-shelf alternative to S-CAR-grafted T cells to cure HBV.