bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro assembly of the trehalose bi-enzyme complex with artificial scaffold protein
Authors: Wang Xiangyi , Jiang Yi , Liu Hongling , Zhang Xinyi , Yuan Haibo , Huang Di , Wang Tengfei 
Published: August 2023

Introduction: Trehalose is a significant rare sugar known for its stable properties and ability to protect biomolecules from environmental factors.Methods: In this study, we present a novel approach utilizing a scaffold protein-mediated assembly method for the formation of a trehalose bi-enzyme complex. This complex consists of maltooligosyltrehalose synthase (MTSase) and maltooligosyltrehalose trehalohydrolase (MTHase), which work in tandem to catalyze the substrate and enhance the overall catalytic efficiency. Utilizing the specific interaction between cohesin and dockerin, this study presents the implementation of an assembly, an analysis of its efficiency, and an exploration of strategies to enhance enzyme utilization through the construction of a bi-enzyme complex under optimal conditions in vitro.Results and Discussion: The bi-enzyme complex demonstrated a trehalose production level 1.5 times higher than that of the free enzyme mixture at 40 h, with a sustained upward trend. Compared to free enzyme mixtures, the adoption of a scaffold protein-mediated bi-enzyme complex may improve cascade reactions and catalytic effects, thus presenting promising prospects.
The impact of concurrent bacterial lung infection on immunotherapy in patients with non-small cell lung cancer: a retrospective cohort study
Authors: Cao Qiang , Wu Xinyan , Chen Yuquan , Wei Qi , You Yanwei , Qiang Yi , Cao Guangzhu 
Published: August 2023

ObjectiveTo find out how bacterial lung infections (BLI) affect the effectiveness of therapy and the rate of pneumonia caused by pneumonia related to checkpoint inhibitors (CIP) in patients with non-small cell lung cancer (NSCLC) who are getting immunotherapy with checkpoint inhibitors (ICIs).Patients and methods507 NSCLC patients who received at least two ICI treatments between June 2020 and December 2022 at the Affiliated Hospital of Kunming University of Science and Technology(AHKUST) were included in a retrospective cohort study. Based on whether there was a concurrent BLI diagnosis from high-resolution CT scans of the chest, the patients were divided into two groups: 238 in the NSCLC with BLI group (NSCLC-BLI group), and 269 in the NSCLC alone group. The collected therapeutic outcome measures included the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the incidence rate of CIP. We analyzed the effect of BLI on the therapeutic efficacy of ICI treatment and the incidence rate of CIP in NSCLC patients.Inclusion criteria based on NSCLC patients staged I to IV according to the 8th edition of the International Association for Lung Cancer Research (IASLC)ResultsThe NSCLC-BLI group showed superior ORR to the NSCLC group when treated with ICIs. Multifactorial logistic regression and Cox analyses, adjusted for confounders, identified BLI as an independent positive prognostic factor for ORR (HR=0.482, 95%CI: 0.391-0.550; P&lt;0.001) and PFS (HR=0.619; 95%CI: 0.551-0.771; P&lt;0.001). No correlation between BLI and OS was found. Out of 26 cases of CIP, 12 were in the NSCLC-BLI group and 14 in the NSCLC group, with no significant difference in incidence (P=0.145).ConclusionNSCLC patients with BLI receiving ICI treatment show superior ORR and PFS compared to NSCLC alone without an increased CIP risk, positioning BLI as a predictive factor for improved outcomes in NSCLC patients receiving ICIs. However, the study has limitations including its retrospective nature and lacking data on BLI bacteria types and levels, which could influence therapy outcomes.
The causal relationship between autoimmune diseases and osteoporosis: a study based on Mendelian randomization
Authors: Wu Shaofeng , Ye Zhen , Yan Yi , Zhan Xinli , Ren Liang , Zhou Chenxing , Chen Tianyou , Yao Yuanlin , Zhu Jichong , Wu Siling , Ma Fengzhi , Liu Lu , Fan Binguang , Liu Chong 
Published: August 2023

ObjectiveThe relationship between different autoimmune diseases and bone mineral density (BMD) and fractures has been reported in epidemiological studies. This study aimed to explore the causal relationship between autoimmune diseases and BMD, falls, and fractures using Mendelian randomization (MR).MethodsThe instrumental variables were selected from the aggregated statistical data of these diseases from the largest genome-wide association study in Europe. Specifically, 12 common autoimmune diseases were selected as exposure. Outcome variables included BMD, falls, and fractures. Multiple analysis methods were utilized to comprehensively evaluate the causal relationship between autoimmune diseases and BMD, falls, and fractures. Additionally, sensitivity analyses, including Cochran’s Q test, MR-Egger intercept test, and one analysis, were conducted to verify the result’s reliability.ResultsStrong evidence was provided in the results of the negatively association of ulcerative colitis (UC) with forearm BMD. UC also had a negatively association with the total body BMD, while inflammatory bowel disease (IBD) depicted a negatively association with the total body BMD at the age of 45–60 years. Horizontal pleiotropy or heterogeneity was not detected through sensitivity analysis, indicating that the causal estimation was reliable.ConclusionThis study shows a negative causal relationship between UC and forearm and total body BMD, and between IBD and total body BMD at the age of 45–60 years. These results should be considered in future research and when public health measures and osteoporosis prevention strategies are formulated.
The clinical and therapeutic profiles of prolactinomas associated with germline pathogenic variants in the aryl hydrocarbon receptor interacting protein (AIP) gene
Authors: Vroonen Laurent , Beckers Albert , Camby Severine , Cuny Thomas , Beckers Pablo , Jaffrain-Rea Marie-Lise , Cogne Muriel , Naves Luciana , Ferriere Amandine , Romanet Pauline , Elenkova Atanaska , Karhu Auli , Brue Thierry , Barlier Anne , Pétrossians Patrick , Daly Adrian F. 
Published: August 2023

IntroductionProlactinomas are the most frequent type of pituitary adenoma encountered in clinical practice. Dopamine agonists (DA) like cabergoline typically provide sign/ symptom control, normalize prolactin levels and decrease tumor size in most patients. DA-resistant prolactinomas are infrequent and can occur in association with some genetic causes like MEN1 and pathogenic germline variants in the AIP gene (AIPvar).MethodsWe compared the clinical, radiological, and therapeutic characteristics of AIPvar-related prolactinomas (n=13) with unselected hospital-treated prolactinomas (“unselected”, n=41) and genetically-negative, DA-resistant prolactinomas (DA-resistant, n=39).ResultsAIPvar-related prolactinomas occurred at a significantly younger age than the unselected or DA-resistant prolactinomas (p&lt;0.01). Males were more common in the AIPvar (75.0%) and DA- resistant (49.7%) versus unselected prolactinomas (9.8%; p&lt;0.001). AIPvar prolactinomas exhibited significantly more frequent invasion than the other groups (p&lt;0.001) and exhibited a trend to larger tumor diameter. The DA-resistant group had significantly higher prolactin levels at diagnosis than the AIPvar group (p&lt;0.001). Maximum DA doses were significantly higher in the AIPvar and DA-resistant groups versus unselected. DA-induced macroadenoma shrinkage (&gt;50%) occurred in 58.3% in the AIPvar group versus 4.2% in the DA-resistant group (p&lt;0.01). Surgery was more frequent in the AIPvar and DA- resistant groups (43.8% and 61.5%, respectively) versus unselected (19.5%: p&lt;0.01). Radiotherapy was used only in AIPvar (18.8%) and DA-resistant (25.6%) groups.DiscussionAIPvar confer an aggressive phenotype in prolactinomas, with invasive tumors occurring at a younger age. These characteristics can help differentiate rare AIPvar related prolactinomas from DA-resistant, genetically-negative tumors.
Cellular immunity to SARS-CoV-2 following intrafamilial exposure in seronegative family members
Authors: Jay Cecilia , Adland Emily , Csala Anna , Dold Christina , Edmans Matthew , Hackstein Carl-Philipp , Jamsen Anni , Lim Nicholas , Longet Stephanie , Ogbe Ane , Sampson Oliver , Skelly Donal , Spiller Owen B. , Stafford Lizzie , Thompson Craig P. , Turtle Lance , Barnes Ellie , Dunachie Susanna , Carroll Miles , Klenerman Paul , Conlon Chris , Goulder Philip , Jones Lucy C. 
Published: August 2023

IntroductionFamily studies of antiviral immunity provide an opportunity to assess virus-specific immunity in infected and highly exposed individuals, as well as to examine the dynamics of viral infection within families. Transmission of SARS-CoV-2 between family members represented a major route for viral spread during the early stages of the pandemic, due to the nature of SARS-CoV-2 transmission through close contacts.MethodsHere, humoral and cellular immunity is explored in 264 SARS-CoV-2 infected, exposed or unexposed individuals from 81 families in the United Kingdom sampled in the winter of 2020 before widespread vaccination and infection.ResultsWe describe robust cellular and humoral immunity into COVID-19 convalescence, albeit with marked heterogeneity between families and between individuals. T-cell response magnitude is associated with male sex and older age by multiple linear regression. SARS-CoV-2-specific T-cell responses in seronegative individuals are widespread, particularly in adults and in individuals exposed to SARS-CoV-2 through an infected family member. The magnitude of this response is associated with the number of seropositive family members, with a greater number of seropositive individuals within a family leading to stronger T-cell immunity in seronegative individuals.DiscussionThese results support a model whereby exposure to SARS-CoV-2 promotes T-cell immunity in the absence of an antibody response. The source of these seronegative T-cell responses to SARS-CoV-2 has been suggested as cross-reactive immunity to endemic coronaviruses that is expanded upon SARS-CoV-2 exposure. However, in this study, no association between HCoV-specific immunity and seronegative T-cell immunity to SARS-CoV-2 is identified, suggesting that de novo T-cell immunity may be generated in seronegative SARS-CoV-2 exposed individuals.
Non-alcoholic fatty liver disease fibrosis score is a useful index for predicting all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis
Authors: Whang Jeong Yeop , Park Pil Gyu , Park Yong-Beom , Huh Ji Hye , Lee Sang-Won 
Published: August 2023

BackgroundThis study investigated whether the non-alcoholic fatty liver disease fibrosis score (NFS) could predict all-cause mortality during follow-up among patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).MethodsThe medical records of 256 AAV patients were retrospectively reviewed. AAV patients with clinically critical chronic liver diseases were excluded. NFS was calculated using the following equation: NFS = −1.675 + 0.037 - age + 0.094 – body mass index +1.13 × impaired fasting glucose/diabetes mellitus +0.99 × aspartate aminotransferase/alanine aminotransferase ratio - 0.013 × platelet count - 0.66 × serum albumin.ResultsThe median age was 59.0 years, and 35.2% of the patients were male. The median Birmingham Vasculitis Activity Score (BVAS), five-factor score (FFS), and NFS were 12.0, 1.0, and − 4.7, respectively. Of the 256 patients, 33 (12.9%) died. Using the receiver operating characteristic curve, the optimal cut-off of NFS for all-cause mortality was obtained as-3.97. AAV patients with NFS at diagnosis ≥ − 3.97 exhibited a lower cumulative patients’ survival rate than those with NFS at diagnosis &lt;−3.97. The multivariable Cox analysis revealed that NFS at diagnosis ≥ − 3.97 (HR 2.232, 95% CI 1.011, 4.925) was independently associated with all-cause mortality in AAV patients.ConclusionThis study was the first to demonstrate that NFS at AAV diagnosis was clinically useful in predicting all-cause mortality during follow-up, regardless of both the degree of liver fibrosis and abnormal or normal liver function results.
Atelectasis in obese patients undergoing laparoscopic bariatric surgery are not increased upon discharge from Post Anesthesia Care Unit
Authors: Braun Matthias , Ruscher Lea , Fuchs Alexander , Kämpfer Martina , Huber Markus , Luedi Markus M. , Riva Thomas , Vogt Andreas , Riedel Thomas 
Published: August 2023

BackgroundObese patients frequently develop pulmonary atelectasis upon general anesthesia. The risk is increased during laparoscopic surgery. This prospective, observational single-center study evaluated atelectasis dynamics using Electric Impedance Tomography (EIT) in patients undergoing laparoscopic bariatric surgery.MethodsWe included adult patients with ASA physical status I–IV and a BMI of ≥40. Exclusion criteria were known severe pulmonary hypertension, home oxygen therapy, heart failure, and recent pulmonary infections. The primary outcome was the proportion of poorly ventilated lung regions (low tidal variation areas) and the global inhomogeneity (GI) index assessed by EIT before discharge from the Post Anesthesia Care Unit compared to these same measures prior to initiation of anesthesia.ResultsThe median (IQR) proportion of low tidal variation areas at the different analysis points were T1 10.8% [3.6–15.1%] and T5 10.3% [2.6–18.9%], and the mean difference was −0.7% (95% CI: −5.8% −4.5%), i.e., lower than the predefined non-inferiority margin of 5% (p = 0.022). There were no changes at the four additional time points compared to T1 or postoperative pulmonary complications during the 14 days following the procedure.ConclusionWe found that obese patients undergoing laparoscopic bariatric surgery do not leave the Post Anesthesia Care Unit with increased low tidal variation areas compared to the preoperative period.
The mutational profile in a South African cohort with inherited neuropathies and spastic paraplegia
Authors: Mahungu Amokelani C. , Steyn Elizabeth , Floudiotis Niki , Wilson Lindsay A. , Vandrovcova Jana , Reilly Mary M. , Record Christopher J. , Benatar Michael , Wu Gang , Raga Sharika , Wilmshurst Jo M. , Naidu Kireshnee , Hanna Michael , Nel Melissa , Heckmann Jeannine M. 
Published: August 2023

IntroductionLimited diagnostics are available for inherited neuromuscular diseases (NMD) in South Africa and (excluding muscle disease) are mainly aimed at the most frequent genes underlying genetic neuropathy (GN) and spastic ataxias in Europeans. In this study, we used next-generation sequencing to screen 61 probands with GN, hereditary spastic paraplegia (HSP), and spastic ataxias for a genetic diagnosis.MethodsAfter identifying four GN probands with PMP22 duplication and one spastic ataxia proband with SCA1, the remaining probands underwent whole exome (n = 26) or genome sequencing (n = 30). The curation of coding/splice region variants using gene panels was guided by allele frequencies from internal African-ancestry control genomes (n = 537) and the Clinical Genome Resource's Sequence Variant Interpretation guidelines.ResultsOf 32 GN probands, 50% had African-genetic ancestry, and 44% were solved: PMP22 (n = 4); MFN2 (n = 3); one each of MORC2, ATP1A1, ADPRHL2, GJB1, GAN, MPZ, and ATM. Of 29 HSP probands (six with predominant ataxia), 66% had African-genetic ancestry, and 48% were solved: SPG11 (n = 3); KIF1A (n = 2); and one each of SPAST, ATL1, SPG7, PCYT2, PSEN1, ATXN1, ALDH18A1, CYP7B1, and RFT1. Structural variants in SPAST, SPG11, SPG7, MFN2, MPZ, KIF5A, and GJB1 were excluded by computational prediction and manual visualisation.DiscussionIn this preliminary cohort screening panel of disease genes using WES/WGS data, we solved ~50% of cases, which is similar to diagnostic yields reported for global cohorts. However, the mutational profile among South Africans with GN and HSP differs substantially from that in the Global North.
Comparison between regular additional endobiliary radiofrequency ablation and photodynamic therapy in patients with advanced extrahepatic cholangiocarcinoma under systemic chemotherapy
Authors: Möhring Christian , Khan Oliver , Zhou Taotao , Sadeghlar Farsaneh , Mahn Robert , Kaczmarek Dominik J. , Dold Leona , Toma Marieta , Marinova Milka , Glowka Tim R. , Matthaei Hanno , Manekeller Steffen , Kalff Jörg C. , Strassburg Christian P. , Weismüller Tobias J. , Gonzalez-Carmona Maria A. 
Published: August 2023

Background and aimsExtrahepatic cholangiocarcinoma (eCCA) remains a malignancy with a dismal prognosis. The first-line standard of care includes systemic chemotherapy (SC) and biliary drainage through stenting. Endobiliary ablative techniques, such as photodynamic therapy (ePDT) and radio-frequency ablation (eRFA), have demonstrated feasibility and favorable survival data. This study aimed to compare the oncologic outcome in patients treated with SC and concomitant eRFA or ePDT.MethodAll patients with eCCA were evaluated for study inclusion. Sixty-three patients receiving a combination of SC and at least one endobiliary treatment were retrospectively compared.ResultsPatients were stratified into three groups: SC + ePDT (n = 22), SC + eRFA (n = 28), and SC + ePDT + eRFA (n = 13). The median overall survival (OS) of the whole cohort was 14.2 months with no statistically significant difference between the three therapy groups but a trend to better survival for the group receiving ePDT as well as eRFA, during SC (ePDT + SC, 12.7 months; eRFA + SC, 13.8 months; ePDT + eRFA + SC, 20.2 months; p = 0.112). The multivariate Cox regression and subgroup analysis highlighted the beneficial effect of eRFA on OS. Overall, combined therapy was well tolerated. Only cholangitis occurred more often in the SC + eRFA group.ConclusionAdditional endobiliary ablative therapies in combination with SC were feasible. Both modalities, eRFA and ePDT, showed a similar benefit in terms of survival. Interestingly, patients receiving both regimes showed the best OS indicating a possible synergism between both ablative therapeutic techniques.
Feasibility of combination of Gun-Chil-Jung and cytokine-induced killer cells-based immunotherapy for terminal hepatocellular carcinoma patient: a case report
Authors: Park Chan-Ran , Bae Hye-Ri , Lee Ga-Young , Son Chang-Gue , Cho Jung-Hyo , Cho Chong-Kwan , Lee Nam-Hun 
Published: August 2023

Introduction: Terminal-stage hepatocellular carcinoma (HCC) is inoperable and currently has no form of adjuvant therapy. This study examined the anticancer herbal extract Gun-Chil-Jung (GCJ) combined with cytokine-induced killer (CIK)-cell-based immunotherapy as a palliative therapy for terminal HCC. We report the case of an HCC patient with extended overall survival and improved symptoms and tumor marker levels following combination therapy with GCJ and CIK cell-based immunotherapy.Baseline Characteristics: From March to July 2020, a 57-year-old man who had been diagnosed with HCC underwent combination treatment with GCJ and CIK cell-based immunotherapy. By August 2021, he was prescribed GCJ. After treatment, the patient’s condition was evaluated with respect to overall survival, tumor markers, symptoms, abdominal computed tomography findings, chest x-ray results, and Eastern Cooperative Oncology Group (ECOG) grade.Results: The patient’s overall survival, tumor marker levels, ECOG grade, and symptoms, including ascites, lower limb edema, jaundice, pleural effusion, and fatigue, were largely alleviated.Conclusion: We expect that this combination therapy may be an option for palliative therapy of terminal HCC.
The combined effect of fire and nitrogen addition on biodiversity and herbaceous aboveground productivity in a coastal shrubland
Authors: Qi Luyu , Song Yixin , Zhang Puyi , Sun Wenlong , Wang Wei , Yi Shijie , Li Jing , Liu Haifang , Bi Zhenggang , Du Ning , Guo Weihua 
Published: August 2023

IntroductionFire and nitrogen (N) deposition each impact biodiversity and ecosystem productivity. However, the effect of N deposition on ecosystem recovery after fire is still far from understood, especially in coastal wetlands.MethodsWe selected a typical coastal shrubland to simulate three N deposition levels (0, 10, and 20 g N m−2 year−1) under two different burned conditions (unburned and burned) in the Yellow River Delta of North China. Soil properties, soil microbial biodiversity, shrub growth parameters, herbaceous biodiversity, and aboveground productivity were determined after experimental treatments for 1 year.ResultsWe found that fire had a stronger influence on the ecosystem than N addition. One year after the fire, shrub growth had significantly decreased, while soil pH, soil electrical conductivity, herbaceous biodiversity, soil microbial biodiversity, and herbaceous aboveground productivity significantly increased. Conversely, a single year of N addition only slightly increased herbaceous aboveground productivity. The combined effect of fire and N addition was only significant for fungus biodiversity and otherwise had minimal influence. Interestingly, we found that herbaceous aboveground productivity was positively associated with fungal community diversity under unburned conditions but not in burned shrublands. Fire showed a great impact on soil parameters and biodiversity in the coastal wetland ecosystem even after a full year of recovery.DiscussionFire may also diminish the influence of several belowground factors on herbaceous aboveground productivity, which ultimately reduces recovery and stability. Appropriate N addition may be an effective way to improve the ecosystem productivity in a wetland dominated by shrub species.