bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune response in ofatumumab treated multiple sclerosis patients after SARS-CoV-2 vaccination
Authors: Faissner Simon , Heitmann Neele , Plaza-Sirvent Carlos , Trendelenburg Paulina , Ceylan Ulas , Motte Jeremias , Bessen Clara , Urlaub Doris , Watzl Carsten , Overheu Oliver , Reinacher-Schick Anke , Hellwig Kerstin , Pfaender Stephanie , Schmitz Ingo , Gold Ralf 
Published: August 2022

ObjectiveThe pandemic induced by SARS-CoV-2 has huge implications for patients with immunosuppression that is caused by disorders or specific treatments. Especially approaches targeting B cells via anti-CD20 therapy are associated with impaired humoral immune response but sustained cellular immunity. Ofatumumab is a human anti-CD20 directed antibody applied in low dosages subcutaneously, recently licensed for Multiple Sclerosis (MS). Effects of early ofatumumab treatment on alterations of immune cell composition and immune response towards SARS-CoV-2 are incompletely understood.MethodsWe here investigated immune cell alterations in early ofatumumab (Ofa) treated patients and effects on humoral (titer, neutralization capacity against wild type, Delta and Omicron) and cellular immune responses in Ofa treated MS patients following a third vaccination against SARS-CoV-2 compared to healthy controls.ResultsWe show that a mean treatment duration of three months in the Ofa group led to near complete B cell depletion in line with altered composition of certain CD4+ T cell subpopulations such as enhanced frequencies of naive and a decrease of non-suppressive regulatory T cells (Tregs). Titer and neutralization capacity against SARS-CoV-2 variants was impaired while cellular immune response was sustained, characterized by a strong T helper 1 profile (Th1).InterpretationIn summary, low dosage ofatumumab treatment elicits sustained depletion of B cells in line with alterations of immune cells, mainly Tregs. This is associated with impaired humoral immune response towards SARS-CoV-2 vaccination but preserved, Th1 driven cellular immunity adding crucial information regarding early effects of low dosage anti-CD20 therapy on humoral and cellular immunity.
Impact of protocolized fluid management on electrolyte stability in patients undergoing continuous renal replacement therapy
Authors: Baeg Song In , Jeon Junseok , Kang Danbee , Na Soo Jin , Cho Juhee , Kim Kyunga , Yang Jeong Hoon , Chung Chi Ryang , Lee Jung Eun , Huh Wooseong , Suh Gee Young , Kim Yoon-Goo , Kim Dae Joong , Jang Hye Ryoun 
Published: August 2022

ObjectiveContinuous renal replacement therapy (CRRT) is the standard treatment for critically ill patients with acute kidney injury (AKI). Electrolyte disturbance such as hypokalemia or hypophosphatemia occurs paradoxically in patients undergoing CRRT due to high clearance. We developed a fluid management protocol for dialysate and replacement fluid that depends on serum electrolytes and focuses on potassium and phosphate levels to prevent electrolyte disturbance during CRRT. The impact of our new fluid protocol on electrolyte stability was evaluated.MethodsAdult patients who received CRRT between 2013 and 2017 were included. Patients treated 2 years before (2013–2014; pre-protocol group) and 2 years following development of the fluid protocol (2016–2017; protocol group) were compared. The primary outcomes were individual coefficient of variation (CV) and abnormal event rates of serum phosphate and potassium. Secondary outcomes were frequency of electrolyte replacement and incidence of cardiac arrhythmias. Individual CV and abnormal event rates for each electrolyte were analyzed using the Wilcoxon rank-sum test and Chi-square test with Yates’ continuity correction.ResultsA total of 1,448 patients was included. Both serum phosphate and potassium were higher in the protocol group. The CVs of serum phosphate (pre-protocol vs. protocol, 0.275 [0.207–0.358] vs. 0.229 [0.169–0.304], p &lt; 0.01) and potassium (0.104 [0.081–0.135] vs. 0.085 [0.064–0.110], p &lt; 0.01) were significantly lower in the protocol group. The abnormal event rates of serum phosphate (rate [95% CI], 0.410 [0.400–0.415] vs. 0.280 [0.273–0.286], p &lt; 0.01) and potassium (0.205 [0.199–0.211] vs. 0.083 [0.079–0.087], p &lt; 0.01) were also significantly lower in the protocol group.ConclusionThe protocolized management of fluid in CRRT effectively prevented hypophosphatemia and hypokalemia by inducing excellent stability of serum phosphate and potassium levels.
Recirculation in single lumen cannula venovenous extracorporeal membrane oxygenation: A non-randomized bi-centric trial
Authors: Fisser Christoph , Palmér Oscar , Sallisalmi Marko , Paulus Michael , Foltan Maik , Philipp Alois , Malfertheiner Maximilian V. , Lubnow Matthias , Müller Thomas , Broman Lars Mikael 
Published: August 2022

BackgroundRecirculation is a common problem in venovenous (VV) extracorporeal membrane oxygenation (ECMO). The aims of this study were to compare recirculation fraction (Rf) between femoro-jugular and jugulo-femoral VV ECMO configurations, to identify risk factors for recirculation and to assess the impact on hemolysis.MethodsPatients in the medical intensive care unit (ICU) at the University Medical Center Regensburg, Germany receiving VV ECMO with femoro-jugular, and jugulo-femoral configuration at the ECMO Center Karolinska, Sweden, were included in this non-randomized prospective study. Total ECMO flow (QEC), recirculated flow (QREC), and recirculation fraction Rf= QREC/QECwere determined using ultrasound dilution technology. Effective ECMO flow (QEFF) was defined as QEFF= QEC* (1–Rf). Demographics, cannula specifics, and markers of hemolysis were assessed. Survival was evaluated at discharge from ICU.ResultsThirty-seven patients with femoro-jugular configuration underwent 595 single-point measurements and 18 patients with jugulo-femoral configuration 231 measurements. Rfwas lower with femoro-jugular compared to jugulo-femoral configuration [5 (0, 11) vs. 19 (13, 28) %, respectively (p&lt; 0.001)], resulting in similar QEFF[2.80 (2.21, 3.39) vs. 2.79 (2.39, 3.08) L/min (p= 0.225)] despite lower QECwith femoro-jugular configuration compared to jugulo-femoral [3.01 (2.40, 3.70) vs. 3.57 (3.05, 4.06) L/min, respectively (p&lt; 0.001)]. In multivariate regression analysis, the type of configuration, distance between the two cannula tips, ECMO flow, and heart rate were significantly associated with Rf [B (95% CI): 25.8 (17.6, 33.8), p &lt; 0.001; 960.4 (960.7, 960.1),p= 0.009; 4.2 (2.5, 5.9), p &lt; 0.001; 960.1 (960.2, 0.0), p = 0.027]. Hemolysis was similar in subjects with Rf &gt; 8 vs. ≤ 8%. Explorative data on survival showed comparable results in the femoro-jugular and the jugulo-femoral group (81 vs. 72%,p= 0.455).ConclusionVV ECMO with femoro-jugular configuration caused less recirculation. Further risk factors for higher Rfwere shorter distance between the two cannula tips, higher ECMO flow, and lower heart rate. Rfdid not affect hemolysis.
Persisting sicca complaints in sarcoidosis
Authors: Hofauer Benedikt , Wiesner Miriam , Zhu Zhaojun , Stock Konrad , Peltz Friedhelm , Thuermel Klaus , Strassen Ulrich , Johnson Felix , Knopf Andreas 
Published: August 2022

BackgroundSarcoidosis is a systemic inflammatory disease that is characterized by non-caseating granulomas. Besides the lung as classical site of involvement, extrapulmonary manifestations are common, for example cervical lymph nodes or the salivary glands. The aim of this investigation is the analysis of the long-term course of glandular symptoms with a focus on persisting sicca symptoms.Materials and methodsAll patients with the diagnosis of sarcoidosis over a period of 20 years in the departments of otorhinolaryngology, nephrology and pneumology were identified. In addition to clinical examinations and functional evaluation of the salivary glands, a sonographic examination of the salivary glands was carried out.ResultsA total of 76 patients were included in the study (age 35.1 ± 21.6 years). At baseline, 32 out of 76 patients were suffering from xerostomia, 36 from dry eyes. While other salivary gland symptoms, such as gland enlargement, pain or facial nerve impairment, dissolved during the further course of the disease, xerostomia was still present in 29 and dry eyes in 35 out of 76 patients at the time of follow-up (which took place on average after 88.2 months).ConclusionSicca symptoms persist in patients with the diagnosis of sarcoidosis, while other salivary gland symptoms completely dissolve during the further course of the disease. This development appears to be independent of the type of therapy and should be considered during the follow-up of these patients, since sicca symptoms can cause further ocular, oral and dental damage.
A bibliometric analysis and visualization of tension-type headache
Authors: Fan Xueming , Fu Guojing , Wang Liuding , Shen Wei , Zhang Yunling 
Published: August 2022

BackgroundTension-type headache (TTH) is the most prevalent headache in the clinical practice, leading to impaired social activities, work-related disability, and heavy financial burdens. Previous studies have described possible inducement, potential pathophysiology, and clinical management of TTH; however, due to the lack of attention, literature involving bibliometric analysis is sporadic. Therefore, this study aimed to explore the current hotspots and future directions of the TTH field by bibliometric analysis.MethodsBy using CiteSpace and VOSviewer, literature regarding TTH between 2002 and 2021 from the Web of Science database was summarized and extracted. Annual publication trend, the most productive countries/regions and institutions, distribution of categories, co-citation of journals and references, and co-occurrence of keywords were analyzed.ResultsA total of 3,379 publications were included in the final visualization, indicating a stable trend in current research and a lack of breakthroughs over the past decades. These studies were mainly conducted in 120 countries/regions led by the United States and more than 600 institutions. Four eternal core themes were identified in TTH, including neurosciences, nursing, developmental psychology, and general/internal medicine. Cephalalgia ranked first, with the highest number of literature, and is the most influential journal in this area. Keyword analysis demonstrated that the similarities and differences between migraine and TTH, epidemiological studies, clinical double-blind trials, and potential populations have become key issues in the TTH field.ConclusionTTH has received less attention and breakthroughs in the past 20 years. To promote coordinated development between regions to fight headaches, cooperation and exchanges between countries and institutions are essential in the future. Relevant studies about headaches in children and adolescents, inducing factors such as emotional triggers and sleep disorders, concomitant diseases, possible pathogenesis, and headache treatments, are in the spotlight in recent years. This study offers a powerful roadmap for further research in this field.
Treatment of depression in the elderly with repetitive transcranial magnetic stimulation using theta-burst stimulation: Study protocol for a randomized, double-blind, controlled trial
Authors: Valiengo Leandro , Pinto Bianca S. , Marinho Kalian A. P. , Santos Leonardo A. , Tort Luara C. , Benatti Rafael G. , Teixeira Bruna B. , Miranda Cristiane S. , Cardeal Henriette B. , Suen Paulo J. C. , Loureiro Julia C. , Vaughan Renata A. R. , Dini Mattar Roberta A. M. P. F. , Lessa Maíra , Oliveira Pedro S. , Silva Valquíria A. , Gattaz Wagner Farid , Brunoni André R. , Forlenza Orestes Vicente 
Published: August 2022

IntroductionTranscranial magnetic stimulation (TMS) is a consolidated procedure for the treatment of depression, with several meta-analyses demonstrating its efficacy. Theta-burst stimulation (TBS) is a modification of TMS with similar efficacy and shorter session duration. The geriatric population has many comorbidities and a high prevalence of depression, but few clinical trials are conducted specifically for this age group. TBS could be an option in this population, offering the advantages of few side effects and no pharmacological interactions. Therefore, our aim is to investigate the efficacy of TBS in geriatric depression.Clinical trial registration[https://clinicaltrials.gov/ct2/], identifier [NCT04842929].
Role of mitochondrial translation in remodeling of energy metabolism in ER/PR(+) breast cancer
Authors: Koc Emine C. , Koc Fatih C. , Kartal Funda , Tirona Maria , Koc Hasan 
Published: August 2022

Remodeling of mitochondrial energy metabolism is essential for the survival of tumor cells in limited nutrient availability and hypoxic conditions. Defects in oxidative phosphorylation (OXPHOS) and mitochondrial biogenesis also cause a switch in energy metabolism from oxidative to aerobic glycolysis contributing to the tumor heterogeneity in cancer. Specifically, the aberrant expressions of mitochondrial translation components such as ribosomal proteins (MRPs) and translation factors have been increasingly associated with many different cancers including breast cancer. The mitochondrial translation is responsible for the synthesis 13 of mitochondrial-encoded OXPHOS subunits of complexes. In this study, we investigated the contribution of mitochondrial translation in the remodeling of oxidative energy metabolism through altered expression of OXPHOS subunits in 26 ER/PR(+) breast tumors. We observed a significant correlation between the changes in the expression of mitochondrial translation-related proteins and OXPHOS subunits in the majority of the ER/PR(+) breast tumors and breast cancer cell lines. The reduced expression of OXPHOS and mitochondrial translation components also correlated well with the changes in epithelial-mesenchymal transition (EMT) markers, E-cadherin (CHD1), and vimentin (VIM) in the ER/PR(+) tumor biopsies. Data mining analysis of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) breast cancer proteome further supported the correlation between the reduced OXPHOS subunit expression and increased EMT and metastatic marker expression in the majority of the ER/PR(+) tumors. Therefore, understanding the role of MRPs in the remodeling of energy metabolism will be essential in the characterization of heterogeneity at the molecular level and serve as diagnostic and prognostic markers in breast cancer.
Phase II INTERACT-ION study: ezabenlimab (BI 754091) and mDCF (docetaxel, cisplatin, and 5-fluorouracil) followed by chemoradiotherapy in patients with Stage III squamous cell anal carcinoma
Authors: Kim Stefano , Boustani Jihane , Vernerey Dewi , Vendrely Véronique , Evesque Ludovic , Francois Eric , Quero Laurent , Ghiringhelli Francois , de la Fouchardière Christelle , Dahan Laëtitia , Bouché Oliver , Chibaudel Benoist , Hajbi Farid El , Vernet Chloé , Rebucci-Peixoto Magali , Feuersinger Alexandra , Maritaz Christophe , Borg Christophe 
Published: August 2022

BackgroundChemoradiotherapy alone is the standard treatment for locally advanced squamous cell anal carcinoma (SCAC). However, up to 50% of patients will experience recurrence; thus, there is a need for new treatments to improve outcomes. Modified docetaxel, cisplatin and 5-fluorouracil (mDCF) is a treatment option for first-line metastatic SCAC, having shown efficacy in the Epitopes-HPV01 and -02 trials (NCT01845779 and NCT02402842). mDCF treatment also plays a role in the modulation of anti-tumor immunity, suggesting it may be a good combination partner for immunotherapy in patients with SCAC. Anti-programmed death protein-1 (PD-1) immunotherapy has been shown to be effective in metastatic SCAC. We therefore designed the INTERACT-ION study to assess the combination of mDCF with ezabenlimab (BI 754091), an anti-PD-1 antibody, followed by chemoradiotherapy, in patients with Stage III SCAC.MethodsINTERACT-ION is a pivotal, open-label, single-arm phase II study in patients with treatment-naïve Stage III SCAC. Patients will receive induction treatment with mDCF (docetaxel 40 mg/m2 and cisplatin 40 mg/m2 on Day 1, 5-fluorouracil 1200 mg/m2/day for 2 days) every 2 weeks for 4 cycles and ezabenlimab (240 mg given intravenously) every 3 weeks for 3 cycles. In the absence of disease progression at 2 months, two additional cycles of mDCF and one additional cycle of ezabenlimab will be administered. Patients with radiological objective response, pathological complete/near-complete response and biological complete response will then receive an involved-node radiotherapy with intensity-modulated radiation therapy and concurrent chemotherapy, followed by ezabenlimab alone for seven cycles. All other patients will receive standard chemoradiotherapy. The primary endpoint is the clinical complete response rate 10 months after the first cycle of mDCF plus ezabenlimab. Major secondary endpoints are major pathological response and biological complete response after induction treatment. An extensive ancillary biomarker study in tumor tissue and peripheral blood will also be conducted.DiscussionThe addition of immunotherapy to chemotherapy is an area of active interest in metastatic anal cancer. This pivotal study will evaluate this combination in the locally advanced setting. Ancillary biomarker studies will contribute to the understanding of predictors of response or resistance to treatment.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT04719988, identifier NCT04719988.
Comprehensive analysis of TP53 and SPOP mutations and their impact on survival in metastatic prostate cancer
Authors: Zhou Jie , Lai Yiming , Peng Shengmeng , Tang Chen , Chen Yongming , Li Lingfeng , Huang Hai , Guo Zhenghui 
Published: August 2022

BackgroundAlthough TP53 and SPOP are frequently mutated in metastatic prostate cancer (PCa), their prognostic value is ambiguous, and large sample studies are lacking, especially when they co-occur with other genetic alterations.MethodsGenomic data and patients’ clinical characteristics in PCa were downloaded from the cBioPortal database. We extensively analyzed other gene alterations in different mutation status of TP53 and SPOP. We further subdivided TP53 and SPOP mutation into subgroups based on different mutation status, and then evaluated the prognostic value. Two classification systems for TP53 survival analysis were used.ResultsA total of 2,172 patients with PCa were analyzed in our study, of which 1,799 were metastatic PCa patients. The mutual exclusivity analysis showed that TP53 and SPOP mutation has a strong mutual exclusion (p&lt;0.001). In multivariable analysis, truncating TP53 mutations (HR=1.773, 95%CI:1.403-2.239, p&lt;0.001) and other TP53 mutations(HR=1.555, 95%CI:1.267-1.908, p&lt;0.001) were independent negative prognostic markers in metastatic PCa, whereas SPOP mutations(HR=0.592, 95%CI:0.427-0.819, p&lt;0.001) were an independent prognostic factor for better prognosis. Mutations in TP53 were significantly associated with wild-type status for SPOP and CDK12, structural variants/fusions for TMPRSS2 and ERG, AR amplification and PTEN deletion (p&lt;0.001). And truncating TP53 mutations have higher AR amplification rates than other TP53 mutations (p=0.022). Consistently, truncating TP53 mutations had a worse prognosis than other TP53 mutations (p&lt;0.05). Then Kaplan-Meier survival curve showed that Co-occurring TP53 mutations in AR amplification or PTEN deletion tumors significantly reduced survival (p&lt;0.05). Furthermore, those with SPOP-mutant tumors with co-occurring TP53 truncating mutations had shorter overall survival than those with SPOP-mutant tumors with wild-type or other TP53 mutations.ConclusionsThis study found that TP53 and SPOP mutations were mutually exclusive and both were independent prognostic markers for metastatic PCa. Genomic alteration and survival analysis revealed that TP53 and SPOP mutations represented distinct molecular subtypes. Our data suggest that molecular stratification on the basis of TP53 and SPOP mutation status should be implemented for metastatic PCa to optimize and modify clinical decision-making.
Effect of corticosteroids combined with cyclophosphamide or mycophenolate mofetil therapy for IgA nephropathy with stage 3 or 4 chronic kidney disease: A retrospective cohort study
Authors: Jia Qing , Ma Feng , Zhao Jin , Yang Xiaoxia , Sun Ruiling , Li Rong , Sun Shiren 
Published: August 2022

Background: To determine the safety and efficacy of corticosteroids (CS) combined with cyclophosphamide (CTX), compared with CS combined with mycophenolate mofetil (MMF) for IgA nephropathy (IgAN) patients with stage 3 and 4 CKD and proteinuria ≥1.0 g/24 h in a 10-year real-world study.Methods: We recruited 296 IgAN patients with renal insufficiency and proteinuria ≥1.0 g/24 h who received uncontrolled supportive care (USC) (n = 44), CS + CTX therapy (n = 164) and CS + MMF therapy (n = 88) in Xijing Hospital from July 2008 to December 2019. The combined event was defined as a ≥50% decrease in eGFR, ESRD, or death.Results: The median of the follow-up period was 39.3 months. One hundred and twenty-five patients experienced the combined event, 65.9, 37.8, and 38.6% in the USC, CS + CTX, and CS + MMF group, respectively. In multivariate Cox regression analyses, CS combined with CTX (HR = 0.457, 95% CI 0.238-0.878, p = 0.019) significantly reduced the incidence of the combined event, whereas CS + MMF (HR = 0.523, 95% CI 0.246-1.109, p = 0.091) did not reduce the risk of the combined event, compared with USC. The incidence of pneumonia and death due to infection in the CS + MMF group was higher than other two groups.Conclusion: Compared with USC and CS + MMF therapy, CS + CTX therapy was more safety and possibly more effective. The results need to be further confirmed by large randomized controlled studies.
Nontargeted metabolomics to characterize the effects of isotretinoin on skin metabolism in rabbit with acne
Authors: Ou-Yang Xiao-Liang , Zhang Deng , Wang Xiu-Ping , Yu Si-Min , Xiao Zhen , Li Wei , Li Chun-Ming 
Published: August 2022

Background: Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit. This study aimed to explore the pathogenesis of acne and the therapeutic mechanism of isotretinoin from the metabolic perspective in coal tar-induced acne in rabbits.Methods: Ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-qTOF-MS) based metabolomics was used to identify skin metabolites in groups C (blank control), M (model group) and T (isotretinoin group). Multivariate statistical analysis was used to process the metabolomics data.Results: 98 differential metabolites in group C and group M were identified. The highest proportion of differential metabolites were organic acids and derivatives, lipid metabolites, organic heterocyclic compounds, and nucleoside metabolites. The most significant metabolic pathways included protein digestion and absorption, central carbon metabolism in cancer, ABC transporters, aminoacyl-tRNA biosynthesis, biosynthesis of amino acids, and sphingolipid signaling pathway. Isotretinoin treatment normalized eight of these metabolites.Conclusions: Our study will help to further elucidate the pathogenesis of acne, the mechanism of isotretinoin at the metabolite level, and identify new therapeutic targets for treating acne.