bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct percutaneous puncture versus transarterial embolization for head and neck paragangliomas: A systematic review and meta-analysis
Authors: Schartz Derrek , Manganaro Mark , Szekeres Denes , Ismail Rahim , Hoang Timothy , Worley Logan , Finkelstein Alan , Schartz Chelsey , Akkipeddi Sajal Medha K. , Bender Matthew T. , Kessler Alex 
Published: July 2023

Introduction Embolization of head and neck paragangliomas (HNPs) is a well-established treatment strategy and adjunctive therapy. However, the optimal mode of intervention, whether by direct percutaneous puncture (DP) or via transarterial embolization (TAE), remains unclear. Methods The aim of this study was to complete a systematic literature review and meta-analysis to compare the safety and efficacy of DP versus TAE for HNP embolization. The Cochrane Library and MEDLINE databases were used to identify studies describing the clinical outcomes of either DP or TAE for HNP embolization. Outcome measures included: complete angiographic devascularization, major complications, and minor complications. Pooled rates were calculated for each variable which were then compared with meta-regression using a random effects model. Results Thirty-one retrospective studies met inclusion criteria, detailing 394 patients with 411 HNPs. Overall, DP was associated with a higher rate of complete devascularization (91.5%, 95% confidence interval [CI]: 85.6% to 97.4%; I2 = 0%) when compared to TAE technique (40.1%, CI: 27.2% to 58.9%; I2 = 93%). However, there was no difference regarding major complication rates between DP (6%, CI:1.3% to 10.8%; I2 = 0%) and TAE for HNP embolization (3.3%, CI: 1.4% to 5.3%; I2 = 0%) (p = 0.370), nor in minor complications between the techniques (p = 0.211). Subgroup analysis of TAE embolic agents revealed that particle embolics were associated with a significantly lower rate of major complications (2.5%; 0.4% to 4.6%; I2 = 0%) when compared to liquid embolics (10.6%, CI:4% to 17.3%; I2 = 48%; p = 0.022). Conclusions A DP approach for HNP embolization results in a higher rate of complete devascularization and with a similar complication profile when compared to TAE. These findings also suggest that particle embolics are associated with fewer major complications compared to liquid embolics when TAE is utilized.
The net benefit for time-to-event outcome in oncology clinical trials with treatment switching
Authors: Fukuda Musashi , Sakamaki Kentaro , Oba Koji 
Published: July 2023

BackgroundThe net benefit is an effect measure for any type of endpoint, including the time-to-event outcome, and can provide intuitive and clinically meaningful interpretation. It is defined as the probability of a randomly selected subject from the experimental arm surviving by at least a clinically relevant time longer than a randomly selected subject from the control arm. In oncology clinical trials, an intercurrent event such as treatment switching is common, which potentially causes informative censoring; nevertheless, conventional methods for the net benefit are not able to deal with it. In this study, we proposed a new estimator using the inverse probability of censoring weighting (IPCW) method and illustrated an oncology clinical trial with treatment switching (the SHIVA study) to apply the proposed method under the estimand framework.MethodsThe net benefit can be estimated using the survival functions of each treatment group. The proposed estimator was based on the survival functions estimated by the inverse probability of the censoring weighting method that can handle covariate-dependent censoring. The simulation study was undertaken to evaluate the operating characteristics of the proposed estimator under several scenarios; we varied the shapes of the survival curves, treatment effect, covariates effect on censoring, proportion of the censoring, threshold of the net benefit, and sample size. We also applied conventional methods (the scoring rules by Péron or Gehan) and the proposed method to the SHIVA study.ResultsOur simulation study showed that the proposed estimator provided less biased results under the covariate-dependent censoring than existing estimators. When applying the proposed method to the SHIVA study, we were able to estimate the net benefit by incorporating the information of the covariates with different estimand strategies to address the intercurrent event of the treatment switching. However, the estimates of the proposed method and those of the aforementioned conventional methods were similar under the hypothetical strategy.ConclusionsWe proposed a new estimator of the net benefit that can include covariates to account for the possibly informative censoring. We also provided an illustrative analysis of the proposed method for the oncology clinical trial with treatment switching using the estimand framework. Our proposed new estimator is suitable for handling the intercurrent events that can potentially cause covariate-dependent censoring.
Long-term sutimlimab improves quality of life for patients with cold agglutinin disease: CARDINAL 2-year follow-up
Authors: Röth Alexander , Broome Catherine M. , Barcellini Wilma , Tvedt Tor Henrik Anderson , Miyakawa Yoshitaka , D’Sa Shirley , Cella David , Bozzi Sylvie , Jayawardene Deepthi , Yoo Ronnie , Shafer Frank , Wardęcki Marek , Weitz Ilene C. 
Published: July 2023

Abstract
Cold agglutinin disease (CAD) is a rare form of autoimmune hemolytic anemia with a substantial burden on patient’s quality of life. CARDINAL was a 2-part, open-label, single-arm, multicenter phase 3 study evaluating the C1s inhibitor, sutimlimab, for treatment of CAD. Part A consisted of the pivotal study phase, with the part B extension phase assessing long-term safety and durability of response including patient-reported outcomes, which is the focus of this report. Altogether, 22 patients continued from part A to part B, majority female (68.2%) with a median age of 71.5 years (range, 55-85). Throughout treatment, score improvement on the Functional Assessment of Chronic Illness Therapy (FACIT)–Fatigue scale exceeded a predefined, group-level clinically important change of ≥5 points vs baseline, with a mean (standard error [SE]) change of 11.7 (3.7) points at week 135. The 12-Item Short Form Health Survey physical and mental component scores remained above baseline, with week 123 mean change (SE) exceeding clinically important changes of 3.9 for physical and 2.8 for mental component scores at 4.7 (2.8) and 3.8 (5.7) points, respectively. EuroQol Visual Analogue Scale, scoring patients’ self-rated health, also remained above baseline with a change of 17.1 (5.6) points at week 135. Patient Global Impression of (fatigue) Severity improved vs baseline, corroborating FACIT-Fatigue scores. Patient Global Impression of Change indicated a reduction in perceived disease burden. Data from CARDINAL part B support sustained alleviation of CAD disease burden after long-term treatment with sutimlimab over 2 years, returning toward baseline upon treatment cessation. This trial was registered at www.clinicaltrials.gov as #NCT03347396.
Talin2 and KANK2 functionally interact to regulate microtubule dynamics, paclitaxel sensitivity and cell migration in the MDA-MB-435S melanoma cell line
Authors: Lončarić Marija , Stojanović Nikolina , Rac-Justament Anja , Coopmans Kaatje , Majhen Dragomira , Humphries Jonathan D. , Humphries Martin J. , Ambriović-Ristov Andreja 
Published: July 2023

AbstractBackgroundFocal adhesions (FAs) are integrin-containing, multi-protein structures that link intracellular actin to the extracellular matrix and trigger multiple signaling pathways that control cell proliferation, differentiation, survival and motility. Microtubules (MTs) are stabilized in the vicinity of FAs through interaction with the components of the cortical microtubule stabilizing complex (CMSC). KANK (KN motif and ankyrin repeat domains) family proteins within the CMSC, KANK1 or KANK2, bind talin within FAs and thus mediate actin-MT crosstalk. We previously identified in MDA-MB-435S cells, which preferentially use integrin αVβ5 for adhesion, KANK2 as a key molecule enabling the actin-MT crosstalk. KANK2 knockdown also resulted in increased sensitivity to MT poisons, paclitaxel (PTX) and vincristine and reduced migration. Here, we aimed to analyze whether KANK1 has a similar role and to distinguish which talin isoform binds KANK2.MethodsThe cell model consisted of human melanoma cell line MDA-MB-435S and stably transfected clone with decreased expression of integrin αV (3αV). For transient knockdown of talin1, talin2, KANK1 or KANK2 we used gene-specific siRNAs transfection. Using previously standardized protocol we isolated integrin adhesion complexes. SDS-PAGE and Western blot was used for protein expression analysis. The immunofluorescence analysis and live cell imaging was done using confocal microscopy. Cell migration was analyzed with Transwell Cell Culture Inserts. Statistical analysis using GraphPad Software consisted of either one-way analysis of variance (ANOVA), unpaired Student’st-test or two-way ANOVA analysis.ResultsWe show that KANK1 is not a part of the CMSC associated with integrin αVβ5 FAs and its knockdown did not affect the velocity of MT growth or cell sensitivity to PTX. The talin2 knockdown mimicked KANK2 knockdown i.e. led to the perturbation of actin-MT crosstalk, which is indicated by the increased velocity of MT growth and increased sensitivity to PTX and also reduced migration.ConclusionWe conclude that KANK2 functionally interacts with talin2 and that the mechanism of increased sensitivity to PTX involves changes in microtubule dynamics. These data elucidate a cell-type-specific role of talin2 and KANK2 isoforms and we propose that talin2 and KANK2 are therefore potential therapeutic targets for improved cancer therapy.Graphical Abstract
Dimensionality of genomic information and its impact on genome-wide associations and variant selection for genomic prediction: a simulation study
Authors: Jang Sungbong , Tsuruta Shogo , Leite Natalia Galoro , Misztal Ignacy , Lourenco Daniela 
Published: July 2023

Abstract
Background
Identifying true positive variants in genome-wide associations (GWA) depends on several factors, including the number of genotyped individuals. The limited dimensionality of genomic information may give insights into the optimal number of individuals to be used in GWA. This study investigated different discovery set sizes based on the number of largest eigenvalues explaining a certain proportion of variance in the genomic relationship matrix (G). In addition, we investigated the impact on the prediction accuracy by adding variants, which were selected based on different set sizes, to the regular single nucleotide polymorphism (SNP) chips used for genomic prediction.

Methods
We simulated sequence data that included 500k SNPs with 200 or 2000 quantitative trait nucleotides (QTN). A regular 50k panel included one in every ten simulated SNPs. Effective population size (Ne) was set to 20 or 200. GWA were performed using a number of genotyped animals equivalent to the number of largest eigenvalues of G (EIG) explaining 50, 60, 70, 80, 90, 95, 98, and 99% of the variance. In addition, the largest discovery set consisted of 30k genotyped animals. Limited or extensive phenotypic information was mimicked by changing the trait heritability. Significant and large-effect size SNPs were added to the 50k panel and used for single-step genomic best linear unbiased prediction (ssGBLUP).

Results
Using a number of genotyped animals corresponding to at least EIG98 allowed the identification of QTN with the largest effect sizes when Ne was large. Populations with smaller Ne required more than EIG98. Furthermore, including genotyped animals with a higher reliability (i.e., a higher trait heritability) improved the identification of the most informative QTN. Prediction accuracy was highest when the significant or the large-effect SNPs representing twice the number of simulated QTN were added to the 50k panel.

Conclusions
Accurately identifying causative variants from sequence data depends on the effective population size and, therefore, on the dimensionality of genomic information. This dimensionality can help identify the most suitable sample size for GWA and could be considered for variant selection, especially when resources are restricted. Even when variants are accurately identified, their inclusion in prediction models has limited benefits.
A mutation responsible for impaired detection by the Xpert SARS-CoV-2 assay independently emerged in different lineages during the SARS-CoV-2 pandemic
Authors: Peñas-Utrilla Daniel , Sanz Amadeo , Catalán Pilar , Veintimilla Cristina , Alcalá Luis , Alonso Roberto , Muñoz Patricia , Pérez-Lago Laura , García de Viedma Darío ,   on behalf of the Gregorio Marañón Microbiology-ID COVID 19 Study Group, Aldámiz Teresa , Álvarez-Uría Ana , Bermúdez Elena , Bouza Emilio , Buenestado-Serrano Sergio , Burillo Almudena , Carrillo Raquel , Catalán Pilar , Cercenado Emilia , Cobos Alejandro , Díez Cristina , Escribano Pilar , Estévez Agustín , Fanciulli Chiara , Galar Alicia , García Mª Dolores , Gijón Paloma , Guillén Helmuth , Guinea Jesús , Herranz Marta , Irigoyen Álvaro , Kestler Martha , López Juan Carlos , Machado Marina , Marín Mercedes , Martín-Rabadán Pablo , Molero-Salinas Andrea , Montilla Pedro , Padilla Belén , Palomino-Cabrera Rosalía , Palomo María , Pérez-Granda María Jesús , Pérez Leire , Reigadas Elena , Rincón Cristina , Rodríguez Belén , Rodríguez Sara , Rodríguez-Grande Cristina , Rojas Adriana , Ruiz-Serrano María Jesús , Sánchez Carlos , Sánchez Mar , Serrano Julia , Tejerina Francisco , Valerio Maricela , Veintimilla Mª Cristina , Vesperinas Lara , Vicente Teresa , de la Villa Sofía 
Published: July 2023

Abstract
Background
COVID-19 diagnosis lies on the detection of SARS-CoV-2 on nasopharyngeal specimens by RT-PCR. The Xpert-Xpress SARS-CoV-2 assay provides results in less than one hour from specimen reception, which makes it suitable for clinical/epidemiological circumstances that require faster responses. The analysis of a COVID-19 outbreak suspected in the neonatology ward from our institution showed that the Ct values obtained for the targeted genes in the Xpert assay were markedly different within each specimen (N Ct value > 20 cycles above the E Ct value).

Results
We identified the mutation C29200T in the N gene as responsible for an impairment in the N gene amplification by performing whole genome sequencing of the specimens involved in the outbreak (Omicron variant). Subsequently, a retrospective analysis of all specimens sequenced in our institution allowed us to identify the same SNP as responsible for similar impairments in another 12 cases (42% of the total cases reported in the literature). Finally, we found that the same SNP emerged in five different lineages independently, throughout almost all the COVID-19 pandemic.

Conclusions
We demonstrated for the first time the impact of this SNP on the Xpert assay, when harbored by new Omicron variants. We extend our observation period throughout almost all the COVID-19 pandemic, offering the most updated observations of this phenomenon, including sequences from the seventh pandemic wave, until now absent in the reports related to this issue. Continuous monitoring of emerging SNPs that could affect the performance of the most commonly used diagnostic tests, is required to redesign the tests to restore their correct performance.
Prevalence and mechanisms of ciprofloxacin resistance in Escherichia coli isolated from hospitalized patients, healthy carriers, and wastewaters in Iran
Authors: Neyestani Zohreh , Khademi Farzad , Teimourpour Roghayeh , Amani Mojtaba , Arzanlou Mohsen 
Published: July 2023

Abstract
Background
This study was aimed to evaluate the prevalence and molecular characteristics of ciprofloxacin resistance among 346 Escherichia coli isolates collected from clinical specimens (n = 82), healthy children (n = 176), municipal wastewater (n = 34), hospital wastewater (n = 33), poultry slaughterhouse wastewater (n = 12) and livestock (n = 9) slaughterhouse wastewater in Iran.

Methods
Ciprofloxacin minimum inhibitory concentration (MIC) was determined by agar dilution assay. Phylogroups and plasmid-mediated quinolone resistance (PMQR) genes were identified using PCR. Mutations in gyrA, gyrB, parC, and parE genes and amino acid alterations were screened through sequencing assay. The effect of efflux pump inhibitor (PAβN) on ciprofloxacin MICs in ciprofloxacin-resistant isolates was investigated using the microdilution method.

Results
In total, 28.03% of E. coli isolates were phenotypically resistant to ciprofloxacin. Based on sources of isolation, 64.63%, 51.51%, 33.33%, 14.70%, 10.22% and 8.33% of isolates from clinical specimens, hospital wastewater, livestock wastewater, municipal wastewater, healthy children and poultry wastewater were ciprofloxacin-resistant, respectively. Eighty-one point eighty-one percent (Ser-83 → Leu + Asp-87 → Asn; 78.78% and Ser-83 → Leu only; 3.03% (of ciprofloxacin-resistant E. coli isolates showed missense mutation in GyrA subunit of DNA gyrase, while no amino-acid substitution was noted in the GyrB subunit. DNA sequence analyses of the ParC and ParE subunits of topoisomerase IV exhibited amino-acid changes in 30.30% (Ser-80 → Ile + Glu-84 → Val; 18.18%, Ser-80 → Ile only; 9.10% and Glu-84 → Val only; 3.03%0 (and 15.38% (Ser-458 → Ala) of ciprofloxacin-resistant E. coli isolates, respectively. The PMQR genes, aac(6')-Ib-cr, qnrS, qnrB, oqxA, oqxB, and qepA were detected in 43.29%, 74.22%, 9.27%, 14.43%, 30.92% and 1.03% of ciprofloxacin-resistant isolates, respectively. No isolate was found to be positive for qnrA and qnrD genes. In isolates harboring the OqxA/B efflux pump, the MIC of ciprofloxacin was reduced twofold in the presence of PAβN, as an efflux pump inhibitor. The phylogroups B2 (48.45%) and A (20.65%) were the most predominant groups identified in ciprofloxacin-resistant isolates.

Conclusions
This study proved the high incidence of ciprofloxacin-resistant E. coli isolates in both clinical and non-clinical settings in Iran. Chromosomal gene mutations and PMQR genes were identified in ciprofloxacin resistance among E. coli population.
Concomitant aortic regurgitation predicts better left ventricular reverse remodeling after transcatheter aortic valve replacement
Authors: Yang Hao-Ran , Xiong Tian-Yuan , Zhang Yi , He Jing-Jing , Feng Yuan , Chen Mao 
Published: July 2023

Abstract
Background
We aim to determine predictors of inadequate left ventricular mass index (LVMi) regression at mid-term after transcatheter aortic valve replacement (TAVR), including the potential role of epicardial adipose tissue (EAT).

Methods
We retrospectively reviewed patients with both echocardiographic assessments and multi-slice computed tomography (MSCT) obtained one year after TAVR. The change of LVMi, the volume and the average CT attenuation of EAT from baseline to one-year follow-up was calculated. Patients were divided into two groups by the percentage change of LVMi at a cut-off of 15%.

Results
A total of 152 patients were included with a median age of 74 years (interquartile range [IQR] 69–78 years) and 56.6% being male. LVMi decreased (P < 0.0001) while EAT volume increased and the average CT attenuation decreased (both P < 0.0001) at one year. Baseline atrial fibrillation (P = 0.042), mitral regurgitation ≥ mild (P = 0.006), aortic regurgitation (AR) > mild (P = 0.001) and the change in the average CT attenuation of EAT (P = 0.026) were different between the decrease of LVMi ≥ 15% and < 15%. AR > mild at baseline was the only statistically significant predictor of a decrease of LVMi < 15% at one year (OR 0.33, 95% CI: 0.13 to 0.84, P = 0.021) in multivariate regression.

Conclusions
Concomitant more-than-mild AR might predict better left ventricular reverse remodeling regression after TAVR.
Single-center experience with catheter-directed thrombolysis and balloon angioplasty for acute upper-extremity deep vein thrombosis: a case series study
Authors: Jenab Yaser , Tofighi Saeed , Ayati Aryan , Rezvanimehr Ali , Moosavi Najme-sadat , Jalaie Houman , Barbati Mohammad Esmaeil 
Published: July 2023

Abstract
Background
Effective treatment of upper extremity deep vein thrombosis (UEDVT) is crucial to prevent further complications. Various treatments, including percutaneous mechanical thrombectomy (PMT), catheter-directed thrombolysis (CDT), decompression surgery, and venoplasty are suggested for UEDVT. However, no prospective study has yet favored any of these treatments. This study presents a review of our experience with CDT followed by balloon venoplasty in patients with acute primary UEDVT.

Methods
We enrolled all patients diagnosed with acute UEDVT from January 2020 to June 2021. Subjects with UEDVT due to secondary causes like malignancies, indwelling catheters, or leads were excluded. CDT was performed through brachial vein access, using a perfusion catheter, and rt-PA administration. Balloon venoplasty was performed if the treated segment had remaining stenosis after CDT. Patients were followed up at the vein clinic for any signs and symptoms in the upper extremity and lifestyle changes. Follow-up ultrasonography was done 12 months after discharge.

Results
Twelve patients with a mean age of 41.08 ± 14.0 years were included in the study. The mean duration of CDT was 25.00 ± 10.56 h. After CDT, all patients had remaining occlusions, with seven having more than 50% remaining stenosis. However, after balloon venoplasty, no patient had significant (more than 50%) stenosis. There was no serious complication after both procedures. Patients were followed up for a mean duration of twelve months after their admission, with a mean time of maintenance anticoagulation was 10.73 ± 5.77 months. Only one patient had recurrent symptoms in his target limb which required a decompression surgery, while the rest were free of symptoms in their treated extremity. No subject developed pulmonary emboli (PE) during admission or the follow-up period. There was no evidence of hospital readmission for any reason. Upper extremity color-doppler sonography of the patients at twelve months after their procedure showed normal venous flow without any significant stenosis in 8 (66.7%), and partially normal flow with patent target vein in 4 (33.3%) patients.

Conclusions
CDT followed by balloon venoplasty may be an effective treatment for selected patients with acute primary UEDVT, providing desirable long-term results and potentially avoiding the need for decompression surgery in the short or long term.