bluuebunny/crossref_metadata_2025_split huggingface dataset:
Passive pre-exposure immunization by tixagevimab/cilgavimab in patients with hematological malignancy and COVID-19: matched-paired analysis in the EPICOVIDEHA registry
Authors: Marchesi Francesco , Salmanton-García Jon , Buquicchio Caterina , Itri Federico , Besson Caroline , Dávila-Valls Julio , Martín-Pérez Sonia , Fianchi Luana , Rahimli Laman , Tarantini Giuseppe , Grifoni Federica Irene , Sciume Mariarita , Labrador Jorge , Cordoba Raul , López-García Alberto , Fracchiolla Nicola S. , Farina Francesca , Ammatuna Emanuele , Cingolani Antonella , García-Bordallo Daniel , Gräfe Stefanie K. , Bilgin Yavuz M. , Dargenio Michelina , González-López Tomás José , Guidetti Anna , Lahmer Tobias , Lavilla-Rubira Esperanza , Méndez Gustavo-Adolfo , Prezioso Lucia , Schönlein Martin , Van Doesum Jaap , Wolf Dominik , Hersby Ditte Stampe , Magyari Ferenc , Van Praet Jens , Petzer Verena , Tascini Carlo , Falces-Romero Iker , Glenthøj Andreas , Cornely Oliver A. , Pagano Livio 
Published: April 2023

AbstractOnly few studies have analyzed the efficacy of tixagevimab/cilgavimab to prevent severe Coronavirus disease 2019 (COVID-19) and related complications in hematologic malignancies (HM) patients. Here, we report cases of breakthrough COVID-19 after prophylactic tixagevimab/cilgavimab from the EPICOVIDEHA registry). We identified 47 patients that had received prophylaxis with tixagevimab/cilgavimab in the EPICOVIDEHA registry. Lymphoproliferative disorders (44/47, 93.6%) were the main underlying HM. SARS-CoV-2 strains were genotyped in 7 (14.9%) cases only, and all belonged to the omicron variant. Forty (85.1%) patients had received vaccinations prior to tixagevimab/cilgavimab, the majority of them with at least two doses. Eleven (23.4%) patients had a mild SARS-CoV-2 infection, 21 (44.7%) a moderate infection, while 8 (17.0%) had severe infection and 2 (4.3%) critical. Thirty-six (76.6%) patients were treated, either with monoclonal antibodies, antivirals, corticosteroids, or with combination schemes. Overall, 10 (21.3%) were admitted to a hospital. Among these, two (4.3%) were transferred to intensive care unit and one (2.1%) of them died. Our data seem to show that the use of tixagevimab/cilgavimab may lead to a COVID-19 severity reduction in HM patients; however, further studies should incorporate further HM patients to confirm the best drug administration strategies in immunocompromised patients.
PARP1 negatively regulates MAPK signaling by impairing BRAF-X1 translation
Authors: Marranci Andrea , Prantera Antonella , Masotti Simona , De Paolo Raffaella , Baldanzi Caterina , Podda Maurizio S. , Mero Serena , Vitiello Marianna , Franchin Cinzia , Laezza Mariavittoria , Comelli Laura , Arrigoni Giorgio , Cervelli Tiziana , Del Pozzo Giovanna , Poliseno Laura 
Published: April 2023

AbstractIn human cells BRAF oncogene is invariably expressed as a mix of two coding transcripts: BRAF-ref and BRAF-X1. These two mRNA isoforms, remarkably different in the sequence and length of their 3′UTRs, are potentially involved in distinct post-transcriptional regulatory circuits. Herein, we identify PARP1 among the mRNA Binding Proteins that specifically target the X1 3′UTR in melanoma cells. Mechanistically, PARP1 Zinc Finger domain down-regulates BRAF expression at the translational level. As a consequence, it exerts a negative impact on MAPK pathway, and sensitizes melanoma cells to BRAF and MEK inhibitors, both in vitro and in vivo. In summary, our study unveils PARP1 as a negative regulator of the highly oncogenic MAPK pathway in melanoma, through the modulation of BRAF-X1 expression.
Platform combining statistical modeling and patient-derived organoids to facilitate personalized treatment of colorectal carcinoma
Authors: Ramzy George M. , Norkin Maxim , Koessler Thibaud , Voirol Lionel , Tihy Mathieu , Hany Dina , McKee Thomas , Ris Frédéric , Buchs Nicolas , Docquier Mylène , Toso Christian , Rubbia-Brandt Laura , Bakalli Gaetan , Guerrier Stéphane , Huelsken Joerg , Nowak-Sliwinska Patrycja 
Published: April 2023

Abstract
Background
We propose a new approach for designing personalized treatment for colorectal cancer (CRC) patients, by combining ex vivo organoid efficacy testing with mathematical modeling of the results.

Methods
The validated phenotypic approach called Therapeutically Guided Multidrug Optimization (TGMO) was used to identify four low-dose synergistic optimized drug combinations (ODC) in 3D human CRC models of cells that are either sensitive or resistant to first-line CRC chemotherapy (FOLFOXIRI). Our findings were obtained using second order linear regression and adaptive lasso.

Results
The activity of all ODCs was validated on patient-derived organoids (PDO) from cases with either primary or metastatic CRC. The CRC material was molecularly characterized using whole-exome sequencing and RNAseq. In PDO from patients with liver metastases (stage IV) identified as CMS4/CRIS-A, our ODCs consisting of regorafenib [1 mM], vemurafenib [11 mM], palbociclib [1 mM] and lapatinib [0.5 mM] inhibited cell viability up to 88%, which significantly outperforms FOLFOXIRI administered at clinical doses. Furthermore, we identified patient-specific TGMO-based ODCs that outperform the efficacy of the current chemotherapy standard of care, FOLFOXIRI.

Conclusions
Our approach allows the optimization of patient-tailored synergistic multi-drug combinations within a clinically relevant timeframe.

Graphical Abstract
Tracheostomy timing and outcome in critically ill patients with stroke: a meta-analysis and meta-regression
Authors: Premraj Lavienraj , Camarda Christopher , White Nicole , Godoy Daniel Agustin , Cuthbertson Brian H. , Rocco Patricia R. M. , Pelosi Paolo , Robba Chiara , Suarez Jose I. , Cho Sung-Min , Battaglini Denise 
Published: April 2023

Abstract
Background
Stroke patients requiring mechanical ventilation often have a poor prognosis. The optimal timing of tracheostomy and its impact on mortality in stroke patients remains uncertain. We performed a systematic review and meta-analysis of tracheostomy timing and its association with reported all-cause overall mortality. Secondary outcomes were the effect of tracheostomy timing on neurological outcome (modified Rankin Scale, mRS), hospital length of stay (LOS), and intensive care unit (ICU) LOS.

Methods
We searched 5 databases for entries related to acute stroke and tracheostomy from inception to 25 November 2022. We adhered to PRISMA guidance for reporting systematic reviews and meta-analyses. Selected studies included (1) ICU-admitted patients who had stroke (either acute ischaemic stroke, AIS or intracerebral haemorrhage, ICH) and received a tracheostomy (with known timing) during their stay and (2) > 20 tracheotomised. Studies primarily reporting sub-arachnoid haemorrhage (SAH) were excluded. Where this was not possible, adjusted meta-analysis and meta-regression with study-level moderators were performed. Tracheostomy timing was analysed continuously and categorically, where early (< 5 days from initiation of mechanical ventilation to tracheostomy) and late (> 10 days) timing was defined per the protocol of SETPOINT2, the largest and most recent randomised controlled trial on tracheostomy timing in stroke patients.

Results
Thirteen studies involving 17,346 patients (mean age = 59.8 years, female 44%) met the inclusion criteria. ICH, AIS, and SAH comprised 83%, 12%, and 5% of known strokes, respectively. The mean time to tracheostomy was 9.7 days. Overall reported all-cause mortality (adjusted for follow-up) was 15.7%. One in five patients had good neurological outcome (mRS 0–3; median follow-up duration was 180 days). Overall, patients were ventilated for approximately 12 days and had an ICU LOS of 16 days and a hospital LOS of 28 days. A meta-regression analysis using tracheostomy time as a continuous variable showed no statistically significant association between tracheostomy timing and mortality (β = − 0.3, 95% CI = − 2.3 to 1.74, p = 0.8). Early tracheostomy conferred no mortality benefit when compared to late tracheostomy (7.8% vs. 16.4%, p = 0.7). Tracheostomy timing was not associated with secondary outcomes (good neurological outcome, ICU LOS and hospital LOS).

Conclusions
In this meta-analysis of over 17,000 critically ill stroke patients, the timing of tracheostomy was not associated with mortality, neurological outcomes, or ICU/hospital LOS.
Trial registration: PROSPERO—CRD42022351732 registered on 17th of August 2022.
Effects of 10 Hz individualized repetitive transcranial magnetic stimulation on patients with disorders of consciousness: a study protocol for an exploratory double-blind crossover randomized sham-controlled trial
Authors: Xu Chengwei , Zhu Zhaohua , Wu Wanchun , Zheng Xiaochun , Zhong Haili , Huang Xiyan , Xie Qiuyou , Qian Xinyi 
Published: April 2023

Abstract
Background
Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive brain stimulation technique, has shown potentials for consciousness recovery of patients with disorders of consciousness (DoC), as, to a certain extent, it is effective in regulating the excitability of central nervous system. However, it is difficult to achieve satisfactory effect with “one size fits all” rTMS treatment due to different clinical conditions of patients. There is an urgent need to develop individualized strategy to improve the effectiveness of rTMS on patients with DoC.

Methods
Our protocol is a randomized double-blind sham-controlled crossover trial that includes 30 DoC patients. Each patient will received 20 sessions, in which 10 sessions will be rTMS-active stimulus, and the other 10 sessions will be sham stimulus, separated by no less than 10 days’ washout period. The rTMS-active will include 10 Hz rTMS over the individualized-targeted selection area for each patient according to the different insult regions of the brain. Coma Recovery Scale-Revised (CRS-R) will be used as primary outcome at baseline, after the first stage of stimulation, at the end of the washout period, and after the second stage of stimulation. Secondary outcomes will be measured at the same time, including efficiency, relative spectral power, and functional connectivity of high-density electroencephalograph (EEG). Adverse events will be recorded during the study.

Discussion
rTMS has obtained grade A evidence in treating patients with several central nervous system diseases, and there has been some evidence showing partial improvement on level of consciousness in DoC patients. However, the effectiveness of rTMS in DoC is only 30~36%, mostly due to the non-specific target selection. In this protocol, we present a double-blind crossover randomized sham-controlled trial based on the individualized-targeted selection strategy that aims to study the effectiveness of rTMS therapy for DoC, and the result may provide new insights to non-invasive brain stimulation.

Trial registration
ClinicalTrials.gov: NCT05187000. Registered on January 10, 2022.
Lenient rate control versus strict rate control for atrial fibrillation: a statistical analysis plan for the Danish Atrial Fibrillation (DanAF) randomized clinical trial
Authors: Cold Isak Mazanti , Feinberg Joshua Buron , Brandes Axel , Davidsen Ulla , Dixen Ulrik , Dominguez Helena , Gang Uffe Jakob Ortved , Gluud Christian , Hadad Rakin , Kristensen Kit Engedal , van Le Doan Tuyet , Nielsen Emil Eik , Olsen Michael Hecht , Pedersen Ole Dyg , Raymond Ilan Esra , Sajadieh Ahmad , Soja Anne Merete Boas , Jakobsen Janus Christian 
Published: April 2023

Abstract
Background
A key decision in the treatment of atrial fibrillation is choosing between a rhythm control strategy or a rate control strategy as the main strategy. When choosing rate control, the optimal heart rate target is uncertain. The Danish Atrial Fibrillation trial is a randomized, multicenter, two-group, superiority trial comparing strict rate control versus lenient rate control in patients with either persistent or permanent atrial fibrillation at inclusion. To prevent bias arising from selective reporting and data-driven analyses, we developed a predefined description of the statistical analysis.

Methods
The primary outcome of this trial is the physical component score of the SF-36 questionnaire. A total of 350 participants will be enrolled based on a minimal important difference of 3 points on the physical component score of the SF-36 questionnaire, a standard deviation of 10 points, a statistical power of 80% (beta of 20%), and an acceptable risk of type I error of 5%. All secondary, exploratory, and echocardiographic outcomes will be hypothesis-generating. The analyses of all outcomes will be based on the intention-to-treat principle. We will analyze continuous outcomes using linear regression adjusting for “site,” type of atrial fibrillation at inclusion (persistent/ permanent), left ventricular ejection fraction (≥ 40% or < 40%), and the baseline value of the outcome (all as fixed effects). We define our threshold for statistical significance as a p-value of 0.05 and assessments of clinical significance will be based on the anticipated intervention effects defined in the sample size and power estimations. Thresholds for both statistical and clinical significance will be assessed according to the 5-step procedure proposed by Jakobsen and colleagues.

Discussion
This statistical analysis plan will be published prior to enrolment completion and before any data are available and is sought to increase the validity of the DANish Atrial Fibrillation trial.

Trial registration
Clinicaltrials.gov NCT04542785. Registered on Sept 09, 2020.
The impact of insulin resistance on the association between metabolic syndrome and lung function: the Kangbuk Samsung Health Study
Authors: Lee Jonghoo , Park Hye Kyeong , Kwon Min-Jung , Ham Soo-Youn , Gil Hyun-Il , Lim Si-Young , Song Jae-Uk 
Published: April 2023

Abstract
Background/Objective
Metabolic syndrome (MS) is related to lung dysfunction. However, its impact according to insulin resistance (IR) remains unknown. Therefore, we evaluated whether the relation of MS with lung dysfunction differs by IR.

Subject/Methods
This cross-sectional study included 114,143 Korean adults (mean age, 39.6 years) with health examinations who were divided into three groups: metabolically healthy (MH), MS without IR, and MS with IR. MS was defined as presence of any MS component, including IR estimated by HOMA-IR ≥ 2.5. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for lung dysfunction were obtained in MS, MS without IR, and MS with IR groups compared with the MH (reference) group.

Results
The prevalence of MS was 50.7%. The percent predicted forced expiratory volume in 1 s (FEV1%) and forced vital capacity (FVC%) showed statistically significant differences between MS with IR and MH and between MS with IR and MS without IR (all P < 0.001). However, those measures did not vary between MH and MS without IR (P = 1.000 and P = 0.711, respectively). Compared to MH, MS was not at risk for FEV1% < 80% (1.103 (0.993–1.224), P = 0.067) or FVC% < 80% (1.011 (0.901–1.136), P = 0.849). However, MS with IR was clearly associated with FEV1% < 80% (1.374 (1.205–1.566) and FVC% < 80% (1.428 (1.237–1.647) (all p < 0.001), though there was no evident association for MS without IR (FEV1%: 1.078 (0.975–1.192, P = 0.142) and FVC%: 1.000 (0.896–1.116, p = 0.998)).

Conclusion
The association of MS with lung function can be affected by IR. However, longitudinal follow-up studies are required to validate our findings.
Psychometric properties of the Arabic version of the Intuitive Eating Scale-2 (IES-2) in a sample of community adults
Authors: Fekih-Romdhane Feten , Jiang Chen , Obeid Sahar , Malaeb Diana , Chammas Nancy , Fawaz Mirna , Soufia Michel , Meng Runtang , Hallit Souheil 
Published: April 2023

Abstract
Background
There is a growing attention on intuitive eating (IE) styles in the Western world that has not yet reached Arab countries, which is likely due to the lack of psychometrically sound measures of the IE construct for Arabic-speaking people. The current study aims to examine the psychometric properties of an Arabic translation of the most widely used measure of IE—the Intuitive Eating Scale-2 (IES-2), in an Arabic-speaking community population from Lebanon.

Methods
Two samples of Arabic-speaking community adults from Lebanon (sample 1: n = 359, 59.9% females, age 22.75 ± 7.04 years; sample 2: n = 444, 72.7% females, age 27.25 ± 9.53 years) were recruited through online convenience sampling. The translation and back-translation method was applied to the IES-2 for linguistic validation. Factorial validity was investigated using an Exploratory Factor Analysis & Confirmatory Factor Analysis strategy. Composite reliability and sex invariance were examined. We also tested convergent and criterion-related validity through correlations with other theoretically plausible constructs.

Results
Nine out of the original 23 items were removed because they either loaded below 0.40 and/or cross-loaded too highly on multiple factors. This resulted in four domains (Unconditional Permission to Eat, Eating for Physical Rather than Emotional Reasons, Reliance on Hunger and Satiety Cues, and Body-Food Choice Congruence) and 14 items retained. Internal reliability estimates were excellent, with McDonald’s ω values ranging from 0.828 to 0.923 for the four factors. Multigroup analysis established configural, thresholds, metric, scalar, strict invariance across gender. Finally, higher IES-2 total scores were significantly correlated with lower body dissatisfaction scores and more positive eating attitudes, thus attesting to convergent and criterion-related validity of the scale.

Conclusions
The current findings provide preliminary evidence for the appropriate psychometric qualities of the Arabic 14-item, four-factor structure IES-2; thereby supporting its use at least among Arabic-speaking community adults.
Adequacy of energy and macronutrients intake in differently active slovenian adolescents
Authors: Vilhar Emanuela Čerček , Golja Petra , Starc Gregor , Seljak Barbara Koroušić , Kotnik Katja Zdešar 
Published: April 2023

Abstract
Objective
Evaluate the adequacy of energy/macronutrient intake in adolescents according to the Slovenian national recommendations adopted from the recommendations of the German Nutrition Society and to identify differences in energy/macronutrient intake between differently active adolescents.

Methods
Data on energy and macronutrient intake (24-hour dietary recall), physical activity (SHAPES questionnaire), and anthropometric characteristics (body mass and height) of adolescents were obtained on a representative sample of first-year secondary school students (average (SD) age: 15.3 (0.5) years; N = 341), who were included in the national survey The Analysis of Children’s Development in Slovenia (ACDSi) in 2013/14.

Results
75% of adolescents met the national recommendations for carbohydrates and proteins and 44% for fats, whereas only 10% of adolescents met the recommendations for energy intake. Energy/macronutrient intakes were significantly higher in vigorously physically active (VPA) boys compared to moderately (MPA) and less (LPA) physically active boys. No such differences were observed between girls of different physical activity levels.

Conclusion
Adolescents need to be encouraged to meet their energy needs according to gender and physical activity (especially VPA girls) and to reach for higher quality foods in adequate macronutrient proportions.
Women Have Greater Endothelin-B Receptor Function and Lower Mitochondrial Capacity Compared to Men With Type 1 Diabetes
Authors: Derella Cassandra C , Thomas Jeffery , Harris Ryan A 
Published: April 2023

Abstract

Context
Type 1 diabetes (T1D) negatively affects both the endothelin system and muscle oxidative capacity. The endothelin pathway is a critical regulator of microcirculatory function and may exhibit sexual dichotomy by which healthy premenopausal women have greater endothelin-B receptor (ETBR) function compared to men. Moreover, T1D may differentially alter muscle oxidative capacity in men and women; however, whether ETBR function is impaired in women compared to men with T1D and its relationship with muscle oxidative capacity has yet to be explored.

Objective
The purpose of this investigation was to determine if ETBR-mediated dilation is impaired in women compared to men with T1D and if this is related to their skeletal muscle oxidative capacity.

Methods
Men (n = 9; glycated hemoglobin A1c [HbA1c] = 7.8 ± 1.0%) and women (N = 10 women; HbA1c = 8.4 ± 1.3%) with uncomplicated T1D were recruited for this investigation. Near-infrared spectroscopy (NIRS) and intradermal microdialysis (750 nM BQ-123 + ET-1 [10−20–10−8 mol/L]) were used to evaluate skeletal muscle oxidative capacity and assess ETBR-mediated vasodilation, respectively.

Results
Skeletal muscle oxidative capacity was significantly lower (P = .031) in women compared with men with T1D. However, ETBR-mediated dilation induced a significantly greater (P = .012) vasodilatory response in women compared to men with T1D, and the area under the curve was negatively associated with skeletal muscle oxidative capacity (r = −.620; P = .042).

Conclusion
Compared to men with uncomplicated T1D, muscle oxidative capacity was lower and ETBR-mediated vasodilation was higher in women with uncomplicated T1D. ETBR-induced vasodilatory capacity was inversely related to skeletal muscle oxidative capacity, suggesting there may be compensatory mechanisms occurring to preserve microvascular blood flow in women with T1D.
Traumatic Brain Injury Mortality and Correlates in Low- and Middle-Income Countries: A Meta-Epidemiological Study
Authors: Naik Anant , Bederson Maria M. , Detchou Donald , Dharnipragada Rajiv , Hassaneen Wael , Arnold Paul M. , Germano Isabelle M. 
Published: April 2023

BACKGROUND:
It is estimated that up to 69 million people per year experience traumatic brain injury (TBI) with the highest prevalence found in low- and middle-income countries (LMICs). A paucity of data suggests that the mortality rate after severe TBI is twice as high in LMICs than in high-income countries.

OBJECTIVE:
To analyze TBI mortality in LMICs and to evaluate what country-based socioeconomic and demographic parameters influence TBI outcomes.

METHODS:
Four databases were searched for the period January 1, 2002, to January 1, 2022, for studies describing TBI outcomes in LMICs. Multivariable analysis was performed using multivariable linear regression, with the outcome as the pooled mortality by country and the covariates as the adjusted parameters.

RESULTS:
Our search yielded 14 376 records of which 101 were included in the final analysis, totaling 59 197 patients and representing 31 LMICs. The pooled TBI-related mortality was 16.7% (95% CI: 13.7%-20.3%) without significant differences comparing pediatrics vs adults. Pooled severe TBI-related mortality was significantly higher than mild. Multivariable analysis showed a significant association between TBI-related mortality and median income (P = .04), population percentage below poverty line (P = .02), primary school enrollment (P = .01), and poverty head ratio (P = .04).

CONCLUSION:
TBI-related mortality in LMICs is 3-fold to 4-fold higher than that reported in high-income countries. Within LMICs, parameters associated with poorer outcomes after TBI include factors recognized as social determinants of health. Addressing social determinants of health in LMICs might expedite the quest to close the care delivery gap after TBI.