bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fiberscope-Based Measurement of Coaptation Height for Intraoperative Assessment of Mitral Valve Repair
Authors: Recco Dominic P. , Kneier Nicholas E. , Earley Patrick D. , Kizilski Shannen B. , Hammer Peter E. , Hoganson David M. 
Published: February 2024

Background Restoring adequate coaptation height is a key principle of mitral valve (MV) repair. This study aimed to evaluate the utility of fiberscope (FS) technology to assess MV coaptation height for intraoperative use. Methods Ex-vivo testing was performed on five adult porcine hearts. The left atrium (LA) was resected, and the left ventricle (LV) was pressurized retrograde to 27 ± 1mm Hg. An endoscope was inserted into the LV apex, centered under the MV orifice. An FS system (Milliscope II camera, LED light source, and 0.7 mm diameter × 15 cm long) 90° semirigid scope with 1.2 mm focal length) was mounted above the MV annulus in a custom alignment and measuring fixture. Three blinded measurements were taken at two locations on each MV, A2 and P2 segment, from the top of coaptation to the leaflet edge identified by the FS. Accurate positioning was verified using the LV endoscope. A control (metal rod of similar thickness) was used for comparison, with coaptation height recorded when the control was seen via the endoscope. Results Coaptation heights were similar for the control and FS methods across all hearts at A2 (11.6 ± 2.6 mm control vs 11.8 ± 2.2 mm FS) and P2 (13.3 ± 2.6 mm control vs 13.4 ± 2.9 mm FS) segments, with similar measurement variability (control SD 0.1-1.0 mm; FS SD 0.1-0.9 mm). One outlier was excluded from analysis (n = 19/20). The maximum absolute difference and percent error between measurement methods were less than 1.1 mm (median [IQR], 0.6 [0.3-0.9] mm) and less than 14% (4.1 [2.2-7.6]%). Conclusions Utilization of a miniaturized FS enabled precise and accurate quantification of MV coaptation. This technique is promising for evaluating post-repair valve competence and coaptation height.
Implementation successes and lessons learnt from a randomised controlled trial of a complex school-based intervention
Authors: Kingsley Ellen , Biggs Katie , Solaiman Kiera , Packham Anna , Nekooi Roshanak , Bursnall Matthew , McKendrick Kirsty , Cooper Cindy L , Wright Barry 
Published: February 2024

Background The UK has seen a recent shift towards children’s mental health being supported and treated in school settings. Several current school-based interventions focus on autism and social skills, with education professional involvement in their delivery increasing. The study of these interventions poses specific implementation challenges. This paper discusses implementation successes and learnings from the I-SOCIALISE research study which delivered and evaluated efficacy of LEGO® based therapy (now Play Brick Therapy) for autistic children and young people delivered in schools. Detailed Methods and results of the trial are reported elsewhere. Methods The I-SOCIALISE study was a pragmatic large-scale NIHR-funded cluster randomised controlled trial. Children and young people, their parents/guardians, and schoolteachers or teaching assistants were recruited from mainstream schools in the UK. They completed outcome measures and were randomised to receive either 12-week of LEGO® based therapy and usual support or usual support only. Various methods to achieve successful recruitment and retention were used and learnings were documented. Results The study recruited to time and target with successful delivery of this complex intervention in schools. Several lessons were learnt about recruitment methods, data collection, participant burden and retention, blinding, and the importance of relationships with key school contacts. Main recommendations based on these learnings are provided. Conclusions This study demonstrated that it is possible to undertake large scale, robust evaluation of pragmatically delivered complex school-based interventions. Recommendations are made to address the logistical challenges of undertaking research in this setting which are intended to facilitate future research.
Reversal of cylindrical bronchial dilatations in a subset of adults with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor
Authors: Cazier Paul , Chassagnon Guillaume , Dhote Théo , Da Silva Jennifer , Kanaan Reem , Honoré Isabelle , Carlier Nicolas , Revel Marie-Pierre , Canniff Emma , Martin Clémence , Burgel Pierre-Régis 
Published: February 2024

BackgroundThis study sought to evaluate the impact of elexacaftor/tezacaftor/ivacaftor (ETI) on lung structural abnormalities in adults with cystic fibrosis (awCF) with a specific focus on the reversal of bronchial dilatations.MethodsChest computed tomography (CT) scans performed prior to and 12 months after initiation of ETI were visually reviewed for possible reversal of bronchial dilatations. AwCF with and without reversal of bronchial dilatations (the latter served as controls, with three controls per case) were selected. Visual Brody score, bronchial and arterial diameters, and lung volume were measured on CT.ResultsReversal of bronchial dilatations was found in 12/235 (5%) awCF treated with ETI. 12 awCF with and 36 without reversal of bronchial dilatations were further analysed (male 56%, mean±sdage 31.6±8.5 years, F508del/F508delCFTR54% and mean forced expiratory volume in 1 s 58.8±22.3% predicted). The Brody score improved overall from 79.4±29.8 to 54.8±32.3 (p<0.001). Reversal of bronchial dilatations was confirmed by a decrease in bronchial lumen diameter in cases from 3.9±0.9 to 3.2±1.1 mm (p<0.001), whereas it increased in awCF without reversal of bronchial dilatations (from 3.5±1.1 to 3.6±1.2 mm; p=0.002). Reversal of bronchial dilatations occurred in cylindrical (not varicose or saccular) bronchial dilatations. Lung volumes decreased by −6.6±10.7% in awCF with reversal of bronchial dilatations but increased by +2.3±9.6% in controls (p=0.007).ConclusionsAlthough bronchial dilatations are generally considered irreversible, ETI was associated with reversal, which was limited to the cylindrical bronchial dilatation subtype, and occurred in a small subset of awCF. Initiating ETI earlier in life may reverse early bronchial dilatations.
Genomic diversity and clinical relevance ofMycobacterium simiae
Authors: Wetzstein Nils , Diricks Margo , Andres Sönke , Kuhns Martin , Marschall Lisa , Biciusca Teodora , Smaczny Christina , Friesen Inna , Niemann Stefan , Wichelhaus Thomas A. 
Published: February 2024

IntroductionMycobacterium simiaeis a slow-growing non-tuberculous mycobacterium that can cause non-tuberculous mycobacterium (NTM) pulmonary disease and extrapulmonary infections. Until now, detailed genomic and clinical characteristics, as well as possible transmission routes of this rare pathogen remain largely unknown.MethodsWe conducted whole genome sequencing of availableM. simiaeisolates collected at a tertiary care centre in Central Germany from 2006 to 2020 and set them into context with publicly availableM. simiaecomplex sequences through phylogenetic analysis. Resistance, virulence and stress genes, as well as known Mycobacteriaceae plasmid sequences were detected in whole genome raw reads. Clinical data and course were retrieved and correlated with genomic data.ResultsWe included 33M. simiae sensu strictoisolates from seven patients.M. simiaeshowed low clinical relevance with only two patients fulfilling American Thoracic Society (ATS) criteria in our cohort and three receiving NTM-effective therapy. The bacterial populations were highly stable over time periods of up to 14 years, and no instances of mixed or re-infections with other strains ofM. simiaewere observed. Clustering with <12 single nucleotide polymorphisms distance was evident among isolates from different patients; however, proof for human-to-human transmission could not be established from epidemiological data.ConclusionOverall, the available sequence data forM. simiaecomplex was significantly extended and new insights into its pathogenomic traits were obtained. We demonstrate high longitudinal genomic stability within single patients. Although we cannot exclude human-to-human transmission, we consider it unlikely in the light of available epidemiological data.
Multiple-breath washout to detect lung disease in patients with inborn errors of immunity
Authors: Busack Leonie M. , Thee Stephanie , Liu Yvonne , Allomba Christine , Ziegahn Niklas , Tosolini Apolline , Pioch Charlotte O. , Schnorr Alexandra N. , Fuhlrott Bent R. , Staudacher Olga , Völler Mirjam , Steinke Eva , Hanitsch Leif G. , Röhmel Jobst , Wahn Volker , Krüger Renate , Mall Marcus A. , von Bernuth Horst , Stahl Mirjam 
Published: February 2024

BackgroundPulmonary manifestations are the major cause of morbidity and mortality in patients with inborn errors of immunity (IEI). New and more sensitive diagnostic methods can potentially lead to earlier recognition and treatment of IEI lung disease and improve outcome. The aim of this study was to compare multiple-breath washout (MBW) and spirometry in patients with IEI and cystic fibrosis (CF) as well as healthy controls (HC) and to evaluate the sensitivity of lung clearance index (LCI) to assess lung disease in IEI.MethodsIEI patients (n=114) were recruited from our paediatric and adult immunodeficiency outpatient clinics and compared to age-matched CF patients (n=114) and HC (n=114). MBW measurements and spirometry were performed in the study participants, and MBW testing was repeated after 63–707 days in IEI patients (n=70).ResultsThe LCI was significantly higher in IEI patients than in HC (p<0.001) and significantly lower than in CF patients (p<0.001). The forced expiratory volume in 1 s (FEV1) z-score was significantly lower in IEI patients than in HC (p<0.01) and significantly higher than in CF patients (p<0.01). LCI and FEV1z-score correlated moderately negatively in the total cohort, the IEI group and the CF group. Nineteen (20.7%) of 92 IEI patients and 35 (33.3%) of 105 CF patients had an elevated LCI but a normal FEV1z-score. After a median of 364 days, the median LCI of 70 IEI patients increased significantly by 0.2.ConclusionMBW is useful to detect lung disease in IEI and is more sensitive than spirometry.
Factors associated to the presence of headache in patients with influenza infection and its consequences: a 2010–2020 surveillance-based study
Authors: García-Azorín David , Santana-López Laura , Lozano-Alonso José Eugenio , Ordax-Díez Ana , Vega-Alonso Tomas , Macias Saint-Gerons Diego , González-Osorio Yésica , Rojo-Rello Silvia , Eiros José M. , Sánchez-Martínez Javier , Sierra-Mencía Álvaro , Recio-García Andrea , Martín-Toribio Alejandro , Sanz-Muñoz Ivan , Guerrero-Peral Ángel Luis 
Published: February 2024

AbstractHeadache is a common symptom of influenza infection; however, its causes and consequences remain uncertain. In this manuscript, we analyzed which demographic and clinical factors were associated with the presence of headache during the course of influenza infection and whether patients with headache had a different prognosis, evaluated by need of hospitalization, sick leave or school absenteeism. The influence study (NCT05704335) was an observational study that analyzed data routinely collected from the Health Sentinel Network between 2010 and 2020. During the study period, 7832 cases were considered, among which, 5275 (67.4%) reported headache. The presence of headache was independently associated with myalgia (2.753; 95%CI: 2.456–3.087, P < 0.001), asthenia (OR: 1.958; 95%CI: 1.732–2.214, P < 0.001), shivering (OR: 1.925; 95%CI: 1.718–2.156, P < 0.001), nasopharyngeal erythema (OR: 1.505; 95%CI: 1.293–1.753, P < 0.001), fever (OR: 1.469; 95%CI: 1.159–1.861; P = 0.001), sudden onset of symptoms (OR: 1.380; 95%CI: 1.120–1.702, p = 0.004), female sex (OR: 1.134; 95%CI: 1.023–1.257, P = 0.018), and gastrointestinal symptoms (OR: 1.169; 95%CI: 1.039–1.315; P = 0.01). Patients with headache had a sex and age adjusted lower odds of being referred to the hospital (OR: 0.463; 95%CI: 0.264–0.812, P = 0.007) and a higher odd of having a sick leave and/or school absenteeism (absenteeism (OR: 1.342; 95%CI: 1.190–1.514, P < 0.001). In conclusion, the presence of headache seems associated with symptoms caused by the innate immune response. These findings support a headache pathophysiology linked with the innate immune response. Due to the potential negative consequences and its treatable nature, clinicians should systematically evaluate it and, whenever necessary, treat it too.
Investigation of mitochondria-dependent apoptosis pathway and lipid peroxidation level induced by biosynthesized silver nanoparticles: caspase-3 activation, BAK1/BCLx regulation and malondialdehyde production
Authors: Xiong Haiwei , Nie Xiaoyan , Cao Wei , Zhu Jia , Chen Jian , Liu Ruihao , Li Yingliang 
Published: February 2024

AbstractNowadays, silver nanoparticles (AgNPs) have attracted the attention of many researchers due to their special physical, chemical, and biological properties. There is strong evidence that biogenic AgNPs can act as potent anticancer agents through the production of reactive oxygen species (ROS) and initiate the mitochondrial pathway of apoptosis. That is why we decided to use Nepeta bracteata Benth flower extract for the first time to bio-synthesize AgNPs and study their cytotoxic and apoptotic effects on SK-BR-3 cells. AgNPs were biosynthesized at 70 °C after mixing silver nitrate and flower extract with a specific ratio and concentration, then were characterized using various analytical techniques, such as FESEM, FTIR, EDS, and zeta potential. Studies have shown that AgNPs have an irregular and circular shape, with about 99% by weight of silver, carbon, and oxygen. On the other hand, the appropriate size (below 57 nm) and surface charge (− 11.52 mV) make them stable in biological fluids. The better cytotoxic effect of AgNPs compared to flower extract on SK-BR-3 cells was investigated using the MTT method. The positive effect of AgNPs on inhibiting the growth of SK-BR-3 breast cancer cells was again confirmed by the sulforhodamine B staining method, so that AgNPs were able to decrease the density of cancer cells in a concentration-dependent manner. In addition, the flow cytometry test proved that biosynthesized AgNPs using Nepeta bracteata Benth flower extract can induce apoptosis in SK-BR-3 cancer cells. Real-time PCR then proved that the ratio of Bak1/Bclx, as well as caspase-3 expression, was increased due to active ROS-producing biomolecules present in the plant extract, and therefore, AgNPs can activate the mitochondria-dependent apoptosis pathway in breast cancer cells. Finally, their negligible oxidative stress on erythrocytes was confirmed by the lipid peroxidation method and showed that biosynthesized AgNPs can be used for breast cancer treatment without showing adverse effects on erythrocytes.
Sex-biased genetic regulation of inflammatory proteins in the Dutch population
Authors: Boahen Collins K. , Abee Hannah , Ponce Isis Ricaño , Joosten Leo A. B. , Netea Mihai G. , Kumar Vinod 
Published: February 2024

Abstract
Background
Significant differences in immune responses, prevalence or susceptibility of diseases and treatment responses have been described between males and females. Despite this, sex-differentiation analysis of the genetic architecture of inflammatory proteins is largely unexplored. We performed sex-stratified meta-analysis after protein quantitative trait loci (pQTL) mapping using inflammatory biomarkers profiled using targeted proteomics (Olink inflammatory panel) of two population-based cohorts of Europeans.

Results
Even though, around 67% of the pQTLs demonstrated shared effect between sexes, colocalization analysis identified two loci in the males (LINC01135 and ITGAV) and three loci (CNOT10, SRD5A2, and LILRB5) in the females with evidence of sex-dependent modulation by pQTL variants. Furthermore, we identified pathways with relevant functions in the sex-biased pQTL variants. We also showed through cross-validation that the sex-specific pQTLs are linked with sex-specific phenotypic traits.

Conclusion
Our study demonstrates the relevance of genetic sex-stratified analysis in the context of genetic dissection of protein abundances among individuals and reveals that, sex-specific pQTLs might mediate sex-linked phenotypes. Identification of sex-specific pQTLs associated with sex-biased diseases can help realize the promise of individualized treatment.
Estimating cutoff values for diagnostic tests to achieve target specificity using extreme value theory
Authors: Pugh Sierra , Fosdick Bailey K. , Nehring Mary , Gallichotte Emily N. , VandeWoude Sue , Wilson Ander 
Published: February 2024

AbstractBackgroundRapidly developing tests for emerging diseases is critical for early disease monitoring. In the early stages of an epidemic, when low prevalences are expected, high specificity tests are desired to avoid numerous false positives. Selecting a cutoff to classify positive and negative test results that has the desired operating characteristics, such as specificity, is challenging for new tests because of limited validation data with known disease status. While there is ample statistical literature on estimating quantiles of a distribution, there is limited evidence on estimating extreme quantiles from limited validation data and the resulting test characteristics in the disease testing context.MethodsWe propose using extreme value theory to select a cutoff with predetermined specificity by fitting a Pareto distribution to the upper tail of the negative controls. We compared this method to five previously proposed cutoff selection methods in a data analysis and simulation study. We analyzed COVID-19 enzyme linked immunosorbent assay antibody test results from long-term care facilities and skilled nursing staff in Colorado between May and December of 2020.ResultsWe found the extreme value approach had minimal bias when targeting a specificity of 0.995. Using the empirical quantile of the negative controls performed well when targeting a specificity of 0.95. The higher target specificity is preferred for overall test accuracy when prevalence is low, whereas the lower target specificity is preferred when prevalence is higher and resulted in less variable prevalence estimation.DiscussionWhile commonly used, the normal based methods showed considerable bias compared to the empirical and extreme value theory-based methods.ConclusionsWhen determining disease testing cutoffs from small training data samples, we recommend using the extreme value based-methods when targeting a high specificity and the empirical quantile when targeting a lower specificity.
Efficacy of endoscopic submucosal resection with a ligation device for small rectal neuroendocrine tumor: study protocol of a multicenter open-label randomized control trial (BANDIT trial)
Authors: Takada Kazunori , Imai Kenichiro , Yamada Takanori , Ohata Ken , Kanesaka Takashi , Nagami Yasuaki , Yamasaki Yasushi , Kobara Hideki , Inokuchi Yasuhiro , Chino Akiko , Yamaguchi Shinjiro , Ikehara Hisatomo , Kawamura Takuji , Yabuuchi Yohei , Mizuguchi Yasuhiko , Ikematsu Hiroaki , Yokoi Chizu , Hattori Santa , Ohno Kazuya , Yoshizawa Yashiro , Fukuzawa Masakatsu , Tsuji Yosuke , Konishi Jun , Yamamura Takeshi , Osawa Satoshi , Oka Shiro , Hikichi Takuto , Togashi Kazutomo , Hirasawa Kingo , Uraoka Toshio , Takeuchi Yoji , Chiba Hideyuki , Komeda Yoriaki , Doyama Hisashi , Oba Mari S. , Saito Yutaka 
Published: February 2024

Abstract
Background
Endoscopic resection is widely accepted as a local treatment for rectal neuroendocrine tumors sized ≤ 10 mm. However, there is no consensus on the best method for the endoscopic resection of rectal neuroendocrine tumors. As a simplified endoscopic procedure, endoscopic submucosal resection with a ligation device (ESMR-L) indicates a histologically complete resection rate comparable to that of endoscopic submucosal dissection (ESD). We hypothesized that ESMR-L than ESD would be preferred for rectal neuroendocrine tumors. Hence, this trial aimed to verify whether ESMR-L is non-inferior to ESD in terms of histologically complete resection rate.

Methods
This is a prospective, open-label, multicenter, non-inferiority, randomized controlled trial of two parallel groups, conducted at the Shizuoka Cancer Center and 31 other institutions in Japan. Patients with a lesion endoscopically diagnosed as a rectal neuroendocrine tumor ≤ 10 mm are eligible for inclusion. A total of 266 patients will be recruited and randomized to undergo either ESD or ESMR-L. The primary endpoint is the rate of en bloc resection with histologically tumor-free margins (R0 resection). Secondary endpoints include en bloc resection rate, procedure time, adverse events, hospitalization days, total devices and agents cost, adverse event rate between groups with and without resection site closure, outcomes between expert and non-expert endoscopists, and factors associated with R0 resection failure. The sample size is determined based on the assumption that the R0 resection rate will be 95.2% in the ESD group and 95.3% in the ESMR-L group, with a non-inferiority margin of 8%. With a one-sided significance level of 0.05 and a power of 80%, 226 participants are required. Assuming a dropout rate of 15%, 266 patients will be included in this study.

Discussion
This is the first multicenter randomized controlled trial comparing ESD and ESMR-L for the R0 resection of rectal neuroendocrine tumors ≤ 10 mm. This will provide valuable information for standardizing endoscopic resection methods for rectal neuroendocrine tumors.

Trial registration
Japan Registry of Clinical Trials, jRCTs042210124. Registered on Jan 6, 2022.