bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of sequential (first- to third-generation) EGFR-TKI treatment on corrected QT interval in NSCLC patients
Authors: Gan Tian , Chen Jindong , Wang Hao , Shang Conghui , Xi Siqi , Fan Zixu , He Ben , Zhang Min , Zhao Liang 
Published: May 2024

ObjectiveTo evaluate the impact of sequential (first- to third-generation) epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment on top-corrected QT interval (top-QTc) in non-small cell lung cancer (NSCLC) patients.MethodsWe retrospectively reviewed the medical records of NSCLC patients undergoing sequential EGFR-TKI treatment at Shanghai Chest Hospital between October 2016 and August 2021. The heart rate (HR), top-QT interval, and top-QTc of their ECGs were extracted from the institutional database and analyzed. Logistic regression was performed to identify predictors for top-QTc prolongation.ResultsOverall, 228 patients were enrolled. Compared with baseline (median, 368 ms, same below), both first-generation (376 ms vs. 368 ms, p &lt; 0.001) and sequential third-generation EGFR-TKIs (376 ms vs. 368 ms, p = 0.002) prolonged top-QT interval to a similar extent (p = 0.635). Top-QTc (438 ms vs. 423 ms, p &lt; 0.001) and HR (81 bpm vs.79 bpm, p = 0.008) increased after first-generation EGFR-TKI treatment. Further top-QTc prolongation (453 ms vs. 438 ms, p &lt; 0.001) and HR increase (88 bpm vs. 81 bpm, p &lt; 0.001) occurred after treatment advanced. Notably, as HR elevated during treatment, top-QT interval paradoxically increased rather than decreased, and the top-QTc increased rather than slightly fluctuated. Moreover, such phenomena were more significant after treatment advanced. After adjusting for confounding factors, pericardial effusion and lower serum potassium levels were independent predictors of additional QTc prolongation during sequential third-generation EGFR-TKI treatment.ConclusionFirst-generation EGFR-TKI could prolong top-QTc, and sequential third-generation EGFR-TKI induced further prolongation. Top-QT interval paradoxically increased and top-QTc significantly increased as HR elevated, which was more significant after sequential EGFR-TKI treatment. Pericardial effusion and lower serum potassium levels were independent predictors of additional QTc prolongation after sequential EGFR-TKI treatment.
The comparison of contrast-enhanced ultrasound and gadoxetate disodium-enhanced MRI LI-RADS for nodules ≤2 cm in patients at high risk for HCC: a prospective study
Authors: Qin Zhengyi , Zhou Yan , Zhang Xiang , Ding Jianmin , Zhou Hongyu , Wang Yandong , Zhao Lin , Chen Chen , Jing Xiang 
Published: May 2024

ObjectivesTo investigate the consistency of LI-RADS of CEUS and EOB-MRI in the categorization of liver nodules ≤2cm in patients at high risk for HCC.MethodsPatients at high risk for HCC with nodules ≤2cm who underwent CEUS and EOB-MRI in our hospital were prospectively enrolled. The CEUS images and EOB-MRI imaging of each liver nodule were observed to evaluate inter-observer consistency and category according to CEUS LI-RADS V2017 and CT/MRI LI-RADS V2017 criteria double blinded. Pathology and/or follow-up were used as reference standard.ResultsA total of 127 nodules in 119 patients met the inclusion criteria. The inter-observer agreement was good on CEUS and EOB-MRI LI-RADS (kappa = 0.76, 0.76 p &lt; 0.001). The inter-modality agreement was fair (kappa=0.21, p &lt; 0.001). There was no statistical difference in PPV and specificity between CEUS and EOB-MRI LR-5 for HCC, while the difference in AUC was statistically significant. We used new criteria (CEUS LR-5 and EOB-MRI LR-4/5 or CEUS LR-4/5 and EOB-MRI LR-5) to diagnose HCC. The sensitivity, specificity, and AUC of this criteria was 63.4%, 95.6%, and 0.80.ConclusionsCEUS and EOB-MRI showed fair inter-modality agreement in LI-RADS categorization of nodules ≤2 cm. The inter-observer agreement of CEUS and EOB-MRI LI-RADS were substantial. CEUS and EOB-MRI LR-5 have equally good positive predictive value and specificity for HCC ≤ 2cm, and combining these two modalities may better diagnose HCC ≤ 2 cm.Clinical Trial Registrationhttps://clinicaltrials.gov/, identifier NCT04212286.
Case report: Treatment with Phesgo® in a patient receiving hemodialysis
Authors: Pulido Catarina , Albuquerque Joana , Correia Jorge , Passos-Coelho José Luís 
Published: May 2024

IntroductionPatients with metastatic HER2-positive breast cancer have multiple therapeutic options. However, most are not studied in the renal replacement therapy (RRT) setting.Case reportWe report the use of Phesgo® (subcutaneous fixed-dose combination of trastuzumab and pertuzumab) combined with exemestane as a first-line treatment of metastatic HER2-positive breast cancer in a hemodialysis patient with multiple comorbidities. Partial response was attained, with disease progression after 8 months without evidence of significant toxicity.DiscussionsThis case report is, to our knowledge, the first published case documenting the use of Phesgo® in a hemodialysis patient. No new safety signs were seen, and activity was documented, adding support to the use of this drug combination in such a patient population.
The impact of time between surgery and adjuvant chemoradiotherapy in advanced oral cavity squamous cell carcinoma
Authors: Mrosk Friedrich , Absah Majd , Richter Maximilian , Sprünken Erin , Doll Christian , Kreutzer Kilian , Rendenbach Carsten , Beck Marcus , Klinghammer Konrad , Heiland Max , Koerdt Steffen 
Published: May 2024

ObjectiveIn advanced oral squamous cell carcinoma (OSCC), adjuvant therapy (AT) is an important part of the treatment to ensure extended locoregional control after primary surgical resection. The impact of the time interval between surgery and AT on the oncological prognosis remains unclear, particularly in high-risk constellations. The aim of this study is to categorize treatment delays and to determine their impact on the oncological prognosis within the context of the histopathological risk parameters of patients with advanced OSCC.MethodsIn this single-institutional retrospective cohort study, all patients treated for OSCC between 2016 and 2021 and who received postoperative chemoradiation (POCRT) were included. Patients were divided into two groups: Group I: ≤ 6 weeks between surgery and POCRT; and Group II: &gt; 6 weeks between surgery and POCRT.ResultsOverall, 202 patients were included (Group I: 156 (77.2%) vs. Group II: 46 (22.8%)). There were no statistically significant differences in epidemiological aspects and histopathological risk factors between the two groups. The maximum time to initiation of POCRT was 11 weeks. Delayed POCRT initiation had no statistically significant influence on the 5-year OS (61.6% vs. 57.3%, p = 0.89), locoregional control rate (38.6% vs. 43.3%, p = 0.57), and RFS (32.3% vs. 30.4%, p = 0.21). On multivariate analysis, extracapsular spread (HR: 2.21, 95% CI: 1.21 – 4.04, p = 0.01) and incomplete surgical resection (HR: 2.01, 95% CI: 1.10 – 3.69, p = 0.02) were significantly correlated with OS. For RFS, ECS (HR: 1.82, 95% CI: 1.15 – 2.86, p = 0.01), incomplete resection (HR: 1.67, 95% CI: 1.04 – 2.71, p = 0.04), and vascular infiltration of the tumor (V-stage; HR: 2.15, 95% CI: 1.08 – 4.27, p = 0.03) were significant risk predictors.ConclusionDelays in POCRT initiation up to 11 weeks after surgical resection for advanced OSCC were not statistically significantly associated with impaired survival. In cases of prolonged surgical treatment due to management of complications, a small delay in AT beyond the recommended time limit may be justified and AT should still be pursued.
The long-term negative impact of childhood stroke on language
Authors: Heimgärtner Magdalena , Gschaidmeier Alisa , Schnaufer Lukas , Staudt Martin , Wilke Marko , Lidzba Karen 
Published: May 2024

ObjectivesThis study aims to investigate the long-term language outcome in children with unilateral childhood stroke in comparison to those with perinatal strokes and typically developing individuals and to explore the impact of lesion-specific modifiers.MethodsWe examined nine patients with childhood stroke, acquired between 0;2 and 16;1 years (CHILD; 3 female, median = 13.5 years, 6 left-sided), 23 patients with perinatal strokes (PERI; 11 female, median = 12.5 years, 16 left-sided), and 33 age-matched typically developing individuals (CONTROL; 15 female, median = 12.33 years). The language outcome was assessed using age-appropriate tasks of the Potsdam Illinois Test of Psycholinguistic Abilities (P-ITPA) or the Peabody Picture Vocabulary Test (PPVT). For group comparisons, study-specific language z-scores were calculated. Non-verbal intelligence was assessed using the Test of Non-verbal Intelligence (TONI-4), language lateralization with functional MRI, and lesion size with MRI-based volumetry.ResultsAll four patients with childhood stroke who initially presented with aphasic symptoms recovered from aphasia. Patients with childhood stroke showed significantly lower language scores than those in the control group, but their scores were similar to those of the patients with perinatal stroke, after adjusting for general intelligence (ANCOVA, language z-score CHILD = −0.30, PERI = −0.38, CONTROL = 0.42). Among the patients with childhood stroke, none of the possible modifying factors, including lesion side, correlated significantly with the language outcome.ConclusionChildhood stroke, regardless of the affected hemisphere, can lead to chronic language deficits, even though affected children show a “full recovery.” The rehabilitation of children and adolescents with childhood stroke should address language abilities, even after the usually quick resolution of clear aphasic symptoms.
Inadequate weight gain and factors influencing it among preterm neonates in neonatal intensive care units in the Amhara region, Ethiopia, in 2022
Authors: Semanew Yaregal , Tesfaye Eleny , Tesgera Debrework 
Published: May 2024

BackgroundAdequate weight gain is crucial for the health and development of preterm neonates admitted to neonatal intensive care units (NICUs). Understanding the factors influencing weight gain in this vulnerable population is essential for improving outcomes. This study aimed to assess the weight gain status and associated factors among preterm neonates admitted to NICUs in specialized hospitals in the Amhara region of Ethiopia.MethodsA cross-sectional study design involving 363 preterm neonates admitted to NICUs in specialized hospitals within the Amhara region was used. Data were collected using structured questionnaires and the Kobo Tool Box. Daily weight measurements were recorded for three consecutive days. Descriptive statistics, logistic regression analysis, and graphical presentations were utilized for data analysis and presentation.ResultsThe study revealed that a significant proportion (80.8%) of preterm neonates experienced poor weight gain during their NICU stay. The factors significantly associated with poor weight gain were older maternal age, delayed initiation of enteral feeding, lack of kangaroo mother care (KMC), and inadequate antenatal care visits.ConclusionAddressing the identified factors, such as providing adequate support during the antenatal period, promoting a timely initiation of enteral feeding, and encouraging KMC practices, is crucial for improving weight gain outcomes in preterm neonates. The findings highlight the importance of a comprehensive approach to neonatal care targeting both maternal and neonatal factors. Policymakers and healthcare providers should prioritize interventions aimed at optimizing weight gain in preterm neonates to improve these neonates’ overall well-being and long-term outcomes.
The coupling coordination between health service supply and regional economy in China: spatio-temporal evolution and convergence
Authors: Deng Jing , Song Qianwen , Liu Huan , Jiang Zicheng , Ge Chengzhi , Li Dexun 
Published: May 2024

BackgroundThe coordination of health service supply and regional economy is an integral path to promote China’s prosperity.MethodsBased on the coupling mechanism of health service supply and regional economy, we sampled the data from 30 provinces in China from 2009 to 2021 in this study and constructed the evaluation index system. Additionally, we calculated the coupling coordination degree (HED) of the two through the coupling coordination degree model. We further used the kernel density estimation, Moran’s I index, and spatial β convergence model to assess the dynamic evolution trends, spatial aggregation effect, and spatial convergence characteristics of coupling coordination.Conclusion(1) HED in China showed a rising trend during the study period but with large regional differences, forming a gradient distribution pattern of “high in the east and low in the west.” (2) The results of Kernel density estimation show that HED has formed a gradient differentiation phenomenon within each region in China. (3) HED has modeled spatial clustering characteristics during the study period, with high-value clusters mainly appearing in the eastern region and low-value clusters appearing in the northwestern region. (4) There are absolute β-convergence and conditional β-convergence trends in HED in China and the three major regions during the study period, but there is an obvious regional heterogeneity in the control factors. The research provides a reference for accurately implementing policies according to different levels of health service supply and economic development, in addition to narrowing the regional differences of the coupling coordination between the regional economy and health service supply.
Priorities for contraceptive method and service delivery attributes among adolescent girls and young women in Kenya: a qualitative study
Authors: Harrington Elizabeth K. , Hauber Brett , Ouma Dismas Congo , Kimanthi Syovata , Dollah Annabell , Onono Maricianah , Bukusi Elizabeth A. 
Published: May 2024

IntroductionDespite increasing global commitment to meeting the family planning needs of adolescent girls and young women (AGYW), there is limited research on how they prioritize contraceptive method and service delivery characteristics. In this qualitative study, we examine the specific elements that drive the contraceptive choices of Kenyan AGYW, and apply our findings to the development of attributes and levels for a discrete choice experiment (DCE).MethodsOur four-stage approach included data collection, data reduction, removing inappropriate attributes, and optimizing wording. Between June-October 2021, we conducted in-depth interviews with 30 sexually-active 15–24 year-old AGYW in Kisumu county, Kenya who were non-pregnant and desired to delay pregnancy. Interviews focused on priorities for contraceptive attributes, how AGYW make trade-offs between among these attributes, and the influences of preferences on contraceptive choice. Translated transcripts were qualitatively coded and analyzed with a constant comparative approach to identify key concepts. We developed and iteratively revised a list of attributes and levels, and pre-tested draft DCE choice tasks using cognitive interviews with an additional 15 AGYW to optimize comprehension and relevance.ResultsIn-depth interview participants' median age was 18, 70% were current students, and 93% had a primary sexual partner. AGYW named a variety of priorities and preferences related to choosing and accessing contraceptive methods, which we distilled into six key themes: side effects; effectiveness; user control; privacy; source of services; and cost. Bleeding pattern was top of mind for participants; amenorrhea was generally considered an intolerable side effect. Many participants felt more strongly about privacy than effectiveness, though some prioritized duration of use and minimizing chance of pregnancy above other contraceptive characteristics. Most AGYW preferred a clinic setting for access, as they desired contraceptive counseling from a provider, but pharmacies were considered preferable for reasons of privacy. We selected, refined, and pre-tested 7 DCE attributes, each with 2–4 levels.ConclusionsIdentifying AGYW preferences for contraceptive method and service delivery characteristics is essential to developing innovative strategies to meet their unique SRH needs. DCE methods may provide valuable quantitative perspectives to guide and tailor contraceptive counseling and service delivery interventions for AGYW who want to use contraception.
INSCYD physiological performance software is valid to determine the maximal lactate steady state in male and female cyclists
Authors: Poffé Chiel , Van Dael Kaat , Van Schuylenbergh Reinout 
Published: May 2024

IntroductionThe maximal lactate steady state (MLSS) is defined as the highest workload that can be maintained without blood lactate accumulation over time. The power output at MLSS (PMLSS) is regularly implemented to define training zones, quantify training progress, or predict race performance. The gold standard methodology for MLSS determination requires two to five trials of constant-load exercise, which limits the practical application in training. The INSCYD software can calculate the PMLSS (PMLSSINSCYD) based on physiological data that can be obtained during a ∼1 h laboratory visit. However, to the best of our knowledge, the validity of the most recent software version has not yet been investigated. This study aimed to assess the validity of the software's calculations on PMLSS in cycling.MethodsThe data for this study were retrieved from two published scientific sources. Thirty-one cyclists (19 males, 12 females) performed a 15 s sprint to estimate the VLamax, a ramp test for the V˙O2max assessment, and two to five constant-load tests to determine the PMLSS. The INSCYD software was used to calculate the PMLSS based on the V˙O2max, VLamax, sex, body mass, and body composition.ResultsThe PMLSSINSCYD was higher than the PMLSS in the entire sample (mean difference: 4.6 W, p &lt; 0.05, 95% CI 0.8–8.3 W) and in men (mean difference: 6.6 W, p &lt; 0.05, 95% CI 1.3–11.8 W), but not in women (mean difference: 0.8 W, n.s., 95% CI −3.7 to 5.3 W), which was within the typical error of the PMLSS estimations (∼3%). In 12 subjects (nine males, three females), the PMLSSINSCYD differed by 3.1–7.3% compared to the MLSS. The Pearson correlations between the measured PMLSS and the calculated PMLSS (PMLSSINSCYD) were very strong in men (r = 0.974, p &lt; 0.001, 95% CI 0.933–0.99), women (r = 0.984, p &lt; 0.001, 95% CI 0.931–0.996), and for the entire sample (r = 0.992, p &lt; 0.001, 95% CI 0.982–0.996).DiscussionIn conclusion, the PMLSS can be accurately calculated using the INSCYD software, but it still requires advanced testing equipment to collect valid V˙O2max and VLamax data.
RSV infection of humanized lung-only mice induces pathological changes resembling severe bronchiolitis and bronchopneumonia
Authors: De Chandrav , Pickles Raymond J. , Yao Wenbo , Liao Baolin , Boone Allison , Cleary Rachel A. , Garcia J. Victor , Wahl Angela 
Published: May 2024

Respiratory syncytial virus (RSV) is a substantial cause of severe lower respiratory tract infections in infants, young children, older adults, and immunocompromised individuals. There is a vital need for effective therapeutics to prevent and/or treat severe RSV infection in these high-risk individuals. The development and pre-clinical testing of candidate RSV therapeutics could be accelerated by their evaluation in animal models that recapitulate bronchiolitis and bronchopneumonia, both hallmark features of severe RSV infection in humans. Previously, we demonstrated that implanted human lung tissue in humanized lung-only mice (LoM) can be infected with RSV, resulting in sustained virus replication. Here we analyzed RSV-associated human lung pathology in the human lung implants of RSV-infected LoM. RSV-infected epithelial cells lining the airway and the alveolar regions of human lung implants result in hallmark histological features of RSV bronchiolitis and bronchopneumonia, including distal airway and alveolar lumens clogged with (1) sloughed and necrotic RSV-infected epithelial cells, (2) neutrophil-containing inflammatory infiltrates, and (3) MUC5B-dominated mucus secretions. We also show that treatment of LoM with a small molecule antiviral (ribavirin) or a neutralizing antibody (palivizumab) significantly suppressed and/or prevented RSV infection in vivo. Our data together show that RSV infection of human lung implants in vivo exhibits appropriate cellular tropism and results in the hallmark pathological characteristics of severe bronchiolitis and bronchopneumonia in humans. They also offer proof-of-principle of the utility of this model to evaluate novel approaches for the prevention/treatment of RSV infection.
Genetic Analysis of the ts-Lethal Mutant Δpa0665/pTS-pa0665 Reveals Its Role in Cell Morphology and Oxidative Phosphorylation in Pseudomonas aeruginosa
Authors: Zhu Jiayin , Zhao Hulin , Yang Zhili 
Published: May 2024

Pa0665 in Pseudomonas aeruginosa shares homologous sequences with that of the essential A-type iron–sulfur (Fe-S) cluster insertion protein ErpA in Escherichia coli. However, its essentiality in P. aeruginosa and its complementation with E. coli erpA has not been experimentally examined. To fulfill this task, we constructed plasmid-based ts-mutant Δpa0665/pTS-pa0665 using a three-step protocol. The mutant displayed growth defects at 42 °C, which were complemented by expressing ec.erpA. Microscopic observations indicated a petite cell phenotype for Δpa0665/pTS-pa0665 at 42 °C, correlated with the downregulation of the oprG gene. RNA sequencing revealed significant transcriptional changes in genes associated with the oxidative phosphorylation (OXPHOS) system, aligning with reduced ATP levels in Δpa0665/pTS-pa0665 under 42 °C. Additionally, the ts-mutant showed heightened sensitivity to H2O2 at 42 °C. Overall, our study demonstrates the essential role of pa0665 for OXPHOS function and is complemented by ec.erpA. We propose that the plasmid-based ts-allele is useful for genetic analysis of essential genes of interest in P. aeruginosa.