bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced Deep-Inspiration Breath Hold Superior to High-Frequency Percussive Ventilation for Respiratory Motion Mitigation: A Physiology-Driven, MRI-Guided Assessment Toward Optimized Lung Cancer Treatment With Proton Therapy
Authors: Emert Frank , Missimer John , Eichenberger Philipp A. , Walser Marc , Gmür Celina , Lomax Antony J. , Weber Damien C. , Spengler Christina M. 
Published: April 2021

Background: To safely treat lung tumors using particle radiation therapy (PRT), motion-mitigation strategies are of critical importance to ensure precise irradiation. Therefore, we compared applicability, effectiveness, reproducibility, and subjects' acceptance of enhanced deep-inspiration breath hold (eDIBH) with high-frequency percussive ventilation (HFPV) by MRI assessment within 1 month.Methods: Twenty-one healthy subjects (12 males/9 females; age: 49.5 ± 5.8 years; BMI: 24.7 ± 3.3 kg/m−2) performed two 1.5 T MRI scans in four visits at weekly intervals under eDIBH and HFPV conditions, accompanied by daily, home-based breath-hold training and spirometric assessments over a 3-week period. eDIBH consisted of 8-min 100% O2 breathing (3 min resting ventilation, 5 min controlled hyperventilation) prior to breath hold. HFPV was set at 200–250 pulses min−1 and 0.8–1.2 bar. Subjects' acceptance and preference were evaluated by questionnaire. To quantify inter- and intrafractional changes, a lung distance metric representing lung topography was computed for 10 reference points: a motion-invariant spinal cord and nine lung structure contours (LSCs: apex, carina, diaphragm, and six vessels as tumor surrogates distributed equally across the lung). To parameterize individual LSC localizability, measures of their spatial variabilities were introduced and lung volumes calculated by automated MRI analysis.Results: eDIBH increased breath-hold duration by &gt; 100% up to 173 ± 73 s at visit 1, and to 217 ± 67 s after 3 weeks of home-based training at visit 4 (p &lt; 0.001). Measures of vital capacity and lung volume remained constant over the 3-week period. Two vessels in the lower lung segment and the diaphragm yielded a two- to threefold improved positional stability with eDIBH, whereby absolute distance variability was significantly smaller for five LSCs; ≥70% of subjects showed significantly better intrafractional lung motion mitigation under reproducible conditions with eDIBH compared with HFPV with smaller ranges most apparent in the anterior-posterior and cranial-caudal directions. Approximately 80% of subjects preferred eDIBH over HFPV, with “less discomfort” named as most frequent reason.Conclusions: Both, eDIBH, and HFPV were well-tolerated. eDIBH duration was long enough to allow for potential PRT. Variability in lung volume was smaller and position of lung structures more precise with eDIBH. Subjects preferred eDIBH over HFPV. Thus, eDIBH is a very promising tool for lung tumor therapy with PRT, and further investigation of its applicability in patients is warranted.
Ultrasound-Based Radiomics Analysis for Predicting Disease-Free Survival of Invasive Breast Cancer
Authors: Xiong Lang , Chen Haolin , Tang Xiaofeng , Chen Biyun , Jiang Xinhua , Liu Lizhi , Feng Yanqiu , Liu Longzhong , Li Li 
Published: April 2021

BackgroundAccurate prediction of recurrence is crucial for personalized treatment in breast cancer, and whether the radiomics features of ultrasound (US) could be used to predict recurrence of breast cancer is still uncertain. Here, we developed a radiomics signature based on preoperative US to predict disease-free survival (DFS) in patients with invasive breast cancer and assess its additional value to the clinicopathological predictors for individualized DFS prediction.MethodsWe identified 620 patients with invasive breast cancer and randomly divided them into the training (n = 372) and validation (n = 248) cohorts. A radiomics signature was constructed using least absolute shrinkage and selection operator (LASSO) Cox regression in the training cohort and validated in the validation cohort. Univariate and multivariate Cox proportional hazards model and Kaplan–Meier survival analysis were used to determine the association of the radiomics signature and clinicopathological variables with DFS. To evaluate the additional value of the radiomics signature for DFS prediction, a radiomics nomogram combining the radiomics signature and clinicopathological predictors was constructed and assessed in terms of discrimination, calibration, reclassification, and clinical usefulness.ResultsThe radiomics signature was significantly associated with DFS, independent of the clinicopathological predictors. The radiomics nomogram performed better than the clinicopathological nomogram (C-index, 0.796 vs. 0.761) and provided better calibration and positive net reclassification improvement (0.147, P = 0.035) in the validation cohort. Decision curve analysis also demonstrated that the radiomics nomogram was clinically useful.ConclusionUS radiomics signature is a potential imaging biomarker for risk stratification of DFS in invasive breast cancer, and US-based radiomics nomogram improved accuracy of DFS prediction.
The Potential of MET Immunoreactivity for Prediction of Lymph Node Metastasis in Early Oral Tongue Squamous Cell Carcinoma
Authors: De Herdt Maria J. , van der Steen Berdine , van der Toom Quincy M. , Aaboubout Yassine , Willems Stefan M. , Wieringa Marjan H. , Baatenburg de Jong Robert J. , Looijenga Leendert H. J. , Koljenović Senada , Hardillo Jose A. 
Published: April 2021

ObjectiveMET positivity is independently associated with survival in oral squamous cell carcinoma (OSCC). Since MET is a known orchestrator of invasive tumor growth, we investigated its association with LNM in early oral tongue squamous cell carcinoma (OTSCC). As it is recommended by the NCCN to use tumor depth of invasion (DOI) in making decisions on elective neck dissection (END), the results obtained for MET positivity were aligned with those for DOI &gt; 4 mm. The cutoff value used in our institution.MethodsTumor samples from patients who underwent primary tumor resection and neck dissection between 1995 and 2013, were collected from the archives of the Leiden and Erasmus University Medical Center. Immunohistochemistry with D1C2 was performed to identify MET negative (&lt; 10% uniform positivity) and MET positive (≥ 10% uniform positivity) cancers. ROC curve analysis and the Chi-squared test were used to investigate the association of MET positivity with LNM (pN+ and occult). Binary logistic regression was used to investigate the association of MET positivity with LNM.ResultsForty-five (44.1%) of the 102 cancers were MET positive. Ninety were cN0 of which 20 were pN+ (occult metastasis). The remaining 12 cancers were cN+, of which 10 were proven pN+ and 2 were pN0. MET positivity was associated with LNM with a positive predictive value (PPV) of 44.4% and a negative predictive value (NPV) of 82.5% for pN+. For the occult group, the PPV was 36.8% and the NPV was 88.5%. Regression analysis showed that MET positivity is associated with pN+ and occult LNM (p-value &lt; 0.05).ConclusionMET positivity is significantly associated with LNM in early OTSCC, outperforming DOI. The added value of MET positivity could be in the preoperative setting when END is being considered during the initial surgery. For cases with DOI ≤ 4 mm, MET positivity could aid in the clinical decision whether regular follow-up, watchful waiting, or END is more appropriate. Realizing that these preliminary results need to be independently validated in a larger patient cohort, we believe that MET positivity could be of added value in the decision making on END in early OTSCC.
Para-Aortic Nodal Radiation in the Definitive Management of Node-Positive Cervical Cancer
Authors: Sanders Jason C. , Muller Donald A. , Dutta Sunil W. , Corriher Taylor J. , Ring Kari L. , Showalter Timothy N. , Romano Kara D. 
Published: April 2021

ObjectivesTo investigate the safety and outcomes of elective para-aortic (PA) nodal irradiation utilizing modern treatment techniques for patients with node positive cervical cancer.MethodsPatients with pelvic lymph node positive cervical cancer who received radiation were included. All patients received radiation therapy (RT) to either a traditional pelvic field or an extended field to electively cover the PA nodes. Factors associated with survival were identified using a Cox proportional hazards model, and toxicities between groups were compared with a chi-square test.Results96 patients were identified with a mean follow up of 40 months. The incidence of acute grade ≥ 2 toxicity was 31% in the elective PA nodal RT group and 15% in the pelvic field group (Chi-square p = 0.067. There was no significant difference in rates of grade ≥ 3 acute or late toxicities between the two groups (p&gt;0.05). The KM estimated 5-year OS was not statistically different for those receiving elective PA nodal irradiation compared to a pelvic only field, 54% vs. 73% respectively (log-rank p = 0.11).ConclusionsElective PA nodal RT can safely be delivered utilizing modern planning techniques without a significant increase in severe (grade ≥ 3) acute or late toxicities, at the cost of a possible small increase in non-severe (grade 2) acute toxicities. In this series there was no survival benefit observed with the receipt of elective PA nodal RT, however, this benefit may have been obscured by the higher risk features of this population. While prospective randomized trials utilizing a risk adapted approach to elective PA nodal coverage are the only way to fully evaluate the benefit of elective PA nodal coverage, these trials are unlikely to be performed and instead we must rely on interpretation of results of risk adapted approaches like those used in ongoing clinical trials and retrospective data.
Driver Genes Associated With the Incidence of Venous Thromboembolism in Patients With Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Qian Xiaohan , Fu Mengjiao , Zheng Jing , Zhou Jianya , Zhou Jianying 
Published: April 2021

BackgroundThe association between driver genes and the incidence of thromboembolic events (TEs) in patients diagnosed with non-small-cell lung cancer (NSCLC) needs to be quantified to guide clinical management.MethodsWe interrogated PubMed, Embase, Web of Science and Cochrane library databases for terms related to venous thromboembolism (VTE) and arterial thromboembolism (ATE) in patients diagnosed with non-small-cell lung cancer harboring driver genes. This search was conducted for studies published between 1 January, 2000 and 31 December, 2020. A random-effects meta-analysis was performed to analyze the pooled incidence and odds ratios of VTE in patients with different driver genes.ResultsOf the 2,742 citations identified, a total of 25 studies that included 21,156 patients met eligibility criteria. The overall pooled incidence of VTE in patients with driver genes was 23% (95% CI 18-29). Patients with ROS1 rearrangements had the highest incidence of VTE (37%, 95%CI 23-52). ALK rearrangements were associated with increased VTE risks (OR=2.08,95% CI 1.69-2.55), with the second highest incidence of VTE (27%, 95%CI 20-35). Both groups of patients with EGFR and KRAS mutations did not show a significantly increased risk for VTE (OR=1.33, 95% CI 0.75-2.34; OR=1.31, 95% CI 0.40-4.28).ConclusionsALK rearrangements were shown to be associated with increased VTE risks in patients diagnosed with non-small lung cancer, while there was no significant relation observed between VTE risks and EGFR or KRAS mutations in lung cancer patients.
Pre-eclampsia Complicated With Maternal Renal Dysfunction Is Associated With Poor Neurological Development at 3 Years Old in Children Born Before 34 Weeks of Gestation
Authors: Yoneda Noriko , Yoneda Satoshi , Tsuda Sayaka , Ito Mika , Shiozaki Arihiro , Niimi Hideki , Yoshida Taketoshi , Nakashima Akitoshi , Saito Shigeru 
Published: April 2021

Objective: The purpose of this study was to investigate perinatal factors associated with a poor neurodevelopmental outcome in preterm infants.Methods: A retrospective study was conducted by searching our clinical database between January 2006 and December 2016. A total of 165 singleton children who were born between 23 and 33 weeks of gestation were included. We defined poor neurological development outcomes as follows: cerebral palsy; intellectual disability; developmental disorder including autism and attention-deficit/hyperactivity disorder; low score (&lt;85 points) on Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III); or low score of Kyoto Scale of Psychological Development corrected at 3 years old. We diagnosed maternal renal dysfunction according to the Clinical Practice Guideline for chronic kidney disease 2018 and the Best Practice Guide 2015 for Care and Treatment of Hypertension in Pregnancy.Results: The rate of poor neurological development was 25/165 (15.2%): cerebral palsy (n = 1), intellectual disability (n = 1), developmental disorder (n = 2), low score of Bayley-III (n = 20), and low score of Kyoto Scale of Psychological Development (n = 1). Preeclampsia complicated with maternal renal dysfunction (P = 0.045) and delivery at &lt;30 weeks of gestation (P = 0.007) were independent risk factors for poor neurological development.Conclusions: In addition to previous risk factors such as delivery at &lt;30 weeks of gestation, preeclampsia complicated with renal dysfunction was also associated with poor neurodevelopmental outcomes corrected at 3 years old.
Polyphenols and Pharmacological Screening of a Monarda fistulosa L. dry Extract Based on a Hydrodistilled Residue By-Product
Authors: Shanaida Mariia , Hudz Nataliia , Jasicka-Misiak Izabela , Wieczorek Piotr P. 
Published: April 2021

This study aimed to determine the composition and content of polyphenols in the dry extract obtained from the hydrodistilled residue by-product of the wild bergamot (Monarda fistulosa L., Lamiaceae Martinov family) herb (MFDE) and to evaluate its safety and pharmacological properties. The total phenolic content (TPC) in the MFDE was 120.64 mg GAE/g. The high-performance liquid chromatography (HPLC) analysis showed the presence of a plethora of phenolic compounds, including hydroxycinnamic acids and flavone derivatives in the MFDE, with rosmarinic acid and luteolin-7-O-glucoside being the main components. With an IC50 value of 0.285 mg/mL, it was found to be a strong DPPH radical scavenger. The acute toxicity study results indicate that the oral administration of MFDE to rats at the doses of 500–5,000 mg/kg did not produce any side effects or death in animals which indicates its safety. The results of the in vivo assay showed that the MFDE dose-dependently inhibited paw oedema and significantly reduced the number of writings in mice induced by the acetic acid injection suggesting its potent anti-inflammatory and analgesic activities, respectively. The conducted studies revealed that M. fistulosa hydrodistilled residue by-product could be regarded as a new natural source of polyphenols with valuable pharmacological properties.
Harmonizing Formula Prescription Patterns in Patients With Chronic Kidney Disease: A Population-Based Cross-Sectional Study
Authors: Lin Hung-Lung , Lin Ming-Yen , Tsai Cheng-Hsun , Wang Yi-Hsiu , Chen Chung-Jen , Hwang Shang-Jyh , Yen Ming-Hong , Chiu Yi-Wen 
Published: April 2021

Objective: Harmonizing formulas are associated with beneficial renal outcomes in chronic kidney disease (CKD), but the therapeutic mechanisms are unclear. The study aims to explore the associations of intentions and independent factors with harmonizing formulas prescriptions for patients with CKD.Methods: We conducted a population-based cross-sectional study to explore factors associated with harmonizing formulas prescription. Patients who had been prescribed harmonizing formulas after CKD diagnosis was defined as the using harmonizing formulas group. Disease diagnoses when having harmonizing formula prescriptions and patient characteristics related to these prescriptions were collected.Results: In total, 24,971 patients were enrolled in this analysis, and 5,237 (21%) patients were prescribed harmonizing formulas after CKD diagnosis. The three most frequent systematic diseases and related health problems for which harmonizing formula prescriptions were issued in CKD were symptoms, signs, and ill-defined conditions (24.5%), diseases of the digestive system (20.67%), and diseases of the musculoskeletal system (12.9%). Higher likelihoods of harmonizing formula prescriptions were associated with young age (adjusted odds ratio: 0.98, 95% confidence interval: 0.97–0.98), female sex (1.79, 1.68–1.91), no diabetes (1.20, 1.06–1.36), no hypertension (1.38, 1.27–1.50), no cerebrovascular disease (1.34, 1.14–1.56), less disease severity (0.85, 0.83–0.88), using nonsteroidal anti-inflammatory drugs (NSAIDs) (1.65, 1.54–1.78), and using analgesic drugs other than NSAIDs (1.47, 1.35–1.59).Conclusion: Harmonizing formulas are commonly used for treating symptoms of the digestive and musculoskeletal systems in CKD cases. Further research on harmonizing formula effectiveness with regard to particular characteristics of CKD patients is warranted.
Translational Studies on Anti-Atrial Fibrillatory Action of Oseltamivir by its in vivo and in vitro Electropharmacological Analyses
Authors: Kambayashi Ryuichi , Izumi-Nakaseko Hiroko , Goto Ai , Tsurudome Kazuya , Ohshiro Hironori , Izumi Taku , Hagiwara-Nagasawa Mihoko , Chiba Koki , Nishiyama Ryota , Oyama Satomi , Nunoi Yoshio , Takei Yoshinori , Matsumoto Akio , Sugiyama Atsushi 
Published: April 2021

Oseltamivir has been shown to prolong the atrial conduction time and effective refractory period, and to suppress the onset of burst pacing-induced atrial fibrillation in vitro. To better predict its potential clinical benefit as an anti-atrial fibrillatory drug, we performed translational studies by assessing in vivo anti-atrial fibrillatory effect along with in vivo and in vitro electropharmacological analyses. Oseltamivir in intravenous doses of 3 (n = 6) and 30 mg/kg (n = 7) was administered in conscious state to the persistent atrial fibrillation model dogs to confirm its anti-atrial fibrillatory action. The model was prepared by tachypacing to the atria of chronic atrioventricular block dogs for &gt; 6 weeks. Next, oseltamivir in doses of 0.3, 3 and 30 mg/kg was intravenously administered to the halothane-anesthetized intact dogs to analyze its in vivo electrophysiological actions (n = 4). Finally, its in vitro effects of 10–1,000 μM on IK,ACh, IKur, IKr, INa and ICaL were analyzed by using cell lines stably expressing Kir3.1/3.4, KV1.5, hERG, NaV1.5 or CaV1.2, respectively (n = 3 for IK,ACh and IKr or n = 6 for IKr, INa and ICaL). Oseltamivir in doses of 3 and 30 mg/kg terminated the atrial fibrillation in 1 out of 6 and in 6 out of 7 atrial fibrillation model dogs, respectively without inducing any lethal ventricular arrhythmia. Its 3 and 30 mg/kg delayed inter-atrial conduction in a frequency-dependent manner, whereas they prolonged atrial effective refractory period in a reverse frequency-dependent manner in the intact dogs. The current assay indicated that IC50 values for IK,ACh and IKr were 160 and 231 μM, respectively, but 1,000 µM inhibited INa, ICaL and IKur by 22, 19 and 13%, respectively. The extent of INa blockade was enhanced at faster beating rate and more depolarized resting membrane potential. Oseltamivir effectively terminated the persistent atrial fibrillation, which may be largely due to the prolongation of the atrial effective refractory period and inter-atrial conduction time induced by IK,ACh and IKr inhibitions along with INa suppression. Thus, oseltamivir can exert a powerful anti-atrial fibrillatory action through its ideal multi-channel blocking property; and oseltamivir would become a promising seed compound for developing efficacious and safe anti-atrial fibrillatory drugs.
Cannabidiol and Amisulpride Improve Cognition in Acute Schizophrenia in an Explorative, Double-Blind, Active-Controlled, Randomized Clinical Trial
Authors: Leweke F. Markus , Rohleder Cathrin , Gerth Christoph W. , Hellmich Martin , Pukrop Ralf , Koethe Dagmar 
Published: April 2021

Cannabidiol (CBD), a principal phytocannabinoid constituent, has demonstrated antipsychotic properties in recent clinical trials. While it has also been suggested a promising candidate for the treatment of neurodegenerative disorders, it failed to demonstrate efficacy in cognitive impairments associated with schizophrenia as an add-on treatment (600 mg/day for 6 weeks) in 18 chronically ill patients co-treated with a variety of psychopharmacologic drugs. Here, we report on the results of parallel-group, active-controlled, mono-therapeutic, double-blind, randomized clinical trial (CBD-CT1; ClinicalTrials.gov identifier: NCT00628290) in 42 acute paranoid schizophrenic patients receiving either CBD (up to 800 mg/day) or amisulpride (AMI, up to 800 mg/day) for four weeks in an inpatient setting with neurocognition as a secondary objective. Twentynine patients (15 and 14 in the CBD and AMI group, respectively) completed two cognitive assessments at baseline and the end of the treatment period. We investigated the following cognitive domains: pattern recognition, attention, working memory, verbal and visual memory and learning, processing speed, and verbal executive functions. When applying the Bonferroni correction for multiple testing, p &lt; 0.0004 would indicate statistical significance. There was no relevant difference in neurocognitive performance between the CBD and the AMI group at baseline, and we observed no post-treatment differences between both groups. However, we observed improvements within both groups from pre-to post-treatment (standardized differences reported as Cohen’s d) in visual memory (CBD: 0.49, p = 0.015 vs. AMI: 0.63, p = 0.018) and processing speed (CBD: 0.41, p = 0.004 vs. AMI: 0.57, p = 0.023). Furthermore, CBD improved sustained attention (CBD: 0.47, p = 0.013, vs. AMI: 0.52, p = 0.085), and visuomotor coordination (CBD: 0.32, p = 0.010 vs. AMI: 0.63, p = 0.088) while AMI led to enhanced working memory performance in two different paradigms (Subject Ordered Pointing Task–AMI: 0.53, p = 0.043 vs. CBD: 0.03, p = 0.932 and Letter Number Sequencing–AMI: 0.67, p = 0.017 vs. CBD: 0.08 p = 0.755). There was no relevant correlation between changes in neurocognitive parameters and psychotic symptoms or anandamide serum levels. This study shows that both CBD and AMI improve neurocognitive functioning with comparable efficacy in young and acutely ill schizophrenia patients via an anandamide-independent mechanism.