bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutron Radiation Dose Measurements in a Scanning Proton Therapy Room: Can Parents Remain Near Their Children During Treatment?
Authors: Mares Vladimir , Farah Jad , De Saint-Hubert Marijke , Domański Szymon , Domingo Carles , Dommert Martin , Kłodowska Magdalena , Krzempek Katarzyna , Kuć Michał , Martínez-Rovira Immaculada , Michaś Edyta , Mojżeszek Natalia , Murawski Łukasz , Ploc Ondrej , Romero-Expósito Maite , Tisi Marco , Trompier François , Van Hoey Olivier , Van Ryckeghem Laurent , Wielunski Marek , Harrison Roger M. , Stolarczyk Liliana , Olko Pawel 
Published: July 2022

PurposeThis study aims to characterize the neutron radiation field inside a scanning proton therapy treatment room including the impact of different pediatric patient sizes.Materials and MethodsWorking Group 9 of the European Radiation Dosimetry Group (EURADOS) has performed a comprehensive measurement campaign to measure neutron ambient dose equivalent, H*(10), at eight different positions around 1-, 5-, and 10-year-old pediatric anthropomorphic phantoms irradiated with a simulated brain tumor treatment. Several active detector systems were used.ResultsThe neutron dose mapping within the gantry room showed that H*(10) values significantly decreased with distance and angular deviation with respect to the beam axis. A maximum value of about 19.5 µSv/Gy was measured along the beam axis at 1 m from the isocenter for a 10-year-old pediatric phantom at 270° gantry angle. A minimum value of 0.1 µSv/Gy was measured at a distance of 2.25 m perpendicular to the beam axis for a 1-year-old pediatric phantom at 140° gantry angle.The H*(10) dependence on the size of the pediatric patient was observed. At 270° gantry position, the measured neutron H*(10) values for the 10-year-old pediatric phantom were up to 20% higher than those measured for the 5-year-old and up to 410% higher than for the 1-year-old phantom, respectively.ConclusionsUsing active neutron detectors, secondary neutron mapping was performed to characterize the neutron field generated during proton therapy of pediatric patients. It is shown that the neutron ambient dose equivalent H*(10) significantly decreases with distance and angle with respect to the beam axis. It is reported that the total neutron exposure of a person staying at a position perpendicular to the beam axis at a distance greater than 2 m from the isocenter remains well below the dose limit of 1 mSv per year for the general public (recommended by the International Commission on Radiological Protection) during the entire treatment course with a target dose of up to 60 Gy. This comprehensive analysis is key for general neutron shielding issues, for example, the safe operation of anesthetic equipment. However, it also enables the evaluation of whether it is safe for parents to remain near their children during treatment to bring them comfort. Currently, radiation protection protocols prohibit the occupancy of the treatment room during beam delivery.
Sintilimab Combined with Lenvatinib for Advanced Intrahepatic Cholangiocarcinoma in Second-Line Setting—A Multi-Center Observational Study
Authors: Ding Xiaoyan , Li Guangxin , Sun Wei , Shen Yanjun , Teng Ying , Xu Yawen , Li Wendong , Liu Mei , Chen Jinglong 
Published: July 2022

BackgroundPatients with advanced intrahepatic cholangiocarcinoma (iCCA) have a poor prognosis and a substantial unmet clinical need. The study was aimed to investigate the efficacy and safety of sintilimab combined with lenvatinib for advanced iCCA in second-line setting.MethodsThe patients at multiple centers, who progressed after the first-line chemotherapy or could not tolerate chemotherapy, were treated with the combination of sintilimab plus lenvatinib. The primary endpoint was time to progression (TTP), and the secondary endpoints included tumor objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. Prognostic factors were analyzed using Cox regression analysis.ResultsA total of 41 patients with advanced iCCA were enrolled for this multi-center observational study. Under a median follow-up of 12.1 months, the median age was 59 years (range, 33–75 years). Sixteen patients died of disease progression, with a median TTP of 6.6 months (95% CI, 4.9–8.3). ORR and DCR were 46.3% and 70.3%, respectively. The patients with PD-L1 TPS ≥10% reported a significantly higher ORR compared to those with PD-L1 TPS &lt;10%, 93.8% (15/16) vs. 16.0% (4/25), p&lt;0.001. The median TTP was significantly improved in patients with PD-L1 TPS ≥10%, 16.9 months (95% CI, 7.5–26.3) vs. 4.1 months (95% CI, 1.8–6.4), p=0.001. Attaining treatment response predicts favorable TTP in a multivariate Cox model. Treatment-emergent adverse events occurred with 70.3% probability, and no treatment-related death had been reported.ConclusionThe combination of sintilimab plus lenvatinib is effective and well tolerated for advanced iCCA in the second-line setting. PD-L1 TPS expression may predict the efficacy of the combination therapy. Further investigation is warranted to investigate this combination regimen in advanced iCCA.
A “3S+f” Nephrometry Score System to Predict the Clinical Outcomes of Laparoscopic Nephron-Sparing Surgery
Authors: Zhang Shudong , Qin Zijian , Bi Hai , Tao Liyuan , Zhang Fan , Zhang Hongxian , Wang Wei , Wu Jitao , Huang Yi , Ma Lulin 
Published: July 2022

BackgroundWhen we treat renal cell carcinoma by laparoscopic nephron-sparing surgery (NSS), it is essential to use an evaluation system to predict clinical outcomes. Hitherto, there are more than a dozen nephrometry score systems. In this study, through assessing the correlations between nephrometry score systems and clinical outcomes, we aim to provide a novel nephrometry score system—the “3S+f” score system—to simplify the evaluation of technical complexity of partial nephrectomy.MethodsWe retrospectively collected the data of 131 patients who underwent NSS, which was performed by a single surgeon (SZ) from January 2013 to July 2018 at Peking University Third Hospital. The “3S+f” score system contains four parameters: “size, side, site, and fat”, all of which can be obtained from preoperative imaging data. We evaluated the correlations between the “3S+f” score and clinical outcomes, and compared R.E.N.A.L. score and PADUA score.ResultsAll the three nephrometry score systems were related to some clinical outcomes in univariate analyses. In multivariate regression models, the “3S+f” score, the R.E.N.A.L. score, and the PADUA score were significantly associated with operative time (p = 0.016, p = 0.035, and p = 0.001, respectively) and warm ischemia time (all p = 0.008, p &lt; 0.001, and p &lt; 0.001, respectively). “3S+f” was also significantly related to extubation time &gt; 5 days (p = 0.018). In predicting operative time &gt; 120 min and extubation time &gt;5 days from ROC curves, the AUCs of the “3S+f” score (0.717 and 0.652, respectively) were larger than both the R.E.N.A.L (0.598 and 0.554, respectively) and PADUA (0.600 and 0.542, respectively) score systems.ConclusionA novel nephrometry score system—the “3S+f” score system—shows equivalent correlation and the ability in predicting clinical outcomes when compared to the R.E.N.A.L. score system and the PADUA score system, which can describe renal tumors.
The Prognostic Value of Tumor Size, Volume and Tumor Volume Reduction Rate During Concurrent Chemoradiotherapy in Patients With Cervical Cancer
Authors: Sun Chang , Wang Shubin , Ye Wenjing , Wang RanLin , Tan Mingyu , Zhang Hanyi , Zhou Jie , Li Minglun , Wei Lichun , Xu Peng , Zhu Guiquan , Lang Jinyi , Lu Shun 
Published: July 2022

ObjectiveThis study aimed to investigate the relationship between prognostic and tumor parameters of cervical cancer patients, such as tumor size (TS), tumor volume (TV), and tumor volume reduction rate (TVRR) after external beam radiotherapy.MethodsA total of 217 patients with advanced cervical cancer, classified as Federation of Gynecology and Obstetrics (FIGO) IIa–IVa, were enrolled in the study. Pre- and mid-RT pelvic magnetic resonance imaging (MRI) were performed twice, during RT and just before brachytherapy.ResultsThe median follow-up time was 51 months (range, 7–111 months). The 5-year overall survival (OS), progression-free survival (PFS), and local failure-free survival (LFFS) rates were 81.3, 85.1, and 92.9%, respectively. Multivariate analysis revealed that tumor parameters including FIGO stage &gt;II (Hazard Ratio, 2.377 and 95% confidence interval [CI], 1.091–5.182; P = 0.029), pre-RT TV &gt;61.6 cm3 (HR, 0.417 and 95% CI, 0.188–0.926; P = 0.032), and mid-RT TV &gt;11.38 cm3 (HR, 3.192 and 95% CI, 1.094–9.316; P = 0.034) were observably associated with OS. Univariate analysis showed that the tumor volume reduction rate (TVRR) was dramatically associated with overall survival (HR, 0.204 and 95% CI 0.033–1.282; P &lt;0.001) and local failure-free survival (P = 0.050).ConclusionsIn this retrospective study, TVRR and mid-radiotherapy tumor volume are independent and strong prognostic parameters for patients with local advanced cervical cancer receiving CCRT.
Ononin Shows Anticancer Activity Against Laryngeal Cancer via the Inhibition of ERK/JNK/p38 Signaling Pathway
Authors: Ye Ben , Ma Jianhua , Li Zhaoxia , Li Yang , Han Xiaopan 
Published: July 2022

BackgroundLaryngeal cancer is a type of head and neck tumor with a poor prognosis and survival rate. The new cases of laryngeal cancer increased rapidly with a higher mortality rate around the world.ObjectiveThe current research work was focused to unveil the in vitro antitumor effects of ononin against the laryngeal cancer Hep-2 cells.MethodologyThe cytotoxic effects of ononin against the laryngeal cancer Hep-2 cells and normal HuLa-PC laryngeal cells were studied using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The intracellular Reactive Oxygen Species (ROS) generation, apoptotic cell death, Mitochondrial Membrane Potential (MMP), and cell adhesion on the 25 and 50 µM ononin-treated Hep-2 cells were detected using respective staining assays. The levels of TBARS and antioxidants were assayed using specific kits. The expressions of c-Jun N-terminal kinase 1/2 (JNK1/2), Extracellular Signal-regulated Kinase 1/2 (ERK1/2), p38, Phosphatidylinositol-3 Kinase 1/2 (PI3K1/2), and protein kinase-B (Akt) in the ononin-treated Hep-2 cells were investigated using Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assay.ResultsThe ononin treatment effectively inhibited the Hep-2 cell viability but did not affect the viability of HuLa-PC cells. Furthermore, the ononin treatment effectively improved the intracellular ROS accumulation, depleted the MMP, and triggered apoptosis in Hep-2 cells. The Thiobarbituric acid reactive substances (TBARS) were improved, and Glutathione (GSH) levels and Superoxide dismutase (SOD) were depleted in the ononin-administered Hep-2 cells. The ononin treatment substantially inhibited the JNK/ERK/p38 axis in the Hep-2 cells.ConclusionTogether, the outcomes of this exploration proved that the ononin has remarkable antitumor activity against laryngeal cancer Hep-2 cells.
Pharmacokinetic Characterization and Comparative Bioavailability of an Innovative Orodispersible Fixed-Dose Combination of Ivermectin and Albendazole: A Single Dose, Open Label, Sequence Randomized, Crossover Clinical Trial in Healthy Volunteers
Authors: Algorta Jaime , Krolewiecki Alejandro , Pinto Filipe , Gold Silvia , Muñoz Jose 
Published: July 2022

Soil-transmitted helminths are intestinal worm diseases transmitted through the soil. Available treatments are albendazole and/or ivermectin. The co-administration of existing drugs is an appropriate strategy. A fixed-dose combination adds practical advantages mainly considering mass drug administration. The aim is to characterize pharmacokinetics and to evaluate the comparative bioavailability of an innovative fixed-dose combination of ivermectin/albendazole 18/400 mg compared with the marketed references. Seventy-eight healthy volunteers were included in this laboratory-blinded, randomized, three-treatment, three-period crossover study. Each subject received a single dose of ivermectin/albendazole 18/400 mg (1 tablet); ivermectin 3 mg (6 tablets); and albendazole 400 mg (1 tablet). Serial blood samples for the pharmacokinetic analysis were obtained pre-dose and up to 72 h post-dose. Plasma concentrations of ivermectin H2B1a, ivermectin H2B1b, albendazole, and albendazole sulfoxide were analyzed by LC-MS/MS. Pharmacokinetic parameters were estimated by a non-compartmental analysis and bioavailability compared through a bioequivalence analysis. Safety and tolerability were assessed throughout the study. Main pharmacokinetic parameters of the fixed combination were estimated for both, ivermectin [Cmax (mean, confidence interval): 86.40 (30.42–39.23) ng/ml; AUC0-72 (mean, CI): 1,040 (530–1,678) ng·h/mL; tmax (median, min., and max.); 4.50 (2.50–5.50)] and albendazole [Cmax (mean, CI): 22.27 (1.89–111.78) ng/ml; AUC0-72 (mean, CI): 94.65 (11.65–507.78) ng·h/mL; tmax (median, min., and max.): 2.50 (1.00–12.00) h]. The 90% confidence interval of the geometric mean ratios demonstrated the bioequivalence in the case of ivermectin (Cmax: 110.68%–120.49%; AUC0-72: 110.46%–119.60%) but not in the case of albendazole (Cmax: 53.10%–70.34%; AUC0-72: 61.13%–76.54%). The pharmacokinetic profile of a new fixed-dose combination of ivermectin and albendazole was characterized. The bioequivalence versus the reference ivermectin was demonstrated, though bioequivalence versus albendazole was not shown. The three medications analyzed were well tolerated. The results allow the advancement to the next phase of the clinical program to demonstrate efficacy and safety in patients affected by soil-transmitted helminths.Clinical Trial Registration:https://www.clinicaltrialsregister.eu/ctr-search/search/, identifier Nr. 2020-003438-19
Inhibition of HDAC6 With CAY10603 Ameliorates Diabetic Kidney Disease by Suppressing NLRP3 Inflammasome
Authors: Hou Qing , Kan Shuyan , Wang Zhuang , Shi Jinsong , Zeng Caihong , Yang Dahai , Jiang Song , Liu Zhihong 
Published: July 2022

Background: Diabetic nephropathy (DN) is one of the leading causes of chronic kidney disease (CKD) worldwide, tubular injury is the driving force during the pathogenesis and progression of DN. Thus, we aim to utilize the connectivity map (CMap) with renal tubulointerstitial transcriptomic profiles of biopsy-proven DN to identify novel drugs for treating DN.Methods: We interrogated the CMap profile with tubulointerstitial transcriptomic data from renal biopsy-proven early- and late-stage DN patients to screen potential drugs for DN. Therapeutic effects of candidate drug were assessed in Murine model of diabetic kidney disease (STZ-induced CD-1 mice), and HK-2 cells and immortalized bone marrow-derived macrophages (iBMDMs).Results: We identified CAY10603, a specific inhibitor of histone deacetylase 6 (HDAC6), as a potential drug that could significantly reverse the altered genes in the tubulointerstitial component. In DN patients and mice, upregulation of HDAC6 was mainly observed in renal tubular cells and infiltrated macrophages surrounding the diluted tubules. In both early- and late-onset diabetic mice, daily CAY10603 administration effectively alleviated renal dysfunction and reduced macrophage infiltration, tubular injury and tubulointerstitial fibrosis. Mechanistically, CAY10603 suppressed NLRP3 activation in both HK-2 cells and iBMDMs.Conclusion: CAY10603 exhibited therapeutic potential for DN by suppressing NLRP3 inflammasome activation in both tubular cells and macrophages.
Calorie Restriction Rescues Mitochondrial Dysfunction in Adck2-Deficient Skeletal Muscle
Authors: Hernández-Camacho Juan Diego , Fernández-Ayala Daniel J. M. , Vicente-García Cristina , Navas-Enamorado Ignacio , López-Lluch Guillermo , Oliva Clara , Artuch Rafael , Garcia-Villoria Judith , Ribes Antonia , de Cabo Rafael , Carvajal Jaime J. , Navas Plácido 
Published: July 2022

ADCK2 haploinsufficiency-mediated mitochondrial coenzyme Q deficiency in skeletal muscle causes mitochondrial myopathy associated with defects in beta-oxidation of fatty acids, aged-matched metabolic reprogramming, and defective physical performance. Calorie restriction has proven to increase lifespan and delay the onset of chronic diseases associated to aging. To study the possible treatment by food deprivation, heterozygous Adck2 knockout mice were fed under 40% calorie restriction (CR) and the phenotype was followed for 7 months. The overall glucose and fatty acids metabolism in muscle was restored in mutant mice to WT levels after CR. CR modulated the skeletal muscle metabolic profile of mutant mice, partially rescuing the profile of WT animals. The analysis of mitochondria isolated from skeletal muscle demonstrated that CR increased both CoQ levels and oxygen consumption rate (OCR) based on both glucose and fatty acids substrates, along with mitochondrial mass. The elevated aerobic metabolism fits with an increase of type IIa fibers, and a reduction of type IIx in mutant muscles, reaching WT levels. To further explore the effect of CR over muscle stem cells, satellite cells were isolated and induced to differentiate in culture media containing serum from animals in either ad libitum or CR diets for 72 h. Mutant cells showed slower differentiation alongside with decreased oxygen consumption. In vitro differentiation of mutant cells was increased under CR serum reaching levels of WT isolated cells, recovering respiration measured by OCR and partially beta-oxidation of fatty acids. The overall increase of skeletal muscle bioenergetics following CR intervention is paralleled with a physical activity improvement, with some increases in two and four limbs strength tests, and weights strength test. Running wheel activity was also partially improved in mutant mice under CR. These results demonstrate that CR intervention, which has been shown to improve age-associated physical and metabolic decline in WT mice, also recovers the defective aerobic metabolism and differentiation of skeletal muscle in mice caused by ADCK2 haploinsufficiency.
Child Homicide Amounting to Murder in Malaysia: Descriptive Analysis of the Statistics and Causes
Authors: Razali Salmi , Jaris Nor Hidayah , Muuti Muhamad Zaid , Abdullah Nuraisyah Chua 
Published: July 2022

ObjectiveTo describe the child homicide rates and examine the circumstances of homicides of children in Malaysia from January 2010 to June 2021.MethodsThis is a retrospective secondary analysis of police records on child homicides in Malaysia. Background demographic characteristics of victims, suspected offenders, motives of homicide, and rates of child homicide in Malaysia were analyzed descriptively.ResultsThree hundred thirty-two child homicide cases involving 349 children aged 18 years old and below by 458 suspected offenders were described. The Malaysian rates of child homicide from 2010 to 2018 fluctuated between 0.28 and 0.37 per 100,000 population of children aged 18 and below. The rates show decreasing trend to 0.19 and 0.17 per 100,000 population of children aged 18 in 2019 and 2020, respectively. Most of the victims were Malay and Indians, boys, aged 0–5 years old and 16–18 years old. Offenders were likely to be someone known to the victims, including parents, stepparents, and friends, and have unstable incomes. The main possible motives of homicide are jealousy and revenge, child abuse, and feeling distress.ConclusionThe rates of child homicide in Malaysia are lower compared to other countries and show decreasing trend during this COVID-19 pandemic. These findings perhaps are underestimated and should be cautiously interpreted. Nevertheless, the results should inform immediate intervention to target the at-risk groups.
Healthcare Worker Mental Health and Wellbeing During COVID-19: Mid-Pandemic Survey Results
Authors: Young Kevin P. , Kolcz Diana L. , Ferrand Jennifer , O’Sullivan David M. , Robinson Kenneth 
Published: July 2022

Introduction/BackgroundHealthCare worker (HCW) mental health and wellbeing are uniquely affected by the complexities of COVID-19 due to exposure to the virus, isolation from family and friends, risk and uncertainty. Little if any inquiry has examined the effects on an entire healthcare system, particularly immediately post-surge. We sought to examine the prevalence of psychiatric symptoms and behavioral health difficulties as a healthcare system transitioned out of the first wave. We assessed the effects of work role, setting and individual diversity factors on employee distress and coping strategies.Materials and MethodsThis was an Institutional Review Board approved, unfunded, voluntary survey sent via REDCap link, to all employees of Hartford HealthCare, a mid-sized healthcare system (N ≈ 29,900) between May 15th and June 26th, 2020. Two system-wide emails and two emails targeting managers were sent during this time frame. Eight thousand four hundred and ninety four employees (28.4% of all e-mails distributed) participated in the survey, representing clinical, support, administrative, and medical staff across hospital, outpatient, residential, and business settings. The survey contained items assessing personal background, work environment/culture, and formal measures, including: patient health questionnaire-9 (PHQ-9), general anxiety disorder-7 (GAD-7), primary care post-traumatic stress disorder screen for DSM-5 (PC-PTSD), alcohol use disorders identification test (AUDIT-C), and the insomnia severity index (ISI).ResultsAlmost 1/3 of respondents (31%) reported symptoms of clinically significant anxiety; 83% moderate to severe depression; and 51% moderate to severe insomnia. Thirteen percent screened positive for post-traumatic stress disorder. Frontline staff (p ≤ 0.001 vs. others) and females (p &lt; 0.001 vs. males) endorsed the highest levels of distress, while race (p ≤ 0.005) and ethnicity (p &lt; 0.03 for anxiety, PTSD and insomnia) had a complex and nuanced interaction with symptoms.ConclusionPandemic stress effects all healthcare employees, though not equally. The effects of work role and environment are intuitive though critical. These data suggest individual diversity factors also play an important role in mental health and wellbeing. All must be considered to optimize employee functioning.