bluuebunny/crossref_metadata_2025_split huggingface dataset:
YAP1-MAML2 Fusion as a Diagnostic Biomarker for Metaplastic Thymoma
Authors: Zhao Jikai , Zhao Ruiying , Xiang Chan , Shao Jinchen , Guo Lianying , Han Yuchen 
Published: July 2021

BackgroundMetaplastic thymoma is a very rare tumor with only a few case reports documented in literature. Hence, its molecular features have not been well explored.Material and MethodsSeventeen specimens of metaplastic thymoma were sequenced and retrospectively analyzed by fluorescence in situ hybridization (FISH) and immunohistochemistry in the study. In addition, seven cases of micronodular thymoma with lymphoid stroma and nine cases of type A thymoma were also investigated.ResultsAmong these metaplastic thymomas, fifteen cases showed classical histological features, and two cases displayed characteristic micronodular-like growth patterns. DNA and RNA based next-generation sequencing identified and confirmed highly recurrent Yes Associated Protein 1 (YAP1) - Mastermind Like Transcriptional Coactivator 2 (MAML2) translocation (13/17, 76.5%) in metaplastic thymoma but not in micronodular thymoma with lymphoid stroma (0/7, 0%) and type A thymoma (0/9, 0%). In addition, six nonsense mutations were also detected in the metaplastic thymoma. FISH in microdissection specimens indicated that both epithelioid and spindle cell components harbored YAP1-MAML2 gene rearrangements.ConclusionsOur study explored the genetic alterations in epithelioid and spindle cell components in metaplastic thymoma. Furthermore, YAP1-MAML2 gene rearrangements emerged as a potential diagnostic biomarker helpful for distinguishing metaplastic thymoma from type A and micronodular thymoma with lymphoid stroma.
Virtual Patient-Specific Quality Assurance of IMRT Using UNet++: Classification, Gamma Passing Rates Prediction, and Dose Difference Prediction
Authors: Huang Ying , Pi Yifei , Ma Kui , Miao Xiaojuan , Fu Sichao , Chen Hua , Wang Hao , Gu Hengle , Shao Yan , Duan Yanhua , Feng Aihui , Wang Jiyong , Cai Ruxin , Zhuo Weihai , Xu Zhiyong 
Published: July 2021

The dose verification in radiotherapy quality assurance (QA) is time-consuming and places a heavy workload on medical physicists. To provide a clinical tool to perform patient specific QA accurately, the UNet++ is investigated to classify failed or pass fields (the GPR lower than 85% is considered “failed” while the GPR higher than 85% is considered “pass”), predict gamma passing rates (GPR) for different gamma criteria, and predict dose difference from virtual patient-specific quality assurance in radiotherapy. UNet++ was trained and validated with 473 fields and tested with 95 fields. All plans used Portal Dosimetry for dose verification pre-treatment. Planar dose distribution of each field was used as the input for UNet++, with QA classification results, gamma passing rates of different gamma criteria, and dose difference were used as the output. In the test set, the accuracy of the classification model was 95.79%. The mean absolute error (MAE) were 0.82, 0.88, 2.11, 2.52, and the root mean squared error (RMSE) were 1.38, 1.57, 3.33, 3.72 for 3%/3mm, 3%/2 mm, 2%/3 mm, 2%/2 mm, respectively. The trend and position of the predicted dose difference were consistent with the measured dose difference. In conclusion, the Virtual QA based on UNet++ can be used to classify the field passed or not, predict gamma pass rate for different gamma criteria, and predict dose difference. The results show that UNet++ based Virtual QA is promising in quality assurance for radiotherapy.
Identification of the Extradural and Intradural Extension of Pituitary Adenomas to the Suprasellar Region: Classification, Surgical Strategies, and Outcomes
Authors: Yang YouQing , Bao YouYuan , Xie ShenHao , Tang Bin , Wu Xiao , Yang Le , Wu Jie , Ding Han , Li ShaoYang , Zheng SuYue , Hong Tao 
Published: July 2021

ObjectiveSuprasellar pituitary adenomas (PAs) can be located in either extradural or intradural spaces, which impacts surgical strategies and outcomes. This study determined how to distinguish these two different types of PAs and analyzed their corresponding surgical strategies and outcomes.MethodsWe retrospectively analyzed 389 patients who underwent surgery for PAs with suprasellar extension between 2016 to 2020 at our center. PAs were classified into two main grades according to tumor topography and their relationships to the diaphragm sellae (DS) and DS-attached residual pituitary gland (PG). Grade 1 tumors were located extradurally and further divided into grades 1a and 1b, while grade 2 tumors were located intradurally.ResultsOf 389 PAs, 292 (75.1%) were surrounded by a bilayer structure formed by the DS and the residual PG and classified as grade 1a, 63 (16.2%) had lobulated or daughter tumors resulting from the thinning or absence of the residual PG and subsequently rendering the bilayer weaker were classified as Grade 1b, and the remaining 34 (8.7%) PAs that broke through the DS or traversed the diaphragmic opening and encased suprasellar neurovascular structures were classified as Grade 2. We found that the gross total removal of the suprasellar part of grade 1a, 1b, and 2 PAs decreased with grading (88.4%, 71.4%, and 61.8%, respectively). The rate of major operative complications, including cerebrospinal fluid leakage, hemorrhage, and death, increased with grading.ConclusionsIt is essential to identify whether PAs with suprasellar extension are located extradurally or intradurally, which depends on whether the bilayer structure is intact. PAs with an intact bilayer structure were classified as grade 1. These were extradural and usually had good surgical outcomes and lower complications. PAs with no bilayer structure surrounding them were classified as grade 2. These were intradural, connected to the cranial cavity, and had increased surgical complications and a lower rate of gross total removal. Different surgical strategies should be adopted for extradural and intradural PAs.
Overlapping Features in Kawasaki Disease-Related Arthritis and Systemic-Onset Juvenile Idiopathic Arthritis: A Nationwide Study in Japan
Authors: Kanemasa Hikaru , Nanishi Etsuro , Takada Hidetoshi , Ishimura Masataka , Nishio Hisanori , Honjo Satoshi , Masuda Hiroshi , Nagai Noriko , Nishihara Takahiro , Ishii Tohru , Adachi Takenori , Hara Satoshi , Lin Lisheng , Tomita Yoshie , Kamizono Junji , Komiyama Osamu , Kohdera Urara , Tanabe Saori , Sato Atsuo , Hida Shinya , Yashiro Mayumi , Makino Nobuko , Nakamura Yosikazu , Hara Toshiro , Ohga Shouichi 
Published: July 2021

Background: Arthritis may occur after the diagnosis of Kawasaki disease (KD). Most cases are self-limiting; however, some patients require prolonged treatment.Method: To characterize KD-related arthritis, 14 patients who required arthritis treatment within 30 days after the diagnosis of KD were recruited from the 23rd KD survey in Japan. Twenty-six additional patients were included from our tertiary center and literature review cohorts.Results: The estimated prevalence of KD-related arthritis in Japan was 48 per 100,000 KD patients. Patients with KD-related arthritis had an older age at onset (52 vs. 28 months, P = 0.002) and higher rate of intravenous immunoglobulin (IVIG) resistance in comparison to those without arthritis (86 vs. 17%, P &lt; 0.001). Among 40 patients, 18 had arthritis in the acute phase KD (continued fever-onset type) and 22 did in the convalescent phase (interval fever-onset type). Both showed a similar rate of complete KD or IVIG response. Interval-type patients required biologics for arthritis control less frequently (5 vs. 39%, P = 0.02) and had a higher 2-year off-treatment rate (100 vs. 43%, P = 0.009) than continued-type ones. Interval-types showed lower serum ferritin and interleukin-18 levels than continued-types. When continued-types were grouped according to whether or not they required biologics (n = 7 and n = 11, respectively), the former subgroup had higher ferritin and interleukin-18 levels (P = 0.01 and 0.02, respectively). A canonical discriminant analysis differentiated interval-type from continued-type with the combination of age, time to arthritis, and the ferritin and matrix metalloproteinase-3 levels.Conclusion: Arthritis requiring treatment is a rare complication of KD. KD-associated arthritis includes interval-type (KD-reactive) and continued-type (true systemic-onset juvenile idiopathic arthritis [JIA] requiring biologics), and overlapping arthritis, suggesting the pathophysiological continuity of autoinflammation between KD and JIA.
Physiologically Based Pharmacokinetic Modelling for Nicotine and Cotinine Clearance in Pregnant Women
Authors: Amice Basile , Ho Harvey , Zhang En , Bullen Chris 
Published: July 2021

Introduction: Physiologically based pharmacokinetic (PBPK) models for the absorption, disposition, metabolism and excretion (ADME) of nicotine and its major metabolite cotinine in pregnant women (p-PBPK) are rare. The aim of this short research report is to present a p-PBPK model and its simulations for nicotine and cotinine clearance.Methods: The maternal-placental-fetal compartments of the p-PBPK model contain a total of 16 compartments representing major maternal and fetal organs and tissue groups. Qualitative and quantitative data of nicotine and cotinine disposition and clearance have been incorporated into pharmacokinetic parameters.Results: The p-PBPK model reproduced the higher clearance rates of nicotine and cotinine in pregnant women than non-pregnant women. Temporal profiles for their disposition in organs such as the brain were also simulated. Nicotine concentration reaches its maximum value within 2 min after an intravenous injection.Conclusion: The proposed p-PBPK model produces results consistent with available data sources. Further pharmacokinetic experiments are required to calibrate clearance parameters for individual organs, and for the fetus.
Antileishmanial Activity of Flavones-Rich Fraction From Arrabidaea chica Verlot (Bignoniaceae)
Authors: Silva-Silva João Victor , Moragas-Tellis Carla Junqueira , Chagas Maria do Socorro dos Santos , Souza Paulo Victor Ramos de , Souza Celeste da Silva Freitas de , Hardoim Daiana de Jesus , Taniwaki Noemi Nosomi , Moreira Davyson de Lima , Dutra Behrens Maria , Calabrese Kátia da Silva , Almeida-Souza Fernando 
Published: July 2021

Acknowledging the need of identifying new compounds for the treatment of leishmaniasis, this study aimed to evaluate, from in vitro trials, the activity of flavones from Arrabidaea chica against L. amazonensis. The chromatographic profiles of the hydroethanolic extract and a flavone-rich fraction (ACFF) from A. chica were determined by high-performance liquid chromatography coupled with a diode-array UV-Vis detector (HPLC-DAD-UV) and electrospray ionization mass spectrometry in tandem (LC-ESI-MS-MS). The flavones luteolin (1) and apigenin (2), isolated from chromatographic techniques and identified by Nuclear Magnetic Resonance of 1H and 13C, were also quantified in ACFF, showing 190.7 mg/g and apigenin 12.4 mg/g, respectively. The other flavones were identified by comparing their spectroscopic data with those of the literature. The in vitro activity was assayed against promastigotes and intramacrophagic amastigote forms of L. amazonensis. Cytotoxicity tests were performed with peritoneal macrophages of BALB/c mice. Nitrite quantification was performed with Griess reagent. Ultrastructural investigations were obtained by transmission electron microscopy. Anti-Leishmania assays indicated that the IC50 values for ACFF, apigenin, and luteolin were obtained at 40.42 ± 0.10 and 31.51 ± 1.13 μg/mL against promastigotes, respectively. ACFF and luteolin have concentration-dependent cytotoxicity. ACFF and luteolin also inhibited the intra-macrophagic parasite (IC50 3.575 ± 1.13 and 11.78 ± 1.24 μg/mL, respectively), with a selectivity index of 11.44 for ACFF. Promastigotes exposed to ACFF and luteolin exhibited ultrastructural changes, such as intense cytoplasm vacuolization and mitochondrial swelling. These findings data evidence the antileishmanial action of flavone-rich fractions of A. chica against L. amazonensis, encouraging further studies.
Case Report: Predicting the Range of Lamotrigine Concentration Using Pharmacokinetic Models Based on Monte Carlo Simulation: A Case Study of Antiepileptic Drug-Related Leukopenia
Authors: Zhu Xiuqing , Xiao Tao , Huang Shanqing , Liu Shujing , Li Xiaolin , Shang Dewei , Wen Yuguan 
Published: July 2021

Lamotrigine (LTG), a wide-spectrum antiepileptic drug, is frequently associated with cutaneous side-effects, whereas hematological side-effects such as leukopenia have rarely been reported for it. We report the case of a 15-year-old Chinese female epileptic patient weighing 60 kg who developed combined asymptomatic leukopenia after receiving concomitant therapy with LTG and valproate acid (VPA). In this case report, antiepileptic drug-related leukopenia may have occurred in definite relation to an increase in LTG concentration and reversed with the discontinuation of VPA. Monte Carlo (MC) simulations were performed to estimate the steady-state serum concentrations (Css) of LTG for different dosing regimens in adolescent Chinese epileptic patients weighing the same as the patient considered in the case study, based on pharmacokinetic (PK) models published in past research. Adjustments to the dosage of LTG for the patient were analyzed to illustrate the application of MC simulations and verify the results. The predicted LTG concentrations within a prediction interval between the 10th and 90th percentiles that represented 80% of the simulated populations, could adequately capture the measured LTG concentrations of the patient, indicating that MC simulations are a useful tool for estimating drug concentrations. Clinicians may benefit from the timely probabilistic predictions of the range of drug concentration based on an MC simulation that considers a large sample of virtual patients. The case considered here highlights the importance of therapeutic drug monitoring (TDM) and implementing model-informed precision dosing in the course of a patient’s individualized treatment to minimize adverse reactions.
Analgesic Effect of Ziziphus abyssinica Involves Inhibition of Inflammatory Mediators and Modulation of KATP Channels, Opioidergic and Nitrergic Pathways
Authors: Henneh Isaac Tabiri , Armah Francis Ackah , Ameyaw Elvis Ofori , Biney Robert Peter , Obese Ernest , Boakye-Gyasi Eric , Adakudugu Emmanuel Awintiig , Ekor Martins 
Published: July 2021

The diversity offered by natural products has timelessly positioned them as a good source for novel therapeutics for the management of diverse medical conditions, including pain. This study evaluated hydro-ethanolic root bark extract of Ziziphus abyssinica (ZAE) as well as β-amyrin and polpunonic acid isolated from the plant for analgesic property. The study also investigated the mechanism responsible for this action in the extract. The antinociceptive potential of ZAE (30, 100, and 300 mg/kg, p. o.) was assessed using the tail-immersion test (TIT), acetic acid-induced writhing test (AAT), and formalin test (FT). The extract’s effect on acute and chronic musculoskeletal pain was also assessed by administering carrageenan unilaterally into the rat gastrocnemius muscles and measuring pain at 12 h and 10 days for acute and chronic pain respectively. The involvement of pro-inflammatory mediators (prostaglandin E2, bradykinin, TNF-α, and IL-1β) was assessed. The possible pathways mediating the observed analgesic effect of ZAE were further assessed using the antagonists: naloxone, glibenclamide, NG-L-nitro-arginine methyl ester (L-NAME), atropine, nifedipine, and yohimbine in the FT. Also the analgesic effect of two triterpenoid compounds, β-amyrin and polpunonic acid, previously isolated from the plant was assessed using the TIT. The anti-nociceptive activity of ZAE was demonstrated in the TIT by the significant (p &lt; 0.05) increase in tail withdrawal threshold in ZAE-treated mice. ZAE also markedly reduced writhing and paw licking responses in both AAT and FT and significantly (p &lt; 0.05) attenuated both acute and chronic musculoskeletal pain. ZAE also significantly reversed hyperalgesia induced by intraplantar injection of PGE2, bradykinin, TNF-α, and IL-1β. Furthermore, data revealed the involvement of opioidergic, ATP-sensitive K+ channels and NO-cGMP pathways in the analgesic effect of ZAE. Both β-amyrin and polpunonic acid exhibited analgesic activity in the tail suspension test. Our study demonstrates ZAE as an important source of new therapeutic agents for pain management.
The Khoekhoegowab Personality Inventory: The Comparative Validity of a Locally Derived Measure of Traits
Authors: Thalmayer Amber Gayle , Saucier Gerard , Shino Elizabeth N. , Job Sylvanus 
Published: July 2021

Objective: This study explores a personality inventory derived from the results of an indigenous lexical study of personality. From the 272 most commonly used personality descriptors in Khoekhoegowab, the most-spoken of extant Khoesan click languages of southern Africa, an 11-factor model of personality-trait structure was identified. Here, the Khoekhoegowab Personality Inventory (KPI) was created based on those results. Its psychometric properties, the convergent and divergent validity of its scales, and its incremental validity over Big Five and Six traits for predicting physical and mental health, religious practice and attitudes, and income are reported.Methods: Two to five key terms were selected for each of 10 KPI scales: Temperance, Prosocial Diligence, Gossip, Honesty/Morality, Temper, Implacability, Humility, Vanity, Resiliency vs. Agitation, and Courage vs. Fear. These 38 total items were administered to a large sample of adult speakers of Khoekhoegowab in Namibia (N = 632), together with five imported inventories translated into Khoekhoegowab: the 30-item Questionnaire Big Six (QB6), General Self-Reported Health, the Cascades Mental Health Assessment, the Satisfaction with Life Scale, the Duke Religion Index. The properties and intercorrelations of KPI subscales are explored, and their predictive ability for the other variables is compared to that of the QB6.Results: Due to the small number of items on each scale, poor internal consistency was anticipated, but the KPI scales' properties were somewhat better than those of the QB6. R-square change by the inventories as a whole, after accounting for age and gender, indicted that the KPI scales explained more variance than the QB6 scales in almost all criterion variables. Replication of established associations for Big Six traits was mixed: associations were largely as expected for Resiliency, Conscientiousness, and Honesty, but less so for Agreeableness and Extraversion.Conclusions: The KPI had some advantages over the QB6 in predicting physical and mental health. In particular, the four items of Resiliency vs. Agitation predicted lower scores on all physical and mental problem scales. Given psychological-care needs in Namibia, this might be used as a non-intrusive screener. Measurement challenges common to both surveys are discussed, possible solutions, and the utility of higher-order structures are discussed.
Psychosocial Impacts of COVID-19 on Healthcare Workers During the Nationwide Partial Lockdown in Vietnam in April 2020
Authors: Nguyen Thao Thanh , Le Xuan Thi Thanh , Nguyen Nguyen Thao Thi , Nguyen Quang Nhat , Le Huong Thi , Pham Quan Thi , Ta Nhung Kim Thi , Nguyen Quynh Thi , Nguyen Anh Ngoc , Hoang Men Thi , Pham Hai Quang , Vu Linh Gia , Luong Anh Mai , Koh David , Nguyen Trang Ha , Tran Bach Xuan , Latkin Carl A. , Ho Cyrus S.H. , Ho Roger C.M. 
Published: July 2021

Background: The psychosocial impact of COVID-19 is greater among healthcare workers (HCWs) than the general population. This study aims to identify psychosocial problems faced by HCWs in Vietnam during the national partial lockdown between 1 and 22 April 2020 and to identify risk factors associated with psychosocial issues among this population.Methods: A cross-sectional study was conducted in the second week of April 2020 during the national lockdown in Vietnam. Snowball sampling technique was used to recruit participants through web-based surveys. The Impact of Events Scale-Revised (IES-R) was used to assess the impact of COVID-19 on HCWs through online surveys.Results: Of the 349 HCWs, we found 22.6% reported psychosocial problems. Most of participants reported having exposure to COVID-19 daily (48.7%). The majority of them also felt that their job put them at risk of SARS-CoV-2 infections (90.3%) and expressed fear of potential infection (85.7%). Despite COVID-19 risks, 95.4% of participants, however, expressed their willingness to continue working at their current health facility. In addition, 94.8% of participants believed if they or their family members had been infected, their agency leaders would have provided them with appropriate medical care. Lastly, HCWs who worked in the internal medicine department who did not take care of COVID-19 patients or expressed fear of becoming infected were more likely to have higher total IES-R scores.Conclusion: Our findings suggest that the support of healthcare leaders and assurance of care might be helpful in mitigating the psychological effects of COVID-19 among HCWs in Vietnam. These resources should be tailored to HCWs who are working in different areas of health services, including staff who are not working directly with COVID-19 patients. In addition, psychosocial health resources should be provided for not only physicians but also nursing staff.
Maternal Shared Pleasure, Infant Withdrawal, and Developmental Outcomes in a High Risk Setting in South Africa
Authors: Lachman Anusha , Burger Marlette , Jordaan Esmè R. , Leppanen Jukka , Puura Kaija , Niehaus Dana J. H. 
Published: July 2021

Background:Infants in lower middle income countries are often exposed to early adversities which may lead to suboptimal caregiving environments and place them at risk of not achieving their developmental potential. Synchrony and positive engagement in the mother-infant relationship plays a critical role in buffering the impact of early adversity. Shared Pleasure (SP) is considered a marker of high intensity positive interaction and may hold a promise of improving developmental outcomes.Methods:This study was part of a prospective observational study of mothers with and without mental illness in South Africa. Dyadic videos were assessed for SP and infant withdrawal (using the Alarm Distress Baby Scale) at 6 months. Infant developmental outcomes were assessed using the Bayley's Scales for Infant and Toddler Development, third edition at 18 months.Results:Ninety-one dyads were assessed for SP. The occurrence of SP was low (20%). There was no significant association with an EPDS measure of maternal depression (p= 0.571) and SP moments. Infant withdrawal was high (72%) and associated with male infant gender (p= 0.025). There was a significant association between the occurrence of SP and a lower score of infant withdrawal (estimate = −1.29; SE = 0.4;p= 0.0002). The number of SP moments at 6 months was significantly associated with motor (estimate = 2.4; SE = 0.9;p= 0.007) and marginally significant with cognitive scores (estimate = 1.9; SE = 1.0;p= 0.052) at 18 months. Regression modelling differential outcomes showed a greater improvement in cognitive scores at 18 months in infants with an SP moment compared to those without an SP moment [SP average difference (AD) = 7.4 (2.4), no SP AD = 10.4 (1.2);p= 0.012]. Infants without an SP moment experienced a larger decrease in motor scores at 18 months compared to those with an SP moment [SP AD = −3 (3.0); no SP AD = −10.6 (1.5),p= 0.027].Conclusion:While the occurrence of SP in this sample was low and the rates of infant withdrawal were high, there were promising results suggesting early positive SP interactions may contribute to improvements in subsequent developmental outcomes.