bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic-pharmacodynamic modelling and simulation of ustekinumab for inflammatory bowel disease
Authors: Kimura Koji , Yoshida Atsushi 
Published: March 2022

Abstract
Ustekinumab (UST) therapy is effective for induction and maintenance therapy for inflammatory bowel disease (IBD). Although there are differences in dosage regimen among countries and indications, and the differences have implications for efficacy, the implications have yet to be analysed by a model-informed approach. The aim of this study is to evaluate the implications for efficacy of the different dosage regimens of UST for IBD using our pharmacokinetic-pharmacodynamic (PK/PD) model. We constructed a PK/PD model based on an indirect response model with an effect compartment and simulated the sequential changes of therapeutic effect following various dosage regimens. Sequential changes in the therapeutic effect obtained with our model were in good agreement with the observed values following repeated administration of UST for IBD patients. The simulation indicated the importance of an initial intravenous administration of UST for IBD patients. Furthermore, the dose interval of maintenance therapy at every 8 weeks was marginally more effective than at every 12 weeks, though there was almost no difference in the fluctuation range, and a stable therapeutic effect was obtained by both dosage regimens. The results showed that the presented PK/PD model is capable of predicting sequential changes in the therapeutic effect of UST for IBD, and the implications for efficacy of the different dosage regimens could be evaluated by simulation with various dosage regimens.
Primary Sebaceous Carcinoma of Esophagus: The First Case Report and Literature Review
Authors: Zhou Jing , Cheng Na , Zhao Chang , Zhang Yiwang , Wang Jiani , Zhang Nana 
Published: March 2022

Abstract
Background：Sebaceous carcinoma (SC) is an uncommon neoplasm that usually occur in the skin of head and neck region with a predilection of periocular sites. This tumor is thought to arise from sebaceous glands in the skin and thus may arise anywhere on the body where these glands exist. However, the noncutaneous SC in where the sebaceous glands are anatomically absent have also been reported sporadically, and the pre-existing ectopic sebaceous glands are speculated to be the basis of its origination. Though ectopic sebaceous glands are not uncommon in esophagus, primary SC in esophagus has not been reported thus far. Aims: To report for the first time one primary esophageal SC in a 66-year-old man, investigated its clinicopathological features, diagnostic points and differential diagnosis from other malignancy. Methods：Clinical and radiological data were collected; the tumor morphology and immunohistochemical pattern were analyzed. Related literatures were reviewed. Results：The tumor cells diffusely expressed P40, CK5/6, AR and P53, and EMA staining highlighted the sebocytes with a foam-like pattern in cytoplasm. With the auxiliary immunohistochemical staining, we finally made an unequivocal diagnosis of SC. Conclusions：SC is a rare entity in esophagus which have not been reported before and may bring up diagnostic puzzles to pathologists. The tumor morphology is complex and with a similar immunohistochemical expression profiles just like SC reported in other sites. This unique tumor occur in esophagus extends the spectrum of extraocular, extracutaneous SC from existing case reports.
The D-model for GDP nowcasting
Authors: Degiannakis Stavros 
Published: March 2022

Abstract
The paper provides a disaggregated mixed frequency framework for the estimation of GDP. The GDP is disaggregated into components that can be forecasted based on information available at higher sampling frequency; i.e. monthly, weekly or daily. The model framework is applied for Greek GPD nowcasting. The results provide evidence that the more accurate nowcasting estimations require i ) the disaggregation of GDP, ii ) the use of a multilayer mixed frequency framework, iii ) the inclusion of financial information on a daily frequency. The simulation study provides evidence in favor of the disaggregation into components despite the inclusion of multiple sources of forecast errors.
A Comprehensive Voltammetric Characterization of In Vivo Histamine Dynamics Reveals Critical Modulatory Roles of This Elusive Messenger
Authors: Berger Shane , Baumberger Beatrice , Samaranayake S , Hersey M , Mena Sergio , Bain Ian , Duncan W , Reed M C , Nijhout F , Best J , Hashemi Parastoo 
Published: March 2022

Abstract
Histamine is well known for mediating peripheral inflammation, however, histamine is found in high concentrations in the brain where amongst other roles, this amine is a neuromodulator. Histamine modulation is critical for brain function, yet dynamic histamine chemistry is very difficult to measure and thus several fundamental aspects of the mechanisms that control the extracellular and modulatory behavior of this messenger remain undefined. In this work we undertake an in-depth characterization of in vivo histamine dynamics using fast-scan cyclic voltammetry at carbon fiber microelectrodes. We measure electrically evoked histamine in the mouse hypothalamus and find that histamine release is sensitive to pharmacological manipulation of synthesis, packaging, autoreceptor control of release, and metabolism. We find two breakthrough aspects of histamine modulation. First, there are differences in H3 receptor regulation of histamine between sexes showing that histamine release in female mice is more much tightly regulated than in male mice under H3 or inflammatory drug challenge. We hypothesize that this finding may contribute to hormone-mediated neuroprotection mechanisms in female mice. Second, we find that a high dose of a commonly available antihistamine, the H1 receptor antagonist diphenhydramine, rapidly decreased serotonin levels. This high dose is considered overdose; however, this finding highlights the sheer significance of better consideration of the modulatory nuances of histamine on serotonin when studying/designing histamine targeting pharmaceuticals. We, thus, present the first in depth in vivo characterization of fast histamine dynamics and presents two breakthrough regulatory aspects of this elusive modulator.
Zhongfeng capsule protects against cerebral ischemia-reperfusion injury via mediating PI3K/Akt and TLR4/NF-κB signal pathway regulated neuronal apoptosis and inflammatory reaction
Authors: Yan Chunlu , An Fangyu , Wang Jiayu , Shi Yao , Yuan Lingqing , Lv Donghui , Zhao Yanzhen , Liu Yongqi , Wang Yongfeng 
Published: March 2022

Abstract
Inflammation reactions and neuronal apoptosis are the major pathophysiological mechanism of cerebral ischemia/reperfusion injury (CI/RI). Zhongfeng capsules
(ZFCs), composed of panax notoginseng, hirudo, red ginseng, eupolyphaga,
pangolin scales, rhubarb, and radix salviae miltiorrhizae. It has been reported that
composition of ZFCs has a definite curative effect on CI/RI. Thus far, the specific
molecular mechanisms of ZFCs remain unclear. This article would set rats model
of middle cerebral artery occlusion(MCAO) to research the probable mechanisms
of ZFCs underlying inflammation reactions and neuronal apoptosis signaling
pathways. Our analyses revealed that in the ZFCs treatment group, there was an
obvious decrease in neurologic impairment, as well as alleviation of the area of
cerebral infarction, cerebral edema, histopathologyrats and neuronal apoptosis were
also alleviated. The IL-1β, IL-6, and TNF-α were found to be down-regulated
expression in the ZFC treatment group as well as the expression of Bcl-2, p-PI3K,
p-Akt, and I-κBα was increased and the expression level of TLR4, NF-κB, Bax,
caspase-3 was tended to decrease. The results indicated that ZFCs was effective in
protecting the brain against CI/RI. One of their neuro-protective mechanisms may be
associated with TLR4/NF-κB signalling, and they may negatively regulate the
transcriptional activity of NF-κB and the secretion of downstream inﬂammatory
factors. Another of their neuro-protective mechanisms may occur by regulating the
expression of Bcl-2-Bax proteins of PI3K/Akt pathway. Our findings could facilitate
that the suppressing PI3K/Akt signal pathway-mediated neuronal apoptosis,
suppressing TLR4/NF-κB signal pathway-mediated inflammatory reaction were the
potential mechanisms for the regulations, activation of PI3K/Akt pathway can inhibit
the secretion of proinflammatory cytokines, which may be another functional
mechanism of ZFCs against CI/RI.
A Risk Assessment Model for Prognosis Prediction: The Ferroptosis-related Gene Signature Based on Thyroid Cancer Mechanism Exploration from Multiple Perspectives
Authors: Fan Xin , Zhong Yun , Fan Yating , Zhang Lingling , Xie Fei , Zhang Zhi-yuan 
Published: March 2022

Abstract
Background: Ferroptosis is an iron-dependent, new type of programmed cell death different from apoptosis, necrosis, and autophagy. At present, ferroptosis has been confirmed to be closely related to the prognosis and treatment of cancer. However, the relationship between ferroptosis and the progression and prognosis of different types of thyroid cancer (THCA) is unclear.Methods: First, we performed differential expression analysis on the data of the two databases to obtain differentially expressed ferroptosis-related genes (DE-FRGs). Through differential expression, univariate Cox and lasso regression analysis, we identified 14 prognostic-related differently expressed ferroptosis-related genes (PR-DE-FRGs) for building risk assessment models. Subsequently, various validation methods are used to test the performance of the model. Then, we explored the mechanism of ferroptosis in the development and prognosis of THCA from the aspects of gene set enrichment analysis (GSEA), tumor microenvironment (TME), high frequency gene mutation, cell stemness and AL928654.4/miR-1287-5p/GPX4 regulatory axis. Finally, we verified the promising clinical application of the model.Results: ANGPTL7, DRD4, SRXN1, TXNRD1, CDKN2A, MIOX, PGD and TFRC (HR>1) were identified as prognostic risk factors, whereas CAPG, GPX4, ARNTL, ISCU, BID and DPP4 (HR<1) were the opposite. Immunohistochemical (IHC) images and Gene Expression Omnibus (GEO) data validated differential expression of 7 and 12 PR-DE-FRGs, respectively. Through the study of the tumor microenvironment, we obtained the immune landscape of THCA and revealed to us that ferroptosis may influence the prognosis of THCA patients by affecting anti-tumor immunity. Subsequently, we found that the predicted and validated AL928654.4/miR-1287-5p/GPX4 regulatory axis may play an important role in regulating cancer cell apoptosis and ferroptosis. Finally, immunophenoscore, chemotherapeutic drug sensitivity analysis, ICIs related genes, and Nomogram were performed to prove the good clinical application prospects of the risk assessment model.Conclusion: The risk assessment model can effectively predict the treatment effect and prognosis of THCA patients, and achieve the effect that can guide clinical treatment. Ferroptosis may be involved.
Rectourethral Fistula After External Beam Radiotherapy for Prostate Cancer in a Patient With Thromboangiitis Obliterans: a Case Report
Authors: Ohira Keiichi , Konishi Kenta , Aramaki Shuhei , Kokubo Ryo , Wakabayashi Kouhei , Hirata Masanori , Imai Michiko , Nakamura Katsumasa 
Published: March 2022

Abstract
Background: Thromboangiitis obliterans (TAO) is a rare disease of unknown cause that causes segmental vasculitis in peripheral blood vessels. It is uncertain whether its presence is a cause of serious adverse events in patient receiving external beam radiotherapy.Case presentation: A 73-year-old Japanese man with prostate cancer underwent external beam radiotherapy. After the completion of radiotherapy, pain in his fingertips occurred and led to the diagnosis of TAO. The patient was instructed to stop smoking but was unable to do so. Nine months after the completion of radiotherapy, fecaluria appeared, and a rectourethral fistula was diagnosed by contrast enema. The patient's TAO was poorly controlled, and the patient died from aspiration pneumonia at 33 months after the completion of the radiotherapy regimen. No tumor recurrence was observed during this process, and there were no risk factors which may form a rectourethral fistula other than TAO.Conclusion: This is the first report on rectourethral fistula caused by external beam radiotherapy for prostate cancer in which TAO was suspected to be involved. Although little is known about the relationship between TAO and radiotherapy, it should be noted that radiotherapy itself may increase the risk of normal tissue toxicity in patients with TAO.
The effect of posterior pericardiotomy after thoracic aortic surgery
Authors: Maze Yasumi , Tokui Toshiya , Murakami Masahiko , Yamaguchi Daisuke , Inoue Ryosai , Hirano Koji , Nakamura Bun , Itou Hisato 
Published: March 2022

Abstract
BackgroundPostoperative atrial fibrillation is a common complication of cardiovascular surgery. We aimed to examine the effectiveness of posterior pericardiotomy in reducing the incidence of postoperative atrial fibrillation after thoracic aortic surgery.MethodsThe study included 201 patients who underwent thoracic aortic open surgery between January 2014 and November 2021. We compared surgical outcomes between patients who underwent posterior pericardiotomy and those who did not. We also compared the preoperative characteristics and surgical outcomes between patients who showed postoperative atrial fibrillation and those who did not. Multivariate analysis was performed to determine the risk factors for postoperative atrial fibrillation.ResultsThe group that did not undergo posterior pericardiotomy had significantly longer mechanical ventilation duration than the group who did in the overall (p=0.005) and propensity-matched cohorts (p=0.001). The lengths of intensive care unit and hospital stays were significantly longer in the group that did not undergo posterior pericardiotomy than in the group that did in the overall and propensity-matched cohorts. Postoperative atrial fibrillation occurrence did not differ significantly between the two groups. Late pericardial tamponade occurred significantly more frequently in the group that did not undergo posterior pericardiotomy than in the group that did in the overall (p=0.03) and propensity-matched cohorts (p=0.03). Advanced age was independent predictors of postoperative atrial fibrillation. ConclusionsPosterior pericardiotomy has no effect on reducing postoperative atrial fibrillation after thoracic aortic surgery. Posterior pericardiotomy reduced the occurrence of late pericardial tamponade, length of ICU stay, length of hospital stay, and mechanical ventilation duration after surgery.
Clinical and procedural implications of ommaya reservoirs implantation in cystic brain metastases followed by radiosurgery treatment
Authors: Han Weidong , Lv Junhui , Wu Zhuoxuan , Wang Kun , Wang Yirong , Yang Shuxu 
Published: March 2022

Abstract
Background: The therapy to large or deep cystic brain metastases is a troublesome problem in clinical department. Stereotactic cyst aspiration combined with Gamma Knife radiosurgery can be an effective treatment for cystic brain metastases. However, there is still a possibility that reaccumulation of cystic fluid may lead to poor efficacy or even reoperation.Case presentation: We present a case of a 67-year-old man who diagnosed with brain metastasis of lung cancer. The intracranial lesion represented in imaging appeared to be cystic and located deep in the brain with the patient’s limb dysfunction. The patient did not respond well to chemotherapy and underwent cyst aspiration with ommaya reservoir implantation. Although turbid fluid may lead to postoperative tube blockage, we still implanted an ommaya reservoir. Repeated cystic fluid reaccumulation and exacerbation of symptoms occurred during treatment. Fortunately, the ommaya reservoir is not blocked. We performed repeated aspiration via ommaya reservoir to cope with such a situation and combined with radiotherapy. During the follow-up period of 14 months, the intracranial tumor was effectively and satisfactorily controlled.Conclusions: We highlight that an ommaya reservoir implantation during stereotactic cyst aspiration is necessary to prevent fluid reacclumulation avoiding the need for a second surgical procedure.
Changes in Thrombosis-Related Parameters After AstraZeneca COVID-19 Vaccination in A Male Volunteer: A Case Report
Authors: Hong Sae-Yong , Jun Sang-Sin , Seo Sang-Wook , Park Jeong-Rae , Im Joung-Il 
Published: March 2022

Abstract
Background
We speculated that subclinical thrombosis may occur frequently through crosstalk between immune/inflammatory reactions and hemostasis after corona virus disease-2019 (COVID-19) vaccination. To test this hypothesis, we measured thrombosis-related parameters after COVID-19 vaccination in a male volunteer for 21 days.
Case presentation:
The following parameters were measured a day before vaccination and on days 1, 3, 7, 14, and 21 after vaccination (AstraZeneca COVID-19 vaccine: ChAdOx1-S/nCoV-19, CTMAV563): complete blood count, platelet indices, thrombin receptor activating peptide-induced platelet aggregation, prothrombin time, activated partial thromboplastin time, D-dimer, thrombin–antithrombin III complex(TAT), plasmin-α2 antiplasmin complex (PAP), von Willebrand factor (vWF) antigen and activity, plasminogen activator inhibitor-1 (PAI-1), protein C and protein S antigen and activity, lupus anticoagulant, fibrinogen-degradation product, and plasminogen.TAT increased significantly from 0.7 ng/mL (baseline) to 21.7 ng/mL (day 1).There was a transient increase in the PAI-1 level from 7.2 ng/mL (baseline) to 10.9 ng/mL (day 3), followed by a decreased PAP level from 0.9 µg/mL (baseline) to 0.3 µg/mL (day 7), suggesting that plasmin generation is suppressed by PAI-1.
Conclusions
Increased thrombotic factors (such as decreased protein S) and decreased fibrinolytic activity due to increased PAI-1 were potential factors causing thrombogenesis after COVID-19 vaccination. Sequential measurement of platelet indices, TAT, PAP, protein C, protein S, vWF, D-dimer, and PAI-1 following COVID-19 vaccination was informative.
Gas distribution and optimal PEEP with lowest transpulmonary driving pressure (without esophageal pressure) during a PEEP trial. A post hoc analysis in patients with acute respiratory failure.
Authors: Grivans Christina , Stenqvist Ola 
Published: March 2022

Abstract
Background: A protective ventilation strategy should be based on assessment of lung mechanics and transpulmonary pressure (PTP), as this is the pressure that directly “hits” the lung. Protective ventilation with tidal volumes of 6 ml/kg ideal body weight is generally accepted, but there is no consensus on selection of optimal PEEP. We have shown that the change in end-expiratory lung volume (ΔEELV) is determined by the size of the PEEP step and the elastic properties of the lung (only), ΔEELV/ΔPEEP. Consequently, lung elastance (EL) can be determined as ΔPEEP/ΔEELV.The aim was to determine the PEEP level with lowest (least injurious) transpulmonary driving pressure and to identify what signifies high or low PEEP response.Methods: In ten patients with acute respiratory failure, global and ventral-dorsal tidal volume and ΔEELV were determined by inspiratory tidal volume calibrated EIT during a PEEP step procedure from 0 to 16 cmH2O. As the lung pressure/volume (P/V) curve coincides with the line connecting the end-expiratory airway P/V points, a complete lung P/V curve can be obtained for the whole lung or by combination with EIT, for the ventral and dorsal lung separately. Results: Global lung P/V curves showed marked individual variation with overall lung elastance of 7.0 – 23.2 cmH2O/L. Optimal PEEP level was 12.9 cmH2O (10-16) with ΔPTP of 4.1 cmH2O (2.8-7.6). The ratio of ΔPTP to airway driving pressure (ΔPAW), ΔPTP/ΔPAW, varied between patients and changed with changes of PEEP, making ΔPAW a less suitable surrogate for ΔPTP in individual patients. The two patients with highest EL were non-responders to PEEP with increasing global, ventral and dorsal lung elastance at high PEEP levels, indicating non-dependent over-distension. In patients with lower lung elastance, there was positive response to PEEP with successively lower lung elastance when increasing PEEP, especially in dorsal (dependent) lung. Conclusion: Only a two PEEP step up-down procedure is required for obtaining a full best-fit lung P/V curve, from which the PEEP level with the lowest transpulmonary driving pressure could be calculated. High PEEP response is signified by low lung elastance, which increases at high PEEP levels both globally and in dorsal lung.
“Compared to COVID, HIV is nothing”: exploring how onshore international students in an Australian City navigate COVID-19 versus BBV/STI risk
Authors: Okeke Sylvester Reuben 
Published: March 2022

Abstract
BackgroundThis study explored how the COVID-19 pandemic may be shaping BBV/STI risk and protective practices among international students. MethodsThis qualitative study interviewed 16 international university students in Sydney. Generated data were processed using NVivo and analysis was guided by reflexive thematic analysis.ResultsParticipants experienced elevated mental health distress because of the COVID-19 pandemic and some reported engaging in casual sexual hook-ups as a strategy to seek relief from the mental health distress they experienced. Some of those sexual hook-ups were condomless partly because COVID-related disruptions impacted condom accessibility during lockdowns. Also, the preventive practices of some participants who reported being sexually active during the lockdowns were focused on preventing COVID-19 while BBV/STI got lesser attention.ConclusionThis study indicates a need for comprehensive public health response to the near-endemic COVID-19 situation, that focuses on preventing the spread of COVID-19 and the sexual spread of BBVs and infections.
Willingness and motivations towards volunteering during the COVID-19 pandemic: a cross-sectional survey among final year medical students in Lagos, Nigeria
Authors: Adejimi Adebola Afolake , Okunade Kehinde Sharafadeen , Odukoya Olukemi Ololade , Roberts Alero Ann , Odugbemi Babatunde Adeniran , Osibogun Akin 
Published: March 2022

Abstract
Introduction: Increasing manpower capacity to meet the demands in the healthcare system is important during health emergencies. Medical students have roles to play during a pandemic but their involvement in these duties should be voluntary. The objective of this study was to assess the willingness and motivations of final year medical students in Lagos, Nigeria towards volunteering during the COVID-19 pandemic.Methods: A descriptive cross-sectional study was conducted among medical students in their sixth (final) year of study at the two public Universities in Lagos, Nigeria using total population sampling technique. A web-based questionnaire was used for data collection and data were analysed using SPSS. Logistic regression analysis was used to predict the willingness to volunteer.Results: The mean age of the respondents was 23.4years±2.6SD and 62.6% were female. About 65.9% of the medical students were willing to volunteer. Motivational factors which include self-rated good health status [OR: 2.1(95%CI: 1.16-3.6)], self-rated competence to work as a COVID-19 volunteer [OR: 6.5(95%CI: 3.61-11.54)] and availability of adequate protection and personal protective equipment [OR: 3.3(95%CI: 1.74-6.33)] significantly increased the odds of willingness to volunteer after controlling for other variables. Respondents’ opinions on settings where medical students can serve as volunteers during the COVID-19 pandemic include case management (21.7%) and telemedicine (85.8%).Conclusion: Medical students are willing to volunteer during the COVID-19 pandemic. There is a need to prepare and motivate the final year medical students by developing their skills to improve their competence and by providing adequate protection for the willing students to function as volunteers.