bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical evaluation of an authorized medical equipment based on high performance liquid chromatography for measurement of serum voriconazole concentration
Authors: Oda Kazutaka , Uchino Shota , Kurogi Kayo , Horikawa Mai , Matsumoto Naoya , Yonemaru Kou , Arakaki Hitomi , Katsume Taiki , Matsuyama Kaho , Katanoda Tomomi , Narita Yuki , Iwamura Koji , Jono Hirofumi , Saito Hideyuki 
Published: November 2021

Abstract
Background
Therapeutic drug monitoring for voriconazole is recommended for its optimum pharmacotherapy. Although the feedback of the measurement result of serum voriconazole concentration by outsourcing needs a certain time (days within a 1 week), there was no medical equipment for the measurement available in clinical practice. Recently, a medical equipment based on high performance liquid chromatography, named LM1010, has been developed and authorized for clinical use. In this study, to validate the clinical performance of LM1010, we compared the measured serum voriconazole concentrations by LM1010 with those by outsourcing measurement using liquid chromatography-tandem mass spectrometry.

Methods
We conducted the observational study approved by the institutional review board of Kumamoto University Hospital (No. 1786). Residual serum samples harvested for therapeutic drug monitoring were separated. Measured concentrations by LM1010 by the standard filter method (needs serum volume of > 400 μL) or the dilute method (needs serum volume of 150 μL) were compared with those by outsourcing, respectively. Acceptable measurement error range of 0.72–1.33 was considered. There were 69 serum samples, where the 35 or 34 samples were employed for evaluation of the standard filter method or the dilute method, respectively.

Results
The measured concentration using the standard filter method/outsourcing was 2.22/2.10 μg/mL as the median, 1.57–3.40/1.53–3.62 as the interquartile range, < 0.2–10.76/< 0.2–11.46 μg/mL as the range, while those using the dilute method/outsourcing was 2.36/2.29 μg/mL as the median, 1.08–2.94/1.03–3.06 as the interquartile range, 0.24–10.00/< 0.2–10.85 μg/mL as the range. The regression line for the standard filter method or the dilute method were y = 0.935x + 0.154 or y = 0.933x + 0.162, respectively. The standard filter method or the dilute method showed 11.4% samples (4/35, 95%CI 3.2–26.7%) or 8.8% samples (3/34, 95%CI 1.9–23.7%) out of the acceptable measurement error range, respectively.

Conclusion
Measurement of serum voriconazole concentration by LM1010 can be acceptable in clinical TDM practice.
Efficacy and safety of Cineole (Soledum®) in the treatment of patients with acute bronchitis: results of an open-label randomized clinical phase III study
Authors: Kardos Peter , Khaletskaya Olga , Kropova Olga 
Published: November 2021

Abstract
Background
Cineole has documented anti-inflammatory, expectorant, and mucolytic properties and has shown to be a valuable treatment option in different airway diseases. Our study examined whether a therapy with Cineole as add on to an antiviral therapy can relieve symptoms of acute bronchitis, and accelerate recovery in everyday practice.

Methods
In an open-label, randomized, parallel-group phase III clinical trial, 132 patients diagnosed with “acute bronchitis” or “acute tracheobronchitis” were included and treated with 3 × 200 mg of Cineole on top of antiviral treatment, or antiviral treatment alone (Ingavirin® 90 mg), per day for 4–9 days. The primary outcome measure was the change in cough frequency assessed in a Cough Frequency Assessment Scale, secondary outcomes were the total Bronchitis Severity Scale (BSS), as well as individual symptoms of the BSS score. Adverse events were collected for safety analysis. The study sites were located in Russia.

Results
After 4 days of therapy, there was a significant difference between the groups in favour of the patients treated with Cineole which persisted until the end of the study. At that time, cough during the day, assessed by the Cough Frequency Assessment Scale, was absent in 14 patients in the Cineole group (21.5%), compared to 4 (6.2%) patients in the control arm (p = 0.0203), which was replicated using the BSS individual cough score. In addition, significant improvements in the individual symptoms of the BSS in patients taking Cineole were documented.
The study drug showed good tolerability without differences to antiviral treatment and results were in line with previous experiences with this drug.

Conclusions
Assessment after 4 days of treatment with additional Cineole showed a significant reduction of cough frequency and other symptoms of acute bronchitis compared to antiviral treatment alone. In addition, patients recovered faster from the disease. Additional treatment with Cineole is a valuable treatment option in acute bronchitis.

Trial registration
Ministry of Health, Russia, No. 592. Registered 19 October 2015.
Drivers of understory plant communities in Sierra Nevada mixed conifer forests with pyrodiversity
Authors: Wilkin Kate , Ponisio Lauren , Fry Danny L. , Collins Brandon M. , Moody Tadashi , Stephens Scott L. 
Published: November 2021

Abstract
Background
Fire suppression in western North America increased and homogenized overstory cover in conifer forests, which likely affected understory plant communities. We sought to characterize understory plant communities and their drivers using plot-based observations from two contemporary reference sites in the Sierra Nevada, USA. These sites had long-established natural fire programs, which have resulted in restored natural fire regimes. In this study, we investigated how pyrodiversity—the diversity of fire size, severity, season, and frequency—and other environment factors influenced species composition and cover of forest understory plant communities.

Results
Understory plant communities were influenced by a combination of environmental, plot-scale recent fire history, and plot-neighborhood pyrodiversity within 50 m. Canopy cover was inversely proportional to understory plant cover, Simpson’s diversity, and evenness. Species richness was strongly influenced by the interaction of plot-based fire experience and plot-neighborhood pyrodiversity within 50 m.

Conclusions
Pyrodiversity appears to contribute both directly and indirectly to diverse understory plant communities in Sierra Nevada mixed conifer forests. The indirect influence is mediated through variability in tree canopy cover, which is partially related to variation in fire severity, while direct influence is an interaction between local and neighborhood fire activity.
Role of DWI in evaluation of HCC after radiofrequency ablation compared to dynamic MRI using MRI (3 T)
Authors: Elrefaey Hasan Bahaa Mohamed , Abd ElHamid Hanaa Abd ElKader , Khater Nivan Hany , ElGendy Waseem , Abdelrahman Ahmed S. 
Published: November 2021

Abstract
Background
The purpose of this study was to investigate the diagnostic performance of diffusion weight imaging (DWI), apparent diffusion coefficient (ADC) map, normalized ADC liver, and normalized ADC spleen compared to the dynamic contrast-enhanced MRI (DCE-MRI) in the evaluation of residual hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) using 3 T (T) magnetic resonance imaging (MRI).

Results
A prospective study was performed on 40 patients with radiofrequency-ablated HCC, and 15 (37.5%) patients had viable lesion post-RFA, while 25 (62.5%) had non-viable lesions. DCE-MRI had a sensitivity, specificity, and accuracy of 100%, 100%, and 100%, respectively, compared to DWI which had a sensitivity, specificity, and accuracy of 80%, 88%, and 85%, respectively, for identifying post-RFA viable HCC. The sensitivity, specificity, and accuracy of ADC at a cutoff value of 1.01 × 10−3 mm2/s were 80%, 100%, and 97.1%, respectively. The optimal cutoff value of normalized ADC liver was 0.81 with a sensitivity of 73.3%, specificity of 96%, and accuracy of 92.8%. The sensitivity, specificity, and accuracy of normalized ADC spleen at a cutoff value of 1.22 were 80%, 92%, and 91.1%, respectively.

Conclusions
DWI-MRI is a reliable technique for assessing HCC after radiofrequency ablation. DWI-MRI with ADC may be used as an alternate sequence for assessing radiofrequency-ablated lesions in individuals who have a contraindication to the contrast media, and the normalized ADC value may be of additional benefit.
The Tietz syndrome associated with cardiac malformation: a case report with literature review
Authors: Lakhdar Youssef , Abou El Houda Hind , Mounji Houda , Elfakiri Mehdi , Rochdi Youssef , Moutaouakil Abdeljalil , Raji Abdelaziz 
Published: November 2021

Abstract
Background
Tietz syndrome is a very rare clinical entity characterized by the association of profound bilateral congenital sensorineural deafness and generalized hypopigmentation of skin, eyes, and integuments (snow white appearance). It is an autosomal dominant syndrome due to a mutation in the melanocyte inducing transcription factor (MITF) gene. The association of a heart malformation has never been reported in this syndrome.

Case presentation
We report two cases of two cousins aged 5 years and 20 months respectively with a history of first degree consanguineous parents. Both girls presented with diffuse hypopigmentation of the skin, blond hair, blue eyes, and bilateral diffuse retinal hypopigmentation at ocular fundus exam. Bilateral profound sensorineural hearing loss was confirmed by auditory brainstem response in both cases. Echocardiography revealed a cardiac malformation such as interventricular communication in the older cousin and interatrial communication in the younger cousin. The family investigation did not reveal a similar case among ancestors. The diagnosis of Tietz syndrome was based on clinical criteria and pedigree. The older cousin underwent a total optical correction and a right unilateral cochlear implantation followed by speech therapy with a satisfactory result after a follow-up of two years. Unfortunately, the little cousin died following a head trauma.

Conclusions
Tietz syndrome is a rare autosomal dominant genetic disorder, characterized by generalized albinism with bilateral profound hearing loss. It results from a nontruncating mutation in the basic domain of in the MITF gene. Its management must include, in addition to hearing and ophthalmic rehabilitation, the research and treatment of cardiac malformations which may be life-threatening.
CAR-T Cells Targeting TSHR Demonstrate Safety and Potent Preclinical Activity Against Differentiated Thyroid Cancer
Authors: Li Hanning , Zhou Xiang , Wang Ge , Hua Dongyu , Li Shuyu , Xu Tao , Dong Menglu , Cui Xiaoqing , Yang Xue , Wu Yonglin , Cai Miaomiao , Liao Xinghua , Zhang Tongcun , Yang Zhifang , Du Yaying , Li Xingrui 
Published: November 2021

Abstract

Background
Chimeric antigen receptor T cells (CAR-Ts) have demonstrated remarkable efficacy in hematological cancers but have not yet translated in treating solid tumors. The significant hurdles limiting CAR-T therapy were from a paucity of differentially expressed cell surface molecules on solid tumors that can be safely targeted. Here, we present TSH receptor (TSHR) as a putative target for CAR-T therapy of differentiated thyroid cancer (DTC).

Methods
We undertook a large-scale screen on thyroid cancer tissues and multiple internal organs through bioinformatical analysis and immunohistochemistry to date TSHR expression. Using 3 previously described monoclonal antibodies, we generated 3 third-generation CAR-Ts. We tested anti-TSHR CAR-T in vitro activity by T-cell function and killing assay. Then we tested preclinical therapeutical efficacy in a xenograft mouse model of DTC and analyzed mice’s physical conditions and histological abnormalities to evaluate anti-TSHR CAR-T’s safety.

Results
TSHR is highly and homogeneously expressed on 90.8% (138/152) of papillary thyroid cancer, 89.2% (33/37) of follicular thyroid cancer, 78.2% (18/23) of cervical lymph node metastases, and 86.7% of radioactive iodine resistance diseases. We developed 3 novel anti-TSHR CAR-Ts from monoclonal antibodies M22, K1-18, and K1-70; all 3 CAR-Ts mediate significant antitumor activity in vitro. Among these, we demonstrate that K1-70 CAR-T can have therapeutical efficacy in vivo, and no apparent toxicity has been observed.

Conclusion
TSHR is a latent target antigen of CAR-T therapy for DTC. Anti-TSHR CAR-T could represent a therapeutic option for patients with locoregional relapsed or distant metastases of thyroid cancer and should be tested in carefully designed clinical trials.
Primary Hyperparathyroidism Is Associated With Shorter QTc Intervals, but Not Arrhythmia
Authors: Stewart Latoya A , Steinl Gabrielle K , Huang Bernice L , McManus Catherine , Lee James A , Kuo Jennifer H , Walker Marcella D 
Published: November 2021

Abstract

Context
Primary hyperparathyroidism (PHPT) is associated with subclinical cardiovascular disease, but data regarding cardiac conduction abnormalities are limited.

Objective and Design
Retrospective cross-sectional comparison of cardiac conduction in patients with PHPT or thyroid disease (TD).

Participants and Setting
Patients ≥40 years old who underwent parathyroidectomy or thyroidectomy at a single tertiary institution from 2013 to 2018.

Methods and Outcomes
Demographics and preoperative electrocardiogram (EKG) parameters were compared using the Mann-Whitney U, chi-square test, and linear regression.

Results
A total of 1242 patients were included: 49.8% PHPT (n = 619) and 50.2% TD (n = 623). Median age was 60.5 years [interquartile range (IQR) 53.6-67.9]. Compared to controls, PHPT patients had higher median serum calcium [10.7 mg/dL (IQR 10.4-11.1) vs 9.5 mg/dL (IQR 9.3-9.8), P &lt; 0.001] as expected, as well as, a higher prevalence of hyperlipidemia (49% vs 36%, P &lt; 0.001) and hypertension (50.1% vs 42.2%, P &lt; 0.01). Based on EKG, there was no difference in PR interval or the prevalence of arrhythmia, atrioventricular block, ST segment/T wave changes, premature ventricular complexes, right bundle branch block, or left bundle branch block after adjusting for covariates. The PHPT group had a lower mean corrected QT interval (414 ± 24) ms vs 422 ± 24 ms, P &lt; 0.01), adjusted for covariates. Serum calcium predicted QTc independently of age, sex, and other covariates.

Conclusions
In the largest study to date, PHPT patients had shorter QTc intervals compared to TD controls but no increased prevalence of arrhythmia based on preoperative EKG.
Are simple verbal instructions sufficient to ensure that bladder volume does not deteriorate prostate position reproducibility during spot scanning proton therapy?
Authors: Nishioka Kentaro , Gotoh Kento , Hashimoto Takayuki , Abe Takashige , Osawa Takahiro , Matsumoto Ryuji , Yokota Isao , Katoh Norio , Kinoshita Rumiko , Yasuda Koichi , Yakabe Toshiaki , Yoshimura Takaaki , Takao Seishin , Shinohara Nobuo , Aoyama Hidefumi , Shimizu Shinichi , Shirato Hiroki 
Published: November 2021

Objectives: The purpose of this study is to investigate whether verbal instructions are sufficient for bladder volume (BV) control not to deteriorate prostate position reproducibility in image-guided spot scanning proton therapy (SSPT) for localized prostate cancer. Methods: A total of 268 treatment sessions in 12 consecutive prostate cancer patients who were treated with image-guided SSPT with fiducial markers were retrospectively analyzed. In addition to strict rectal volume control procedures, simple verbal instructions to void urine one hour before the treatment were used here. The BV was measured by a Bladder Scan just before the treatment, and the prostate motion was measured by intraprostatic fiducial markers and two sets of X-ray fluoroscopy images. The correlation between the BV change and prostate motion was assessed by linear mixed-effects models and systematic and random errors according to the reproducibility of the BV. Results: The mean absolute BV change during treatment was from −98.7 to 86.3 ml (median 7.1 ml). The mean absolute prostate motion of the patients in the left-right direction was −1.46 to 1.85 mm; in the cranial-caudal direction it was −6.10 to 3.65 mm, and in the anteroposterior direction −1.90 to 5.23 mm. There was no significant relationship between the BV change and prostate motion during SSPT. The early and late genitourinary and gastrointestinal toxicity was minimal with a minimum follow up of 4.57 years. Conclusions: Simple verbal instructions about urination was suggested to be sufficient to control the BV not to impact on the prostate motion and clinical outcomes in image-guided SSPT. Careful attention to BV change is still needed when the seminal vesicle is to be treated. Advances in knowledge: Our data demonstrated that there was no apparent relationship between BV changes and prostate position reproducibility and simple verbal instruction about urination could be sufficient for image-guided SSPT.
KnowMore: an automated knowledge discovery tool for the FAIR SPARC datasets
Authors: Quey Ryan , Schiefer Matthew A. , Kiran Anmol , Patel Bhavesh 
Published: November 2021

Background: This manuscript provides the methods and outcomes of KnowMore, the Grand Prize winning automated knowledge discovery tool developed by our team during the 2021 NIH SPARC FAIR Data Codeathon. The National Institutes of Health Stimulating Peripheral Activity to Relieve Conditions (NIH SPARC) program generates rich datasets from neuromodulation researches, curated according to the Findable, Accessible, Interoperable, and Reusable (FAIR) SPARC data standards. Currently, the process of simultaneously comparing and analyzing multiple SPARC datasets is tedious because it requires investigating each dataset of interest individually and downloading all of them to conduct cross-analyses. It is crucial to enhance this process to enable rapid discoveries across SPARC datasets. Methods: To fill this need, we created KnowMore, a tool integrated into the SPARC Portal that only requires the user to select their datasets of interest to launch an automated discovery process. KnowMore uses several SPARC resources (Pennsieve, o²S²PARC, SciCrunch, protocols.io, Biolucida), data science methods, and machine learning algorithms in the back end to generate various visualizations in the front end intended to help the user identify potential similarities, differences, and relations across the datasets. These visualizations can lead to a new discovery, new hypothesis, or simply guide the user to the next logical step in their discovery process. Results: The outcome of this project is a SPARC portal-ready code architecture that helps researchers to use SPARC datasets more efficiently and fully leverages their FAIR characteristics. The tool has been built and documented such that more data analysis methods and visualization items could be easily added. Conclusions: The potential for automated discoveries from SPARC datasets is huge given the unique SPARC data ecosystem promoting FAIR data practices, and KnowMore has only demonstrated a small highlight of what could be achieved to speed up discoveries from SPARC datasets.
Socio-demographic and social support factors related to substance use in South African in-school adolescents: Insights from the Girls Achieve Power (GAP Year) trial in three peri-urban settings
Authors: Gordon Kerry , Kutywayo Alison , Frade Sasha , Naidoo Nicolette , Mullick Saiqa 
Published: November 2021

Background: Substance use is a significant public health problem worldwide, with consequences including violence, risky behaviours, and even death. Substance use amongst adolescents is increasing in South Africa, and limited research on frequency, risk and protective factors means that prevention interventions are difficult to design. This paper aims to describe and discuss factors associated with substance use among school-going adolescents in three peri-urban South African settings. Methods: A cross-sectional analysis was conducted using baseline data from participants in the Girls Achieve Power (GAP Year) trial. Grade 8 learners (N=2383), aged 11-18, were recruited from 26 lowest quintile public high schools in three townships: Soweto and Thembisa in Gauteng Province, and Khayelitsha in Western Cape Province. A baseline survey gathered demographic and behavioural data. Questions relevant to substance use and social support were used for this analysis. Multivariate logistic regression analyses were conducted to identify factors associated with substance use. The final variables were included in an unadjusted and adjusted logistic regression for current substance use, and a multinomial logistic regression for frequency of substance use. Results: A total of 22.5% (534) of participants indicated they had ever used substances. Being male was strongly associated with substance use (P<0.001), and less strongly with frequency of substance use. Age significantly predicted substance use, with older adolescents being more likely to engage in substance use (P<0.001); having a parent/guardian employed was negatively associated with substance use (P=0.021). Family-related social support variables were predictive of substance use. Being able to count on friends when things went wrong was predictive of lower frequency of substance use (P=0.019). Conclusions: These results can inform the targeting of prevention interventions to males and younger learners, as well as ensuring youth interventions build family and peer support to make substance use less likely and less frequent.
Effect of resident and assessor gender on entrustment-based observational assessment in an internal medicine residency program
Authors: Weber Danielle E. , Kinnear Benjamin , Kelleher Matthew , Klein Melissa , Sall Dana , Schumacher Daniel J. , Zhang Nanhua , Warm Eric , Schauer Daniel P. 
Published: November 2021

Background: Implicit gender bias leads to differences in assessment. Studies examining gender differences in resident milestone assessment data demonstrate variable results. The purpose of this study was to determine if observational entrustment scores differ by resident and assessor gender in a program of assessment based on discrete, observable skills. Methods: We analyzed overall entrustment scores and entrustment scores by Accreditation Council for Graduate Medical Education (ACGME) core competency for 238 residents (49% female) from 396 assessors (38% female) in one internal medicine residency program from July 2012 to June 2019. We conducted analyses at 1-12 months, 1-36 months, 1-6 months, 7-12 months, and 31-36 months. We used linear mixed-effect models to assess the role of resident and assessor gender, with resident-specific and assessor-specific random effect to account for repeated measures. Results: Statistically significant interactions existed between resident and assessor gender for overall entrustment at 1-12 months (p < 0.001), 1-36 months (p< 0.001), 1-6 months (p<0.001), 7-12 months (p=0.04), and 31-36 months (p<0.001). However, group differences were not statistically significant. In several instances an interaction was significant between resident and assessor gender by ACGME core competency, but there were no statistically significant group differences for all competencies at any time point. When applicable, subsequent analysis of main effect of resident or assessor gender independently of one another revealed no statistically significant differences. Conclusions: No significant differences in entrustment scores were found based on resident or assessor gender in our large, robust entrustment-based program of assessment. Determining the reasons for our findings may help identify ways to mitigate gender bias in assessment.