bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiologically Based Pharmacokinetic Modeling Approaches for Patients With SARS‐CoV‐2 Infection: A Case Study With Imatinib
Authors: Adiwidjaja Jeffry , Adattini Josephine A. , Boddy Alan V. , McLachlan Andrew J. 
Published: April 2022

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, which causes coronavirus disease 2019 (COVID‐19), manifests as mild respiratory symptoms to severe respiratory failure and is associated with inflammation and other physiological changes. Of note, substantial increases in plasma concentrations of α1‐acid‐glycoprotein and interleukin‐6 have been observed among patients admitted to the hospital with advanced SARS‐CoV‐2 infection. A physiologically based pharmacokinetic (PBPK) approach is a useful tool to evaluate and predict disease‐related changes on drug pharmacokinetics. A PBPK model of imatinib has previously been developed and verified in healthy people and patients with cancer. In this study, the PBPK model of imatinib was successfully extrapolated to patients with SARS‐CoV‐2 infection by accounting for disease‐related changes in plasma α1‐acid‐glycoprotein concentrations and the potential drug interaction between imatinib and dexamethasone. The model demonstrated a good predictive performance in describing total and unbound imatinib concentrations in patients with SARS‐CoV‐2 infection. PBPK simulations highlight that an equivalent dose of imatinib may lead to substantially higher total drug concentrations in patients with SARS‐CoV‐2 infection compared to that in patients with cancer, while the unbound concentrations remain comparable between the 2 patient populations. This supports the notion that unbound trough concentration is a better exposure metric for dose adjustment of imatinib in patients with SARS‐CoV‐2 infection, compared to the corresponding total drug concentration. Potential strategies for refinement and generalization of the PBPK modeling approach in the patient population with SARS‐CoV‐2 are also provided in this article, which could be used to guide study design and inform dose adjustment in the future.
Green synthesis, characterization, antibacterial activity of metal nanoparticles and composite oxides using leaves extract of Ocimum basilicum L
Authors: Rahman Taj Ur , Anwar Muhammad Rashad , Zeb Muhammad Aurang , Liaqat Wajiha 
Published: April 2022

AbstractNanoparticles plays a key role in the development of novel antibacterial substances against various pathogenic microorganisms. These nanoparticles due to their smaller size could be very effective as they can improve the antibacterial activity through lysis of bacterial cell wall. In the present research work, ZnO, MgO, NiO, AlO nanoparticles, and MgNiO, and AlZnO composite oxides were synthesized by green method from Ocimum basilicum leaves extract. The nanoparticles formed were evaluated using FTIR, XRD, EDX, and SEM to confirm the formation of NPs and to determine the morphology, elemental composition, shape and size, composition, and nature of bonds present in the NPs. Further, the NPs were tested for their antibacterial activity. In particular, ZnO NPs showed a good inhibitory effect against Pseudomonas aeruginosa with 20 mm zone of inhibition. Hence, the process reported herein could be optimized for large‐scale preparation of NPs.Research Highlights
Green synthesis of ZnO, MgO, NiO, AlO nanoparticles, and MgNiO, and AlZnO composite oxides using Ocimum basilicum leaves extract
NPs were characterized by various established characterization techniques like FTIR, XRD, EDX, and SEM.
NPs showed antibacterial activity which was investigated by agar well diffusion method against Bacillus cereus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus.
The method proved to be very simple, cost‐efficient, and convenient.
Mechanism evolution and prediction of carbamazepine sorption by mangrove plant residue–derived biochars
Authors: Wu Lin , Li Yasong , Kong Xiangke , Zhu Xiaohua 
Published: April 2022

AbstractA mechanism for carbamazepine (CBZ) sorption by mangrove plant residue–derived biochars pyrolyzed at 200–700 °C (referred as MPR200–MPR700) was elucidated in this study. The experimental results demonstrated that the dominant sorption mechanism of biochars for CBZ was evolved from partition to adsorption with increasing pyrolysis temperature. The CBZ concentration–dependent contributions of partition and adsorption were controlled by the relative noncarbonized and carbonized fractions of biochars. The partition medium changed from a polymeric aliphatic fraction (mangrove plant residue [MPR]200–MPR400) to a more condensed aromatic phase (MPR500–MPR600), which made the partition less favorable. Meanwhile, the adsorption was selectively regulated by polarity (MPR200–MPR300) and porosity (MPR400–MPR700) for different biochars. A pragmatic model including the sorbent aromaticity index (H/C) was put forward to predict CBZ sorption to MPR200–MPR700 and other carbonaceous materials reported in the literature. The findings can be helpful in understanding CBZ–biochar interactions and developing effective sorbents (such as biochars) for pollutant sequestration.
Cardiology clinic patient attitudes toward and potential personal utility of genetic testing: Findings from a unique multiracial clinical sample
Authors: Erickson Claire M. , Clark Lindsay R. , Umucu Emre , Vo Nhi H. , Volgman Annabelle Santos , Chin Nathaniel A. , Ketchum Fred B. , Jones Carolyn H. , Gleason Carey E. , Aggarwal Neelum T. 
Published: April 2022

AbstractAs more is understood about the hereditary nature of disease risk, the utility of genetic testing within cardiovascular medicine is increasingly being explored. Although testing may afford more personalized risk stratification, there is a paucity of information regarding patient knowledge, attitudes, and beliefs toward genetic testing among cardiology patients. Participants (n = 530) recruited primarily from a cardiology clinic filled out a 41‐item written questionnaire assessing knowledge, beliefs, and attitudes toward genetic testing, motivators and detractors for considering genetic testing, and perceived likelihood for behavior change after hypothetical genetic testing risk stratification. Path analysis was used to test the hypothetical models predicting the likelihood of getting a genetic test and making behavior changes following genetic testing. The patient population was late‐middle‐aged (59.0 ± 14.5 years), majority women (61.5%), and about half reported having a bachelor's degree. 58.1% of participants self‐identified as White, 25.7% as African American or Black, 6.8% as Spanish, Latino, or Hispanic, 3.0% as Asian or Pacific Islander, and 0.5% as Native American. Gender (being a woman) and more years of education were related to greater knowledge about genetic testing. Racial identity and years of education were related to beliefs about genetic testing. Beliefs, but not knowledge, were related to more positive attitudes and a higher likelihood of pursuing genetic testing. Positive attitudes were related to greater perceived personal control (PPC). Furthermore, attitudes and PPC were related to higher likelihood of lifestyle change after genetic testing. These results highlight the need to integrate the experiences of racialized communities into education/counseling efforts. Most educational counseling efforts lack a nuanced discussion of social determinants of health or beliefs. In addition to factual information, educational counseling must also address people's beliefs, concerns, and the intersecting experiences and identities, which shape patients' relationships with the evolving landscape of healthcare and personalized medicine.
Improving gender‐affirming care in genetic counseling: Using educational tools that amplify transgender and/or gender non‐binary community voices
Authors: Huser Nicole , Hulswit Bailey B. , Koeller Diane R. , Yashar Beverly M. 
Published: April 2022

AbstractTransgender and/or gender non‐binary (TGNB) individuals face significant health care disparities, including deficiencies in provider knowledge. To address this knowledge gap for genetic counselors, we developed, implemented, and analyzed an educational intervention on gender‐affirming genetic counseling (GC) and care for TGNB patients. In partnership with the TGNB community, we designed a 5‐module (length = 146 min ± 94 min) genetic counseling‐targeted online learning program focused on gender‐affirming care (Amplify). Content included elements of gender‐affirming care, core components of gender‐inclusive GC sessions, and cancer risk assessment/management. Video testimonials featuring TGNB individuals complemented learning within each module. Educational outcomes measured included comfort working with TGNB patients (n = 2 multiple choice questions (MCQs)), impact of education on knowledge (n = 25 MCQs), and clinical self‐efficacy based on the Accreditation Council for Genetic Counseling competencies (n = 35 skills). Participants (n = 40), recruited through state and national GC organizations, completed all modules, and pre‐ and post‐education/self‐efficacy assessments. Pre‐Amplify, 65% (n = 26/40) of participants endorsed feeling ‘somewhat comfortable’ working with TGNB patients. The average knowledge score was 77.6% (SD = 11.2%) with the lowest scores related to the gender affirmation process. After Amplify, overall knowledge improvement was statistically significant with an average 16.9% (p < 0.001) increase in score. Pre‐Amplify, the average self‐efficacy score was 78.4% (SD = 15.8%) with lowest scores seen in statements surrounding information gathering of family and medical histories. Post‐Amplify, overall self‐efficacy improvement was statistically significant with an average 13.8% (p < 0.001) increase in score. Linear regression did not identify an impact of practice specialty on participants’ knowledge gains or self‐efficacy. This study shows online modules are an effective form of gender‐affirming care education for GCs. This intervention can positively improve the care practicing genetic counselors provide to patients and inform future decision‐making about the development of gender‐affirming care education for genetic counselors.
Investigating factors that influence genetic counselors’ decisions to refer patients to mental health providers
Authors: Hayes Taylor , Cunningham Mitchell , Trepanier Angela 
Published: April 2022

AbstractGenetic counselors (GC) serve patients who are often in distress at the time of their consultation. GC competency includes providing short‐term, client‐centered counseling, while using community resources, such as mental health providers (MHPs), for psychosocial support. The purpose of this study was to assess the mental health referral practices of GCs; specifically, the rate of referrals, factors influencing a GC’s decision to refer, and barriers to referrals. GCs working in direct patient care for at least one year were recruited to take a novel 27 question survey created based on the results of a previous qualitative study. A link to the web‐based survey was distributed through the National Society of Genetic Counselors Student Research Program and American Board of Genetic Counselors by email. A total of 144 individuals opened the survey for an estimated response rate of 3%. A majority of respondents (54.3%) reported they assess a patient's need for a mental health referral at least half of the time. The mean number of referrals made in the past 12 months was 5.13. After post‐hoc analyses, there were no differences in referral rates between specialties. Common referral indications included patient history of mental illness, distress about having a genetic condition, and limited social support. Common barriers to referral were financial or insurance related, patient receptiveness, and the patient not perceiving a benefit. GCs felt that providing psychosocial support is within their scope of practice, but that MHPs are better equipped to manage long‐term needs and those related to a mental health condition. This study provides insight into how GCs decide when they can manage patient distress, circumstances that prompt a referral to MHPs, and barriers. Recognizing common referral indications and barriers may lead to better strategies for connecting patients with such services.
Steroid therapy still plays a crucial role and could serve as a bridge to the next promising treatments in patients with IgG4‐related sclerosing cholangitis: Results of a Japanese nationwide study
Authors: Kubota Kensuke , Kamisawa Terumi , Nakazawa Takahiro , Tanaka Atsushi , Naitoh Itaru , Takikawa Hajime , Unno Michiaki , Kawa Shigeyuki , Masamune Atsushi , Nakamura Seiji , Okazaki Kazuichi ,   Collaborators
Published: April 2022

AbstractObjectiveThe acceptable duration of steroid therapy for patients with IgG4‐sclerosing cholangitis (SC) has been under debate. Our aim is to clarify the feasible duration of steroid treatment.DesignWe retrospectively reviewed the data of patients with IgG4‐SC and analyzed the following: biliary status during the steroid therapy, incidence of remission, relapse, relapse‐free survival rate, and steroid‐related complications (SRCs).ResultsRemission was achieved in 99.5% (763/767) of patients who received steroid therapy, while the remission rate dropped to 63.6% (78/129) of patients who did not receive it. Relapse was noted in 19.7% (151/763) of the patients who received steroid. Besides, relapse rate went up 38.4% (30/78) of the counterpart. Normalization of the serum total bilirubin and serum alkaline phosphatase levels were achieved at 2 weeks regardless of biliary drainage. Multivariate analysis identified younger onset, MST less than 3 years, immunosuppressant, and steroid cessation as independent risk factors for relapse. Steroid‐free was achieved in the patients underwent MST only 3.4% over 54 months. SRCs were recorded in a total of 99 patients (12.9%) despite sufficient preemptive medications. Multivariate analysis identified history of malignancy and immunosuppressant as independent risk factors for SRCs.ConclusionSteroid therapy should be continued for no <3 years to reduce the risk of relapse, with use of preemptive measures taken around 5 years. The biliary drainage might not be mandatory. Steroid as 1st line therapy could serve as a bridge to further promising treatments.
Influence of early identification and therapy on long‐term outcomes in early‐onset MTHFR deficiency
Authors: Yverneau Mathilde , Leroux Stéphanie , Imbard Apolline , Gleich Florian , Arion Alina , Moreau Caroline , Nassogne Marie‐Cécile , Szymanowski Marie , Tardieu Marine , Touati Guy , Bueno María , Chapman Kimberly A. , Chien Yin‐Hsiu , Huemer Martina , Ješina Pavel , Janssen Mirian C. H. , Kölker Stefan , Kožich Viktor , Lavigne Christian , Lund Allan Meldgaard , Mochel Fanny , Morris Andrew , Pons Mónica Ruiz , Porras‐Hurtado Gloria Liliana , Benoist Jean‐François , Damaj Léna , Schiff Manuel ,   E‐HOD Consortium
Published: April 2022

AbstractMTHFR deficiency is a severe inborn error of metabolism leading to impairment of the remethylation of homocysteine to methionine. Neonatal and early‐onset patients mostly exhibit a life‐threatening acute neurologic deterioration. Furthermore, data on early‐onset patients' long‐term outcomes are scarce. The aims of this study were (1) to study and describe the clinical and laboratory parameters of early‐onset MTHFR‐deficient patients (i.e., ≤3 months of age) and (2) to identify predictive factors for severe neurodevelopmental outcomes in a cohort with early and late onset MTHFR‐deficient patients. To this end, we conducted a retrospective, multicentric, international cohort study on 72 patients with MTHFR deficiency from 32 international metabolic centres. Characteristics of the 32 patients with early‐onset MTHFR deficiency were described at time of diagnosis and at the last follow‐up visit. Logistic regression analysis was used to identify predictive factors of severe neurodevelopmental outcome in a broader set of patients with early and non‐early‐onset MTHFR deficiency. The majority of early‐onset MTHFR‐deficient patients (n = 32) exhibited neurologic symptoms (76%) and feeding difficulties (70%) at time of diagnosis. At the last follow‐up visit (median follow‐up time of 8.1 years), 76% of treated early‐onset patients (n = 29) exhibited a severe neurodevelopmental outcome. Among the whole study population of 64 patients, pre‐symptomatic diagnosis was independently associated with a significantly better neurodevelopmental outcome (adjusted OR 0.004, [0.002–0.232]; p = 0.003). This study provides evidence for benefits of pre‐symptomatic diagnosis and appropriate therapeutic management, highlighting the need for systematic newborn screening for MTHFR deficiency and pre‐symptomatic treatment that may improve outcome.
Reproductive genetic carrier screening and inborn errors of metabolism: The voice of the inborn errors of metabolism community needs to be heard
Authors: Kirk Edwin P. , Delatycki Martin B. , Laing Nigel 
Published: April 2022

AbstractReproductive genetic carrier screening (RGCS) has a history spanning more than 50 years, but for most of that time has been limited to screening for one or a few conditions in targeted population groups. The advent of massively parallel sequencing has led to rapid growth in screening for panels of up to hundreds of genes. Such panels typically include numerous genes associated with inborn errors of metabolism (IEM). There are considerable potential benefits for families from screening, but there are also risks and potential pitfalls. The IEM community has a vital role to play in guiding gene selection and assisting with the complexities that arise from screening, including interpreting complex biochemical assays and counselling at‐risk couples about phenotypes and treatments.
Gender and victim stereotypes in perceptions of child sexual abuse in Puerto Rico
Authors: Vázquez‐Tirado Sigrid 
Published: April 2022

AbstractFactors such as cultural norms and stereotypes influence how child sexual abuse (CSA) is perceived in relation to gender of the offender and perceptions of responsibility and harm in Puerto Rico. Finkelhor and Browne's traumagenic dynamics model served as the theoretical framework for the investigation because it addresses four key factors related to the experience of CSA victims. A total of 525 people living in Puerto Rico participated in the study. They were asked to read a hypothetical case of CSA by a teacher with a minor student and answer related questions. Point‐biserial correlational analyses were used to assess the influence of gender of the offender on perceptions of CSA. Results of the study indicated the male offender was attributed more responsibility and harm for the offence. Both male and female minor victims were identified by participants as partly responsible for the offence. Male and female offenders were identified as victims. Findings of this study could help to improve understanding of cultural differences in perceptions of CSA cases and its consequences.
Accelerating Cardiac Diffusion Tensor Imaging With a U‐Net Based Model: Toward Single Breath‐Hold
Authors: Ferreira Pedro F. , Banerjee Arjun , Scott Andrew D. , Khalique Zohya , Yang Guang , Rajakulasingam Ramyah , Dwornik Maria , De Silva Ranil , Pennell Dudley J. , Firmin David N. , Nielles‐Vallespin Sonia 
Published: April 2022

BackgroundIn vivo cardiac diffusion tensor imaging (cDTI) characterizes myocardial microstructure. Despite its potential clinical impact, considerable technical challenges exist due to the inherent low signal‐to‐noise ratio.PurposeTo reduce scan time toward one breath‐hold by reconstructing diffusion tensors for in vivo cDTI with a fitting‐free deep learning approach.Study typeRetrospective.PopulationA total of 197 healthy controls, 547 cardiac patients.Field strength/sequenceA 3 T, diffusion‐weighted stimulated echo acquisition mode single‐shot echo‐planar imaging sequence.AssessmentA U‐Net was trained to reconstruct the diffusion tensor elements of the reference results from reduced datasets that could be acquired in 5, 3 or 1 breath‐hold(s) (BH) per slice. Fractional anisotropy (FA), mean diffusivity (MD), helix angle (HA), and sheetlet angle (E2A) were calculated and compared to the same measures when using a conventional linear‐least‐square (LLS) tensor fit with the same reduced datasets. A conventional LLS tensor fit with all available data (12 ± 2.0 [mean ± sd] breath‐holds) was used as the reference baseline.Statistical testsWilcoxon signed rank/rank sum and Kruskal–Wallis tests. Statistical significance threshold was set at P = 0.05. Intersubject measures are quoted as median [interquartile range].ResultsFor global mean or median results, both the LLS and U‐Net methods with reduced datasets present a bias for some of the results. For both LLS and U‐Net, there is a small but significant difference from the reference results except for LLS: MD 5BH (P = 0.38) and MD 3BH (P = 0.09). When considering direct pixel‐wise errors the U‐Net model outperformed significantly the LLS tensor fit for reduced datasets that can be acquired in three or just one breath‐hold for all parameters.Data conclusionDiffusion tensor prediction with a trained U‐Net is a promising approach to minimize the number of breath‐holds needed in clinical cDTI studies.Evidence Level4Technical EfficacyStage 1
Modified volumetric modulated arc therapy technique with reduced planning and treatment time for craniospinal irradiation utilising two isocentres
Authors: Nguyen Minh , Dang Thu , Deegan Liz , Henry Kelsie , Jones Scott , Pullar Andrew , Cheuk Robyn , Gibbs Adrian , Sim Lucy , Hargrave Catriona 
Published: April 2022

AbstractIntroductionPaediatric patients (individuals below 18 years of age) requiring cranial‐spinal irradiation (CSI) at our institution are commonly planned and treated using a three isocentre (3‐ISO) volumetric modulated arc therapy (VMAT) technique. A modified two isocentre (2‐ISO) VMAT technique was investigated with the aim to improve workflow and reduce planning and treatment time.MethodsFive CSI paediatric patients previously treated with a 3‐ISO VMAT technique were retrospectively replanned using a 2‐ISO VMAT technique. The 2‐ISO VMAT plans were reviewed and approved by a radiation oncologist (RO) before undergoing patient‐specific quality assurance (QA) procedures, performed by a radiation oncology medical physicist (ROMP). Planning target volume (PTV) coverage, organ‐at‐risk (OAR) dose as well as planning and treatment durations of the first five patients utilising 2‐ISO technique were compared with 3‐ISO technique.ResultsThe average percentage difference in PTV coverage by 95% reference dose between the 2‐ISO and 3‐ISO is 0.14%, and the average difference in OAR median dose is 0.68 Gy. Conformity and homogeneity indices have the same averages at 1.18 and 0.4 respectively. Patient‐specific physics QA results were all comparable with the 3‐ISO averages at 98.84% and the 2‐ISO at 98.71%. Planning duration for the 2‐ISO was reduced by up to 75%, and daily treatment duration was reduced by up to 50%. Of all the previously treated CSI patients using a 3‐ISO technique, 45% were suitable for the 2‐ISO technique.ConclusionThe 2‐ISO VMAT technique provided comparable dose distribution based on PTV coverage, OAR dose and plan metric indices. Reduced planning and treatment duration with the 2‐ISO technique facilitated improved workflow with decreased sedation time for paediatric patients requiring a general anaesthesia.