bluuebunny/crossref_metadata_2025 huggingface dataset:
Pretreatment lymphocyte count as independent prognostic factor in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy
Authors: Thiangphak Ekasak , Pruegsanusak Korrawit , Buhachat Rakchai
Published: April 2022

Objective

To evaluate the association between pretreatment total lymphocyte counts (TLC) and survival outcome in locally advanced cervical cancer (LACC) patients treated with definite concurrent chemoradiotherapy (CCRT).

Methods

We retrospectively reviewed the data of 789 patients diagnosed with cervical cancer stage IIB to IVA treated with CCRT between January 2011 and December 2015. We assessed the association of pretreatment TLC with 5‐year disease‐free survival (DFS) and overall survival (OS) rates.

Results

Fifty‐two patients had pretreatment TLC < 1000 cells/mm3. The median pretreatment TLC in TLC groups <1000 cell/mm3 and ≥1000 cell/mm3 were 573.9 cells/mm3 (range, 350.9–827.7 cells/mm3) and 2211.3 cells/mm3 (range, 1751.3–2785.8 cells/mm3), respectively. Patients in pretreatment TLC < 1000 cell/mm3 group had a lower number of treatment responses. The 5‐year DFS and OS rates were significantly higher in patients with pretreatment TLC ≥ 1000 cells/mm3 than their counterparts (67.7% vs. 35.4% [P < 0.0001] and 57.6% vs. 25.7% [P < 0.0001], respectively). In multivariate analysis, pretreatment TLC ≥ 1000 cells/mm3 was an independent predictor of DFS (HR, 0.39; 95% confidence interval [CI] 0.26–0.59, P < 0.001) and OS (HR, 0.59; 95% CI 0.42–0.84, P = 0.006).

Conclusion

Pretreatment TLC was associated with treatment response and survival outcome in patients with LACC treated with definite CCRT.
Longitudinal assessment of the effect of alkali burns on corneal biomechanical properties using optical coherence elastography
Authors: Mekonnen Taye , Lin Xiao , Zevallos‐Delgado Christian , Singh Manmohan , Aglyamov Salavat R. , Coulson‐Thomas Vivien J. , Larin Kirill V.
Published: April 2022

Eye injury due to alkali burn is a severe ocular trauma that can profoundly affect corneal structure and function, including its biomechanical properties. Here, we assess the changes in the mechanical behavior of mouse corneas in response to alkali‐induced injury by conducting longitudinal measurements using optical coherence elastography (OCE). A non‐contact air‐coupled ultrasound transducer was used to induce elastic waves in control and alkali‐injured mouse corneas in vivo, which were imaged with phase‐sensitive optical coherence tomography. Corneal mechanical properties were estimated using a modified Rayleigh–Lamb wave model, and results show that Young's modulus of alkali‐burned corneas were significantly greater than that of their healthy counterparts on days 7 (p = 0.029) and 14 (p = 0.026) after injury. These findings, together with the changes in the shear viscosity coefficient postburn, indicate that the mechanical properties of the alkali‐burned cornea are significantly modulated during the wound healing process.
Detection of intralayer alignment in multicomponent lipids by dynamic speckle pattern analysis
Authors: Panahi Majid , Rad Vahideh Farzam , Sasan Shiva , Jamali Ramin , Moradi Ali‐Reza , Darudi Ahmad
Published: April 2022

Multicomponent mixtures of bilayer lipids, thanks to the coexistence of liquid‐crystalline phases in their structures, may be used in the development of functional membranes. In such membranes interlayer ordering distributes across membrane lamellae, resulting in long‐range alignment of phase‐separated domains. In this paper, we explore the dynamics of this phenomenon by laser speckle pattern analysis. We show that cholesterol content decreases the activity, and the rate of the domains size development is related to the change of physical roughness of the multicomponent lipid mixture. Our results are in agreement with the previous experimental reports. However, our experimental procedure is an easy‐to‐implement and effective methodology.
Prediction of acid pKa values in the solvent acetone based on COSMO‐RS
Authors: Sülzner Niklas , Haberhauer Julia , Hättig Christof , Hellweg Arnim
Published: April 2022

In this contribution we extent the use of the conductor‐like screening model for realistic solvation (COSMO‐RS) to the prediction of pKa values in acetone, a commonly used dipolar aprotic solvent. For this, we calculated the Gibbs free energy of dissociation of 120 organic acids (nine acrylic acids, 87 benzoic acids, nine phenols, and 15 benzenesulfonamides) using COSMO‐RS at the two levels BP‐TZVP and BP‐TZVPD‐FINE and determined the parameters for a linear free energy relation for the prediction by performing linear fits to experimental values. Our results suggest that the data set dissects into two groups, with the phenols being different from the other three subsets. The acrylic and benzoic acids and the sulfonamides can be treated together and yield an excellent linear correlation () with an RMSD of only ~0.3. The slope is found to be significantly smaller than the theoretical value (), only 45% of it, which is in accordance with findings in the literature. The phenols, however, while similarly well correlated in their own subset with an RMSD of 1.7–1.9, exhibit a slope larger than one. We discuss both a higher uncertainty in the reference values as well as physical origins as possible reasons.
A theoretical investigation into gallic acid pyrolysis
Authors: Kraus Jakob , Kortus Jens
Published: April 2022

Thermodynamic and kinetic information on the first two steps of gallic acid pyrolysis, a decarboxylation followed by a dehydrogenation, is obtained based on density functional theory and quantum chemistry. For the kinetics, transition states are identified with the help of the climbing image nudged elastic band method. Both reactions exhibit two transition states. One of them is related to the rotation of OH groups, and the other one is related to the breaking and forming of bonds. The gallic acid pyrolysis as a whole is judged to be endothermal, and it changes from endergonic to exergonic between 500 and 750 K. The second reaction, the dehydrogenation of pyrogallol, is identified as the rate‐determining step of gallic acid pyrolysis, with reaction rate constants below 1 s−1 for temperatures below 1250 K.
Structural studies of silica‐supported spinel magnesium ferrite nanorods for photocatalytic degradation of methyl orange
Authors: Kazi Subiya K. , Inamdar Shaukatali N. , Kamble Dhanraj P. , Lohar Kishan S. , Suryawanshi Appasaheb W. , Tigote Radhakrishnan M.
Published: April 2022

A novel, well‐designed, silica‐supported magnesium ferrite nanorods were successfully developed at room temperature using the co‐precipitation method. The synthesized nanorods show an optical band gap of 3.1 eV, with the maximum wavelength absorptive at 334 nm. The average particle size is 36 nm with the FCC crystal structure by the X‐ray Diffraction technique (XRD). TGA achieved thermal stability of targeted mesoporous materials at 600°C. Field Emission Scanning Electron Microscopy (FE‐SEM) and High‐Resolution Transmission Electron Microscopy (HR‐TEM) techniques confirm the rod‐like structure. Energy Dispersive Spectroscopy (EDS) and X‐Ray Fluorescence (XRF) studies reveal the presence of all elements in the composition. The synthesized nanorods are highly magnetic by the vibrating sample magnetometer (VSM) technique, which shows a high coercivity value, that is, MgFe2O4@SiO2 is photocatalytically active. From BET analysis, the surface area, pore volume, and pore diameter are 19.2 m2 g−1, 2.46 cm3 g−1, and 5.10 nm, respectively. The experimental outcomes predict that the degradation efficiency (79%) of methyl orange dye was accomplished using MgFe2O4SiO2 nanorods within 270 min.
SARS‐CoV‐2 infection of human‐induced pluripotent stem cells‐derived lung lineage cells evokes inflammatory and chemosensory responses by targeting mitochondrial pathways
Authors: Surendran Harshini , Kumar Saurabh , Narasimhaiah Swathi , Ananthamurthy Anuradha , Varghese PS , D'Souza George A. , Medigeshi Guruprasad , Pal Rajarshi
Published: April 2022

The COVID‐19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) primarily affects the lung, particularly the proximal airway and distal alveolar cells. NKX2.1+ primordial lung progenitors of the foregut (anterior) endoderm are the developmental precursors to all adult lung epithelial lineages and are postulated to play an important role in viral tropism. Here, we show that SARS‐CoV‐2 readily infected and replicated in human‐induced pluripotent stem cell‐derived proximal airway cells, distal alveolar cells, and lung progenitors. In addition to the upregulation of antiviral defense and immune responses, transcriptomics data uncovered a robust epithelial cell‐specific response, including perturbation of metabolic processes and disruption in the alveolar maturation program. We also identified spatiotemporal dysregulation of mitochondrial heme oxygenase 1 (HMOX1), which is associated with defense against antioxidant‐induced lung injury. Cytokines, such as TNF‐α, INF‐γ, IL‐6, and IL‐13, were upregulated in infected cells sparking mitochondrial ROS production and change in electron transport chain complexes. Increased mitochondrial ROS then activated additional proinflammatory cytokines leading to an aberrant cell cycle resulting in apoptosis. Notably, we are the first to report a chemosensory response resulting from SARS‐CoV‐2 infection similar to that seen in COVID‐19 patients. Some of our key findings were validated using COVID‐19‐affected postmortem lung tissue sections. These results suggest that our in vitro system could serve as a suitable model to investigate the pathogenetic mechanisms of SARS‐CoV‐2 infection and to discover and test therapeutic drugs against COVID‐19 or its consequences.
Population Pharmacokinetics of Nifurtimox in Adult and Pediatric Patients With Chagas Disease
Authors: Ince Ibrahim , Prins Klaas , Willmann Stefan , Sutter Gabriele , Hanze Eva , Sadre‐Marandi Farrah , Stass Heino , Garmann Dirk
Published: April 2022

Nifurtimox (LAMPIT) has been used for decades for the treatment of Chagas disease, a chronic and potentially life‐threatening disease caused by the parasite Trypanosoma cruzi. The pharmacokinetic (PK) information on nifurtimox in humans derived from controlled clinical studies is very limited. The objective was to investigate and compare the population PK of nifurtimox in adult and pediatric patients with Chagas disease to confirm the clinical dosing regimen in children, which was based on allometric approaches using the concept that a dose‐equivalent exposure would reach equivalent antiparasitic efficacy as in adults. The resulting adult model adequately described the PK in adults. Significant predictors of the availability in PK were food intake, tablet formulation (fast‐ vs slow‐dissolution tablet), study, and body weight. As the resulting adult model could not adequately predict the sparse sampled pediatric patient data, these data were analyzed separately to derive exposure estimates for comparison with adult exposure. In the population PK model for pediatric patients, significant covariates were body weight and age. As compared to adults, children aged >2 years were estimated to have 50.6% higher apparent clearance. No hints of dose nonlinearity were observed in a dose range of 30 to 240 mg single dose in adults and 15 to 300 mg 3 times daily (8‐20 mg/kg) in children. Altogether, this study retroactively showed that the current mg/kg dosing regimen in children reached similar exposure as in adults receiving an 8 mg/kg total daily dose.
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

Severe 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

Nanoparticles 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

A 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

As 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

Transgender 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

Genetic 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

Objective

The 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.

Design

We 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).

Results

Remission 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.

Conclusion

Steroid 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

MTHFR 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

Reproductive 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

Factors 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

Background

In 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.

Purpose

To reduce scan time toward one breath‐hold by reconstructing diffusion tensors for in vivo cDTI with a fitting‐free deep learning approach.

Study type

Retrospective.

Population

A total of 197 healthy controls, 547 cardiac patients.

Field strength/sequence

A 3 T, diffusion‐weighted stimulated echo acquisition mode single‐shot echo‐planar imaging sequence.

Assessment

A 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 tests

Wilcoxon 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].

Results

For 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 conclusion

Diffusion tensor prediction with a trained U‐Net is a promising approach to minimize the number of breath‐holds needed in clinical cDTI studies.

Evidence Level

4

Technical Efficacy

Stage 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

Introduction

Paediatric 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.

Methods

Five 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.

Results

The 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.

Conclusion

The 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.
The additive effect of periodontitis with hypertension on risk of systemic disease and mortality
Authors: Larvin Harriet , Kang Jing , Aggarwal Vishal R. , Pavitt Sue , Wu Jianhua
Published: April 2022

Background

Recent evidence suggests that periodontitis (PD) causes hypertension, which is a precursor to development of other systemic diseases. The aim of this study was to examine the effect of hypertension and PD on the risk of subsequent systemic disease.

Methods

This longitudinal cohort study included 244,393 UK Biobank participants who were free of systemic disease other than hypertension at baseline. Self‐reported responses of painful gums or loose teeth were surrogates for PD. Hypertensives were identified by clinical diagnosis, or elevated blood pressure (≥140/90 mmHg). Systemic diseases including cancer, cardiovascular disease (CVD), and diabetes were identified from linked diagnostic codes. Multivariable Cox proportional hazard models were used to quantify the risk of systemic diseases and all‐cause mortality, stratified by hypertensive and PD status.

Results

The average age of the study population was 55.4 years (standard deviation [SD:] 8.1 years), and 130,220 (53.3%) participants were female. At baseline, 131,566 (53.8%) participants were hypertensive and 4.5% reported PD. The incidence rates of all systemic diseases were higher in hypertensive than non‐hypertensive participants of the same PD status. In hypertensives, an additive effect was observed for PD on the risks of CVD (adjusted hazard ratio [HR]: 1.35, 95% confidence interval [CI]: 1.21–1.53) and respiratory disease (HR: 1.11, 95% CI: 0.95–1.30) compared to hypertensive healthy controls.

Conclusions

Hypertensives with PD have exacerbated risks of several systemic diseases. Future interventional studies should consider the effect of periodontal treatment on systemic outcomes in targeted hypertensive populations.
The impact of probiotic yogurt versus ordinary yogurt on serum sTWEAK, sCD163, ADMA, LCAT and BUN in patients with chronic heart failure: a randomized, triple‐blind, controlled trial
Authors: Pourrajab Behnaz , Naderi Nasim , Janani Leila , Hajahmadi Marjan , Mofid Vahid , Dehnad Afsaneh , Sohouli Mohammad Hassan , Hosseini Sharieh , Shidfar Farzad
Published: April 2022

Background

To date, no study has investigated the effects of probiotic yogurt as a functional food in patients with chronic heart failure (CHF). Therefore, the aim of this study was to compare the impact of probiotic yogurt versus ordinary yogurt on inflammatory, endothelial, lipid and renal indices in CHF patients. In this randomized, triple‐blind clinical trial, 90 patients with CHF were randomly allocated into two groups to take either probiotic or ordinary yogurt for 10 weeks. Serum levels of soluble tumor necrosis factor‐like weak inducer of apoptosis (sTWEAK), soluble cluster of differentiation 163 (sCD163), asymmetric dimethylarginine (ADMA), and lecithin cholesterol acyltransferase (LCAT) were measured by using ELISA kits, and blood urea nitrogen (BUN) was measured by calorimetry method at baseline and at the end of trial. The P‐value <0.05 was defined as statistically significant.

Results

Seventy‐eight patients completed the study. At the end of the intervention, the levels of sTWEAK in both groups increased significantly, and this increase was greater in the probiotic yogurt group [691.84 (335.60, 866.95)] compared to control group [581.96 (444.99, 929.40)], and the difference between the groups was statistically significant after adjusting for confounders (P‐value: 0.257, adjusted P‐value: 0.038). However, no significant differences were found between the groups in the cases of other study indices.

Conclusion

Probiotic yogurt may be useful for improving the inflammatory status in patients with CHF through increasing sTWEAK levels, however, further studies are needed in this area. © 2022 Society of Chemical Industry.
In vivo fluid transport in human intervertebral discs varies by spinal level and disc region
Authors: Martin John T. , Wesorick Benjamin , Oldweiler Alexander B. , Kosinski Andrzej S. , Goode Adam P. , DeFrate Louis E.
Published: April 2022

Background

The lumbar discs are large, dense tissues that are primarily avascular, and cells residing in the central region of the disc are up to 6–8 mm from the nearest blood vessel in adults. To maintain homeostasis, disc cells rely on nutrient transport between the discs and adjacent vertebrae. Thus, diminished transport has been proposed as a factor in age‐related disc degeneration.

Methods

In this study, we used magnetic resonance imaging (MRI) to quantify diurnal changes in T2 relaxation time, an MRI biomarker related to disc hydration, to generate 3D models of disc fluid distribution and determine how diurnal changes in fluid varied by spinal level. We recruited 10 participants (five males/five females; age: 21–30 years; BMI: 19.1–29.0 kg/m2) and evaluated the T2 relaxation time of each disc at 8:00 AM and 7:00 PM, as well as degeneration grade (Pfirrmann). We also measured disc height, volume, and perimeter in a subset of individuals as a preliminary comparison of geometry and transport properties.

Results

We found that the baseline (AM) T2 relaxation time and the diurnal change in T2 relaxation time were greatest in the cranial lumbar discs, decreasing along the lumbar spine from cranial to caudal. In cranial discs, T2 relaxation times decreased in each disc region (nucleus pulposus [NP], inner annulus fibrosus [IAF], and outer annulus fibrosus [OAF]), whereas in caudal discs, T2 relaxation times decreased in the NP but increased in the AF.

Conclusions

Fluid transport varied by spinal level, where transport was greatest in the most cranial lumbar discs and decreased from cranial to caudal along the lumbar spine. Future work should evaluate what level‐dependent factors affect transport.
Enantioselective high‐performance liquid chromatography of aryl‐substituted oxazolines as an efficient tool for determination of chiral purity of serine medicinal components
Authors: Pomeisl Karel , Vaňkátová Petra , Hamplová Věra
Published: April 2022

A new approach for the evaluation of chiral purity of serine esterification products bearing long‐chain alkyl substituents was developed. The compounds were simply converted to aryl‐substituted oxazolines which: (i) facilitates effective chromatographic enantioseparation and (ii) enables direct detection using ultraviolet absorption. The method employs a polysaccharide‐based chiral stationary phase and allows enantioseparation of highly stable oxazoline products in less than 6 min using a simple binary mobile phase. As opposed to the previously used normal phase method the developed method was performed in the reversed‐phase mode. Aside from the benefits of switching to less hazardous solvents with regard to the principles of Green Chemistry, this has also led to a reduction in the analysis time. In comparison with known serine chromophores, the best enantioseparation of aryloxazoline rigid structure may be achieved only based on non‐polar interactions with the chiral stationary phase. In contrast, the substitution of the chromophore moiety with hydroxyl substituent affected intra and intermolecular interactions that caused enantioseparation differences. Concurrently, we found high chirality retention of (R)‐ and (S)‐configuration oxazoline standards (≥99% enantiomeric excess) during the introduction of the ultraviolet label. The method is suitable for rapid injection of the mixture containing the ultraviolet absorption marker without prior purification.
Synthetic pharmaceutical peptides characterization by chromatography principles and method development
Authors: Sharma Nitish , Kukreja Divya , Giri Tushar , Kumar Sumit , Shah Ravi P
Published: April 2022

As per the United States Food and Drug Administration, any polymer/chain composed of 40 or fewer amino acids is called a peptide, where more than 40 amino acids are considered proteins. On many occasions, there is a change in the source of manufacturing of the peptide active pharmaceutical ingredient, where one has to prove the sameness of that product with the existing formulation by considering several aspects like the presence of impurities/degradation products, the extent of aggregations, and so forth. For the same, several chromatographic characterization techniques such as reversed‐phase high‐performance liquid chromatography‐ultraviolet/high‐resolution mass spectrometry, supercritical fluid chromatography, size‐exclusion chromatography, ion‐exchange chromatography, and so forth, are widely used in the pharmaceutical industry. It is well known that the method development of peptide molecules is often challenging as many variables are to be kept in mind which can affect the separation, recovery, and stability of the molecule. The present review focuses on the basics of peptide degradation and method development by using various chromatographic techniques for characterization. It also covers a deep insight of method development parameters and variables to be considered which might directly or indirectly affect the chromatographic separation and recovery and also provides a guide on the selection of chromatographic parameters.
Ligand fishing based on tubular microchannel modified with monoamine oxidase B for screening of the enzyme's inhibitors from Crocus sativus and Edgeworthia gardneri
Authors: Qi Xu‐Wei , Liu Yi‐Ming , Hu Yi‐Kao , Yuan Hao , Ayeni Emmanuel Ayodeji , Liao Xun
Published: April 2022

A novel strategy of performing ligand fishing with enzyme‐modified open tubular microchannel was proposed for screening bioactive components present in medicinal plants. Monoamine oxidase B was immobilized onto the surface of the microchannel for the first time to specifically extract its ligands when the plant's extracts solution flows through the channel. The thermal and the storage stability of immobilized monoamine oxidase B were significantly enhanced after immobilization. Crocin I and Ⅱ were extracted from Crocus sativus, and tiliroside was extracted from Edgeworthia gardneri. All the three compounds were inhibitors of the enzyme with the half‐maximal inhibitory concentration values of 26.70 ± 0.91, 19.88 ± 2.78, and 15.65 ± 0.85 μM, respectively. The enzyme inhibition kinetics and molecular docking were investigated. This is the first report on the inhibitory effects of tiliroside and crocin Ⅱ. The novel ligand fishing method proposed in this work possesses advantages of rapidness, high efficiency, and tiny sample consumption compared to routine ligand fishing, with promising potential for screening active natural products in complex mixtures.
Ultrasound‐Estimated Bladder Weight Correlates With Videourodynamic Studies in Neurogenic Bladder Dysfunction
Authors: Hwang Misun , Back Susan J. , Van Batavia Jason , Tierradentro‐Garcia Luis Octavio , Darge Kassa , Zderic Stephen A.
Published: April 2022

Purpose

This retrospective study was designed to evaluate which lower urinary tract ultrasound parameter(s) could predict the results of invasive urodynamic testing which are the current reference standard in the evaluation of bladder dysfunction in children with spina bifida.

Materials and Methods

Fifty eight children with spina bifida undergoing video urodynamic evaluation and a renal bladder ultrasound as their standard of care were evaluated. Quantitative and qualitative ultrasound parameters were then correlated with the videourodynamic study results which served as the reference standard.

Results

For bladders with ending storage pressures above 15 cm H2O, there were increases in these ultrasound measured parameters: 1) bladder mass (P = .00019), 2) bladder/body mass ratio (P = .0059), and 3) wall thickness (P = .01). We defined the storage cost as the final storage pressure divided by the percentage of expected bladder capacity attained. These data were analyzed to compute receiver operating curves with assuming end storage pressures cutoff points of 15, 20, 30, and 40 cm H2O. The optimal area under the curve was found for a bladder weight of 65 g and a pressure cutoff of 30 cm H2O with a sensitivity of 75% with a specificity of 84%.

Conclusion

Bladder weight is independent of luminal volume, can be normalized to body weight, and may serve as a clinically valuable tool for noninvasive screening to define a subset of patients with neurogenic bladder with a higher likelihood of having abnormal videourodynamic results.