bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of Non-Isothermal Pressure-Driven Flow of Generalized Viscoelastic-Fluid-Based Nanofluids in a Channel
Authors: Khan Idrees , Chinyoka Tiri , Gill Andrew
Published: February 2022

The investigation considers numerical analysis and computational solution of unsteady, pressure-driven channel flow of a generalized viscoelastic-fluid-based nanofluid (GVFBN) subject to exothermic reactions. Temperature-dependent fluid thermal conductivity is considered, and the flow is subject to convective cooling at the walls. The non-isothermal generalized Giesekus constitutive model is employed for the GVFBN. A Carreau model is used to describe the shear-rate dependence of fluid viscosity, and exothermic reactions are assumed to follow Arrhenius kinetics. An efficient semi-implicit numerical technique based on the finite-difference method is applied to obtain computational solutions to the model equations. The computational methodologies are built into the MATLAB software. The effects of various fluid and flow parameters, specifically the nanoparticle volume fraction, are explored. The results demonstrate that those parameters which only directly couple to the energy equation (but are otherwise indirectly coupled to momentum and stress-constitutive equations, say via the temperature-dependent viscosities and relaxation times) would only show prominent effects on fluid temperature but not on the fluid velocity or the polymer stresses. The results also demonstrate, as in the literature on exothermic flows, that the values of exothermic-reaction parameter must be carefully controlled as large values would lead to thermal runway phenomena. The illustrated results are consistent with the existing literature and additionally add novel new contributions to non-isothermal and pressure-driven channel flow of GVFBN under convective cooling conditions.
The Attenuation of Chronic Ulcerative Colitis by (R)-salbutamol in Repeated DSS-Induced Mice
Authors: Deng Liangjun , Guo Haihua , Wang Shanping , Liu Xiaoming , Lin Yue , Zhang Rui , Tan Wen
Published: February 2022

Racemic salbutamol ((RS)-sal), which consist of the same amount of (R)-sal and (S)-sal, has been used for asthma and COPD due to its bronchodilation effect. However, the effect of (R)-sal on repeated dextran sulfate sodium (DSS)-induced chronic colitis has not yet been investigated. In this study evaluated the potential effect of (R)-, (S)-, and (RS)-sal in mice with repeated DSS-induced chronic colitis and investigated the underlying mechanisms. Here, we verified that chronic colitis was significantly attenuated by (R)-sal, which was evidenced by notably mitigated body weight loss, disease activity index (DAI), splenomegaly, colonic lengths shortening, and histopathological scores. (R)-sal treatment noticeably diminished the levels of inflammatory cytokines (such as TNF-α, IL-6, IL-1β, and IFN-γ). Notably, the efficacy of (R)-sal was better than that of (RS)-sal. Further research revealed that (R)-sal mitigated colonic CD4 leukocyte infiltration, decreased NF-κB signaling pathway activation, improved the Nrf-2/HO-1 signaling pathway, and increased the expression of ZO-1 and occludin. In addition, (R)-sal suppressed the levels of TGF-β1, α-SMA, and collagen in mice with chronic colitis. Furthermore, the 16S rDNA sequences analyzed of the intestinal microbiome revealed that (R)-sal could mitigate the intestinal microbiome structure and made it more similar to the control group, which mainly by relieving the relative abundance of pathogens (such as Bacteroides) and increasing the relative abundance of probiotics (such as Akkermansia). Therefore, (R)-sal ameliorates repeated DSS-induced chronic colitis in mice by improving inflammation, suppressing oxidative stress, mitigating intestinal barrier function, relieving intestinal fibrosis, and regulating the intestinal microbiome community. These results indicate that (R)-sal maybe a novel treatment alternative for chronic colitis.
Abnormal Sleep Duration as Predictor for Cardiovascular Diseases: A Systematic Review of Prospective Studies
Authors: Laksono Sidhi , Yanni Mefri , Iqbal Mohammad , Prawara Ananta Siddhi
Published: February 2022

Study Objective. This study is aimed at figuring out the role of abnormal sleep duration in predicting cardiovascular diseases. Methods. We searched the online database PubMed on 30 August 2020 for our data collection. We used the following keywords: sleep duration AND (cardiovascular disease OR cardiovascular event) AND (cohort OR prospective OR retrospective). We identified 653 studies, and after excluding studies that were published before 2015, we obtained 306 studies. After filtering the 306 studies through title and abstract screening and applying the inclusion and exclusion criteria, we further reviewed fourteen studies with full-text reading. We excluded three studies because of insufficient data required and included eleven studies in this systematic review. Results. A total of 361,041 participants from ten studies were included in this systematic review. The incidence of hypertension, myocardial infarction, coronary artery disease, heart failure, cardiovascular events, and cardiovascular diseases in the short sleep duration group is 46.12%, 0.59%, 5.43%, 0.09%, 7.18%, 1.48%, and 6.8%, consecutively, while the incidence of hypertension, myocardial infarction, coronary artery disease, and heart failure in the long sleep duration group is 30.71%, 0.61%, 6.55%, 1.11%, and 6.04%, consecutively. Nine studies reported an association between sleep duration and cardiovascular diseases while one study reported no association. Seven studies reported that short sleep duration was significantly associated with CVD. Short sleep duration in this study was associated with hypertension and heart failure. Atrial fibrillation and coronary artery disease were associated with both short and long sleep duration. Conclusion. Abnormal sleep duration (short and long sleep duration) may act as the predictor of cardiovascular diseases. The importance of having normal sleep duration should be stressed with other lifestyle modification to avoid the risk of getting cardiovascular diseases. However, further studies are needed to overcome the limitation of this systematic review.
BAP1 Immunostain Status in Intraocular Biopsy Specimens for Uveal Melanoma Highly Correlates with Other Prognostic Markers
Authors: Ida Cristiane M. , Pulido Jose , Greipp Patricia T. , Garcia Joaquin J. , Olsen Timothy W. , Dalvin Lauren , Salomão Diva Regina
Published: February 2022

Introduction: Loss of BAP1 protein expression emerged as a negative prognostic marker in uveal melanoma (UM) and has primarily been studied in enucleations. Intraocular biopsy is frequently performed prior to UM globe-conserving therapy. Methods: We retrospectively evaluated BAP1 immunostaining of UM in 16 biopsies and 8 subsequent enucleations, and results were correlated with the UM-specific gene expression profile (GEP; n = 11), chromosome 3 status by FISH and/or chromosomal microarray (n = 12; 9 also had GEP), and clinical outcomes. Results: UM involved the choroid in 15 (of 16) cases. Biopsy was performed for prognostication (n = 12) or diagnosis (n = 4). Treatment included brachytherapy (n = 13; 5 followed by enucleation) or enucleation only (n = 3). BAP1 nuclear immunostaining was positive in 9, negative in 4, and equivocal in 3 biopsies. For the 3 equivocal biopsies, BAP1 immunostaining was positive in 2 (of 3) subsequent enucleations. BAP1 immunostaining was concordant between all 5 remaining biopsies and enucleations. BAP1-positive biopsies had disomy 3 (n = 6) or 3p loss (n = 1) and class 1 GEP (n = 6). BAP1-negative biopsies had monosomy 3 (n = 3) and class 2 GEP (n = 2). Median follow-up was 62.5 months (range, 17–150). For BAP1-positive UM patients, 8 were alive (7 without metastatic disease) and 3 had died (1 melanoma-related death). Among BAP1-negative UM patients, 2 were alive (1 with metastatic disease) and 3 had melanoma-related deaths. Conclusion: BAP1 immunostaining in biopsies highly correlates with results in subsequent enucleations and with well-established UM prognostic markers, representing a potential additional prognostic tool for UM biopsies.
Lack of Increased Risk of Lymphoma with Thiopurine Therapy Regardless of Dose and Duration of Treatment in Japanese Patients with Inflammatory Bowel Diseases
Authors: Kobayashi Taku , Udagawa Eri , Hibi Toshifumi
Published: February 2022

Background: Immunomodulator therapy (e.g., thiopurines) has been linked to an increased malignancy risk, in patients with inflammatory bowel diseases (IBDs), which increases with treatment duration, based on studies mainly in Caucasian patients. However, our previous real-world study, of Japanese patients with IBDs, indicated no overall increased risk of non-Hodgkin lymphoma (NHL) with thiopurine treatment. Objectives: This subanalysis investigated the influence of thiopurine IBD treatment dose and duration, on incidence of NHL in Japanese patients. Method: The Medical Data Vision (MDV) claims database (17.8 million patients; April 2008–January 2018) was used to analyze incidence rate ratios (IRRs) of NHL, in eligible patients (≥1 diagnosis of ulcerative colitis or Crohn’s disease) and no malignancy at diagnosis or first prescription of a thiopurine. Age- and sex-adjusted IRRs and 95% confidence interval for NHL were calculated as the incident cases compared in the subgroups versus the overall IBD population. Results: Among 75,673 patients with IBDs, 103 cases of NHL were recorded. There was no overall increase in the risk of developing NHL among Japanese patients treated with thiopurines. The IRRs relative to the overall IBD population were 1.88, 1.42, and 0.38 for <1 year, 1–3 years, and ≥3 years of thiopurine treatment. There were no differences in NHL incidence when grouping patients by mean daily thiopurine dose prescribed, age, or disease subgroups. Conclusion: Dose or duration of thiopurine treatment did not explain a lack of increased risk of NHL with thiopurine use in Japanese patients with IBDs.
Small-Cell Carcinoma of the Lung: What We Learned about It?
Authors: Righi Luisella , Volante Marco , Papotti Mauro
Published: February 2022

Small-cell lung carcinoma (SCLC) is a high-grade aggressive disease that belongs to the neuroendocrine (NE) group of lung tumors that also includes typical carcinoid, atypical carcinoid, and large-cell NE carcinoma. SCLC has specific histological diagnostic criteria that are sometimes troublesome to be assessed in cytological samples that indeed represent the most frequent source of diagnostic material due to the typical advanced presentation at the onset of SCLC. However, cytological preparations could be in some instances more reliable than histology due to the better preservation of nuclear details. Cytological criteria for diagnosis of SCLC include high cellularity, small cell size, scant cytoplasm, coarsely granulated chromatin with “salt-and-pepper” appearance, inconspicuous or absent nucleoli, Azzopardi crush effect, and necrotic debris in the background. Despite being distinctive, these features could be incomplete to differentiate SCLC with other small-cell neoplasia. Therefore, immunocytochemical determination of diagnostic biomarkers is crucial to achieve a confident diagnosis. Furthermore, recent findings on molecular and transcriptomic studies of SCLC revealed the potential rise of new predictive and prognostic biomarkers that, whenever validated by immunocytochemistry, may potentially assist to tailor the best therapy, including immune checkpoint inhibition.
Prevalence of Overweight, Obesity, and Dietary Behaviors among Adolescents in Dubai Schools: A Complex Design Survey 2019
Authors: Abdullatif Mona , AlAbady Kadhim , Altheeb Ayesha , Rishmawi Fidaa , Jaradat Hana , Farooq Sobya
Published: February 2022

Background: Overweight and obesity in adolescence have become a public health challenge. Health effects due to overweight and obesity appear during adolescence and continue into adulthood. Modifiable factors associated with overweight and obesity include unhealthy dietary behaviors and lack of exercise. Assessment of the prevalence of overweight and obesity and unhealthy dietary behaviors is essential to plan for preventive programs at the population level. Objectives: The aim of the study was to estimate the prevalence of overweight, obesity, and unhealthy dietary behaviors among adolescents of grades 8–12 in Dubai schools, 2019. Method: The Adolescents Risk Behavioral Survey (ARBS) is a 2-stage stratified cluster study. The 1st stage involved randomly selecting schools with a probability proportional to the size and the 2nd stage was randomly selecting classes, and all students in the selected classes were invited to participate; the total participants were 1,683 adolescents from grades 8–12 from 28 private and government schools. Students answered a self-administrated electronic questionnaire. Anthropometric measures including height and weight were assessed by a trained school nurse. Body mass index was calculated and classified according to World Health Organization (WHO) growth charts for sex and age. Data were analyzed with adjustment for weight, primary sampling unit, and stratum. Results: Among the adolescents of Dubai schools studying in grades 8–12, the prevalence of overweight was 25.3% (95% confidence interval [CI]: 22.7–28.2) and obesity was 15% (95% CI: 13.0–18.9). Overweight did not vary between male and female students, but obesity was higher among male students 19.9% (95% CI: 15.4–25.1) than female students 11.8% (95% CI: 8.7–15.6) (p = 0.0261). Age and grade were not found to be associated with overweight or obesity. The prevalence of unhealthy dietary behaviors was common. Examining dietary habits from 30 days prior to the survey, 21.3% of adolescents (95% CI: 17.2–26.1) reported not eating fruits and 19.7% (95% CI: 15.7–24.4) not eating vegetables. With regard to consuming dairy, 3.3% of adolescents (95% CI: 10.9–16.1) did not drink milk or consume dairy products in the 7 days prior to the survey, 31% of adolescents (95% CI: 26.8–35.5) consumed a carbonated drink daily, and 18.4% did not eat breakfast on all 7 days during and before the survey. Eating fast food was high among adolescents as 78.9% reported eating fast food one or more days in the week preceding the survey. Conclusion: School programs for overweight and obesity need further strengthening and to extend their scope to outside of the school community.
Intestinal Ischemia as a Complication of COVID-19
Authors: Abufool Lamis K. , Al-Ozaibi Labib S.
Published: February 2022

Background: Extrapulmonary complications of COVID-19 including acute mesenteric ischemia are being increasingly reported and are a reason of poorer clinical outcome and increased inpatient mortality rate. Case: Here, we present a case of a young obese male who developed acute superior mesenteric artery thrombosis as a result of COVID-19. Discussion: Some direct causes of mesenteric thrombosis in COVID-19 patients have been hypothesized. Furthermore, immobilization, endothelial injury, and increased prothrombotic factor production are proven causes of thromboembolism in COVID-19. Conclusion: Early detection and management of acute mesenteric ischemia in COVID-19 cases is crucial to improve the prognosis.
Sex Differences in the Association between Different Obesity Parameters and Cognitive Function in Older Adults: A Cross-Sectional Study in Rural China
Authors: Hu Yuxin , Xia Caixia , Chen Hao , Song Wenjun , Zhou Quanxiang , Yang Xing , Yang Jingyuan
Published: February 2022

Background: Early identification of risk factors for cognition decline may contribute to the interventions for Alzheimer’s disease. Obesity is a common modifiable risk factor for chronic diseases. The association between obesity and cognition in older adults is limited, and sex differences in this area have not been well recognized. Objective: The aim of the study was to observe the sex differences in the relationship between obesity and cognition in a rural community-dwelling older population of Guizhou, China. Methods: Data were gathered from the baseline survey of a cohort study of older people in rural areas of Guizhou, China. Demographic and behavioral data (sex, age, education, household income, smoking history, drinking history, history of head injury, diet, and level of physical exercise time) were collected. The Mini-Mental State Examination (MMSE) was used to assess cognitive function. Body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) were used as different measures of obesity. Comparisons between the groups were made by the Wilcoxon rank-sum test or Kruskal-Wallis H test. Restricted cubic spline regression was used to examine a dose-response relationship between obesity indicators and cognitive function. Linear relationships were performed by the multivariable linear regression model. Results: A total of 1,654 participants including 964 women and 690 men were enrolled in this study. After adjustment, BMI showed a nonlinear relationship with MMSE scores in women. There was a significant trend toward increasing MMSE scores at the low end of BMI (13.52–20.10 kg/m2, p = 0.014). The multivariable linear regression model showed that MMSE increased by 0.631 (p < 0.001) for every one standard deviation increase in HC in women. No association was found between obesity parameters and cognitive function in men. Conclusion: Our results suggest that there are significant sex differences in some obesity parameters and cognition in an older Chinese population. BMI and HC are positively associated with cognitive function in women. No association was found between obesity measures and cognitive function in men.
Developing a Stroke Risk Prediction Model Using Cardiovascular Risk Factors: The Suita Study
Authors: Arafa Ahmed , Kokubo Yoshihiro , Sheerah Haytham A. , Sakai Yukie , Watanabe Emi , Li Jiaqi , Honda-Kohmo Kyoko , Teramoto Masayuki , Kashima Rena , Nakao Yoko M. , Koga Masatoshi
Published: February 2022

Introduction: Stroke remains a major cause of death and disability in Japan and worldwide. Detecting individuals at high risk for stroke to apply preventive approaches is recommended. This study aimed to develop a stroke risk prediction model among urban Japanese using cardiovascular risk factors. Methods: We followed 6,641 participants aged 30–79 years with neither a history of stroke nor coronary heart disease. The Cox proportional hazard model estimated the risk of stroke incidence adjusted for potential confounders at the baseline survey. The model’s performance was assessed using the receiver operating characteristic curve and the Hosmer-Lemeshow statistics. The internal validity of the risk model was tested using derivation and validation samples. Regression coefficients were used for score calculation. Results: During a median follow-up duration of 17.1 years, 372 participants developed stroke. A risk model including older age, current smoking, increased blood pressure, impaired fasting blood glucose and diabetes, chronic kidney disease, and atrial fibrillation predicted stroke incidence with an area under the curve = 0.76 and p value of the goodness of fit = 0.21. This risk model was shown to be internally valid (p value of the goodness of fit in the validation sample = 0.64). On a risk score from 0 to 26, the incidence of stroke for the categories 0–5, 6–7, 8–9, 10–11, 12–13, 14–15, and 16–26 was 1.1%, 2.1%, 5.4%, 8.2%, 9.0%, 13.5%, and 18.6%, respectively. Conclusion: We developed a new stroke risk model for the urban general population in Japan. Further research to determine the clinical practicality of this model is required.
Family Formation and Socio-Economic Status among 35-Year-Old Men Who Have Survived Cancer in Childhood and Early Adulthood: A Register-Based Cohort Study
Authors: Sylvest Randi , Vassard Ditte , Schmidt Lone , Schmiegelow Kjeld , Macklon Kirsten Tryde , Forman Julie Lyng , Pinborg Anja
Published: February 2022

Introduction: The number of children and young adults who survive cancer has steadily increased over the past decades. Consequently, life circumstances after cancer have gained increasing importance. The aim of this study was to explore family formation and socio-economic status among 35-year-old men having survived cancer in childhood or early adulthood compared to an age-matched comparison group. Methods: This study is a national, register-based cohort study among 35-year-old men. Men diagnosed with cancer in childhood and early adulthood were registered between 1978 and 2016. At the time of diagnosis, each patient was randomly matched with 150 men without cancer from the background population within the same birth year. Those still alive at the age of 35 years were included in the study population. Results: The study population consisted of 4,222 men diagnosed with cancer in childhood or early adulthood and 794,589 men in the age-matched comparison group. Men who have survived cancer during childhood or early adulthood have a reduced probability of having children, and lower probability of getting married or of cohabitation than those from an age-matched comparison group. Men who have survived CNS cancer also have a lower probability of having a higher education than high school and a higher probability of being outside the workforce than those from an age-matched comparison group. Discussion/Conclusion: Many men who have survived cancer during childhood or early adulthood are influenced by their cancer later in life, which was apparent in family formation, educational achievements, and labour market attachment. Continued focus on rehabilitation and needs for support among the male survivors of childhood and youth cancer is warranted.
Harnessing Digital Health to Objectively Assess Functional Performance in Veterans with Chronic Obstructive Pulmonary Disease
Authors: Zhou He , Park Catherine , Poursina Olia , Zahiri Mohsen , Nguyen Hung , Torres Ruiz Ilse , Nguyen Christina K. , Bryant Mon S. , Sharafkhaneh Amir , Bandi Venkata D. , Najafi Bijan
Published: February 2022

Introduction: An early detection of impaired functional performance is critical to enhance symptom management for patients with chronic obstructive pulmonary disease (COPD). However, conventional functional measures based on walking assessments are often impractical for small clinics where the available space to administrate gait-based test is limited. This study examined the feasibility and effectiveness of an upper-extremity frailty meter (FM) in identifying digital measures of functional performance and assessing frailty in COPD patients. Methods: Forty-eight patients with COPD (age = 68.8 ± 8.5 years, body mass index [BMI] = 28.7 ± 5.8 kg/m2) and 49 controls (age = 70.0 ± 3.0 years, BMI = 28.7 ± 6.1 kg/m2) were recruited. All participants performed a 20-s repetitive elbow flexion-extension test using a wrist-worn FM sensor. Functional performance was quantified by FM metrics, including speed (slowness), range of motion (rigidity), power (weakness), flexion and extension time (slowness), as well as speed and power reduction (exhaustion). Conventional functional measures, including timed-up-and-go test, gait and balance tests, and 5 repetition sit-to-stand test, were also performed. Results: Compared to controls, COPD patients exhibited deteriorated performances in all conventional functional assessments (d = 0.64–1.26, p < 0.010) and all FM metrics (d = 0.45–1.54, p < 0.050). FM metrics had significant agreements with conventional assessment tools (|r| = 0.35–0.55, p ≤ 0.001). FM metrics efficiently identified COPD patients with pre-frailty and frailty (d = 0.82–2.12, p < 0.050). Conclusion: This study proposes the feasibility of using a 20-s repetitive elbow flexion-extension test and wrist-worn sensor-derived frailty metrics as an alternative and practical solution to evaluate functional performance in COPD patients. Its simplicity and low risk for test administration may also facilitate its application for remote patient monitoring. Furthermore, in settings where the administration of walking test is impractical, for example, when ventilator support is needed or space is limited, FM may be used as an alternative solution. Future studies are encouraged to use the FM to quantitatively monitor the progressive decline in functional performance and quantify outcomes of rehabilitation interventions.
Lentivirus-shRNA Mediated Prolyl Hydroxylase 2 Knockdown Increases HIF-1α and Inhibits Nucleus Pulposus Cells Degeneration
Authors: Chen Qi , Shi Fangfang , Yang Chen , Mao Guangfeng , Zhou Chunguang , Liu Limin , Yang Xi , Song Yueming
Published: February 2022

Hypoxia-inducible factor (HIF) plays a crucial role in regulating the hypoxia-inducible state of nucleus pulposus cells in the intervertebral disc. In addition, the oxygen-dependent conversion of HIF-1α in nucleus pulposus cells is controlled by the protein proline 4-hydroxylase domain (PHD) family. To explore whether HIF-1α can be regulated by modulating PHD homologs to inhibit nucleus pulposus degeneration, PHD2-shRNAs were designed and a PHD2 interference vector was constructed. The expression of HIF-1α and PHD2 genes in the nucleus pulposus cells in the experimental group was detected by RT-PCR, and the expression of HIF-1α, MMP-2, Aggrecan, and Col II proteins in the P0-P3 cells in the experimental group and the control group was detected by Western blotting. The apoptosis of P0-P3 nucleus pulposus cells was detected by flow cytometry. After lentivirus infection, the interference efficiency of the PHD2 gene decreased with cell passage. The apoptosis of P1-P3 cells in the experimental group was significantly lower than that in the control group or degeneration group. Compared to the control group, the expression of HIF-1α, Aggrecan, and Col II proteins increased significantly, and the expression of MMP-2 protein decreased significantly. In conclusion, interference with PHD2 can upregulate the expression of HIF-1α, accelerate anabolism, reduce catabolism, inhibit apoptosis of nucleus pulposus cells, and then these can inhibit degeneration of nucleus pulposus cells. Our results can provide an effective therapeutic target in intervertebral discs during intervertebral disc degeneration, and this may have important clinical significance.
Establishing a Molecular Genetic Diagnosis in Children with Differences of Sex Development: A Clinical Approach
Authors: O’Connell Michele A. , Atlas Gabby , Ayers Katie , Sinclair Andrew
Published: February 2022

Background: Despite distinct underlying aetiologies, the clinical phenotypes and hormonal profiles of children with various differences of sex development (DSD) are often similar, which presents challenges to ascertaining an accurate diagnosis on clinical grounds alone. Associated features and important clinical outcomes can, however, vary significantly in different DSD, thus establishing an accurate molecular diagnosis may have important implications for decision-making and management planning in a given individual. Summary: The wider availability of next-generation sequencing techniques in recent years has led to recommendations for earlier integration of genetic testing in the diagnostic pathway of children with DSD. This review provides a practical overview of the clinical applications, advantages, and limitations of the more commonly available diagnostic genetic tests and outlines a suggested approach to testing. The potential clinical implications of a confirmed genetic diagnosis, subsequent management pathways for individuals with DSD, and challenges that remain to be addressed are also outlined. Key Messages: Despite significant improvements in our understanding of the complex genetic pathways that underlie DSD, an accurate diagnosis still eludes many affected individuals. Establishing a molecular diagnosis provides aetiological certainty, enabling improved information for families and individualized clinical management, including monitoring or prophylactic intervention where additional health risks exist. A stepwise approach to genomic testing is recommended to afford highest diagnostic yield from available resources. Looking forward, collaborative multicentre prospective studies will be required to assess the true impact of a genetic diagnosis on improving clinical care pathways and health, well-being and patient-reported outcomes for individuals with DSD.
Airgun Wound with Superior Sagittal Sinus Involvement in a Child: Case Report and Review of the Literature
Authors: Di Rita Andrea , Giacalone Martina , Peraio Simone , Salomi Francesco , Nucci Alessia , Genitori Lorenzo , Giordano Flavio
Published: February 2022

Introduction: Although still considered quite harmless, nonpowder guns (NPG) may cause severe head injuries in children. We present the case of a depressed skull fracture with superior sagittal sinus involvement following NPG injury. Decision-making and surgical management are discussed, and the current literature concerning NPG-related pediatric head injuries is reviewed. Case Presentation: A 4-year-old boy hit by a compressed-air rifle came to our center. CT scan showed a depressed skull fracture of the occipital bone on the midline and intracranial penetration of some fragments of the pellet. CT angiography documented a compression of the superior sagittal sinus without thrombosis. Soon after hospital admission, the patient showed deterioration of the neurological status suggesting intracranial hypertension. Surgery was performed with fracture elevation, removal of metal fragments, and wound debridement. The patient had a full recovery without subsequent neurological deficits. Discussion/Conclusion: Modern airguns may produce severe penetrating head injuries in children. Parents and physicians should be aware of the danger of NPG. Depressed skull fracture and dural venous sinus involvement can occur, and even a stable neurological condition may worsen. In such instances, a thorough preoperative assessment including vascular imaging is mandatory. The surgical risk is not negligible due to the possible injury of the sinus wall and subsequent intraoperative bleeding. This has to be weighted against potential complications of the penetrating injury, such as infection, sinus thrombosis, and intracranial hypertension. Our case suggests that prompt surgical treatment can be a safe and effective option.
The Effect of Intravitreal Bevacizumab Dose on Retinal Vascular Progression in Retinopathy of Prematurity
Authors: Bayramoglu Sadik Etka , Sayin Nihat
Published: February 2022

Introduction: In this study, we investigated the effect of drug dose on the progression of retinal vascularization in eyes treated with different doses of intravitreal bevacizumab (IVB). Methods: The patient charts of 259 eyes of 142 patients who were administered 0.3125 mg or 0.625 mg IVB as primary therapy for type 1 retinopathy of prematurity (ROP) or aggressive ROP (A-ROP) were retrospectively evaluated. Eighty-four eyes of 42 infants met all study inclusion criteria and underwent further morphological evaluation. Eyes treated with 0.3125 mg and 0.625 mg bevacizumab were grouped as the low dose and standard dose groups, respectively. Horizontal disc diameter (DD), optic disc-to-fovea distance (FD), and the length of temporal retinal vascularization (LTRV) were measured on pretreatment photographs (PPs) and final fluorescein angiography (FA) images. LTRV, measured in pixels, was converted to DD and FD units and analyzed. All PPs and FA images were captured with 130° PanoCam Pro camera. The difference between final LTRV and pretreatment LTRV was defined as the difference of LTRV. The ratio of difference of LTRV to pretreatment LTRV was defined as the rate of increase of LTRV. Results: Of the 255 eyes, re-treatment rate before 55 weeks postmenstrual age (PMA) was 23% in the eyes treated with 0.3125 mg IVB and 19% in the eyes treated with 0.625 mg IVB (p = 0.362). Of the 42 infants included for further morphological evaluation, the median age at the time of treatment was 36 (35–38) weeks PMA, and the median age at the time of FA imaging was 66 (62–75) weeks PMA. While the difference of LTRV by unit of DD was higher in the low dose group (p = 0.017), this difference was similar between groups by unit of FD (p = 0.412). The ratio of the increase of the LTRV was similar between groups by units of DD and FD (p = 0.081, p = 0.390; respectively). The FD/DD ratio was 4.13 ± 0.49 and 3.26 ± 0.33 at the pretreatment and final sessions, respectively (p = 0.000). Conclusion: The ratio of FD to DD decreased significantly with increasing age. The additional treatment rate and progression of retinal vascularization by unit of FD were similar between the groups. The difference of LTRV by unit of DD was higher in the low dose group. The usage of dif­ferent formulas and methods may affect the evaluation of the progression of retinal vascularization.
An Electrochemical Protocol for CRISPR-Mediated Gene-Editing of Sheep Embryonic Fibroblast Cells
Authors: Eghbalsaied Shahin , Kues Wilfried A.
Published: February 2022

Genetic engineering of farm animals is commonly carried out via cell-mediated transfection followed by somatic cell nuclear transfer. However, efficient transfer of exogenous DNA into ovine embryonic fibroblast (EF) cells without compromising cell viability has remained a challenging issue. Here, we aimed to develop a protocol for electrotransfection of sheep EF cells. First, we optimized the pulsing condition using an OptiMEM-GlutaMAX medium as the electroporation buffer and found 2 pulses of 270 V, each for 10 ms and 10 s interval, is the most efficient condition to have a high rate of transfection and cell survival. Moreover, supplementing 3% dimethyl sulfoxide (DMSO) into the electroporation medium considerably improved the cell viability after the electroporation process. The electroporation procedure resulted in >98% transfection efficiency and >97% cell survival rate using reporter plasmids. Finally, using CRISPR/Cas9-encoding vectors, we targeted BMP15 and GDF9 genes in sheep EF cells. The electroporated cells are associated with a 52% indels rate using single gRNAs as well as a highly efficient target deletion using 2 gRNAs. In conclusion, we have developed an electrotransfection protocol using the OptiMEM-GlutaMAX medium supplemented with 3% DMSO for sheep EF cells. The electroporation method can be used for cell-mediated gene-editing in sheep.
Properties of Relative Timing and Phonetic Complexity in Adults with Dysarthria Secondary to Amyotrophic Lateral Sclerosis
Authors: Romö Nina , Lee Jimin , Robb Michael P.
Published: February 2022

Introduction: This study examined the relative timing in individuals with dysarthria secondary to amyotrophic lateral sclerosis (ALS). The aim was to examine whether the relative timing was influenced by severity of dysarthria and phonetic complexity of the speech being produced. Methods: Twenty-one adults with dysarthria secondary to ALS, who presented with a range of dysarthria severity, participated in the study. A group of nonimpaired, age-matched adults served as controls. All participants produced a single phrase, across which four measures of relative timing were calculated, and the phonetic composition (complexity) of each measure was considered. Both participant groups completed the Sentence Intelligibility Test, which provided measures of speech intelligibility and speaking rate. Results: Relative timing did not significantly differ between speaker groups across the four measures, regardless of phonetic complexity. Neither Sentence Intelligibility Test score nor speaking rate were significantly correlated with relative timing. Discussion: Relative timing of phrase-level speech appears to remain intact regardless of the phonetic complexity of speech among individuals with dysarthria secondary to ALS. The potential of an internal phonological system organizing speech gestures is discussed to explain why the consistency in relative timing occurs.
Intrafamilial Phenotypic Heterogeneity in a Chinese Family with a POLR1D p.Q31Rfs*10 Variant: A Challenge in Prenatal Diagnosis
Authors: Yang Yan-Dong , Zhen Li , Li Dong-Zhi
Published: February 2022

Introduction: Treacher Collins syndrome (TCS), also known as mandibulofacial dysostosis, is an inherited craniofacial defect. Here, we report a TCS family in which the members carry the same POLR1D variant but present with phenotypic variability. Case Presentation: A 19-year-old healthy primigravida was revealed by ultrasound at 12 weeks of gestation to have a fetus with micrognathia. Prenatal genetic testing detected a heterozygous single-nucleotide deletion (NM_015972:c.91del, p.Q31Rfs*10) in the POLR1D gene, inherited from the healthy mother. Variants of POLR1D have been reported to be associated with TCS. Family studies found that a paternal healthy cousin of the mother had a similar pregnancy outcome, with a fetus of TCS and the same POLR1D variant. Discussion: Our study results pose a great challenge to prenatal diagnosis of TCS. The prenatal diagnosis cannot only rely on genetic testing. Instead, an early detailed sonographic survey will be helpful for the identification of TCS.
Supportive Care Needs and the Impact of Loss of Functioning and Symptom Burden on the Quality of Life in Patients with Advanced Colorectal Cancer
Authors: Miniotti Marco , Bassino Stefania , Fanchini Laura , Ritorto Giuliana , Leombruni Paolo
Published: February 2022

Background/Aims: Relationships between loss of functioning, symptom burden, supportive care needs, and quality of life (QoL) have been suggested in cancer populations. This cross-sectional study further investigates these relationships through mediation analyses. Methods: A total of 276 advanced colorectal cancer (CRC) patients completed validated instruments to assess cancer-related functioning, symptoms, supportive care needs, and QoL. Pearson’s correlations and multiple mediation models with bootstrapping method were performed. Results: QoL had negative correlations with supportive care needs, positive correlations with functioning measures, and negative correlations with symptom scales. Supportive care needs had negative correlations with functioning measures and positive correlations with symptom scales. Mediation analyses showed significant indirect effects of CRC-related functioning and symptoms on QoL through supportive care needs. Conclusions: Significant links between CRC-related loss of functioning, symptom burden, QoL, and supportive care needs have been established. Longitudinal studies are planned to clarify cause-and-effects relationships and establish sequences of events.
Content and Quality of Information about Stroke in Wikipedia across Multiple Languages
Authors: Marquez-Romero Juan Manuel , Lee Ángel , Soto-Cabrera Elizabeth , Hernández-Curiel Bernardo César , Prado-Aguilar Carlos Alberto
Published: February 2022

Background: Given the high contribution of stroke to the global burden of disease, there is a need for good-quality information on Web platforms such as Wikipedia. Aims: This study aimed to describe the quality of the Wikipedia articles on stroke written in different languages. Methods: We studied the world’s 30 most spoken languages. With the DISCERN score, we evaluated the quality of the information within the Wikipedia articles. Three investigators assessed each of the texts translated to English. We also registered the word count, the number of references, and if the text referred to the emergency status of stroke, cues to suspect a stroke, and allusions to endovascular treatment. Results: There is a Wikipedia article for stroke in 23 out of the 30 languages. The mean DISCERN score was 35 29.9 ± 9.2. Overall quality ranged from 3/5 in 26.1% to 1/5 in 17.4%. Word count had a mean of 36 3,145.8 ± 3,048.9 words, and the texts included a mean of 43.1 ± 57.3 references; 69.6% of the articles referred to stroke as a medical emergency, 52.2% included awareness symptoms, and 34.8% included endovascular management among the stroke treatments. Three pages included steroids as part of the stroke treatment. The DISCERN score was not correlated with the number of speakers, but it was positively correlated with the number of references (r = 0.90, p < 0.001) and the number of words (r = 0.78, p < 0.001) in the articles. Conclusion: The analyzed Wikipedia articles do not contain relevant and up-to-date information to the general population. Further, the content varies widely across the different languages and is missing for some of them. The missing versions disproportionally affect millions of potential information seekers in undeveloped countries.
Body Mass Index of Elderly Patients with Normal Renal Function as a Determining Factor for Initial Vancomycin Regimen Designing
Authors: Sakurai Norihiro , Kawaguchi Hiroshi , Kuwabara Gaku , Imoto Waki , Shibata Wataru , Yamada Koichi , Nakamura Yasutaka , Kakeya Hiroshi
Published: February 2022

Introduction: Currently, the use of actual body weight is recommended for dosing in vancomycin regimen designs, and it is important to perform therapeutic drug monitoring for efficacy and safety. However, the method to determine the appropriate vancomycin regimen for underweight or obese patients remains controversial. The aim of this study was to evaluate the impact of body mass index (BMI) on the relationship among vancomycin doses, trough concentration, and area under the curve (AUC). In addition, we identified the group of patients who were potentially more affected by BMI and evaluated the optimal dosing regimen to achieve the target AUC. Methods: We retrospectively collected data from 462 patients who received vancomycin at the Osaka City University Hospital between January 2013 and September 2019. Patients were classified by their BMI group (underweight <18.5, normal weight 18.5–24.9, and obese ≥25.0 kg/m2). We assessed the association between vancomycin dose versus trough concentration or AUC as well as dose-adjusted trough concentration and AUC in each BMI subgroup to determine the doses for achieving the target AUC. Results: The dose-adjusted trough concentration and AUC in elderly patients with normal renal function appeared to increase significantly with an increase in BMI (p < 0.05). Vancomycin doses that enabled the achievement of AUC400 in elderly patients with normal renal function decreased with increasing BMI: 17.7, 15.8, and 12.9 mg/kg per time in the underweight, normal weight, and obesity groups, respectively (p < 0.05). Conclusion: Elderly patients with normal renal function were the most affected by BMI on vancomycin trough concentration and AUC. The vancomycin regimen design in these patients should be adjusted carefully, not only based on the patient’s renal function but also based on BMI.
Integrating Al-Hijamah into the Healthcare System in Saudi Arabia: Hospital Staff’s Perception, Possible Use, and Acceptability
Authors: Buran-Omar Anabelle P. , Alaban Antonieto G.
Published: February 2022

Introduction: Al-Hijamah must be integrated into the conventional healthcare system in Saudi Arabia to respond to the unmet needs in modern medicine. This quantitative, cross-sectional study explores hospital staff’s perception, possible use, and acceptability of Al-Hijamah as an alternative medicine for their patients. Materials and Methods: 359 physicians and nurses were randomly selected as respondents across ten government hospitals in Eastern Region. The awareness and acceptability of Al-Hijamah were determined using proportion estimation. In contrast, logistic regression was used in determining the associations between awareness of Al-Hijamah and the acceptability of its integration into conventional healthcare services. Results: The majority (75%) of the hospital staff exhibited a high level of knowledge regarding Al-Hijamah and a high level of acceptance (72%) on incorporating Al-Hijamah into their practice. Hospital staff with a high level of knowledge were 3.5 times more likely to incorporate Al-Hijamah in their practice (p < 0.001). Moreover, all 13 integration concepts have a positive acceptance rate (50% and above), showing a high degree of acceptance among hospital staff. Conclusion: This study paves the way for the modification of current policies in the practice of complementary and alternative medicine in Saudi Arabia and suggests areas where the present healthcare system may be failing to meet patients’ holistic care needs.
Postoperative Pain Therapy with Laser Acupuncture after Cesarean Section under Spinal Anesthesia: A Double-Blinded, Randomized, Placebo-Controlled Trial
Authors: Brase Annika , Brauchle Dominik , Kermad Azzeddine , Volk Thomas , Morinello Emanuela , Gottschling Sven , Schneider Sven Oliver
Published: February 2022

Purpose: The aim of our prospective, randomized, double-blind, placebo-controlled study was to investigate the effect of laser acupuncture on postoperative pain in women undergoing cesarean section. Methods: 99 women (mean age 32 ± 5 years) scheduled for cesarean section under spinal anesthesia at Saarland University Hospital Medical Center, Homburg (Germany) were enrolled in this trial after giving written consent. Patients were randomized in two groups receiving a course of 3 treatments over 3 days with either active or placebo laser. Each acupuncture session treated Di-4 and Shen-men of both hands and ears. Primary outcome was defined as the pain severity at rest measured by Numeric Rating Scale (NRS) on the first postoperative day. Secondary outcome measures included analgesic consumption, time to mobilization, and length of stay. Treatment occurred on the operation day and on the following 2 days. Data were collected by a standardized questionnaire. Results: From 95 included patients, 80 were analyzed. No statistical difference between both groups were observed for pain severity at rest on the first postoperative day after cesarean section (Mann-Whitney U test, p = 0.850, verum group [mean ± standard deviation]: 3.3 ± 2.1 vs. placebo group: 3.2 ± 1.9). Secondary outcome measures regarding analgesic consumption showed no difference in NSAID or opioid between treatment and placebo group. Laser acupuncture showed no effect on time to mobilization and length of stay. Conclusion: Our study could not demonstrate significant effects by the application of laser acupuncture on postoperative pain in women undergoing cesarean section.
Low Risk of Serological Cross-Reactivity between the Dengue Virus and SARS-CoV-2-IgG Antibodies Using Advanced Detection Assays
Authors: Shurrab Farah M. , Al-Sadeq Duaa W. , Amanullah Fatima Humaira , Al-Absi Enas S. , Qotba Hamda , Yassine Hadi M. , Abu-Raddad Laith J. , Nasrallah Gheyath K.
Published: February 2022

Several studies have reported serological cross-reactivity of the immune responses between SARS-CoV-2 and DENV. Most of the available studies are based on the point-of-care rapid testing kits. However, some rapid test kits have low specificity and can generate false positives. Hence, we aimed to investigate the potential serological cross-reactivity between SARS-CoV-2 and DENV-IgG antibodies using advanced assays including chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) test. A total of 90 DENV-IgG-ELISA-positive and 90 DENV-IgG-ELISA-negative prepandemic sera were tested for anti-SARS-CoV-2-IgG using the automated CL-900i CLIA assay. Furthermore, a total of 91 SARS-CoV-2-IgG-CLIA-positive and 91 SARS-CoV-2-IgG-CLIA-negative postpandemic sera were tested for anti-DENV-IgG using the NovaLisa ELISA kit. The DENV-IgG-positive sera resulted in five positives and 85 negatives for SARS-CoV-2-IgG. Similarly, the DENV-IgG-negative sera also resulted in 5 positives and 85 negatives for SARS-CoV-2-IgG. No statistically significant difference in specificity between the DENV-IgG-positive and DENV-IgG-negative sera was found (p value = 1.00). The SARS-CoV-2-IgG-positive sera displayed 43 positives, 47 negatives, and 1 equivocal for DENV-IgG, whereas the SARS-CoV-2-IgG-negative sera resulted in 50 positives, 40 negatives, and 1 equivocal for DENV-IgG. No statistically significant difference in the proportion that is DENV-IgG positive between the SARS-CoV-2-IgG-positive and SARS-CoV-2-IgG-negative sera (p value = 0.58). In conclusion, there is a low risk of serological cross-reactivity between the DENV and SARS-CoV-2-IgG antibodies when using advanced detection assays.