bluuebunny/crossref_metadata_2025 huggingface dataset:
Reassessment of Surgical Procedures for Complex Obstructive Genital Malformations: A Case Series on Different Surgical Approaches
Authors: Hoeller Alice , Steinmacher Sahra , Schlammerl Katharina , Hoopmann Markus , Reisenauer Christl , Hattermann Valerie , Brucker Sara Y. , Rall Katharina
Published: August 2022

The objective of this case series was to describe different uterus-preserving surgical approaches and outcomes in patients with complex obstructive Müllerian duct malformation caused by cervical and/or vaginal anomalies. A retrospective analysis was performed including patients undergoing uterovaginal anastomosis (n = 6) or presenting for follow-up (n = 2) at the Department for Gynecology at the University of Tuebingen between 2017 and 2022. Uterovaginal anastomosis was performed with a one-step combined vaginal and laparoscopic approach (method A), a two-step/primary open abdominal approach with primary vaginal reconstruction followed by abdominal uterovaginal anastomosis after vaginal epithelization (method B) or an attempted one-step approach followed by secondary open abdominal uterovaginal anastomosis due to reobstruction (method A/B). Patients presented at a mean age of 15 years. Two patients were treated by method A, four by method B and two by method A/B. Functional anastomosis was established in seven of eight patients, with normal vaginal length in all patients. Concerning uterovaginal anastomosis, the primary open abdominal approach with or without previous vaginal reconstruction seems to have a higher success rate with fewer procedures and should be implemented as standard surgical therapy for complex obstructive genital malformations including the cervix.
Cryostripping—A Safe and Efficient Alternative Procedure in Chronic Venous Disease Treatment
Authors: Matei Sergiu-Ciprian , Matei Mervat , Anghel Flavia Medana , Murariu Marius-Sorin , Olariu Sorin
Published: August 2022

Objective: The presentation of cryostripping as an alternative procedure useful in venous insufficiency treatment. Methods: This retrospective study presents the results of 1087 operated patients, including follow-ups. Cryostripping was practised in all mentioned cases. Patient follow-up was performed at one week, one month, and six months postoperatively by clinical examination, Doppler ultrasonography, CIVIQ-20 and r-VCSS questionnaires. Outcomes, complications, surgery and hospitalisation period, and benefits of the method were analysed. Results: Generally, good functional and aesthetic outcomes defined by clinical symptom remission, absence of insufficient veins on Doppler ultrasonography, QoL and r-VCSS improvement (p < 0.001) were obtained. Complications included bruising ⌀ < 2 cm (32.38%), haematoma (8.92%), saphenous nerve injury (3.49%), deep vein thrombosis (0.18%). Recurrence was noted in 2.94% cases. Mean duration of procedure was 42 ± 12.5 min, mean duration of hospitalisation was 1.05 ± 0.36 days. Compared to high ligation and conventional stripping, the postoperative complications were reduced; compared to other minimally invasive procedures, the costs were reduced. Conclusions: Cryostripping seems to combine the radicality and efficacy of the stripping technique with the cosmetic advantage of the endothermal procedures, being an effective therapeutic method perfectly adapted to the economic conditions of middle-income countries health system. It is also suitable as day-case surgery.
Susceptibility to Postoperative Changes in Music Appreciation in Elderly Cochlear Implant Recipients
Authors: Chung Jee-Hye , Kim Min-Kyu , Heo Da Beom , Lee Jong Bin , Choi Jin Woong
Published: August 2022

With the rise in life expectancy and the consequent increase in the elderly population, the use of cochlear implants (CI) in elderly patients with hearing loss is also increasing. The aim of this study was to investigate whether music appreciation in elderly CI users differs from that of non-elderly users. Forty-nine adult CI recipients participated in the study, and the Korean version of the Music Background Questionnaire was utilized preoperatively and postoperatively to evaluate music appreciation. The changes between the preoperative and postoperative values were compared after categorizing the participants into a non-elderly group (<65 years; n = 31) and an elderly group (≥65 years; n = 18). When compared to the non-elderly group, the elderly individuals exhibited a significant decrease in music listening times, without a significant change in the genre of music listened to following CI surgery. Moreover, the elderly group demonstrated significant decreases in music appreciation scores in terms of music quality and music elements, perceiving music as less natural, less clear, and more complex. They also exhibited significant changes in scores with respect to perception of rhythm, melody, timbre, and lyrics. This susceptibility to postoperative changes in music appreciation among elderly CI users should be considered in surgical counseling and music training programs.
Influence of Mild Thyroid Dysfunction on Outcomes after Off-Pump Coronary Artery Bypass Surgery
Authors: Joe Young-Eun , Shin Yu Rim , Kwak Young-Lan , Shim Jae Hang , Shon Young Suk , Shim Jae-Kwang
Published: August 2022

We retrospectively evaluated the association between preoperative mild thyroid dysfunction (subclinical hypothyroidism [SCH] or low triiodothyronine [T3] syndrome) and outcomes in patients who underwent off-pump coronary surgery (OPCAB). Further, 800 patients (2015–2020) were divided into euthyroid, low T3, and SCH groups. The primary outcome assessed the association with composite endpoints (myocardial infarction, prolonged mechanical ventilation [>24 h], acute kidney injury, and 30-day/in-hospital mortality). The secondary outcome assessed the association with long-term mortality and 10% and 8% of the patients exhibited low T3 and SCH, respectively. Incidences of composite endpoints were significantly higher in the low T3 and SCH groups versus the euthyroid group (50.6%, 45.2%, 17.4%, respectively, p < 0.001). Multivariable regression analysis revealed chronic kidney disease, anemia, EuroSCORE, low T3, and SCH as independent risk factors of composite endpoints. The long-term mortality rate (median follow-up, 30 months) was higher in the low T3 and SCH groups than in the euthyroid group (9.6%, 11.3%, 2.4%, respectively, p < 0.001). In the absence of overt thyroid dysfunction, low T3 and SCH were associated with increased risk of adverse outcomes after OPCAB. Moreover, the adverse influences of low T3 and SCH seem to extend to long-term mortality, implying that routine thyroid function tests may enhance accurate risk stratification.
Transepithelial Enhanced Fluence Pulsed Light M Accelerated Crosslinking for Early Progressive Keratoconus with Chemically Enhanced Riboflavin Solutions and Air Room Oxygen
Authors: Mazzotta Cosimo , Balamoun Ashraf Armia , Chabib Ayoub , Rechichi Miguel , D’Oria Francesco , Hafezi Farhad , Bagaglia Simone Alex , Ferrise Marco
Published: August 2022

Purpose: To assess the 3-year clinical results of the 18 mW 7 J/cm2 transepithelial enhanced fluence pulsed light M accelerated crosslinking in the treatment of progressive keratoconus (KC) with chemically enhanced hyper-concentrated riboflavin solutions without iontophoresis and with air-room oxygenation. Setting: Siena Crosslinking Center, Siena, Italy. Methods: Prospective pilot, open non-randomized interventional study including 40 eyes of 30 young adult patients over 21 years old (10 simultaneous bilateral) with early (Stage I and II) progressive KC undergoing TE-EFPL 18 mW/7 J/cm2 ACXL (EFPL M TECXL). The 12 min and 58 s pulsed light (1 s on/1 s off) UV-A exposure treatments were performed with a biphasic corneal soaking using Paracel I 0.25% for 4 min and Paracel II 0.22% for 6 min riboflavin solutions and New KXL I UV-A emitter (Glaukos-Avedro, Waltham, USA) at an air room of 21% oxygenation. All patients completed the 3-year follow-up. Results: CDVA showed a statistically significant improvement in the third postoperative month (Δ + 0.17 d. e.) with a final gain of +0.22 d. eq. AK showed a statistically significant decrease in the sixth postoperative month (Δ − 1.15 diopters). K itmax showed a statistically significant decrease at 1-year follow-up (Δ − 1.3 diopters). The coma value improved significantly by the sixth month (Δ − 0.54 µm). MCT remained stable during the entire follow-up. No adverse events were recorded. Corneal OCT revealed a mean demarcation line depth at 282.6 ± 23.6 μm. Conclusions: Transepithelial enhanced fluence pulsed light M accelerated crosslinking with chemically enhanced riboflavin solution halted KC progression in young adult patients without iontophoresis and no intraoperative oxygen supplementation addressing the importance of increased fluence.
The Potential Role of Serum Tau Protein (MAPT), Neuronal Cell Adhesion Molecule (NrCAM) and Neprilysin (NEP) in Neurodegenerative Disorders Development in Psoriasis—Preliminary Results
Authors: Baran Anna , Nowowiejska Julia , Hermanowicz Justyna Magdalena , Sieklucka Beata , Krahel Julita Anna , Kiluk Paulina , Pawlak Dariusz , Flisiak Iwona
Published: August 2022

Psoriasis is one of the most common dermatoses, which shortens patients’ lives because of the wide comorbidity. However, little is known about its association with neurodegenerative diseases (NDs). We aimed to investigate whether psoriatics are at increased risk of NDs. Sixty patients with plaque-type psoriasis were enrolled into the study. Serum concentrations of tau protein (MAPT), neuronal cell adhesion molecule (NrCAM) and neprilysin (NEP), which are NDs biomarkers and have been hardly studied in psoriasis before, were measured before and after 12 weeks of treatment with acitretin or methotrexate. NrCAM and NEP concentrations were significantly lower in patients than controls, whereas MAPT higher (all p < 0.05). There was no association between these markers and psoriasis severity, BMI or disease duration. After the treatment the concentration of NrCAM and NEP significantly increased and MAPT decreased (p < 0.001, p < 0.05, p < 0.01, respectively). Methotrexate had significant influence on the concentrations of all markers, hence it seems to have neuroprotective properties. Psoriasis severity and duration do not seem to affect the risk of neurodegenerative process. Our results suggest that NDs could be considered as another comorbidity of psoriasis and that further research are needed in order to establish their definite association.
Correlation between the Outcome of Vitrectomy for Proliferative Diabetic Retinopathy and Erythrocyte Hematocrit Level and Platelet Function
Authors: Sato Keiji , Jujo Tatsuya , Sekine Reio , Uchiyama Naoto , Kakehashi Kota , Kogo Jiro
Published: August 2022

We investigate-d whether biomarkers such as red blood cell hematocrit (Hct), platelet count (PLT), mean platelet volume (MPV), and platelet distribution width (PDW) are useful prognostic indicators of postoperative macular edema (ME) after vitrectomy for proliferative diabetic retinopathy (PDR). A total of 42 eyes of 42 patients with PDR who underwent vitrectomy between January 2018 and May 2020 were analyzed retrospectively. We divided them into two groups according to whether treatment was required for postoperative ME and compared the relationship between Hct, PLT, MPV, and PDW and the onset of postoperative ME. The group that received postoperative treatment (group T) comprised 11 eyes of 11 patients, and the group that did not (group N) comprised 31 eyes of 31 patients. The age (years) was 52.0 ± 3.1 in group T and 60.0 ± 11.6 in group N. When appropriate statistical analysis was performed for comparison between groups, significant differences were found in age (p = 0.05), insulin use (p = 0.03), preoperative intraocular pressure (p = 0.05), diastolic blood pressure (p = 0.03), and Hct (p = 0.04). Multivariate logistic regression analysis was performed, and a significant difference was found in Hct (p = 0.02). These results suggest that Hct might be useful as a predictor of ME after PDR surgery.
Tube–Iris Distance and Corneal Endothelial Cell Damage Following Ahmed Glaucoma Valve Implantation
Authors: Kim Yitak , Cho Won Jeong , Kim Jung Dong , Cho Hyuna , Bae Hyoung Won , Kim Chan Yun , Choi Wungrak
Published: August 2022

The most significant factor for endothelial cell loss should be readily identified, since prevention is the most crucial treatment. Here, we investigate risk factors for corneal endothelial cell density (ECD) decline following Ahmed glaucoma valve (AGV) implantation and determine the optimal cut-off values. This study included 103 eyes (95 patients) with glaucoma that underwent AGV implantation between January 2006 and January 2021 at a single medical center (Severance Hospital). We conducted consecutive t-tests between two groups separated by the ECD change rate to determine the survival state of the enrolled patients. Associations were evaluated using univariable and multivariable linear regressions. Optimal cut-off values for identified risk factors were analyzed using a Cox proportional hazards model and a receiver operating characteristic (ROC) curve based on logistic regression. Mean follow-up duration was 4.09 ± 2.20 years. After implementing consecutive t-tests, only patients with an ECD change rate greater than −6.1%/year were considered to have survived. Tube–iris distance (TID) was the only statistically significant factor identified in both the univariable and multivariable linear regressions. The cut-off value determined from the consecutive Cox regression method was 0.33 mm (smallest p-value of 0.0087), and the cut-off value determined from the ROC method was 0.371 mm (area under the receiver operating characteristic curve [AUC], 0.662). Patients with short TIDs showed a better ECD prognosis following AGV surgery; we suggest optimal TID cut-off values of 0.33 mm and 0.371 mm based on the implemented Cox regression and ROC methodology, respectively.
Prognostic Effect of the Dose of Radiation Therapy and Extent of Lymphadenectomy in Patients Receiving Neoadjuvant Chemoradiotherapy for Esophageal Squamous Carcinoma
Authors: Pai Chu-Pin , Chien Ling-I , Huang Chien-Sheng , Hsu Han-Shui , Hsu Po-Kuei
Published: August 2022

Neoadjuvant chemoradiotherapy has been used for patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal dose of radiation therapy and the effect of lymphadenectomy after neoadjuvant therapy on patient outcomes are uncertain. We retrospectively reviewed the data of patients who received neoadjuvant therapy followed by surgery for ESCC. Overall survival (OS), disease-free survival (DFS), and perioperative outcomes were compared between patients who received radiation doses of 45.0 Gy (PF4500) and 50.4 Gy (PF5040). Subgroup analysis was performed based on the number of lymph nodes removed through lymph node dissection (LND). Data from a total of 126 patients were analyzed. No significant differences were found in 3-year OS and DFS between the PF4500 and PF5040 groups (OS: 45% versus 54%, p = 0.218; DFS: 34% versus 37%, p = 0.506). In both groups, no significant differences were found in 3-year locoregional-specific DFS between patients with a total LND number ≤17 and >17 (PF4500, 35% versus 50%, p = 0.291; PF5040 group, 45% versus 46%, p = 0.866). The PF5040 and PF4500 groups were comparable in terms of survival outcomes and local control. Although no additional survival benefits were identified, the extent of LND should not be altered according to the radiation dose.
The Anticancer Efficacy of Thiourea-Mediated Reduced Graphene Oxide Nanosheets against Human Colon Cancer Cells (HT-29)
Authors: Vimalanathan Babu , Vijaya J. Judith , Mary B. Carmel Jeeva , Ignacimuthu Savarimuthu , Daniel Magesh , Jayavel Ramasamy , Bououdina Mohamed , Bellucci Stefano
Published: August 2022

The current research focuses on the fabrication of water-soluble, reduced graphene oxide (rGO) employing thiourea (T) using a simple cost-effective method, and subsequently examining its anticancer characteristics. The cytotoxicity caused by graphene oxide (GO) and T-rGO is investigated in detail. Biological results reveal a concentration-dependent toxicity of GO and T-rGO in human colon cancer cells HT-29. A decrease in cell viability alongside DNA fragmentation is observed. Flow cytometry analysis confirms the cytotoxic effects. The novelty in this work is the use of raw graphite powder, and oxidants such as KMNO4, NaNO3, and 98 percent H2SO4 to produce graphene oxide by a modified Hummers method. This study demonstrates a simple and affordable procedure for utilising thiourea to fabricate a water-soluble reduced graphene oxide, which will be useful in a variety of biomedical applications.
Effect of Different Solvents on the Extraction of Compounds from Different Parts of Undaria pinnatifida (Harvey) Suringar
Authors: Lee Hyun-Hwa , Kim Jin-Sol , Jeong Jun-Han , Park Su Mi , Sathasivam Ramaraj , Lee Sook Young , Kim Chun Sung
Published: August 2022

Asian kelp (Undaria pinnatifida) is a brown alga mainly grown and consumed in East Asian countries such as China, Japan, and Korea. To date, studies on the various biological activities of Asian kelp have been conducted; however, studies focusing on the different parts of Asian kelp and their use for other than food are limited. Therefore, in this study, different parts of Asian kelp, namely, whole U. pinnatifida (UP), U. pinnatifida blade (UPB), U. pinnatifida stipe (UPS), and U. pinnatifida sporophylls (UPSP), were extracted by using different solvents including ethanol, methanol, and hot water. The antioxidant activity, antiaging effect, and phenolic content of the extracts were investigated. The results revealed that the UPB methanolic extract had significantly higher polyphenol and flavonoid contents, with the respective values of 5.61 mg TAN/g and 7.80 mg QUE/g, than the other extracts. The DPPH and ABTS radical scavenging activities and FRAP values were the highest in the 95% ethanolic (IC50 12.73 mg/mL), methanolic (63.83%), and ethanolic (75.75%) extracts of UPB, respectively. Superoxide dismutase, catalase, and ascorbate peroxidase enzymatic activities were also measured, and the results showed that the activities of these enzymes were higher in the UPB methanolic extract than in the other extracts. Similarly, the highest elastase and tyrosinase inhibitory activity was observed in the UPB methanolic extract. The highest phenolic content was found in the hot water extract of UP (4-hydroxybenzoic acid) and the ethanolic extracts of all parts (naringin and naringenin). The phenolic content of the Asian kelp differed depending on the parts and extraction solvents used. Finally, the antioxidant activity of the UPB extract showed a close correlation with the polyphenol and flavonoid contents. The methanol extract of UPB exhibited excellent antioxidant and antiaging activities, indicating its potential use in the development of functional materials using Asian kelp and in other new applications.
Robust Direction Finding via Acoustic Vector Sensor Array with Axial Deviation under Non-Uniform Noise
Authors: Wang Weidong , Li Xiangshui , Zhang Kai , Shi Juan , Shi Wentao , Ali Wasiq
Published: August 2022

To minimize the major decline in direction of arrival (DOA) estimation performance for an acoustic vector sensor array (AVSA) with the coexistence of axial deviation and non-uniform noise, a two-step iterative minimization (TSIM) method is proposed in this paper. Initially, the axial deviation measurement model of an AVSA is formulated by incorporating the disturbance parameter into the signal model, and then a novel AVSA manifold matrix is defined to estimate the sparse signal power and noise power mutually. After that, to mitigate a joint optimization problem to achieve the sparse signal power, the noise power and the axial deviation matrix, two auxiliary cost functions, are presented based on the covariance matrix fitting (CMF) criterion and the weighted least squares (WLS), respectively. Furthermore, their analytical expressions are also derived. In addition, to further enhance their prediction accuracy, the estimated axial deviation matrix is modified based on its specific structural properties. The simulation results demonstrate the superiority and robustness of the proposed technique over several conventional algorithms.
Magnetomechanical Stress-Induced Colon Cancer Cell Growth Inhibition
Authors: Spyridopoulou Katerina , Aindelis Georgios , Sarafidis Charalampos , Kalogirou Orestis , Chlichlia Katerina
Published: August 2022

The application of magnetomechanical stress in cells using internalized magnetic nanoparticles (MNPs) actuated by low-frequency magnetic fields has been attracting considerable interest in the field of cancer research. Recent developments prove that magnetomechanical stress can inhibit cancer cells’ growth. However, the MNPs’ type and the magnetic field’s characteristics are crucial parameters. Their variability allows multiple combinations, which induce specific biological effects. We previously reported the antiproliferative effects induced in HT29 colon cancer cells by static-magnetic-field (200 mT)-actuated spherical MNPs (100 nm). Herein, we show that similar growth inhibitory effects are induced in other colon cancer cell lines. The effect of magnetomechanical stress was also examined in the growth rate of tumor spheroids. Moreover, we examined the biological mechanisms involved in the observed cell growth inhibition. Under the experimental conditions employed, no cell death was detected by PI (propidium iodide) staining analysis. Flow cytometry and Western blotting revealed that G2/M cell cycle arrest might mediate the antiproliferative effects. Furthermore, MNPs were found to locate in the lysosomes, and a decreased number of lysosomes was detected in cells that had undergone magnetomechanical stress, implying that the mechanical activation of the internalized MNPs could induce lysosome membrane disruption. Of note, the lysosomal acidic conditions were proven to affect the MNPs’ magnetic properties, evidenced by vibrating sample magnetometry (VSM) analysis. Further research on the combination of the described magnetomechanical stress with lysosome-targeting chemotherapeutic drugs could lay the groundwork for the development of novel anticancer combination treatment schemes.
Involvement of the Autophagy Protein Atg1 in Development and Virulence in Botryosphaeria dothidea
Authors: Liu Na , Zhu Meiqi , Zhang Yihan , Wang Zhongqiang , Li Baohua , Ren Weichao
Published: August 2022

Botryosphaeria canker and fruit rot caused by the fungus Botryosphaeria dothidea is one of the most destructive diseases of apple worldwide. Autophagy is an evolutionarily conserved self-degradation process that is important for maintaining homeostasis to ensure cellular functionality. To date, the role of autophagy in B. dothidea is not well elucidated. In this study, we identified and characterized the autophagy-related protein Atg1 in B. dothidea. The BdAtg1 deletion mutant ΔBdAtg1 showed autophagy blockade and phenotypic defects in mycelial growth, conidiation, ascosporulation and virulence. In addition, ΔBdAtg1 exhibited an increased number of nuclei in the mycelial compartment. Comparative transcriptome analysis revealed that inactivation of BdAtg1 significantly influenced multiple metabolic pathways. Taken together, our results indicate that BdAtg1 plays an important role in vegetative differentiation and the pathogenicity of B. dothidea. The results of this study will provide a reference for the development of new target-based fungicides.
GR-2397: Review of the Novel Siderophore-like Antifungal Agent for the Treatment of Invasive Aspergillosis
Authors: Shaw Karen Joy
Published: August 2022

GR-2397 (previously VL-2397, ASP2397) is a first-in-class antifungal agent for the treatment of invasive aspergillosis. This siderophore-like molecule resembles ferrichrome; however, it is differentiated by three amino acid changes and an aluminum rather than iron chelate. GR-2397 is transported into fungal cells via the Sit1 transporter, which is not found in humans, leading to fungal specificity. Although the precise mechanism of action is currently unknown, GR-2397 is active against Aspergillus spp. including azole-resistant strains, Fusarium solani, and Candida glabrata in addition to other organisms. Efficacy has been demonstrated in several animal models of invasive aspergillosis, including a 24 h delayed-treatment model where rapid fungicidal activity was observed. Phase 1 single- and multiple-ascending intravenous dose studies showed that GR-2397 was safe and well-tolerated in humans. No signs of GR-2397 accumulation were observed following IV infusions of 300, 600, and 1200 mg every 24 h (q24h) for 7 days. The favorable safety, tolerability and drug–drug interaction profile, along with good tissue distribution, support further development of GR-2397 as a new treatment option for patients with invasive aspergillosis. This systematic review summarizes the published findings of GR-2397.
Biosynthesis of Sesquiterpenes in Basidiomycetes: A Review
Authors: Wu Jiajun , Yang Xiaoran , Duan Yingce , Wang Pengchao , Qi Jianzhao , Gao Jin-Ming , Liu Chengwei
Published: August 2022

Sesquiterpenes are common small-molecule natural products with a wide range of promising applications and are biosynthesized by sesquiterpene synthase (STS). Basidiomycetes are valuable and important biological resources. To date, hundreds of related sesquiterpenoids have been discovered in basidiomycetes, and the biosynthetic pathways of some of these compounds have been elucidated. This review summarizes 122 STSs and 2 fusion enzymes STSs identified from 26 species of basidiomycetes over the past 20 years. The biological functions of enzymes and compound structures are described, and related research is discussed.
Thermal Boost Combined with Interstitial Brachytherapy in Early Breast Cancer Conserving Therapy—Initial Group Long-Term Clinical Results and Late Toxicity
Authors: Chicheł Adam , Burchardt Wojciech , Chyrek Artur J. , Bielęda Grzegorz
Published: August 2022

(1) In breast-conserving therapy (BCT), adjuvant radiation, including tumor bed boost, is mandatory. Safely delivered thermal boost (TB) based on radio-sensitizing interstitial microwave hyperthermia (MWHT) preceding standard high-dose-rate (HDR) brachytherapy (BT) boost has the potential for local control (LC) improvement. The study is to report the long-term results regarding LC, disease-free survival (DFS), overall survival (OS), toxicity, and cosmetic outcome (CO) of HDR-BT boost ± MWHT for early breast cancer (BC) patients treated with BCT. (2) In the years 2006 and 2007, 57 diverse stages and risk (IA-IIIA) BC patients were treated with BCT ± adjuvant chemotherapy followed by 42.5–50.0 Gy whole breast irradiation (WBI) and 10 Gy HDR-BT boost. Overall, 25 patients (group A; 43.9%) had a BT boost, and 32 (group B; 56.1%) had an additional pre-BT single session of interstitial MWHT on a tumor bed. Long-term LC, DFS, OS, CO, and late toxicity were evaluated. (3) Median follow-up was 94.8 months (range 1.1–185.5). LC was 55/57, or 96.5% (1 LR in each group). DFS was 48/57, or 84.2% (4 failures in group A, 5 in B). OS was 46/57, or 80.7% (6 deaths in group A, 5 in B). CO was excellent in 60%, good in 36%, and satisfactory in 4% (A), and in 53.1%, 34.4%, and 9.4% (B), respectively. One poor outcome was noted (B). Late toxicity as tumor bed hardening occurred in 19/57, or 33.3% of patients (9 in A, 10 in B). In one patient, grade 2 telangiectasia occurred (group A). All differences were statistically insignificant. (4) HDR-BT boost ± TB was feasible, well-tolerated, and highly locally effective. LC, DFS, and OS were equally distributed between the groups. Pre-BT MWHT did not increase rare late toxicity.
Pharmacogenetic Expression of CYP2C19 in a Pediatric Population
Authors: Pierre-François Marie Josette Déborah , Gagné Vincent , Brukner Ivan , Krajinovic Maja
Published: August 2022

Genetic variability in CYP2C19 may be associated with both lack of efficacy and toxicity of drugs due to its different metabolic status based on the presence of particular alleles. This literature review summarizes current knowledge relative to the association or treatment adaptation based on CYP2C19 genetics in a pediatric population receiving drugs metabolized by CYP2C19, such as voriconazole, antidepressants, clopidogrel and proton pump inhibitors. Additionally, we also presented one of the approaches that we developed for detection of variant alleles in the CYP2C19 gene. A total of 25 articles on PubMed were retained for the study. All studies included pediatric patients (age up to 21 years) having benefited from an assessment of CYP2C19. CYP2C19 poor and intermediate metabolizers exhibit a higher trough plasma concentration of voriconazole, and PPIs compared to the rapid and ultra-rapid metabolizers. The pharmacogenetic data relative to CYP2C19 and clopidogrel in the pediatric population are not yet available. CYP2C19 poor metabolizers have a higher trough plasma concentration of antidepressants compared to the rapid and the ultra-rapid metabolizers. Modification of allele-specific PCR through the introduction of artificial mismatch is presented. CYP2C19 genotyping remains a powerful tool needed to optimize the treatment of children receiving voriconazole, PPIs, and anti-depressants.
Statistical Validation of Risk Alleles in Genetic Addiction Risk Severity (GARS) Test: Early Identification of Risk for Alcohol Use Disorder (AUD) in 74,566 Case–Control Subjects
Authors: Blum Kenneth , Han David , Gupta Ashim , Baron David , Braverman Eric R. , Dennen Catherine A. , Kazmi Shan , Llanos-Gomez Luis , Badgaiyan Rajendra D. , Elman Igor , Thanos Panayotis K. , Downs Bill W. , Bagchi Debasis , Gondre-Lewis Marjorie C. , Gold Mark S. , Bowirrat Abdalla
Published: August 2022

Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including GWAS. To develop an accurate test to help identify those at risk for at least Alcohol Use Disorder (AUD), Blum’s group developed the Genetic Addiction Risk Severity (GARS) test, consisting of ten genes and eleven associated risk alleles. In order to statistically validate the selection of these risk alleles measured by GARS, we applied strict analysis to studies that investigated the association of each polymorphism with AUD or AUD-related conditions published from 1990 until 2021. This analysis calculated the Hardy–Weinberg Equilibrium of each polymorphism in cases and controls. If available, the Pearson’s χ2 test or Fisher’s exact test was applied to comparisons of the gender, genotype, and allele distribution. The statistical analyses found the OR, 95% CI for OR, and a post-risk for 8% estimation of the population’s alcoholism prevalence revealed a significant detection. The OR results showed significance for DRD2, DRD3, DRD4, DAT1, COMT, OPRM1, and 5HTT at 5%. While most of the research related to GARS is derived from our laboratory, we are encouraging more independent research to confirm our findings.
Association of Blood Pressure Indices with Right and Left Cardio-Ankle Vascular Index (CAVI) and Its Mathematically Corrected Form (CAVI0) for the Evaluation of Atherosclerosis
Authors: Hung Tzu-Jen , Hsieh Nan-Chen , Alizargar Elaheh , Bai Chyi-Huey , Wang Kai-Wei K. , Hatefi Shahrokh , Alizargar Javad
Published: August 2022

Background and Objectives: The cardio-ankle vascular index (CAVI) is an index for arterial stiffness that is theoretically independent of blood pressure. CAVI0 is the mathematically corrected formula of CAVI that has been claimed to be less dependent on blood pressure changes. The association of right and left CAVI and CAVI0 with blood pressure indices can reveal the importance of considering the blood pressure of the patient despite their theoretical independency. In this study, we assessed the right and left CAVI and CAVI0 and evaluated the main effect of blood pressure indices on them with respect to age. Materials and Methods: We collected the following data of 136 community-dwelling individuals: age; sex; weight; height; body mass index; right and left CAVI and CAVI0; and systolic (SBP), diastolic (DBP), and mean blood pressure (MBP). The association of right and left CAVI and CAVI0 with blood pressure indices was evaluated using regression analysis. Results: Regression analysis revealed that SBP, DBP, and MBP were associated with right and left CAVI (independent of age). Moreover, SBP was associated with both right and left CAVI0 (independent of age), whereas DBP was not associated with right or left CAVI0. Conclusion: Right and left arterial stiffness measured using CAVI has no different associations with SBP, DBP, and MBP. Both right and left CAVI0 were independently associated with SBP, whereas neither left nor right CAVI0 was independently associated with DBP. MBP was only associated with the right-side CAVI0 in community-dwelling individuals.
A Predictive Model of Regional Dementia Prevalence Using Geographic Weighted Regression Analysis
Authors: Lim Jihye , Park Jong-Ho
Published: August 2022

Globally, dementia is one of the highest priority public health policy issues. This study was conducted to analyze the spatial distribution pattern of dementia prevalence using geographic weighted regression analysis and to identify preventable risk factors at the regional level of dementia prevalence. For the data to be analyzed, this work used the 2020 regional dementia prevalence index of the Korea Central Dementia Center and the regional health statistics of the Korea Centers for Disease Control and Prevention Agency (KDCA). Spatial autocorrelation analysis, hot spot analysis, and geographic weighted regression analysis were performed to identify regional associations of dementia prevalence, cluster regions with high dementia prevalence, and risk factors for regional dementia prevalence. As a result of the hot spot analysis, the regions corresponding to the hot spots with the high prevalence of dementia were found to be adjacent to each other, such as in Jeonnam, Jeonbuk, and Gyeongbuk, and the regions corresponding to the cold spots with the low prevalence of dementia were adjacent to each other, such as Seoul, Gyeonggi, Incheon, Busan, and Ulsan. The results of geographic weighted regression analysis showed that educational level, walking practice rate, hypertension prevalence, and a low-sodium diet preference were found to be risk factors for the prevalence of dementia. These results suggest that there is a need for a dementia prevalence management strategy to increase the walking practice rate and low-sodium diet preference rate, and decrease the hypertension prevalence, centering on the hot spot area, which is a cluster area with high dementia prevalence. This study is expected to be useful as basic data that can help in prioritizing health policies considering spatial characteristics for community health promotion.
Prospective Evaluation of Two Wall Orbital Fractures Involving the Medial Orbital Wall: PSI Reconstruction versus PDS Repair—Worth the Effort?
Authors: Wilkat Max , Hufendiek Karsten , Karahisarlioglu Merve , Borrelli Maria , Sproll Christoph , Rana Majeed
Published: August 2022

Proper treatment of the two-wall fractured orbit is still controversial. Specifically, there is no consensus on the issue of the necessity of medial orbital wall repair. With anatomically critical structures at risk during the surgical approach, surgeons’ view on the necessity of medial orbital wall repair often is restricted and an aesthetically disturbing enophthalmos is more likely to be accepted. Therefore, treatment options range from leaving the medial wall without repair to reconstruction with autogenous tissue or alloplastic materials, which can lead to moderate to severe side effects. However, emerging technologies such as patient-specific implants (PSI) offer a reliable and anatomically correct reconstruction of the bony orbit. This study aimed to evaluate the outcome of full orbital reconstruction using PSIs compared to only orbital floor repair using PDS (bioresorbable polydioxanone) foils leaving the medial orbital wall untouched in traumatic two-wall orbital fractures. Of all patients treated at the University Hospital of Düsseldorf between 2017 and 2019 who suffered from traumatic orbital fracture, only patients with a two-wall orbital fracture involving both the orbital floor and the medial wall (n = 68) were included. Patients were treated either with a PSI (n = 35) or a PDS foil (n = 33). Primary outcome parameters were ophthalmological disturbances analyzed via clinical investigation and intra-orbital angles, volumes and implant position analyzed with radiological 3D-datasets. While a two-wall reconstruction using PSIs led to a significant improvement of the enophthalmos, the rate of postoperative enophthalmos was significantly increased in cases of only orbital floor repair with PDS foils. Radiologically, a significant reconstruction of the three-dimensional bony orbit succeeded with the simple use of PSIs leading to a significant reduction in the traumatically enlarged orbital volume. PSI also led to a significant reduction in the traumatically enlarged medial angle of the orbit. This was not the case for single-floor repair with PDS foil. The results of this study suggest that complex orbital fractures can be reconstructed at an even higher degree of accuracy with selective laser-melted PSIs than PDS foils. In order to achieve a true to original reconstruction of the bony orbit, surgical treatment of the medial orbital wall can be advocated for in the long term depending on the indication.
Relationship between Antenatal Mental Health and Facial Emotion Recognition Bias for Children’s Faces among Pregnant Women
Authors: Takubo Youji , Tsujino Naohisa , Aikawa Yuri , Fukiya Kazuyo , Uchino Takashi , Katagiri Naoyuki , Ito Megumu , Akiba Yasuo , Mizuno Masafumi , Nemoto Takahiro
Published: August 2022

The importance of identification of facial emotion recognition (FER) bias for a child’s face has been reinforced from the perspective of risk screening for future peripartum mental health problems. We attempted to clarify the relationship of FER bias for children’s faces with antenatal depression and bonding failure among pregnant women, taking into consideration their broad social cognitive abilities and experience in child raising. This study had a cross-sectional design, and participants were women in their second trimester of pregnancy. Seventy-two participants were assessed by the Edinburgh Postnatal Depression Scale (EPDS), the Mother-to-Infant Bonding Questionnaire (MIBQ), and a series of social cognitive tests. FER bias for a child’s face was assessed by Baby Cue Cards (BCC), and a larger number of disengagement responses suggest greater sensitivity to a child’s disengagement facial expressions. In a regression analysis conducted using EPDS as the dependent variable, a larger number of disengagement responses to the BCC (β = 0.365, p = 0.001) and the primipara status (β = −0.263, p = 0.016) were found to significantly contribute to antenatal depressive symptoms. Also, more disengagement responses to the BCC also significantly contributed to bonding failure as measured by the MIBQ (β = 0.234, p = 0.048). Maternal sensitivity to the child’s disengagement cues was associated with antenatal depressive symptoms and bonding failure more than the other social cognitive variables. The effects of FER bias on postpartum mental health and abusive behavior needs to be clarified by further longitudinal studies.
Effectiveness of Cement Augmentation on Early Postoperative Mobility in Patients Treated for Trochanteric Fractures with Cephalomedullary Nailing: A Prospective Cohort Study
Authors: Mochizuki Yusuke , Yamamoto Norio , Fujii Tatsuya , Tomita Yosuke
Published: August 2022

Fixation using cephalomedullary nails (CMNs) with additional cement augmentation (CA) was developed as a novel treatment option for the osteosynthesis of osteoporotic trochanteric fractures, though the effectiveness of CA on early postoperative mobility remains uncertain. This multicenter prospective cohort study aimed to estimate the effectiveness of CA on early postoperative mobility in patients with trochanteric fractures. We enrolled patients with femoral trochanteric fractures aged >60 years who were able to walk independently before the injury. The primary outcome was the postoperative 3-day cumulated ambulation score (CAS); the secondary outcome was the visual analog scale (VAS) pain score at rest and during movement on postoperative days 1–3. The outcomes of the patients treated using CMNs with or without CA were compared. Sixty-three eligible patients were categorized into CA (n = 32) and control (n = 31) groups. In univariate analysis, the CA group had significantly higher CAS values, lower VAS scores at rest on day 1 postoperatively, and lower VAS scores during movement on day 3. In multivariable linear regression analyses, the CA group had significantly higher CAS values (beta, 2.1; 95% confidence interval, 0.5 to 3.6; p = 0.01). The CA group had a negative adjusted beta value in their VAS scores during movement. This study indicated that CA was associated with a high CAS value in patients with geriatric trochanteric fractures. However, CA was not associated with pain reduction at rest and during movement during the initial postoperative days.
A Systematic Review of Polygenic Models for Predicting Drug Outcomes
Authors: Siemens Angela , Anderson Spencer J. , Rassekh S. Rod , Ross Colin J. D. , Carleton Bruce C.
Published: August 2022

Polygenic models have emerged as promising prediction tools for the prediction of complex traits. Currently, the majority of polygenic models are developed in the context of predicting disease risk, but polygenic models may also prove useful in predicting drug outcomes. This study sought to understand how polygenic models incorporating pharmacogenetic variants are being used in the prediction of drug outcomes. A systematic review was conducted with the aim of gaining insights into the methods used to construct polygenic models, as well as their performance in drug outcome prediction. The search uncovered 89 papers that incorporated pharmacogenetic variants in the development of polygenic models. It was found that the most common polygenic models were constructed for drug dosing predictions in anticoagulant therapies (n = 27). While nearly all studies found a significant association with their polygenic model and the investigated drug outcome (93.3%), less than half (47.2%) compared the performance of the polygenic model against clinical predictors, and even fewer (40.4%) sought to validate model predictions in an independent cohort. Additionally, the heterogeneity of reported performance measures makes the comparison of models across studies challenging. These findings highlight key considerations for future work in developing polygenic models in pharmacogenomic research.
Elevated Expression of RGS2 May Underlie Reduced Olfaction in COVID-19 Patients
Authors: Avnat Eden , Shapira Guy , Gurwitz David , Shomron Noam
Published: August 2022

Anosmia is common in COVID-19 patients, lasting for weeks or months following recovery. The biological mechanism underlying olfactory deficiency in COVID-19 does not involve direct damage to nasal olfactory neurons, which do not express the proteins required for SARS-CoV-2 infection. A recent study suggested that anosmia results from downregulation of olfactory receptors. We hypothesized that anosmia in COVID-19 may also reflect SARS-CoV-2 infection-driven elevated expression of regulator of G protein signaling 2 (RGS2), a key regulator of odorant receptors, thereby silencing their signaling. To test our hypothesis, we analyzed gene expression of nasopharyngeal swabs from SARS-CoV-2 positive patients and non-infected controls (two published RNA-sequencing datasets, 580 individuals). Our analysis found upregulated RGS2 expression in SARS-CoV-2 positive patients (FC = 14.5, Padj = 1.69 × 10−5 and FC = 2.4; Padj = 0.001, per dataset). Additionally, RGS2 expression was strongly correlated with PTGS2, IL1B, CXCL8, NAMPT and other inflammation markers with substantial upregulation in early infection. These observations suggest that upregulated expression of RGS2 may underlie anosmia in COVID-19 patients. As a regulator of numerous G-protein coupled receptors, RGS2 may drive further neurological symptoms of COVID-19. Studies are required for clarifying the cellular mechanisms by which SARS-CoV-2 infection drives the upregulation of RGS2 and other genes implicated in inflammation. Insights on these pathway(s) may assist in understanding anosmia and additional neurological symptoms reported in COVID-19 patients.
Financial Inclusion and Intersectionality: A Case of Business Funding in the South African Informal Sector
Authors: Simatele Munacinga , Kabange Martin
Published: August 2022

Financial inclusion is a critical tool in the fight against poverty. This is especially important in economies where informal markets are prevalent due to the pervasion of market failures. Marginal identities such as gender, income and race are generally noted in the literature as factors influencing access to finance. However, these marginalities are often investigated linearly, with little attention paid to the fact that they interact to compound financial exclusion. Using a survey of informal traders, the paper investigates how having multiple marginalities influences the choice of start-up capital. A sample is drawn from three different provinces in South Africa. A multinomial logit model is estimated. Using a simulation of representative groups, the paper shows that multiple marginalities matter in accessing finance. Education emerges as the most important factor that can temper the effect of other marginalities in the financial sector. Both females and blacks with higher levels of education have better access to more stable sources of start-up capital.
Risks and Challenges Associated with NEOM Project in Saudi Arabia: A Marketing Perspective
Authors: Algumzi Areej
Published: August 2022

Saudi Arabia has proposed a new project, NEOM city, planned on the coast of the Red Sea with various unique and challenging features as a part of its vision 2030 to transform itself from an oil-dependent economy to knowledge-based economy. However, there are various risks and challenges associated with the project, the study of which is essential to effectively design and implement marketing and promotional strategies. Considering the large scale and scope of the project, the purpose of this study is to identify and evaluate the major contexts and associated risks in accordance with the planned city’s objectives. An online questionnaire-based survey was used to collecting data related to the severity of the risks identified and classified in a literature review. A purposive sampling approach was adopted to select experts from various governmental institutions to participate in the study. A final sample of 417 expert participants was achieved from various ministries and departments in Saudi Arabia. Eleven risk factors and challenges were identified, including design challenges, as well as legal, contractual, operational, force majeure, human resources, financial, technological, political, environmental, and sociocultural risks. Risks related to human resources (mean impact = 4) and technology factors (mean impact = 4), as well as contractual risks (mean impact = 3.9), were identified to be very high, whereas environmental (mean impact = 2.7), legal (mean impact = 2.5), and force majeure (mean impact = 2.2) risks were identified to be of low severity. Managing mega projects requires effective planning and implementation, along with risk identification and mitigation mechanisms. In addition, it is essential to manage various influencing factors (especially government decisions) in the process of implementation to achieve success.