bluuebunny/crossref_metadata_2025 huggingface dataset:
A Personalized Longitudinal Strategy in Low-Grade Glioma Patients: Predicting Oncological and Neural Interindividual Variability and Its Changes over Years to Think One Step Ahead
Authors: Duffau Hugues
Published: October 2022

Diffuse low-grade glioma (LGG) is a rare cerebral cancer, mostly involving young adults with an active life at diagnosis. If left untreated, LGG widely invades the brain and becomes malignant, generating neurological worsening and ultimately death. Early and repeat treatments for this incurable tumor, including maximal connectome-based surgical resection(s) in awake patients, enable postponement of malignant transformation while preserving quality of life owing to constant neural network reconfiguration. Due to considerable interindividual variability in terms of LGG course and consecutive cerebral reorganization, a multistage longitudinal strategy should be tailored accordingly in each patient. It is crucial to predict how the glioma will progress (changes in growth rate and pattern of migration, genetic mutation, etc.) and how the brain will adapt (changes in patterns of spatiotemporal redistribution, possible functional consequences such as epilepsy or cognitive decline, etc.). The goal is to anticipate therapeutic management, remaining one step ahead in order to select the optimal (re-)treatment(s) (some of them possibly kept in reserve), at the appropriate time(s) in the evolution of this chronic disease, before malignization and clinical worsening. Here, predictive tumoral and non-tumoral factors, and their ever-changing interactions, are reviewed to guide individual decisions in advance based on patient-specific markers, for the treatment of LGG.
A Paradigm Shift in Understanding the Pathological Basis of Autism Spectrum Disorder: From the Womb to the Tomb
Authors: Noda Yoshihiro
Published: October 2022

Autism Spectrum Disorder (ASD) is currently diagnosed based on clinical assessment of behavioral characteristics [...]
The Safety and Efficacy of Hepatic Transarterial Embolization Using Microspheres and Microcoils in Patients with Symptomatic Polycystic Liver Disease
Authors: Coussy Alexis , Jambon Eva , Le Bras Yann , Combe Christian , Chiche Laurence , Grenier Nicolas , Marcelin Clément
Published: October 2022

Purpose: We investigated the long-term safety and efficacy of hepatic transarterial embolization (TAE) in patients with symptomatic polycystic liver disease (PLD). Materials and Methods: A total of 26 patients were included, mean age of 52.3 years (range: 33–78 years), undergoing 32 TAE procedures between January 2012 and December 2019 were included in this retrospective study. Distal embolization of the segmental hepatic artery was performed with 300–500 µm embolic microspheres associated with proximal embolization using microcoils. The primary endpoint was clinical efficacy, defined by an improvement in health-related quality of life using a modified Short Form-36 Health Survey and improvement in symptoms (digestive or respiratory symptoms and chronic abdominal pain), without invasive therapy during the follow-up period. Secondary endpoints were a decrease in total liver volume and treated liver volume and complications. Results: Hepatic embolization was performed successfully in 30 of 32 procedures with no major adverse events. Clinical efficacy was 73% (19/26). The mean reduction in hepatic volume was −12.6% at 3 months and −27.8% at the last follow-up 51 ± 15.2 months after TAE (range: 30–81 months; both ps < 0.01). The mean visual analog scale pain score was 5.4 ± 2.8 before TAE and decreased to 2.7 ± 1.9 after treatment. Three patients had minor adverse events, and one patient had an adverse event of moderate severity. Conclusion: Hepatic embolization using microspheres and microcoils is a safe and effective treatment for PLD that improves symptoms and reduces the volume of hepatic cysts.
Glioblastoma-Specific Strategies of Vascularization: Implications in Anti-Angiogenic Therapy Resistance
Authors: Buccarelli Mariachiara , Castellani Giorgia , Ricci-Vitiani Lucia
Published: October 2022

Angiogenesis has long been implicated as a crucial process in GBM growth and progression. GBM can adopt several strategies to build up its abundant and aberrant vasculature. Targeting GBM angiogenesis has gained more and more attention in anti-cancer therapy, and many strategies have been developed to interfere with this hallmark. However, recent findings reveal that the effects of anti-angiogenic treatments are temporally limited and that tumors become refractory to therapy and more aggressive. In this review, we summarize the GBM-associated neovascularization processes and their implication in drug resistance mechanisms underlying the transient efficacy of current anti-angiogenic therapies. Moreover, we describe potential strategies and perspectives to overcome the mechanisms adopted by GBM to develop resistance to anti-angiogenic therapy as new potential therapeutic approaches.
Pharmacological, Nutritional, and Rehabilitative Interventions to Improve the Complex Management of Osteoporosis in Patients with Chronic Obstructive Pulmonary Disease: A Narrative Review
Authors: de Sire Alessandro , Lippi Lorenzo , Aprile Vittorio , Calafiore Dario , Folli Arianna , D’Abrosca Francesco , Moalli Stefano , Lucchi Marco , Ammendolia Antonio , Invernizzi Marco
Published: October 2022

Osteoporosis is a highly prevalent condition affecting a growing number of patients affected by chronic obstructive pulmonary disease (COPD), with crucial implications for risk of fragility fractures, hospitalization, and mortality. Several risk factors have been identified to have a role in osteoporosis development in COPD patients, including corticosteroid therapy, systemic inflammation, smoke, physical activity levels, malnutrition, and sarcopenia. In this scenario, a personalized multitarget intervention focusing on the pathological mechanisms underpinning osteoporosis is mandatory to improve bone health in these frail patients. Specifically, physical exercise, nutritional approach, dietary supplements, and smoke cessation are the cornerstone of the lifestyle approach to osteoporosis in COPD patients, improving not only bone health but also physical performance and balance. On the other hand, pharmacological treatment should be considered for both the prevention and treatment of osteoporosis in patients at higher risk of fragility fractures. Despite these considerations, several barriers still affect the integration of a personalized approach to managing osteoporosis in COPD patients. However, digital innovation solutions and telemedicine might have a role in optimizing sustainable networking between hospital assistance and community settings to improve bone health and reduce sanitary costs of the long-term management of COPD patients with osteoporosis.
Statin Therapy to Improve Outcome of COVID-19 Patients: Useful or Not Useful?
Authors: Mégarbane Bruno
Published: October 2022

About one year ago, the journal published a large population-based cohort study from South Korea investigating the potential benefits associated with statins at preventing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection or improving the outcome of hospitalized coronavirus disease-2019 (COVID-19) patients [...]
Implementation of Routine Endoscopy with Narrow Band Imaging in the Evaluation of Oral and Upper Airways Lesions in Oral Chronic Graft-Versus-Host Disease: A Preliminary Study
Authors: Nitro Letizia , Pipolo Carlotta , Castellarin Paolo , Sardella Andrea , Bulfamante Antonio Mario , De Marco Beatrice , Magliano Gabriele , Grillo Giovanni , Felisati Giovanni , Saibene Alberto Maria
Published: October 2022

(1) Background: The aim of our study is to investigate the main oral lesion patterns in patients with oral graft-versus-host disease and to describe and validate the use of endoscopy enhanced with narrow-band imaging (NBI) as a personalized, reliable and user-friendly tool for the early detection of oral potentially diseases. (2) Methods: We retrospectively evaluated the medical records of 20 patients with chronic GVHD and with oral manifestations, who were referred to our “Interdisciplinary Center for Oropharyngeal Pathology (CIPO)” from January 2017 to July 2022. (3) Results: Data on GVHD, oral localization and NBI endoscopic evaluation are collected. A total of six mucositis, one mucosal erythematous change, ten lichenoid-like changes, eight erosive lesions, one leukoplakia, two erythroplakia and two case of blisters were observed. Two vascular abnormalities were seen with NBI, leading to one excisional biopsy. The patient was diagnosed with squamous cell carcinoma. (4) Conclusion: Our study is the first to highlight the relevance of the routine use of endoscopy with NBI in patients with oral chronic GVHD. We highlighted its role as a reliable, reproducible, easy-to-use and tailor-made tool in the follow-up of those patients and to allow an earlier identification of aberrant neoangiogenesis related to oral potentially malignant disorders and oral cancer.
Prevention of Spinal Cord Injury during Thoracoabdominal Aortic Aneurysms Repair: What the Anaesthesiologist Should Know
Authors: Marturano Federico , Nisi Fulvio , Giustiniano Enrico , Benedetto Francesco , Piccioni Federico , Ripani Umberto
Published: October 2022

Thoraco-abdominal aortic repair is a high-risk surgery for both mortality and morbidity. A major complication is paraplegia-paralysis due to spinal cord injury. Modern thoracic and abdominal aortic aneurysm repair techniques involve multiple strategies to reduce the risk of spinal cord ischemia during and after surgery. These include both surgical and anaesthesiologic approaches to optimize spinal cord perfusion by staging the procedure, guaranteeing perfusion of the distal aorta through various techniques (left atrium–left femoral artery by-pass) by pharmacological and monitoring interventions or by maximizing oxygen delivery and inducing spinal cord hypothermia. Lumbar CSF drainage alone or in combination with other techniques remains one of the most used and effective strategies. This narrative review overviews the current techniques to prevent or avoid spinal cord injury during thoracoabdominal aortic aneurysms repair.
Trace Elements in Tears: Comparison of Rural and Urban Populations Using Particle Induced X-ray Emission
Authors: Girshevitz Olga , Cohen-Sinai Noa , Zahavi Alon , Vardizer Yoav , Fixler Dror , Goldenberg-Cohen Nitza
Published: October 2022

We aimed to evaluate the types and concentrations of trace elements in tears of individuals living in urban and rural environments using particle induced X-ray emission (PIXE) and the possible association with exposure to air pollution and suggest a novel method for tear-based biomonitoring studies. This cross-sectional pilot study comprised 42 healthy subjects, 28 living in a rural area and 14 in an industrial city. Tears were collected with Schirmer paper and characterized by PIXE. Trace element concentrations from both eyes were averaged together with environmental pollution data. Main outcome measures were between-group differences in types and concentrations of trace elements in tears and comparison to environmental data. The rural group included 12/28 men, mean age 45.2 ± 14.8 years. The urban group consisted of 11/14 men of mean age 27 ± 5.9 years. Six rural and all urban were active smokers. Air pollution data showed more toxic elements in the rural environment. On PIXE analysis, chlorine, sodium, and potassium were found in similar concentrations in all samples. Normalizing to chlorine yielded higher values of aluminum, iron, copper, and titanium in the rural group; aluminum was found only in the rural group. The higher levels of certain trace elements in the rural group may, in part, be a consequence of exposure to specific environmental conditions. No direct association was found with air pollution data. PIXE is useful to analyze trace elements in tears, which might serve as a marker for individual exposure to environmental pollutants in biomonitoring studies.
Association between Gut Microbiota and Emotional-Behavioral Symptoms in Children with Attention-Deficit/Hyperactivity Disorder
Authors: Lee Min-Jing , Lai Hsin-Chih , Kuo Yu-Lun , Chen Vincent Chin-Hung
Published: October 2022

Previous studies have explored the role of the microbiome in attention-deficit/hyperactivity disorder (ADHD). However, whether the microbiome is correlated with emotional–behavioral disturbances, the most common comorbid symptom of ADHD, remains unclear. We established a cross-sectional study in which 6- to 18-year-old children with ADHD who were receiving no medication and a healthy control group of children without ADHD were recruited to analyze their microbiome composition. Microbiota of fecal samples were collected and analyzed using a 16s rRNA gene sequencing approach. In comparison with the healthy control group, the gut microbiota in children with ADHD exhibited significantly lower beta diversity. The abundance of the phylum Proteobacteria and the genera Agathobacter, Phascolarctobacterium, Prevotella_2, Acidaminococcus, Roseburia, and Ruminococcus gnavus group was increased in the ADHD group compared with the healthy group. Linear discriminant effect size (LEfSe) analysis was used to highlight specific bacteria phylotypes that were differentially altered between the ADHD and control groups. A regression analysis was performed to investigate the association between microbiota and emotional–behavioral symptoms in children with ADHD. A significant association was noted between withdrawal and depression symptoms and Agathobacter (p = 0.044), and between rule-breaking behavior and the Ruminococcus gnavus group (p = 0.046) after adjusting for sex, age, and the ADHD core symptoms score. This study advances the knowledge of how gut microbiota composition may contribute to emotional–behavioral symptoms in children with ADHD. The detailed mechanisms underlying the role of the gut microbiota in ADHD pathophysiology still require further investigation.
Salivary Tests: A New Personalized Approach for the Early Diagnosis of Oral and Periodontal Diseases
Authors: Isola Gaetano
Published: October 2022

Periodontitis is a chronic bacterial infection of the periodontium that results in the destruction of bone and connective tissue [...]
Classification of Central Venous Catheter Tip Position on Chest X-ray Using Artificial Intelligence
Authors: Jung Seungkyo , Oh Jaehoon , Ryu Jongbin , Kim Jihoon , Lee Juncheol , Cho Yongil , Yoon Myeong Seong , Jeong Ji Young
Published: October 2022

Recent studies utilizing deep convolutional neural networks (CNN) have described the central venous catheter (CVC) on chest radiography images. However, there have been no studies for the classification of the CVC tip position with a definite criterion on the chest radiograph. This study aimed to develop an algorithm for the automatic classification of proper depth with the application of automatic segmentation of the trachea and the CVC on chest radiographs using a deep CNN. This was a retrospective study that used plain chest supine anteroposterior radiographs. The trachea and CVC were segmented on images and three labels (shallow, proper, and deep position) were assigned based on the vertical distance between the tracheal carina and CVC tip. We used a two-stage approach model for the automatic segmentation of the trachea and CVC with U-net++ and automatic classification of CVC placement with EfficientNet B4. The primary outcome was a successful three-label classification through five-fold validations with segmented images and a test with segmentation-free images. Of a total of 808 images, 207 images were manually segmented and the overall accuracy of the five-fold validation for the classification of three-class labels (mean (SD)) of five-fold validation was 0.76 (0.03). In the test for classification with 601 segmentation-free images, the average accuracy, precision, recall, and F1-score were 0.82, 0.73, 0.73, and 0.73, respectively. We achieved the highest accuracy value of 0.91 in the shallow position label, while the highest F1-score was 0.82 in the deep position label. A deep CNN can achieve a comparative performance in the classification of the CVC position based on the distance from the carina to the CVC tip as well as automatic segmentation of the trachea and CVC on plain chest radiographs.
Contemporary Management of Severely Calcified Coronary Lesions
Authors: Angsubhakorn Natthapon , Kang Nicolas , Fearon Colleen , Techorueangwiwat Chol , Swamy Pooja , Brilakis Emmanouil S. , Bharadwaj Aditya S.
Published: October 2022

Coronary artery calcification is increasingly prevalent in our patient population. It significantly limits the procedural success of percutaneous coronary intervention and is associated with a higher risk of adverse cardiovascular events both in the short-term and long-term. There are several modalities for modifying calcified plaque, such as balloon angioplasty (including specialty balloons), coronary atheroablative therapy (rotational, orbital, and laser atherectomy), and intravascular lithotripsy. We discuss each modality’s relative advantages and disadvantages and the data supporting their use. This review also highlights the importance of intravascular imaging to characterize coronary calcification and presents an algorithm to tailor the calcium modification therapy based on specific coronary lesion characteristics.
Evaluation of Tele-Dentistry and Face-to-Face Appointments during the Provision of Dental Services in Poland
Authors: Migas Klaudia , Kozłowski Remigiusz , Sierocka Aleksandra , Marczak Michał
Published: October 2022

Tele-dentistry is a rapidly growing field, especially in the era of the COVID-19 pandemic. Due to the COVID-19 pandemic, remote services are of increasing interest to both patients and dental personnel. They allow for reduced person-to-person contact and thus a reduced risk of transmission of the SARS-CoV2 virus. The COVID-19 pandemic has affected the functioning of all areas of life, including dental treatment. The aim of the study was to assess the possibility of using tele-dentistry for dental services and analyse the attitudes of patients and dentists towards this solution. The period analysed was between March 2019 and February 2021 in five healthcare entities in Cracow in Central Europe. The study’s retrospective analysis shows a positive attitude of patients towards tele-dentistry at every stage of treatment, from diagnosis through postoperative care, and a significant reluctance of dentists in the majority of dental specialties towards tele-dentistry. Consequently, a significant percentage of patients were invited to dental offices for a face-to-face appointment during the COVID-19 pandemic. The negative attitude of dental personnel towards tele-dentistry compared with the positive attitude of patients towards tele-dentistry is somewhat worrying in view of the possibility of a further pandemic. At the same time, it provides important information about the need to educate and support dental personnel in tele-dental solutions and improve solutions for the future. Taking into account the potential reduction in dental care costs for patients and countries after the implementation of tele-dentistry solutions, this is an important topic, while current studies do not comprehensively address the attitudes of patients and dental personnel towards tele-dentistry. In other parts of the world, a similar approach to tele-dentistry is used by patients and dentists.
Minimal Margin Surgery and Intraoperative Neuromonitoring in Benign Parotid Gland Tumors: Retrospective Clinical Study
Authors: Massimilla Eva Aurora , Motta Giovanni , Magaldi Michelangelo , Montella Marco , Messina Gaetana , Testa Domenico , Cantone Elena , Motta Gaetano
Published: October 2022

Extracapsular dissection (ECD) was introduced for the removal of superficial and small benign parotid tumors. According to a recent proposal, ECD is reserved for tumors that are 3 cm or less, mobile, and close to the parotid borders in cases of pleomorphic adenoma. The aim of the study is to evaluate the effectiveness of ECD for treatment of benign parotid tumors also in cases of tumors that were larger than 3 cm and deeper. All ECD for benign parotid neoplasms conducted between 2007 and 2017 were reviewed. The lesions included were limited to primary parotid tumors and categorized by Quer proposal. Facial nerve monitoring was used in all cases. Facial nerve palsy and local recurrences were assessed. The 88 ECD performed met inclusion criteria. The mean lesion size was 4.26 cm. Of the tumors, 68 were less than 3 cm in diameter and 20 were larger, 64 were superficial, and 24 were deep. The most common lesion types were pleomorphic adenoma (88.6%). There was no significant difference in complication rates between the size of tumor (p = 0.9) and location (p = 0.91). Our results suggest that extracapsular dissection could be considered an option for first-time diagnosed benign parotid tumors, even in cases of large dimensions and deep lobe involvement.
Venous Wall of Patients with Chronic Venous Disease Exhibits a Glycolytic Phenotype
Authors: Fraile-Martinez Oscar , García-Montero Cielo , Alvarez-Mon Miguel Ángel , Gomez-Lahoz Ana M. , Monserrat Jorge , Llavero-Valero Maria , Ruiz-Grande Fernando , Coca Santiago , Alvarez-Mon Melchor , Buján Julia , García-Honduvilla Natalio , Saz Jose V. , Ortega Miguel A.
Published: October 2022

Chronic venous disease (CVeD) is a rising medical condition characterized by a broad spectrum of disorders in the venous system. Varicose veins (VVs) represent a frequent clinical manifestation of CVeD, particularly in the lower limbs. Prior histopathological studies have defined a set of alterations observed in the venous wall of patients with VVs, affecting their structure and behavior. Metabolic changes in the veins appear to be a critical biological mechanism aiding our understanding of the pathogenesis of CVeD. In this sense, previous studies have identified a potential role of a glycolytic phenotype in the development of different vascular disorders; however, its precise role in CVeD remains to be fully explored. Thus, the aim of the present study was to analyze the gene and protein expression of glucose transporter 1 (GLUT-1) and the glycolytic enzymes PGK-1, ALD, GA3PDH and LDH in the VVs of patients with CVeD (n = 35) in comparison to those expressed in healthy subjects. Our results display enhanced gene and protein expression of GLUT-1, PGK-1, ALD, GA3PDH and LDH in patients with CVeD, suggesting a glycolytic switch of the venous tissue. Greater understanding of the impact of this glycolytic switch in patients with CVeD is required to define a possible pathophysiological role or therapeutic implications of these changes.
The Potential Applications of Raman Spectroscopy in Kidney Diseases
Authors: Delrue Charlotte , Speeckaert Marijn M.
Published: October 2022

Raman spectroscopy (RS) is a spectroscopic technique based on the inelastic interaction of incident electromagnetic radiation (from a laser beam) with a polarizable molecule, which, when scattered, carries information from molecular vibrational energy (the Raman effect). RS detects biochemical changes in biological samples at the molecular level, making it an effective analytical technique for disease diagnosis and prognosis. It outperforms conventional sample preservation techniques by requiring no chemical reagents, reducing analysis time even at low concentrations, and working in the presence of interfering agents or solvents. Because routinely utilized biomarkers for kidney disease have limitations, there is considerable interest in the potential use of RS. RS may identify and quantify urinary and blood biochemical components, with results comparable to reference methods in nephrology.
Hypnotics Use Is Associated with Elevated Incident Atrial Fibrillation: A Propensity-Score Matched Analysis of Cohort Study
Authors: Hu Xiang , Jong Gwo-Ping , Wang Liang , Lin Mei-Chen , Gong Shao-Qing , Zhang Xue-Hong , Lin Jiun-Jie , Adeniran Esther , Liu Yan-Long , Chen Hung-Yi , Yang Bo
Published: October 2022

We aimed to investigate the association between either or both of benzodiazepines (BZDs) and non-BZDs and the incidence of atrial fibrillation (AF) in the Taiwan National Health Insurance Database. The participants with at least two prescriptions of BZDs and/or non-BZDs were identified as hypnotics users, whereas those without any prescription of hypnotics were non-hypnotics users. The hypnotics and non-hypnotics cohorts were 1:1 matched on their propensity scores. A total of 109,704 AF-free individuals were included; 610 AF cases occurred in the 54,852 hypnotics users and 166 in the 54,852 non-hypnotics users during the 602,470 person-years of follow-up, with a higher risk of new-onset AF in the users than the non-users (hazard ratio (HR): 3.61, 95% confidence interval [CI]: 3.04–4.28). The users at the highest tertiles of the estimated defined daily doses per one year (DDD) had a greater risk for AF than the non-users, with the risk increasing by 7.13-fold (95% CI: 5.86–8.67) for >0.74-DDD BZDs, 10.68-fold (95% CI: 6.13–18.62) for >4.72-DDD non-BZDs, and 3.26-fold (95% CI: 2.38–4.47) for > 1.65-DDD combinations of BZDs with non-BZDs, respectively. In conclusion, hypnotics use was associated with elevated incidence of AF in the Taiwanese population, which highlighted that the high-dose usage of hypnotics needs more caution in clinical cardiological practice.
Hypoxia-Nitric Oxide Axis and the Associated Damage Molecular Pattern in Cutaneous Melanoma
Authors: Ene Corina Daniela , Nicolae Ilinca
Published: October 2022

Hypoxia was intensively studied in cancer during the last few decades, being considered a characteristic of the tumor microenvironment. The aim of the study was to evaluate the capacity of tumor cells to adapt to the stress generated by limited oxygen tissue in cutaneous melanoma. We developed a case–control prospective study that included 52 patients with cutaneous melanoma and 35 healthy subjects. We focused on identifying and monitoring hypoxia, the dynamic of nitric oxide (NO) serum metabolites and posttranslational metabolic disorders induced by NO signaling according to the clinical, biological and tumoral characteristics of the melanoma patients. Our study showed high levels of hypoxia-inducible factor-1a (HIF-1a) and hypoxia-inducible factor-2a (HIF-2a) in the melanoma patients. Hypoxia-inducible factors (HIFs) control the capacity of tumor cells to adapt to low levels of oxygen. Hypoxia regulated the nitric oxide synthase (NOS) expression and activity. In the cutaneous melanoma patients, disorders in NO metabolism were detected. The serum levels of the NO metabolites were significantly higher in the melanoma patients. NO signaling influenced the tumor microenvironment by modulating tumoral proliferation and sustaining immune suppression. Maintaining NO homeostasis in the hypoxic tumoral microenvironment could be considered a future therapeutic target in cutaneous melanoma.
Personalized Prescription of Chemotherapy Based on Assessment of mRNA Expression of BRCA1, RRM1, ERCC1, TOP1, TOP2α, TUBβ3, TYMS, and GSTP1 Genes in Tumors Compared to Standard Chemotherapy in the Treatment of Non-Small-Cell Lung Cancer
Authors: Tsyganov Matvey M. , Rodionov Evgeny O. , Ibragimova Marina K. , Miller Sergey V. , Cheremisina Olga V. , Frolova Irina G. , Tuzikov Sergey A. , Litviakov Nikolai V.
Published: October 2022

Objectives: A growing body of evidence suggests the important role of chemosensitive gene expression in the prognosis of patients with lung cancer. However, studies on combined gene expression assessments for personalized prescriptions of chemotherapy regimens in patients have not yet been conducted. The aim of this work was to conduct a prospective study on the appointment of personalized chemotherapy in patients with non-small-cell lung cancer. Materials and methods: The present study analyzed 85 patients with lung cancer (stage IIB-IIIB). Within this group, 48 patients received individualized chemotherapy, and 37 patients received classical chemotherapy. In the individualized chemotherapy group, the mRNA expression levels of ERCC1, RRM1, TUBB3, TYMS, TOP1, TOP2α, BRCA1, and GSTP1 in lung tissues were measured by quantitative real-time PCR (qPCR), and an individual chemotherapy regimen was developed for each patient according to the results. Patients in the classical chemotherapy group received the vinorelbine/carboplatin regimen. Survival analyses were performed using the Kaplan–Meier method. Prognostic factors of metastasis-free survival (MFS) and overall survival (OS) of patients were identified via Cox’s proportional hazards regression model. Results: MFS and OS were significantly better in the personalized chemotherapy group compared to the classic chemotherapy group (MFS, 46.22 vs. 22.9 months, p = 0.05; OS, 58.6 vs. 26.9 months, p < 0.0001). Importantly, the best metastasis-free survival rates in the group with personalized ACT were achieved in patients treated with the paclitaxel/carboplatin regimen. Based on an assessment of chemosensitivity gene expression in the tumors, the classical chemotherapy strategy also increased the risk of death (HR = 14.82; 95% CI: 3.33–65.86; p < 0.000) but not metastasis (HR = 1.95; 95% CI: 0.96–3.98; p = 0.06) compared to the group of patients with chemotherapy. Conclusions: The use of combined ERCC1, RRM1, TUBB3, TYMS, TOP1, TOP2α, BRCA1, and GSTP1 gene expression results for personalized chemotherapy can improve treatment efficacy and reduce unnecessary toxicity.
Cancer Genetics and Clinical Research
Authors: Allegra Sarah
Published: October 2022

Understanding how complex diseases as well as cancers arise is one of the great challenges of modern medicine [...]
Poly(Styrene-Co-Maleic Acid)-Conjugated 6-Aminofluorescein and Rhodamine Micelle as Macromolecular Fluorescent Probes for Micro-Tumors Detection and Imaging
Authors: Bharate Gahininath Y. , Qin Haibo , Fang Jun
Published: October 2022

Styrene-co-maleic acid (SMA) copolymer was evaluated as a polymer platform to conjugate with two fluorescent dyes, i.e., 6-aminofluorescein (AF) and Rhodamine (Rho); which spontaneously self-assembles in an aqueous medium and forms a micelle through a non-covalent interaction. These SMA-dye conjugates showed the nanosized micelle formation through dynamic light scattering (DLS) with discrete distributions having mean particle sizes of 135.3 nm, and 190.9 nm for SMA-AF, and SMA-Rho, respectively. The apparent molecular weight of the micelle was evaluated using Sephadex G-100 gel chromatography and it was found that the 49.3 kDa, and 28.7 kDa for SMA-AF, and SMA-Rho, respectively. Moreover, the biodistribution study showed the selective accumulation of the SMA-dye conjugates in the tumor of mice. Taken together, the SMA-dye conjugated micelles appear in high concentrations in the tumor by utilizing the enhanced permeability and retention (EPR) effect of the tumor-targeted delivery. These results indicate that SMA-dye conjugates have the advanced potential as macromolecular fluorescent probes for microtumor imaging by means of a photodynamic diagnosis.
Simultaneous PSI-Based Orthognathic and PEEK Bone Augmentation Surgery Leads to Improved Symmetric Facial Appearance in Craniofacial Malformations
Authors: Kerkfeld Valentin , Schorn Lara , Depprich Rita , Lommen Julian , Wilkat Max , Kübler Norbert , Rana Majeed , Meyer Ulrich
Published: October 2022

(1) The aim of the present study was to compare the outcome of facial symmetry after simultaneous digitally planned patient-specific implant (PSI-) based orthognathic surgery and polyether ether ketone (PEEK) bone augmentation in patients with craniofacial malformations. (2) To evaluate the outcome of the two different surgical approaches (conventional PSI-based orthognathic surgery versus simultaneous PSI-based orthognathic surgery with PEEK bone augmentation), a comparison of five different groups with a combination of the parameters (A) with vs. without laterognathia, (B) syndromic vs. non-syndromic, and (C) surgery with vs. without PEEK bone augmentation was conducted. The digital workflow comprised cone beam CT (CBCT) scans and virtual surgery planning for all patients in order to produce patient specific cutting guides and osteosynthesis plates. Additionally, deformed skulls were superimposed by a non-deformed skull and/or the healthy side was mirrored to produce PSI PEEK implants for augmentation. Retrospective analyses included posterior–anterior conventional radiographs as well as en face photographs taken before and nine months after surgery. (3) Simultaneous orthognathic surgery with PEEK bone augmentation significantly improves facial symmetry compared to conventional orthognathic surgery (6.5%P (3.2–9.8%P) (p = 0.001). (4) PSI-based orthognathic surgery led to improved horizontal bone alignment in all patients. Simultaneous PEEK bone augmentation enhanced facial symmetry even in patients with syndrome-related underdevelopment of both soft and hard tissues.
Metabolic Hormones in Schizophrenia Patients with Antipsychotic-Induced Metabolic Syndrome
Authors: Boiko Anastasiia S. , Mednova Irina A. , Kornetova Elena G. , Goncharova Anastasiia A. , Semke Arkadiy V. , Bokhan Nikolay A. , Ivanova Svetlana A.
Published: October 2022

Metabolic syndrome (MetS) is a common complication of schizophrenia that is quite exacerbated by long-term use of (atypical) antipsychotics. The mechanism of MetS has neuronal, neuroendocrine, and neuroimmunological components and shows some overlap with those of aspects of schizophrenia. We examined 195 patients with schizophrenia (90 with and 105 without MetS) for the association of serum levels of ghrelin, insulin, and leptin with metabolic abnormalities. Serum glucose levels and lipid profiles were routinely measured with colorimetric enzymatic methods and hormone levels with multiplex analyzers. Leptin levels were highly significantly increased (p < 0.001) in people with MetS (9.966 [5.882; 21.496] vs. 6.35 [2.005; 11.753], Me [Q1; Q3]) and ghrelin levels were actually significantly decreased (p = 0.045). Insulin levels did not differ significantly between those with and without MetS (p = 0.162). In Spearman’s correlation analysis between the hormone levels, body characteristics, and biochemical parameters, significant correlations were seen somewhat more often in people without MetS than in those with MetS and also less often for ghrelin than for the other hormones. We conclude that evidence exists for a role in the development of MetS especially for leptin, but that less is supporting a role for ghrelin.
Liver Function—How to Screen and to Diagnose: Insights from Personal Experiences, Controlled Clinical Studies and Future Perspectives
Authors: Buechter Matthias , Gerken Guido
Published: October 2022

Acute and chronic liver disease is a relevant problem worldwide. Liver function plays a crucial role in the course of liver diseases not only in estimating prognosis but also with regard to therapeutic interventions. Within this review, we discuss and evaluate different tools from screening to diagnosis and give insights from personal experiences, controlled clinical studies and future perspectives. Finally, we offer our novel diagnostic algorithm to screen patients with presumptive acute or chronic liver disease in the daily clinical routine.
Do Not Go Gentle into That Deaf Night: A Holistic Perspective on Cochlear Implant Use as Part of Healthy Aging
Authors: Illg Angelika , Lukaschyk Julia , Kludt Eugen , Lesinski-Schiedat Anke , Billinger-Finke Mareike
Published: October 2022

Research suggests that cochlear implant (CI) use in elderly people improves speech perception and health-related quality of life (HRQOL). CI provision could also prevent dementia and other comorbidities and support healthy aging. The aim of this study was (1) to prospectively investigate potential changes in HRQOL and speech perception and (2) to identify clinical action points to improve CI treatment. Participants (n = 45) were CI recipients aged 60–90 with postlingual deafness. They were divided into groups, according to age: Group 1 (n = 20) received a CI between the age of 60–70 years; group 2 (n = 25) between the age of 71–90 years. HRQOL and speech perception were assessed preoperatively, and three and twelve months postoperatively. HRQOL and speech perception increased significantly within one year postoperatively in both groups. No difference between groups was found. We conclude that CI treatment improves speech perception and HRQOL in elderly users. Improvement of the referral process for CI treatment and a holistic approach when discussing CI treatment in the elderly population could prevent auditory deprivation and the deterioration of cognitive abilities.
Design of a Functional Eye Dressing for Treatment of the Vitreous Floater
Authors: Fan Wen-Shuang , Huang Shuan-Yu , Nguyen Hong-Thai , Ho Wen-Tsung , Chao Wen-Hung , Lin Fen-Chi , Wang Hsiang-Chen
Published: October 2022

With the rapid development of display technology, related diseases of the human eye are also increasing day by day. Eye floaters are one of the diseases that affect humans. Herein, we present a functional ophthalmic dressing that can permeate the skin tissues of the eyes through oxygen and hydrogen to improve the symptoms of floaters. In clinical tests, the symptoms of sensory floaters improved in 28 patients, and the recovery rates of mild, moderate, and severe floaters were about 70%, 66.7%, and 83.3%, respectively.
Personalized Medicine: Pharmacokinetics
Authors: Daali Youssef
Published: October 2022

The “one-size fits all” model that has been used for decades is now replaced by the concept of the “right dose of the right drug for the right patient” [...]
High-Frequency Transcranial Random Noise Stimulation over the Left Prefrontal Cortex Increases Resting-State EEG Frontal Alpha Asymmetry in Patients with Schizophrenia
Authors: Yeh Ta-Chuan , Huang Cathy Chia-Yu , Chung Yong-An , Im Jooyeon Jamie , Lin Yen-Yue , Ma Chin-Chao , Tzeng Nian-Sheng , Chang Chuan-Chia , Chang Hsin-An
Published: October 2022

Reduced left-lateralized electroencephalographic (EEG) frontal alpha asymmetry (FAA), a biomarker for the imbalance of interhemispheric frontal activity and motivational disturbances, represents a neuropathological attribute of negative symptoms of schizophrenia. Unidirectional high-frequency transcranial random noise stimulation (hf-tRNS) can increase the excitability of the cortex beneath the stimulating electrode. Yet, it is unclear if hf-tRNS can modulate electroencephalographic FAA in patients with schizophrenia. We performed a randomized, double-blind, sham-controlled clinical trial to contrast hf-tRNS and sham stimulation for treating negative symptoms in 35 schizophrenia patients. We used electroencephalography to investigate if 10 sessions of hf-tRNS delivered twice-a-day for five consecutive weekdays would modulate electroencephalographic FAA in schizophrenia. EEG data were collected and FAA was expressed as the differences between common-log-transformed absolute power values of frontal right and left hemisphere electrodes in the alpha frequency range (8–12.5 Hz). We found that hf-tRNS significantly increased FAA during the first session of stimulation (p = 0.009) and at the 1-week follow-up (p = 0.004) relative to sham stimulation. However, FAA failed to predict and surrogate the improvement in the severity of negative symptoms with hf-tRNS intervention. Together, our findings suggest that modulating electroencephalographic frontal alpha asymmetry by using unidirectional hf-tRNS may play a key role in reducing negative symptoms in patients with schizophrenia.
Quantifying Intracellular Viral Pathogen: Specimen Preparation, Visualization and Quantification of Multiple Immunofluorescent Signals in Fixed Human Airway Epithelium Cultured at Air-Liquid Interface
Authors: Wong Sharon L. , Pandzic Elvis , Kardia Egi , Allan Katelin M. , Whan Renee M. , Waters Shafagh A.
Published: October 2022

Infection control and aggressive antibiotic therapy play an important role in the management of airway infections in individuals with cystic fibrosis (CF). The responses of airway epithelial cells to pathogens are likely to contribute to the pathobiology of CF lung disease. Primary airway epithelial cells obtained from individuals with CF, cultured and differentiated at air-liquid interface (ALI), effectively mimic the structure and function of the in vivo airway epithelium. With the recent respiratory viral pandemics, ALI cultures were extensively used to model respiratory infections in vitro to facilitate physiologically relevant respiratory research. Immunofluorescence staining and imaging were used as an effective tool to provide a fundamental understanding of host–pathogen interactions and for exploring the therapeutic potential of novel or repurposed drugs. Therefore, we described an optimized quantitative fluorescence microscopy assay for the wholemount staining and imaging of epithelial cell markers to identify distinct cell populations and pathogen-specific targets in ALI cultures of human airway epithelial cells grown on permeable support insert membranes. We present a detailed methodology using a graphical user interface (GUI) package to quantify the detected signals on a tiled whole membrane. Our method provided an imaging strategy of the entire membrane, overcoming the common issue of undersampling and enabling unbiased quantitative analysis.
Can Extended Chemotherapy Improve Glioblastoma Outcomes? A Retrospective Analysis of Survival in Real-World Patients
Authors: Gherasim-Morogai Natalia , Afrasanie Vlad-Adrian , Gafton Bogdan , Marinca Mihai Vasile , Alexa-Stratulat Teodora
Published: October 2022

Standard treatment for glioblastoma multiforme (GBM) is surgery followed by radiotherapy plus concurrent chemotherapy with daily temozolomide (TMZ), and six subsequent TMZ 5/28-day cycles. Research has focused on identifying more effective alternatives to the current protocol, including extension of the number of adjuvant TMZ cycles. We performed a retrospective analysis of all GBM patients treated in our hospital (160 patients, 2011–2020). Median follow-up was 16.0 months. Analysis of prognostic factors was performed with a particular focus on the benefit of extending TMZ chemotherapy. Improved survival correlated with younger age, female gender, good performance status, absence of cognitive dysfunctions, no steroid use, and total tumor resection. Median progression-free survival (PFS) was 12 months and median overall survival (OS) was 20.0 months for the entire cohort. Median OS by adjuvant TMZ was 10.0 months if no adjuvant chemotherapy given (group 0), 15.0 months for patients that did not complete six TMZ cycles (group A), 24.0 months for those that did (group B), and 29.0 months for patients having received more than six cycles (group C) (p < 0.0001). At the three-year mark, 15.9% patients were alive in group A, 24.4% in group B and 38.1% in group C. Carefully selected GBM patients may derive benefit from extending the standard adjuvant chemotherapy beyond six TMZ cycles, but more data is required.
Bladder Oversensitivity Is Associated with Bladder Outlet Obstruction in Men
Authors: Verhovsky Guy , Baberashvili Ilia , Rappaport Yishai H. , Zilberman Dorit E. , Neheman Amos , Gal Jonathan , Zisman Amnon , Stav Kobi
Published: October 2022

Objective: The aim of this study was to assess whether there is an objective association between bladder outlet obstruction (BOO) and abnormal sensation parameters during filling cystometry in men. Methods: This was a prospective study. Consecutive patients referred for urodynamic examination were assessed for eligibility. Patients with permanent catheters, BPH related surgery, neurologic disease, or inability to complete the urodynamic study were excluded. All patients underwent full physical examination, as well as renal and bladder ultrasound including prostate size estimation, post void residual volume, and PSA, and they completed the International Prostate Symptoms Score (IPSS) questionnaire. The cohort was divided into obstructed and un-obstructed groups according to the Bladder Outlet Obstruction Index. Results: Ninety of the 115 patients recruited were obstructed (78%). Obstructed patients had significantly higher PSA, larger prostate volume, and higher IPSS. Detrusor overactivity did not differ between the two groups (45.6% vs. 48.1%, p = 0.83). First, normal, strong, and urgent desires to void were significantly lower in obstructed men: median (IQR) 118 (57–128) vs. 180 (80–200), 171 (85–257) vs. 227 (125–350), 221 (150–383) vs. 307 (180–477), and 276 (197–480) vs. 344 (280–535), respectively. First desire to void (FDV) had the highest area under the curve (AUC = 0.83, 95% CI = 0.76–0.90, p < 0.001) for predicting BOO with a Youden index of 0.78 at 140 mL. Conclusions: Our results suggest that there is a strong association between bladder oversensitivity and BOO in men. Men with FDV <140 mL had a significantly increased probability of being obstructed. These findings may shed a light on the pathophysiological connection between obstruction and enhanced afferent signaling from the bladder.
A Taxonomy of Product–Service System Perturbations through a Systematic Literature Review
Authors: Wang Hanfei , Mitake Yuya , Tsutsui Yusuke , Alfarisi Salman , Shimomura Yoshiki
Published: October 2022

Perturbations have a negative influence on the operation of the business system, which may weaken business performance. However, in the field of the product–service system (PSS), perturbation is still a rarely discussed concept. Researchers and managers have a limited understanding of perturbations in the context of PSS. This hinders PSS designers and managers to prepare for mitigation due to a lack of knowledge and information. Thus, this paper aims to build a taxonomy of PSS perturbation through a systematic literature review. To achieve this target, the authors have reviewed 171 papers and found 18 effective papers. Twenty-five items are considered effective ones that are directly related to PSS perturbation. The result of the review shows that PSS perturbations could be classified into six categories, namely, behavioral, social, environmental, competence, resource, and organizational perturbations. The proposed terminology and taxonomy appear to be effective, which could enable researchers to understand the scope of PSS perturbations on a conceptual level. This finding is also expected to provide useful knowledge and information for researchers who are interested in vulnerability analysis and the robust design of PSS.
The Impacts of the COVID-19 Pandemic on the Tour Operator Market—The Case of Slovakia
Authors: Derco Ján
Published: October 2022

The aim of the research is to determine the impact of the COVID-19 pandemic (and subsequent state aid) on selected financial indicators of tour operators operating on Slovakia’s market. The article analyses the changes in the market between 2018 and 2020 (market concentration, insolvency insurance). For the purposes of describing the financial position of tour operators, the medians of selected financial indicators were processed. At the same time, a two-sample t-test was used to test the hypotheses of the medians of these indicators for tour operators with a valid insolvency protection contract and without such a contract. The Herfindahl–Hirschman index was used to quantify the impact of the pandemic on the tour operator market concentration ratio. The state aid provided prevented tour operators from going bankrupt. Based on the Herfindahl–Hirschman index, we can say that there was an increase in concentration in this market. At the same time, however, there was a decline in profitability and an increase in their Liabilities to Assets ratio. However, currently insured tour operators do not have higher values of these indicators. These data are important for the discussion on the legal regulation of the protection of tour operators against insolvency.