bluuebunny/crossref_metadata_2025 huggingface dataset:
Waist Circumference as a Risk Factor for Non-Alcoholic Fatty Liver Disease in Older Adults in Guayaquil, Ecuador
Authors: Cabrera Dayana , Moncayo-Rizzo Jorge , Cevallos Karen , Alvarado-Villa Geovanny
Published: April 2023

Non-alcoholic liver steatosis is currently considered an epidemic. It involves a broad spectrum of liver diseases, in which older adults constitute a susceptible group. The aim of this study is to identify the role of waist circumference as a risk factor for non-alcoholic fatty liver disease. Methods: A cross-sectional study was carried out in 99 older adults who regularly attended five gerontological centers in the city of Guayaquil, Ecuador. The variables studied were age, gender, independent life, access to complete meals, waist circumference, and NAFLD diagnosed by ultrasound. Results: A significant relationship exists between waist circumference, body mass index, and fat mass percentage. However, only age and waist circumference were significant in the multivariate logistic regression model. Our results suggest that in the presence of waist circumference, body mass index loses its significance and age may be a protective factor due to adipose tissue loss and redistribution. Conclusion: Anthropometric measurements such as waist circumference can be used as complement indicators of NAFLD.
Psychological Functioning of Women Diagnosed with Lichen Planus and Other Diseases of the Oral Cavity—Explorative Study
Authors: Sajewicz-Radtke Urszula , Radtke Bartosz M. , Jurek Paweł , Olech Michał , Skurska Anna , Ślebioda Zuzanna , Dorocka-Bobkowska Barbara , Pietuch Katarzyna , Sulewska Magdalena , Błażek Magdalena
Published: April 2023

The role of psychosocial factors in the development of changes in lichen planus and other diseases of the oral cavity has been implicated, but is still understudied. Therefore, the aim of our study was to describe the specific profile of psychological functioning of patients with these diseases, including the role of temperamental traits, action-oriented personality components, and self-esteem. In total, 94 adult women participated in the study: (1) with lichen planus (LP; n = 46; Mage = 54.80, SD = 12.53), (2) with other oral conditions (n = 25; Mage = 34.76, SD = 16.03), (3) without chronic disease (n = 24; Mage = 40.96, SD = 13.33). The following questionnaires were used: ZKA-PQ/SF, Polish Adaptive and Maladaptive Perfectionism Questionnaire, ACS-90, PROCOS, and MSEI. Results indicated no significant differences in temperament dimensions between studied groups. However, women diagnosed with LP presented lower levels of maladaptive perfectionism and social support than healthy women. Furthermore, women with LP also obtained lower scores for social resourcefulness and higher scores for moral self-approval than healthy women. Summarizing, patients with LP often use compensatory mechanisms that negatively affect their social functioning; thus diagnostic/therapeutic programs directed towards those group should be holistic, including psychologists and psychiatrists who support patients’ psychological well-being.
How Many People Experience Unsafe Medical Care in Thailand, and How Much Does It Cost under Universal Coverage Scheme?
Authors: Luankongsomchit Vilawan , Boonma Chulathip , Soboon Budsadee , Ranron Papada , Isaranuwatchai Wanrudee , Pimsarn Nopphadol , Limpanyalert Piyawan , Sukkul Ake-Chitra , Panmon Netnapa , Teerawattananon Yot
Published: April 2023

Adverse events and medical harm comprise major health concerns for people all over the world, including Thailand. The prevalence and burden of medical harm must always be monitored, and a voluntary database should not be used to represent national value. The purpose of this study is to estimate the national prevalence and economic impact of medical harm in Thailand using routine administrative data from the inpatient department electronic claim database under the Universal Coverage scheme from 2016 to 2020. Our findings show that there are approximately 400,000 visits with potentially unsafe medical care per year (or 7% of all inpatient visits under the Universal Coverage scheme). The annual cost of medical harm is estimated to be approximately USD 278 million (approximately THB 9.6 billion), with an average of 3.5 million bed-days per year. This evidence can be used to raise safety awareness and support medical harm prevention policies. Future work should focus on improving medical harm surveillance using better data quality and more comprehensive data on medical harm.
Assessing Inhaler Techniques of Asthma Patients Using Aerosol Inhalation Monitors (AIM): A Cross-Sectional Study
Authors: Alotaibi Mansour M. , Hughes Louise , Ford William R.
Published: April 2023

A high percentage of asthma patients have symptoms that are not well controlled, despite effective drugs being available. One potential reason for this may be that poor inhaler technique limits the dose delivered to the lungs, thereby reducing the therapeutic efficacy. The aim of this study was to assess the prevalence of poor inhaler technique in an asthma patient population and to probe the impact of various demographic parameters on technique quality. This study was conducted at community pharmacies across Wales, UK. Patients diagnosed with asthma and 12 years or older were invited to participate. An aerosol inhalation monitor (AIM, Vitalograph®) was used to measure the quality of patient inhaler technique. A total of 295 AIM assessments were carried out. There were significant differences in the quality of inhaler technique across the different inhaler types (p < 0.001, Chi squared). The best technique was associated with dry-powder inhalers (DPI devices, 58% of 72 having good technique), compared with pressurized metered-dose inhalers (pMDI) or pMDIs with a spacer device (18% of 174 and 47% of 49 AIM assessments, respectively). There were some significant associations between gender, age, and quality of inhaler technique, as determined with adjusted odds ratios. It seems that the majority of asthmatic patients were not using their inhalers appropriately. We recommend that healthcare professionals place more emphasis on assessing and correcting inhaler technique, as poor inhaler technique might be responsible for the observed lack of symptom control in the asthma patient population.
Effects of Attrition Shoes on Balance Control Ability and Postural Stability Following a Single-Leg Drop Jump Landing
Authors: Chen Shane-Fei , Wang Yan , Peng Yinghu , Zhang Ming
Published: April 2023

The purpose of the study is to determine the influence of lateral-heel-worn shoes (LHWS) on balance control ability through the single-leg drop jump test. The results could be beneficial by preventing lower limb injuries. Eighteen healthy participants performed the single-leg drop jump test. Times to stabilization for ground reaction forces (TTSG) in the anterior/posterior, medial/lateral, and vertical directions were calculated to quantify dynamic balance control ability. Outcome variables of the center of pressure (COP) were used to examine the main effect of LHWS during the static phase. The postural control ability was assessed through time to stabilization for the center of mass (TTSC) in the three directions. TTSG and TTSC for the LHWS group were found to be longer than those for the new shoes (NS) group in the M/L direction (p < 0.05). An increase in the TTS revealed an increased risk of falls during physical activities. However, no significant effects for both TTSG and TTSC were found in the other two directions between LHWS and NS groups. A static phase was cropped using TTSG for each trial, which indicated a phase after participants obtained balance. Outcome measures derived from COP showed no significant effects in the static phase. In conclusion, LHWS weakened balance control ability and postural stability in the M/L direction when compared to the NS group. During the static phase, no significant differences were found between the LHWS group and the NS group in balance control ability and postural stability. Consequently, lateral-worn shoes might increase the risk of fall injuries. The results could serve as an evaluation of shoe degradation for individuals with the aim of avoiding the risk of falls.
The Impact of Opioid Prescribing Limits on Drug Usage in South Carolina: A Novel Geospatial and Time Series Data Analysis
Authors: Sahebi-Fakhrabad Amirreza , Sadeghi Amir Hossein , Kemahlioglu-Ziya Eda , Handfield Robert , Tohidi Hossein , Vasheghani-Farahani Iman
Published: April 2023

The opioid crisis in the United States has had devastating effects on communities across the country, leading many states to pass legislation that limits the prescription of opioid medications in an effort to reduce the number of overdose deaths. This study investigates the impact of South Carolina’s prescription limit law (S.C. Code Ann. 44-53-360), which aims to reduce opioid overdose deaths, on opioid prescription rates. The study utilizes South Carolina Reporting and Identification Prescription Tracking System (SCRIPTS) data and proposes a distance classification system to group records based on proximity and evaluates prescription volumes in each distance class. Prescription volumes were found to be highest in classes with pharmacies located further away from the patient. An Interrupted Time Series (ITS) model is utilized to assess the policy impact, with benzodiazepine prescriptions as a control group. The ITS models indicate an overall decrease in prescription volume, but with varying impacts across the different distance classes. While the policy effectively reduced opioid prescription volumes overall, an unintended consequence was observed as prescription volume increased in areas where prescribers were located at far distances from patients, highlighting the limitations of state-level policies on doctors. These findings contribute to the understanding of the effects of prescription limit laws on opioid prescription rates and the importance of considering location and distance in policy design and implementation.
Pharmacovigilance and Adverse Drug Reaction Reporting among the General Public in Lithuania: A Cross-Sectional Study
Authors: Valinciute Agne , Gerbutaviciene Rima Jurate , Paukstaitiene Renata , Kubiliene Loreta
Published: April 2023

Background: Despite the fact that for over ten years, Lithuanian consumers have been able to report adverse drug reactions (ADR) directly to the competent authority, reporting rates remain low. A comprehensive understanding of consumer perceptions and experiences regarding ADRs is needed to ascertain further factors impacting their engagement in ADR reporting. This study aimed to assess consumer knowledge of, attitude toward, and practice of reporting ADRs. Methods: A questionnaire-guided cross-sectional survey among 404 consumers between October 2021 and June 2022 was conducted. The semi-structured questionnaire comprised open-ended and closed-ended questions to explore the sociodemographic characteristics and general knowledge of ADRs and pharmacovigilance. Other question items evaluated attitudes toward ADR reporting and ADR reporting practice. The data were summarised using descriptive statistics, while the chi-square test was used to assess categorical variables at p < 0.05. The overall percent score in the knowledge and attitude domains was divided into groups of “poor”, “moderate”, and “good” knowledge, as well as “positive” and “negative” attitudes. Results: While having a generally poor understanding, this study demonstrates that Lithuanian consumers have a favourable attitude toward pharmacovigilance, particularly regarding issues involving the requirement for reporting. The data also revealed the justifications for reporting and not reporting ADRs. Conclusions: The current study provided the first understanding of consumer awareness and ADR reporting intentions, which can help to develop educational campaigns and interventions addressing pharmacovigilance and ADR reporting.
Emotional Problems, Quality of Life and Symptom Burden in Patients with Chordoma
Authors: Wu Youtu , Li Chuzhong , Zhang Huifang , Wang Guoqin , Jing Linkai , Yi Guo , Yang Xuejun , Gui Songbai , Gao Hua , Zhang Yazhuo , Wang Guihuai , Bai Jiwei
Published: April 2023

Chordomas are very rare malignant bone tumors. Following surgery, their effects on neurological, physical, psychological, social, and emotional functioning are substantial and can have a major impact on a patients’ quality of life (QOL). In this survey, we aimed to characterize the postoperation health-related QOL and emotional problem in patients with chordoma using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and Hamilton Depression Rating Scale (HAMD). The cohort included 100 patients who underwent resection surgery between 2014 and 2020. Being single or divorced, living in a rural area, receiving a diagnosis of sacrococcygeal chordoma, Karnofsky performance status (KPS) ≤ 70, and weight loss were associated with increased likelihood of depression (p < 0.05). Patients who were single or divorced, with KPS ≤ 70, and experiencing weight loss had a higher likelihood of a worse QOL (p < 0.05). The uni- and multivariate logistic regression analyses indicated that the KPS level (p = 0.000) and postoperative radiation therapy (p = 0.009) were related to depression; marital status (p = 0.029), KPS level (p = 0.006), and tumor location (p = 0.033) were related to worse QOL. Certain characteristics placed patients with chordoma at increased risk of emotional problems, which are associated with a lowered QOL and a higher symptom burden. Further knowledge regarding emotional problems is key to improving the QOL for patients with chordoma.
Mitochondrial Bioenergy in Neurodegenerative Disease: Huntington and Parkinson
Authors: Tassone Annalisa , Meringolo Maria , Ponterio Giulia , Bonsi Paola , Schirinzi Tommaso , Martella Giuseppina
Published: April 2023

Strong evidence suggests a correlation between degeneration and mitochondrial deficiency. Typical cases of degeneration can be observed in physiological phenomena (i.e., ageing) as well as in neurological neurodegenerative diseases and cancer. All these pathologies have the dyshomeostasis of mitochondrial bioenergy as a common denominator. Neurodegenerative diseases show bioenergetic imbalances in their pathogenesis or progression. Huntington’s chorea and Parkinson’s disease are both neurodegenerative diseases, but while Huntington’s disease is genetic and progressive with early manifestation and severe penetrance, Parkinson’s disease is a pathology with multifactorial aspects. Indeed, there are different types of Parkinson/Parkinsonism. Many forms are early-onset diseases linked to gene mutations, while others could be idiopathic, appear in young adults, or be post-injury senescence conditions. Although Huntington’s is defined as a hyperkinetic disorder, Parkinson’s is a hypokinetic disorder. However, they both share a lot of similarities, such as neuronal excitability, the loss of striatal function, psychiatric comorbidity, etc. In this review, we will describe the start and development of both diseases in relation to mitochondrial dysfunction. These dysfunctions act on energy metabolism and reduce the vitality of neurons in many different brain areas.
Integrated Metabolomic and Transcriptomic Analyses Reveals Sugar Transport and Starch Accumulation in Two Specific Germplasms of Manihot esculenta Crantz
Authors: Cai Jie , Xue Jingjing , Zhu Wenli , Luo Xiuqin , Lu Xiaohua , Xue Maofu , Wei Zhuowen , Cai Yuqi , Ou Wenjun , Li Kaimian , An Feifei , Chen Songbi
Published: April 2023

As a starchy and edible tropical plant, cassava (Manihot esculenta Crantz) has been widely used as an industrial raw material and a dietary source. However, the metabolomic and genetic differences in specific germplasms of cassava storage root were unclear. In this study, two specific germplasms, M. esculenta Crantz cv. sugar cassava GPMS0991L and M. esculenta Crantz cv. pink cassava BRA117315, were used as research materials. Results showed that sugar cassava GPMS0991L was rich in glucose and fructose, whereas pink cassava BRA117315 was rich in starch and sucrose. Metabolomic and transcriptomic analysis indicated that sucrose and starch metabolism had significantly changing metabolites enrichment and the highest degree of differential expression genes, respectively. Sugar transport in storage roots may contribute to the activities of sugar, which will eventually be exported to transporters (SWEETs), such as (MeSWEET1a, MeSWEET2b, MeSWEET4, MeSWEET5, MeSWEET10b, and MeSWEET17c), which transport hexose to plant cells. The expression level of genes involved in starch biosynthesis and metabolism were altered, which may result in starch accumulation. These results provide a theoretical basis for sugar transport and starch accumulation and may be useful in improving the quality of tuberous crops and increasing yield.
Novel Therapeutic Targets for Tumor Microenvironment in Cancer
Authors: Bei Roberto , Masuelli Laura
Published: April 2023

The various immune effector cells that infiltrate the tumor microenvironment (TME) play a key role in directing the outcome of tumor growth [...]
Human Sinoatrial Node Pacemaker Activity: Role of the Slow Component of the Delayed Rectifier K+ Current, IKs
Authors: Verkerk Arie O. , Wilders Ronald
Published: April 2023

The pacemaker activity of the sinoatrial node (SAN) has been studied extensively in animal species but is virtually unexplored in humans. Here we assess the role of the slowly activating component of the delayed rectifier K+ current (IKs) in human SAN pacemaker activity and its dependence on heart rate and β-adrenergic stimulation. HEK-293 cells were transiently transfected with wild-type KCNQ1 and KCNE1 cDNA, encoding the α- and β-subunits of the IKs channel, respectively. KCNQ1/KCNE1 currents were recorded both during a traditional voltage clamp and during an action potential (AP) clamp with human SAN-like APs. Forskolin (10 µmol/L) was used to increase the intracellular cAMP level, thus mimicking β-adrenergic stimulation. The experimentally observed effects were evaluated in the Fabbri–Severi computer model of an isolated human SAN cell. Transfected HEK-293 cells displayed large IKs-like outward currents in response to depolarizing voltage clamp steps. Forskolin significantly increased the current density and significantly shifted the half-maximal activation voltage towards more negative potentials. Furthermore, forskolin significantly accelerated activation without affecting the rate of deactivation. During an AP clamp, the KCNQ1/KCNE1 current was substantial during the AP phase, but relatively small during diastolic depolarization. In the presence of forskolin, the KCNQ1/KCNE1 current during both the AP phase and diastolic depolarization increased, resulting in a clearly active KCNQ1/KCNE1 current during diastolic depolarization, particularly at shorter cycle lengths. Computer simulations demonstrated that IKs reduces the intrinsic beating rate through its slowing effect on diastolic depolarization at all levels of autonomic tone and that gain-of-function mutations in KCNQ1 may exert a marked bradycardic effect during vagal tone. In conclusion, IKs is active during human SAN pacemaker activity and has a strong dependence on heart rate and cAMP level, with a prominent role at all levels of autonomic tone.
Structural and Pathogenic Impacts of ABCA4 Variants in Retinal Degenerations—An In-Silico Study
Authors: Cevik Senem , Biswas Subhasis B. , Biswas-Fiss Esther E.
Published: April 2023

The retina-specific ATP-binding cassette transporter protein ABCA4 is responsible for properly continuing the visual cycle by removing toxic retinoid byproducts of phototransduction. Functional impairment caused by ABCA4 sequence variations is the leading cause of autosomal recessive inherited retinal disorders, including Stargardt disease, retinitis pigmentosa, and cone-rod dystrophy. To date, more than 3000 ABCA4 genetic variants have been identified, approximately 40 percent of which have not been able to be classified for pathogenicity assessments. This study examined 30 missense ABCA4 variants using AlphaFold2 protein modeling and computational structure analysis for pathogenicity prediction. All variants classified as pathogenic (n = 10) were found to have deleterious structural consequences. Eight of the ten benign variants were structurally neutral, while the remaining two resulted in mild structural changes. This study’s results provided multiple lines of computational pathogenicity evidence for eight ABCA4 variants of uncertain clinical significance. Overall, in silico analyses of ABCA4 can provide a valuable tool for understanding the molecular mechanisms of retinal degeneration and their pathogenic impact.
Dynamic Changes of BVRA Protein Levels Occur in Response to Insulin: A Pilot Study in Humans
Authors: Cimini Flavia Agata , Tramutola Antonella , Barchetta Ilaria , Ceccarelli Valentina , Gangitano Elena , Lanzillotta Simona , Lanzillotta Chiara , Cavallo Maria Gisella , Barone Eugenio
Published: April 2023

Biliverdin reductase-A (BVRA) is involved in the regulation of insulin signaling and the maintenance of glucose homeostasis. Previous research showed that BVRA alterations are associated with the aberrant activation of insulin signaling in dysmetabolic conditions. However, whether BVRA protein levels change dynamically within the cells in response to insulin and/or glucose remains an open question. To this aim, we evaluated changes of intracellular BVRA levels in peripheral blood mononuclear cells (PBMC) collected during the oral glucose tolerance test (OGTT) in a group of subjects with different levels of insulin sensitivity. Furthermore, we looked for significant correlations with clinical measures. Our data show that BVRA levels change dynamically during the OGTT in response to insulin, and greater BVRA variations occur in those subjects with lower insulin sensitivity. Changes of BVRA significantly correlate with indexes of increased insulin resistance and insulin secretion (HOMA-IR, HOMA-β, and insulinogenic index). At the multivariate regression analysis, the insulinogenic index independently predicted increased BVRA area under curve (AUC) during the OGTT. This pilot study showed, for the first time, that intracellular BVRA protein levels change in response to insulin during OGTT and are greater in subjects with lower insulin sensitivity, supporting the role of BVR-A in the dynamic regulation of the insulin signaling pathway.
Automatic Generation of SBML Kinetic Models from Natural Language Texts Using GPT
Authors: Maeda Kazuhiro , Kurata Hiroyuki
Published: April 2023

Kinetic modeling is an essential tool in systems biology research, enabling the quantitative analysis of biological systems and predicting their behavior. However, the development of kinetic models is a complex and time-consuming process. In this article, we propose a novel approach called KinModGPT, which generates kinetic models directly from natural language text. KinModGPT employs GPT as a natural language interpreter and Tellurium as an SBML generator. We demonstrate the effectiveness of KinModGPT in creating SBML kinetic models from complex natural language descriptions of biochemical reactions. KinModGPT successfully generates valid SBML models from a range of natural language model descriptions of metabolic pathways, protein–protein interaction networks, and heat shock response. This article demonstrates the potential of KinModGPT in kinetic modeling automation.
Nordalbergin Exerts Anti-Neuroinflammatory Effects by Attenuating MAPK Signaling Pathway, NLRP3 Inflammasome Activation and ROS Production in LPS-Stimulated BV2 Microglia
Authors: Lo Jung , Wu Hsin-En , Liu Ching-Chih , Chang Kun-Che , Lee Po-Yen , Liu Po-Len , Huang Shu-Pin , Wu Pei-Chang , Lin Tzu-Chieh , Lai Yu-Hung , Chang Yo-Chen , Chen Yuan-Ru , Lee Sheng-I , Huang Yu-Kai , Wang Shu-Chi , Li Chia-Yang
Published: April 2023

Microglia-associated neuroinflammation is recognized as a critical factor in the pathogenesis of neurodegenerative diseases; however, there is no effective treatment for the blockage of neurodegenerative disease progression. In this study, the effect of nordalbergin, a coumarin isolated from the wood bark of Dalbergia sissoo, on lipopolysaccharide (LPS)-induced inflammatory responses was investigated using murine microglial BV2 cells. Cell viability was assessed using the MTT assay, whereas nitric oxide (NO) production was analyzed using the Griess reagent. Secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was detected by the ELISA. The expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, mitogen-activated protein kinases (MAPKs) and NLRP3 inflammasome-related proteins was assessed by Western blot. The production of mitochondrial reactive oxygen species (ROS) and intracellular ROS was detected using flow cytometry. Our experimental results indicated that nordalbergin ≤20 µM suppressed NO, IL-6, TNF-α and IL-1β production; decreased iNOS and COX-2 expression; inhibited MAPKs activation; attenuated NLRP3 inflammasome activation; and reduced both intracellular and mitochondrial ROS production by LPS-stimulated BV2 cells in a dose-dependent manner. These results demonstrate that nordalbergin exhibits anti-inflammatory and anti-oxidative activities through inhibiting MAPK signaling pathway, NLRP3 inflammasome activation and ROS production, suggesting that nordalbergin might have the potential to inhibit neurodegenerative disease progression.
Sustainable Exploitation of Posidonia oceanica Sea Balls (Egagropili): A Review
Authors: Restaino Odile Francesca , Giosafatto Concetta Valeria L. , Mirpoor Seyedeh Fatemeh , Cammarota Marcella , Hejazi Sondos , Mariniello Loredana , Schiraldi Chiara , Porta Raffaele
Published: April 2023

Posidonia oceanica (L.) Delile is the main seagrass plant in the Mediterranean basin that forms huge underwater meadows. Its leaves, when decomposed, are transported to the coasts, where they create huge banquettes that protect the beaches from sea erosion. Its roots and rhizome fragments, instead, aggregate into fibrous sea balls, called egagropili, that are shaped and accumulated by the waves along the shoreline. Their presence on the beach is generally disliked by tourists, and, thus, local communities commonly treat them as waste to remove and discard. Posidonia oceanica egagropili might represent a vegetable lignocellulose biomass to be valorized as a renewable substrate to produce added value molecules in biotechnological processes, as bio-absorbents in environmental decontamination, to prepare new bioplastics and biocomposites, or as insulating and reinforcement materials for construction and building. In this review, the structural characteristics, and the biological role of Posidonia oceanica egagropili are described, as well as their applications in different fields as reported in scientific papers published in recent years.
Reverse Screening of Boronic Acid Derivatives: Analysis of Potential Antiproliferative Effects on a Triple-Negative Breast Cancer Model In Vitro
Authors: Ortiz-Flores Miguel , González-Pérez Marcos , Portilla Andrés , Soriano-Ursúa Marvin A. , Pérez-Durán Javier , Montoya-Estrada Araceli , Ceballos Guillermo , Nájera Nayelli
Published: April 2023

It has been demonstrated that different organoboron compounds interact with some well-known molecular targets, including serine proteases, transcription factors, receptors, and other important molecules. Several approaches to finding the possible beneficial effects of boronic compounds include various in silico tools. This work aimed to find the most probable targets for five aromatic boronic acid derivatives. In silico servers, SuperPred, PASS-Targets, and Polypharmacology browser 2 (PPB2) suggested that the analyzed compounds have anticancer properties. Based on these results, the antiproliferative effect was evaluated using an in vitro model of triple-negative breast cancer (4T1 cells in culture). It was demonstrated that phenanthren-9-yl boronic acid and 6-hydroxynaphthalen-2-yl boronic acid have cytotoxic properties at sub-micromolar concentrations. In conclusion, using in silico approaches and in vitro analysis, we found two boronic acid derivatives with potential anticancer activity.
Biventricular or Conduction System Pacing for Cardiac Resynchronization Therapy: A Strategy for Cardiac Resynchronization Based on a Hybrid Approach
Authors: Santoro Amato , Landra Federico , Marallo Carmine , Taddeucci Simone , Sisti Nicolò , Pica Andrea , Stefanini Andrea , Tavera Maria Cristina , Pagliaro Antonio , Baiocchi Claudia , Cameli Matteo
Published: April 2023

Background: Cardiac resynchronization therapy (CRT) is usually performed with biventricular pacing (BiVP), but recently, conduction system pacing (CSP) has been proposed as an alternative in case of BiVP failure. The aim of this study is to define an algorithm to choose between BiVP and CSP resynchronization using the interventricular conduction delays (IVCD) as a guide. Methods: Consecutive patients from January 2018 to December 2020 with an indication for CRT were prospectively enrolled in the study group (delays-guided resynchronization group, DRG). A treatment algorithm based on IVCD was used to decide whether to leave the left ventricular (LV) lead to perform BiVP or pull it out and perform CSP. Outcomes from the DRG group were compared to a historical cohort of CRT patients who underwent CRT procedures between January 2016 and December 2017 (resynchronization standard guide group, SRG). The primary endpoint was a composite of cardiovascular mortality, heart failure (HF) hospitalization, or HF event at 1 year after the date of intervention. Results: The study population consisted of 292 patients, of which 160 (54.8%) were in the DRG and 132 (45.2%) in the SRG. In the DRG, 41 of 160 patients underwent CSP based on the treatment algorithm (25.6%). The primary endpoint was significantly higher in the SRG (48/132, 36.4%) compared to the DRG (35/160, 21.8%) (hazard ratio (HR): 1.72; 95% confidence interval (CI): 1.12–2.65; p = 0.013). Conclusions: A treatment algorithm based on IVCD shifted one patient out of every four from BiVP to CSP, with consequent reduction in the primary endpoint after implantation. Therefore, its application could be useful to determine whether to perform BiVP or CSP.
Evaluation of the Pinhole Method Using Carbon Dioxide Laser on Facial Telangiectasia
Authors: Woo Sang Seok , Gwak Hongki , Han Seung Seog , Suh In Suck , Kim Seong Hwan
Published: April 2023

Facial telangiectasias are small, dilated blood vessels frequently located on the face. They are cosmetically disfiguring and require an effective solution. We aimed to investigate the effect of the pinhole method using a carbon dioxide (CO2) laser to treat facial telangiectasias. This study included 155 facial telangiectasia lesions in 72 patients who visited the Kangnam Sacred Heart Hospital, Hallym University. Treatment efficacy and improvement were evaluated by quantitative measurements performed by two trained evaluators who assessed the percentage of residual lesion length using the same tape measure. Lesions were evaluated before laser therapy and 1, 3, and 6 months after the first treatment. Based on the initial lesion length (100%), the average percentages of the residual length at 1, 3, and 6 months were 48.26% (p < 0.01), 4.25% (p < 0.01), and 1.41% (p < 0.01), respectively. Complications were evaluated using the Patient and Observer Scar Assessment Scale (POSAS). The average POSAS scores improved from 46.09 at the first visit to 23.42 (p < 0.01), and 15.24 (p < 0.01) at the 3- and 6-month follow-up. No recurrence was noted at the 6-month follow-up. CO2 laser treatment using the pinhole method to treat facial telangiectasias is a safe, inexpensive, and effective treatment that provides patients with excellent aesthetic satisfaction.
Association between Chronic Kidney Disease and Sudden Sensorineural Hearing Loss: A Longitudinal Follow-Up Studies Using ICD-10 Codes in a National Health Screening Cohort
Authors: Shim Ye Ji , Choi Hyo Geun , Wee Jee Hye
Published: April 2023

This study aims to investigate the association between chronic kidney disease (CKD) and sudden sensorineural hearing loss (SSNHL) using a population-based cohort study. We used data from the Korean National Health Insurance Service–Health Screening Cohort. Participants were selected based on diagnosis and treatment codes, and CKD participants were 1:4 matched with control participants. Covariates, including demographic and lifestyle factors, and comorbidities were considered in the analysis. We calculated the incidence rate and hazards ratio of SSNHL. A total of 16,713 CKD participants and 66,852 matched controls were enrolled. The CKD group had a higher incidence rate of SSNHL compared to the control group at 2.16 and 1.74 per 1000 person-years, respectively. The CKD group exhibited a higher risk for SSNHL compared to the control group with adjusted HR 1.21. In the subgroup analysis, the presence of cardiovascular risk factors was associated with a diminished effect of CKD on the risk of developing SSNHL. This study provides strong evidence of an association between CKD per se and an increased risk of SSNHL even after adjusting for various demographic and comorbidity factors. The findings suggest that CKD patients may require more comprehensive monitoring for hearing loss.
Endometriosis and the Temporomandibular Joint—Preliminary Observations
Authors: Wójcik Małgorzata , Goździewicz Tomasz , Hudáková Zuzana , Siatkowski Idzi
Published: April 2023

(1) Background: The complete picture of the disease is not fully recognized and extends far beyond the pelvis. The disease’s impacts lead to systemic inflammation, in turn resulting in sensitization to pain. The aim of this study was to check whether statistical correlations exist in women with endometriosis with regard to their experience of pain: headache, pelvic pain, temporomandibular joint pain, along with teeth clenching and the treatment of the disease. We constructed contingency tables, followed by Pearson’s chi-square test and Cramer’s V coefficient values. (2) Methods: A survey was conducted among 128 women aged 33.43 ± 5.79 with a diagnosis of endometriosis (disease duration 6.40 ± 5.88 years). (3) Results: There was a correlation between the occurrence of pain on the right and left sides of the pelvis and pain on the right and left sides of the temporomandibular joint, p-value = 0.0397, V = 0.2350, and between the presence of pelvic pain and the treatment of endometriosis, p-value = 0.0104, V = 0.3709, and between the presence of pain outside the pelvis and the treatment of endometriosis, p-value = 0.0311, V = 0.4549. There was a highly significant correlation between teeth clenching and temporomandibular joint pain, p-value = 0.0005, V = 0.3695. (4) Conclusions: The study revealed a correlation between pelvic endometriosis symptoms and symptoms in the temporomandibular joint.
Microcirculatory and Rheological Adaptive Mechanisms at High Altitude in European Lowlander Hikers and Nepalese Highlanders
Authors: Salvi Paolo , Grillo Andrea , Brunacci Fausto , Severi Francesca , Montaguti Luca , Gautier Sylvie , Salvi Lucia , Pretolani Enzo , Parati Gianfranco , Benetos Athanase
Published: April 2023

Background: Physical activity at high-altitudes is increasingly widespread, both for tourist trekking and for the growing tendency to carry out sports and training activities at high-altitudes. Acute exposure to this hypobaric–hypoxic condition induces several complex adaptive mechanisms involving the cardiovascular, respiratory and endocrine systems. A lack of these adaptive mechanisms in microcirculation may cause the onset of symptoms of acute mountain sickness, a frequent disturbance after acute exposure at high altitudes. The aim of our study was to evaluate the microcirculatory adaptive mechanisms at different altitudes, from 1350 to 5050 m a.s.l., during a scientific expedition in the Himalayas. Methods: The main haematological parameters, blood viscosity and erythrocyte deformability were assessed at different altitudes on eight European lowlanders and on a group of eleven Nepalese highlanders. The microcirculation network was evaluated in vivo by conjunctival and periungual biomicroscopy. Results: Europeans showed a progressive and significant reduction of blood filterability and an increase of whole blood viscosity which correlate with the increase of altitude (p < 0.02). In the Nepalese highlanders, haemorheological changes were already present at their residence altitude, 3400 m a.s.l. (p < 0.001 vs. Europeans). With the increase in altitude, a massive interstitial oedema appeared in all participants, associated with erythrocyte aggregation phenomena and slowing of the flow rate in the microcirculation. Conclusions: High altitude causes important and significant microcirculatory adaptations. These changes in microcirculation induced by hypobaric–hypoxic conditions should be considered when planning training and physical activity at altitude.
Analysis of Movement and Activities of Handball Players Using Deep Neural Networks
Authors: Host Kristina , Pobar Miran , Ivasic-Kos Marina
Published: April 2023

This paper focuses on image and video content analysis of handball scenes and applying deep learning methods for detecting and tracking the players and recognizing their activities. Handball is a team sport of two teams played indoors with the ball with well-defined goals and rules. The game is dynamic, with fourteen players moving quickly throughout the field in different directions, changing positions and roles from defensive to offensive, and performing different techniques and actions. Such dynamic team sports present challenging and demanding scenarios for both the object detector and the tracking algorithms and other computer vision tasks, such as action recognition and localization, with much room for improvement of existing algorithms. The aim of the paper is to explore the computer vision-based solutions for recognizing player actions that can be applied in unconstrained handball scenes with no additional sensors and with modest requirements, allowing a broader adoption of computer vision applications in both professional and amateur settings. This paper presents semi-manual creation of custom handball action dataset based on automatic player detection and tracking, and models for handball action recognition and localization using Inflated 3D Networks (I3D). For the task of player and ball detection, different configurations of You Only Look Once (YOLO) and Mask Region-Based Convolutional Neural Network (Mask R-CNN) models fine-tuned on custom handball datasets are compared to original YOLOv7 model to select the best detector that will be used for tracking-by-detection algorithms. For the player tracking, DeepSORT and Bag of tricks for SORT (BoT SORT) algorithms with Mask R-CNN and YOLO detectors were tested and compared. For the task of action recognition, I3D multi-class model and ensemble of binary I3D models are trained with different input frame lengths and frame selection strategies, and the best solution is proposed for handball action recognition. The obtained action recognition models perform well on the test set with nine handball action classes, with average F1 measures of 0.69 and 0.75 for ensemble and multi-class classifiers, respectively. They can be used to index handball videos to facilitate retrieval automatically. Finally, some open issues, challenges in applying deep learning methods in such a dynamic sports environment, and direction for future development will be discussed.
Study of Overtopping Flow Velocity and Overtopping Layer Thickness on Composite Breakwater under Regular Wave
Authors: Adibhusana Made Narayana , Lee Jong-In , Kim Young-Taek , Ryu Yonguk
Published: April 2023

Overtopping flow velocity (OFV) and overtopping layer thickness (OTL) are essential parameters in breakwater design. Several empirical equations to predict these parameters are available in many works of literature, but most of the equations were derived based on impermeable structures such as sea dikes. In this study, we experimented with overtopping waves over a composite breakwater with tetrapod armor units. In the experiments, wave overtopping was generated from regular waves. We used a digital image-based velocimetry method, bubble image velocimetry (BIV), to measure the OFV and digitize the corresponding image to obtain the OLT. The patterns of OFV and OTL with respect to time steps, wave conditions, and corresponding events were provided and discussed. The application of the widely used empirical equations for sea dike to breakwater was also tested by calibrating the coefficients. New empirical coefficients and roughness factors were suggested to reduce the difference between predicted and measured OFV and OLT on breakwater through the bootstrap resampling technique. This study provides modified empirical equations on wave overtopping, which is further applicable to breakwater design.
Discrete Element Modeling of the Effect of Hydrate Distribution Heterogeneity on the Mechanical Behavior of Cemented Hydrate-Bearing Sediments
Authors: Wang Tianju , Ding Yanlu , Wang Rui , Qian Anna , Lu Hailong , Zhou Boyu
Published: April 2023

Hydrate distribution heterogeneity is often observed in natural and artificial hydrate-bearing sediments (HBSs). To capture hydrate distribution heterogeneity, a pore-scale method is proposed to model cemented HBSs using the discrete element method (DEM). This method takes into account the quantitative effect of hydrate saturation in a sediment pore on the contact bond parameters surrounding the pore. A series of DEM specimens with different macroscopically and microscopically heterogeneous hydrate distributions are prepared. The mechanical behavior of heterogeneous HBSs is investigated by performing biaxial compression tests with flexible boundaries. The simulation results show that both macroscopic and microscopic hydrate distribution heterogeneity can influence the mechanical properties of HBSs. The shear strength is promoted in both macroscopically and microscopically heterogeneous HBSs. Longitudinally heterogeneous HBSs have a higher secant modulus, while transversely heterogeneous HBSs have a lower secant modulus than homogeneous HBSs. The secant modulus of microscopically heterogeneous HBSs first increases and then decreases with increasing pore hydrate saturation. It is found that the deformation behavior and bond breakage evolution of HBSs depend on hydrate distribution heterogeneity. These findings can provide insights into understanding the mechanical behavior of natural HBSs with heterogeneous hydrate distributions.
Prospects of Novel and Repurposed Immunomodulatory Drugs against Acute Respiratory Distress Syndrome (ARDS) Associated with COVID-19 Disease
Authors: Nayak Smruti , Naidu Akshayata , Sudhakaran Sajitha , Vino Sundararajan , Selvaraj Gurudeeban
Published: April 2023

Acute respiratory distress syndrome (ARDS) is intricately linked with SARS-CoV-2-associated disease severity and mortality, especially in patients with co-morbidities. Lung tissue injury caused as a consequence of ARDS leads to fluid build-up in the alveolar sacs, which in turn affects oxygen supply from the capillaries. ARDS is a result of a hyperinflammatory, non-specific local immune response (cytokine storm), which is aggravated as the virus evades and meddles with protective anti-viral innate immune responses. Treatment and management of ARDS remain a major challenge, first, because the condition develops as the virus keeps replicating and, therefore, immunomodulatory drugs are required to be used with caution. Second, the hyperinflammatory responses observed during ARDS are quite heterogeneous and dependent on the stage of the disease and the clinical history of the patients. In this review, we present different anti-rheumatic drugs, natural compounds, monoclonal antibodies, and RNA therapeutics and discuss their application in the management of ARDS. We also discuss on the suitability of each of these drug classes at different stages of the disease. In the last section, we discuss the potential applications of advanced computational approaches in identifying reliable drug targets and in screening out credible lead compounds against ARDS.
Feasibility and Toxicity of Interval-Compressed Chemotherapy in Asian Children and Young Adults with Sarcoma
Authors: Huang Jia-Hui , Chen Shu-Huey , Liao Yu-Mei , Kao Yu-Chien , Ho Wan-Ling , Chang Hsi , Tsai Min-Lan , Lee Hsin-Lun , Kuo Chia-Chun , Tseng Sung-Hui , Chang Chia-Yau , Hsieh Kevin Li-Chun , Lu Long-Sheng , Chen Yin-Ju , Chiou Jeng-Fong , Hsieh Tsung-Han , Liu Yun-Ru , Hsu Wayne , Li Wei-Tang , Wu Yu-Chung , Wu Wei-Ciao , Wang Jinn-Li , Tsai Jia-Jia , Terashima Keita , Kiyotani Chikako , Wong Tai-Tong , Miser James S. , Liu Yen-Lin
Published: April 2023

Twelve Asian patients with sarcoma received interval-compressed (ic-) chemotherapy scheduled every 14 days with a regimen of vincristine (2 mg/m2), doxorubicin (75 mg/m2), and cyclophosphamide (1200–2200 mg/m2) (VDC) alternating with a regimen of ifosfamide (9000 mg/m2) and etoposide (500 mg/m2) (IE), with filgrastim (5–10 mcg/kg/day) between cycles. Carboplatin (800 mg/m2) was added for CIC-rearranged sarcoma. The patients were treated with 129 cycles of ic-VDC/IE with a median interval of 19 days (interquartile range [IQR], 15–24 days. Median nadirs (IQR) were neutrophil count, 134 (30–396) × 106/L at day 11 (10–12), recovery by day 15 (14–17) and platelet count, 35 (23–83) × 109/L at day 11 (10–13), recovery by day 17 (14–21). Fever and bacteremia were observed in 36% and 8% of cycles, respectively. The diagnoses were Ewing sarcoma (6), rhabdomyosarcoma (3), myoepithelial carcinoma (1), malignant peripheral nerve sheath tumor (1), and CIC-DUX4 Sarcoma (1). Seven of the nine patients with measurable tumors responded (one CR and six PR). Interval-compressed chemotherapy is feasible in the treatment of Asian children and young adults with sarcomas.
HIV-Indicator Condition Guided Testing in a Hospital Setting
Authors: Barbanotti Diletta , Tincati Camilla , Tavelli Alessandro , Santoro Andrea , Sala Matteo , Bini Teresa , De Bona Anna , d’Arminio Monforte Antonella , Marchetti Giulia Carla
Published: April 2023

Late diagnosis is still a major issue in HIV infection management, leading to important consequences for both patients and community. In this perspective, HIV screening targeted on some clinical conditions (HIV indicator conditions—HIVICs) emerged as a useful strategy, also involving patients not considered at high behavioral risk. We organized an in-hospital HIVICs guided screening campaign named ICEBERG in Milan, Italy, between 2019 and 2021. Among the 520 subjects enrolled, mainly presenting with viral hepatitis or mononucleosis-like syndrome, 20 resulted HIV positive (3.8% prevalence). A significant proportion of them had multiple conditions and advanced immunosuppression, with 40% being AIDS-presenters. As adherence to the screening campaign was modest for non-ID specialists, educational interventions to raise clinicians’ sensitivity are urgently needed. HIV-ICs guided testing was confirmed as a useful tool, but a combined approach with other screening strategies seems to be essential for early HIV diagnosis.