bluuebunny/crossref_metadata_2025 huggingface dataset:
Imprints of Millennial-Scale Monsoonal Events during the MIS3 Revealed by Stalagmite δ13C Records in China
Authors: Shen Rongyu , Zhang Peng , Cong Jiaqi , Liao Jing , Luo Xuelin , Tan Liangcheng , Dong Jinguo , Liang Yijia
Published: May 2023

Regions located on the Chinese Loess Plateau are sensitive to changes in the Asian monsoon because they are on the edge of the monsoon region. Based on six 230Th experiments and 109 sets of stable isotope data of LH36 from Lianhua Cave, Yangquan City, Shanxi Province, we obtained a paleoclimate record with an average resolution of 120 years from 54.5 to 41.1 ka BP during the MIS3 on the Chinese Loess Plateau. Both the Hendy test and the replication test indicated an equilibrium fractionation of stable isotopes during the stalagmite deposition. Comparison with four other independently-dated, high-resolution stalagmite δ13C records between 29°N and 41°N in the Asian monsoon region shows that the stalagmite δ13C records from different caves have good reproducibility during the overlapped growth period. We suggest that speleothem δ13C effectively indicates soil CO2 production in the overlying area of the cave, reflecting changes in the cave’s external environment and in the Asian summer monsoon. Five millennial-scale Asian summer monsoon intensification events correspond to the Dansgaard–Oeschger 10–14 cycles recorded in the Greenland ice core within dating errors, and the weak monsoon processes are closely related to stadials in the North Atlantic. The spatial consistency of stalagmite δ13C records in China suggests that the Asian summer monsoon and the related regional ecological environment fluctuations sensitively respond to climate changes at northern high latitudes through sea-air coupling on the millennial timescale.
Critical Failure Factors of Flood Early Warning and Response Systems (FEWRS): A Structured Literature Review and Interpretive Structural Modelling (ISM) Analysis
Authors: Samansiri Srimal , Fernando Terrence , Ingirige Bingunath
Published: May 2023

Flood warning and response systems are essential components of risk reduction strategies with the potential to reduce loss of life and impact on personal assets. However, recent flood incidents have caused significant loss of human lives due to failures in current flood warning and response mechanisms. These failures are broadly related to policies concerning, and governance aspects within, warning generation, the behaviour of communities in responding to early warnings, and weaknesses in associated tools and technologies used in communicating early warnings and responding. Capturing critical failure factors affecting flood warning and response systems can provide opportunities for making corrective measures and for developing a more advanced and futuristic system for early flood warnings. This paper reports the findings of a structured review that was conducted to identify critical failure factors in flood early warning and response systems. This study found twenty-four critical failure factors (CFFs). The interpretive structural modelling (ISM) approach conducted in this study resulted in identifying four different types of failure factors (autonomous, dependent, linkage, and independent) with varying dependence and driving powers. Analysis shows that governance, leadership, finance, standard operating procedures (SoP), and community engagement are the most dominating factors with the highest driving factor, which can overcome other dependent factors. The outcome of this review could be helpful for policymakers and practitioners in overcoming failure factors and implementing effective early warning and response systems.
The Prognostic Role of Automated Office Blood Pressure Measurement in Hypertensive Patients with Chronic Kidney Disease
Authors: Psounis Konstantinos , Andreadis Emmanuel , Oikonomaki Theodora , Roumeliotis Stefanos , Margellos Vasileios , Thodis Elias , Passadakis Ploumis , Panagoutsos Stylianos
Published: May 2023

Background: The aim of this study was to evaluate the prognostic value of automated office blood pressure (AOBP) measurement in patients with hypertension and chronic kidney disease (CKD) stage 3–5 not on dialysis. Methods: At baseline, 140 patients were recruited, and blood pressure (BP) measurements with 3 different methods, namely, office blood pressure (OBP), AOBP, and ambulatory blood pressure measurement (ABPM), were recorded. All patients were prospectively followed for a median period of 3.4 years. The primary outcome of this study was a composite outcome of cardiovascular (CV) events (both fatal and nonfatal) or a doubling of serum creatine or progression to end-stage kidney disease (ESKD), whichever occurred first. Results: At baseline, the median age of patients was 65.2 years; 36.4% had diabetes; 21.4% had a history of CV disease; the mean of estimated glomerular filtration rate (eGFR) was 33 mL/min/1.73 m2; and the means of OBP, AOBP, and daytime ABPM were 151/84 mm Hg, 134/77 mm Hg, and 132/77 mm Hg, respectively. During the follow-up, 18 patients had a CV event, and 37 patients had a renal event. In the univariate cox regression analysis, systolic AOBP was found to be predictive of the primary outcome (HR per 1 mm Hg increase in BP, 1.019, 95% CI 1.003–1.035), and after adjustment for eGFR, smoking status, diabetes, and a history of CV disease and systolic and diastolic AOBP were also found to be predictive of the primary outcome (HR per 1 mm Hg increase in BP, 1.017, 95% CI 1.002–1.032 and 1.033, 95% CI 1.009–1.058, respectively). Conclusions: In patients with CKD, AOBP appears to be prognostic of CV risk or risk for kidney disease progression and could, therefore, be considered a reliable means for recording BP in the office setting.
Regional Analysis of Tracer Tests in the Karstic Basin of the Gacka River (Croatian Dinaric Karst)
Authors: Stroj Andrej , Briški Maja , Lukač Reberski Jasmina , Frangen Tihomir
Published: May 2023

Tracer testing is the only method in karst hydrogeology that can definitively determine whether a particular site belongs to a watershed of a particular karst spring. Therefore, it is an essential technique for delineating groundwater basins in karst areas. The availability of tracer test results is often limited due to the complicated and relatively expensive application of this approach, especially for large regional watersheds. The Croatian part of the Dinaric karst region extends for several hundred kilometers along the Adriatic coast and consists almost entirely of highly karstified carbonate rocks. The groundwater basins in these areas almost never match the surface morphology of the terrain. In practice, all available results of previous surveys are often used to define watersheds, regardless of the methodology and age of their implementation. This is also true for the earlier delineations of the Gacka River watershed, a regional karst basin in the Croatian Dinaric karst. However, tracer testing methods, especially the accuracy of tracer determination and monitoring, have improved significantly during this time. In order to assess the reliability of past tracing results in this significant karst basin, we reviewed reports of previous tracer tests. More recent tests, in particular the most recent multitracer injection test with continuous tracer detection on the major springs, produced high-quality data that allowed us to assess the reliability of the findings from prior research. A number of large karst springs with partially overlapping subcatchments feed the Gacka River. After discarding unreliable tracing data, we reevaluated the subcatchments of the main springs as well as the characteristics of the regional groundwater flow patterns throughout the basin, which is particularly important for water quality protection measures of the springs. The Gacka River basin is used as a case study to emphasize the importance of thoroughly assessing the reliability of previous tracing data before using them in regional analyses.
Surface Functionalization of Bioactive Hybrid Adsorbents for Enhanced Adsorption of Organic Dyes
Authors: Riyad Yasser M. , Elmorsi Taha M. , Alam Mohd Gulfam , Abel Bernd
Published: May 2023

In this study, a valuable adsorbent was functionalized using commercial ZnO and a mango seed extract (MS-Ext) as a green approach for synthesis. Fourier-transform infrared spectroscopy, transmission electron microscopy, scanning electron microscopy, and energy-dispersive X-ray analysis spectraconfirmed the presence of bioactive phenolic compounds and Cu2+ ions on the surface of ZnO. Functionalized Cu-doped ZnO/MS-Ext exhibits high efficacy in acidic, neutral, and alkaline medium, as indicated by 98.3% and 93.7% removal of methylene blue (MB) and crystal violet (CV) dyes, respectively. Cu-doped ZnO/MS-Ext has a zeta potential significantly lower than pristine zinc oxide (p-ZnO), which results in enhanced adsorption of cationic MB and CV dyes. In binary systems, both MB and CV were significantly removed in acidic and alkaline media, with 92% and 87% being removed for CV in acidic and alkaline media, respectively. In contrast, the removal efficiency of methyl orange dye (MO) was 16.4%, 6.6% and 11.2% for p-ZnO, ZnO/Ext and Cu-doped ZnO/Ext, respectively. In general, the adsorption kinetics of MB on Cu-doped ZnO/MS-Ext follow this order: linear pseudo-second-order (PSO) > nonlinear pseudo-second-order (PSO) > nonlinear Elovich model > linear Elovich model. The Langmuir isotherm represents the adsorption process and indicates that MB, CV, and MO are chemisorbed onto the surface of the adsorbent at localized active centers of the MS-extract functional groups. In a binary system consisting of MB and CV, the maximum adsorption capacity (qm) was 72.49 mg/g and 46.61 mg/g, respectively. The adsorption mechanism is governed by electrostatic attraction and repulsion, coordination bonds, and π–π interactions between cationic and anionic dyes upon Cu-doped ZnO/Ext surfaces.
“Ultimately, You Realize You’re on Your Own”: The Impact of Prostate Cancer on Gay and Bisexual Men Couples
Authors: Daniels Joseph , Stephenson Rob , Langer Shelby , Northouse Laurel , Odouli Roxana , Amarasekera Channa , Vandeneeden Stephen , Langston Marvin
Published: May 2023

An estimated one in three gay and bisexual (GB) male couples receive a prostate cancer (PCa) diagnosis over their life course with limited understanding of the impacts on their relationships. Psychological distress related to PCa diagnosis and treatment-related side effects have been shown to disrupt established GB partnership dynamics. Communication barriers often develop within GB relationships affected by PCa, further exacerbating couple tensions, isolating partners, and lowering quality of life for both patients and partners. In order to elaborate on these phenomena following a PCa diagnosis, we conducted focus group discussions with GB men in relationships. Men were recruited nationally through PCa support groups, and after completing consent procedures, they were invited to one of two focus group discussions conducted through video conference. Topics discussed included the diagnosis and medical decision making pertaining to PCa; healthcare provider experiences; the emotional, physical, and sexual impact of PCa diagnosis and treatment; sources of support and appraisal of resources; and partner involvement and communication. There were twelve GB men who participated in focus group discussions that were audio-recorded and transcribed, and analyzed using a thematic approach. GB couple experiences with PCa during and after treatment choice and recovery identified common patient–provider communication barriers. In particular, GB men reported difficulties in disclosing their sexuality and relationship to their providers, limiting conversations about treatment choice and partner engagement in care. Both patients and partners experienced times of being alone after treatment, either by choice or to give space to their partner. However, partners often did not explicitly discuss their preferences for being alone or together, which resulted in partners’ disengagement in their relationship and the prostate cancer healthcare process. This disengagement could blunt the notable PCa survival benefits of partnership for GB men.
Antiviral Activity of Zinc Oxide Nanoparticles against SARS-CoV-2
Authors: Wolfgruber Stella , Rieger Julia , Cardozo Olavo , Punz Benjamin , Himly Martin , Stingl Andreas , Farias Patricia M. A. , Abuja Peter M. , Zatloukal Kurt
Published: May 2023

The highly contagious SARS-CoV-2 virus is primarily transmitted through respiratory droplets, aerosols, and contaminated surfaces. In addition to antiviral drugs, the decontamination of surfaces and personal protective equipment (PPE) is crucial to mitigate the spread of infection. Conventional approaches, including ultraviolet radiation, vaporized hydrogen peroxide, heat and liquid chemicals, can damage materials or lack comprehensive, effective disinfection. Consequently, alternative material-compatible and sustainable methods, such as nanomaterial coatings, are needed. Therefore, the antiviral activity of two novel zinc-oxide nanoparticles (ZnO-NP) against SARS-CoV-2 was investigated in vitro. Each nanoparticle was produced by applying highly efficient “green” synthesis techniques, which are free of fossil derivatives and use nitrate, chlorate and sulfonate salts as starting materials and whey as chelating agents. The two “green” nanomaterials differ in size distribution, with ZnO-NP-45 consisting of particles ranging from 30 nm to 60 nm and ZnO-NP-76 from 60 nm to 92 nm. Human lung epithelial cells (Calu-3) were infected with SARS-CoV-2, pre-treated in suspensions with increasing ZnO-NP concentrations up to 20 mg/mL. Both “green” materials were compared to commercially available ZnO-NP as a reference. While all three materials were active against both virus variants at concentrations of 10–20 mg/mL, ZnO-NP-45 was found to be more active than ZnO-NP-76 and the reference material, resulting in the inactivation of the Delta and Omicron SARS-CoV-2 variants by a factor of more than 106. This effect could be due to its greater total reactive surface, as evidenced by transmission electron microscopy and dynamic light scattering. Higher variations in virus inactivation were found for the latter two nanomaterials, ZnO-NP-76 and ZnO-NP-ref, which putatively may be due to secondary infections upon incomplete inactivation inside infected cells caused by insufficient NP loading of the virions. Taken together, inactivation with 20 mg/mL ZnO-NP-45 seems to have the greatest effect on both SARS-CoV-2 variants tested. Prospective ZnO-NP applications include an antiviral coating of filters or PPE to enhance user protection.
Redox-Cycling “Mitocans” as Effective New Developments in Anticancer Therapy
Authors: Bakalova Rumiana , Lazarova Dessislava , Sumiyoshi Akira , Shibata Sayaka , Zhelev Zhivko , Nikolova Biliana , Semkova Severina , Vlaykova Tatyana , Aoki Ichio , Higashi Tatsuya
Published: May 2023

Our study proposes a pharmacological strategy to target cancerous mitochondria via redox-cycling “mitocans” such as quinone/ascorbate (Q/A) redox-pairs, which makes cancer cells fragile and sensitive without adverse effects on normal cells and tissues. Eleven Q/A redox-pairs were tested on cultured cells and cancer-bearing mice. The following parameters were analyzed: cell proliferation/viability, mitochondrial superoxide, steady-state ATP, tissue redox-state, tumor-associated NADH oxidase (tNOX) expression, tumor growth, and survival. Q/A redox-pairs containing unprenylated quinones exhibited strong dose-dependent antiproliferative and cytotoxic effects on cancer cells, accompanied by overproduction of mitochondrial superoxide and accelerated ATP depletion. In normal cells, the same redox-pairs did not significantly affect the viability and energy homeostasis, but induced mild mitochondrial oxidative stress, which is well tolerated. Benzoquinone/ascorbate redox-pairs were more effective than naphthoquinone/ascorbate, with coenzyme Q0/ascorbate exhibiting the most pronounced anticancer effects in vitro and in vivo. Targeted anticancer effects of Q/A redox-pairs and their tolerance to normal cells and tissues are attributed to: (i) downregulation of quinone prenylation in cancer, leading to increased mitochondrial production of semiquinone and, consequently, superoxide; (ii) specific and accelerated redox-cycling of unprenylated quinones and ascorbate mainly in the impaired cancerous mitochondria due to their redox imbalance; and (iii) downregulation of tNOX.
The Relationship between Insomnia and the Pathophysiology of Major Depressive Disorder: An Evaluation of a Broad Selection of Serum and Urine Biomarkers
Authors: Drinčić Tina , van Dalfsen Jens H. , Kamphuis Jeanine , Jentsch Mike C. , van Belkum Sjoerd M. , Meddens Marcus J. M. , Penninx Brenda W. J. H. , Schoevers Robert A.
Published: May 2023

Insomnia exhibits a clinically relevant relationship with major depressive disorder (MDD). Increasing evidence suggests that insomnia is associated with neurobiological alterations that resemble the pathophysiology of MDD. However, research in a clinical population is limited. The present study, therefore, aimed to investigate the relationship between insomnia and the main pathophysiological mechanisms of MDD in a clinical sample of individuals with MDD. Data were extracted from three cohorts (N = 227) and included an evaluation of depression severity (Quick Inventory of Depressive Symptomatology, QIDS-SR16) and insomnia severity (QIDS-SR16 insomnia items) as well as serum and urine assessments of 24 immunologic (e.g., tumour necrosis factor α receptor 2 and calprotectin), neurotrophic (e.g., brain-derived neurotrophic factor and epidermal growth factor), neuroendocrine (e.g., cortisol and aldosterone), neuropeptide (i.e., substance P), and metabolic (e.g., leptin and acetyl-L-carnitine) biomarkers. Linear regression analyses evaluating the association between insomnia severity and biomarker levels were conducted with and without controlling for depression severity (M = 17.32), antidepressant use (18.9%), gender (59.0% female; 40.5% male), age (M = 42.04), and the cohort of origin. The results demonstrated no significant associations between insomnia severity and biomarker levels. In conclusion, for the included biomarkers, current findings reveal no contribution of insomnia to the clinical pathophysiology of MDD.
Beneficial Effects of Probiotic Bifidobacterium longum in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats
Authors: Zubareva Olga E. , Dyomina Alexandra V. , Kovalenko Anna A. , Roginskaya Anna I. , Melik-Kasumov Tigran B. , Korneeva Marina A. , Chuprina Alesya V. , Zhabinskaya Alesya A. , Kolyhan Stepan A. , Zakharova Maria V. , Gryaznova Marusya O. , Zaitsev Aleksey V.
Published: May 2023

Epilepsy is a challenging brain disorder that is often difficult to treat with conventional therapies. The gut microbiota has been shown to play an important role in the development of neuropsychiatric disorders, including epilepsy. In this study, the effects of Bifidobacterium longum, a probiotic, on inflammation, neuronal degeneration, and behavior are evaluated in a lithium–pilocarpine model of temporal lobe epilepsy (TLE) induced in young adult rats. B. longum was administered orally at a dose of 109 CFU/rat for 30 days after pilocarpine injection. The results show that B. longum treatment has beneficial effects on the TLE-induced changes in anxiety levels, neuronal death in the amygdala, and body weight recovery. In addition, B. longum increased the expression of anti-inflammatory and neuroprotective genes, such as Il1rn and Pparg. However, the probiotic had little effect on TLE-induced astrogliosis and microgliosis and did not reduce neuronal death in the hippocampus and temporal cortex. The study suggests that B. longum may have a beneficial effect on TLE and may provide valuable insights into the role of gut bacteria in epileptogenesis. In addition, the results show that B. longum may be a promising drug for the comprehensive treatment of epilepsy.
Inflammasome Coordinates Senescent Chronic Wound Induced by Thalassophryne nattereri Venom
Authors: Lima Carla , Andrade-Barros Aline Ingrid , Carvalho Fabiana Franco , Falcão Maria Alice Pimentel , Lopes-Ferreira Monica
Published: May 2023

Thalassophryne nattereri toadfish (niquim) envenomation, common in the hands and feet of bathers and fishermen in the north and northeast regions of Brazil, is characterized by local symptoms such as immediate edema and intense pain. These symptoms progress to necrosis that lasts for an extended period of time, with delayed healing. Wound healing is a complex process characterized by the interdependent role of keratinocytes, fibroblasts, and endothelial and innate cells such as neutrophils and macrophages. Macrophages and neutrophils are actively recruited to clear debris during the inflammatory phase of wound repair, promoting the production of pro-inflammatory mediators, and in the late stage, macrophages promote tissue repair. Our hypothesis is that injury caused by T. nattereri venom (VTn) leads to senescent wounds. In this study, we provide valuable information about the mechanism(s) behind the dysregulated inflammation in wound healing induced by VTn. We demonstrate in mouse paws injected with the venom the installation of γH2AX/p16Ink4a-dependent senescence with persistent neutrophilic inflammation in the proliferation and remodeling phases. VTn induced an imbalance of M1/M2 macrophages by maintaining a high number of TNF-α-producing M1 macrophages in the wound but without the ability to eliminate the persistent neutrophils. Chronic neutrophilic inflammation and senescence were mediated by cytokines such as IL-1α and IL-1β in a caspase-1- and caspase-11-dependent manner. In addition, previous blocking with anti-IL-1α and anti-IL-β neutralizing antibodies and caspase-1 (Ac YVAD-CMK) and caspase-11 (Wedelolactone) inhibitors was essential to control the pro-inflammatory activity of M1 macrophages induced by VTn injection, skewing towards an anti-inflammatory state, and was sufficient to block neutrophil recruitment and senescence.
Pathogenic Variants of SLC22A12 (URAT1) and SLC2A9 (GLUT9) in Spanish Patients with Renal Hypouricemia: Founder Effect of SLC2A9 Variant c.374C>T; p.(T125M)
Authors: Perdomo-Ramirez Ana , Cordoba-Lanus Elizabeth , Trujillo-Frias Carmen Jane , Gonzalez-Navasa Carolina , Ramos-Trujillo Elena , Luis-Yanes Maria Isabel , Garcia-Nieto Victor , Claverie-Martin Felix
Published: May 2023

Renal hypouricemia (RHUC) is a rare inherited disorder characterized by impaired urate reabsorption in the proximal tubule resulting in low urate serum levels and increased urate excretion. Some patients may present severe complications such as exercise-induced acute renal failure and nephrolithiasis. RHUC is caused by inactivating mutations in the SLC22A12 (RHUC type 1) or SLC2A9 (RHUC type 2) genes, which encode urate transporters URAT1 and GLUT9, respectively. In this study, our goal was to identify mutations associated with twenty-one new cases with RHUC through direct sequencing of SLC22A12 and SLC2A9 coding exons. Additionally, we carried out an SNPs-haplotype analysis to determine whether the rare SLC2A9 variant c.374C>T; p.(T125M), which is recurrent in Spanish families with RHUC type 2, had a common-linked haplotype. Six intragenic informative SNPs were analyzed using PCR amplification from genomic DNA and direct sequencing. Our results showed that ten patients carried the SLC22A12 mutation c.1400C>T; p.(T467M), ten presented the SLC2A9 mutation c.374C>T, and one carried a new SLC2A9 heterozygous mutation, c.593G>A; p.(R198H). Patients carrying the SLC2A9 mutation c.374C>T share a common-linked haplotype, confirming that it emerged due to a founder effect.
GABAA Receptor β3 Subunit Mutation N328D Heterozygous Knock-in Mice Have Lennox–Gastaut Syndrome
Authors: Nwosu Gerald Ikemefuna , Shen Wangzhen , Zavalin Kirill , Poliquin Sarah , Randhave Karishma , Flamm Carson , Biven Marshall , Langer Katherine , Kang Jing-Qiong
Published: May 2023

Lennox–Gastaut Syndrome (LGS) is a developmental and epileptic encephalopathy (DEE) characterized by multiple seizure types, electroencephalogram (EEG) patterns, and cognitive decline. Its etiology has a prominent genetic component, including variants in GABRB3 that encodes the GABAA receptor (GABAAR) β3 subunit. LGS has an unknown pathophysiology, and few animal models are available for studying LGS. The objective of this study was to evaluate Gabrb3+/N328D knock-in mice as a model for LGS. We generated a heterozygous knock-in mouse expressing Gabrb3 (c.A982G, p.N238D), a de novo mutation identified in a patient with LGS. We investigated Gabrb3+/N328D mice for features of LGS. In 2–4-month-old male and female C57BL/J6 wild-type and Gabrb3+/N328D mice, we investigated seizure severity using video-monitored EEG, cognitive impairment using a suite of behavioral tests, and profiled GABAAR subunit expression by Western blot. Gabrb3+/N328D mice showed spontaneous seizures and signs of cognitive impairment, including deficits in spatial learning, memory, and locomotion. Moreover, Gabrb3+/N328D mice showed reduced β3 subunit expression in the cerebellum, hippocampus, and thalamus. This phenotype of epilepsy and neurological impairment resembles the LGS patient phenotype. We conclude that Gabrb3+/N328D mice provide a good model for investigating the pathophysiology and therapeutic intervention of LGS and DEEs.
McCune–Albright Syndrome: A Case Report and Review of Literature
Authors: Nicolaides Nicolas C. , Kontou Maria , Vasilakis Ioannis-Anargyros , Binou Maria , Lykopoulou Evangelia , Kanaka-Gantenbein Christina
Published: May 2023

McCune–Albright syndrome (MAS) is a rare sporadic condition defined by the classic triad of fibrous dysplasia of bone, café au lait skin macules, and hyperfunctioning endocrinopathies. The molecular basis of MAS has been ascribed to the post-zygotic somatic gain-of-function mutations in the GNAS gene, which encodes the alpha subunit of G proteins, leading to constitutive activation of several G Protein-Coupled Receptors (GPCRs). The co-occurrence of two of the above-mentioned cardinal clinical manifestations sets the diagnosis at the clinical level. In this case report, we describe a 27-month-old girl who presented with gonadotropin-independent precocious puberty secondary to an estrogen-secreting ovarian cyst, a café au lait skin macule and growth hormone, and prolactin excess, and we provide an updated review of the scientific literature on the clinical features, diagnostic work-up, and therapeutic management of MAS.
The Biological and Molecular Action of Ozone and Its Derivatives: State-of-the-Art, Enhanced Scenarios, and Quality Insights
Authors: Travagli Valter , Iorio Eugenio Luigi
Published: May 2023

The ultimate objective of this review is to encourage a multi-disciplinary and integrated methodological approach that, starting from the recognition of some current uncertainties, helps to deepen the molecular bases of ozone treatment effects on human and animal well-being and to optimize their performance in terms of reproducibility of results, quality, and safety. In fact, the common therapeutic treatments are normally documented by healthcare professionals’ prescriptions. The same applies to medicinal gases (whose uses are based on their pharmacological effects) that are intended for patients for treatment, diagnostic, or preventive purposes and that have been produced and inspected in accordance with good manufacturing practices and pharmacopoeia monographs. On the contrary, it is the responsibility of healthcare professionals, who thoughtfully choose to use ozone as a medicinal product, to achieve the following objectives: (i) to understand the molecular basis of the mechanism of action; (ii) to adjust the treatment according to the clinical responses obtained in accordance with the principles of precision medicine and personalized therapy; (iii) to ensure all quality standards.
Corticosteroids in ARDS
Authors: Kuperminc Emmanuelle , Heming Nicholas , Carlos Miguel , Annane Djillali
Published: May 2023

Acute respiratory distress syndrome (ARDS) is frequently associated with sepsis. ARDS and sepsis exhibit a common pathobiology, namely excessive inflammation. Corticosteroids are powerful anti-inflammatory agents that are routinely used in septic shock and in oxygen-dependent SARS-CoV-2 related acute respiratory failure. Recently, corticosteroids were found to reduce mortality in severe community-acquired pneumonia. Corticosteroids may therefore also have a role to play in the treatment of ARDS. This narrative review was undertaken following a PubMed search for English language reports published before January 2023 using the terms acute respiratory distress syndrome, sepsis and steroids. Additional reports were identified by examining the reference lists of selected articles and based on personnel knowledge of the authors of the field. High-quality research is needed to fully understand the role of corticosteroids in the treatment of ARDS and to determine the optimal timing, dosing and duration of treatment.
Role of Lung Ultrasound in the Follow-Up of Children with Previous SARS-CoV-2 Infection: A Case-Control Assessment of Children with Long COVID or Fully Recovered
Authors: Buonsenso Danilo , Morello Rosa , Mariani Francesco , De Rose Cristina , Cortese Rossella , Vetrugno Luigi , Valentini Piero
Published: May 2023

Lung ultrasound (LUS) can detect lower respiratory tract involvement in children with acute SARS-CoV-2 infection. However, its role in follow-up assessments is still unclear. To describe LUS findings in children after SARS-CoV-2 infection, we conducted a prospective study in a population of pediatric patients referred to the post-COVID unit in a tertiary center during the study period from February 2021 to May 2022. Children were classified as recovered from acute infection or with persisting symptoms. LUS was performed in all children and a LUS score (ranging from 0 to 36 points) was calculated according to the Italian Academy of Thoracic Ultrasound. Six hundred forty-seven children (304 females, 47%) were enrolled. The median follow-up evaluation was two months. The median age was 7.9 (IQR: 6) years. At the follow-up evaluation, 251 patients (38.8%) had persistent symptoms, of whom 104 (16.1%) had at least one respiratory symptom. The median LUS level was 2 (IQR: 4). LUS findings and LUS scores did not differ in children with Long COVID compared to the group of children fully recovered from the initial infection. In conclusion, after SARS-CoV-2 infection, LUS was mostly normal or showed minimal artifacts in all groups of children.
The Gastropack Access System as a Model to Access Gastroenterology Services for Gastroscopy Appropriateness in Patients with Upper Gastrointestinal Symptoms: A Comparison with the Open Access System
Authors: Ceroni Liza , Lodato Francesca , Tubertini Paolo , Marasco Giovanni , Gazzola Alessia , Biselli Maurizio , Fabbri Cristiano , Buonfiglioli Federica , Ferrara Francesco , Schiumerini Ramona , Fabbri Andrea , Tassoni Alessandra , Descovich Carlo , Mondini Sandra , Tosetti Cesare , Veduti Valerio , De Negri Mario , Fini Alessandro , Guicciardi Stefano , Romanelli Massimo , Navarra Giuseppe Giovanni , Barbara Giovanni , Cennamo Vincenzo ,   on behalf of Gastropack System Study Group
Published: May 2023

Esophagogastroduodenoscopy (EGD) appropriateness in Open-Access System (OAS) is a relevant issue. The Gastropack Access System (GAS) is a new system to access gastroenterological services, based on the partnership between Gastroenterologists and GPs. This study aims to evaluate if GAS is superior to OAS in terms of EGDS appropriateness. Secondarily, we evaluated the diagnostic yield of EGDS according to ASGE guidelines. The GAS was developed in an area of Bologna where General Practitioners (GPs) could decide to directly prescribe EGDS through OAS or referring to GAS, where EGDS can be scheduled after contact between GPs and specialists sharing a patient’s clinical information. Between 2016 and 2019, 2179 cases (M:F = 861:1318, median age 61, IQR 47.72) were referred to GAS and 1467 patients (65%) had a prescription for EGDS; conversely, 874 EGDS were prescribed through OAS (M:F = 383:491; median age 58 yrs, IQR 45.68). Indication was appropriate in 92% in GAS (1312/1424) versus 71% in OAS (618/874), p < 0.001. The rate of clinically significant endoscopic findings (CSEF) was significantly higher in GAS (49% vs. 34.8%, p < 0.001). Adherence to ASGE guidelines was not related to CSEF; however, surveillance for pre-malignant conditions was independently related to CSEF. All neoplasm were observed in appropriate EGD. GAS is an innovative method showing extremely high rates of appropriateness. ASGE guidelines confirmed their validity for cancer detection, but their performance for the detection of other conditions needs to be refined.
Hospital Memories and Six-Month Psychological Outcome: A Prospective Study in Critical Ill Patients with COVID-19 Respiratory Failure
Authors: Pozzi Matteo , Ripa Claudio , Meroni Valeria , Ferlicca Daniela , Annoni Alice , Villa Marta , Strepparava Maria Grazia , Rezoagli Emanuele , Piva Simone , Lucchini Alberto , Bellani Giacomo , Foti Giuseppe ,   the Monza Follow-Up Study Group
Published: May 2023

ICU survivors suffer from various long-term physical and psychological impairments. Memories from the critical illness may influence long-term psychological outcome. In particular, the role of ICU memories in COVID-19 critically ill patients is unknown. In a prospective observational study, we aimed to investigate patients’ memories from the experience of critical illness and their association with a six-month psychological outcome involving quality of life evaluation. Patients’ memories were investigated with ICU Memory tool, while psychological outcome and quality of life were evaluated by means of a battery of validated questionnaires during an in-person interview at the follow-up clinic. 149 adult patients were enrolled. 60% retained memories from pre-ICU days spent on a general ward, while 70% reported memories from the in-ICU period. Delusional memories (i.e., memories of facts that never happened) were reported by 69% of patients. According to a multivariable analysis, the lack of pre-ICU memories was an independent predictor of worse psychological outcomes in terms of anxiety, depression and Post-traumatic Stress Disorder (PTDS). Factors associated with long-term outcome in ICU survivors are not still fully understood and patients’ experience during the day spent before ICU admission may be associated with psychological sequelae.
Treatment Modalities for Internet Addiction in Children and Adolescents: A Systematic Review of Randomized Controlled Trials (RCTs)
Authors: Ayub Shahana , Jain Lakshit , Parnia Shanli , Bachu Anil , Farhan Rabeea , Kumar Harendra , Sullivan Amanda , Ahmed Saeed
Published: May 2023

Background: In recent years, the use of the internet among children and adolescents has dramatically increased, leading to growing concerns regarding the potential risks of excessive internet use and addiction. Addressing these concerns, this systematic review aims to summarize current evidence on the effectiveness of treatment interventions for internet addiction among children and adolescents. Method: We performed a systematic review using PubMed, Web of Science, PsycInfo, and Google Scholar with search terms including “internet addiction”, “problematic internet use”, “children” or “adolescents”, “treatment” and “randomized controlled trial”. We found 10 Randomized Controlled Trials (RCTs) meeting the criteria and included them in this systematic review. Results: This systematic review analyzed 10 randomized controlled trials focused on treatment interventions for internet addiction in adolescents and young adults. The interventions used were diverse, including cognitive-behavioral therapy (CBT), medication, electro-acupuncture (EA), and solution-focused approaches. The measures used to assess the effectiveness of the interventions also varied, but most studies reported moderate to large effect sizes for at least some outcomes. Overall, the studies suggest that interventions such as CBT and EA can be effective in reducing symptoms of internet addiction, internet gaming disorder, and unspecified internet use disorders. School-based programs and brief manualized CBT programs also show promise, though more research is needed to determine their long-term effectiveness. Conclusion: Promising treatment approaches for internet addiction are emerging, but inconsistencies in conceptualization, language, and diagnostic criteria present some challenges. The growing recognition of problematic internet use, as shown by the DSM-5′s recognition of Internet Gaming Disorder, highlights the need for a multidisciplinary approach and standardized criteria to facilitate accurate reporting across studies. Continued research is needed to identify effective treatments and diagnostic criteria for internet addiction, with the potential to offer practical insights into effective medications and therapies.
Clinical Analysis of Repeat Penetrating Keratoplasty in Children
Authors: Sun Yajie , Lin Qi , Song Peng , Li Xu , Pan Zhiqiang
Published: May 2023

(1) Background: To analyze the indications, graft survival, and graft failure-related risk factors of repeat penetrating keratoplasty (RPK) in children. (2) Methods: In this case series, children younger than 12 years who received RPK at Beijing Tongren Hospital were reviewed. The indications for RPK, postoperative complications, and graft survival were analyzed. The analysis of the potential variables associated with graft survival was performed using Cox proportional hazards regression. (3) Results: A total of 30 RPK eyes of 29 children were included in this study. The mean follow-up time was 26.98 ± 18.75 months. The most common indication for RPK was a vascularized corneal scar (86.67%). Postoperative complications occurred in 27 eyes (90%), including immune rejection (46.67%), epithelial defects (36.67%), and glaucoma (26.67%). About 60% of the regrafts remained clear one year after RPK, while the overall graft survival rate was 30% at the last visit. The most common cause of regraft failure was irreversible immune rejection (8/21). The significant risks of graft failure included an age of less than 60 months at surgery (p = 0.009), corneal vascularization (p = 0.018), and a postoperative epithelial defect (p = 0.037). (4) Conclusions: A vascularized corneal scar is the most common indication of RPK in children. Immune rejection is the most prevalent complication, and irreversible immune rejection always causes regraft failure.
Treat-to-Target in Systemic Lupus Erythematosus: Reality or Pipe Dream
Authors: Zucchi Dina , Cardelli Chiara , Elefante Elena , Tani Chiara , Mosca Marta
Published: May 2023

Treat-to-target is a therapeutic approach based on adjustments to treatment at set intervals in order to achieve well-defined, clinically relevant targets. This approach has been successfully applied to many chronic conditions, and in rheumatology promising results have emerged for rheumatoid arthritis. For systemic lupus erythematosus (SLE), defining the most meaningful treatment targets has been challenging, due to disease complexity and heterogeneity. Control of disease activity, the reduction of damage accrual and the patient’s quality of life should be considered as the main targets in SLE, and several new drugs are emerging to achieve these targets. This review is focused on describing the target to achieve in SLE and the methods to do so, and it is also aimed at discussing if treat-to-target could be a promising approach also for this complex disease.
Extracorporeal Shockwave Therapy Improves Outcome after Primary Anterior Cruciate Ligament Reconstruction with Hamstring Tendons
Authors: Weninger Patrick , Thallinger Christoph , Chytilek Manuel , Hanel Yannis , Steffel Caterina , Karimi Ramin , Feichtinger Xaver
Published: May 2023

Purpose: The decision regarding the timepoint of a return to sports after anterior cruciate ligament (ACL) reconstruction is complex and depends on many factors, including objectively tested physical and psychological readiness as well as biological healing. The aim of this study was to investigate the influence of repetitive extracorporeal shockwave therapy (ESWT) on return-to-sports duration, clinical results and MRI results after ACL reconstruction with hamstring tendons (HT). Material and Methods: In this prospective controlled study, all patients with acute ACL ruptures were treated by ACL reconstruction with HT. Patients were randomized into two groups (Group A: ESWT group; Group B: control group). Patients in the ESWT group received focused shockwave therapy 4, 5 and 6 weeks after ACL surgery. Follow-up investigations including IKDC score, Lysholm score, VAS and evaluation regarding return-to-sports timepoints that were conducted 3-, 6-, 9- and 12-months post-operation. An MRI investigation was performed 12-months post-operation and graft maturation (signal intensity ratio (SIR)) as well as femoral and tibial tunnel characteristics (bone marrow oedema, tunnel fluid effusion) were assessed. Results: In total, 65 patients (27.65 ± 7.07 years; 35 male/30 female) were included in this study. The mean timepoint for “return-to-pivoting-sports” was 27.92 weeks (±2.99) in the ESWT group as well as 42.64 weeks (±5.18) in the control group (p < 0.001). In the ESWT group 31 patients (vs. control group: n = 6) attained the “pre-injury activity level”, whereas 6 patients (vs. control group: n = 22) did not reach this level within 12 months post-operation. The IKDC score, Lysholm score, and VAS showed significant improvement in the ESWT group compared with the control group for all time-points (p < 0.001). The mean SIR in the ESWT group revealed 1.81 (±0.88), whereas the control group showed a mean SIR of 2.68 (±1.04) (p < 0.01). Discussion: In conclusion, this is the first study investigating the effect of repetitive ESWT on ACL reconstruction with clinical outcome measurements, including the duration of return-to-sports activity and an MRI follow-up examination. Return-to-sports parameters, clinical scores and graft maturation were significantly improved in the ESWT group. This study may support an earlier return-to-sports timepoint by ESWT and is of high clinical relevance as ESWT is a cost-effective treatment option with no relevant side effects.
Association between Body Composition and the Risk of Portopulmonary Hypertension Assessed by Computed Tomography in Patients with Liver Cirrhosis
Authors: Miwa Takao , Hanai Tatsunori , Nishimura Kayoko , Tajirika Satoko , Nakahata Yuki , Imai Kenji , Suetsugu Atsushi , Takai Koji , Yamamoto Mayumi , Shimizu Masahito
Published: May 2023

The aim of this study is to investigate the impact of body composition on the risk of portopulmonary hypertension using computed tomography (CT) in patients with liver cirrhosis. We retrospectively included 148 patients with cirrhosis treated at our hospital between March 2012 and December 2020. POPH high-risk was defined as main pulmonary artery diameter (mPA-D) ≥ 29 mm or mPA-D to ascending aorta diameter ratio ≥ 1.0, based on chest CT. Body composition was assessed using CT images of the third lumbar vertebra. The factors associated with POPH high-risk were evaluated using logistic regression and decision tree analyses, respectively. Among the 148 patients, 50% were females, and 31% were found to be high-risk cases on evaluation of chest CT images. Patients with a body mass index (BMI) of ≥25 mg/m2 had a significantly higher prevalence of POPH high-risk than those with a BMI < 25 mg/m2 (47% vs. 25%, p = 0.019). After adjusting for confounding factors, BMI (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.10–1.33), subcutaneous adipose tissue index (OR, 1.02; 95% CI, 1.01–1.03), and visceral adipose tissue index (OR, 1.03; 95% CI, 1.01–1.04) were associated with POPH high-risk, respectively. In the decision tree analysis, the strongest classifier of POPH high-risk was BMI, followed by the skeletal muscle index. Body composition may affect the risk of POPH based on chest CT assessment in patients with cirrhosis. Since the present study lacked data on right heart catheterization, further studies are required to confirm the results of our study.
Overcoming the DDoS Attack Vulnerability of an ISO 19847 Shipboard Data Server
Authors: Lee Changui , Lee Seojeong
Published: May 2023

The maritime industry, which transports approximately 90% of the world’s goods, plays a crucial role in the global economy. However, increasing reliance on digital technologies has made the industry vulnerable to cybersecurity threats that may compromise the safety and security of maritime operations, thereby potentially affecting global supply chain integrity and public safety. This study examines the vulnerability of the ISO 19847:2018 standard shipboard data server to distributed denial-of-service (DDoS) attacks and proposes a method to mitigate this vulnerability. To this end, we propose modifications to the MQTT v5 protocol used by the shipboard data server, which provides streaming data-transfer services, and conduct verification experiments. These modifications allow the shipboard data server to control the frequency of messages published by the MQTT publisher, thereby preventing it from being overwhelmed by massive amounts of traffic in the event of a DDoS attack. Therefore, the proposed method can enhance the overall cybersecurity of the maritime sector by preventing the misuse of onboard MQTT publishers and reducing the impact of DDoS attacks.
Subassembly Partition of Hull Block Based on Two-Dimensional PSO Algorithm
Authors: Liu Bo , Li Rui , Wang Ji , Liu Yujun , Li Sheng
Published: May 2023

Subassembly partition is an important process in hull block building as it greatly affects the efficiency and quality of the assembly work. Recently, an experience-based method has been widely applied to the subassembly partition process, which consumes much design time and manpower, thus causing more challenges toward a more highly automated and efficient stage in this process. To shorten the gap, an automated subassembly partition method is presented in this study. First, the assembly information model is defined with essential attributes and topological relations of the parts. Second, an optimization model is established with consideration of a trade-off between the intra-cluster cohesion and cluster number on the premise of satisfying certain constraints. After that, considering the fuzziness and diversity of the subassembly partition problem, a two-dimensional coding discrete particle swarm optimization (PSO) algorithm is developed. Finally, two blocks are demonstrated as instances to verify the proposed method, and the results show that the proposed method is feasible and applicable to the block with a flat structure.
Lung and Gut Microbiome in COPD
Authors: Karakasidis Efstathios , Kotsiou Ourania S. , Gourgoulianis Konstantinos I.
Published: May 2023

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. The association between lung and gut microbiomes in the pathogenesis of COPD has been recently uncovered. The goal of this study was to discuss the role of the lung and gut microbiomes in COPD pathophysiology. A systematic search of the PubMed database for relevant articles submitted up to June 2022 was performed. We examined the association between the lung and gut microbiome dysbiosis, reflected in bronchoalveolar lavage (BAL), lung tissue, sputum, and feces samples, and the pathogenesis and progression of COPD. It is evident that the lung and gut microbiomes affect each other and both play a vital role in the pathogenesis of COPD. However, more research needs to be carried out to find the exact associations between microbiome diversity and COPD pathophysiology and exacerbation genesis. Another field that research should focus on is the impact of treatment interventions targeting the human microbiome in preventing COPD genesis and progression.