bluuebunny/crossref_metadata_2025 huggingface dataset:
Programmed Death Ligand 1 Regulatory Crosstalk with Ubiquitination and Deubiquitination: Implications in Cancer Immunotherapy
Authors: Kim Soon-Bin , Hwang Soonjae , Cha Ji-Young , Lee Ho-Jae
Published: March 2024

Programmed death ligand 1 (PD-L1) plays a pivotal role in cancer immune evasion and is a critical target for cancer immunotherapy. This review focuses on the regulation of PD-L1 through the dynamic processes of ubiquitination and deubiquitination, which are crucial for its stability and function. Here, we explored the intricate mechanisms involving various E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) that modulate PD-L1 expression in cancer cells. Specific ligases are discussed in detail, highlighting their roles in tagging PD-L1 for degradation. Furthermore, we discuss the actions of DUBs that stabilize PD-L1 by removing ubiquitin chains. The interplay of these enzymes not only dictates PD-L1 levels but also influences cancer progression and patient response to immunotherapies. Furthermore, we discuss the therapeutic implications of targeting these regulatory pathways and propose novel strategies to enhance the efficacy of PD-L1/PD-1-based therapies. Our review underscores the complexity of PD-L1 regulation and its significant impact on the tumor microenvironment and immunotherapy outcomes.
Update on Antioxidant Therapy with Edaravone: Expanding Applications in Neurodegenerative Diseases
Authors: Yamashita Toru , Abe Koji
Published: March 2024

The brain is susceptible to oxidative stress, which is associated with various neurological diseases. Edaravone (MCI-186, 3-methyl-1 pheny-2-pyrazolin-5-one), a free radical scavenger, has promising effects by quenching hydroxyl radicals (∙OH) and inhibiting both ∙OH-dependent and ∙OH-independent lipid peroxidation. Edaravone was initially developed in Japan as a neuroprotective agent for acute cerebral infarction and was later applied clinically to treat amyotrophic lateral sclerosis (ALS), a neurodegenerative disease. There is accumulating evidence for the therapeutic effects of edaravone in a wide range of diseases related to oxidative stress, including ischemic stroke, ALS, Alzheimer’s disease, and placental ischemia. These neuroprotective effects have expanded the potential applications of edaravone. Data from experimental animal models support its safety for long-term use, implying broader applications in various neurodegenerative diseases. In this review, we explain the unique characteristics of edaravone, summarize recent findings for specific diseases, and discuss its prospects for future therapeutic applications.
Neutrophils and NADPH Oxidases Are Major Contributors to Mild but Not Severe Ischemic Acute Kidney Injury in Mice
Authors: Révész Csaba , Kaucsár Tamás , Godó Mária , Bocskai Krisztián , Krenács Tibor , Mócsai Attila , Szénási Gábor , Hamar Péter
Published: March 2024

Upregulation of free radical-generating NADPH oxidases (NOX), xanthine oxidoreductase (XOR), and neutrophil infiltration-induced, NOX2-mediated respiratory burst contribute to renal ischemia–reperfusion injury (IRI), but their roles may depend on the severity of IRI. We investigated the role of NOX, XOR, and neutrophils in developing IRI of various severities. C57BL/6 and Mcl-1ΔMyelo neutrophil-deficient mice were used. Oxidases were silenced by RNA interference (RNAi) or pharmacologically inhibited. Kidney function, morphology, immunohistochemistry and mRNA expression were assessed. After reperfusion, the expression of NOX enzymes and XOR increased until 6 h and from 15 h, respectively, while neutrophil infiltration was prominent from 3 h. NOX4 and XOR silencing or pharmacological XOR inhibition did not protect the kidney from IRI. Attenuation of NOX enzyme-induced oxidative stress by apocynin and neutrophil deficiency improved kidney function and ameliorated morphological damage after mild but not moderate/severe IRI. The IR-induced postischemic renal functional impairment (BUN, Lcn-2), tubular necrosis score, inflammation (TNF-α, F4/80), and decreases in the antioxidant enzyme (GPx3) mRNA expression were attenuated by both apocynin and neutrophil deficiency. Inhibition of NOX enzyme-induced oxidative stress or the lack of infiltration by NOX2-expressing neutrophils can attenuate reperfusion injury after mild but not moderate/severe renal IR.
Verification of Key Target Molecules for Intramuscular Fat Deposition and Screening of SNP Sites in Sheep from Small-Tail Han Sheep Breed and Its Cross with Suffolk
Authors: Fu Lingjuan , Shi Jinping , Meng Quanlu , Tang Zhixiong , Liu Ting , Zhang Quanwei , Cheng Shuru
Published: March 2024

Intramuscular fat (IMF) is vital for meat tenderness and juiciness. This study aims to explore the IMF deposition mechanism and the related molecular markers in sheep. Two populations, Small-tail Han Sheep (STH) and STH × Suffolk (SFK) F1 (SFK × STH), were used as the research object. Histological staining techniques compared the differences in the longissimus dorsi muscle among populations. A combination of transcriptome sequencing and biological information analysis screened and identified IMF-related target genes. Further, sequencing technology was employed to detect SNP loci of target genes to evaluate their potential as genetic markers. Histological staining revealed that the muscle fiber gap in the SFK × STH F1 was larger and the IMF content was higher. Transcriptome analysis revealed that PIK3R1 and PPARA were candidate genes. Histological experiments revealed that the expressions of PIK3R1 mRNA and PPARA mRNA were lower in SFK × STH F1 compared with the STH. Meanwhile, PIK3R1 and PPARA proteins were located in intramuscular adipocytes and co-located with the lipid metabolism marker molecule (FASN). SNP locus analysis revealed a mutation site in exon 7 of the PIK3R1 gene, which served as a potential genetic marker for IMF deposition. This study’s findings will provide a new direction for meat quality breeding in sheep.
Hypolipidemic Effect of Rice Bran Oil Extract Tocotrienol in High-Fat Diet-Induced Hyperlipidemia Zebrafish (Danio Rerio) Induced by High-Fat Diet
Authors: Liu Naicheng , Zhang Peng , Xue Mingyang , Zhang Mengwei , Huang Zhenyu , Xu Chen , Meng Yan , Fan Yuding , Liu Wei , Zhang Feixiang , Chen Peng , Zhou Yong
Published: March 2024

In recent years, the potent influence of tocotrienol (T3) on diminishing blood glucose and lipid concentrations in both Mus musculus (rats) and Homo sapiens (humans) has been established. However, the comprehensive exploration of tocotrienol’s hypolipidemic impact and the corresponding mechanisms in aquatic species remains inadequate. In this study, we established a zebrafish model of a type 2 diabetes mellitus (T2DM) model through high-fat diet administration to zebrafish. In the T2DM zebrafish, the thickness of ocular vascular walls significantly increased compared to the control group, which was mitigated after treatment with T3. Additionally, our findings demonstrate the regulatory effect of T3 on lipid metabolism, leading to the reduced synthesis and storage of adipose tissue in zebrafish. We validated the expression patterns of genes relevant to these processes using RT-qPCR. In the T2DM model, there was an almost two-fold upregulation in pparγ and cyp7a1 mRNA levels, coupled with a significant downregulation in cpt1a mRNA (p < 0.01) compared to the control group. The ELISA revealed that the protein expression levels of Pparγ and Rxrα exhibited a two-fold elevation in the T2DM group relative to the control. In the T3-treated group, Pparγ and Rxrα protein expression levels consistently exhibited a two-fold decrease compared to the model group. Lipid metabolomics showed that T3 could affect the metabolic pathways of zebrafish lipid regulation, including lipid synthesis and decomposition. We provided experimental evidence that T3 could mitigate lipid accumulation in our zebrafish T2DM model. Elucidating the lipid-lowering effects of T3 could help to minimize the detrimental impacts of overfeeding in aquaculture.
Pulmonary Adenocarcinoma In Situ and Minimally Invasive Adenocarcinomas in European Patients Have Less KRAS and More EGFR Mutations Compared to Advanced Adenocarcinomas
Authors: Petterson Jennie , Mustafa Dyar , Bandaru Sashidar , Eklund Ella Äng , Hallqvist Andreas , Sayin Volkan I. , Gagné Andréanne , Fagman Henrik , Akyürek Levent M.
Published: March 2024

Pulmonary adenocarcinoma (ADC) is a very diverse disease, both genetically and histologically, which displays extensive intratumor heterogeneity with numerous acquired mutations. ADC is the most common type of lung cancer and is believed to arise from adenocarcinoma in situ (AIS) which then progresses to minimally invasive adenocarcinoma (MIA). In patients of European ethnicity, we analyzed genetic mutations in AIS (n = 10) and MIA (n = 18) and compared the number of genetic mutations with advanced ADC (n = 2419). Using next-generation sequencing, the number of different mutations detected in both AIS (87.5%) and MIA (94.5%) were higher (p < 0.001) than in advanced ADC (53.7%). In contrast to the high number of mutations in Kirsten rat sarcoma virus gene (KRAS) in advanced ADC (34.6%), there was only one case of AIS with KRAS G12C mutation (3.5%; p < 0.001) and no cases of MIA with KRAS mutation (p < 0.001). In contrast to the modest prevalence of epidermal growth factor receptor (EGFR) mutations in advanced ADC (15.0%), the fraction of EGFR mutant cases was higher in both in AIS (22.2%) and MIA (59.5%; p < 0.001). The EGFR exon 19 deletion mutation was more common in both MIA (50%; n = 6/12) and ADC (41%; n = 149/363), whereas p.L858R was more prevalent in AIS (75%; n = 3/4). In contrast to pulmonary advanced ADC, KRAS driver mutations are less common, whereas mutations in EGFR are more common, in detectable AIS and MIA.
Mass Spectrometric Proteomics 2.0
Authors: Iadarola Paolo , Viglio Simona
Published: March 2024

This Special Issue, “Mass Spectrometric Proteomics 2 [...]
Challenges in the Therapeutic Targeting of KCa Channels: From Basic Physiology to Clinical Applications
Authors: Van Nhung Thi Hong , Kim Woo Kyung , Nam Joo Hyun
Published: March 2024

Calcium-activated potassium (KCa) channels are ubiquitously expressed throughout the body and are able to regulate membrane potential and intracellular calcium concentrations, thereby playing key roles in cellular physiology and signal transmission. Consequently, it is unsurprising that KCa channels have been implicated in various diseases, making them potential targets for pharmaceutical interventions. Over the past two decades, numerous studies have been conducted to develop KCa channel-targeting drugs, including those for disorders of the central and peripheral nervous, cardiovascular, and urinary systems and for cancer. In this review, we synthesize recent findings regarding the structure and activating mechanisms of KCa channels. We also discuss the role of KCa channel modulators in therapeutic medicine. Finally, we identify the major reasons behind the delay in bringing these modulators to the pharmaceutical market and propose new strategies to promote their application.
Photodynamic Therapy and Cardiovascular Diseases
Authors: Oskroba Aleksander , Bartusik-Aebisher Dorota , Myśliwiec Angelika , Dynarowicz Klaudia , Cieślar Grzegorz , Kawczyk-Krupka Aleksandra , Aebisher David
Published: March 2024

Cardiovascular diseases are the third most common cause of death in the world. The most common are heart attacks and stroke. Cardiovascular diseases are a global problem monitored by many centers, including the World Health Organization (WHO). Atherosclerosis is one aspect that significantly influences the development and management of cardiovascular diseases. Photodynamic therapy (PDT) is one of the therapeutic methods used for various types of inflammatory, cancerous and non-cancer diseases. Currently, it is not practiced very often in the field of cardiology. It is most often practiced and tested experimentally under in vitro experimental conditions. In clinical practice, the use of PDT is still rare. The aim of this review was to characterize the effectiveness of PDT in the treatment of cardiovascular diseases. Additionally, the most frequently used photosensitizers in cardiology are summarized.
The Role of Circular RNA for Early Diagnosis and Improved Management of Patients with Cardiovascular Diseases
Authors: Goina Claudia Alexandrina , Goina Daniela Marcela , Farcas Simona Sorina , Andreescu Nicoleta Ioana
Published: March 2024

Cardiovascular diseases (CVDs) are responsible for approximately 17.9 million deaths every year. There is growing evidence that circular RNAs (circRNAs) may play a significant role in the early diagnosis and treatment of cardiovascular diseases. As regulatory molecules, circular RNAs regulate gene expression, interact with proteins and miRNAs, and are translated into proteins that play a key role in a wide variety of biological processes, including the division and proliferation of cells, as well as the growth and development of individuals. An overview of the properties, expression profiles, classification, and functions of circRNAs is presented here, along with an explanation of their implications in cardiovascular diseases including heart failure, hypertension, ischemia/reperfusion injury, myocardial infarction, cardiomyopathies, atherosclerosis, and arrhythmia.
A Serological Multiplexed Immunoassay (MIA) Detects Antibody Reactivity to SARS-CoV-2 and Other Viral Pathogens in Liberia and Is Configurable as a Multiplexed Inhibition Test (MINT)
Authors: Haun Brien K. , To Albert , Williams Caitlin A. , Ball Aquena , Fong Karalyn , Wong Teri Ann S. , Shobayo Bode , Teahton Julius , Ching Lauren , Kamara Varney , Tekah Davidetta M. , Humphrey Peter , Berestecky John , Nerurkar Vivek R. , Lehrer Axel T.
Published: March 2024

The SARS-CoV-2 pandemic ignited global efforts to rapidly develop testing, therapeutics, and vaccines. However, the rewards of these efforts were slow to reach many low- to middle-income countries (LMIC) across the African continent and globally. Therefore, two bead-based multiplexed serological assays were developed to determine SARS-CoV-2 exposure across four counties in Liberia. This study was conducted during the summer of 2021 on 189 samples collected throughout Grand Bassa, Bong, Margibi, and Montserrado counties. Our multiplexed immunoassay (MIA) detected elevated exposure to SARS-CoV-2 and multiple variant antigens. Additionally, we detected evidence of exposure to Dengue virus serotype 2, Chikungunya virus, and the seasonal coronavirus NL63. Our multiplexed inhibition test (MINT) was developed from the MIA to observe antibody-mediated inhibition of SARS-CoV-2 spike protein binding to its cognate cellular receptor ACE-2. We detected inhibitory antibodies in the tested Liberian samples, which were collectively consistent with a convalescent serological profile. These complementary assays serve to supplement existing serological testing needs and may enhance the technical capacity of scientifically underrepresented regions globally.
Numerical Analysis of a High-Velocity Projectile’s Impact on Shallow Steel Tunnels in Soft Sandstone
Authors: Sarmah Rupali , Dutta Troyee Tanu , Rao K. Seshagiri
Published: March 2024

Tunnels are underground infrastructures intended for diverse community applications as well as military applications. During impact loading due to high-velocity projectiles such as ballistic missiles, materials experience a high strain rate. Moreover, there is a superficial augmentation of the dynamic strength when geomaterials such as rock are subjected to a high strain rate. Despite this strength enhancement, tunnels can get damaged by the impact load of a projectile hitting at a high velocity if they are present at a shallow depth. The present study is an effort to comprehend the response of a shallow tunnel in soft sandstone due to the impact load by a ballistic projectile using the FEM-based software ABAQUS/CAE 6.11. The Drucker–Prager damage model and the Johnson–Cook damage model were used to define the properties of the rock mass and steel tunnel lining, respectively. The crown of the 3 m diameter tunnel was kept at different depths from 1 m to 5 m from the surface. A striking velocity of 1000 m/s at a normal position to the target was given to the projectile. The projectile caused noticeable damage to the tunnel lining up to 3 m crown depth. Increasing the crown depth had a positive effect on the maximum depth of the projectile penetration up to 4 m tunnel crown depth, after which the effect reversed, making the tunnel safer. The maximum von Mises stress on the tunnel lining reduced in a logarithmic trend with an increase in the crown depth, gradually lowering to an impact load lesser than the yield stress of the tunnel lining material after a crown depth of 4.5 m.
Non-Covalent Interactions in Coordination Chemistry
Authors: Kubasov Alexey S. , Avdeeva Varvara V.
Published: March 2024

Non-covalent interactions [...]
Spotted Fever Group Rickettsia spp. Molecular and Serological Evidence among Colombian Vectors and Animal Hosts: A Historical Review
Authors: Gual-Gonzalez Lídia , Torres Myriam E. , Self Stella C. W. , Cantillo-Barraza Omar , Nolan Melissa S.
Published: March 2024

Spotted fever group Rickettsia spp. (SFGR) are a large group of tick-borne bacteria causing important emerging and re-emerging diseases that affect animals and humans. While SFGR are found worldwide, a lack of surveillance and misdiagnosis particularly affect South American countries. Colombia is a high burdened country in South America, yet rickettsioses are not deemed a nationally reportable condition limiting disease-specific public health resources. As mortality rates are high for one Rickettsia pathogen species, there is a great need to better understand the epidemiological and ecological factors that increase SFGR transmission risk regionally. This literature review provides an overview of Colombia-based SFGR studies connecting knowledge about both vectors and hosts.
Intergenerational Effects of Sublethal Lambda-Cyhalothrin Exposure on Aphis gossypii Glover (Hemiptera: Aphididae) Reproduction and Development
Authors: Qiu Yuepeng , Chen Zhaorong
Published: March 2024

Aphis gossypii Glover, a widespread insect, presents a substantial danger to global agriculture. Lambda-cyhalothrin is a pyrethroid insecticide that has been widely studied for its effects on arthropods. Studies have reported that sublethal doses of insecticides can produce various consequences on arthropod reproduction. Hence, the objective of this research was to examine the potential effects of a sublethal dose of lambda-cyhalothrin (LC30, 1.15 mg/L) on A. gossypii, for which we created life tables and conducted qPCR analysis. Adult longevity, fecundity, net reproductive rate (R0), body length, width, weight, and the expression of vitellogenin (Vg) and vitellogenin receptor (VgR) genes were not significantly altered by lambda-cyhalothrin treatment at LC30 concentration in the F0 generation of A. gossypii adults. The intrinsic rate of increase (r) and finite rates of increase (λ) decreased significantly, while the mean generation time (T) increased. In addition, Vg and VgR gene expression levels were significantly higher in the F1 and F2 generations, whereas body length, width, and weight were notably reduced. The developmental duration, longevity, r, and λ did not differ significantly from those of the control group. Thus, the sublethal and intergenerational stimulatory effects of lambda-cyhalothrin were observed in A. gossypii, and the alterations in Vg and VgR in A. gossypii were strongly associated with sublethal effects. The results of this research offer valuable knowledge regarding the indirect impacts of lambda-cyhalothrin on A. gossypii, which can be utilized as a theoretical foundation for the prudent utilization of insecticides to combat this pest and devise strategies for managing resistance.
Scattering Polarimetry in the Hard X-ray Range
Authors: Costa Enrico
Published: March 2024

In one and a half years, the Imaging X-ray Polarimetry Explorer has demonstrated the role and the potentiality of Polarimetry in X-ray Astronomy. The next steps include extension to higher energies. There is margin for an extension of the photoelectric approach up to 20–25 keV, but above that energy the only technique is Compton Scattering. Grazing incidence optics can focus photons up to 80 keV, not excluding a marginal extension to 150–200 keV. Given the physical constraints involved, the passage from photoelectric to scattering approach can make less effective the use of optics because of the high background. I discuss the choices in terms of detector design to mitigate the problem and the guidelines for future technological developments.
Effectiveness of Topical Oxygen Therapy in Gingivitis and Periodontitis: Clinical Case Reports and Review of the Literature
Authors: Basudan Amani M. , Abas Irfan , Shaheen Marwa Y. , Alghamdi Hamdan S.
Published: March 2024

Gingivitis and periodontitis are common oral pathological conditions. Several optional adjunctive local therapies are used clinically. While antibiotics and chlorhexidine are the most common agents of choice, their long-term use is associated with several adverse effects. Some of these include staining of teeth and restorations, cellular cytotoxicity and hypersensitivity. Topical oxygen therapy has been recently introduced and could be clinically capable of inhibiting plaque bacterial biofilm growth. Available as a mouthwash, toothpaste and oral gel, this formulation comprises cellulose, glycerol and sodium peroxoborate, and releases topical oxygen in a controlled manner. Moreover, it releases topical oxygen, in a controlled manner, and lactoferrin, which are capable of antibacterial action and stimulation of bone cells, respectively. The aim of this paper is to report a case of gingivitis and another case of periodontitis, both of which were successfully treated clinically with adjunctive local oxygen therapy (blue®m). Additionally, this paper aims to review the relevant literature in terms of adjunct topical or local therapies used in the treatment of gingivitis and periodontitis, in order to understand how local therapies are helpful and to know if local oxygen therapy is a suitable clinical alternative.
Monopolar Transurethral Enucleoresection of Prostate: Feasibility of Modified Nesbit’s Enucleoresection with Apical Release
Authors: Kumar Nitesh , Somani Bhaskar
Published: March 2024

Background: Transurethral resection of the prostate (TURP) has been the standard surgical treatment for Benign Hyperplasia of the Prostate (BPH) for decades. Our objective was to evaluate the outcome of our new technique: Monopolar Transurethral Enucleoresection of the Prostate (TUERP) with apical release (bring it all to centre). Methods: A prospective study of all cases undergoing TUERP at a tertiary centre from January 2020 to October 2022 was performed. Patient demographics, intraoperative variables and postoperative results along with follow-up data were collected. Data of all the cases who had completed a one-year follow-up post-surgery were included and analysed. Results: A total of 240 patients with complete data including a one-year follow-up were included. Mean prostatic volume was 55.3 ± 11.6 gm, and 28 (11.67%) cases were >100 gm. The mean operative time was 31.7 ± 7.6, and mean haemoglobin drop at 24 h was 0.73 ± 1.21 gm/dL. The overall complication rate was 16.67%, with only two (0.83%) Clavien–Dindo III complications (haematuria and clots needing evacuation) and the other complications being Clavien–Dindo I/II complications. Sustained improvement at 1 year of follow-up was noted: Qmax: 25.2 ± 5.6 mL/s, IPSS: 4.7 ± 2.5 and PVR: 22.5 ± 9.6 mL. Conclusions: Monopolar TUERP with a modified Nesbit’s enucleoresection with apical release can be considered a promising technique, which needs further studies to be validated with appropriate comparisons.
The Impact of Interaction between Body Posture and Movement Pattern Quality on Injuries in Amateur Athletes
Authors: Koźlenia Dawid , Kochan-Jacheć Katarzyna
Published: March 2024

Background: this study aimed to examine the impact of interaction between body posture and the quality of movement patterns on injury frequencies in amateur athletes. Methods: The study sample consisted of 89 young amateur athletes. Movement pattern quality was assessed by the Functional Movement Screen (FMS), test and body posture in the frontal plane was assessed by the moire method for the parameters Shoulder Slope Angle, Lower Scapula Protrusion Difference, and Pelvic Tilt Angle. Injury data were collected through completion of the Injury History Questionnaire for the past 12 months. Results: Using cluster analysis, participants were allocated into a either category with good (BPg) body posture or poor (BPp), and using FMS cutoff points (14), either a category of good movement pattern quality (MPg) or poor (MPp). Two-way ANOVA was performed, and the Bonferroni post-hoc test revealed a reduction in injuries among participants from the MPg-BPg group compared to the other three groups (p < 0.05). However, no interaction between factors was revealed. No statistically significant differences were observed among the remaining three groups in the case of injury prevalence (p > 0.05). Conclusions: A combination of proper body posture and high-quality movement patterns is associated with a lower frequency of injuries, without direct interaction between chosen factors, which suggests that they impact injury risk independently. Practicing suitable BP and ensuring high-quality MPs should be regarded as a strategy in injury prevention.
Co-Morbidity Clusters in Post-COVID-19 Syndrome
Authors: Sárközi Anna Teréz , Tornyi Ilona , Békési Erik , Horváth Ildikó
Published: March 2024

Background: Post-COVID-19 syndrome, characterized by persistent symptoms emerging more than 12 weeks after acute infection, displays diverse manifestations. This study aimed to analyze co-existing organ dysfunctions in post-COVID-19 patients and explore their potential association with the acute COVID-19 episode and functional impairment. Methods: Data from 238 patients attending post-COVID-19 outpatient care between 1 March 2021 and 1 March 2022, after previous hospitalization for acute COVID-19, were retrospectively analyzed with 80 having comprehensive mapping of organ involvement. Results: The average time between acute episode and post-COVID-19 care was 149 days. Spirometry indicated significant abnormalities in lung function. Predominant symptoms included respiratory (75%), fatigue (73%), neurological (62.5%), and ear-nose-throat issues (51.25%). Multiorgan dysfunctions were observed in 87.5% of patients, contributing to an 18.33% reduction in health quality compared to pre-acute COVID-19 levels. Subgroup analysis identified four distinct post-COVID-19 syndrome subgroups, highlighting the coexistence of respiratory and neurological disorders as potential indicators and drivers of further organ involvement. Our results reveal that most patients with post-COVID-19 syndrome suffer from multiorgan disorders. Conclusions: The presence of coexisting respiratory and neurological symptoms suggests the involvement of other organ systems as well. The complexity of multiorgan involvement requires further studies to provide insights into the different symptom clusters and identify potential targets for personalized preventive and therapeutic interventions to improve patient outcome.
Changes in Endometriosis-Associated Symptoms Following Immunization against SARS-CoV-2: A Cross-Sectional Study
Authors: Lukac Stefan , Friedl Thomas W. P. , Gruber Tobias , Schmid Marinus , Leinert Elena , Janni Wolfgang , Hancke Katharina , Dayan Davut
Published: March 2024

Background: There are many reports about variations in the menstrual cycle after infection with SARS-CoV-2 or vaccination against it. However, data on SARS-CoV-2 infection or vaccination-related changes in menstruation-associated endometriosis-typical symptoms such as dysmenorrhea, dyspareunia, dyschezia, dysuria, and bloating are rare or missing. Methods: This retrospective study was performed as an online survey among employees and students at the University Hospital Ulm, Germany. Changes regarding the presence of mentioned symptoms and after immunization (vaccination and/or infection) were evaluated with the McNemar Test. Additionally, the risk factors associated with these changes and associations between a subjectively perceived general change in menstruation and changes in the symptoms were evaluated. Results: A total of 1589 respondents were included in the final analysis. Less than 4% of respondents reported the occurrence of new symptoms that they had not experienced before immunization. Overall, there was a significant reduction in the presence of dysmenorrhea, back pain, dyschezia, bloating, and dyspareunia after immunization against coronavirus (p < 0.001). Only 2.3% of all participants reported to have been diagnosed with endometriosis. Factors associated with changes in endometriosis-typical symptoms following immunization were body mass index, age, endometriosis, and thyroid disease. Conclusions: Our results provide unique data about a reduction in the incidence of endometriosis-associated symptoms as dysmenorrhea, dyschezia, and dyspareunia after immunization against COVID-19.
Effect of Denosumab on Bone Health, Vascular Calcification, and Health-Related Quality of Life in Hemodialysis Patients with Osteoporosis: A Prospective Observational Study
Authors: Kim Hyunsook , Lee Eun Ju , Woo Siyun , Rho Sohee , Jung Ji Yong
Published: March 2024

Background: Osteoporosis is common in hemodialysis (HD) patients, contributing to cardiovascular risks. Limited research exists on denosumab’s efficacy in this group. Our study explores denosumab’s effects on bone turnover markers (BTMs) and vascular calcification in chronic kidney disease–mineral bone disorder (CKD-MBD) patients. Methods: In a prospective single-center study, we investigated the effects of denosumab over 2 years on 30 HD patients from a cohort of 185. Annual assessments of bone mineral density (BMD), vascular calcification, and health-related quality of life (HRQL) were conducted and compared with an untreated group. Mineral and bone parameters were analyzed at specific intervals in the treatment group. Results: Denosumab notably raised femoral BMD in the initial year. Most bone turnover markers (BTMs) decreased, except for osteocalcin. Changes in T50 correlated with BTMs. Pre-denosumab supplementation of calcium and vitamin D helped manage mineral imbalances. Post denosumab, parathyroid hormone (PTH) levels increased initially, stabilizing after 3 months. No significant changes occurred in vascular calcification or HRQL. Conclusions: Denosumab exhibited varying effects on BMD improvement, with a stronger impact in the first year that diminished in the second year. Early PTH monitoring was crucial, and extending the administrative period may enhance BMD outcomes compared to the general population.
Hepatomegaly and Splenomegaly: An Approach to the Diagnosis of Lysosomal Storage Diseases
Authors: Jerves Serrano Teodoro , Gold Jessica , Cooper James A. , Church Heather J. , Tylee Karen L. , Wu Hoi Yee , Kim Sun Young , Stepien Karolina M.
Published: March 2024

Clinical findings of hepatomegaly and splenomegaly, the abnormal enlargement of the liver and spleen, respectively, should prompt a broad differential diagnosis that includes metabolic, congestive, neoplastic, infectious, toxic, and inflammatory conditions. Among the metabolic diseases, lysosomal storage diseases (LSDs) are a group of rare and ultrarare conditions with a collective incidence of 1 in 5000 live births. LSDs are caused by genetic variants affecting the lysosomal enzymes, transporters, or integral membrane proteins. As a result, abnormal metabolites accumulate in the organelle, leading to dysfunction. Therapeutic advances, including early diagnosis and disease-targeted management, have improved the life expectancy and quality of life of people affected by certain LSDs. To access these new interventions, LSDs must be considered in patients presenting with hepatomegaly and splenomegaly throughout the lifespan. This review article navigates the diagnostic approach for individuals with hepatosplenomegaly particularly focusing on LSDs. We provide hints in the history, physical exam, laboratories, and imaging that may identify LSDs. Additionally, we discuss molecular testing, arguably the preferred confirmatory test (over biopsy), accompanied by enzymatic testing when feasible.
Comparing Charlson Comorbidity Index Scores between Anesthesiologists, Patients, and Administrative Data: A Prospective Observational Study
Authors: Röhrig Eike J. , Schenkat Henning , Hochhausen Nadine , Röhl Anna B. , Derwall Matthias , Rossaint Rolf , Kork Felix
Published: March 2024

(1) Background: Patients’ comorbidities play an immanent role in perioperative risk assessment. It is unknown how Charlson Comorbidity Indices (CCIs) from different sources compare. (2) Methods: In this prospective observational study, we compared the CCIs of patients derived from patients’ self-reports and from physicians’ assessments with hospital administrative data. (3) Results: The data of 1007 patients was analyzed. Agreement between the CCI from patients’ self-report compared to administrative data was fair (kappa 0.24 [95%CI 0.2–0.28]). Agreement between physicians’ assessment and the administrative data was also fair (kappa 0.28 [95%CI 0.25–0.31]). Physicians’ assessment and patients’ self-report had the best agreement (kappa 0.33 [95%CI 0.30–0.37]). The CCI calculated from the administrative data showed the best predictability for in-hospital mortality (AUROC 0.86 [95%CI 0.68–0.91]), followed by equally good prediction from physicians’ assessment (AUROC 0.80 [95%CI 0.65–0.94]) and patients’ self-report (AUROC 0.80 [95%CI 0.75–0.97]). (4) Conclusions: CCIs derived from patients’ self-report, physicians’ assessments, and administrative data perform equally well in predicting postoperative in-hospital mortality.
A Non-Coronary, Peripheral Arterial Atherosclerotic Disease (Carotid, Renal, Lower Limb) in Elderly Patients—A Review: Part I—Epidemiology, Risk Factors, and Atherosclerosis-Related Diversities in Elderly Patients
Authors: Piechocki Marcin , Przewłocki Tadeusz , Pieniążek Piotr , Trystuła Mariusz , Podolec Jakub , Kabłak-Ziembicka Anna
Published: March 2024

Atherosclerosis is a generalized and progressive disease. Ageing is a key risk factor for atherosclerosis progression that is associated with the increased incidence of ischemic events in supplied organs, including stroke, coronary events, limb ischemia, or renal failure. Cardiovascular disease is the leading cause of death and major disability in adults ≥ 75 years of age. Atherosclerotic occlusive disease affects everyday activity and quality of life, and it is associated with reduced life expectancy. Although there is evidence on coronary artery disease management in the elderly, there is insufficient data on the management in older patients presented with atherosclerotic lesions outside the coronary territory. Despite this, trials and observational studies systematically exclude older patients, particularly those with severe comorbidities, physical or cognitive dysfunctions, frailty, or residence in a nursing home. This results in serious critical gaps in knowledge and a lack of guidance on the appropriate medical treatment and referral for endovascular or surgical interventions. Therefore, we attempted to gather data on the prevalence, risk factors, and management strategies in patients with extra-coronary atherosclerotic lesions.
Tricuspid Regurgitation and TAVR: Outcomes, Risk Factors and Biomarkers
Authors: Puehler Thomas , Pommert Nina Sophie , Freitag-Wolf Sandra , Seoudy Hatim , Ernst Markus , Haneya Assad , Sathananthan Janarthanan , Sellers Stephanie L. , Meier David , Schöttler Jan , Müller Oliver J. , Salehi Ravesh Mona , Saad Mohammed , Frank Derk , Lutter Georg
Published: March 2024

Background. The significance of concomitant tricuspid regurgitation (TR) in the context of transcatheter aortic valve replacement (TAVR) remains unclear. This study aimed to analyze the severity of TR before and after TAVR with regard to short- and long-term survival and to analyze the influencing factors. Methods. In our retrospective analysis, TR before and after TAVR was examined and patients were classified into groups accordingly. Special attention was paid to patients with post-interventional changes in TR. Mortality after TAVR was considered the primary endpoint of the analysis and major complications according to the Valve Academic Research Consortium 3 (VARC3) were compared. Moreover, biomarkers and risk factors for worsening or improvement of TR through TAVR were analyzed. Results. Among 775 patients who underwent TAVR in our center between January 2009 and December 2019, 686 patients (89%) featured low- and 89 patients (11%) high-grade TR. High-grade pre-TAVR TR was associated with worse short- (30-day), mid- (2-year) and long-term survival up to 8 years. Even though in nearly half of the patients with high-grade TR the regurgitation improved within seven days after TAVR (n = 42/89), this did not result in a survival benefit for this subgroup. On the other hand, a worsening of low-grade TR was seen in more than 10% of the patients (n = 73/686), which was also associated with a worse prognosis. Predictors of worsening of TR after TAVR were adipositas, impaired right ventricular function and the presence of mild TR. Age, atrial fibrillation, COPD, impaired renal function and elevated cardiac biomarkers were risk factors for mortality after TAVR independent from the grade of TR. Conclusions. Not only pre-interventional, but also post-TAVR high-grade TR is associated with a worse prognosis after TAVR. TAVR can change concomitant tricuspid regurgitation, but improvement does not have any impact on short- and long-term survival. Worsening of TR after TAVR is possible and impairs the prognosis.
Intravascular Lithotripsy-Assisted Transfemoral Transcatheter Aortic Valve Implantation in Patients with Severe Iliofemoral Calcifications: Expanding Transfemoral Indications
Authors: Linder Matthias , Grundmann David , Kellner Caroline , Demal Till , Waldschmidt Lara , Bhadra Oliver , Ludwig Sebastian , Voigtländer Lisa , von der Heide Ina , Nebel Nicole , Hannen Laura , Schirmer Johannes , Reichenspurner Hermann , Blankenberg Stefan , Conradi Lenard , Schofer Niklas , Schäfer Andreas , Seiffert Moritz
Published: March 2024

(1) Background: Transfemoral transcatheter aortic valve implantation (TAVI) has become the standard treatment for most patients with severe symptomatic aortic stenosis. Intravascular lithotripsy may facilitate transfemoral TAVI (IVL-TAVI) even in patients with severely calcified iliofemoral disease. We assessed technical aspects and clinical outcomes of this novel approach compared to alternative transaxillary access (TAX-TAVI). (2) Methods: IVL-TAVI was performed for severe iliofemoral calcifications precluding standard transfemoral access in 30 patients from 2019 to 2022 at a single academic heart center. IVL was performed as part of the TAVI procedure in all cases. Results were compared to a control group of 44 TAX-TAVI procedures performed for the same indication from 2016 to 2021. The safety outcome was a composite of all-cause death, stroke, access-related bleeding ≥ type 2 within 24 h and major vascular access site complications at 30 days. The efficacy outcome was defined as a technical success according to VARC-3. (3) Results: Median age was 78.2 [74.3, 82.6] years, 45.9% were female and mean STS-PROM was 3.6% [2.3, 6.0]. Iliofemoral calcifications were more severe in the IVL-TAVI vs. TAX-TAVI groups (lesion length: 63.0 mm [48.6, 80.3] vs. 48.5 mm [33.1, 68.8]; p = 0.043, severe calcification at target lesion: 90.0% vs. 68.2%; p = 0.047, and median arc calcification 360.0° [297.5, 360.0] vs. 360.0° [180.0, 360.0]; p = 0.033). Technical success was achieved in 93.3% vs. 81.8% (p = 0.187) in IVL- and TAX-TAVI and the safety outcome occurred in 10.0% vs. 31.8% in IVL- and TAX-TAVI (p = 0.047), respectively. (4) Conclusions: IVL-assisted transfemoral TAVI was feasible and safe with favorable outcomes compared to TAX-TAVI. IVL may further expand the number of patients eligible for transfemoral TAVI and may help overcome limitations of an alternative access.
Correlation of Comfort Score and Narcotrend Index during Procedural Sedation with Midazolam and Propofol in Children
Authors: Bruns Nora , Joist Carolina A. , Joist Constantin M. , Daniels Anna , Felderhoff-Müser Ursula , Dohna-Schwake Christian , Tschiedel Eva
Published: March 2024

Background/Objectives: Precise assessment of hypnotic depth in children during procedural sedation with preserved spontaneous breathing is challenging. The Narcotrendindex (NI) offers uninterrupted information by continuous electrocortical monitoring without the need to apply a stimulus with the risk of assessment-induced arousal. This study aimed to explore the correlation between NI and the Comfort Scale (CS) during procedural sedation with midazolam and propofol and to identify an NI target range for deep sedation. Methods: A prospective observational study was conducted on 176 children (6 months to 17.9 years) undergoing procedural sedation with midazolam premedication and continuous propofol infusion. Statistical analyses included Pearson correlation of NI and CS values, logistic regression, and receiver operating curves. Results: Median NI values varied with CS and age. The correlation coefficient between CS and NI was 0.50 and slightly higher in procedure-specific subgroup analyses. The optimal NI cut-off for deep sedation was between 50 and 60 depending on the analyzed subgroup and displayed high positive predictive values for sufficient sedation throughout. Conclusion: Our study found a moderate correlation between NI and CS, demonstrating reliable identification of adequately sedated patients.
Elevating Chest X-ray Image Super-Resolution with Residual Network Enhancement
Authors: Khishigdelger Anudari , Salem Ahmed , Kang Hyun-Soo
Published: March 2024

Chest X-ray (CXR) imaging plays a pivotal role in diagnosing various pulmonary diseases, which account for a significant portion of the global mortality rate, as recognized by the World Health Organization (WHO). Medical practitioners routinely depend on CXR images to identify anomalies and make critical clinical decisions. Dramatic improvements in super-resolution (SR) have been achieved by applying deep learning techniques. However, some SR methods are very difficult to utilize due to their low-resolution inputs and features containing abundant low-frequency information, similar to the case of X-ray image super-resolution. In this paper, we introduce an advanced deep learning-based SR approach that incorporates the innovative residual-in-residual (RIR) structure to augment the diagnostic potential of CXR imaging. Specifically, we propose forming a light network consisting of residual groups built by residual blocks, with multiple skip connections to facilitate the efficient bypassing of abundant low-frequency information through multiple skip connections. This approach allows the main network to concentrate on learning high-frequency information. In addition, we adopted the dense feature fusion within residual groups and designed high parallel residual blocks for better feature extraction. Our proposed methods exhibit superior performance compared to existing state-of-the-art (SOTA) SR methods, delivering enhanced accuracy and notable visual improvements, as evidenced by our results.
Examining the Interplay between the Cognitive and Emotional Aspects of Gender Differences in Spatial Processing
Authors: Fioriti Cynthia M. , Martell Raeanne N. , Daker Richard J. , Malone Eleanor P. , Sokolowski H. Moriah , Green Adam E. , Levine Susan C. , Maloney Erin A. , Ramirez Gerardo , Lyons Ian M.
Published: March 2024

Women reliably perform worse than men on measures of spatial ability, particularly those involving mental rotation. At the same time, females also report higher levels of spatial anxiety than males. What remains unclear, however, is whether and in what ways gender differences in these cognitive and affective aspects of spatial processing may be interrelated. Here, we tested for robust gender differences across six different datasets in spatial ability and spatial anxiety (N = 1257, 830 females). Further, we tested for bidirectional mediation effects. We identified indirect relations between gender and spatial skills through spatial anxiety, as well as between gender and spatial anxiety through spatial skills. In the gender → spatial anxiety → spatial ability direction, spatial anxiety explained an average of 22.4% of gender differences in spatial ability. In the gender → spatial ability → spatial anxiety direction, spatial ability explained an average of 25.9% of gender differences in spatial anxiety. Broadly, these results support a strong relation between cognitive and affective factors when explaining gender differences in the spatial domain. However, the nature of this relation may be more complex than has been assumed in previous literature. On a practical level, the results of this study caution the development of interventions to address gender differences in spatial processing which focus primarily on either spatial anxiety or spatial ability until such further research can be conducted. Our results also speak to the need for future longitudinal work to determine the precise mechanisms linking cognitive and affective factors in spatial processing.
Parametric Optimization of Selective Laser Melted 13Ni400 Maraging Steel by Taguchi Method
Authors: Patil Viraj Vishwas , Mohanty Chinmaya P. , Prashanth K. G.
Published: March 2024

This study’s novel 13Ni400 maraging steel parts are additively manufactured through a selective laser melting process. The Taguchi approach is adopted to evaluate the combined influence of process variables (energy density), viz., laser power, layer thickness, hatch spacing, and scan speed, on responses like relative density, microhardness, surface roughness, and tensile strength. The powder and material characterization studies are conducted in terms of an optical microscope, scanning electron microscope (SEM), electron backscatter diffraction (EBSD), X-ray diffraction (XRD), and fractography analysis to explore the pre- and post-fabrication scenarios of the build parts. The consequences of energy density and process variables are studied through meticulous parametric studies. Finally, the optimum level of built parameters is identified and validated by a confirmative test predicting an average error of ~1.80%. This work is proficient in producing defect-free parts with maximum densification and improved mechanical properties for newly developed 13Ni-400 maraging steel by the selective laser melting (SLM) technique.