bluuebunny/crossref_metadata_2025 huggingface dataset:
Are Antimicrobial Peptides a 21st-Century Solution for Atopic Dermatitis?
Authors: Machado Manuela , Silva Sara , Costa Eduardo M.
Published: August 2023

Atopic dermatitis (AD) is a chronic inflammatory skin disorder that is the result of various environmental, bacterial and genetic stimuli, which culminate in the disruption of the skin’s barrier function. Characterized by highly pruritic skin lesions, xerosis and an array of comorbidities among which skin infections are the most common, this condition results in both a significant loss of quality of life and in the need for life-long treatments (e.g., corticosteroids, monoclonal antibodies and regular antibiotic intake), all of which may have harmful secondary effects. This, in conjunction with AD’s rising prevalence, made the development of alternative treatment strategies the focus of both the scientific community and the pharmaceutical industry. Given their potential to both manage the skin microbiome, fight infections and even modulate the local immune response, the use of antimicrobial peptides (AMPs) from more diverse origins has become one of the most promising alternative solutions for AD management, with some being already used with some success towards this end. However, their production and use also exhibit some limitations. The current work seeks to compile the available information and provide a better understanding of the state of the art in the understanding of AMPs’ true potential in addressing AD.
Identification and Characterization of the BBX Gene Family in Bambusa pervariabilis × Dendrocalamopsis grandis and Their Potential Role under Adverse Environmental Stresses
Authors: Liu Yi , Wang Yaxuan , Liao Jiao , Chen Qian , Jin Wentao , Li Shuying , Zhu Tianhui , Li Shujiang
Published: August 2023

Zinc finger protein (ZFP) transcription factors play a pivotal role in regulating plant growth, development, and response to biotic and abiotic stresses. Although extensively characterized in model organisms, these genes have yet to be reported in bamboo plants, and their expression information is lacking. Therefore, we identified 21 B-box (BBX) genes from a transcriptome analysis of Bambusa pervariabilis × Dendrocalamopsis grandis. Consequently, multiple sequence alignments and an analysis of conserved motifs showed that they all had highly similar structures. The BBX genes were divided into four subgroups according to their phylogenetic relationships and conserved domains. A GO analysis predicted multiple functions of the BBX genes in photomorphogenesis, metabolic processes, and biological regulation. We assessed the expression profiles of 21 BBX genes via qRT-PCR under different adversity conditions. Among them, eight genes were significantly up-regulated under water deficit stress (BBX4, BBX10, BBX11, BBX14, BBX15, BBX16, BBX17, and BBX21), nine under salt stress (BBX2, BBX3, BBX7, BBX9, BBX10, BBX12, BBX15, BBX16, and BBX21), twelve under cold stress (BBX1, BBX2, BBX4, BBX7, BBX10, BBX12, BBX14, BBX15, BBX17, BBX18, BBX19, and BBX21), and twelve under pathogen infestation stress (BBX1, BBX2, BBX4, BBX7, BBX10, BBX12, BBX14, BBX15, BBX17, BBX18, BBX19, and BBX21). Three genes (BBX10, BBX15, and BBX21) were significantly up-regulated under both biotic and abiotic stresses. These results suggest that the BBX gene family is integral to plant growth, development, and response to multivariate stresses. In conclusion, we have comprehensively analyzed the BDBBX genes under various adversity stress conditions, thus providing valuable information for further functional studies of this gene family.
Pyk2/FAK Signaling Is Upregulated in Recurrent Glioblastoma Tumors in a C57BL/6/GL261 Glioma Implantation Model
Authors: Ortiz Rivera Jescelica , Velez Crespo Grace , Inyushin Mikhail , Kucheryavykh Yuriy , Kucheryavykh Lilia
Published: August 2023

The majority of glioblastomas (GBMs) recur shortly after tumor resection and recurrent tumors differ significantly from newly diagnosed GBMs, phenotypically and genetically. In this study, using a Gl261-C57Bl/6 mouse glioma implantation model, we identified significant upregulation of proline-rich tyrosine kinase Pyk2 and focal adhesion kinase (FAK) phosphorylation levels—pPyk2 (579/580) and pFAK (925)—without significant modifications in total Pyk2 and FAK protein expression in tumors regrown after surgical resection, compared with primary implanted tumors. Previously, we demonstrated that Pyk2 and FAK are involved in the regulation of tumor cell invasion and proliferation and are associated with reduced overall survival. We hypothesized that the use of inhibitors of Pyk2/FAK in the postsurgical period may reduce the growth of recurrent tumors. Using Western blot analysis and confocal immunofluorescence approaches, we demonstrated upregulation of Cyclin D1 and the Ki67 proliferation index in tumors regrown after resection, compared with primary implanted tumors. Treatment with Pyk2/FAK inhibitor PF-562271, administered through oral gavage at 50 mg/kg daily for two weeks beginning 2 days before tumor resection, reversed Pyk2/FAK signaling upregulation in recurrent tumors, reduced tumor volume, and increased animal survival. In conclusion, the use of Pyk2/FAK inhibitors can contribute to a delay in GBM tumor regrowth after surgical resection.
The Anti-Calcitonin Gene-Related Peptide (Anti-CGRP) Antibody Fremanezumab Reduces Trigeminal Neurons Immunoreactive to CGRP and CGRP Receptor Components in Rats
Authors: Vogler Birgit , Kuhn Annette , Mackenzie Kimberly D. , Stratton Jennifer , Dux Mária , Messlinger Karl
Published: August 2023

Treatment with the anti-CGRP antibody fremanezumab is successful in the prevention of chronic and frequent episodic migraine. In preclinical rat experiments, fremanezumab has been shown to reduce calcitonin gene-related peptide (CGRP) release from trigeminal tissues and aversive behaviour to noxious facial stimuli, which are characteristic pathophysiological changes accompanying severe primary headaches. To further decipher the effects of fremanezumab that underlie these antinociceptive effects in rats, immunohistochemistry and ELISA techniques were used to analyse the content and concentration of CGRP in the trigeminal ganglion, as well as the ratio of trigeminal ganglion neurons which are immunoreactive to CGRP and CGRP receptor components, 1–10 days after subcutaneous injection of fremanezumab (30 mg/kg) compared to an isotype control antibody. After fremanezumab treatment, the fraction of trigeminal ganglion neurons which were immunoreactive to CGRP and the CGRP receptor components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) was significantly lowered compared to the control. The content and concentration of CGRP in trigeminal ganglia were not significantly changed. A long-lasting reduction in CGRP receptors expressed in trigeminal afferents may contribute to the attenuation of CGRP signalling and antinociceptive effects of monoclonal anti-CGRP antibodies in rats.
Oxygen Variations—Insights into Hypoxia, Hyperoxia and Hyperbaric Hyperoxia—Is the Dose the Clue?
Authors: Balestra Costantino , Mrakic-Sposta Simona , Virgili Fabio
Published: August 2023

Molecular oxygen (O2) is one of the four most important elements on Earth (alongside carbon, nitrogen and hydrogen); aerobic organisms depend on it to release energy from carbon-based molecules [...]
Refolding Increases the Chaperone-like Activity of αH-Crystallin and Reduces Its Hydrodynamic Diameter to That of α-Crystallin
Authors: Muranov Konstantin O. , Poliansky Nicolay B. , Borzova Vera A. , Kleimenov Sergey Y.
Published: August 2023

αH-Crystallin, a high molecular weight form of α-crystallin, is one of the major proteins in the lens nucleus. This high molecular weight aggregate (HMWA) plays an important role in the pathogenesis of cataracts. We have shown that the chaperone-like activity of HMWA is 40% of that of α-crystallin from the lens cortex. Refolding with urea significantly increased—up to 260%—the chaperone-like activity of α-crystallin and slightly reduced its hydrodynamic diameter (Dh). HMWA refolding resulted in an increase in chaperone-like activity up to 120% and a significant reduction of Dh of protein particles compared with that of α-crystallin. It was shown that the chaperone-like activity of HMWA, α-crystallin, and refolded α-crystallin but not refolded HMWA was strongly correlated with the denaturation enthalpy measured with differential scanning calorimetry (DSC). The DSC data demonstrated a significant increase in the native protein portion of refolded α-crystallin in comparison with authentic α-crystallin; however, the denaturation enthalpy of refolded HMWA was significantly decreased in comparison with authentic HMWA. The authors suggested that the increase in the chaperone-like activity of both α-crystallin and HMWA could be the result of the correction of misfolded proteins during renaturation and the rearrangement of protein supramolecular structures.
Sodium Butyrate Induces Mitophagy and Apoptosis of Bovine Skeletal Muscle Satellite Cells through the Mammalian Target of Rapamycin Signaling Pathway
Authors: Ding Yanling , Wang Pengfei , Li Chenglong , Zhang Yanfeng , Yang Chaoyun , Zhou Xiaonan , Wang Xiaowei , Su Zonghua , Ming Wenxuan , Zeng Ling , Shi Yuangang , Li Cong-Jun , Kang Xiaolong
Published: August 2023

Sodium butyrate (NaB) is one of the short-chain fatty acids and is notably produced in large amounts from dietary fiber in the gut. Recent evidence suggests that NaB induces cell proliferation and apoptosis. Skeletal muscle is rich in plenty of mitochondrial. However, it is unclear how NaB acts on host muscle cells and whether it is involved in mitochondria-related functions in myocytes. The present study aimed to investigate the role of NaB treatment on the proliferation, apoptosis, and mitophagy of bovine skeletal muscle satellite cells (BSCs). The results showed that NaB inhibited proliferation, promoted apoptosis of BSCs, and promoted mitophagy in a time- and dose-dependent manner in BSCs. In addition, 1 mM NaB increased the mitochondrial ROS level, decreased the mitochondrial membrane potential (MMP), increased the number of autophagic vesicles in mitochondria, and increased the mitochondrial DNA (mtDNA) and ATP level. The effects of the mTOR pathway on BSCs were investigated. The results showed that 1 mM NaB inhibited the mRNA and protein expression of mTOR and genes AKT1, FOXO1, and EIF4EBP1 in the mTOR signaling pathway. In contrast, the addition of PP242, an inhibitor of the mTOR signaling pathway also inhibited mRNA and protein expression levels of mTOR, AKT1, FOXO1, and EIF4EBP1 and promoted mitophagy and apoptosis, which were consistent with the effect of NaB treatment. NaB might promote mitophagy and apoptosis in BSCs by inhibiting the mTOR signaling pathway. Our results would expand the knowledge of sodium butyrate on bovine skeletal muscle cell state and mitochondrial function.
Blood Proteome Profiling Reveals Biomarkers and Pathway Alterations in Fragile X PM at Risk for Developing FXTAS
Authors: Zafarullah Marwa , Li Jie , Salemi Michelle R. , Phinney Brett S. , Durbin-Johnson Blythe P. , Hagerman Randi , Hessl David , Rivera Susan M. , Tassone Flora
Published: August 2023

Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is a neurodegenerative disorder associated with the FMR1 premutation. Currently, it is not possible to determine when and if individual premutation carriers will develop FXTAS. Thus, with the aim to identify biomarkers for early diagnosis, development, and progression of FXTAS, along with associated dysregulated pathways, we performed blood proteomic profiling of premutation carriers (PM) who, as part of an ongoing longitudinal study, emerged into two distinct groups: those who developed symptoms of FXTAS (converters, CON) over time (at subsequent visits) and those who did not (non-converters, NCON). We compared these groups to age-matched healthy controls (HC). We assessed CGG repeat allele size by Southern blot and PCR analysis. The proteomic profile was obtained by liquid chromatography mass spectrometry (LC-MS/MS). We identified several significantly differentiated proteins between HC and the PM groups at Visit 1 (V1), Visit 2 (V2), and between the visits. We further reported the dysregulated protein pathways, including sphingolipid and amino acid metabolism. Our findings are in agreement with previous studies showing that pathways involved in mitochondrial bioenergetics, as observed in other neurodegenerative disorders, are significantly altered and appear to contribute to the development of FXTAS. Lastly, we compared the blood proteome of the PM who developed FXTAS over time with the CSF proteome of the FXTAS patients recently reported and found eight significantly differentially expressed proteins in common. To our knowledge, this is the first report of longitudinal proteomic profiling and the identification of unique biomarkers and dysregulated protein pathways in FXTAS.
The Mitochondrial m.3243A>G Mutation on the Dish, Lessons from In Vitro Models
Authors: Ryytty Sanna , Hämäläinen Riikka H.
Published: August 2023

The m.3243A>G mutation in the tRNA Leu(UUR) gene (MT-TL1) is one of the most common pathogenic point mutations in human mtDNA. Patient symptoms vary widely and the severity of the disease ranges from asymptomatic to lethal. The reason for the high heterogeneity of m.3243A>G-associated disease is still unknown, and the treatment options are limited, with only supportive interventions available. Furthermore, the heteroplasmic nature of the m.3243A>G mutation and lack of specific animal models of mtDNA mutations have challenged the study of m.3243A>G, and, besides patient data, only cell models have been available for studies. The most commonly used cell models are patient derived, such as fibroblasts and induced pluripotent stem cell (iPSC)-derived models, and cybrid models where the mutant DNA is transferred to an acceptor cell. Studies on cell models have revealed cell-type-specific effects of the m.3243A>G mutation and that the tolerance for this mutation varies between cell types and between patients. In this review, we summarize the literature on the effects of m.3243A>G in cell models.
Influence of Pre-Analytic Conditions on Quantity of Lymphocytes
Authors: Proschmann Undine , Shalchi Amirkhiz Puya , Andres Pauline , Haase Rocco , Inojosa Hernan , Ziemssen Tjalf , Akgün Katja
Published: August 2023

Lymphocytes are key players in the pathogenesis of multiple sclerosis and a distinct target of several immunomodulatory treatment strategies. In this study, we aim to evaluate the effect of various pre-analytic conditions on immune cell counts to conclude the relevance for clinical implications. Twenty healthy donors were assessed for the effects of distinct storage temperatures and times after blood draws, different durations of tourniquet application, body positions and varying aspiration forces during blood draws. Immune cell frequencies were analyzed using multicolor flowcytometry. While storage for 24 h at 37 °C after blood draws was associated with significantly lower cell counts, different durations of tourniquet application, body positions and varying aspirations speeds did not have significant impacts on the immune cell counts. Our data suggest that immune cell counts are differently affected by pre-analytic conditions being more sensitive to storage temperature. Pre-analytic conditions should be carefully considered when interpreting the laboratory values of immune cell subpopulations.
Synthesis, X-ray Structure, Hirshfeld Surface Analysis and Antimicrobial Assessment of Tetranuclear s-Triazine Hydrazine Schiff Base Ligand
Authors: Al-Rasheed Hessa H. , AL-khamis Sarah A. , El-Faham Ayman , Barakat Assem , Slawin Alexandra M. Z. , Woollins John Derek , Soliman Saied M.
Published: August 2023

The unexpected tetranuclear [Cu4(DPPT)2Cl6] complex was obtained by self-assembly of CuCl2.2H2O and (E)-2,4-di(piperidin-1-yl)-6-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)-1,3,5-triazine, (HDPPT) in ethanol. In this tetranuclear [Cu4(DPPT)2Cl6] complex, the organic ligand acts as mononegative chelate bridging two crystallographically independent Cu(II) sites. The DPPT− anion acts as a bidentate ligand with respect to Cu(1), while it is a tridentate for Cu(2). The Cu(1)N2Cl3 and Cu(2)N3Cl spheres have square pyramidal and square planar coordination geometries with some distortion, respectively. Two of the chloride ions coordinating the Cu(1) are bridging between two crystallographically related Cu(1) sites connecting two [Cu2(DPPT)Cl3] units together, leading to the tetranuclear formula [Cu4(DPPT)2Cl6]. The packing of the [Cu4(DPPT)2Cl6] complex is dominated by C-H…Cl contacts, leading to one-dimensional hydrogen-bond polymeric structure. According to Hirshfeld surface analysis of molecular packing, the non-covalent interactions H…H, Cl…H, Cl…C, C…H, and N…H are the most significant. Their percentages are 52.8, 19.0, 3.2, 7.7, and 9.7%, respectively. Antimicrobial assessment showed good antifungal activity of the Cu(II) complex against A. fumigatus and C. albicans compared to Ketoconazole as positive control. Moreover, the [Cu4(DPPT)2Cl6] complex has higher activity against Gram-positive bacteria than Gentamycin as positive control. The opposite was observed when testing the tetranuclear [Cu4(DPPT)2Cl6] complex against the Gram-negative bacteria.
Boron Applications in Prevention, Diagnosis and Therapy for High Global Burden Diseases
Authors: Soriano-Ursúa Marvin A.
Published: August 2023

The role of boron-containing compounds (BCCs) in medicine is growing [...]
The Critical Role of Ligand Flexibility on the Activity of Free and Immobilized Mn Superoxide Dismutase Mimics
Authors: Richezzi Micaela , Signorella Sharon , Palopoli Claudia , Pellegri Nora , Hureau Christelle , Signorella Sandra R.
Published: August 2023

In low-molecular-weight Mn superoxide dismutase (SOD) mimics, the ligand plays a key role in tuning the reactivity of the metal center with O2•−. We used three ligands differing in their donor sites, flexibility and/or charge, to compare the redox properties and SOD activity of the resulting Mn complexes: 1,3-bis[(pyridin-2-ylmethyl)(propargyl)amino]propane (pypapn), 1,3-bis(pyridin-2-ylmethyleneamino)propane (py2pn) and 1,4-bis(salicylidenamino)butane (H2salbn). These ligands afford Mn complexes that, in aqueous solution, exist as mononuclear species [Mn(II)(pypapn)(H2O)2]2+, [Mn(II)(py2pn)(H2O)2]2+ and [Mn(III)(salbn)(H2O)2]+. The relative reactivity of these compounds with O2•− at pH 7.8, [Mn(pypapn)(H2O)2]2+ > [Mn(salbn)(H2O)2]+ > [Mn(py2pn)(H2O)2]2+, is independent of the redox potential but strongly depends on the ligand flexibility which becomes a critical feature when the reaction occurs through an inner-sphere electron-transfer mechanism. Immobilization was used to isolate and protect the catalyst from dissociation or dimerization during catalysis. [Mn(pypapn)(H2O)2]2+, with the alkyne group, was covalently grafted to azide functionalized mesoporous silica through click chemistry, while [Mn(py2pn)(solv)2]2+ and [Mn(salbn)(solv)2]+ were encapsulated in SBA-15 mesoporous silica through ionic exchange. The retention or enhancement of the SOD activity and the improved stability of the covalently attached catalyst and the doubly charged complex encapsulated in the silica pores, make them suitable for use in aqueous media.
Changes in Parameters after High Tibial Osteotomy: Comparison of EOS System and Computed Tomographic Analysis
Authors: Yoo Hyun-Jin , Choi Jae-Kyu , Heo Youn-Moo , Moon Sung-Jun , Oh Byung-Hak
Published: August 2023

Unintended rotation of the distal tibia occurs during medial open-wedge high tibial osteotomy (MOWHTO). Computed tomography (CT) is the standard method of measuring lower limb alignment; however, the new low-dose EOS system allows three-dimensional limb modeling with automated measurements of lower limb alignment. This study investigated the differences between the changes in lower limb alignment profiles obtained using the EOS system and CT in patients who underwent MOWHTO. We investigated whether any factors contributed to the degree of deformation. Thirty patients were prospectively enrolled between October 2019 and February 2023. Changes in femoral and tibial torsion, femorotibial rotation, and posterior tibial slope were measured using pre- and post-MOWHTO CT and EOS images. We found no significant difference in pre- and postoperative tibial torsion or posterior tibial slope between CT and EOS. No variables showed a significant correlation with changes in the tibial torsion or posterior tibial slope. This study confirmed the possibility that the EOS system could replace CT in measuring changes in several parameters pre- and postoperatively. Furthermore, we confirmed that the distal tibia tended to be internally rotated after MOWHTO; however, we found no significantly related parameters related to deformation caused by MOWHTO.
Does Prehospital Suspicion of Sepsis Shorten Time to Administration of Antibiotics in the Emergency Department? A Retrospective Study in One University Hospital
Authors: Bollinger Matthias , Frère Nadja , Shapeton Alexander Daniel , Schary Weronika , Kohl Matthias , Kill Clemens , Riße Joachim
Published: August 2023

Early treatment is the mainstay of sepsis therapy. We suspected that early recognition of sepsis by prehospital healthcare providers may shorten the time for antibiotic administration in the emergency department. We retrospectively evaluated all patients above 18 years of age who were diagnosed with sepsis or severe infection in our emergency department between 2018 and 2020. We recorded the suspected diagnosis at the time of presentation, the type of referring healthcare provider, and the time until initiation of antibiotic treatment. Differences between groups were calculated using the Kruskal–Wallis rank sum test. Of the 277 patients who were diagnosed with severe infection or sepsis in the emergency department, an infection was suspected in 124 (44.8%) patients, and sepsis was suspected in 31 (11.2%) patients by referring healthcare providers. Time to initiation of antibiotic treatment was shorter in patients where sepsis or infection had been suspected prior to arrival for both patients with severe infections (p = 0.022) and sepsis (p = 0.004). Given the well-described outcome benefits of early sepsis therapy, recognition of sepsis needs to be improved. Appropriate scores should be used as part of routine patient assessment to reduce the time to antibiotic administration and improve patient outcomes.
Risk Factors for Lower Extremity Amputation in Patients with End-Stage Kidney Disease: A Nationwide Cohort Study
Authors: Seo Min Jun , Lee Dong Geon , Ko Se Yun , Song Ga Yeong , Lee Geon Yeong , Kim Sung Hwa , Kang Dae Ryong , Kim Jiye , Lee Jun Young
Published: August 2023

Individuals with end-stage kidney disease (ESKD) on dialysis are at a high risk of developing foot ulcerations and undergoing subsequent lower extremity amputation (LEA), which can exert significant impacts on their quality of life and contribute to rising healthcare costs. We aimed to identify risk factors associated with LEA in patients with ESKD to predict LEA progression and eventually prevent it. We used 18 years (2002–2019) of data from the Korean National Health Insurance Service (KNHIS). Data were collected from patients with ESKD who underwent renal replacement therapy (RRT) and had no history of amputation caused by trauma or toxins. The risk factors were compared between patients with or without LEA. We collected data from 220,838 patients newly diagnosed with ESKD, including 6348 in the LEA group and 214,490 in the non-LEA group. The total incidence of LEA was 2.9%. Older age, male gender, lower income, non-metropolitan residence, diabetes mellitus, dialysis treatment (compared to kidney transplantation), microvascular disease, peripheral vascular disease, endovascular procedure, and endovascular operation were associated with an increased risk of LEA. Thus, individuals with ESKD who are at a higher risk for LEA should be closely monitored, and kidney transplantation should be considered as a preventative measure.
A Clinical and Ethical Dilemma: Expectant Management for Ectopic Pregnancy with a Vital Fetus in a Low-Resource Setting
Authors: Orsi Michele , Janneh Foday Musa , Sesay Amadu , Bah Abdul Karim , Tiru Nitsuh Addis
Published: August 2023

Background: Guidelines recommend the prompt surgical removal of any ectopic pregnancy (EP) in the presence of a vital embryo. This treatment impacts future fertility, particularly in low-resource settings where access to assisted reproductive techniques is limited. In addition, growing evidence is reporting live births after conservative management of initially undiagnosed abdominal pregnancies. Therefore, the discussion on the acceptability of expectant management in selected cases has been recently raised. Case: We present and discuss the case of a woman with vital first trimester EP who refused surgical treatment at Princess Christian Maternity Hospital, Freetown, Sierra Leone. She was initially diagnosed with a 12 week pregnancy located in the left adnexal region without hemoperitoneum. She refused both surgical treatment and hospital admission and did not come back to the hospital for antenatal care until 26 weeks of gestational age. Therefore, she was admitted and finally delivered, at 34 weeks of gestation, a 1.9 kg healthy baby which was alive. To disentangle the potential conflict between the ethical principles of medical treatment’s beneficence and the patient’s autonomy, we provide an update on counselling for a patient with early vital EP in a resource-limited setting and discuss the knowledge gap in this area. Conclusions: Limited access to fertility treatment in low- and middle-income countries may justify the discussion of expectant management as an option in selected cases of uncomplicated vital EP.
The Long-Term Observation of the Beneficial Effects of Treatment: 0.12 mg Anti-VEGF Monotherapy or Anti-VEGF Combined Therapy and Diode-Laser in Various Stages of Retinopathy of Prematurity—Series of Cases
Authors: Modrzejewska Monika , Nazwalska Martyna
Published: August 2023

Background 2-year observations of ranibizumab monotherapy and combined therapy with diode laser for severe ROP in extremely prematures. Materials and methods: In a group of 18 prematures (n = 36 eyes; 5 study groups); 25.8 ± 1.5 Hbd, birth weight 796.5 ± 166.1 g. Apgar 4.62 ± 1.88) with A-ROP (n = 22; 61%) and 3 ROP (plus) (n = 14; 39%), ranibizumab monotherapy (n = 4 eyes) in dose 0.12 mg/0.12 mL or with diode laser (n = 32 eyes) were applied. The first intervention was carried out in PMA of 33 (gr. 4 and 5) and 34 in (gr. 1, 2, 3), mean follow-up time 21.44 ± 8.7 months. One-way analysis of variance (ANOVA) with Welch’s correction, non-parametric Kruskal-Wallis test, Chi square test of independence were used. A retrospective observational study based on a case series. Results Retinal attachment was achieved in 92.3% of the studied eyes. Bilateral retinal detachment was noted in 1 infant (2 eyes). Myopization (−0.75 to −7.5 D) was observed in 5 infants (45%); mild hyperopia (+0.5 to +4.5 D) was observed in the rest infants (55%). Conclusions Individualization strategies in severe ROP with lower dose 0.12 mg Ranibizumab or combined laser-therapy resulted in effective outcomes. Myopia has not been reported in patients where Ranibizumab was the first drug administered in the ROP treatment strategy.
Sex Differences in Quality of Life in Patients with Ischemia with No Obstructive Coronary Artery Disease (INOCA): A Patient Self-Report Retrospective Survey from INOCA International
Authors: Ranasinghe Sachini , Merz C. , Khan Najah , Wei Janet , George Maria , Berry Colin , Chieffo Alaide , Camici Paolo , Crea Filippo , Kaski Juan , Marzilli Mario , Gulati Martha
Published: August 2023

Women with obstructive coronary artery disease (CAD) have a relatively lower quality of life (QoL) compared to men, but our understanding of sex differences in QoL in ischemia with no obstructive coronary artery disease (INOCA) is limited. We conducted a survey of patient members of INOCA International with an assessment of self-reported health measures. Functional capacity was retrospectively estimated using the Duke Activity Status Index (DASI), assessing levels of activities performed before and after INOCA symptom onset. Of the 1579 patient members, the overall survey completion rate was 21%. Women represented 91% of the respondents. Estimated functional capacity, expressed as metabolic equivalents (METs), was higher before compared to after INOCA diagnosis comparably for both women and men. For every one MET decline in functional capacity, there was a significantly greater decline in QoL for men compared with women in physical health (4.0 ± 1.1 vs. 2.9 ± 0.3 days/month, p < 0.001), mental health (2.4 ± 1.2 vs. 1.8 ± 0.3 days/month, p = 0.001), and social health/recreational activities (4.1 ± 1.0 vs. 2.9 ± 0.3 days/month, p = 0.0001), respectively. In an international survey of patients living with INOCA, despite similar diagnoses, clinical comorbidities, and symptoms, INOCA-related functional capacity declines are associated with a greater adverse impact on QoL in men compared to women.
Detection of zeb1 Gene in Granulosa Cells in Women Undergoing IVF Treatment
Authors: Chrysanthopoulos Ioannis , Mavrogianni Despoina , Drakaki Eirini , Potiris Anastasios , Zikopoulos Athanasios , Zachariou Athanasios , Domali Ekaterini , Drakakis Peter , Stavros Sofoklis
Published: August 2023

Background: ZEB1 plays a role in epithelial-to-mesenchymal transition and acts as a repressor of E-cadherin, TGF-β, and Wnt/β-catenin. Since ZEB1 protein is expressed in estrogen-responsive tissues, and expression of the gene in the normal ovary and endometrium is positively correlated with high estrogen levels, we performed a direct analysis of granulosa cell samples to determine whether there are any significant changes in zeb1 expression during folliculogenesis. Methods: ZEB1 expression levels were measured in the granulosa cells of 56 infertile women undergoing IVF treatment. RNA extraction from granulosa cells was performed along with reverse transcription quantitative polymerase chain reaction (RT-qPCR) with SYBR Green I to determine zeb1 gene expression levels. Statistical analysis was performed by using t-test, while possible correlations of the expression of ZEB1 protein with body mass index (BMI), age, number of oocytes, and oocyte maturation were investigated. Results: Zeb1 gene expression levels correlate significantly with body mass index (BMI) and age, but not with oocyte number and oocyte maturation stage. Obese women demonstrate a higher expression level of zeb1 gene compared to normal and overweight women. Moreover, zeb1 gene is overexpressed in women aged 35–40 years old and is under-expressed in women >40 years old. Conclusions: ZEB1 expression should be further investigated as it may unveil new potential findings of the zeb1 gene’s role in female fertility and its use as a biomarker in fertility workups.
Numerical Assessment of the Resistance of a Solar Catamaran in Shallow Water
Authors: Martić Ivana , Degiuli Nastia , Borčić Kornelija , Grlj Carlo Giorgio
Published: August 2023

In this paper, a numerical assessment of the effect of shallow water on the total resistance of the solar catamaran SolarCat is carried out using computational fluid dynamics within the software package STAR–CCM+. The unsteady viscous fluid flow was modelled based on the Reynolds-averaged Navier–Stokes (RANS) equations with the application of the k−ω SST (k−ω Shear Stress Transport) turbulence model. The RANS equations were discretized by the finite volume method, and the position of the free surface is determined by the volume of fluid method. In shallow water conditions, a mesh morphing algorithm is applied. Numerical simulations were carried out for the deep water and limited depths corresponding to h/T=7.6, h/T=4, and h/T=2 at two speeds. The verification study was carried out and the total numerical uncertainty was calculated for the total resistance and sinkage of the catamaran. A detailed analysis of the flow around the catamaran was carried out.
Characteristics of Early Neoproterozoic Stromatolites from Southern Liaoning, North China: Insights into the Formation of Stromatolites
Authors: Zhang Yongli , Lai Guanming , Gong Enpu , Yuan Dingcheng , Wilson Mark A. , Li Yu
Published: August 2023

Stromatolites, among the earliest fossils in Earth’s history, are widely distributed on the margins of the North China Precambrian carbonate platform. The formation processes of stromatolites reveal the biomineralization and evolution of early life in the Precambrian. The well-preserved stromatolitic dolostones recorded in the Ganjingzi Formation are developed around Yuanjiagou village, in southern Liaoning Province. The morphology of the Ganjingzi stromatolites manifests in stratiform, columnar, and domal forms. A tripartite lamina structure including light laminae and two types of dark laminae is observed in thin sections. The origins of dark laminae were related to microbial metabolism, while the light laminae were the result of the recrystallization of synsedimentary marine cement. Hardground substrate and carbonate fragments were suitable for microbes to colonize, suggesting that microbes can adapt to various current energy settings. A comparison of the growth environment, morphology, and laminae features between the Ganjingzi stromatolites and modern carbonate stromatolites from Hamelin Pool and Lagoa Vermelha suggest that the Ganjingzi stromatolites may have been formed in a restricted tidal-flat setting with high salinity and evaporation. The role of microbes that form modern stromatolites in inducing precipitation of carbonate or binding sediments, might contribute to the formation of the Ganjingzi stromatolites. The formation process of the Ganjingzi stromatolites indicates that the microbial communities, favorable substrate, and synsedimentary marine cement were the key factors in promoting the development of the Neoproterozoic stromatolites on the northeastern margin of the North China Craton.
Research on the Transport of Typical Pollutants in the Yellow Sea with Flow and Wind Fields
Authors: Wang Nan , Cao Ruichen , Lv Xianqing , Shi Honghua
Published: August 2023

In this study, we developed a transport model for typical pollutants in the Yellow Sea using the Lagrangian particle tracking method to analyze the trajectories of fish feed, a common pollutant in the Yellow Sea. The model incorporates the influence of ocean currents and surface winds on pollutant transport and utilizes a series of numerical experiments to simulate pollutant transport. Through statistical analysis of the numerical experiment results, we identified characteristic circles that represent the pollutant distribution patterns. Furthermore, based on the current and wind information within these characteristic circles, we derived an empirical formula to describe pollutant distribution. This formula enables us to predict the spatial distribution of pollutants using available current and wind data. Using this empirical formula, we designed an effective path to avoid pollutant contamination. This approach not only optimizes the utilization of computational resources within the study area but also contributes to the rational planning of navigation routes for aquaculture vessels. Overall, our study provides valuable insights into the transport behavior of fish feed pollutants in the Yellow Sea. The establishment of the empirical formula and the design of effective routes to avoid pollution contribute to the efficient management of pollution and facilitate the planning of marine activities in the region.
Novel High-Precision and High-Robustness Localization Algorithm for Underwater-Environment-Monitoring Wireless Sensor Networks
Authors: Ma Junling , Xian Jiangfeng , Wu Huafeng , Yang Yongsheng , Mei Xiaojun , Zhang Yuanyuan , Chen Xinqiang , Zhou Chao
Published: August 2023

In marine ecological environment monitoring, the acquisition of node location information is crucial, and the absence of location information can render the collected data meaningless. Compared to the rest of the distance-based localization methods, the received signal strength (RSS)-based localization technique has gained significant interest due to its low cost and the absence of time synchronization. However, the acoustic signal propagates in the complex and changeable aqueous medium, and, in addition to the time-varying path loss factor (PLF), there is often a certain absorption loss, which seriously deteriorates the localization accuracy of the RSS-based technique. To address the above challenges, we propose a novel high-precision and high-robustness localization (NHHL) algorithm that introduces an estimation parameter to conjointly estimate the marine node location and the ambient PLF. Firstly, the original non-convex localization problem is converted into an alternating nonnegative constrained least squares (ANCLS) framework with the unknown PLF and absorption loss, and a two-step localization method based on the primitive dual interior point method and block co-ordinate update method is presented to find the optimal solution. In the first step, the penalty function is utilized to reformulate the localization problem and find an approximate solution. Nevertheless, due to inherent errors, it is unable to approximate the constraint boundary and the global optimum solution. Subsequently, in the second step, the original localization problem is further transformed into a generalized trust region sub-problem (GTRS) framework, and the approximate solution of the interior point method is utilized as the initial estimation, and then iteratively solved by block co-ordinate update to obtain the precise location and PLF conjointly. Furthermore, the closed-form expression of the Cramér–Rao lower bound (CRLB) for the case of the unknown path loss factor and absorption loss is derived to evaluate the our NHHL algorithm. Finally, the simulation results demonstrate the superiority of the presented NHHL algorithm compared with the selected benchmark methods in various marine simulation scenarios.
Lippia origanoides Essential Oil or Thymol in Combination with Fluconazole Produces Damage to Cells and Reverses the Azole-Resistant Phenotype of a Candida tropicalis Strain
Authors: Zapata-Zapata Carolina , Rojas-López Mauricio , García Liliana T. , Quintero Wendy , Terrón María C. , Luque Daniel , Mesa-Arango Ana C.
Published: August 2023

Candida tropicalis is one of the most pathogenic species within the genus. Increased antifungal resistance has been reported, which is in part due to the organism’s ability to form biofilms. In natural products derived from plants, such as essential oils (EOs) or their major components, there is significant potential to develop new antifungals or to both enhance the efficacy and reduce the toxicity of conventional antifungals. This study aimed to evaluate the effect of combining an EO of Lippia origanoides or thymol with fluconazole on an azole-resistant C. tropicalis strain. Synergism was observed in the combination of fluconazole with the EO and with thymol, and minimal inhibitory concentrations for fluconazole decreased at least 32-fold. As a consequence of the synergistic interactions, mitochondrial membrane potential was reduced, and mitochondrial superoxide production increased. Alteration in nuclear morphology, cell surface, and ultrastructure was also observed. In conclusion, the synergistic interaction between L. origanoides EO or thymol with fluconazole reverted the azole-resistant C. tropicalis phenotype. These findings suggest that L. origanoides EO or thymol alone, or in combination with fluconazole, have the potential for development as antifungal therapies for this yeast, including resistant strains.
Revisiting Oral Antiseptics, Microorganism Targets and Effectiveness
Authors: Garrido Lisetty , Lyra Patrícia , Rodrigues Joana , Viana João , Mendes José João , Barroso Helena
Published: August 2023

A good oral health status is mostly dependent on good oral hygiene habits, which knowingly impacts systemic health. Although controversial, chemical oral antiseptics can be useful in adjunct use to mechanical dental plaque control techniques in the prevention and management of local and overall health and well-being. This review aims to revisit, gather and update evidence-based clinical indications for the use of the most popular oral antiseptics, considering different types, microorganism targets and effectiveness in order to establish updated clinical recommendations.
Relationship between the Tokyo Guidelines and Pathological Severity in Acute Cholecystitis
Authors: Park Tae Young , Do Jae Hyuk , Oh Hyoung-Chul , Choi Yoo Shin , Lee Seung Eun , Kang Hyun , Hong Soon Auck
Published: August 2023

Background: It is not well understood whether the severity of acute cholecystitis (AC) correlates with the extent of gallbladder (GB) inflammation or laboratory findings. This study aimed to assess whether the severity of AC, in accordance with the Tokyo Guidelines (TGs), is consistent with the extent of GB inflammation on histopathological and laboratory findings, including microbiological isolation in blood and bile. Methods: The medical records of patients who underwent cholecystectomy for AC between January 2017 and May 2020 were reviewed. Demographic data, laboratory findings, the microbiologic culture of blood and bile, the extent of GB inflammation, and stone composition were compared in accordance with the TGs. Results: A total of 217 patients were divided into three groups of increasing severity—Grade I (n = 146), Grade II (n = 51), and Grade III (n = 20)—in accordance with the TGs. The Grade III group contained significantly older patients compared with the Grade I or Grade II groups (Grade I, 56.9 ± 13.9; Grade II, 64.3 ± 15.4; Grade III, 69.9 ± 9.9; p-value < 0.001). Patients in the Grade III group showed significantly higher levels of CRP, WBC, creatinine, and bilirubin and lower levels of platelets and albumin compared with the Grade I or Grade II group. As the grade of severity increased, the rate of microbiological isolation in blood (Grade I, 0% [0/146]; Grade II, 2.0% [1/51]; Grade III, 20% [4/20]; p-value < 0.001) and bile (Grade I, 19.9% [29/146]; Grade II, 33.3% [17/51]; Grade III, 70% [14/20]; p-value < 0.001) also increased significantly. However, there were no significant differences in the extent of GB inflammation between grades. Conclusions: AC severity, as stated by the TGs, does not correlate with the extent of GB inflammation on histopathological and laboratory findings. However, microbiological isolation in blood and bile was increased proportionally to the grade of the TGs.
An Efficient, Lightweight, Tiny 2D-CNN Ensemble Model to Detect Cardiomegaly in Heart CT Images
Authors: Doppala Bhanu Prakash , Al Bataineh Ali , Vamsi Bandi
Published: August 2023

Cardiomegaly is a significant global health concern, especially in developing nations. Although advanced clinical care is available for newly diagnosed patients, many in resource-limited regions face late diagnoses and consequent increased mortality. This challenge is accentuated by a scarcity of radiography equipment and radiologists. Hence, we propose the development of a computer-aided diagnostic (CAD) system, specifically a lightweight, tiny 2D-CNN ensemble model, to facilitate early detection and, potentially, reduce mortality rates. Deep learning, with its subset of convolutional neural networks (CNN), has shown potential in visual applications, especially in medical image diagnosis. However, traditional deep CNNs often face compatibility issues with object-oriented human factor technology. Our proposed model aims to bridge this gap. Using CT scan images sourced from the Mendeley data center, our tiny 2D-CNN ensemble learning model achieved an accuracy of 96.32%, offering a promising tool for efficient and accurate cardiomegaly detection.
Carpal Tunnel Syndrome Associated with Immune Checkpoint Inhibitors
Authors: Yakobson Alexander , Rouvinov Keren , Cohen Aharon Y. , Goldstein Iris , Abu Saleh Omar , Solomon Adam , Dudnik Yulia , Shalata Walid
Published: August 2023

Immune checkpoint inhibitors (ICIs) have transformed the therapeutic approach to diverse malignancies, leading to substantial enhancements in patient prognosis. However, along with their benefits, ICIs also increase the incidence of immune-related adverse events (irAEs). In the present paper, we highlight four cases of carpal tunnel syndrome (CTS) as an uncommon manifestation of toxicity induced by ICIs. Although diagnosed with different malignancies, the patients were undergoing ICI therapy when they developed CTS-consistent side effects accompanied by severe neuropathy. Prompt treatment with corticosteroids, intravenous immunoglobulins, or methotrexate resulted in complete symptomatic relief for all patients. This article therefore emphasizes the importance of recognizing and managing rare adverse events associated with ICI use to ensure optimal patient care.
High Frequency of Osteophytes Detected by High-Resolution Ultrasound at the Finger Joints of Asymptomatic Factory Workers
Authors: Giulini Mario , Brinks Ralph , Vordenbäumen Stefan , Acar Hasan , Richter Jutta G. , Baraliakos Xenofon , Ostendorf Benedikt , Schneider Matthias , Sander Oliver , Sewerin Philipp
Published: August 2023

Hand Osteoarthritis (HOA) is a frequently occurring musculoskeletal disease that impacts health. Diagnostic criteria often incorporate osteophytes documented through imaging procedures. Radiographic imaging is considered the gold standard; however, more sensitive and safer methods like ultrasound imaging are becoming increasingly important. We conducted a population-based cross-sectional study to examine the prevalence, grade, and pattern of osteophytes using high-resolution ultrasound investigation. Factory workers were recruited on-site for the study. Each participant had 26 finger joints examined using ultrasonography to grade the occurrence of osteophytes on a semi-quantitative scale ranging from 0–3, where higher scores indicate larger osteophytes. A total of 427 participants (mean age 53.5 years, range 20–79 years) were included, resulting in 11,000 joints scored. At least one osteophyte was found in 4546 out of 11,000 (41.3%) joints or in 426 out of 427 (99.8%) participants, but only 5.0% (553) of the joints showed grade 2 or 3 osteophytes. The total osteophyte sum score increased by 0.18 per year as age increased (p < 0.001). The distal interphalangeal joints were the most commonly affected, with 61%, followed by the proximal interphalangeal joints with 48%, carpometacarpal joint 1 with 39%, and metacarpophalangeal joints with 16%. There was no observed impact of gender or workload. In conclusion, ultrasound imaging proves to be a practical screening tool for osteophytes and HOA. Grade 1 osteophytes are often detected in the working population through ultrasound assessments and their incidence increases with age. The occurrence of grade 2 or 3 osteophytes is less frequent and indicates the clinical presence of HOA. Subsequent evaluations are imperative to ascertain the predictive significance of early osteophytes.