bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin D in Central Nervous System: Implications for Neurological Disorders
Authors: Sailike Bayan , Onzhanova Zhadyra , Akbay Burkitkan , Tokay Tursonjan , Molnár Ferdinand
Published: July 2024

Vitamin D, obtained from diet or synthesized internally as cholecalciferol and ergocalciferol, influences bodily functions through its most active metabolite and the vitamin D receptor. Recent research has uncovered multiple roles for vitamin D in the central nervous system, impacting neural development and maturation, regulating the dopaminergic system, and controlling the synthesis of neural growth factors. This review thoroughly examines these connections and investigates the consequences of vitamin D deficiency in neurological disorders, particularly neurodegenerative diseases. The potential benefits of vitamin D supplementation in alleviating symptoms of these diseases are evaluated alongside a discussion of the controversial findings from previous intervention studies. The importance of interpreting these results cautiously is emphasised. Furthermore, the article proposes that additional randomised and well-designed trials are essential for gaining a deeper understanding of the potential therapeutic advantages of vitamin D supplementation for neurological disorders. Ultimately, this review highlights the critical role of vitamin D in neurological well-being and highlights the need for further research to enhance our understanding of its function in the brain.
Melatonin as a Circadian Marker for Plasmodium Rhythms
Authors: Dias Bárbara K. M. , Mohanty Abhinab , Garcia Célia R. S.
Published: July 2024

Plasmodium, a digenetic parasite, requires a host and a vector for its life cycle completion. Most Plasmodium species display circadian rhythmicity during their intraerythrocytic cycle within the host, aiding in immune evasion. This rhythmicity, however, diminishes in in vitro cultures, highlighting the importance of host-derived signals for synchronizing the parasite’s asexual cycle. Studies indicate a species–specific internal clock in Plasmodium, dependent on these host signals. Melatonin, a hormone the pineal gland produces under circadian regulation, impacts various physiological functions and is extensively reviewed as the primary circadian marker affecting parasite rhythms. Research suggests that melatonin facilitates synchronization through the PLC-IP3 signaling pathway, activating phospholipase C, which triggers intracellular calcium release and gene expression modulation. This evidence strongly supports the role of melatonin as a key circadian marker for parasite synchronization, presenting new possibilities for targeting the melatonin pathway when developing novel therapeutic approaches.
MRAP2a Binds and Modulates Activity and Localisation of Prokineticin Receptor 1 in Zebrafish
Authors: Fullone Maria Rosaria , Maftei Daniela , Vincenzi Martina , Lattanzi Roberta , Miele Rossella
Published: July 2024

The prokineticin system plays a role in hypothalamic neurons in the control of energy homeostasis. Prokineticin receptors (PKR1 and PKR2), like other G-protein-coupled receptors (GPCRs) are involved in the regulation of energy intake and expenditure and are modulated by the accessory membrane protein 2 of the melanocortin receptor (MRAP2). The aim of this work is to characterise the interaction and regulation of the non-melanocortin receptor PKR1 by MRAP2a in zebrafish (zMRAP2a) in order to use zebrafish as a model for the development of drugs targeting accessory proteins that can alter the localisation and activity of GPCRs. To this end, we first showed that zebrafish PKR1 (zPKR1) is able to interact with both zMRAP2a and human MRAP2 (hMRAP2). This interaction occurs between the N-terminal region of zPKR1 and the C-terminal domain of zMRAP2a, which shows high sequence identity with hMRAP2 and a similar propensity for dimer formation. Moreover, we demonstrated that in Chinese hamster ovary (CHO) cells, zMRAP2a or hMRAP2 are able to modulate zPKR1 activation induced by zebrafish PK2 (zPK2) resulting in an impaired ERK and STAT3 activation.
PTEN Depletion Increases Radiosensitivity in Response to Ataxia Telangiectasia-Related-3 (ATR) Inhibition in Non-Small Cell Lung Cancer (NSCLC)
Authors: Dunne Victoria L. , Ghita-Pettigrew Mihaela , Redmond Kelly M. , Small Donna M. , Weldon Sinéad , Taggart Clifford C. , Prise Kevin M. , Hanna Gerard G. , Butterworth Karl T.
Published: July 2024

Radiotherapy (RT) treatment is an important strategy for the management of non-small cell lung cancer (NSCLC). Local recurrence amongst patients with late-stage NSCLC remains a challenge. The loss of PTEN has been associated with radio-resistance. This study aimed to examine the efficacy of RT combined with ataxia telangiectasia-mutated Rad3-related (ATR) inhibition using Ceralasertib in phosphatase and tensin homolog (PTEN)-depleted NSCLC cells and to assess early inflammatory responses indicative of radiation pneumonitis (RP) after combined-modality treatment. Small hairpin RNA (shRNA) transfections were used to generate H460 and A549 PTEN-depleted models. Ceralasertib was evaluated as a single agent and in combination with RT in vitro and in vivo. Histological staining was used to assess immune cell infiltration in pneumonitis-prone C3H/NeJ mice. Here, we report that the inhibition of ATR in combination with RT caused a significant reduction in PTEN-depleted NSCLC cells, with delayed DNA repair and reduced cell viability, as shown by an increase in cells in Sub G1. Combination treatment in vivo significantly inhibited H460 PTEN-depleted tumour growth in comparison to H460 non-targeting PTEN-expressing (NT) cell-line-derived xenografts (CDXs). Additionally, there was no significant increase in infiltrating macrophages or neutrophils except at 4 weeks, whereby combination treatment significantly increased macrophage levels relative to RT alone. Overall, our study demonstrates that ceralasertib and RT combined preferentially sensitises PTEN-depleted NSCLC models in vitro and in vivo, with no impact on early inflammatory response indicative of RP. These findings provide a rationale for evaluating ATR inhibition in combination with RT in NSCLC patients with PTEN mutations.
Simultaneous High-Performance Recovery and Extended Acid-Catalyzed Hydrolysis of Oleuropein and Flavonoid Glycosides of Olive (Olea europaea) Leaves: Hydrothermal versus Ethanol Organosolv Treatment
Authors: Refai Hela , Derwiche Feyrouz , Grigorakis Spyros , Makris Dimitris P.
Published: July 2024

Olive leaves (OLLs) are an exceptional bioresource of natural polyphenols with proven antioxidant activity, yet the applicability of OLL extracts is constrained by the relatively high polarity of the major polyphenols, which occur as glycosides. To overcome this limitation, OLLs were subjected to both hydrothermal and ethanol organosolv treatments, fostered by acid catalysis to solicit in parallel increased polyphenol recovery and polyphenol modification into simpler, lower-polarity substances. After an initial screening of natural organic acids, oxalic acid (OxAc) was found to be the highest-performing catalyst. The extraction behavior using OxAc-catalyzed hydrothermal and ethanol organosolv treatments was appraised using kinetics, while treatment optimization was accomplished by deploying response-surface methodology. The comparative assessment of the composition extracts produced under optimal conditions of residence time and temperature was performed with liquid chromatography–tandem mass spectrometry and revealed that OLLs treated with 50% ethanol/1.5% HCl suffered extensive oleuropein and flavone glycoside hydrolysis, affording almost 23.4 mg hydroxytyrosol and 2 mg luteolin per g dry weight. On the other hand, hydrothermal treatment with 5% OxAc provided 20.2 and 0.12 mg of hydroxytyrosol and luteolin, respectively. Apigenin was in all cases a minor extract constituent. The study presented herein demonstrated for the first time the usefulness of using a natural, food-grade organic acid to perform such a task, yet further investigation is needed to maximize the desired effect.
Genome-Wide Identification and Expression Analysis of ADK Gene Family Members in Cotton under Abiotic Stress
Authors: Huang Peijun , Lin Ziwei , Zhang Yuzhi , Gao Yu , Tan Songjuan , Wang Shuai , Cao Xiaoyu , Shi Hongyan , Sun Chao , Bai Jiangping , Ma Xiongfeng
Published: July 2024

Adenosine kinase (ADK) is a key enzyme widely distributed in plants, playing an important role in maintaining cellular energy homeostasis and regulating plant growth, development, and responses to environmental stresses. However, research on ADK genes in cotton (Gossypium hirsutum), an economically significant crop, has been limited. This study identified 92 ADK genes from four cotton species (G. arboreum, G. raimondii, G. hirsutum, and G. barbadense) using HMMER and Local BLASTP methods and classified them into six groups. Chromosomal localization revealed a random distribution of ADK genes in G. hirsutum, with 13 genes located on the At subgenome and 14 genes on the Dt subgenome. Gene structure analysis showed consistency in exon–intron organization within subgroups, while conserved motif analysis identified subgroup-specific motifs, indicating functional diversity. Synteny and collinearity mapping analysis revealed that the primary expansion mechanisms of the ADK gene family in cotton are polyploidy and segmental duplication. Cis-regulatory elements in GhADK promoters were classified into light response, hormone response, developmental regulation, and stress response. We also analyzed the expression patterns of GhADK genes under a low temperature (4 °C) and drought conditions. Most GhADK genes responded to cold stress with different expression patterns, indicating their roles in rapid response and long-term cold adaptation. Under drought stress, expression patterns varied, with some genes showing sustained high expression levels. The qRT-PCR validation of transcriptomic data confirmed the stress-induced expression patterns of selected GhADK genes. Functional analysis through the VIGS silencing of GhADK25 demonstrated its importance in cold and drought stress responses, with silencing resulting in poor growth under stress, highlighting its significance in stress tolerance. This study provides a basis for further understanding the evolutionary relationships and functions of the cotton ADK gene family.
Eucalyptol Ameliorates Retinal Microvascular Defects through Modulating ER Stress and Angiopoietin–Tie Signaling in Diabetic Eyes
Authors: Kim Dong Yeon , Park Sin-Hye , Yoon Zaee , Kim Jimin , Kang Min-Kyung , Kang Young-Hee
Published: July 2024

Loss of the inner blood–retinal barrier (BRB) integrity is a main feature of ocular diseases such as diabetic macular edema. However, there is a lack of clarity on how inner BRB function is modulated within the diabetic retina. The current study examined whether eucalyptol inhibited inner BRB destruction and aberrant retinal angiogenesis in 33 mM glucose-exposed human retinal microvascular endothelial (RVE) cells and db/db mice. This study further examined the molecular mechanisms underlying endothelial dysfunction including retinal endoplasmic reticulum (ER) stress and angiopoietin (Ang)/Tie axis in conjunction with vascular endothelial growth factor (VEGF). Eucalyptol is a naturally occurring monoterpenoid and an achiral aromatic component of many plants including eucalyptus leaves. Nontoxic eucalyptol reduced the production of amyloid-β (Aβ) protein in glucose-loaded RVE cells and in diabetic mice. This natural compound blocked apoptosis of Aβ-exposed RVE cells in diabetic mouse eyes by targeting ER stress via the inhibition of PERK-eIF2α-ATF4-CHOP signaling. Eucalyptol promoted activation of the Ang-1/Tie-2 pathway and dual inhibition of Ang-2/VEGF in Aβ-exposed RVE cells and in diabetic eyes. Supply of eucalyptol reversed the induction of junction proteins in glucose/Aβ-exposed RVE cells within the retina and reduced permeability. In addition, oral administration of eucalyptol reduced vascular leaks in diabetic retinal vessels. Taken together, these findings clearly show that eucalyptol inhibits glucose-induced Aβ-mediated ER stress and manipulates Ang signaling in diabetic retinal vessels, which ultimately blocks abnormal angiogenesis and loss of inner BRB integrity. Therefore, eucalyptol provides new treatment strategies for diabetes-associated RVE defects through modulating diverse therapeutic targets including ER stress, Ang-1/Tie-2 signaling, and Ang-2/VEGF.
Vascular Endothelial Growth Factor C (VEGF-C) Sensitizes Lymphatic Endothelial Cells to Oxidative-Stress-Induced Apoptosis through DNA Damage and Mitochondrial Dysfunction: Implications for Lymphedema
Authors: Hossain Lazina , Gomes Karina Pereira , Yang Xiaoyan , Liu Emily , Du Toit Jacques , von der Weid Pierre-Yves , Gibson Spencer Bruce
Published: July 2024

Secondary lymphedema is caused by damage to the lymphatic system from surgery, cancer treatment, infection, trauma, or obesity. This damage induces stresses such as oxidative stress and hypoxia in lymphatic tissue, impairing the lymphatic system. In response to damage, vascular endothelial growth factor C (VEGF-C) levels increase to induce lymphangiogenesis. Unfortunately, VEGF-C often fails to repair the lymphatic damage in lymphedema. The underlying mechanism contributing to lymphedema is not well understood. In this study, we found that surgery-induced tail lymphedema in a mouse model increased oxidative damage and cell death over 16 days. This corresponded with increased VEGF-C levels in mouse tail lymphedema tissue associated with macrophage infiltration. Similarly, in the plasma of patients with secondary lymphedema, we found a positive correlation between VEGF-C levels and redox imbalance. To determine the effect of oxidative stress in the presence or absence of VEGF-C, we found that hydrogen peroxide (H2O2) induced cell death in human dermal lymphatic endothelial cells (HDLECs), which was potentiated by VEGF-C. The cell death induced by VEGF-C and H2O2 in HDLECs was accompanied by increased reactive oxygen species (ROS) levels and a loss of mitochondrial membrane potential. Antioxidant pre-treatment rescued HDLECs from VEGF-C-induced cell death and decreased ROS under oxidative stress. As expected, VEGF-C increased the number of viable and proliferating HDLECs. However, upon H2O2 treatment, VEGF-C failed to increase either viable or proliferating cells. Since oxidative stress leads to DNA damage, we also determined whether VEGF-C treatment induces DNA damage in HDLECs undergoing oxidative stress. Indeed, DNA damage, detected in the form of gamma H2AX (γH2AX), was increased by VEGF-C under oxidative stress. The potentiation of oxidative stress damage induced by VEFG-C in HDLECs was associated with p53 activation. Finally, the inhibition of vascular endothelial growth factor receptor-3 (VEGFR-3) activation blocked VEGF-C-induced cell death following H2O2 treatment. These results indicate that VEGF-C further sensitizes lymphatic endothelial cells to oxidative stress by increasing ROS and DNA damage, potentially compromising lymphangiogenesis.
Mitochondrial ATP Synthase beta-Subunit Affects Plastid Retrograde Signaling in Arabidopsis
Authors: Liu Hao , Liu Zhixin , Qin Aizhi , Zhou Yaping , Sun Susu , Liu Yumeng , Hu Mengke , Yang Jincheng , Sun Xuwu
Published: July 2024

Plastid retrograde signaling plays a key role in coordinating the expression of plastid genes and photosynthesis-associated nuclear genes (PhANGs). Although plastid retrograde signaling can be substantially compromised by mitochondrial dysfunction, it is not yet clear whether specific mitochondrial factors are required to regulate plastid retrograde signaling. Here, we show that mitochondrial ATP synthase beta-subunit mutants with decreased ATP synthase activity are impaired in plastid retrograde signaling in Arabidopsis thaliana. Transcriptome analysis revealed that the expression levels of PhANGs were significantly higher in the mutants affected in the AT5G08670 gene encoding the mitochondrial ATP synthase beta-subunit, compared to wild-type (WT) seedlings when treated with lincomycin (LIN) or norflurazon (NF). Further studies indicated that the expression of nuclear genes involved in chloroplast and mitochondrial retrograde signaling was affected in the AT5G08670 mutant seedlings treated with LIN. These changes might be linked to the modulation of some transcription factors (TFs), such as LHY (Late Elongated Hypocotyl), PIF (Phytochrome-Interacting Factors), MYB, WRKY, and AP2/ERF (Ethylene Responsive Factors). These findings suggest that the activity of mitochondrial ATP synthase significantly influences plastid retrograde signaling.
Charge Transfer in He+ − He → He(1s4l, l ≥ 2) − He+ Collisions in Intermediate Energy Range
Authors: Kamiński Patryk , Drozdowski Ryszard
Published: July 2024

The anticrossing spectra of the helium line λ1s4l D3,F−1s2p P3=447.2 nm emitted after electron capture by He+ ions in He+−He collisions were measured for projectile energies of 10–29 keV. Furthermore, considering the excited states’ time evolution, the theoretical intensity functions were calculated. The electric field and density distributions of the target He atoms in the collision volume were taken into account, and by fitting the theoretical intensities to the measured ones, the post-collisional states of the charge-transferred He atoms were determined. The results indicate that for the intermediate projectile energy range, the electronic charge distributions were asymmetric, but the electric dipole moments did not change, as in the case of the target atoms excited directly in the collisions. This result shows that the Paul trap mechanism may play an important role in the charge transfer excitation in this energy range.
Functional Characterization of Six Eukaryotic Translation Initiation Factors of Toxoplasma gondii Using the CRISPR-Cas9 System
Authors: Kou Yong-Jie , Gao Jin , Li Rui , Ma Zhi-Ya , Elsheikha Hany M. , Wu Xiao-Jing , Zheng Xiao-Nan , Wang Meng , Zhu Xing-Quan
Published: July 2024

Eukaryotic translation initiation factors (eIFs) are crucial for initiating protein translation and ensuring the correct assembly of mRNA-ribosomal subunit complexes. In this study, we investigated the effects of deleting six eIFs in the apicomplexan parasite Toxoplasma gondii using the CRISPR-Cas9 system. We determined the subcellular localization of these eIFs using C-terminal endogenous tagging and immunofluorescence analysis. Four eIFs (RH::315150-6HA, RH::286090-6HA, RH::249370-6HA, and RH::211410-6HA) were localized in the cytoplasm, while RH::224235-6HA was localized in the apicoplast. Additionally, RH::272640-6HA was found in both the basal complex and the cytoplasm of T. gondii. Functional characterization of the six RHΔeIFs strains was conducted using plaque assay, cell invasion assay, intracellular growth assay and egress assay in vitro, and virulence assay in mice. Disruption of five eIF genes (RHΔ315150, RHΔ272640, RHΔ249370, RHΔ211410, and RHΔ224235) did not affect the ability of the T. gondii RH strain to invade, replicate, form plaques and egress in vitro, or virulence in Kunming mice (p > 0.05). However, the RHΔ286090 strain showed slightly reduced invasion efficiency and virulence (p < 0.01) compared to the other five RHΔeIFs strains and the wild-type strain. The disruption of the TGGT1_286090 gene significantly impaired the ability of tachyzoites to differentiate into bradyzoites in both type I RH and type II Pru strains. These findings reveal that the eukaryotic translation initiation factor TGGT1_286090 is crucial for T. gondii bradyzoite differentiation and may serve as a potential target for drug development and an attenuated vaccine against T. gondii.
Straw Incorporation with Exogenous Degrading Bacteria (ZJW-6): An Integrated Greener Approach to Enhance Straw Degradation and Improve Rice Growth
Authors: Wei Xiaoshuang , Li Wanchun , Song Ze , Wang Shiwen , Geng Shujuan , Jiang Hao , Wang Zhenhui , Tian Ping , Wu Zhihai , Yang Meiying
Published: July 2024

Rice straw is an agricultural waste, the disposal of which through open burning is an emerging challenge for ecology. Green manufacturing using straw returning provides a more avant-garde technique that is not only an effective management measure to improve soil fertility in agricultural ecosystems but also nurtures environmental stewardship by reducing waste and the carbon footprint. However, fresh straw that is returned to the field cannot be quickly decomposed, and screening microorganisms with the capacity to degrade straw and understanding their mechanism of action is an efficient approach to solve such problems. This study aimed to reveal the potential mechanism of influence exerted by exogenous degradative bacteria (ZJW-6) on the degradation of straw, growth of plants, and soil bacterial community during the process of returning rice straw to the soil. The inoculation with ZJW-6 enhanced the driving force of cellulose degradation. The acceleration of the rate of decomposition of straw releases nutrients that are easily absorbed by rice (Oryza sativa L.), providing favorable conditions for its growth and promoting its growth and development; prolongs the photosynthetic functioning period of leaves; and lays the material foundation for high yields of rice. ZJW-6 not only directly participates in cellulose degradation as degrading bacteria but also induces positive interactions between bacteria and fungi and enriches the microbial taxa that were related to straw degradation, enhancing the rate of rice straw degradation. Taken together, ZJW-6 has important biological potential and should be further studied, which will provide new insights and strategies for the appropriate treatment of rice straw. In the future, this degrading bacteria may provide a better opportunity to manage straw in an ecofriendly manner.
TABLET TOSCANA to Develop Innovative Organizational Models for Tele-Rehabilitation in Subjects with Congenital and Acquired Developmental Disabilities: A Wait-List Control Group Trial Protocol
Authors: Barzacchi Veronica , Mangani Gloria , Del Lucchese Benedetta , Menici Valentina , Bombonato Clara , Beani Elena , Biagioni Enrico , Palla Ilaria , Posteraro Federico , Trieste Leopoldo , Turchetti Giuseppe , Sgandurra Giuseppina , Cioni Giovanni ,   on behalf of Tablet Toscana Consortium
Published: July 2024

Background/Objectives: In recent years, the advent of new technologies has fostered their application in neuro-psychomotor and language rehabilitation, particularly since the COVID-19 pandemic. Tele-rehabilitation has emerged as an innovative and timely solution, enabling personalized interventions monitored by clinicians. TABLET TOSCANA project aims to develop innovative tele-rehabilitation organizational models in children, adolescents and young adults with congenital and acquired developmental disabilities, using the Virtual Reality Rehabilitation System (VRRS) Home Kit and the MedicoAmico APP. Methods: The trial is designed according to the CONSORT statement guidelines. The project encompasses three phases: adapting the technologies for pediatric use, validating them through a wait-list study, and analyzing feasibility and effectiveness data to define new organizational models. A randomized wait-list-control study with 100 subjects aged 6 to 30 years will compare tele-rehabilitation versus prosecution of standard care. Discussion: Although literature highlights tele-rehabilitation benefits such as improved access, cost savings, and enhanced treatment adherence, practical implementation remains limited (i.e., the definition of standardized procedures). TABLET TOSCANA project seeks to address these gaps by focusing on multi-domain treatments for neurodevelopmental disabilities and emphasizing the integration of tele-rehabilitation into local health services. Conclusion: The project aims to improve the continuity and intensity of care through innovative models that integrate tele-rehabilitation into local health services. The results could inform healthcare policies and promote the development of innovative and collaborative models of care, paving the way for more effective and widespread tele-rehabilitation solutions and fostering collaborative networks among professionals.
Hidden Appendicoliths and Their Impact on the Severity and Treatment of Acute Appendicitis
Authors: Dölling Maximilian , Rahimli Mirhasan , Pachmann Jonas , Szep Malik , Al-Madhi Sara , Andric Mihailo , Kahlert Ulf D. , Hofmann Tobias , Boettcher Michael , Muñoz Luis E. , Herrmann Martin , Perrakis Aristotelis , Croner Roland S.
Published: July 2024

Background/Objectives: In patients diagnosed with uncomplicated acute appendicitis (UAA), the absence of calcified deposits or stones, called appendicoliths, often leads to consideration of non-operative treatment (NOT), despite the notable treatment failure rate associated with this approach. Previous research has indirectly estimated the prevalence of appendicoliths to range between 15% and 38% retrospectively by CT scan, intraoperative palpation, and pathology report, thereby potentially missing certain concrements. Our hypothesis proposes that this reported prevalence significantly underestimates the occurrence of appendicoliths, which could explain the high failure rate of 29% of patients with appendicitis observed with NOT. Methods: In our prospective study, conducted with a cohort of 56 adult patients diagnosed with acute appendicitis (AA), we employed intraoperative extracorporeal incisions of the vermiform appendix, in addition to standard diagnostic methods. Results: Our findings revealed 50% more appendicoliths by intraoperative incision (n = 36, p < 0.001) compared to preoperative imaging (n = 24). Appendicoliths were present in 71.4% (n = 40, p < 0.001) of AA patients. Conclusions: These results suggest that conventional diagnostic procedures plausibly underestimate the actual prevalence of appendicoliths, potentially elucidating the frequent treatment failures observed in NOT approaches applied to patients with UAA.
Patient Reported Outcome Measures in Adults with Fontan Circulatory Failure
Authors: Agorrody Guillermo , Begun Isaac , Verma Subodh , Mazer C. David , Garagiola Maria Luz , Fernandez-Campos Beatriz , Acuña Ronald , Kearney Katherine , Buckley Alvan , Dhingra Nitish K. , Ghamarian Ehsan , Roche S. Lucy , Alonso-Gonzalez Rafael , Wald Rachel M.
Published: July 2024

Background: Patient reported outcomes (PROs) are important measures in acquired heart disease but have not been well defined in Adult Congenital Heart Disease (ACHD). Our aim was to explore the discriminatory capacity of PRO survey tools in Fontan circulatory failure (FCF). Methods: Consecutive adults were enrolled from our ambulatory clinics. Inclusion criteria were age ≥18 years, a Fontan circulation or a hemodynamically insignificant shunt lesion, and sufficient cognitive/language abilities to complete PROs. A comprehensive package of PRO measures, designed to assess perceived health-related quality of life (HRQOL) was administered (including the Kansas City Cardiomyopathy Questionnaire [KCCQ-12], EuroQol-5-dimension [EQ5D], Short Form Health Status Survey [SF-12], self-reported New York Heart Association [NYHA] Functional Class, and Specific Activity Scale [SAS]). Results: We compared 54 Fontan patients (35 ± 10 years) to 25 simple shunt lesion patients (34 ± 11 years). The KCCQ-12 score was lower in Fontan versus shunt lesion patients (87 [IQR 79, 95] versus 100 [IQR 97, 100], p-value < 0.001). The FCF subgroup was associated with lower KCCQ-12 scores as compared with the non-FCF subgroup (82 [IQR 56, 89] versus 93 [IQR 81, 98], p-value = 0.002). Although the KCCQ-12 had the best discriminatory capacity for determination of FCF of all PRO tools studied (c-statistic 0.75 [CI 0.62, 0.88]), superior FCF discrimination was achieved when the KCCQ-12 was combined with all PRO tools (c-statistic 0.82 [CI 0.71, 0.93]). Conclusions: The KCCQ-12 questionnaire demonstrated good discriminatory capacity for the identification of FCF, which was further improved through the addition of complementary PRO tools. Further research will establish the value of PRO tools to guide management strategies in ACHD.
Adverse Events in Open Surgical vs. Ultrasound-Guided Percutaneous Brachial Access for Endovascular Interventions
Authors: Ozcinar Evren , Dikmen Nur , Kayan Ahmet , Baran Cagdas , Yazicioglu Levent
Published: July 2024

Background: Advances in endovascular interventions have made endovascular approaches the first option for treating peripheral arterial diseases. Although radial artery access is commonly used for coronary procedures, the common femoral artery remains the most frequent site for endovascular treatments due to better ergonomics and proven technical success. Meanwhile, data on using upper extremity access via the brachial artery during complex endovascular aortic interventions are lacking. This study aimed to compare the incidence of access site complications between ultrasound-guided percutaneous brachial access (UPA) and open surgical incisional brachial access (OSA) in the management of peripheral arterial diseases. Methods: Patients who underwent treatment for peripheral arterial and aortic disease using brachial access from 2019 to 2023 were included in this study. The primary endpoint was the complication rate at the access site 30 days postoperatively. Access-related complications included bleeding requiring re-exploration, acute upper limb ischemia, thrombosis, pseudoaneurysm, arteriovenous fistula, and nerve injury associated with the brachial access. Results: Brachial access was performed on 485 patients (UPA, n = 320; OSA, n = 165). The mean operation time was 164.5 ± 45.4 min for the percutaneous procedure and 289.2 ± 79.4 min for the cutdown procedure (p = 0.003). Postprocedural hematoma occurred in 15 patients in the UPA group and 2 patients in the OSA group (p = 0.004). Thromboembolic events were observed in 9 patients in the percutaneous group and 3 patients in the OSA group. Reoperation was required for 23 patients in the percutaneous group and 8 patients in the cutdown group. Conclusions: The findings indicate that patients undergoing endovascular arterial interventions have a higher rate of brachial access complications in the UPA group compared to the OSA group.
Oral Reconstruction with Locoregional Flaps after Cancer Ablation: A Systematic Review of the Literature
Authors: Accorona Remo , Di Furia Domenico , Cremasco Alice , Gazzini Luca , Mevio Niccolò , Pilolli Francesco , Achena Andrea , Iftikhar Haissan , Awny Shadi , Ormellese Giorgio Luigi , Dragonetti Alberto Giulio , De Virgilio Armando
Published: July 2024

Introduction: The planning of oral reconstruction after tumor resection is a pivotal point for head and neck surgeons. It is mandatory to consider two aspects: the size of the surgical defect and the complexity of the oral cavity as an anatomical region. We offer a review of the literature that focuses on four types of locoregional flaps that can be profitably used for such reconstruction: infrahyoid (IF), nasolabial (NF), platysma (PF), and submental (SF). Methods: The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review was carried out according to the PICOS acronym through a comprehensive electronic search on PubMed/MEDLINE, Cochrane Library, and Google Scholar databases. For each selected article, we extrapolated eight main parameters, of which all mean values were compared through an ANOVA test. The dimensions of the oral defects were referred to as “small” (<7 cm2), “medium” (7–50 cm2), or “large” (>50 cm2). Results: A total of 139 articles were selected with a total of 5898 patients. The mean ages for each type of flap were not statistically significant (p = 0.30, p > 0.05). Seven sublocations of oral defects were reported: The most common was the tongue (2003 [34.0%] patients), followed by the floor of the mouth (1786 [30.4%]), buccal mucosa (981 [16.6%]), cheek (422 [7.2%]), hard palate (302 [5.1%]), alveolar ridge (217 [3.7%]), and retromolar trigone (187 [3.2%]). The defects were mainly medium-sized (4507 [76.4%] patients), and fewer were small-sized (1056 [17.9%]) or large-sized (335 [5.7%]). Complications were noted, the most frequent of which was flap necrosis, seen in 0.57% of cases. The functional and esthetical results were mainly positive. Conclusions: Locoregional flaps represent a good alternative in medium-sized defects as well as a fairly good alternative in small- and large-sized defects when other options are ruled out.
The Impact of Comorbidities and Motor Impairment on the Quality of Life of Patients with Spinal Muscular Atrophy: A Case–Control Study
Authors: Błauciak Małgorzata , Ubysz Jakub , Pokryszko-Dragan Anna , Koszewicz Magdalena
Published: July 2024

Introduction: Spinal muscular atrophy (SMA) is a genetically determined disease primarily leading to muscle weakness, but now, it is considered a systemic disease with changes in various tissues and organs. In our study, we aimed to compare quality of life (QoL) outcomes in patients with SMA in relation to the degree of motor limitation and comorbidities, mainly internal medicine diseases. Methods: We included 35 adult patients with SMA and 36 healthy volunteers. Thorough medical histories were taken focusing on comorbidities, and neurological examinations incorporating assessments using functional motor scales were performed. QoL was assessed based on the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) questionnaire. Results: SMA patients and controls were comparable in terms of scores in the questionnaire’s main domains. SMA patients presented significantly higher levels of satisfaction with their medical care than controls. Patients with more advanced SMA had significantly better scores on certain questions, e.g., those related to health satisfaction or leisure activities. A total of 71.4% of SMA patients had comorbidities, ranging from one to three in individual patients. SMA patients with comorbidities did not show worse QoL. Negative correlations were found between the number of comorbidities in SMA patients and individual questions on the WHOQOL-BREF questionnaire. Conclusions: Patients with SMA were satisfied with their medical care. Better scores on some questions in more advanced SMA may have been due to better adaptation to disease-related limitations. The presence of single comorbidities did not affect QoL, but a higher number of comorbidities negatively correlated with QoL.
Analysis of Pain and Effectiveness in Digital Block of the First Toe Using Syringe vs. Carpule: Frost’s H vs. Modified Frost’s H Randomized Clinical Trial
Authors: Rayo-Pérez Ana Mª , Rayo-Rosado Rafael , Rayo-Martín Rafael , Reina-Bueno María
Published: July 2024

Background: Currently, there is no scientific evidence regarding pain in the anesthetic block of the first toe according to the method of application. However, clinical evidence has highlighted the use of the carpule due to the low pain it causes during the administration of the anesthetic. Most studies on anesthesia and pain, especially using the carpule and distraction methods, belong to the field of dentistry. Objective: To compare the pain and effectiveness between the anesthetic block of the first toe using a carpule and syringe with Frost’s H technique and the modified Frost’s H technique. Method: A total of 564 subjects were selected and divided into four groups. Subjects were subjected to experimental conditions (randomization through the Random Allocation Software program 2.0), and divided into group 1 = 138 subjects, corresponding to the block with syringe and Frost’s H, group 2 = 141 subjects, corresponding to the syringe group and modified Frost’s H, group 3 = 141 subjects, corresponding to the carpule group and modified Frost’s H, and group 4 = 144 subjects, corresponding to the carpule group and Frost’s H. The same researcher generated the random allocation sequence, enrolled the participants, and assigned them to the interventions. Each subject was unaware of the anesthetic procedure assigned by the researcher. Outcome parameters were pain after anesthetic infiltration and its effectiveness. Results: The anesthetic block with carpule showed a lower pain score compared to the anesthetic block with syringe (2.8 vs. 5.3; p < 0.001). However, when analyzing effectiveness, a higher efficacy rate was obtained in the anesthetic blocks performed using the modified Frost’s H technique (97.5% vs. 88.1%; p < 0.001). Conclusions: The anesthetic block with carpule and the modified Frost’s H technique is less painful and more effective than the traditional anesthetic block.
Robotic Living Donor Hysterectomy for Uterus Transplantation: An Update on Donor and Recipient Outcomes
Authors: Jacques Andrew , Testa Giuliano , Johannesson Liza
Published: July 2024

Background/Objectives: Uterus transplantation (UTx) has evolved into a clinical reality for women with absolute uterine infertility. The international experience with UTx has predominantly utilized living donor grafts—and strategies to minimize harm to donors remain paramount. Robotic living donor hysterectomy represents a minimally invasive approach to facilitate rapid donor recovery, improve pelvic visualization and operative access, and maintain UTx recipient outcomes. The aim of this study is to describe donor, recipient, graft, and pregnancy outcomes after adoption of a robotic living donor hysterectomy program. Methods: The Dallas UtErus Transplant Study (DUETS) incorporated a robotic living donor hysterectomy operative protocol, including transvaginal extraction, from April 2019. Prospectively collected data were analyzed, and a case series presented, to describe donor intra- and post-operative outcomes and recipient intra-operative outcomes, graft viability, established pregnancies, and live births. Early cases were compared to later cases to better describe the learning curve associated with the technique. Results: Sixteen robotic living donor hysterectomies were performed with 100% graft viability after implantation demonstrated by myometrial flow and onset of menses. Early experience (eight cases) demonstrated two cases of ureteric injury. Later experience (eight cases) demonstrated a reduction in operative time (11 h 10 min vs. 6 h 38 min), with no ureteric injuries and a reduction in major operative morbidity from 25% to 12.5% (Clavien–Dindo grade ≥3). At the time of reporting, nine successful live births have occurred, with six ongoing pregnancies. Conclusions: Robotic living donor hysterectomy represents a safe approach to minimize donor harm without compromising UTx recipient, graft, and pregnancy-related outcomes. A learning curve is demonstrated with the adoption of the novel technique—with particularly care required to prevent ureteric injuries, and ongoing vigilance and reporting necessary given the small case numbers of robotic living donor hysterectomy reported internationally.
Noninvasive Quantification of Glucose Metabolism in Mice Myocardium Using the Spline Reconstruction Technique
Authors: Vrachliotis Alexandros , Gaitanis Anastasios , Protonotarios Nicholas E. , Kastis George A. , Costaridou Lena
Published: July 2024

The spline reconstruction technique (SRT) is a fast algorithm based on a novel numerical implementation of an analytic representation of the inverse Radon transform. The purpose of this study was to compare the SRT, filtered back-projection (FBP), and the Tera-Tomo 3D algorithm for various iteration numbers, using small-animal dynamic PET data obtained from a Mediso nanoScan® PET/CT scanner. For this purpose, Patlak graphical kinetic analysis was employed to noninvasively quantify the myocardial metabolic rate of glucose (MRGlu) in seven male C57BL/6 mice (n=7). All analytic reconstructions were performed via software for tomographic image reconstruction. The analysis of all PET-reconstructed images was conducted with PMOD software (version 3.506, PMOD Technologies LLC, Fällanden, Switzerland) using the inferior vena cava as the image-derived input function. Statistical significance was determined by employing the one-way analysis of variance test. The results revealed that the differences between the values of MRGlu obtained via SRT versus FBP, and the variants of he Tera-Tomo 3D algorithm were not statistically significant (p > 0.05). Overall, the SRT appears to perform similarly to the other algorithms investigated, providing a valid alternative analytic method for preclinical dynamic PET studies.
The Effect of Model Input Uncertainty on the Simulation of Typical Pollutant Transport in the Coastal Waters of China
Authors: Wang Nan , Zhao Zihan , Cao Ruichen , Lv Xianqing , Shi Honghua
Published: July 2024

Route planning to evade potential pollution holds critical importance for aquaculture vessels. This study establishes a fish-feed pollutant drift model based on the Lagrangian particle tracking algorithm and designs four sets of sensitivity experiments in the East China Sea. The research investigates the impact of model input uncertainties on the drift trajectory, centroid position, and sweeping area of the fish-feed pollutants. Numerical results indicate that the uncertainty in the background flow field significantly affects the uncertainty in the centroid position and sweeping area in the numerical simulations. Specifically, when a 35% random error is added to the background flow field, the centroid shift distance reaches its maximum, and the sweeping area also attains its largest value. The uncertainty in the background wind field affects the centroid position of particles but to a much lesser extent compared to the background flow field. When considering only the uncertainty of the background wind field, the sweeping area does not significantly differ from the control experiment as the uncertainty of the background wind field increases. The initial release position has little effect on the drift direction of the fish-feed pollutants but does affect the drift distance; it has minimal impact on the trajectory but significantly affects the final position of the pollutant centroid. By analyzing the model uncertainties, this study reveals the key factors influencing the drift of fish-feed pollutants. This information is crucial for aquaculture vessels in planning routes, considering environmental factors, and reducing potential pollution risks.
Response of Cyclonic Eddies to Typhoon Surigae and Their Weakening Effect on the Kuroshio Current in the Western North Pacific Ocean
Authors: Zhang Yanzeng , Han Shuzong
Published: July 2024

This study investigated the dynamic and thermal responses of cyclonic eddies (CEs) to Typhoon Surigae in the western North Pacific Ocean using satellite data and a coupled ocean–atmosphere model. Observations and simulations revealed that the typhoon enhanced the two preexisting CEs (C1 and C2). After the typhoon passed the two eddies, the sea surface height (SSH) lowered and the eddy velocity increased above 200 m. C1 was stretched with elliptical deformation accompanied by an SSH trough and jets on the sides of the typhoon track at the eddy edge. The comparative experiments indicated that the typhoon caused the SSH of C1 and C2 to lower by 53.52% and 25.14% compared to conditions without the typhoon, respectively, and the kinetic energy of C1 and C2 to increase by 12 times and 65.76%, respectively. The positive vorticity anomaly input from the typhoon to the CEs was the main mechanism for the enhancement of the CEs. The enhanced CEs modulated the typhoon-induced sea surface temperature (SST) cooling, causing the temperature within the eddies to decrease by upwelling and mixing, and the SST cooling became significant at the center of the CEs and propagated westward with the eddies. This study also revealed that typhoons can significantly perturb eddy dynamic structures by enhancing or generating cyclonic cold eddies and eradicating anticyclonic eddies, thereby weakening the Kuroshio Current transport via eddy–Kuroshio interactions.
Unveiling the Arsenal of Apple Bitter Rot Fungi: Comparative Genomics Identifies Candidate Effectors, CAZymes, and Biosynthetic Gene Clusters in Colletotrichum Species
Authors: Khodadadi Fatemeh , Luciano-Rosario Dianiris , Gottschalk Christopher , Jurick Wayne M. , Aćimović Srđan G.
Published: July 2024

The bitter rot of apple is caused by Colletotrichum spp. and is a serious pre-harvest disease that can manifest in postharvest losses on harvested fruit. In this study, we obtained genome sequences from four different species, C. chrysophilum, C. noveboracense, C. nupharicola, and C. fioriniae, that infect apple and cause diseases on other fruits, vegetables, and flowers. Our genomic data were obtained from isolates/species that have not yet been sequenced and represent geographic-specific regions. Genome sequencing allowed for the construction of phylogenetic trees, which corroborated the overall concordance observed in prior MLST studies. Bioinformatic pipelines were used to discover CAZyme, effector, and secondary metabolic (SM) gene clusters in all nine Colletotrichum isolates. We found redundancy and a high level of similarity across species regarding CAZyme classes and predicted cytoplastic and apoplastic effectors. SM gene clusters displayed the most diversity in type and the most common cluster was one that encodes genes involved in the production of alternapyrone. Our study provides a solid platform to identify targets for functional studies that underpin pathogenicity, virulence, and/or quiescence that can be targeted for the development of new control strategies. With these new genomics resources, exploration via omics-based technologies using these isolates will help ascertain the biological underpinnings of their widespread success and observed geographic dominance in specific areas throughout the country.
Alternaria alternata Pathogen from Cuscuta japonica Could Serve as a Potential Bioherbicide
Authors: Liu Yinglong , Ahmed Ayesha , Munir Shahzad , Chen Lei , He Pengfei , He Yueqiu , Tang Ping , Kong Baohua , Wu Yixin , He Pengbo
Published: July 2024

Dodder (Cuscuta spp.) is a dangerous parasitic plant that causes serious damage to crop production and is challenging to eliminate. Herbicide application is a common strategy to control dodder in the field, but it is costly, ineffective, and further results in hazardous outcomes. Therefore, our study aims to identify the potential pathogens in naturally occurring dodder infections which may provide efficient biocontrol options. In this regard, the pathogens were isolated from the infected plants, their pathogenicity was validated through inoculation, and the optimal culture conditions for their growth were identified by determining the pathogenicity difference. The pathogenicity range was determined in vitro using the leaves of common horticultural plants and crops. Furthermore, a small range of horticultural plants parasitized by Cuscuta reflexa in the field were inoculated with the pathogen to determine their biosafety and biocontrol potential, and the pathogens were identified by morphological and molecular characterization. We found 7 strains that were isolated after pathogen enrichment culture. Among them, Cbp6 and Cbp7 showed the highest pathogenicity against C. reflexa. After testing the inoculation of more than 50 species of plants, only 9 species showed varying degrees of lesions on leaves, which proved the high biosafety for common plants. Field spraying of these pathogens showed a good control effect on C. reflexa after 21 days; the disease severityreached 66.0%, while its host plant did not display obvious symptoms. In conclusion, the pathogens Cbp6 and Cbp7 were identified as Alternaria alternata, and the results of this study provide a theoretical basis for the biological control of dodder.