bluuebunny/crossref_metadata_2025 huggingface dataset:
Encapsulation of Nanoparticles with Statistical Copolymers with Different Surface Charges and Analysis of Their Interactions with Proteins and Cells
Authors: Megahed Saad , Wutke Nicole , Liu Yang , Klapper Markus , Schulz Florian , Feliu Neus , Parak Wolfgang J.
Published: May 2024

Encapsulation with polymers is a well-known strategy to stabilize and functionalize nanomaterials and tune their physicochemical properties. Amphiphilic copolymers are promising in this context, but their structural diversity and complexity also make understanding and predicting their behavior challenging. This is particularly the case in complex media which are relevant for intended applications in medicine and nanobiotechnology. Here, we studied the encapsulation of gold nanoparticles and quantum dots with amphiphilic copolymers differing in their charge and molecular structure. Protein adsorption to the nanoconjugates was studied with fluorescence correlation spectroscopy, and their surface activity was studied with dynamic interfacial tensiometry. Encapsulation of the nanoparticles without affecting their characteristic properties was possible with all tested polymers and provided good stabilization. However, the interaction with proteins and cells significantly depended on structural details. We identified statistical copolymers providing strongly reduced protein adsorption and low unspecific cellular uptake. Interestingly, different zwitterionic amphiphilic copolymers showed substantial differences in their resulting bio-repulsive properties. Among the polymers tested herein, statistical copolymers with sulfobetaine and phosphatidylcholine sidechains performed better than copolymers with carboxylic acid- and dimethylamino-terminated sidechains.
Editorial for the Special Issue “Recent Advances in Nanomaterials Science”
Authors: Lee Gang Ho
Published: May 2024

Nanoparticles and nanomaterials are important, because they are potentially applicable to energy, storage, bioimaging, biosensors, catalysts, nanomedicine, batteries, solar energy, bioenergy, and so on (Figure 1) [...]
Therapeutic Potential of Bovine Milk-Derived Extracellular Vesicles
Authors: Prasadani Madhusha , Kodithuwakku Suranga , Pennarossa Georgia , Fazeli Alireza , Brevini Tiziana A. L.
Published: May 2024

Milk is a fundamental component of the human diet, owing to its substantial nutritional content. In addition, milk contains nanoparticles called extracellular vesicles (EVs), which have indicated their potential beneficial roles such as cell-to-cell communication, disease biomarkers, and therapeutics agents. Amidst other types of EVs, milk EVs (MEVs) have their significance due to their high abundance, easy access, and stability in harsh environmental conditions, such as low pH in the gut. There have been plenty of studies conducted to evaluate the therapeutic potential of bovine MEVs over the past few years, and attention has been given to their engineering for drug delivery and targeted therapy. However, there is a gap between the experimental findings available and clinical trials due to the many challenges related to EV isolation, cargo, and the uniformity of the material. This review aims to provide a comprehensive comparison of various techniques for the isolation of MEVs and offers a summary of the therapeutic potential of bovine MEVs described over the last decade, analyzing potential challenges and further applications. Although a number of aspects still need to be further elucidated, the available data point to the role of MEVs as a potential candidate with therapeutics potential, and the supplementation of MEVs would pave the way to understanding their in-depth effects.
Antimicrobial Activity of Arthrospira (Former Spirulina) and Dunaliella Related to Recognized Antimicrobial Bioactive Compounds
Authors: Ilieva Yana , Zaharieva Maya Margaritova , Najdenski Hristo , Kroumov Alexander Dimitrov
Published: May 2024

With the increasing rate of the antimicrobial resistance phenomenon, natural products gain our attention as potential drug candidates. Apart from being used as nutraceuticals and for biotechnological purposes, microalgae and phytoplankton have well-recognized antimicrobial compounds and proved anti-infectious potential. In this review, we comprehensively outline the antimicrobial activity of one genus of cyanobacteria (Arthrospira, formerly Spirulina) and of eukaryotic microalgae (Dunaliella). Both, especially Arthrospira, are mostly used as nutraceuticals and as a source of antioxidants for health supplements, cancer therapy and cosmetics. Their diverse bioactive compounds provide other bioactivities and potential for various medical applications. Their antibacterial and antifungal activity vary in a broad range and are strain specific. There are strains of Arthrospira platensis with very potent activity and minimum inhibitory concentrations (MICs) as low as 2–15 µg/mL against bacterial fish pathogens including Bacillus and Vibrio spp. Arthrospira sp. has demonstrated an inhibition zone (IZ) of 50 mm against Staphylococcus aureus. Remarkable is the substantial amount of in vivo studies of Arthrospira showing it to be very promising for preventing vibriosis in shrimp and Helicobacter pylori infection and for wound healing. The innovative laser irradiation of the chlorophyll it releases can cause photodynamic destruction of bacteria. Dunaliella salina has exhibited MIC values lower than 300 µg/mL and an IZ value of 25.4 mm on different bacteria, while Dunaliella tertiolecta has demonstrated MIC values of 25 and 50 μg/mL against some Staphylococcus spp. These values fulfill the criteria for significant antimicrobial activity and sometimes are comparable or exceed the activity of the control antibiotics. The bioactive compounds which are responsible for that action are fatty acids including PUFAs, polysaccharides, glycosides, peptides, neophytadiene, etc. Cyanobacteria, such as Arthrospira, also particularly have antimicrobial flavonoids, terpenes, alkaloids, saponins, quinones and some unique-to-them compounds, such as phycobiliproteins, polyhydroxybutyrate, the peptide microcystin, etc. These metabolites can be optimized by using stress factors in a two-step process of fermentation in closed photobioreactors (PBRs).
Murine iPSC-Loaded Scaffold Grafts Improve Bone Regeneration in Critical-Size Bone Defects
Authors: Kessler Franziska , Arnke Kevin , Eggerschwiler Benjamin , Neldner Yvonne , Märsmann Sonja , Gröninger Olivier , Casanova Elisa A. , Weber Fabienne A. , König Matthias A. , Stark Wendelin J. , Pape Hans-Christoph , Cinelli Paolo , Tiziani Simon
Published: May 2024

In certain situations, bones do not heal completely after fracturing. One of these situations is a critical-size bone defect where the bone cannot heal spontaneously. In such a case, complex fracture treatment over a long period of time is required, which carries a relevant risk of complications. The common methods used, such as autologous and allogeneic grafts, do not always lead to successful treatment results. Current approaches to increasing bone formation to bridge the gap include the application of stem cells on the fracture side. While most studies investigated the use of mesenchymal stromal cells, less evidence exists about induced pluripotent stem cells (iPSC). In this study, we investigated the potential of mouse iPSC-loaded scaffolds and decellularized scaffolds containing extracellular matrix from iPSCs for treating critical-size bone defects in a mouse model. In vitro differentiation followed by Alizarin Red staining and quantitative reverse transcription polymerase chain reaction confirmed the osteogenic differentiation potential of the iPSCs lines. Subsequently, an in vivo trial using a mouse model (n = 12) for critical-size bone defect was conducted, in which a PLGA/aCaP osteoconductive scaffold was transplanted into the bone defect for 9 weeks. Three groups (each n = 4) were defined as (1) osteoconductive scaffold only (control), (2) iPSC-derived extracellular matrix seeded on a scaffold and (3) iPSC seeded on a scaffold. Micro-CT and histological analysis show that iPSCs grafted onto an osteoconductive scaffold followed by induction of osteogenic differentiation resulted in significantly higher bone volume 9 weeks after implantation than an osteoconductive scaffold alone. Transplantation of iPSC-seeded PLGA/aCaP scaffolds may improve bone regeneration in critical-size bone defects in mice.
The Reduction of PSMB4 in T24 and J82 Bladder Cancer Cells Inhibits the Angiogenesis and Migration of Endothelial Cells
Authors: Lin Yi-Hsuan , Chen Tzu-Min , Tsai Yu-Ling , Tsai Wen-Chiuan , Wang Hisao-Hsien , Chen Ying , Wu Sheng-Tang
Published: May 2024

Bladder cancer (BC) is a malignant tumor of the urinary system with high mortality and recurrence rates. Proteasome subunit type 4 (PSMB4) is highly expressed and has been identified as having oncogenic properties in a variety of cancer types. This study aimed to explore the effect of PSMB4 knockdown on the survival, migration, and angiogenesis of human bladder cancer cells with different degrees of malignancy. We analyzed the effects of PSMB4 knockdown in bladder cancer cells and endothelial cells in the tumor microenvironment. PSMB4 was highly expressed in patients with low- and high-grade urothelial carcinoma. Inhibition of PSMB4 reduced protein expression of focal adhesion kinase (FAK) and myosin light chain (MLC), leading to reduced migration. Furthermore, the suppression of PSMB4 decreased the levels of vascular endothelial factor B (VEGF-B), resulting in lower angiogenic abilities in human bladder cancer cells. PSMB4 inhibition affected the migratory ability of HUVECs and reduced VEGFR2 expression, consequently downregulating angiogenesis. In the metastatic animal model, PSMB4 knockdown reduced the relative volumes of lung tumors. Our findings suggest the role of PSMB4 as a potential target for therapeutic strategies against human bladder cancer.
Identification and Expression Profile of NCED Genes in Arachis hypogaea L. during Drought Stress
Authors: Chen Ao , Li Jingyan , Wang Heping , Zhao Puyan
Published: May 2024

Peanut (Arachis hypogaea L.) is an important crop that provides essential proteins and oils for human and animal consumption. 9-cis-epoxycarotenoid dioxygenase (NCED) have been found can play a vital role in abscisic acid (ABA) biosynthesis and may be a response to drought stress. Until now, in Arachis hypogaea, no information about the NCED gene family has been reported and the importance of NCED-related drought tolerance is unclear. In this study, eight NCED genes in Arachis hypogaea, referred to as AhNCEDs, are distributed across eight chromosomes, with duplication events in AhNCED1 and AhNCED2, AhNCED3 and AhNCED4, and AhNCED6 and AhNCED7. Comparative analysis revealed that NCED genes are highly conserved among plant species, including Pisum sativum, Phaseolus vulgaris, Glycine max, Arabidopsis thaliana, Gossypium hirsutum, and Oryza sativa. Further promoter analysis showed AhNCEDs have ABA-related and drought-inducible elements. The phenotyping of Arachis hypogaea cultivars NH5 and FH18 demonstrated that NH5 is drought-tolerant and FH18 is drought-sensitive. Transcriptome expression analysis revealed the differential regulation of AhNCEDs expression in both NH5 and FH18 cultivars under drought stress. Furthermore, compared to the Arachis hypogaea cultivar FH18, the NH5 exhibited a significant upregulation of AhNCED1/2 expression under drought. To sum up, this study provides an insight into the drought-related AhNCED genes, screened out the potential candidates to regulate drought tolerance and ABA biosynthesis in Arachis hypogaea.
EGFR and PI3K Signalling Pathways as Promising Targets on Circulating Tumour Cells from Patients with Metastatic Gastric Adenocarcinoma
Authors: Piper Ann-Katrin , Penney Chelsea , Holliday Jacqueline , Tincknell Gary , Ma Yafeng , Napaki Sarbar , Pantel Klaus , Brungs Daniel , Ranson Marie
Published: May 2024

The prognosis for metastatic gastric adenocarcinoma (mGAC) remains poor. Gene alterations in receptor tyrosine kinases (RTKs) such as epidermal growth factor receptor (EGFR) and their downstream effectors including catalytic subunit alpha of the phosphatidylinositol 3-kinase (PIK3CA) are common in mGAC. Targeted RTK and phosphatidylinositol-3-kinase (PI3K) treatments have demonstrated clinical benefits in other solid tumours and are key potential targets for clinical development against mGAC given the presence of recurrent alterations in these pathways. Furthermore, combination RTK/PI3K treatments may overcome compensatory mechanisms that arise using monotherapies, leading to improved patient outcomes. Herein, we investigated RTK/PI3K single and combination drug responses against our unique human mGAC-derived PIK3CA gain-of-function mutant, human epidermal growth factor receptor 2 (HER2)-negative, EGFR-expressing circulating tumour cell line, UWG02CTC, under two- and three-dimensional culture conditions to model different stages of metastasis. UWG02CTCs were highly responsive to the PI3K p110α-subunit targeted drugs PIK-75 (IC50 = 37.0 ± 11.1 nM) or alpelisib (7.05 ± 3.7 µM). Drug sensitivities were significantly increased in 3D conditions. Compensatory MAPK/ERK pathway upregulation by PI3K/Akt suppression was overcome by combination treatment with the EGFR inhibitor gefitinib, which was strongly synergistic. PIK-75 plus gefitinib significantly impaired UWG02CTC invasion in an organotypic assay. In conclusion, UWG02CTCs are a powerful ex vivo mGAC drug responsiveness model revealing EGFR/PI3K-targeted drugs as a promising combination treatment option for HER2-negative, RAS wild-type mGAC patients.
Macrocephaly and Finger Changes: A Narrative Review
Authors: Lazea Cecilia , Vulturar Romana , Chiș Adina , Encica Svetlana , Horvat Melinda , Belizna Cristina , Damian Laura-Otilia
Published: May 2024

Macrocephaly, characterized by an abnormally large head circumference, often co-occurs with distinctive finger changes, presenting a diagnostic challenge for clinicians. This review aims to provide a current synthetic overview of the main acquired and genetic etiologies associated with macrocephaly and finger changes. The genetic cause encompasses several categories of diseases, including bone marrow expansion disorders, skeletal dysplasias, ciliopathies, inherited metabolic diseases, RASopathies, and overgrowth syndromes. Furthermore, autoimmune and autoinflammatory diseases are also explored for their potential involvement in macrocephaly and finger changes. The intricate genetic mechanisms involved in the formation of cranial bones and extremities are multifaceted. An excess in growth may stem from disruptions in the intricate interplays among the genetic, epigenetic, and hormonal factors that regulate human growth. Understanding the underlying cellular and molecular mechanisms is important for elucidating the developmental pathways and biological processes that contribute to the observed clinical phenotypes. The review provides a practical approach to delineate causes of macrocephaly and finger changes, facilitate differential diagnosis and guide for the appropriate etiological framework. Early recognition contributes to timely intervention and improved outcomes for affected individuals.
Apigenin: Molecular Mechanisms and Therapeutic Potential against Cancer Spreading
Authors: Naponelli Valeria , Rocchetti Maria Teresa , Mangieri Domenica
Published: May 2024

Due to its propensity to metastasize, cancer remains one of the leading causes of death worldwide. Thanks in part to their intrinsic low cytotoxicity, the effects of the flavonoid family in the prevention and treatment of various human cancers, both in vitro and in vivo, have received increasing attention in recent years. It is well documented that Apigenin (4′,5,7-trihydroxyflavone), among other flavonoids, is able to modulate key signaling molecules involved in the initiation of cancer cell proliferation, invasion, and metastasis, including JAK/STAT, PI3K/Akt/mTOR, MAPK/ERK, NF-κB, and Wnt/β-catenin pathways, as well as the oncogenic non-coding RNA network. Based on these premises, the aim of this review is to emphasize some of the key events through which Apigenin suppresses cancer proliferation, focusing specifically on its ability to target key molecular pathways involved in angiogenesis, epithelial-to-mesenchymal transition (EMT), maintenance of cancer stem cells (CSCs), cell cycle arrest, and cancer cell death.
Effect of Applying 1% Metformin on Guided Bone Regeneration Processes with Bovine-Derived Xenografts
Authors: Montalbán-Vadillo Oier , Pérez-Pevida Esteban , Viteri-Agustín Iratxe , Chávarri-Prado David , Estrada-Martínez Alejandro , Diéguez-Pereira Markel , Sánchez-Lasheras Fernando , Brizuela-Velasco Aritza
Published: May 2024

Background: Although xenografts have shown successful results in GBR procedures due to their osteoconductive properties, many authors have opted to add co-adjuvant drugs to favor osteogenesis and differentiate cells into an osteoblastic lineage. Metformin has been shown to have bone-protective properties, regulating osteoclast differentiation, as well as the ability to promote osteoblast mineralization and differentiation. The present study aimed to evaluate the effect of the local application of a 1% metformin solution on bone neoformation in the treatment of an experimental bone defect in a guided bone regeneration animal model with a particulated bovine hydroxyapatite xenograft with hyaluronate. Methods: With this purpose in mind, two critical defects with 8 mm diameter and 0.5 mm depth were created in eight male New Zealand rabbit calvarias. Titanium cylinders were fixed in each defect and filled with particulate hydroxyapatite of bovine origin and sodium hyaluronate, with sterile injectable saline added to the control group and sterile 1% metformin solution added to the test group. At 6 weeks, the animals were euthanized, and samples were obtained and prepared for histomorphometric analysis. Results: A higher percentage of new bone formation was observed in the metformin samples than in the control samples, both in the region closest to the animal’s calvaria and in the most distal region analyzed. A higher average bone–biomaterial contact percentage was observed in the samples, with metformin in both the proximal and distal regions. There was no statistically significant difference in the mean value in either region in both parameters. Conclusion: The local application of a 1% metformin solution in an animal model of guided bone regeneration with particulate bovine hydroxyapatite and hyaluronate resulted in greater bone neoformation and xenograft osseointegration than in the control group.
Impacts of ADHD Symptomatology on the Response to Cognitive-Behavioural Therapy with Gilles de la Tourette Syndrome Patients
Authors: Mazur-Lainé Emmanuelle , Soubata Houda , Leclerc Julie B. , Blanchet Pierre J. , O’Connor Kieron P. , Lavoie Marc E.
Published: May 2024

(1) Background: Gilles de la Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics. Attention deficit and hyperactivity disorder (ADHD) is a common comorbidity of TS that adds further impairment. Cognitive-behavioural therapy (CBT) has shown efficacy in treating tics, yet its effectiveness in individuals with TS and comorbid ADHD remains unclear. Also, it is suggested that ADHD characteristics like executive dysfunction and inattention could hinder the response to CBT. This study aims to compare the response to CBT for tics and its maintenance six months post-therapy among TS individuals with and without ADHD symptoms. (2) Methods: In this study, 55 TS participants who completed 14-week CBT for tics were split into high (TS+) or low (TS−) ADHD symptomatology groups. Outcomes were evaluated using the Yale Global Tic Severity Scale (YGTSS) regarding global tic severity and motor and vocal tic frequency post-CBT and at a 6-month follow-up. (3) Results: No significant group difference was found regarding improvements post-CBT (n = 55), nor the maintenance six months later (n = 45). (4) Conclusions: ADHD symptoms may not hinder the response to CBT or its maintenance, suggesting that TS individuals with ADHD symptoms may not require specialized CBT interventions.
Pulsed Field Energy in Atrial Fibrillation Ablation: From Physical Principles to Clinical Applications
Authors: Pierucci Nicola , Mariani Marco Valerio , Laviola Domenico , Silvetti Giacomo , Cipollone Pietro , Vernile Antonio , Trivigno Sara , La Fazia Vincenzo Mirco , Piro Agostino , Miraldi Fabio , Vizza Carmine Dario , Lavalle Carlo
Published: May 2024

Atrial fibrillation, representing the most prevalent sustained cardiac arrhythmia, significantly impacts stroke risk and cardiovascular mortality. Historically managed with antiarrhythmic drugs with limited efficacy, and more recently, catheter ablation, the interventional approach field is still evolving with technological advances. This review highlights pulsed field ablation (PFA), a revolutionary technique gaining prominence in interventional electrophysiology because of its efficacy and safety. PFA employs non-thermal electric fields to create irreversible electroporation, disrupting cell membranes selectively within myocardial tissue, thus preventing the non-selective damage associated with traditional thermal ablation methods like radiofrequency or cryoablation. Clinical studies have consistently shown PFA’s ability to achieve pulmonary vein isolation—a cornerstone of AF treatment—rapidly and with minimal complications. Notably, PFA reduces procedure times and has shown a lower incidence of esophageal and phrenic nerve damage, two common concerns with thermal techniques. Emerging from oncological applications, the principles of electroporation provide a unique tissue-selective ablation method that minimizes collateral damage. This review synthesizes findings from foundational animal studies through to recent clinical trials, such as the MANIFEST-PF and ADVENT trials, demonstrating PFA’s effectiveness and safety. Future perspectives point towards expanding indications and refinement of techniques that promise to improve AF management outcomes further. PFA represents a paradigm shift in AF ablation, offering a safer, faster, and equally effective alternative to conventional methods. This synthesis of its development and clinical application outlines its potential to become the new standard in AF treatment protocols.
The Role of Prognostic Scores in Assessing the Prognosis of Patients Admitted in the Cardiac Intensive Care Unit: Emphasis on Heart Failure Patients
Authors: Rammos Aidonis , Bechlioulis Aris , Chatzipanteliadou Stefania , Sioros Spyros Athanasios , Floros Christos D. , Stamou Ilektra , Lakkas Lampros , Kalogeras Petros , Bouratzis Vasileios , Katsouras Christos S. , Michalis Lampros K. , Naka Katerina K.
Published: May 2024

Background/Objectives: Patient care in Cardiac Intensive Care Units (CICU) has evolved but data on patient characteristics and outcomes are sparse. This retrospective observational study aimed to define clinical characteristics and risk factors of CICU patients, their in-hospital and 30-day mortality, and compare it with established risk scores. Methods: Consecutive patients (n = 294, mean age 70 years, 74% males) hospitalized within 15 months were studied; APACHE II, EHMRG, GWTG-HF, and GRACE II were calculated on admission. Results: Most patients were admitted for ACS (48.3%) and acute decompensated heart failure (ADHF) (31.3%). Median duration of hospitalization was 2 days (IQR = 1, 4). In-hospital infection occurred in 20%, 18% needed mechanical ventilation, 10% renal replacement therapy and 4% percutaneous ventricular assist devices (33%, 29%, 20% and 4%, respectively, for ADHF). In-hospital and 30-day mortality was 18% and 11% for all patients (29% and 23%, respectively, for ADHF). Established scores (especially APACHE II) had a good diagnostic accuracy (area under the curve-AUC). In univariate and multivariate analyses in-hospital intubation and infection, history of coronary artery disease, hypotension, uremia and hypoxemia on admission were the most important risk factors. Based on these, a proposed new score showed a diagnostic accuracy of 0.954 (AUC) for in-hospital mortality, outperforming previous scores. Conclusions: Patients are admitted mainly with ACS or ADHF, the latter with worse prognosis. Several patients need advanced support; intubation and infections adversely affect prognosis. Established scores predict mortality satisfactorily, but larger studies are needed to develop CICU-directed scores to identify risk factors, improve prediction, guide treatment and staff training.
Association between Female Reproductive Factors and Risk of Dementia
Authors: Pszczołowska Magdalena , Walczak Kamil , Miśków Weronika , Mroziak Magdalena , Kozłowski Gracjan , Beszłej Jan Aleksander , Leszek Jerzy
Published: May 2024

Women have an over 50% greater risk of dementia than men, which is a main topic of much research. This review aims to investigate the impact of a woman’s reproductive history on dementia risk. The consequences of stillbirth are long-term health and psychosocial problems for women. Because of the awareness of an endangered pregnancy, many parents experience deep anxiety and stress in subsequent pregnancies. There are contradictory conclusions from research about abortion and the risk of dementia correlation. When it comes to the late age of first birth, which is said to be above 35 years old, it was observed that older mothers have a decreased risk of dementia compared to those who gave birth in their 20s; however, being a child of the older mother is connected with a higher risk of developing dementia. Using hormonal contraception can result in decreased risk of dementia as estrogen stimulates microglia-related Aβ removal and reduces tau hyperphosphorylation. The influence of postmenopausal hormonal therapy and the duration of the reproductive period on developing dementia remains unclear. Although female disorders like endometriosis and polycystic ovary syndrome are reported to increase the risk of dementia, the research on this topic is very limited, especially when it comes to endometriosis, and needs further investigation. Interestingly, there is no conclusion on whether hypertensive disorders of pregnancy increase the risk of dementia, but most articles seem to confirm this theory.
Challenges of Managing Type 3c Diabetes in the Context of Pancreatic Resection, Cancer and Trauma
Authors: Wayne Colton D. , Benbetka Chahrazed , Besner Gail E. , Narayanan Siddharth
Published: May 2024

Type 3c diabetes mellitus (T3cDM), also known as pancreatogenic or pancreoprivic diabetes, is a specific type of DM that often develops as a result of diseases affecting the exocrine pancreas, exhibiting an array of hormonal and metabolic characteristics. Several pancreatic exocrine diseases and surgical procedures may cause T3cDM. Diagnosing T3cDM remains difficult as the disease characteristics frequently overlap with clinical presentations of type 1 DM (T1DM) or type 2 DM (T2DM). Managing T3cDM is likewise challenging due to numerous confounding metabolic dysfunctions, including pancreatic endocrine and exocrine insufficiencies and poor nutritional status. Treatment of pancreatic exocrine insufficiency is of paramount importance when managing patients with T3cDM. This review aims to consolidate the latest information on surgical etiologies of T3cDM, focusing on partial pancreatic resections, total pancreatectomy, pancreatic cancer and trauma.
The Clinical Management of Electrical Stimulation Therapies in the Rehabilitation of Individuals with Spinal Cord Injuries
Authors: Dolbow David R. , Bersch Ines , Gorgey Ashraf S. , Davis Glen M.
Published: May 2024

Background: People with spinal cord injuries (SCIs) often have trouble remaining active because of paralysis. In the past, exercise recommendations focused on the non-paralyzed muscles in the arms, which provides limited benefits. However, recent studies show that electrical stimulation can help engage the paralyzed extremities, expanding the available muscle mass for exercise. Methods: The authors provide an evidence-based approach using expertise from diverse fields, supplemented by evidence from key studies toward the management of electrical stimulation therapies in individuals with SCIs. Literature searches were performed separately using the PubMed, Medline, and Google Scholar search engines. The keywords used for the searches included functional electrical stimulation cycling, hybrid cycling, neuromuscular electrical stimulation exercise, spinal cord injury, cardiovascular health, metabolic health, muscle strength, muscle mass, bone mass, upper limb treatment, diagnostic and prognostic use of functional electrical stimulation, tetraplegic hands, and hand deformities after SCI. The authors recently presented this information in a workshop at a major rehabilitation conference. Additional information beyond what was presented at the workshop was added for the writing of this paper. Results: Functional electrical stimulation (FES) cycling can improve aerobic fitness and reduce the risk of cardiovascular and metabolic diseases. The evidence indicates that while both FES leg cycling and neuromuscular electrical stimulation (NMES) resistance training can increase muscle strength and mass, NMES resistance training has been shown to be more effective for producing muscle hypertrophy in individual muscle groups. The response to the electrical stimulation of muscles can also help in the diagnosis and prognosis of hand dysfunction after tetraplegia. Conclusions: Electrical stimulation activities are safe and effective methods for exercise and testing for motor neuron lesions in individuals with SCIs and other paralytic or paretic conditions. They should be considered part of a comprehensive rehabilitation program in diagnosing, prognosing, and treating individuals with SCIs to improve function, physical activity, and overall health.
Supplementing Best Care with Specialized Rehabilitation Treatment in Parkinson’s Disease: A Retrospective Study by Different Expert Centers
Authors: Ghilardi Maria Felice , Quartarone Angelo , Di Rocco Alessandro , Calabrò Rocco Salvatore , Luo Sheng , Liu Hongliang , Norcini Monica , Canesi Margherita , Cian Veronica , Zarucchi Marianna , Ortelli Paola , Volpe Daniele , Bakdounes Leila , Castelli Davide , Di Fonzo Alessio , Franco Giulia , Frattini Emanuele , Avanzino Laura , Pelosin Elisa , Ogliastro Carla , Ceravolo Roberto , Palermo Giovanni , Tommasini Luca , Frosini Daniela , Parnetti Lucilla , Tambasco Nicola , Nigro Pasquale , Simoni Simone , Schmidt Peter
Published: May 2024

Background: This is a retrospective longitudinal study comparing 374 patients with Parkinson’s disease (PD) who were treated in centers offering a specialized program of enhanced rehabilitation therapy in addition to expert outpatient care to 387 patients with PD, who only received expert outpatient care at movement disorders centers in Italy. Methods: The data are from subjects recruited in the Parkinson’s Outcome Project (POP) at six Italian centers that are part of a multicenter collaboration for care quality improvement (the Fresco Network). The effects were measured with a baseline and a follow-up clinical evaluation of the Timed-Up-and-Go test (TUG), Parkinson’s Disease Questionnaire (PDQ-39), and Multidimensional Caregiver Strain Index (MCSI), the number of falls and hospitalizations for any cause. We used a generalized linear mixed model with the dependent variables being the response variable, which included the covariates demographics, evaluation, and treatment variables. Results: We found that the subjects who underwent specialized enhanced rehabilitation had a better motor outcome over time than those who were managed by expert neurologists but had participated in community programs for exercise and other allied health interventions. The greatest effects were seen in patients in the early stages of the disease with a high amount of vigorous exercise per week in the last six months. Similar effects were seen for PDQ39, MCSI, the number of falls, and hospitalization. Conclusions: Long-term benefits to motor function and the quality of life in patients with PD and burden reduction in their caregivers can be achieved through a systematic program of specialized enhanced rehabilitation interventions.
Comparing Outcomes of Community-Acquired Pneumonia Patients Discharged from General Medicine and Respiratory Units in Australia: A Propensity Score-Matched Analysis
Authors: Sharma Yogesh , Mangoni Arduino A. , Shahi Rashmi , Horwood Chris , Thompson Campbell
Published: May 2024

Background/Objectives: Community-acquired pneumonia (CAP) is a common emergency presentation in Australia, with the choice of admitting specialty unit often influenced by pneumonia severity and comorbidities. However, it remains unclear whether there are between-specialty differences in patient characteristics and outcomes. We sought to address this issue by investigating the characteristics and outcomes of CAP patients admitted to General Medicine (GM) versus Respiratory units. Methods: This retrospective observational study utilised data from the two largest metropolitan hospitals in South Australia, encompassing all non-COVID-19-related CAP admissions throughout 2021 to 2023. The hospital length of stay (LOS), in-patient and 30-day mortality, and 30-day readmission rates were assessed by propensity score matching (PSM) using 17 variables. Results: Of the 3004 cases of non-COVID-19 CAP admitted across the two hospitals during the study period, 2673 (71.8%) were admitted under GM units and 331 (9.1%) under Respiratory units. GM patients were, on average, a decade older, presented with a significantly higher burden of comorbidities, exhibited a greater prevalence of frailty, and had higher pneumonia severity compared to those admitted under a Respiratory unit (p < 0.05). Unadjusted analysis revealed a shorter median LOS among GM-admitted patients (5.9 vs. 4.1 days, p < 0.001). After PSM adjustment, patients admitted under the Respiratory units had an 8-fold higher odds of a longer LOS compared to GM (adjusted odds ratio [aOR] 8.53, 95% CI 1.96–37.25, p = 0.004). Other clinical outcomes were comparable between the two groups. Conclusions: Our findings indicate that GM units compared to Respiratory units provide efficient and safe care for patients requiring hospitalisation for CAP.
Artificial Intelligence and Colposcopy: Automatic Identification of Cervical Squamous Cell Carcinoma Precursors
Authors: Mascarenhas Miguel , Alencoão Inês , Carinhas Maria João , Martins Miguel , Cardoso Pedro , Mendes Francisco , Fernandes Joana , Ferreira João , Macedo Guilherme , Zulmira Macedo Rosa
Published: May 2024

Background/Objectives: Proficient colposcopy is crucial for the adequate management of cervical cancer precursor lesions; nonetheless its limitations may impact its cost-effectiveness. The development of artificial intelligence models is experiencing an exponential growth, particularly in image-based specialties. The aim of this study is to develop and validate a Convolutional Neural Network (CNN) for the automatic differentiation of high-grade (HSIL) from low-grade dysplasia (LSIL) in colposcopy. Methods: A unicentric retrospective study was conducted based on 70 colposcopy exams, comprising a total of 22,693 frames. Among these, 8729 were categorized as HSIL based on histopathology. The total dataset was divided into a training (90%, n = 20,423) and a testing set (10%, n = 2270), the latter being used to evaluate the model’s performance. The main outcome measures included sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and the area under the receiving operating curve (AUC-ROC). Results: The sensitivity was 99.7% and the specificity was 98.6%. The PPV and NPV were 97.8% and 99.8%, respectively. The overall accuracy was 99.0%. The AUC-ROC was 0.98. The CNN processed 112 frames per second. Conclusions: We developed a CNN capable of differentiating cervical cancer precursors in colposcopy frames. The high levels of accuracy for the differentiation of HSIL from LSIL may improve the diagnostic yield of this exam
Docking Proteins Upregulate IL-1β Expression in Lower Esophageal Sphincter Muscle in Esophageal Achalasia
Authors: Kanda Tsutomu , Saiki Karen , Kurumi Hiroki , Yoshida Akira , Ikebuchi Yuichiro , Sakaguchi Takuki , Urabe Shigetoshi , Minami Hitomi , Yamaguchi Naoyuki , Nakao Kazuhiko , Inoue Haruhiro , Isomoto Hajime
Published: May 2024

Background/Objectives: Esophageal achalasia is an archetypal esophageal motility disorder characterized by abnormal peristalsis of the esophageal body and impaired lower esophageal sphincter (LES) relaxation. Methods: In this study, the mRNA expression of docking proteins 1 and 2 (DOK1 and DOK2, respectively) were analyzed and the mechanisms underlying achalasia onset were investigated. Results: DOK1 and DOK2 mRNA levels significantly increased in the LES of patients with achalasia. Moreover, significant correlations were observed between IL-1β and DOK1, IL-1β and DOK2, ATG16L1 and DOK1, and HSV1-miR-H1-3p and DOK2 expression levels. However, a correlation between ATG16L1 and DOK2 or between HSV-miR-H1-3p and DOK1 expression was not observed. In addition, a positive correlation was observed between patient age and DOK1 expression. Microarray analysis revealed a significant decrease in the expression of hsa-miR-377-3p and miR-376a-3p in the LES muscle of patients with achalasia. Conclusions: These miRNAs possessed sequences targeting DOK. The upregulation of DOK1 and DOK2 expression induces IL-1β expression in the LES of achalasia patients, which may contribute to the development of esophageal motility disorder.
Predictive Factors of Anxiety and Depression in Patients with Type 2 Diabetes Mellitus
Authors: Albai Oana , Timar Bogdan , Braha Adina , Timar Romulus
Published: May 2024

Background: Diabetes mellitus (DM) is a chronic condition associated with multiple complications and comorbidities. Some of these comorbidities are anxiety and depression, with a negative impact on the quality of life, non-adherence to treatment, and poor prognosis. The main aim of this study was to evaluate depression and anxiety in a group of patients with DM and their impact on quality of life and identify factors that improve the prognosis and increase the life expectancy and quality of life of patients with DM. Methods: A total of 209 patients with type 2 DM (T2DM) were enrolled cross-sectionally. Patients were screened for psychiatric disorders, cognitive impairment, and metabolic parameters. Results: Included patients had a median age of 66.0 (58; 70) years, a median DM duration of 9 (6; 15) years, and a suboptimal glycemic control reflected by a median HbA1c of 7.8 (7; 9.2) mg/dL. Patients presented anxiety at different stages in 51.5% of cases, and similarly, depression in 37.5% of cases. Age, duration of DM, HbA1c, and postprandial hyperglycemia (PPG) were predictive factors for anxiety and depression in patients with T2DM. An age > 57 years (sensitivity 84.3, specificity 33.7, AUROC 0.621, p = 0.002) and an HbA1c > 8.5% (sensitivity 45.8, specificity 83.1, AUROC = 0.635, p < 0.0001) predict a higher rate of anxiety, respectively, of depression in these patients. Conclusions: Patients with T2DM have an increased rate of anxiety and depression due to persistent hyperglycemia and aging, which is expressed in a lower quality of life.
Complementary Thoracic Endovascular Aortic Repair (TEVAR) after Frozen Elephant Trunk for Residual Type A Aortic Dissection: Perioperative and Mid-Term Outcomes
Authors: Mylonas Spyridon N. , Mammadov Ravan , Dorweiler Bernhard
Published: May 2024

Objectives: The aim of this retrospective study was to evaluate the results of complementary TEVAR following the frozen elephant trunk (FET) procedure for patients with residual type A aortic dissection (rTAAD) in terms of technical feasibility, safety and mid-term outcomes. Methods: This was a retrospective single-centre analysis of patients who received TEVAR after FET for rTAAD from January 2012 up to December 2021. The primary endpoint was technical success. Safety parameters included 30-day/in-hospital morbidity and mortality. Furthermore, mid-term clinical and morphological outcomes were evaluated. Results: Among 587 TEVAR procedures, 60 patients (11 with connective tissue disorders) who received TEVAR after FET for rTAAD were identified. The median interval between FET and TEVAR was 28.5 months. Indications for TEVAR after FET were true lumen collapse distal to FET prosthesis (n = 7), dSINE (n = 2), planned completion (n = 13) and aortic diameter progression (n = 38). In forty-seven patients, TEVAR was performed in an elective setting; eight and six patients were operated on in an urgent or emergency setting, respectively. All TEVAR procedures were successfully completed. The 30-day mortality and spinal cord ischemia rates were 1.7%. During a median follow-up of 37 months, two further patients died. Nine patients had to undergo a further aortic intervention: fenestrated stent-graft (n = 3) or open repair of the infrarenal abdominal aorta (n = 6). Conclusions: Complementary TEVAR following FET for rTAAD showed excellent technical success and low perioperative risk, supporting the feasibility and safety of this strategy. Despite the favourable mid-term survival, certain patients might require a further aortic procedure.
Outcomes of Corneal Compound Myopic Astigmatism with Presbyopia by Zeiss PRESBYOND® Laser Blended Vision LASIK Using Default CRS-Master® Target Refractions for Reduced Anisometropia
Authors: Hernández-Lucena Julia , Alonso-Aliste Federico , Amián-Cordero Jonatan , Sánchez-González José-María
Published: May 2024

Background/Objectives: Presbyopia, a common age-related refractive error, affects over a billion people globally and significantly impacts daily life. Methods: This retrospective study analyzed 288 eyes of 144 patients undergoing LBV PRESBYOND® treatment for myopic presbyopia with astigmatism, aiming to evaluate precision, efficacy, safety, and stability over six months. Results: Key findings include high efficacy, with 99% of distance-eyes achieving uncorrected distance visual acuity (UDVA) of 20/25 or better, and 85% of near-eyes achieving UDVA of 20/32 or better. The results show excellent refractive outcomes, with 99% of long-sighted eyes and 97% of near-sighted eyes having a postoperative spherical equivalent within ±1.00 D. Safety was demonstrated by no loss of two or more Snellen lines after treatment, with 94% of patients maintaining corrected distance visual acuity (CDVA) before and after surgery. Conclusions: Overall, LBV PRESBYOND® proved effective, safe, and well tolerated for myopic presbyopia correction, offering satisfactory visual outcomes and potential spectacle independence for various distances. This study underscores the importance of individualized treatment based on patient age, highlighting the positive impact of binocular summation on visual function. This study contributes to the growing body of evidence supporting LBV PRESBYOND® as a viable option for addressing presbyopic myopia, offering insights into its efficacy and safety profile. Further research could explore postoperative stereopsis and long-term outcomes to enhance understanding and refine treatment protocols.
Stress, Dysregulation of Rhythms, and Bipolar Disorder: A Challenging Field of Research
Authors: Carta Mauro Giovanni , Karam Elie Georges , Cossu Giulia
Published: May 2024

Clarifying the mechanisms by which circadian rhythms regulate biology is a central issue in directing life choices in the immediate future and presents an interesting challenge for current scientific research [...]
Mechanism of Vegetation Greenness Change and Its Correlation with Terrestrial Water Storage in the Tarim River Basin
Authors: Xia Tingting , Xue Xuan , Wang Haowei , Zhu Zhen , Li Zhi , Wang Yang
Published: May 2024

The response of dryland vegetation to climate change is particularly sensitive in the context of global climate change. This paper analyzes the characteristics of spatial and temporal dynamics of vegetation cover in the Tarim River Basin, China, and its driving factors in order to investigate the response of vegetation growth to water storage changes in the basin. The Enhanced Vegetation Index (EVI), the GRACE gravity satellite, and meteorological data from 2002 to 2022 are used to decipher the characteristics of the response of water storage changes to vegetation changes, which is of great significance to the realization of regional ecological development and sustainable development. The results of the study show the following: (1) The vegetation in the Tarim River Basin has an overall increasing trend, which is mainly distributed in the Aksu Basin and the Weigangkuche River Basin and is spatially distributed in the form of a ring. (2) Vegetation distribution greatly improved during the 20-year study period, dominated by high-cover vegetation, with a change rate of 200.36%. Additionally, vegetation changes are centered on the watersheds and expand to the surrounding area, with a clear increase in vegetation in the Kumukuri Basin. Areas with a vegetation Hurst index of <0.5 account for 63.27% of the study area, and the areas with a continuous decrease were mainly located in the outer contour area of the Tarim River and Kumu Kuri Basins. (3) There are obvious spatial differences in the correlation between EVI and temperature and precipitation elements. The proportion of areas with positive correlation with temperature within the study area is 64.67%. EVI tends to be consistent with the direction of migration of the center of gravity of the population and GDP, and the areas with positive correlation between vegetation and terrestrial water reserves are mainly distributed in the northern slopes of the Kunlun Mountains, with an area proportion of about 50.513%. The Kumukuli Basin also shows significantly positive correlation.
Legislative Foundations: Exploring Land Take Laws and Urban Regeneration Policies in Italy and Europe
Authors: Felli Annamaria , Zullo Francesco
Published: May 2024

Soil is now a central issue on the European as well as the national political agenda, as it represents a fundamental ecosystem for human survival on the planet. Today, more than ever, its protection and proper use in various contexts (agricultural, natural, urban) require stringent policies that can be implemented immediately. The difficult reversibility of urban transformations is the main threat to the ecosystem integrity of soil. Starting from this statement, the main objective of the proposed work is to analyze how the main European countries (Italy, France, Germany, and Spain) are addressing the issue of the goal of zero net land take by 2050 by examining the current laws and strategies. The results highlight how the regulatory aspect plays a key role in managing the phenomenon and how the absence of a national framework law can generate strong distortions and different interpretations of the soil ecosystem. The analysis of the Nature Restoration Law, adopted by the European Commission in July 2023, enables us to assess whether the regulations and measures adopted by the major European countries align with the European Union’s trends. Through a comparative perspective, the study aims to contribute to a comprehensive understanding of sustainable development practices and provide valuable insights for policymakers, urban planners, and academics.