bluuebunny/crossref_metadata_2025 huggingface dataset:
Leucine-Rich Glioma-Inactivated 1 (LGI1) Protein Stimulates Proliferation and IL-10 Production in Peripheral Blood Mononuclear Cells of Patients with LGI1 Antibody-Mediated Autoimmune Encephalitis In Vitro
Authors: Goihl Alexander , Reinhold Dirk , Reinhold Annegret , Schraven Burkhart , Körtvelyessy Peter
Published: February 2024

Limbic encephalitis (LE) due to anti-leucine-rich glioma-inactivated 1 (LGI1) antibodies is an autoimmune disease characterized by distinct clinical features unique to LGI1 LE, such as faciobrachial dystonic seizures. However, it is unclear whether an additional disease-related LGI1 antigen-specific T cell response is involved in the pathogenesis of this disease. To address this question, we studied the effect of recombinant LGI1 on the proliferation and effector-specific cytokine production (IFN-γ, IL-5, IL-10, and IL-17) of peripheral blood mononuclear cells (PBMCs) from patients with LGI1 LE and healthy controls. We observed that recombinant LGI1 stimulated the proliferation of PBMCs from patients with LGI1 LE, but not from healthy controls. Cytokine measurement of cell culture supernatants from PBMCs incubated with recombinant LGI1 revealed a highly significant increase in IL-10 release in PBMCs from patients with LGI1 LE in comparison with healthy controls. These results suggest that LGI1-mediated stimulation of PBMCs from patients with LGI1 LE leads to the establishment of an IL-10-dominated immunosuppressive cytokine milieu, which may inhibit Th1 differentiation and support B cell proliferation, IgG production, and IgG subclass switching.
The Predictive Value of Gut Microbiota Composition for Sustained Immunogenicity following Two Doses of CoronaVac
Authors: Ng Ho-Yu , Liao Yunshi , Zhang Ruiqi , Chan Kwok-Hung , To Wai-Pan , Hui Chun-Him , Seto Wai-Kay , Leung Wai K. , Hung Ivan F. N. , Lam Tommy T. Y. , Cheung Ka-Shing
Published: February 2024

CoronaVac immunogenicity decreases with time, and we aimed to investigate whether gut microbiota associate with longer-term immunogenicity of CoronaVac. This was a prospective cohort study recruiting two-dose CoronaVac recipients from three centres in Hong Kong. We collected blood samples at baseline and day 180 after the first dose and used chemiluminescence immunoassay to test for neutralizing antibodies (NAbs) against the receptor-binding domain (RBD) of wild-type SARS-CoV-2 virus. We performed shotgun metagenomic sequencing performed on baseline stool samples. The primary outcome was the NAb seroconversion rate (seropositivity defined as NAb ≥ 15AU/mL) at day 180. Linear discriminant analysis [LDA] effect size analysis was used to identify putative bacterial species and metabolic pathways. A univariate logistic regression model was used to derive the odds ratio (OR) of seropositivity with bacterial species. Of 119 CoronaVac recipients (median age: 53.4 years [IQR: 47.8–61.3]; male: 39 [32.8%]), only 8 (6.7%) remained seropositive at 6 months after vaccination. Bacteroides uniformis (log10LDA score = 4.39) and Bacteroides eggerthii (log10LDA score = 3.89) were significantly enriched in seropositive than seronegative participants. Seropositivity was associated with B. eggerthii (OR: 5.73; 95% CI: 1.32–29.55; p = 0.022) and B. uniformis with borderline significance (OR: 3.27; 95% CI: 0.73–14.72; p = 0.110). Additionally, B. uniformis was positively correlated with most enriched metabolic pathways in seropositive vaccinees, including the superpathway of adenosine nucleotide de novo biosynthesis I (log10LDA score = 2.88) and II (log10LDA score = 2.91), as well as pathways related to vitamin B biosynthesis, all of which are known to promote immune functions. In conclusion, certain gut bacterial species (B. eggerthii and B. uniformis) and metabolic pathways were associated with longer-term CoronaVac immunogenicity.
Deletion of Gadd45a Expression in Mice Leads to Cognitive and Synaptic Impairment Associated with Alzheimer’s Disease Hallmarks
Authors: Griñán-Ferré Christian , Jarne-Ferrer Júlia , Bellver-Sanchis Aina , Ribalta-Vilella Marta , Barroso Emma , Salvador Jesús M. , Jurado-Aguilar Javier , Palomer Xavier , Vázquez-Carrera Manuel , Pallàs Mercè
Published: February 2024

Gadd45 genes have been implicated in survival mechanisms, including apoptosis, autophagy, cell cycle arrest, and DNA repair, which are processes related to aging and life span. Here, we analyzed if the deletion of Gadd45a activates pathways involved in neurodegenerative disorders such as Alzheimer’s Disease (AD). This study used wild-type (WT) and Gadd45a knockout (Gadd45a−/−) mice to evaluate AD progression. Behavioral tests showed that Gadd45a−/− mice presented lower working and spatial memory, pointing out an apparent cognitive impairment compared with WT animals, accompanied by an increase in Tau hyperphosphorylation and the levels of kinases involved in its phosphorylation in the hippocampus. Moreover, Gadd45a−/− animals significantly increased the brain’s pro-inflammatory cytokines and modified autophagy markers. Notably, neurotrophins and the dendritic spine length of the neurons were reduced in Gadd45a−/− mice, which could contribute to the cognitive alterations observed in these animals. Overall, these findings demonstrate that the lack of the Gadd45a gene activates several pathways that exacerbate AD pathology, suggesting that promoting this protein’s expression or function might be a promising therapeutic strategy to slow down AD progression.
Gengricin®: A Nutraceutical Formulation for Appetite Control and Therapeutic Weight Management in Adults Who Are Overweight/Obese
Authors: Schiano Elisabetta , Iannuzzo Fortuna , Stornaiuolo Mariano , Guerra Fabrizia , Tenore Gian Carlo , Novellino Ettore
Published: February 2024

In the field of nutritional science and metabolic disorders, there is a growing interest in natural bitter compounds capable of interacting with bitter taste receptors (TAS2Rs) useful for obesity management and satiety control. This study aimed to evaluate the effect of a nutraceutical formulation containing a combination of molecules appropriately designed to simultaneously target and stimulate these receptors. Specifically, the effect on CCK release exerted by a multi-component nutraceutical formulation (Cinchona bark, Chicory, and Gentian roots in a 1:1:1 ratio, named Gengricin®) was investigated in a CaCo-2 cell line, in comparison with Cinchona alone. In addition, these nutraceutical formulations were tested through a 3-month randomized controlled trial (RCT) conducted in subjects who were overweight–obese following a hypocaloric diet. Interestingly, the Gengricin® group exhibited a significant greater weight loss and improvement in body composition than the Placebo and Cinchona groups, indicating its effectiveness in promoting weight regulation. Additionally, the Gengricin® group reported higher satiety levels and a significant increase in serum CCK levels, suggesting a physiological basis for the observed effects on appetite control. Overall, these findings highlight the potential of natural nutraceutical strategies based on the combination of bitter compounds in modulating gut hormone release for effective appetite control and weight management.
Evaluating the Therapeutic Potential of Curcumin and Synthetic Derivatives: A Computational Approach to Anti-Obesity Treatments
Authors: Moetlediwa Marakiya T. , Jack Babalwa U. , Mazibuko-Mbeje Sithandiwe E. , Pheiffer Carmen , Titinchi Salam J. J. , Salifu Elliasu Y. , Ramharack Pritika
Published: February 2024

Natural compounds such as curcumin, a polyphenolic compound derived from the rhizome of turmeric, have gathered remarkable scientific interest due to their diverse metabolic benefits including anti-obesity potential. However, curcumin faces challenges stemming from its unfavorable pharmacokinetic profile. To address this issue, synthetic curcumin derivatives aimed at enhancing the biological efficacy of curcumin have previously been developed. In silico modelling techniques have gained significant recognition in screening synthetic compounds as drug candidates. Therefore, the primary objective of this study was to assess the pharmacokinetic and pharmacodynamic characteristics of three synthetic derivatives of curcumin. This evaluation was conducted in comparison to curcumin, with a specific emphasis on examining their impact on adipogenesis, inflammation, and lipid metabolism as potential therapeutic targets of obesity mechanisms. In this study, predictive toxicity screening confirmed the safety of curcumin, with the curcumin derivatives demonstrating a safe profile based on their LD50 values. The synthetic curcumin derivative 1A8 exhibited inactivity across all selected toxicity endpoints. Furthermore, these compounds were deemed viable candidate drugs as they adhered to Lipinski’s rules and exhibited favorable metabolic profiles. Molecular docking studies revealed that both curcumin and its synthetic derivatives exhibited favorable binding scores, whilst molecular dynamic simulations showed stable binding with peroxisome proliferator-activated receptor gamma (PPARγ), csyclooxygenase-2 (COX2), and fatty acid synthase (FAS) proteins. The binding free energy calculations indicated that curcumin displayed potential as a strong regulator of PPARγ (−60.2 ± 0.4 kcal/mol) and FAS (−37.9 ± 0.3 kcal/mol), whereas 1A8 demonstrated robust binding affinity with COX2 (−64.9 ± 0.2 kcal/mol). In conclusion, the results from this study suggest that the three synthetic curcumin derivatives have similar molecular interactions to curcumin with selected biological targets. However, in vitro and in vivo experimental studies are recommended to validate these findings.
The Effect of Oxidative Stress on the Human Voice
Authors: Hirano Shigeru , Inufusa Haruhiko , You Fukka
Published: February 2024

The vocal fold vibrates in high frequency to create voice sound. The vocal fold has a sophisticated histological “layered structure” that enables such vibration. As the vibration causes fricative damage to the mucosa, excessive voicing can cause inflammation or injury to the mucosa. Chronic inflammation or repeated injury to the vocal fold occasionally induces scar formation in the mucosa, which can result in severe dysphonia, which is difficult to treat. Oxidative stress has been proven to be an important factor in aggravating the injury, which can lead to scarring. It is important to avoid excessive oxidative stress during the wound healing period. Excessive accumulation of reactive oxygen species (ROS) has been found in the injured vocal folds of rats during the early phase of wound healing. Antioxidants proved to be useful in preventing the accumulation of ROS during the period with less scar formation in the long-term results. Oxidative stress is also revealed to contribute to aging of the vocal fold, in which the mucosa becomes thin and stiff with a reduction in vibratory capacity. The aged voice can be characterized as weak and breathy. It has been confirmed that ROS gradually increases in rat vocal fold mucosa with age, which may cause further damage to the vocal fold. Antioxidants have also proved effective in avoiding aging of the vocal fold in rat models. Recently, human trials have shown significant effects of the antioxidant Twendee X for maintaining the voice of professional opera singers. In conclusion, it is suggested that oxidative stress has a great impact on the damage or deterioration of the vocal folds, and the use of antioxidants is effective for preventing damage of the vocal fold and maintaining the voice.
Orexins/Hypocretins: Gatekeepers of Social Interaction and Motivation
Authors: Ouaidat Sara , Amaral Inês M. , Monteiro Diogo G. , Harati Hayat , Hofer Alex , El Rawas Rana
Published: February 2024

Ever since the discovery of the brain’s orexin/hypocretin system, most research was directed toward unveiling its contribution to the normal functioning of individuals. The investigation of reward-seeking behaviors then gained a lot of attention once the distribution of orexinergic neurons was revealed. Here, we discuss findings on the involvement of orexins in social interaction, a natural reward type. While some studies have succeeded in defining the relationship between orexin and social interaction, the controversy regarding its nature (direct or inverse relation) raises questions about what aspects have been overlooked until now. Upon examining the literature, we identified a research gap concerning conditions influencing the impact of orexins on social behavior expression. In this review, we introduce a number of factors (e.g., stress, orexin’s source) that must be considered while studying the role of orexins in social interaction. Furthermore, we refer to published research to investigate the stage at which orexins affect social interaction and we highlight the nucleus accumbens (NAc) shell’s role in social interaction and other rewarding behaviors. Finally, the underlying orexin molecular pathway influencing social motivation in particular illnesses is proposed. We conclude that orexin’s impact on social interaction is multifactorial and depends on specific conditions available at a time.
Pterostilbene Induces Apoptosis from Endoplasmic Reticulum Stress Synergistically with Anticancer Drugs That Deposit Iron in Mitochondria
Authors: Nishiguch Yukiko , Fujiwara-Tani Rina , Nukaga Shota , Nishida Ryoichi , Ikemoto Ayaka , Sasaki Rika , Mori Shiori , Ogata Ruiko , Kishi Shingo , Hojo Yudai , Shinohara Hisashi , Sho Masayuki , Kuniyasu Hiroki
Published: February 2024

Anticancer agents are playing an increasing role in the treatment of gastric cancer (GC); however, novel anticancer agents have not been fully developed. Therefore, it is important to investigate compounds that improve sensitivity to the existing anticancer drugs. We have reported that pterostilbene (PTE), a plant stilbene, enhances the antitumor effect of low doses of sunitinib in gastric cancer cells accumulating mitochondrial iron (II) (mtFe) at low doses. In this study, we investigated the relationship between the mtFe deposition and the synergistic effect of PTE and different anticancer drugs. For this study, we used 5-fluorouracil (5FU), cisplatin (CPPD), and lapatinib (LAP), which are frequently used in the treatment of GC, and doxorubicin (DOX), which is known to deposit mtFe. A combination of low-dose PTE and these drugs suppressed the expression of PDZ domain-containing 8 (PDZD8) and increased mtFe accumulation and mitochondrial H2O2. Consequently, reactive oxygen species-associated hypoxia inducible factor-1α activation induced endoplasmic reticulum stress and led to apoptosis, but not ferroptosis. In contrast, 5FU and CDDP did not show the same changes as those observed with PTE and DOX or LAP, and there was no synergistic effect with PTE. These results indicate that the combination of PTE with iron-accumulating anticancer drugs exhibits a strong synergistic effect. These findings would help in developing novel therapeutic strategies for GC. However, further clinical investigations are required.
Recent Aspects of Periodontitis and Alzheimer’s Disease—A Narrative Review
Authors: Cichońska Dominika , Mazuś Magda , Kusiak Aida
Published: February 2024

Periodontitis is an inflammatory condition affecting the supporting structures of the teeth. Periodontal conditions may increase the susceptibility of individuals to various systemic illnesses, including Alzheimer’s disease. Alzheimer’s disease is a neurodegenerative condition characterized by a gradual onset and progressive deterioration, making it the primary cause of dementia, although the exact cause of the disease remains elusive. Both Alzheimer’s disease and periodontitis share risk factors and clinical studies comparing the associations and occurrence of periodontitis among individuals with Alzheimer’s disease have suggested a potential correlation between these conditions. Brains of individuals with Alzheimer’s disease have substantiated the existence of microorganisms related to periodontitis, especially Porphyromonas gingivalis, which produces neurotoxic gingipains and may present the capability to breach the blood–brain barrier. Treponema denticola may induce tau hyperphosphorylation and lead to neuronal apoptosis. Lipopolysaccharides—components of bacterial cell membranes and mediators of inflammation—also have an impact on brain function. Further research could unveil therapeutic approaches targeting periodontal pathogens to potentially alleviate AD progression.
Breast Cancer Molecular Subtyping in Practice: A Real-World Study of the APIS Breast Cancer Subtyping Assay in a Consecutive Series of Breast Core Biopsies
Authors: Di Palma Silvana , Koliou Panagiotis , Simonovic Alex , Costa Daniela , Faulkes Catherine , Kobutungi Brenda , Paterson Felicity , Horsnell Jonathan David , Pakzad Farrokh , Irvine Tracey , Partlett Polly , Clayton Elizabeth , Collins Nadine
Published: February 2024

The APIS Breast Cancer Subtyping Kit is an mRNA-based assessment of the seven parameters including three biomarkers routinely assessed in all the newly diagnosed breast cancers (BC), oestrogen receptor (ER), progesterone receptor (PR) and HER-2 and an additional four genes that create a novel proliferation signature, MKI67, PCNA, CCNA2 and KIF23. Taken together, the data are used to produce a molecular subtype for every sample. The kit was evaluated against the current standard protocol of immunohistochemistry (IHC) and/or in situ hybridisation (ISH) in breast cancer patients. The data were presented at the weekly breast multidisciplinary team (MDT) meeting. A total of 98 consecutive cases of pre-operative breast cancer core biopsies and two core biopsies of nodal metastases yielding 100 cases were assessed. IHC and APIS results were available for 100 and 99 cases. ER was concordant in 97% cases, PR was concordant in 89% and HER-2 results were concordant with IHC/ISH in 100% of the cases. Ki-67 IHC was discordant in 3% of cases when compared with MK167 alone but discordant in 24% when compared with the four-gene proliferation signature. In conclusion, our study indicates that the APIS Breast Cancer Subtyping Kit is highly concordant when compared to the results produced for ER/PR/HER-2 by IHC and/or ISH. The assay could play a role in the routine assessment of newly diagnosed breast cancer (BC) specimens.
The Role of Opioid Receptor Antagonists in Regulation of Blood Pressure and T-Cell Activation in Mice Selected for High Analgesia Induced by Swim Stress
Authors: Skiba Dominik , Jaskuła Kinga , Nawrocka Agata , Poznański Piotr , Łazarczyk Marzena , Szymański Łukasz , Żera Tymoteusz , Sacharczuk Mariusz , Cudnoch-Jędrzejewska Agnieszka , Gaciong Zbigniew
Published: February 2024

Opioid peptides and their G protein-coupled receptors are important regulators within the cardiovascular system, implicated in the modulation of both heart and vascular functions. It is known that naloxone—an opioid antagonist—may exert a hypertensive effect. Recent experimental and clinical evidence supports the important role of inflammatory mechanisms in hypertension. Since opioids may play a role in the regulation of both blood pressure and immune response, we studied these two processes in our model. We aimed to evaluate the effect of selective and non-selective opioid receptor antagonists on blood pressure and T-cell activation in a mouse model of high swim stress-induced analgesia. Blood pressure was measured before and during the infusion of opioid receptor antagonists using a non-invasive tail–cuff measurement system. To assess the activation of T-cells, flow cytometry was used. We discovered that the non-selective antagonism of the opioid system by naloxone caused a significant elevation of blood pressure. The selective antagonism of μ and κ but not δ opioid receptors significantly increased systolic blood pressure. Subsequently, a brief characterization of T-cell subsets was performed. We found that the blockade of μ and δ receptors is associated with the increased expression of CD69 on CD4 T-cells. Moreover, we observed an increase in the central memory CD4 and central memory CD8 T-cell populations after the δ opioid receptor blockade. The antagonism of the μ opioid receptor increased the CD8 effector and central memory T-cell populations.
Adult Neurogenesis of the Medial Geniculate Body: In Vitro and Molecular Genetic Analyses Reflect the Neural Stem Cell Capacity of the Rat Auditory Thalamus over Time
Authors: Engert Jonas , Spahn Bjoern , Sommerer Sabine , Ehret Kasemo Totta , Hackenberg Stephan , Rak Kristen , Voelker Johannes
Published: February 2024

Neural stem cells (NSCs) have been recently identified in the neonatal rat medial geniculate body (MGB). NSCs are characterized by three cardinal features: mitotic self-renewal, formation of progenitors, and differentiation into all neuroectodermal cell lineages. NSCs and the molecular factors affecting them are particularly interesting, as they present a potential target for treating neurologically based hearing disorders. It is unclear whether an NSC niche exists in the rat MGB up to the adult stage and which neurogenic factors are essential during maturation. The rat MGB was examined on postnatal days 8, 12, and 16, and at the adult stadium. The cardinal features of NSCs were detected in MGB cells of all age groups examined by neurosphere, passage, and differentiation assays. In addition, real-time quantitative polymerase chain reaction arrays were used to compare the mRNA levels of 84 genes relevant to NSCs and neurogenesis. In summary, cells of the MGB display the cardinal features of NSCs up to the adult stage with a decreasing NSC potential over time. Neurogenic factors with high importance for MGB neurogenesis were identified on the mRNA level. These findings should contribute to a better understanding of MGB neurogenesis and its regenerative capacity.
Predicting Kidney Transplantation Outcomes from Donor and Recipient Characteristics at Time Zero: Development of a Mobile Application for Nephrologists
Authors: Pérez Valdivia Miguel Ángel , Calvillo Arbizu Jorge , Portero Barreña Daniel , Castro de la Nuez Pablo , López Jiménez Verónica , Rodríguez Benot Alberto , Mazuecos Blanca Auxiliadora , de Gracia Guindo Mª Carmen , Bernal Blanco Gabriel , Gentil Govantes Miguel Ángel , Bedoya Pérez Rafael , Rocha Castilla José Luis
Published: February 2024

(1) Background: We report on the development of a predictive tool that can estimate kidney transplant survival at time zero. (2) Methods: This was an observational, retrospective study including 5078 transplants. Death-censored graft and patient survivals were calculated. (3) Results: Graft loss was associated with donor age (hazard ratio [HR], 1.021, 95% confidence interval [CI] 1.018–1.024, p < 0.001), uncontrolled donation after circulatory death (DCD) (HR 1.576, 95% CI 1.241–2.047, p < 0.001) and controlled DCD (HR 1.567, 95% CI 1.372–1.812, p < 0.001), panel reactive antibody percentage (HR 1.009, 95% CI 1.007–1.011, p < 0.001), and previous transplants (HR 1.494, 95% CI 1.367–1.634, p < 0.001). Patient survival was associated with recipient age (> 60 years, HR 5.507, 95% CI 4.524–6.704, p < 0.001 vs. < 40 years), donor age (HR 1.019, 95% CI 1.016–1.023, p < 0.001), dialysis vintage (HR 1.0000263, 95% CI 1.000225–1.000301, p < 0.01), and male sex (HR 1.229, 95% CI 1.135–1.332, p < 0.001). The C-statistics for graft and patient survival were 0.666 (95% CI: 0.646, 0.686) and 0.726 (95% CI: 0.710–0.742), respectively. (4) Conclusions: We developed a mobile app to estimate survival at time zero, which can guide decisions for organ allocation.
Severe Cholestasis in Neonates with Hemolytic Disease of the Fetus and Newborn—A Case Report
Authors: Drozdowska-Szymczak Agnieszka , Proczka Julia , Mazanowska Natalia , Ludwin Artur , Krajewski Paweł
Published: February 2024

Hemolytic disease of the fetus and newborn (HDFN) may cause severe cholestasis with direct bilirubin concentrations reaching up to 50 times the upper limit of normal. This case report describes twins whose highest direct bilirubin concentrations were 32.2 mg/dL and 50.2 mg/dL, with no significant signs of hepatic impairment. The index pregnancy was complicated by Rhesus factor immunization with anti-D antibodies present in maternal serum, which caused fetal anemia requiring intrauterine blood transfusions. Complementary tests demonstrated Rhesus D alloimmunization as the sole cause of cholestasis. To the best of our knowledge, this is the first study to describe such elevated direct bilirubin concentrations caused by HDFN.
Validation of a Three-Dimensional Weight-Bearing Measurement Protocol for Medial Open-Wedge High Tibial Osteotomy
Authors: Hodel Sandro , Hasler Julian , Roth Tabitha Arn , Flury Andreas , Sutter Cyrill , Fucentese Sandro F. , Fürnstahl Philipp , Vlachopoulos Lazaros
Published: February 2024

Three-dimensional (3D) deformity assessment and leg realignment planning is emerging. The aim of this study was to (1) validate a novel 3D planning modality that incorporates the weight-bearing (WB) state (3D WB) by comparing it to existing modalities (3D non-weight-bearing (NWB), 2D WB) and (2) evaluate the influence of the modality (2D vs. 3D) and the WB condition on the measurements. Three different planning and deformity measurement protocols were analyzed in 19 legs that underwent medial open-wedge high tibial osteotomy (HTO): (1) a 3D WB protocol, after 2D/3D registration of 3D CT models onto the long-leg radiograph (LLR) (3D WB), (2) a 3D NWB protocol based on the 3D surface models obtained in the supine position (3D NWB), and (3) a 2D WB protocol based on the LLR (2D WB). The hip–knee–ankle angle (HKA), joint line convergence angle (JLCA), and the achieved surgical correction were measured for each modality and patient. All the measurement protocols demonstrated excellent intermodal agreement for the achieved surgical correction, with an ICC of 0.90 (95% CI: 0.76–0.96)) (p < 0.001). Surgical correction had a higher mean absolute difference compared to the 3D opening angle (OA) when measured with the WB protocols (3D WB: 2.7 ± 1.8°, 3D NWB: 1.9 ± 1.3°, 2D WB: 2.2 ± 1.3°), but it did not show statistical significance. The novel planning modality (3D WB) demonstrated excellent agreement when measuring the surgical correction after HTO compared to existing modalities.
The Value of Subjective Olfactometry as a Predictive Biomarker of Neurodegenerative Diseases: A Systematic Review
Authors: Ramos-Casademont Laia , Martin-Jimenez Daniel , Villarreal-Garza Brenda , Sánchez-Gomez Serafín , Callejon-Leblic María Amparo
Published: February 2024

Background: Olfactory disorders (ODs) are reported to be an early non-motor sign before the onset of deterioration in neurodegenerative diseases (NDs) such as Alzheimer’s and Parkinson’s. This systematic revision aims to review the current literature and the value of subjective olfactometry (SO) in the early diagnosis of cognitive decline and NDs. Methods: A systematic literature review was conducted following the PRISMA framework. Four different authors reviewed six different databases. The main variables analyzed were olfactory function and cognitive status. The quality of results was evaluated using the Oxford Centre of Evidence-based Medicine Levels. Results: Twenty-one cross-sectional and cohort studies and six meta-analyses were included. Most of them found an association between ODs and NDs. A prevalence of ODs greater than 80% was shown in Parkinson’s disease, proportional to the severity of symptoms. In Alzheimer’s, ODs were associated with early diagnosis and prognosis. All SO tests employed in the literature showed enough predictive value to correlate with early stages of cognitive decline. Conclusions: SO should be considered a pivotal tool when diagnosing NDs due to their association with early symptoms and prognosis. However, in the current literature, no firm consensus exists on the optimal SO tests and protocols that should be applied to the study of NDs, which prevents the interpretability and comparability of results among studies.
Neuropancreatology: The Nervous System and Pain Management in Pancreatic Diseases
Authors: Nicoletti Alberto , Vitale Federica , Paratore Mattia , Quero Giuseppe , Negri Marcantonio , Nista Enrico Celestino , Alfieri Sergio , Gasbarrini Antonio , Zileri Dal Verme Lorenzo
Published: February 2024

The intricate network of the pancreatic nervous system plays a fundamental role in physiologic functions of the endocrine and exocrine pancreas. Several pancreatic diseases affect the normal functionality of the pancreatic nervous system. This chronic derangement leads to anatomical alterations, such as neural hypertrophy and increased nerve density. Perineural invasion is a prominent feature of pancreatic cancer, contributing to cancer progression and metastasis. Despite the fact that these pathogenic mechanisms are still incompletely studied and understood, the constant occurrence of these alterations highlights their importance in the pathophysiology of the pancreatic diseases. The occurrence of anatomical changes is strictly linked to the appearance of pain. Pancreatic pain has peculiar features, and its management is complex in clinical practice. In the present review, the evidence on lifestyle, pharmacological and interventional approaches for the management of pancreatic pain is presented. Analgesic therapy is the cornerstone of pain treatment. However, it is important to identify the individual characteristic of the patients and personalize the approach to pain management. Nevertheless, the incomplete efficacy of these strategies makes this field an area of unmet needs. The study of neuroplasticity is crucial to understand the mechanisms that regulate the pathophysiology of pancreatic diseases. Several trials testing new drugs with specific neuromodulatory effects are ongoing. However, further studies are needed to investigate crucial targets to develop novel therapies for the modulation of the nervous system and the prevention of complications of pancreatic diseases. This comprehensive review summarizes the importance of the nervous system in pancreatic diseases with a special focus on its anatomy and physiology, its pathophysiological features and clinical relevance in pancreatic disease, the treatment of pancreatic pain, and the identification of future trends of research.
The Influence of Non-Gaussian Roughness and Spectral Properties on Mixed Lubrication for Heavily Loaded Counterformal Contacts
Authors: Prajapati Deepak K. , Björling Marcus
Published: February 2024

The impact of non-Gaussian height distribution and spectral properties on the lubrication performance of counterformal (point) contacts is quantitatively studied (film parameter, Λ, and asperity load ratio, La) by developing a mixed lubrication model. The Weibull height distribution function and power spectral density (PSD) are used to generate artificial surface topographies (non-Gaussian and Gaussian, isotropic), as these surface topographies are found in many tribological components. The set of variables needed to parametrize and their effect on mixed lubrication is discussed, including the shape parameter, the autocorrelation length, the wavelength ratio, and the Hurst coefficient. It is revealed that a rough surface with a lower shape parameter exhibits higher hydrodynamic lift. The spectral properties (the autocorrelation length and the wavelength ratio) of rough surfaces significantly affect the film parameter and the hydrodynamic and asperity pressures. The film parameter is slightly influenced by the Hurst coefficient.
Dual Role of Beam Polarization and Power in Nematic Liquid Crystals: A Comprehensive Study of TE- and TM-Beam Interactions
Authors: Kwaśny Michał , Klus Bartłomiej Wojciech , Laudyn Urszula Anna
Published: February 2024

Optical spatial solitons are self-guided wave packets that maintain their transverse profile due to the self-focusing effect of light. In nematic liquid crystals (NLC), such light beams, called nematicons, can be induced by two principal mechanisms: light-induced reorientation of the elongated molecules and thermal changes in the refractive index caused by partial light absorption. This paper presents a detailed investigation of the propagation dynamics of light beams in nematic liquid crystals (NLCs) doped with Sudan Blue dye. Building on the foundational understanding of reorientational and thermal solitons in NLCs and the effective breaking of the action–reaction principle in spatial solitons, this study examines the interaction of infrared (IR) and visible beams in a [-4-(trans-4′-exylcyclohexyl)isothiocyanatobenzene] (6CHBT) NLC. Our experimental results highlight the intricate interplay of beam polarizations, power levels, and the nonlinear properties of NLCs, offering new insights into photonics and nonlinear optics in liquid crystals.
Chloride Permeability of Alkali-Activated Slag Concretes after Exposure to High Temperatures
Authors: Zhou Baomeng , Ma Qianmin , Guo Rongxin , Li Ping
Published: February 2024

The number of fires in buildings and on bridges has increased worldwide in recent years. As a structural material, the strength of alkali-activated slag (AAS) concrete after exposure to high temperatures has been given much attention. However, research of its durability is still lacking, which limits the application of this type of concrete on a larger scale. In this context, as one of the most important aspects of durability, the chloride permeability of AAS concretes after exposure to high temperatures was examined in this study. The influence of the alkali concentration (Na2O%) and the modulus (Ms) of the activator, as well as the influence of heating regimes, including the heating rate, duration of exposure to the target temperature, and cooling method, was also discussed. The results show that the chloride permeability of the AAS concretes increased with temperature elevation. Due to the interference of pore solution conductivity, the influence of the Na2O% and the Ms of the activator on the chloride permeability of the AAS concretes was not made clear by using the ASTM C 1202 charge passed method; however, after exposure to high temperatures, AAS with a lower Na2O% and lower Ms has lower porosity and may have lower chloride permeability, which needs further investigation. Faster heating for a longer duration at the target temperature and water cooling reduced the resistance of the AAS concretes to chloride permeability as a result of their increased porosity.
Natural Products Derived from Marine Sponges with Antitumor Potential against Lung Cancer: A Systematic Review
Authors: Ortigosa-Palomo Alba , Quiñonero Francisco , Ortiz Raul , Sarabia Francisco , Prados Jose , Melguizo Consolación
Published: February 2024

Non-small-cell lung cancer (NSCLC), the most commonly diagnosed cancer and the leading cause of cancer-related death worldwide, has been extensively investigated in the last decade in terms of developing new therapeutic options that increase patient survival. In this context, marine animals are a source of new, interesting bioactive molecules that have been applied to the treatment of different types of cancer. Many efforts have been made to search for new therapeutic strategies to improve the prognosis of lung cancer patients, including new bioactive compounds and cytotoxic drugs from marine sponges. Their antitumoral effect can be explained by several cellular and molecular mechanisms, such as modulation of the cell cycle or induction of apoptosis. Thus, this systematic review aims to summarize the bioactive compounds derived from marine sponges and the mechanisms by which they show antitumor effects against lung cancer, exploring their limitations and the challenges associated with their discovery. The search process was performed in three databases (PubMed, SCOPUS, and Web of Science), yielding a total of 105 articles identified in the last 10 years, and after a screening process, 33 articles were included in this systematic review. The results showed that these natural sponge-derived compounds are a valuable source of inspiration for the development of new drugs. However, more research in this field is needed for the translation of these novel compounds to the clinic.
Pretreatment of Glucose–Fructose Syrup with Ceramic Membrane Ultrafiltration Coupled with Activated Carbon
Authors: Hang Fangxue , Xu Hongmei , Xie Caifeng , Li Kai , Wen Tao , Meng Lidan
Published: February 2024

Ceramic membranes are applied to remove non-sugar impurities, including proteins, colloids and starch, from glucose–fructose syrup that is dissolved from raw sugar using acid. The performance of ceramic membranes with 0.05 μm pores in clarifying high-fructose syrup was investigated under various operating conditions. The flux decreased rapidly at the start of the experiment and then tended to stabilize at a temperature of 90 °C, a transmembrane pressure of 2.5 bar, and cross-flow velocity of 5 m/s under total reflux operation. Moreover, the steady-state flux was measured at 181.65 Lm−2 h−1, and the turbidity of glucose–fructose syrup was reduced from 92.15 NTU to 0.70 NTU. Although membrane fouling is inevitable, it can be effectively controlled by developing a practical approach to regenerating membranes. Mathematical model predictions, scanning electron microscopy, energy dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy revealed that foulants primarily responsible for fouling are composed of polysaccharides, proteins, sucrose, phenols, and some metal elements, such as calcium, aluminum, and potassium. Due to the removal of suspended colloidal solids, the membrane-filtered glucose–fructose syrup was decolorized using activated carbon; the filtration rate was effectively improved. A linear relationship between volume increase in syrup and time was observed. A decolorization rate of 90% can be obtained by adding 0.6 (w/w) % of activated carbon. The pretreatment of glucose–fructose syrup using a ceramic membrane coupled with activated carbon results in low turbidity and color value. This information is essential for advancing glucose–fructose syrup and crystalline fructose production technology.
Ni,Fe,Co-LDH Coated Porous Transport Layers for Zero-Gap Alkaline Water Electrolyzers
Authors: Zaffora Andrea , Megna Bartolomeo , Seminara Barbara , Di Franco Francesco , Santamaria Monica
Published: February 2024

Next-generation alkaline water electrolyzers will be based on zero-gap configuration to further reduce costs related to technology and to improve performance. Here, anodic porous transport layers (PTLs) for zero-gap alkaline electrolysis are prepared through a facile one-step electrodeposition of Ni,Fe,Co-based layered double hydroxides (LDH) on 304 stainless steel (SS) meshes. Electrodeposited LDH structures are characterized using Scanning Electron Microscopy (SEM) confirming the formation of high surface area catalytic layers. Finally, bi and trimetallic LDH-based PTLs are tested as electrodes for oxygen evolution reaction (OER) in 1 M KOH solution. The best electrodes are based on FeCo LDH, reaching 10 mA cm−2 with an overpotential value of 300 mV. These PTLs are also tested with a chronopotentiometric measurement carried out for 100 h at 50 mA cm−2, showing outstanding durability without signs of electrocatalytic activity degradation.
Chloroplast Genome Provides Insights into Molecular Evolution and Species Relationship of Fleabanes (Erigeron: Tribe Astereae, Asteraceae) in the Juan Fernández Islands, Chile
Authors: Kim Seon-Hee , Yang JiYoung , Cho Myong-Suk , Stuessy Tod F. , Crawford Daniel J. , Kim Seung-Chul
Published: February 2024

Erigeron represents the third largest genus on the Juan Fernández Islands, with six endemic species, five of which occur exclusively on the younger Alejandro Selkirk Island with one species on both islands. While its continental sister species is unknown, Erigeron on the Juan Fernández Islands appears to be monophyletic and most likely evolved from South American progenitor species. We characterized the complete chloroplast genomes of five Erigeron species, including accessions of E. fernandezia and one each from Alejandro Selkirk and Robinson Crusoe Islands, with the purposes of elucidating molecular evolution and phylogenetic relationships. We found highly conserved chloroplast genomes in size, gene order and contents, and further identified several mutation hotspot regions. In addition, we found two positively selected chloroplast genes (ccsA and ndhF) among species in the islands. The complete plastome sequences confirmed the monophyly of Erigeron in the islands and corroborated previous phylogenetic relationships among species. New findings in the current study include (1) two major lineages, E. turricola–E. luteoviridis and E. fernandezia–E. ingae–E. rupicola, (2) the non-monophyly of E. fernandezia occurring on the two islands, and (3) the non-monophyly of the alpine species E. ingae complex.
God and Space
Authors: Craig William Lane
Published: February 2024

This paper inquires into the nature of God’s relationship to space. It explores two different views, one that God transcends space or exists aspatially and the other that God exists throughout space and so is spatially extended. It seeks to adjudicate the debate between these competing perspectives by weighing the principal arguments for and against each view.
User Study to Validate the Performance of an Offline Robot Programming Method That Enables Robot-Independent Kinesthetic Instruction through the Use of Augmented Reality and Motion Capturing
Authors: Müller Fabian , Koch Michael , Hasse Alexander
Published: February 2024

The paper presents a novel offline programming (OLP) method based on programming by demonstration (PbD), which has been validated through user study. PbD is a programming method that involves physical interaction with robots, and kinesthetic teaching (KT) is a commonly used online programming method in industry. However, online programming methods consume significant robot resources, limiting the speed advantages of PbD and emphasizing the need for an offline approach. The method presented here, based on KT, uses a virtual representation instead of a physical robot, allowing independent programming regardless of the working environment. It employs haptic input devices to teach a simulated robot in augmented reality and uses automatic path planning. A benchmarking test was conducted to standardize equipment, procedures, and evaluation techniques to compare different PbD approaches. The results indicate a 47% decrease in programming time when compared to traditional KT methods in established industrial systems. Although the accuracy is not yet at the level of industrial systems, users have shown rapid improvement, confirming the learnability of the system. User feedback on the perceived workload and the ease of use was positive. In conclusion, this method has potential for industrial use due to its learnability, reduction in robot downtime, and applicability across different robot sizes and types.
Research on Lane-Changing Decision Making and Planning of Autonomous Vehicles Based on GCN and Multi-Segment Polynomial Curve Optimization
Authors: Feng Fuyong , Wei Chao , Zhao Botong , Lv Yanzhi , He Yuanhao
Published: February 2024

This paper considers the interactive effects between the ego vehicle and other vehicles in a dynamic driving environment and proposes an autonomous vehicle lane-changing behavior decision-making and trajectory planning method based on graph convolutional networks (GCNs) and multi-segment polynomial curve optimization. Firstly, hierarchical modeling is applied to the dynamic driving environment, aggregating the dynamic interaction information of driving scenes in the form of graph-structured data. Graph convolutional neural networks are employed to process interaction information and generate ego vehicle’s driving behavior decision commands. Subsequently, collision-free drivable areas are constructed based on the dynamic driving scene information. An optimization-based multi-segment polynomial curve trajectory planning method is employed to solve the optimization model, obtaining collision-free motion trajectories satisfying dynamic constraints and efficiently completing the lane-changing behavior of the vehicle. Finally, simulation and on-road vehicle experiments are conducted for the proposed method. The experimental results demonstrate that the proposed method outperforms traditional decision-making and planning methods, exhibiting good robustness, real-time performance, and strong scenario generalization capabilities.
Relationship of Knee Abduction Moment to Trunk and Lower Extremity Segment Acceleration during Sport-Specific Movements
Authors: Ekdahl Mitchell , Ulman Sophia , Butler Lauren
Published: February 2024

The knee abduction moment (KAM) has been identified as a significant predictor of anterior cruciate ligament (ACL) injury risk; however, the cost and time demands associated with collecting three-dimensional (3D) kinetic data have prompted the need for alternative solutions. Wearable inertial measurement units (IMUs) have been explored as a potential solution for quantitative on-field assessment of injury risk. Most previous work has focused on angular velocity data, which are highly susceptible to bias and noise relative to acceleration data. The purpose of this pilot study was to assess the relationship between KAM and body segment acceleration during sport-specific movements. Three functional tasks were selected to analyze peak KAM using optical motion capture and force plates as well as peak triaxial segment accelerations using IMUs. Moderate correlations with peak KAM were observed for peak shank acceleration during single-leg hop; peak trunk, thigh, and shank accelerations during a deceleration task; and peak trunk, pelvis, and shank accelerations during a 45° cut. These findings provide preliminary support for the use of wearable IMUs to identify peak KAM during athletic tasks.
Reliability of Domestic Gas Flow Sensors with Hydrogen Admixtures
Authors: Ficco Giorgio , Dell’Isola Marco , Graditi Giorgio , Monteleone Giulia , Gislon Paola , Kulaga Pawel , Jaworski Jacek
Published: February 2024

Static flow sensors (e.g., thermal gas micro electro-mechanical sensors—MEMS—and ultrasonic time of flight) are becoming the prevailing technology for domestic gas metering and billing since they show advantages in respect to the traditional volumetric ones. However, they are expected to be influenced in-service by changes in gas composition, which in the future could be more frequent due to the spread of hydrogen admixtures in gas networks. In this paper, the authors present the results of an experimental campaign aimed at analyzing the in-service reliability of both static and volumetric gas meters with different hydrogen admixtures. The results show that the accuracy of volumetric and ultrasonic meters is always within the admitted limits for subsequent verification and even within those narrower of the initial verification. On the other hand, the accuracy of the first generation of thermal mass gas flow sensors is within the limits of the verification only when the hydrogen admixture is below 2%vol. At higher hydrogen content, in fact, the absolute weighted mean error ranges between 3.5% (with 5%vol of hydrogen) and 15.8% (with 10%vol of hydrogen).