bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between Alcohol Intake and Chronic Pain with Depressive Symptoms: A Cross-Sectional Analysis of the Shika Study
Authors: Amatsu Takashi , Tsujiguchi Hiromasa , Hara Akinori , Miyagi Sakae , Kannon Takayuki , Suzuki Keita , Shimizu Yukari , Nguyen Thao Thi Thu , Pham Kim-Oanh , Suzuki Fumihiko , Kasahara Tomoko , Nakamura Masaharu , Hayashi Koichiro , Shibata Aki , Ogino Noriyoshi , Konoshita Tadashi , Kambayashi Yasuhiro , Tsuboi Hirohito , Tajima Atsushi , Nakamura Hiroyuki
Published: February 2022

Although alcohol intake is associated with chronic pain (CP) and analgesia, epidemiological studies have not yet examined the factors affecting the relationship between alcohol intake and CP in detail. Therefore, the present cross-sectional study investigated the relationship between alcohol intake and CP in community-dwelling middle-aged and elderly individuals with/without depressive symptoms. Participants comprised 2223 inhabitants of Shika town in Ishikawa prefecture, located on the Noto Peninsula facing the Sea of Japan, and included 1007 males and 1216 females. CP, depressive symptoms, and alcohol intake were assessed using a CP questionnaire, the Geriatric Depression Scale-15 and the brief-type self-administered diet history questionnaire, respectively. In males without depressive symptoms, mean alcohol intake was significantly higher at 5.70% energy (27.92 g/day) in the CP group than that of 3.75% energy (20.00 g/day) in the non-CP group. The prevalence of low back/knee pain was also significantly higher in males with than in those without depressive symptoms. The present results suggest that long-term alcohol intake is related to CP by reducing the pain threshold and enhancing nociceptive pain as a possible mechanism. However, even a low alcohol intake was associated with psychogenic pain in participants with depressive symptoms. Further studies to investigate the involvement of depressive symptoms and alcohol intake in CP and its prevention are needed.
A Policy Framework for Producing Age-Friendly Communities from the Perspective of Production of Space
Authors: Han Jianbo , Chan Edwin H. W. , Yung Esther H. K. , Qian Queena K. , Lam Patrick T. I.
Published: February 2022

Given various hindrances in the macro context, how to efficiently develop age-friendly community policies requires further research. Currently, such kinds of frameworks are lacking. This paper aims to develop a policy framework to minimise cost and resolve conflict of interest between different generations in age-friendly community development. The study adopted a scientometric method to review the theoretical development of age-friendly community studies. Firstly, with a search for the keywords “age-friendly” and “community” on Web of Science, 72 English academic papers were found containing explicit theories. Most of the studies were conducted in the Global North. Then, a mixed analytical method was used to find a suitable theory, “the production of space”, to develop the policy framework. Lastly, a policy framework was developed to overcome barriers to age-friendly community development strategically. Echoing previous studies, this paper proposes a way to counter financial austerity in age-friendly initiative investment and balance the consideration for older and younger populations in urban development. For practice, the policy framework can provide a reference for more efficient age-friendly community policymaking in different regions. For future research, the framework provides a model for more empirical studies considering the social dynamics in age-friendly community development.
Socioeconomic Disparities in Hypertension by Levels of Green Space Availability: A Cross-Sectional Study in Philadelphia, PA
Authors: Koh Celina , Kondo Michelle C. , Rollins Heather , Bilal Usama
Published: February 2022

Green spaces have been proposed as equigenic factors, potentially mitigating health disparities. We used data from the 3887 participants residing in Philadelphia who participated in the Public Health Management Corporation’s Southeastern Pennsylvania Household Health Survey in 2014–2015 to assess whether socioeconomic disparities in hypertension are modified by availability of neighborhood-level green spaces. Socioeconomic status (SES) was measured using individual-level education and neighborhood-level median household income. Green space availability was measured using surrounding percent tree canopy cover, mean normalized difference vegetation index (NDVI), and proximity to nearest park. Using logistic regression models adjusted for age, sex, and race/ethnicity, we found that adults with higher educational attainment had significantly lower levels of hypertension (OR = 0.63, 0.57, and 0.36 for high school, some college, and college graduates, respectively, as compared to those with less than high school education), and this pattern was similar for median household income (higher prevalence in lower income areas). We found no significant interaction between education and percent tree canopy cover (p = 0.83), meaning that educational disparities in hypertension were similar across all levels of green space availability. These results held when using mean NDVI or distance to nearest park as availability measures, or when considering neighborhood-level median household income as the socioeconomic measure, although the specific patterns and significance of interactions varied by exposure and modifier. While socioeconomic disparities in hypertension are strong for adults residing in Philadelphia, green spaces did not seem to modify them.
A Cohort Study on Cancer Incidence among Women Exposed to Environmental Asbestos in Childhood with a Focus on Female Cancers, including Breast Cancer
Authors: Dalsgaard Sofie Bünemann , Würtz Else Toft , Hansen Johnni , Røe Oluf Dimitri , Omland Øyvind
Published: February 2022

Objectives: To examine the risk of cancer in former school children exposed to environmental asbestos in childhood with a focus on female cancers, including breast cancer. Methods: We retrieved a cohort of females (n = 6024) attending four schools located in the neighborhood of a large asbestos cement plant in Denmark. A reference cohort was frequency-matched 1:9 (n = 54,200) in sex and five-year age intervals. Using Danish registries, we linked information on historical employments, relatives’ employments, cancer, and vital status. We calculated standardized incidence rates (SIRs) for all and specific cancers, comparing these rates with the reference cohort. Hazard ratios were calculated for selected cancers adjusted for occupational and familial asbestos exposure. Results: For cancer of the corpus uteri (SIR 1.29, 95% CI 1.01–1.66) and malignant mesothelioma (SIR 7.26, 95% CI 3.26–16.15), we observed significantly increased incidences. Occupationally, asbestos exposure had a significantly increased hazard ratio for cancer in the cervix, however, a significantly lower risk of ovarian cancer. The overall cancer incidence was similar to that of the reference cohort (SIR 1.02, 95% CI 0.96–1.07). The risk of cancer of the lung was increased for those exposed to occupational asbestos, those with family members occupationally exposed to asbestos and for tobacco smokers. Conclusions: In our study, environmental asbestos exposure in childhood is associated with an increased risk of cancer of the corpus uteri and malignant mesothelioma in women.
Cause Mechanism of Metro Collapse Accident Based on Risk Coupling
Authors: Fang Ming , Zhang Yi , Zhu Mengjue , Chen Shaopei
Published: February 2022

A metro collapse accident is the main type of metro construction accidents. How to scientifically analyze the key cause factors and their interaction coupling mechanism of the existing metro collapse accidents is crucial to reduce the occurrence of metro collapse. Based on the Fault Tree Analysis (FTA) and the Behavior security “2-4” Model (24Model), the FTA-24Model accident cause analysis framework was constructed by combing their respective characteristics. To be more specific, a logical analysis program was developed to analyze the accident causes by the four-module analysis method. An empirical study was carried out by taking the “12.1” major cave-in accident at the construction site of the Metro Line 11 in Guangzhou as an example. Compared with the case accident report, the FTA-24Model framework analysis method can not only systematically deduce the logical relationship between the accident causes and provides a panorama of the accident cause chain and its evolution process, but also identify the key causes of accidents and their coupling risk effects. For a metro construction accident, this method can not only effectively investigate the accident causes, but also provide a reference for the formulation of prevention strategies.
Morphometric Analysis of Permanent Canines: Preliminary Findings on Odontometric Sex Dimorphism
Authors: Alanazi Abdulelah A. , Almutair Abdulmohsen Musaad , Alhubayshi Abdullah , Almalki Abdullah , Naqvi Zuber Ahamed , Alassaf Abdullah , Almulhim Basim , Alghamdi Sara Ayid , Mallineni Sreekanth Kumar
Published: February 2022

Aim: This study aims to investigate the morphometrics of permanent canines in establishing sexual dimorphism in the native Arabian population. Methods: Thirty (male = 12; female = 18) native Arabian subjects, with ages ranging between 20–45 years. The mesiodistal (MD), cericoincisal (CI) and labiolingual (LL) widths of the teeth 13, 23, 33, and 43 and the inter-canine distance in maxillary (MaxICW) and mandibular (ManICW) arches were measured using a digital caliper. The gran method was used for establishing sex dimorphism among the study subjects. Descriptive statistics were employed using SPSS version 20.0 (Armonk, NY, USA, IBM Corp.). Results: The comparison of either of the measurements (MD, CI, LL, MaxICW and ManICW) were shown to be statistically significant (p > 0.05). The overall mean values of teeth 13, 23, 33, and 43 for CI, LL, MaxICW, and ManICW were lower for females than males (p > 0.05). The MD width was higher in females than that of males (p > 0.05). The sex dimorphism value for teeth 13, 23, 33, and 43 were 0.98, 0.99, 1, and 0.99, respectively. The standard canine index was high for mandibular teeth and lower for mandibular teeth, and SCI values for teeth 13, 23, 33, and 43 were 0.219, 0.218, 0.257 and 0.256, respectively. Conclusion: The morphometrics of permanent canines are helpful in sex determination with the aid of odontometric analysis.
Prediction and Analysis of Tokyo Olympic Games Swimming Results: Impact of the COVID-19 Pandemic on Swimmers’ Performance
Authors: Demarie Sabrina , Chirico Emanuele , Galvani Christel
Published: February 2022

Due to the COVID-19 pandemic in the 2019–2020 season, swimming competitions and training have been limited leading to a setback in performances. The study analyzed if, during the subsequent season, swimmers’ have been able to regain the lost performance. Swimming time trends were analyzed comparing Tokyo with Rio Olympics and with mathematically predicted results. The gap between the gold medalist and the last finalist, and the differences between men and women have also been considered. Swimming competition results of females and males, in 100 m and 200 m Freestyle and Backstroke, were collected from the Olympics’ official website. Results showed that at Tokyo Olympics almost all swimmers’ times improved as compared to Rio’s. Analysis of performance trends highlighted that performance progression does not proceed in a linear fashion and that is best predicted by more recent results. Women’s progression was higher than men’s and the gap between the first and last finalist constantly decreased, except for the Tokyo Olympics. In conclusion, the unprecedented Tokyo Olympic Games and qualification year seems not to have disrupted all Olympic swimmers’ performance, suggesting that stakeholders support and athlete’s coping ability might safeguard the subsistence of performance.
The Effect of Occupational Health Risk Perception on Job Satisfaction
Authors: Shan Biaoan , Liu Xiaoju , Gu Anwei , Zhao Runxuan
Published: February 2022

This study explored the relationship between occupational health risk perception and job satisfaction. Based on the job demand-resources model and resource conservation theory, eight hypotheses were proposed in this study. In a survey of 237 production line workers and managers, we found that perceived occupational health risks significantly negatively affected job satisfaction. Both work stress and organizational commitment mediate the relationships between perceived occupational health risks and job satisfaction. We also examined whether safety culture could weaken the negative impact of perceived occupational health risks on job satisfaction. However, the results of our study did not support this hypothesis. This study not only helped managers to realize the hazards of occupational health risks, but also encouraged employees to actively participate in safety construction and pay attention to their own health. In addition, we also put forward some targeted intervention measures to reduce the negative impact of perceived occupational health risks on job satisfaction. Therefore, this study had certain practical implications.
Sustaining an HIV Prevention and Wellness Program for Sexual Gender Minorities during the COVID-19 Pandemic
Authors: Pichon Latrice C. , Wilkins Megan L. , Guerrero Gisela , Stubbs Andrea L. Williams , Wiley Edward D. , Dodson Justin , London Carla , Teti Michelle
Published: February 2022

Improving mental health, body image, and financial stability is paramount to achieving viral suppression and maintaining HIV-negative status for minoritized communities. The purpose of this paper is to describe the lessons learned from maintenance of an HIV prevention and wellness program during the COVID-19 pandemic. A three-session program was implemented in a hybrid format to account for county-wide restrictions and reopening processes. Lessons learned include the utility of a hybrid format, importance of CBPR partnership, innovation in virtual platform, value of social media presence and upkeep, and use of multiple methods to ascertain evaluative data. Sustaining an HIV prevention and wellness program requires strong research collaborations and ongoing engagement with priority populations and the flexibility to pivot as needed.
Aging, Cellular Senescence, and Alzheimer’s Disease
Authors: Liu Rui-Ming
Published: February 2022

Aging is the greatest risk factor for late-onset Alzheimer’s disease (LOAD), which accounts for >95% of Alzheimer’s disease (AD) cases. The mechanism underlying the aging-related susceptibility to LOAD is unknown. Cellular senescence, a state of permanent cell growth arrest, is believed to contribute importantly to aging and aging-related diseases, including AD. Senescent astrocytes, microglia, endothelial cells, and neurons have been detected in the brain of AD patients and AD animal models. Removing senescent cells genetically or pharmacologically ameliorates β-amyloid (Aβ) peptide and tau-protein-induced neuropathologies, and improves memory in AD model mice, suggesting a pivotal role of cellular senescence in AD pathophysiology. Nonetheless, although accumulated evidence supports the role of cellular senescence in aging and AD, the mechanisms that promote cell senescence and how senescent cells contribute to AD neuropathophysiology remain largely unknown. This review summarizes recent advances in this field. We believe that the removal of senescent cells represents a promising approach toward the effective treatment of aging-related diseases, such as AD.
Interdisciplinary Study of the Effects of Dipeptidyl-Peptidase III Cancer Mutations on the KEAP1-NRF2 Signaling Pathway
Authors: Matić Sara , Tomašić Paić Ana , Sobočanec Sandra , Pinterić Marija , Pipalović Goran , Martinčić Monika , Matovina Mihaela , Tomić Sanja
Published: February 2022

Dipeptidyl peptidase III (DPP III) is associated with cancer progression via interaction with KEAP1, leading to upregulation of the KEAP1-NRF2 oxidative stress pathway. Numerous DPP III mutations have been found in human tumor genomes, and it is suggested that some of them may alter affinity for KEAP1. One such example is the DPP III-R623W variant, which in our previous study showed much higher affinity for the Kelch domain of KEAP1 than the wild-type protein. In this work, we have investigated the effects of this mutation in cultured cells and the effects of several other DPP III mutations on the stability of KEAP1-DPP III complex using an interdisciplinary approach combining biochemical, biophysical and molecular biology methods with computational studies. We determined the affinity of the DPP III variants for the Kelch domain experimentally and by molecular modeling, as well as the effects of the R623W on the expression of several NRF2-controlled genes. We confirmed that the R623W variant upregulates NQO1 expression at the transcriptional level. This supports the hypothesis from our previous study that the increased affinity of the R623W variant for KEAP1 leads to upregulation of the KEAP1-NRF2 pathway. These results provide a new perspective on the involvement of DPP III in cancer progression and prognosis.
Stressor-Induced Increases in Circulating, but Not Colonic, Cytokines Are Related to Anxiety-like Behavior and Hippocampal Inflammation in a Murine Colitis Model
Authors: Maltz Ross , Marte-Ortiz Pedro , Rajasekera Therese , Loman Brett , Gur Tamar , Bailey Michael
Published: February 2022

Stressor exposure increases colonic inflammation. Because inflammation leads to anxiety-like behavior, we tested whether stressor exposure in mice recovering from dextran-sulfate-sodium (DSS)-induced colitis enhances anxiety-like behavior. Mice received 2% DSS for five consecutive days prior to being exposed to a social-disruption (SDR) stressor (or being left undisturbed). After stressor exposure, their behavior was tested and colitis was assessed via histopathology and via inflammatory-cytokine measurement in the serum and colon. Cytokine and chemokine mRNA levels in the colon, mesenteric lymph nodes (MLNs), hippocampus, and amygdala were measured with RT-PCR. SDR increased anxiety-like behaviors, which correlated with serum and hippocampal IL-17A. The stressor also reduced IL-1β, CCL2, and iNOS in the colonic tissue, but increased iNOS, IFNγ, IL-17A, and TNFα in the MLNs. A network analysis indicated that reductions in colonic iNOS were related to elevated MLN iNOS and IFNγ. These inflammatory markers were related to serum and hippocampal IL-17A and associated with anxiety-like behavior. Our data suggest that iNOS may protect against extra-colonic inflammation, and when suppressed during stress it is associated with elevated MLN IFNγ, which may coordinate gut-to-brain inflammation. Our data point to hippocampal IL-17A as a key correlate of anxiety-like behavior.
The Protein Phosphatase GhAP2C1 Interacts Together with GhMPK4 to Synergistically Regulate the Immune Response to Fusarium oxysporum in Cotton
Authors: Guo Dezheng , Hao Cuihong , Hou Junbin , Zhao Guangdong , Shan Wenlu , Guo Huijuan , Wang Chen , Guo Xingqi
Published: February 2022

The plant mitogen-activated protein kinase (MAPK) cascade plays an important role in mediating responses to biotic and abiotic stresses and is the main pathway through which extracellular stimuli are transduced intracellularly as signals. Our previous research showed that the GhMKK6-GhMPK4 cascade signaling pathway plays an important role in cotton immunity. To further analyze the role and regulatory mechanism of the GhMKK6-GhMPK4 cascade signaling pathway in cotton resistance to Fusarium wilt, we functionally analyzed GhMPK4. Our results show that silencing GhMPK4 reduces cotton tolerance to Fusarium wilt and reduces the expression of several resistance genes. Further experiments revealed that GhMPK4 is similar to GhMKK6, both of whose overexpression cause unfavorable cotton immune response characteristics. By using a yeast two-hybrid screening library and performing a bioinformatics analysis, we screened and identified a negative regulator of the MAPK kinase-protein phosphatase AP2C1. Through the functional analysis of AP2C1, it was found that, after being silenced, GhAP2C1 increased resistance to Fusarium wilt, but GhAP2C1 overexpression caused sensitivity to Fusarium wilt. These findings show that GhAP2C1 interacts together with GhMPK4 to regulate the immune response of cotton to Fusarium oxysporum, which provides important data for functionally analyzing and studying the feedback regulatory mechanism of the MAPK cascade and helps to clarify the regulatory mechanism through which the MAPK cascade acts in response to pathogens.
The Impact of Early Saliva Interaction on Dental Implants and Biomaterials for Oral Regeneration: An Overview
Authors: Kunrath Marcel Ferreira , Dahlin Christer
Published: February 2022

The presence of saliva in the oral environment is relevant for several essential health processes. However, the noncontrolled early saliva interaction with biomaterials manufactured for oral rehabilitation may generate alterations in the superficial properties causing negative biological outcomes. Therefore, the present review aimed to provide a compilation of all possible physical–chemical–biological changes caused by the early saliva interaction in dental implants and materials for oral regeneration. Dental implants, bone substitutes and membranes in dentistry possess different properties focused on improving the healing process when in contact with oral tissues. The early saliva interaction was shown to impair some positive features present in biomaterials related to quick cellular adhesion and proliferation, such as surface hydrophilicity, cellular viability and antibacterial properties. Moreover, biomaterials that interacted with contaminated saliva containing specific bacteria demonstrated favorable conditions for increased bacterial metabolism. Additionally, the quantity of investigations associating biomaterials with early saliva interaction is still scarce in the current literature and requires clarification to prevent clinical failures. Therefore, clinically, controlling saliva exposure to sites involving the application of biomaterials must be prioritized in order to reduce impairment in important biomaterial properties developed for rapid healing.
Acrylamide Neurotoxicity as a Possible Factor Responsible for Inflammation in the Cholinergic Nervous System
Authors: Kopańska Marta , Łagowska Anna , Kuduk Barbara , Banaś-Ząbczyk Agnieszka
Published: February 2022

Acrylamide (ACR) is a chemical compound that exhibits neurotoxic and genotoxic effects. It causes neurological symptoms such as tremors, general weakness, numbness, tingling in the limbs or ataxia. Numerous scientific studies show the effect of ACR on nerve endings and its close connection with the cholinergic system. The cholinergic system is part of the autonomic nervous system that regulates higher cortical functions related to memory, learning, concentration and attention. Within the cholinergic system, there are cholinergic neurons, anatomical cholinergic structures, the neurotransmitter acetylcholine (ACh) and cholinergic receptors. Some scientific reports suggest a negative effect of ACR on the cholinergic system and inflammatory reactions within the body. The aim of the study was to review the current state of knowledge on the influence of acrylamide on the cholinergic system and to evaluate its possible effect on inflammatory processes. The cholinergic anti-inflammatory pathway (CAP) is a neuroimmunomodulatory pathway that is located in the blood and mucous membranes. The role of CAP is to stop the inflammatory response in the appropriate moment. It prevents the synthesis and the release of pro-inflammatory cytokines and ultimately regulates the local and systemic immune response. The cellular molecular mechanism for inhibiting cytokine synthesis is attributed to acetylcholine (ACh), the major vagal neurotransmitter, and the α7 nicotinic receptor (α7nAChR) subunit is a key receptor for the cholinergic anti-inflammatory pathway. The combination of ACh with α7nAChR results in inhibition of the synthesis and release of pro-inflammatory cytokines. The blood AChE is able to terminate the stimulation of the cholinergic anti-inflammatory pathway due to splitting ACh. Accordingly, cytokine production is essential for pathogen protection and tissue repair, but over-release of cytokines can lead to systemic inflammation, organ failure, and death. Inflammatory responses are precisely regulated to effectively protect against harmful stimuli. The central nervous system dynamically interacts with the immune system, modulating inflammation through the humoral and nervous pathways. The stress-induced rise in acetylcholine (ACh) level acts to ease the inflammatory response and restore homeostasis. This signaling process ends when ACh is hydrolyzed by acetylcholinesterase (AChE). There are many scientific reports indicating the harmful effects of ACR on AChE. Most of them indicate that ACR reduces the concentration and activity of AChE. Due to the neurotoxic effect of acrylamide, which is related to the disturbance of the secretion of neurotransmitters, and its influence on the disturbance of acetylcholinesterase activity, it can be concluded that it disturbs the normal inflammatory response.
Chicoric Acid Prevents Neuroinflammation and Neurodegeneration in a Mouse Parkinson’s Disease Model: Immune Response and Transcriptome Profile of the Spleen and Colon
Authors: Wang Ning , Li Rui , Feng Bainian , Cheng Yuliang , Guo Yahui , Qian He
Published: February 2022

Chicoric acid (CA), a polyphenolic acid compound extracted from chicory and echinacea, possesses antiviral, antioxidative and anti-inflammatory activities. Growing evidence supports the pivotal roles of brain–spleen and brain–gut axes in neurodegenerative diseases, including Parkinson’s disease (PD), and the immune response of the spleen and colon is always the active participant in the pathogenesis and development of PD. In this study, we observe that CA prevented dopaminergic neuronal lesions, motor deficits and glial activation in PD mice, along with the increment in striatal brain-derived neurotrophic factor (BDNF), dopamine (DA) and 5-hydroxyindoleacetic acid (5-HT). Furthermore, CA reversed the level of interleukin-17(IL-17), interferon-gamma (IFN-γ) and transforming growth factor-beta (TGF-β) of PD mice, implicating its regulatory effect on the immunological response of spleen and colon. Transcriptome analysis revealed that 22 genes in the spleen (21 upregulated and 1 downregulated) and 306 genes (190 upregulated and 116 downregulated) in the colon were significantly differentially expressed in CA-pretreated mice. These genes were functionally annotated with GSEA, GO and KEGG pathway enrichment, providing the potential target genes and molecular biological mechanisms for the modulation of CA on the spleen and gut in PD. Remarkably, CA restored some gene expressions to normal level. Our results highlighted that the neuroprotection of CA might be associated with the manipulation of CA on brain–spleen and brain–gut axes in PD.
Structure-Based Cyclic Glycoprotein Ibα-Derived Peptides Interfering with von Willebrand Factor-Binding, Affecting Platelet Aggregation under Shear
Authors: Hrdinova Johana , Fernández Delia I. , Ercig Bogac , Tullemans Bibian M. E. , Suylen Dennis P. L. , Agten Stijn M. , Jurk Kerstin , Hackeng Tilman M. , Vanhoorelbeke Karen , Voorberg Jan , Reutelingsperger Chris P. M. , Wichapong Kanin , Heemskerk Johan W. M. , Nicolaes Gerry A. F.
Published: February 2022

The plasmatic von Willebrand factor (VWF) circulates in a compact form unable to bind platelets. Upon shear stress, the VWF A1 domain is exposed, allowing VWF-binding to platelet glycoprotein Ib-V-IX (GPIbα chain). For a better understanding of the role of this interaction in cardiovascular disease, molecules are needed to specifically interfere with the opened VWF A1 domain interaction with GPIbα. Therefore, we in silico designed and chemically synthetized stable cyclic peptides interfering with the platelet-binding of the VWF A1 domain per se or complexed with botrocetin. Selected peptides (26–34 amino acids) with the lowest-binding free energy were: the monocyclic mono- vOn Willebrand factoR-GPIbα InTerference (ORbIT) peptide and bicyclic bi-ORbIT peptide. Interference of the peptides in the binding of VWF to GPIb-V-IX interaction was retained by flow cytometry in comparison with the blocking of anti-VWF A1 domain antibody CLB-RAg35. In collagen and VWF-dependent whole-blood thrombus formation at a high shear rate, CLB-RAg35 suppressed stable platelet adhesion as well as the formation of multilayered thrombi. Both peptides phenotypically mimicked these changes, although they were less potent than CLB-RAg35. The second-round generation of an improved peptide, namely opt-mono-ORbIT (28 amino acids), showed an increased inhibitory activity under flow. Accordingly, our structure-based design of peptides resulted in physiologically effective peptide-based inhibitors, even for convoluted complexes such as GPIbα-VWF A1.
Genetic Deletion of HLJ1 Does Not Affect Blood Coagulation in Mice
Authors: Hsu Man-Chen , Luo Wei-Jia , Guo Bei-Chia , Chen Chia-Hui , Hu Po-An , Tsai Yi-Hsuan , Su Kang-Yi , Lee Tzong-Shyuan
Published: February 2022

HLJ1 (also called DNAJB4) is a member of the DNAJ/Hsp40 family and plays an important role in regulating protein folding and activity. However, there is little information about the role of HLJ1 in the regulation of physiological function. In this study, we investigated the role of HLJ1 in blood coagulation using wild-type C57BL/6 mice and HLJ1-null (HLJ1-/-) mice. Western blot analysis and immunohistochemistry were used to assess the expression and distribution of HLJ1 protein, respectively. The tail bleeding assay was applied to assess the bleeding time and blood loss. A coagulation test was used for measuring the activity of extrinsic, intrinsic and common coagulation pathways. Thromboelastography was used to measure the coagulation parameters in the progression of blood clot formation. The results showed that HLJ1 was detectable in plasma and bone marrow. The distribution of HLJ1 was co-localized with CD41, the marker of platelets and megakaryocytes. However, genetic deletion of HLJ1 did not alter blood loss and the activity of extrinsic and intrinsic coagulation pathways, as well as blood clot formation, compared to wild-type mice. Collectively, these findings suggest that, although HLJ1 appears in megakaryocytes and platelets, it may not play a role in the function of blood coagulation under normal physiological conditions.
Anti-Septic Functions of Cornuside against HMGB1-Mediated Severe Inflammatory Responses
Authors: Kim Nayeon , Kim Chaeyeong , Ryu Soo Ho , Lee Wonhwa , Bae Jong-Sup
Published: February 2022

High mobility group box 1 (HMGB1) is acknowledged to have critical functions; therefore, targeting this protein may have therapeutic effects. One example is potential antiseptic activity obtained by suppressing HMGB1 secretion, leading to the recovery of vascular barrier integrity. Cornuside (CN), which is a product extracted from the fruit of Cornusofficinalis Seib, is a natural bis-iridoid glycoside with the therapeutic effects of suppressing inflammation and regulating immune responses. However, the mechanism of action of CN and impact on sepsis is still unclear. We examined if CN could suppress HMGB1-induced excessive permeability and if the reduction of HMGB1 in response to LPS treatment increased the survival rate in a mouse model of sepsis. In human endothelial cells stimulated by LPS and mice with septic symptoms of cecal ligation and puncture (CLP), we examined levels of proinflammatory proteins and biomarkers as an index of tissue damage, along with decreased vascular permeability. In both LPS-treated human umbilical vein endothelial cells (HUVECs) and the CLP-treated mouse model of sepsis, we applied CN after the induction processes were over. CN suppressed excessive permeability and inhibited HMGB1 release, leading to the amelioration of vascular instability, reduced mortality, and improved histological conditions in the CLP-induced septic mouse model. Overall, we conclude that the suppressed release of HMGB1 and the increased survival rate of mice with CLP-induced sepsis caused by CN may be an effective pharmaceutical treatment for sepsis.
Molecular Tissue Responses to Mechanical Loading
Authors: Orgel Joseph
Published: February 2022

The intention of this special edition is to highlight the benefits of a holistic approach to computational and experimental approaches in the context of aiding the diagnosis and remediation of disease and injury, especially in neurological and connective tissues and organs [...]
Gel-Based Proteomic Identification of Suprabasin as a Potential New Candidate Biomarker in Endometrial Cancer
Authors: Celsi Fulvio , Monasta Lorenzo , Arrigoni Giorgio , Battisti Ilaria , Licastro Danilo , Aloisio Michelangelo , Di Lorenzo Giovanni , Romano Federico , Ricci Giuseppe , Ura Blendi
Published: February 2022

Endometrial cancer (EC) is the most frequent gynaecologic cancer in postmenopausal women. We used 2D-DIGE and mass spectrometry to identify candidate biomarkers in endometrial cancer, analysing the serum protein contents of 10 patients versus 10 control subjects. Using gel-based proteomics, we identified 24 candidate biomarkers, considering only spots with a fold change in volume percentage ≥ 1.5 or intensity change ≤ 0.6, which were significantly different between cases and controls (p < 0.05). We used Western blotting analysis both in the serum and tissue of 43 patients for data validation. Among the identified proteins, we selected Suprabasin (SBSN), an oncogene previously associated with poor prognosis in different cancers. SBSN principal isoforms were subjected to Western blotting analysis in serum and surgery-excised tissue: both isoforms were downregulated in the tissue. However, in serum, isoform 1 was upregulated, while isoform 2 was downregulated. Data-mining on the TCGA and GTEx projects, using the GEPIA2.0 interface, indicated a diminished SBSN expression in the Uterine Corpus Endometrial Cancer (UCEC) database compared to normal tissue, confirming proteomic results. These results suggest that SBSN, specifically isoform 2, in tissue or serum, could be a potential novel biomarker in endometrial cancer.
Ordered Weighted Averaging (OWA), Decision Making under Uncertainty, and Deep Learning: How Is This All Related?
Authors: Kreinovich Vladik
Published: February 2022

Among many research areas to which Ron Yager contributed are decision making under uncertainty (in particular, under interval and fuzzy uncertainty) and aggregation—where he proposed, analyzed, and utilized ordered weighted averaging (OWA). The OWA algorithm itself provides only a specific type of data aggregation. However, it turns out that if we allow several OWA stages, one after another, we obtain a scheme with a universal approximation property—moreover, a scheme which is perfectly equivalent to modern ReLU-based deep neural networks. In this sense, Ron Yager can be viewed as a (grand)father of ReLU-based deep learning. We also recall that the existing schemes for decision making under uncertainty are also naturally interpretable in OWA terms.
Illumina Short-Read Sequencing of the Mitogenomes of Novel Scarites subterraneus Isolates Allows for Taxonomic Refinement of the Genus Scarites Fabricius 1775, within the Carabidae Family
Authors: Kyndt Elliot C. , Kyndt John A.
Published: February 2022

We sequenced the complete mitogenomes, 18S and 28S rRNA of two new Scarites isolates, collected in Eastern Nebraska and Northern Arkansas (US). Based on molecular sequence data comparison and morphological characteristics, the new isolates were identified as a subspecies of Scarites subterraneus Fabricius 1775, for which we propose the subspecies names ‘nebraskensis’ and ‘arkansensis’. The new 18S and 28S rRNA sequences were found to be 99% and 98% identical to Scarites subterraneus. There are no other Scarites 18S or 28S rRNA sequences in the Genbank database, however, phylogenetic analysis of the Cox1 genes showed S. vicinus Chaudoir, 1843, and S. aterrimus Morawitz, 1863, as the closest relatives. This is the first report of a mitogenome for S. subterraneus, and only the second mitogenome for that genus. The nucleotide sequence identity between the mitogenomes of the two isolates is 98.8%, while the earlier sequenced S. buparius Forster 1771 mitogenome is more distantly related, with only 90% (to ssp. nebraskensis) and 89% (to ssp. arkansensis) overall nucleotide sequence identity. These new mitogenomes, and their phylogenetic analysis, firmly establish the position of Scarites on the Carabidae family tree and further refine the genus. In addition to the molecular data provided for the Scarites species, this approach also allowed us to identify bacterial and viral signatures for Providencia, Myroides, Spiroplasma, and a giant Nucleocytoviricota virus, associated with the Scarites species. We hereby present a simple and efficient protocol for identification and phylogenetic analysis of Scarites, that is applicable to other Coleoptera, based on total DNA extraction and Illumina short-read Next-Gen sequencing.
Nematodes in the Pine Forests of Northern and Central Greece
Authors: Karmezi Maria , Bataka Alkmini , Papachristos Dimitrios , Avtzis Dimitrios N.
Published: February 2022

In the context of plants or plant products protection by harmful organisms, measures have been taken by EU countries in order to prevent their introduction and establishment into the EU, and also limit their expansion in case they do enter. Such a case is Bursaphelenchus xylophilus (Parasitaphelenchidae, Nematoda), already recorded in Portugal and Spain. So, Member States should take all the appropriate steps in order to monitor and confine if necessary susceptible plants and/or plant products. Such measures include annual surveys even in countries where pine wilt disease does not occur yet. Therefore, national survey programs are widely established, sampling and examining samples from pine trees showing suspicious symptoms that could potentially be attributed to B. xylophilus. In this direction, such a network has also been established in Greece collecting and examining wood samples nationwide. In total, 123 wood samples were collected from conifer trees of Northern and Central Greece. Though B. xylophilus was absent from all samples examined, four other Bursaphelenchus species were identified. In addition, other nematode taxa were also recorded, including several phytophagous, microbivorous as well as predatory nematode species. This highlights the fact that besides preventing the introduction of B. xylophilus in Greece, national survey programs can significantly contribute to and enhance our knowledge of the indigenous nematode species.
Abdominal Aortic Aneurysm Morphology as an Essential Criterion for Stratifying the Risk of Aneurysm Rupture
Authors: Niklas Natalia , Gutowski Piotr , Kazimierczak Arkadiusz , Rynio Paweł
Published: February 2022

The current stratification model of aneurysm rupture seems to be insufficient in some clinical cases. In our study, we determined the differences in wall structure between ruptured and unruptured aneurysms. We obtained computed tomography angiograms and categorized them into the following three groups, consisting of 49 patients each: the group with ruptured abdominal aortic aneurysms (rAAA), symptomatic (sAAA), and asymptomatic (aAAA). The three-dimensional AAA anatomy was digitally reconstructed for each patient through semi-automatically obtained segmentation, and each aneurysm was distinguished by the following three parameters: AFL (aneurysm flow lumen), ILT (intraluminal thrombus), and calcifications. The AFL volume was greater in rAAA compared with aAAA (p = 0.004), the ILT volume was greater in aAAA than in rAAA (p = 0.013), and the AFL/ILT surface ratio was bigger in rAAA than in aAAA (p < 0.001), sAAA than in aAAA (p = 0.033), and rAAA than in sAAA (p = 0.016). AFL/ILT surface*100 was defined as an independent predictive factor of rAAA to aAAA (OR 1.187; 95% CI 1.099–1.281), to sAAA (OR 1.045; 95% CI 1.004–1.087), and in sAAA vs. aAAA (OR 1.067; 95% CI 1.017–1.119). Consequently, the wall of rAAA differs significantly from unruptured aneurysms. The AFL/ILT surface ratio might indicate an increased risk of aneurysm rupture and the occurrence of symptoms in AAA.
Nonalcoholic Fatty Liver Disease Is a Precursor of New-Onset Metabolic Syndrome in Metabolically Healthy Young Adults
Authors: Yoo Jeong-Ju , Cho Eun Ju , Chung Goh Eun , Chang Young , Cho Yuri , Park Sang-Hyun , Jeong Su-Min , Kim Bo-Yeon , Shin Dong Wook , Kim Yun Joon , Yoon Jung-Hwan , Han Kyungdo , Yu Su Jong
Published: February 2022

Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome (MetS). However, the temporal relationship between NAFLD and MetS has yet to be evaluated, especially in young adults. In this study, we investigated whether NAFLD could be a precursor for MetS in metabolically healthy young adults. Using the Korean nationwide health screening database, we analyzed subjects aged 20–39 years who were free from any component of MetS between 2009 and 2012. A total of 1,659,192 subjects without excessive alcohol consumption or concomitant liver disease were categorized into three groups according to the fatty liver index (FLI): (1) NAFLD (FLI ≥ 60); (2) borderline NAFLD (30 ≤ FLI < 60); and (3) control (FLI < 30). During the 6,699,462 person-years of follow-up, 109,239 subjects developed MetS (16.3 per 1000-person-years). The NAFLD group and the borderline NAFLD group were associated with a higher risk of MetS than the control group (incidence rate ratios, 2.9 (95% confidence interval (CI), 2.7–3.1) for the NAFLD group and 2.1 (95% CI, 2.1–2.2) for the borderline NAFLD group, respectively). In addition, all of the metabolic components were positively associated with FLI in a proportional manner. NAFLD is associated with the future onset of MetS in young adults. Therefore, active lifestyle intervention is required for young adults diagnosed with NAFLD to prevent MetS and other metabolic diseases.
Histological Scores in Patients with Inflammatory Bowel Diseases: The State of the Art
Authors: Vespa Edoardo , D’Amico Ferdinando , Sollai Mauro , Allocca Mariangela , Furfaro Federica , Zilli Alessandra , Dal Buono Arianna , Gabbiadini Roberto , Danese Silvio , Fiorino Gionata
Published: February 2022

The histological assessment has been advocated as a detailed and accurate measure of disease activity in inflammatory bowel diseases (IBD). In ulcerative colitis (UC), histological activity has been demonstrated to be associated with higher rates of relapse, prolonged corticosteroid use and long-term complications, even when endoscopic remission is achieved. Therefore, histological healing may represent a potential treatment target. Several histological scores have been developed and are available today. The Robarts histopathology index (RHI) and the Nancy index (NI) are the only two recommended by the European Crohn’s and Colitis Organization (ECCO) for use in patients with UC. Conversely, in Crohn’s disease (CD), the discontinuous nature of lesions has limited standardized histological assessment. Most of the available histological scoring systems in CD are complex and not validated. The aim of this review is to comprehensively summarize the latest evidence regarding histological scoring systems in IBD. We guide the reader through understanding the importance of an accurate microscopic evaluation using validated scoring systems, highlighting the strengths and pitfalls of each score. The priorities of future research needs are also addressed.
Pain-Related Coping Behavior in ALS: The Interplay between Maladaptive Coping, the Patient’s Affective State and Pain
Authors: Schlichte Ina , Petri Susanne , Dengler Reinhard , Meyer Thomas , Haghikia Aiden , Vielhaber Stefan , Vogt Susanne
Published: February 2022

Background: Pain is a common symptom in patients with amyotrophic lateral sclerosis (ALS). Coping plays a central role in adjustment to pain. Objective: This study evaluates the use of different pain coping strategies in patients with ALS and investigates the interplay of maladaptive coping, and the patient’s affective state and pain. Methods: One hundred and fifty ALS patients from three German outpatient clinics completed the Brief Pain Inventory (BPI), the ALS-Functional Rating Scale-Extension (ALSFRS-EX), the ALS Depression Inventory (ADI-12), the subscale “emotional functioning” of the ALS Assessment Questionnaire (ALSAQ-40) and the Coping Strategies Questionnaire (CSQ). Based upon the results of correlational analyses, multiple regression analyses were performed to identify predictors of pain severity and to explore factors contributing to maladaptive coping. Results: Pain was prevalent in 56% (n = 84) of the patients. Patients applied different adaptive coping strategies as well as the maladaptive strategy “catastrophizing”. Regression analysis indicated that the CSQ-subscale “catastrophizing” significantly predicted pain intensity, explaining 34.0% of the variance (p < 0.001). Pain-related catastrophizing was associated with higher pain-related functional impairments and worse emotional functioning. The ADI-12 sum score as an indicator for depressive symptoms contributed significantly to the maladaptive coping strategy “catastrophizing” (p < 0.001) and explained 40.8% of the variance. Conclusion: Patients with ALS apply different strategies to cope with pain. Catastrophizing is an important determinant of higher pain intensity ratings and is associated with higher pain interferences and decreased emotional well-being. Pain-related catastrophizing is promoted by depressive symptoms. Catastrophizing and depressive symptoms thus represent important targets of individualized pain-management strategies.
rTMS Reduces Craving and Alcohol Use in Patients with Alcohol Use Disorder: Results of a Randomized, Sham-Controlled Clinical Trial
Authors: Belgers Maarten , Van Eijndhoven Philip , Markus Wiebren , Schene Aart , Schellekens Arnt
Published: February 2022

(1) Background: Current evidence-based treatments for alcohol use disorder (AUD) are moderately effective. Studies testing repetitive transcranial magnetic stimulation (rTMS) in AUD commonly apply a limited number of rTMS sessions with different rTMS settings, showing inconsistent effects on craving for alcohol. This study tested the efficacy of a robust rTMS protocol on craving and alcohol use. (2) Methods: In a single-blind randomized controlled trial in recently detoxified patients with AUD, ten days of high-frequency rTMS over the right dorsolateral prefrontal cortex on top of treatment as usual (n = 14) was compared with sham rTMS (n = 16). Outcome measures were alcohol craving and use over a follow-up period of one year. Analysis was performed by means of repeated measures multivariate analysis of variance. (3) Results: The results showed a main group-by-time interaction effect on craving (Wilks’ Λ = 0.348, F (12, 17) = 2.654, p = 0.032) and an effect of group on alcohol use (Wilk’s Λ = 0.44, F (6, 23) = 4.9, p = 0.002), with lower alcohol craving and use in the group with active rTMS compared to the control group. Differences in craving between groups were most prominent three months after treatment. At 12 months follow-up, there was no effect of rTMS on craving or abstinence. (4) Conclusions: This small-scale randomized controlled trial showed the efficacy of high-frequency rTMS over the right dlPFC diminished alcohol craving and use in recently detoxified patients with AUD during the first months after detoxification. These findings suggest that rTMS might be an effective add-on in treating patients with AUD and warrant replication in future large-scale studies.