bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide Identification and Expression Analysis of SWEET Family Genes in Sweet Potato and Its Two Diploid Relatives
Authors: Dai Zhuoru , Yan Pengyu , He Shaozhen , Jia Licong , Wang Yannan , Liu Qingchang , Zhai Hong , Zhao Ning , Gao Shaopei , Zhang Huan
Published: December 2022

Sugar Will Eventually be Exported Transporter (SWEET) proteins are key transporters in sugar transportation. They are involved in the regulation of plant growth and development, hormone crosstalk, and biotic and abiotic stress responses. However, SWEET family genes have not been explored in the sweet potato. In this study, we identified 27, 27, and 25 SWEETs in cultivated hexaploid sweet potato (Ipomoea batatas, 2n = 6x = 90) and its two diploid relatives, Ipomoea trifida (2n = 2x = 30) and Ipomoea triloba (2n = 2x = 30), respectively. These SWEETs were divided into four subgroups according to their phylogenetic relationships with Arabidopsis. The protein physiological properties, chromosome localization, phylogenetic relationships, gene structures, promoter cis-elements, protein interaction networks, and expression patterns of these 79 SWEETs were systematically investigated. The results suggested that homologous SWEETs are differentiated in sweet potato and its two diploid relatives and play various vital roles in plant growth, tuberous root development, carotenoid accumulation, hormone crosstalk, and abiotic stress response. This work provides a comprehensive comparison and furthers our understanding of the SWEET genes in the sweet potato and its two diploid relatives, thereby supplying a theoretical foundation for their functional study and further facilitating the molecular breeding of sweet potato.
S-Glutathionylation and S-Nitrosylation in Mitochondria: Focus on Homeostasis and Neurodegenerative Diseases
Authors: Vrettou Sofia , Wirth Brunhilde
Published: December 2022

Redox post-translational modifications are derived from fluctuations in the redox potential and modulate protein function, localization, activity and structure. Amongst the oxidative reversible modifications, the S-glutathionylation of proteins was the first to be characterized as a post-translational modification, which primarily protects proteins from irreversible oxidation. However, a growing body of evidence suggests that S-glutathionylation plays a key role in core cell processes, particularly in mitochondria, which are the main source of reactive oxygen species. S-nitrosylation, another post-translational modification, was identified >150 years ago, but it was re-introduced as a prototype cell-signaling mechanism only recently, one that tightly regulates core processes within the cell’s sub-compartments, especially in mitochondria. S-glutathionylation and S-nitrosylation are modulated by fluctuations in reactive oxygen and nitrogen species and, in turn, orchestrate mitochondrial bioenergetics machinery, morphology, nutrients metabolism and apoptosis. In many neurodegenerative disorders, mitochondria dysfunction and oxidative/nitrosative stresses trigger or exacerbate their pathologies. Despite the substantial amount of research for most of these disorders, there are no successful treatments, while antioxidant supplementation failed in the majority of clinical trials. Herein, we discuss how S-glutathionylation and S-nitrosylation interfere in mitochondrial homeostasis and how the deregulation of these modifications is associated with Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis and Friedreich’s ataxia.
Remarkable Plasticity of Bone Iron Homeostasis in Hibernating Daurian Ground Squirrels (Spermophilus dauricus) May Be Involved in Bone Maintenance
Authors: He Yue , Kong Yong , Yin Rongrong , Yang Huajian , Zhang Jie , Wang Huiping , Gao Yunfang
Published: December 2022

Iron overload is an independent risk factor for disuse osteoporosis. Hibernating animals are natural models of anti-disuse osteoporosis; however, whether iron metabolism is involved in bone adaptation and maintenance during hibernation is unclear. To investigate this question, Daurian ground squirrels (Spermophilus dauricus) (n = 5–6/group) were used to study changes in bone iron metabolism and its possible role in anti-disuse osteoporosis during hibernation. Iron content in the femur and liver first decreased in the torpor group (vs. summer group, −66.8% and −25.8%, respectively), then recovered in the post-hibernation group, suggesting remarkable plasticity of bone iron content. The expression of ferritin in the femur and hepcidin in the liver also initially decreased in the torpor group (vs. summer group, −28.5% and −38.8%, respectively), then increased in the inter-bout arousal (vs. torpor group, 126.2% and 58.4%, respectively) and post-hibernation groups (vs. torpor group, 153.1% and 27.1%, respectively). In conclusion, bone iron metabolism in hibernating Daurian ground squirrels showed remarkable plasticity, which may be a potential mechanism to avoid disuse bone loss during extended periods of inactivity. However, the specific location of iron during low-iron hibernation and the source of iron in post-hibernation recovery need to be further explored.
GABA Release from Astrocytes in Health and Disease
Authors: Kilb Werner , Kirischuk Sergei
Published: December 2022

Astrocytes are the most abundant glial cells in the central nervous system (CNS) mediating a variety of homeostatic functions, such as spatial K+ buffering or neurotransmitter reuptake. In addition, astrocytes are capable of releasing several biologically active substances, including glutamate and GABA. Astrocyte-mediated GABA release has been a matter of debate because the expression level of the main GABA synthesizing enzyme glutamate decarboxylase is quite low in astrocytes, suggesting that low intracellular GABA concentration ([GABA]i) might be insufficient to support a non-vesicular GABA release. However, recent studies demonstrated that, at least in some regions of the CNS, [GABA]i in astrocytes might reach several millimoles both under physiological and especially pathophysiological conditions, thereby enabling GABA release from astrocytes via GABA-permeable anion channels and/or via GABA transporters operating in reverse mode. In this review, we summarize experimental data supporting both forms of GABA release from astrocytes in health and disease, paying special attention to possible feedback mechanisms that might govern the fine-tuning of astrocytic GABA release and, in turn, the tonic GABAA receptor-mediated inhibition in the CNS.
Overview of Anti-Inflammatory and Anti-Nociceptive Effects of Polyphenols to Halt Osteoarthritis: From Preclinical Studies to New Clinical Insights
Authors: Gambari Laura , Cellamare Antonella , Grassi Francesco , Grigolo Brunella , Panciera Alessandro , Ruffilli Alberto , Faldini Cesare , Desando Giovanna
Published: December 2022

Knee osteoarthritis (OA) is one of the most multifactorial joint disorders in adults. It is characterized by degenerative and inflammatory processes that are responsible for joint destruction, pain and stiffness. Despite therapeutic advances, the search for alternative strategies to target inflammation and pain is still very challenging. In this regard, there is a growing body of evidence for the role of several bioactive dietary molecules (BDMs) in targeting inflammation and pain, with promising clinical results. BDMs may be valuable non-pharmaceutical solutions to treat and prevent the evolution of early OA to more severe phenotypes, overcoming the side effects of anti-inflammatory drugs. Among BDMs, polyphenols (PPs) are widely studied due to their abundance in several plants, together with their benefits in halting inflammation and pain. Despite their biological relevance, there are still many questionable aspects (biosafety, bioavailability, etc.) that hinder their clinical application. This review highlights the mechanisms of action and biological targets modulated by PPs, summarizes the data on their anti-inflammatory and anti-nociceptive effects in different preclinical in vitro and in vivo models of OA and underlines the gaps in the knowledge. Furthermore, this work reports the preliminary promising results of clinical studies on OA patients treated with PPs and discusses new perspectives to accelerate the translation of PPs treatment into the clinics.
A Decade of CRISPR-Cas Gnome Editing in C. elegans
Authors: Kim Hyun-Min , Hong Yebin , Chen Jiani
Published: December 2022

CRISPR-Cas allows us to introduce desired genome editing, including mutations, epitopes, and deletions, with unprecedented efficiency. The development of CRISPR-Cas has progressed to such an extent that it is now applicable in various fields, with the help of model organisms. C. elegans is one of the pioneering animals in which numerous CRISPR-Cas strategies have been rapidly established over the past decade. Ironically, the emergence of numerous methods makes the choice of the correct method difficult. Choosing an appropriate selection or screening approach is the first step in planning a genome modification. This report summarizes the key features and applications of CRISPR-Cas methods using C. elegans, illustrating key strategies. Our overview of significant advances in CRISPR-Cas will help readers understand the current advances in genome editing and navigate various methods of CRISPR-Cas genome editing.
Rare Amyloid Precursor Protein Point Mutations Recapitulate Worldwide Migration and Admixture in Healthy Individuals: Implications for the Study of Neurodegeneration
Authors: Abondio Paolo , Bruno Francesco , Bruni Amalia Cecilia , Luiselli Donata
Published: December 2022

Genetic discoveries related to Alzheimer’s disease and other dementias have been performed using either large cohorts of affected subjects or multiple individuals from the same pedigree, therefore disregarding mutations in the context of healthy groups. Moreover, a large portion of studies so far have been performed on individuals of European ancestry, with a remarkable lack of epidemiological and genomic data from underrepresented populations. In the present study, 70 single-point mutations on the APP gene in a publicly available genetic dataset that included 2504 healthy individuals from 26 populations were scanned, and their distribution was analyzed. Furthermore, after gametic phase reconstruction, a pairwise comparison of the segments surrounding the mutations was performed to reveal patterns of haplotype sharing that could point to specific cross-population and cross-ancestry admixture events. Eight mutations were detected in the worldwide dataset, with several of them being specific for a single individual, population, or macroarea. Patterns of segment sharing reflected recent historical events of migration and admixture possibly linked to colonization campaigns. These observations reveal the population dynamics of the considered APP mutations in worldwide human groups and support the development of ancestry-informed screening practices for the improvement of precision and personalized approaches to neurodegeneration and dementia.
The Iridoid Glycoside Loganin Modulates Autophagic Flux Following Chronic Constriction Injury-Induced Neuropathic Pain
Authors: Cheng Kuang-I , Chang Yu-Chin , Chu Li-Wen , Hsieh Su-Ling , An Li-Mei , Dai Zen-Kong , Wu Bin-Nan
Published: December 2022

Autophagy facilitates the degradation of organelles and cytoplasmic proteins in a lysosome-dependent manner. It also plays a crucial role in cell damage. Whether loganin affects autophagy in chronic constriction injury (CCI)-induced neuropathic pain remains unclear. We investigated the neuroprotective effect of loganin on the autophagic–lysosomal pathway in the rat CCI model. Sprague–Dawley rats were divided into sham, CCI, sham + loganin, and CCI + loganin. Loganin (5 mg/kg/day) was intraperitoneally injected once daily, and rats were sacrificed on day 7 after CCI. This study focused on the mechanism by which loganin modulates autophagic flux after CCI. CCI enhanced the autophagic marker LC3B-II in the ipsilateral spinal cord. The ubiquitin-binding protein p62 binds to LC3B-II and integrates into autophagosomes, which are degraded by autophagy. CCI caused the accumulation of p62, indicating the interruption of autophagosome turnover. Loganin significantly attenuated the expression of Beclin-1, LC3B-II, and p62. Double immunofluorescence staining was used to confirm that LC3B-II and p62 were reduced by loganin in the spinal microglia and astrocytes. Loganin also lessened the CCI-increased colocalization of both proteins. Enhanced lysosome-associated membrane protein 2 (LAMP2) and pro-cathepsin D (pro-CTSD) in CCI rats were also attenuated by loganin, suggesting that loganin improves impaired lysosomal function and autophagic flux. Loganin also attenuated the CCI-increased apoptosis protein Bax and cleaved caspase-3. Loganin prevents CCI-induced neuropathic pain, which could be attributed to the regulation of neuroinflammation, neuronal autophagy, and associated cell death. These data suggest autophagy could be a potential target for preventing neuropathic pain.
Normalization of the Immunological Microenvironment and Sustained Minimal Residual Disease Negativity: Do We Need Both for Long-Term Control of Multiple Myeloma?
Authors: Bertuglia Giuseppe , Cani Lorenzo , Larocca Alessandra , Gay Francesca , D’Agostino Mattia
Published: December 2022

Over the past two decades, the treatment landscape for multiple myeloma (MM) has progressed significantly, with the introduction of several new drug classes that have greatly improved patient outcomes. At present, it is well known how the bone marrow (BM) microenvironment (ME) exerts an immunosuppressive action leading to an exhaustion of the immune system cells and promoting the proliferation and sustenance of tumor plasma cells. Therefore, having drugs that can reconstitute a healthy BM ME can improve results in MM patients. Recent findings clearly demonstrated that achieving minimal residual disease (MRD) negativity and sustaining MRD negativity over time play a pivotal prognostic role. However, despite the achievement of MRD negativity, patients may still relapse. The understanding of immunologic changes in the BM ME during treatment, complemented by a deeper knowledge of plasma cell genomics and biology, will be critical to develop future therapies to sustain MRD negativity over time and possibly achieve an operational cure. In this review, we focus on the components of the BM ME and their role in MM, on the prognostic significance of MRD negativity and, finally, on the relative contribution of tumor plasma cell biology and BM ME to long-term disease control.
The Role of G Protein-Coupled Receptor Kinase 6 Regulation in Inflammation and Pain
Authors: Stegen Maike , Frey Ulrich H.
Published: December 2022

The G protein-coupled receptor kinase 6 is associated with inflammation and pathological pain. Impairment of GRK6 expression was described in chronic inflammatory diseases such as rheumatoid arthritis and this was shown to be accompanied by an imbalance of downstream signaling pathways. Here, we discuss novel aspects of GRK6 interaction and its impact upon hyperalgesia and inflammatory processes. In this review, we compile important findings concerning GRK6 regulation for a better pathophysiological understanding of the intracellular interaction in the context of inflammation and show clinical implications—for example, the identification of possible therapy goals in the treatment of chronic inflammatory hyperalgesia.
The Genetic Diversity and Dysfunctionality of Catalase Associated with a Worse Outcome in Crohn’s Disease
Authors: Iborra Marisa , Moret Inés , Busó Enrique , García-Giménez José Luis , Ricart Elena , Gisbert Javier P. , Cabré Eduard , Esteve Maria , Márquez-Mosquera Lucía , García-Planella Esther , Guardiola Jordi , Pallardó Federico V. , Serena Carolina , Algaba-Chueca Francisco , Domenech Eugeni , Nos Pilar , Beltrán Belén
Published: December 2022

Chronic gut inflammation in Crohn’s disease (CD) is associated with an increase in oxidative stress and an imbalance of antioxidant enzymes. We have previously shown that catalase (CAT) activity is permanently inhibited by CD. The purpose of the study was to determine whether there is any relationship between the single nucleotide polymorphisms (SNPs) in the CAT enzyme and the potential risk of CD associated with high levels of oxidative stress. Additionally, we used protein and regulation analyses to determine what causes long-term CAT inhibition in peripheral white mononuclear cells (PWMCs) in both active and inactive CD. We first used a retrospective cohort of 598 patients with CD and 625 age-matched healthy controls (ENEIDA registry) for the genotype analysis. A second human cohort was used to study the functional and regulatory mechanisms of CAT in CD. We isolated PWMCs from CD patients at the onset of the disease (naïve CD patients). In the genotype-association SNP analysis, the CAT SNPs rs1001179, rs475043, and rs525938 showed a significant association with CD (p < 0.001). Smoking CD patients with the CAT SNP rs475043 A/G genotype had significantly more often penetrating disease (p = 0.009). The gene expression and protein levels of CAT were permanently reduced in the active and inactive CD patients. The inhibition of CAT activity in the PWMCs of the CD patients was related to a low concentration of CAT protein caused by the downregulation of CAT-gene transcription. Our study suggests an association between CAT SNPs and the risk of CD that may explain permanent CAT inhibition in CD patients together with low CAT gene and protein expression.
Prediagnosis Depression Rather Than Anxiety Symptoms Is Associated with Decreased Ovarian Cancer Survival: Findings from the Ovarian Cancer Follow-Up Study (OOPS)
Authors: Li Yi-Zi , Qin Xue , Liu Fang-Hua , Chen Wen-Xiao , Wei Yi-Fan , Wang Na , Yan Shi , Kang Ye , Zhao Yu-Hong , Gao Song , Gong Ting-Ting , Wu Qi-Jun
Published: December 2022

Background: The relationship between prediagnosis depression, anxiety symptoms, and ovarian cancer (OC) survival is unknown. We aimed to explore these associations to provide further epidemiological evidence. Methods: We investigated the relationship between prediagnosis depression, anxiety symptoms, and OC survival in a prospective cohort study of newly diagnosed OC patients aged 18–79 years. Depression and anxiety symptoms were assessed using the Patient Health Questionnaire 9 and Generalized Anxiety Disorder 7 at diagnosis, respectively. Deaths were ascertained until 31 March 2021 via medical records and active follow-up. Multivariable-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with prediagnosis depression and anxiety symptoms and all-cause mortality of OC. Results: We found 56 (9.4%) and 235 (39.3%) OC patients with depression and anxiety symptoms, respectively. During a median follow-up of 37.2 months (interquartile range 24.7–50.2 months), 130 deaths were confirmed. Compared with non-depression symptoms, patients with prediagnosis depressive symptoms showed a significantly increased risk of OC mortality (HR = 2.10, 95% CI: 1.20–3.70). Of note, the association was still robust when focusing on the OC patients with severe depressive symptoms (HR = 2.10, 95% CI: 1.07–4.12). However, we observed no association between prediagnosis anxiety symptoms of different severity and OC mortality. Interestingly, OC patients with combined moderate depression and anxiety symptoms had a significantly increased risk of OC mortality (HR = 3.23, 95% CI: 1.14–9.11) compared to those with no symptoms of depression and anxiety. Notably, Wilms’s tumor 1 was significantly associated with depression and anxiety symptoms (p < 0.05). Conclusions: Prediagnosis depression increases the risk of OC mortality. Large multicenter studies are required to confirm this finding.
Association of Fabry Disease with Hearing Loss, Tinnitus, and Sudden Hearing Loss: A Nationwide Population-Based Study
Authors: Cheng Yen-Fu , Xirasagar Sudha , Chen Chin-Shyan , Niu Dau-Ming , Lin Herng-Ching
Published: December 2022

Hearing loss and the related otologic manifestations are receiving increased scrutiny as significant causes of morbidity in Fabry disease. However, the relative risks of auditory deficits among patients with Fabry disease relative to the general population without a diagnosis of Fabry disease have not been studied. This study aims to explore the associations between Fabry disease and hearing-related manifestations using a nationwide population-based dataset. We identified study patients for this cross-sectional study from the 2015–2017 claims databases of the Taiwan Longitudinal Health Insurance Database 2005. We first identified 2312 patients aged over 20 years with a diagnosis of Fabry disease. We used propensity score matching to select five comparison patients per patient with Fabry disease and 11,560 comparison patients without Fabry disease. We used multivariable logistic regressions to estimate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for tinnitus, hearing loss, and sudden deafness among Fabry disease patients vs. comparison patients. Chi-square tests showed statistically significant differences between patients with and without Fabry disease in the prevalence rates of tinnitus (16.7% vs. 11.7%, p < 0.001), hearing loss (7.5% vs. 6.2%, p = 0.014) and sudden deafness (1.7% vs. 1.0%, p = 0.005). Multiple logistic regression revealed that patients with Fabry disease were more likely to suffer from tinnitus, hearing loss and sudden deafness, with adjusted odds ratios of 1.513 (95% CI = 1.336–1.713), 1.246 (95% CI = 1.047–1.483), and 1.681 (95% CI = 1.166–2.423), respectively. We found that Fabry disease is significantly associated with certain auditory manifestations, including hearing loss, sudden deafness, and tinnitus.
Heightened Procoagulation after Post-Operative Thromboprophylaxis Completion in Patients with Metastatic Bone Disease from Primary Colorectal Cancer
Authors: Yamaura Lisa , Young Daniel , Skeith Leslie , Monument Michael J. , Jenne Craig N. , Dufour Antoine , Schneider Prism , Agbani Ejaife O.
Published: December 2022

Background: Platelets play a role in venous thromboembolism (VTE) and in mediating colorectal cancer (CRC) progression. Still, platelets’ role in hypercoagulability after surgical intervention for metastatic bone disease (MBD) is ill-defined. Methods: In this quantitative observational study, we utilized a high-resolution imaging approach to temporally examine platelet procoagulant membrane dynamics (PMD) in four patients with MBD from primary CRC (CRC/MBD), before and after surgical intervention, over a 6-month period. We coupled this investigation with thrombelastography, quantitative plasma shotgun proteomics, and biochemical analysis. Results: The plasma of CRC/MBD patients was enriched in ADAM1a, ADAMTS7, and physiological ligands for platelet glycoprotein-VI/spleen tyrosine kinase (GPVI/Syk) activation. Thromboprophylaxis attenuated procoagulation upon its initial prescription (post-operative day one, POD1); however, all patients experienced rebound procoagulation between POD3 and POD14, which was associated with Syk activation (Y525/Y526) in all patients, and a VTE event in two patients. Plasma levels of DNA-histone complexes increased steadily after surgery and remained elevated throughout the study period. Additionally, we increasingly sighted both homotypic and heterotypic platelet microaggregates after surgery in CRC/MBD patients, but not in healthy control participants’ plasma. Conclusions: Our data elucidates the cell biology of a prothrombo-inflammatory state caused by disease and vascular injury, and recalcitrant to thromboprophylaxis. New mechanistic insights into hypercoagulability in CRC/MBD patients may identify novel drug targets for effective thromboprophylaxis type and duration after orthopaedic surgery.
Current and Emerging Treatment Options in Sinus and Nasal Diseases: A Promising Future in the Appropriate Therapies
Authors: Lin Lin , Cheng Lei
Published: December 2022

Chronic rhinosinusitis (CRS) is an inflammatory condition of the nose and paranasal sinuses defined by clinical symptoms, including two or more symptoms, one of which should be either nasal blockage or nasal discharge with or without facial pain/pressure or reduction in/loss of sense of smell [...]
Pancreatic Adenosquamous Carcinoma: A Rare Pathological Subtype of Pancreatic Cancer
Authors: Xiong Qunli , Zhang Zhiwei , Xu Yongfeng , Zhu Qing
Published: December 2022

Pancreatic adenosquamous carcinoma (PASC) is a rare pathological subtype of pancreatic cancer (PC), with a worse prognosis than pancreatic ductal adenocarcinoma (PDAC). Due to its rarity, our knowledge of PASC and its biological characteristics are limited. In this review, we provide an overview of the histogenesis, genetic features, diagnosis, treatment, and prognosis of PASC, as well as pancreatic squamous cell carcinoma (PSCC). The information provided here may help to clarify our understanding of PASC and provide useful avenues for further research on this disease.
Effect of Folic Acid Treatment for Patients with Traumatic Brain Injury (TBI)-Related Hospital Acquired Pneumonia (HAP): A Retrospective Cohort Study
Authors: Wu Hao , Geng Xin , Liu Chenan , Ballah Augustine K. , Li Feixiang , Han Tangrui , Gao Shuai , Wang Chunhong , Ji Hongming , Nie Xiaoqi , Cheng Gang , Wang Xiangyu , Cheng Rui , Wang Yonghong
Published: December 2022

Hospital Acquired Pneumonia (HAP) is one of the most common complications and late causes of death in TBI patients. Targeted prevention and treatment of HAP are of great significance for improving the prognosis of TBI patients. In the previous clinical observation, we found that folic acid treatment for TBI patients has a good effect on preventing and treating HAP. We conducted this retrospective cohort study to demonstrate what we observed by selecting 293 TBI patients from two medical centers and analyzing their hospitalization data. The result showed that the incidence of HAP was significantly lower in TBI patients who received folic acid treatment (44.1% vs. 63.0%, p = 0.012). Multivariate logistic regression analysis showed that folic acid treatment was an independent protective factor for the occurrence of HAP in TBI patients (OR = 0.418, p = 0.031), especially in high-risk groups of HAP, such as the old (OR: 1.356 vs. 2.889), ICU (OR: 1.775 vs. 5.996) and severe TBI (OR: 0.975 vs. 5.424) patients. At the same time, cohort studies of HAP patients showed that folic acid also had a good effect on delaying the progression of HAP, such as reducing the chance of tracheotomy (26.1% vs. 50.8%, p = 0.041), and reduced the length of hospital stay (15 d vs. 19 d, p = 0.029) and ICU stay (5 d vs. 8 d, p = 0.046). Therefore, we believe that folic acid treatment in TBI patients has the potential for preventing and treating HAP, and it is worthy of further clinical research.
Angioplasty of Dysfunctional Dialysis Fistula or Graft with Resveratrol-Excipient and Paclitaxel-Coated Balloon Improves Primary Patency Rates Compared to Plain Angioplasty Alone
Authors: Novak Matej , Matras Patrik , Kavan Jan , Lambert Lukas , Burgetova Andrea
Published: December 2022

In this prospective randomized single-blinded study (reg. ISRCTN11414306), 76 patients with a dysfunctional dialysis fistula or graft due to a single de novo or recurrent stenosis in the access circuit were randomized to receive either conventional PTA (POBA) as a standard of care (n = 38) or PTA + adjunctive PTA with a drug-coated (paclitaxel–resveratrol matrix) SeQuent® Please OTW balloon (n = 38, DCB). Patients were scheduled for follow-up PTA at 3, 6, 9, and 12 months. The time of clinically driven target-lesion reintervention rate (primary patency rate) after the index procedure was analyzed using the log-rank test. The primary patency rates at 12 months after the index procedure were 17% (DCB) vs. 11% (POBA). At 3 months, they were 87% vs. 74%, at 6 months they were 53% vs. 26%, and at 9 months they were 22% vs. 11%. The hazard ratio for DCB was 0.55 (95%CI 0.32 to 0.95). The median time needed for target-lesion reintervention was longer in the DCB group (181 days) than in the conventional PTA group (98 days, p = 0.019). We conclude that PTA with the paclitaxel–resveratrol drug-coated SeQuent® Please OTW balloon in patients with de novo or recurrent stenosis in dialysis arteriovenous fistulas or grafts prolongs the time needed for target lesion reintervention and improves primary patency rates in the first year after the index procedure.
Treatment of Femoral Shaft Pseudarthrosis, Case Series and Medico-Legal Implications
Authors: Basile Giuseppe , Fozzato Stefania , Petrucci Quirino Alessandro , Gallina Mario , Bianco Prevot Luca , Accetta Riccardo , Zaami Simona
Published: December 2022

Pseudarthrosis (PSA) is a possible complication of femoral shaft fracture treatment. It is often associated with reduced bone quality and can, therefore, adversely affect quality of life. Its treatment poses a major challenge for orthopaedic surgeons. Several authors have set forth different surgical approaches for the treatment of pseudarthrosis, such as internal fixation with plate and screws, replacement of an intramedullary nail or prosthetic replacement. In cases associated with bone loss, osteopenia, or comminution of fracture fragments, autologous or homologous bone grafts may also be used. The chronic outcomes of the surgical treatment of femoral shaft pseudarthrosis, even when consolidation is achieved, are linked to disabling sequelae of clinical-functional relevance, deserving an adequate medico-legal evaluation. The purpose of this retrospective study is to analyse a clinical case series of patients treated for atrophic femoral shaft pseudarthrosis at the IRCCS Orthopaedic Institute Galeazzi, Milan, Italy, from 2014 to 2020 and their orthopaedic-traumatological and medico-legal implications.
Association between Pulmonary Function and Body Composition in Children and Adolescents with and without Obesity
Authors: Ferreira Mariana Simões , Marson Fernando Augusto Lima , Wolf Vaneza Lira Waldow , Zambon Mariana Porto , Antonio Maria Ângela Reis de Góes Monteiro , Ribeiro José Dirceu , Mendes Roberto Teixeira
Published: December 2022

Lung function in children and adolescents with obesity must consider the coexistence of two complex and related phenomena: obesity and growth. The assessment of body composition can identify changes in respiratory dynamics arising, exclusively or jointly, from adiposity and lean body mass. This study aimed to compare pulmonary function and the dysanapsis indices of children and adolescents without asthma, with and without obesity, considering body composition, pubertal development, and physical activity practice. We performed a cross-sectional study with 69 participants, 41 (59.42%) of whom have obesity. All participants carried out spirometry and the assessment of, respectively, body composition by dual-energy X-ray absorptiometry, vital signs, pubertal development, and physical activity practice. In our data, the group with obesity had higher values of forced vital capacity (FVC) and lower values of the ratio between forced expiratory volume in one second and FVC (FEV1/FVC). Analyzing the entire sample, we found a positive correlation between FVC and a negative correlation between FEV1/FVC with fat mass markers. At the same time, inspiratory capacity, expiratory reserve volume, and peak expiratory flow were correlated with lean body mass markers. In addition, participants with obesity presented a lower dysanapsis index. In conclusion, children and adolescents with obesity showed increased FVC and reduced FEV1/FVC. Our findings are possibly related to the increase in fat mass, not to lean body mass. We hypothesize that these findings are associated with the dysanaptic growth pattern, which is higher in obesity, evidenced by the reduction of the dysanapsis index.
Microstructural Evaluation and Fracture Behavior of AZ31/Nb2O5 Metal Matrix Composite
Authors: Huang Song-Jeng , Sarkar Manas , Kannaiyan Sathiyalingam
Published: December 2022

There have been remarkable improvements in the research field of magnesium over the last few decades, especially in the magnesium metal matrix composite in which micro and nanoparticles are used as reinforcement. The dispersion phase of nanoparticles shows a better microstructural morphology than pure magnesium. The magnesium metal matrix nanocomposite shows improved strength with a balance of plasticity as compared to the traditional magnesium metal matrix composite. In this research, Nb2O5 (0 wt.%, 3 wt.%, and 6 wt.%) nanoparticles were used to reinforce AZ31 with the stir casting method, followed by heat treatment, and finally, an investigation was conducted using microstructural analysis. Factors such as the degree of crystallinity, crystallite size, and dislocation density are affected by the concentration of Nb2O5 and heat treatment. With the compositional increase in Nb2O5 weight percentage, the grain size decreases up to 3% Nb2O5 and then increases gradually. The SEM image analysis showed a grain size reduction of up to 3% Nb2O5 and fracture morphology changed from basal slip to a mixture of basal slip and adiabatic shear band.
Pelvic Venous Insufficiency: Input of Short Tau Inversion Recovery Sequence
Authors: Jambon Eva , Le Bras Yann , Cazalas Gregoire , Grenier Nicolas , Marcelin Clement
Published: December 2022

Objectives: To evaluate indirect criteria of pelvic venous insufficiency (PVI) of a short tau inversion recovery (STIR) sequence retrospectively compared with phlebographic findings. Methods: Between 2008 and 2018, 164 women who had received MRI and phlebography for pelvic congestion syndrome (60), varicose veins in the lower limbs (45), both (43), or other symptoms (16) were included. The presence of periuterine varicosities and perivaginal varicosities were compared to the findings of phlebography: grading of left ovarian vein reflux and presence of internal pudendal or obturator leak. Results: There was a correlation between the grading of LOV reflux on phlebography and the diameter of periuterine varicosities on STIR sequence (p = 0.008, rho = 0.206, CIrho [0.0549 to 0.349]). Periuterine varicosities had a positive predictive value of 93% for left ovarian reflux (95% CI [88.84% to 95.50%]). Obturator or internal pudendal leaks were found for 118 women (72%) and iliac insufficiency for 120 women (73%). Conclusions: Non-injected MRI offers a satisfactory exploration of PVI with STIR sequence. STIR sequences alone enabled the detection of left ovarian and iliac insufficiency.
Optimal Prandial Timing of Insulin Bolus in Youths with Type 1 Diabetes: A Systematic Review
Authors: Mozzillo Enza , Franceschi Roberto , Di Candia Francesca , Ricci Alessia , Leonardi Letizia , Girardi Martina , Rosanio Francesco Maria , Marcovecchio Maria Loredana
Published: December 2022

The aim of this systematic review was to report the evidence on optimal prandial timing of insulin bolus in youths with type 1 diabetes. A systematic search was performed including studies published in the last 20 years (2002–2022). A PICOS framework was used in the selection process and evidence was assessed using the GRADE system. Up to one third of children and adolescents with type 1 diabetes injected rapid-acting insulin analogues after a meal. Moderate–high level quality studies showed that a pre-meal bolus compared with a bolus given at the start or after the meal was associated with a lower peak blood glucose after one to two hours, particularly after breakfast, as well as with reduced HbA1c, without any difference in the frequency of hypoglycemia. There were no differences related to the timing of bolus in total daily insulin and BMI, although these results were based on a single study. Data on individuals’ treatment satisfaction were limited but did not show any effect of timing of bolus on quality of life. In addition, post-prandial administration of fast-acting analogues was superior to rapid-acting analogues on post-prandial glycemia. There was no evidence for any difference in outcomes related to the timing of insulin bolus across age groups in the two studies. In conclusion, prandial insulin injected before a meal, particularly at breakfast, provides better post-prandial glycemia and HbA1c without increasing the risk of hypoglycemia, and without affecting total daily insulin dose and BMI. For young children who often have variable eating behaviors, fast-acting analogues administered at mealtime or post-meal could provide an additional advantage.
NLRP6 Induces Lung Injury and Inflammation Early in Brucella and Influenza Coinfection
Authors: Shi Bochang , Han Hui , Li Huabin , Tan Lingyun , Li Xinyu , Wang Keyu , Li Bo , He Wei , Tian Chongyu , Yan Fang , Shi Yanchun , Zheng Yuanqiang , Zhao Zhongpeng
Published: December 2022

(1) Background: With the resurgence of brucellosis epidemics in China in recent years, the chances of a brucella coinfection with other common respiratory pathogens, such as the influenza virus, have increased dramatically. However, little is known about the pathogenicity or the mechanisms of brucella and influenza coinfections. (2) Methods: To clarify the interventions in the early stages of lung damage due to brucella and influenza coinfections, we evaluated the effect of the coinfection on disease progression and mortality using a coinfection model in WT mice and NLRP6−/− mice, and we verified the function of NLRP6 in infection and proinflammation. (3) Results: The coinfection induced significant respiratory symptoms, weight loss, and a high mortality rate in WT mice. Influenza in the coinfection group significantly increased brucella proliferation in a synergistic manner. Meanwhile, a histological examination showed severe lung tissue destruction and excessive inflammatory responses in coinfected WT animals, and the expression of NLRP6 and IL-18 was dramatically increased in the lung tissues. Furthermore, NLRP6 deletion attenuated lung injuries and inflammation, a reduced bacterial load, and decreased IL-18 protein expression. (4) Conclusions: Our findings indicated that NLRP6 plays a critical role and might be a promising potential therapeutic target for brucella–influenza coinfections.
Clinical-Epidemiology of Tension-Type Headache among the Medical and Dental Undergraduates of King Khalid University, Abha, Saudi Arabia
Authors: Sabah Zia Ul , Aziz Shahid , Narapureddy Bayapa Reddy , Alasiri Hassan Ahmed A. , Asiri Hassan Yahya M. , Asiri Abdulkhaliq Hadi H. , Alsulami Ahmad Abdullah H. , Hassan Nawaf Khalid Ahmad , Mohammed Asif Shaik , Alsyd Shmookh Mohsen
Published: December 2022

Introduction (background): Headache is the primary complaint among students. Headaches mostly have multifactorial causes. The degree of headache severity significantly impacts attitudes, behavior, and academic performance. Objectives: Here, we investigate the demographic epidemiology of tension-type headaches (T.T.H.), and determine the clinical presentation and triggers of the tension-type among headache sufferers. Methods (settings, design): An institutional-based cross-sectional study (descriptive) was conducted on the medical and dental undergraduates at King Khalid University, Abha, Saudi Arabia, from 1 July 2021 to 31 December 2021. Data were gathered using a pre-designed questionnaire. A consecutive sampling method was used in a COVID-19-constrained environment. After preliminary screening of the study population, 460 samples were included. An electronic questionnaire was shared with them, and they were requested to respond. Results: More than half of the participants (258, 56.1%) experienced tension-type headaches, while the remaining 202 (43.9%) never felt a headache. Tension-type headaches manifested as heaviness of the head (44, 17.0%), tightness (126, 48.8%), and dull aching pain (66, 25.7%). Conclusions: T.T.H. is a prevalent condition with a significant impingement on academic work, and psychological health. Tension-type headache sufferers are advised to keep daily diaries to determine triggers, and plan for prevention and treatment progression.
Forecasting Detrended Volatility Risk and Financial Price Series Using LSTM Neural Networks and XGBoost Regressor
Authors: Raudys Aistis , Goldstein Edvinas
Published: December 2022

It is common practice to employ returns, price differences or log returns for financial risk estimation and time series forecasting. In De Prado’s 2018 book, it was argued that by using returns we lose memory of time series. In order to verify this statement, we examined the differences between fractional differencing and logarithmic transformations and their impact on data memory. We employed LSTM (long short-term memory) recurrent neural networks and an XGBoost regressor on the data using those transformations. We forecasted risk (volatility) and price value and compared the results of all models using original, unmodified prices. From the results, models showed that, on average, a logarithmic transformation achieved better volatility predictions in terms of mean squared error and accuracy. Logarithmic transformation was the most promising transformation in terms of profitability. Our results were controversial to Marco Lopez de Prado’s suggestion, as we managed to achieve the most accurate volatility predictions in terms of mean squared error and accuracy using logarithmic transformation instead of fractional differencing. This transformation was also most promising in terms of profitability.
Cross-County Characteristics of Water–Ecology–Economy Coupling Coordination in the Wuding River Watershed, China
Authors: Tao Jian , Xie Yujie , Zhou Haoyuan , Xu Yuqian , Zhao Guangshuai
Published: December 2022

Investigating the coupling coordination relationship between water resources, ecology and the economy is the basis process for watershed governing to achieve sustainable development. Taking the Wuding River watershed (one of the largest tributaries of the Yellow River) as an example, we used the coupling coordination model to analyze the coupling coordination relationship of the water–ecology–economy system between 2001 and 2020, and then used grey correlation and partial correlation analyses to explore the main influencing factors and cross-county characteristic of the coupling coordination. The results show that the water, ecology and economy subsystems changed slightly before 2007. After 2007, the economy developed rapidly, while the water and ecology increased for a short time and then decreased after 2013. The water–ecology–economy coupling coordination was on the verge of dysfunctional decline. Water and ecology were the main influencing factors on the coupling coordination. The coupling coordination showed a cross-county characteristic. Water and ecology in upstream counties had significant positive correlations with the coupling coordination in downstream counties. The economy subsystem in upstream counties, however, had significant negative correlations with water and ecology in downstream counties. Our findings provide an empirical mode to measure transregional characteristics of coupling coordination and could support the construction of a coordination governance mode in the Wuding River watershed.
The Impact of Climate Change on China and Brazil’s Soybean Trade
Authors: Ali Tariq , Zhou Bo , Cleary David , Xie Wei
Published: December 2022

In the recent past, China has expanded its grain production to achieve high food security and increased its partial dependence on imported agricultural commodities, of which soybean supply is highly import-dependent. This study systematically reviews the past trends in China’s soybean demand, Brazil’s soybean production and export, factors contributing to the soybean trade between China and Brazil, and future uncertainty in China’s demand and Brazil’s supply under climate change. We find that recently China imported ~64% of soybean from Brazil, while ~73% of Brazil’s soybean exports were destined for China, making them key stakeholders in their international soybean trade. China’s accession to the World Trade Organization, China–Brazil trade cooperation, and diversion from trade with the USA have played a pivotal role in China’s increasing soybean imports from Brazil. China’s soybean import has brought increasing virtual land to China (from 3.57 million hectares (Mha) in 2005 to 19.63 mha in 2020). This growing virtual land import could be one of the reasons behind Brazil’s soybean harvested area, which increased from 22.95 Mha in 2005 to 37.19 Mha in 2020. In the future, climate change impacts on soybean production in Brazil can seriously affect China’s soybean imports from Brazil and its domestic food security. We analyze these effects using a climate-crop–economic modeling approach, where yield changes from the crop model are incorporated into the economic model as lower land productivity. Our results show that Brazil’s future soybean production and gross exports can drop up to 13.1% and 15.2% under the highest emissions scenario (RCP8.5). Consequently, China would face a decrease in its soybean imports from Brazil (−9.94 Mt). Due to these import reductions, China’s domestic soybean supply will be reduced (−9.94 Mt). There would also be some reduction in China’s meat supply and a drop in China’s consumer welfare. Our results can contribute to devising policies to ensure China’s food security and promote global sustainable development goals.
Baseline Ang-2 Serum Levels as a Predictive Factor for Survival in NSCLC and SCLC
Authors: Nikolakopoulou Asimina , Tsakogiannis Dimitris , Zagouri Flora , Zografos Eleni , Tzioga Lamprini , Stratakos Grigorios , Koulouris Nikolaos , Syrigos Konstantinos , Bletsa Garyfalia
Published: December 2022

Angiopoietin-2 (Ang-2) has been implicated in the development of several types of cancer, including lung malignancy. In the present study, we examined the impact of Ang-2 serum concentration on the development, dissemination, and 5-year overall survival of NSCLC and SCLC. A total of 99 patients with lung cancer were tested. The OS of NSCLC and SCLC patients was estimated using Kaplan–Meier curves and compared through log-rank test. The median serum level of Ang-2 at baseline in both NSCLC and SCLC patients was significantly higher than that of controls (p < 0.0001). The Ang-2 serum concentration was not related to metastasis, neither in NSCLC nor in SCLC cases. The OS was found to be significantly shorter for stage IIIβ NSCLC patients with a high baseline Ang-2 serum concentration (p = 0.012), while Cox regression analysis showed that Ang-2 is a significant independent factor for poor prognosis for stage IIIβ NSCLC (hazard ratio = 2.97, 95% CI: 1.05–8.40, p = 0.04). The concentration of Ang-2 has no impact on the prognosis of SCLC. Ang-2 could be considered as a significant molecular marker that enables the prediction of NSCLC and SCLC development, and is involved in the poor prognosis of stage IIIβ NSCLC.