bluuebunny/crossref_metadata_2025 huggingface dataset:
Will Gold Prices Persist Post Pandemic Period? An Econometric Evidence
Authors: Kumaraswamy Sumathi , Abdulla Yomna , Panigrahi Shrikant Krupasindhu
Published: December 2022

Recurrent stock market fall and rise sequel by COVID-19, rising global inflation, increase in Fed interest rates, the unprecedented meltdown of technology stocks, fear of trade wars, tightening of governments’ fiscal policies call for a new trend in international investing. It is time for the investors to rethink, rebalance and reset their investment strategies to position and protect their portfolios during and post-pandemic period. This paper attempts to forecast the gold prices for the post-pandemic era and explores whether gold will serve as a decisive hedge during this transition period. The techniques of ARCH, GARCH, E-GARCH, A-PARCH, and GARCH-M is employed in forecasting the conditional volatility of gold spot price from Multi Commodity Exchange (MCX) of India. A total of 3631 observations were collected from the daily spot prices of gold from January 2009 to December 2022. The findings show that the gold prices in India are highly persistent similar to other emerging markets and that gold will remain a safe haven for investors and institutional investors in the post-pandemic period. This paper is the first of its kind to forecast gold prices for the post-pandemic period. The forecast price of 10-gram gold is expected to trade for 65,948 ₹ in the Indian MCX by 2026 if the gold prices behold its previous momentum. This forecast will help the investors to plan their portfolio diversification for the post-pandemic period.
Using Deep Reinforcement Learning with Hierarchical Risk Parity for Portfolio Optimization
Authors: Millea Adrian , Edalat Abbas
Published: December 2022

We devise a hierarchical decision-making architecture for portfolio optimization on multiple markets. At the highest level a Deep Reinforcement Learning (DRL) agent selects among a number of discrete actions, representing low-level agents. For the low-level agents, we use a set of Hierarchical Risk Parity (HRP) and Hierarchical Equal Risk Contribution (HERC) models with different hyperparameters, which all run in parallel, off-market (in a simulation). The information on which the DRL agent decides which of the low-level agents should act next is constituted by the stacking of the recent performances of all agents. Thus, the modelling resembles a statefull, non-stationary, multi-arm bandit, where the performance of the individual arms changes with time and is assumed to be dependent on the recent history. We perform experiments on the cryptocurrency market (117 assets), on the stock market (46 assets) and on the foreign exchange market (28 pairs) showing the excellent robustness and performance of the overall system. Moreover, we eliminate the need for retraining and are able to deal with large testing sets successfully.
Transcriptomic Analysis Reveals That Retinal Neuromodulation Is a Relevant Mechanism in the Neuroprotective Effect of Sitagliptin in an Experimental Model of Diabetic Retinopathy
Authors: Ramos Hugo , Bogdanov Patricia , Simó Rafael , Deàs-Just Anna , Hernández Cristina
Published: December 2022

Synaptic dysfunction and neuronal damage have been extensively associated with diabetic retinopathy (DR). Our group evidenced that chronic hyperglycemia reduces the retinal expression of presynaptic proteins, which are crucial for proper synaptic function. The aim of the study was to explore the effect of topically administered sitagliptin, an inhibitor of the enzyme dipeptidyl peptidase-4, on the retinal expression patterns of an experimental model of DR. Transcriptome analysis was performed, comparing the retinas of 10 diabetic (db/db) mice randomly treated with sitagliptin eye drops (10 mg/mL) twice daily and the retinas of 10 additional db/db mice that received vehicle eye drops. Ten non-diabetic mice (db/+) were used as a control group. The Gene Ontology (GO) and Reactome databases were used to perform the gene set enrichment analysis (GSEA) in order to explore the most enriched biological pathways among the groups. The most differentiated genes of these pathways were validated through quantitative RT-PCR. Transcriptome analysis revealed that sitagliptin eye drops have a significant effect on retinal expression patterns and that neurotransmission is the most enriched biological process. Our study evidenced enriched pathways that contain genes involved in membrane trafficking, transmission across chemical synapses, vesicle-mediated transport, neurotransmitter receptors and postsynaptic signal transmission with negative regulation of signaling as a consequence of neuroprotector treatment with sitagliptin. This improves the modulation of the macromolecule biosynthetic process with positive regulation of cell communication, which provides beneficial effects for the neuronal metabolism. This study suggests that topical administration of sitagliptin ameliorates the abnormalities on presynaptic and postsynaptic signal transmission during experimental DR and that this improvement is one of the main mechanisms behind the previously demonstrated beneficial effects.
Integration Host Factor Binds DNA Holliday Junctions
Authors: Lin Shawn H. , Zhao Dacheng , Deng Vivian , Birdsall Veronica K. , Ho Suzanne , Buzovetsky Olga , Etson Candice M. , Mukerji Ishita
Published: December 2022

Integration host factor (IHF) is a nucleoid-associated protein involved in DNA packaging, integration of viral DNA and recombination. IHF binds with nanomolar affinity to duplex DNA containing a 13 bp consensus sequence, inducing a bend of ~160° upon binding. We determined that IHF binds to DNA Four-way or Holliday junctions (HJ) with high affinity regardless of the presence of the consensus sequence, signifying a structure-based mechanism of recognition. Junctions, important intermediates in DNA repair and homologous recombination, are dynamic and can adopt either an open or stacked conformation, where the open conformation facilitates branch migration and strand exchange. Using ensemble and single molecule Förster resonance energy transfer (FRET) methods, we investigated IHF-induced changes in the population distribution of junction conformations and determined that IHF binding shifts the population to the open conformation. Further analysis of smFRET dynamics revealed that even in the presence of protein, the junctions remain dynamic as fast transitions are observed for the protein-bound open state. Protein binding alters junction conformational dynamics, as cross correlation analyses reveal the protein slows the transition rate at 1 mM Mg2+ but accelerates the transition rate at 10 mM Mg2+. Stopped flow kinetic experiments provide evidence for two binding steps, a rapid, initial binding step followed by a slower step potentially associated with a conformational change. These measurements also confirm that the protein remains bound to the junction during the conformer transitions and further suggest that the protein forms a partially dissociated state that allows junction arms to be dynamic. These findings, which demonstrate that IHF binds HJs with high affinity and stabilizes junctions in the open conformation, suggest that IHF may play multiple roles in the processes of integration and recombination in addition to stabilizing bacterial biofilms.
Understanding the Biophysical Interaction of LTX-315 with Tumoral Model Membranes
Authors: Klaiss-Luna Maria C. , Jemioła-Rzemińska Małgorzata , Strzałka Kazimierz , Manrique-Moreno Marcela
Published: December 2022

Host defense peptides are found primarily as natural antimicrobial agents among all lifeforms. These peptides and their synthetic derivatives have been extensively studied for their potential use as therapeutic agents. The most accepted mechanism of action of these peptides is related to a nonspecific mechanism associated with their interaction with the negatively charged groups present in membranes, inducing bilayer destabilization and cell death through several routes. Among the most recently reported peptides, LTX-315 has emerged as an important oncolytic peptide that is currently in several clinical trials against different cancer types. However, there is a lack of biophysical studies regarding LTX-315 and its interaction with membranes. This research focuses primarily on the understanding of the molecular bases of LTX-315′s interaction with eukaryotic lipids, based on two artificial systems representative of non-tumoral and tumoral membranes. Additionally, the interaction with individual lipids was studied by differential scanning calorimetry and Fourier-transformed infrared spectroscopy. The results showed a strong interaction of LTX-315 with the negatively charged phosphatidylserine. The results are important for understanding and facilitating the design and development of improved peptides with anticancer activity.
Amyotrophic Lateral Sclerosis Pathoetiology and Pathophysiology: Roles of Astrocytes, Gut Microbiome, and Muscle Interactions via the Mitochondrial Melatonergic Pathway, with Disruption by Glyphosate-Based Herbicides
Authors: Anderson George
Published: December 2022

The pathoetiology and pathophysiology of motor neuron loss in amyotrophic lateral sclerosis (ALS) are still to be determined, with only a small percentage of ALS patients having a known genetic risk factor. The article looks to integrate wider bodies of data on the biological underpinnings of ALS, highlighting the integrative role of alterations in the mitochondrial melatonergic pathways and systemic factors regulating this pathway across a number of crucial hubs in ALS pathophysiology, namely glia, gut, and the muscle/neuromuscular junction. It is proposed that suppression of the mitochondrial melatonergic pathway underpins changes in muscle brain-derived neurotrophic factor, and its melatonergic pathway mimic, N-acetylserotonin, leading to a lack of metabolic trophic support at the neuromuscular junction. The attenuation of the melatonergic pathway in astrocytes prevents activation of toll-like receptor agonists-induced pro-inflammatory transcription factors, NF-kB, and yin yang 1, from having a built-in limitation on inflammatory induction that arises from their synchronized induction of melatonin release. Such maintained astrocyte activation, coupled with heightened microglia reactivity, is an important driver of motor neuron susceptibility in ALS. Two important systemic factors, gut dysbiosis/permeability and pineal melatonin mediate many of their beneficial effects via their capacity to upregulate the mitochondrial melatonergic pathway in central and systemic cells. The mitochondrial melatonergic pathway may be seen as a core aspect of cellular function, with its suppression increasing reactive oxygen species (ROS), leading to ROS-induced microRNAs, thereby altering the patterning of genes induced. It is proposed that the increased occupational risk of ALS in farmers, gardeners, and sportsmen and women is intimately linked to exposure, whilst being physically active, to the widely used glyphosate-based herbicides. This has numerous research and treatment implications.
Caffeic Acid and Diseases—Mechanisms of Action
Authors: Pavlíková Nela
Published: December 2022

Caffeic acid belongs to the polyphenol compounds we consume daily, often in the form of coffee. Even though it is less explored than caffeic acid phenethyl ester, it still has many positive effects on human health. Caffeic acid can affect cancer, diabetes, atherosclerosis, Alzheimer’s disease, or bacterial and viral infections. This review focuses on the molecular mechanisms of how caffeic acid achieves its effects.
Interaction between Nanoparticles, Membranes and Proteins: A Surface Plasmon Resonance Study
Authors: de Macedo Erenildo Ferreira , Santos Nivia Salles , Nascimento Lucca Silva , Mathey Raphaël , Brenet Sophie , de Moura Matheus Sacilotto , Hou Yanxia , Tada Dayane Batista
Published: December 2022

Regardless of the promising use of nanoparticles (NPs) in biomedical applications, several toxic effects have increased the concerns about the safety of these nanomaterials. Although the pathways for NPs toxicity are diverse and dependent upon many parameters such as the nature of the nanoparticle and the biochemical environment, numerous studies have provided evidence that direct contact between NPs and biomolecules or cell membranes leads to cell inactivation or damage and may be a primary mechanism for cytotoxicity. In such a context, this work focused on developing a fast and accurate method to characterize the interaction between NPs, proteins and lipidic membranes by surface plasmon resonance imaging (SPRi) technique. The interaction of gold NPs with mimetic membranes was evaluated by monitoring the variation of reflectivity after several consecutive gold NPs injections on the lipidic membranes prepared on the SPRi biochip. The interaction on the membranes with varied lipidic composition was compared regarding the total surface concentration density of gold NPs adsorbed on them. Then, the interaction of gold and silver NPs with blood proteins was analyzed regarding their kinetic profile of the association/dissociation and dissociation constants (koff). The surface concentration density on the membrane composed of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine and cholesterol (POPC/cholesterol) was 2.5 times higher than the value found after the injections of gold NPs on POPC only or with dimethyldioctadecylammonium (POPC/DDAB). Regarding the proteins, gold NPs showed preferential binding to fibrinogen resulting in a value of the variation of reflectivity that was 8 times higher than the value found for the other proteins. Differently, silver NPs showed similar interaction on all the tested proteins but with a variation of reflectivity on immunoglobulin G (IgG) 2 times higher than the value found for the other tested proteins.
Blocking Muscarinic Receptor 3 Attenuates Tumor Growth and Decreases Immunosuppressive and Cholinergic Markers in an Orthotopic Mouse Model of Colorectal Cancer
Authors: Kuol Nyanbol , Davidson Majid , Karakkat Jimsheena , Filippone Rhiannon T. , Veale Margaret , Luwor Rodney , Fraser Sarah , Apostolopoulos Vasso , Nurgali Kulmira
Published: December 2022

Tumor cells have evolved to express immunosuppressive molecules allowing their evasion from the host’s immune system. These molecules include programmed death ligands 1 and 2 (PD-L1 and PD-L2). Cancer cells can also produce acetylcholine (ACh), which plays a role in tumor development. Moreover, tumor innervation can stimulate vascularization leading to tumor growth and metastasis. The effects of atropine and muscarinic receptor 3 (M3R) blocker, 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP), on cancer growth and spread were evaluated in vitro using murine colon cancer cell line, CT-26, and in vivo in an orthotopic mouse model of colorectal cancer. In the in vitro model, atropine and 4-DAMP significantly inhibited CT-26 cell proliferation in a dose dependent manner and induced apoptosis. Atropine attenuated immunosuppressive markers and M3R via inhibition of EGFR/AKT/ERK signaling pathways. However, 4-DAMP showed no effect on the expression of PD-L1, PD-L2, and choline acetyltransferase (ChAT) on CT-26 cells but attenuated M3R by suppressing the phosphorylation of AKT and ERK. Blocking of M3R in vivo decreased tumor growth and expression of immunosuppressive, cholinergic, and angiogenic markers through inhibition of AKT and ERK, leading to an improved immune response against cancer. The expression of immunosuppressive and cholinergic markers may hold potential in determining prognosis and treatment regimens for colorectal cancer patients. This study’s results demonstrate that blocking M3R has pronounced antitumor effects via several mechanisms, including inhibition of immunosuppressive molecules, enhancement of antitumor immune response, and suppression of tumor angiogenesis via suppression of the AKT/ERK signaling pathway. These findings suggest a crosstalk between the cholinergic and immune systems during cancer development. In addition, the cholinergic system influences cancer evasion from the host’s immunity.
Cutaneous Melanoma and Hormones: Focus on Sex Differences and the Testis
Authors: Cosci Ilaria , Grande Giuseppe , Di Nisio Andrea , Rocca Maria Santa , Del Fiore Paolo , Benna Clara , Mocellin Simone , Ferlin Alberto
Published: December 2022

Cutaneous melanoma, the most aggressive type of skin cancer, remains one the most represented forms of cancer in the United States and European countries, representing, in Australia, the primary cause of cancer-related deaths. Recently, many studies have shown that sex disparities previously observed in most cancers are particularly accentuated in melanoma, where male sex is consistently associated with an increased risk of disease progression and a higher mortality rate. The causes of these sex differences rely on biological mechanisms related to sex hormones, immune homeostasis and oxidative processes. The development of newer therapies, such as immune checkpoint inhibitors (ICIs) (i.e., anti–PD-1 and anti–CTLA-4 monoclonal antibodies) has dramatically changed the treatment landscape of metastatic melanoma patients, though ICIs can interfere with the immune response and lead to inflammatory immune-related adverse events (irAEs). Recently, some studies have shown a potential adverse influence of this immunotherapy treatment also on male fertility and testicular function. However, while many anticancer drugs are known to cause defects in spermatogenesis, the effects of ICIs therapy remain largely unknown. Notwithstanding the scarce and conflicting information available on this topic, the American Society of Clinical Oncology guidelines recommend sperm cryopreservation in males undergoing ICIs. As investigations regarding the long-term outcomes of anticancer immunotherapy on the male reproductive system are still in their infancy, this review aims to support and spur future research in order to understand a potential gonadotoxic effect of ICIs on testicular function, spermatogenesis and male fertility.
Modeling of Neurodegenerative Diseases: ‘Step by Step’ and ‘Network’ Organization of the Complexes of Model Systems
Authors: Pasko Viacheslav Igorevich , Churkina Aleksandra Sergeevna , Shakhov Anton Sergeevich , Kotlobay Anatoly Alexeevich , Alieva Irina Borisovna
Published: December 2022

Neurodegenerative diseases have acquired the status of one of the leading causes of death in developed countries, which requires creating new model systems capable of accurately reproducing the mechanisms underlying these pathologies. Here we analyzed modern model systems and their contribution to the solution of unexplored manifestations of neuropathological processes. Each model has unique properties that make it the optimal tool for modeling certain aspects of neurodegenerative disorders. We concluded that to optimize research, it is necessary to combine models into complexes that include organisms and artificial systems of different organizational levels. Such complexes can be organized in two ways. The first method can be described as “step by step”, where each model for studying a certain characteristic is a separate step that allows using the information obtained in the modeling process for the gradual study of increasingly complex processes in subsequent models. The second way is a ‘network’ approach. Studies are carried out with several types of models simultaneously, and experiments with each specific type are adjusted in conformity with the data obtained from other models. In our opinion, the ‘network‘ approach to combining individual model systems seems more promising for fundamental biology as well as diagnostics and therapy.
Advances in Human Mitochondria-Based Therapies
Authors: Zhong Gang , Venkatesan Jagadeesh K. , Madry Henning , Cucchiarini Magali
Published: December 2022

Mitochondria are the key biological generators of eukaryotic cells, controlling the energy supply while providing many important biosynthetic intermediates. Mitochondria act as a dynamic, functionally and structurally interconnected network hub closely integrated with other cellular compartments via biomembrane systems, transmitting biological information by shuttling between cells and tissues. Defects and dysregulation of mitochondrial functions are critically involved in pathological mechanisms contributing to aging, cancer, inflammation, neurodegenerative diseases, and other severe human diseases. Mediating and rejuvenating the mitochondria may therefore be of significant benefit to prevent, reverse, and even treat such pathological conditions in patients. The goal of this review is to present the most advanced strategies using mitochondria to manage such disorders and to further explore innovative approaches in the field of human mitochondria-based therapies.
Cathepsin L Contributes to Reproductive Diapause by Regulating Lipid Storage and Survival of Coccinella septempunctata (Linnaeus)
Authors: Chen Junjie , Guo Penghui , Li Yuyan , He Weiwei , Chen Wanbin , Shen Zhongjian , Zhang Maosen , Mao Jianjun , Zhang Lisheng
Published: December 2022

Cathepsin L protease, which belongs to the papain-like cysteine proteases family, is an important player in many physiological and pathological processes. However, little was known about the role of cathepsin L in ladybird beetles (Coccinella septempuctata Linnaeus) during diapause. Here, we analyzed the characteristics of cathepsin L (CsCatL) in the females of C. septempunctata and its role during the diapause of the ladybeetle. CsCatL was cloned and identified from beetle specimens by rapid amplification of cDNA-ends (RACE). The cDNA sequence of CsCatL was 971 bp in length, including an 843 bp open reading frame encoding a protein of 280 amino acids. It was identified as the cathepsin L group by phylogenetic analysis. Knockdown of CsCatL by RNA interference led to decreased expression levels of fatty acid synthase 2 (fas 2) genes and suppressed lipid accumulation. Furthermore, silencing the CsCatL gene distinctly reduced diapause-related features and the survival of female C. spetempunctata under diapause-inducing conditions. The results suggested that the CsCatL gene was involved in fatty acid biosynthesis and played a crucial role in the survival of adult C. septempunctata during the diapause preparation stage.
Contribution of −Omics Technologies in the Study of Porphyromonas gingivalis during Periodontitis Pathogenesis: A Minireview
Authors: Nuñez-Belmar Josefa , Morales-Olavarria Mauricio , Vicencio Emiliano , Vernal Rolando , Cárdenas Juan P. , Cortez Cristian
Published: December 2022

Periodontitis is a non-communicable chronic inflammatory disease characterized by the progressive and irreversible breakdown of the soft periodontal tissues and resorption of teeth-supporting alveolar bone. The etiology of periodontitis involves dysbiotic shifts in the diversity of microbial communities inhabiting the subgingival crevice, which is dominated by anaerobic Gram-negative bacteria, including Porphyromonas gingivalis. Indeed, P. gingivalis is a keystone pathogen with a repertoire of attributes that allow it to colonize periodontal tissues and influence the metabolism, growth rate, and virulence of other periodontal bacteria. The pathogenic potential of P. gingivalis has been traditionally analyzed using classical biochemical and molecular approaches. However, the arrival of new techniques, such as whole-genome sequencing, metagenomics, metatranscriptomics, proteomics, and metabolomics, allowed the generation of high-throughput data, offering a suitable option for bacterial analysis, allowing a deeper understanding of the pathogenic properties of P. gingivalis and its interaction with the host. In the present review, we revise the use of the different −omics technologies and techniques used to analyze bacteria and discuss their potential in studying the pathogenic potential of P. gingivalis.
Genome-Wide Analysis of the AAAP Gene Family in Populus and Functional Analysis of PsAAAP21 in Root Growth and Amino Acid Transport
Authors: Du Jiujun , Du Changjian , Ge Xiaolan , Wen Shuangshuang , Zhou Xinglu , Zhang Lei , Hu Jianjun
Published: December 2022

The adventitious root (AR) is the basis for successful propagation by plant cuttings and tissue culture and is essential for maintaining the positive traits of a variety. Members of the amino acid/auxin permease (AAAP) gene family play indispensable roles in various plant metabolisms and have few studies on root growth and amino acid transport. In this study, with a systematic bioinformatics analysis of the Populus AAAP family, 83 PtrAAAPs were identified from Populus trichocarpa and grouped into 8 subfamilies. Subsequently, chromosomal distribution, genetic structure, cis-elements analysis, and expression pattern analysis of the AAAP family were performed and the potential gene AAAP21 regulating root development was screened by combining the results of RNA-Seq and QTL mapping. PsAAAP21 was proven as promoting root development by enhancing AR formation. Differentially expressed genes (DEGs) from RNA-seq results of overexpressing lines were enriched to multiple amino acid-related pathways, and the amino acid treatment to transgenic lines indicated that PsAAAP21 regulated amino acid transport, including tyrosine, methionine, and arginine. Analysis of the AAAP gene family provided a theoretical basis for uncovering the functions of AAAP genes. The identification of PsAAAP21 on root promotion and amino acid transport in Populus will help with breeding new woody plant species with strong rooting ability.
Autophagy and Apoptosis: Current Challenges of Treatment and Drug Resistance in Multiple Myeloma
Authors: Al-Odat Omar S. , Guirguis Daniel A. , Schmalbach Nicole K. , Yao Gabriella , Budak-Alpdogan Tulin , Jonnalagadda Subash C. , Pandey Manoj K.
Published: December 2022

Over the past two decades, the natural history of multiple myeloma (MM) has evolved dramatically, owing primarily to novel agents targeting MM in the bone marrow microenvironment (BMM) pathways. However, the mechanisms of resistance acquisition remain a mystery and are poorly understood. Autophagy and apoptosis are tightly controlled processes and play a critical role in the cell growth, development, and survival of MM. Genetic instability and abnormalities are two hallmarks of MM. During MM progression, plasma malignant cells become genetically unstable and activate various signaling pathways, resulting in the overexpression of abnormal proteins that disrupt autophagy and apoptosis biological processes. Thus, achieving a better understanding of the autophagy and apoptosis processes and the proteins that crosslinked both pathways, could provide new insights for the MM treatment and improve the development of novel therapeutic strategies to overcome resistance. This review presents a sufficient overview of the roles of autophagy and apoptosis and how they crosslink and control MM progression and drug resistance. Potential combination targeting of both pathways for improving outcomes in MM patients also has been addressed.
Prevalence and Risk Factors Associated with Mental Health in Adolescents from Northern Chile in the Context of the COVID-19 Pandemic
Authors: Moya-Vergara Rodrigo , Portilla-Saavedra Diego , Castillo-Morales Katherin , Espinoza-Tapia Ricardo , Sandoval Pastén Sandra
Published: December 2022

The COVID-19 pandemic has affected the world population; however, there is limited knowledge about its impact on adolescents. The aim of this study was to estimate the prevalence and risk factors associated with mental health in the context of the COVID-19 pandemic in young people in northern Chile. The sample consisted of 1315 young people between the ages of 14 and 18. Univariate analysis and multiple logistic regression were performed to identify the risk factors associated to the considered symptomatology. Depressive symptomatology was reported at 36.3%, anxiety at 6%, and social phobia at 27.8%. Adolescent females reported a higher probability of presenting depressive (OR, 3.409), anxious (OR, 3.949), and social phobia (OR, 3.027) symptomatology. Young women between the ages of 17 and 18 were more likely to present anxiety (OR, 2.172); moreover, being a migrant was related to lower odds of presenting anxiety (OR, 0.259) and depression (OR, 0.662). Having a family member diagnosed with COVID-19 was associated with depressive symptomatology (OR, 1.369). The COVID-19 pandemic can have serious repercussions on the mental health of adolescents. It is important to generate interventions to meet the needs of youth during the post-confinement period.
The Correlation between Chronic Endometritis and Tubal-Factor Infertility
Authors: Zou Yujie , Li Saijiao , Ming Lei , Yang Yan , Ye Peng , Zou Jinjing
Published: December 2022

Objective: To identify the prevalence and risk factors for chronic endometritis (CE) with tubal factors and the correlation between chronic endometritis and tubal factors among infertile populations. Method: A total of 52 patients with chronic endometritis (CE group) who underwent laparoscopy and hysteroscopic surgery were recruited between July 2020 and December 2021. A total of 38 patients without chronic endometritis (non-CE group) were included as a control. Patients with endometriosis and intra-uterine abnormalities were excluded. Endometrial samples were collected during surgery for CD138 immunohistochemistry staining for the diagnosis of CE. Preoperative information (including age, reproductive health characteristics, previous medical and surgical history), intra-operative information (including the patency of the fallopian tube, the presence of hydrosalpinx, score and the grade of tubal lesion condition) and post-operative information (counts of CD138-positive HPF in the endometrial specimen) were collected. Result: A multivariate analysis revealed that tubal factors with unilateral or bilateral occlusion were significantly higher in the CE group (OR 3.066, 95% CI 1.020–9.213, p = 0.046). The bilateral occlusion of fallopian tubes (OR 8.785, 95% CI 1.408–54.818, p = 0.020) rather than unilateral occlusion (OR 2.860, 95% CI 0.893–9.162, p = 0.077) was significantly associated with chronic endometritis. The presence of a hydrosalpinx on one side (OR 7.842, 95% CI 1.279–48.086, p = 0.026) or both sides (OR 9.450, 95% CI 1.037–86.148, p = 0.046) was significantly associated with chronic endometritis. The comparison of CD138-positive HPF counts among the tubal occlusion patients without hydrosalpinx, patients with unilateral hydrosalpinx and patients with bilateral hydrosalpinx were as follows: 1 HPF (50.00% vs. 12.50% vs. 11.11%, p = 0.051), 2 HPF (38.89% vs. 25.00% vs. 22.22%, p = 0.615), ≥3 HPF (11.11% vs. 62.50% vs. 66.67%, p = 0.005). The stage of tubal condition was positively correlated with CD138-positive HPF counts in women with chronic endometritis (r = 0.460, p = 0.001). Conclusion: CE was closely related to the blockage of fallopian tubes and hydrosalpinx. The severity degree of the fallopian lesion condition was associated with inflammation of the endometrium.
Tunneling of Mesh during Ventral Rectopexy: Technical Aspects and Long-Term Functional Results
Authors: Campennì Paola , Marra Angelo Alessandro , De Simone Veronica , Litta Francesco , Parello Angelo , Ratto Carlo
Published: December 2022

Avoiding the extensive damage of pelvic structures during ventral rectopexy could minimize secondary disfunctions. The objective of our observational study is to assess the safety and functional efficacy of a modified ventral rectopexy. In the modified ventral rectopexy, a retroperitoneal tunnel was created along the right side of rectum, connecting two peritoneal mini-incisions at the Douglas pouch and sacral promontory. The proximal edge of a polypropylene mesh, sutured over the ventral rectum, was pulled up through the retroperitoneal tunnel and fixed to the sacral promontory. In all patients, radiopaque clips were placed on the mesh, making it radiographically “visible”. Before surgery and at follow up visits, Altomare, Longo, CCSS, PAC-SYM, and CCFI scores were collected. From March 2010 to September 2021, 117 patients underwent VR. Modified ventral rectopexy was performed in 65 patients, while the standard ventral rectopexy was performed in 52 patients. The open approach was used in 97 cases (55 and 42 patients in modified and standard VR, respectively), while MI surgery was used in 20 cases (10 and 10 patients in modified and standard VR, respectively). A slightly shorter operative time and hospital stay were observed following modified ventral rectopexy (though this was not statistically significant). Similar overall complication rates were registered in the modified vs. standard ventral rectopexies (4.6% vs. 5.8%, p = 0.779). At follow-up, the Longo score (14.0 ± 8.6 vs. 11.0 ± 8.2, p = 0.042) and “delta” values of Altomare (9.2 ± 6.1 vs. 5.9 ± 6.3, p = 0.008) and CCSS (8.4 ± 6.3 vs. 6.1 ± 6.1, p = 0.037) scores were significantly improved in the modified ventral rectopexy group. A similar occurrence of symptoms recurrence was diagnosed in the two groups. Radiopaque clips helped to accurately diagnose mesh detachment/dislocation. The proposed modified VR seems to be feasible and safe. Marking the mesh intraoperatively seems useful.
A Proposal to Differentiate ACO, Asthma and COPD in Vietnam
Authors: Chu Ha Thi , Nguyen Thuy Chau , Godin Isabelle , Michel Olivier
Published: December 2022

Background: In low- and middle-income countries, such as Vietnam, the population is exposed to multiple risks, leading to frequent allergic asthma, COPD and their overlap (ACO). We aimed to differentiate asthma and COPD, so that recommended treatments can be applied. Methods: We hypothesized that during life, the cumulative exposure to noxious particles increases the relative prevalence of COPD, while due to immuno-senescence, the prevalence of allergic asthma decreases with age. Among 568 patients with chronic respiratory symptoms, five phenotypes were defined, based on responsiveness to a bronchodilator (BD), diffusion capacity and cumulative smoking. Then the relative prevalence of each phenotype was related with age. Results: the smoker BD irreversible patients were considered “COPD”, while the full BD responders and non-smoking BD incomplete responders were “asthmatics”. The other patients were ACO, distributed as “like-COPD” or “like-asthma”, based on decreased or normal diffusion capacity. The relative prevalence of asthma, COPD and ACO were 26, 42 and 32% (18% “like-asthma”, 14% “like-COPD”). Conclusion: Vietnamese patients with chronic respiratory symptoms were considered as falling into asthma or COPD groups, based on cumulative smoking, spirometry with reversibility and diffusion capacity. The relative prevalence of asthma and COPD were 44 and 56%, respectively, most of which did not require corticosteroids.
New Regimen of Combining Hepatic Arterial Infusion Chemotherapy and Lipiodol Embolization in Treating Hepatocellular Carcinoma with Main Portal Vein Invasion
Authors: Li Ming-Feng , Liang Huei-Lung , Chiang Chia-Ling , Tsai Wei-Lun , Chen Wen-Chi , Tsai Cheng-Chung , Chen I-Shu
Published: December 2022

Background: The prognosis of HCC patients with main portal vein invasion (Vp4) is poor. We retrospectively reviewed the therapeutic outcomes with our new HAIC regimen in treating Vp4 HCC patients. Patients and Methods: Seventy-one patients received the new regimen of combining HAIC (daily infusion of cisplatin (10 mg/m2), mitomycin-C (2 mg/m2) and Leucovorin (15 mg/m2) plus 100 mg/m2 of 5-fluorouracil (5-FU) using an infusion pump for 5 consecutive days) with Lipiodol embolization between 2002 and 2018. Twenty-two patients (31.0%) also received sorafenib. The Kaplan–Meier curve was used to calculate progression-free survival (PFS) and overall survival (OS). The OS of patients with or without additional sorafenib use or extrahepatic spread (EHS) was also compared. Results: Fifty-six patients (78.9%) had Child-Pugh A liver function. The mean maximal tumor size was 10.3 cm. Twenty patients (28.2%) had EHS at their initial diagnosis. The objective response rate according to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST) and median OS were 64.8% and 13 months. The 1-, 2- and 3-year survival rates were 53.1%, 21.5% and 18.7%, respectively. In the subgroup analysis, there were no significant survival difference between patients with HAIC only vs. HAIC plus sorafenib (14 vs. 13 months) and between patients with vs. without EHS (12 vs. 13 months). Conclusions: Our new HAIC regimen is effective in treating Vp4 HCC patients. Additional sorafenib use with our new HAIC regimen provided no survival benefit.
Sentinel Lymph Node in Non-Small Cell Lung Cancer: Assessment of Feasibility and Safety by Near-Infrared Fluorescence Imaging and Clinical Consequences
Authors: Stasiak Florent , Seitlinger Joseph , Streit Arthur , Wollbrett Christophe , Piccoli Juliette , Siat Joelle , Gauchotte Guillaume , Renaud Stéphane
Published: December 2022

Occult micrometastases can be missed by routine pathological analysis. Mapping of the pulmonary lymphatic system by near-infrared (NIR) fluorescence imaging can identify the first lymph node relay. This sentinel lymph node (SLN) can be analyzed by immunohistochemistry (IHC), which may increase micrometastasis detection and improve staging. This study analyzed the feasibility and safety of identifying SLNs in thoracic surgery by NIR fluorescence imaging in non-small cell lung cancer (NSCLC). This was a prospective, observational, single-center study. Eighty adult patients with suspected localized stage NSCLC (IA1 to IIA) were included between December 2020 and May 2022. All patients received an intraoperative injection of indocyanine green (ICG) directly in the peri tumoural area or by electromagnetic navigational bronchoscopy (ENB). The SLN was then assessed using an infrared fluorescence camera. SLN was identified in 60 patients (75%). Among them, 36 SLNs associated with a primary lung tumor were analyzed by IHC. Four of them were invaded by micrometastases (11.1%). In the case of pN0 SLN, the rest of the lymphadenectomy was cancer free. The identification of SLNs in thoracic surgery by NIR fluorescence imaging seems to be a feasible technique for improving pathological staging.
Neutrophil-to-Lymphocyte Ratio as an Early Predictor of Symptomatic Anastomotic Leakage in Patients after Rectal Cancer Surgery: A Propensity Score-Matched Analysis
Authors: Tan Fei , Xu Kai , Qi Xinyu , Gao Pin , Liu Maoxing , Yao Zhendan , Zhang Nan , Yang Hong , Zhang Chenghai , Xing Jiadi , Cui Ming , Su Xiangqian
Published: December 2022

Background: This study aimed to explore the role of postoperative neutrophil-to-lymphocyte ratio in predicting symptomatic anastomotic leakage in patients who underwent laparoscopic low anterior resection for rectal cancer. Methods: In this retrospective cohort study, we analyzed data of patients who underwent laparoscopic low anterior resection from May 2009 to May 2019. A receiver operating characteristic curve analysis was performed to evaluate the cut-off values with the best predictive efficacy of a symptomatic anastomotic leakage. In addition, a propensity score-matched analysis was performed by considering all covariate variables, and 61 patients with or without symptomatic anastomotic leakage were included in the analysis. Results: The present study included 306 patients; of these, 17 (5.56%) developed symptomatic anastomotic leakage after surgery. On postoperative day 5, compared with patients without symptomatic anastomotic leakage, those with leakage had significantly higher neutrophil-to-lymphocyte levels. Notably, a neutrophil-to-lymphocyte cut-off score of 6.54 indicated the best area under the curve of 0.818 (95% confidence interval: 0.697–0.940, p < 0.001) in predicting symptomatic anastomotic leakage, with a sensitivity and specificity of 76.5% and 79.4%, respectively. Conclusions: Although evidence for the predictive role of neutrophil-to-lymphocyte ratio is accumulating, it remains inconclusive. In addition, neutrophil-to-lymphocyte levels should be considered a predictive biomarker for symptomatic anastomotic leakage; however, it can more accurately be viewed as an adjunct that helps increase the clinical suspicion of emerging symptomatic anastomotic leakage.
Barriers to Native Plantings in Private Residential Yards
Authors: Davis Amélie , Stoyko Jessica
Published: December 2022

In urban areas, private yards can make up large portions of the available “green space” which can be used to provide resources for many species, including birds, and pollinators. If residents are persuaded or willing to plant certain native plants, the aggregate effect of these plantings could be hugely beneficial for key pollinator species. The objectives of this study are to uncover impediments to adding different types of pollinator-beneficial plants to private yards, as well as ascertain which incentives to plant these native plants might be most persuasive, and finally determine if there are procedural knowledge gaps in how to plant, care for, or where to purchase three pollinator-beneficial plants. In this study, we randomly selected properties in two counties in southwestern Ohio along two gradients: parcel size and parcel valuation (as a proxy for income). Two hundred surveys were distributed and 113 were returned (57% response rate). We find that, in aggregate, respondents do not have a strong intent to plant these native plants, especially Asclepias syriaca (a milkweed that serves as host plant to the iconic monarch butterfly; Danaus plexippus) and, surprisingly, the intent to plant these does not differ statistically even when help with costs, labor, or the provision of online resources are offered. We also find that the reported knowledge of where to purchase wildflowers is significantly higher than how to care for them and how to plant them. Lastly, respondents are much more confident in how to take care of trees compared to the three pollinator-beneficial plants shown in the survey. We discuss the implications of these findings for outreach and extension purposes.
Redox Regulation of Autophagy in Cancer: Mechanism, Prevention and Therapy
Authors: He Jingqiu , Dong Lixia , Luo Li , Wang Kui
Published: December 2022

Reactive oxygen species (ROS), products of normal cellular metabolism, play an important role in signal transduction. Autophagy is an intracellular degradation process in response to various stress conditions, such as nutritional deprivation, organelle damage and accumulation of abnormal proteins. ROS and autophagy both exhibit double-edged sword roles in the occurrence and development of cancer. Studies have shown that oxidative stress, as the converging point of these stimuli, is involved in the mechanical regulation of autophagy process. The regulation of ROS on autophagy can be roughly divided into indirect and direct methods. The indirect regulation of autophagy by ROS includes post-transcriptional and transcriptional modulation. ROS-mediated post-transcriptional regulation of autophagy includes the post-translational modifications and protein interactions of AMPK, Beclin 1, PI3K and other molecules, while transcriptional regulation mainly focuses on p62/Keap1/Nrf2 pathway. Notably, ROS can directly oxidize key autophagy proteins, such as ATG4 and p62, leading to the inhibition of autophagy pathway. In this review, we will elaborate the molecular mechanisms of redox regulation of autophagy in cancer, and discuss ROS- and autophagy-based therapeutic strategies for cancer treatment.
Synergistic Lubrication and Antioxidation Efficacies of Graphene Oxide and Fullerenol as Biological Lubricant Additives for Artificial Joints
Authors: Wu Qian , Li Honglin , Wu Liangbin , Bo Zihan , Wang Changge , Cheng Lei , Wang Chao , Peng Chengjun , Li Chuanrun , Hu Xianguo , Li Chuan , Wu Bo
Published: December 2022

The service life of artificial joints has gradually failed to meet the needs of patients. Herein, the synergistic lubrication and antioxidant efficacies of graphene oxide (GO) and fullerenol (Fol) as biological lubricant additives for artificial joints were investigated. The lubrication mechanisms of biological lubricant containing GO and Fol at the friction interface of artificial joints were then revealed. Tribological tests showed that the average friction coefficients of Al2O3–Ti6Al4V pairs and Ti6Al4V–UHMWPE pairs for artificial joints could be reduced by 30% and 22%, respectively, when GO and Fol were used as biological lubricant additives simultaneously. The lubrication mechanism showed that some incommensurate sliding contact surfaces could be formed between the GO nanosheets and spherical Fol at the interface, which reduced the interaction forces of friction pairs. The maximum scavenging rates of •OH and DPPH free radicals by the biological lubricant containing GO and Fol were 35% and 45%, respectively, showing a good antioxidant efficacy of the biological lubricant. This can be attributed to the GO and Fol scavenging free radicals through electron transfer and hydrogen transfer. This study provides a theoretical basis for the development and application of carbon nanomaterials as biological lubricant additives for artificial joints in the future.
In Situ Observation of Hyaluronan Molecular Weight Effectiveness within Articular Cartilage Lubrication
Authors: Rebenda David , Ranuša Matúš , Čípek Pavel , Toropitsyn Evgeniy , Vrbka Martin
Published: December 2022

Degradation of the articular cartilage (AC) structure due to osteoarthritis significantly influences its friction and lubrication mechanisms. Injection with exogenous hyaluronic acid (HA) is one of the ways to slow down the progress of these changes. The present paper aims to determine the effect of HA on the friction and lubrication processes of the synovial joint model. The main emphasis is placed on the effect of HA molecular weight (MW) on the coefficient of friction (COF) and the interactions between HA and other constituents of synovial fluid (SF). Frictional measurements between the AC surface and the glass were performed with simultaneous in situ observation of the contact zone by fluorescence microscopy. Using this methodology, a decrease in AC COF with an increase in the fluorescence intensity emitted from contact with HA was observed, while the phenomenon was found to be MW-dependent. These findings demonstrate that high-MW HA is more effective within a resumption of healthy AC lubrication due to a better adhesion to the AC surface.