bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific transcriptional programs differentiate ICOS from CD28 costimulatory signaling in human Naïve CD4+ T cells
Authors: Gigliotti Casimiro Luca , Boggio Elena , Favero Francesco , Incarnato Danny , Santoro Claudio , Oliviero Salvatore , Rojo Josè Maria , Zucchelli Silvia , Persichetti Francesca , Baldanzi Gianluca , Dianzani Umberto , Corà Davide
Published: September 2022

Costimulatory molecules of the CD28 family play a crucial role in the activation of immune responses in T lymphocytes, complementing and modulating signals originating from the T-cell receptor (TCR) complex. Although distinct functional roles have been demonstrated for each family member, the specific signaling pathways differentiating ICOS- from CD28-mediated costimulation during early T-cell activation are poorly characterized. In the present study, we have performed RNA-Seq-based global transcriptome profiling of anti-CD3-treated naïve CD4+ T cells upon costimulation through either inducible costimulator (ICOS) or CD28, revealing a set of signaling pathways specifically associated with each signal. In particular, we show that CD3/ICOS costimulation plays a major role in pathways related to STAT3 function and osteoarthritis (OA), whereas the CD3/CD28 axis mainly regulates p38 MAPK signaling. Furthermore, we report the activation of distinct immunometabolic pathways, with CD3/ICOS costimulation preferentially targeting glycosaminoglycans (GAGs) and CD3/CD28 regulating mitochondrial respiratory chain and cholesterol biosynthesis. These data suggest that ICOS and CD28 costimulatory signals play distinct roles during the activation of naïve T cells by modulating distinct sets of immunological and immunometabolic genes.
Decreases in encounter rate of endangered Northeast Pacific humpback whales in Southern Costa Rica: Possible changes in migration pattern due to warming events
Authors: Pelayo-González Lili , Herra-Miranda David , Pacheco-Polanco Juan Diego , Guzmán Héctor M. , Goodman Sierra , Oviedo Lenin
Published: September 2022

Warming events in the Pacific Ocean are becoming more frequent, intense, and on a larger temporal and spatial scale. This has caused critical habitats of marine species to lose their quality and marine organisms respond by modifying their critical feeding and reproduction behaviors, as well as their distribution. The Northeast Pacific humpback whale of the Central America distinct population segment (DPS) remains Endangered due to its small population size and because its response to climate change and human interventions is unknown. In this work, we showed the encounter rates of humpback whales in their breeding grounds in Costa Rica for breeding seasons comprised in the period 2000-2020. We analyze the influence of climatic indices that influence the Pacific and environmental variables related to temperature and productivity in the feeding grounds of this population (United States). We hypothesize that the more intense the warming events, the fewer humpback whales complete their migration to Costa Rica. We conclude that the humpback whales of this population could be finding thermally favorable areas in intermediate latitudes (p. e.g., Mexican-Guatemala coasts), which could be related to the decreases in the presence of humpback whale adults and calves in Costa Rica. These observed changes could inform how humpback whales might respond to climate change.
Abrupt fluctuations in North Pacific Intermediate Water modulated changes in deglacial atmospheric CO2
Authors: Liu Yanguang , Qiu Yue , Li Dongling , Artemova Antonina V. , Zhang Yuying , Bosin Aleksandr A. , Gorbarenko Sergey A. , Liu Qingsong , Zhao Debo , Sha Longbin , Zhong Yi
Published: September 2022

As a major reservoir of heat and CO2, the Pacific Ocean is an important component of the global climate system, but the nature of its circulation under different climatic conditions remains poorly understood. We present sedimentary records of surface water hydrography and nutrient dynamics from the subarctic Pacific Ocean, with the aim of investigating changes in sea-ice coverage, biological productivity, and sea surface temperature in the subarctic Northwest Pacific since 32 kyr. Our records indicate an enhanced North Pacific surface water stratification from the last glacial to Heinrich Stadial 1, which generally limited the siliceous productivity supply to the surface water. A productivity peak during the Bølling/Allerød warm interval was associated with an increase in the atmospheric pCO2, and it was driven by the increased supply of nutrient- and CO2-rich waters. This process can be attributed to the collapse of the North Pacific Intermediate Water formation at the onset of the Bølling/Allerød interstadial. Moreover, a northward shift of the westerly winds and the gyre boundary could have modulated the expansion of the subpolar gyre, driving changes in poleward heat transport, biogeochemistry, and the hydroclimate of the North Pacific. Our results are consistent with modern evidence for a northward shift of the westerlies in response to global warming, which will likely result in CO2 outgassing from the subarctic Pacific Ocean in the future.
Rapid changes in heatwaves pose dual challenge in Eastern China and its adjacent seas
Authors: Yao Yulong , Wang Junjie , Zou Xinqing
Published: September 2022

This paper performs a comparative analysis of the spatiotemporal variations of the statistical characteristics of both atmospheric heatwaves over the land (AHWs) in eastern China and marine heatwaves (MHWs) in adjacent seas using a unified heatwave definition. The multi-year average total days and frequency of MHWs during 1982-2019 were 5 and 2 times higher than those of AHWs, respectively, while the mean intensities of AHWs and MHWs were unchanged. The future frequency and duration of AHWs will continue to increase, leading to a superimposed increase in AHW total days. The decreasing frequency and increasing duration of MHWs will result in nearly year-round MHWs from 2060. Under the control of high-pressure systems, clear skies dominate the summer weather conditions in eastern China and its adjacent seas, which will trigger heatwaves. Heatwaves in turn can release substantial ocean latent heat. Enhanced convection and heating will further drive a stronger anticyclone over the western North Pacific, leading to a stronger and more westward-extending western North Pacific subtropical high (WNPSH). Moreover, super El Niño can promote an anomalous WNPSH in decaying summer, which may cause more serious heatwaves. The multi-year average persons affected by AHWs (PAHWs) during 1982-2019 were larger in the North China Plain, Yangtze River Delta, and Sichuan Basin with the regional sum exceeding 3 million. The future maximum PAHWs under SSP2-4.5 and SSP5-8.5 scenarios will be 3.9 billion in 2076 and 4.7 billion in 2085, respectively. Marine ecosystems like artificial ranches and coral reefs will be more threatened by longer-lasting MHWs.
Dementia-related genetic variants in an Italian population of early-onset Alzheimer’s disease
Authors: Bartoletti-Stella Anna , Tarozzi Martina , Mengozzi Giacomo , Asirelli Francesca , Brancaleoni Laura , Mometto Nicola , Stanzani-Maserati Michelangelo , Baiardi Simone , Linarello Simona , Spallazzi Marco , Pantieri Roberta , Ferriani Elisa , Caffarra Paolo , Liguori Rocco , Parchi Piero , Capellari Sabina
Published: September 2022

Early-onset Alzheimer’s disease (EOAD) is the most common form of early-onset dementia. Although three major genes have been identified as causative, the genetic contribution to the disease remains unsolved in many patients. Recent studies have identified pathogenic variants in genes representing a risk factor for developing Alzheimer’s disease (AD) and in causative genes for other degenerative dementias as responsible for EOAD. To study them further, we investigated a panel of candidate genes in 102 Italian EOAD patients, 45.10% of whom had a positive family history and 21.74% with a strong family history of dementia. We found that 10.78% of patients carried pathogenic or likely pathogenic variants, including a novel variant, in PSEN1, PSEN2, or APP, and 7.84% showed homozygosity for the ε4 APOE allele. Additionally, 7.84% of patients had a moderate risk allele in PSEN1, PSEN2, or TREM2 genes. Besides, we observed that 12.75% of our patients carried only a variant in genes associated with other neurodegenerative diseases. The combination of these variants contributes to explain 46% of cases with a definite familiarity and 32% of sporadic forms. Our results confirm the importance of extensive genetic screening in EOAD for clinical purposes, to select patients for future treatments and to contribute to the definition of overlapping pathogenic mechanisms between AD and other forms of dementia.
Applications of graphene-based composites in the anode of lithium-ion batteries
Authors: Liu Zhiming , Tian Yu , Wang Peng , Zhang Guoxin
Published: September 2022

Limited by the disadvantages of low theoretical capacity, sluggish lithium ion deintercalation kinetics as well as inferior energy density, traditional graphite anode material has failed to meet the ever-increasing specific energy demand for lithium-ion battery technologies. Therefore, constructing high-efficiency and stable anodes is of great significance for the practical application of lithium-ion batteries. In response, graphene-based composite anodes have recently achieved much-enhanced electrochemical performance due to their unique two-dimensional cellular lattice structure, excellent electrical conductivity, high specific surface area and superior physicochemical stability. In this review, we start with the geometric and electronic properties of graphene, and then summarize the recent progresses of graphene preparation in terms of both methods and characteristics. Subsequently, we focus on the applications of various graphene based lithium-ion battery anodes and their inherent structure-activity relationships. Finally, the challenges and advisory guidelines for graphene composites are discussed. This review aims to provide a fresh perspective on structure optimization and performance modulation of graphene-based composites as lithium-ion battery anodes.
Use of long non-coding RNAs for the molecular diagnosis of papillary thyroid cancer
Authors: Kim Daham , Yu Juyeon , Kim Jiwon , Hwang Yoon-a , Kim Jin Kyong , Ku Cheol Ryong , Yoon Jung Hyun , Kwak Jin Young , Nam Kee-Hyun , Lee Eun Jig
Published: September 2022

Objective

Improved molecular testing for common somatic mutations and the identification of mRNA and microRNA expression classifiers are promising approaches for the diagnosis of thyroid nodules. However, there is a need to improve the diagnostic accuracy of such tests for identifying thyroid cancer. Recent findings have revealed a crucial role of long non-coding RNAs (lncRNAs) in gene modulation. Thus, we aimed to evaluate the diagnostic value of selected lncRNAs from The Atlas of Noncoding RNAs in Cancer (TANRIC) thyroid cancer dataset.

Methods

LncRNAs in TANRIC thyroid cancer dataset that have significantly increased or decreased expression in papillary thyroid cancer (PTC) tissues were selected as candidates for PTC diagnosis. Surgical specimens from patients who underwent thyroidectomy were used to determine the separation capability of candidate lncRNAs between malignant and benign nodules. Fine needle aspiration samples were obtained and screened for candidate lncRNAs to verify their diagnostic value.

Results

LRRC52-AS1, LINC02471, LINC02082, UNC5B-AS1, LINC02408, MPPED2-AS1, LNCNEF, LOC642484, ATP6V0E2-AS1, and LOC100129129 were selected as the candidate lncRNAs. LRRC52-AS1, LINC02082, UNC5B-AS1, MPPED2-AS1, LNCNEF, and LOC100129129 expression levels were significantly increased or decreased in malignant nodules compared to those in benign nodules and paired normal thyroid tissues. The combination of LRRC52-AS1, LINC02082, and UNC5B-AS1 showed favorable results for the diagnosis of PTC from fine needle aspirates, with 88.9% sensitivity and 100.0% specificity.

Conclusions

LncRNA expression analysis is a promising approach for advancing the molecular diagnosis of PTC. Further studies are needed to identify lncRNAs of additional diagnostic value.
A comparison of cemented and cementless intra-neck curved stem use during hip-preserving reconstruction following massive femoral malignant tumor removal
Authors: You Qi , Lu Minxun , Min Li , Luo Yi , Zhang Yuqi , Wang Yitian , Zheng Chuanxi , Zhou Yong , Tu Chongqi
Published: September 2022

Background

Patients who undergo massive femoral malignant tumor (MFMT) resection often exhibit shortened femoral metaphyseal juxta-articular segments. The use of a customized femoral endoprosthesis (CFE) with an intra-neck curved stem (INCS) has emerged as a viable reconstructive surgical strategy for these individuals. Relative to a cemented INCS, it remains unclear as to whether cementless INCS use is associated with improvements in functionality or reconstructive longevity. As such, the present study was conducted to compare functional outcomes, endoprosthetic survival, and endoprosthesis-related complication rates in patients undergoing cemented and cementless INCS implantation.

Methods

A total of 24 patients undergoing lower limb salvage and reconstructive surgical procedures utilizing cemented or cementless INCS endoprostheses were retrospectively included. Patient-functional outcomes, endoprosthetic survival, and complication rates were compared as a function of age; diagnosis; the length of femoral resection; residual proximal femur length; Musculoskeletal Tumor Society (MSTS) scores; visual analog scale (VAS) scores; and the rates of implant breakage, periprosthetic infections, periprosthetic fractures, and aseptic loosening.

Results

The mean follow-up was 56 months. Significant differences in the length of femoral resection (p<0.001) and residual proximal femur length were observed (p<0.001) between the cemented and cementless INCS groups. There were no differences in overall patient survival and aseptic loosening-associated endoprosthesis survival in the cemented and cementless groups. None of the included patients experienced periprosthetic fractures, infections, or implant breakage. Average respective MSTS and VAS scores did not differ between groups.

Conclusion

For patients undergoing treatment for MFMTs, the use of a CFE with an INCS has emerged as a viable approach to hip-preserving reconstructive surgery. With appropriately designed individualized rehabilitative programs, good functional outcomes can be achieved for these endoprostheses, which are associated with low complication rates. Moreover, the selection between cemented or cementless INCS in the clinic should be made based on patient-specific factors, with cementless INCS implementation being preferable in younger patients with good-quality bone, the potential for long-term survival, and the osteotomy site near the lesser trochanter, whereas cemented INCS use should be favored for individuals who are older, have a shorter life expectancy, or have poor bone quality.
What can we learn from more than 1,000 Brazilian patients at risk of hereditary cancer?
Authors: Leite Ana Carolina Rathsam , Suzuki Daniele Assad , Pereira Allan Anderson Lima , Machado Natalia Polidorio , Barroso-Sousa Romualdo , Correa Tatiana Strava , Moura Fernanda Cesar , Morbeck Igor Alexandre Protzner , Gumz Brenda Pires , Faria Luiza Dib Batista Bugiato , Fernandes Gustavo dos Santos , Sandoval Renata Lazari
Published: September 2022

Background

Identifying individuals at a higher risk of developing cancer is a major concern for healthcare providers. Cancer predisposition syndromes are the underlying cause of cancer aggregation and young-onset tumors in many families. Germline genetic testing is underused due to lack of access, but Brazilian germline data associated with cancer predisposition syndromes are needed.

Methods

Medical records of patients referred for genetic counseling at the Oncogenetics Department at the Hospital Sírio-Libanês (Brasília, DF, Brazil) from July 2017 to January 2021 were reviewed. The clinical features and germline findings were described. Detection rates of germline pathogenic/likely pathogenic variant (P/LPV) carriers were compared between international and Brazilian guidelines for genetic testing.

Results

A total of 1,091 individuals from 985 families were included in this study. Most patients (93.5%) had a family history of cancer, including 64% with a family member under 50 with cancer. Sixty-six percent of patients (720/1091) had a personal history of cancer. Young-onset cancers (<50 years old) represented 62% of the patients affected by cancer and 17% had multiple primary cancers. The cohort included patients with 30 different cancer types. Breast cancer was the most prevalent type of cancer (52.6%). Germline testing included multigene panel (89.3%) and family variant testing (8.9%). Approximately 27% (236/879) of the tested patients harbored germline P/LPVs in cancer susceptibility genes. BRCA2, BRCA1, and TP53 were the most frequently reported genes, corresponding to 18.6%, 14.4%, and 13.5% of the positive results, respectively. Genetic testing criteria from international guidelines were more effective in identifying carriers than the Brazilian National Agency of Supplementary Health (ANS) criteria (92% vs. 72%, p<0.001). Forty-six percent of the cancer-unaffected patients who harbored a germline P/LPV (45/98) would not be eligible for genetic testing according to ANS because they did not have a family variant previously identified in a cancer-affected relative.

Conclusion

The high detection rate of P/LPVs in the present study is possibly related to the genetic testing approach with multigene panels and cohort’s characteristics, represented mainly by individuals with a personal or family history of young-onset cancer. Testing asymptomatic individuals with suspicious family history may also have contributed to a higher detection rate. A significant number of carriers would not have been identified using ANS criteria for genetic testing.
The role of CircRNA/miRNA/mRNA axis in breast cancer drug resistance
Authors: Ghazimoradi Mohammad H. , Babashah Sadegh
Published: September 2022

Multidrug resistance is one of the major obstacles in the treatment of cancers. This undesirable feature increases the mortality rate of cancers, including breast cancer. Circular RNA (CircRNA)/microRNA (miRNA)/messenger RNA (mRNA) is one of the important axes with major roles in the promotion and resistance of breast cancer. This heterogeneous pathway includes mRNA of oncogenes and tumor suppressors, which are controlled by miRNAs and CircRNAs. Unfortunately, this network could be easily deregulated, resulting in drug resistance and tumor development. Therefore, understanding these dysregulations may thus help to identify effective therapeutic targets. On this basis, we try to review the latest findings in the field, which could help us to better comprehend this significant axis in breast cancer.
Neoadjuvant chemotherapy improves overall survival in resectable colorectal liver metastases patients with high clinical risk scores—— A retrospective, propensity score matching analysis
Authors: Chen Feng-Lin , Wang Yan-Yan , Liu Wei , Xing Bao-Cai
Published: September 2022

Background

The use of neoadjuvant chemotherapy (NAC) in resectable colorectal liver metastases (CRLM) patients is controversial. High-risk patients are more likely to benefit from NAC despite its hepatotoxic effects. Since patients with a high tumor burden receive NAC more frequently, previous retrospective studies have imbalanced baseline characteristics. The results of randomized controlled trials are still pending. This study aimed to assess the efficacy of NAC in resectable CRLM patients with high clinical risk scores (CRS) proposed by Fong et al. after balancing baseline characteristics by propensity score matching (PSM).

Methods

Resectable CRLM patients with high CRS (3-5) undergoing hepatectomy between January 2003 and May 2021 were retrospectively studied. Patients were divided into the NAC and the upfront surgery group. Survival outcomes and surgical outcomes were compared after PSM.

Results

The current study included 322 patients with a median follow-up of 40 months. After one-to-two PSM, patients were matched into the upfront surgery group (n = 56) and the NAC group (n = 112). Baseline characteristics were balanced after matching. There was no difference in long-term progression-free survival (PFS), while overall survival (OS) from the initial diagnosis was improved in the NAC group (P = 0.048). Postoperative hospital stays were shorter in the NAC group (P = 0.020). Surgical outcomes were similar, including major hepatectomy rate, intraoperative ablation rate, blood loss, operative time, perioperative blood transfusion, positive surgical margin, and postoperative intensive care unit stay. In multivariable analysis, RAS mutation, maximum tumor diameter≥3cm, and no NAC were independent risk factors for OS. The 1-year PFS in the NAC group was improved, although it failed to reach a statistical difference (P = 0.064).

Conclusions

NAC could improve OS in resectable CRLM patients with high CRS (3-5) and have a shorter postoperative hospital stay.
EML4-ALK rearrangement in primary malignant fibrous histiocytoma of the lung treated with alectinib: A case report
Authors: Zhang Shuai , Liao Xuqiang , Chen Jiawei
Published: September 2022

Primary malignant fibrous histiocytoma of the lung (PMFHL) is extremely rare. It is more common in the right lung and has no specific symptoms. Lymph node metastasis is rare, but hematogenous metastasis is more common. The common metastatic sites are the brain and bone. In this study, a 59-year-old male patient was diagnosed with PMFHL with brain metastasis due to persistent cough and blood in the sputum for the past week. Genetic testing revealed EML4-ALK gene rearrangement (fusion). We first used alectinib in a patient with advanced PMFHL with EML4-ALK gene rearrangement (fusion) accompanied by brain metastasis. The treatment was effective and successfully delayed the development of the disease. Satisfactory results were observed, with an overall survival time of 19 months. Therefore, genetic testing in PMFHL and the choice of treatment plan are important. Local treatment methods, including surgery and radiotherapy, are important when the disease is less advanced. Multidisciplinary discussion is recommended for the best prognosis.
Drug repurposing of ivermectin abrogates neutrophil extracellular traps and prevents melanoma metastasis
Authors: Zhang Hongjun , Xu XiaoZhu , Xu Rui , Ye Tao
Published: September 2022

Neutrophil extracellular traps (NETs) have recently been identified to play a crucial role in cancer metastasis. However, the therapeutic target in NETs of melanoma cancer metastasis is still unknown. In this work, we screened a collection of 231 small molecule compounds. We identified ivermectin (IVM), a widely used antiparasitic drug, significantly inhibits neutrophil extracellular traps (NETs) formation after cathepsin B (CTSB) treatment. In vivo, IVM treatment showed no effects of melanoma tumor growth, while the orthotopic melanoma to lung metastasis was significantly suppressed by IVM. Serum level of myeloperoxidase-DNA and neutrophil elastase-DNA were suppressed after IVM treatment. Tumor infiltrated myeloid-derived suppressor cells (MDSCs) were significantly suppressed while tumor infiltrated CD8+T cells in lung was increased after IVM treatment in mouse melanoma model. Mechanistically, IVM targeted a pyroptotic driving factor gasdermin D (GSDMD), and exhibited a Kd of 267.96 nM by microscale thermophoresis (MST) assay. Furthermore, the direct interaction of IVM and GSDMD significantly suppressed GSDMD oligomerization, which are essential for GSDMD-dependent NETs formation. In vitro, treatment with CTSB in bone marrow neutrophils significantly promotes NETs formation, and the release of extracellular DNA was significantly suppressed by IVM pretreatment. Collectively, our results reveal that with the regulation role of IVM in neutrophils and NETs, IVM may potentially be used as a viable therapeutic approach for the treatment of melanoma cancer metastasis.
The beneficial role of companion animals in translational pain research
Authors: Lascelles B. Duncan X. , Brown Dottie C. , Conzemius Michael G. , Gill Marie , Oshinsky Michael L. , Sharkey Michelle
Published: September 2022

The use of spontaneous painful disease in companion pet animals has been highlighted as one of the changes that could be made to help improve translation of basic science to new therapeutics, acting as a bridge between preclinical and clinical studies, with the goal of accelerating the approval of new therapeutics. This review focuses on the utility of companion pet dogs for translational research by reviewing what outcome measures can be measured, and importantly, the relevance of these outcome measures to human translational research. It also details the practical considerations involved in incorporating companion dogs into human therapeutic development.
Electroacupuncture reduces chronic itch via cannabinoid CB1 receptors in the ventrolateral periaqueductal gray
Authors: Ge Wen-Qiang , Zhan-Mu Ou-Yang , Chen Chao , Zhang Hong , Wang Xiao-Yu , Liu Xin , Li Li , Lan Yu-Ye , Li Chen-Nan , Sun Jia-Can , Shi Run-Lin , Dou Zi-Yue , Pan Hui-Lin , Li Hong-Ping , Jing Xiang-Hong , Li Man
Published: September 2022

Chronic itch severely reduces the quality of life of patients. Electroacupuncture (EA) is widely used to treat chronic itch. However, the underlying mechanism of this therapeutic action of EA is largely unknown. Cannabinoid CB1 receptors in the ventrolateral periaqueductal gray (vlPAG) mediate the analgesic effect of EA. Using a dry skin-induced itch model in mice, we determined whether EA treatment reduces chronic itch via CB1 receptors in the vlPAG. We showed that the optimal inhibitory effect of EA on chronic itch was achieved at the high frequency and high intensity (100 Hz and 3 mA) at “Quchi” (LI11) and “Hegu” (LI14) acupoints, which are located in the same spinal dermatome as the cervical skin lesions. EA reversed the increased expression of CB1 receptors in the vlPAG and decreased the concentration of 5-hydroxytryptamine (5-HT) in the medulla oblongata and the expression of gastrin-releasing peptide receptors (GRPR) in the cervical spinal cord. Furthermore, knockout of CB1 receptors on GABAergic neurons in the vlPAG attenuated scratching behavior and the 5-HT concentration in the medulla oblongata. In contrast, knockout of CB1 receptors on glutamatergic neurons in the vlPAG blocked the antipruritic effects of EA and the inhibitory effect of EA on the 5-HT concentration in the medulla oblongata. Our findings suggest that EA treatment reduces chronic itch by activation of CB1 receptors on glutamatergic neurons and inhibition of CB1 receptors on GABAergic neurons in the vlPAG, thereby inhibiting the 5-HT release from the medulla oblongata to GRPR-expressing neurons in the spinal cord. Our findings suggest that EA attenuates chronic itch via activating CB1 receptors expressed on glutamatergic neurons and downregulating CB1 receptors on GABAergic neurons in the vlPAG, leading to the reduction in 5-HT release in the rostroventral medulla and GRPR signaling in the spinal cord. Our study not only advances our understanding of the mechanisms of the therapeutic effect of EA on chronic itch but also guides the selection of optimal parameters and acupoints of EA for treating chronic itch.
Motor cortico-nigral and cortico-entopeduncular information transmission and its modulation by buspirone in control and after dopaminergic denervation
Authors: Vegas-Suárez Sergio , Morera-Herreras Teresa , Requejo Catalina , Lafuente José Vicente , Moratalla Rosario , Miguélez Cristina , Ugedo Luisa
Published: September 2022

Cortical information is transferred to the substantia nigra pars reticulata (SNr) and the entopeduncular nucleus (EP), the output structures of the basal ganglia (BG), through three different pathways: the hyperdirect trans-subthalamic and the direct and indirect trans-striatal pathways. The nigrostriatal dopamine (DA) and the activation of 5-HT1A receptors, distributed all along the BG, may modulate cortical information transmission. We aimed to investigate the effect of buspirone (5-HT1A receptor partial agonist) and WAY-100635 (5-HT1A receptor antagonist) on cortico-nigral and cortico-entopeduncular transmission in normal and DA loss conditions. Herein, simultaneous electrical stimulation of the motor cortex and single-unit extracellular recordings of SNr or EP neurons were conducted in urethane-anesthetized sham and 6-hydroxydopamine (6-OHDA)-lesioned rats before and after drug administrations. Motor cortex stimulation evoked monophasic, biphasic, or triphasic responses, combination of an early excitation, an inhibition, and a late excitation in both the SNr and EP, while an altered pattern of evoked response was observed in the SNr after 6-OHDA lesion. Systemic buspirone potentiated the direct cortico-SNr and cortico-EP transmission in sham animals since increased duration of the inhibitory response was observed. In DA denervated animals, buspirone administration enhanced early excitation amplitude in the cortico-SNr transmission. In both cases, the observed effects were mediated via a 5-HT1A-dependent mechanism as WAY-100635 administration blocked buspirone’s effect. These findings suggest that in control condition, buspirone potentiates direct pathway transmission and DA loss modulates responses related to the hyperdirect pathway. Overall, the results may contribute to understanding the role of 5-HT1A receptors and DA in motor cortico-BG circuitry functionality.
Unprescribed and unnoticed: Retrospective chart review of adverse events of interactions between antidepressants and over-the-counter drugs
Authors: Woroń Jarosław , Chrobak Adrian Andrzej , Ślęzak Daniel , Siwek Marcin
Published: September 2022

Aim: To systematically evaluate prevalence and clinical characteristics of adverse effects of antidepressants and OTC drugs interactions in a retrospective chart review.

Methodology: Dataset of 1,145 registered adverse events were evaluated. Reports were selected for further analysis if pharmacoepidemiological avaluation indicated the presence of high probability of a causal relationship between antidepressants and OTC interaction and the occurrence of side effect. Following variables were extracted from the records: sex, age, medical comorbidities, antidepressant and other concomitant medications, clinical consequences ant the possible interaction mechanisms.

Results: 368 showed causal relationship with the simultaneous use of antidepressant with another drug. 15 adverse events (4%) were related to the use of OTC medicine, particularly omeprazole, diphenhydramine, Japanese ginkgo biloba, ibuprofen, diclofenac and sildenafil. All of the analysed side effects were categorized as the result of pharmacokinetic interactions. Here we report identified OTC drugs with corresponding antidepressants and clinical manifestations of DDI. Omeprazole: agomelatine (nausea, abnormal dreams), fluoxetine (extrapyramidal symptoms, paresthesias), sertraline (vertigo, yawning), escitalopram (oral vesiculation). Diphenhydramine: sertraline (diaphoresis, insomnia, vertigo), paroxetine (pruritus, headache), duloxetine (oropharyngeal pain). Japanese ginkgo biloba: citalopram (bradycardia), trazodone (vertigo, taste pervesion), mianserine (restless legs syndrome). Diclofenac: escitalopram (oral vesiculation), and fluoxetine (restless legs syndrome). Ibuprofen: agomelatine (anxiety and nausea), sertraline and omeprazole (QTc prolongation). Sildenafil: fluoxetine (genital oedema) and sertraline (myocardial infarction).

Conclusion: The use of OTC drugs by the patients should be monitored. Pharmacokinetic interactions between nonprescribed medicines and antidepressants may increase concentration and severity of side effects of latter ones.
The evolution of vimentin and desmin in Pectoralis major muscles of broiler chickens supports their essential role in muscle regeneration
Authors: Soglia Francesca , Bordini Martina , Mazzoni Maurizio , Zappaterra Martina , Di Nunzio Mattia , Clavenzani Paolo , Davoli Roberta , Meluzzi Adele , Sirri Federico , Petracci Massimiliano
Published: September 2022

Vimentin (VIM) and desmin (DES) are muscle-specific proteins having crucial roles in maintaining the lateral organization and alignment of the sarcomeric structure during myofibrils’ regeneration. The present experiment was designed to ascertain the evolution of VIM and DES in Pectoralis major muscles (PM) of fast-growing (FG) and medium-growing (MG) meat-type chickens both at the protein and gene levels. MG broilers were considered as a control group whereas the evolution of VIM and DES over the growth period was evaluated in FG by collecting samples at different developmental stages (7, 14, 21, 28, 35, and 42 days). After performing a preliminary classification of the samples based on their histological features, 5 PM/sampling time/genotype were selected for western blot, immunohistochemistry (IHC), and gene expression analyses. Overall, the findings obtained at the protein level mirrored those related to their encoding genes, although a potential time lag required to observe the consequences of gene expression was evident. The two- and 3-fold higher level of the VIM-based heterodimer observed in FG at d 21 and d 28 in comparison with MG of the same age might be ascribed to the beginning and progressive development of the regenerative processes. This hypothesis is supported by IHC highlighting the presence of fibers to co-expressing VIM and DES. In addition, gene expression analyses suggested that, unlike VIM common sequence, VIM long isoform may not be directly implicated in muscle regeneration. As for DES content, the fluctuating trends observed for both the native protein and its heterodimer in FG might be ascribed to its importance for maintaining the structural organization of the regenerating fibers. Furthermore, the higher expression level of the DES gene in FG in comparison with MG further supported its potential application as a marker of muscle fibers’ regeneration. In conclusion, the findings of the present research seem to support the existence of a relationship between the occurrence of muscle regeneration and the growth rate of meat-type chickens and corroborate the potential use of VIM and DES as molecular markers of these cellular processes.
An all-deoxyribonucleic acid circuit for detection of human telomerase activity in solution and on paper
Authors: Zhou Zhixue , Gu Jimmy , Brennan John D. , Li Yingfu
Published: September 2022

We report on the design of a simple all-DNA circuit with dual functions of signal amplification and signal reporting and its use for detection of human telomerase activity from cancer cells. The system utilizes a catalytic hairpin assembly (CHA) reaction for amplification, which produces split G-quadruplex outputs that assemble to form complete guanine quadruplex structures as reporting modules. As designed, a linear DNA sequence (the target) functions as a catalyst to drive cyclic programmed assembly of two hairpins, producing a DNA duplex with two guanine-rich sequences that assemble to form a complete Gq structure. The formation of the Gq element allows either fluorescence or colorimetric detection of the target. Examples are provided to demonstrate fluorescence detection of cancer cells’ telomerase activities in solution and the first example of a CHA-modulated colorimetric assay for detecting telomerase activities of cancer cells using a simple paper device.
The aneuploidy testing of blastocysts developing from 0PN and 1PN zygotes in conventional IVF through TE-biopsy PGT-A and minimally invasive PGT-A
Authors: Zhao Haijing , Yuan Ping , Chen Xiaoli , Lin Haiyan , Zhao Jun , Huang Jia , Qiu Qi , Ji Xiaohui , Zhang Qingxue , Wang Wenjun
Published: September 2022

Zygotes without a pronuclear (0PN) or with one pronuclear (1PN) were defined as abnormal fertilization in conventional in vitro fertilization (IVF). The removal of 0PN and 1PN zygotes from conventional IVF cycles has always been controversial. This study aimed to investigate the chromosomal aneuploidy rates of 0PN- and 1PN-derived blastocysts in conventional IVF cycles and to assess the concordance rate between TE-biopsy PGT-A and miPGT-A. TE biopsies and culture media with blastocoel fluid (CM-BF) samples were whole-genome amplified by multiple annealing and looping-based amplification cycle-based single-cell ChromInst method. Next generation sequencing was performed for comprehensive chromosomal screening on a NextSeq550 sequencer using the NextSeq 500/550 High Output kit v2. The aneuploidy rates of 0PN-derived blastocysts were 19.7% for TE-biopsy PGT-A, and 36.1% for miPGT-A; the concordance rate for ploidy was 77.0%; and the sensitivity and specificity were 83.3% and 75.5%, respectively. The aneuploidy rates of 1PN-derived blastocysts were 37.5% and 37.5% by TE-biopsy PGT-A and miPGT-A, respectively; the concordance rate between TE biopsies and CM-BF samples was 83.3%; and the sensitivity and specificity were 77.8% and 86.7%, respectively. Regarding TE-biopsy PGT-A, there were no significant differences in aneuploidy rates among 0PN-, 1PN- and 2PN-derived blastocysts (PGT-M cycles) (19.7% vs. 37.5% vs. 24.3%, P = 0.226), but the aneuploidy rate of 1PN-derived blastocysts was slightly higher than the other two groups. An increase in aneuploidy rates was observed for 0PN/1PN-derived day 6 blastocysts compared to 0PN/1PN-derived day 5 blastocysts (TE-biopsy PGT-A: 35.7% vs. 19.3%, P = 0.099; miPGT-A: 39.3% vs. 35.1%, P = 0.705). The present study is the first that contributes to understanding the chromosomal aneuploidies in 0PN- and 1PN-derived blastocysts in conventional IVF cycles using TE-biopsy PGT-A and miPGT-A. The clinical application value of 0PN- and 1PN-derived blastocysts in conventional IVF should be assessed using TE-biopsy PGT-A or miPGT-A due to the existence of chromosomal aneuploidies.. In terms of consistency, the miPGT-A using blastocoel fluid enriched culture medium is promising as an alternative to TE-biopsy PGT-A for aneuploidy testing of 0PN- or 1PN-derived blastocysts in conventional IVF.
Lateral orbital wall reconstruction after basal cell carcinoma penetration—Case report
Authors: Popić Bruno , Kopić Andrijana , Holik Dubravka , Dinjar Kristijan , Kopić Vlatko , Matijević Marko , Popić Fran
Published: September 2022

Advanced periorbital basal cell carcinomas may necessitate orbital exenteration and consequent vision loss, which significantly reduces patients’ life quality. Orbital reconstruction is a demanding surgical procedure due to the complex orbital anatomy and vital structures located in the orbit. In this report, we presented an 83-year-old patient with advanced basal cell carcinoma that had expanded into the orbit. An orbitotomy was performed to remove the tumor completely while preserving the eye function. Orbital reconstruction was performed by a standard surgical method using a titanium mesh modeled according to a natural phantom skull. This maintained the eye function and achieved satisfactory facial esthetics.
Imaging and pathological comparison of inflammatory pseudotumor-like follicular dendritic cell sarcoma of the spleen: A case report and literature review
Authors: Chen Fuxing , Li Junqiang , Xie Pingkun
Published: September 2022

Background

Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) is a rare subtype of follicular dendritic cell sarcoma (FDCS) that is mainly located in the liver and spleen (1). Splenic IPT-like FDCS is a rare low-grade malignancy with non-specific clinical manifestations and laboratory findings. Herein, we reported the pathological and imaging features of a case with splenic IPT-like FDCS.

Case presentation

A 57-year-old woman was found to have a mass in the spleen during a physical examination and was hospitalized for further treatment. Her laboratory results were within the normal range. Unenhanced and contrast-enhanced computed tomography scans of the whole abdomen showed a round mass in the spleen, with a diameter of about 5 cm. After further examination with enhanced MRI, a provisional diagnosis of splenic hemangioma or splenic hamartoma was made. The patient underwent splenectomy, and the pathological diagnosis was splenic IPT-like FDCS. No tumor recurrence or metastasis was found during the 1-year follow-up after the operation.

Conclusions

Herein, we reported a case of splenic IPT-like FDCS. Although the clinical examination and laboratory examination lack specificity, the imaging of this case showed that the lesion was a solid mass with progressive enhancement, and the central scar showed the characteristics of delayed enhancement, which facilitated the diagnosis.
Case Report: Articular Gout in Four Dogs and One Cat
Authors: Kim Hyo-Sung , Hwang Hyun-Jeong , Kim Han-Jun , Do Sun Hee
Published: September 2022

Background

There is widespread prejudice in veterinary medicine that gout does not occur in non-human mammalians. However, we recently discovered monosodium urate crystals in the synovial fluid obtained from a few dogs and a cat. Since it is the definitive and gold standard to diagnose gout, we report these cases as newly emerging diseases in companion animals.

Case Presentation

Four dogs and one cat were presented at our hospital because of lameness due to an unknown cause. Even after the routine examinations, including radiographic imaging, laboratory examination, and arthrocentesis, we were unable to find a clear cause of polyarthritis. However, we later discovered monosodium urate crystals in the synovial fluid of the animals, confirmed by polarized microscopy. In one of the two dogs treated with immunosuppressants, the disease relapsed, and the other did not show any symptoms for 3 months. The other two dogs were treated with xanthine oxidase inhibitor, where one died, and the other did not show any symptoms for 3 years. The cat was treated with drainage and intra-articular dexamethasone injection, but the disease recurred after 6 months.

Conclusion

This is the first report to confirm that articular gout can occur in dogs and cats. Care must be taken not to neglect needle-shaped materials in the synovial fluid. Gout should also be included in the differential diagnosis of arthritis and further research is needed in these animals.
Capitulaciones matrimoniales: acto jurídico aliado del matrimonio
Authors: Lara-Andrade Isi Verónica , Balcazar-Lievano Ángel Marío
Published: September 2022

Al hablar del matrimonio, se debe de ponderar la Regulación Jurídica de las Capitulaciones matrimoniales, es decir, que durante el proceso del matrimonio, las parejas deben de conocer el beneficio de contar como requisito las capitulaciones matrimoniales, es un régimen económico, de certidumbre jurídica, cuando se debe liquidar la unión matrimonial, del negativo pensamiento que se tiene de lo que representa el matrimonio y su administración. Las capitulaciones es un acto jurídico aliado del matrimonio, que sin duda puede fortalecer el apoyo para ambas partes, desafortunadamente no se llevan a cabo estos tipos de trámites, y cuando se disuelve el matrimonio con el divorcio, inicia el conflicto, donde los consortes, no quieren compartir ni liquidar el patrimonio conyugal.
Methodical approach to bankruptcy prediction model development
Authors: Samarina Natalia S , Oslopova Marina V , Gadzhibek Victoria P
Published: September 2022

There stands a possibility of crises in organizations, which are defined by objective elements, including unforeseen fluctuations in market circumstances, periodic technological modernizations, alterations in the production’s organization, staff change or external circumstances, and oftentimes political conditions. Bankruptcy is regarded as a crucial factor of crisis notion at enterprises. In fact, bankruptcy is a substantial factor in the structure of the market system, and its primary aim is to preserve social-economic procedures from the outcomes of inefficient actions of their participants and the failure to meet their tasks. As a result, this article mainly intends to analyze the methodical means and techniques for bankruptcy prediction model development. To that aim, several methods, including synthesis, assessment, analysis, comparison, generalization method, and system analysis are utilized. Based on the results, it can be concluded that the international authors incorporate the indicators calculated utilizing the information on financial outcomes as the most crucial indicators. In contrast,  Russian scholars and analysts are more concerned with the application of the enterprise property state.
Regulations for functioning budget development to manage trading network
Authors: Bubnovskaya Tatyana. V , Gadzhibek Victoria. P , Kim Tatyana. V
Published: September 2022

In the prevailing state of market circumstances, the revival and efficient operation of trade companies are on the basis of a proper data support system, the primary factors of which are control and budgeting. This current study attempts to focus on budgeting as an efficient means to curb and manage a retail trade network. Budgeting serves as the foundation for planning in the management procedure, for making managerial and economic decisions, evaluating financial solvency, and finally to reinforce economic disciplines. To meet the study’s aim, several general methods, including synthesis, analysis, assessment, comparison, generalization method, and system analysis are taken into account. Based on the results, it can be perceived that the regulation of the budgeting tool used in management is dependent upon the company’s action type immediately. The needs are established, based on which the efficiency of that controlling and managing means is defined. They defined the particulars of network retail and the trading actions that impact the operating budgets’ structure, which is the beginning point in the procedure of budgeting.
Customer Acceptance of Self-Service Technology at Fast Service Restaurants in Tshwane
Authors: Siwela Bella , Ebewo Patrick E , Faku Ephraim M.
Published: September 2022

Objective: Technological advances have prompted many businesses to introduce self-service technology (SST) to improve customer waiting times and reduce operational costs. This study aims to determine the factors linked to the acceptance of self-service technology by customers at fast-service restaurants. Research Design & Methods: This research uses a quantitative method by surveying 172 customers who had visited self-service restaurants within the preceding six months. The Unified Theory of acceptance and use of technology (UTAUT) was used to determine the factors linked to the acceptance of self-service technology at quick-service restaurants. The Statistical Package for Social Sciences was used for analysis. Findings: It was found that age and gender moderate the relationship between the construct: performance expectancy ratio and SST usage intention, effort expectancy and SST usage intention, social influence and usage intention and lastly, age moderates the relationship between facilitating conditions and SST usage behaviour. Contribution & Value Added: The design of future self-service technology at restaurants should be constructed in a manner that would appeal to customers of all ages and gender. An education drive should be prioritised to educate customers about the benefits of self-service while ensuring that they also understand that technology does not reduce employment but may be used to create employment in other forms. Future studies should also investigate whether technology education might have a moderating effect on technology.