bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploration of molecular features of PCOS with different androgen levels and immune-related prognostic biomarkers associated with implantation failure
Authors: Gao Qinyu , Ma Cong , Meng Shuyu , Wang Guanxiong , Xing Qiong , Xu Yuping , He Xiaojin , Wang Tianjuan , Cao Yunxia
Published: August 2022

Background

Polycystic ovary syndrome (PCOS), the most common heterogeneous reproductive disease afflicting women of childbearing age, has been recognized as a chronic inflammatory disease recently. Most PCOS patients have hyperandrogenism, indicating a poor prognosis and poor pregnancy outcomes. The molecular mechanism underlying PCOS development is still unknown. In the present study, we investigated the gene expression profiling characteristics of PCOS with hyperandrogenism (HA) or without hyperandrogenism (NHA) and identified immune-related factors that correlated with embryo implantation failure.

Methods

PCOS and recurrent implantation failure (RIF) microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. ClueGO software was used to perform enrichment analysis of differentially expressed genes (DEGs) in PCOS with varying androgen levels. The Weighted Co-Expression Network Analysis (WGCNA) was used to identify co-expressed modules and shared gene signatures between HA PCOS and RIF. Moreover, the upregulated DEGs of HA PCOS and RIF were intersected with shared gene signatures screening by WGCNA to excavate further key prognostic biomarkers related to implantation failure of HA PCOS. The selected biomarker was verified by qRT-PCR.

Results

A total of 271 DEGs were found in HA PCOS granulosa cell samples, and 720 DEGs were found in NHA PCOS. According to CuleGO enrichment analysis, DEGs in HA PCOS are enriched in immune activation and inflammatory response. In contrast, DEGs in NHA PCOS are enriched in mesenchymal cell development and extracellular space. Using WGCNA analysis, we discovered 26 shared gene signatures between HA PCOS and RIF, which were involved in corticosteroid metabolism, bone maturation and immune regulation. DAPK2 was furtherly screened out and verified to be closely related with the development of HA PCOS, acting as an independent predictor biomarker of the embryo implantation failure. DAPK2 expression was negatively correlated to the embryo implantation rate (r=-0.474, P=0.003). The immune infiltration results suggested that upregulated DAPK2 expression was closely related with NK cell infiltration and macrophage M2, playing an essential role in the pathogenesis of implantation failure in HA PCOS.

Conclusion

Our research revealed the expression profiling of PCOS with different androgen levels and identified DAPK2 as a critical prognostic biomarker for implantation failure in PCOS.
The efficacy and safety of evogliptin for type 2 diabetes mellitus: A systematic review and meta-analysis
Authors: Tang Qizhi , Pan Weiyu , Peng Liangyue
Published: August 2022

Introduction

The dipeptidyl peptidase-4 inhibitor (DPP-4i) drugs, such as evogliptin, as the second-line drugs for type 2 diabetes mellitus (T2DM) treatment have been reported to facilitate insulin secretion by reducing glucagon and inhibiting glucagon like peptides. With a vague consensus, the advantageous and non-inferior effects of evogliptin relative to other DPP-4i drugs were recently demonstrated on hemoglobin A1c (HbA1c) levels and overall adverse events in T2DM patients. Thus, the aim was to evaluate the overall influence of evogliptin on HbA1c levels and the adverse events in T2DM patients compared to sitagliptin and linagliptin.

Methods

Complying with PRISMA guidelines, we conducted a systematic literature search in databases and a meta-analysis. Data about HbA1c levels and the adverse events of T2DM patients were collected and analyzed.

Results

From 1,397 studies, we found five matched studies involving 845 subjects (mean age: 54.7 ± 3 years). The meta-analysis revealed that evogliptin was non-inferior to sitagliptin/linagliptin with a mean difference of 0.062 (95% CI: -0.092 to 0.215. I2: 0%. P = 0.431) regarding the HbA1c level reduction, and the risk ratio was -0.006 (95% CI: -0.272 to 0.260. I2: 1.7%. P = 0.966) regarding the adverse effects, indicating no significant difference between evogliptin and linagliptin or sitagliptin in affecting the HbA1c level and adverse effects.

Conclusion

The study provides preliminary evidence regarding the similarity in the efficacy of evogliptin compared to other DPP-4i drugs, including sitagliptin and linagliptin, for managing HbA1c levels and adverse events.
Remaining useful cycle life prediction of lithium-ion battery based on TS fuzzy model
Authors: Hou Enguang , Wang Zhixue , Qiao Xin , Liu Guangmin
Published: August 2022

Accurately predicting the remaining useful cycle life of a lithium-ion battery is essential for health management of battery systems. Aiming at the time-varying and nonlinear problems of lithium-ion batteries, a remaining useful cycle life estimation method based on Takagi-Sugeno fuzzy model is proposed, which not only reduces the amount of data calculation, but also reduces massive data and has high accuracy. First, collect the rate of change of working voltage in the charging process, and analyze the relationship between the position of voltage rate curve and the number of cycles. Second, in order to reduce the amount of historical data, the interval with obvious mapping relationship is selected, and the recursive least square method is used to fit the curve off-line, which reduces the amount of data calculation and is easy to achieve in battery management system engineering. And then, the Takagi-Sugeno fuzzy model is applied to establish the remaining useful cycle life method based on Takagi-Sugeno fuzzy model. Finally, battery management system application shows that the proposed method can achieve high prediction accuracy and also provides a new perspective for remaining useful cycle life prediction.
Heavy metal pollution and risk assessment of farmland soil around abandoned domestic waste dump in Kaifeng City
Authors: Wang Lin , Zeraatpisheh Mojtaba , Wei Zhangdong , Xu Ming
Published: August 2022

In order to understand the heavy metal pollution and potential ecological risk of farmland soil around the waste dump in the eastern suburb of Kaifeng clearly and provide a scientific basis for the remediation of heavy metals in farmland soil, the single factor pollution index method, Nemero comprehensive pollution index method and Hakanson potential ecological risk method were used to evaluate the heavy metal pollution status and potential ecological risk degree of farmland in this area at the same time. The ArcGIS software was employed to map the spatial distribution of heavy metal pollution and potential ecological risks. The results show that the average values of heavy metals in this area are higher than the soil Background Value of Kaifeng City, and the problem of excessive heavy metals in the soil is significant. Of the 41 surface soil samples, Cd’s heavy and moderate pollution rates were up to 15% and 38%, respectively, and the potential ecological risk caused by Cd element was quite serious, and more than 35% of the soil samples were at higher potential ecological risk. The comprehensive review results showed that 38% of the samples were heavy pollution, and 23% of the sample soils were at higher potential ecological risk. The spatial distribution characterized by the levels of most heavy metals and the extent of potential ecological risk showed high levels in the center of the dump, with a gradual decrease towards the outward radiation zone. This means dust and leachate from waste dump are major causes of heavy metal contamination and potential ecological risks. In addition, the retrieval of the waste mound soil from landfills by villagers as soil fertilizer for rapeseed also caused, to some extent, the transfer of the waste mound contaminants.
Seasonal variation, sources, and risk assessment of PM2.5-bound PAHs in Nantong, China: A pre- and post-COVID-19 case study
Authors: Guo Xinying , Chen Feng , Lu Juan , Zhang Weibing
Published: August 2022

Between 2018 and 2022, a total of 231 PM2.5 samples were collected in Nantong, China, and analyzed online for 16 US EPA PAHs utilizing a variety of analytical methodologies, including high-performance liquid chromatography data analysis, principal component analysis, and characteristic ratio analysis. The seasonal variation and pollution characteristics of 16 PAHs in PM2.5 over a long period in Nantong, China, were analyzed, and correlations and traceability changes with a variety of emission sources were established. Additionally, health assessment models for BaP equivalent concentration, daily exposure dose, lifetime excess risk of cancer, and life expectancy loss were constructed for various ages and genders. The results indicated that the total number of days with BaP concentrations less than the national limit standard of 1.0 ng/m3 was 60.17% (139/231), with rates of 25.40%, 35.71%, and 94.05% from 2019 to 2021, respectively; the total concentration range of 16 PAHs demonstrated a downward trend, but pollution was relatively severe in winter. The seasonal variation showed winter > autumn > spring > summer. The detection rates of 4 and 5 rings were generally high and fluctuated between dropping and increasing. Principal factor analysis and characteristic ratio traceability analysis indicated that PAH pollution is primarily caused by local coal-fired sources and traffic emissions, with a new trend of biomass combustion. Furthermore, BaP remains the primary contributor to carcinogenic factors, and the health risk is higher in females than in males, and in adults than in children. A low level of PAHs in the air may have health benefits. Traffic control and flow restrictions, as well as production restrictions, are all part of Nantong’s COVID-19 pandemic prevention and control policies. These policies contributed to PAH risk prevention and control, as well as pollution reduction.
Nexus between government debt, economic policy uncertainty, government spending, and governmental effectiveness in BRIC nations: Evidence for linear and nonlinear assessments
Authors: Ma Ru , Qamruzzaman Md
Published: August 2022

Quality institutions augment economic sustainability by ensuring domestic resource optimization with equitable development principles. Therefore, ensuring this equitable development and quality institutions is required. This study assessed the effects of government debt, uncertainty of economic policies, and government spending on institutional quality, as measured by governmental effectiveness in BRIC (Brazil, Russia, India, and China) nations from1990–2020. This study applied several econometrical techniques for empirical nexus assessment, including Augmented ARDL, nonlinear Autoregressive Distributed Lagged (ARDL), and Fourier Toda-Yamamoto causality tests. This study documented long-run cointegration in both symmetry and asymmetric assessments. In the long run, both government debt and uncertain economic policies were significantly negatively associated with institutional quality, while government spending and institutional quality were positively associated. Furthermore, the results of asymmetric ARDL revealed both long- and short-run asymmetric relationships between institutional quality and government debt, EPU, and government spending. The directional causality test documented bidirectional causality between debt and institutional quality in all nations, whereas mixed causalities were detected for uncertain economic policy, institutional quality, and government spending. Regarding policy, the results of this study suggested that economic stability was indispensable for efficient institutional quality in BRIC nations.
Physical education and emergency response system using deep learning: A step toward sustainable development of physical education environment
Authors: Guangde Zhao
Published: August 2022

The physical education (PE) system’s key goal is to educate individuals and the large community of participating students to achieve self-fulfillment. Deep learning uses integrated expertise to help students master challenging conditions in unfamiliar contexts. It is normal to get injuries while training or playing, and as an emergency response to mitigating students’ future risks by the availability of first aid, safety steps are promptly taken. Therefore, this article suggests a “physical education and emergency response system using deep learning” (PSERS-DL) to handle such situations effectively. In real-time, the PE environment can be tracked using a global positioning system-enabled surveillance system to immediately provide the wounded student with protective measures. The acquired visuals are immediately analyzed using a deep learning model, convolutional neural network (CNN). The 27 layers proposed in the CNN model have been evaluated compared with other deep learning models. The simulation results showed that the proposed PSERS-DL can assure the emergency response with the highest accuracy of 97.61%. The experimental results showed that the proposed PSERS-DL model enhances an accuracy ratio of 95.6%, a performance ratio of 97.6%, movement detection analysis ratio of 96.3%, a learning rate of 95.2%, an efficiency ratio of 98.1%, a security ratio of 93.5%, a delay time ratio of 33.2%, and a behavior analysis ratio of 90.7% when compared to other existing approaches.
Behaviour drives contemporary evolution in a failing insect-parasitoid importation biological control programme
Authors: Shields Morgan W. , Wratten Steve D. , Van Koten Chikako , Phillips Craig B. , Gerard Philippa J. , Goldson Stephen L.
Published: August 2022

Biological control of pests continues to become more important in agriculture as pesticides are being withdrawn. However, successful control can be compromised by contemporary evolution. Recent work in New Zealand has shown that the once-successful biological control programme of the sexually reproducing grassland weevil pest Listronotus bonariensis by the asexual parasitoid Microctonus hyperodae has now failed. To explain the mechanisms associated with this, weevil parasitism rates were intensively monitored between 1994 and 2019. Frequent sampling took place at widely dispersed New Zealand sites spanning the warmer northern regions to the cooler south. Based on elapsed heat accumulation above the parasitoid’s development temperature threshold of 10.2°C degree-day (DD), the results over c. 25 years indicated that the extent of parasitism decline at a given location was directly related to the accumulated DD. The latter, in turn, was taken to be indicative of parasitoid activity and selection pressure. Accordingly, laboratory microcosm experiments measuring the response of weevils collected from the North–South distribution to a common population of parasitoids showed that the weevils from the warmer northern region showed higher rates of avoidance of the searching parasitoids than those from the cooler south. This strongly supported the hypothesis that the weevil resistance mechanism is related to levels of parasitoid avoidance behaviour arising from long-term parasitoid selection pressure. This study of the behaviourally based acquisition of resistance to a biological control agent illustrates a general need to consider the potential capability of an exotic target host to develop resistance to imported biological control agents. This includes identifying existing host adaptations that selection pressure could potentially act upon that may compromise otherwise successful biological control programmes. Such a requirement points to the need for long-term monitoring of biological control systems and understanding of parasitoid/host dynamics.
Insights to maternal regulation of the paternal genome in mammalian livestock embryos: A mini-review
Authors: Daigneault Bradford W.
Published: August 2022

This mini-review focuses on current knowledge regarding maternal regulation of the paternal genome in early embryos of mammalian livestock species. Emphasis has been placed on regulatory events described for maternally imprinted genes and further highlights transcriptional regulation of the post-fertilization paternal genome by maternal factors. Specifically, the included content aims to summarize genomic and epigenomic contributions of paternally expressed genes, their regulation by the maternal embryo environment, and chromatin structure that are indispensable for early embryo development. The accumulation of current knowledge will summarize conserved allelic function among species to include molecular and genomic studies across large domestic animals and humans with reference to founding experimental animal models.
Inflammatory bowel disease and celiac disease: A bidirectional Mendelian randomization study
Authors: Shi Yue , Feng Sijia , Yan Mengdie , Wei Shuyan , Yang Kejia , Feng Yue
Published: August 2022

Objective: Although previous epidemiological studies have reported substantial links between inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), and celiac disease (CeD), the causal relationship between the two remains unknown. The purpose of the current study was to evaluate the bidirectional causation between IBD and CeD using Mendelian randomization (MR).

Method: We obtained genome-wide association study (GWAS) summary data of IBD (CD and UC) and CeD of thoroughly European ancestry from the IEU GWAS database. We screened eligible instrumental variables (IVs) according to the three assumptions of MR. MR was performed using MR-Egger, weighted median (WM), and inverse variance weighted (IVW) methods. The MR-Egger intercept and MR-PRESSO method investigated the horizontal pleiotropy effect. A leave-one-out analysis was performed to prevent bias caused by a single SNP.

Results: The study assessed a bidirectional causal effect between CD and CeD; CD increased the risk of CeD (IVW odds ratio (OR) = 1.27, 95% confidence interval (CI) = 1.19–1.35, p = 3.75E-13) and vice-a-versa (IVW OR = 1.09, 95% CI = 1.05–1.13, p = 1.39E-05). Additionally, CeD was influenced by IBD (IVW OR = 1.24, 95% CI = 1.16–1.34, p = 9.42E-10) and UC (IVW OR = 0.90, 95% CI = 0.83–0.98, p = 0.017). However, we observed no evidence of a causal relationship between CeD and IBD (IVW OR = 1.00, 95% CI = 0.97–1.04, p = 0.900) or UC (IVW OR = 0.96, 95% CI = 0.92–1.02, p = 0.172).

Conclusion: The present study revealed that IBD and CeD have a bidirectional causal relationship. However, it is slightly different from the results of previous observational studies, recommending that future studies focus on the mechanisms of interaction between CD and CeD.
Centaur antibodies: Engineered chimeric equine-human recombinant antibodies
Authors: Rosenfeld Ronit , Alcalay Ron , Zvi Anat , Ben-David Alon , Noy-Porat Tal , Chitlaru Theodor , Epstein Eyal , Israeli Ofir , Lazar Shirley , Caspi Noa , Barnea Ada , Dor Eyal , Chomsky Inbar , Pitel Shani , Makdasi Efi , Zichel Ran , Mazor Ohad
Published: August 2022

Hyper-immune antisera from large mammals, in particular horses, are routinely used for life-saving anti-intoxication intervention. While highly efficient, the use of these immunotherapeutics is complicated by possible recipient reactogenicity and limited availability. Accordingly, there is an urgent need for alternative improved next-generation immunotherapies to respond to this issue of high public health priority. Here, we document the development of previously unavailable tools for equine antibody engineering. A novel primer set, EquPD v2020, based on equine V-gene data, was designed for efficient and accurate amplification of rearranged horse antibody V-segments. The primer set served for generation of immune phage display libraries, representing highly diverse V-gene repertoires of horses immunized against botulinum A or B neurotoxins. Highly specific scFv clones were selected and expressed as full-length antibodies, carrying equine V-genes and human Gamma1/Lambda constant genes, to be referred as “Centaur antibodies”. Preliminary assessment in a murine model of botulism established their therapeutic potential. The experimental approach detailed in the current report, represents a valuable tool for isolation and engineering of therapeutic equine antibodies.
Concurrence of leukocyte chemotactic factor 2-associated amyloidosis and autoimmune diseases: A case report
Authors: Wang Shuang , Yu Xiao-juan , Li Dan-yang , Xu Jin , Wang Su-xia
Published: August 2022

Leukocyte chemotactic factor 2-associated (ALECT2) amyloidosis is one of the recently reported types of amyloidosis, which is caused by the extracellular deposition of leukocyte chemotactic factor 2 (LECT2). There have not been any reports involving the concurrence of ALECT2 amyloidosis with Sjögren’s syndrome (SS) or systemic lupus erythematosus (SLE)s. Herein, we report a case of a 68-year-old Chinese woman presenting with long duration of sicca symptoms. The clinical evaluation and laboratory findings showed that she had SS overlapped with SLE. Kidney biopsy revealed a membranoproliferative glomerulonephritis (MPGN) with glomerular deposition of dominant IgG3-kappa by immunofluorescene, which was related to SS/SLE. Furthermore, patchy congophilic amyloid deposits in the tubulointerstitium were detected, which were positive for LECT2 protein by immunohistochemical staining and immunoelectron microscopy. This is the first case of ALECT2 amyloidosis that coexisted with SS/SLE, and the causal relationship between ALECT2 amyloidosis and autoimmune diseases remain unclear.
Comparative population dynamics of two sympatric Palaemon shrimps (Palaemon adspersus Rathke, 1836 and Palaemon elegans Rathke, 1836) from the Southeast Caspian Sea
Authors: Vejan Alti , Patimar Rahman , Jafaryan Hojjatallah , Gholizadeh Mohammad , Adineh Hossein , Aghilinezhad Seyyed Mostafa
Published: August 2022

This study provides comparative information about population dynamics for the Palaemon adspersus Rathke, 1836 and P. elegans Rathke, 1836 shrimps on the southeastern coast of the Caspian Sea. Specimens were collected on a monthly basis between April 2019 and May 2020. A total of 9,643 specimens (8,478 P. adspersus and 1,165 P. elegans) were captured and examined. The highest abundance of both shrimps was observed in autumn. The male P. elegans ranged between 16.80 and 61.99 mm in total length and the females between 16.80 and 61.99 mm. The total length for male and female P. adspersus ranged from 21.46 to 69.29 mm and 18.24 to 75.46 mm, respectively. The mean ( ± SD) total length for the males and females of P. elegans was 33.65 ± 4.12 and 40.81 ± 6.59, whereas that of P. adspersus was 48.41 ± 6.27 for males and 54.68 ± 9.90 for females. Based on the b-value of LWR, the growth type of P. adspersus is positively allometric. Likewise, the relationships of female and pooled-sexes P. elegans was positively allometric, while that of male P. elegans was negatively allometric. The estimation of the VBGF parameters resulted as Total Length∞ (TL∞)=71.93 mm, K=0.72 y-1, and t0=-0.176 for males, and TL∞=78.23 mm, K=0.64 y-1, and t0=-0.194 for the females of P. adspersus, while for P. elegans as TL∞=56.13 mm, K=0.91 y-1, and t0=-0.147 for males and TL∞=65.63 mm, K=0.87 y-1, and t0=-0.148 for females. The size-frequency analysis showed that both shrimps were made up of two age groups. The recruitment pattern of the shrimps was continuous with a unimodal pulse for both males and females and showed that P. adspersus is mainly recruited during the autumn and early winter while for P. elegans, during mid-summer and early autumn. The estimated maximum age was 3.35/year for the males and 2.66/year for the females of P. adspersus and 3.78/year for the males and 3.33/year for the females of P. elegans. Therefore, in this case, P. elegans shrimp is more sensitive to death than P. adspersus. The findings point to the underlying notable differentiation of the growth of the shrimps governing the processes of population dynamics. We assume that these differences result from the contrasting life-history strategies of these two Palaemon shrimps.
Immunotherapy in triple-negative breast cancer: Insights into tumor immune landscape and therapeutic opportunities
Authors: Ribeiro Rita , Carvalho Maria João , Goncalves João , Moreira João Nuno
Published: August 2022

Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer that represents 15–20% of breast tumors and is more prevalent in young pre-menopausal women. It is the subtype of breast cancers with the highest metastatic potential and recurrence at the first 5 years after diagnosis. In addition, mortality increases when a complete pathological response is not achieved. As TNBC cells lack estrogen, progesterone, and HER2 receptors, patients do not respond well to hormone and anti-HER2 therapies, and conventional chemotherapy remains the standard treatment. Despite efforts to develop targeted therapies, this disease continues to have a high unmet medical need, and there is an urgent demand for customized diagnosis and therapeutics. As immunotherapy is changing the paradigm of anticancer treatment, it arises as an alternative treatment for TNBC patients. TNBC is classified as an immunogenic subtype of breast cancer due to its high levels of tumor mutational burden and presence of immune cell infiltrates. This review addresses the implications of these characteristics for the diagnosis, treatment, and prognosis of the disease. Herein, the role of immune gene signatures and tumor-infiltrating lymphocytes as biomarkers in TNBC is reviewed, identifying their application in patient diagnosis and stratification, as well as predictors of efficacy. The expression of PD-L1 expression is already considered to be predictive of response to checkpoint inhibitor therapy, but the challenges regarding its value as biomarker are described. Moreover, the rationales for different formats of immunotherapy against TNBC currently under clinical research are discussed, and major clinical trials are highlighted. Immune checkpoint inhibitors have demonstrated clinical benefit, particularly in early-stage tumors and when administered in combination with chemotherapy, with several regimens approved by the regulatory authorities. The success of antibody–drug conjugates and research on other emerging approaches, such as vaccines and cell therapies, will also be addressed. These advances give hope on the development of personalized, more effective, and safe treatments, which will improve the survival and quality of life of patients with TNBC.
Pathogenesis and research progress in leukoaraiosis
Authors: Sun Lingqi , Hui Lin , Li Yi , Chen Xian , Liu Rong , Ma Ji
Published: August 2022

Leukoaraiosis is a common imaging marker of cerebral small vessel disease. In recent years, with the continuous advances in brain imaging technology, the detection rate of leukoaraiosis is higher and its clinical subtypes are gradually gaining attention. Although leukoaraiosis has long been considered an incidental finding with no therapeutic necessity, there is now growing evidence linking it to, among other things, cognitive impairment and a high risk of death after stroke. Due to different research methods, some of the findings are inconsistent and even contradictory. Therefore, a comprehensive and in-depth study of risk factors for leukoaraiosis is of great clinical significance. In this review, we summarize the literature on leukoaraiosis in recent years with the aim of elucidating the disease in terms of various aspects (including pathogenesis, imaging features, and clinical features, etc.).
Specific sensorimotor interneuron circuits are sensitive to cerebellar-attention interactions
Authors: Mirdamadi Jasmine L. , Meehan Sean K.
Published: August 2022

Background: Short latency afferent inhibition (SAI) provides a method to investigate mechanisms of sensorimotor integration. Cholinergic involvement in the SAI phenomena suggests that SAI may provide a marker of cognitive influence over implicit sensorimotor processes. Consistent with this hypothesis, we previously demonstrated that visual attention load suppresses SAI circuits preferentially recruited by anterior-to-posterior (AP)-, but not posterior-to-anterior (PA)-current induced by transcranial magnetic stimulation. However, cerebellar modulation can also modulate these same AP-sensitive SAI circuits. Yet, the consequences of concurrent cognitive and implicit cerebellar influences over these AP circuits are unknown.

Objective: We used cerebellar intermittent theta-burst stimulation (iTBS) to determine whether the cerebellar modulation of sensory to motor projections interacts with the attentional modulation of sensory to motor circuits probed by SAI.

Methods: We assessed AP-SAI and PA-SAI during a concurrent visual detection task of varying attention load before and after cerebellar iTBS.

Results: Before cerebellar iTBS, a higher visual attention load suppressed AP-SAI, but not PA-SAI, compared to a lower visual attention load. Post-cerebellar iTBS, the pattern of AP-SAI in response to visual attention load, was reversed; a higher visual attention load enhanced AP-SAI compared to a lower visual attention load. Cerebellar iTBS did not affect PA-SAI regardless of visual attention load.

Conclusion: These findings suggest that attention and cerebellar networks converge on overlapping AP-sensitive circuitry to influence motor output by controlling the strength of the afferent projections to the motor cortex. This interaction has important implications for understanding the mechanisms of motor performance and learning.
Relationship between front-of-pack labeling and nutritional characteristics of food products: An attempt of an analytical approach
Authors: Martini Daniela , Marangoni Franca , Banterle Alessandro , Donini Lorenzo Maria , Riccardi Gabriele , Poli Andrea , Pellegrini Nicoletta
Published: August 2022

The adoption of supplementary nutrition information, i.e., front-of-pack labeling (FOPL), on pre-packed food products is advocated as a tool to improve the consumers' knowledge of the nutrient content or the nutritional quality of foods, but also to drive products reformulation by the food industry. Ultimately, FOPL should help people to select foods in order to compose an overall balanced diet, which is essential for health. However, the extent to which the different FOPL systems proposed in the European Union (EU) (interpretative or informative) are effectively able to convey the information useful to improve both food choices and dietary habits of the consumers is still under debate and needs to be analyzed in detail. The use of 3 FOPL schemes proposed within the EU (Nutri-Score, Keyhole and NutrInform Battery) to compare products available on the Italian market within different food categories, highlights some critical issues: (1) different FOPL provide to consumers different kinds of information; (2) systems based on similar theoretical approaches can provide conflicting information; (3) the algorithms on which interpretative FOPL are based can give the same summary information for products differing in nutrient composition, impact on the overall dietary balance and therefore on the health of people with different characteristics, physiological/pathological conditions, and nutritional requirements; (4) on the other hand, products with similar nutrient composition can obtain different interpretative FOPL; (5) informative systems are generally more complex and require greater both attention and knowledge from the consumer; (6) FOPL based on 100 g of product overlook the role of portion (and frequency of consumption) in determining the nutrient intake without informing on the contribution of a single food to the overall diet; (7) FOPL based on scoring systems could promote the reformulation of selected products, especially with a composition very close to the threshold limits; (8) for the portion-based informative FOPL systems, the incentive for reformulation could essentially involve the reduction of portion size. Finally, the importance of nutritional education interventions, which are required to encourage the use by consumers of informative FOPL systems, cannot be neglected to improve the quality of diets regardless of the FOPL used.
Predicting the molecular subtypes of breast cancer using nomograms based on three-dimensional ultrasonography characteristics
Authors: Xu Xiaojing , Lu Liren , Zhu Luoxi , Tan Yanjuan , Yu Lifang , Bao Lingyun
Published: August 2022

Background

Molecular subtyping of breast cancer is commonly doneforindividualzed cancer management because it may determines prognosis and treatment. Therefore, preoperativelyidentifying different molecular subtypes of breast cancery can be significant in clinical practice.Thisretrospective study aimed to investigate characteristic three-dimensional ultrasonographic imaging parameters of breast cancer that are associated with the molecular subtypes and establish nomograms to predict the molecular subtypes of breast cancers.

Methods

A total of 309 patients diagnosed with breast cancer between January 2017and December 2019 were enrolled. Sonographic features were compared between the different molecular subtypes. A multinomial logistic regression model was developed, and nomograms were constructed based on this model.

Results

The performance of the nomograms was evaluated in terms of discrimination and calibration.Variables such as maximum diameter, irregular shape, non-parallel growth, heterogeneous internal echo, enhanced posterior echo, lymph node metastasis, retraction phenomenon, calcification, and elasticity score were entered into the multinomial model.Three nomograms were constructed to visualize the final model. The probabilities of the different molecular subtypes could be calculated based on these nomograms. Based on the receiver operating characteristic curves of the model, the macro-and micro-areaunder the curve (AUC) were0.744, and 0.787. The AUC was 0.759, 0.683, 0.747 and 0.785 for luminal A(LA), luminal B(LB), human epidermal growth factor receptor 2-positive(HER2), and triple-negative(TN), respectively.The nomograms for the LA, HER2, and TN subtypes provided good calibration.

Conclusions

Sonographic features such as calcification and posterior acoustic features were significantly associated with the molecular subtype of breast cancer. The presence of the retraction phenomenon was the most important predictor for the LA subtype. Nomograms to predict the molecular subtype were established, and the calibration curves and receiver operating characteristic curves proved that the models had good performance.
Respiratory system toxicity induced by immune checkpoint inhibitors: A real-world study based on the FDA adverse event reporting system database
Authors: Cui Chanjuan , Deng Lei , Wang Wenqing , Ren Xiayang , Wang Yanfeng , Cui Wei
Published: August 2022

Background

Immune checkpoint inhibitors (ICIs), the treatment of multiple cancer types, can be associated with respiratory system adverse events (AEs). The aim of this study is to quantify the association of respiratory system AEs and ICIs and to characterize the profiles of ICI-related respiratory system complications from Food and Drug Administration Adverse Event Reporting System (FAERS) data.

Methods

The disproportionality of respiratory system AE-related ICIs based on FAERS data from January 2014 to September 2021 was analyzed using the reporting odds ratio (ROR) and information component (IC) as measures of potential risk increase.

Results

A total of 38,415,849 records were involved; among these, 36,923 records related to respiratory system AEs after ICI treatment were identified. In the first 3 months, the cumulative proportion of respiratory system AEs was 75.40%. Men had a slightly higher reporting frequency than that of women (ROR = 1.74, 95% CI: 1.70–1.78). Death cases had a slightly higher reporting frequency in ICI-associated respiratory system AEs than that of other drug-associated respiratory system AEs (ROR = 1.40, 95% CI: 1.38–1.41). Anti-programmed cell death 1 (PD-1) drugs and anti-programmed cell death ligand 1 (PD-L1) drugs were significantly associated with respiratory system toxicities. However, anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) drugs did not demonstrate an association with respiratory system toxicities. Interstitial lung disease and pneumonitis were found to be significantly associated with all eight types of ICIs. In addition, 7 in 10 class-specific respiratory system AEs (lower respiratory tract disorders, pleural disorders, pulmonary vascular disorders, respiratory disorders not elsewhere classified (NEC), respiratory tract infections, respiratory tract neoplasms, and thoracic disorders) were associated with ICIs. The signal values of IC025 were from 0.08 to 2.66.

Conclusions

Overall, this study showed a high reporting frequency of respiratory system toxicities caused by ICIs. Early recognition and management of ICI-related respiratory system AEs are of vital importance in practice. Maximizing the benefit while reducing potential respiratory system toxicities of ICIs should become a priority.
Prognostic role of the platelet to lymphocyte ratio (PLR) in the clinical outcomes of patients with advanced lung cancer receiving immunotherapy: A systematic review and meta-analysis
Authors: Zhou Ke , Cao Jie , Lin Huahang , Liang Linchuan , Shen Zhongzhong , Wang Lei , Peng Zhiyu , Mei Jiandong
Published: August 2022

Background

It remains controversial whether the platelet to lymphocyte ratio (PLR) serves as a potential indicator for the efficacy of immunotherapy in advanced lung cancer. This meta-analysis aimed to address this concern.

Methods

Up to March 2022, we searched PubMed, Embase, Web of Science and the Cochrane Library to retrieve potentially eligible articles. Combined hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated to assess the relationship between PLR and progression-free survival (PFS) as well as overall survival (OS), while the combined odds ratios (ORs) and 95% CIs were estimated to evaluate the relationship between PLR and the objective response rate (ORR) as well as the disease control rate (DCR). Subgroup analyses were further performed to detect the source of heterogeneity and potential predictive value of PLR in different groups in terms of OS and PFS.

Results

A total of 21 included studies involving 2312 patients with advanced lung cancer receiving immunotherapy were included. The combined results suggested that elevated PLR was associated with poorer OS (HR=2.24; 95% CI: 1.87-2.68; I² =44%; P=0.01) and PFS (HR=1.66; 95% CI: 1.36-2.04; I² =64%; P<0.01). Furthermore, elevated PLR showed a lower ORR (OR= 0.61; 95% CI: 0.43-0.87, I²=20%; P=0.29) and DCR (OR= 0.44; 95% CI: 0.27-0.72, I²=61%; P=0.02). In subgroup analyses, pretreatment PLR was significantly associated with adverse OS and PFS. The same results were observed in different PLRs in terms of cutoff value (>200 vs. ≤200). Furthermore, high PLR was significantly associated with poor OS and PFS in advanced non-small cell lung cancer (NSCLC); however, PLR was not associated with OS and PFS in advanced small cell lung cancer (SCLC). In addition, PLR predicted poor OS irrespective of regions and types of immune checkpoint inhibitors (ICIs).

Conclusion

On the whole, patients with low PLR had better OS and PFS, as well as higher ORR and DCR when receiving immunotherapy in advanced lung cancer especially for advanced NSCLC. And further investigations are warranted to confirm the prognostic value of PLR in advanced SCLC.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022315976.
IL-8 and its role as a potential biomarker of resistance to anti-angiogenic agents and immune checkpoint inhibitors in metastatic renal cell carcinoma
Authors: Rizzo Mimma , Varnier Luca , Pezzicoli Gaetano , Pirovano Marta , Cosmai Laura , Porta Camillo
Published: August 2022

The therapeutic armamentarium of metastatic Renal Cell Carcinoma (mRCC) has consistently expanded in recent years, with the introduction of VEGF/VEGFR (Vascular Endothelial Growth Factor/Vascular Endothelial Growth Factor Receptor) inhibitors, mTOR (mammalian Target Of Rapamycin) inhibitors and Immune Checkpoint (IC) inhibitors. Currently, for the first-tline treatment of mRCC it is possible to choose between a VEGFR-TKI (VEGFR-Tyrosine Kinase Inhibitor) monotherapy, an ICI-ICI (Immune Checkpoint Inhibitor) combination and an ICI-VEGFRTKI combination. However, a consistent part of patients does not derive benefit from first-line therapy with ICIs; moreover, the use of combination regimens exposes patients to significant toxicities. Therefore, there is a critical need to develop prognostic and predictive biomarkers of response to VEGFR-TKIs and ICIs, and measurement of serum IL-8 is emerging as a potential candidate in this field. Recent retrospective analyses of large phase II and phase III trials found that elevated baseline serum IL-8 correlated with higher levels of tumor and circulating immunosuppressive myeloid cells, decreased T cell activation and poor response to treatment. These findings must be confirmed in prospective clinical trials; however, they provide evidence for a potential use of serum IL-8 as biomarker of resistance to VEGFR-TKIs and ICIs. Considering the amount of new agents and treatment regimens which are transforming the management of metastatic renal cell carcinoma, serum IL-8 could become a precious resource in tailoring the best therapy for each individual patient with the disease.
Postnatal probiotic supplementation can prevent and optimize treatment of childhood asthma and atopic disorders: A systematic review of randomized controlled trials
Authors: Uwaezuoke Samuel N. , Ayuk Adaeze C. , Eze Joy N. , Odimegwu Chioma L. , Ndiokwelu Chibuzo O. , Eze Ikenna C.
Published: August 2022

Background

Although several randomized controlled trials (RCTs) published over the past 5 years show that prenatal or postnatal probiotics may prevent or optimize the treatment of childhood asthma and atopic disorders, findings from the systematic reviews and meta-analyses of these studies appear inconsistent. More recent RCTs have focused on postnatal probiotics, and linked specific probiotic strains to better disease outcomes.

Objective

This systematic review aimed to determine if postnatal probiotics are as effective as prenatal probiotics in preventing or treating childhood asthma and atopic disorders.

Methods

We searched the PubMed, Medline, Google Scholar, and EMBASE databases for RCTs published within the past 5 years (from 2017 to 2022). We included only full-text RCTs on human subjects published in or translated into the English language. We retrieved relevant data items with a preconceived data-extraction form and assessed the methodological quality of the selected RCTs using the Cochrane Collaboration's tool for assessing the risk of bias in randomized trials. We qualitatively synthesized the retrieved data to determine any significant differences in study endpoints of the probiotic and placebo groups.

Results

A total of 1,320 participants (688 and 632 in the probiotic and placebo groups) from six RCTs were investigated. One RCT showed that early Lactobacillus rhamnosus GG (LGG) led to a reduction in the cumulative incidence rate of asthma. Another study demonstrated that mixed strains of Lactobacillus paracasei and Lactobacillus fermentum could support clinical improvement in children with asthma while one trial reported a significant reduction in the frequency of asthma exacerbations using a mixture of Ligilactobacillus salivarius and Bifidobacterium breve. Three trials showed that a combination of LGG and Bifidobacterium animalis subsp lactis, Lactobacillus rhamnosus alone, and a probiotic mixture of Lactobacillus ŁOCK strains improved clinical outcomes in children with atopic dermatitis and cow-milk protein allergy.

Conclusions

Postnatal strain-specific probiotics (in single or mixed forms) are beneficial in preventing and treating atopic dermatitis and other allergies. Similarly, specific strains are more effective in preventing asthma or improving asthma outcomes. We recommend more interventional studies to establish the most useful probiotic strain in these allergic diseases.
Using network pharmacology to explore the mechanism of Danggui-Shaoyao-San in the treatment of diabetic kidney disease
Authors: Yang Jinfei , Li Chenrui , Liu Yan , Han Yachun , Zhao Hao , Luo Shilu , Zhao Chanyue , Jiang Na , Yang Ming , Sun Lin
Published: August 2022

Danggui-Shaoyao-San (DSS) is one of traditional Chinese medicine, which recently was found to play a protective role in diabetic kidney disease (DKD). However, the pharmacological mechanisms of DSS remain obscure. This study would explore the molecular mechanisms and bioactive ingredients of DSS in the treatment of DKD through network pharmacology. The potential target genes of DKD were obtained through OMIM database, the DigSee database and the DisGeNET database. DSS-related targets were acquired from the BATMAN-TCM database and the STITCH database. The common targets of DSS and DKD were selected for analysis in the STRING database, and the results were imported into Cytoscape to construct a protein-protein interaction network. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis and Gene Ontology (GO) enrichment analysis were carried out to further explore the mechanisms of DSS in treating DKD. Molecular docking was conducted to identify the potential interactions between the compounds and the hub genes. Finally, 162 therapeutic targets of DKD and 550 target genes of DSS were obtained from our screening process. Among this, 28 common targets were considered potential therapeutic targets of DSS for treating DKD. Hub signaling pathways including HIF-1 signaling pathway, TNF signaling pathway, AMPK signaling pathway, mTOR signaling pathway, and PI3K-Akt signaling pathway may be involved in the treatment of DKD using DSS. Furthermore, TNF and PPARG, and poricoic acid C and stigmasterol were identified as hub genes and main active components in this network, respectively. In this study, DSS appears to treat DKD by multi-targets and multi-pathways such as inflammatory, oxidative stress, autophagy and fibrosis, which provided a novel perspective for further research of DSS for the treatment of DKD.