bluuebunny/crossref_metadata_2025 huggingface dataset:
Host immune response against DENV and ZIKV infections
Authors: Sekaran Shamala Devi , Ismail Amni Adilah , Thergarajan Gaythri , Chandramathi Samudi , Rahman S. K. Hanan , Mani Ravishankar Ram , Jusof Felicita Fedelis , Lim Yvonne A. L. , Manikam Rishya
Published: September 2022

Dengue is a major public health concern, affecting almost 400 million people worldwide, with about 70% of the global burden of disease in Asia. Despite revised clinical classifications of dengue infections by the World Health Organization, the wide spectrum of the manifestations of dengue illness continues to pose challenges in diagnosis and patient management for clinicians. When the Zika epidemic spread through the American continent and then later to Africa and Asia in 2015, researchers compared the characteristics of the Zika infection to Dengue, considering both these viruses were transmitted primarily through the same vector, the Aedes aegypti female mosquitoes. An important difference to note, however, was that the Zika epidemic diffused in a shorter time span compared to the persisting feature of Dengue infections, which is endemic in many Asian countries. As the pathogenesis of viral illnesses is affected by host immune responses, various immune modulators have been proposed as biomarkers to predict the risk of the disease progression to a severe form, at a much earlier stage of the illness. However, the findings for most biomarkers are highly discrepant between studies. Meanwhile, the cross-reactivity of CD8+ and CD4+ T cells response to Dengue and Zika viruses provide important clues for further development of potential treatments. This review discusses similarities between Dengue and Zika infections, comparing their disease transmissions and vectors involved, and both the innate and adaptive immune responses in these infections. Consideration of the genetic identity of both the Dengue and Zika flaviviruses as well as the cross-reactivity of relevant T cells along with the actions of CD4+ cytotoxic cells in these infections are also presented. Finally, a summary of the immune biomarkers that have been reported for dengue and Zika viral infections are discussed which may be useful indicators for future anti-viral targets or predictors for disease severity. Together, this information appraises the current understanding of both Zika and Dengue infections, providing insights for future vaccine design approaches against both viruses.
Effect of standardized vs. local preoperative enteral feeding practice on the incidence of NEC in infants with duct dependent lesions: Protocol for a randomized control trial
Authors: Seliga-Siwecka Joanna , Płotko Ariel , Wójcik-Sep Agata , Bokiniec Renata , Latka-Grot Julita , Żuk Małgorzata , Furmańczyk Konrad , Zieliński Wojciech , Chrzanowska Mariola
Published: September 2022

Background

Infants with duct dependent heart lesions often require invasive procedures during the neonatal or early infancy period. These patients remain a challenge for pediatric cardiologists, neonatologists, and intensive care unit personnel. A relevant portion of these infant suffer from respiratory, cardiac failure and may develop NEC, which leads to inadequate growth and nutrition, causing delayed or complicated cardiac surgery.

Methods

This randomized control trial will recruit term infants diagnosed with a duct dependant lesion within the first 72 h of life. After obtaining written parental consent patients will be randomized to either the physician led enteral feeding or protocol-based feeding group. The intervention will continue up to 28 days of life or day of cardiosurgical treatment, whichever comes first. The primary outcomes include NEC and death related to NEC. Secondary outcomes include among others, number of interrupted feedings, growth velocity, daily protein and caloric intake, days to reach full enteral feeding and on mechanical ventilation.

Discussion

Our study will be the first randomized control trial to evaluate if standard (as in healthy newborns) initiation and advancement of enteral feeding is safe, improves short term outcomes and does not increase the risk of NEC. If the studied feeding regime proves to be intact, swift implementation and advancement of enteral nutrition may become a recommendation.

Trial registration

The study protocol has been approved by the local ethical board. It is registered at ClinicalTrials.gov NCT05117164.
Targets of statins intervention in LDL-C metabolism: Gut microbiota
Authors: Sun ChangXin , Wang ZePing , Hu LanQing , Zhang XiaoNan , Chen JiYe , Yu ZongLiang , Liu LongTao , Wu Min
Published: September 2022

Increasing researches have considered gut microbiota as a new “metabolic organ,” which mediates the occurrence and development of metabolic diseases. In addition, the liver is an important organ of lipid metabolism, and abnormal lipid metabolism can cause the elevation of blood lipids. Among them, elevated low-density lipoprotein cholesterol (LDL-C) is related with ectopic lipid deposition and metabolic diseases, and statins are widely used to lower LDL-C. In recent years, the gut microbiota has been shown to mediate statins efficacy, both in animals and humans. The effect of statins on microbiota abundance has been deeply explored, and the pathways through which statins reduce the LDL-C levels by affecting the abundance of microbiota have gradually been explored. In this review, we discussed the interaction between gut microbiota and cholesterol metabolism, especially the cholesterol-lowering effect of statins mediated by gut microbiota, via AMPK-PPARγ-SREBP1C/2, FXR and PXR-related, and LPS-TLR4-Myd88 pathways, which may help to explain the individual differences in statins efficacy.
Pairwise comparison scale extension using core linking sets
Authors: Humphry Stephen , Bredemeyer Ken
Published: September 2022

Pairwise comparisons can be used to equate two sets of educational performances. In this article, a simple method for the joint scaling of two or more sets of assessment performances is described and illustrated. This method is applicable where a scale of student abilities has already been formed, and the scale is to be extended to include additional performances. It requires a subset of already scaled performances, which is designated as a core linking set for the purpose of scale extension. The article illustrates the application of the method to construct a scale with a larger range of latent abilities, using fewer additional comparisons compared to the standard method of pairwise comparisons. The design differs from standard pairwise comparisons in the way performances are paired. The method of pairing performances can also be used to efficiently place individual performances on an existing scale.
Pituitary carcinoma - case series and review of the literature
Authors: Du Four Stephanie , Van Der Veken Jorn , Duerinck Johnny , Vermeulen Elle , Andreescu Corina E. , Bruneau Michael , Neyns Bart , Velthoven Van , Velkeniers Brigitte
Published: September 2022

Although pituitary adenomas (PAs) account for 15% of intracranial tumors, pituitary carcinomas (PCs) are a rare entity. Most commonly, PCs evolve from aggressive PAs invading the surrounding structures and eventually leading to metastatic lesions. Due to the low incidence, the diagnosis and treatment remains challenging. We report a case series of five patients with pituitary carcinoma (PC) treated in our center. At first diagnosis 3 patients had an ACTH-producing adenoma, 1 a prolactinoma and 1 a double secreting adenoma (GH and prolactin). The mean time interval from initial diagnosis to diagnosis of PC was 10.7 years (range 5-20 years). All patients underwent multiple surgical resections and radiotherapy. Four patients were treated with temozolomide for metastatic disease. One patient with concomitant radiochemotherapy for local recurrence. Temozolomide led to a stable disease in 2 patients. One patient had a progressive disease after 9 cycles of temozolomide. In absence of standard treatment, immunotherapy was initiated, resulting in a stable disease.

We report five cases of PCs. Three patients obtained a stable disease after tailored multidisciplinary treatment. Additionally, one patient was treated with immunotherapy, opening a new treatment option in PCs. Overall, PCs are rare intracranial neoplasms occurring several years after the initial diagnosis of aggressive PAs. Currently, the absence of predictive factors for an aggressive clinical course, provokes a challenging management.
Visceral adiposity measures are strongly associated with cardiovascular disease among female participants in Southwest China: A population-based prospective study
Authors: Wang Yingying , Zhao Xiaodeng , Chen Yun , Yao Yuntong , Zhang Yixia , Wang Na , Liu Tao , Fu Chaowei
Published: September 2022

Background and aims

Controversy remains regarding the prediction effects of different adiposity measure indicators for the risk of cardiovascular disease (CVD). Our study aimed to assess the associations of three traditional anthropometric indicators, namely, waist circumference (WC), waist-to-height ratio (WHtR), and body mass index (BMI) as well as three non-traditional anthropometric indicators, namely, the Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP), and body shape index (ABSI), with the risk of CVD among Southwest Chinese population.

Methods

Our study was based on the Guizhou Population Health Cohort Study (GPHCS) conducted from 2010 to 2020. A total of 9,280 participants were recruited from 12 areas in Guizhou Province, China, from November 2010 to December 2012, and followed up for major chronic diseases until December 2020. A total of 7,837 individuals with valid data were included in this analysis. The gender-specific associations of WC, WHtR, BMI, CVAI, LAP, and ABSI with CVD were evaluated using Cox proportional hazards models. Receiver operating characteristic (ROC) curve analysis was used to estimate the prediction powers of different indicators for CVD.

Results

No association of six indicators with CVD was observed among male participants. Female participants with either WC-based central obesity (HR: 1.82, 95% CI: 1.12–2.97) or WHtR-based central obesity (HR: 1.68, 95% CI: 1.07–2.64) had a higher risk of CVD, after adjusted for age, area, ethnic group, smoking, alcohol drinking, MET, previous history of diabetes, hypertension and dyslipidemia, medication use, and nutraceutical intake. Compared with female participants in the lowest quartile (Q1), those in the highest quartile (Q4) of WHtR (HR: 2.24, 95% CI: 1.17–4.27), CVAI (HR: 3.98, 95% CI: 1.87–8.49), and ABSI (HR: 1.94, 95% CI: 1.06–3.52) had an increased risk for incident CVD. CAVI showed the maximum predictive power of CVD with the biggest AUC of 0.687 (95% CI: 0.654–0.720) compared to other indicators in female participants.

Conclusions

Visceral adiposity measures, especially CVAI, are stronger predictive indicators of CVD among female and not male participants in Southwest China. Different anthropometric indexes need to be combined to comprehensively assess health risks.
Metabolomic comparison followed by cross-validation of enzyme-linked immunosorbent assay to reveal potential biomarkers of diabetic retinopathy in Chinese with type 2 diabetes
Authors: Wang Zongyi , Tang Jiyang , Jin Enzhong , Ren Chi , Li Siying , Zhang Linqi , Zhong Yusheng , Cao Yu , Wang Jianmin , Zhou Wei , Zhao Mingwei , Huang Lvzhen , Qu Jinfeng
Published: September 2022

Purpose

To identify the biomarkers in the critical period of development in diabetic retinopathy (DR) in Chinese with type 2 diabetes using targeted and untargeted metabolomics, and to explore the feasibility of their clinical application

Methods

This case-control study described the differential metabolites between 83 Chinese type 2 diabetes mellitus (T2DM) samples with disease duration ≥ 10 years and 27 controls matched cases. Targeted metabolomics using high-resolution mass spectrometry with liquid chromatography was performed on plasma samples of subjects. The results were compared to our previous untargeted metabolomics study and ELISA was performed to validate the mutual differential metabolites of targeted and untargeted metabolomics on plasma. Multiple linear regression analyses were performed to adjust for the significance of different metabolites between groups.

Result

Mean age of the subjects was 66.3 years and mean T2DM duration was 16.5 years. By cross-validating with results from previous untargeted metabolomic assays, we found that L-Citrulline (Cit), indoleacetic acid (IAA), 1-methylhistidine (1-MH), phosphatidylcholines (PCs), hexanoylcarnitine, chenodeoxycholic acid (CDCA) and eicosapentaenoic acid (EPA) were the most distinctive metabolites biomarkers to distinguish the severity of DR for two different metabolomic approaches in our study. We mainly found that samples in the DR stage showed lower serum level of Cit and higher serum level of IAA compared with samples in the T2DM stage, while during the progression of diabetic retinopathy, the serum levels of CDCA and EPA in PDR stage were significantly lower than NPDR stage. Among them, 4 differential key metabolites including Cit, IAA, CDCA and EPA were confirmed with ELISA.

Conclusion

This is the first study to compare the results of targeted and untargeted metabolomics via liquid chromatography-mass spectrometry to find the serum biomarkers which could reflect the metabolic variations among different stages of DR in Chinese. The progression of DR in Chinese at different critical stages was related to the serum levels of specific differential metabolites, of which there is a significant correlation between DR progression and increased IAA and decreased Cit, hexanoylcarnitine, CDCA, and EPA. However, larger studies are needed to confirm our results. Based on this study, it could be inferred that the accuracy of targeted metabolomics for metabolite expression in serum is to some extent higher than that of untargeted metabolomics.
Ecosystem-based disaster risk reduction can benefit biodiversity conservation in a Japanese agricultural landscape
Authors: Kasada Minoru , Uchida Kei , Shinohara Naoto , Yoshida Takehito
Published: September 2022

Ecosystem-based disaster risk reduction (Eco-DRR) has attracted increased attention as a sustainable way to achieve both disaster risk reduction and biodiversity conservation, although there have been few quantitative evaluations of the potential impacts of Eco-DRR on biodiversity. Here, we examined the influences of flood hazard and land-use patterns on biodiversity by focusing on the species richness of plants, butterflies and odonates, and the abundance of two frog species in a rural landscape of Wakasa town, Fukui Prefecture, Japan. The direct effect of exposure to flood hazard on the studied taxa was not significant, whereas landscape factors associated with flood hazard significantly influenced either of the taxa in different magnitudes. We then exercised a scenario analysis by replacing urban land-use by non-urban, agricultural land-use (paddy fields in this case) to reduce exposure to flood hazard and projected the impacts on biodiversity. Our results demonstrated that the land-use replacement potentially reduces the risk of flooding by up to 5.19 billion yen (ca. 46 million US$) and, at the same time, positively influences the species richness and abundance, although the ecological impacts are different depending on taxon and spatial location. The land-use replacement was expected to result in the increase of plant richness and abundance of Daruma pond frog at a location by up to 16 and 25%, respectively. On the other hand, butterfly richness at a location was presumed to decrease by until −68%, probably due to their dependence on domestic gardens. The abundance of Japanese wrinkled frog did not show such a clear spatial variation. This study highlights the significance of land-use replacement as an Eco-DRR measure to reduce the disaster risk and conserve biodiversity in the agricultural landscape.
Decreased efficiency of pollen collection due to Sulfoxaflor exposure leads to a reduction in the size of bumble bee workers in late European summer
Authors: Boff Samuel , Keller Alexander , Raizer Josué , Lupi Daniela
Published: September 2022

Bumble bees (Bombus terrestris) are important pollinators of wild and crop plants. Despite their importance in the process of fruit and seed production on crop sites, their activity may be impaired due to exposure to pesticides. This species has a yearly life cycle and colony success may rely on effective foraging of workers on ruderal plants late in summer when most crops are no longer flowering. In the current study, we investigated the effect of chronic exposure to Sulfoxaflor on aspects of the foraging behavior of bumble bees and whether Sulfoxaflor influences the body size of workers of B. terrestris in a crop landscape. We found that 2 weeks of continuous exposure to Sulfoxaflor influenced workers’ foraging dynamics and collection of resources. However, there was no evidence that the 5 ppb dose of the pesticide impacted the ability of bees to handle flowers with different traits. Workers from colonies exposed to Sulfoxaflor were smaller. The effect on worker size may be explained as a consequence of the reduced pollen income per unit of worker foraging. Thus, if the effects of Sulfoxaflor applied directly to crops had the same effect as that observed on commercial bumble bees after our chronic exposure, it might negatively impact colony success due to the impact on pollen collection and the reduction in the size of workers.
Coexisting with the alien: Evidence for environmental control on trophic interactions between a native (Atherina boyeri) and a non-indigenous fish species (Gambusia holbrooki) in a Mediterranean coastal ecosystem
Authors: Andolina Cristina , Signa Geraldina , Cilluffo Giovanna , Iannucci Simona , Mazzola Antonio , Vizzini Salvatrice
Published: September 2022

Biological invasions are a widespread problem worldwide, as invasive non-indigenous species (NIS) may affect native populations through direct (e. g., predation) or indirect (e.g., competition) trophic interactions, leading to changes in the food web structure. The trophic relationships of the invasive eastern mosquitofish Gambusia holbrooki and the native big-scale sand smelt Atherina boyeri coexisting in three Mediterranean coastal ponds characterized by different trophic statuses (from oligotrophic to hypereutrophic) were assessed in spring through isotopic niche analysis and Bayesian mixing models. The two fish relied on the distinctive trophic pathways in the different ponds, with the evidence of minimal interspecific niche overlap indicating site-specific niche divergence mechanisms. In more detail, under hypereutrophic and mesotrophic conditions, the two species occupied different trophic positions but relying on a single trophic pathway, whereas, under oligotrophic conditions, both occupied a similar trophic position but belonging to distinct trophic pathways. Furthermore, the invaders showed the widest niche breadth while the native species showed a niche compression and displacement in the ponds at a higher trophic status compared to the oligotrophic pond. We argue that this may be the result of an asymmetric competition arising between the two species because of the higher competitive ability of G. holbrooki and may have been further shaped by the trophic status of the ponds, through a conjoint effect of prey availability and habitat complexity. While the high trophic plasticity and adaptability of both species to different environmental features and resource availability may have favored their coexistence through site-specific mechanisms of niche segregation, we provide also empirical evidence of the importance of environmental control in invaded food webs, calling for greater attention to this aspect in future studies.
Human placenta-based genome-wide mRNA sequencing to identify TEK/IGF1/CSF1/ANGPT2 as crucial segments in the pathogenesis of pre-eclampsia
Authors: Wang Lifeng , Zhang Lin , Fan Yuqin , Peng Yanjie , Song Dandan , Fu Jinfeng , Wang Xietong
Published: September 2022

Pre-eclampsia is a pregnancy-specific disease commonly occurring in late pregnancy and has always been threatening maternal and fetal lives, yet the etiology and pathogenesis of pre-eclampsia are still uncertain. To depict the overall changes of genes at the genome-wide level and identify potential biomarkers for early diagnosis of pre-eclampsia, we conducted this study by collecting placenta samples donated by six pregnancy women, among whom three healthy women were included as controls and three women were diagnosed with pre-eclampsia. The placental sample tissues were then subjected to high-throughput sequencing. Furthermore, we proceeded with bioinformatics analysis and formulated the hypothesis of pre-eclampsia development and verified the potential targets of pre-eclampsia by immunohistochemistry. Demographically, we found that the baseline characteristics of study subjects were highly homogeneous except for gestational weeks and blood pressure, where the blood pressure was higher and gestational weeks were shorter in the pre-eclampsia group (systolic blood pressure 123.33 ± 4.62 vs. 148.67 ± 3.79 mmHg, p = 0.046; diastolic blood pressure 79.00 ± 5.20 vs. 88.33 ± 2.89 mmHg, p = 0.068; gestational weeks 39.33 ± 1.03 vs. 35.76 ± 2.41, p = 0.050). Specific pathological changes were identified, shown as syncytial knots, fibrinoid necrosis, perivillous fibrin deposition, and vasculitis. For high-throughput sequencing, a total of 1,891 dysregulated genes were determined, of which 960 genes were downregulated and 931 genes were upregulated. The bioinformatics analysis indicated that these genes, with different molecular functions in different parts of cells, were primarily responsible for endothelium development and vascular process in the circulatory system, and more than 10 signaling pathways were involved. By focusing on the PI3K-Akt signaling pathway, Rap1 signaling pathway, and disease enrichment analysis item pre-eclampsia, TEK, CSF1, IGF1, and ANGPT2 were identified to promote the development of pre-eclampsia. After confirming the placental expression of these genes at the protein level, we proposed the pathogenesis of pre-eclampsia as follows: the downregulation of TEK, CSF1, IGF1, and ANGPT2 may inhibit trophoblast proliferation and affect the remodeling of spiral arteries, causing maternal and fetal malperfusion and impeding nutrient exchange, thereby leading to clinical manifestations of pre-eclampsia.
Exposure to salinity induces oxidative damage and changes in the expression of genes related to appetite regulation in Nile tilapia (Oreochromis niloticus)
Authors: Martins Amanda W. S. , Dellagostin Eduardo N. , Blödorn Eduardo B. , Silveira Tony Leandro R. , Sampaio Luis A. , Komninou Eliza R. , Varela Junior Antonio S. , Corcini Carine D. , Nunes Leandro S. , Remião Mariana H. , Collares Gilberto L. , Domingues William B. , Campos Vinicius F.
Published: September 2022

Variations in water salinity and other extrinsic factors have been shown to induce changes in feeding rhythms and growth in fish. However, it is unknown whether appetite-related hormones mediate these changes in Nile tilapia (Oreochromis niloticus), an important species for aquaculture in several countries. This study aimed to evaluate the expression of genes responsible for appetite regulation and genes related to metabolic and physiological changes in tilapia exposed to different salinities. Moreover, the study proposed to sequence and to characterize the cart, cck, and pyy genes, and to quantify their expression in the brain and intestine of the fish by quantitative polymerase chain reaction (qPCR). The animals were exposed to three salinities: 0, 6, and 12 parts per thousand (ppt) of salt for 21 days. Furthermore, lipid peroxidation, reactive oxygen species, DNA damage, and membrane fluidity in blood cells were quantified by flow cytometry. The results indicated an increased expression of cart, pyy, and cck and a decreased expression of npy in the brain, and the same with cck and npy in the intestine of fish treated with 12 ppt. This modulation and other adaptive responses may have contributed to the decrease in weight gain, specific growth rate, and final weight. In addition, we showed oxidative damage in blood cells resulting from increasing salinity. These results provide essential data on O. niloticus when exposed to high salinities that have never been described before and generate knowledge necessary for developing biotechnologies that may help improve the production of economically important farmed fish.
Common aquatic pollutants modify hemocyte immune responses in Biomphalaria glabrata
Authors: Lynch Adam E. , Noble Leslie R. , Jones Catherine S. , Routledge Edwin J.
Published: September 2022

Disruptions to reproductive health in wildlife species inhabiting polluted environments is often found to occur alongside compromised immunity. However, research on impacts of aquatic pollution on freshwater mollusc immune responses is limited despite their importance as vectors of disease (Schistosomiasis) in humans, cattle and wild mammals. We developed an in vitro ‘tool-kit’ of well-characterized quantitative immune tests using Biomphalaria glabrata hemocytes. We exposed hemocytes to environmentally-relevant concentrations of common aquatic pollutants (17β-estradiol, Bisphenol-A and p,p’-DDE) and measured key innate immune responses including motility, phagocytosis and encapsulation. Additionally, we tested an extract of a typical domestic tertiary treated effluent as representative of a ‘real-world’ mixture of chemicals. Encapsulation responses were stimulated by p,p’-DDE at low doses but were suppressed at higher doses. Concentrations of BPA (above 200 ng/L) and p,p’-DDE (above 500 ng/L) significantly inhibited phagocytosis compared to controls, whilst hemocyte motility was reduced by all test chemicals and the effluent extract in a dose-dependent manner. All responses occurred at chemical concentrations considered to be below the cytotoxic thresholds of hemocytes. This is the first time a suite of in vitro tests has been developed specifically in B. glabrata with the purpose of investigating the impacts of chemical pollutants and an effluent extract on immunity. Our findings indicate that common aquatic pollutants alter innate immune responses in B. glabrata, suggesting that pollutants may be a critical, yet overlooked, factor impacting disease by modulating the dynamics of parasite transmission between molluscs and humans.
The regulatory roles of T helper cells in distinct extracellular matrix characterization in breast cancer
Authors: Tian Qi , Gao Huan , Ma Yingying , Zhu Lizhe , Zhou Yan , Shen Yanwei , Wang Bo
Published: September 2022

Background

Tumors are characterized by extracellular matrix (ECM) remodeling and stiffening. The ECM has been recognized as an important determinant of breast cancer progression and prognosis. Recent studies have revealed a strong link between ECM remodeling and immune cell infiltration in a variety of tumor types. However, the landscape and specific regulatory mechanisms between ECM and immune microenvironment in breast cancer have not been fully understood.

Methods

Using genomic data and clinical information of breast cancer patients obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we conducted an extensive multi-omics analysis to explore the heterogeneity and prognostic significance of the ECM microenvironment. Masson and Sirius red staining were applied to quantify the contents of collagen in the ECM microenvironment. Tissue immunofluorescence (IF) staining was applied to identify T helper (Th) cells.

Results

We classified breast cancer patients into two ECM-clusters and three gene-clusters by consensus clustering. Significant heterogeneity in prognosis and immune cell infiltration have been found in these distinct clusters. Specifically, in the ECM-cluster with better prognosis, the expression levels of Th2 and regulatory T (Treg) cells were reduced, while the Th1, Th17 and T follicular helper (Tfh) cells-associated activities were significantly enhanced. The correlations between ECM characteristics and Th cells infiltration were then validated by clinical tissue samples from our hospital. The ECM-associated prognostic model was then constructed by 10 core prognostic genes and stratified breast cancer patients into two risk groups. Kaplan-Meier analysis showed that the overall survival (OS) of breast cancer patients in the high-risk group was significantly worse than that of the low-risk group. The risk scores for breast cancer patients obtained from our prognostic model were further confirmed to be associated with immune cell infiltration, tumor mutation burden (TMB) and stem cell indexes. Finally, the half-maximal inhibitory concentration (IC50) values of antitumor agents for patients in different risk groups were calculated to provide references for therapy targeting distinct ECM characteristics.

Conclusion

Our findings identify a novel strategy for breast cancer subtyping based on the ECM characterization and reveal the regulatory roles of Th cells in ECM remodeling. Targeting ECM remodeling and Th cells hold potential to be a therapeutic alternative for breast cancer in the future.
A role for an HTLV-1 vaccine?
Authors: Ratner Lee
Published: September 2022

HTLV-1 is a global infection with 5-20 million infected individuals. Although only a minority of infected individuals develop myelopathy, lymphoproliferative malignancy, or inflammatory disorders, infection is associated with immunosuppression and shorter survival. Transmission of HTLV-1 is through contaminated blood or needles, mother-to-child exposure through breast-feeding, and sexual intercourse. HTLV-1 is a delta retrovirus that expresses immunogenic Gag, Envelope, TAX, and Hbz proteins. Neutralizing antibodies have been identified directed against the surface envelope protein, and cytotoxic T-cell epitopes within TAX have been characterized. Thus far, there have been few investigations of vaccines directed against each of these proteins, with limited responses, thus far. However, with new technologies developed in the last few years, a renewed investigation is warranted in search for a safe and effective HTLV-1 vaccine.
PD-1 and ICOS counter-regulate tissue resident regulatory T cell development and IL-10 production during flu
Authors: McGee Michael C. , Zhang Tianyi , Magazine Nicholas , Islam Rezwanul , Carossino Mariano , Huang Weishan
Published: September 2022

Regulatory T cells that express the transcription factor Foxp3 (Treg cells) are a highly heterogenous population of immunoregulatory cells critical for maintaining immune homeostasis and preventing immunopathology during infections. Tissue resident Treg (TR-Treg) cells are maintained within nonlymphoid tissues and have been shown to suppress proinflammatory tissue resident T cell responses and promote tissue repair. Human populations are repetitively exposed to influenza infections and lung tissue resident effector T cell responses are associated with flu-induced long-term pulmonary sequelae. The kinetics of TR-Treg cell development and molecular features of TR-Treg cells during repeated and/or long-term flu infections are unclear. Utilizing a Foxp3RFP/IL-10GFPdual reporter mouse model along with intravascular fluorescentin vivolabeling, we characterized the TR-Treg cell responses to repetitive heterosubtypic influenza infections. We found lung tissue resident Treg cells accumulated and expressed high levels of co-inhibitory and co-stimulatory receptors post primary and secondary infections. Blockade of PD-1 or ICOS signaling reveals that PD-1 and ICOS signaling pathways counter-regulate TR-Treg cell expansion and IL-10 production, during secondary influenza infection. Furthermore, the virus-specific TR-Treg cell response displayed distinct kinetics, when compared to conventional CD4+tissue resident memory T cells, during secondary flu infection. Our results provide insight into the tissue resident Foxp3+regulatory T cell response during repetitive flu infections, which may be applicable to other respiratory infectious diseases such as tuberculosis and COVID.
Based on different immune responses under the glucose metabolizing type of papillary thyroid cancer and the response to anti-PD-1 therapy
Authors: Xie Wenjun , Zeng Yu , Hu Linfei , Hao Jiaru , Chen Yuzheng , Yun Xinwei , Lin Qiang , Li Huashui
Published: September 2022

Glucose metabolism-related genes play an important role in the development and immunotherapy of many tumours, but their role in thyroid cancer is ambiguous. To investigate the role of glucose metabolism-related genes in the development of papillary thyroid cancer (PTC) and their correlation with the clinical outcome of PTC, we collected transcriptomic data from 501 PTC patients in the Cancer Genome Atlas (TCGA). We performed nonnegative matrix decomposition clustering of 2752 glucose metabolism-related genes from transcriptome data and classified PTC patients into three subgroups (C1 for high activation of glucose metabolism, C2 for low activation of glucose metabolism and C3 for moderate activation of glucose metabolism) based on the activation of different glucose metabolism-related genes in 10 glucose metabolism-related pathways. We found a positive correlation between the activation level of glucose metabolism and the tumour mutation burden (TMB), neoantigen number, mRNA stemness index (mRNAsi), age, and tumour stage in PTC patients. Next, we constructed a prognostic prediction model for PTC using six glucose metabolism-related genes (PGBD5, TPO, IGFBPL1, TMEM171, SOD3, TDRD9) and constructed a nomogram based on the risk score and clinical parameters of PTC patients. Both the prognostic risk prediction model and nomogram had high stability and accuracy for predicting the progression-free interval (PFI) in PTC patients. Patients were then divided into high-risk and low-risk groups by risk score. The high-risk group was sensitive to paclitaxel and anti-PD-1 treatment, and the low-risk group was sensitive to sorafenib treatment. We found that the high-risk group was enriched in inflammatory response pathways and associated with high level of immune cell infiltration. To verify the accuracy of the prognostic prediction model, we knocked down PGBD5 in PTC cells and found that the proliferation ability of PTC cells was significantly reduced. This suggests that PGBD5 may be a relatively important oncogene in PTC. Our study constructed a prognostic prediction model and classification of PTC by glucose metabolism-related genes, which provides a new perspective on the role of glucose metabolism in the development and immune microenvironment of PTC and in guiding chemotherapy, targeted therapy and immune checkpoint blockade therapy of PTC.
Responses of adult spotted lanternflies to artificial aggregations composed of all males or females
Authors: Cooperband Miriam F. , Murman Kelly
Published: September 2022

Spotted lanternflies (SLF) Lycorma delicatula are economically important invasive planthoppers discovered in North America in 2014. SLF are gregarious, but how they locate each other, or who finds whom and when, is poorly understood. Here we describe adult SLF behavior and phenology on their preferred host, Ailanthus altissima, under field conditions, in the context of both aggregation and mate-location, since SLF demonstrated aggregation prior to mating. We documented aggregation behavior of adults and found we could manipulate free-living SLF populations in both number and sex ratio by the placement of confined populations of SLF males or females on trees. Trap capture of arriving SLF was significantly higher on trees with confined SLF aggregations than on control trees, and was corroborated with photographic data, demonstrating the manipulation of attraction and aggregation behavior. Sex ratios of trapped SLF arrivals were significantly more male-biased on trees with confined males and more female-biased on trees with confined females, evidence that the male- and female-biased sex ratios observed on trees naturally can be explained by sex-specific conspecific signals. SLF sex ratios shifted over time in the same pattern over two consecutive years. A mark-release-recapture study over time found that 1) SLF behavior is density dependent and strongly influenced by natural populations, 2) released females were captured significantly more on trees with caged females, particularly prior to mating, and 3) released males were captured significantly more on trees with caged females starting at mating time. Photographic data revealed that most clustering behavior (a measure of courtship) of free-living SLF began on trees with caged females during mating time, but not on trees with caged males or controls. We describe adult male and female SLF phenology whereby 1) aggregation behavior occurs, 2) males and females arrive at different times, 3) females began to aggregate several weeks prior to mating, 4) males subsequently joined aggregations at the time of mating, and 5) aggregation continued into oviposition. Population density and aggregation behavior were found to be key factors in their natural history which can be manipulated, providing a foothold for future research. Possible mechanisms for future exploration are discussed.
Modelling livestock test-and-treat: A novel One Health strategy to control schistosomiasis and mitigate drug resistance
Authors: Díaz Adriana V. , Lambert Sebastien , Neves M. Inês , Borlase Anna , Léger Elsa , Diouf Nicolas D. , Sène Mariama , Webster Joanne P. , Walker Martin
Published: September 2022

Schistosomiasis, a neglected tropical disease, is a widespread chronic helminthiasis reported in 78 countries, predominantly those within sub-Saharan Africa, as well as Latin America, Asia, and most recently, even Europe. Species of the causative blood fluke infect not only humans but also animals, and hybrids between previously assumed human-specific and animal-specific schistosomes are being increasingly reported. Existing control programs across Africa focus on humans and rely heavily on mass drug administration of praziquantel, the sole drug available against schistosomiasis. Praziquantel is safe and highly efficacious but could become ineffective if resistance emerges. To reach the revised World Health Organization goal of elimination of schistosomiasis as a public health problem, and interruption of transmission within selected regions, by 2030, new consideration of the role of animal reservoirs in human transmission in general, and whether to also treat livestock with praziquantel in particular, has been raised. However, whilst there are no dedicated control programs targeting animals outside of Asia, there are emerging reports of the use and misuse of praziquantel in livestock across Africa. Therefore, to effectively treat livestock in Africa and to help mitigate against the potential evolution of praziquantel resistance, structured control strategies are required. Here, using a transmission modelling approach, we evaluate the potential effectiveness of a theoretical test-and-treat (TnT) strategy to control bovine schistosomiasis using a currently available point-of-care diagnostic test (developed for human use) to detect circulating cathodic antigen (POC-CCA). We show that implementing TnT at herd-level from 2022 to 2030 could be highly effective in suppressing infection in cattle and even, in lower prevalence settings, reaching nominal ‘elimination’ targets. We highlight the importance of enhancing the specificity of POC-CCA for use in livestock to avoid unnecessary treatments and discuss the outstanding challenges associated with implementing TnT as part of a holistic One Health approach to tackling human and animal schistosomiasis.
Species composition, abundance, size distribution, sex ratios, and movement of Scylla mud crabs within the mangrove ecosystem at Setiu Wetland, Terengganu, Malaysia
Authors: Fazhan Hanafiah , Azra Mohamad N. , Halim Siti Aisah , Naimullah Muhamad , Abualreesh Muyassar H. , Shu-Chien Alexander Chong , Wang Youji , Fujaya Yushinta , Syahnon Mohammad , Ma Hongyu , Waiho Khor , Ikhwanuddin Mhd
Published: September 2022

The aim of the present study was to determine the movement patterns of mud crabs, genus Scylla, within the mangrove area of the Setiu Wetland in Terengganu, Malaysia. Mark-release-recapture technique were conducted during 24 sampling trips. A fluorescent visible implant elastomer (VIE) tag was inserted within the crab’s shell and they were released at the same capture stations over an interval of two weeks before the next sampling. A total of 288 crabs of various sizes, sex and species were identified, measured, tagged and recorded. The numbers of male crabs were higher than females. Three species were present, dominated by S. olivacea at 54.2% and S.tranquebarica at 26.4%, with S. paramamosain in third place at 19.4%. Among the 288 crabs that were tagged and released, 26.38% were recaptured. The tagged crabs did not move very far from the release station based on the recapture data. The greatest mean chance of being recaptured within 24 h was 44.5%, and there were no tagged crabs recaptured after 48 h even on sampling trips at several points from the release site. Knowledge of movement patterns is essential to understand migration and population dynamics and the relationship between reproduction and local distribution.
Rethinking clinical decision-making to improve clinical reasoning
Authors: Corrao Salvatore , Argano Christiano
Published: September 2022

Improving clinical reasoning techniques is the right way to facilitate decision-making from prognostic, diagnostic, and therapeutic points of view. However, the process to do that is to fill knowledge gaps by studying and growing experience and knowing some cognitive aspects to raise the awareness of thinking mechanisms to avoid cognitive errors through correct educational training. This article examines clinical approaches and educational gaps in training medical students and young doctors. The authors explore the core elements of clinical reasoning, including metacognition, reasoning errors and cognitive biases, reasoning strategies, and ways to improve decision-making. The article addresses the dual-process theory of thought and the new Default Mode Network (DMN) theory. The reader may consider the article a first-level guide to deepen how to think and not what to think, knowing that this synthesis results from years of study and reasoning in clinical practice and educational settings.
Benzodiazepines and Z-hypnotics consumption in long-COVID-19 patients: Gender differences and associated factors
Authors: Carrasco-Garrido Pilar , Fernández-de-Las-Peñas Cesar , Hernández-Barrera Valentín , Palacios-Ceña Domingo , Jiménez-Trujillo Isabel , Gallardo-Pino Carmen
Published: September 2022

Background

Psychotropic drug consumption has increased during the COVID-19 pandemic. We describe here the prevalence and identifying factors associated with Benzodiazepine (BZD) and Z-hypnotics use among a sample of Spanish adults suffering from long-COVID-19 syndrome, from a gender perspective.

Materials and methods

Data were anonymously collected between 15th December 2021 and 15th March 2022. The collection form consisted of several questions gathering sociodemographic information, post-COVID symptom, health profile, and pharmacological drug intake. Using logistic multivariate regression models, we estimated the independent effect of each of these variables on self-medicated consumption. Three models were generated (female, male, and both gender).

Results

Prevalence of BZD and Z-hypnotics use was 44.9% (46.5% for women; 37.8% for men). Zolpidem was the most consumed drug among male (20.7%), and lorazepam in female (31.1%). Patterns of drug consumption among female were related with number of post-COVID symptoms and smoking habit (AOR 2.76, 95%CI 1.16–6.52). Males under 40 years of age are more likely to consume BZD and Z-hypnotics (AOR 5.52, 95%CI 1.08–28.27).

Conclusion

The prevalence of consumption of BZD and Z-hypnotics in those subjects with long-COVID-19 in our study reaches values of 44.9%. Women with long-COVID-19 declare a higher prevalence of consumption than men. Predictors of BZD and Z-hypnotic in men were, age and number of medication use. Smoking habit and the number of post-COVID symptoms were predictive variables in women.
Perceptions and experiences of undergraduate pharmacy students and alumni toward research after exposure to undergraduate research courses
Authors: Mukhalalati Banan , Elshami Sara , Adlan Ola , Elshazly Marwa , Awaisu Ahmed , Stewart Derek , Al-Badriyeh Daoud , Alali Feras
Published: September 2022

Introduction

Academic institutions have a duty to equip health professional students with the requisite research skills to ensure the implementation of evidence-based practice. This study aims to determine the perceptions of pharmacy students and alumni toward research after completing Undergraduate Research in Pharmacy Courses (URPCs) at the College of Pharmacy–Qatar University (CPH–QU).

Methods

A cross-sectional survey was conducted. All CPH-QU alumni (n = 238), and all third- and fourth-year professional students who had completed at least one URPC at the time of conducting the study (n = 42) were approached. The questionnaire contained items relating to research experience and perceptions of significance, confidence in conducting research, actual and anticipated outcomes, and motivation for future research. A Theoretical Domains Framework informed the development of selected items.

Results

The response rate was 72.1% (202/280); however, the usable rate was 95.5% (193/202). The participants gave positive responses relating to their perceptions of research significance {Median = 5.0 [Interquartile range (IQR) = 1.0], Minimum–Maximum = 1–5}, confidence in conducting research [Median = 4.0 (IQR = 1.0), Minimum–Maximum = 1–5], actual and anticipated outcomes [Median = 4.0 (IQR = 1.0), Minimum–Maximum = 1–5], and motivation for future research plans [Median = 4.0 (IQR = 1.0), Minimum–Maximum = 1–5]. The majority of participants perceived non-confidence in using data analysis software [72 (39.4% non-confidence)] and a high proportion of participants were non-confident in conducting data analysis [45 (24.6% non-confidence)]. More than half reported publishing at least one peer-reviewed article [99 (54.4% agreement)] from their courses and were highly motivated to consider post-graduate degrees in pharmacy [132 (73.3% agreement)].

Conclusions

Incorporating URPCs into CPH–QU curriculum has potentially improved students and alumni's perceptions of research. Action is needed to improve confidence in different aspects of research.