bluuebunny/crossref_metadata_2025 huggingface dataset:
Malaysian dental deans’ consensus on impact of COVID-19 and recommendations for sustaining quality dental education
Authors: Mohd-Dom Tuti Ningseh , Lim Kai Xin , Rani Haslina , Yew Hsu Zenn
Published: August 2022

The COVID-19 pandemic has significantly affected the training of dental students and the impact can be felt not just by the students, but patients seen at dental school operated clinics. We used the modified-Delphi method to investigate the response from deans of all Malaysian dental schools on the impact of COVID-19, and to solicit their views on policy recommendations to sustain quality dental education during and beyond the infectious disease outbreak. Our analysis revealed that all dental deans are in agreement with strong consensus to 10 out of fifteen items listed to be the challenges they faced due to the COVID-19 pandemic particularly these three items: “Patients under care of students experienced interrupted dental treatment which increases their risk of having their dental and overall wellbeing affected”; “Increased clinical budget for daily operations of Students’ clinics to cater for extra PPE and related expenses,” and; “The Students’ ability to meet clinical requirements for safe and competent practice.” All deans agreed with a strong consensus to the policy statements formulated based on the WHO’s Six Building Blocks to sustain quality dental education. In view of the results, we further discussed the importance of acknowledging that university-led dental clinics as an important part of the national healthcare system. Hence, we proposed that dental education need to have clear policies on having adequate number of trained staff, sufficient funds, information, supplies, transport, communications and overall guidance, and direction to function. Having a National Dental Education Policy that addresses the unique challenges identified in this study will serve as a monumental cornerstone to sustain quality dental education during times of calamity.
Classification of pyroptosis patterns and construction of a novel prognostic model for prostate cancer based on bulk and single-cell RNA sequencing
Authors: Fu Jianhan , Li Guoqiang , Luo Ruixiang , Lu Zhijie , Wang Yinhuai
Published: August 2022

Background

Emerging evidence suggests an important role for pyroptosis in tumorigenesis and recurrence, but it remains to be elucidated in prostate cancer (PCa). Considering the low accuracy of common clinical predictors of PCa recurrence, we aimed to develop a novel pyroptosis-related signature to predict the prognosis of PCa patients based on integrative analyses of bulk and single-cell RNA sequencing (RNA-seq) profiling.

Methods

The RNA-seq data of PCa patients was downloaded from several online databases. PCa patients were stratified into two Classes by unsupervised clustering. A novel signature was constructed by Cox and the Least Absolute Shrinkage and Selection Operator (LASSO) regression. The Kaplan-Meier curve was employed to evaluate the prognostic value of this signature and the single sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to analysis tumor-infiltrating immune cells. At single-cell level, we also classified the malignant cells into two Classes and constructed cell developmental trajectories and cell-cell interaction networks. Furthermore, RT-qPCR and immunofluorescence were used to validate the expression of core pyroptosis-related genes.

Results

Twelve prognostic pyroptosis-related genes were identified and used to classify PCa patients into two prognostic Classes. We constructed a signature that identified PCa patients with different risks of recurrence and the risk score was proven to be an independent predictor of the recurrence free survival (RFS). Patients in the high-risk group had a significantly lower RFS (P<0.001). The expression of various immune cells differed between the two Classes. At the single-cell level, we classified the malignant cells into two Classes and described the heterogeneity. In addition, we observed that malignant cells may shift from Class1 to Class2 and thus have a worse prognosis.

Conclusion

We have constructed a robust pyroptosis-related signature to predict the RFS of PCa patients and described the heterogeneity of prostate cancer cells in terms of pyroptosis.
Triglyceride-glucose index and stroke recurrence in elderly patients with ischemic stroke
Authors: Wang Fang , Wang Jinjing , Han Yunfei , Shi Xuan , Xu Xiaohui , Hou Chao , Gao Jie , Zhu Shuanggen , Liu Xinfeng
Published: August 2022

Background and purpose

This study aimed to explore the association between triglyceride–glucose (TyG) index and stroke recurrence in elderly patients with ischemic stroke in China.

Methods

We enrolled ischemic stroke patients aged ≥ 65 years from the Nanjing Stroke Registry Program. The primary endpoint was defined as recurrent stroke within one year after the index stroke. We used multivariable Cox proportional hazards regression models to investigate the association between TyG index and stroke recurrence. We assessed the discriminative ability of TyG index with the receiver operative characteristic and the area under the curve.

Results

A total of 955 patients (median age, 70.0 [67.0, 75.0]; male sex, 67.2%) from the Nanjing Stroke Registry Program were enrolled. During one year follow-up, 97 (10.2%) elderly patients experienced stroke recurrence. In multivariable analyses, the association between TyG index and stroke recurrence remained significant after adjusting for confounders (quartile 4 versus quartile 1; hazard ratio, 2.073, 95% confidence interval, 1.158-3.711; P = 0.014). The restricted cubic spline showed an increasing trend for TyG index and stroke recurrence (P for non-linearity = 0.072). The area under the curve to predict stroke recurrence with TyG index was 0.719 (95% confidence interval, 0.666-0.772). Besides, TyG index slightly improved the prediction for stroke recurrence.

Conclusion

Elevated TyG index was associated with stroke recurrence in elderly patients with ischemic stroke. Further studies are warranted to assess the role of TyG index in the development of stroke recurrence in the elderly.
Intrauterine interventions for women with two or more implantation failures: A systematic review and network meta-analysis
Authors: Jin Xin Hang , Li Yang , Li Dan
Published: August 2022

Objective

To compare the effectiveness of different intrauterine interventions for women with two or more unexplained implantation failures.

Design

A systematic review and network meta-analysis of randomized controlled trials (RCTs).

Patient(s)

Women with two or more implantation failures undergoing fresh or frozen embryo transfer (ET).

Intervention(s)

An electronic search of the following databases: Pubmed, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase.

Main Outcome Measure(s)

Clinical pregnancy, live birth/ongoing pregnancy, and miscarriage.

Result(s)

We included 21 RCTs(3079 women) in the network meta-analysis. The network meta-analysis showed that compared with control treatment, platelet-rich plasma(PRP), peripheral blood mononuclear cells (PBMC), granulocyte colony-stimulating factor(G-CSF), human chorionic gonadotropin(HCG), and endometrial scratch(ES) significantly increased clinical pregnancy(OR 3.78, 95% CI 2.72 to 5.25; 2.79, 95% CI 1.75 to 4.45; 1.93, 95% CI 1.37 to 2.72; 1.80, 95% CI 1.18 to 2.72; 1.75, 95% CI 1.29 to 2.36, respectively). PRP ranked the highest in improving clinical pregnancy, followed by PBMC, G-CSF, HCG, and ES. Compared with control treatment, PRP, PBMC, and ES significantly increased live birth/ongoing pregnancy (OR 5.96, 95% CI 3.38 to 10.52; OR 2.55, 95% CI 1.27 to 5.11; OR 1.70, 95% CI 1.07 to 2.69, respectively). PRP ranked the highest in improving live birth/ongoing pregnancy, followed by PBMC, and ES.

Conclusion(s)

PRP is the most effective intrauterine intervention in improving pregnancy outcome in women with two or more implantation failures.
Outcome of giant pituitary tumors requiring surgery
Authors: Gaillard Stephan , Adeniran Sosthène , Villa Chiara , Jouinot Anne , Raffin-Sanson Marie-Laure , Feuvret Loic , Verrelle Pierre , Bonnet Fidéline , Dohan Anthony , Bertherat Jérôme , Assié Guillaume , Baussart Bertrand
Published: August 2022

Objective

The management of giant pituitary tumors is complex, with few publications and recommendations. Consequently, patient’s care mainly relies on clinical experience. We report here a first large series of patients with giant pituitary tumors managed by a multidisciplinary expert team, focusing on treatments and outcome.

Methods

A retrospective cohort study was conducted. Giant pituitary tumors were defined by a main diameter > 40mm. Macroprolactinomas sensitive to dopamine agonists were excluded. All patients were operated by a single neurosurgical team. After surgery, multimodal management was proposed, including hormone replacement, radiotherapy and anti-tumor medical therapies. Outcome was modeled using Kaplan-Meyer representation. A logistic regression model was built to identify the risk factors associated with surgical complications.

Results

63 consecutive patients presented a giant adenoma, most often with visual defects. Patients were operated once, twice or three times in 59%, 40% and 1% of cases respectively, mainly through endoscopic endonasal approach. Giant adenomas included gonadotroph, corticotroph, somatotroph, lactotroph and mixed GH-PRL subtypes in 67%, 14%, 11%, 6% and 2% of patients respectively. Vision improved in 89% of patients with prior visual defects. Severe surgical complications occurred in 11% of patients, mainly for tumors > 50 mm requiring microscopic transcranial approach. Additional radiotherapy was needed for 29% of patients, 3 to 56 months after first surgery. For 6% of patients, Temozolomide treatment was required, 19 to 66 months after first surgery.

Conclusions

Giant pituitary tumors require multimodal management, with a central role of surgery. Most often, tumor control can be achieved by expert multidisciplinary teams.
Fabrication of 3D graphene/MoS2 spherical heterostructure as anode material in Li-ion battery
Authors: Wenelska K. , Adam V. , Thauer E. , Singer L. , Klingeler R. , Chen X. , Mijowska E.
Published: August 2022

Three-dimensional (3D) graphene-based nanocomposites have received considerable attention in both fundamental research and industrial applications, as they combine the functionalities of well-controlled nano-architectures and the integrity of bulk materials. Actually, among these materials, spherical structures are attracting more and more attention worldwide due to their excellent performance in various fields such as drug delivery, heterogeneous catalysis, encapsulation of support, and electrode materials for lithium-ion batteries. Herein, a facile route to fabricate a three-dimensional hierarchical graphene/MoS2 nanocomposite is presented. The molecular heterostructure is derived from graphene oxide flakes and precursors of molybdenum ((NH4)2Mo7O4·4H2O) and sulfur (L-cysteine). Spherical morphology (GO/MoS2) is obtained via self-assembly of the precursor. This 3D nanocomposite exhibits MoS2-nanosheets strongly linked to graphene oxide flakes, which renders it particularly suited to exploit the conversion reaction of MoS2 for electrochemical energy storage. When assembled into an electrode in lithium-ion batteries, as-prepared GO/MoS2 electrodes indeed deliver a high initial charge capacity of 783 mA h g−1 at a current density of 100 mA/g and Coulombic efficiency of more than 96% from the second cycle on exceeding the theoretical capacity of the pristine 2D MoS2 and graphene. Overall, the study sheds some light on the design of 3D heterostructure as a promising anode material in Li-ion batteries.
Synergistic enhancement of coalbed methane hydration process by magnetic field and NiMnGa micro-nano fluid
Authors: Wu Qiong , Lin Nengyu , Li Li , Chen Feng , Xv Xianfu , Zhang Baoyong , Wu Qiang , Liu Chuanhai
Published: August 2022

Coalbed methane is an important renewable energy source. Gas hydration technology is a new method for enhancing the utilization of coalbed methane and reducing environmental pollution. Long induction periods, sluggish formation rates, low hydrate yields, and difficulty removing heat during hydrate formation are all issues with gas hydration technology. In this paper, 3 wt% NiMnGa (NMG) phase-change micro/nanoparticles and 0.05% sodium dodecyl sulphate (SDS) were compounded, and gas hydration experiments were conducted under various initial pressures and gas sample conditions to investigate. The findings revealed that NMG has efficient mass transfer properties as well as phase-change heat absorption properties, which significantly improved the kinetic process of the gas hydrate by mass and heat transfer, shortened the induction time, increased gas consumption, and increased the gas consumption rate during the rapid hydrate growth period. When the initial pressure was 6.2 MPa, the induction time was reduced by 89.26%, 92.48%, and 95.64%, and the maximum gas consumption rate was increased by 238.18%, 175.55%, and 113.60%, respectively, when using different concentrations of methane in the NMG-SDS system compared to the pure SDS system. The NMG used in this paper showed potential for future use in mixed gas hydration technology.
The impact of environmental taxes on economic benefits and technology innovation input of heavily polluting industries in China
Authors: Wang Zhengyan , Zhu Naiping , Wang Jianuo , Hu Yingyun , Nkana Mwansa
Published: August 2022

This paper defined heavily polluting enterprises as the treatment group based on relevant data on the listed companies in the 5 years from 2016 to 2020. Companies other than the heavily polluting enterprises were defined as the control group. An empirical analysis applying the double-difference technique was performed to assess the impact of China’s environmental tax on the economic performance and technological innovation input of industries that pollute heavily. The findings demonstrated an increased positive effects of environmental taxes on the economic performance and technology innovation input of heavily polluting industries since the inception of the environmental tax in China. As some enterprises in heavily polluting industries are under increased financial pressure owing to green upgrades and the low environmental tax rate in some regions, recommendations are presented to improve the environmental regulation system, adapt environmental taxes to local conditions, and strengthen the implementation and supervision of environmental taxes through big data technology.
Decoupling between PM2.5 concentrations and aerosol optical depth at ground stations in China
Authors: Fu Weijie , Yue Xu , Li Zhengqiang , Tian Chenguang , Zhou Hao , Li Kaitao , Chen Yuwen , Zhao Xu , Zhao Yuan , Hu Yihan
Published: August 2022

Surface PM2.5 concentrations and aerosol optical depth (AOD) are two air pollution metrics tightly connected. Many studies have used AOD to derive PM2.5 concentrations without investigating their inconsistencies. Here, we explored the associations between surface PM2.5 and AOD using ground-level data from 19 stations in China during 2017–2019. Unexpectedly, we found low correlation coefficients of 0.03–0.60 between daily PM2.5 and AOD for most sites. Such decoupling between PM2.5 and AOD is further compared to simultaneous meteorological factors such as air temperature, specific humidity, sea level pressure, and wind speed. We found that specific humidity dominates the correlations with normalized PM2.5-AOD differences at 14 out of 19 sites. On average, specific humidity increases from 2.83 g kg−1 for the cases with low AOD but high PM2.5–11.89 g kg−1 for those with high AOD but low PM2.5, indicating that hygroscopic growth of aerosols may play an important role in decoupling the associations between PM2.5 and AOD. Random forest (RF) models using AOD as the only input yield a low R of 0.49 between the predicted and observed PM2.5 concentrations. The inclusion of specific humidity in the RF model increases the R to 0.74, close to the R of 0.81 with three additional meteorological factors. Our study revealed a strong decoupling between PM2.5 and AOD and suggested including specific humidity as a key parameter in the retrieval of long-term PM2.5 using AOD data in China.
Identification of hub genes related to CD4+ memory T cell infiltration with gene co-expression network predicts prognosis and immunotherapy effect in colon adenocarcinoma
Authors: Tang Lingxue , Yu Sheng , Zhang Qianqian , Cai Yinlian , Li Wen , Yao Senbang , Cheng Huaidong
Published: August 2022

Background: CD4+ memory T cells (CD4+ MTCs), as an important part of the microenvironment affecting tumorigenesis and progression, have rarely been systematically analyzed. Our purpose was to comprehensively analyze the effect of CD4+ MTC infiltration on the prognosis of colon adenocarcinoma (COAD).

Methods: Based on RNA-Seq data, weighted gene co-expression network analysis (WGCNA) was used to screen the CD4+ MTC infiltration genes most associated with colon cancer and then identify hub genes and construct a prognostic model using the least absolute shrinkage and selection operator algorithm (LASSO). Finally, survival analysis, immune efficacy analysis, and drug sensitivity analysis were performed to evaluate the role of the prognostic model in COAD.

Results: We identified 929 differentially expressed genes (DEGs) associated with CD4+ MTCs and constructed a prognosis model based on five hub genes (F2RL2, TGFB2, DTNA, S1PR5, and MPP2) to predict overall survival (OS) in COAD. Kaplan–Meier analysis showed poor prognosis in the high-risk group, and the analysis of the hub gene showed that overexpression of TGFB2, DTNA, S1PR5, or MPP2 was associated with poor prognosis. Clinical prediction nomograms combining CD4+ MTC-related DEGs and clinical features were constructed to accurately predict OS and had high clinical application value. Immune efficacy and drug sensitivity analysis provide new insights for individualized treatment.

Conclusion: We constructed a prognostic risk model to predict OS in COAD and analyzed the effects of risk score on immunotherapy efficacy or drug sensitivity. These studies have important clinical significance for individualized targeted therapy and prognosis.
TRIB3 promoter 33 bp VNTR is associated with the risk of cerebrovascular disease in type 2 diabetic patients
Authors: Lai Jiaqi , Ouyang Jiaying , Lin Weijie , Liu Mouze , Yang Yang , Wang Ruiqi , Yang Haikui , Meng Qian , Dong Jiamei , Zhang Jianping , Li Ling , He Fazhong
Published: August 2022

Previous studies have demonstrated that TRIB3 is closely related to insulin resistance, metabolic disorders and vascular diseases. Recently, it was reported that a 33 bp variable number of tandem repeats (VNTR) located in the TRIB3 promoter could considerably alter its transcriptional activity. Nonetheless, whether the shift of TRIB3 transcriptional activity has the effect of inducing diabetic vascular complications is still unclear. Therefore, in our study, we aimed to explore the relationship between the TRIB3 33bp VNTR and diabetic vascular complications. The TRIB3 33bp VNTR polymorphisms were determined by PCR and Sanger sequencing, a total of 798 eligible Chinese patients with type 2 diabetes (T2DM) were included in our study and then evaluated with clinical data. After adjusting for age, gender, BMI, smoking history, drinking history and duration of diabetes, we found that the high number of 33 bp tandem repeats (repeats>8) was significantly associated with an increase in the risk of cerebrovascular diseases compared with the low number of 33 bp tandem repeats (repeats≤6) in patients with T2DM(OR 2.66, 95% CI 1.29–5.47, p = 0.008). The intermediate number of 33bp tandem repeats (6 < repeat≤8) was markedly associated with a decreased risk of diabetic retinopathy compared with the low number of tandem repeats (OR 0.65, 95% CI 0.46–0.91, p = 0.012). Adjusting for gender, age and BMI, there was a significant difference in DBP levels among patients with the number of different 33 bp tandem repeats (Low vs. Intermediate vs. High, 81.6 ± 12.8 vs. 79.8 ± 12.4 vs. 78.7 ± 12.6 mmHg; p = 0.045). Subgroup analysis found that TRIB3 VNTR was significantly correlated with the difference in systolic blood pressure (SBP) in T2DM patients taking ACEI/ARB drugs (Low vs. Intermediate vs. High, 146.27 ± 18.23 vs. 140.01 ± 19.91 vs. 140.77 ± 18.64 mmHg; p = 0.018). Our results indicated that TRIB3 promoter 33bp VNTR is related to vascular diseases in T2DM patients, and may serve as a new biomarker for individualized prevention and therapy of T2DM.
GNB3 c.825c>T polymorphism influences T-cell but not antibody response following vaccination with the mRNA-1273 vaccine
Authors: Čiučiulkaitė Ieva , Möhlendick Birte , Thümmler Laura , Fisenkci Neslinur , Elsner Carina , Dittmer Ulf , Siffert Winfried , Lindemann Monika
Published: August 2022

Background: Immune responses following vaccination against COVID-19 with different vaccines and the waning of immunity vary within the population. Genetic host factors are likely to contribute to this variability. However, to the best of our knowledge, no study on G protein polymorphisms and vaccination responses against COVID-19 has been published so far.

Methods: Antibodies against the SARS-CoV-2 spike protein and T-cell responses against a peptide pool of SARS-CoV-2 S1 proteins were measured 1 and 6 months after the second vaccination with mRNA-1273 in the main study group of 204 participants. Additionally, antibodies against the SARS-CoV-2 spike protein were measured in a group of 597 participants 1 month after the second vaccination with mRNA-1273. Genotypes of GNB3 c.825C>T were determined in all participants.

Results: The median antibody titer against the SARS-CoV-2 spike protein and median values of spots increment in the SARS-CoV-2 IFN-γ ELISpot assay against the S1-peptide pool were significantly decreased from months 1 to 6 (p < 0.0001). Genotypes of GNB3 c.825C>T had no influence on the humoral immune response. At month 1, CC genotype carriers had significantly increased T-cell responses compared to CT (p = 0.005) or TT (p = 0.02) genotypes. CC genotype carriers had an almost 6-fold increased probability compared to TT genotype carriers and an almost 3-fold increased probability compared to T-allele carriers to mount a SARS-CoV-2-specific T-cell response above the median value.

Conclusion: CC genotype carriers of the GNB3 c.825C>T polymorphism have an increased T-cell immune response to SARS-CoV-2, which may indicate better T-cell-mediated protection against COVID-19 after vaccination with mRNA-1273.
Experimental verification and validation of immune biomarkers based on chromatin regulators in ischemic stroke
Authors: Yu Beibei , Tian Yunze , Zhang Yongfeng , Lv Boqiang , Li Jianzhong , Gong Shouping
Published: August 2022

Ischemic stroke (IS) is a disease characterized by rapid progression and high mortality and disability rates. Its pathophysiological process is inseparable from immune dysfunction. Recently, chromatin regulators (CRs) have been described as a class of enzymes that can recognize, form, and maintain the epigenetic state of an organism, and are closely associated with immune regulation. Nevertheless, the role of CR-related genes in IS has not been fully elucidated. In this study, seven CR-related immune biomarkers in the GSE58294 and GSE22255 datasets were identified by combining differential gene expression analysis, weighted correlation network analysis, and single sample gene set enrichment analysis. After experimental validation using quantitative polymerase chain reaction, four genes (DPF2, LMNB1, MLLT3, and JAK2) were screened as candidate immune biomarkers. These four biomarkers demonstrated good predictive power in the clinical risk model (area under the curve, 0.775). Molecular docking simulations revealed that mevastatin, WP1066, cladribine, trichostatin A, mequitazine, and zuclomiphene may be potential immunomodulatory drugs for IS. Overall, the results of this study contribute to the identification of CR-related immune therapeutics target in IS and provide an important reference for further research.
Economic empowerment of the pilot reintegration program for female genital fistula survivors in Kenya during the COVID-19 pandemic
Authors: McCammon Mary Ann , Otondo Norah Amisi , Kay Nancy
Published: August 2022

Objective

To determine whether a pilot reintegration program for female genital fistula survivors that included a combination of financial support, psychosocial support, and mentoring would result in their long-term economic empowerment during the COVID-19 pandemic.

Results

Nine fistula survivors participated in a 29-month pilot reintegration program offered by Kenya Quilts for Empowerment (KQFE), a registered Community Based Organization in Kenya. Originally, the program was intended to last for 18 months, but as a result of the pandemic, this was extended to achieve the long-term economic empowerment of women. The program was based on best practices for poverty alleviation that included multiple sources of income, psychosocial support, and mentoring, sustained over the entire 29-month period. All the women were severely impoverished at the baseline assessment, with one having some savings, and a few having productive assets, which were primarily chickens. Financial training and an initial non-refundable cash transfer provided start-up funds for small businesses; these initially flourished before floundering during the pandemic and eventually recovering. Funds were also used to buy livestock. A key component of the program was the provision of national health insurance for each woman and her family, which helped them stay healthy without having to sell any income-generating livestock. Other key components were the psychosocial support and mentoring provided within their support group. After 29 months, every woman had achieved long-term economic empowerment and “graduated” to become a KQFE ambassador, tasked with identifying fistula survivors within their communities, and referring them for surgery and participation in a reintegration support group.
Characterization of a novel cysteine protease inhibitor in Baylisascaris schroederi migratory larvae and its role in regulating mice immune cell response
Authors: Xu Jingyun , Gu Xiaobin , Xie Yue , He Ran , Xu Jing , Xiong Lang , Peng Xuerong , Yang Guangyou
Published: August 2022

Baylisascaris schroederi (B. schroederi) is a severe threat to the survival of giant pandas. Currently, the immune regulation mechanism of B. schroederi is poorly understood. Cysteine protease inhibitors (CPI) play important roles in the regulation of host immune responses against certain nematodes. In this study, a recombinant CPI of B. schroederi migratory larvae (rBsCPI-1) was cloned and expressed, and the effects of rBsCPI-1 on the physiological activities and antigen presentation of monocyte-derived macrophages (MDMs) were analyzed. We also analyzed the regulatory effects of rBsCPI-1 on the proliferation and differentiation of CD4+ T cells. And further identified the signaling pathways which play important roles in this process. The results showed that rBsCPI-1 activated the TLR2/4-small Rho GTPases-PAK1 pathway. On the one hand, it increased the phagocytosis and migration of MDMs. On the other hand, it activated downstream MAPK and NF-κB signaling pathways to induce apoptosis of MDMs. rBsCPI-1 also induced MDMs to polarize to the M2 subtype, thereby exerting an immunosuppressive effect. Meanwhile, rBsCPI-1 inhibited the antigen presentation process by decreasing the expression of MHC-II molecules, further inhibiting the proliferation of CD4+ T cells and inducing a Th1/Th2 mixed immune response. Treg cells with immunosuppressive effects were increased. The PD-L2/PD-1 and CD80/CTLA-4 signaling pathways between MDMs and CD4+ T cells were also activated by rBsCPI-1. In conclusion, this study preliminarily confirmed that rBsCPI-1 affects the physiological activities and polarization of MDMs through the TLR2/4 signaling pathway, and further interferes with antigen presentation response, inducing CD4+ T cells to play an immunosuppressive cellular response during the migratory process of B. schroederi. Thus, this study will provide a reference for elucidating the immune evasion mechanism of B. schroederi and developing new drugs and protective vaccines against B. schroederi.
Establishment of a colony of Anopheles darlingi from French Guiana for vector competence studies on malaria transmission
Authors: Puchot Nicolas , Lecoq Marie-Thérèse , Carinci Romuald , Duchemin Jean Bernard , Gendrin Mathilde , Bourgouin Catherine
Published: August 2022

Anopheles darlingi is a major vector of both Plasmodium falciparum and Plasmodium vivax in South and Central America including French Guiana. However, the vector competence and physiology of this mosquito species have been scarcely studied due to difficulties in rearing it in the laboratory. Here, we report the successful establishment of a robust colony, from a mosquito collection in French Guiana. We describe our mosquito colonization procedure with relevant information on environmental conditions, mating ability, larval development, and survival, recorded over the first six critical generations. Experimental infection showed that our An. darlingi colony has a moderate permissiveness to in vitro produced gametocytes of the P. falciparum NF54 strain originating from Africa. This colony, which has reached its 21st generation, will allow further characterization of An. darlingi life-history traits and of Plasmodium–mosquito interactions with South American malaria parasites.
Filtration Rate of the Solitary, Pleated Tunicate Styela plicata on the Brown Tide-Forming Pelagophytes Aureoumbra lagunensis and Aureococcus anophagefferens
Authors: Klarmann Phyllis A. , Scarpa John , Hartmann James X.
Published: August 2022

Recurring brown tide algal blooms of the pelagophyte Aureoumbra lagunensis in the northern Indian River, Mosquito, and Banana River lagoons on the Atlantic coast of central Florida, USA, have resulted in marked ecological impacts. Recent studies have investigated whether suspension feeding invertebrates could contribute to top-down control of these and other bloom-forming phytoplankton. While most studies focused on the effects A. lagunensis has on on bivalve filter feeding in the Indian River Lagoon, this study focused on feeding by the solitary pleated tunicate Styela plicata. Hourly filtration rates (FR) of individual S. plicata were measured after exposure to 5.0 x 105 cells mL–1 of either A. lagunensis or another pelagophyte Aureococcus anophagefferens. The latter species has not been observed in Florida estuaries but can also inhibit feeding. Tisochrysis lutea, an alga commonly used as feed in aquaculture was used as a control. Differences in hourly FR of either brown tide species compared to the control alga were statistically significant (p < 0.0001). Mean hourly FR of tunicates exposed to Aureoumbra lagunensis ranged from -282 mL hr−1 to 542 mL hr−1, whereas tunicates exposed to the control species Tisochrysis lutea had FR from 285 mL hr−1 to 2648 mL hr−1. Mean hourly FR of tunicates exposed to Aureococcus anophagefferens ranged from 343 mL hr−1 to 593 mL hr−1 compared to tunicates exposed to T. lutea which ranged from 600 mL hr−1 to 2482 mL hr−1. Further, to test whether cell density and a longer exposure time affected FR, individual S. plicata were initially exposed to cell densities of 103, 104, or 105 cells mL–1 of either A. lagunensis or T. lutea (control) for 24 hours. Subsequent measurement of hourly FR and showed cell density removal was not significantly different (p = 0.28 and 0.77, respectively). These results add to the body of literature on how organisms in the Indian River Lagoon filter-feeder community respond to brown tide exposure. The pleated tunicate may be an additional species contributing to top-down control of these bloom-forming microalgae.
Effect of codend mesh sizes on the size selectivity and exploitation pattern of cocktail shrimp (Trachypenaeus curvirostris) in shrimp trawl fishery of the South China Sea
Authors: Yang Bingzhong , Herrmann Bent
Published: August 2022

This study aims at improving fishery management by testing and comparing the size selectivity and exploitation pattern of diamond-mesh codends, with mesh sizes ranging from 25 to 54 mm, for cocktail shrimp (Trachypenaeus curvirostris) in the South China Sea (SCS). Beginning from 25 mm, the minimum mesh size regulated by the shrimp trawl fishery industry, we investigated how the mesh sizes of the codends would affect the size selectivity and exploitation pattern in reference to the minimum conservation reference size (MCRS, 7.0 cm total length) of cocktail shrimp in the SCS. According to our results, the selective properties of the codend mesh sized at 25 mm in line with the regulation failed to protect the undersized individuals of cocktail shrimp because of its 50% retention length of 5.85 cm (confidence interval, CI: 5.16–6.18 cm), far less than the MCRS of cocktail shrimp. As the retention probability of a shrimp with a MCRS length was as high as 97.45 % (CI: 86.86–100.00%), more than 40% of the undersized shrimp was retained. It was proved that increasing the codend mesh size did not significantly improve the size selectivity and exploitation pattern which might be improved by other gear modifications.
Typical response of CD14++CD16– monocyte to knee synovial derived mediators as a key target to overcome the onset and progression of osteoarthritis
Authors: Saffery Nik Syazana Izyan , Genasan Krishnamurithy , Chan Chee Ken , Ayob Khairul Anwar , Teo Seow Hui , Al-Fayyadh Mohamed Zubair Mohamed , Othman Iekhsan , Abidin Syafiq Asnawi Zainal , Raman Murali Malliga , Raghavendran Hanumantha Rao Balaji , Kamarul Tunku
Published: August 2022

Objective

Synovitis with increased infiltration of immune cells is observed in osteoarthritis (OA). Given the inflammatory condition of synovitis, we explored the protein profile of OA synovium (OAS) and its effect on circulating monocytes activation, migration, and functional commitments.

Methods

Knee-synovium was acquired from end-stage OA (N= 8) and trauma patients (Trauma baseline control: TBC;N= 8) for characterization using H&E histology, IHC (iNOS), LCMS-QTOF, and MALDI-imaging. Response of peripheral blood monocytes to OAS conditioned-media (OACM) was observed using transwell (n= 6). The migrated cells were captured in SEM, quantified using phase-contrast microphotographs, and their activation receptors (CCR2, CXCR2, CX3CR1, and CD11b), pro-inflammatory genes, and phagocytic potential were studied using flow cytometry, gene expression array/qPCR, and latex beads (LB) phagocytosis assay, respectively.

Results

The Venn diagram displayed 119 typical proteins in OAS, while 55 proteins in TBCS. The STRING protein network analysis indicated distinctive links between proteins and gene ontology (GO) and revealed proteins associated with leukocyte-mediated immunity in OAS as compared to TBC. The MALDI-imaging showed typical localized proteins at 2234.97, 2522.61, 2627.21, 3329.50, and 3539.69m/zand IHC confirmed pro-inflammatory iNOS expression in OA synovium. CD14++CD16–classical monocytes significantly migrated in OACM and expressed CCR2, CXCR2, and CD11b receptors, TNFRSF11A, MAPK1, S100A8, HSPB1, ITGAL, NFATC1, IL13RA1, CD93, IL-1β, TNF-α, and MYD88 genes and increased LB uptake as compared to SFM.

Conclusion

Our findings suggest that the differential protein profile of OA synovium and the classical monocytes migrated, activated, and functionally committed in response to these mediators could be of therapeutic advantage.
Development and validation of models for predicting the overall survival and cancer-specific survival of patients with primary vaginal cancer: A population-based retrospective cohort study
Authors: Zhou Wei-Li , Yue Yang-Yang
Published: August 2022

Background

No models have been developed to predict the survival probability for women with primary vaginal cancer (VC) due to VC’s extreme rareness. We aimed to develop and validate models to predict the overall survival (OS) and cancer-specific survival (CSS) of VC patients.

Methods

A population-based multicenter retrospective cohort study was carried out using the 2004–2018 Surveillance, Epidemiology, and End Results Program database in the United States. The final multivariate Cox model was identified using the Brier score and Harrell’s C concordance statistic (C-statistic). The decision curve, calibration plot, and area under the time-dependent receiver operating characteristic curve (AUC) were used to evaluate model prediction performance. Multiple imputation followed by bootstrap was performed. Bootstrap validation covered the entire statistic procedure from model selection to baseline survival and coefficient calculation. Nomograms predicting OS and CSS were generated.

Results

Of the 2,417 eligible patients, 1,692 and 725 were randomly allocated to the training and validation cohorts. The median age (Interquartile range) was 66 (56–78) and 65 (55–76) for the two cohorts, respectively. Our models had larger net benefits in predicting the survival of VC patients than the American Joint Committee on Cancer stage, presenting great discrimination ability and excellent agreement between the expected and observed events. The performance metrics of our models were calculated in three cohorts: the training cohort, complete cases of the validation cohort, and the imputed validation cohort. For the OS model in the three cohorts, the C-statistics were 0.761, 0.752, and 0.743. The slopes of the calibration plots were 1.017, 1.005, and 0.959. The 3- and 5-year AUCs were 0.795 and 0.810, 0.768 and 0.771, and 0.770 and 0.767, respectively. For the CSS model in the three cohorts, the C-statistics were 0.775, 0.758, and 0.755. The slopes were 1.021, 0.939, and 0.977. And the 3- and 5-year AUCs were 0.797 and 0.793, 0.786 and 0.788, and 0.757 and 0.757, respectively.

Conclusion

We were the first to develop and validate exemplary survival prediction models for VC patients and generate corresponding nomograms that allow for individualized survival prediction and could assist clinicians in performing risk-adapted follow-up and treatment.
How to learn with intentional mistakes: NoisyEnsembles to overcome poor tissue quality for deep learning in computational pathology
Authors: Mayer Robin S. , Gretser Steffen , Heckmann Lara E. , Ziegler Paul K. , Walter Britta , Reis Henning , Bankov Katrin , Becker Sven , Triesch Jochen , Wild Peter J. , Flinner Nadine
Published: August 2022

There is a lot of recent interest in the field of computational pathology, as many algorithms are introduced to detect, for example, cancer lesions or molecular features. However, there is a large gap between artificial intelligence (AI) technology and practice, since only a small fraction of the applications is used in routine diagnostics. The main problems are the transferability of convolutional neural network (CNN) models to data from other sources and the identification of uncertain predictions. The role of tissue quality itself is also largely unknown. Here, we demonstrated that samples of the TCGA ovarian cancer (TCGA-OV) dataset from different tissue sources have different quality characteristics and that CNN performance is linked to this property. CNNs performed best on high-quality data. Quality control tools were partially able to identify low-quality tiles, but their use did not increase the performance of the trained CNNs. Furthermore, we trained NoisyEnsembles by introducing label noise during training. These NoisyEnsembles could improve CNN performance for low-quality, unknown datasets. Moreover, the performance increases as the ensemble become more consistent, suggesting that incorrect predictions could be discarded efficiently to avoid wrong diagnostic decisions.
Molecular transmission network of pretreatment drug resistance among human immunodeficiency virus-positive individuals and the impact of virological failure on those who received antiretroviral therapy in China
Authors: Chen Hongli , Hu Jing , Song Chang , Li Miaomiao , Zhou Yesheng , Dong Aobo , Kang Ruihua , Hao Jingjing , Zhang Jiaxin , Liu Xiu , Li Dan , Feng Yi , Liao Lingjie , Ruan Yuhua , Xing Hui , Shao Yiming
Published: August 2022

Objectives

We investigated the prevalence of pretreatment drug resistance (PDR), the molecular transmission network among HIV-positive individuals, and the impact of virological failure on those who received antiretroviral therapy (ART) in China.

Methods

Based on the World Health Organization (WHO) surveillance guidelines for PDR, a baseline survey and follow-up were conducted in 2018 and 2021, respectively. Demographic information and plasma samples were obtained from all participants. HIV pol gene region sequences were used to analyze the PDR and molecular transmission networks using the Stanford HIV database algorithm and HIV-TRACE, respectively. This study assessed the odds ratios (OR) of PDR to virological failure (viral load ≥ 50 copies/mL) after 3 years of ART using multivariable logistic regression.

Results

Of the 4,084 individuals, 370 (9.1%) had PDR. The prevalence of PDR to non-nucleoside reverse transcriptase inhibitors (5.2%) was notably higher than that to nucleoside reverse transcriptase inhibitors (0.7%, p < 0.001), protease inhibitors (3.0%, p < 0.001), and multidrug resistance (0.3%, p < 0.001). A total of 1,339 (32.8%) individuals from 361 clusters were enrolled in the molecular transmission network. Of the 361 clusters, 22 included two or more individuals with PDR. The prevalence of virological failure among HIV-positive individuals after 3 years of ART without PDR, those with PDR to Chinese listed drugs, and those with PDR to other drugs was 7.9, 14.3, and 12.6%, respectively. Compared with that in HIV-positive individuals without PDR, virological failure after 3 years of ART was significantly higher (OR: 2.02, 95% confidence interval (CI): 1.25–3.27) and not significantly different (OR: 1.72, 95% CI: 0.87–3.43) in individuals with PDR to Chinese listed drugs and those with PDR to other drugs, respectively. Missed doses in the past month were significantly associated with virological failure (OR, 2.82; 95% CI: 4.08–5.89).

Conclusion

The overall prevalence of PDR was close to a high level and had an impact on virological failure after 3 years of ART. Moreover, HIV drug-resistant strains were transmitted in the molecular transmission network. These results illustrate the importance of monitoring PDR and ensuring virological suppression through drug adherence.
Psoriasis and medical ramifications: A comprehensive analysis based on observational meta-analyses
Authors: Zhou Yun , Zhong Lixian , Shen Lianli , Chen Sisi , Zeng Qiuting , Lai Leizhen , Tang Shaohui
Published: August 2022

Purpose

Based on a large number of systematic reviews and meta-analyses exploring the relationship between psoriasis and various health outcomes, we conducted an comprehensive analysis to assess the strength and evidence for the association between psoriasis and medical end-point ramifications in patients.

Methods

We searched related meta-analyses, investigating the links between psoriasis and medical ramifications from three databases. All summary effect sizes, 95% CIs, heterogeneity, and small-study effects in the included meta-analyses were recalculated. We assessed the methodological quality of included articles with the AMSTAR 2 tool and graded the epidemiological evidence. Subgroup analysis based on the severity of psoriasis and study design were also performed.

Results

A total of 38 articles comprising 85 unique meta-analyses were included in this study. Although 69 outcomes were statistically significant, only 8 outcomes (nonvascular dementia, ulcerative colitis, pediatric dyslipidemia, gestational diabetes, gestational hypertension, fracture, multiple sclerosis, and schizophrenia) showed a high quality of epidemiological evidence.

Conclusion

We found that psoriasis increased the risk of 69 health outcomes, and 8 outcomes were graded as high-quality evidence. No evidence was found that psoriasis was beneficial for any medical end point. However, to verify our results, more large-sample, multi-center prospective cohort studies are needed.
Functional characterization of a gamma-glutamyl phosphate reductase ProA in proline biosynthesis and promoting expression of type three secretion system in Ralstonia solanacearum
Authors: Guan Yue , Wang Rongsheng , Chen Nan , Zhu Yalan , Han Liangliang , Chen Xinping , Li Jing , Zhang Yong
Published: August 2022

Ralstonia solanacearum RSc2741 has been predicted as a gamma-glutamyl phosphate reductase ProA catalyzing the second reaction of proline formation from glutamate. Here, we experimentally demonstrated that proA mutants were proline auxotrophs that failed to grow in a minimal medium, and supplementary proline, but not glutamate, fully restored the diminished growth, confirming that ProA is responsible for the biosynthesis of proline from glutamate in R. solanacearum. ProA was previously identified as one of the candidates regulating the expression of genes for type three secretion system (T3SS), one of the essential pathogenicity determinants of R. solanacearum. Supplementary proline significantly enhanced the T3SS expression both in vitro and in planta, indicating that proline is a novel inducer of the T3SS expression. Deletion of proA substantially impaired the T3SS expression both in vitro and in planta even under proline-supplemented conditions, indicating that ProA plays additional roles apart from proline biosynthesis in promoting the expression of the T3SS genes. It was further revealed that the involvement of ProA in the T3SS expression was mediated through the pathway of PrhG-HrpB. Both the proA mutants and the wild-type strain grew in the intercellular spaces of tobacco leaves, while their ability to invade and colonize tobacco xylem vessels was substantially impaired, which was about a 1-day delay for proA mutants to successfully invade xylem vessels and was about one order of magnitude less than the wild-type strain to proliferate to the maximum densities in xylem vessels. It thus resulted in substantially impaired virulence of proA mutants toward host tobacco plants. The impaired abilities of proA mutants to invade and colonize xylem vessels were not due to possible proline insufficiency in the rhizosphere soil or inside the plants. All taken together, these results extend novel insights into the understanding of the biological function of ProA and sophisticated regulation of the T3SS and pathogenicity in R. solanacearum.