bluuebunny/crossref_metadata_2025 huggingface dataset:
New frontiers review of some recent conservation techniques of organic and inorganic archaeological artefacts against microbial deterioration
Authors: Geweely Neveen S.
Published: March 2023

The information on the advances and technology of some recent conservation methods (2020–2023) of organic and inorganic archaeological objects against microbial deterioration is recorded. An outline of comparative new protective methods for conserving plant-origin organic artefacts {Fibers (manuscripts, textile) and wood}, animal-origin organic artefacts (painting, parchment and mummies) and inorganic stone artefacts were investigated. The work not only contributes to the development of safe revolutionary ways for more efficient safe conservation of items of historical and cultural worth but also serves as a significant diagnostic signature for detecting the sorts of microbial identification and incidents in antiques. Biological technologies (environmentally friendly green biocides) are the most used recent, efficient and safe strategy acceptable as alternatives to stop microbial deterioration and prevent any potential interactions between the biological agent and the artefacts. Also, a synergistic effect of combining natural biocides with mechanical cleaning or chemical treatments was suggested. The recommended exploration techniques should be considered for future applications.
Automation of unstructured production environment by applying reinforcement learning
Authors: Nambiar Sanjay , Wiberg Anton , Tarkian Mehdi
Published: March 2023

Implementation of Machine Learning (ML) to improve product and production development processes poses a significant opportunity for manufacturing industries. ML has the capability to calibrate models with considerable adaptability and high accuracy. This capability is specifically promising for applications where classical production automation is too expensive, e.g., for mass customization cases where the production environment is uncertain and unstructured. To cope with the diversity in production systems and working environments, Reinforcement Learning (RL) in combination with lightweight game engines can be used from initial stages of a product and production development process. However, there are multiple challenges such as collecting observations in a virtual environment which can interact similar to a physical environment. This project focuses on setting up RL methodologies to perform path-finding and collision detection in varying environments. One case study is human assembly evaluation method in the automobile industry which is currently manual intensive to investigate digitally. For this case, a mannequin is trained to perform pick and place operations in varying environments and thus automating assembly validation process in early design phases. The next application is path-finding of mobile robots including an articulated arm to perform pick and place operations. This application is expensive to setup with classical methods and thus RL enables an automated approach for this task as well.
Impact of hypertensive disorders of pregnancy on short- and long-term outcomes of pregnancy-associated hemorrhagic stroke
Authors: Fang Mei , Wang Jiayan , Wang Zexu , Chen Yuqi , Xu Wei , Tao Chuanyuan , Ma Lu , You Chao , Hu Xin , Xia Fan
Published: March 2023

Background and purpose

Though hypertension disorders of pregnancy (HDP) are recognized as independent pregnancy-associated stroke risk factors, few studies have considered their impact on stroke prognosis. Therefore, we intended to evaluate the impact of HDP on short- and long-term outcomes of pregnancy-associated hemorrhagic stroke (HS).

Methods

We conducted a retrospective analysis of patients admitted to our hospital from May 2009 to December 2021 with a diagnosis of pregnancy-associated HS. After dividing patients into two groups by the presence of a diagnosis of HDP or not, the short- (at the time of discharge) and long-term (after discharge follow-up) outcomes were compared by mRS (modified Rankin Scale) scores, and poor functional outcome defined as mRS > 2. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were reported.

Results

Twenty-two HDP and 72 non-HDP pregnancy-associated HS patients were enrolled and follow-up after 4.7 ± 3.6 years. There was no significant difference between the two groups regarding short-term outcomes, but patients with HDP were more likely to reach poor functional outcomes at long-term follow-up (aOR = 4.47, 95% CI = 1.28–15.67, p = 0.019).

Conclusions

In this retrospective study, women with hypertension disorders of pregnancy did not show worse short-term outcomes of pregnancy-associated hemorrhagic stroke compared to those without but had poorer long-term functional outcomes. This underlines the importance of prevention, recognition, and treatment of hypertension disorders in these women.
Repetitive transcranial magnetic stimulation for post-stroke depression: An overview of systematic reviews
Authors: Gao Wanning , Xue Fuyu , Yu Bin , Yu Shuo , Zhang Weimin , Huang Haipeng
Published: March 2023

Objective

There is conflicting published research about the clinical effectiveness of repetitive transcranial magnetic stimulation (rTMS) for the treatment of post-stroke depression (PSD). In order to provide trustworthy information for upcoming therapeutic treatments, this review attempts to compile and assess the data from pertinent systematic reviews and meta-analyses.

Methods

The systematic evaluation of repetitive transcranial magnetic stimulation for post-stroke depression was collected by searching CNKI, VIP, Wanfang Database, CBM, PubMed, EMBASE, Web of Science, and Cochrane Library. The retrieval time is from database construction to September 2022. After selection, the included literature was evaluated for methodological quality, reporting quality, and evidence quality using AMSTAR2, PRISMA statements, and the GRADE system.

Results

There were a total of 13 studies included, with three having generally comprehensive reporting according to the PRISMA statement, eight having some reporting issues, two having pretty substantial information issues, and 13 having extremely poor methodological quality according to the AMSTAR2. The GRADE was used to grade the quality of the evidence, and the included literature had 0 high-level evidence, eight medium-level evidence, 12 low-level evidence, and 22 very low-level evidence.

Limitations

The results of this study are from researchers' subjective evaluation and only qualitative analysis, not quantitative evaluation. Although repeated cross-evaluation of researchers is carried out, the results will be personal. The interventions included in the study were complex, and it was impossible to analyze their effect values quantitatively.

Conclusion

Patients with post-stroke depression may benefit from repetitive transcranial magnetic stimulation. However, in terms of the quality of the reports, the methodology, and the quality of the evidence, published systematic evaluations/meta-analyses are of low quality. We list the drawbacks of the current clinical trials of repetitive transcranial magnetic stimulation for post-stroke depression as well as potential therapeutic mechanisms. This information may serve as a guide for future clinical trials aiming to establish a solid foundation for the clinical efficacy of repetitive transcranial magnetic stimulation in the treatment of post-stroke depression.
Intelligent diagnosis of major depression disease based on multi-layer brain network
Authors: Long Dan , Zhang Mengda , Yu Jing , Zhu Qi , Chen Fengnong , Li Fangyin
Published: March 2023

Introduction

Resting-state brain network with physiological and pathological basis has always been the ideal data for intelligent diagnosis of major depression disease (MDD). Brain networks are divided into low-order networks and high-order networks. Most of the studies only use a single-level network to classify while ignoring that the brain works cooperatively with different levels of networks. This study hopes to find out whether varying levels of networks will provide complementary information in the process of intelligent diagnosis and what impact will be made on the final classification results by combining the characteristics of different networks.

Methods

Our data are from the REST-meta-MDD project. After the screening, 1,160 subjects from ten sites were included in this study (597 MDD and 563 normal controls). For each subject, we constructed three different levels of networks according to the brain atlas: the traditional low-order network based on Pearson’s correlation (low-order functional connectivity, LOFC), the high-order network based on topographical profile similarity (topographical information-based high-order functional connectivity, tHOFC) and the associated network between them (aHOFC). Two sample t-test is used for feature selection, and then features from different sources are fused. Finally, the classifier is trained by a multi-layer perceptron or support vector machine. The performance of the classifier was evaluated using the leave-one-site cross-validation method.

Results

The classification ability of LOFC is the highest among the three networks. The classification accuracy of the three networks combined is similar to the LOFC network. These are seven features chosen in all networks. In the aHOFC classification, six features were selected in each round but not seen in other classifications. In the tHOFC classification, five features were selected in each round but were unique. These new features have crucial pathological significance and are essential supplements to LOFC.

Conclusion

A high-order network can provide auxiliary information for low-order networks but cannot improve classification accuracy.
Altered static and dynamic spontaneous neural activity in patients with ischemic pontine stroke
Authors: Wang Xin , Wang Caihong , Liu Jingchun , Guo Jun , Miao Peifang , Wei Ying , Wang Yingying , Li Zhen , Li Jie , Wang Kaiyu , Zhang Yong , Cheng Jingliang , Ren Cuiping
Published: March 2023

Objective

The purpose of the study was to investigate the abnormality both of static spontaneous brain activity and dynamic temporal variances following a pontine infarction.

Methods

Forty-six patients with chronic left pontine infarction (LPI), thirty-two patients with chronic right pontine infarction (RPI), and fifty healthy controls (HCs) were recruited for the study. The static amplitude of low-frequency fluctuations (sALFF), static regional homogeneity (sReHo), dynamic ALFF (dALFF), and dynamic ReHo (dReHo) were employed to detect the alterations in brain activity induced by an infarction. The Rey Auditory Verbal Learning Test and Flanker task were used to evaluate the verbal memory and visual attention function, respectively. Receiver operating characteristic curve analysis was used to reveal the potential capacity of these metrics to distinguish the patients from HCs.

Results

There were significant variations of these static and dynamic metrics in patients with chronic pontine infarction. The altered regions involved the supratentorial regions, including cortex and subcortical. Moreover, the altered metrics were significantly correlated with verbal memory and visual attention. In addition, these static and dynamic metrics also showed potential in distinguishing stroke patients with behavior deficits from HCs.

Conclusion

The pontine infarction-induced cerebral activation changes are observed in both motor and cognitive systems, indicating the functional damage and reorganization across the global cerebral level in these patients with subtentorial infarction, and there is a reciprocal effect between motor and cognitive impairment and repair.
Evolution of visual guanylyl cyclases and their activating proteins with respect to clade and species-specific visual system adaptation
Authors: Gesemann Matthias , Neuhauss Stephan C. F.
Published: March 2023

Membrane guanylyl cyclase receptors are important regulators of local cGMP production, critically influencing cell growth and differentiation as well as ion transport, blood pressure and calcium feedback of vertebrate phototransduction. Currently, seven different subtypes of membrane guanylyl cyclase receptors have been characterized. These receptors have tissue specific expression and are activated either by small extracellular ligands, changing CO2 concentrations or, in the case of visual guanylyl cyclases, intracellularly interacting Ca2+-dependent activating proteins. In this report, we focus on the visual guanylyl cyclase receptors (GCs) GC-E (gucy2d/e) and GC-F (gucy2f) and their activating proteins (GCAP1/2/3; guca1a/b/c). While gucy2d/e has been detected in all analyzed vertebrates, GC-F receptors are missing in several clades (reptiles, birds, and marsupials) and/or individual species. Interestingly, the absence of GC-F in highly visual sauropsida species with up to 4 different cone-opsins is compensated by an increased number of guanylyl cyclase activating proteins, whereas in nocturnal or visually impaired species with reduced spectral sensitivity it is consolidated by the parallel inactivation of these activators. In mammals, the presence of GC-E and GC-F is accompanied by the expression of one to three GCAPs, whereas in lizards and birds, up to five different GCAPs are regulating the activity of the single GC-E visual membrane receptor. In several nearly blind species, a single GC-E enzyme is often accompanied by a single variant of GCAP, suggesting that one cyclase and one activating protein are both sufficient and required for conferring the basic detection of light.
The impact of preoperative nutritional screening, ERAS protocol, and mini-invasive surgery in surgical oncology: A multi-institutional SEM analysis of patients with digestive cancer
Authors: Lorenzon Laura , Caccialanza Riccardo , Casalone Valentina , Santoro Gloria , Delrio Paolo , Izzo Francesco , Tonello Marco , Mele Maria Cristina , Pozzo Carmelo , Pedrazzoli Paolo , Pietrabissa Andrea , Fenu Piero , Mellano Alfredo , Fenocchio Elisabetta , Avallone Antonio , Bergamo Francesca , Nardi Maria Teresa , Persiani Roberto , Biondi Alberto , Tirelli Flavio , Agnes Annamaria , Ferraris Renato , Quarà Virginia , Milanesio Michela , Ribero Dario , Rinaldi Marilena , D'Elia Paola , Rho Maurizio , Cenzi Carola , D'Ugo Domenico
Published: March 2023

Background

Mini-invasive surgery (MIS), ERAS, and preoperative nutritional screening are currently used to reduce complications and the length of hospital stay (LOS); however, inter-variable correlations have seldom been explored. This research aimed to define inter-variable correlations in a large series of patients with gastrointestinal cancer and their impact on outcomes.

Methods

Patients with consecutive cancer who underwent radical gastrointestinal surgery between 2019 and 2020 were analyzed. Age, BMI, comorbidities, ERAS, nutritional screening, and MIS were evaluated to determine their impact on 30-day complications and LOS. Inter-variable correlations were measured, and a latent variable was computed to define the patients' performance status using nutritional screening and comorbidity. Analyses were conducted using structural equation modeling (SEM).

Results

Of the 1,968 eligible patients, 1,648 were analyzed. Univariable analyses documented the benefit of nutritional screening for LOS and MIS and ERAS (≥7 items) for LOS and complications; conversely, being male and comorbidities correlated with complications, while increased age and BMI correlated with worse outcomes. SEM analysis revealed that (a) the latent variable is explained by the use of nutritional screening (p0·004); (b) the variables were correlated (age–comorbidity, ERAS–MIS, and ERAS–nutritional screening, p < 0·001); and (c) their impact on the outcomes was based on direct effects (complications: sex, p0·001), indirect effects (LOS: MIS-ERAS-nutritional screening, p < 0·001; complications: MIS-ERAS, p0·001), and regression-based effects (LOS: ERAS, MIS, p < 0·001, nutritional screening, p0·021; complications: ERAS, MIS, p < 0·001, sex, p0·001). Finally, LOS and complications were correlated (p < 0·001).

Conclusion

Enhanced recovery after surgery (ERAS), MIS, and nutritional screening are beneficial in surgical oncology; however, the inter-variable correlation is reliable, underlying the importance of the multidisciplinary approach.
Antioxidant potential of the diet in Italian children with food allergies
Authors: Pendezza Erica , Nava Chiara , Leone Alessandro , Riccaboni Francesca , Bosetti Alessandra , Zuccotti Gian Vincenzo , Bertoli Simona , D’Auria Enza
Published: March 2023

A reduced fruit and vegetable consumption, which implies a decreased intake of antioxidant compounds, seems to play a role in allergic diseases onset. Data on the antioxidant capacity of diet in children with food allergies, who are on an avoidance diet, are still lacking. This pilot study aims to assess the antioxidant potential of diet in Italian children with food allergies, compared to healthy children, using the oxygen radical absorbance capacity (ORAC) method. 95 children (54 with confirmed food allergies and 41 controls), with a median age of 7.8 years, were enrolled and underwent a nutritional assessment. Mean nutrient intakes were compared using the Mann–Whitney test. ORAC resulted significantly lower in allergic children (median 2,908, IQR: 1450;4,716) compared to control children (median 4,392, IQR: 2523;5,836; p = 0.049). Among micronutrients with antioxidant properties, vitamin A intakes were significantly higher in controls than in allergic children. Using Spearman’s correlation, a moderate-to-strong correlation between ORAC and vitamin C, potassium and magnesium was observed (ρ = 0.648, p < 0.001; ρ = 0.645, p < 0.001; ρ = 0.500, p < 0.001, respectively). Iron, phosphorus, vitamin E and vitamin A intakes were also moderately-to-low correlated with ORAC values (ρ = 0.351, p < 0.001; ρ = 0.367, p < 0.001; ρ = 0.346, p < 0.001; and ρ = 0.295, p = 0.004, respectively). We hypothesize that the reduced antioxidant potential of the diet might be related to a reduced variety of the diet in children with food allergies. Our study suggests that the diet of children with food allergies has a lower antioxidant potential (expressed as ORAC value) compared to the diet of healthy children, regardless of the allergenic food excluded from the diet. This issue should be further investigated in prospective, powered studies.
Effect of multimodal chemotherapy on survival of gastric cancer with liver metastasis – a population based analysis
Authors: Li Xinghui , Chen Zhiqiang , Zhang Yue , Zhang Hong , Niu Haiyan , Zheng Cheng , Jing Xiaoying , Qiao Hui , Wang Guanhua , Yang Wenjun
Published: March 2023

Objectives

Limited efforts have been made to evaluate the effect of multimodal chemotherapy on the survival of gastric cancer patients with liver metastases (LMGC). This study aimed to identify prognostic factors in LMGC patients and the superiority of multimodal chemotherapy with respect to overall survival (OS) in these patients.

Methods

We conducted a retrospective cohort study of 1298 patients with M1 stage disease between January 2012 and December 2020. The effects of clinicopathological variables and preoperative chemotherapy (PECT), postoperative chemotherapy (POCT), and palliative chemotherapy on survival in patients with liver metastases (LM group) and non-liver metastases (non-LM group) were compared.

Results

Of the 1298 patients analysed, 546 (42.06%) were in the LM group and 752 (57.94%) were in the non-LM group. The median (interquartile range) age was 60 (51–66) years. The 1-year, 3-year and 5-year overall survival (OS) rates in the LM group were 29.3%, 13.9%, and 9.2%, respectively, and those in the non-LM group were. 38.2%, 17.4%, and 10.0%, respectively (P < 0.05, > 0.05, and > 0.05, respectively.) The Cox proportional hazards model revealed that palliative chemotherapy was a significant independent prognostic factor in both the LM and non-LM groups. Age ≥55 years, N stage, and Lauren classification were also independent predictors of OS in the LM group (P < 0.05). Palliative chemotherapy and POCT were associated with improved OS compared with PECT in the LM group (26.3% vs. 36.4% vs. 25.0%, P < 0.001).

Conclusion

LMGC patients had a worse prognosis than non- LMGC. Number of metastatic sites more than 1, liver and other metastatic sites, no CT treatment and HER2-negative had a poor prognosis. LMGC patient may benefit more from palliative chemotherapy and POCT than from PECT. Further well-designed, prospective studies are needed to validate these findings.
Malignant ascites in pancreatic cancer: Pathophysiology, diagnosis, molecular characterization, and therapeutic strategies
Authors: Han Margaret Y. , Borazanci Erkut H.
Published: March 2023

Malignant ascites is the accumulation of fluid in the peritoneum as a result of advanced cancer and often signifies the terminal phase of the disease. Management of malignant ascites remains a clinical challenge as symptom palliation is the current standard of cure. Previously, studies examining malignant ascites largely focused on ovarian and gastric cancer. In recent years, there has been a significant increase in research on malignant ascites in pancreatic cancer. Malignant ascites is usually diagnosed based on positive cytology, but cytology is not always diagnostic, indicating the need for novel diagnostic tools and biomarkers. This review aims to summarize the current understanding of malignant ascites in pancreatic cancer and the recent advances in the molecular characterization of malignant ascites fluid from patients with pancreatic cancer including analysis of soluble molecules and extracellular vesicles. Current standard of care treatment options such as paracenteses and diuretics are outlined along with new emerging treatment strategies such as immunotherapy and small-molecule based therapies. New potential investigative directions resulting from these studies are also highlighted.
Aggressive angiomyxoma of the pelvis and abdominal wall: Dramatic response to chemical ablation therapy
Authors: Li Liu , Chuang He , He-Nan Liu , Dong-Yuan Li , Qing-Hua Liang , Wei Li , Liang-Shan Li , Ting-Yuan Li , Xue-Quan Huang
Published: March 2023

Objective

Aggressive angiomyxoma (AAM) is a rare, locally aggressive soft tissue neoplasm with a marked tendency for local recurrence after surgery. Although hormone therapy, radiation therapy, and vascular embolization can be performed, we investigated the safety and efficacy of a new chemical ablation protocol for AAM.

Methods

This study included two female AAM patients from 2012 to 2016. The patients’ clinical and imaging data were collected. The amount of anhydrous ethanol and glacial acetic acid used for chemical ablation was documented, and the management of any complications was detailed.

Results

The maximum dimensions of the residual tumor were 12.6 cm and 14.0 cm. In one case, the lesion was in the pelvis and protruded into the vulva. Eighty milliliters of liquid with a mixture of glacial acetic acid, anhydrous ethanol, and iohexol (10:9:1) was used for chemical ablation therapy via multipoint injections with a single needle. However, a pelvic fistula developed 1 month later. In another case, the lesion was located in the abdominal wall. The ablation procedure was improved by performing chemical ablation therapy with multiple needles for multi-point injections of smaller than 30 ml injections for each procedure. To date, no recurrence or metastasis has been observed in the two cases.

Conclusion

The preferred treatment for AAM is complete resection. Chemical ablation therapy is a novel adjuvant therapy for AMM. Nonetheless, more research is needed to confirm these findings.
Cuproptosis signature and PLCD3 predicts immune infiltration and drug responses in osteosarcoma
Authors: Hu Hai , Yin Yuesong , Jiang Binbin , Feng Zhennan , Cai Ting , Wu Song
Published: March 2023

Osteosarcoma (OS) is a cancer that is frequently found in children and adolescents and has made little improvement in terms of prognosis in recent years. A recently discovered type of programmed cell death called cuproptosis is mediated by copper ions and the tricarboxylic acid (TCA) cycle. The expression patterns, roles, and prognostic and predictive capabilities of the cuproptosis regulating genes were investigated in this work. TARGET and GEO provided transcriptional profiling of OS. To find different cuproptosis gene expression patterns, consensus clustering was used. To identify hub genes linked to cuproptosis, differential expression (DE) and weighted gene co-expression network analysis (WGCNA) were used. Cox regression and Random Survival Forest were used to build an evaluation model for prognosis. For various clusters/subgroups, GSVA, mRNAsi, and other immune infiltration experiments were carried out. The drug-responsive study was carried out by the Oncopredict algorithm. Cuproptosis genes displayed two unique patterns of expression, and high expression of FDX1 was associated with a poor outcome in OS patients. The TCA cycle and other tumor-promoting pathways were validated by the functional study, and activation of the cuproptosis genes may also be connected with immunosuppressive state. The robust survival prediction ability of a five-gene prognostic model was verified. This rating method also took stemness and immunosuppressive characteristics into account. Additionally, it can be associated with a higher sensitivity to medications that block PI3K/AKT/mTOR signaling as well as numerous chemoresistances. U2OS cell migration and proliferation may be encouraged by PLCD3. The relevance of PLCD3 in immunotherapy prediction was verified. The prognostic significance, expressing patterns, and functions of cuproptosis in OS were revealed in this work on a preliminary basis. The cuproptosis-related scoring model worked well for predicting prognosis and chemoresistance.
Management of pain in patients with bone metastases
Authors: Jing Doudou , Zhao Qian , Zhao Yibo , Lu Xiangdong , Feng Yi , Zhao Bin , Zhao Xiaofeng
Published: March 2023

Cancer-induced bone pain (CIBP) has a considerable impact on patients’ quality of life as well as physical and mental health. At present, patients with CIBP are managed according to the three-step analgesic therapy algorithm proposed by the World Health Organization. Opioids are commonly used as the first-line treatment for moderate-to-severe cancer pain but are limited due to addiction, nausea, vomiting and other gastrointestinal side effects. Moreover, opioids have a limited analgesic effect in some patients. In order to optimize the management of CIBP, we must first identify the underlying mechanisms. In some patients, surgery, or surgery combined with radiotherapy or radiofrequency ablation is the first step in the management of CIBP. Various clinical studies have shown that anti-nerve growth factor (NGF) antibodies, bisphosphonates, or RANKL inhibitors can reduce the incidence and improve the management of cancer pain. Herein, we review the mechanisms of cancer pain and potential therapeutic strategies to provide insights for optimizing the management of CIBP.
Anlotinib combined with Sintilimab is win-win cooperation for primary squamous cell carcinoma of the thyroid: A case report and literature review
Authors: Liu Zichang , Yu Maosheng , Zhao Feng , Zhu Chenfang
Published: March 2023

Background

Primary squamous cell carcinoma of the thyroid (PSCCT) is a rare malignant tumor. The incidence rate of PSCCT is less than 1%. However, the diagnosis and treatment of PSCCT are limited. Surgical resection is considered to be one of the few effective intervention methods. In this article, we reported a case of taking tyrosine kinase inhibitors (TKIs) combined with immune checkpoint inhibitors (ICIs) for PSCCT.

Case summary

An 80-year-old male was admitted to our hospital with dyspnea, cough, wheezing, and hoarseness for a giant thyroid mass. He underwent bronchoscopy and tracheal stent implantation to alleviate the respiratory obstruction. Then he accepted right partial thyroid and right lymph node biopsy. Postoperative pathology revealed squamous cell carcinoma. Subsequently, he underwent an endoscopy to exclude upper gastrointestinal squamous cell carcinoma. Finally, he was diagnosed with PSCCT. The patient was tentatively treated with a combination of Anlotinib and Sintilimab. After two courses, the tumor volume significantly reduced in MRI images and shrank further after five courses of combined treatment. Unfortunately, the patient died of fulminant liver failure and autoimmune liver disease after 5-month-treatment.

Conclusion

TKIs combined with ICIs may be an effective and novel way for PSCCT treatment, but immune-related complications, especially liver damage, should be cared.
Using qPCR to compare the detection of Plasmodium vivax oocysts and sporozoites in Anopheles farauti mosquitoes between two DNA extraction methods
Authors: Timinao Lincoln , Jamea Esther W. , Katusele Michelle , Burkot Thomas R. , Karl Stephan
Published: March 2023

Background

Currently, the gold standard to assess parasite developmental stages in mosquitoes is light microscopy. Microscopy can miss low-density infections, is time-consuming and not species-specific. Enzyme-linked immunosorbent assay (ELISA) has been the alternative technique to evaluate the infectivity of mosquitoes especially in field studies however it is semi-quantitative. Molecular techniques that have been used to detect the mosquito stages of malaria parasites including P. vivax. Here, we present a quantitative real-time assay (qPCR) that can be used to detect low-density P. vivax oocyst and sporozoite infections while comparing parasites extracted by the conventional DNA extraction and heating methods.

Methods

Colony reared Anopheles farauti mosquitoes were exposed to blood samples collected from infected individuals using a direct membrane feeding assay. The fully fed mosquitoes were kept for 7 and 14 days post-feed before dissection to confirm presence of oocysts and sporozoites. Infected mosquito guts and the salivary glands (with the head and thorax) were stored and DNA was extracted either by heating or by performing conventional column-based DNA extraction. Following DNA extraction the infected samples were subjected to qPCR to detect P. vivax parasites.

Results

DNA extraction of 1 or more oocysts by heating resulted in an overall sensitivity of 78% (57/73) and single oocysts infections were detected with a sensitivity of 82% (15/17) in the heating arm. We observed a 60% (18/30) sensitivity with sporozoites where DNA was extracted using the conventional DNA extraction method. We show that the heating method significantly improved the detection of oocysts over conventional DNA extraction. There was no significant difference in the DNA copy numbers when comparing the detection of oocysts from the conventional DNA extraction versus heating. However, we observed that the DNA copy numbers of the sporozoites detected in the heating arm was significantly higher than in the conventional DNA extraction arm.

Conclusion

We have adapted a qPCR assay which, when coupled with heating to release DNA reduces sample processing time and cost. Direct qPCR after heating will be a useful tool when investigating transmission blocking vaccines or antimalarials or when evaluating field caught mosquitoes for the presence of malaria parasites.
Integrated omics analysis reveals the epigenetic mechanism of visceral hypersensitivity in IBS-D
Authors: Lu Yaoyao , Chai Yuna , Qiu Jianli , Zhang Jingmin , Wu Menglin , Fu Zhe , Wang Yongfu , Qin Chongzhen
Published: March 2023

Background and objective: IBS-D is a common functional bowel disease with complex etiology and without biomarker. The pathological and physiological basis of IBS-D focuses on visceral hypersensitivity. However, its epigenetic mechanism remains elusive. Our study aimed to integrate the relationship between differentially expressed miRNAs, mRNAs and proteins in IBS-D patients in order to reveal epigenetic mechanism of visceral hypersensitivity from transcription and protein levels and provide the molecular basis for discovering biomarkers of IBS-D.

Methods: The intestinal biopsies from IBS-D patients and healthy volunteers were obtained for high-throughput sequencing of miRNAs and mRNAs. The differential miRNAs were selected and verified by q-PCR experiment followed by target mRNA prediction. Biological functions were respectively analyzed for target mRNAs, differential mRNAs and the previously identified differential proteins in order to explore the characteristic involved visceral hypersensitivity. At last, interaction analysis of miRNAs, mRNAs and proteins was performed for the epigenetic regulation mechanism from transcription and protein levels.

Results: Thirty-three miRNAs were found to be differentially expressed in IBS-D and five of them were further confirmed, including upregulated hsa-miR-641, hsa-miR-1843, hsa-let-7d-3p and downregulated hsa-miR-219a-5p, hsa-miR-19b-1-5p. In addition, 3,812 differential mRNAs were identified. Thirty intersecting molecules were found from the analysis on the target mRNAs of miRNAs and mRNAs. Fourteen intersecting molecules were obtained from the analysis on the target mRNAs and proteins, and thirty-six intersecting molecules were identified from analysis on the proteins and different mRNAs. According to the integrated analysis of miRNA-mRNA-protein, we noticed two new molecules COPS2 regulated by hsa-miR-19b-1-5p and MARCKS regulated by hsa-miR-641. Meanwhile some critical signaling pathways in IBS-D were found such as MAPK, GABAergic synapse, Glutamatergic synapse, and Adherens junction.

Conclusion: The expressions of hsa-miR-641, hsa-miR-1843, hsa-let-7d-3p, hsa-miR-219a-5p, and hsa-miR-19b-1-5p in the intestinal tissues of IBS-D patients were significantly different. Moreover, they could regulate a variety of molecules and signaling pathways, which were involved in the multifaceted and multilevel mechanism of visceral hypersensitivity of IBS-D.
Functional enhancement strategies to potentiate the therapeutic properties of mesenchymal stromal cells for respiratory diseases
Authors: Lopes-Pacheco Miquéias , Rocco Patricia R. M.
Published: March 2023

Respiratory diseases remain a major health concern worldwide because they subject patients to considerable financial and psychosocial burdens and result in a high rate of morbidity and mortality. Although significant progress has been made in understanding the underlying pathologic mechanisms of severe respiratory diseases, most therapies are supportive, aiming to mitigate symptoms and slow down their progressive course but cannot improve lung function or reverse tissue remodeling. Mesenchymal stromal cells (MSCs) are at the forefront of the regenerative medicine field due to their unique biomedical potential in promoting immunomodulation, anti-inflammatory, anti-apoptotic and antimicrobial activities, and tissue repair in various experimental models. However, despite several years of preclinical research on MSCs, therapeutic outcomes have fallen far short in early-stage clinical trials for respiratory diseases. This limited efficacy has been associated with several factors, such as reduced MSC homing, survival, and infusion in the late course of lung disease. Accordingly, genetic engineering and preconditioning methods have emerged as functional enhancement strategies to potentiate the therapeutic actions of MSCs and thus achieve better clinical outcomes. This narrative review describes various strategies that have been investigated in the experimental setting to functionally potentiate the therapeutic properties of MSCs for respiratory diseases. These include changes in culture conditions, exposure of MSCs to inflammatory environments, pharmacological agents or other substances, and genetic manipulation for enhanced and sustained expression of genes of interest. Future directions and challenges in efficiently translating MSC research into clinical practice are discussed.
Evaluation of the effect of managing oxycodone/acetaminophen as a psychotropic medicine: An interrupted time-series study
Authors: Xiang Cheng , Li Sha , Zhang Jinwei , Zhang Jieqiong , Hu Shuchen , Pan Mengyuan , Yang Caijun , Zhang Kanghuai
Published: March 2023

Background: Oxycodone/acetaminophen has been reported for misuse for many times in China. To cope with that, Chinese national authorities jointly issued a policy, requiring that oxycodone/acetaminophen should be managed as a psychotropic medicine starting 1 September 2019. This paper aimed to evaluate the effect of this policy in medical institutions.

Methods: We used interrupted time-series analysis to examine the immediate level and slope changes in the mean number of tablets prescribed, proportion of oxycodone/acetaminophen prescription exceeding 30 pills, days supplied per prescription and the proportion of days supplied exceeding 10 days with prescription data from 5 tertiary hospitals in Xi’an city between 1 January 2018 and 30 June 2021 (42 months). We divided the prescriptions into two groups, one for long-term drug users, and the other for short-term drug users.

Results: In total, 12,491 prescriptions were included in the final study, with 8,941 and 3,550 prescriptions for the short-term and long-term drug users, respectively. Significant differences in the proportion of prescriptions issued by various departments, were observed between pre- and post-implementation of the policy for both short-term and long-term drug users (p < 0.001). For short-term drug users, the policy implementation was only associated with an immediate level decrease in proportion of prescriptions exceeding 30 tablets (−4.09%, p < 0.001). For long-term drug users, after the policy, the mean number of tablets prescribed and the mean proportion of prescriptions exceeding 30 tablets experienced a level decrease of 22.96 tablets (p < 0.001) and a level decrease of 41.13% (p < 0.001), respectively; the mean number of days supplied showed a significant level decrease (6.88 days per prescription) and slope increase (0.19 days per month), and the mean proportion of days supplied exceeding 10 days showed a significant level decrease (−10.51% per prescription) and a slope increase (0.27% per month).

Conclusion: Implementation of stricter management for oxycodone/acetaminophen achieved its goal of reducing the risk of misuse in short-term drug users. For those long-term drug users, policy needed to be strengthened as the prescription exceeding 10 days was still at a high level after the intervention. Policies targeting patients with different drug demands are needed. Many other strategies can be implemented, including establishing specific guidelines/principles and conducting training programs.
Recent evaluation about inflammatory mechanisms in nonalcoholic fatty liver disease
Authors: Song Chong , Long Xian , He Jianbin , Huang Yongpan
Published: March 2023

Non-alcoholic fatty liver disease (NAFLD) is common chronic metabolic liver disorder which is associated with fat accumulation in the liver. It causes a wide range of pathological effects such as insulin resistance, obesity, hypertension, diabetes, non-alcoholic steatohepatitis (NASH) and cirrhosis, cardiovascular diseases. The molecular mechanisms that cause the initiation and progression of NAFLD remain fully unclear. Inflammation is regarded as a significant mechanism which could result in cell death and tissue injury. Accumulation of leukocytes and hepatic inflammation are important contributors in NAFLD. Excessive inflammatory response can deteriorate the tissue injury in NAFLD. Thus, inhibition of inflammation improves NAFLD by reducing intrahepatic fat content, increasing β-oxidation of fatty acids, inducing hepato-protective autophagy, overexpressing peroxisome proliferator-activated receptor- γ (PPAR-γ), as well as attenuating hepatocyte apoptosis and increasing insulin sensitivity. Therefore, understanding the molecules and signaling pathways suggests us valuable information about NAFLD progression. This review aimed to evaluate the inflammation in NAFLD and the molecular mechanism on NAFLD.
A minireview of the medicinal and edible insects from the traditional Chinese medicine (TCM)
Authors: Zhang Enming , Ji Xin , Ouyang Fang , Lei Yang , Deng Shun , Rong Haibo , Deng Xuangen , Shen Hai
Published: March 2023

Entomoceuticals define a subset of pharmaceuticals derived from insects. The therapeutic effect of insect-derived drugs has been empirically validated by the direct use of various folk medicines originating from three sources in particular: the glandular secretions of insects (e.g., silk, honey, venom), the body parts of the insect or the whole used live or by various processing (e.g., cooked, toasted, ground), and active ingredients extracted from insects or insect-microbe symbiosis. Insects have been widely exploited in traditional Chinese medicine (TCM) relative to other ethnomedicines, especially in the prospect of insect species for medicinal uses. It is noticeable that most of these entomoceuticals are also exploited as health food for improving immune function. In addition, some edible insects are rich in animal protein and have high nutritional value, which are used in the food field, such as insect wine, health supplements and so on. In this review, we focused on 12 insect species that have been widely used in traditional Chinese herbal formulae but have remained less investigated for their biological properties in previous studies. We also combined the entomoceutical knowledge with recent advances in insect omics. This review specifies the underexplored medicinal insects from ethnomedicine and shows their specific medicinal and nutritional roles in traditional medicine.
Alcohol consumption modulates prelimbic cortex response to cocaine following sequential cocaine and alcohol polysubstance use in the rat
Authors: Mesa Javier R. , Carter Emily , Padovan-Hernandez Yasmin , Knackstedt Lori A.
Published: March 2023

Polysubstance use (PSU), involves the consumption of more than one drug within a period of time and is prevalent among cocaine users. Ceftriaxone, a beta-lactam antibiotic, reliably attenuates reinstatement of cocaine seeking in pre-clinical models by restoring glutamate homeostasis following cocaine self-administration but fails to do so when rats consume both cocaine and alcohol (cocaine + alcohol PSU). We previously found that cocaine + alcohol PSU rats reinstate cocaine seeking similarly to cocaine-only rats, but demonstrate differences in reinstatement-induced c-Fos expression throughout the reward system, including a lack of change upon ceftriaxone treatment. Here, we used this model to determine if previous findings were caused by tolerance or sensitization to the pharmacological effects of cocaine. Male rats underwent intravenous cocaine self-administration immediately followed by 6 h of home cage access to water or unsweetened alcohol for 12 days. Rats subsequently underwent 10 daily instrumental extinction sessions, during which time they were treated with either vehicle or ceftriaxone. Rats then received a non-contingent cocaine injection and were perfused for later immunohistochemical analysis of c-Fos expression in the reward neurocircuitry. c-Fos expression in the prelimbic cortex correlated with total alcohol intake in PSU rats. There were no effects of either ceftriaxone or PSU on c-Fos expression in the infralimbic cortex, nucleus accumbens core and shell, basolateral amygdala, or ventral tegmental area. These results support the idea that PSU and ceftriaxone alter the neurobiology underlying drug-seeking behavior in the absence of pharmacological tolerance or sensitization to cocaine.
Small-molecule BCL6 inhibitor protects chronic cardiac transplant rejection and inhibits T follicular helper cell expansion and humoral response
Authors: Xia Yuxuan , Jin Sheng , Wu Yuming
Published: March 2023

Background: B cell lymphoma 6 (BCL6) is an important transcription factor of T follicular helper (Tfh) cells, which regulate the humoral response by supporting the maturation of germinal center B cells and plasma cells. The aim of this study is to investigate the expansion of T follicular helper cells and the effect of the BCL6 inhibitor FX1 in acute and chronic cardiac transplant rejection models.

Methods: A mouse model of acute and chronic cardiac transplant rejection was established. Splenocytes were collected at different time points after transplantation for CXCR5+PD-1+ and CXCR5+BCL6+ Tfh cells detection by flow cytometry (FCM). Next, we treated the cardiac transplant with BCL6 inhibitor FX1 and the survival of grafts was recorded. The hematoxylin and eosin, Elastica van Gieson, and Masson staining of cardiac grafts was performed for the pathological analysis. Furthermore, the proportion and number of CD4+ T cells, effector CD4+ T cells (CD44+CD62L−), proliferating CD4+ T cells (Ki67+), and Tfh cells in the spleen were detected by FCM. The cells related to humoral response (plasma cells, germinal center B cells, IgG1+ B cells) and donor-specific antibody were also detected.

Results: We found that the Tfh cells were significantly increased in the recipient mice on day 14 post transplantation. During the acute cardiac transplant rejection, even the BCL6 inhibitor FX1 did not prolong the survival or attenuate the immune response of cardiac graft, the expansion of Tfh cell expansion inhibit. During the chronic cardiac transplant rejection, FX1 prolonged survival of cardiac graft, and prevented occlusion and fibrosis of vascular in cardiac grafts. FX1 also decreased the proportion and number of splenic CD4+ T cells, effector CD4+ T cells, proliferating CD4+ T cells, and Tfh cells in mice with chronic rejection. Moreover, FX1 also inhibited the proportion and number of splenic plasma cells, germinal center B cells, IgG1+ B cells, and the donor-specific antibody in recipient mice.

Conclusion: We found BCL6 inhibitor FX1 protects chronic cardiac transplant rejection and inhibits the expansion of Tfh cells and the humoral response, which suggest that BCL6 is a potential therapeutic target of the treatment for chronic cardiac transplant rejection.
The role of RNA methyltransferase METTL3 in gynecologic cancers: Results and mechanisms
Authors: Zhang Yuxiang , Zhang Na
Published: March 2023

N6-methyladenosine (m6A) methylation is the most prevalent mRNA modification in eukaryotes, and it is defined as the methylation of nitrogen atoms on the six adenine (A) bases of RNA in the presence of methyltransferases. Methyltransferase-like 3 (Mettl3), one of the components of m6A methyltransferase, plays a decisive catalytic role in m6A methylation. Recent studies have confirmed that m6A is associated with a wide spectrum of biological processes and it significantly affects disease progression and prognosis of patients with gynecologic tumors, in which the role of Mettl3 cannot be ignored. Mettl3 is involved in numerous pathophysiological functions, such as embryonic development, fat accumulation, and tumor progression. Moreover, Mettl3 may serve as a potential target for treating gynecologic malignancies, thus, it may benefit the patients and prolong survival. However, there is a need to further study the role and mechanism of Mettl3 in gynecologic malignancies. This paper reviews the recent progression on Mettl3 in gynecologic malignancies, hoping to provide a reference for further research.