bluuebunny/crossref_metadata_2025 huggingface dataset:
Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis
Authors: Cao Limin , An Yu , Liu Huiyuan , Jiang Jinguo , Liu Wenqi , Zhou Yuhan , Shi Mengyuan , Dai Wei , Lv Yanling , Zhao Yuhong , Lu Yanhui , Chen Liangkai , Xia Yang
Published: March 2024

Background

Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels.

Methods

Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression.

Results

A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2–31.6%) and 26.2% (23.9–28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively.

Conclusions

The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.
Geochemical dispersion of gold-bearing quartz veins in the Wadi Abu Khusheiba area in Southern Jordan
Authors: Mosleh Mariam , Aziz Jasmi Hafiz Abdul , Roselee Muhammad Hatta , Al-Shorman Ahmed , Al Tamimi Mahmoud , Alsoudi Abdelkarim
Published: March 2024

This study delves into the geochemical dispersion of gold-bearing quartz veins in the Wadi Abu Khusheiba area, southern Jordan, with a focus on uncovering the complex patterns of mineralization and their geological significance. Employing an in-depth geochemical analysis of 24 rock samples from the region, we identified that these samples are predominantly hosted by oversaturated rhyolitic rocks, characterized by high SiO2 content and abundant free Quartz and orthoclase minerals. The mineralized zone of the quartz veins is particularly notable for its gold and silver concentrations, with maximum values reaching up to 5 ppm for gold and 18 ppm for silver. Our investigation into the elemental correlations revealed nuanced relationships, dependent on the 21 sample and analyzed at confidence level of (85%). Contrary to initial assumptions, we did not find a significant positive correlation between gold (Au) and arsenic (As), nor significant negative correlations between gold and other trace elements. These insights are critical for understanding the geochemical behavior of gold in the area and offer a nuanced view of elemental associations. The results of this study are significant for both academic research and practical exploration. They enhance our comprehension of the geological history and mineralization processes in Wadi Abu Khusheiba, providing valuable data that can inform future exploration strategies and deepen our understanding of mineral deposition in similar geological settings. This research not only contributes to the scientific community’s knowledge of the area’s geochemistry but also has potential implications for the mining and exploration industries.
RGS20 promotes non-small cell lung carcinoma proliferation via autophagy activation and inhibition of the PKA-Hippo signaling pathway
Authors: Ding Xiaoyan , Li Xiaoxia , Jiang Yanxia , Li Yujun , Li Hong , Shang Lipeng , Feng Guilin , Zhang Huhu , Xu Ziyuan , Yang Lina , Li Bing , Zhao Robert Chunhua
Published: March 2024

Background

Novel therapeutic targets are urgently needed for treating drug-resistant non-small cell lung cancer (NSCLC) and overcoming drug resistance to molecular-targeted therapies. Regulator of G protein signaling 20 (RGS20) is identified as an upregulated factor in many cancers, yet its specific role and the mechanism through which RGS20 functions in NSCLC remain unclear. Our study aimed to identify the role of RGS20 in NSCLC prognosis and delineate associated cellular and molecular pathways.

Methods

Immunohistochemistry and lung cancer tissue microarray were used to verify the expression of RGS20 between NSCLC patients. CCK8 and cell cloning were conducted to determine the proliferation ability of H1299 and Anip973 cells in vitro. Furthermore, Transcriptome sequencing was performed to show enrichment genes and pathways. Immunofluorescence was used to detect the translocation changes of YAP to nucleus. Western blotting demonstrated different expressions of autophagy and the Hippo-PKA signal pathway. In vitro and in vivo experiments verified whether overexpression of RGS20 affect the proliferation and autophagy of NSCLC through regulating the Hippo pathway.

Results

The higher RGS20 expression was found to be significantly correlated with a poorer five-year survival rate. Further, RGS20 accelerated cell proliferation by increasing autophagy. Transcriptomic sequencing suggested the involvement of the Hippo signaling pathway in the action of RGS20 in NSCLC. RGS20 activation reduced YAP phosphorylation and facilitated its nuclear translocation. Remarkably, inhibiting Hippo signaling with GA-017 promoted cell proliferation and activated autophagy in RGS20 knock-down cells. However, forskolin, a GPCR activator, increased YAP phosphorylation and reversed the promoting effect of RGS20 in RGS20-overexpressing cells. Lastly, in vivo experiments further confirmed role of RGS20 in aggravating tumorigenicity, as its overexpression increased NSCLC cell proliferation.

Conclusion

Our findings indicate that RGS20 drives NSCLC cell proliferation by triggering autophagy via the inhibition of PKA-Hippo signaling. These insights support the role of RGS20 as a promising novel molecular marker and a target for future targeted therapies in lung cancer treatment.
Adult mosquitoes of the sibling species Anopheles gambiae and Anopheles coluzzii exhibit contrasting patterns of susceptibility to four neonicotinoid insecticides along an urban-to-rural gradient in Yaoundé, Cameroon
Authors: Ashu Fred A. , Fouet Caroline , Ambadiang Marilene M. , Penlap-Beng Véronique , Kamdem Colince
Published: March 2024

Background

Neonicotinoids are potential alternatives for controlling pyrethroid-resistant mosquitoes, but their efficacy against malaria vector populations of sub-Saharan Africa has yet to be investigated. The aim of the present study was to test the efficacy of four neonicotinoids against adult populations of the sibling species Anopheles gambiae and Anopheles coluzzii sampled along an urban-to-rural gradient.

Methods

The lethal toxicity of three active ingredients for adults of two susceptible Anopheles strains was assessed using concentration–response assays, and their discriminating concentrations were calculated. The discriminating concentrations were then used to test the susceptibility of An. gambiae and An. coluzzii mosquitoes collected from urban, suburban and rural areas of Yaoundé, Cameroon, to acetamiprid, imidacloprid, clothianidin and thiamethoxam.

Results

Lethal concentrations of neonicotinoids were relatively high suggesting that this class of insecticides has low toxicity against Anopheles mosquitoes. Reduced susceptibility to the four neonicotinoids tested was detected in An. gambiae populations collected from rural and suburban areas. By contrast, adults of An. coluzzii that occurred in urbanized settings were susceptible to neonicotinoids except acetamiprid for which 80% mortality was obtained within 72 h of insecticide exposure. The cytochrome inhibitor, piperonyl butoxide (PBO), significantly enhanced the activity of clothianidin and acetamiprid against An. gambiae mosquitoes.

Conclusions

These findings corroborate susceptibility profiles observed in larvae and highlight a significant variation in tolerance to neonicotinoids between An. gambiae and An. coluzzii populations from Yaoundé. Further studies are needed to disentangle the role of exposure to agricultural pesticides and of cross-resistance mechanisms in the development of neonicotinoid resistance in some Anopheles species.
Circulating concentrations of bile acids and prevalent chronic kidney disease among newly diagnosed type 2 diabetes: a cross-sectional study
Authors: Geng Tingting , Lu Qi , Jiang Limiao , Guo Kunquan , Yang Kun , Liao Yun-Fei , He Meian , Liu Gang , Tang Huiru , Pan An
Published: March 2024

Background

The relationship between circulating bile acids (BAs) and kidney function among patients with type 2 diabetes is unclear. We aimed to investigate the associations of circulating concentrations of BAs, particularly individual BA subtypes, with chronic kidney disease (CKD) in patients of newly diagnosed type 2 diabetes.

Methods

In this cross-sectional study, we included 1234 newly diagnosed type 2 diabetes who participated in an ongoing prospective study, the Dongfeng-Tongji cohort. Circulating primary and secondary unconjugated BAs and their taurine- or glycine-conjugates were measured using ultraperformance liquid chromatography-tandem mass spectrometry. CKD was defined as eGFR < 60 ml/min per 1.73 m2. Logistic regression model was used to compute odds ratio (OR) and 95% confidence interval (CI).

Results

After adjusting for multiple testing, higher levels of total primary BAs (OR per standard deviation [SD] increment: 0.78; 95% CI: 0.65–0.92), cholate (OR per SD: 0.78; 95% CI: 0.66–0.92), chenodeoxycholate (OR per SD: 0.81; 95% CI: 0.69–0.96), glycocholate (OR per SD: 0.81; 95% CI: 0.68–0.96), and glycochenodeoxycholate (OR per SD: 0.82; 95% CI: 0.69–0.97) were associated with a lower likelihood of having CKD in patients with newly diagnosed type 2 diabetes. No significant relationships between secondary BAs and odds of CKD were observed.

Conclusions

Our findings showed that higher concentrations of circulating unconjugated primary BAs and their glycine-conjugates, but not taurine-conjugates or secondary BAs, were associated with lower odds of having CKD in patients with type 2 diabetes.
Facile synthesis of Gd/Ru-doped fluorescent carbon dots for fluorescent/MR bimodal imaging and tumor therapy
Authors: Shi Yupeng , Xia Yaning , Zhou Mengyang , Wang Yifei , Bao Jianfeng , Zhang Yong , Cheng Jingliang
Published: March 2024

Functional metal doping endows fluorescent carbon dots with richer physical and chemical properties, greatly expanding their potential in the biomedical field. Nonetheless, fabricating carbon dots with integrated functionality for diagnostic and therapeutic modalities remains challenging. Herein, we develop a simple strategy to prepare Gd/Ru bimetallic doped fluorescent carbon dots (Gd/Ru-CDs) via a one-step microwave-assisted method with Ru(dcbpy)3Cl2, citric acid, polyethyleneimine, and GdCl3 as precursors. Multiple techniques were employed to characterize the morphology and properties of the obtained carbon dots. The Gd/Ru-CDs are high mono-dispersity, uniform spherical nanoparticles with an average diameter of 4.2 nm. Moreover, X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FTIR) confirmed the composition and surface properties of the carbon dots. In particular, the successful doping of Gd/Ru enables the carbon dots not only show considerable magnetic resonance imaging (MRI) performance but also obtain better fluorescence (FL) properties, especially in the red emission area. More impressively, it has low cytotoxicity, excellent biocompatibility, and efficient reactive oxygen species (ROS) generation ability, making it an effective imaging-guided tumor treatment reagent. In vivo experiments have revealed that Gd/Ru-CDs can achieve light-induced tumor suppression and non-invasive fluorescence/magnetic resonance bimodal imaging reagents to monitor the treatment process of mouse tumor models. Thus, this simple and efficient carbon dot manufacturing strategy by doping functional metals has expanded avenues for the development and application of multifunctional all-in-one theranostics.
Flagellar beating forces of human spermatozoa with different motility behaviors
Authors: Tufoni Cristina , Battistella Alice , Luppi Stefania , Boscolo Rita , Ricci Giuseppe , Lazzarino Marco , Andolfi Laura
Published: March 2024

Background

One of the causes of male infertility is associated with altered spermatozoa motility. These sperm features are frequently analyzed by image-based approaches, which, despite allowing the acquisition of crucial parameters to assess sperm motility, they are unable to provide details regarding the flagellar beating forces, which have been neglected until now.

Results

In this work we exploit Fluidic Force Microscopy to investigate and quantify the forces associated with the flagellar beating frequencies of human spermatozoa. The analysis is performed on two groups divided according to the progressive motility of semen samples, as identified by standard clinical protocols. In the first group, 100% of the spermatozoa swim linearly (100% progressive motility), while, in the other, spermatozoa show both linear and circular motility (identified as 80 − 20% progressive motility). Significant differences in flagellar beating forces between spermatozoa from semen sample with different progressive motility are observed. Particularly, linear motile spermatozoa exhibit forces higher than those with a circular movement.

Conclusions

This research can increase our understanding of sperm motility and the role of mechanics in fertilization, which could help us unveil some of the causes of idiopathic male infertility.
Silencing PinX1 enhances radiosensitivity and antitumor-immunity of radiotherapy in non-small cell lung cancer
Authors: Qiu Jieping , Xia Ying , Bao Yawei , Cheng Jingjing , Liu Lei , Qian Dong
Published: March 2024

Background

We aimed to investigate the effects of PinX1 on non-small cell lung cancer(NSCLC) radiosensitivity and radiotherapy-associated tumor immune microenvironment and its mechanisms.

Methods

The effect of PinX1 silencing on radiosensitivity in NSCLC was assessed by colony formation and CCK8 assay, immunofluorescence detection of γ- H2AX and micronucleus assay. Western blot was used to assess the effect of PinX1 silencing on DNA damage repair pathway and cGAS-STING pathway. The nude mouse and Lewis lung cancer mouse model were used to assess the combined efficacy of PinX1 silencing and radiotherapy in vivo. Changes in the tumor immune microenvironment were assessed by flow cytometry for different treatment modalities in the Lewis luuse model. The interaction protein RBM10 was screened by immunoprecipitation-mass spectrometry.

Results

Silencing PinX1 enhanced radiosensitivity and activation of the cGAS-STING pathway while attenuating the DNA damage repair pathway. Silencing PinX1 further increases radiotherapy-stimulated CD8+ T cell infiltration and activation, enhances tumor control and improves survival in vivo; Moreover, PinX1 downregulation improves the anti-tumor efficacy of radioimmunotherapy, increases radioimmune-stimulated CD8+ T cell infiltration, and reprograms M2-type macrophages into M1-type macrophages in tumor tissues. The interaction of PinX1 and RBM10 may promote telomere maintenance by assisting telomerase localization to telomeres, thereby inhibiting the immunostimulatory effects of IR.

Conclusions

In NSCLC, silencing PinX1 significantly contributed to the radiosensitivity and promoted the efficacy of radioimmunotherapy. Mechanistically, PinX1 may regulate the transport of telomerase to telomeres through interacting with RBM10, which promotes telomere maintenance and DNA stabilization. Our findings reveal that PinX1 is a potential target to enhance the efficacy of radioimmunotherapy in NSCLC patients.
Antigenic drift and immunity gap explain reduction in protective responses against influenza A(H1N1)pdm09 and A(H3N2) viruses during the COVID-19 pandemic: a cross-sectional study of human sera collected in 2019, 2021, 2022, and 2023
Authors: Fossum Even , Rohringer Andreas , Aune Torstein , Rydland Kjersti Margrethe , Bragstad Karoline , Hungnes Olav
Published: March 2024

Background

Non-pharmaceutical interventions implemented during the COVID-19 pandemic resulted in a marked reduction in influenza infections globally. The absence of influenza has raised concerns of waning immunity, and potentially more severe influenza seasons after the pandemic.

Methods

To evaluate immunity towards influenza post-COVID-19 pandemic we have assessed influenza A epidemics in Norway from October 2016 to June 2023 and measured antibodies against circulating strains of influenza A(H1N1)pdm09 and A(H3N2) in different age groups by hemagglutination inhibition (HAI) assays in a total of 3364 serum samples collected in 2019, 2021, 2022 and 2023.

Results

Influenza epidemics in Norway from October 2016 until June 2023 were predominately influenza As, with a mixture of A(H1N1)pdm09 and A(H3N2) subtype predominance. We did not observe higher numbers of infections during the influenza epidemics following the COVID-19 pandemic than in pre-COVID-19 seasons. Frequencies of protective HAI titers against A(H1N1)pdm09 and A(H3N2) viruses were reduced in sera collected in 2021 and 2022, compared to sera collected in 2019. The reduction could, however, largely be explained by antigenic drift of new virus strains, as protective HAI titers remained stable against the same strain from one season to the next. However, we observed the development of an immunity gap in the youngest children during the pandemic which resulted in a prominent reduction in HAI titers against A(H1N1)pdm09 in 2021 and 2022. The immunity gap was partially closed in sera collected in 2023 following the A(H1N1)pdm09-dominated influenza seasons of 2022/2023. During the 2022/2023 epidemic, drift variants of A(H1N1)pdm09 belonging to the 5a.2a.1 clade emerged, and pre-season HAI titers were significantly lower against this clade compared to the ancestral 5a.2 clade.

Conclusion

The observed reduction in protective antibodies against A(H1N1)pdm09 and A(H3N2) viruses post COVID-19 is best explained by antigenic drift of emerging viruses, and not waning of antibody responses in the general population. However, the absence of influenza during the pandemic resulted in an immunity gap in the youngest children. While this immunity gap was partially closed following the 2022/2023 influenza season, children with elevated risk of severe infection should be prioritized for vaccination.
Aspergillus fumigatus secretes a protease(s) that displays in silico binding affinity towards the SARS-CoV-2 spike protein and mediates SARS-CoV-2 pseudovirion entry into HEK-293T cells
Authors: Mjokane Nozethu , Akintemi Eric O. , Sabiu Saheed , Gcilitshana Onele M. N. , Albertyn Jacobus , Pohl Carolina H. , Sebolai Olihile M.
Published: March 2024

Background

The novel coronavirus disease of 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Data from the COVID-19 clinical control case studies showed that this disease could also manifest in patients with underlying microbial infections such as aspergillosis. The current study aimed to determine if the Aspergillus (A.) fumigatus culture media (i.e., supernatant) possessed protease activity that was sufficient to activate the SARS-CoV-2 spike protein.

Methods

The supernatant was first analysed for protease activity. Thereafter, it was assessed to determine if it possessed proteolytic activity to cleave a fluorogenic mimetic peptide of the SARS-CoV-2 spike protein that contained the S1/S2 site and a full-length spike protein contained in a SARS-CoV-2 pseudovirion. To complement this, a computer-based tool, HADDOCK, was used to predict if A. fumigatus alkaline protease 1 could bind to the SARS-CoV-2 spike protein.

Results

We show that the supernatant possessed proteolytic activity, and analyses of the molecular docking parameters revealed that A. fumigatus alkaline protease 1 could bind to the spike protein. To confirm the in silico data, it was imperative to provide experimental evidence for enzymatic activity. Here, it was noted that the A. fumigatus supernatant cleaved the mimetic peptide as well as transduced the HEK-293T cells with SARS-CoV-2 pseudovirions.

Conclusion

These results suggest that A. fumigatus secretes a protease(s) that activates the SARS-CoV-2 spike protein. Importantly, should these two infectious agents co-occur, there is the potential for A. fumigatus to activate the SARS-CoV-2 spike protein, thus aggravating COVID-19 development.
Istore: a project on innovative statistical methodologies to improve rare diseases clinical trials in limited populations
Authors: Schoenen Stefanie , Verbeeck Johan , Koletzko Lukas , Brambilla Isabella , Kuchenbuch Mathieu , Dirani Maya , Zimmermann Georg , Dette Holger , Hilgers Ralf-Dieter , Molenberghs Geert , Nabbout Rima
Published: March 2024

Background

The conduct of rare disease clinical trials is still hampered by methodological problems. The number of patients suffering from a rare condition is variable, but may be very small and unfortunately statistical problems for small and finite populations have received less consideration. This paper describes the outline of the iSTORE project, its ambitions, and its methodological approaches.

Methods

In very small populations, methodological challenges exacerbate. iSTORE’s ambition is to develop a comprehensive perspective on natural history course modelling through multiple endpoint methodologies, subgroup similarity identification, and improving level of evidence.

Results

The methodological approaches cover methods for sound scientific modeling of natural history course data, showing similarity between subgroups, defining, and analyzing multiple endpoints and quantifying the level of evidence in multiple endpoint trials that are often hampered by bias.

Conclusion

Through its expected results, iSTORE will contribute to the rare diseases research field by providing an approach to better inform about and thus being able to plan a clinical trial. The methodological derivations can be synchronized and transferability will be outlined.
Meiotic and developmental competence of growing pig oocytes derived from small antral follicles is enhanced in culture medium containing FGF2, LIF, and IGF1 (FLI medium)
Authors: Bartková Alexandra Rosenbaum , Němcová Lucie , Kinterová Veronika , Radová Dominika , Strejček František , Toralová Tereza , Laurinčík Jozef , Procházka Radek
Published: March 2024

Background

Oocytes of large animal species isolated from small ovarian follicles (< 2 mm) are less competent to support early embryonic development after in vitro maturation and fertilization than their counterparts isolated from medium-sized and preovulatory follicles. This study aimed to assess the effect of a new maturation medium containing FGF2, LIF, and IGF1 (FLI medium) on the meiotic and developmental competence of pig cumulus-oocytes complexes (COCs) derived from the small and medium-sized follicles.

Methods

The growing oocytes were isolated from 1 to 2 (small follicle; SF) and the fully-grown ones from 3 to 6 (large follicle; LF) mm follicles and matured in a control M199 medium with gonadotropins and EGF and the FLI medium enriched by the triplet of growth factors. The matured oocytes were parthenogenetically activated and cultured to the blastocyst stage. Chromatin configuration before and during the culture and MAP kinase activity were assessed in the oocytes. Finally, the expression of cumulus cell genes previously identified as markers of oocyte quality was assessed.

Results

The maturation and blastocyst rates of oocytes gained from LF were significantly higher than that from SF in the control medium. In contrast, similar proportions of oocytes from LF and SF completed meiosis and developed to blastocysts when cultured in FLI. Most of the oocytes freshly isolated from SF possessed germinal vesicles with fine filaments of chromatin (GV0) or chromatin surrounding the nucleolus (GVI; 30%); the oocytes from LF were mainly in GVI (or GVII) exhibiting a few small lumps of chromatin beneath the nuclear membrane. When cultured in the FLI medium for 16 h, an acceleration of the course of maturation in oocytes both from SF and LF compared to the control medium was observed and a remarkable synchrony in the course of chromatin remodeling was noticed in oocytes from SF and LF.

Conclusions

This work demonstrates that the enrichment of culture medium by FGF2, LIF, and IGF1 can enhance the meiotic and developmental competence of not only fully-grown, but also growing pig oocytes and significantly thus expanding the number of oocytes available for various assisted reproductive technology applications.
Application of smart chemometric models for spectra resolution and determination of challenging multi-action quaternary mixture: statistical comparison with greenness assessment
Authors: Mouhamed Aya A. , Nadim Ahmed H. , Mostafa Nadia M. , Eltanany Basma M.
Published: March 2024

A multivariate spectrophotometric method is a potential approach that enables discrimination of spectra of components in complex matrices (e.g., pharmaceutical formulation) serving as a substitution method for chromatography. Four green smart multivariate spectrophotometric models were proposed and validated, including principal component regression (PCR), partial least-squares (PLS), multivariate curve resolution-alternating least squares (MCR-ALS), and artificial neural networks (ANN). The developed chemometric models were compared to resolve highly overlapping spectra of Paracetamol (PARA), Chlorpheniramine maleate (CPM), Caffeine (CAF), and Ascorbic acid (ASC). The four multivariate calibration models were assessed via recoveries percent, and root mean square error of prediction. Hence, the proposed models were efficiently applied with no need for any preliminary separation step. The models were utilized to analyze the studied components in their combined pharmaceutical formulation (Grippostad® C capsules). Analytical GREEnness Metric Approach (AGREE) and eco-scale tools were applied to assess the greenness of the established models and found to be 0.77 and 85, respectively. Moreover, the proposed models have been compared to official ones showing no considerable variations in accuracy and precision. Therefore, these models can be highly advantageous for conducting standard pharmaceutical analysis of the substances researched within product testing laboratories.
Time of exposure and assessment influence the mortality induced by insecticides against metabolic resistant mosquitoes
Authors: Odufuwa Olukayode G. , Bradley John , Ngonyani Safina , Mpelepele Ahmadi Bakari , Matanila Isaya , Muganga Joseph B. , Bosselmann Rune , Skovmand Ole , Mboma Zawadi Mageni , Moore Sarah Jane
Published: March 2024

Background

Increasing metabolic resistance in malaria vector mosquitoes resulted in the development of insecticide-treated nets (ITNs) with active ingredients (AI) that target them. Bioassays that accurately measure the mortality induced by these AIs on ITNs are needed. Mosquito metabolic enzyme expression follows a circadian rhythm. Thus, this study assessed (i) influence of the time of day of mosquito exposure and (ii) timing of assessment of mortality post exposure (24 and 72 h) to ITNs against vectors that are susceptible to pyrethroids and those with metabolic and knockdown resistance mechanisms.

Methods

Two cone bioassay experiments were conducted following World Health Organization (WHO) guidelines. Firstly, on ITNs incorporated with 2 g AI/kg of deltamethrin (DM) alone, or combined with 8 g AI/kg piperonyl butoxide (PBO) synergist, during the day (9:00–14:00 h) and repeated in the evening (18:00–20:00 h). This was followed by a confirmatory experiment during the afternoon (12:00–14:00 h) and repeated in the night (22:00–24:00 h) using mosquitoes unexposed or pre-exposed to PBO for 1 h before exposure to DM ITNs. Each net piece was tested with a minimum of eight cones per time (N = 24). The outcome was mortality after 24 h (M24) or 72 h (M72) of holding.

Results

The cone bioassays performed using metabolic resistant mosquitoes during the evening showed significantly lower M24 than those performed in the day for DM: odds ratio (OR) 0.14 [95% confidence interval (CI) 0.06–0.30, p < 0.0001] and DM PBO [OR 0.29 (95% CI 0.18—0.49, p < 0.0001). M72 was higher than M24 for metabolic resistant mosquitoes exposed to DM [OR 1.44 (95% CI 1.09–1.88), p = 0.009] and DM PBO [OR 1.82 (95% CI 1.42–2.34), p < 0.0001]. An influence of hour of experiment and time of assessment was not observed for mosquitoes that had knockdown resistance or that were pyrethroid-susceptible.

Conclusions

Time of day of experiment and hour of assessment of delayed mortality after exposure of mosquitoes are important considerations in evaluating insecticides that interact with mosquito metabolism to counter metabolic resistant mosquitoes. This is important when evaluating field-aged ITNs that may have lower concentrations of AI.

Graphical Abstract
Characterization of environmental drivers influencing the abundance of Anopheles maculipennis complex in Northern Italy
Authors: Gilioli Gianni , Defilippo Francesco , Simonetto Anna , Heinzl Alessandro , Migliorati Manlio , Calzolari Mattia , Canziani Sabrina , Lelli Davide , Lavazza Antonio
Published: March 2024

Background

In Italy, malaria was endemic until the 1970s, when it was declared eradicated by WHO. Nowadays, with the persistence of competent mosquito populations, the effect of climate change, and increased possibility of importing malaria parasites from endemic counties due to growing migration, a malaria resurgence in Italy has become more likely. Hence, enhancing the understanding of the current distribution of the Anopheles maculipennis complex and the factors that influence the presence of this malaria vector is crucial, especially in Northern Italy, characterised by a high density of both human population and livestock.

Methods

To assess the presence and abundance of malaria vectors, a 4-year field survey in the plain areas of Lombardy and Emilia-Romagna region in Italy was conducted. Every sampling point was characterised in space by the land use in a 500-m radius and in time considering meteorological data collected in the short and long time periods before sampling. We combined the results of a linear regression model with a random forest analysis to understand the relative importance of the investigated niche dimensions in determining Anopheles mosquito presence and abundance.

Results

The estimated normalised variable importance indicates that rice fields were the most important land use class explaining the presence of Anopheles, followed by transitional woodlands and shrubland. Farm buildings were the third variable in terms of importance, likely because of the presence of animal shelters, followed by urbanised land. The two most important meteorological variables influencing the abundance of Anopheles in our study area were mean temperature in the 24 h before the sampling date and the sum of degree-days with temperature between 18 °C and 30 °C in the 14 days before the sampling date.

Conclusions

The results obtained in this study could be helpful in predicting the risk of autochthonous malaria transmission, based on local information on land cover classes that might facilitate the presence of malaria vectors and presence of short- and medium-term meteorological conditions favourable to mosquito development and activity. The results can support the design of vector control measures through environmental management.

Graphical Abstract
Inguinal endometriosis: a case series and review of the literature
Authors: Haghgoo Ameneh , Faegh Ali , Mostafavi Seyyed Reza Saadat , Zamani Hamid Reza , Ghahremani Mehran
Published: March 2024

Background

Inguinal endometriosis is one of the most common forms of endometriosis. The present study introduces 8 cases of inguinal endometriosis and discusses probable theories of inguinal endometriosis by reviewing the literature.

Case presentation

8 Iranian cases of inguinal endometriosis with a mean age of 36 years were presented. Catamenial groin pain and swelling were the most common complications. Also, patients usually had accompanying symptoms such as pelvic pain and dysmenorrhea. One-half of patients had a history of previous abdominal surgery. Ultrasound was diagnostic in 4 patients (50%), and magnetic resonance imaging was used in two patients (25%). Among 6 patients who underwent hormonal therapy, 4 experienced an endometriosis size increase. Inguinal endometriosis was right-sided in 87.5% of patients, and among 4 patients who underwent surgery, 75% had proximal site involvement of the round ligament.

Conclusion

According to the rarity of inguinal endometriosis, it is more likely to be a misdiagnosis with other inguinal disorders such as inguinal hernia. Inguinal endometriosis should be considered in patients who undergo inguinal herniorrhaphy, with suspected findings such as thickening of the hernia sac wall, bloody fluid inside the sac, or thickening of the extraperitoneal round ligament during the surgery.
Simulating 2-D magnetotelluric responses using vector-quantized temporal associative memory artificial neural network-based approaches
Authors: Mukwachi Phongphan , Arnonkijpanich Banchar , Sarakorn Weerachai
Published: March 2024

In this research, we explore the application of artificial neural networks, specifically the vector-quantized temporal associative memory (VQTAM) and VQTAM coupled with locally linear embedding (VQTAM-LLE) techniques, for simulating 2-D magnetotelluric forward modeling. The study introduces the concepts of VQTAM and VQTAM-LLE in the context of simulating 2-D magnetotelluric responses, outlining their underlying principles. We rigorously evaluate the accuracy and efficiency of both VQTAM variants through extensive numerical experiments conducted on diverse benchmark resistivity and real-terrain models. The results demonstrate the remarkable capability of VQTAM and VQTAM-LLE in accurately and efficiently predicting apparent resistivity and impedance phases, surpassing the performance of traditional numerical methods. This study underscores the potential of VQTAM and VQTAM-LLE as valuable computational alternatives for simulating magnetotelluric responses, offering a viable choice alongside conventional methods.
Motiv8: a study protocol for a cluster-randomised feasibility trial of a weight management intervention for adults with severe mental illness in secure forensic services
Authors: Carney Rebekah , El-Metaal Hany , Law Heather , Savage Siobhan , Small Ingrid , Hann Mark , Shields Gemma , Shiers David , Carmichael-Murphy Parise , Jones Richard , Kimber Elizabeth , McDonald Andrew , Parker Sophie
Published: March 2024

Introduction

People with severe mental illness have physical comorbidities which result in significant reductions in quality of life and premature mortality. Effective interventions are required that are suitable for people in secure forensic mental health services. We conducted pilot work of a multidisciplinary weight management intervention (Motiv8) which showed improvements in physical and mental health and high levels of satisfaction. We aim to test the feasibility of Motiv8 under cluster randomised conditions, with an aim to investigate the acceptability, feasibility and potential effectiveness of this intervention to supplement standard secure care.

Methods and analysis

A randomised waitlist-controlled feasibility trial of a lifestyle intervention (Motiv8) + TAU compared with TAU (+ Motiv8 waitlist) for adults on secure mental health units will be conducted. Thirty-two people (4 cohorts) will be recruited from secure services in Greater Manchester Mental Health NHS Foundation Trust. Participants will be randomly allocated to Motiv8 or TAU + Motiv8 waitlist. All participants will receive Motiv8 during the trial. Assessor-blinded physical/mental health and lifestyle assessments will be conducted at baseline, 10 weeks (post-intervention/waitlist), and after 12 weeks (post-waitlist intervention/follow-up). Motiv8 is a multidisciplinary intervention including exercise sessions, cooking/nutrition classes, physical health education, psychology sessions, sleep hygiene, peer support and medication review by pharmacy. A nested qualitative study will be conducted with a subsample of participants (n = 10) to explore their experiences of taking part. The analysis will focus on feasibility outcomes and tabulated success indicators of the study (e.g. Recruitment rates, retention rates, follow-up retention and response rates, attendance at sessions, the experience of involvement in the trial and delivery of the intervention, assessment of safety, development of a manualised intervention). Thematic analysis will be conducted through qualitative interviews. The analysis will aim to inform the development of a definitive trial.

Ethics and dissemination

The trial has been granted ethical approval from the NHS Health Research Authority and adopted onto the UK Clinical Research Network Portfolio. Findings will be disseminated via peer-reviewed publications, professional and public networks, conferences and clinical services.

Trial registration

ISRCTN13539285.
Differences in chamber structure contribute to the incidence of venous air trap chamber coagulation during AN69ST-CHF: clinical and in vitro evaluation
Authors: Shimizu Kota , Moriyama Kazuhiro , Kuriyama Naohide , Nakamura Tomoyuki , Kawaji Takahiro , Komatsu Satoshi , Nishida Osamu
Published: March 2024

Background

During continuous kidney replacement therapy (CKRT) in patients with sepsis and critical conditions, circuit coagulation can occur, often for unclear reasons. In this study, we investigate how the structure of the venous air trap chamber may contribute to venous air trap chamber coagulation. Clinical data were evaluated and experiments were performed.

Methods

The clinical evaluation involved patients who underwent continuous hemofiltration (CHF) using an acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) hemofilter (AN69ST-CHF) and either an ACH-Σ or Prismaflex CKRT machine in our ICU from April to July 2019. The patient data were divided into two groups based on CKRT machine and the percentage of CHF procedures that could continuously be performed for 22 h (CHF target achievement rate), and coagulation sites were evaluated. Statistical analysis was performed by the Mann–Whitney U test and Pearson’s chi-square test. For in vitro experiments, a system was constructed to circulate a 33% glycerol solution at a flow rate of 150 ml/min. In a venous air trap chamber, fluid dye disappearance times and fluid movements were visually evaluated.

Results

The clinical evaluation included 22 procedures (8 patients) in the ACH-Σ group and 22 procedures (11 patients) in the Prismaflex group, without significant differences in patient backgrounds between the groups. The CHF target achievement rate was 72.7% (16/22) in the ACH-Σ group and 77.3% (17/22) in the Prismaflex group, revealing no significant difference (p = 0.73). However, significantly fewer venous air trap chamber coagulations were observed in the Prismaflex group (1/5) than in the ACH-Σ group (5/6) (p < 0.01). In vitro evaluation found that the dye disappearance time was significantly shorter when using the Prismaflex device (17.5 s ± 0.7 s) than the ACH-Σ device (51.2 s ± 0.7 s; p < 0.05). Visual evaluation revealed that in the ACH-Σ venous air trap chamber the upper layer of the accumulated fluid was quite stagnant, whereas fluid flowed with uniform agitation through the Prismaflex venous air trap chamber. Hence, differences were observed in fluid flow and retention in the vein air trap chambers, depending on the chamber structure.

Conclusion

Chamber structure may contribute to the occurrence of venous air trap chamber coagulation during CKRT.
Mapping the knowledge structure of research on insulin resistance and metabolic syndrome: a global perspective
Authors: Zyoud Sa’ed H. , Shakhshir Muna , Abushanab Amani S. , Koni Amer , Shahwan Moyad , Jairoun Ammar A. , Taha Adham Abu , Abushamma Faris , Al-Jabi Samah W.
Published: March 2024

Background

Insulin resistance is a major pathogenic factor that plays a crucial role in the development of metabolic syndrome and has been proposed as one of its underlying causes. Most diagnostic criteria for metabolic syndrome do not directly include insulin resistance. Furthermore, research on insulin resistance continues to provide information on the development and treatment of metabolic syndromes and related health conditions. Therefore, this bibliometric analysis aimed to investigate the current research status and identify possible future research hotspots in the area of metabolic syndrome and insulin resistance by analyzing Scopus-based studies.

Methods

To collect published data on metabolic syndrome and insulin resistance, this study used the Scopus database as its data source without a particular starting date but including records up to December 31, 2022. The gathered documents were then exported to VOSviewer v.1.6.18 to analyze and visualize country collaborations and identify research areas of high interest.

Results

The study presents an overview of 1932 records between 1988 and 2022, focusing on metabolic syndrome and insulin resistance. Of these records, 77.33% were original journal articles, while 13.30% were review articles. Additionally, 9.35% of the documents fall under other types of publication, including letters, notes, and editorials. The United States came out on top with 463 items, accounting for 23.96% of the contributions in this field, followed by Japan in second place with 119 items (6.16%). China (n = 113, 5.85%) and the United Kingdom (n = 113, 5.85%) ranked third. Most publications on metabolic syndrome and insulin resistance focus on key terms related to the pathogenesis of insulin resistance syndrome, the use of waist circumference as a crucial clinical indicator to evaluate the risk of metabolic syndrome, and the association between metabolic syndrome and oxidative stress and a pro-inflammatory state.

Conclusions

This study presents the first bibliometric analysis of publications focusing on metabolic syndrome and insulin resistance. The findings of this study offer a comprehensive global perspective on the research carried out on metabolic syndrome and insulin resistance and can be an invaluable source for future research.
Maxwell’s Demon in MLP-Mixer: towards transferable adversarial attacks
Authors: Lyu Haoran , Wang Yajie , Tan Yu-an , Zhou Huipeng , Zhao Yuhang , Zhang Quanxin
Published: March 2024

Models based on MLP-Mixer architecture are becoming popular, but they still suffer from adversarial examples. Although it has been shown that MLP-Mixer is more robust to adversarial attacks compared to convolutional neural networks (CNNs), there has been no research on adversarial attacks tailored to its architecture. In this paper, we fill this gap. We propose a dedicated attack framework called Maxwell’s demon Attack (MA). Specifically, we break the channel-mixing and token-mixing mechanisms of the MLP-Mixer by perturbing inputs of each Mixer layer to achieve high transferability. We demonstrate that disrupting the MLP-Mixer’s capture of the main information of images by masking its inputs can generate adversarial examples with cross-architectural transferability. Extensive evaluations show the effectiveness and superior performance of MA. Perturbations generated based on masked inputs obtain a higher success rate of black-box attacks than existing transfer attacks. Moreover, our approach can be easily combined with existing methods to improve the transferability both within MLP-Mixer based models and to models with different architectures. We achieve up to 55.9% attack performance improvement. Our work exploits the true generalization potential of the MLP-Mixer adversarial space and helps make it more robust for future deployments.
Funding for research on cryptococcal disease: an analysis based on the G-finder report
Authors: Duarte Iraine , Rodrigues Marcio L.
Published: March 2024

Members of the genus Cryptococcus are the causative agents of cryptococcal meningitis, a disease mainly associated with HIV-induced immunosuppression. Patients with cryptococcal meningitis are at a serious risk of death. Most patients suffering from cryptococcosis belong to neglected populations. With reduced support for research, new therapies are unlikely to emerge. In this essay, we used the Policy Cures/G-finder platform as a reference database for funding research on cryptococcal disease. Funding for cryptococcal research started being tracked by G-finder in 2013 and has continued to appear in the annual reports ever since. In total, 15 institutions were reported as major funders for research on cryptococcal disease over the years. The US National Institutes of Health (NIH) was the main funder, followed by the UK's Wellcome Trust. The annual analysis suggested slow yearly growth in funding from 2013 to 2021. The development of new tools to prevent and fight cryptococcal disease is urgent but requires improved funding.
Regorafenib in Patients With Solid Tumors With BRAF Alterations: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study
Authors: Sahai Vaibhav , Rothe Michael , Mangat Pam K. , Garrett-Mayer Elizabeth , Suhag Vijay , Dib Elie G. , Mehmi Inderjit , Kadakia Kunal C. , Pisick Evan , Duvivier Herbert L. , Le Phat , Li Rui , Michelin David P. , Wilcox Ryan E. , Grantham Gina N. , Hinshaw Dominique C. , Gregory Abigail , Halabi Susan , Schilsky Richard L.
Published: March 2024

PURPOSE

Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer with genomic alterations known to be drug targets. Results of a cohort of patients with solid tumors with BRAF alterations treated with regorafenib are reported.

METHODS

Eligible patients had measurable disease (RECIST v.1.1), Eastern Cooperative Oncology Group performance status 0-1, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as investigator assessment of patients with complete or partial response (PR) or stable disease of at least 16-weeks duration (SD16+). Low accruing histology-specific cohorts with BRAF alterations treated with regorafenib were collapsed into a single histology-pooled cohort for this analysis. The results were evaluated on the basis of a one-sided exact binomial test with a null DC rate of 15% versus 35% (power, 0.84; α, .10). Secondary end points were objective response (OR), progression-free survival, overall survival, duration of response, duration of stable disease, and safety.

RESULTS

Twenty-eight patients with 12 tumor types with BRAF alterations were enrolled from June 2016 to June 2021. All patients were evaluable for efficacy. Two patients with PR and four with SD16+ were observed for DC and OR rates of 21% (90% CI, 12 to 100) and 7% (95% CI, 1 to 24), respectively. The null hypothesis of 15% DC rate was not rejected ( P = .24). Eight patients had at least one grade 3 adverse event or serious adverse event at least possibly related to regorafenib.

CONCLUSION

Regorafenib did not meet prespecified criteria to declare a signal of activity in patients with solid tumors with BRAF alterations.