bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of two novel large deletions in FBN1 gene by next-generation sequencing and multiplex ligation-dependent probe amplification
Authors: Lu Xinxin , Wang Ren , Li Mingjie , Zhang Biao , Rao Huiying , Huang Xiaoli , Chen Xijun , Wu Yan’an
Published: February 2024

Background

Mutations in fibrillin-1 (FBN1) are known to be associated with Marfan syndrome (MFS), an autosomal dominant connective tissue disorder. Most FBN1 mutations are missense or nonsense mutations. Traditional molecular genetic testing for the FBN1 gene, like Sanger sequencing, may miss disease-causing mutations in the gene’s regulatory regions or non-coding sequences, as well as partial or complete gene deletions and duplications.

Methods

Next-generation sequencing, multiplex ligation-dependent probe amplification and gap PCR were conducted on two MFS patients to screen for disease-causing mutations.

Results

We identified two large deletions in FBN1 from two MFS patients. One patient had a 0.23 Mb deletion (NC_000015.9:g.48550506_48779360del) including 5’UTR-exon6 of FBN1. The other patient harbored a 1416 bp deletion (NC_000015.9:g.48410869_48412284del) affecting the last exon, exon 66, of the FBN1 gene.

Conclusion

Our results expanded the number of large FBN1 deletions and highlighted the importance of screening for large deletions in FBN1 in clinical genetic testing, especially for those with the classic MFS phenotype.
Clinical application of bronchoalveolar lavage fluid metagenomics next-generation sequencing in cancer patients with severe pneumonia
Authors: Wang Chao , Yin Xiaojuan , Ma Wenqing , Zhao Li , Wu Xuhong , Ma Nan , Cao Yuepeng , Zhang Quanli , Ma Shuliang , Xu Lin , Wang Xuerong
Published: February 2024

Objective

Metagenomic next-generation sequencing (mNGS), as an emerging technique for pathogen detection, has been widely used in clinic. However, reports on the application of mNGS in cancer patients with severe pneumonia remain limited. This study aims to evaluate the diagnostic performance of bronchoalveolar lavage fluid (BALF) mNGS in cancer patients complicated with severe pneumonia.

Methods

A total of 62 cancer patients with severe pneumonia simultaneously received culture and mNGS of BALF were enrolled in this study. We systematically analyzed the diagnostic significance of BALF mNGS. Subsequently, optimization of anti-infective therapy based on the distribution of pathogens obtained from BALF mNGS was also assessed.

Results

For bacteria and fungi, the positive detection rate of mNGS was significantly higher than culture method (91.94% versus 51.61%, P < 0.001), especially for poly-microbial infections (70.97% versus 12.90%, P < 0.001). Compared with the culture method, mNGS exhibited a diagnostic sensitivity of 100% and a specificity of 16.67%, with the positive predictive value (PPV) and negative predictive value (NPV) being 56.14% and 100%, respectively. The agreement rate between these two methods was 59.68%, whereas kappa consensus analysis indicated a poor concordance (kappa = 0.171). After receipt of BALF mNGS results, anti-infective treatment strategies in 39 out of 62 cases (62.90%) were optimized. Moreover, anti-tumor therapy was a high-risk factor for mixed infections (87.18% versus 65.22%, P = 0.04).

Conclusions

The present study showed that cancer patients with severe pneumonia, especially those received anti-tumor therapy, were more likely to have poly-microbial infections. BALF mNGS can provide a rapid and comprehensive pathogen distribution of pulmonary infection, making it a promising technique in clinical practice, especially for optimizing therapeutic strategies for cancer patients.
Role of multidrug-resistant bacteria in weaning from invasive mechanical ventilation
Authors: Michels-Zetsche Julia D. , Gassmann Vicky , Jasuja Jasmin K. , Neetz Benjamin , Höger Philipp , Meis Jan , Britsch Simone , Sommerwerck Urte , Fähndrich Sebastian , Bornitz Florian , Müller Michael M. , Herth Felix J.F. , Trudzinski Franziska C.
Published: February 2024

Background

Although multidrug-resistant bacteria (MDR) are common in patients undergoing prolonged weaning, there is little data on their impact on weaning and patient outcomes.

Methods

This is a retrospective analysis of consecutive patients who underwent prolonged weaning and were at a university weaning centre from January 2018 to December 2020. The influence of MDR colonisation and infection on weaning success (category 3a and 3b), successful prolonged weaning from invasive mechanical ventilation (IMV) with or without the need for non-invasive ventilation (NIV) compared with category 3c (weaning failure 3cI or death 3cII) was investigated. The pathogen groups considered were: multidrug-resistant gram-negative bacteria (MDRGN), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp. (VRE).

Results

A total of 206 patients were studied, of whom 91 (44.2%) showed evidence of MDR bacteria (32% VRE, 1.5% MRSA and 16% MDRGN), with 25 patients also meeting the criteria for MDR infection. 70.9% of the 206 patients were successfully weaned from IMV, 8.7% died. In 72.2% of cases, nosocomial pneumonia and other infections were the main cause of death. Patients with evidence of MDR (infection and colonisation) had a higher incidence of weaning failure than those without evidence of MDR (48% vs. 34.8% vs. 21.7%). In multivariate analyses, MDR infection (OR 4.9, p = 0.004) was an independent risk factor for weaning failure, along with male sex (OR 2.3, p = 0.025), Charlson Comorbidity Index (OR 1.2, p = 0.027), pH (OR 2.7, p < 0.001) and duration of IMV before admission (OR 1.01, p < 0.001). In addition, MDR infection was the only independent risk factor for death (category 3cII), (OR 6.66, p = 0.007).

Conclusion

Patients with MDR infection are significantly more likely to die during the weaning process. There is an urgent need to develop non-antibiotic approaches for the prevention and treatment of MDR infections as well as clinical research on antibiotic stewardship in prolonged weaning as well as in ICUs.
Using cryoprobes of different sizes combined with cone-beam computed tomography-derived augmented fluoroscopy and endobronchial ultrasound to diagnose peripheral pulmonary lesions: a propensity-matched study
Authors: Lin Ching-Kai , Ruan Sheng-Yuan , Fan Hung-Jen , Chang Hao-Chun , Lin Yen-Ting , Ho Chao-Chi
Published: February 2024

Background

Endobronchial ultrasound (EBUS) and cone-beam computed tomography-derived augmented fluoroscopy (CBCT-AF) are utilized for the diagnosis of peripheral pulmonary lesions (PPLs). Combining them with transbronchial cryobiopsy (TBC) can provide sufficient tissue for genetic analysis. However, cryoprobes of different sizes have varying degrees of flexibility, which can affect their ability to access the target bronchus and potentially impact the accuracy. The aim of this study was to compare the diagnostic efficacy of cryoprobes of varying sizes in CBCT-AF and EBUS for the diagnosis of PPLs.

Methods

Patients who underwent endobronchial ultrasound-guided transbronchial biopsy (EBUS-TBB) and TBC combined with CBCT-AF for PPLs diagnosis between January 2021 and May 2022 were included. Propensity score matching and competing-risks regression were utilized for data analysis. Primary outcome was the diagnostic accuracy of TBC.

Results

A total of 284 patients underwent TBC, with 172 using a 1.7-mm cryoprobe (1.7 group) and 112 using a 1.1-mm cryoprobe (1.1 group). Finally, we included 99 paired patients following propensity score matching. The diagnostic accuracy of TBC was higher in the 1.1 group (80.8% vs. 69.7%, P = 0.050), with a similar rate of complications. Subgroup analysis also revealed that the 1.1 group had better accuracy when PPLs were located in the upper lobe (85.2% vs. 66.1%, P = 0.020), when PPLs were smaller than 20 mm (78.8% vs. 48.8%, P = 0.008), and when intra-procedural CBCT was needed to be used (79.5% vs. 42.3%, P = 0.001). TBC obtained larger specimens than TBB in both groups. There is still a trend of larger sample size obtained in the 1.7 group, but there is no statistically different between our two study groups (40.8 mm2 vs. 22.0 mm2, P = 0.283).

Conclusions

The combination of TBC with CBCT-AF and EBUS is effective in diagnosing PPLs, and a thin cryoprobe is preferred when the PPLs located in difficult areas.
Viral coinfection in hospitalized patients during the COVID-19 pandemic in Southern Brazil: a retrospective cohort study
Authors: Rhoden Jaqueline , Hoffmann Andressa Taíz , Stein Janaína Franciele , Rocha Bruna Seixas da , Barros Vinícius Monteagudo de , Silva Eduardo Viegas da , Fleck Juliane Deise , Rigotto Caroline
Published: February 2024

Purpose

Since the worldwide spread of SARS-CoV-2, different strategies have been followed to combat the pandemic and limit virus transmission. In the meantime, other respiratory viruses continued to circulate, though at decreased rates.

Methods

This study was conducted between June and July 2022, in a hospital in the metropolitan region of Rio Grande do Sul state, in the southernmost state of Brazil. The 337 hospitalized patients included those with respiratory symptoms without delimitation of age. Reverse transcription-quantitative real-time polymerase chain reaction detected 15 different respiratory viruses and confirmed coinfections in the samples. Different statistical tests were applied to evaluate the association between associations of clinical characteristics and coinfection.

Results

Sampling corresponds to 337 selected and 330 patients analyzed. The principal clinical outcome found was hospital discharge in 309 (94%) cases, while 21 (6%) resulted in death. The principal viral agents related to coinfections were Human rhinovirus, Human enterovirus, and Respiratory syncytial virus. The most frequent viral agent detected was SARS-CoV-2, with 60 (18%) infections, followed by 51 (15%) cases of Respiratory syncytial virus B (15%) and 44 (13%) cases of Human rhinovirus 1. Coinfection was mainly observed in children, while adults and the elderly were more affected by a single infection. Analyzing COVID-19 vaccination, 175 (53%) were unvaccinated while the remainder had at least one dose of the vaccine.

Conclusions

This study presents information to update the understanding of viral circulation in the region. Furthermore, the findings clarify the behavior of viral infections and possible coinfections in hospitalized patients, considering different ages and clinical profiles. In addition, this knowledge can help to monitor the population’s clinical manifestations and prevent future outbreaks of respiratory viruses.
Effectiveness of artemether–lumefantrine for treating uncomplicated malaria in low- and high-transmission areas of Ghana
Authors: Mawuli Mawusi Adepa , Amoah Linda Eva , Cui Liwang , Quashie Neils Ben , Afrane Yaw Asare
Published: February 2024

Background

Artemisinin-based combination therapy (ACT) has been effective in the supervised treatment of uncomplicated malaria in Ghana. Since ACT usage is primarily unsupervised, this study aimed to determine the effectiveness of artemether–lumefantrine (AL) for treating malaria patients in two transmission settings in Ghana.

Methods

Eighty-four individuals with uncomplicated Plasmodium falciparum malaria were recruited from Lekma Hospital (LH) in Accra (low-transmission area; N = 28), southern Ghana, and King’s Medical Centre (KMC) in Kumbungu (high-transmission area; N = 56), northern Ghana. Participants were followed up for 28 days after unsupervised treatment with AL. The presence of asexual parasites was determined by microscopic examination of Giemsa-stained blood smears. Plasmodium species identification was confirmed using species-specific primers targeting the 18S rRNA gene. Parasite recrudescence or reinfection was determined by genotyping the Pfmsp 1 and Pfmsp 2 genes.

Results

After AL treatment, 3.6% (2/56) of the patients from KMC were parasitaemic on day 3 compared to none from the LH patients. One patient from KMC with delayed parasite clearance on day 3 remained parasite-positive by microscopy on day 7 but was parasite-free by day 14. While none of the patients from LH experienced parasite recurrence during the 28-day follow-up, three and two patients from KMC had recurrent parasitaemia on days 21 and 28, respectively. Percentage reduction in parasite densities from day 1, 2, and 3 for participants from the KMC was 63.2%, 89.5%, and 84.5%. Parasite densities for participants from the LH reduced from 98.2%, 99.8% on day 1, and 2 to 100% on day 3. The 28-day cumulative incidence rate of treatment failure for KMC was 12.8% (95% confidence interval: 1.9–23.7%), while the per-protocol effectiveness of AL in KMC was 89.47%. All recurrent cases were assigned to recrudescence after parasite genotyping by Pfmsp 1 and Pfmsp 2.

Conclusion

While AL is efficacious in treating uncomplicated malaria in Ghana, when taken under unsupervised conditions, it showed an 89.4% PCR-corrected cure rate in northern Ghana, which is slightly below the WHO-defined threshold.
Standardizing digital biobanks: integrating imaging, genomic, and clinical data for precision medicine
Authors: Brancato Valentina , Esposito Giuseppina , Coppola Luigi , Cavaliere Carlo , Mirabelli Peppino , Scapicchio Camilla , Borgheresi Rita , Neri Emanuele , Salvatore Marco , Aiello Marco
Published: February 2024

Advancements in data acquisition and computational methods are generating a large amount of heterogeneous biomedical data from diagnostic domains such as clinical imaging, pathology, and next-generation sequencing (NGS), which help characterize individual differences in patients. However, this information needs to be available and suitable to promote and support scientific research and technological development, supporting the effective adoption of the precision medicine approach in clinical practice. Digital biobanks can catalyze this process, facilitating the sharing of curated and standardized imaging data, clinical, pathological and molecular data, crucial to enable the development of a comprehensive and personalized data-driven diagnostic approach in disease management and fostering the development of computational predictive models. This work aims to frame this perspective, first by evaluating the state of standardization of individual diagnostic domains and then by identifying challenges and proposing a possible solution towards an integrative approach that can guarantee the suitability of information that can be shared through a digital biobank. Our analysis of the state of the art shows the presence and use of reference standards in biobanks and, generally, digital repositories for each specific domain. Despite this, standardization to guarantee the integration and reproducibility of the numerical descriptors generated by each domain, e.g. radiomic, pathomic and -omic features, is still an open challenge. Based on specific use cases and scenarios, an integration model, based on the JSON format, is proposed that can help address this problem. Ultimately, this work shows how, with specific standardization and promotion efforts, the digital biobank model can become an enabling technology for the comprehensive study of diseases and the effective development of data-driven technologies at the service of precision medicine.
The progressive trend of modeling and drug screening systems of breast cancer bone metastasis
Authors: Kolahi Azar Hanieh , Gharibshahian Maliheh , Rostami Mohammadreza , Mansouri Vahid , Sabouri Leila , Beheshtizadeh Nima , Rezaei Nima
Published: February 2024

Bone metastasis is considered as a considerable challenge for breast cancer patients. Various in vitro and in vivo models have been developed to examine this occurrence. In vitro models are employed to simulate the intricate tumor microenvironment, investigate the interplay between cells and their adjacent microenvironment, and evaluate the effectiveness of therapeutic interventions for tumors. The endeavor to replicate the latency period of bone metastasis in animal models has presented a challenge, primarily due to the necessity of primary tumor removal and the presence of multiple potential metastatic sites.

The utilization of novel bone metastasis models, including three-dimensional (3D) models, has been proposed as a promising approach to overcome the constraints associated with conventional 2D and animal models. However, existing 3D models are limited by various factors, such as irregular cellular proliferation, autofluorescence, and changes in genetic and epigenetic expression. The imperative for the advancement of future applications of 3D models lies in their standardization and automation. The utilization of artificial intelligence exhibits the capability to predict cellular behavior through the examination of substrate materials' chemical composition, geometry, and mechanical performance. The implementation of these algorithms possesses the capability to predict the progression and proliferation of cancer. This paper reviewed the mechanisms of bone metastasis following primary breast cancer. Current models of breast cancer bone metastasis, along with their challenges, as well as the future perspectives of using these models for translational drug development, were discussed.
Low-dose acetylsalicylic acid reduces local inflammation and tissue perfusion in dense breast tissue in postmenopausal women
Authors: Lundberg Peter , Abrahamsson Annelie , Kihlberg Johan , Tellman Jens , Tomkeviciene Ieva , Karlsson Anette , Kristoffersen Wiberg Maria , Warntjes Marcel , Dabrosin Charlotta
Published: February 2024

Purpose

One major risk factor for breast cancer is high mammographic density. It has been estimated that dense breast tissue contributes to ~ 30% of all breast cancer. Prevention targeting dense breast tissue has the potential to improve breast cancer mortality and morbidity. Anti-estrogens, which may be associated with severe side-effects, can be used for prevention of breast cancer in women with high risk of the disease per se. However, no preventive therapy targeting dense breasts is currently available. Inflammation is a hallmark of cancer. Although the biological mechanisms involved in the increased risk of cancer in dense breasts is not yet fully understood, high mammographic density has been associated with increased inflammation. We investigated whether low-dose acetylsalicylic acid (ASA) affects local breast tissue inflammation and/or structural and dynamic changes in dense breasts.

Methods

Postmenopausal women with mammographic dense breasts on their regular mammography screen were identified. A total of 53 women were randomized to receive ASA 160 mg/day or no treatment for 6 months. Magnetic resonance imaging (MRI) was performed before and after 6 months for a sophisticated and continuous measure breast density by calculating lean tissue fraction (LTF). Additionally, dynamic quantifications including tissue perfusion were performed. Microdialysis for sampling of proteins in vivo from breasts and abdominal subcutaneous fat, as a measure of systemic effects, before and after 6 months were performed. A panel of 92 inflammatory proteins were quantified in the microdialysates using proximity extension assay.

Results

After correction for false discovery rate, 20 of the 92 inflammatory proteins were significantly decreased in breast tissue after ASA treatment, whereas no systemic effects were detected. In the no-treatment group, protein levels were unaffected. Breast density, measured by LTF on MRI, were unaffected in both groups. ASA significantly decreased the perfusion rate. The perfusion rate correlated positively with local breast tissue concentration of VEGF.

Conclusions

ASA may shape the local breast tissue microenvironment into an anti-tumorigenic state. Trials investigating the effects of low-dose ASA and risk of primary breast cancer among postmenopausal women with maintained high mammographic density are warranted.

Trial registration EudraCT: 2017-000317-22.
Off-label use of large diameter Concerto fibered coils through a 0.017 inch microcatheter for transvenous embolization of indirect carotid-cavernous fistulas: two case reports
Authors: Hsieh Justin T. , Chia Ghim Song , Wong Chen Pong , Lim Winston Eng Hoe , Wen David W.
Published: February 2024

Background

A carotid-cavernous fistula is an abnormal communication between the arteries and veins within the cavernous sinus. While conservative management may be prudent in low risk cases, many patients require intervention and endovascular embolization has evolved as the preferred method of treatment. Embolization can be performed via either the transarterial or transvenous approach. One major challenge of the transvenous approach is the complex and variable compartmentation of the cavernous sinus, which often requires the use of low profile microcatheters to navigate and reach the fistulous point. Fibered coils are also preferred when performing transvenous embolization of carotid-cavernous fistula, as they are of higher thrombogenicity and allow for faster occlusion of the fistula. However, most low profile (0.017-inch) microcatheters are not able to deploy fibered coils based on the manufacturer’s instructions.

Case presentation

We present two successful cases of off-label use of Medtronic Concerto fibered coils via a 0.017-inch microcatheter during transvenous embolization of carotid-cavernous fistula in a 60-year-old and an 80-year-old Chinese female, respectively.

Conclusion

Our case series highlight the possibility of deploying large diameter (up to 10 mm) Concerto fibered coils through a low profile (0.017-inch) microcatheter in an off-label manner for transvenous embolization of indirect carotid-cavernous fistula.
The role of Helicobacter suis, Fusobacterium gastrosuis, and the pars oesophageal microbiota in gastric ulceration in slaughter pigs receiving meal or pelleted feed
Authors: Taillieu Emily , Taelman Steff , De Bruyckere Sofie , Goossens Evy , Chantziaras Ilias , Van Steenkiste Christophe , Yde Peter , Hanssens Steven , De Meyer Dimitri , Van Criekinge Wim , Stock Michiel , Maes Dominiek , Chiers Koen , Haesebrouck Freddy
Published: February 2024

This study investigated the role of causative infectious agents in ulceration of the non-glandular part of the porcine stomach (pars oesophagea). In total, 150 stomachs from slaughter pigs were included, 75 from pigs that received a meal feed, 75 from pigs that received an equivalent pelleted feed with a smaller particle size. The pars oesophagea was macroscopically examined after slaughter. (q)PCR assays for H. suis, F. gastrosuis and H. pylori-like organisms were performed, as well as 16S rRNA sequencing for pars oesophagea microbiome analyses. All 150 pig stomachs showed lesions. F. gastrosuis was detected in 115 cases (77%) and H. suis in 117 cases (78%), with 92 cases (61%) of co-infection; H. pylori-like organisms were detected in one case. Higher infectious loads of H. suis increased the odds of severe gastric lesions (OR = 1.14, p = 0.038), while the presence of H. suis infection in the pyloric gland zone increased the probability of pars oesophageal erosions [16.4% (95% CI 0.6–32.2%)]. The causal effect of H. suis was mediated by decreased pars oesophageal microbiome diversity [−1.9% (95% CI − 5.0–1.2%)], increased abundances of Veillonella and Campylobacter spp., and decreased abundances of Lactobacillus, Escherichia-Shigella, and Enterobacteriaceae spp. Higher infectious loads of F. gastrosuis in the pars oesophagea decreased the odds of severe gastric lesions (OR = 0.8, p = 0.0014). Feed pelleting had no significant impact on the prevalence of severe gastric lesions (OR = 1.72, p = 0.28). H. suis infections are a risk factor for ulceration of the porcine pars oesophagea, probably mediated through alterations in pars oesophageal microbiome diversity and composition.
Comparison of fish oil supplements and corn oil effects on serum lipid profile: a systematic review and meta-analysis of randomized controlled trials
Authors: Safaei Payam , Bayat Ghazal , Mohajer Afsaneh
Published: February 2024

Background

The present study aimed to investigate the effects of fish oil supplements compared to corn oil on serum lipid profiles by performing a meta-analysis of randomized controlled trials (RCTs).

Methods

Online databases including PubMed, Web of Science, and Scopus were searched until 30 December 2022. Pooled effect sizes were reported as the weighted mean difference (WMD) with 95% confidence intervals (CI). The Cochrane Collaboration’s risk-of-bias tool was utilized to evaluate the quality of the studies. Lipid parameters, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL), were assessed in the meta-analysis.

Results

Overall, 16 eligible trials were included in this systematic review and meta-analysis. The results revealed that the fish oil supplements significantly reduced TG (WMD: − 25.50 mg/dl, 95% CI: − 42.44, − 8.57, P = 0.000) levels compared to corn oil. Also, in this study, fish oil supplements had a positive and significant effect on HDL (WMD: 2.54 mg/dl, 95% CI: 0.55, 4.52). There were no significant changes in TC and LDL.

Conclusions

Our findings showed the effects of fish oil supplements on reducing TG and increasing HDL-c compared to corn oil. Further larger and well-designed RCTs are required to confirm these data.
Multiple positive solutions for Schrödinger-Poisson system with singularity on the Heisenberg group
Authors: Tian Guaiqi , An Yucheng , Suo Hongmin
Published: February 2024

In this work, we study the following Schrödinger-Poisson system $$ \textstyle\begin{cases} -\Delta _{H}u+\mu \phi u=\lambda u^{-\gamma}, &\text{in } \Omega , \\ -\Delta _{H}\phi =u^{2}, &\text{in } \Omega , \\ u>0, &\text{in } \Omega , \\ u=\phi =0, &\text{on } \partial \Omega , \end{cases} $$

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Stability analysis of fractional order breast cancer model in chemotherapy patients with cardiotoxicity by applying LADM
Authors: Mohammadpoor Hajar , Eghbali Nasrin , Sajedi Leila , Nosrati Sahlan Monireh
Published: February 2024

Breast cancer is the most common type of cancer in women. Chemotherapy is primarily used for patients with stage 2 to 4 breast cancer. Most chemotherapy drugs are effective at destroying rapidly growing and proliferating cancer cells. However, drugs also damage normal, rapidly growing cells, which can lead to serious side effects. Breast cancer treatment with chemotherapy can affect heart health. Side effects of chemotherapy on the heart are called cardiotoxicity. Therefore, we have constructed a mathematical model from the breast cancer patient population. In this article, we utilize the Caputo–Fabrizio fractional order derivative for mathematical modeling of the breast cancer stages in chemotherapy patients. The use of Caputo–Fabrizio fractional derivative provides a more valuable insight into the complexity of the breast cancer model. The stability of the fractional order model is also proven by the $\mathscr{P}$
P
-stable approach of the fixed point theorem. Also, the numerical simulations are performed via Laplace Adomian decomposition method to establish the dependence of the breast cancer dynamics on the order of the fractional derivatives. Based on the geometric results in the figures, we can conclude that the magnitude of the fractional order has a considerable impact on the days, which the maximum or minimum of the system solutions are reached, with a shift in the time at which this happens as the fractional order decreases from 1. However, it is obvious that the solutions of Caputo–Fabrizio fractional model approach the relevant results of the classical integer order system, when the fractional order approaches to 1.
Simultaneous determination of sulfonylurea herbicides in tomatoes using the QuEChERS method coupled with HPLC
Authors: Han Sang Gyu , Nam Tae Gyu
Published: February 2024

The simultaneous determination of trace pesticides in complex matrices containing high concentrations of natural pigments remains challenging. In this study, quick, easy, cheap, effective, rugged, and safe (QuEChERS) sample preparation together with high-performance liquid chromatography with ultraviolet detection (HPLC–UV) was applied for the multi-residue analysis of seven sulfonylurea herbicides (SUHs) in tomatoes. SUH residue was extracted using the QuEChERS procedure, followed by solid-phase extraction (SPE) and dispersive SPE (d-SPE). To reduce the amount of carotenoids in tomato extracts, several d-SPE clean-up procedures were compared, and octadecylsilane (C18) provided the best color removal rate (%) of tomato extracts and recoveries (%) for all the tested SUHs. The validation results indicate good linearity (R2 > 0.9970), accuracy, and precision. Recoveries of 70–120% and relative standard deviations < 20% were achieved for all analytes at three spiked concentrations. The limits of detection and quantification for the 7 SUHs were 0.003 mg kg−1 and 0.008–0.009 mg kg−1, respectively. The developed method was subsequently used to quantify multi-residue SUHs during real sample analysis. None of the tested samples had SUH residue levels higher than the maximum residue limits established by the Korean Ministry of Food and Drug Safety. The results suggest that QuEChERS sample preparation employing a combination of C18 is a high-throughput and rapid clean-up procedure for the multi-residue analysis of SUHs in tomatoes.
Gut microbiota-derived LCA mediates the protective effect of PEDV infection in piglets
Authors: Xing Jun-Hong , Niu Tian-Ming , Zou Bo-Shi , Yang Gui-Lian , Shi Chun-Wei , Yan Qing-Song , Sun Ming-Jie , Yu Tong , Zhang Shu-Min , Feng Xi-Ze , Fan Shu-Hui , Huang Hai-Bin , Wang Jun-Hong , Li Ming-Han , Jiang Yan-Long , Wang Jian-Zhong , Cao Xin , Wang Nan , Zeng Yan , Hu Jing-Tao , Zhang Di , Sun Wu-Sheng , Yang Wen-Tao , Wang Chun-Feng
Published: February 2024

Background

The gut microbiota is a critical factor in the regulation of host health, but the relationship between the differential resistance of hosts to pathogens and the interaction of gut microbes is not yet clear. Herein, we investigated the potential correlation between the gut microbiota of piglets and their disease resistance using single-cell transcriptomics, 16S amplicon sequencing, metagenomics, and untargeted metabolomics.

Results

Porcine epidemic diarrhea virus (PEDV) infection leads to significant changes in the gut microbiota of piglets. Notably, Landrace pigs lose their resistance quickly after being infected with PEDV, but transplanting the fecal microbiota of Min pigs to Landrace pigs alleviated the infection status. Macrogenomic and animal protection models identified Lactobacillus reuteri and Lactobacillus amylovorus in the gut microbiota as playing an anti-infective role. Moreover, metabolomic screening of the secondary bile acids’ deoxycholic acid (DCA) and lithocholic acid (LCA) correlated significantly with Lactobacillus reuteri and Lactobacillus amylovorus, but only LCA exerted a protective function in the animal model. In addition, LCA supplementation altered the distribution of intestinal T-cell populations and resulted in significantly enriched CD8+ CTLs, and in vivo and in vitro experiments showed that LCA increased SLA-I expression in porcine intestinal epithelial cells via FXR receptors, thereby recruiting CD8+ CTLs to exert antiviral effects.

Conclusions

Overall, our findings indicate that the diversity of gut microbiota influences the development of the disease, and manipulating Lactobacillus reuteri and Lactobacillus amylovorus, as well as LCA, represents a promising strategy to improve PEDV infection in piglets.
LINC01559 promotes lung adenocarcinoma metastasis by disrupting the ubiquitination of vimentin
Authors: Feng Hao , Xu Dengfei , Jiang Chenyang , Chen Yuming , Wang Junru , Ren Zirui , Li Xiang , Zhang Xu Dong , Cang Shundong
Published: February 2024

Background

Distant metastasis is the major cause of lung adenocarcinoma (LUAD)-associated mortality. However, molecular mechanisms involved in LUAD metastasis remain to be fully understood. While the role of long non-coding RNAs (lncRNAs) in cancer development, progression, and treatment resistance is being increasingly appreciated, the list of dysregulated lncRNAs that contribute to LUAD pathogenesis is also rapidly expanding.

Methods

Bioinformatics analysis was conducted to interrogate publicly available LUAD datasets. In situ hybridization and qRT-PCR assays were used to test lncRNA expression in human LUAD tissues and cell lines, respectively. Wound healing as well as transwell migration and invasion assays were employed to examine LUAD cell migration and invasion in vitro. LUAD metastasis was examined using mouse models in vivo. RNA pulldown and RNA immunoprecipitation were carried out to test RNA–protein associations. Cycloheximide-chase assays were performed to monitor protein turnover rates and Western blotting was employed to test protein expression.

Results

The expression of the lncRNA LINC01559 was commonly upregulated in LUADs, in particular, in those with distant metastasis. High LINC01559 expression was associated with poor outcome of LUAD patients and was potentially an independent prognostic factor. Knockdown of LINC01559 diminished the potential of LUAD cell migration and invasion in vitro and reduced the formation of LUAD metastatic lesions in vivo. Mechanistically, LINC01559 binds to vimentin and prevents its ubiquitination and proteasomal degradation, leading to promotion of LUAD cell migration, invasion, and metastasis.

Conclusion

LINC01559 plays an important role in LUAD metastasis through stabilizing vimentin. The expression of LINC01559 is potentially an independent prognostic factor of LUAD patients, and LINC01559 targeting may represent a novel avenue for the treatment of late-stage LUAD.
Altered amyloid-β structure markedly reduces gliosis in the brain of mice harboring the Uppsala APP deletion
Authors: Pagnon de la Vega María , Syvänen Stina , Giedraitis Vilmantas , Hooley Monique , Konstantinidis Evangelos , Meier Silvio R. , Rokka Johanna , Eriksson Jonas , Aguilar Ximena , Spires-Jones Tara L. , Lannfelt Lars , Nilsson Lars N. G. , Erlandsson Anna , Hultqvist Greta , Ingelsson Martin , Sehlin Dag
Published: February 2024

Deposition of amyloid beta (Aβ) into plaques is a major hallmark of Alzheimer’s disease (AD). Different amyloid precursor protein (APP) mutations cause early-onset AD by altering the production or aggregation properties of Aβ. We recently identified the Uppsala APP mutation (APPUpp), which causes Aβ pathology by a triple mechanism: increased β-secretase and altered α-secretase APP cleavage, leading to increased formation of a unique Aβ conformer that rapidly aggregates and deposits in the brain. The aim of this study was to further explore the effects of APPUpp in a transgenic mouse model (tg-UppSwe), expressing human APP with the APPUpp mutation together with the APPSwe mutation. Aβ pathology was studied in tg-UppSwe brains at different ages, using ELISA and immunohistochemistry. In vivo PET imaging with three different PET radioligands was conducted in aged tg-UppSwe mice and two other mouse models; tg-ArcSwe and tg-Swe. Finally, glial responses to Aβ pathology were studied in cell culture models and mouse brain tissue, using ELISA and immunohistochemistry. Tg-UppSwe mice displayed increased β-secretase cleavage and suppressed α-secretase cleavage, resulting in AβUpp42 dominated diffuse plaque pathology appearing from the age of 5–6 months. The γ-secretase cleavage was not affected. Contrary to tg-ArcSwe and tg-Swe mice, tg-UppSwe mice were [11C]PiB-PET negative. Antibody-based PET with the 3D6 ligand visualized Aβ pathology in all models, whereas the Aβ protofibril selective mAb158 ligand did not give any signals in tg-UppSwe mice. Moreover, unlike the other two models, tg-UppSwe mice displayed a very faint glial response to the Aβ pathology. The tg-UppSwe mouse model thus recapitulates several pathological features of the Uppsala APP mutation carriers. The presumed unique structural features of AβUpp42 aggregates were found to affect their interaction with anti-Aβ antibodies and profoundly modify the Aβ-mediated glial response, which may be important aspects to consider for further development of AD therapies.
Prediction of [177Lu]Lu-DOTA-TATE therapy response using the absorbed dose estimated from [177Lu]Lu-DOTA-TATE SPECT/CT in patients with metastatic neuroendocrine tumour
Authors: Ha Sejin , Kim Yong-il , Oh Jungsu S. , Yoo Changhoon , Ryoo Baek-Yeol , Ryu Jin-Sook
Published: February 2024

Background

Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE has shown efficacy in patients with metastatic neuroendocrine tumours (NETs). Personalised dosimetry is crucial to optimise treatment outcomes and minimise adverse events. In this study, we investigated the correlation between the tumour-absorbed dose (TAD) estimated from [177Lu]Lu-DOTA-TATE SPECT/CT and the therapeutic response.

Method

A retrospective analysis was conducted on patients with advanced well-differentiated NETs grades 1–3 who underwent PRRT and exhibited greater uptake than liver on pre-therapeutic [68Ga]Ga-DOTA-TOC PET/CT. Target lesions were selected based on the RECIST 1.1 and PERCIST 1.0 criteria using [177Lu]Lu-DOTA-TATE SPECT/CT and pre-therapeutic contrast-enhanced CT scans. For anatomical image analysis, the sum of the longest diameter (SLD) of the target lesions was measured using the RECIST 1.1 criteria for patient-based analysis and the longest diameter (LD) of the target lesion using the RECIST-L criteria for lesion-based analysis. Standardised uptake values (SUVs) were measured on SPECT/CT images, and TADs were calculated based on the SUVs. Dosimetry was performed using a single SPECT/CT imaging time point at day 4–5 post-therapy. Statistical analyses were conducted to investigate correlations and determine the target lesion responses.

Results

Twenty patients with primary tumour sites and hepatic metastases were included. Fifty-five target lesions, predominantly located in the pancreas and liver, were analysed. The cumulative TAD (lesion-based analysis: r = 0.299–0.301, p = 0.025–0.027), but not the cycle 1 SUV (lesion-based analysis: r = 0.198–0.206, p = 0.131–0.147) or cycle 1 TAD (lesion-based analysis: r = 0.209–0.217, p = 0.112–0.126), exhibited a significant correlation with the change in LD of the target lesion. Binary logistic regression analysis identified the significance of the cumulative TAD in predicting disease control according to the RECIST-L criteria (odds ratio = 1.031–1.051, p = 0.024–0.026).

Conclusions

The cumulative TAD estimated from [177Lu]Lu-DOTA-TATE SPECT/CT revealed a significant correlation with change in LD, which was significantly higher for the cumulative TAD than for the cycle 1 SUV or TAD. A higher cumulative TAD was associated with disease control in the target lesion. However, considering the limitations inherent to a confined sample size, careful interpretation of these findings is required. Estimation of the cumulative TAD of [177Lu]Lu-DOTA-TATE therapy could guide the platform towards personalised therapy.
Rethinking diaspora remittances in the post-Mugabe era in Zimbabwe
Authors: Moyo Inocent
Published: February 2024

Based on a qualitative study of Zimbabwean migrants based in South Africa, who regularly remitted goods and money to Zimbabwe between 2010 and 2020, this paper suggests that at a local level, remittances alleviated poverty with very limited if any transformation of the political economy at the national level. Such remittances promoted consumerism without sustainable investment that can structurally transform the economy. In addition, the dependence on remittances entrenches the culture of migration at the local level, which also contributes to or promotes ethno-tribal fissiparity. In rethinking diaspora remittances in the post-Mugabe era, it is advanced that the seemingly intractable economic and political quagmire in Zimbabwe must be resolved to inspire confidence in the diaspora to pull remittances together for a national socio-economic cause and not local-level band-aid accomplishments which remittances currently do.
Navigating meaningful engagement: lessons from partnering with youth and families in brain-based disability research
Authors: Nguyen Linda , Pozniak Kinga , Strohm Sonya , Havens Jessica , Dawe-McCord Claire , Thomson Donna , Putterman Connie , Arafeh Dana , Galuppi Barb , Ley Alicia Via-Dufresne , Doucet Shelley , Amaria Khush , Kovacs Adrienne H. , Marelli Ariane , Rozenblum Ronen , Gorter Jan Willem ,   CHILD-BRIGHT READYorNot™ Brain-Based Disabilities Trial Study Group
Published: February 2024

Background

While patient and family engagement in research has become a widespread practice, meaningful and authentic engagement remains a challenge. In the READYorNot™ Brain-Based Disabilities Study, we developed the MyREADY Transition™ Brain-Based Disabilities App to promote education, empowerment, and navigation for the transition from pediatric to adult care among youth with brain-based disabilities, aged 15–17 years old. Our research team created a Patient and Family Advisory Council (PFAC) to engage adolescents, young adults, and parent caregivers as partners throughout our multi-year and multi-stage project.

Main body

This commentary, initiated and co-authored by members of our PFAC, researchers, staff, and a trainee, describes how we corrected the course of our partnership in response to critical feedback from partners. We begin by highlighting an email testimonial from a young adult PFAC member, which constituted a “critical turning point,” that unveiled feelings of unclear expectations, lack of appreciation, and imbalanced relationships among PFAC members. As a team, we reflected on our partnership experiences and reviewed documentation of PFAC activities. This process allowed us to set three intentions to create a collective goal of authentic and meaningful engagement and to chart the course to get us there: (1) offering clarity and flexibility around participation; (2) valuing and acknowledging partners and their contributions; and (3) providing choice and leveraging individual interests and strengths. Our key recommendations include: (1) charting the course with a plan to guide our work; (2) learning the ropes by developing capacity for patient-oriented research; (3) all hands on deck by building a community of engagement; and (4) making course corrections and being prepared to weather the storms by remaining open to reflection, re-evaluation, and adjustment as necessary.

Conclusions

We share key recommendations and lessons learned from our experiences alongside examples from the literature to offer guidance for multi-stage research projects partnering with adolescents, young adults, and family partners. We hope that by sharing challenges and lessons learned, we can help advance patient and family engagement in research.
The effectiveness of glucocorticoid treatment in post-COVID-19 pulmonary involvement
Authors: Mizera Jan , Genzor Samuel , Sova Milan , Stanke Ladislav , Burget Radim , Jakubec Petr , Vykopal Martin , Pobeha Pavol , Zapletalová Jana
Published: February 2024

Rationale

Persistent respiratory symptoms following Coronavirus Disease 2019 (COVID-19) are associated with residual radiological changes in lung parenchyma, with a risk of development into lung fibrosis, and with impaired pulmonary function. Previous studies hinted at the possible efficacy of corticosteroids (CS) in facilitating the resolution of post-COVID residual changes in the lungs, but the available data is limited.

Aim

To evaluate the effects of CS treatment in post-COVID respiratory syndrome patients.

Patients and methods

Post-COVID patients were recruited into a prospective single-center observational study and scheduled for an initial (V1) and follow-up visit (V2) at the Department of Respiratory Medicine and Tuberculosis, University Hospital Olomouc, comprising of pulmonary function testing, chest x-ray, and complex clinical examination. The decision to administer CS or maintain watchful waiting (WW) was in line with Czech national guidelines.

Results

The study involved 2729 COVID-19 survivors (45.7% male; mean age: 54.6). From 2026 patients with complete V1 data, 131 patients were indicated for CS therapy. These patients showed significantly worse radiological and functional impairment at V1. Mean initial dose was 27.6 mg (SD ± 10,64), and the mean duration of CS therapy was 13.3 weeks (SD ± 10,06). Following therapy, significantly better improvement of static lung volumes and transfer factor for carbon monoxide (DLCO), and significantly better rates of good or complete radiological and subjective improvement were observed in the CS group compared to controls with available follow-up data (n = 894).

Conclusion

Better improvement of pulmonary function, radiological findings and subjective symptoms were observed in patients CS compared to watchful waiting. Our findings suggest that glucocorticoid therapy could benefit selected patients with persistent dyspnea, significant radiological changes, and decreased DLCO.
Liver and mucous secretion enzymatic biomarkers of Eobania vermiculata treated with some newly synthesized acrylamide derivatives
Authors: Emara Esam M. , El-Sawaf Maher A. , Khalifa Rasha F.
Published: February 2024

Background

Acrylamide derivatives have a potential biological activity as well as acting as precursors in many organic syntheses. Moreover, acrylamides and their derivatives cause convulsions and diffused damage to different sections of the nervous system of infected animals. Novel copper and zinc chelates originated from (E)-3-(4-bromophenyl)-2-cyanoacrylamide (L1), and (E)-2-cyano-3-(4-nitrophenyl)acrylamide (L2) were prepared, and their chemical skeletons were identified by infrared and mass spectra. The obtained compounds were screened in vitro against the brown garden snail, Eobania vermiculata using the contact method along 72 h. Stock solutions of tested compounds were prepared utilizing distilled water and DMSO mixture, and four concentrations of each compound were prepared (50, 150, 250 and 350 ppm). Eobania vermiculata snails were treated with LC50 concentrations of prepared compounds for 3 days, and live snails were used to estimate the level of some liver and mucous secretion enzymatic biomarkers: transaminases enzymes (Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)), Total Protein content (TP), Acid Phosphatases (ACP) and Alkaline Phosphatase (ALP).

Results

The results demonstrated that the examined compounds have a relatively toxic effect toward the screened species. Zinc complexes displayed a higher toxicity than copper ones. The results authenticated considerable high effects of the synthesized compounds on investigated enzymes.

Conclusions

The promising effects of Cu(II), Zn(II) complexes (1, 2) on stimulating the mucous secretion of tested snails are clear through the elevated levels of ALP and ACP enzymes of treated snails. The enhancement or reduction of AST, ALT level and TP content of treated snails demonstrated the effects of prepared compounds on liver functions of these species.