bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular vesicles produced by avian pathogenic Escherichia coli (APEC) activate macrophage proinflammatory response and neutrophil extracellular trap (NET) formation through TLR4 signaling
Authors: Wang Zhongxing , Zhu Dongyu , Zhang Yuting , Xia Fufang , Zhu Jiaying , Dai Jianjun , Zhuge Xiangkai
Published: September 2023

Background

Avian pathogenic Escherichia coli (APEC) is the major pathogen causing important avian diseases in poultry. As an important subtype of extraintestinal pathogenic E. coli, APEC has zoonotic potential and is considered a foodborne pathogen. APEC extracellular vesicles (EVs) may play vital roles in the interaction of the pathogen with its host cells. However, the precise roles played by APEC EVs are still not completely clear, especially in immune cells.

Results

In this study, we investigated the relationships between APEC EVs and immune cells. The production and characteristics of the EVs of APEC isolate CT265 were identified. Toll like receptor 4 (TLR4) triggered the cellular immune responses when it interacted with APEC EVs. APEC EVs induced a significant release of proinflammatory cytokines in THP-1 macrophages. APEC EVs induced the macrophage inflammatory response via the TLR4/MYD88/NF-κB signaling pathway, which participated in the activation of the APEC-EV-induced NLRP3 inflammasome. However, the loss of lipopolysaccharide (LPS) from APEC EVs reduced the activation of the NLRP3 inflammasome mediated by TLR4/MYD88/NF-κB signaling. Because APEC EVs activated the macrophage inflammatory response and cytokines release, we speculated that the interaction between APEC EVs and macrophages activated and promoted neutrophil migration during APEC extraintestinal infection. This study is the first to report that APEC EVs induce the formation of neutrophil extracellular traps (NETs) and chicken heterophil extracellular traps. Treatment with APEC EVs induced SAPK/JNK activation in neutrophils. The inhibition of TLR4 signaling suppressed APEC-EV-induced NET formation. However, although APEC EVs activated the immune response of macrophages and initiated NET formation, they also damaged macrophages, causing their apoptosis. The loss of LPS from APEC EVs did not prevent this process.

Conclusion

APEC-derived EVs induced inflammatory responses in macrophages and NETs in neutrophils, and that TLR4 was involved in the APEC-EV-activated inflammatory response. These findings provided a basis for the further study of APEC pathogenesis.
EZH2-mediated epigenetic silencing of tumor-suppressive let-7c/miR-99a cluster by hepatitis B virus X antigen enhances hepatocellular carcinoma progression and metastasis
Authors: Wu Chen-Shiou , Chien Yi-Chung , Yen Chia‐Jui , Wu Jia-Yan , Bai Li-Yuan , Yu Yung-Luen
Published: September 2023

Background

Hepatitis B virus (HBV)-encoded X antigen, HBx, assists in the development of hepatocellular carcinoma (HCC) through complex mechanisms. Our results provide new insights into the EZH2 epigenetic repression of let-7c that promotes HCC migration induced by HBx. Thus, let-7c and HMGA2 represent key diagnostic markers and potential therapeutic targets for the treatment of HBV-related HCC.

Results

We investigated the epigenetic regulation of let-7c, an important representative miRNA in liver tumor metastasis, in human HCC cells to verify the effect of HBx. Based on quantitative PCR (qPCR) of mRNA isolated from tumor and adjacent non-tumor liver tissues of 24 patients with HBV-related HCC, EZH2 expression was significantly overexpressed in most HCC tissues (87.5%). We executed a miRNA microarray analysis in paired HBV-related HCC tumor and adjacent non-tumorous liver tissue from six of these patients and identified let-7c, miR-199a-3p, and miR-99a as being downregulated in the tumor tissue. Real-time PCR analysis verified significant downregulation of let-7c and miR-99a in both HepG2X and Hep3BX cells, which stably overexpress HBx, relative to parental cells. HBX enhanced EZH2 expression and attenuated let-7c expression to induce HMGA2 expression in the HCC cells. Knockdown of HMGA2 significantly downregulated the metastatic potential of HCC cells induced by HBx.

Conclusions

The deregulation of let-7c expression by HBx may indicate a potential novel pathway through deregulating cell metastasis and imply that HMGA2 might be used as a new prognostic marker and/or as an effective therapeutic target for HCC.
Plasmodium falciparum population structure inferred by msp1 amplicon sequencing of parasites collected from febrile patients in Kenya
Authors: Andika Brian , Mobegi Victor , Gathii Kimita , Nyataya Josphat , Maina Naomi , Awinda George , Mutai Beth , Waitumbi John
Published: September 2023

Background

Multiplicity of infection (MOI) is an important measure of Plasmodium falciparum diversity, usually derived from the highly polymorphic genes, such as msp1, msp2 and glurp as well as microsatellites. Conventional methods of deriving MOI lack fine resolution needed to discriminate minor clones. This study used amplicon sequencing (AmpliSeq) of P. falciparum msp1 ﻿(Pfmsp1) to measure spatial and temporal genetic diversity of P. falciparum.

Methods

264 P. falciparum positive blood samples collected from areas of differing malaria endemicities between 2010 and 2019 were used. Pfmsp1 gene was amplified and amplicon libraries sequenced on Illumina MiSeq. Sequences were aligned against a reference sequence (NC_004330.2) and clustered to detect fragment length polymorphism and amino acid variations.

Results

Children < 5 years had higher parasitaemia (median = 23.5 ± 5 SD, p = 0.03) than the > 5–14 (= 25.3 ± 5 SD), and those > 15 (= 25.1 ± 6 SD). Of the alleles detected, 553 (54.5%) were K1, 250 (24.7%) MAD20 and 211 (20.8%) RO33 that grouped into 19 K1 allelic families (108–270 bp), 14 MAD20 (108–216 bp) and one RO33 (153 bp). AmpliSeq revealed nucleotide polymorphisms in alleles that had similar sizes, thus increasing the K1 to 104, 58 for MAD20 and 14 for RO33. By AmpliSeq, the mean MOI was 4.8 (± 0.78, 95% CI) for the malaria endemic Lake Victoria region, 4.4 (± 1.03, 95% CI) for the epidemic prone Kisii Highland and 3.4 (± 0.62, 95% CI) for the seasonal malaria Semi-Arid region. MOI decreased with age: 4.5 (± 0.76, 95% CI) for children < 5 years, compared to 3.9 (± 0.70, 95% CI) for ages 5 to 14 and 2.7 (± 0.90, 95% CI) for those > 15. Females’ MOI (4.2 ± 0.66, 95% CI) was not different from males 4.0 (± 0.61, 95% CI). In all regions, the number of alleles were high in the 2014–2015 period, more so in the Lake Victoria and the seasonal transmission arid regions.

Conclusion

These findings highlight the added advantages of AmpliSeq in haplotype discrimination and the associated improvement in unravelling complexity of P. falciparum population structure.
Genomic characterization of colistin-resistant Klebsiella pneumoniae isolated from intensive care unit patients in Egypt
Authors: Attalla Eriny T. , Khalil Amal M. , Zakaria Azza S. , Baker Dave J. , Mohamed Nelly M.
Published: September 2023

Background

Egypt has witnessed elevated incidence rates of multidrug-resistant Klebsiella pneumoniae infections in intensive care units (ICUs). The treatment of these infections is becoming more challenging whilst colistin-carbapenem-resistant K. pneumoniae is upsurging. Due to the insufficiently available data on the genomic features of colistin-resistant K. pneumoniae in Egypt, it was important to fill in the gap and explore the genomic characteristics, as well as the antimicrobial resistance, the virulence determinants, and the molecular mechanisms of colistin resistance in such a lethal pathogen.

Methods

Seventeen colistin-resistant clinical K. pneumoniae isolates were collected from ICUs in Alexandria, Egypt in a 6-month period in 2020. Colistin resistance was phenotypically detected by modified rapid polymyxin Nordmann/Poirel and broth microdilution techniques. The isolates susceptibility to 20 antimicrobials was determined using Kirby-Bauer disk diffusion method. Whole genome sequencing and bioinformatic analysis were employed for exploring the virulome, resistome, and the genetic basis of colistin resistance mechanisms.

Results

Out of the tested K. pneumoniae isolates, 82.35% were extensively drug-resistant and 17.65% were multidrug-resistant. Promising susceptibility levels towards tigecycline (88.24%) and doxycycline (52.94%) were detected. Population structure analysis revealed seven sequence types (ST) and K-types: ST383-K30, ST147-K64, ST17-K25, ST111-K63, ST11-K15, ST14-K2, and ST525-K45. Virulome analysis revealed yersiniabactin, aerobactin, and salmochelin siderophore systems in ˃ 50% of the population. Hypervirulence biomarkers, iucA (52.94%) and rmpA/A2 (5.88%) were detected. Extended-spectrum β-lactamase- and carbapenemase-producers accounted for 94.12% of the population, with blaCTX-M-15, blaNDM-5, and blaOXA-48 reaching 64.71%, 82.35%, and 82.35%, respectively. Chromosomal alterations in mgrB (82.35%) were the most prevailing colistin resistance-associated genetic change followed by deleterious mutations in ArnT (23.53%, L54H and G164S), PmrA (11.76%, G53V and D86E), PmrB (11.76%, T89P and T134P), PmrC (11.76%, S257L), PhoQ (5.88%, L322Q and Q435H), and ArnB (5.88%, G47D) along with the acquisition of mcr-1.1 by a single isolate of ST525.

Conclusions

In this study, we present the genotypic colistin resistance mechanisms in K. pneumoniae isolated in Egypt. More effective antibiotic stewardship protocols must be implemented by Egyptian health authorities to restrain this hazard and safeguard the future utility of colistin. This is the first characterization of a complete sequence of mcr-1.1-bearing IncHI2/IncHI2A plasmid recovered from K. pneumoniae clinical isolate belonging to the emerging high-risk clone ST525.
circEIF3I facilitates the recruitment of SMAD3 to early endosomes to promote TGF-β signalling pathway-mediated activation of MMPs in pancreatic cancer
Authors: Zhao Zhongjie , Yang Wenbo , Kong Rui , Zhang Yangyang , Li Le , Song Zengfu , Chen Hongze , Luo Yan , Zhang Tao , Cheng Chundong , Li Guanqun , Liu Danxi , Geng Xinglong , Chen Hua , Wang Yongwei , Pan Shangha , Hu Jisheng , Sun Bei
Published: September 2023

Background

Among digestive tract tumours, pancreatic ductal adenocarcinoma (PDAC) shows the highest mortality trend. Moreover, although PDAC metastasis remains a leading cause of cancer-related deaths, the biological mechanism is poorly understood. Recent evidence demonstrates that circular RNAs (circRNAs) play important roles in PDAC progression.

Methods

Differentially expressed circRNAs in normal and PDAC tissues were screened via bioinformatics analysis. Sanger sequencing, RNase R and actinomycin D assays were performed to confirm the loop structure of circEIF3I. In vitro and in vivo functional experiments were conducted to assess the role of circEIF3I in PDAC. MS2-tagged RNA affinity purification, mass spectrometry, RNA immunoprecipitation, RNA pull-down assay, fluorescence in situ hybridization, immunofluorescence and RNA–protein interaction simulation and analysis were performed to identify circEIF3I-interacting proteins. The effects of circEIF3I on the interactions of SMAD3 with TGFβRI or AP2A1 were measured through co-immunoprecipitation and western blotting.

Results

A microarray data analysis showed that circEIF3I was highly expressed in PDAC cells and correlated with TNM stage and poor prognosis. Functional experiments in vitro and in vivo revealed that circEIF3I accelerated PDAC cells migration, invasion and metastasis by increasing MMPs expression and activity. Mechanistic research indicated that circEIF3I binds to the MH2 domain of SMAD3 and increases SMAD3 phosphorylation by strengthening the interactions between SMAD3 and TGFβRI on early endosomes. Moreover, AP2A1 binds with circEIF3I directly and promotes circEIF3I-bound SMAD3 recruitment to TGFβRI on early endosomes. Finally, we found that circEif3i exerts biological functions in mice similar to those of circEIF3I in humans PDAC.

Conclusions

Our study reveals that circEIF3I promotes pancreatic cancer progression. circEIF3I is a molecular scaffold that interacts with SMAD3 and AP2A1 to form a ternary complex, that facilitates the recruitment of SMAD3 to early endosomes and then activates the TGF-β signalling pathway. Hence, circEIF3I is a potential prognostic biomarker and therapeutic target in PDAC.
“It’s like a safety net for when things go wrong”: key stakeholder and program user perspectives on a peer-led safe space program in Sydney, Australia
Authors: Wadds Phillip , Doran Christopher M. , Shakeshaft Anthony , Tran Dam Anh
Published: September 2023

Background

Safe Spaces are a harm reduction approach commonly utilised in nightlife and festival settings to address alcohol and other drug-related harms. Despite increasing use, there has been little independent evaluation of safe space programs. This study aimed to explore (1) program user satisfaction with and use of a safe space program implemented in Sydney, Australia (The Take Kare Safe Space (TKSS)), and (2) the strengths and weaknesses of TKSS from the perspective of key stakeholders.

Methods

Semi-structured, in-depth, interviews lasting between 30 min to 1 h were conducted with 38 key program stakeholders, including staff from police (n = 4), ambulance (n = 4), a local hospital accident and emergency room (n = 4), local council (n = 2), city ‘rangers’ (n = 2), the TKSS program (n = 4), licensed venues and other nightlife service providers (n = 4), and program users (n = 14). Purposive sampling was used to identify key stakeholders to participate in interviews.

Results

Stakeholders stated that the TKSS program had a number of core benefits, including that it filled a service gap in nightlife settings; improved the efficiency and effectiveness of emergency services and other stakeholders operating in nightlife precincts; provided welfare services through proactive and non-judgmental interventions; and facilitated a means to de-escalate conflict without engaging police. Perceived weaknesses of the program included a lack of public awareness about the program; staff and volunteer levels; and misunderstandings regarding the scope and function of the TKSS program by some stakeholders.

Conclusion

This study demonstrates the complex relationships that exist around the delivery of harm reduction in nightlife settings. In particular, it highlights the relative lack of servicing of public nightlife settings and the value of safe spaces/peer-to-peer safety ambassador programs in linking up care and filling this service gap. Further, it documents the extended benefit across key stakeholder groups of delivering proactive and non-judgemental harm reduction services and, in doing so, provides critical evidence around their efficacy in reducing AOD-related harms in the night-time economy.
Establishment of a high-fidelity patient-derived xenograft model for cervical cancer enables the evaluation of patient’s response to conventional and novel therapies
Authors: Liu Liting , Wu Min , Huang Anni , Gao Chun , Yang Yifan , Liu Hong , Jiang Han , Yu Long , Huang Yafei , Wang Hui
Published: September 2023

Background

Recurrent or metastatic cervical cancer (r/m CC) often has poor prognosis owing to its limited treatment options. The development of novel therapeutic strategies has been hindered by the lack of preclinical models that accurately reflect the biological and genomic heterogeneity of cervical cancer (CC). Herein, we aimed to establish a large patient-derived xenograft (PDX) biobank for CC, evaluate the consistency of the biologic indicators between PDX and primary tumor tissues of patients, and explore its utility for assessing patient’s response to conventional and novel therapies.

Methods

Sixty-nine fresh CC tumor tissues were implanted directly into immunodeficient mice to establish PDX models. The concordance of the PDX models with their corresponding primary tumors (PTs) was compared based on the clinical pathological features, protein biomarker levels, and genomic features through hematoxylin & eosin staining, immunohistochemistry, and whole exome sequencing, respectively. Moreover, the clinical information of CC patients, RNA transcriptome and immune phenotyping of primary tumors were integrated to identify the potential parameters that could affect the success of xenograft engraftment. Subsequently, PDX model was evaluated for its capacity to mirror patient’s response to chemotherapy. Finally, PDX model and PDX-derived organoid (PDXO) were utilized to evaluate the therapeutic efficacy of neratinib and adoptive cell therapy (ACT) combination strategy for CC patients with human epidermal growth factor receptor 2 (HER2) mutation.

Results

We established a PDX biobank for CC with a success rate of 63.8% (44/69). The primary features of established PDX tumors, including clinicopathological features, the expression levels of protein biomarkers including Ki67, α-smooth muscle actin, and p16, and genomics, were highly consistent with their PTs. Furthermore, xenograft engraftment was likely influenced by the primary tumor size, the presence of follicular helper T cells and the expression of cell adhesion-related genes in primary tumor tissue. The CC derived PDX models were capable of recapitulating the patient’s response to chemotherapy. In a PDX model, a novel therapeutic strategy, the combination of ACT and neratinib, was shown to effectively inhibit the growth of PDX tumors derived from CC patients with HER2-mutation.

Conclusions

We established by far the largest PDX biobank with a high engraftment rate for CC that preserves the histopathological and genetic characteristics of patient’s biopsy samples, recapitulates patient’s response to conventional therapy, and is capable of evaluating the efficacy of novel therapeutic modalities for CC.
Integration of proprioception in upper limb prostheses through non-invasive strategies: a review
Authors: Papaleo Ermanno Donato , D’Alonzo Marco , Fiori Francesca , Piombino Valeria , Falato Emma , Pilato Fabio , De Liso Alfredo , Di Lazzaro Vincenzo , Di Pino Giovanni
Published: September 2023

Proprioception plays a key role in moving our body dexterously and effortlessly. Nevertheless, the majority of investigations evaluating the benefits of providing supplemental feedback to prosthetics users focus on delivering touch restitution. These studies evaluate the influence of touch sensation in an attempt to improve the controllability of current robotic devices. Contrarily, investigations evaluating the capabilities of proprioceptive supplemental feedback have yet to be comprehensively analyzed to the same extent, marking a major gap in knowledge within the current research climate. The non-invasive strategies employed so far to restitute proprioception are reviewed in this work. In the absence of a clearly superior strategy, approaches employing vibrotactile, electrotactile and skin-stretch stimulation achieved better and more consistent results, considering both kinesthetic and grip force information, compared with other strategies or any incidental feedback. Although emulating the richness of the physiological sensory return through artificial feedback is the primary hurdle, measuring its effects to eventually support the integration of cumbersome and energy intensive hardware into commercial prosthetic devices could represent an even greater challenge. Thus, we analyze the strengths and limitations of previous studies and discuss the possible benefits of coupling objective measures, like neurophysiological parameters, as well as measures of prosthesis embodiment and cognitive load with behavioral measures of performance. Such insights aim to provide additional and collateral outcomes to be considered in the experimental design of future investigations of proprioception restitution that could, in the end, allow researchers to gain a more detailed understanding of possibly similar behavioral results and, thus, support one strategy over another.
A deep learning model for rapid classification of tea coal disease
Authors: Xu Yang , Mao Yilin , Li He , Sun Litao , Wang Shuangshuang , Li Xiaojiang , Shen Jiazhi , Yin Xinyue , Fan Kai , Ding Zhaotang , Wang Yu
Published: September 2023

Background

The common tea tree disease known as “tea coal disease” (Neocapnodium theae Hara) can have a negative impact on tea yield and quality. The majority of conventional approaches for identifying tea coal disease rely on observation with the human naked eye, which is labor- and time-intensive and frequently influenced by subjective factors. The present study developed a deep learning model based on RGB and hyperspectral images for tea coal disease rapid classification.

Results

Both RGB and hyperspectral could be used for classifying tea coal disease. The accuracy of the classification models established by RGB imaging using ResNet18, VGG16, AlexNet, WT-ResNet18, WT-VGG16, and WT-AlexNet was 60%, 58%, 52%, 70%, 64%, and 57%, respectively, and the optimal classification model for RGB was the WT-ResNet18. The accuracy of the classification models established by hyperspectral imaging using UVE-LSTM, CARS-LSTM, NONE-LSTM, UVE-SVM, CARS-SVM, and NONE-SVM was 80%, 95%, 90%, 61%, 77%, and 65%, respectively, and the optimal classification model for hyperspectral was the CARS-LSTM, which was superior to the model based on RGB imaging.

Conclusions

This study revealed the classification potential of tea coal disease based on RGB and hyperspectral imaging, which can provide an accurate, non-destructive, and efficient classification method for monitoring tea coal disease.
One-hole split endoscopy technique versus unilateral biportal endoscopy technique for L5-S1 lumbar disk herniation: analysis of clinical and radiologic outcomes
Authors: Zhang Yuhong , Feng Bo , Hu Peng , Dai Guohua , Su Weiliang
Published: September 2023

Background

Lumbar disk herniation (LDH) is one of the most common diseases of the spine, especially occurring in L4-5 and L5-S1 intervertebral disks, and surgery is a choice when conservative treatment is ineffective. The purpose of this study is to investigate the clinical efficacy and radiologic outcomes of one-hole split endoscopy (OSE) technique versus unilateral biportal endoscopy (UBE) technique in the treatment of L5-S1 lumbar disk herniation (LDH).

Methods

A total of 133 patients of a single center surgically treated for L5-S1 LDH between 2019 and 2021 were retrospectively included in this study, of which 70 were treated by UBE technique and the rest were treated by OSE technique. Hospitalization time, operative time, intraoperative blood loss, fluoroscopy times, incision length and related complications were recorded. Bone resection area (BRA), articular process resection rate, range of motion (ROM), sagittal translation (ST), disk height (DH), Visual Analog Score (VAS), Oswestry Disability Index (ODI) and Macnab criteria were used to evaluated the clinical efficacy.

Results

There was no statistically significant difference in hospitalization time or fluoroscopy times between the two groups. The operation time was shorter in the UBE group than that in the OSE group; however, the incision length was longer. Intraoperative blood loss and BRA were larger in the UBE group than in the OSE group. There was no significant difference in ROM, ST, DH, or postoperative facet resection rate between the two groups. There was no significant difference in ROM, ST, or postoperative facet resection rate compared with preoperative indicators in each group, but there was a significant difference in DH among distinct groups. At any time point, the lower back and leg VAS and ODI in each group were significantly improved compared to those before the operation, with no significant difference between the two groups. There was one case of dural tear in the UBE group. One case of transient hypoesthesia occurred in each of the two groups. The excellent–good rates of the UBE group and the OSE group were 88.6% and 90.5%, respectively.

Conclusion

The OSE technique is an effective minimally invasive surgical option as well as the UBE technique in the treatment of L5-S1 LDH.
Surgical options for distal radius fractures of type C in elderly patients over 65 years old: a comparison of external fixation with Kirschner wires and volar locking plate
Authors: Zhang He , Liu Man , Duan Si-Yu , Liang Hai-Rui , Xu Rong-Da , Cai Zhen-Cun
Published: September 2023

Background

ue to the lack of consensus on the optimal surgical treatment for distal radius fractures (DRF) in elderly patients over 65 years old, the purpose of this study was to compare the efficacy of external fixation (EF) with Kirschner wires and volar locking plate (VLP) in the treatment of DRF through a retrospective cohort study. We hypothesized that there would be no significant difference in overall complications and functional recovery between the two methods.

Methods

We retrospectively analyzed 62 patients over 65 years old who underwent surgical treatment for C-type DRF between 2019 and 2022. Based on the different treatment methods, they were divided into the EF group and the VLP group. General data, inpatient data, and postoperative complications during follow-up were recorded. The X-ray images before surgery, after surgery, and at the last follow-up were analyzed, and the results of wrist motion range, Gartland–Werley wrist joint score, and DASH score were evaluated 6 months after surgery for both groups.

Result

Thirty patients underwent closed reduction and external fixation combined with Kirschner wire fixation, while 32 underwent open reduction and VLP fixation. The EF group had significantly shorter operation time, intraoperative blood loss, injury-to-surgery time, and hospital stay compared to the VLP group (all p < 0.001). At the last follow-up, the radiographic parameters (ulnar variance and radial inclination) and wrist joint function (wrist dorsiflexion and forearm supination) were better in the VLP group than in the EF group (p = 0.04, p = 0.01, p = 0.001, p = 0.02, respectively). However, there was no significant difference in overall Gartland-Werley wrist joint score, DASH score, and incidence of postoperative complications between the two groups (p = 0.31, p = 0.25, p = 0.47, respectively).

Conclusion

For patients aged 65 and above with distal radius fractures (DRF) of type C, VLP and external fixation with Kirschner wires yield comparable functional outcome and complications rate at the short term. However, VLP allowed restoration of better radiological parameters.
ApoC3 is expressed in oocytes and increased expression is associated with PCOS progression
Authors: Zhou Jiahe , Mo Hui , Feng Qian , Li Li , La Jiahui
Published: September 2023

Background

Polycystic ovary syndrome (PCOS) is a lifelong metabolic disorder and the most common cause of anovulatory infertility affecting women in reproductive age. Our recent study reported that apolipoprotein C3 (ApoC3) could be a potential diagnostic serum marker for metabolism disturbance in PCOS patients, but whether it is present in the ovaries and what role it plays has not yet been described.

Objective

Aimed to investigate ApoC3 expression in ovary of PCOS, and to discuss its potential role in PCOS progression.

Methods

ApoC3 expression in ovarian tissue samples from 12 PCOS patients along with 12 healthy controls were measured via immunohistochemistry (IHC). Also, the level of ApoC3 in follicular fluid from 14 patients diagnosed with PCOS and 13 control subjects were detected by ELISA. The expression and location of ApoC3 in ovaries of PCOS mice were tested weekly for three consecutive weeks during PCOS formation using real time PCR, Western Blot, IHC and immunofluorescence. The relation of ApoC3 and sex hormones was analyzed in mouse plasma. Additionally, the dynamic changes of ApoC3 level in ovaries of healthy mice during postnatal development was also investigated.

Results

ApoC3 levels in ovarian tissue and follicular fluid were significantly higher in PCOS patients than in controls (33.87 ± 4.11 vs. 27.71 ± 3.65, P < 0.01; 0.87 ± 0.09 vs. 0.51 ± 0.32 ng/mL, P < 0.05), respectively. In ovary, ApoC3 was found to be located in the cytoplasm of oocyte, and its expression gradually increased with PCOS progression (P < 0.05). Furthermore, correlation analysis showed that plasma ApoC3 level was closely associated with luteinizing hormone (r = 0.709, P = 0.001), testosterone (r = 0.627, P = 0.005) and anti-mullerian hormone (r = 0.680, P = 0.002) in PCOS mice. In addition, ApoC3 level in oocyte was physiologically increased and peaked on postnatal age 21 (P21), then decreased following P21 in healthy mice.

Conclusions

We identified ApoC3 expression in oocyte. It may be involved in PCOS progression and possibly participate in the regulation of oocyte development.
A small clinical trial of vaporized cannabis for PTSD: suggestive results and directions for future study
Authors: Walsh Zach , Mitchell Ian , Crosby Kim , St. Pierre Michelle , DeClerck Drew , Ong Kaye , Lucas Philippe
Published: September 2023

The last few decades have seen increasing interest in the use of cannabis for post-traumatic stress disorder (PTSD). Recent attempts to evaluate the clinical efficacy of cannabis for PTSD were inconclusive and generalizability was limited by undesirable features of the study drug. The present clinical trial evaluated the effects of a commercially available chemovar that was delivered by vaporization. The study was designed as a randomized placebo-controlled cross-over study with three conditions; however, only five individuals completed the trial, and analysis of the placebo effect was not possible. Results identified positive changes consistent with medium-sized within-subject effects for cannabis in the treatment of PTSD. Positive trending results and high patient need mandate future studies of cannabis for the treatment of PTSD.
Effect of nanosecond pulsed electric fields (nsPEFs) on coronavirus survival
Authors: Cantu Jody C. , Barnes Ronald A. , Gamboa Bryan M. , Keister Allen S. , Echchgadda Ibtissam , Ibey Bennett L.
Published: September 2023

Previous work demonstrated inactivation of influenza virus by GHz frequency electromagnetic fields. Despite theoretical and experimental results, the underlying mechanism driving this inactivation remains unknown. One hypothesis is that the electromagnetic field is causing damage to the virion membrane (and therefore changing spike protein orientation) rendering the virus unable to attach and infect host cells. Towards examining this hypothesis, our group employed nanosecond pulsed electric fields (nsPEFs) as a surrogate to radiofrequency (RF) exposure to enable exploration of dose response thresholds of electric field-induced viral membrane damage. In summary, Bovine coronavirus (BCoV) was exposed, in suspension, to mono and bipolar 600-ns pulsed electric fields (nsPEFs) at two amplitudes (12.5 and 25 kV/cm) and pulse numbers [0 (sham), 1, 5, 10, 100, and 1000] at a 1 Hz (Hz) repetition rate. The temperature rise immediately after exposure(s) was measured using thermocouples to differentiate effects of the electric field (E-field) and heating (i.e., the thermal gradient). Inactivation of BCoV was evaluated by infecting HRT-18G host cells and assessing differences in virus infectivity days after exposure. Our results show that 600 nsPEFs, both bipolar and monopolar, can reduce the infectivity of coronaviruses at various amplitudes, pulse numbers, and pulse polarity. Interestingly, we observed that bipolar exposures appeared to be more efficient at lower exposure intensities than monopolar pulses. Future work should focus on experiments to identify the mechanism underlying nsPEF-induced viral inactivation.
Research on the effectiveness and safety of bronchial thermoplasty in patients with chronic obstructive pulmonary disease
Authors: Wang Tao , Fu Peng , Long Fa , Liu Shengming , Hu Siyu , Wang Qiongping , Huang Zhihui , Long Liang , Huang Wenting , Hu Fengbo , Gan Jingfan , Dong Hongbo , Yan Guomei
Published: September 2023

Objectives

To investigate the clinical efficacy and safety of bronchial thermoplasty (BT) in treating patients with chronic obstructive pulmonary disease (COPD).

Methods

Clinical data of 57 COPD patients were randomized into the control (n = 29, conventional inhalation therapy) or intervention group (n = 28, conventional inhalation therapy plus BT). Primary outcomes were differences in clinical symptom changes, pulmonary function-related indicators, modified Medical Research Council (mMRC), 6-min walk test (6MWT), COPD assessment test (CAT) score and acute exacerbation incidence from baseline to an average of 3 and 12 months. Safety was assessed by adverse events.

Results

FEV1, FEV1(%, predicted) and FVC in both groups improved to varying degrees post-treatment compared with those pre-treatment (P < 0.05). The Intervention group showed greater improving amplitudes of FEV1 (Ftime × between groups = 21.713, P < 0.001) and FEV1(%, predicted) (Ftime × between groups = 31.216, P < 0.001) than the control group, and there was no significant difference in FVC variation trend (Ftime × between groups = 1.705, P = 0.193). mMRC, 6MWT and CAT scores of both groups post-treatment improved to varying degrees (Ps < 0.05), but the improving amplitudes of mMRC (Ftime × between groups = 3.947, P = 0.025), 6MWT (Ftime × between groups = 16.988, P < 0.001) and CAT score (Ftime × between groups = 16.741, P < 0.001) in the intervention group were greater than the control group. According to risk assessment of COPD acute exacerbation, the proportion of high-risk COPD patients with acute exacerbation in the control and intervention groups at 1 year post-treatment (100% vs 65%, 100% vs 28.6%), inpatient proportion (100% vs 62.1%; 100% vs 28.6%), COPD acute exacerbations [3.0 (2.50, 5.0) vs 1.0 (1.0, 2.50); 3.0(3.0, 4.0) vs 0 (0, 1.0)] and hospitalizations [2.0 (2.0, 3.0) vs 1.0 (0, 2.0); 2.0 (2.0, 3.0) vs 0 (0, 1.0)] were significantly lower than those pre-treatment (P < 0.05). Besides, data of the intervention group were significantly lower than the control group at each timepoint after treatment (P < 0.05).

Conclusions

Combined BT therapy is superior to conventional medical treatment in improving lung function and quality of life of COPD patients, and it also significantly reduces the COPD exacerbation risk without causing serious adverse events.
MicroRNAs as the critical regulators of Forkhead box protein family during gynecological and breast tumor progression and metastasis
Authors: Taghehchian Negin , Lotfi Malihe , Zangouei Amir Sadra , Akhlaghipour Iman , Moghbeli Meysam
Published: September 2023

Gynecological and breast tumors are one of the main causes of cancer-related mortalities among women. Despite recent advances in diagnostic and therapeutic methods, tumor relapse is observed in a high percentage of these patients due to the treatment failure. Late diagnosis in advanced tumor stages is one of the main reasons for the treatment failure and recurrence in these tumors. Therefore, it is necessary to assess the molecular mechanisms involved in progression of these tumors to introduce the efficient early diagnostic markers. Fokhead Box (FOX) is a family of transcription factors with a key role in regulation of a wide variety of cellular mechanisms. Deregulation of FOX proteins has been observed in different cancers. MicroRNAs (miRNAs) as a group of non-coding RNAs have important roles in post-transcriptional regulation of the genes involved in cellular mechanisms. They are also the non-invasive diagnostic markers due to their high stability in body fluids. Considering the importance of FOX proteins in the progression of breast and gynecological tumors, we investigated the role of miRNAs in regulation of the FOX proteins in these tumors. MicroRNAs were mainly involved in progression of these tumors through FOXM, FOXP, and FOXO. The present review paves the way to suggest a non-invasive diagnostic panel marker based on the miRNAs/FOX axis in breast and gynecological cancers.
Comparison of methods for deriving phenotypes from incomplete observation data with an application to age at puberty in dairy cattle
Authors: Stephen Melissa A. , Burke Chris R. , Pryce Jennie E. , Steele Nicole M. , Amer Peter R. , Meier Susanne , Phyn Claire V. C. , Garrick Dorian J.
Published: September 2023

Background

Many phenotypes in animal breeding are derived from incomplete measures, especially if they are challenging or expensive to measure precisely. Examples include time-dependent traits such as reproductive status, or lifespan. Incomplete measures for these traits result in phenotypes that are subject to left-, interval- and right-censoring, where phenotypes are only known to fall below an upper bound, between a lower and upper bound, or above a lower bound respectively. Here we compare three methods for deriving phenotypes from incomplete data using age at first elevation (> 1 ng/mL) in blood plasma progesterone (AGEP4), which generally coincides with onset of puberty, as an example trait.

Methods

We produced AGEP4 phenotypes from three blood samples collected at about 30-day intervals from approximately 5,000 Holstein–Friesian or Holstein–Friesian × Jersey cross-bred dairy heifers managed in 54 seasonal-calving, pasture-based herds in New Zealand. We used these actual data to simulate 7 different visit scenarios, increasing the extent of censoring by disregarding data from one or two of the three visits. Three methods for deriving phenotypes from these data were explored: 1) ordinal categorical variables which were analysed using categorical threshold analysis; 2) continuous variables, with a penalty of 31 d assigned to right-censored phenotypes; and 3) continuous variables, sampled from within a lower and upper bound using a data augmentation approach.

Results

Credibility intervals for heritability estimations overlapped across all methods and visit scenarios, but estimated heritabilities tended to be higher when left censoring was reduced. For sires with at least 5 daughters, the correlations between estimated breeding values (EBVs) from our three-visit scenario and each reduced data scenario varied by method, ranging from 0.65 to 0.95. The estimated breed effects also varied by method, but breed differences were smaller as phenotype censoring increased.

Conclusion

Our results indicate that using some methods, phenotypes derived from one observation per offspring for a time-dependent trait such as AGEP4 may provide comparable sire rankings to three observations per offspring. This has implications for the design of large-scale phenotyping initiatives where animal breeders aim to estimate variance parameters and estimated breeding values (EBVs) for phenotypes that are challenging to measure or prohibitively expensive.
Immersive VR-based instruction in vocational schools: effects on domain-specific knowledge and wellbeing of retail trainees
Authors: Kablitz David , Conrad Matthias , Schumann Stephan
Published: September 2023

Immersive virtual reality (IVR) based simulation and training is gaining increasing importance in vocational education and training (VET). However, while IVR is primarily investigated and utilized in technical domains, its implementation and the resulting effects in commercial education remain largely unexplored. Moreover, the experience of motion sickness is a widely reported phenomenon while using IVR, which can interfere with cognitive processes and should therefore be considered more closely in terms of learning and instruction. This explorative study focuses on domain-specific knowledge acquisition in vocational apprenticeship for retailers and the accompanying side effects on students’ wellbeing in an IVR-based learning environment. For this purpose, an IVR-based scenario in a virtual supermarket was developed and tested with trainees in the field of retail at a German commercial vocational school. Using a quasi-experimental pretest-posttest design, we compared the effects of IVR-based and conventional instruction on domain-specific knowledge acquisition in a sample of first-year trainees (N = 79). The findings indicate an advantage of IVR in the acquisition of domain-specific knowledge (ɳ2 = .261). Although moderate motion sickness symptoms were reported in the experimental group, no direct links between the experience of motion sickness and learning outcomes could be identified. These findings advance the current knowledge about learning-related effects of IVR-based instruction in the field of VET and provide further understanding about the special conditions of IVR scenarios conducive to learning.
Classification of long-term clinical course of Parkinson’s disease using clustering algorithms on social support registry database
Authors: Park Dougho , Lee Su Yun , Kim Jong Hun , Kim Hyoung Seop
Published: September 2023

Although Parkinson’s disease (PD) has a heterogeneous disease course, it remains challenging to establish subtypes. We described and clustered the natural course of Parkinson’s disease (PD) with respect to functional disability and mortality. This retrospective cohort study utilized the Korean National Health Insurance Service database, which contains the social support registry database for patients with PD. We extracted patients newly diagnosed with PD in 2009 and followed them up until the end of 2018. Functional disability was assessed based on the long-term care insurance (LTCI) and National Disability Registry data. Further, we measured all-cause mortality during the observation period. We included 2944 eligible patients. The surviving patients were followed up for 113.7 ± 3.3 months. Among the patients who died, patients with and without disability registration were followed up for 61.4 ± 30.1 and 43.2 ± 32.0 months, respectively. The cumulative survival rate was highest in cluster 1 and decreased from Cluster 1 to Cluster 6. In the multivariable Cox regression analysis, the defined clusters were significantly associated with increased long-term mortality (adjusted hazard ratio [aHR], 3.440; 95% confidence interval [CI], 3.233–3.659; p < 0.001). Further, age (aHR, 1.038; 95% CI, 1.031–1.045; p < 0.001), diabetes (aHR, 1.146; 95% CI, 1.037–1.267; p = 0.007), and chronic kidney disease (aHR, 1.382; 95% CI, 1.080–1.768; p = 0.010) were identified as independent risk factors for increased risk of long-term mortality. Contrastingly, the female gender (aHR, 0.753; 95% CI, 0.681–0.833; p < 0.001) and a higher LTCI grade (aHR, 0.995; 95% CI, 0.992–0.997; p < 0.001) were associated with a significantly decreased long-term mortality risk. We identified six clinical course clusters for PD using longitudinal data regarding the social support registry and mortality. Our results suggest that PD progression is heterogeneous in terms of disability and mortality.
Recognizing patient partner contributions to health research: a systematic review of reported practices
Authors: Fox Grace , Lalu Manoj M. , Sabloff Tara , Nicholls Stuart G. , Smith Maureen , Stacey Dawn , Almoli Faris , Fergusson Dean A.
Published: September 2023

Background

Patient engagement in research refers to collaboration between researchers and patients (i.e., individuals with lived experience including informal caregivers) in developing or conducting research. Offering non-financial (e.g., co-authorship, gift) or financial (e.g., honoraria, salary) compensation to patient partners can demonstrate appreciation for patient partner time and effort. However, little is known about how patient partners are currently compensated for their engagement in research. We sought to assess the prevalence of reporting patient partner compensation, specific compensation practices (non-financial and financial) reported, and identify benefits, challenges, barriers and enablers to offering financial compensation.

Methods

We conducted a systematic review of studies citing the Guidance for Reporting the Involvement of Patients and the Public (GRIPP I and II) reporting checklists (October 2021) within Web of Science and Scopus. Studies that engaged patients as research partners were eligible. Two independent reviewers screened full texts and extracted data from included studies using a standardized data abstraction form. Data pertaining to compensation methods (financial and non-financial) and reported barriers and enablers to financially compensating patient partners were extracted. No formal quality assessment was conducted since the aim of the review is to describe the scope of patient partner compensation. Quantitative data were presented descriptively, and qualitative data were thematically analysed.

Results

The search identified 843 studies of which 316 studies were eligible. Of the 316 studies, 91% (n = 288) reported offering a type of compensation to patient partners. The most common method of non-financial compensation reported was informal acknowledgement on research outputs (65%, n = 206) and co-authorship (49%, n = 156). Seventy-nine studies (25%) reported offering financial compensation (i.e., honoraria, salary), 32 (10%) reported offering no financial compensation, and 205 (65%) studies did not report on financial compensation. Two key barriers were lack of funding to support compensation and absence of institutional policy or guidance. Two frequently reported enablers were considering financial compensation when developing the project budget and adequate project funding.

Conclusions

In a cohort of published studies reporting patient engagement in research, most offered non-financial methods of compensation to patient partners. Researchers may need guidance and support to overcome barriers to offering financial compensation.
Working collaboratively with an online advisory group of people with learning disabilities in covid-times: carrier pigeons, cats and drones
Authors: Leishman Eppie , Quilgars Deborah , Abbott David , Clark Sam , Cooper Becca , Pollin Andy , Hodgkins Stephen , Scarrott Paul
Published: September 2023

While much attention and emphasis have been given to the role and value of advisory groups in social science research, less has been published on the experiences of those involved in such collaborative efforts. This article reflects on the experiences of academics, collaborators and self-advocacy experts who formed an advisory group for a research project focused on people with learning disabilities’ experiences of renting their own homes. Our paper describes the collaboration, how it changed because of Covid and because of changing relationships, and what worked well and what was challenging. This is in part because these more transparent accounts of working together are sometimes missing from research. We discuss issues relating to bureaucratic research systems which are largely inaccessible to people with learning disabilities and how we approached these. We also highlight the joys and benefits of the research approach that we adopted as well as the challenging and more difficult aspects.