bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of cognitive functional therapy and movement system impairment treatment in chronic low back pain patients: a randomized controlled trial
Authors: Ahmad Sahar Nazary Soltan , Letafatkar Amir , Brewer Britton W. , Sharifnezhad Ali
Published: August 2023

Background

This study aimed to compare the effects of cognitive functional therapy (CFT) and movement system impairment (MSI)-based treatment on pain intensity, disability, Kinesiophobia, and gait kinetics in patients with chronic non-specific low back pain (CNSLBP).

Methods

In a single-blind randomized clinical trial, we randomly assigned 91 patients with CNSLBP into CFT (n = 45) and MSI-based treatment (n = 46) groups. An 8-week training intervention was given to both groups. The researchers measured the primary outcome, which was pain intensity (Numeric rating scale), and the secondary outcomes, including disability (Oswestry disability index), Kinesiophobia (Tampa Kinesiophobia Scale), and vertical ground reaction force (VGRF) parameters at self-selected and faster speed (Force distributor treadmill). We evaluated patients at baseline, at the end of the 8-week intervention (post-treatment), and six months after the first treatment. We used mixed-model ANOVA to evaluate the effects of the interaction between time (baseline vs. post-treatment vs. six-month follow-up) and group (CFT vs. MSI-based treatment) on each measure.

Results

CFT showed superiority over MSI-based treatment in reducing pain intensity (P < 0.001, Effect size (ES) = 2.41), ODI (P < 0.001, ES = 2.15), and Kinesiophobia (P < 0.001, ES = 2.47) at eight weeks. The CFT also produced greater improvement in VGRF parameters, at both self-selected (FPF[P < 0.001, ES = 3], SPF[P < 0.001, ES = 0.5], MSF[P < 0.001, ES = 0.67], WAR[P < 0.001, ES = 1.53], POR[P < 0.001, ES = 0.8]), and faster speed, FPF(P < 0.001, ES = 1.33, MSF(P < 0.001, ES = 0.57), WAR(P < 0.001, ES = 0.67), POR(P < 0.001, ES = 2.91)] than the MSI, except SPF(P < 0.001, ES = 0.0) at eight weeks.

Conclusion

This study suggests that the CFT is associated with better results in clinical and cognitive characteristics than the MSI-based treatment for CNSLBP, and the researchers maintained the treatment effects at six-month follow-up. Also, This study achieved better improvements in gait kinetics in CFT. CTF seems to be an appropriate and applicable treatment in clinical setting.

Trial registration

The researchers retrospectively registered the trial 10/11/2022, at https://www.umin.ac.jp/ with identifier number (UMIN000047455).
Treatment effects after maxillary expansion using invisalign first system vs. acrylic splint expander in mixed dentition: a prospective cohort study
Authors: Lu Lanxin , Zhang Lingling , Li Chengri , Yi Fang , Lei Lei , Lu Yanqin
Published: August 2023

Background

Invisalign First System (First) is a new type of orthodontic appliance for maxillary arch expansion in mixed dentition children. Till now, few studies have evaluated the expansion effects of First versus other appliances. What’s more, most studies of arch expansion did not include a natural group to rule out growth effects. This prospective cohort study aimed to evaluate the dental and dentoalveolar effects using First or acrylic splint rapid maxillary expander (RME) in adolescents excluding growth factors.

Materials and methods

After screening by strict inclusion criteria and propensity score matching (PSM), fifty-one patients were included: First group (n = 17), RME group (n = 17), and natural growth (NG) group (n = 17). Nine indicators including dental arch width, dentoalveolar arch width, and inclination of the molars were measured on digital dental casts at baseline (T0) and six-month follow-up (T1). Paired t-tests were used for intra-group results, and two-sample independent t-tests were used for inter-group comparisons.

Results

There was no significant increase in all indicators within six months in the NG group (p > 0.05). In the First group and RME group, all width indicators were significantly increased after treatment (p < 0.05). The RME group exhibited greater expansion than the First group in intercanine width, first interpremolar width, second interdeciduous molar width, first intermolar width, arch perimeter, intercanine dentoalveolar width, intermolar dentoalveolar width, and inclination of the molars (p < 0.05). Whereas, there was no significant difference in arch depth between the two treated groups.

Conclusions

Both First and RME can expand the maxillary arch in mixed dentition. In case of mild to moderate maxillary transverse deficiency (MTD), Invisalign First System could be a reasonable option. RME shows significant better efficiency of dental arch expansion than First, recommended for patients with severe MTD.

Trial registration

This prospective study was registered on ClinicalTrials.gov (01/02/2022, registration number: ChiCTR2200056220). The trial was approved by the Ethical Committee of the Hunan Xiangya Stomatological Hospital Central South University (20,200,088), and informed consent was obtained from all subjects and their legal guardian(s).
Association of physical activity with psychological distress and happiness in mothers of children with autism spectrum disorders during the COVID-19 pandemic
Authors: Tsunoda Kenji , Nagase Kai , Fujita Kumi
Published: August 2023

Background

The coronavirus disease 2019 (COVID-19) pandemic may have severely impacted the psychological status of mothers of children with autism spectrum disorder (ASD). Although a previous study reported that physical activity (PA) moderated psychological distress in parents of children with ASD during the COVID-19 pandemic, the effect of PA on the happiness levels of such parents during the pandemic remains unclear. This study investigated the associations among PA, psychological distress, and happiness in mothers of children with ASD during the COVID-19 pandemic.

Methods

This cross-sectional study was designed to evaluate mothers of children with disabilities. Questionnaires were collected from mothers living in Yamaguchi and Okayama Prefectures, Japan, between February and December 2022. During this period, three large waves of the COVID-19 pandemic occurred in Japan. Of the 601 respondents, 334 mothers had children with ASD and offered valid data. PA was assessed using the short form of the International Physical Activity Questionnaire. Psychological distress and happiness were assessed using the six-item Kessler Psychological Distress Scale (K6) and the Subjective Happiness Scale (SHS).

Results

The mothers had markedly higher K6 scores (6.49) and more than half of them had moderate-to-severe psychological distress, whereas the SHS scores (4.46) were similar to that of the general Japanese population. In a multivariable-adjusted model based on the analysis of covariance, the K6 score was not associated with any PA items. In contrast, SHS scores were positively associated with moderate-intensity PA (MPA) and total moderate- to vigorous-intensity PA (MVPA), independent of K6. In the post-hoc test, mothers who did some (4.52) or enough (≥ 150 min/week) MPA (4.56) had a higher SHS score than those who did not (4.09). Similarly, mothers who engaged in sufficient (≥ 600 MET-min/week) total MVPA had higher SHS scores (4.57) than those who did not engage in MVPA (4.12).

Conclusions

The mothers of children with ASD during the COVID-19 pandemic had markedly higher psychological distress, though none of the PA items were associated with stress levels. However, PA was positively associated with happiness in mothers of children with ASD independent of their stress levels.
The mechanism of Qijing Mingmu decoction on cellular senescence of conjunctivochalasis
Authors: Xiang Minhong , Liu Jiang , Ma Kai , Sha Yongyi , Zhan Yueping , Zhang Wei , Kong Xueqing
Published: August 2023

Background

Qijing Mingmu decoction (QJMM), a compound Chinese medicine preparation, which consists of Lycium barbarum, Polygonatum, Ophiopogon japonicus, Poria cocos, Glycyrrhiza, Eclipta prostrata and Ligusticum striatum, has been confirmed to be effective for the treatment of conjunctivochalasis (CCH) in clinic and reduce cellular senescence. However, the underlying mechanism is still unknown. Our previous study revealed that p38-mediated cellular senescence contributed to the pathogenesis of CCH.

Methods

To explore whether p38 might be the potential therapeutic target of QJMM for CCH, CCH fibroblasts were treated with QJMM granule and then the effect of QJMM granule on the expression and promoter activity of p38α was determined by western blot and dual luciferase reporter gene assay, respectively. Meanwhile, the influence of QJMM granule on cell proliferation, oxidative stress, cellular senescence and the expression of the cellular senescence-associated genes were measured by corresponding methods.

Results

QJMM granule significantly decreased the protein expression of p38α and p-p38α in CCH fibroblasts in a dose-dependent manner and inhibited p38α promoter activity. QJMM granule as well as the p38 inhibitor SB203580 reduced the level of reactive oxygen species and increased the activity of superoxide dismutase in CCH fibroblasts. QJMM granule and SB203580 promoted cell proliferation and reduced the percentage of SA-β-Gal-positive cells. The mRNA and protein expression of p53 and p21 was remarkably down-regulated by QJMM granule as well as SB203580 and that of SMP30 was up-regulated in CCH fibroblasts.

Conclusions

Our findings demonstrated that QJMM granule was effective for alleviating cellular senescence of CCH fibroblasts by p38 MAPK signaling and the followed p53/p21 signaling.
Improving self-directed learning ability of medical students using the blended teaching method: a quasi-experimental study
Authors: Lu Si Ying , Ren Xiang Peng , Xu Huang , Han Dong
Published: August 2023

Background

Self-directed learning (SDL) is one of the most important abilities for medical students in terms of their future clinical medical practice. During the blended teaching process, teachers can design a variety of learning activities to cultivate students’ SDL abilities. This study aimed to assess the differences between the SDL abilities of medical students using blended and traditional didactic teaching.

Methods

This study included 239 medical students from eight administrative classes. The students were divided into two groups: (1) the experimental group (EG), which included 119 students from four administrative classes, and (2) the control group (CG), which included 120 students from the remaining four classes. From February to July 2022, blended teaching methods were applied to the EG group, and SDL abilities were assessed in comparison to the CG group receiving traditional didactic teaching methods.

Results

At the end of the semester, significant differences (p < 0.05) were observed between EG and CG in all six SDL ability factors. Furthermore, when k-means cluster analysis was used to analyze the learning behavior of students in the EG after classifying them as comprehensive, interactive, and passive types, significant differences were observed in all six Self-directed learning factors of students with the comprehensive type, whereas significant differences were observed in four factors (setting learning goals and plans, self-monitoring and regulation, information processing, and communication and cooperation) of students with the interactive type. For students with passive type, only one factor of SDL (information processing) showed significant improvement. There were on differences between comprehensive, interactive, and passive types of CG.

Conclusion

The blended teaching approach is better than the conventional didactic teaching for cultivating clinical medical students’ SDL abilities.
Association of integrin-β2 polymorphism and expression with the risk of rheumatoid arthritis and osteoarthritis in Egyptian patients
Authors: Selim Aliaa M. , Elsabagh Yumn A. , El-Sawalhi Maha M. , Ismail Nabila A. , Senousy Mahmoud A.
Published: August 2023

Background

The genetic architecture of rheumatoid arthritis (RA) and osteoarthritis (OA) are still unclear. Although RA and OA have quite different causes, they share synovial inflammation, risk factors, and some disease-associated genes, including the integrin subunit β2 (ITGB2)/CD18 gene involved in extracellular matrix interactions and immune cell signaling. However, the functional role of ITGB2 genetic variants, its circulating expression pattern, and their clinical usefulness in RA and OA remain unexplored. Our study appraised the association of ITGB2 rs2070946 single nucleotide polymorphism with the vulnerability to RA and OA and its influence on ITGB2 mRNA expression, along with the potential of serum ITGB2 expression in RA and OA diagnosis.

Methods

This study included 70 RA patients, 70 primary OA patients, and 60 healthy volunteers. Genotyping and gene expression analysis were performed using qPCR. Bioinformatics analysis was employed to construct the protein-protein interaction (PPI) network of ITGB2.

Results

Serum ITGB2 mRNA expression was upregulated in both RA and OA compared to healthy controls. ITGB2 rs2070946 was associated with escalating risk of both diseases. RA patients harboring the rs2070946 CC or TC + CC genotypes had higher serum ITGB2 expression than the TT genotype carriers. Likewise, OA patients having the minor homozygote CC genotype had higher serum ITGB2 expression than those carrying the TT, TC or TT + TC genotypes. Serum ITGB2 expression showed profound diagnostic potential for RA and OA in receiver-operating characteristic analysis. In RA, serum ITGB2 expression positively correlated with rheumatoid factor and disease activity score 28 (DAS28). The ITGB2-PPI network enriched in cell-cell adhesion, ICAM-3 receptor activity, T-cell activation, leukocyte adhesion, complement binding, and NF-κB, tumor necrosis factor, and interleukin signaling pathways.

Conclusion

These findings embrace the impact of ITGB2 rs2070946 as a novel genetic biomarker of both RA and OA, which could alter the ITGB2 expression. Serum ITGB2 expression could aid in timely diagnosis of RA and OA.
Prognostic factors for the outcomes of COVID-19 patients infected with SARS-CoV-2 Omicron and Delta variants
Authors: Gunadi  , Hakim Mohamad Saifudin , Wibawa Hendra , Vujira Khanza Adzkia , Puspitarani Dyah Ayu , Supriyati Endah , Trisnawati Ika , Iskandar Kristy , Khair Riat El , Afiahayati  , Siswanto  , Puspadewi Yunika , Irianingsih Sri Handayani , Nugrahaningsih Dwi Aris Agung , Eryvinka Laudria Stella , Utami Fadila Dyah Trie , Devana Edita Mayda , Aditama Lanang , Kinasih Nathania Christi Putri , Hediningsih Yekti , Ananda Nur Rahmi , Marcellus  , Arguni Eggi , Nuryastuti Titik , Wibawa Tri
Published: August 2023

Background

The SARS-CoV-2 Omicron variant has replaced the previously dominant Delta variant because of high transmissibility. However, studies on the impact of the Omicron variant on the severity of COVID-19 are still limited in developing countries. Our study aimed to determine the prognostic factors for the outcomes of patients infected with SARS-CoV-2 Omicron and Delta variants, including age, sex, comorbidities, and smoking.

Methods

In this retrospective cross-sectional study, we involved 352 patients with COVID-19 from Yogyakarta and Central Java provinces, Indonesia, from May 2021 to February 2022, consisting of 164 males and 188 females. We included all patients with the PCR’s Ct value of less than 30 for further whole-genome sequencing.

Results

Ct value and mean age of COVID-19 patients were not significantly different between both groups (p = 0.146 and 0.273, respectively). Patients infected with Omicron (n = 139) and Delta (n = 213) variants showed similar hospitalization (p = 0.396) and mortality rates (p = 0.565). Multivariate analysis of both groups showed that older age (≥ 65 years) had a higher risk for hospitalization (OR = 3.86 [95% CI = 1.29–11.5]; p = 0.015) and fatalities (OR = 3.91 [95% CI = 1.35–11.42]; p = 0.012). In both groups, patients with cardiovascular disease had a higher risk for hospitalization (OR = 5.36 [95% CI = 1.08–26.52]; p = 0.039), whereas patients with diabetes revealed a higher risk for fatalities (OR = 9.47 [95% CI = 3.23–27.01]; p = < 0.001).

Conclusions

Our study shows that patients infected with Omicron and Delta variants reveal similar clinical outcomes, including hospitalization and mortality. Our findings further confirm that older age, cardiovascular disease, and diabetes are substantial prognostic factors for the outcomes of COVID-19 patients. Our findings imply that COVID-19 patients with older age, cardiovascular disease, or diabetes should be treated comprehensively and cautiously to prevent further morbidity and mortality. Furthermore, incomplete data on vaccination status hampered us from analyzing further its impact on hospitalization and mortality in our patients.
IL-25 induces airway remodeling in asthma by orchestrating the phenotypic changes of epithelial cell and fibrocyte
Authors: Yao Xiujuan , Chen Qinglin , Wang Xiangdong , Liu Xiaofang , Zhang Luo
Published: August 2023

Background

Previous studies have shown that IL-25 levels are increased in patients with asthma with fixed airflow limitation (FAL). However, the mechanism by which IL-25 contributes to airway remodeling and FAL remains unclear. Here, we hypothesized that IL-25 facilitates pro-fibrotic phenotypic changes in bronchial epithelial cells (BECs) and circulating fibrocytes (CFs), orchestrates pathological crosstalk from BECs to CFs, and thereby contributes to airway remodeling and FAL.

Methods

Fibrocytes from asthmatic patients with FAL and chronic asthma murine models were detected using flow cytometry, multiplex staining and multispectral imaging analysis. The effect of IL-25 on BECs and CFs and on the crosstalk between BECs and CFs was determined using cell culture and co-culture systems.

Results

We found that asthmatic patients with FAL had higher numbers of IL-25 receptor (i.e., IL-17RB)+-CFs, which were negatively correlated with forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC). The number of airway IL-17RB+-fibrocytes was significantly increased in ovalbumin (OVA)- and IL-25-induced asthmatic mice versus the control subjects. BECs stimulated with IL-25 exhibited an epithelial-mesenchymal transition (EMT)-like phenotypic changes. CFs stimulated with IL-25 produced high levels of extracellular matrix (ECM) proteins and connective tissue growth factors (CTGF). These profibrotic effects of IL-25 were partially blocked by the PI3K-AKT inhibitor LY294002. In the cell co-culture system, OVA-challenged BECs facilitated the migration and expression of ECM proteins and CTGF in CFs, which were markedly blocked using an anti-IL-17RB antibody.

Conclusion

These results suggest that IL-25 may serve as a potential therapeutic target for asthmatic patients with FAL.
Antibacterial peptide PMAP-37(F34-R), expressed in Pichia pastoris, is effective against pathogenic bacteria and preserves plums
Authors: Dong Chunming , Xu Lijun , Lu Weitao , Li Mengru , Zhang Rui , Sun Yanyan , Liu Jian , Chu Xinlei
Published: August 2023

Background

Recently, researchers have focused on the search for alternatives to conventional antibiotics. Antimicrobial peptides are small bioactive peptides that regulate immune activation and have antibacterial activity with a reduced risk of bacterial resistance. Porcine myeloid antibacterial peptide 37 (PMAP-37) is a small-molecule peptide with broad-spectrum antibacterial activity isolated from pig bone marrow, and PMAP-37(F34-R) is its analogue. In this study, PMAP-37(F34-R) was recombinantly expressed in Pichia pastoris, and the recombinant peptide was further investigated for its antibacterial properties, mechanism and preservative in plums.

Results

To obtain a Pichia pastoris strain expressing PMAP-37(F34-R), we constructed a plasmid expressing recombinant PMAP-37(F34-R) (pPICZα-PMAP-37(F34-R)-A) and introduced it into Pichia pastoris. Finally, we obtained a highly active recombinant peptide, PMAP-37(F34-R), which inhibited the activity of both Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration is 0.12–0.24 µg/mL, and it can destroy the integrity of the cell membrane, leading to cell lysis. It has good stability and is not easily affected by the external environment. Hemolysis experiments showed that 0.06 µg/mL-0.36 µg/mL PMAP-37(F34-R) had lower hemolysis ability to mammalian cells, and the hemolysis rate was below 1.5%. Additionally, 0.36 µg/mL PMAP-37(F34-R) showed a good preservative effect in plums. The decay and weight loss rates of the treated samples were significantly lower than those of the control group, and the respiratory intensity of the fruit was delayed in the experimental group.

Conclusions

In this study, we constructed a recombinant Pichia pastoris strain, which is a promising candidate for extending the shelf life of fruits and has potential applications in the development of new preservatives.

Graphical Abstract
MiRNA-related metastasis in oral cancer: moving and shaking
Authors: Eslami Meghdad , Khazeni Saba , Khanaghah Xaniar Mohammadi , Asadi Mohammad Hossein , Ansari Mohamad Amin , Garjan Javad Hayati , Lotfalizadeh Mohammad Hassan , Bayat Mobina , Taghizadieh Mohammad , Taghavi Seyed Pouya , Hamblin Michael R , Nahand Javid Sadri
Published: August 2023

Across the world, oral cancer is a prevalent tumor. Over the years, both its mortality and incidence have grown. Oral cancer metastasis is a complex process involving cell invasion, migration, proliferation, and egress from cancer tissue either by lymphatic vessels or blood vessels. MicroRNAs (miRNAs) are essential short non-coding RNAs, which can act either as tumor suppressors or as oncogenes to control cancer development. Cancer metastasis is a multi-step process, in which miRNAs can inhibit or stimulate metastasis at all stages, including epithelial-mesenchymal transition, migration, invasion, and colonization, by targeting critical genes in these pathways. On the other hand, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), two different types of non-coding RNAs, can regulate cancer metastasis by affecting gene expression through cross-talk with miRNAs. We reviewed the scientific literature (Google Scholar, Scopus, and PubMed) for the period 2000–2023 to find reports concerning miRNAs and lncRNA/circRNA-miRNA-mRNA networks, which control the spread of oral cancer cells by affecting invasion, migration, and metastasis. According to these reports, miRNAs are involved in the regulation of metastasis pathways either by directly or indirectly targeting genes associated with metastasis. Moreover, circRNAs and lncRNAs can induce or suppress oral cancer metastasis by acting as competing endogenous RNAs to inhibit the effect of miRNA suppression on specific mRNAs. Overall, non-coding RNAs (especially miRNAs) could help to create innovative therapeutic methods for the control of oral cancer metastases.
A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods
Authors: Alfano Massimo , Alchera Elisa , Sacchi Angelina , Gori Alessandro , Quilici Giacomo , Locatelli Irene , Venegoni Chiara , Lucianò Roberta , Gasparri Anna Maria , Colombo Barbara , Taiè Giulia , Jose Jithin , Armanetti Paolo , Menichetti Luca , Musco Giovanna , Salonia Andrea , Corti Angelo , Curnis Flavio
Published: August 2023

Background

Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments.

Results

In an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5β1 integrin expressed by bladder cancer cells. This product (called GNRs@PEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5β1 and α5β1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5β1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5β1-negative), pointing to a specific targeting mechanism.

Conclusion

GNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions.

Graphical Abstract
Identifying prognostic markers in spatially heterogeneous breast cancer microenvironment
Authors: Liu Guohong , Wang Liping , Ji Lili , He Dan , Zeng Lihua , Zhuo Guangzheng , Zhang Qian , Wang Dujuan , Pan Yunbao
Published: August 2023

To gain deeper insights into the microenvironment of breast cancer, we utilized GeoMx Digital Spatial Profiling (DSP) technology to analyze transcripts from 107 regions of interest in 65 untreated breast cancer tissue samples. Our study revealed spatial heterogeneity in the expression of marker genes in tumor cell enriched, immune cell enriched, and normal epithelial areas. We evaluated a total of 55 prognostic markers in tumor cell enriched regions and 15 in immune cell enriched regions, identifying that tumor cell enriched regions had higher levels of follicular helper T cells, resting dendritic cells, and plasma cells than immune cell enriched regions, while the levels of resting CD4 memory in T cells and regulatory (Treg) T cells were lower. Additionally, we analyzed the heterogeneity of HLA gene families, immunological checkpoints, and metabolic genes in these areas. Through univariate Cox analysis, we identified 5 prognosis-related metabolic genes. Furthermore, we conducted immunostaining experiments, including EMILIN2, SURF4, and LYPLA1, to verify our findings. Our investigation into the spatial heterogeneity of the breast cancer tumor environment has led to the discovery of specific diagnostic and prognostic markers in breast cancer.
Successful experience of tofacitinib treatment in patients with Fibrodysplasia Ossificans Progressiva
Authors: Nikishina Irina P. , Arsenyeva Svetlana V. , Matkava Valeria G. , Arefieva Alia N. , Kaleda Mariya I. , Smirnov Alexandr V. , Blank Leonid M. , Kostik Mikhail M.
Published: August 2023

Fibrodysplasia ossificans progressive (FOP) is an ultra-rare genetic disorder that is caused by a mutation in the ACVR1 gene and provokes severe heterotopic ossification. Since flares of the disease are associated with inflammation, it is assumed that JAK inhibitors can control active FOP due to blocking multiple signaling pathways.
Screening and optimisation of in vitro pollen germination medium for sweetpotato (Ipomoea batatas)
Authors: Weng Zongkuan , Deng Yitong , Tang Fen , Zhao Lukuan , Zhao Lingxiao , Wang Yuan , Dai Xibin , Zhou Zhilin , Cao Qinghe
Published: August 2023

Background

Sweetpotato is an important vegetable and food crop that is bred through sexual crosses and systematic selection. The use of in vitro germination of sweetpotato pollen to test its viability has important theoretical and practical implications for improving the efficiency of sweetpotato crossbreeding by controlling pollination and conducting research on sweetpotato pollen biology.

Results

In this study, we observed the morphological structure of sweetpotato pollen under a scanning electron microscope (SEM), developed an effective method for the in vitro germination of sweetpotato pollen, and examined the viability of sweetpotato pollen after treating plants at different temperatures before blossoming. Sweetpotato pollen grains are spherical, with an average diameter of 87.07 ± 3.27 μm (excluding spines), with multiple germination pores and reticulate pollen surface sculpture. We applied numerous media to sweetpotato pollen germination in vitro to screen the initial medium and optimised the medium components through single-factor design. The most effective liquid medium for in vitro sweetpotato pollen germination contained 50 g/L Sucrose, 50 g/L Polyethylene glycol 4000 (PEG4000), 100 mg/L Boric acid and 300 mg/L Calcium nitrate, with a pH = 6.0. The optimum growth temperature for pollen development in sweetpotato was from 25 to 30 °C. Neither staining nor in situ germination could accurately determine the viability of sweetpotato pollen.

Conclusions

In vitro germination can be used to effectively determine sweetpotato pollen viability. The best liquid medium for in vitro germination of sweetpotato pollen contained 50 g/L Sucrose, 50 g/L Polyethylene glycol 4000 (PEG4000), 100 mg/L Boric acid and 300 mg/L Calcium nitrate, with the pH adjusted to 6.0. This study provides a reliable medium for the detection of sweetpotato pollen viability, which can provide a theoretical reference for sweetpotato genetics and breeding.
‘Single-Seed-SpeedBulks:’ a protocol that combines ‘speed breeding’ with a cost-efficient modified single-seed descent method for rapid-generation-advancement in oat (Avena sativa L.)
Authors: Kigoni Milcah , Choi Megan , Arbelaez Juan David
Published: August 2023

Background

In plant breeding, one of the most cost-effective and efficient ways to increase genetic gain is to reduce the breeding cycle time. In general, modern breeding methods for self-pollinated crops should strive to develop fixed lines at the lowest possible cost and in the minimum possible amount of time. Previous studies on spring oat (Avena sativa L.) showed that combining high plant density with limited soil fertility and moisture levels in a growth media like sand effectively decreases the time and cost of generating fixed single-seed descent lines. More recently, ‘speed breeding,’ or the exposure to prolonged photoperiod regimes of 22 h, has been shown to decrease flowering time in oat significantly. The goal of this study was to combine ‘speed breeding’ with high-density planting in a limited soil fertility media to reduce further the costs and time required to develop oat single-seed-descent lines.

Results

We grew oat plants at low density in potting-mix (control), high density in potting-mix (HD-soil), and high density in sand (HD-sand) under 16 and 22 h of day length. We observed that oat plants grown in HD-sand and exposed to 22 h day length reduced their flowering time by around 20 and 5 days on average compared to those grown in control conditions at 16 and 22 h, respectively. We also observed that 85% of plants grown at high density in sand produced a single seed when grown in bulk conditions. In contrast, only 40% of plants grown at high density in potting-mix produced a single seed.

Conclusions

Our novel protocol showed that oat plants grown in high-density bulks, using sand media and 22-hour day length, reduced their flowering time by 20 days compared to control conditions and produced plants with single seeds, following closely single-seed descent assumptions while significantly reducing labor costs and greenhouse space. This methodology can be deployed in oat breeding programs to help them accelerate their rate of genetic grain for multiple traits.
Nicotine dependence and associated factors among persons who use electronic e-cigarettes in Malaysia - an online survey
Authors: Sreeramareddy Chandrashekhar T. , Shroff Sameeha Misriya , Gunjal Shilpa
Published: August 2023

Background

Nicotine dependence, factors associated with dependence, and self-reported side effects among people who use e-cigarettes are scarce in developing countries.

Methods

A sample of 302 persons who currently use e-cigarettes was recruited from discussion forums on Reddit, Facebook, and the forum ‘lowyat’. The online Google form survey collected data on demographics, e-cigarette use, and the reasons, for cigarette smoking, Fagerstorm Test for Nicotine Dependence adapted for e-cigarettes (eFTND), and side effects experienced.

Results

The mean age was 25.5 years (6.5), 60.6% were males and 86% had higher education. About 47% were using e-cigarettes only, 27.8% were currently using dual products (both electronic and conventional cigarettes), and 25.2% had also smoked cigarettes in the past. ‘Less harmful than cigarettes’ (56.3%), ‘because I enjoy it’ (46.7%), and ‘it has a variety of flavors (40.4%) were the common reasons for e-cigarette use. The mean eFTND score was 3.9 (SD = 2.2), with a median of four side effects (IQR 3–6), sore or dry mouth/throat (41.4%), cough 33.4%, headache (20.5%), dizziness (16.2%) were commonly reported side effects. eFTND score and side effects were higher among persons using dual products. By multiple linear regression analysis, males (β = 0.56 95% CI 0.45, 1.05, p = 0.033), dual-use (β = 0.95 95% CI 0.34, 1.56, p < 0.003), and use of nicotine-containing e-cigarettes (β = 0.66 95% CI 0.07, 1.25 p = 0.024) had higher eFTND score.

Conclusion

Our findings of the study call for the placement of disclaimers about possible nicotine addiction and side effects of e-cigarette products.
Analysis of clinical and physical dosimetric factors that determine the outcome of severe acute radiation pneumonitis in lung cancer patients
Authors: Zhao Jing , Ma Chenying , Gan Guanghui , Xu Xiaoting , Zhou Juying
Published: August 2023

Objective

We conducted a retrospective statistical analysis of clinical and physical dosimetric factors of lung cancer patients who had previously undergone lung and/or mediastinal radiotherapy and died of or survived severe acute radiation pneumonitis (SARP). Our study was the first to reveal the heterogeneity in clinical factors, physical dosimetric factors, and SARP onset time that determined the clinical outcomes of lung cancer patients who developed SARP.

Materials and methods

The clinical characteristics, physical dosimetry factors, and SARP onset time of deceased and surviving patients were retrospectively analyzed. SPSS 20.0 was used for data analysis. Student’s t-test was used for intergroup comparison, and a Mann–Whitney U test was used for data with skewed distribution. Qualitative data were represented using frequencies (%), and Fisher’s exact test or χ2 test was used for intergroup comparison of nonparametric data. Binary logistic analysis was used for univariate and multivariate analyses. Differences with a P < 0.05 were considered statistically significant.

Results

Univariate analysis revealed that the potential predictors of SARP death were as follows: ipsilateral lung V5 and V30, contralateral lung V5, V10, and V30, total lung V5, V10, and V30, mean lung dose, mean heart dose, and maximum spinal cord dose. Multivariate analysis showed that ipsilateral lung V5 and total lung V5 were predictors that determined the final outcome of SARP patients. In addition, we analyzed the time from the completion of radiotherapy to SARP onset, and found significant difference between the two groups.

Conclusions

There was no decisive correlation between clinical characteristics and SARP outcome (i.e., death or survival) in lung radiotherapy patients. Ipsilateral lung V5 and total lung V5 were independent predictors of death in SARP patients.
Evaluation of enterotoxigenic Bacteroides fragilis correlation with the expression of cellular signaling pathway genes in Iranian patients with colorectal cancer
Authors: Dadgar-Zankbar Leila , Shariati Aref , Bostanghadiri Narjess , Elahi Zahra , Mirkalantari Shiva , Razavi Shabnam , Kamali Fatemeh , Darban-Sarokhalil Davood
Published: August 2023

Background

Colorectal cancer (CRC) is one of the most common cancers all over the world, and dysbiosis in the gut microbiota may play a role in colorectal carcinogenesis.Bacteroides fragiliscan lead to tumorigenesis by changing signaling pathways, including the WNT/β-catenin pathway. Therefore, in the present study, we investigated the correlation between the enterotoxigenicB. fragilisamount and the expression of signaling pathway genes involved in CRC.

Materials and methods

B. fragiliswas determined in 30 tumors and adjacent healthy tissues by the qPCR method. Next, the relationship between enterotoxigenicB. fragilisand the expression of signaling pathway genes, including CCND1, TP53, BCL2, BAX, WNT, TCF, AXIN, APC, and CTNNB1 was investigated. Additionally, possible correlations between clinicopathological features of the tumor samples and the abundance ofB. fragiliswere analyzed.

Results

The results showed thatB. fragiliswas detected in 100% of tumor samples and 86% of healthy tissues. Additionally, enterotoxigenicB. fragiliscolonized 47% of all samples, andbft-1toxin was the most frequently found isotype among the samples. The analysis showed that the high level ofB. fragilishas a significant relationship with the high expression of AXIN, CTNNB1, and BCL2 genes. On the other hand, our results did not show any possible correlation between this bacterium and the clinicopathological features of the tumor sample.

Conclusion

B. fragilishad a higher abundance in the tumor samples than in healthy tissues, and this bacterium may lead to CRC by making changes in cellular signaling pathways and genes. Therefore, to better understand the physiological effects ofB. fragilison the inflammatory response and CRC, future research should focus on dissecting the molecular mechanisms by which this bacterium regulates cellular signaling pathways.
Exosome nanovesicles as potential biomarkers and immune checkpoint signaling modulators in lung cancer microenvironment: recent advances and emerging concepts
Authors: Khan Naushad Ahmad , Asim Mohammad , Biswas Kabir H. , Alansari Amani N , Saman Harman , Sarwar Mohammad Zahid , Osmonaliev Kudaibergen , Uddin Shahab
Published: August 2023

Lung cancer remains the leading cause of cancer-related deaths globally, and the survival rate remains low despite advances in diagnosis and treatment. The progression of lung cancer is a multifaceted and dynamic phenomenon that encompasses interplays among cancerous cells and their microenvironment, which incorporates immune cells. Exosomes, which are small membrane-bound vesicles, are released by numerous cell types in normal and stressful situations to allow communication between cells. Tumor-derived exosomes (TEXs) possess diverse neo-antigens and cargoes such as proteins, RNA, and DNA and have a unique molecular makeup reflecting tumor genetic complexity. TEXs contain both immunosuppressive and immunostimulatory factors and may play a role in immunomodulation by influencing innate and adaptive immune components. Moreover, they transmit signals that contribute to the progression of lung cancer by promoting metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and immunosuppression. This makes them a valuable resource for investigating the immune environment of tumors, which could pave the way for the development of non-invasive biomarkers that could aid in the prognosis, diagnosis, and immunotherapy of lung cancer. While immune checkpoint inhibitor (ICI) immunotherapy has shown promising results in treating initial-stage cancers, most patients eventually develop adaptive resistance over time. Emerging evidence demonstrates that TEXs could serve as a prognostic biomarker for immunotherapeutic response and have a significant impact on both systemic immune suppression and tumor advancement. Therefore, understanding TEXs and their role in lung cancer tumorigenesis and their response to immunotherapies is an exciting research area and needs further investigation. This review highlights the role of TEXs as key contributors to the advancement of lung cancer and their clinical significance in lung immune-oncology, including their possible use as biomarkers for monitoring disease progression and prognosis, as well as emerging shreds of evidence regarding the possibility of using exosomes as targets to improve lung cancer therapy.
Use of simulation models when developing and testing hospital evacuation plans: a tool for improving emergency preparedness
Authors: Rådestad Monica , Holmgren Cecilia , Blidegård Ellinor Linde , Montán Kristina Lennquist
Published: August 2023

Background

In recent decades, analyses of hospitals evacuations have generated valuable knowledge. Unfortunately, these evacuation case studies often lack crucial details and policies that would be helpful in evacuation preparedness. The aim of this study was to use a simulation model to illustrate how it can aid emergency planners in the development, testing, and revising of hospitals evacuation plans. This study includes evacuation exercises at two emergency hospitals in Region Stockholm, Sweden.

Methods

A scientifically validated simulation system for “table top” exercises was used for interactive training of hospital medical staff, prehospital staff and collaborating agencies. All participants acted in their usual professionals’ roles. The exercises were run in real-time and mirrored actual hospital resources with the aid of moveable magnetic symbols illustrating patients, staff and transport, presented on whiteboards. During the exercises, observers and independent instructors documented actions taken and post-exercise surveys were conducted to obtain reactions and compare results.

Results

The simulation system allowed the emergency planner to test the whole evacuation process, making it possible to train and evaluate the important functions of management, coordination, and communication. Post-exercise surveys explored participants perception of the exercises. Analysis of open-ended questions included areas for improvement and resulted in five main categories: (1) management and liaison; (2) communication; (3) logistics; (4) medical care and patient prioritisation; and (5) resource utilisation.

Conclusions

This study has shown that “table top” exercises using a validated simulation system can serve to guide emergency planners when developing evacuation plans, procedures, and protocols as well in training of all medical staff. The system also served to train adaptive thinking, leadership, communication, and clarification of critical functions.
Cross-species oncogenomics offers insight into human muscle-invasive bladder cancer
Authors: Wong Kim , Abascal Federico , Ludwig Latasha , Aupperle-Lellbach Heike , Grassinger Julia , Wright Colin W. , Allison Simon J. , Pinder Emma , Phillips Roger M. , Romero Laura P. , Gal Arnon , Roady Patrick J. , Pires Isabel , Guscetti Franco , Munday John S. , Peleteiro Maria C. , Pinto Carlos A. , Carvalho Tânia , Cota João , Du Plessis Elizabeth C. , Constantino-Casas Fernando , Plog Stephanie , Moe Lars , de Brot Simone , Bemelmans Ingrid , Amorim Renée Laufer , Georgy Smitha R. , Prada Justina , del Pozo Jorge , Heimann Marianne , de Carvalho Nunes Louisiane , Simola Outi , Pazzi Paolo , Steyl Johan , Ubukata Rodrigo , Vajdovich Peter , Priestnall Simon L. , Suárez-Bonnet Alejandro , Roperto Franco , Millanta Francesca , Palmieri Chiara , Ortiz Ana L. , Barros Claudio S. L. , Gava Aldo , Söderström Minna E. , O’Donnell Marie , Klopfleisch Robert , Manrique-Rincón Andrea , Martincorena Inigo , Ferreira Ingrid , Arends Mark J. , Wood Geoffrey A. , Adams David J. , van der Weyden Louise
Published: August 2023

Background

In humans, muscle-invasive bladder cancer (MIBC) is highly aggressive and associated with a poor prognosis. With a high mutation load and large number of altered genes, strategies to delineate key driver events are necessary. Dogs and cats develop urothelial carcinoma (UC) with histological and clinical similarities to human MIBC. Cattle that graze on bracken fern also develop UC, associated with exposure to the carcinogen ptaquiloside. These species may represent relevant animal models of spontaneous and carcinogen-induced UC that can provide insight into human MIBC.

Results

Whole-exome sequencing of domestic canine (n = 87) and feline (n = 23) UC, and comparative analysis with human MIBC reveals a lower mutation rate in animal cases and the absence of APOBEC mutational signatures. A convergence of driver genes (ARID1A, KDM6A, TP53,FAT1, andNRAS) is discovered, along with common focally amplified and deleted genes involved in regulation of the cell cycle and chromatin remodelling. We identify mismatch repair deficiency in a subset of canine and feline UCs with biallelic inactivation ofMSH2. Bovine UC (n = 8) is distinctly different; we identify novel mutational signatures which are recapitulated in vitro in human urinary bladder UC cells treated with bracken fern extracts or purified ptaquiloside.

Conclusion

Canine and feline urinary bladder UC represent relevant models of MIBC in humans, and cross-species analysis can identify evolutionarily conserved driver genes. We characterize mutational signatures in bovine UC associated with bracken fern and ptaquiloside exposure, a human-linked cancer exposure. Our work demonstrates the relevance of cross-species comparative analysis in understanding both human and animal UC.
The With Or Without Olecranon K-wire (WOW OK) Trial of tension band wire fixation versus cerclage fixation without K-wires in displaced stable olecranon fractures: study protocol for a randomized controlled trial
Authors: Cornefjord Gustav , Kostogiannis Ioannis , Rogmark Cecilia , Jerrhag Daniel , Wenger Daniel
Published: August 2023

Background

Displaced olecranon fractures with a stable elbow joint are classified as Mayo type 2a or 2b and are commonly operated with tension band wiring, i.e. two K-wires and a cerclage. Retrospective studies have reported fewer reoperations and complications with cerclage fixation alone when compared to tension band wiring, though with similar long-term results. We decided to compare tension band wiring to cerclage fixation of displaced, stable olecranon fractures in adults in a randomized controlled trial.

Methods

All patients ≥ 18 years old with Mayo type 2a and 2b fractures presenting at Skåne University hospital will be eligible for study inclusion, unless exclusion criteria are met. Two hundred participants will be included and randomized 1:1 to cerclage fixation or tension band wiring.

Outpatient physiotherapist follow-up appointments will be scheduled at 2 and 6 weeks and at 3, 12, and 36 months at the Dept. of Orthopaedics. A lateral view radiograph of the elbow will be analysed at 6 months. The primary outcome of our study is the rate of reoperations. Secondary outcomes are complication rates, severity of complications, and patient-reported outcome measures (QuickDASH, Short Musculoskeletal Function Assessment, pain level, and patient satisfaction). The sample size was calculated to give 80% power for detecting a statistically significant difference in reoperation rates (with alpha-value 0.05), based on a previous retrospective study.

Discussion

Reoperation and complication rates after tension band wiring of olecranon fractures are high. Treatment of these injuries is debated, and several ongoing trials compare tension band wiring with plate fixation, suture fixation, and non-operative treatment. As data from retrospective studies indicate that cerclage fixation may be superior to tension band wiring, we see a need for a randomized controlled trial comparing these methods. The WOW-OK Trial aims to obtain level-1 evidence that may influence treatment choice for this type of fracture.

Trial registration

ClinicalTrials.gov NCT05657899. Registered on 16 November 2022. The trial complies with SPIRIT and CONSORT guidelines. The SPIRIT figure is found in Table 2.