bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive transcriptomic analysis unveils the interplay of mRNA and LncRNA expression in shaping collagen organization and skin development in Dezhou donkeys
Authors: Wang Xinrui , Peng Yongdong , Liang Huili , Zahoor Khan Muhammad , Ren Wei , Huang Bingjian , Chen Yinghui , Xing Shishuai , Zhan Yandong , Wang Changfa
Published: February 2024

The primary focus of donkey hide gelatin processing lies in the dermal layer of donkey hide due to its abundant collagen content. However, the molecular mechanism involved in collagen organization and skin development in donkey skin tissue across various developmental stages remains incomplete. The current study aims to investigate the transcriptomic screening of lncRNAs and mRNA associated with skin development and collagen organization across different ages in Dezhou donkeys’ skin. In the pursuit of this objective, we used nine skin tissue samples obtained from Dezhou donkeys at various ages including 8-month fetal stage, followed by 2 and 8 years. RNA-seq analysis was performed for the transcriptomic profiling of differentially expressed genes (DEGs) and lncRNAs associated with skin development in different age groups. Our investigation revealed the presence of 6,582, 6,455, and 405 differentially expressed genes and 654, 789, and 29 differentially expressed LncRNAs within the skin tissues of Dezhou donkeys when comparing young donkeys (YD) vs. middle-aged donkeys (MD), YD vs. old donkeys (OD), and MD vs. OD, respectively. Furthermore, we identified Collagen Type I Alpha 1 Chain (COL1A1), Collagen Type III Alpha 1 Chain (COL3A1), and Collagen Type VI Alpha 5 Chain (COL6A5) as key genes involved in collagen synthesis, with COL1A1 being subject to cis-regulation by several differentially expressed LncRNAs, including ENSEAST00005041187, ENSEAST00005038497, and MSTRG.17248.1, among others. Interestingly, collagen organizational and skin development linked pathways including Protein digestion and absorption, metabolic pathways, Phosphatidylinositol 3-Kinase-Protein Kinase B signaling pathway (PI3K-Akt signaling pathway), Extracellular Matrix-Receptor Interaction (ECM-receptor interaction), and Relaxin signaling were also reported across different age groups in Dezhou donkey skin. These findings enhance our comprehension of the molecular mechanisms underlying Dezhou donkey skin development and collagen biosynthesis and organization, thus furnishing a solid theoretical foundation for future research endeavors in this domain.
Case report: Preimplantation genetic testing for infantile GM1 gangliosidosis
Authors: Zagaynova Valeria A. , Nasykhova Yulia A. , Tonyan Ziravard N. , Danilova Maria M. , Dvoynova Natalya M. , Lazareva Tatyana E. , Ivashchenko Tatyana E. , Shabanova Elena S. , Krikheli Inna O. , Lesik Elena A. , Bespalova Olesya N. , Kogan Igor Yu. , Glotov Andrey S.
Published: February 2024

Ganglioside-monosialic acid (GM1) gangliosidosis (ICD-10: E75.1; OMIM: 230500, 230600, 230650) is a rare autosomal recessive hereditary disease, lysosomal storage disorder caused by mutations in the GLB1 gene that lead to the absence or insufficiency of β-galactosidase. In this study, we report a case of a Russian family with a history of GM1 gangliosidosis. The family had a child who, from the age of 6 months, experienced a gradual loss of developmental skills, marked by muscle flaccidity, psychomotor retardation, hepatosplenomegaly, and the onset of tonic seizures by the age of 8 months. Funduscopic examination revealed a «cherry red spot» in the macula, which is crucial for the diagnosis of lipid storage disorders. To find the pathogenic variants responsible for these clinical symptoms, the next-generation sequencing approach was used. The analysis revealed two variants in the heterozygous state: a frameshift variant c.699delG (rs1452318343, ClinVar ID 928700) in exon 6 and a missense variant c.809A>C (rs371546950, ClinVar ID 198727) in exon 8 of the GLB1 gene. The spouses were advised to plan the pregnancy with assisted reproductive technology (ART), followed by preimplantation genetic testing for monogenic disorder (PGT-M) on the embryos. Trophectoderm biopsy was performed on 8 out of 10 resulting embryos at the blastocyst stage. To perform PGT-M, we developed a novel testing system, allowing for direct analysis of disease-causing mutations, as well as haplotype analysis based on the study of polymorphic markers—short tandem repeats (STR), located upstream and downstream of the GLB1 gene. The results showed that four embryos were heterozygous carriers of pathogenic variants in the GLB1 gene (#1, 2, 5, 8). Two embryos had a compound heterozygous genotype (#3, 4), while the embryos #7 and 9 did not carry disease-causing alleles of the GLB1 gene. The embryo #7 without pathogenic variants was transferred after consideration of its morphology and growth rate. Prenatal diagnosis in the first trimester showed the absence of the variants analyzed in the GLB1 gene in the fetus. The pregnancy resulted in the delivery of a female infant who did not inherit the disease-causing variants in the GLB1 gene.
KLF4 and CD55 expression and function depend on each other
Authors: An Feng-Qi , Zhou Guangjin , Harland Micah T. , Hussain Wasim , Strainic Michael G. , Jain Mukesh K. , Medof M. Edward
Published: February 2024

The transcription factor Kruppel-like factor 4 (KLF4) regulates the expression of immunosuppressive and anti-thrombotic proteins. Despite its importance in maintaining homeostasis, the signals that control its expression and the mechanism of its transactivation remain unclarified. CD55 [aka decay accelerating factor (DAF)], now known to be a regulator of T and B cell responses, biases between pro- and anti-inflammatory processes by controlling autocrine C3a and C5a receptor (C3ar1/C5ar1) signaling in cells. The similarity in CD55’s and KLF4’s regulatory effects prompted analyses of their functional relationship. In vascular endothelial cells (ECs), CD55 upregulation accompanied KLF4 expression via a p-CREB and CREB Binding Protein (CBP) mechanism. In both ECs and macrophages, CD55 expression was essential for KLF4’s downregulation of pro-inflammatory/pro-coagulant proteins and upregulation of homeostatic proteins. Mechanistic studies showed that upregulation of KLF4 upregulated CD55. The upregulated CD55 in turn enabled the recruitment of p-CREB and CBP to KLF4 needed for its transcription. Activation of adenylyl cyclase resulting from repression of autocrine C3ar1/C5ar1 signaling by upregulated CD55 concurrently led to p-CREB and CBP recruitment to KLF4-regulated genes, thereby conferring KLF4’s transactivation. Accordingly, silencing CD55 in statin-treated HUVEC disabled CBP transfer from the E-selectin to the eNOS promoter. Importantly, silencing CD55 downregulated KLF4’s expression. It did the same in untreated HUVEC transitioning from KLF4low growth to KLF4hi contact inhibition. KLF4’s and CD55’s function in ECs and macrophages thus are linked via a novel mechanism of gene transactivation. Because the two proteins are co-expressed in many cell types, CD55’s activity may be broadly tied to KLF4’s immunosuppressive and antithrombotic activities.
Export production in a continental shelf with multisource nutrient supply
Authors: Zhang Jing , Zhu Lei , Guo Xinyu , Wang Yucheng , Feng Jianlong , Zhao Liang
Published: February 2024

Export production, which is defined as the export of organic matter fixed by photosynthesis, is crucial for sustaining oceanic carbon uptake. The export route in the open ocean is the sinking of biogenic particles through the bottom of the euphotic layer. In contrast, the export routes in the shelf seas are the sinking of biogenic particles to the sediment and the horizontal transport of biogenic particles across the boundary of the shelf seas to the open ocean. The biogenic particles in the shelf seas are supported by multisource nutrients including riverine and oceanic ones. Their exports depend on the hydrodynamic conditions and biogeochemical processes responsible for different sources of nutrients. Here, a unique physical-biological coupled model with a tracking approach is applied to evaluate the export production supported by multisource dissolved inorganic nitrogen (DIN) over the East China Sea. The total export production is 6.83 kmol N s-1 (=17.16 Tg C yr-1), which is slightly lower than the reported atmospheric CO2 absorption. Approximately 80% of particulate organic nitrogen (PON) is exported via off-shelf transport, and the remaining 20% is buried in the sediment. The PON supported by DIN from rivers accounts for 8% of export production, with an e-ratio (export production/primary production) of 0.09. In comparison, that from the Kuroshio accounts for 64%, with an e-ratio of 0.22. This suggests that offshore areas here are more efficient in exporting local production than nearshore ones, largely supported by oceanic nutrients.
Effects of 5-aminolevulinic acid photodynamic therapy for cervical low-grade squamous intraepithelial lesions with HR-HPV infections
Authors: Li Yu , Chen Jing , Hu Yan , Xu Qingyang , Jiang Rongzhen , Teng Yincheng , Xu Yanli , Ma Li
Published: February 2024

Objective

To determine the effectiveness and safety of 5-aminolevulinic acid mediated photodynamic therapy (5-ALA PDT) in HR-HPV infected patients with cervical low-grade squamous intraepithelial lesions (LSIL) and to explore possible factors affecting treatment outcomes.

Methods

This retrospective study included 96 patients with histologically confirmed cervical LSIL and high-risk human papillomavirus (HR-HPV) infection. They received 5-ALA PDT treatment once a week for a total of 3 courses. All patients were evaluated by cytology tests, HPV DNA assay, colposcopy, and biopsy at 2 weeks, 3 months, and 6 months checkpoint. The chi-square test were used to evaluate the differences in various clinical data, and a p value <0.05 was considered statistically significant.

Results

At 2 weeks, 3 months, and 6 months checkpoint, colposcopies showed that the cervical iodine-unstained area under VILI (visual inspection with Lugol’s iodine) significantly reduced (p < 0.01) with no structure changes. At 3 months and 6 months checkpoint, the pathological regression rate reached 87.5% (84/96) and 94.79% (91/96), while the HR-HPV clearance rates reached 80.21% (77/96) and 93.75% (90/96) respectively. We also examined the efficacy in the HPV 16/18-related group and non-HPV 16/18-related group. The HR-HPV clearance rate in the HPV16/18 group [94.87% (37/39)] was significantly higher than that of the non-HPV 16/18 group [70.17% (40/57)]. However, at 6 months after treatment, the clearance rate of the HPV 16/18 group [94.87% (37/39)] showed no statistical difference from the non-HPV 16/18 group [92.30% (53/57)].

Conclusion

Topical 5-ALA PDT can effectively eliminate HR-HPV infection and treat low-grade cervical squamous intraepithelial lesions, it offers an alternative treatment option for patients with LSIL, especially for those with fertility requirements and who wish to preserve cervical structure or function.
From PsO to PsA: the role of TRM and Tregs in psoriatic disease, a systematic review of the literature
Authors: Lobão Bárbara , Lourenço Diana , Giga Ana , Mendes-Bastos Pedro
Published: February 2024

Introduction

Psoriasis (PsO) is a chronic skin condition driven by immune mediators like TNFα, INFγ, IL-17, and IL-23. Psoriatic arthritis (PsA) can develop in PsO patients. Although psoriatic lesions may apparently resolve with therapy, subclinical cutaneous inflammation may persist. The role of tissue-resident memory T-cells (TRM), and regulatory T cells (Tregs) that also contribute to chronic inflammation are being explored in this context. This systematic review explores TRM and Tregs in psoriatic disease (PsD) and its progression.

Methods

A systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was performed using Pubmed® and Web of Science™ databases on June 3rd 2023, using patient/population, intervention, comparison, and outcomes (PICO) criteria limited to the English language.

Results

A total of 62 reports were identified and included. In PsO, chronic inflammation is driven by cytokines including IL-17 and IL-23, and cellular mediators such as CD8+ and CD4+ T cells. TRM contributes to local inflammation, while Tregs may be dysfunctional in psoriatic skin lesions. Secukinumab and guselkumab, which target IL-17A and the IL-23p19 subunit, respectively, have different effects on CD8+ TRM and Tregs during PsO treatment. Inhibition of IL-23 may provide better long-term results due to its impact on the Treg to CD8+ TRM ratio. IL-23 may contribute to inflammation persisting even after treatment. In PsA, subclinical enthesitis is perceived as an early occurence, and Th17 cells are involved in this pathogenic process. Recent EULAR guidelines highlight the importance of early diagnosis and treatment to intercept PsA. In PsA, CD8+ TRM cells are present in synovial fluid and Tregs are reduced in peripheral blood. The progression from PsO to PsA is marked by a shift in immune profiles, with specific T-cells subsets playing key roles in perpetuating inflammation. Early intervention targeting TRM cells may hold promising, but clinical studies are limited. Ongoing studies such as IVEPSA and PAMPA aim to improve our knowledge regarding PsA interception in high-risk PsO patients, emphasizing the need for further research in this area.

Conclusion

Early intervention is crucial for PsO patients at high risk of PsA; T cells, particularly type 17 helper T cells, and CD8+ cells are key in the progression from PsO-to-PsA. Early targeting of TRM in PsD shows promise but more research is needed.
Differences in soil bacterial community structure during the remediation of Cd-polluted cotton fields by biochar and biofertilizer in Xinjiang, China
Authors: Zhu Yongqi , An Mengjie , Anwar Tumur , Wang Haijiang
Published: February 2024

Introduction

Heavy metal pollution is a major worldwide environmental problem. Many remediation techniques have been developed, these techniques have different performance in different environments.

Methods

In this study, soil sampling was conducted in multiple cotton fields in Xinjiang, China, and found that cadmium (Cd) was the most abundant soil heavy metal. Then, to find the most suitable technique for the remediation of Cd pollution in cotton fields, a two-year study was conducted to explore the effects of cotton straw-derived biochar (BC, 3%) and Bacillus-based biofertilizer (BF, 1.5%) on cotton Cd uptake and transport and soil microbial community structure under Cd exposure conditions (soil Cd contents: 1, 2, and 4 mg·kg−1).

Results

The results showed that the bioaccumulation coefficients (Cd content of cotton organs / soil available Cd content) of cotton roots, stems, leaves, and buds/bolls reduced by 15.93%, 14.41%, 23.53%, and 20.68%, respectively after the application of BC, and reduced by 16.83%, 17.15%, 22.21%, and 26.25%, respectively after the application of BF, compared with the control (no BC and BF). Besides, the application of BC and BF reduced the transport of Cd from soil to root system, and enhanced the diversity of soil bacterial communities (dominant species: Alphaproteobacteria and Actinobacteria) and the metabolic functions related to amino acid synthesis. It was worth noting that the differential species for BF group vs BC group including Alphaproteobacteria, Gemmatimonadetes, Bacilli, and Vicinamibacteria were associated with the enrichment and transport of Cd, especially the transport of Cd from cotton roots to stems.

Discussion

Therefore, the application of BC and BF changed the soil bacterial diversity in Cd-polluted cotton field, and then promoted the transport of Cd in cotton, ultimately improving soil quality. This study will provide a reference for the selection of soil heavy metal pollution remediation techniques in Xinjiang, China.
Sex-specific nociceptor modulation of the apical periodontitis transcriptome
Authors: Lillis Katherine V. , Grinceviciute Ruta , Diogenes Anibal
Published: February 2024

Introduction: Apical periodontitis (AP) is a painful disease that develops quickly following dental infections and is primarily characterized by robust inflammation surrounding the tissues of the affected tooth, resulting in disruption of bone homeostasis and periradicular bone loss. Moreover, there are distinct clinical presentations, symptoms, and responses to AP treatment between male and female subjects, creating a desperate need to further understand the sex-specific mechanisms of AP.

Methods: With the growing evidence that nociceptors modulate AP development, we utilized RNA sequencing in nociceptor-ablated (Nav1.8 cre+/−, diphtheria toxin Alox+/−) transgenic mice to study the nociceptor regulation of the periapical lesion transcriptome using a rodent model of AP in female mice over 14 days.

Results: Overall, we found that female mice exhibit unique patterns of differentially expressed genes throughout AP infection compared to male mice and that the expression of these genes is regulated by nociceptors. Additionally, nociceptor ablation results in a more significant enrichment of biological processes related to immune responses earlier compared to cre-control (Nav1.8 cre+/−) females and greater expression of genes involved in inflammatory processes and osteolytic activity.

Discussion: Therefore, while nociceptor ablation augments inflammatory and bone resorption responses in both males and females in a mouse model of AP, transcriptomic analyses demonstrate that the mechanisms through which nociceptors modulate AP are distinct between sexes. These studies will provide the foundation needed to study further mechanisms of sex differences in AP, an area with a desperate need for investigation to treat current AP patients. Understanding these mechanisms can ultimately inform treatment options to alleviate suffering for millions of patients suffering from AP.
Commercial roadmap of nanobiosensor development
Authors: Ulucan-Karnak Fulden , Kuru Cansu İlke , Akgöl Sinan
Published: February 2024

A nanobiosensor is a tool that converts a biological stimulus into an electrical output via nanosized transducer elements. Nanobiosensors are promising instruments, especially in biomedical applications in the literature and industry. To develop a nanobiosensor from idea to product, a life-cycle approach that comprises various processes ranging from conception through commercialization is required. Developers and potential investors should examine market requirements, design possibilities, feasibility, financial return, and risk assessments when developing a nanobiosensor development concept. It is critical to establish a well-defined regulatory pathway for bringing innovation to market at a low cost and in a short period. R&D should conduct thorough examinations of nanomaterial toxicity and health effects, involving marketing, advertising, and financial analysis. Stakeholders should discuss technology transfer office protocols for faster, healthier operations.
ADAM: a robotic companion for enhanced quality of life in aging populations
Authors: Mora Alicia , Prados Adrian , Mendez Alberto , Espinoza Gonzalo , Gonzalez Pavel , Lopez Blanca , Muñoz Victor , Moreno Luis , Garrido Santiago , Barber Ramon
Published: February 2024

One of the major problems of today's society is the rapid aging of its population. Life expectancy is increasing, but the quality of life is not. Faced with the growing number of people who require cognitive or physical assistance, new technological tools are emerging to help them. In this article, we present the ADAM robot, a new robot designed for domestic physical assistance. It mainly consists of a mobile base, two arms with grippers and vision systems. All this allows the performance of physical tasks that require navigation and manipulation of the environment. Among ADAM's features are its modularity, its adaptability to indoor environments and its versatility to function as an experimental platform and for service applications. In addition, it is designed to work respecting the user's personal space and is collaborative, so it can learn from experiences taught by them. We present the design of the robot as well as examples of use in domestic environments both alone and in collaboration with other domestic platforms, demonstrating its potential.
Nrf2 functions as a pyroptosis-related mediator in traumatic brain injury and is correlated with cytokines and disease severity: a bioinformatics analysis and retrospective clinical study
Authors: Zhao Gengshui , Zhao Jianfei , Lang Jiadong , Sun Guozhu
Published: February 2024

Background

Traumatic brain injury (TBI) is a serious hazard to human health. Evidence has accumulated that pyroptosis plays an important role in brain trauma. The aim of this study is to screen potential key molecules between TBI and pyroptosis, and further explore their relationships with disease severity and cytokines.

Methods

To acquire differentially expressed genes (DEGs) before and after brain injury, the GSE89866 dataset was downloaded from the Gene Expression Omnibus (GEO) database. Meanwhile, pyroptosis-related genes were obtained from the GeneCards database, and the intersected genes were identified as differentially expressed pyroptosis-related genes (DEPGs). Moreover, the hub genes were screened via four algorithms (namely Maximum Clique Centrality, Edge Percolated Component, BottleNeck and EcCentricity) in Cytoscape software. Blood levels of Nrf2 were measured by ELISA using a commercially available kit. Finally, we further investigated the correlation between Nrf2 levels and medical indicators in TBI such as clinical characteristics, inflammatory cytokines, and severity.

Results

Altogether, we found 1,795 DEGs in GSE89866 and 98 pyroptosis-related genes in the GeneCards database. Subsequently, four hub genes were obtained, and NFE2L2 was adopted for further clinical study. By using Kruskal-Wallis test and Spearman correlation test, we found that the serum Nrf2 levels in severe TBI patients were negatively correlated with GCS scores. On the contrary, there was a positive correlation between serum Nrf2 levels and pupil parameters, Helsinki CT scores, IL-1 β and IL-18.

Conclusions

In summary, bioinformatic analyses showed NFE2L2 plays a significant role in the pathology of TBI. The clinical research indicated the increase in serum Nrf2 levels was closely related to the severity of trauma and cytokines. We speculate that serum Nrf2 may serve as a promising biochemical marker for the assessment of TBI in clinical practice.
The effect of human PBMCs immobilization on their Аβ42 aggregates-dependent proinflammatory state on a cellular model of Alzheimer’s disease
Authors: Kot Kateryna , Kot Yurii , Kurbanov Rustam , Andriiash Hanna , Tigunova Olena , Blume Yaroslav , Shulga Sergiy
Published: February 2024

The leading pathological mechanisms of Alzheimer’s disease are amyloidosis and inflammation. The presented work was aimed to study the effect of human peripheral blood mononuclear cells (hPBMcs) cells-matrix adhesion on their pro-inflammatory state in vitro. Although direct interaction of Аβ42 to PBMC is not a cellular model of Alzheimer’s disease, PBMCs may serve as test cells to detect Аβ42-dependent molecular effects in monitoring disease progression. Peripheral blood mononuclear cells (PBMCs) are used to assess changes in cytokines released in response to diseases or Alzheimer’s disease-specific cytotoxic molecules such as Aβ42. The effect of recombinant amyloid β-peptide rАβ42 on the concentration of endogenous amyloid β-peptide Aβ40 and pro-inflammatory cytokines TNFα and IL-1β in human peripheral blood mononuclear cells that were cultured in suspension and immobilized in alginate microcarriers for 24 h were investigated. The localization and accumulation of Aβ40 and rAβ42 peptides in cells, as well as quantitative determination of the concentration of Aβ40 peptide, TNFα and IL-1β cytokines, was performed by intravital fluorescence imaging. The results were qualitatively similar for both cell models. It was determined that the content of TNFα and Aβ40 in the absence of rAβ42 in the incubation medium did not change for 24 h after incubation, and the content of IL-1β was lower compared to the cells that were not incubated. Incubation of cells in vitro with exogenous rAβ42 led to an increase in the intracellular content of TNFα and Aβ40, and no accumulation of IL-1β in cells was observed. The accumulation of Aβ40 in the cytoplasm was accompanied by the aggregation of rAβ42 on the outer surface of the cell plasma membrane. It was shown that the basic levels of indicators and the intensity of the response of immobilized cells to an exogenous stimulus were significantly greater than those of cells in suspension. To explore whether non-neuronal cells effects in alginate microcarriers were cell-matrix adhesion mediated, we tested the effect of blocking β1 integrins on proamyloidogenic and proinflammation cellular state. Immobilization within alginate hydrogels after incubation with the β1 integrins blocking antibodies showed a remarkable inhibition of TNFα and Aβ40 accumulation in rAβ42-treated cells. It can be concluded that activation of signal transduction and synthesizing activity of a portion of mononuclear cells of human peripheral blood is possible (can significantly increase) in the presence of cell-matrix adhesion.
Effect of high-dose polymeric nanoparticle micellar paclitaxel on improved progression-free survival in patients with optimally resected stage III or IV high-grade carcinoma of the ovary: a prospective cohort study with historical controls
Authors: Park Soo Jin , Son Joo-Hyuk , Kong Tae-Wook , Chang Suk-Joon , Kim Hee Seung
Published: February 2024

Introduction

We evaluated the effect of high-dose polymeric nanoparticle micellar paclitaxel (PM-Pac) on survival in patients with stage III-IV high-grade serous ovarian cancer (HGSC) who underwent upfront surgery.

Methods

We prospectively recruited the patients who received PM-Pac (280 mg/m2) and carboplatin at an area under the curve (AUC) of 5 (cohort 1) in two tertiary centers between October 2015 and June 2019. As historical controls, we retrospectively collected data on those who received paclitaxel (175 mg/m2) and carboplatin (AUC 5; cohort 2) or paclitaxel (175 mg/m2), carboplatin (AUC 5) and bevacizumab (15 mg/kg; cohort 3).

Results

A total of 128 patients were divided into cohorts 1 (n=49, 38.3%), 2 (n=53, 41.4%), and 3 (n=26, 20.3%). Cohort 1 showed better progression-free survival (PFS) than cohort 2 in all patients and those treated with optimal debulking surgery (ODS; median, 35.5 vs. 28.1 and 35.5 vs. 28.9 months; p ≤ 0.01) despite no difference in PFS between cohorts 1 and 3 and between cohorts 2 and 3. In particular, stage III disease was a favorable factor for PFS, whereas cohort 2 was related to worse PFS (adjusted hazard ratios, 0.456 and 1.834; 95% confidence interval, 0.263 – 0.790 and 1.061 – 3.171), showing no difference in PFS between cohorts 1 and 3 in those treated with ODS.

Conclusion

High-dose PM-Pac improved PFS compared to conventional chemotherapy, and the change of paclitaxel to PM-Pac had as much effect on PFS as the addition of bevacizumab in patients with stage III-IV HGSC who underwent ODS.
A historical controlled study of domestic trastuzumab and pertuzumab in combination with docetaxel for the neoadjuvant treatment of early HER2-positive breast cancer
Authors: Xu Dongdong , Wu Jiang , Yu Jing , Yang Yuqing , Wen Xinxin , Yang Jixin , Wei Hongliang , Xu Xiaolong , Li Yike , Yang Liu , Wang Lei , Wang Yijia , Ma Wen , Li Nanlin
Published: February 2024

Background

HER2-positive molecular breast cancer subtypes are characterized by high aggressiveness and malignancy, and their metastasis and mortality rates are among the highest of all types of breast cancer. The use of anti-HER2-targeted agents in neoadjuvant therapy has significantly improved the prognosis of patients with HER2-positive breast cancer. In this study, we investigated the efficacy and safety of a neoadjuvant Chinese THP regimen (docetaxel, trastuzumab biosimilar TQB211 plus the pertuzumab biosimilar TQB2440 or pertuzumab) for ER/PR-negative and HER2-positive breast cancer in China.

Method

All enrolled patients received the THP regimen (T: docetaxel 75 mg/m2 per cycle; H: trastuzumab biosimilar TQB211 8 mg/kg in the first cycle and 6 mg/kg maintenance dose in cycles 2 to 4; P: pertuzumab biosimilar TQB2440 or pertuzumab 840 mg in the first cycle, maintenance dose 420 mg in cycles 2 to 4) every 3 weeks for 4 cycles. The biosimilar TQB2440 pertuzumab and pertuzumab were randomly assigned to patients. Docetaxel, TQB211, and TQB2440 were all developed by Chiatai Tianqing. The primary endpoint was the complete pathological response (pCR) in the breast, and the secondary endpoint was cardiac safety.

Results

Of the 28 eligible patients, 19 (67.9%) achieved tpCR. The tpCR rate was higher than in the NeoSphere trial (pCR63.2%) and the PEONY study (tpCR52.5%). The adverse events that occurred most frequently were leukopenia and neutropenia, with incidence rates of 82.1% and 75.0%, respectively. Of these, grade 3 leukopenia and neutropenia occupied 46.4% and 35.7%. Other grade 3 or higher adverse events were bone marrow suppression (7.1%), lymphopenia (3.6%), and anemia (3.6%). There were no events of heart failure in patients and no patient died during the neoadjuvant phase.

Conclusion

Domestic dual-target HP has a more satisfactory efficacy and safety in the neoadjuvant phase of treatment.

Clinical trial registration

https://clinicaltrials.gov/study/NCT05985187, NCT05985187.
Locking plate versus K-wires and cast fixation in lateral closing-wedge osteotomy for cubitus varus deformity
Authors: Liu Jianghua , He Youzhi , Shi Qiang , Wang Yongfu
Published: February 2024

Background

The aim of this study was to assess the clinical and radiographic outcomes of cubitus varus treatments based on different fixation methods: Locking plate vs. Kirschner-wires (K-wires) and cast fixation.

Methods

This retrospective study of 28 patients was performed in lateral-wedge osteotomy for cubitus varus deformity in our hospital from July 2018 to July 2020. 14 patients in group A were treated by locking plate after lateral closing-wedge osteotomy, whereas other 14 patients were treated by K-wires in group B. We measured the bony union and carrying angle. The clinical and radiographic outcomes were assessed according to the Bellemore criteria.

Results

No nonunion, neurovascular injury or myositis ossificans was noted at follow-up. In group A, 1 patient with lateral condylar prominence was found. In group B, 2 patients with pinning site infection were treated successfully with oral antibiotics and 2 patients needed revision surgery for residual varus. According to the Bellemore criteria, statistically significant difference was noted between the two groups (P = 0.0458). In the present study, no statistically significant difference was noted in the length of incision and operation time between the 2 groups (P > 0.05). However, the postoperative carrying angle was significantly different at final follow-up between the 2 groups (P < 0.01).

Conclusions

Compared with K-wires and cast fixation, we recommend the wedge osteotomy with lateral locking plate to treat the cubitus varus deformity because locking plate could achieve better functional and cosmetic results and stabilize the distal humerus rigidly.
Critical roles of nicotinic acetylcholine receptors in olfactory memory formation and retrieval in crickets
Authors: Matsumoto Yukihisa , Matsumoto Chihiro Sato , Mizunami Makoto
Published: February 2024

Acetylcholine (ACh) is a major excitatory neurotransmitter in the insect central nervous system, and insect neurons express several types of ACh receptors (AChRs). AChRs are classified into two subgroups, muscarinic AChRs and nicotinic AChRs (nAChRs). nAChRs are also divided into two subgroups by sensitivity to α-bungarotoxin (α-BGT). The cricket Gryllus bimaculatus is one of the useful insects for studying the molecular mechanisms in olfactory learning and memory. However, the roles of nAChRs in olfactory learning and memory of the cricket are still unknown. In the present study, to investigate whether nAChRs are involved in cricket olfactory learning and memory, we tested the effects of two different AChR antagonists on long-term memory (LTM) formation and retrieval in a behavioral assay. The two AChR antagonists that we used are mecamylamine (MEC), an α-BGT-insensitive nAChR antagonist, and methyllycaconitine (MLA), an α-BGT-sensitive nAChR antagonist. In crickets, multiple-trial olfactory conditioning induced 1-day memory (LTM), whereas single-trial olfactory conditioning induced 1-h memory (mid-term memory, MTM) but not 1-day memory. Crickets injected with MEC 20 min before the retention test at 1 day after the multiple-trial conditioning exhibited no memory retrieval. This indicates that α-BGT-insensitive nAChRs participate in memory retrieval. In addition, crickets injected with MLA before the multiple-trial conditioning exhibited MTM but not LTM, indicating that α-BGT-sensitive nAChRs participate in the formation of LTM. Moreover, injection of nicotine (an nAChR agonist) before the single-trial conditioning induced LTM. Finally, the nitric oxide (NO)-cGMP signaling pathway is known to participate in the formation of LTM in crickets, and we conducted co-injection experiments with an agonist or inhibitor of the nAChR and an activator or inhibitor of the NO-cGMP signaling pathway. The results suggest that nAChR works upstream of the NO-cGMP signaling system in the LTM formation process.
Isoflavonoid metabolism in leguminous plants: an update and perspectives
Authors: Yang Qilin , Wang Guodong
Published: February 2024

Isoflavonoids constitute a well-investigated category of phenylpropanoid-derived specialized metabolites primarily found in leguminous plants. They play a crucial role in legume development and interactions with the environment. Isoflavonoids usually function as phytoalexins, acting against pathogenic microbes in nature. Additionally, they serve as signaling molecules in rhizobial symbiosis. Notably, owing to their molecular structure resembling human estrogen, they are recognized as phytoestrogens, imparting positive effects on human health. This review comprehensively outlines recent advancements in research pertaining to isoflavonoid biosynthesis, transcriptional regulation, transport, and physiological functions, with a particular emphasis on soybean plants. Additionally, we pose several questions to encourage exploration into novel contributors to isoflavonoid metabolism and their potential roles in plant-microbe interactions.
Post-discharge pharmacological treatment discontinuation of forensic psychiatric patients in Sweden
Authors: Noland Ebba , Virtanen Suvi , Klötz Logan Fia , Chang Zheng , Strandh Mattias
Published: February 2024

Introduction

Most forensic psychiatric patients have chronic psychiatric disorders that require long-term pharmacological treatment even after discharge from care. However, the prevalence and correlates of post-discharge medication discontinuation in this patient group remain unclear.

Objective

The aim of this study was to investigate the prevalence and correlates of post-discharge discontinuation of pharmacological treatment in forensic psychiatric patients in Sweden.

Methods

Data on individuals discharged from forensic psychiatric care between 2009 and 2018 (n = 1,142) with ongoing pharmacological treatment at the time of discharge (n = 856) were identified from the Swedish National Forensic Psychiatric Register. Cox regression models were used to estimate the association between patient characteristics and medication discontinuation.

Results

Of the 856 individuals with pharmacological treatment at discharge, 488 (57%) discontinued treatment within 2 years of discharge. Factors associated with an increased risk of treatment discontinuation varied between different types of psychotropic medications: the most important correlate was comorbidity between psychosis and personality disorder. Higher age at discharge, longer length of stay, having a history of several psychiatric care episodes, having a trustee, having a limited guardian, and a residing in a supported living accommodation at the time of discharge were associated with a decreased rate of medication discontinuation. This applied for antipsychotics, antidepressants, antiepileptics, and any psychotropic medication, but not for psychostimulants or drugs used in addictive disorders.

Conclusion

For many former forensic psychiatric patients, there are situational factors associated with medication discontinuation. This insight holds significance for professionals who are involved in pre-discharge planning within forensic psychiatric care and those who interact with this cohort of former patients post-discharge.
Identifying key factors for successful formulation and implementation of healthcare policies on non-communicable diseases: a multinational analysis
Authors: Babaita Abdulfatai Olamilekan , Jahan Yasmin , Nakamura Ryota , Moriyama Michiko
Published: February 2024

Objectives

Non-communicable diseases (NCDs) are a major public health concern that accounts for 74% of global deaths each year. The increasing burden of NCDs exhausts public health resources and threatens the achievement of the 2030 agenda for sustainable development. The purpose of this study is to thematically analyze the contributory factors in the health policy process and reforms to strengthen the prevention of NCDs across borders, as well as the milestones achieved through the process of policy-making, change, and implementation.

Method

This study informs and draws on the findings of contributory factors in the health policy process for preventing NCDs across borders: United States, England, Sweden, Bangladesh, Singapore, South Korea, and Thailand. Ten experts from the seven countries were recruited purposively for a semi-structured interview (e-Interview) on the NCD policy-making process in their countries, either through health ministries or the authors’ network. This descriptive qualitative study design is guided by the “Three I’s” framework of public policy (institutions, ideas, and interests). In addition to the information obtained from the interviewee, data were also sourced from relevant documents and homepages suggested by the interviewee, as well as health homepages of the countries.

Result

The following themes were generated: (1) environmental policies and social determinants, (2) multistakeholder involvement, (3) interministerial collaboration, (4) independent evidence and review institution, (5) integrated health data, and (6) primary care system. There was a shift from individual-targeted policies to environmental policies and social determinants. Notably, national campaigns were developed through non-governmental organizations (NGOs) for the primary prevention of NCDs.

Conclusion

The shift from behavioral modification and treatment to social determinants is important. NCDs are broad and require a multisector and multilevel approach. Establishing an organization or hierarchical body to overlook NCDs could result in increased awareness, focus, and surveillance and enhance the policy process.
Urban vs. rural: colorectal cancer survival and prognostic disparities from 2000 to 2019
Authors: Fu Ming-sheng , Pan Shu-xian , Cai Xun-quan , Pan Qin-cong
Published: February 2024

This study aimed to analyze the differences in colorectal cancer (CRC) survival between urban and rural areas over the past 20 years, as well as investigate potential prognostic factors for CRC survival in both populations. Using registry data from Surveillance, Epidemiology, and End Results (SEER) from 2000 to 2019, 463,827 CRC cases were identified, with 85.8% in urban and 14.2% in rural areas. The mortality of CRC surpassed its survival rate by the sixth year after diagnosis in urban areas and the fifth year in rural areas. Furthermore, the 5-year overall survival (OS) of CRC increased by 2.9–4.3 percentage points in urban and 0.6–1.5 percentage points in rural areas over the past two decades. Multivariable Cox regression models identified independent prognostic factors for OS and disease-specific survival (DSS) of CRC in urban and rural areas, including age over 40, Black ethnicity, and tumor size greater than 5 cm. In addition, household income below $75,000 was found to be an independent prognostic factor for OS and DSS of CRC in urban areas, while income below $55,000 was a significant factor for rural areas. In conclusion, this study found a notable difference in CRC survival between rural and urban areas. Independent prognostic factors shared among both rural and urban areas include age, tumor size, and race, while household income seem to be area-specific predictive variables. Collaboration between healthcare providers, patients, and communities to improve awareness and early detection of CRC may help to further advance survival rates.
An innovative Indigenous-led model for integrated COVID-19 case management in Auckland, New Zealand: lessons from implementation
Authors: Curtis Elana , Loring Belinda , Latham Kadin , Jordan Anthony , Chee Nigel , Hunia Rangimarie , Snowden Karl , Tari Kerry , Murupaenga Paora , Tipene Roimata , Whitcombe Stevie , Embers Kelleigh , McKree Jansen Rawiri
Published: February 2024

In Aotearoa/New Zealand (NZ), the Indigenous Māori population have been more severely impacted than non-Māori throughout the COVID-19 pandemic, and less well served by NZ’s COVID-19 response. This case-study describes an innovative Indigenous-led service delivery model, which was designed and implemented to improve the case and contact management of Māori with COVID-19 in Auckland. We outline the context in which the conventional public health case and contact management was failing Māori and the factors which enabled Indigenous innovation and leadership. We describe the details of the model and how the approach fundamentally differed to the conventional approach to care. Qualitative and quantitative data on impact of the model are shared, along with the key barriers and enablers in the implementation of the model. The Māori Regional Coordination Hub (MRCH) model offers a valuable alternative to the conventional public health case and contact management approach, and this case study highlights lessons which may be applicable to improving the design and delivery of public health services to other Indigenous and marginalized groups.
School students' burdens and resources after 2 years of COVID-19 in Austria: a qualitative study using content analysis
Authors: Sobotka Marlies , Kern Thomas , Haider Katja , Dale Rachel , Wöhrer Veronika , Pieh Christoph , Probst Thomas , Humer Elke , Jesser Andrea
Published: February 2024

Introduction

The mental health of young people has been severely affected by the COVID-19 pandemic and the measures associated with it. Mental health symptoms increased across various domains during the pandemic and subjective wellbeing decreased.

Methods

This study examined the burdens and resources of Austrian school students (M = 16.63 years old) in the third year of the pandemic and compared them descriptively with the burdens and resources identified in a comparative study in 2021. A cross-sectional online survey with open-ended questions from April to May 2022 provided data that was analyzed using qualitative content analysis. A sub-sample of N = 214 was selected from the larger sample. This sub-sample is representative for the Austrian population aged 15–19 in terms of gender and migrant background.

Results

Analysis of the open-ended questions showed that concerns about the pandemic and the burdens of the measures were no longer on young people's minds at the time of the survey in 2022. On the other hand, stress at school was increasing and the opening of schools and the resumption of face-to-face teaching were challenging for respondents. While resuming social contacts and leisure activities was mentioned as a resource by many respondents, some also expressed a desire for more time off and a retreat into coping strategies such as sleeping more or avoiding problems.

Discussion

Our findings suggest that there is a need for low-threshold support from teachers and parents to help students catch up on missed lessons and to empathize with the mas they make the transition back to “old normal”.
Biological Control Effect of Antagonistic Bacteria on Potato Black Scurf Disease Caused by Rhizoctonia solani
Authors: Lan Qingqing , Liu Yang , Mu Rongrong , Wang Xuetao , Zhou Qian , Islam Rehmat , Su Xu , Tian Yongqiang
Published: February 2024

Potato black scurf, caused by Rhizoctonia solani, is a severe soil-borne disease that affects the quality and production of potatoes worldwide. In our study, we used Paenibacillus polymyxa YF and Bacillus amyloliquefaciens HT to determine the antagonistic ability of R. solani, with a particular focus on the antagonistic action of P. polymyxa YF to R. solani and its biocontrol effect on potato black scurf. In fermentation, filtrate assay, 50% filtrate of P. polymyxa YF and B. amyloliquefaciens HT inhibited the growth of R. solani by 85.55% and 82.86%, respectively. Microscopic observations showed notable morphological changes with mycelial collapse, atrophy, and deformation following treatment with the antagonistic filtrates. Moreover, cell membrane permeability results showed increased conductivity in bacteria-treated samples compared to the control. P. polymyxa YF exhibited stable colonization on potato plants and secreted various extracellular enzymes (protease, amylase, and cellulase), along with the synthetic substances with growth-promoting effects, such as siderophores and Indole-3-acetic acid (IAA). Whether it is in the excised tissue inoculation or potted experiment, the negative control showed the highest rank of disease symptoms. In the pot experiment, after YF treatment, physiological parameters showed remarkable changes in plant height, root length, stem thickness, and dry and fresh weight. Compared to blank control, the activities of the four resistant enzymes increased significantly in the P. polymyxa YF treatment group. The upregulation in the P. polymyxa YF group was 4.04, 0.54, 0.46, and 3.10 times, respectively. PCR analysis identified genes in both bacterial strains coding for antimicrobial lipopeptides, including fenB, ituC, and srfAA, which are associated with fengycin, iturin, and surfactin synthesis. These findings demonstrated that P. polymyxa YF has a prominent antagonistic effect on R. solani, suggesting its potential as an effective biological control agent for controlling potato black scurf.
Evaluation of AquaCrop’s Ability to Simulate Water Stress Based on 2-Year Case Study of Maize Crop
Authors: Zhou Ding , Wang Hui , Wang Xiangxiang , Wang Fangfang , Zhang Jiabao , Ma Donghao
Published: February 2024

To apply AquaCrop to the study of agricultural soil moisture in the North China Plain, a water-treatment experiment on summer maize was carried out at the Fengqiu experimental station of the Chinese Academy of Sciences from 2017 to 2018. A water treatment was used to achieve field water capacities of 20 (W1), 40 (W2), and 60 (W3) cm soil layers under irrigation, and a rain-fed treatment (W0) was added. The model parameters were calibrated using the measured data in 2017. Then, they were applied to 2018 to verify the ability of the model to simulate water stress. The results showed that the variation trends for crop yield, canopy coverage, total soil water content, and the curve in the growth cycle simulated via AquaCrop were consistent with the actual observations; the results of a discrete analysis showed that the values of b (regression coefficient), R2 (determination coefficient), and EF (efficiency) were close to 1, and the values of the RMSE (root mean square error) were close to 0, which proved that the model could simulate dynamic changes in summer maize yield, canopy coverage, and total soil water content well. AquaCrop had good applicability in the North China Plain and could be applied to the study of agricultural water consumption and water-use efficiency in this area. The simulated values obtained can serve as an easily obtainable source of long-term experimental data in areas with frequent non-extreme weather events.