bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial diversity of stingless bee honey in Yunnan, China: isolation and genome sequencing of a novel acid-resistant Lactobacillus pentosus (SYBC-MI) with probiotic and L. tryptophan producing potential via millet fermentation
Authors: Basharat Samra , Meng Tiantian , Zhai Lixin , Hussain Asif , Aqeel Sahibzada Muhammad , Khan Salman , Shah Obaid Ullah , Liao Xiangru
Published: December 2023

Stingless bee (Hymenoptera, Apidae, and Trigona) honey is a remarkable “miracle liquid” with a wide range of medical benefits for conditions including gastroenteritis, cataracts, and wound healing. Our study aimed to isolate, identify, and characterize acid-resistant Lactobacillus spp. from sour honey distributed in Yunnan, China. To assess the safety of an entirely novel Lactobacillus pentosus strain, S4 (OM618128), based on probiotic property evaluation and whole-genome sequencing analysis. A 16S rRNA gene high-throughput sequencing analysis showed that Lactobacillus was abundant at the genus level in sour honey. Seven Lactobacillus strains (viz. S1–7) were isolated from sour honey using a multiple-anaerobic culture enrichment method. One potential acid-resistant isolate, Lactobacillus sp. S4, was obtained after screening the seven Lactobacillus isolates, and it had the highest lactic acid production (17.62 g/L), followed by Lactobacillus sp. S3 (17.07 g/L). Phylogenetic and comparative analyses of conserved sequence regions have shown that all seven strains are phylogenetically located in the Lactobacillus pentosus sub-cluster. In L. pentosus SYBC-MI, there is a circular chromosome (3288615 bps) and 11,466 bps plasmids. GC content is 44.03%. The number of predicted genes is 3,129, with 16 rRNAs and 74 tRNAs present. During the fermentation of foxtail millet by seven Lactobacillus pentosus (S1–7) strains isolated from sour honey, a potential tryptophan accumulating isolate, Lactobacillus pentosus S4, was obtained, which could reach a maximum tryptophan content of 238.43 mgL-1 that is 1.80 times the initial tryptophan content in the fermentation broth. This strain has strong acid tolerance, salt tolerance, and fermentation acid production abilities. This strain degrades nitrite at a rate of over 99%, and it has high probiotic potential as well. This project has established a solid foundation for further exploring the excellent lactic acid bacteria in sour honey. It is also investigating the key taxa and their role in the environment. According to the results of our studies, these LAB isolates provide a lot of potential for use in the future, as a source of probiotics for human, animals, and starter cultures for food applications.
Homemade: building the structure of the neurogenic niche
Authors: Valamparamban Ghanim Fajish , Spéder Pauline
Published: December 2023

Neural stem/progenitor cells live in an intricate cellular environment, the neurogenic niche, which supports their function and enables neurogenesis. The niche is made of a diversity of cell types, including neurons, glia and the vasculature, which are able to signal to and are structurally organised around neural stem/progenitor cells. While the focus has been on how individual cell types signal to and influence the behaviour of neural stem/progenitor cells, very little is actually known on how the niche is assembled during development from multiple cellular origins, and on the role of the resulting topology on these cells. This review proposes to draw a state-of-the art picture of this emerging field of research, with the aim to expose our knowledge on niche architecture and formation from different animal models (mouse, zebrafish and fruit fly). We will span its multiple aspects, from the existence and importance of local, adhesive interactions to the potential emergence of larger-scale topological properties through the careful assembly of diverse cellular and acellular components.
Clinical characteristics and high risk factors of patients with Omicron variant strain infection in Hebei, China
Authors: Wang Lihong , Liu Ting , Yue Hongjuan , Zhang Jiaojiao , Sheng Qihong , Wu Ling , Wang Xiaoyu , Zhang Mei , Wang Jing , Wang Jia , Yu Weifang
Published: December 2023

Objective

The Omicron variant has a weaker pathogenicity compared to the Delta variant but is highly transmissible and elderly critically ill patients account for the majority. This study has significant implications for guiding clinical personalized treatment and effectively utilizing healthcare resources.

Methods

The study focuses on 157 patients infected with the novel coronavirus Omicron variant, from December, 2022, to February, 2023. The objective is to analyze the baseline data, test results, imaging findings and identify risk factors associated with severe illness.

Results

Among the 157 included patients, there were 55 cases in the non-severe group (all were moderate cases) and 102 cases in the severe group (including severe and critical cases). Infection with the Omicron variant exhibits significant differences between non-severe and severe cases (baseline data, blood routine, coagulation, inflammatory markers, cardiac, liver, kidney functions, Chest CT, VTE score, etc.). A multifactorial logistic regression analysis showed that neutrophil percentage >75%, eosinophil percentage <0.4%, D-dimer >0.55 mg/L, PCT >0.25 ng/mL, LDH >250 U/L, albumin <40 g/L, A/G ratio <1.2, cholinesterase<5100 U/L, uric acid >357 mole/L and blood calcium<2.11 mmol/L were the most likely independent risk factors for severe novel coronavirus infection.

Conclusion

Advanced age, low oxygenation index, elevated neutrophil percentage, decreased eosinophil percentage, elevated PCT, elevated LDH, decreased albumin, decreased A/G ratio, elevated uric acid, decreased blood calcium, and elevated D-dimer are independent prognostic risk factors for non-severe patients progressing to severe illness. These factors should be closely monitored and actively treated to prevent or minimize the occurrence of severe illness.
A comprehensive roadmap for MedTech innovations uptake into the public healthcare system in India
Authors: Gupta Prakamya , Rai Charu , Shahi Anjaney , Sharma Manisha , Choudhury Ranjan , Kotwal Atul
Published: December 2023

Background

The burden of communicable, non-communicable diseases and reproductive maternal, newborn, child & adolescent health in India, reflects the necessity to develop tailored solutions. The plethora of MedTech innovations has provided healthcare facilities with more effective, affordable and accessible healthcare for people across the country. However, in spite of the Make-in-India scheme in the country, the indigenously developed healthcare technology is far from making an impact on the healthcare system.

Objective

To present a roadmap for MedTech innovations for their successful deployment into the public healthcare system.

Methodology

In addition to the literature review, recommendations were included from several stakeholders such as innovators, manufacturers, policymakers, subject matter experts, funding organizations, State health officials etc.

Results and conclusion

The journey of healthcare innovation from need identification to ideation, to prototyping and validation has paved the way towards the de novo design that caters to unmet needs. Innovations at the advanced technology readiness level (TRL 7/8 and above) demand a holistic and multidisciplinary approach which includes clinical validation, regulatory approval and Health technology assessment. The deployment of healthcare technology into the public healthcare system must consider resources (e.g., time, staff, budget, investment policies), ethical concerns (privacy, security, regulations, ownership), governance (policy, accountability, responsibility etc.), and Skills (capabilities, culture, etc.). The technologies are considered for field trials before the uptake in the public health system. Technology can be a key tool in achieving Universal Health Coverage but its use has to be strategic, judicious, and cognizant of issues around privacy and patient rights.
The thyroid hormone enhances mouse embryonic fibroblasts reprogramming to pluripotent stem cells: role of the nuclear receptor corepressor 1
Authors: Contreras-Jurado Constanza , Montero-Pedrazuela Ana , Pérez Raúl F. , Alemany Susana , Fraga Mario F. , Aranda Ana
Published: December 2023

Introduction

Pluripotent stem cells can be generated from somatic cells by the Yamanaka factors Oct4, Sox2, Klf4 and c-Myc.

Methods

Mouse embryonic fibroblasts (MEFs) were transduced with the Yamanaka factors and generation of induced pluripotent stem cells (iPSCs) was assessed by formation of alkaline phosphatase positive colonies, pluripotency gene expression and embryod bodies formation.

Results

The thyroid hormone triiodothyronine (T3) enhances MEFs reprogramming. T3-induced iPSCs resemble embryonic stem cells in terms of the expression profile and DNA methylation pattern of pluripotency genes, and of their potential for embryod body formation and differentiation into the three major germ layers. T3 induces reprogramming even though it increases expression of the cyclin kinase inhibitors p21 and p27, which are known to oppose acquisition of pluripotency. The actions of T3 on reprogramming are mainly mediated by the thyroid hormone receptor beta and T3 can enhance iPSC generation in the absence of c-Myc. The hormone cannot replace Oct4 on reprogramming, but in the presence of T3 is possible to obtain iPSCs, although with low efficiency, without exogenous Klf4. Furthermore, depletion of the corepressor NCoR (or Nuclear Receptor Corepressor 1) reduces MEFs reprogramming in the absence of the hormone and strongly decreases iPSC generation by T3 and also by 9cis-retinoic acid, a well-known inducer of reprogramming. NCoR depletion also markedly antagonizes induction of pluripotency gene expression by both ligands.

Conclusions

Inclusion of T3 on reprogramming strategies has a potential use in enhancing the generation of functional iPSCs for studies of cell plasticity, disease and regenerative medicine.
Ghrelin misbalance affects mice embryo implantation and pregnancy success by uterine immune dysregulation and nitrosative stress
Authors: Luque Eugenia Mercedes , Díaz-Luján Cintia María , Paira Daniela Andrea , de Loredo Nicolás , Torres Pedro Javier , Cantarelli Verónica Inés , Fretes Ricardo , Motrich Rubén Darío , Martini Ana Carolina
Published: December 2023

Introduction

In a previous study we found that ghrelin (Ghrl) misbalance during the peri-implantation period significantly impaired fetus development. In this study we aimed to evaluate the putative mechanisms underlying these effects, including embryo implantation success, uterine nitric oxide synthase (NOS) activity, nitric oxide synthesis and the inflammatory/immune uterine profile.

Methods

Ghrelin misbalance was induced by injecting 4nmol/animal/day of Ghrl (hyperghrelinemia) or 6nmol/animal/day of a Ghrl antagonist (Ant: (D-Lys3)GHRP-6) from day 3 to 8 of pregnancy. Control animals (C) were injected with de vehicle. Females were euthanized at pregnancy day 8 and their uteri excised in order to evaluate: the percentage of reabsorbed embryos (microscopically), eNOS, iNOS and nytrotirosine expression (by immunohistochemistry), nitrite synthesis (by Griess technique), VEGF, IL-10, IL-17, IL-6, MMP9 and GM-CSF expression (by qPCR) and leukocyte infiltration by flow cytometry (evaluating T cells, NK cells, granulocytes, dendritic cells and macrophages).

Results

Ant-treatment significantly increased the percentage of reabsorbed embryos and the uterine expression of eNOS, iNOS and nytrotirosine. (D-Lys3)GHRP-6-treatment increased also the expression of the inflammatory cytokines IL-6, IL-17 and MMP9, and decreased that of IL-10 (anti-inflammatory). Moreover, Ant-treatment increased also the NK cells population and that of CD11b+ dendritic cells; and decreased T cells percentages. Similarly, hyperghrelinemia showed a significant increase vs. C on eNOS, iNOS and nytrotirosineuterine expression and a decrease in T cells percentages.

Conclusion

Ghrl misbalance during the peri-implantation period induces pro-inflammatory changes and nitrosative stress in the gravid uterus, impairing significantly embryo implantation and/or development.
Diabetes status and cognitive function in middle-aged and older adults in the Canadian longitudinal study on aging
Authors: Sakib Mohammad Nazmus , Ramezan Reza , Hall Peter A.
Published: December 2023

Objectives

Diabetes is recognized as a significant risk factor for cognitive impairment. However, this association has not been thoroughly examined using large-scale population-based datasets in the Canadian context. The objective of this study was to investigate the potential association between cognitive function and diabetes in a large population-based sample of middle-aged and older Canadians.

Methods

We utilized baseline data from the Canadian Longitudinal Study on Aging (N=30,097) to test our hypotheses, using five indicators of cognitive function (animal fluency, Stroop interference, reaction time, immediate and delayed memory recall). We conducted multivariate multivariable linear regression and subsequently performed tests for moderation analysis with lifestyle factors and health status.

Results

The analysis revealed that type 2 diabetes (T2DM) was associated with lower performance on most cognitive tasks, including those assessing executive function (b=0.60, 95% CI 0.31 to 0.90), reaction time (b=16.94, 95% CI 9.18 to 24.70), immediate memory recall (b=-0.10, 95% CI -0.18 to -0.02), and delayed memory recall (b=-0.12, 95% CI -0.21 to -0.02). However, no significant association was observed between other types of diabetes and cognitive performance. Moderation effects were largely null for T2DM, with the exception of alcohol intake for reaction time, and physical activity for animal fluency.

Conclusions

The study showed that individuals with T2DM exhibit poor performance on tasks that assess executive function, reaction time, and memory. Therefore, optimizing cognitive health among individuals with T2DM should be a priority in primary care. Additionally, further studies should examine this association using longitudinal data.
Prevalence and characteristics of thelarche variant
Authors: Burlo Francesca , Lorenzon Beatrice , Tamaro Gianluca , Fabretto Antonella , Buonomo Francesca , Peinkhofer Martina , Vidonis Viviana , Vittori Giada , Faleschini Elena , Barbi Egidio , Tornese Gianluca
Published: December 2023

Introduction

Girls with early thelarche may show an intermediate clinical picture between isolated premature thelarche (PT) and central precocious puberty (CPP), defined as “thelarche variant” (TV), characterized by an FSH-predominant response, although a univocal definition is lacking.

Methods

Retrospective analysis on 91 girls with early thelarche (<8 years) and advanced bone age and/or accelerated growth who underwent 104 LHRH tests. Patients were classified into CPP (LH peak ≥5 IU/L; n = 28, 31%), TV (FSH peak ≥20 IU/L, LH peak <5 IU/L; n = 15, 16%), or PT (FSH peak <20 IU/L and LH peak <5 IU/L; n = 48, 53%).

Results

TV patients were younger (5.51 years) and with less advanced bone age (+0.8 years). They had higher basal and peak FSH (2.5 and 26.6 IU/L) and lower basal and peak LH/FSH ratios (0.08 and 0.11). The prevalence of presence of ovarian follicles >5 mm in TV (42%) was similar to CPP but significantly higher than PT, whereas maximum ovarian volume was smaller in TV (1.0 cm3). At the last follow-up visit (available in 60% of the cases), 44% of TV developed CPP compared with 14% of PT (p = 0.04). At first evaluation, those who progressed to CPP had a higher basal FSH (3.2 IU/L), lower LH/FSH ratio (0.07), and a higher peak LH (4.1 IU/L) compared with those who did not progress to CPP (basal FSH 1.9 IU/L, p < 0.01; basal LH/FSH ratio 0.12, p < 0.01; peak LH 2.8 IU/L, p = 0.02).

Conclusion

Using laboratory parameters only as a definition, we identified the clinical, laboratory, and imaging features of TV: these girls showed less advanced bone age and FSH predominance also at baseline, with smaller ovaries but with follicles >5 mm. Almost half of girls initially diagnosed as TV developed CPP at last follow-up visit, and these girls had higher baseline FSH, lower baseline LH/FSH ratio, and higher peak LH at first evaluation. Therefore, TV may represent a “precocious prepuberty” in which the FSH predominance may initially limit the progression into proper puberty, but it may eventually trigger full puberty (even CPP, depending on the girls’ age).
Decoding the role of platelets in tumour metastasis: enigmatic accomplices and intricate targets for anticancer treatments
Authors: Zhao Jessie , Huang Angela , Zeller Johannes , Peter Karlheinz , McFadyen James D.
Published: December 2023

The canonical role of platelets as central players in cardiovascular disease by way of their fundamental role in mediating thrombosis and haemostasis is well appreciated. However, there is now a large body of experimental evidence demonstrating that platelets are also pivotal in various physiological and pathophysiological processes other than maintaining haemostasis. Foremost amongst these is the emerging data highlighting the key role of platelets in driving cancer growth, metastasis and modulating the tumour microenvironment. As such, there is significant interest in targeting platelets therapeutically for the treatment of cancer. Therefore, the purpose of this review is to provide an overview of how platelets contribute to the cancer landscape and why platelets present as valuable targets for the development of novel cancer diagnosis tools and therapeutics.
Distinct regulatory machineries underlying divergent chromatin landscapes distinguish innate lymphoid cells from T helper cells
Authors: Zhang Yime , Hu Luni , Ren Guanqun , Zeng Yanyu , Zhao Xingyu , Zhong Chao
Published: December 2023

Innate lymphoid cells (ILCs), as the innate counterpart of CD4+ T helper (Th) cells, play crucial roles in maintaining tissue homeostasis. While the ILC subsets and their corresponding Th subsets demonstrate significant similarities in core programming related to effector function and regulatory mechanisms, their principal distinctions, given their innate and adaptive lymphocyte nature, remain largely unknown. In this study, we have employed an integrative analysis of 294 bulk RNA-sequencing results across all ILC and Th subsets, using scRNA-seq algorithms. Consequently, we identify two genesets that predominantly differentiate ILCs from Th cells, as well as three genesets that distinguish various immune responses. Furthermore, through chromatin accessibility analysis, we find that the ILC geneset tends to rely on specific transcriptional regulation at promoter regions compared with the Th geneset. Additionally, we observe that ILCs and Th cells are under differential transcriptional regulation. For example, ILCs are under stronger regulation by multiple transcription factors, including RORα, GATA3, and NF-κB. Otherwise, Th cells are under stronger regulation by AP-1. Thus, our findings suggest that, despite the acknowledged similarities in effector functions between ILC subsets and corresponding Th subsets, the underlying regulatory machineries still exhibit substantial distinctions. These insights provide a comprehensive understanding of the unique roles played by each cell type during immune responses.
Immunosuppressants alter the immune response associated with Glucantime® treatment for Leishmania infantum infection in a mouse model
Authors: Bernardo Lorena , Solana Jose Carlos , Sánchez Carmen , Torres Ana , Reyes-Cruz Eder Yaveth , Carrillo Eugenia , Moreno Javier
Published: December 2023

Background

Immunosuppression is a major risk factor for the development of visceral leishmaniasis (VL). The number of patients receiving immunosuppressant drugs such as TNF antagonist (anti-TNF) and methotrexate (MTX) is increasing. In these patients, VL is more severe, their response to treatment poorer, and they are at higher risk of relapse, a consequence (largely) of the poor and inappropriate immune response they develop.

Objectives

To examine the effect of immunosuppressive treatment on the host immune response and thus gain insight into the reduced efficacy of pentavalent antimonials in these patients. Experiments were performed using BALB/c mice immunosuppressed with anti-TNF or MTX, infected with Leishmania infantum promastigotes, and then treated with Glucantime® at clinical doses.

Results

Immunosuppression with both agents impeded parasite elimination from the spleen and bone marrow. Low pro-inflammatory cytokine production by CD4+ and CD8+ T cells was detected, along with an increase in PD-1 and IL-10 expression by B and T cells in the immunosuppressed groups after treatment.

Conclusion

The immunosuppressed mice were unable to develop specific cellular immunity to the parasite, perhaps explaining the greater risk of VL relapse seen in pharmacologically immunosuppressed human patients.
PD-1 and PD-L1: architects of immune symphony and immunotherapy breakthroughs in cancer treatment
Authors: Parvez Adil , Choudhary Furqan , Mudgal Priyal , Khan Rahila , Qureshi Kamal A. , Farooqi Humaira , Aspatwar Ashok
Published: December 2023

PD-1 (Programmed Cell Death Protein-1) and PD-L1 (Programmed Cell Death Ligand-1) play a crucial role in regulating the immune system and preventing autoimmunity. Cancer cells can manipulate this system, allowing them to escape immune detection and promote tumor growth. Therapies targeting the PD-1/PD-L1 pathway have transformed cancer treatment and have demonstrated significant effectiveness against various cancer types. This study delves into the structure and signaling dynamics of PD-1 and its ligands PD-L1/PD-L2, the diverse PD-1/PD-L1 inhibitors and their efficacy, and the resistance observed in some patients. Furthermore, this study explored the challenges associated with the PD-1/PD-L1 inhibitor treatment approach. Recent advancements in the combination of immunotherapy with chemotherapy, radiation, and surgical procedures to enhance patient outcomes have also been highlighted. Overall, this study offers an in-depth overview of the significance of PD-1/PD-L1 in cancer immunotherapy and its future implications in oncology.
The relationship between cadmium exposure and preeclampsia: a systematic review and meta-analysis
Authors: Li Chu , Luo Jiamin , Yang Yunping , Wang Qianqian , Zheng Yanmei , Zhong Zixing
Published: December 2023

Background

Cadmium (Cd) is a heavy metal associated with several human disorders. Preeclampsia is a major cause of maternal mortality worldwide. The association between maternal Cd exposure and preeclampsia remains elusive.

Methods

To better understand this relationship, we conducted a systematic review and meta-analysis of eligible studies from five databases (PubMed, Embase, Web of Science, Scopus, and CNKI) from their inception to September 10, 2022. The quality of these studies was evaluated using the Newcastle-Ottawa quality assessment scale (NOS). We use random-effects models to calculate overall standardized mean differences (SMDs) and 95% confidence intervals (CIs). Sensitivity analyses were performed to assess the robustness of our results. We also evaluated publication bias using Egger’s and Begg’s tests. Additionally, we conducted meta-regression and sub-group analyses to identify potential sources of heterogeneity between studies.

Results

Our analysis included a total of 17 studies with 10,373 participants. We found a significant association between maternal cadmium exposure and the risk of preeclampsia (SMD 0.27, 95% CI 0.09–0.44, p < 0.01). No significant publication bias was detected in Begg’s or Egger’s tests. Meta-regression suggested that geographical location, year of publication, cadmium samples, sample size, and measurement methods did not contribute to heterogeneity between studies.

Conclusion

Our findings suggest that maternal blood cadmium levels are associated with an increased risk of preeclampsia. In contrast, the pregnant women’s urine or placental levels of cadmium may not suggest preeclamptic risk during pregnancy. Further high-quality clinical studies and animal experiments are needed to understand this association better.

Systematic review registration

PROSPERO, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=361291, identifier: CRD42022361291.
Identifying the link between serum VEGF and KL-6 concentrations: a correlation analysis for idiopathic pulmonary fibrosis interstitial lung disease progression
Authors: Zhong Bin , Luo Shuixiang
Published: December 2023

Background

Idiopathic pulmonary fibrosis interstitial lung disease (IPF-ILD) is a progressive lung disease characterized by excessive collagen deposition and fibrotic changes in the lungs. Identifying reliable serum markers that correlate with disease progression is crucial for diagnosis and prognosis.

Objective

This study aimed to explore the association between serum markers KL-6 and VEGF and IPF-ILD. Specifically, it assessed their correlation with PaO2, a measure of pulmonary gas function, to provide diagnostic and prognostic indicators.

Methods

Patients with IPF-ILD were included, and their serum levels of KL-6 and VEGF were measured. Correlations with fibrotic damage and PaO2 were analyzed using statistical methods.

Results

The analysis confirmed a positive correlation between the serum marker KL-6 and the degree of fibrotic damage in IPF-ILD. On the other hand, the serum marker VEGF was found to promote disease progression. In terms of correlation with PaO2, both KL-6 and VEGF demonstrated high sensitivity and specificity. Specifically, the correlation between KL-6 and PaO2 suggests that it can be used as a reliable indicator to assess the status of pulmonary oxygenation function in patients with ILD. The correlation between VEGF and PaO2 helps to understand its role in the progression of IPF-ILD and provides an important basis for predicting patient prognosis.

Conclusion

This study confirmed the correlation between KL-6 and VEGF with IPF-ILD and their association with PaO2. KL-6 and VEGF demonstrated high specificity and sensitivity in diagnosing, monitoring, and predicting prognosis in IPF-ILD. These findings contribute to our understanding of the disease and have clinical implications for diagnosis and prognostication.
Novel nomograms to predict risk and prognosis in hospitalized patients with severe fever with thrombocytopenia syndrome
Authors: Li Zhenxing , Zhang Zhaoru , Chen Chong
Published: December 2023

Background

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging and life-threatening infectious disease caused by SFTS virus. Although recent studies have reported the use of nomograms based on demographic and laboratory data to predict the prognosis of SFTS, no study has included viral load, which is an important factor that influences the prognosis, when compared with other risk factors. Therefore, this study aimed to develop a model that predicts SFTS prognosis before it reaches the critical illness stage and to compare the predictive ability of groups with and without viral load.

Methods

Two hundred patients with SFTS were enrolled between June 2018 and August 2023. Data were sourced from the first laboratory results at admission, and two nomograms for mortality risk were developed using multivariate logistic regression to identify the risk variables for poor prognosis in these patients. We calculated the area under the receiver operating characteristic curve (AUC) for the two nomograms to assess their discrimination, and predictive abilities were compared using net reclassification improvement (NRI) and integrated discrimination improvement (IDI).

Results

The multivariate logistic regression analysis identified four independent risk factors: age, bleeding manifestations, prolonged activated partial thromboplastin time, and viral load. Based on these factors, a final nomogram predicting mortality risk in patients with SFTS was constructed; in addition, a simplified nomogram was constructed excluding the viral load. The AUC [0.926, 95% confidence interval (CI): 0.882–0.970 vs. 0.882, 95% CI: 35 0.823–0.942], NRI (0.143, 95% CI, 0.036–0.285), and IDI (0.124, 95% CI, 0.061–0.186) were calculated and compared between the two models. The calibration curves of the two models showed excellent concordance, and decision curve analysis was used to quantify the net benefit at different threshold probabilities.

Conclusion

Two critical risk nomograms were developed based on the indicators for early prediction of mortality risk in patients with SFTS, and enhanced predictive accuracy was observed in the model that incorporated the viral load. The models developed will provide frontline clinicians with a convenient tool for early identification of critically ill patients and initiation of a better personalized treatment in a timely manner.
A 10-year retrospective study of methicillin-resistant Staphylococcus aureus from burn wound infection in southeast China from 2013 to 2022
Authors: Gu Feifei , He Weiping , Zhu Dedong , Yang Peilang , Sun Jingyong , Han Lizhong
Published: December 2023

Background

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most commonly encountered pathogens among burn patients incurring substantial morbidity and mortality. To investigate the epidemiology and features of MRSA in burn wound infections, we conducted a 10-year retrospective study on MRSA isolated from burn patients with burn wound infections from southeast China from 2013 to 2022.

Methods

One hundred MRSA isolates (10 isolates each year) from burn wound infection among burn patients from 2013 to 2022 were randomly selected and enrolled. In addition to the clinical data of the 100 burn patients, MRSA isolates were characterized by antimicrobial susceptibility testing, detection of toxin genes, and molecular typing.

Results

The median time from the onset of burns and admission to MRSA detected was 13 and 5 days, respectively. No MRSA isolate was found resistant to quinupristin/dalfopristin, linezolid, and vancomycin. Toxin gene seg was found most frequently (90%) followed by sea (70%) and eta (64%). CC8 (74%), ST239 (70%), and SCCmec III (72%) were the most common CC, ST, and SCCmec types, respectively.

Conclusion

ST239-III (70%) was the predominant clone found in MRSA from burn wound infection among burn patients in southeast China. ST239-III was less found from 2018 to 2022. A higher diversity of MRSA clones was observed in these recent 5 years than that from 2013 to 2017.
RNA-binding proteins regulating the CD44 alternative splicing
Authors: Maltseva Diana , Tonevitsky Alexander
Published: December 2023

Alternative splicing is often deregulated in cancer, and cancer-specific isoform switches are part of the oncogenic transformation of cells. Accumulating evidence indicates that isoforms of the multifunctional cell-surface glycoprotein CD44 play different roles in cancer cells as compared to normal cells. In particular, the shift of CD44 isoforms is required for epithelial to mesenchymal transition (EMT) and is crucial for the maintenance of pluripotency in normal human cells and the acquisition of cancer stem cells phenotype for malignant cells. The growing and seemingly promising use of splicing inhibitors for treating cancer and other pathologies gives hope for the prospect of using such an approach to regulate CD44 alternative splicing. This review integrates current knowledge about regulating CD44 alternative splicing by RNA-binding proteins.
Rescue of sharp wave-ripples and prevention of network hyperexcitability in the ventral but not the dorsal hippocampus of a rat model of fragile X syndrome
Authors: Leontiadis Leonidas J. , Trompoukis George , Tsotsokou Giota , Miliou Athina , Felemegkas Panagiotis , Papatheodoropoulos Costas
Published: December 2023

Fragile X syndrome (FXS) is a genetic neurodevelopmental disorder characterized by intellectual disability and is related to autism. FXS is caused by mutations of the fragile X messenger ribonucleoprotein 1 gene (Fmr1) and is associated with alterations in neuronal network excitability in several brain areas including hippocampus. The loss of fragile X protein affects brain oscillations, however, the effects of FXS on hippocampal sharp wave-ripples (SWRs), an endogenous hippocampal pattern contributing to memory consolidation have not been sufficiently clarified. In addition, it is still not known whether dorsal and ventral hippocampus are similarly affected by FXS. We used a Fmr1 knock-out (KO) rat model of FXS and electrophysiological recordings from the CA1 area of adult rat hippocampal slices to assess spontaneous and evoked neural activity. We find that SWRs and associated multiunit activity are affected in the dorsal but not the ventral KO hippocampus, while complex spike bursts remain normal in both segments of the KO hippocampus. Local network excitability increases in the dorsal KO hippocampus. Furthermore, specifically in the ventral hippocampus of KO rats we found an increased effectiveness of inhibition in suppressing excitation and an upregulation of α1GABAA receptor subtype. These changes in the ventral KO hippocampus are accompanied by a striking reduction in its susceptibility to induced epileptiform activity. We propose that the neuronal network specifically in the ventral segment of the hippocampus is reorganized in adult Fmr1-KO rats by means of balanced changes between excitability and inhibition to ensure normal generation of SWRs and preventing at the same time derailment of the neural activity toward hyperexcitability.
An integrated workflow for 2D and 3D posture analysis during vestibular system testing in mice
Authors: Wan Yong , Edmond Michaela A. , Kitz Colin , Southern Joseph , Holman Holly A.
Published: December 2023

Introduction

Posture extraction from videos is fundamental to many real-world applications, including health screenings. In this study, we extend the utility and specificity of a well-established protocol, the balance beam, for examining balance and active motor coordination in adult mice of both sexes.

Objectives

The primary objective of this study is to design a workflow for analyzing the postures of mice walking on a balance beam.

Methods

We developed new tools and scripts based on the FluoRender architecture, which can interact with DeepLabCut (DLC) through Python code. Notably, twenty input videos were divided into four feature point groups (head, body, tail, and feet), based on camera positions relative to the balance beam (left and right), and viewing angles (90° and 45° from the beam). We determined key feature points on the mouse to track posture in a still video frame. We extracted a standard walk cycle (SWC) by focusing on foot movements, which were computed by a weighted average of the extracted walk cycles. The correlation of each walk cycle to the SWC was used as the weight.

Results

We learned that positions of the camera angles significantly improved the performance of 2D pose estimation (90°) and 3D (45°). Comparing the SWCs from age-matched mice, we found a consistent pattern of supporting feet on the beam. Two feet were consistently on the beam followed by three feet and another three feet in a 2-3-3 pattern. However, this pattern can be mirrored among individual subjects. A subtle phase shift of foot movement was also observed from the SWCs. Furthermore, we compared the SWCs with speed values to reveal anomalies in mouse walk postures. Some anomalies can be explained as the start or finish of the traversal, while others may be correlated to the distractions of the test environment, which will need further investigation.

Conclusion

Our posture analysis workflow improves the classical behavioral testing and analysis, allowing the detection of subtle, but significant differences in vestibular function and motor coordination.
Inhalation-modulated detection of olfactory BOLD responses in the human brain
Authors: Alahäivälä Aino-Lotta I. , Thaploo Divesh , Wein Simon , Seidel Philipp , Riebel Marco , Hummel Thomas , Schwarzbach Jens Volkmar
Published: December 2023

Introduction

In contrast to other sensory domains, detection of primary olfactory processes using functional magnetic resonance imaging has proven to be notably challenging with conventional block designs. This difficulty arises from significant habituation and hemodynamic responses in olfactory areas that do not appear to align with extended boxcar functions convolved with a generic hemodynamic response model. Consequently, some researchers have advocated for a transition to event-related designs, despite their known lower detection power compared to block designs.

Methods

Here, we conducted a block design experiment with 16s of continuous odorant stimulation alternating with 16s of continuous odorless air stimulation in 33 healthy participants. We compared four statistical analyses that relied either on standard block designs (SBD1-2) or on block designs that were modulated by the participants' individual breathing patterns (MBD1-2).

Results

We found that such modulated block designs were comparatively more powerful than standard block designs, despite having a substantially lower design efficiency. Using whole-brain effect size maps, we observed that the right insular and medial aspects of the left piriform cortex exhibited a preference for a breathing-modulated analysis approach.

Discussion

Research in olfaction that necessitates designs with longer-lasting blocks, such as those employed in the investigation of state-dependent processing, will benefit from the breathing-modulated analyses outlined in this study.
Ribociclib-induced liver injury: a case report
Authors: Schaeffer Sofia , Lutz Christian , Dobbie Michael , Terracciano Luigi M. , Matter Matthias , Vosbeck Jürg , Heim Markus H. , Bernsmeier Christine
Published: December 2023

Background

Idiosyncratic drug-induced liver injury (DILI) is a rare, unpredictable hepatic adverse event and the most common cause of acute liver failure in Europe and the US. Ribociclib is a potent Cyclin-dependent kinase 4 and 6 (CDK4/6)-inhibitor administered for advanced hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Previous reports have shown hepatotoxicity without liver necrosis related to ribociclib.

Case presentation

A 41-year-old female patient with primary metastatic HR-positive, HER2-negative breast cancer developed liver enzyme elevation under treatment with ribociclib. Ribociclib was withdrawn 8 weeks after initiation due to liver enzyme elevation. A liver biopsy, performed due to further enzyme increase (peak ALT 2836 U/l), onset of jaundice (peak bilirubin 353 µmol/l) and coagulopathy (INR 1.8) two weeks later, revealed acute hepatitis with 30% parenchymal necrosis. Roussel Uclaf Causality Assessment Method (RUCAM) score was 7 points (probable). Under treatment with prednisone (60mg), initiated 2 weeks after drug withdrawal, and subsequently N-acetylcysteine (Prescott regimen) liver enzymes normalized within 8 weeks along with prednisone tapering.

Conclusion

This case illustrates the development of a severe idiosyncratic hepatocellular pattern DILI grade 3 (International DILI Expert Working Group) induced by ribociclib. Routine liver enzyme testing during therapy, immediate hepatologic work-up and treatment interruption in case of liver enzyme elevation are highly recommended. Corticosteroid treatment should be considered in cases of severe necroinflammation.
Design, synthesis, and evaluation of 4-(3-(3,5-dimethylisoxazol-4-yl)benzyl)phthalazin-1(2H)-one derivatives: potent BRD4 inhibitors with anti-breast cancer activity
Authors: Li Yingpeng , Chu Xinhong , Yin Yu , Li Hongkun , Fu Hui , Feng Xinchi , Deng Yanru , Ge Jun
Published: December 2023

BRD4 inhibitors have demonstrated promising potential in cancer therapy. However, their therapeutic efficacy in breast cancer varies depending on the breast cancer subtype, particularly in the treatment of TNBC. In this study, we designed and synthesized 94 derivatives of 4-(3-(3,5-dimethylisoxazol-4-yl)benzyl)phthalazin-1(2H)-one to evaluate their inhibitory activities against BRD4. Notably, compound DDT26 exhibited the most potent inhibitory effect on BRD4, with an IC50 value of 0.237 ± 0.093 μM. DDT26 demonstrated significant anti-proliferative activity against both TNBC cell lines and MCF-7 cells. Intriguingly, the phthalazinone moiety of DDT26 mimicked the PAPR1 substrate, resulting in DDT26 displaying a moderate inhibitory effect on PARP1 with an IC50 value of 4.289 ± 1.807 μM. Further, DDT26 was shown to modulate the expression of c-MYC and γ-H2AX, induce DNA damage, inhibit cell migration and colony formation, and arrest the cell cycle at the G1 phase in MCF-7 cells. Our findings present potential lead compounds for the development of potent anti-breast cancer agents targeting BRD4.
The role of external factors on the reactivation of the heritage language of Turkish-German returnees
Authors: Antonova-Unlu Elena , Bayram Fatih
Published: December 2023

Introduction

This study investigates the heritage language performance of Turkish-German returnees upon their reintegration into Turkey and explores the impact of external factors on their proficiency in the (re-)activated heritage language (HL).

Methods

Data collection involved the participation of 28 Turkish heritage speakers and a control group of 28 monolingual speakers. The language proficiency of both groups was assessed through a cloze test and an error correction task with a focus on converbial constructions, evidentiality and direct object case marking in Turkish. A sociolinguistic background questionnaire was used to obtain information about their language experiences. The study focused on understanding the individual and group differences in returnee’s heritage language performance. Additionally, random forest analysis was employed to investigate the relative influence of external factors on individual variability within the returnee group.

Results and Discussion

The analysis of results revealed notable group differences between the returnees and the control group, emphasizing the unique linguistic challenges faced by those who returned to Turkey. Within the returnee group, there was considerable individual variability in heritage language performance. The subsequent exploration of individual variation highlighted the significant role of external factors. Notably, the length of residence in Germany, the age at which participants returned to Turkey, and the frequency of Turkish language use in their migration context emerged as significant predictors of the returnee participants’ proficiency in their (re-)activated HL. Surprisingly, formal contact with the dominant German language did not exert a substantial impact on the returnees’ language proficiency, suggesting the nuanced influence of various external factors on heritage language development.
Future of nature, our future. A preregistered report on future time perspective, social value orientation, and pro-environmental outcomes based on data from Poland and Sweden
Authors: Nowakowska Iwona , Rönnlund Michael
Published: December 2023

Introduction

The objective of the study was to examine the role of social value orientation and future time perspective to account for individual differences in pro-environmental behaviors, intentions, and opinions about the link between pro-environmental action and pandemic threat (three separate models) in Polish and Swedish samples expected to differ in rate of pro-environmental behaviors (higher in Sweden). We hypothesized that for Poland, future time perspective would be linked to pro-environmental outcomes only when social value orientation is average or high. In contrast, for Sweden, we expected a significant link between these variables regardless of social value orientation.

Methods

In total, 301 (150 Polish, 151 Swedish) participants completed online surveys via Prolific.co research panel. We controlled for individualizing/binding moral foundations, present time perspectives, and selected demographic variables in the analyses.

Results

In line with expectations, the individualizing moral foundations were a significant predictor across all three models. The data did not support our focal hypothesis regarding the interaction between future time perspective and social value orientation. For pro-environmental behaviors in the past 6 months, the future time perspective was a predictor only when social value orientation was low.

Discussion

The results suggest that when encouraging more competitive (compared to altruistic) people to behave in a green way, it might be crucial to underline the future consequences and benefits, consistent with the future time perspective. The pro-environmental campaigns could, therefore, highlight how green behavior may bring personal gains in the future, which are typically valued by individualistic people, such as savings or social status.
Participant experiences of guided self-help Acceptance and Commitment Therapy for improving quality of life in muscle disease: a nested qualitative study within the ACTMus randomized controlled trial
Authors: Edwards Victoria , Vari Chiara , Rose Michael , Graham Christopher D. , O'Connell Nicola , Taylor Emma , McCracken Lance M. , Radunovic Aleksandar , Rakowicz Wojtek , Norton Sam , Chalder Trudie
Published: December 2023

Introduction

In adults, muscle disease (MD) is typically a chronic long-term condition that can lead to a reduced quality of life (QoL). Previous research suggests that a psychological intervention, in particular Acceptance and Commitment Therapy (ACT), may help improve QoL for individuals living with chronic conditions such as MD.

Methods

This nested qualitative study was incorporated within a randomized controlled trial which evaluated a guided self-help ACT intervention for people living with MD to explore their experiences of the intervention. Semi-structured interviews (n = 20) were conducted with those who had received ACT. Data were analyzed via thematic analysis.

Results

There were four overarching themes. (1) Views on whether therapy sessions would help with a medical condition: participants' expectations regarding ACT varied. Some participants were skeptical about mindfulness. (2) I was able to look at things in a different way: participants described increased meaningful activity, greater awareness of thoughts and emotions and acceptance or adaptation to mobility problems. Some described improvement in the quality of relationships and a sense of feeling free. (3) Treating the body and the mind together: following the intervention participants noted that a holistic approach to healthcare is beneficial. (4) Intervention delivery: The remote delivery was generally seen as helpful for practical reasons and allowed participants to speak openly. Participants voiced a need for follow-up sessions.

Discussion

Overall, the intervention was experienced as acceptable. Suggested improvements included de-emphasizing the role of mindfulness and adding follow-up sessions.