bluuebunny/crossref_metadata_2025 huggingface dataset:
TRIM26 inhibits clear cell renal cell carcinoma progression through destabilizing ETK and thus inactivation of AKT/mTOR signaling
Authors: Zheng Di , Ning Jinzhuo , Deng Hao , Ruan Yuan , Cheng Fan
Published: May 2024

Background

Tripartite motif-containing 26 (TRIM26), a member of the TRIM protein family, exerts dual function in several types of cancer. Nevertheless, the precise role of TRIM26 in clear cell renal cell carcinoma (ccRCC) has not been investigated.

Methods

The expression of TRIM26 in ccRCC tissues and cell lines were examined through the use of public resources and experimental validation. The impacts of TRIM26 on cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) process were determined via CCK-8, colony formation, EdU incorporation, wound healing, Transwell invasion, Western blot, and Immunofluorescence assays. RNA-seq followed by bioinformatic analyses were used to identify the downstream pathway of TRIM26. The interaction between TRIM26 and ETK was assessed by co-immunoprecipitation, qRT-PCR, Western blot, cycloheximide (CHX) chase, and in vivo ubiquitination assays.

Results

We have shown that TRIM26 exhibits a downregulation in both ccRCC tissues and cell lines. Furthermore, this decreased expression of TRIM26 is closely linked to unfavorable overall survival and diseases-free survival outcomes among ccRCC patients. Gain- and loss-of-function experiments demonstrated that increasing the expression of TRIM26 suppressed the proliferation, migration, invasion, and EMT process of ccRCC cells. Conversely, reducing the expression of TRIM26 had the opposite effects. RNA sequencing, coupled with bioinformatic analysis, revealed a significant enrichment of the mTOR signaling pathway in the control group compared to the group with TRIM26 overexpression. This finding was then confirmed by a western blot assay. Subsequent examination revealed that TRMI26 had a direct interaction with ETK, a non-receptor tyrosine kinase. This interaction facilitated the ubiquitination and degradation of ETK, resulting in the deactivation of the AKT/mTOR signaling pathway in ccRCC. ETK overexpression counteracted the inhibitory effects of TRIM26 overexpression on cell proliferation, migration, and invasion.

Conclusion

Our results have shown a novel mechanism by which TRIM26 hinders the advancement of ccRCC by binding to and destabilizing ETK, thus leading to the deactivation of AKT/mTOR signaling. TRIM26 shows promise as both a therapeutic target and prognostic biomarker for ccRCC patients.
Mesenchymal stromal cell-derived extracellular vesicles therapy openings new translational challenges in immunomodulating acute liver inflammation
Authors: Sitbon Alexandre , Delmotte Pierre-Romain , Pistorio Valéria , Halter Sébastien , Gallet Jérémy , Gautheron Jérémie , Monsel Antoine
Published: May 2024

Inflammation plays a critical role in conditions such as acute liver failure, acute-on-chronic liver failure, and ischemia–reperfusion-induced liver injury. Various pathogenic pathways contribute to liver inflammation, involving inflammatory polarization of macrophages and Küpffer cells, neutrophil infiltration, dysregulation of T cell subsets, oxidative stress, and activation of hepatic stellate cells. While mesenchymal stromal cells (MSCs) have demonstrated beneficial properties, their clinical translation is limited by their cellular nature. However, MSC-derived extracellular vesicles (MSC-EVs) have emerged as a promising cell-free therapeutic approach for immunomodulation. MSC-EVs naturally mirror their parental cell properties, overcoming the limitations associated with the use of MSCs. In vitro and in vivo preclinical studies have demonstrated that MSC-EVs replicate the beneficial effects of MSCs in liver injury. This includes the reduction of cell death and oxidative stress, improvement of hepatocyte function, induction of immunomodulatory effects, and mitigation of cytokine storm. Nevertheless, MSC-EVs face challenges regarding the necessity of defining consistent isolation methods, optimizing MSCs culture conditions, and establishing quality control measures for EV characterization and functional assessment. By establishing standardized protocols, guidelines, and affordable cost mass production, clinicians and researchers will have a solid foundation to conduct further studies, validate the therapeutic efficacy of MSC-EVs, and ultimately pave the way for their clinical implementation in acute liver injury.
Mogroside V reduced the excessive endoplasmic reticulum stress and mitigated the Ulcerative colitis induced by dextran sulfate sodium in mice
Authors: Tan Yue-Rong , Shen Si-Yang , Li Xin-Yi , Yi Peng-Fei , Fu Ben-Dong , Peng Lu-Yuan
Published: May 2024

Ulcerative colitis (UC) is an idiopathic, chronic inflammatory condition of the colon, characterized by repeated attacks, a lack of effective treatment options, and significant physical and mental health complications for patients. The endoplasmic reticulum (ER) is a vital intracellular organelle in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) is induced when the body is exposed to adverse external stimuli. Numerous studies have shown that ERS-induced apoptosis plays a vital role in the pathogenesis of UC. Mogroside V (MV), an active ingredient of Monk fruit, has demonstrated excellent anti-inflammatory and antioxidant effects. In this study, we investigated the therapeutic effects of MV on dextran sulfate sodium (DSS)-induced UC and its potential mechanisms based on ERS. The results showed that MV exerted a protective effect against DSS-induced UC in mice as reflected by reduced DAI scores, increased colon length, reduced histological scores of the colon, and levels of pro-inflammatory cytokines, as well as decreased intestinal permeability. In addition, the expression of ERS pathway including BIP, PERK, eIF2α, ATF4, CHOP, as well as the apoptosis-related protein including Caspase-12, Bcl-2 and Bax, was found to be elevated in UC. However, MV treatment significantly inhibited the UC and reversed the expression of inflammation signaling pathway including ERS and ERS-induced apoptosis. Additionally, the addition of tunicamycin (Tm), an ERS activator, significantly weakened the therapeutic effect of MV on UC in mice. These findings suggest that MV may be a therapeutic agent for the treatment of DSS-induced UC by inhibiting the activation of the ERS-apoptosis pathway, and may provide a novel avenue for the treatment of UC.
Causative role of a novel intronic indel variant in FBN1 and maternal germinal mosaicism in Marfan syndrome
Authors: Bai Ying , Sun Yue , Yu Chenguang , Xia Yanjie , Wu Jing , Wang Li , Gao Yong , Tu Xin , Kong Xiangdong
Published: May 2024

Background

Marfan syndrome (MFS) is an autosomal dominant connective tissue disease with wide clinical heterogeneity, and mainly caused by pathogenic variants in fibrillin-1 (FBN1).

Methods

A Chinese 4-generation MFS pedigree with 16 family members was recruited and exome sequencing (ES) was performed in the proband. Transcript analysis (patient RNA and minigene assays) and in silico structural analysis were used to determine the pathogenicity of the variant. In addition, germline mosaicism in family member (Ι:1) was assessed using quantitative fluorescent polymerase chain reaction (QF-PCR) and short tandem repeat PCR (STR) analyses.

Results

Two cis-compound benign intronic variants of FBN1 (c.3464–4 A > G and c.3464-5G > A) were identified in the proband by ES. As a compound variant, c.3464-5_3464-4delGAinsAG was found to be pathogenic and co-segregated with MFS. RNA studies indicated that aberrant transcripts were found only in patients and mutant-type clones. The variant c.3464-5_3464-4delGAinsAG caused erroneous integration of a 3 bp sequence into intron 28 and resulted in the insertion of one amino acid in the protein sequence (p.Ile1154_Asp1155insAla). Structural analyses suggested that p.Ile1154_Asp1155insAla affected the protein’s secondary structure by interfering with one disulfide bond between Cys1140 and Cys1153 and causing the extension of an anti-parallel β sheet in the calcium-binding epidermal growth factor-like (cbEGF)13 domain. In addition, the asymptomatic family member Ι:1 was deduced to be a gonadal mosaic as assessed by inconsistent results of sequencing and STR analysis.

Conclusions

To our knowledge, FBN1 c.3464-5_3464-4delGAinsAG is the first identified pathogenic intronic indel variant affecting non-canonical splice sites in this gene. Our study reinforces the importance of assessing the pathogenic role of intronic variants at the mRNA level, with structural analysis, and the occurrence of mosaicism.
Facing the complex challenges of people with epidermolysis bullosa in Austria: a mixed methods study on burdens and helpful practices
Authors: Salamon Gudrun , Field-Werners Ursula , Strobl Sophie , Hübl Vinzenz , Diem Anja
Published: May 2024

Background

With approximately 500 people affected in Austria, epidermolysis bullosa (EB) is a rare genetic skin disease reducing the quality of life of those affected and their relatives. The intensive efforts of the patient organisation DEBRA Austria during the last decades have led to a unique situation of those affected and their relatives, with increased support and broader knowledge about the disease in the general population. The aim of the study is to evaluate the current situation of patients and their relatives living in Austria, with a focus on burdens and helpful practices.

Results

The mixed-methods study consisted of two parts: a qualitative interview study to identify psychosocial aspects of EB in those affected and their relatives, and a subsequent online survey to further assess those aspects in a larger sample, resulting in a total of n=78 Austrian participants. The impact of EB on the quality of life of EB patients and their relatives in Austria is related to the current health status, psychological burden, mobility, visibility, financial situation as well as job prospects. Personal and social resources and external support have a significant influence on the individual situation.

Conclusions

The outcome is mapped to concrete implications regarding targeted support for EB patients and their relatives on an individual level and their needs in regard to the Austrian health care system.
Comparative study of different extendable intramedullary rods combined with surgery in the treatment of congenital pseudarthrosis of the tibia
Authors: Liu Yaoxi , Liu Kun , Tan Qian , Yang Ge , Huang Yiyong , Zhu Guanghui , Wu Jiangyan , Mei Haibo
Published: May 2024

Background

When using traditional extensible intramedullary rods to treat congenital pseudarthrosis of the tibia (CPT), there were cases of re-fracture and internal fixation fracture. Therefore, the authors propose a research hypothesis that a thicker distal extensible intramedullary rod can better protect the tibia and reduce the incidence of refracture

Purpose

To investigate the clinical efficacy of new and traditional extensible intramedullary rods in the treatment of CPT in children

Methods

From January 2017 to December 2021, the clinical data of 49 children with CPT who were treated with traditional extensible intramedullary rod combined surgery (group A) and new extensible intramedullary rod combined surgery (group B) in our hospital were collected. Inclusive criteria: ① Crawford type IV CPT children; ② The operation was performed by the same team. Exclusion criteria: patients with multiple tibial angulation. During follow-up, the initial healing, proximal tibial valgus, tibial length, ankle valgus, refracture and intramedullary rod displacement of CPT children in the two groups were evaluated

Results

It was a retrospective investigation. In group A, 26 cases met the inclusion criteria, 24 cases achieved primary healing, with an primary healing rate of 92%, including 1 case of nonunion due to osteomyelitis complications after surgery, and 1 case of delayed healing, with an average healing time of 4.7 ± 0.8 months. 17 cases (68%) had unequal tibia length, with an average difference of 1.6 ± 0.8 cm. Ankle valgus occurred in 10 cases (40%) with an average of 14.4°±4.8°; Proximal tibial valgus occurred in 6 cases (24%) with an average of 7 °± 1.8 °. 20 cases (80%) had tip of the rod migration.10 cases (40%) had re-fracture; The average follow-up time was 2.4 ± 0.4 years. In group B, 22 patients achieved primary healing, and the primary healing rate was 95%, including 1 case with delayed healing. The average healing time was 4.7 ± 1.7months. 14 cases (61%) had unequal tibia length, with an average difference of 1 ± 0.5 cm. Ankle valgus occurred in 4 cases (17%) with an average of 12.3 °±4.9°; The proximal tibia valgus occurred in 9 cases (39%), with an average of 7.7 °±2.5 °. 14 cases (61%) had new type of intramedullary rod displacement. 3 cases (13%) had re-fracture; The average follow-up time was 2.3 ± 0.6years

Conclusion

Compared with the traditional extended intramedullary rod combined operation, the new type of extended intramedullary rod combined operation has a lower incidence of re-fracture after CPT, but it still needs to be verified by large sample and multi-center research
HATCHet2: clone- and haplotype-specific copy number inference from bulk tumor sequencing data
Authors: Myers Matthew A. , Arnold Brian J. , Bansal Vineet , Balaban Metin , Mullen Katelyn M. , Zaccaria Simone , Raphael Benjamin J.
Published: May 2024

Bulk DNA sequencing of multiple samples from the same tumor is becoming common, yet most methods to infer copy-number aberrations (CNAs) from this data analyze individual samples independently. We introduce HATCHet2, an algorithm to identify haplotype- and clone-specific CNAs simultaneously from multiple bulk samples. HATCHet2 extends the earlier HATCHet method by improving identification of focal CNAs and introducing a novel statistic, the minor haplotype B-allele frequency (mhBAF), that enables identification of mirrored-subclonal CNAs. We demonstrate HATCHet2’s improved accuracy using simulations and a single-cell sequencing dataset. HATCHet2 analysis of 10 prostate cancer patients reveals previously unreported mirrored-subclonal CNAs affecting cancer genes.
Diurnal control of iron responsive element containing mRNAs through iron regulatory proteins IRP1 and IRP2 is mediated by feeding rhythms
Authors: Nadimpalli Hima Priyanka , Katsioudi Georgia , Arpa Enes Salih , Chikhaoui Lies , Arpat Alaaddin Bulak , Liechti Angelica , Palais Gaël , Tessmer Claudia , Hofmann Ilse , Galy Bruno , Gatfield David
Published: May 2024

Background

Cellular iron homeostasis is regulated by iron regulatory proteins (IRP1 and IRP2) that sense iron levels (and other metabolic cues) and modulate mRNA translation or stability via interaction with iron regulatory elements (IREs). IRP2 is viewed as the primary regulator in the liver, yet our previous datasets showing diurnal rhythms for certain IRE-containing mRNAs suggest a nuanced temporal control mechanism. The purpose of this study is to gain insights into the daily regulatory dynamics across IRE-bearing mRNAs, specific IRP involvement, and underlying systemic and cellular rhythmicity cues in mouse liver.

Results

We uncover high-amplitude diurnal oscillations in the regulation of key IRE-containing transcripts in the liver, compatible with maximal IRP activity at the onset of the dark phase. Although IRP2 protein levels also exhibit some diurnal variations and peak at the light–dark transition, ribosome profiling in IRP2-deficient mice reveals that maximal repression of target mRNAs at this timepoint still occurs. We further find that diurnal regulation of IRE-containing mRNAs can continue in the absence of a functional circadian clock as long as feeding is rhythmic.

Conclusions

Our findings suggest temporally controlled redundancy in IRP activities, with IRP2 mediating regulation of IRE-containing transcripts in the light phase and redundancy, conceivably with IRP1, at dark onset. Moreover, we highlight the significance of feeding-associated signals in driving rhythmicity. Our work highlights the dynamic nature and regulatory complexity in a metabolic pathway that had previously been considered well-understood.
Genome-wide identification of replication fork stalling/pausing sites and the interplay between RNA Pol II transcription and DNA replication progression
Authors: Rojas Patricia , Wang Jianming , Guglielmi Giovanni , Sadurnì Martina Mustè , Pavlou Lucas , Leung Geoffrey Ho Duen , Rajagopal Vijay , Spill Fabian , Saponaro Marco
Published: May 2024

Background

DNA replication progression can be affected by the presence of physical barriers like the RNA polymerases, leading to replication stress and DNA damage. Nonetheless, we do not know how transcription influences overall DNA replication progression.

Results

To characterize sites where DNA replication forks stall and pause, we establish a genome-wide approach to identify them. This approach uses multiple timepoints during S-phase to identify replication fork/stalling hotspots as replication progresses through the genome. These sites are typically associated with increased DNA damage, overlapped with fragile sites and with breakpoints of rearrangements identified in cancers but do not overlap with replication origins. Overlaying these sites with a genome-wide analysis of RNA polymerase II transcription, we find that replication fork stalling/pausing sites inside genes are directly related to transcription progression and activity. Indeed, we find that slowing down transcription elongation slows down directly replication progression through genes. This indicates that transcription and replication can coexist over the same regions. Importantly, rearrangements found in cancers overlapping transcription-replication collision sites are detected in non-transformed cells and increase following treatment with ATM and ATR inhibitors. At the same time, we find instances where transcription activity favors replication progression because it reduces histone density.

Conclusions

Altogether, our findings highlight how transcription and replication overlap during S-phase, with both positive and negative consequences for replication fork progression and genome stability by the coexistence of these two processes.
High-precision stereotactic irradiation for focal drug-resistant epilepsy versus standard treatment: a randomized waitlist-controlled trial (the PRECISION trial)
Authors: Zegers C. M. L. , Swinnen A. , Roumen C. , Hoffmann A. L. , Troost E. G. C. , van Asch C. J. J. , Brandts L. , Compter I. , Dieleman E. M. T. , Dijkstra J. B. , Granzier M. , Hendriks M. , Hofman P. , Houben R. M. A. , Ramaekers B. , Ronner H. E. , Rouhl R. P. W. , van der Salm S. , Santegoeds R. G. C. , Verhoeff J. J. , Wagner G. L. , Zwemmer J. , Schijns OEMG , Colon A. J. , Eekers D. B. P.
Published: May 2024

Introduction

The standard treatment for patients with focal drug-resistant epilepsy (DRE) who are not eligible for open brain surgery is the continuation of anti-seizure medication (ASM) and neuromodulation. This treatment does not cure epilepsy but only decreases severity. The PRECISION trial offers a non-invasive, possibly curative intervention for these patients, which consist of a single stereotactic radiotherapy (SRT) treatment. Previous studies have shown promising results of SRT in this patient population. Nevertheless, this intervention is not yet available and reimbursed in the Netherlands. We hypothesize that: SRT is a superior treatment option compared to palliative standard of care, for patients with focal DRE, not eligible for open surgery, resulting in a higher reduction of seizure frequency (with 50% of the patients reaching a 75% seizure frequency reduction at 2 years follow-up).

Methods

In this waitlist-controlled phase 3 clinical trial, participants are randomly assigned in a 1:1 ratio to either receive SRT as the intervention, while the standard treatments consist of ASM continuation and neuromodulation. After 2-year follow-up, patients randomized for the standard treatment (waitlist-control group) are offered SRT. Patients aged ≥ 18 years with focal DRE and a pretreatment defined epileptogenic zone (EZ) not eligible for open surgery will be included. The intervention is a LINAC-based single fraction (24 Gy) SRT treatment. The target volume is defined as the epileptogenic zone (EZ) on all (non) invasive examinations. The seizure frequency will be monitored on a daily basis using an electronic diary and an automatic seizure detection system during the night. Potential side effects are evaluated using advanced MRI, cognitive evaluation, Common Toxicity Criteria, and patient-reported outcome questionnaires. In addition, the cost-effectiveness of the SRT treatment will be evaluated.

Discussion

This is the first randomized trial comparing SRT with standard of care in patients with DRE, non-eligible for open surgery. The primary objective is to determine whether SRT significantly reduces the seizure frequency 2 years after treatment. The results of this trial can influence the current clinical practice and medical cost reimbursement in the Netherlands for patients with focal DRE who are not eligible for open surgery, providing a non-invasive curative treatment option.

Trial registration

Clinicaltrials.gov Identifier: NCT05182437. Registered on September 27, 2021.
Telemedicine home-based management in patients with chronic heart failure and diabetes type II: study protocol for a randomized controlled trial
Authors: Bernocchi Palmira , Giudici Vittorio , Borghi Gabriella , Bertolaia Patrizia , D’Isa Salvatore , Trevisan Roberto , Scalvini Simonetta
Published: May 2024

Background

Heart failure and type 2 diabetes are prevalent public health issues in Europe. These complex chronic conditions require extensive pharmacological management, ongoing self-care, and behavioral changes. Despite the known benefits of lifestyle changes, such as regular exercise and better control of blood sugar levels, patients may need help implementing the recommended changes. This study aims to assess the effectiveness of a telemedicine program for managing heart failure and type 2 diabetes at home. The program focuses on promoting lifestyle changes.

Methods and analysis

During scheduled outpatient cardiology evaluations, eligible patients are recruited and randomly assigned to either an intervention or control group in a 1:1 ratio. The intervention group receives support from a nursing case manager through a structured home-based teleassistance program and a trainer for daily physical activity stimulation. They also have access to teleconsultations with cardiologists and diabetes specialists as needed, telemonitoring of vital signs, and daily step tracking. An app records and monitors daily drug treatment, glycemia, blood pressure, heart rate, and other clinical parameters. Patients can also self-report symptoms and communicate via a chat and videoconference system with a Nurse Case Manager. The control group receives routine care. Data collection occurs before intervention and 6 months after baseline during a new outpatient cardiology evaluation. The primary outcome is to measure the difference in the distance walked during a 6-min walk test between baseline and after 6 months. The key secondary outcomes include improving the disease status and physical activity profile. Data will be analyzed according to the intention-to-treat principles.

Discussion

This study will provide evidence on the efficacy of a telemedicine home-based management model to maintain correct lifestyles in patients with both heart failure and type 2 diabetes, improving self-management, their empowerment on the diseases, and increasing their knowledge and ability to recognize symptoms early.

Trial registration

ClinicalTrials.gov NCT05633784. Registered on November 30, 2022.
Su(Hw) interacts with Combgap to establish long-range chromatin contacts
Authors: Vorobyeva Nadezhda E. , Krasnov Alexey N. , Erokhin Maksim , Chetverina Darya , Mazina Marina
Published: May 2024

Background

Insulator-binding proteins (IBPs) play a critical role in genome architecture by forming and maintaining contact domains. While the involvement of several IBPs in organising chromatin architecture in Drosophila has been described, the specific contribution of the Suppressor of Hairy wings (Su(Hw)) insulator-binding protein to genome topology remains unclear.

Results

In this study, we provide evidence for the existence of long-range interactions between chromatin bound Su(Hw) and Combgap, which was first characterised as Polycomb response elements binding protein. Loss of Su(Hw) binding to chromatin results in the disappearance of Su(Hw)-Combgap long-range interactions and in a decrease in spatial self-interactions among a subset of Su(Hw)-bound genome sites. Our findings suggest that Su(Hw)-Combgap long-range interactions are associated with active chromatin rather than Polycomb-directed repression. Furthermore, we observe that the majority of transcription start sites that are down-regulated upon loss of Su(Hw) binding to chromatin are located within 2 kb of Combgap peaks and exhibit Su(Hw)-dependent changes in Combgap and transcriptional regulators’ binding.

Conclusions

This study demonstrates that Su(Hw) insulator binding protein can form long-range interactions with Combgap, Polycomb response elements binding protein, and that these interactions are associated with active chromatin factors rather than with Polycomb dependent repression.
Comparison of cytokine expression and disease severity between plasma cell-dominant and eosinophil-dominant patients in chronic rhinosinusitis with nasal polyps
Authors: Lin Yu-Tsai , Tsai Ming-Hsien , Su Yan-Ye , Huang Shun-Chen
Published: May 2024

Purpose

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease characterized by inflammation of the nasal and sinus mucosa. The inflammatory patterns may differ among patients, leading to different subtypes based on the dominant inflammatory cell type. This study aimed to compare the differences in cytokine expression and disease severity between plasma cell-dominant and eosinophil-dominant subtypes in patients with CRSwNP.

Methods

This study included 53 CRSwNP patients and 19 control subjects who did not have asthma or a history of cigarette smoking. The expression of cytokines and inflammatory cells was assessed via enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively.

Results

Among the cytokines analyzed, only IL-6 was significantly different between the two subtypes. A greater proportion of mast cells and IgE cells was present in plasma cell-dominant CRSwNP patients than in eosinophil-dominant group. For the three disease severity scores (LMK-CT, TPS and SNOT-22), objective scores (LMK-CT and TPS) were greater in the eosinophil-dominant CRSwNP group, while the opposite result was shown for the subjective score (SNOT-22). Additionally, the percentage of plasma cell-dominant cells was significantly positively correlated with disease severity according to the TPS and SNOT-22 scores.

Conclusions

Our data revealed that plasma cell-dominant inflammation, a subtype of type 2 CRS, was significantly correlated with subjective disease severity. The study also highlights the role of IL-6, IgE and mast cells as distinguishing factors between eosinophil-dominant and plasma cell-dominant CRSwNP. This information could be useful for clinical diagnosis and personalized treatment.
A scoping review on bovine tuberculosis highlights the need for novel data streams and analytical approaches to curb zoonotic diseases
Authors: Conteddu Kimberly , English Holly M. , Byrne Andrew W. , Amin Bawan , Griffin Laura L. , Kaur Prabhleen , Morera-Pujol Virginia , Murphy Kilian J. , Salter-Townshend Michael , Smith Adam F. , Ciuti Simone
Published: May 2024

Zoonotic diseases represent a significant societal challenge in terms of their health and economic impacts. One Health approaches to managing zoonotic diseases are becoming more prevalent, but require novel thinking, tools and cross-disciplinary collaboration. Bovine tuberculosis (bTB) is one example of a costly One Health challenge with a complex epidemiology involving humans, domestic animals, wildlife and environmental factors, which require sophisticated collaborative approaches. We undertook a scoping review of multi-host bTB epidemiology to identify trends in species publication focus, methodologies, and One Health approaches. We aimed to identify knowledge gaps where novel research could provide insights to inform control policy, for bTB and other zoonoses. The review included 532 articles. We found different levels of research attention across episystems, with a significant proportion of the literature focusing on the badger-cattle-TB episystem, with far less attention given to tropical multi-host episystems. We found a limited number of studies focusing on management solutions and their efficacy, with very few studies looking at modelling exit strategies. Only a small number of studies looked at the effect of human disturbances on the spread of bTB involving wildlife hosts. Most of the studies we reviewed focused on the effect of badger vaccination and culling on bTB dynamics with few looking at how roads, human perturbations and habitat change may affect wildlife movement and disease spread. Finally, we observed a lack of studies considering the effect of weather variables on bTB spread, which is particularly relevant when studying zoonoses under climate change scenarios. Significant technological and methodological advances have been applied to bTB episystems, providing explicit insights into its spread and maintenance across populations. We identified a prominent bias towards certain species and locations. Generating more high-quality empirical data on wildlife host distribution and abundance, high-resolution individual behaviours and greater use of mathematical models and simulations are key areas for future research. Integrating data sources across disciplines, and a “virtuous cycle” of well-designed empirical data collection linked with mathematical and simulation modelling could provide additional gains for policy-makers and managers, enabling optimised bTB management with broader insights for other zoonoses.
Targeting miR-181a/b in retinitis pigmentosa: implications for disease progression and therapy
Authors: Costa Bruna Lopes da , Quinn Peter M. J. , Wu Wen-Hsuan , Liu Siyuan , Nolan Nicholas D. , Demirkol Aykut , Tsai Yi-Ting , Caruso Salvatore Marco , Cabral Thiago , Wang Nan-Kai , Tsang Stephen H.
Published: May 2024

Background

Retinitis pigmentosa (RP) is a genetically heterogeneous group of degenerative disorders causing progressive vision loss due to photoreceptor death. RP affects other retinal cells, including the retinal pigment epithelium (RPE). MicroRNAs (miRs) are implicated in RP pathogenesis, and downregulating miR-181a/b has shown therapeutic benefit in RP mouse models by improving mitochondrial function. This study investigates the expression profile of miR-181a/b in RPE cells and the neural retina during RP disease progression. We also evaluate how miR-181a/b downregulation, by knocking out miR-181a/b-1 cluster in RPE cells, confers therapeutic efficacy in an RP mouse model and explore the mechanisms underlying this process.

Results

Our findings reveal distinct expression profiles, with downregulated miR-181a/b in RPE cells suggesting a protective response and upregulated miR-181a/b in the neural retina indicating a role in disease progression. We found that miR-181a/b-2, encoded in a separate genomic cluster, compensates for miR-181a/b-1 ablation in RPE cells at late time points. The transient downregulation of miR-181a/b in RPE cells at post-natal week 6 (PW6) led to improved RPE morphology, retarded photoreceptor degeneration and decreased RPE aerobic glycolysis.

Conclusions

Our study elucidates the underlying mechanisms associated with the therapeutic modulation of miR-181a/b, providing insights into the metabolic processes linked to its RPE-specific downregulation. Our data further highlights the impact of compensatory regulation between miR clusters with implications for the development of miR-based therapeutics.

Graphical Abstract
Nested plot designs used in forest inventory do not accurately capture tree species richness in Southwestern European forests
Authors: Moreno-Fernández Daniel , Cañellas Isabel , Hernández Laura , Adame Patricia , Alberdi Iciar
Published: May 2024

Key message

Nested plot designs with concentric plots with increasing radii and size threshold underestimate tree species richness with respect to full census sampling with no tree size restrictions. Regeneration emerged as the most relevant pool for tree species richness estimation.

Context

Nested or concentric plot designs, where trees are sampled according to their size and position, are common in National Forest Inventories (NFI) to reduce the sampling effort. However, this could bias the estimation of tree diversity such as species richness.

Aims

The main goal of this study is to quantify the effect of the nested plot designs with increasing radii and diameter at breast height threshold on the number of tree species as well as to provide values for mean tree species richness per plot at the forest-type level using the Spanish NFI.

Methods

We compared tree species richness according to the Spanish NFI nested plot design (radii ranging from 5 to 25 m with increasing minimum threshold in dbh from 7.5 to 42.5 cm as well as the regeneration compartment) with the richness estimate based on a full census (without restrictions in the location or size) in the Spanish NFI 25 m radius plot.

Results

Our results confirmed the underestimation of tree species richness (around 32.5%) when using the nested design. The species omitted in the nested design sampling are often subordinates, typically with small diameters. Regeneration emerged as the main pool for tree species richness estimation. This pattern holds across the main forest types, indicating that it is a generalized rather than regional or local phenomenon.

Conclusion

We strongly recommend using full census data for assessing tree species richness whenever available, as relying solely on nested designs can significantly underestimate tree species richness.
Food risk assessment in the farm-to-table continuum: report from the conference on good hygiene practices to ensure food safety
Authors: Rhouma Mohamed , Gaucher Marie-Lou , Badredine Souhail , Bekal Sadjia , Sanders Pascal
Published: May 2024

Foodborne diseases (FBDs) are a major worldwide public health concern. In the current context of globalization, it has become crucial to establish effective collaboration between countries to reduce the incidence of FBDs, by creating knowledge-sharing activities to address this challenge. However, despite the importance of this subject, there are limited opportunities for researchers from French-speaking countries to meet and exchange expertise in this field. Researchers from the Faculty of Veterinary Medicine of the Université de Montréal (Canada) and from the Faculty of Science, University of Abdelmalek Essaadi (Morocco) took the initiative to organize the first French-speaking edition of the conference on Good Hygiene Practices to Ensure Food Safety, that was held virtually on May 25 and 26, 2022. Attendees (n = 122) came from academic, food processing and government sectors. The conference was a great opportunity to showcase the practical application of the risk analysis paradigm, with concrete examples of food hazards, as well as the use of the latest high-throughput sequencing technologies as a tool for source attribution and molecular typing of some of the most important foodborne pathogens. In addition, the conference created a valuable forum for the exchange of knowledge between international food safety experts, particularly with respect to Canadian regulations compared with those of other countries. Interestingly, following the success of this first edition, the conference’s scientific committee has decided to continue organizing this event on a biannual basis, to provide a unique forum for French-speaking researchers to learn about the latest advances in food safety.
Maternal supplementation with n-3 fatty acids affects placental lipid metabolism, inflammation, oxidative stress, the endocannabinoid system, and the neonate cytokine concentrations in dairy cows
Authors: dos Santos Silva Priscila , Kra Gitit , Butenko Yana , Daddam Jayasimha Rayalu , Levin Yishai , Zachut Maya
Published: May 2024

Background

The placenta plays a crucial role in supporting and influencing fetal development. We compared the effects of prepartum supplementation with omega-3 (n-3) fatty acid (FA) sources, flaxseed oil (FLX) and fish oil (FO), on the expression of genes and proteins related to lipid metabolism, inflammation, oxidative stress, and the endocannabinoid system (ECS) in the expelled placenta, as well as on FA profile and inflammatory response of neonates. Late-pregnant Holstein dairy cows were supplemented with saturated fat (CTL), FLX, or FO. Placental cotyledons (n = 5) were collected immediately after expulsion, and extracted RNA and proteins were analyzed by RT-PCR and proteomic analysis. Neonatal blood was assessed for FA composition and concentrations of inflammatory markers.

Results

FO increased the gene expression of fatty acid binding protein 4 (FABP4), interleukin 10 (IL-10), catalase (CAT), cannabinoid receptor 1 (CNR1), and cannabinoid receptor 2 (CNR2) compared with CTL placenta. Gene expression of ECS-enzyme FA-amide hydrolase (FAAH) was lower in FLX and FO than in CTL. Proteomic analysis identified 3,974 proteins; of these, 51–59 were differentially abundant between treatments (P ≤ 0.05, |fold change| ≥ 1.5). Top canonical pathways enriched in FLX vs. CTL and in FO vs. CTL were triglyceride metabolism and inflammatory processes. Both n-3 FA increased the placental abundance of FA binding proteins (FABPs) 3 and 7. The abundance of CNR1 cannabinoid-receptor-interacting-protein-1 (CNRIP1) was reduced in FO vs. FLX. In silico modeling affirmed that bovine FABPs bind to endocannabinoids. The FLX increased the abundance of inflammatory CD44-antigen and secreted-phosphoprotein-1, whereas prostaglandin-endoperoxide synthase 2 was decreased in FO vs. CTL placenta. Maternal FO enriched neonatal plasma with n-3 FAs, and both FLX and FO reduced interleukin-6 concentrations compared with CTL.

Conclusion

Maternal n-3 FA from FLX and FO differentially affected the bovine placenta; both enhanced lipid metabolism and modulated oxidative stress, however, FO increased some transcriptional ECS components, possibly related to the increased FABPs. Maternal FO induced a unique balance of pro- and anti-inflammatory components in the placenta. Taken together, different sources of n-3 FA during late pregnancy enhanced placental immune and metabolic processes, which may affect the neonatal immune system.
Applying dynamic contrast-enhanced MRI tracer kinetic models to differentiate benign and malignant soft tissue tumors
Authors: Gao Aixin , Wang Hexiang , Zhang Xiuyun , Wang Tongyu , Chen Liuyang , Hao Jingwei , Zhou Ruizhi , Yang Zhitao , Yue Bin , Hao Dapeng
Published: May 2024

Background

To explore the potential of different quantitative dynamic contrast-enhanced (qDCE)-MRI tracer kinetic (TK) models and qDCE parameters in discriminating benign from malignant soft tissue tumors (STTs).

Methods

This research included 92 patients (41females, 51 males; age range 16–86 years, mean age 51.24 years) with STTs. The qDCE parameters (Ktrans, Kep, Ve, Vp, F, PS, MTT and E) for regions of interest of STTs were estimated by using the following TK models: Tofts (TOFTS), Extended Tofts (EXTOFTS), adiabatic tissue homogeneity (ATH), conventional compartmental (CC), and distributed parameter (DP). We established a comprehensive model combining the morphologic features, time-signal intensity curve shape, and optimal qDCE parameters. The capacities to identify benign and malignant STTs was evaluated using the area under the curve (AUC), degree of accuracy, and the analysis of the decision curve.

Results

TOFTS-Ktrans, EXTOFTS-Ktrans, EXTOFTS-Vp, CC-Vp and DP-Vp demonstrated good diagnostic performance among the qDCE parameters. Compared with the other TK models, the DP model has a higher AUC and a greater level of accuracy. The comprehensive model (AUC, 0.936, 0.884–0.988) demonstrated superiority in discriminating benign and malignant STTs, outperforming the qDCE models (AUC, 0.899–0.915) and the traditional imaging model (AUC, 0.802, 0.712–0.891) alone.

Conclusions

Various TK models successfully distinguish benign from malignant STTs. The comprehensive model is a noninvasive approach incorporating morphological imaging aspects and qDCE parameters, and shows significant potential for further development.
A first report of right-hemicolectomy for ascending colon cancer in Japan with the da Vinci SP surgical robot system
Authors: Noda Ai , Okuya Koichi , Akizuki Emi , Miyo Masaaki , Ishii Masayuki , Miura Ryo , Ichihara Momoko , Toyota Maho , Ito Tatsuya , Ogawa Tadashi , Kimura Akina , Takemasa Ichiro
Published: May 2024

Background

The da Vinci SP robotic surgical system received regulatory approval for use in colorectal cancer surgery in Japan in April 2023. Given the advantages of the precision of a robot and the postoperative cosmesis of single-site surgery, the system is expected to be further utilized for minimally invasive surgeries, in addition to the curative and safety-assured laparoscopic technique.

Case presentation

A 73-year-old man presented at our hospital with positive fecal occult blood. He was diagnosed with cT2N0M0 (Stage I) ascending colon cancer and underwent a right hemicolectomy, which was performed with the da Vinci SP system. The operation was performed safely, and the patient was discharged without complications. Pathology findings showed that complete mesocolic excision was achieved.

Conclusions

Herein, we report the first colorectal cancer surgery performed using the da Vinci SP system in Japan. The use of this robotic surgical system with access forms for right hemicolectomy is safe and oncologically appropriate.
Position statement of the Brazilian society of Rheumatology on mesna use as a preventive therapy for bladder disease in patients with systemic autoimmune diseases and systemic vasculitis under cyclophosphamide treatment
Authors: Souza Alexandre Wagner S. de , Dantas João Gabriel , Montandon Ana Carolina de Oliveira e Silva , Calich Ana Luísa , Mont’ Alverne Andrea Rocha de Saboia , Gasparin Andrese Aline , Bianchi Dante , Yuki Emily Figueiredo Neves , Sacilotto Nathalia , dos Reis Neto Edgard Torres , Monticielo Odirlei André , Pereira Ivanio Alves
Published: May 2024

Objective

To review current literature to support the use of mesna as a preventive therapy for hemorrhagic cystitis and bladder cancer in patients with systemic autoimmune diseases and systemic vasculitis treated with cyclophosphamide.

Materials and methods

The search for articles was conducted systematically through MEDLINE, LILACS, Cochrane Library, and Embase databases. Only articles in English were selected. For available records, titles and abstracts were selected independently by two investigators.

Results

Eighteen studies were selected for analysis. The known adverse effects of cyclophosphamide were hematological toxicity, infections, gonadal toxicity, teratogenicity, increased risk for malignancy and hemorrhagic cystitis. Long-term toxicity was highly dependent on cyclophosphamide cumulative dose. The risk of bladder cancer is especially higher in long-term exposure and with cumulative doses above 36 g. The risk remains high for years after drug discontinuation. Hemorrhagic cystitis is highly correlated with cumulative dose and its incidence ranges between 12 and 41%, but it seems to be lower with new regimens with reduced cyclophosphamide dose. No randomized controlled trials were found to analyze the use of mesna in systemic autoimmune rheumatic diseases and systemic vasculitis. Retrospective studies yielded conflicting results. Uncontrolled prospective studies with positive results were considered at high risk of bias. No evidence was found to support the use of mesna during the treatment with cyclophosphamide for autoimmune diseases or systemic vasculitis to prevent hemorrhagic cystitis and bladder cancer. In the scenarios of high cumulative cyclophosphamide dose (i.e., > 30 g), patients with restricted fluid intake, neurogenic bladder, therapy with oral anticoagulants, and chronic kidney disease, mesna could be considered.

Conclusion

The current evidence was found to be insufficient to support the routine use of mesna for the prophylaxis of hemorrhagic cystitis and bladder cancer in patients being treated for systemic autoimmune diseases and systemic vasculitis with cyclophosphamide. The use may be considered for selected cases.
Challenges in blood transfusion caused by anti-Hr0: A rare case of D-- Phenotype in Asia Abstract
Authors: Luo Yuanyuan , Ma Chunya , Fu Lihui , Yu Yang
Published: May 2024

Introduction

D–Phenotype is linked to abnormal expression of RHCE gene. Consequently, individuals with this condition may develop antibodies against high-prevalence Rh antigens when exposed to a normal Rh phenotype, leading to challenges in blood matching.

Case presentation

A 90-year-old male was admitted to the hospital due to prostatitis and acute retention of urinary. Surgery was planned after evaluation by urologist. A request was made for 2 units of red blood cells (RBC). The result for unexpected antibody screening was positive, and the antibody was identified as anti-Hr0 alloantibody , a rare RHCE * CE-D (5) – CE was discovered by genetic testing. The patient has only one history of blood transfusion, which may result in the production of the anti-Hr0 antibody. Compatible blood donors for this patient were not found, even after extensive screening.

Conclusion

This report records a rare case of a D--  phenotype individual who produced anti-Hr0 alloantibody. Subsequent analysis of RH gene sequencing revealed a genotype that has not been previously reported in Asia.