bluuebunny/crossref_metadata_2025 huggingface dataset:
A web-based geographic information system monitoring wildlife diseases in Abruzzo and Molise regions, Southern Italy
Authors: Di Lorenzo Alessio , Zenobio Valentina , Cioci Daniela , Dall’Acqua Francesca , Tora Susanna , Iannetti Simona , Rulli Marco , Di Sabatino Daria
Published: October 2023

Background

Nowadays there is a worldwide consensus on the importance of conducting wildlife disease surveillance. Indeed, 60% of emerging infectious diseases are zoonotic in nature, and the majority of these (71.8%) originate in wildlife. Surveillance of wildlife diseases is crucial to prevent negative effects on human and animal health. Data digitization and sharing are among the main goals for the present and coming years. Geographic Information Systems (GIS) are increasingly used to analyze the geographical distribution of diseases and the relationships between pathogenic factors and their geographic environments.

Methods

Wild animal’s samples collected in the Abruzzo and Molise regions and delivered to our laboratory are entered in our Laboratory Information System and processed to be displayed through the Web-GIS mash-up presented in this paper. We built it using both open source and proprietary solutions, to produce data driven interactive maps, charts and tables to help to understand the epidemiology of wild animal diseases, their spread and trend.

Results

Since 2013, 9.606 samples collected from wild animals have been analyzed in the laboratories of the IZS-Teramo and have been recorded in the system, facilitating the reporting to the judicial authorities and the identification of highly risky areas to set up control and repression measures. Moreover, thanks to the monitoring health protocol, a canine distemper epidemic in wolves has been detected and monitored in its temporal and spatial evolution, as well as cases of bovine tuberculosis in wild boars.

Conclusions

While it is more evident that the starting point is to choose the right sampling method, it is for sure less obvious that the information system in which data is stored is equally important. In fact, it should give the possibility to consult it in an easy and instructive way. GIS allows immediately grasping the spatial relationships between the data itself and those between the data and the territory; it is an important tool to support veterinary services in managing epidemic and non-epidemic emergencies and performing epidemiological investigations, but also to examine control plans and identify new gaps and challenges.
B-mode ultrasonography and ARFI elastography of articular and peri-articular structures of the hip joint in non-dysplastic and dysplastic dogs as confirmed by radiographic examination
Authors: Carneiro Rafael Kretzer , da Cruz Igor Cezar Kniphoff , Gasser Beatriz , Lima Bruna , Aires Luiz Paulo Nogueira , Ferreira Márcio Poletto , Uscategui Ricardo Andres Ramirez , Giglio Robson Fortes , Minto Bruno Watanabe , Rossi Feliciano Marcus Antônio
Published: October 2023

Background

Canine hip dysplasia is a common orthopedic disease in veterinary practice. The diagnosis is made by radiographic examinations that evaluate bone alterations associated with hip dysplasia. Although radiographic examination is the gold standard for diagnosis, it does not allow a detailed evaluation of soft tissues such as the joint capsule and periarticular muscles. This study aimed to evaluate the accuracy of B-mode ultrasonography and acoustic radiation force impulse (ARFI) elastography in assessing the joint capsule and periarticular muscles of dogs using the Orthopedic Foundation of Animals (OFA) classification and the distraction index (DI) in the early and late diagnosis of hip dysplasia. This study sought to propose a protocol for the ultrasonographic evaluation of the structures involved in canine hip dysplasia.

Methods

Radiographic and ultrasonographic evaluations were performed on 108 hip joints of 54 dogs. Thirty dogs were older than 2 years and 24 were aged between 4 and 10 months.

Results

It was verified that an increase in pectineus muscle stiffness (cutoff value > 2.77 m/s) by elastography in some dysplastic dogs and an increase in the thickness of the joint capsule (cutoff value > 0.9 mm) in B-mode ultrasonography, were associated with a distraction index > 0.5, with both having a positive correlation. In B-mode ultrasonographic evaluation, the presence of signs of degenerative joint disease, such as irregularities of the cranial edge of the acetabulum and femoral head, were associated with a distraction index > 0.5 in canines, with a specificity of 94%. In adult dogs, the findings of degenerative joint disease on ultrasound were associated with a diseased OFA classification (P < 0.05). Measurement of the joint capsule > 1.10 mm was diagnostic for dysplasia in unhealthy dogs by OFA.

Conclusions

ARFI elastography has shown that the pectineus muscle may experience changes in stiffness in dysplastic animals. Additionally, changes in joint capsule thickness can be identified in B-mode in young and adult dogs with dysplastic joints, which contributes to the diagnosis of hip dysplasia.
scFv biofunctionalized nanoparticles to effective and safe targeting of CEA-expressing colorectal cancer cells
Authors: Silveira Maria José , Martins Cláudia , Cruz Tânia , Castro Flávia , Amorim-Costa Ângela , Chester Kerry , Oliveira Maria José , Sarmento Bruno
Published: October 2023

Colorectal cancer (CRC) is one of the deadliest cancers worldwide, with the 5 year survival rate in metastatic cases limited to 12%. The design of targeted and effective therapeutics remains a major unmet clinical need in CRC treatment. Carcinoembryonic antigen (CEA), a glycoprotein overexpressed in most colorectal tumors, may constitute a promising molecule for generating novel CEA-targeted therapeutic strategies for CRC treatment. Here, we developed a smart nanoplatform based on chemical conjugation of an anti-CEA single-chain variable fragment (scFv), MFE-23, with PLGA-PEG polymers to deliver the standard 5-Fluorouracil (5-FU) chemotherapy to CRC cells. We confirmed the specificity of the developed CEA-targeted NPs on the internalization by CEA-expressing CRC cells, with an enhance of threefold in the cell uptake. Additionally, CEA-targeted NPs loaded with 5-FU induced higher cytotoxicity in CEA-expressing cells, after 24 h and 48 h of treatment, reinforcing the specificity of the targeted NPs. Lastly, the safety of CEA-targeted NPs loaded with 5-FU was evaluated in donor-isolated macrophages, with no relevant impact on their metabolic activity nor polarization. Altogether, this proof of concept supports the CEA-mediated internalization of targeted NPs as a promising chemotherapeutic strategy for further investigation in different CEA-associated cancers and respective metastatic sites.Authors: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [Maria José] Last name [Silveira]. Author 7 Given name: [Maria José] Last name [Oliveira]. Also, kindly confirm the details in the metadata are correctokAffiliations: Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.ok

Graphical Abstract
“Flying a plane and building it at the same time”: Lessons learned from the dynamic implementation of mass vaccination clinics in the Region of Waterloo, Ontario, Canada
Authors: Tetui Moses , Tennant Ryan , Adil Maisha , Bala Arthi , Burns Catherine , Waite Nancy , Grindrod Kelly
Published: October 2023

Background

Vaccination plays a critical role during pandemics, and mass vaccination clinics are often an imperative public health measure. These clinics usually consist of multi-disciplinary teams, which can pose significant coordination challenges, yet also present an opportunity for collectively contributing towards mitigating the impact of infection within communities. This study explores the coordination dynamics of the Region of Waterloo’s coronavirus disease of 2019 (COVID-19) mass vaccination clinics in Ontario, Canada, between July 2021 and April 2022.

Methods

This qualitative study included 16 purposively selected participants working in mass vaccination clinics. Participants were individually interviewed for 40–60 min. An inductive and iterative thematic analysis was undertaken, including open coding, grouping, labelling, regrouping and making sense of the themes.

Results

Three interrelated themes were created: (1) unpredictable work environment, which was comprised of changing clinic processes and the impact of clinic adjustments to the running of the clinics; (2) clinic cohesion challenges, which included staff role disparities, limited job preparation and clinic system silos; and (3) adaptable and supportive work environment, which was comprised of staff adaptability, dispositional flexibility and a supportive work environment. While the first two themes created a precarious situation in the clinics, the third countered it, leading to a largely successful clinic implementation.

Conclusions

The rapid evolution and high transmissibility of COVID-19 in communities required a public health response that felt like flying and building a plane simultaneously – a seemingly impossible yet necessary task. However, an adaptable and supportive work environment was critical for establishing an atmosphere that can overcome challenges from a constantly changing pandemic and the guidance of public health officials. Such lessons gained from understanding the dynamic experiences in mass vaccination clinics are essential for improving the development and operation of future immunization campaigns.
Transient intracranial pressure elevations (B waves) are associated with sleep apnea
Authors: Riedel Casper Schwartz , Martinez-Tejada Isabel , Andresen Morten , Wilhjelm Jens E. , Jennum Poul , Juhler Marianne
Published: October 2023

Background

Repetitive transient intracranial pressure waveform elevations up to 50 mmHg (ICP B-waves) are often used to define pathological conditions and determine indications for ICP-reducing treatment. We recently showed that nocturnal transient ICP elevations are present in patients without structural brain lesions or hydrocephalus in whom they are associated with sleep apnea. However, whether this signifies a general association between ICP macropatterns and sleep apnea remains unknown.

Methods

We included 34 patients with hydrocephalus, or idiopathic intracranial hypertension (IIH), who were referred to the Neurosurgical Department, Copenhagen, Denmark, from 2017 to 2021. Every patient underwent diagnostic overnight ICP monitoring for clinical indications, with simultaneous polysomnography (PSG) sleep studies. All transient ICP elevations were objectively quantified in all patients. Three patients were monitored with continuous positive airway pressure (CPAP) treatment for an additional night.

Results

All patients had transient ICP elevations associated with sleep apnea. The mean temporal delay from sleep apnea to transient ICP elevations for all patients was 3.6 s (SEM 0.2 s). Ramp-type transient ICP elevations with a large increase in ICP were associated with rapid eye movement (REM) sleep and sinusoidal-type elevations with non-REM (NREM) sleep. In three patients treated with CPAP, the treatment reduced the number of transient ICP elevations with a mean of 37%. CPAP treatment resulted in insignificant changes in the average ICP in two patients but elevated the average ICP during sleep in one patient by 5.6 mmHg.

Conclusion

The findings suggest that sleep apnea causes a significant proportion of transient ICP elevations, such as B-waves, and sleep apnea should be considered in ICP evaluation. Treatment of sleep apnea with CPAP can reduce the occurrence of transient ICP elevations. More research is needed on the impact of slow oscillating mechanisms on transient ICP elevations during high ICP and REM sleep.
Community-engaged optimization of COVID-19 rapid evaluation and testing experiences: roll-out implementation optimization trial
Authors: Stadnick Nicole A. , Laurent Louise C. , Cain Kelli L. , Seifert Marva , Burola Maria Linda , Salgin Linda , Watson Paul , Oswald William , Munoz Fatima A. , Velasquez Sharon F. , Smith Justin D. , Zou Jingjing , Rabin Borsika A.
Published: October 2023

Background

There continues to be a need for COVID-19 testing that is pragmatic, community-centered, and sustainable. This study will refine and test implementation strategies prioritized by community partners: (1) walk-up no-cost testing, (2) community health worker (promotores)-facilitated testing and preventive care counseling, (3) vending machines that dispense no-cost, self-testing kits.

Methods

A co-designed Theory of Change from an earlier study phase and the Practical, Robust Implementation and Sustainment Model (PRISM) will guide the study design, measures selection, and evaluation. The first aim is to refine and operationalize a multi-component implementation strategy bundle and outcome measures for COVID-19 testing. A Community and Scientific Advisory Board (CSAB) will be established and include community members, clinical providers/staff from the partnering Federally Qualified Health Center (FQHC), public health researchers, policymakers, and a county health department ambassador. Engagement of CSAB members will be assessed through structured ethnography and a survey about the quality and quantity of engagement practices. The second aim is to implement and evaluate the impact of the implementation strategy bundle to optimize COVID-19 testing in communities using a roll-out implementation optimization (ROIO) design. Seven thousand and five hundred community members will be enrolled across four FQHC clinics over 18 months. Participants will be invited to complete an electronic survey about their demographics, health, and COVID-19 testing results and experiences. CSAB members and clinic partners will participate in PRISM fit and determinant assessments prior to each clinic rollout and post-trial. Interviews will be conducted with 60 community participants and 12 providers/staff following a 3-month rollout period at each clinic, inquiring about their experiences with the implementation strategies. Quantitative data will be analyzed using hierarchical multilevel models to determine the impact of implementation strategies. Qualitative data will be analyzed using rapid qualitative approaches to summarize implementation experiences and identify necessary changes prior to subsequent rollouts. A matrix approach will be used to triangulate data from quantitative and qualitative sources based on PRISM domains.

Discussion

This is one of the first pragmatic implementation trials to use a ROIO design and aims to co-create a sustainable and equitable COVID-19 testing program. Findings are likely to generalize to other public health prevention efforts.

Trial registration

NCT05894655 March 2, 2023.
MRI-based inter- and intrafraction motion analysis of the pancreatic tail and spleen as preparation for adaptive MRI-guided radiotherapy in neuroblastoma
Authors: Van Ommen Fasco , le Quellenec Gaelle A.T. , Willemsen-Bosman Mirjam E. , van Noesel Max M. , van den Heuvel-Eibrink Marry M. , Seravalli Enrica , Kroon Petra S. , Janssens Geert O.
Published: October 2023

Background

In pediatric radiotherapy treatment planning of abdominal tumors, dose constraints to the pancreatic tail/spleen are applied to reduce late toxicity. In this study, an analysis of inter- and intrafraction motion of the pancreatic tail/spleen is performed to estimate the potential benefits of online MRI-guided radiotherapy (MRgRT).

Materials and methods

Ten randomly selected neuroblastoma patients (median age: 3.4 years), irradiated with intensity-modulated arc therapy at our department (prescription dose: 21.6/1.8 Gy), were retrospectively evaluated for inter- and intrafraction motion of the pancreatic tail/spleen. Three follow-up MRIs (T2- and T1-weighted ± gadolinium) were rigidly registered to a planning CT (pCT), on the vertebrae around the target volume. The pancreatic tail/spleen were delineated on all MRIs and pCT. Interfraction motion was defined as a center of gravity change between pCT and T2-weighted images in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) direction. For intrafraction motion analysis, organ position on T1-weighted ± gadolinium was compared to T2-weighted. The clinical radiation plan was used to estimate the dose received by the pancreatic tail/spleen for each position.

Results

The median (IQR) interfraction motion was minimal in LR/AP, and largest in CC direction; pancreatic tail 2.5 mm (8.9), and spleen 0.9 mm (3.9). Intrafraction motion was smaller, but showed a similar motion pattern (pancreatic tail, CC: 0.4 mm (1.6); spleen, CC: 0.9 mm (2.8)). The differences of Dmean associated with inter- and intrafraction motions ranged from − 3.5 to 5.8 Gy for the pancreatic tail and − 1.2 to 3.0 Gy for the spleen. In 6 out of 10 patients, movements of the pancreatic tail and spleen were highlighted as potentially clinically significant because of ≥ 1 Gy dose constraint violation.

Conclusion

Inter- and intrafraction organ motion results into unexpected constrain violations in 60% of a randomly selected neuroblastoma cohort, supporting further prospective exploration of MRgRT.
Follow-up of pre-motor symptoms of Parkinson’s disease in adult patients with Gaucher disease type 1 and analysis of their lysosomal enzyme profiles in the CSF
Authors: Wilke Matheus Vernet Machado Bressan , Poswar Fabiano , Borelli Wyllians Vendramini , Michelin Tirelli Kristiane , Randon Dévora Natalia , Lopes Franciele Fátima , Pasetto Fernanda Bender , Sebastião Fernanda Medeiros , Iop Gabrielle Dineck , Faqueti Larissa , da Silva Layzon Antonio , Kubaski Francyne , Schuh Artur Francisco Schumacher , Giugliani Roberto , Schwartz Ida Vanessa Doederlein
Published: October 2023

Background

Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. Its classic motor symptoms may be preceded by non-motor symptoms (NMS). Population studies have identified GBA variants as risk factors for idiopathic PD. The increased risk of PD has also been suggested in other Lysosomal Storage Disorders (LSDs). Objective: To assess the evolution of the prevalence of NMS compatible with PD in a cohort of South Brazilian adult patients with Gaucher Disease (GD) type 1, already evaluated 3 years ago (2018). Cerebrospinal Fluid (CSF) was collected to assess the levels of LSD enzymes (beta-hexosaminidases, beta-glucuronidase) and biomarker of macrophage activation (chitotriosidase, ChT), compared to controls (metachromatic leukodystrophy, MLD). Cognition was evaluated by the Montreal Cognitive Assessment (MoCA) questionnaire, daytime sleepiness by the Epworth Sleepiness Scale (ESS), depression by Beck´s Inventory, constipation by the Unified Multiple System Atrophy Rating Scale (UMSARS) scale, and REM sleep behavior disorder by the single-question screen. Hyposmia was assessed with Sniffin’ Sticks (SST).

Results

Nineteen patients completed the follow-up (mean age of the sample was 44 years; range, 26–71). The patient with the highest number of NMS at the baseline (4 including the lowest SST score) was diagnosed with PD four years later. Apart from an improvement in the ESS score, no other statistical significance was found between the number of NMS between the first and second evaluation, nor between patients with one L444P variant (n = 5) and the rest of the cohort. CSF was collected in five patients (mean age of the sample was 40 years, range 30–53. A significant difference was found in the mean CSF activity levels of beta-hexosaminidases and beta-glucuronidase between GD1 and MLD patients. Mean ChT (CSF) was 62 nmol/h/mL in GD patients and 142 in MLD (n = 6) patients.

Conclusions

The patient with the highest number of NMS in our 2018 cohort was the one that developed PD, corroborating with the importance of this longitudinal follow-up. CSF and plasma analysis might allow a better understanding of the neurodegenerative processes connecting PD and the lysosomal environment. Further analysis is needed to understand this relationship.
Biosynthesis of ternary NiCoFe2O4 nanoflowers: investigating their 3D structure and potential use in gene delivery
Authors: Alijani Hajar Q. , Khatami Mehrdad , Torkzadeh-Mahani Masoud , Michalička Jan , Wang Wu , Wang Di , Heydari Abolfazl
Published: October 2023

Multicomponent nanoparticle systems are known for their varied properties and functions, and have shown potential as gene nanocarriers. This study aims to synthesize and characterize ternary nickel–cobalt-ferrite (NiCoFe2O4) nanoparticles with the potential to serve as gene nanocarriers for cancer/gene therapy. The biogenic nanocarriers were prepared using a simple and eco-friendly method following green chemistry principles. The physicochemical properties of the nanoparticles were analyzed by X-ray diffraction, vibrating sample magnetometer, X-ray photoelectron spectroscopy, and Brunauer–Emmett–Teller. To evaluate the morphology of the nanoparticles, the field emission scanning electron microscopy with energy dispersive X-Ray spectroscopy, high-resolution transmission electron microscopy imaging, and electron tomography were conducted. Results indicate the nanoparticles have a nanoflower morphology with a mesoporous nature and a cubic spinel structure, where the rod and spherical nanoparticles became rose-like with a specific orientation. These nanoparticles were found to have minimal toxicity in human embryonic kidney 293 (HEK-293 T) cells at concentrations of 1 to 250 µg·mL–1. We also demonstrated that the nanoparticles could be used as gene nanocarriers for delivering genes to HEK-293 T cells using an external magnetic field, with optimal transfection efficiency achieved at an N/P ratio of 2.5. The study suggests that biogenic multicomponent nanocarriers show potential for safe and efficient gene delivery in cancer/gene therapy.

Graphical Abstract
Interplay between ESR1/PIK3CA codon variants, oncogenic pathway alterations and clinical phenotype in patients with metastatic breast cancer (MBC): comprehensive circulating tumor DNA (ctDNA) analysis
Authors: Gerratana Lorenzo , Davis Andrew A. , Velimirovic Marko , Clifton Katherine , Hensing Whitney L. , Shah Ami N. , Dai Charles S. , Reduzzi Carolina , D’Amico Paolo , Wehbe Firas , Medford Arielle , Wander Seth A. , Gradishar William J. , Behdad Amir , Puglisi Fabio , Ma Cynthia X. , Bardia Aditya , Cristofanilli Massimo
Published: October 2023

Background

although being central for the biology and druggability of hormone-receptor positive, HER2 negative metastatic breast cancer (MBC), ESR1 and PIK3CA mutations are simplistically dichotomized as mutated or wild type in current clinical practice.

Methods

The study analyzed a multi-institutional cohort comprising 703 patients with luminal-like MBC characterized for circulating tumor DNA through next generation sequencing (NGS). Pathway classification was defined based on previous work (i.e., RTK, RAS, RAF, MEK, NRF2, ER, WNT, MYC, P53, cell cycle, notch, PI3K). Single nucleotide variations (SNVs) were annotated for their oncogenicity through OncoKB. Only pathogenic variants were included in the models. Associations among clinical characteristics, pathway classification, and ESR1/PIK3CA codon variants were explored.

Results

The results showed a differential pattern of associations for ESR1 and PIK3CA codon variants in terms of co-occurring pathway alterations patterns of metastatic dissemination, and prognosis. ESR1 537 was associated with SNVs in the ER and RAF pathways, CNVs in the MYC pathway and bone metastases, while ESR1 538 with SNVs in the cell cycle pathway and liver metastases. PIK3CA 1047 and 542 were associated with CNVs in the PI3K pathway and with bone metastases.

Conclusions

The study demonstrated how ESR1 and PIK3CA codon variants, together with alterations in specific oncogenic pathways, can differentially impact the biology and clinical phenotype of luminal-like MBC. As novel endocrine therapy agents such as selective estrogen receptor degraders (SERDS) and PI3K inhibitors are being developed, these results highlight the pivotal role of ctDNA NGS to describe tumor evolution and optimize clinical decision making.
The impact of an oral nutritional supplement on body weight gain in older adults with malnutrition: an open-label randomized controlled trial
Authors: Jayawardena Ranil , Wickramawardhane Prasani , Dalpatadu Chamila , Hills Andrew P. , Ranasinghe Priyanga
Published: October 2023

Background

The global aging population is expanding rapidly and many individuals have a particularly higher risk of malnutrition. Malnutrition can lead to impaired body function, morbidity, and mortality. Meeting nutritional requirements is a key strategy to minimize multiple debilitating adverse outcomes associated with malnutrition in the elderly.

Oral nutritional supplements (ONS) have been widely used as a dietary intervention for malnutrition in older adults. These supplements provide additional nutrients and calories to support nutritional requirements and have been shown to improve nutritional status, physical function, and quality of life in malnourished older adults.

Methods

This is an open-label, randomized controlled, parallel-group study including 50 institutionalized older adults (aged > 60 years) with malnutrition or at risk of malnutrition, living in a selected elderly care institution in Colombo, Sri Lanka. The aim is to assess improvement in healthy body weight gain and body composition in older adults with malnutrition at risk of malnutrition by using an ONS. Older adults will be screened for malnutrition using the Mini Nutrition Assessment (MNA) tool and eligible participants randomized using the simple random sampling technique to intervention and control groups (1:1 allocation ratio). The intervention group will consume 200 mL of ONS before bed continuously for 12 weeks. The primary outcome is the percentage who achieved at least 5% weight gain in the intervention group compared to the control group. Nutritional status (anthropometric, biochemical, clinical, and dietary), body composition (dual-energy X-ray absorptiometry), frailty, functional capacity (hand grip strength, knee extension, and Barthel index) cognitive status (Montreal Cognitive Assessment), and physical activity will be assessed as secondary outcomes at baseline and at the end of the 12-week intervention. Some measurements (anthropometry, dietary, and functional assessments) will also be performed at the end of the 4th week. Data will be analyzed using SPSS V-23.

Discussion

This study will determine whether the use of an ONS is effective in promoting healthy weight gain in older adults with malnutrition or at risk of malnutrition. In addition, investigating the impact of an ONS on multiple outcomes via clinical, nutritional, functional, and cognitive function will provide a more comprehensive understanding of the potential benefits of these supplements.

Trial registration

Sri Lanka Clinical Trail Registry SLCTR/2022/021. Oct. 6, 2022.
A novel shared decision-making (SDM) tool for anticoagulation management in atrial fibrillation: protocol for a prospective, cluster randomized controlled trial
Authors: Pan Mang-Mang , Zhang Chi , Shen Long , Sha Jing-Jing , Shen Hui , Yan Yi-Dan , Wang Jia , Wang Xin , Lin Hou-Wen , Gu Zhi-Chun
Published: October 2023

Background

Atrial fibrillation (AF) is a common arrhythmia that requires anticoagulation therapy to prevent stroke. However, there is still a significant under-/over-treatment in stroke prevention for patients with AF. The adherence and the risk of bleeding associated with oral anticoagulation therapy (OACs) are major concerns. Shared decision-making (SDM) is an approach that involves patients and healthcare providers in making decisions about treatment options. This study aims to assess the effectiveness of a novel SDM tool for anticoagulation management in AF.

Methods

The study will be a prospective, cluster randomized controlled trial involving 440 patients with AF in 8 community health service centers (clusters) in Shanghai, China. The SDM group will receive anticoagulation management through the novel SDM tool, while the control group will receive standard care. The follow-up period will be at least 2 years. The primary outcome will be any bleeding event, while secondary outcomes include the accordance of stroke prophylaxis for AF according to the current guidelines, time in therapeutic range (TTR), the occurrences of major bleeding and thrombosis events, and patient knowledge, adherence, and satisfaction.

Discussion

This study will provide evidence of the effectiveness of shared decision-making in improving the appropriateness of OAC use in Chinese AF patients. The findings may inform the development of guidelines and policies for the management of AF and anticoagulation therapy in China and other countries.

Trial registration

ChiCTR ChiCTR2200062123. Registered on 23 July 2022.
Integrative bioinformatics analysis and experimental validation of key biomarkers for risk stratification in primary biliary cholangitis
Authors: Tian Siyuan , Hu Yinan , Zhang Miao , Wang Kemei , Guo Guanya , Li Bo , Shang Yulong , Han Ying
Published: October 2023

Background

Primary biliary cholangitis (PBC) is an autoimmune liver disease, whose etiology is yet to be fully elucidated. Currently, ursodeoxycholic acid (UDCA) is the only first-line drug. However, 40% of PBC patients respond poorly to it and carry a potential risk of disease progression. So, in this study, we aimed to explore new biomarkers for risk stratification in PBC patients to enhance treatment.

Methods

We first downloaded the clinical characteristics and microarray datasets of PBC patients from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified and subjected to enrichment analysis. Hub genes were further validated in multiple public datasets and PBC mouse model. Furthermore, we also verified the expression of the hub genes and developed a predictive model in our clinical specimens.

Results

A total of 166 DEGs were identified in the GSE79850 dataset, including 95 upregulated and 71 downregulated genes. Enrichment analysis indicated that DEGs were significantly enriched in inflammatory or immune-related process. Among these DEGs, 15 risk-related genes were recognized and further validated in the GSE119600 cohort. Then, TXNIP, CD44, ENTPD1, and PDGFRB were identified as candidate hub genes. Finally, we proceeded to the next screening with these four genes in our serum samples and developed a three-gene panel. The gene panel could effectively identify those patients at risk of disease progression, yielding an AUC of 0.777 (95% CI, 0.657–0.870).

Conclusions

In summary, combining bioinformatics analysis and experiment validation, we identified TXNIP, CD44, and ENTPD1 as promising biomarkers for risk stratification in PBC patients.
Binding of Trichinella spiralis C-type lectin with syndecan-1 on intestinal epithelial cells mediates larval invasion of intestinal epithelium
Authors: Wang Zhen , Lu Qi Qi , Weng Min Min , Li Yang Li , Han Lu Lu , Song Yan Yan , Shi Yu Long , Liu Ruo Dan , Cui Jing , Wang Zhong Quan
Published: October 2023

C-type lectin (CTL) is a protein that binds to saccharides and plays an important role in parasite adhesion, host cell invasion and immune evasion. Previous studies showed that recombinant T. spiralis C-type lectin (rTsCTL) promotes larval invasion of intestinal epithelium cells (IEC), whereas anti-rTsCTL antibodies inhibits larval invasion. Syndecan-1 (SDC-1) is a member of the heparan sulfate proteoglycan family which is mainly expressed on the surface of IEC and in extracellular matrices where they interact with a plethora of ligands. SDC-1 has a principal role in maintaining cell morphogenesis, establishing cell–cell adhesions, and regulating the gut mucosal barrier. The aim of this study was to investigate whether rTsCTL binds to SDC-1 on IEC, and the binding of rTsCTL with SDC-1 promotes larval invasion and its mechanism. IFA results show that rTsCTL and SDC-1 co-localized on Caco-2 cell membrane. GST pull-down and Co-IP verified the direct interaction between rTsCTL and SDC-1 on Caco-2 cells. qPCR and Western blotting revealed that rTsCTL binding to SDC-1 increased the expression of SDC-1 and claudin-2, and reduced the expression of occludin and claudin-1 in Caco-2 cells incubated with rTsCTL via the STAT3 pathway. β-Xyloside (a syndecan-1 synthesis inhibitor) and Stattic (a STAT3 inhibitor) significantly inhibited rTsCTL binding to syndecan-1 in Caco-2 cells and activation of the STAT3 pathway, abrogated the effects of rTsCTL on the expression of gut tight junctions, and impeded larval invasion. The results demonstrate that binding of rTsCTL to SDC-1 on Caco-2 cells activated the STAT3 pathway, decreased gut tight junction expression, damaged the integrity of the gut epithelial barrier, and mediated T. spiralis invasion of the gut mucosa. TsCTL might be regarded as a candidate vaccine target against T. spiralis invasion and infection.
CD24+LCN2+ liver progenitor cells in ductular reaction contributed to macrophage inflammatory responses in chronic liver injury
Authors: Huang Wei-Jian , Qiu Bi-Jun , Qi Xiao-Shu , Chen Cai-Yang , Liu Wen-Ming , Zhou Shen-ao , Ding Min , Lu Feng-Feng , Zhao Jie , Tang Dan , Zhou Xu , Fu Gong-Bo , Wang Zhen-Yu , Ma Hong-Qian , Wu Yu-Ling , Wu Hong-ping , Chen Xiao-Song , Yu Wei-Feng , Yan He-Xin
Published: October 2023

Background

CD24+CK19+/CD24+SOX9+ resident liver cells are activated and expanded after chronic liver injury in a ductular reaction. However, the sources and functions of these cells in liver damage remain disputed.

Results

The current study combined genetic lineage tracing with in vitro small-molecule-based reprogramming to define liver progenitor cells (LPCs) derived from hepatic parenchymal and non-parenchymal tissues. tdTom+ hepatocytes were isolated from ROSA26tdTomato mice following AAV8-Tbg-Cre-mediated recombination, EpCAM+ biliary epithelial cells (BECs) from wild-type intrahepatic bile ducts and ALB/GFP−EpCAM− cells were isolated from AlbCreERT/R26GFP mice. A cocktail of small molecules was used to convert the isolated cells into LPCs. These in vitro cultured LPCs with CD24 and SOX9 expression regained the ability to proliferate. Transcriptional profiling showed that the in-vitro cultured LPCs derived from the resident LPCs in non-parenchymal tissues expressed Lipocalin-2 (Lcn2) at high levels. Accordingly, endogenous Cd24a+Lcn2+ LPCs were identified by integration of sc-RNA-sequencing and pathological datasets of liver dysfunction which indicates that LPCs produced by ductular reactions might also originate from the resident LPCs. Transplantation of in-vitro cultured Cd24a+Lcn2+ LPCs into CCl4-induced fibrotic livers exacerbated liver damage and dysfunction, possibly due to LCN2-dependent macrophage inflammatory response.

Conclusions

CD24+LCN2+ LPCs constituted the expanding ductular reaction and contributed to macrophage-mediated inflammation in chronic liver damage. The current findings highlight the roles of LPCs from distinct origins and expose the possibility of targeting LPCs in the treatment of chronic hepatic diseases.

Graphical Abstract
The opinions of farm animal veterinarians in Ireland on antibiotic use and their role in antimicrobial stewardship
Authors: O’Connor Sorcha , More Simon J. , Speksnijder David C. , Petti Carloalberto
Published: October 2023

Background

Antibiotic use and resistance in animal production are a concern to public health, and there is an urgent need to reduce antibiotic use in farm animals. To prevent blame shifting, professionals from human medicine, animal medicine and environmental backgrounds must collaborate to tackle this issue. Veterinarians are typically responsible for overseeing and prescribing antibiotic use in animals. There are currently no available studies on the opinions of Irish farm animal veterinarians on antibiotic use, reduction opportunities and their relationships with farmers. A digital survey was developed and sent out to Irish farm animal veterinarians. This paper presents the results of a cross-sectional study of Irish farm animal veterinarians’ attitudes towards antimicrobial stewardship, their prescribing behaviours, antibiotic reduction opportunities and their attitudes for the future of antibiotic use. The veterinarian-farmer relationship is examined and potential interventions to reduce antibiotic use on farms are identified.

Results

In total, 114 complete questionnaires were received, representing approximately 11 per cent of all farm animal veterinarians in Ireland. Respondents were aware of the problem of antibiotic resistance and recognise their role in the fight against it. They realise what actions they must take to reduce antibiotic use and identify barriers that prevent their farmer clients from implementing their advice. Many of them say that they can reduce antibiotic use on farms in the future, but some remain doubtful. There was no statistical difference between veterinarians that had less experience working than those that had more experience in their attitudes towards future reduction in antibiotic use.

Conclusion

Most of the respondents seek to use antibiotics as judiciously as they can. The majority agree that antibiotic overuse is the main contributor to antibiotic resistance. Possible solutions to reduce antibiotic use include the development of antibiotic treatment guidelines, assigning one unique practice to each farm and compulsory CPD (Continuous Professional Development) courses.
RETRACTED ARTICLE: Blockchain managed federated learning for a secure IoT framework
Authors: Chai Jiayong , Li Jian , Wei Muhua , Zhu Chuangying
Published: October 2023

In this work, we present a blockchain-based federated learning (FL) framework that aims achieving high system efficiency while simultaneously addressing issues relating to data sparsity and the disclosure of private information. It is more efficient to build a number of smaller clusters rather than one big cluster for multiple networks. Blockchain-based FL is carried out in each cluster, with the model changes being compiled at the end of the process. Following that, the accumulated updates are swapped across the clusters, which, in practise, improves the updates that are accessible for each cluster. When compared to the extensive interactions that take place in blockchain-based FL, cluster-based FL only sends a limited number of aggregated updates across a substantial distance. This is in contrast to the extensive interactions that take place in blockchain-based FL. In order to conduct an analysis of our system, we have implemented the prototypes of both cluster and blockchain-based FL models. The findings of the experiments show that cluster-based FL model raise the accuracy goes upto 72.6%, and goes down to 11%. The loss goes upto 3.6 and goes down to 0.8. In addition, cluster-based FL model has the potential to hasten the convergence of the model, provided that the same quantity of data is input into it. The reason for this is due to the fact that during a training cycle, cluster-based FL model combines the computational resources of many different clusters.
RETRACTED ARTICLE: Switching mode allocation in planning paths for vehicular network communication
Authors: Lu Dingzhu
Published: October 2023

Because of the increased mobility of vehicle users, it might be difficult to keep communication services in vehicle networks effective and dependable. Huge hurdles have been presented to vehicular networks as a result of the meteoric rise in the amount of data, which comes with the needs of high dependability and low latency. The deployment of access point servers at geographic locations that are closer to the vehicles in order to provide real-time service to applications that are based on the vehicles is one possible option. However, there is a limited amount of cache store space, and there is also a lack of a tractable access mode allocation method. As a result of these factors, it is very difficult to strike a compromise between the network transmission performance and fronthaul savings. Because the signal-to-interference-ratio (SIR) can be enhanced with switching mode in vehicular infrastructure, it may be possible to achieve higher levels of dependability. To serve all of the vehicles, the conventional allocation in vehicular network may not be sufficient on its own for two reasons: (1) the number of vehicles exceeds the number of paths, and (2) a vehicle may be located outside of the coverage path. Therefore, the implementation of switching mode allocation in vehicular communication is very necessary in order to increase the number of vehicles that can be supplied. In this paper, allocation using V2I, V2V, and V2X modes have been analyzed to provide dependable coverage for vehicles. These methods are used for communicating with other vehicles. In this paper, the numerical analysis has been performed such that SIR is optimized. In switching mode allocation, it has been shown that establishing a variable SIR threshold is helpful in achieving a path coverage that can be relied upon. It has been shown beyond a reasonable doubt that the coverage probability is likewise directly dependent on SIR thresholds. The theoretical analysis is verified, and it is confirmed that the suggested method is capable of achieving significant performance improvement in terms of coverage probability and data rate.
Certain investigations of sequential warped product submanifolds on cosymplectic manifolds
Authors: Sharma Anil , Kumar Anuj , Bin Turki Nasser , Shenawy Sameh
Published: October 2023

In a special class of almost contact metric manifolds known as cosymplectic manifolds, the current study aims to establish the existence result and a few inequalities for sequential warped product submanifolds. These results and inequalities represent fruitful connections between the primary intrinsic and extrinsic invariants. Furthermore, findings related to Dirichlet energy have been addressed. Finally, some exceptional cases resulting in several inequities are examined.
A computational framework for improving genetic variants identification from 5,061 sheep sequencing data
Authors: Xie Shangqian , Isaacs Karissa , Becker Gabrielle , Murdoch Brenda M.
Published: October 2023

Background

Pan-genomics is a recently emerging strategy that can be utilized to provide a more comprehensive characterization of genetic variation. Joint calling is routinely used to combine identified variants across multiple related samples. However, the improvement of variants identification using the mutual support information from multiple samples remains quite limited for population-scale genotyping.

Results

In this study, we developed a computational framework for joint calling genetic variants from 5,061 sheep by incorporating the sequencing error and optimizing mutual support information from multiple samples' data. The variants were accurately identified from multiple samples by using four steps: (1) Probabilities of variants from two widely used algorithms, GATK and Freebayes, were calculated by Poisson model incorporating base sequencing error potential; (2) The variants with high mapping quality or consistently identified from at least two samples by GATK and Freebayes were used to construct the raw high-confidence identification (rHID) variants database; (3) The high confidence variants identified in single sample were ordered by probability value and controlled by false discovery rate (FDR) using rHID database; (4) To avoid the elimination of potentially true variants from rHID database, the variants that failed FDR were reexamined to rescued potential true variants and ensured high accurate identification variants. The results indicated that the percent of concordant SNPs and Indels from Freebayes and GATK after our new method were significantly improved 12%−32% compared with raw variants and advantageously found low frequency variants of individual sheep involved several traits including nipples number (GPC5), scrapie pathology (PAPSS2), seasonal reproduction and litter size (GRM1), coat color (RAB27A), and lentivirus susceptibility (TMEM154).

Conclusion

The new method used the computational strategy to reduce the number of false positives, and simultaneously improve the identification of genetic variants. This strategy did not incur any extra cost by using any additional samples or sequencing data information and advantageously identified rare variants which can be important for practical applications of animal breeding.
Stable functional structure despite high taxonomic variability across fungal communities in soils of old-growth montane forests
Authors: Zeng Qingchao , Lebreton Annie , Auer Lucas , Man Xiaowu , Jia Liukun , Wang Gengshen , Gong Sai , Lombard Vincent , Buée Marc , Wu Gang , Dai Yucheng , Yang Zhuliang , Martin Francis M.
Published: October 2023

Background

Major advances over the past decade in molecular ecology are providing access to soil fungal diversity in forest ecosystems worldwide, but the diverse functions and metabolic capabilities of this microbial community remain largely elusive. We conducted a field survey in montane old-growth broadleaved and conifer forests, to investigate the relationship between soil fungal diversity and functional genetic traits. To assess the extent to which variation in community composition was associated with dominant tree species (oak, spruce, and fir) and environmental variations in the old-growth forests in the Jade Dragon Snow Mountain in Yunnan Province, we applied rDNA metabarcoding. We also assessed fungal gene expression in soil using mRNA sequencing and specifically assessed the expression of genes related to organic matter decomposition and nutrient acquisition in ectomycorrhizal and saprotrophic fungi.

Results

Our taxonomic profiling revealed striking shifts in the composition of the saprotrophic and ectomycorrhizal guilds among the oak-, fir-, and spruce-dominated forests. The core fungal microbiome comprised only ~ 20% of the total OTUs across all soil samples, although the overlap between conifer-associated communities was substantial. In contrast, seasonality and soil layer explained only a small proportion of the variation in community structure. However, despite their highly variable taxonomic composition, fungal guilds exhibited remarkably similar functional traits for growth-related and core metabolic pathways across forest associations, suggesting ecological redundancy. However, we found that the expression profiles of genes related to polysaccharide and protein degradation and nutrient transport notably varied between and within the fungal guilds, suggesting niche adaptation.

Conclusions

Overall, our metatranscriptomic analyses revealed the functional potential of soil fungal communities in montane old-growth forests, including a suite of specialized genes and taxa involved in organic matter decomposition. By linking genes to ecological traits, this study provides insights into fungal adaptation strategies to biotic and environmental factors, and sheds light on the importance of understanding functional gene expression patterns in predicting ecosystem functioning.