bluuebunny/crossref_metadata_2025 huggingface dataset:
Launch sequencing of pharmaceuticals with multiple therapeutic indications: evidence from seven countries
Authors: Mills Mackenzie , Michaeli Daniel , Miracolo Aurelio , Kanavos Panos
Published: February 2023

Background

New medicines are increasingly being identified as efficacious across multiple indications. The impact of current pricing and reimbursement policies on launch decisions across these indications remains unclear.

Objective

This paper, first, maps marketing authorisation and HTA coverage recommendation sequences of multi-indication medicines across Germany, France, England, Scotland, Canada, Australia, and the USA, and, second, evaluates the clinical characteristics, clinical development time and coverage recommendation time of multi-indication medicines, drawing comparisons between the first and subsequent indications of an approved molecule.

Methods

Medicine approvals by the Food and Drug Administration between 2009–2019 were screened to identify multi-indication products with approved oncology indications. Data on clinical trial characteristics, clinical performance and HTA outcomes were extracted from publicly available regulatory approval and HTA reports.

Results

Relative to subsequent indications, first indications were more likely to receive conditional marketing authorisation, have an orphan designation, have a single arm phase II pivotal trial and lower MCBS score. Subsequent indications had faster HTA coverage recommendation times in England and Canada. While the majority of first indications received HTA coverage recommendations across all settings, the proportion of subsequent indications with HTA coverage recommendations was lower and uptake varied considerably across settings.

Conclusions

Discordance in the value of first versus subsequent indications can pose major challenges in systems that define price based on the initial indication. Current pricing and reimbursement systems generate significant fragmentation in the approval and availability of multi-indication products across settings.
Heart failure with preserved ejection fraction and atrial fibrillation: recent advances and open questions
Authors: Fauchier Laurent , Bisson Arnaud , Bodin Alexandre
Published: February 2023

Atrial fibrillation (AF) and heart failure (HF) are frequently associated and can be caused or exacerbated by each other through different mechanisms. AF is particularly common in patients with heart failure with preserved ejection fraction (HFpEF) defined as left ventricular ejection fraction (LVEF) ≥ 50%, with a prevalence ranging around 40–60%.

In two recent trials, treatment with SGLT2 inhibitors resulted in a lower risk of worsening heart failure or cardiovascular death than placebo in patients with HFpEF, and SGLT2 inhibitors similarly improved prognosis whether patients had AF or not at enrolment. Analyses for subgroups of interest of patients with HFpEF likely to be at higher risk of AF (particularly those with older age or obesity) similarly indicated a consistent benefit with SGLT2 inhibitors. That subgroup in patients with HFpEF is those with a history of previous HF with LVEF ≤ 40%. The EAST-AFNET 4 trial indicated that early rhythm-control therapy was associated with a lower risk of adverse cardiovascular outcomes than usual care among patients with recent AF and cardiovascular conditions, including those with HF. In patients with AF and HF included in the CABANA trial, catheter ablation produced marked improvements in survival, freedom from AF recurrence, and quality of life compared to drug therapy. When strategies aiming at rhythm control eventually fail in patients with AF and HFpEF, a strategy of rate control with atrioventricular junction ablation and cardiac resynchronisation should be discussed since it may also reduce all-cause mortality.

Finally, and in conclusion, considering that patients with AF and HFpEF may have a variety of cardiovascular and non-cardiovascular additional comorbidities, they are among those likely to have the highest clinical benefit being adherent to a holistic and integrated care management of AF following the ABC (Atrial Fibrillation Better Care) pathway.
Understanding work-related travel and its relation to malaria occurrence in Thailand using geospatial maximum entropy modelling
Authors: Memarsadeghi Natalie , Stewart Kathleen , Li Yao , Sornsakrin Siriporn , Uthaimongkol Nichaphat , Kuntawunginn Worachet , Pidtana Kingkan , Raseebut Chatree , Wojnarski Mariusz , Jongsakul Krisada , Jearakul Danai , Waters Norman , Spring Michele , Takala-Harrison Shannon
Published: February 2023

Background

Estimating malaria risk associated with work locations and travel across a region provides local health officials with information useful to mitigate possible transmission paths of malaria as well as understand the risk of exposure for local populations. This study investigates malaria exposure risk by analysing the spatial pattern of malaria cases (primarily Plasmodium vivax) in Ubon Ratchathani and Sisaket provinces of Thailand, using an ecological niche model and machine learning to estimate the species distribution of P. vivax malaria and compare the resulting niche areas with occupation type, work locations, and work-related travel routes.

Methods

A maximum entropy model was trained to estimate the distribution of P. vivax malaria for a period between January 2019 and April 2020, capturing estimated malaria occurrence for these provinces. A random simulation workflow was developed to make region-based case data usable for the machine learning approach. This workflow was used to generate a probability surface for the ecological niche regions. The resulting niche regions were analysed by occupation type, home and work locations, and work-related travel routes to determine the relationship between these variables and malaria occurrence. A one-way analysis of variance (ANOVA) test was used to understand the relationship between predicted malaria occurrence and occupation type.

Results

The MaxEnt (full name) model indicated a higher occurrence of P. vivax malaria in forested areas especially along the Thailand–Cambodia border. The ANOVA results showed a statistically significant difference between average malaria risk values predicted from the ecological niche model for rubber plantation workers and farmers, the two main occupation groups in the study. The rubber plantation workers were found to be at higher risk of exposure to malaria than farmers in Ubon Ratchathani and Sisaket provinces of Thailand.

Conclusion

The results from this study point to occupation-related factors such as work location and the routes travelled to work, being risk factors in malaria occurrence and possible contributors to transmission among local populations.
Pre-exposure prophylaxis (PrEP) for HIV prevention among people who inject drugs: a global mapping of service delivery
Authors: Shaw Graham , Schaefer Robin , Schmidt Heather-Marie A , Madden Annie , Chang Judy , Mozalevskis Antons , Msimanga-Radebe Busisiwe , Mangadan Konath Nabeel , Verster Annette , Baggaley Rachel , Rodolph Michelle , Macdonald Virginia
Published: February 2023

Background

The World Health Organization (WHO) recommends oral pre-exposure prophylaxis (PrEP) for all people at substantial risk of HIV as part of combination prevention. The extent to which this recommendation has been implemented globally for people who inject drugs is unclear. This study mapped global service delivery of PrEP for people who inject drugs.

Methods

Between October and December 2021, a desk review was conducted to obtain information on PrEP services for people who inject drugs from drug user-led networks and HIV, harm reduction, and human rights stakeholders. Websites of organizations involved in HIV prevention or services for people who inject drugs were searched. Models of service delivery were described in terms of service location, provider, and package.

Results

PrEP services were identified in 27 countries (15 high-income). PrEP delivery models varied within and across countries. In most services, PrEP services were implemented in healthcare clinics without direct links to other harm reduction services. In three countries, PrEP services were also provided at methadone clinics. In 14 countries, PrEP services were provided through community-based models (outside of clinic settings) that commonly involved peer-led outreach activities and integration with harm reduction services.

Conclusions

This study indicates limited PrEP availability for people who inject drugs. There is potential to expand PrEP services for people who inject drugs within harm reduction programs, notably through community-based and peer-led services. PrEP should never be offered instead of evidence-based harm reduction programs for people who inject drugs; however, it could be offered as an additional HIV prevention choice as part of a comprehensive harm reduction program.
Changes in cognitive function, synaptic structure and protein expression after long-term exposure to 2.856 and 9.375 GHz microwaves
Authors: Wang Hui , Liu Yu , Sun Yunbo , Dong Ji , Xu Xinping , Wang Haoyu , Zhao Xuelong , Zhang Jing , Yao Binwei , Zhao Li , Liu Shuchen , Peng Ruiyun
Published: February 2023

Health hazards from long-term exposure to microwaves, especially the potential for changes in cognitive function, are attracting increasing attention. The purpose of this study was to explore changes in spatial learning and memory and synaptic structure and to identify differentially expressed proteins in hippocampal and serum exosomes after long-term exposure to 2.856 and 9.375 GHz microwaves. The spatial reference learning and memory abilities and the structure of the DG area were impaired after long-term exposure to 2.856 and 9.375 GHz microwaves. We also found a decrease in SNARE-associated protein Snapin and an increase in charged multivesicular body protein 3 in the hippocampus, indicating that synaptic vesicle recycling was inhibited and consistent with the large increase in presynaptic vesicles. Moreover, we investigated changes in serum exosomes after 2.856 and 9.375 GHz microwave exposure. The results showed that long-term 2.856 GHz microwave exposure could induce a decrease in calcineurin subunit B type 1 and cytochrome b-245 heavy chain in serum exosomes. While the 9.375 GHz long-term microwave exposure induced a decrease in proteins (synaptophysin-like 1, ankyrin repeat and rabankyrin-5, protein phosphatase 3 catalytic subunit alpha and sodium-dependent phosphate transporter 1) in serum exosomes. In summary, long-term microwave exposure could lead to different degrees of spatial learning and memory impairment, EEG disturbance, structural damage to the hippocampus, and differential expression of hippocampal tissue and serum exosomes.
A novel isolation method for spontaneously released extracellular vesicles from brain tissue and its implications for stress-driven brain pathology
Authors: Gomes Patrícia A. , Bodo Cristian , Nogueras-Ortiz Carlos , Samiotaki Martina , Chen Minghao , Soares-Cunha Carina , Silva Joana M. , Coimbra Bárbara , Stamatakis George , Santos Liliana , Panayotou George , Tzouanou Foteini , Waites Clarissa L. , Gatsogiannis Christos , Sousa Nuno , Kapogiannis Dimitrios , Costa-Silva Bruno , Sotiropoulos Ioannis
Published: February 2023

Background

Extracellular vesicles (EVs), including small EVs (sEVs) such as exosomes, exhibit great potential for the diagnosis and treatment of brain disorders, representing a valuable tool for precision medicine. The latter demands high-quality human biospecimens, especially in complex disorders in which pathological and specimen heterogeneity, as well as diverse individual clinical profile, often complicate the development of precision therapeutic schemes and patient-tailored treatments. Thus, the collection and characterization of physiologically relevant sEVs are of the utmost importance. However, standard brain EV isolation approaches rely on tissue dissociation, which can contaminate EV fractions with intracellular vesicles.

Methods

Based on multiscale analytical platforms such as cryo-EM, label-free proteomics, advanced flow cytometry, and ExoView analyses, we compared and characterized the EV fraction isolated with this novel method with a classical digestion-based EV isolation procedure. Moreover, EV biogenesis was pharmacologically manipulated with either GW4869 or picrotoxin to assess the validity of the spontaneous-release method, while the injection of labelled-EVs into the mouse brain further supported the integrity of the isolated vesicles.

Results

We hereby present an efficient purification method that captures a sEV-enriched population spontaneously released by mouse and human brain tissue. In addition, we tested the significance of the release method under conditions where biogenesis/secretion of sEVs was pharmacologically manipulated, as well as under animals’ exposure to chronic stress, a clinically relevant precipitant of brain pathologies, such as depression and Alzheimer’s disease. Our findings show that the released method monitors the drug-evoked inhibition or enhancement of sEVs secretion while chronic stress induces the secretion of brain exosomes accompanied by memory loss and mood deficits suggesting a potential role of sEVs in the brain response to stress and related stress-driven brain pathology.

Conclusions

Overall, the spontaneous release method of sEV yield may contribute to the characterization and biomarker profile of physiologically relevant brain-derived sEVs in brain function and pathology.
Exploring the neuroprotective effects of montelukast on brain inflammation and metabolism in a rat model of quinolinic acid-induced striatal neurotoxicity
Authors: Tassan Mazzocco Margherita , Murtaj Valentina , Martins Daniel , Schellino Roberta , Coliva Angela , Toninelli Elisa , Vercelli Alessandro , Turkheimer Federico , Belloli Sara , Moresco Rosa Maria
Published: February 2023

Background

One intrastriatal administration of quinolinic acid (QA) in rats induces a lesion with features resembling those observed in Huntington’s disease. Our aim is to evaluate the effects of the cysteinyl leukotriene receptor antagonist montelukast (MLK), which exhibited neuroprotection in different preclinical models of neurodegeneration, on QA-induced neuroinflammation and regional metabolic functions.

Methods

The right and left striatum of Sprague Dawley and athymic nude rats were injected with QA and vehicle (VEH), respectively. Starting from the day before QA injection, animals were treated with 1 or 10 mg/kg of MLK or VEH for 14 days. At 14 and 30 days post-lesion, animals were monitored with magnetic resonance imaging (MRI) and positron emission tomography (PET) using [18F]-VC701, a translocator protein (TSPO)-specific radiotracer. Striatal neuroinflammatory response was measured post-mortem in rats treated with 1 mg/kg of MLK by immunofluorescence. Rats treated with 10 mg/kg of MLK also underwent a [18F]-FDG PET study at baseline and 4 months after lesion. [18F]-FDG PET data were then used to assess metabolic connectivity between brain regions by applying a covariance analysis method.

Results

MLK treatment was not able to reduce the QA-induced increase in striatal TSPO PET signal and MRI lesion volume, where we only detected a trend towards reduction in animals treated with 10 mg/kg of MLK. Post-mortem immunofluorescence analysis revealed that MLK attenuated the increase in striatal markers of astrogliosis and activated microglia in the lesioned hemisphere. We also found a significant increase in a marker of anti-inflammatory activity (MannR) and a trend towards reduction in a marker of pro-inflammatory activity (iNOS) in the lesioned striatum of MLK—compared to VEH-treated rats. [18F]-FDG uptake was significantly reduced in the striatum and ipsilesional cortical regions of VEH-treated rats at 4 months after lesion. MLK administration preserved glucose metabolism in these cortical regions, but not in the striatum. Finally, MLK was able to counteract changes in metabolic connectivity and measures of network topology induced by QA, in both lesioned and non-lesioned hemispheres.

Conclusions

Overall, MLK treatment produced a significant neuroprotective effect by reducing neuroinflammation assessed by immunofluorescence and preserving regional brain metabolism and metabolic connectivity from QA-induced neurotoxicity in cortical and subcortical regions.
Pediatric combined hepatocellular-cholangiocarcinoma (cHCC-CC) with neuroendocrine features: distinguishing genetic alterations detected by chromosomal microarray
Authors: Wilhelm Alyeesha B. , Cunningham Arwyn G. , Kassab Cynthia , Fitz Eric C. , Dong Jianli , Radhakrishnan Ravi S. , Ranganathan Sarangarajan , Tan Dongfeng , Stevenson Heather L.
Published: February 2023

Background

Liver tumors exhibiting hepatocellular, cholangiocarcinoma, and neuroendocrine features are extremely rare, with only five cases reported in the literature.

Case presentation

We present an unusual case of a combined hepatocellular-cholangiocarcinoma (cHCC-CC) with neuroendocrine features in a pediatric patient. A 16-year-old presented with abdominal pain and a 21.0 cm mass in the right hepatic lobe with extension into the left lobe. Histology showed a poorly differentiated tumor with a solid, tubuloglandular, and microcystic architecture. Immunohistochemistry results were negative for hepatic markers, positive for markers of biliary differentiation, and positive for neuroendocrine differentiation. The neoplasm was reviewed at several institutions with differing diagnoses. Single nucleotide polymorphism (SNP) chromosomal microarray (CMA) showed large deletions within chromosomes 6q and 13q in both the hepatocellular-like areas and the cholangiocarcinoma-like areas, with additional large deletions in the cholangiocarcinoma-like areas, supporting origin from hepatocellular carcinoma. The final diagnosis was a cHCC-CC with neuroendocrine features.

Conclusions

Diagnosis of cHCC-CCs relies predominately on histomorphology, as per the 2018 International Consensus Group on the nomenclature of cHCC-CC. These findings in this case support that the pathological classification of these lesions be based on molecular data, which could better direct treatment. Further classification of cHCC-CCs and determination of their clinicopathological relevance will require more interobserver consistency and continued molecular profiling of these lesions.
Traditional Chinese medicine for colorectal cancer treatment: potential targets and mechanisms of action
Authors: Chen Jin-Fang , Wu Shi-Wei , Shi Zi-Man , Hu Bing
Published: February 2023

Colorectal cancer (CRC) is a disease with complex pathogenesis, it is prone to metastasis, and its development involves abnormalities in multiple signaling pathways. Surgery, chemotherapy, radiotherapy, target therapy, and immunotherapy remain the main treatments for CRC, but improvement in the overall survival rate and quality of life is urgently needed. Traditional Chinese medicine (TCM) has a long history of preventing and treating CRC. It could affect CRC cell proliferation, apoptosis, cell cycle, migration, invasion, autophagy, epithelial–mesenchymal transition, angiogenesis, and chemoresistance by regulating multiple signaling pathways, such as PI3K/Akt, NF-κB, MAPK, Wnt/β-catenin, epidermal growth factor receptors, p53, TGF-β, mTOR, Hedgehog, and immunomodulatory signaling pathways. In this paper, the main signaling pathways and potential targets of TCM and its active ingredients in the treatment of CRC were systematically summarized, providing a theoretical basis for treating CRC with TCM and new ideas for further exploring the pathogenesis of CRC and developing new anti-CRC drugs.
Prophylactic treatment with oral azithromycin in cancer patients during the COVID-19 pandemic (OnCoVID): a randomized, single-blinded, placebo-controlled phase 2 trial
Authors: Mair Maximilian J. , Maj-Hes Agnieszka , Nussbaumer-Pröll Alina , Puhr Rainer , Christenheit Agnieszka , Troch Marlene , Puhr Hannah C. , Starzer Angelika M. , Steindl Ariane , Eberl Sabine , Haslacher Helmuth , Perkmann Thomas , Minichsdorfer Christoph , Prager Gerald W. , Lamm Wolfgang W. , Berghoff Anna S. , Kiesewetter Barbara , Zeitlinger Markus , Preusser Matthias , Raderer Markus
Published: February 2023

Background

Patients with cancer are at high risk for severe courses of COVID-19. Based on (pre-)clinical data suggesting a potential protective effect due to the immunomodulating properties of azithromycin, we have initiated a prospective randomized trial.

Methods

This randomized, single-center, single-blinded, placebo-controlled phase 2 trial included adult patients with cancer undergoing systemic treatment. Patients were 1:1 randomized to oral azithromycin (1500 mg once weekly for 8 weeks) or placebo. The primary endpoint was the cumulative number of SARS-CoV-2 infections 12 weeks after treatment initiation.

Results

In total, 523 patients were screened, 68 patients were randomized, and 63 patients received at least one dose of the study drug. Due to low acceptance and a lack of SARS-CoV-2 infections in the study cohort, the study was prematurely closed. With no reported grade III–IV possibly treatment-related adverse events, azithromycin was generally well tolerated. Overall survival (OS) rates after 12 months were 83.5% and 70.3% in the azithromycin and placebo group, respectively (p = 0.37). Non-SARS-CoV-2 infections occurred in 4/32 (12.5%) in the azithromycin and 3/31 (9.7%) in the placebo group (p = 1). No emergence of azithromycin-resistant S. aureus strains could be observed. According to treatment group, longitudinal alterations in systemic inflammatory parameters were detected for neutrophil/lymphocyte and leukocyte/lymphocyte ratios.

Conclusion

Although efficacy could not be assessed due to premature closure and low incidence of SARS-CoV-2 infections, azithromycin was associated with a favorable side effect profile in patients with cancer. As other prophylactic treatments are limited, SARS-CoV-2 vaccination remains a high priority in oncological patients.

ClinicalTrials.gov registration number and date (dd/mm/yyyy): NCT04369365, 30/04/2020.
A novel sucrose-inducible expression system and its application for production of biomass-degrading enzymes in Aspergillus niger
Authors: Wang Lu , Xie Yijia , Chang Jingjing , Wang Juan , Liu Hong , Shi Mei , Zhong Yaohua
Published: February 2023

Background

Filamentous fungi are extensively exploited as important enzyme producers due to the superior secretory capability. However, the complexity of their secretomes greatly impairs the titer and purity of heterologous enzymes. Meanwhile, high-efficient evaluation and production of bulk enzymes, such as biomass-degrading enzymes, necessitate constructing powerful expression systems for bio-refinery applications.

Results

A novel sucrose-inducible expression system based on the host strain Aspergillus niger ATCC 20611 and the β-fructofuranosidase promoter (PfopA) was constructed. A. niger ATCC 20611 preferentially utilized sucrose for rapid growth and β-fructofuranosidase production. Its secretory background was relatively clean because β-fructofuranosidase, the key enzyme responsible for sucrose utilization, was essentially not secreted into the medium and the extracellular protease activity was low. Furthermore, the PfopA promoter showed a sucrose concentration-dependent induction pattern and was not subject to glucose repression. Moreover, the strength of PfopA was 7.68-fold higher than that of the commonly used glyceraldehyde-3-phosphate dehydrogenase promoter (PgpdA) with enhanced green fluorescence protein (EGFP) as a reporter. Thus, A. niger ATCC 20611 coupled with the PfopA promoter was used as an expression system to express a β-glucosidase gene (bgla) from A. niger C112, allowing the production of β-glucosidase at a titer of 17.84 U/mL. The crude β-glucosidase preparation could remarkably improve glucose yield in the saccharification of pretreated corncob residues when added to the cellulase mixture of Trichoderma reesei QM9414. The efficacy of this expression system was further demonstrated by co-expressing the T. reesei-derived chitinase Chi46 and β-N-acetylglucosaminidase Nag1 to obtain an efficient chitin-degrading enzyme cocktail, which could achieve the production of N-acetyl-D-glucosamine from colloidal chitin with a conversion ratio of 91.83%. Besides, the purity of the above-secreted biomass-degrading enzymes in the crude culture supernatant was over 86%.

Conclusions

This PfopA-driven expression system expands the genetic toolbox of A. niger and broadens the application field of the traditional fructo-oligosaccharides-producing strain A. niger ATCC 20611, advancing it to become a high-performing enzyme-producing cell factory. In particular, the sucrose-inducible expression system possessed the capacity to produce biomass-degrading enzymes at a high level and evade endogenous protein interference, providing a potential purification-free enzyme production platform for bio-refinery applications.
β-Glucan alleviates goal-directed behavioral deficits in mice infected with Toxoplasma gondii
Authors: Cui Zeyu , Gong Yuying , Luo Xiaotong , Zheng Niuyi , Tan Shimin , Liu Shuxi , Li Youwei , Wang Qingling , Sun Fenfen , Hu Minmin , Pan Wei , Yang Xiaoying
Published: February 2023

Background

Toxoplasma gondii (T. gondii) is a neuroinvasive parasite causing neuroinflammation, which in turn is associated with a higher risk for several psycho-behavioral disorders. There is an urgent need to identify drugs capable of improving cognitive deficits induced by T. gondii infection. β-Glucan, an active ingredient in mushrooms, could significantly enhance immunity. However, the effects of β-glucan against neuroinflammation and cognitive decline induced by T. gondii infection remain unknown. The present study aimed to investigate the neuroprotective effect of β-glucan on goal-directed behavior of mice chronically infected by T. gondii Wh6 strain.

Methods

A mice model of chronic T. gondii Wh6 infection was established by infecting mice by oral gavage with 10 cysts of T. gondii Wh6. Intraperitoneal injection of β-glucan was manipulated 2 weeks before T. gondii infection. Performance of the infected mice on the Y-maze test and temporal order memory (TOM) test was used to assess the goal-directed behavior. Golgi-Cox staining, transmission electron microscopy, immunofluorescence, real-time PCR and western blot assays were used to detect prefrontal cortex-associated pathological change and neuroinflammation.

Results

The administration of β-glucan significantly prevented T. gondii Wh6-induced goal-directed behavioral impairment as assessed behaviorally by the Y-maze test and TOM test. In the prefrontal cortex, β-glucan was able to counter T. gondii Wh6-induced degeneration of neurites, impairment of synaptic ultrastructure and decrease of pre- and postsynaptic protein levels. Also, β-glucan significantly prevented the hyperactivation of pro-inflammatory microglia and astrocytes, as well as the upregulation of proinflammatory cytokines caused by chronic T. gondii Wh6 infection.

Conclusions

This study revealed that β-glucan prevents goal-directed behavioral impairment induced by chronic T. gondii infection in mice. These findings suggest that β-glucan may be an effective drug candidate to prevent T. gondii-associated psycho-behavioral disorders including goal-directed behavioral injury.

Graphical Abstract
Echocardiographic assessment of Xenopus tropicalis heart regeneration
Authors: Lv Luocheng , Guo Weimin , Guan Wei , Chen Yilin , Huang Ruijin , Yuan Ziqiang , Pu Qin , Feng Shanshan , Zheng Xin , Li Yanmei , Xiao Luanjuan , Zhao Hui , Qi Xufeng , Cai Dongqing
Published: February 2023

Background

Recently, it was reported that the adult X. tropicalis heart can regenerate in a nearly scar-free manner after injury via apical resection. Thus, a cardiac regeneration model in adult X. tropicalis provides a powerful tool for recapitulating a perfect regeneration phenomenon, elucidating the underlying molecular mechanisms of cardiac regeneration in an adult heart, and developing an interventional strategy for the improvement in the regeneration of an adult heart, which may be more applicable in mammals than in species with a lower degree of evolution. However, a noninvasive and rapid real-time method that can observe and measure the long-term dynamic change in the regenerated heart in living organisms to monitor and assess the regeneration and repair status in this model has not yet been established.

Results

In the present study, the methodology of echocardiographic assessment to characterize the morphology, anatomic structure and cardiac function of injured X. tropicalis hearts established by apex resection was established. The findings of this study demonstrated for the first time that small animal echocardiographic analysis can be used to assess the regeneration of X. tropicalis damaged heart in a scar-free perfect regeneration or nonperfect regeneration with adhesion manner via recovery of morphology and cardiac function.

Conclusions

Small animal echocardiography is a reliable, noninvasive and rapid real-time method for observing and assessing the long-term dynamic changes in the regeneration of injured X. tropicalis hearts.
Traceability and quality assessment of Norway spruce (Picea abies (L.) H.Karst.) logs: the TreeTrace_spruce database
Authors: Longuetaud Fleur , Schraml Rudolf , Mothe Frédéric , Ravoajanahary Tojo , Decelle Rémi , Constant Thiéry , Ngo Phuc , Debled-Rennesson Isabelle , Entacher Karl , Petutschnigg Alexander , Brüchert Franka , Uhl Andreas
Published: February 2023

Key message

The TreeTrace_spruce database contains images and measurements of 100 Norway spruce (Picea abies (L.) H.Karst.) logs from Northeastern France, each about 4.5 m long. The image database includes RGB images of large and small ends of the logs and hyperspectral and computed tomography (CT) images of wood discs sampled at both log ends. The 100 logs were also fully X-ray scanned with a CT device for roundwoods and their top surface was scanned with a terrestrial LiDAR device. The measurements performed on discs include wood local density, growth ring widths and pith location. This database is complementary to another one (TreeTrace_Douglas) resulting from the same ANR project TreeTrace, but if the objectives are similar, the protocols and conditions of acquisition are not the same for these two databases. TreeTrace_spruce dataset is available at https://doi.org/10.57745/WKLTJI and associated metadata are available at https://metadata-afs.nancy.inra.fr/geonetwork/srv/fre/catalog.search#/metadata/cffee2f1-18e1-4b53-9f5b-6cc4c66f1cb8.
Mulched and soil-incorporated sugarcane greenchop residue and compost: effects on selected soil components, sugarcane nutrients, Mexican rice borer injury, and yield
Authors: Showler Allan T.
Published: February 2023

Burning sugarcane,Saccharumspp., fields to remove leaves before harvest is a routine practice in many sugarcane production areas, including the United States. The method is environmentally deleterious and has been discontinued in some parts of the world. Alternatively, excised preharvest leaf residue, or greenchop, is used as mulch. This field study examined the effects of greenchop, applied in several ways to sugarcane soil, on soil fertility, selected sugarcane plant physiochemicals, injury inflicted by the Mexican rice borer,Eoreuma loftini(Dyar) (Lepidoptera: Crambidae), and sugarcane yield parameters, compared to plots augmented by soil-incorporated compost and a nontreated control. The compost amended soil had elevated concentrations of many nutrients, and in sugarcane leaves, heightened concentrations of certain sugars and free amino acids. None of the greenchop treatments affected soil and sugarcane leaf nutrients. During the first year of the study,E. loftiniinjury to sugarcane stalks during the first season, however, was generally greater in the greenchop and compost treatments than in the control. In the second growing season, the compost treatment was the only treatment associated with heightenedE. loftiniinfestations. Relationships between soils augmented with organic amendments andE. loftiniinjury to sugarcane are discussed in terms of mediation through physiochemical changes induced by the amendments.
Revealing the complexity of vampire bat rabies “spillover transmission”
Authors: Escobar Luis E. , Velasco-Villa Andres , Satheshkumar Panayampalli S. , Nakazawa Yoshinori , Van de Vuurst Paige
Published: February 2023

Background

The term virus ‘spillover’ embodies a highly complex phenomenon and is often used to refer to viral transmission from a primary reservoir host to a new, naïve yet susceptible and permissive host species. Spillover transmission can result in a virus becoming pathogenic, causing disease and death to the new host if successful infection and transmission takes place.

Main text

The scientific literature across diverse disciplines has used the terms virus spillover, spillover transmission, cross-species transmission, and host shift almost indistinctly to imply the complex process of establishment of a virus from an original host (source/donor) to a naïve host (recipient), which have close or distant taxonomic or evolutionary ties. Spillover transmission may result in unsuccessful onward transmission, if the virus dies off before propagation. Alternatively, successful viral establishment in the new host can occur if subsequent secondary transmission among individuals of the same novel species and among other sympatric susceptible species occurred. As such, virus spillover transmission is a common yet highly complex phenomenon that encompasses multiple subtle stages that can be deconstructed to be studied separately to better understand the drivers of disease emergence. Rabies virus (RABV) is a well-documented viral pathogen which still inflicts heavy impact on humans, companion animals, wildlife, and livestock throughout Latin America due substantial spatial temporal and ecological—natural and expansional—overlap with several virus reservoir hosts. Thereby, the rabies disease system represents a robust avenue through which the drivers and uncertainties surrounding spillover transmission can be unravel at its different subtle stages to better understand how they may be affected by coarse, medium, and fine scale variables.

Conclusions

The continued study of viral spillover transmission necessitates the elucidation of its complexities to better assess the cross-scale impacts of ecological forces linked to the propensity of spillover success. Improving capacities to reconstruct and predict spillover transmission would prevent public health impacts on those most at risk populations across the globe.

Graphical Abstract:
Receiver mount design, transmitter depth, and wind speed affect detection probability of acoustic telemetry transmitters in a Missouri River tributary
Authors: Carlson Tanner L. , LaBrie Lindsey A. P. , Wesner Jeff S. , Chipps Steven R. , Coulter Alison A. , Schall Benjamin J.
Published: February 2023

Background

One of the most important considerations for acoustic telemetry study designs is detection probability between the transmitter and the receiver. Variation in environmental (i.e., wind and flow) and abiotic (i.e., bathymetry) conditions among aquatic systems can lead to differences in detection probability temporally or between systems. In this study we evaluate the effect of distance, receiver mount design, transmitter depth, and wind speed on detection probabilities of two models of acoustic transmitters in a mid-sized river. InnovaSea V16-6H (hereafter V16) and V13-1L (hereafter V13) tags were deployed in the James River, SD at 0.36 m (deep) and 2.29 m (V16 tag) or 1.98 m (V13 tag; shallow) above the benthic surface downstream of InnovaSea VR2W stationary receivers at distances of 100, 200, or 300 m. We used two receiver mount designs that included a fixed position within a PVC pipe on the downstream side of a bridge piling or a metal frame deployed in the middle of the river channel. Tags were deployed for 72 h at each location, and hourly detections were summarized. We evaluated downstream distance, receiver mount design, tag depth, and wind effects on tag detection using Bayesian logistic regression.

Results

Detection probability decreased as distance increased for all combinations of tag types and mount designs and varied from nearly 100% at 100 m to less than 10% at 300 m. The V16 transmitter had greater detection probability by the receiver mounted in the pipe than in the midriver frame. For both mounts, the deep V16 transmitter had greater detection probability than the V16 shallow transmitter. Detection probability of the V13 transmitter was similar between receiver mounts or transmitter depths. Wind speed had a negative impact on detection probabilities of both transmitter types and depths, except the deep V16 transmitter.

Conclusions

Deploying acoustic receivers in PVC pipes rather than midriver frames provided greater downstream detection probabilities for V16 transmitters under conditions evaluated in this study. In addition, V16 transmitters had greater detection probabilities when positioned deep within the water column rather than near the surface. We also demonstrated that wind speed can have a negative impact on detection probabilities.
Assessment and management of disorders of gut–brain interaction in patients with eating disorders
Authors: Atkins Micaela , Burton Murray Helen , Staller Kyle
Published: February 2023

Disorders of gut–brain interaction (DBGI), also known as functional gastrointestinal disorders, are common in individuals with eating disorders, and may precede or perpetuate disordered eating. Understanding the pathophysiology of common gastrointestinal symptoms in DGBI can be important for the care of many patients with eating disorders. In this review, we summarize the literature to date on the complex relationship between DBGI and eating disorders and provide guidance on the assessment and management of the most common symptoms of DBGI by anatomic region: esophageal symptoms (globus and functional dysphagia), gastroduodenal symptoms (functional dyspepsia and nausea), and bowel symptoms (abdominal pain, bloating and constipation).
CNS tumor with EP300::BCOR fusion: discussing its prevalence in adult population
Authors: Tauziède-Espariat Arnault , Uro-Coste Emmanuelle , Sievers Philipp , Nicaise Yvan , Mariet Cassandra , Siegfried Aurore , Pierron Gaëlle , Guillemot Delphine , Benzakoun Joseph , Pallud Johan , Roques Margaux , Bonneville Fabrice , Larrieu-Ciron Delphine , Chaynes Patrick , Saffroy Raphaël , Hamelin Jocelyne , Hasty Lauren , Métais Alice , Chrétien Fabrice , Kool Marcel , Gojo Johannes , Varlet Pascale ,   RENOCLIP-LOC
Published: February 2023

The Central Nervous System (CNS) tumor with BCOR internal tandem duplication (ITD) has recently been added as a novel embryonal histomolecular tumor type to the 2021 World Health Organization (WHO) Classification of CNS Tumors. In addition, other CNS tumors harboring a BCOR/BCORL1 fusion, which are defined by a distinct DNA-methylation profile, have been recently identified in the literature but clinical, radiological and histopathological data remain scarce. Herein, we present two adult cases of CNS tumors with EP300::BCOR fusion. These two cases presented radiological, histopathological, and immunohistochemical homologies with CNS tumors having BCOR ITD in children. To compare these tumors with different BCOR alterations, we performed a literature review with a meta-analysis. CNS tumors with EP300::BCOR fusion seem to be distinct from their BCOR ITD counterparts in terms of age, location, progression-free survival, tumor growth pattern, and immunopositivity for the BCOR protein. CNS tumors from the EP300::BCOR fusion methylation class in adults may be added to the future WHO classification.
Analysis of anticancer potential of Kingiodendron pinnatum (DC.) Harms
Authors: Pareeth Chennattu M. , Meera Nair , Silpa Prabha , Thara Kannoor M. , Raghavamenon Achuthan C. , Babu Thekkekara D.
Published: February 2023

Background

The plant Kingiodendron pinnatum (DC.) Harms, belonging to the family Fabaceae is endemic to the Western Ghats of India and is commonly used for various ailments, especially by the tribes. K. pinnatum is occasionally used as a substitute for Saraca asoca in Asokarishta, a well-known uterine tonic in Ayurveda. Recent studies revealed a pharmacological similarity between the plants. S. asoca is reported to have anti-cancer properties, but there are no reports on K. pinnatum except for antioxidant and antimicrobial activities. Therefore, the study is aimed to investigate the anticancer potential of the plant.

Methods

Cytotoxicity of methanolic bark extract of the plant was analysed on different cancer cell lines by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Dalton's lymphoma ascites (DLA) cell-induced solid and Ehrlich ascites carcinoma (EAC) cell-induced ascites tumour models in mice were used to study the antitumor potential. Phytochemical screening of the extract was also performed.

Results

The extract was found cytotoxic to DLA, EAC, HCT15, MDA-MB-231, T47D and PC3 with inhibitory concentration (IC50) values of 50.09, 74.74, 67.02, 119.22, 149.04 and 194.5 μg/mL, respectively. In the solid tumour model, a significant (P < 0.001) reduction in tumour weight of 0.7 ± 0.15 g was observed in 500 mg/kg b.wt. extract treated group compared to the control group (3.6 ± 0.24 g) by oral administration for 30 days. In the ascites tumour model, a high survival rate of 28.2 ± 8.72 days (P < 0.01) was found by the extract treatment compared to the control animals. Phytochemicals like alkaloids, flavonoids, phenols, phytosterols, saponins, tannins, steroids and terpenoids were detected in the extract.

Conclusion

Results obtained by the cytotoxic and anti-tumour studies revealed the anticancer potential of K. pinnatum. The plant exhibits more cytotoxicity towards cancer cell lines of the reproductive system such as the breast and prostate.
Authenticating GNSS civilian signals: a survey
Authors: Yuan Muzi , Tang Xiaomei , Ou Gang
Published: February 2023

Civilian services of Global Navigation Satellite System are threatened by spoofing attacks since it is hard to determine the authenticity of a navigation signal with a detailed structure open to the public. Signal authentication effectively protects the security of the signal by attaching unforgeable information to one or several elements of the signal. Receivers can verify the authenticity of the signal by extracting and validating this information. Developing good signal authentication schemes requires understanding possible spoofing modes, signal element specialty, and performance evaluation methods. This paper is an overview of navigation signal authentication, where the theories and reported approaches are described in detail. A design/performance matrix that demonstrates the advantages and defects of the signal element and its authentication design is summarized. Recommendations are proposed to improve the robustness, security, efficiency, and implementation hardness for future designs of navigation signal authentication.
Addressing key issues in HIV self-test program implementation for Black and Latino sexual minority men in the Southern United States: a multiphase study protocol
Authors: Guigayoma John , Becker Sara J. , Ong Jason J. , Kanamori Mariano , Hickson DeMarc , Ward Lori M. , Biello Katie B. , Wray Tyler
Published: February 2023

Background

Black and Latino sexual minority men in the Southern United States have the highest HIV infection rates in the country. Increased HIV testing can help decrease onward HIV transmission through detecting previously undiagnosed infections. HIV self-testing is an evidence-based strategy to increase HIV testing among sexual minority men, but the implementation of this intervention in the Southern United States is limited. One implementation barrier is the lack of knowledge of Black and Latino sexual minority men’s preferences for various HIV self-testing program characteristics and their willingness to pay for these preferences. In addition, little is known about facilitators and barriers to initiating HIV self-testing programs from the perspectives of HIV prevention implementation decision-makers in this region.

Methods

We will conduct an online discrete choice experiment among Black and Latino sexual minority men in the Southern United States (n = 300) to estimate this population’s preferences for the following HIV self-testing program characteristics: delivery strategy (home delivery, peer delivery, clinic pickup); delivery speed (same day, next day, 3 days, and 5 days); support (instructions only, during test, and 1 week after delivery); and price ($0, $20, $40, $50, $60). We will also use this choice data to generate willingness-to-pay estimates for each program characteristic. Guided by the Consolidated Framework for Implementation Research, we will then conduct semi-structured interviews (n = 30) with HIV prevention program decision-makers at various health organizations serving Black and Latino sexual minority men in the region to further understand facilitators and barriers to implementation of the most preferred HIV self-testing program design.

Discussion

By gaining perspectives on HIV self-testing implementation from patients and providers, this project will build a roadmap for the initiation of HIV self-testing programs to decrease HIV incidence among one of the most disproportionately impacted populations in the USA.
Multiple hepatic and osseous focal lesions without splenomegaly and/or lymph nodes enlargement
Authors: Elghannam Maged T. , Hassanien Moataz H. , Ameen Yosry A. , ELattar Gamal M. , ELRay Ahmed A. , ELtalkawy Mohammed D. , Montasser Ahmed Y.
Published: February 2023

Background

Hepatic involvement is a common extranodal manifestation of common and some rare hematologic malignancies. Although the imaging features of more common hepatic diseases such as hepatocellular carcinoma, metastases, and infection may overlap with those of hepatic hematologic malignancies, combining the imaging features with clinical manifestations and laboratory findings can facilitate correct diagnosis. Imaging has an important role in the diagnosis of hepatic focal lesions.

Case presentation

A case presented with isolated multiple hepatic focal lesions without nodal or spleen enlargement diagnosed only by immunohistochemical study and turned out to be primary hepatic lymphoma (PHL). PHL is rare with roughly 100 described cases and accounts for less than 1% of all non-Hodgkin lymphomas. Osseous involvement adds more challenge to the diagnosis.

Conclusion

Hepatologists must be aware of PHL as it may be confused with more common hepatic diseases, mainly multifocal HCC and/or hepatic metastasis.