bluuebunny/crossref_metadata_2025 huggingface dataset:
A versatile genomic transgenesis platform with enhanced λ integrase for human Expi293F cells
Authors: Siddiqui Asim Azhar , Peter Sabrina , Ngoh Eve Zi Xian , Wang Cheng-I. , Ng Shirelle , Dangerfield John A. , Gunzburg Walter H. , Dröge Peter , Makhija Harshyaa
Published: June 2023

Reliable cell-based platforms to test and/or produce biologics in a sustainable manner are important for the biotech industry. Utilizing enhanced λ integrase, a sequence-specific DNA recombinase, we developed a novel transgenesis platform involving a fully characterized single genomic locus as an artificial landing pad for transgene insertion in human Expi293F cells. Importantly, transgene instability and variation in expression were not observed in the absence of selection pressure, thus enabling reliable long-term biotherapeutics testing or production. The artificial landing pad for λ integrase can be targeted with multi-transgene constructs and offers future modularity involving additional genome manipulation tools to generate sequential or nearly seamless insertions. We demonstrated broad utility with expression constructs for anti PD-1 monoclonal antibodies and showed that the orientation of heavy and light chain transcription units profoundly affected antibody expression levels. In addition, we demonstrated encapsulation of our PD-1 platform cells into bio-compatible mini-bioreactors and the continued secretion of antibodies, thus providing a basis for future cell-based applications for more effective and affordable therapies.
The effect of layer thickness ratio on the drug release behavior of alternating layered composite prepared by layer-multiplying co-extrusion
Authors: Zheng Huiyu , Zhang Cong , Liu Guiting , Chen Rong , Guo Shaoyun
Published: June 2023

Multi-layered drug delivery (MLDD) system has promising potential to achieve controlled release. However, existing technologies face difficulties in regulating the number of layers and layer-thickness ratio. In our previous works, layer-multiplying co-extrusion (LMCE) technology was applied to regulate the number of layers. Herein, we utilized layer-multiplying co-extrusion technology to modulate the layer-thickness ratio to expand the application of LMCE technology. Four-layered poly (ε-caprolactone)-metoprolol tartrate/poly (ε-caprolactone)-polyethylene oxide (PCL-MPT/PEO) composites were continuously prepared by LMCE technology, and the layer-thickness ratios for PCL-PEO layer and PCL-MPT layer were set to be 1:1, 2:1, and 3:1 just by controlling the screw conveying speed. The in vitro release test indicated that the rate of MPT release increased with decreasing the thickness of the PCL-MPT layer. Additionally, when PCL-MPT/PEO composite was sealed by epoxy resin to eliminate the edge effect, sustained release of MPT was achieved. The compression test confirmed the potential of PCL-MPT/PEO composites as bone scaffolds.
An environmental sustainability roadmap for partially substituting agricultural waste for sand in cement blocks
Authors: Mohammed Sazid Ali , Shakor Pshtiwan , S. Sathvik , Rauniyar Abishek , Krishnaraj L. , Kumar Singh Atul , Laghi Vittoria
Published: June 2023

Agricultural waste can be used in cement block production for a number of reasons, including its environmental, economic, and labor benefits. This study examines the mechanical, durability, and cost-effectiveness characteristics of cement blocks. A cement block made from agriculture waste promotes sustainable construction practices, since waste agriculture is often dumped in landfills and regarded as a waste material. Carbon dioxide (CO2) emissions produced by the construction sector, either from the firing of clay bricks or from the production of cement, contribute significantly to global warming. In many developing countries, air pollution from agricultural activities is primarily accounted for the emissions from agricultural machinery and openly burning agro-waste. Farming is one of the leading causes of water and soil pollution. Hence, adopting agricultural waste into cement production would significantly reduce the environmental impact of concrete structures. The goal of this research is to determine whether agricultural waste products, such as vermiculite, pistachio shells, sugarcane bagasse, and coconut husks, can be used to substitute sand in concrete blocks. The water absorption capacity of waste materials, density, flexural strength, fire resistance, and compressive strength of waste materials as admixtures in concrete were evaluated using experimental tests. In most cases, the concrete blocks made from agricultural waste were strong enough to satisfy ASTM standards. The specimens containing coconut husks and pistachio shells, among others, were found to be fairly strong and durable, even when isolating them from water.
Human cytomegalovirus in cancer: the mechanism of HCMV-induced carcinogenesis and its therapeutic potential
Authors: Yu Chuan , He Suna , Zhu Wenwen , Ru Penghui , Ge Xuemei , Govindasamy Kavitha
Published: June 2023

Cancer is one of the leading causes of death worldwide. Human cytomegalovirus (HCMV), a well-studied herpesvirus, has been implicated in malignancies derived from breast, colorectal muscle, brain, and other cancers. Intricate host-virus interactions are responsible for the cascade of events that have the potential to result in the transformed phenotype of normal cells. The HCMV genome contains oncogenes that may initiate these types of cancers, and although the primary HCMV infection is usually asymptomatic, the virus remains in the body in a latent or persistent form. Viral reactivation causes severe health issues in immune-compromised individuals, including cancer patients, organ transplants, and AIDS patients. This review focuses on the immunologic mechanisms and molecular mechanisms of HCMV-induced carcinogenesis, methods of HCMV treatment, and other studies. Studies show that HCMV DNA and virus-specific antibodies are present in many types of cancers, implicating HCMV as an important player in cancer progression. Importantly, many clinical trials have been initiated to exploit HCMV as a therapeutic target for the treatment of cancer, particularly in immunotherapy strategies in the treatment of breast cancer and glioblastoma patients. Taken together, these findings support a link between HCMV infections and cellular growth that develops into cancer. More importantly, HCMV is the leading cause of birth defects in newborns, and infection with HCMV is responsible for abortions in pregnant women.
Biogenic polymer-based patches for congenital cardiac surgery: a feasibility study
Authors: Richert Emma , Nienhaus Andrea , Ekroll Jahren Silje , Gazdhar Amiq , Grab Maximilian , Hörer Jürgen , Carrel Thierry , Obrist Dominik , Heinisch Paul Philipp
Published: June 2023

Objective

Currently used patch materials in congenital cardiac surgery do not grow, renew, or remodel. Patch calcification occurs more rapidly in pediatric patients eventually leading to reoperations. Bacterial cellulose (BC) as a biogenic polymer offers high tensile strength, biocompatibility, and hemocompatibility. Thus, we further investigated the biomechanical properties of BC for use as patch material.

Methods

The BC-producing bacteria Acetobacter xylinum were cultured in different environments to investigate optimal culturing conditions. For mechanical characterization, an established method of inflation for biaxial testing was used. The applied static pressure and deflection height of the BC patch were measured. Furthermore, a displacement and strain distribution analysis was performed and compared to a standard xenograft pericardial patch.

Results

The examination of the culturing conditions revealed that the BC became homogenous and stable when cultivated at 29°C, 60% oxygen concentration, and culturing medium exchange every third day for a total culturing period of 12 days. The estimated elastic modulus of the BC patches ranged from 200 to 530 MPa compared to 230 MPa for the pericardial patch. The strain distributions, calculated from preloaded (2 mmHg) to 80 mmHg inflation, show BC patch strains ranging between 0.6% and 4%, which was comparable to the pericardial patch. However, the pressure at rupture and peak deflection height varied greatly, ranging from 67 to around 200 mmHg and 0.96 to 5.28 mm, respectively. The same patch thickness does not automatically result in the same material properties indicating that the manufacturing conditions have a significant impact on durability

Conclusions

BC patches can achieve comparable results to pericardial patches in terms of strain behavior as well as in the maximum applied pressure that can be withstood without rupture. Bacterial cellulose patches could be a promising material worth further research.
Physical and chemical characteristics of active sulfur flows observed at Lastarria volcano (northern Chile) in January 2019
Authors: Inostroza Manuel , Fernandez Bárbara , Aguilera Felipe , Layana Susana , Walter Thomas R. , Zimmer Martin , Rodríguez-Díaz Augusto , Oelze Marcus
Published: June 2023

Molten sulfur is found in various subaerial volcanoes. However, limited records of the pools and flows of molten sulfur have been reported: therefore, questions remain regarding the physicochemical processes behind this phenomenon. A suite of new sulfur flows, some of which active, was identified at the Lastarria volcano (northern Chile) and studied using satellite imagery, in situ probing, and temperature and video recording. This finding provides a unique opportunity to better understand the emplacement mechanisms and mineral and chemical compositions of molten sulfur, in addition to gaining insight into its origin. Molten sulfur presented temperatures of 124–158°C, with the most prolonged sulfur flow reaching 12 m from the source. Photogrammetric tools permitted the identification of levees and channel structures, with an estimated average flow speed of 0.069 m/s. Field measurements yielded a total volume of 1.45 ± 0.29 m3 of sulfur (equivalent to ∼2.07 tons) mobilized during the January 2019 event for at least 408 min. Solidified sulfur was composed of native sulfur with minor galena and arsenic- and iodine-bearing minerals. Trace element analysis indicated substantial enrichment of Bi, Sb, Sn, Cd, as well as a very high concentration of As (>40.000 ppm). The January 2019 molten sulfur manifestations in Lastarria appear to be more enriched in As compared to the worldwide known volcanoes with molten sulfur records, such as the Shiretoko-Iozan and Poás volcanoes. Furthermore, their rheological properties suggest that the “time of activity” in events such as this could be underestimated as flows in Lastarria have moved significantly slower than previously thought. The origin of molten sulfur is ascribed to the favorable S-rich chemistry of fumarolic gases and changes in host rock permeability (fracture opening). Molten sulfur in Lastarria correlates with a peak in activity characterized by high emissions of SO2 and other acid species, such as HF and HCl, in addition to ground deformation. Consequently, molten sulfur was framed within a period of volcanic unrest in Lastarria, triggered by changes in the magmatic-hydrothermal system. The appearance of molten sulfur is related to physicochemical perturbations inside the volcanic system and is perhaps a precursor of eruptive activity, as observed in the Poás and Turrialba volcanoes.
A novel frameshift mutation in DNAH6 associated with male infertility and asthenoteratozoospermia
Authors: Huang Fei , Zeng Jun , Liu Dan , Zhang Jing , Liang Boluo , Gao Jingping , Yan Rong , Shi Xiaobo , Chen Jianlin , Song Wanjuan , Huang Hua-Lin
Published: June 2023

Introduction

Asthenoteratozoospermia is one of the most common causes of male infertility. Several genes have been identified as genetic causative factors, but there is a considerable genetic heterogeneity underlying asthenoteratozoospermia. In this study, we performed a genetic analysis of two brothers from a consanguineous Uighur family in China to identify gene mutations causative for asthenoteratozoospermia-related male infertility.

Methods

Two related patients with asthenoteratozoospermia from a large consanguineous family were sequenced by whole-exome sequencing and Sanger sequencing to identify disease-causing genes. Scanning and transmission electron microscopy analysis revealed ultrastructural abnormalities of spermatozoa. Quantitative real-time PCR (qRT-PCR) analysis and immunofluorescence (IF) analysis were used to assess the expression of the mutant messenger RNA (mRNA) and protein.

Results

A novel homozygous frameshift mutation (c.2823dupT, p.Val942Cysfs*21) in DNAH6 was identified in both affected individuals and was predicted to be pathogenic. Papanicolaou staining and electron microscopy revealed multiple morphological and ultrastructural abnormalities of affected spermatozoa. qRT-PCR and IF analysis showed abnormal expression of DNAH6 in affected sperm, probably due to premature termination code and decay of abnormal 3′ untranslated region (UTR) region of mRNA. Furthermore, intracytoplasmic sperm injection could achieve successful fertilization in infertile men with DNAH6 mutations.

Discussion

The novel frameshift mutation identified in DNAH6 may contribute to asthenoteratozoospermia. These findings expand the spectrum of genetic mutations and phenotypes associated with asthenoteratozoospermia and may be useful for genetic and reproductive counseling in male infertility.
Photovoltaic power stations: an opportunity to promote European semi-natural grasslands?
Authors: Lambert Quentin , Bischoff Armin , Enea Morgane , Gros Raphael
Published: June 2023

European semi-natural grasslands are particularly species-rich and provide many ecosystem services but depend on extensive land management. Today, these ecosystems are highly threatened by land abandonment, land use intensification and habitat destruction. The increasing construction of solar parks may contribute to habitat destruction but also provide an opportunity to restore or even create semi-natural grasslands. We studied ten solar parks along a climate gradient in Southern France to evaluate the establishment of semi-natural grasslands managed by grazing. We compared plots outside and under solar panels in terms of plant community composition, soil biodiversity and soil functioning to test whether solar panels hamper this establishment. The different microclimate under solar panels strongly affected the plant species composition and reduced the abundance of soil mesofauna and biomass of fungi and gram-negative bacteria. Outside panels, the vegetation was shaped by a climatic gradient, in particular by variations in temperature and precipitation whereas under panels variations were smaller indicating a homogenizing effect of panels on plant community composition. We found more trophic interactions between panels compared to outside and under panels suggesting a protection effect of panels between rows on the soil food web. However, plots under panels showed the lowest number of interactions demonstrating that the strong shading had a negative effect on the plant-soil food web. Solar panels therefore reduce the plant and soil biodiversity of semi-natural grasslands and disrupt ecosystem functions. In order to improve the ecological integration of solar parks, it is thus necessary to mitigate negative effects of solar panels on biodiversity or to increase the space between panels.
Molecular mechanisms of immunotherapy resistance in triple-negative breast cancer
Authors: Zheng Yiwen , Li Shujin , Tang Hongchao , Meng Xuli , Zheng Qinghui
Published: June 2023

The emergence of immunotherapy has profoundly changed the treatment model for triple-negative breast cancer (TNBC). But the heterogeneity of this disease resulted in significant differences in immunotherapy efficacy, and only some patients are able to benefit from this therapeutic modality. With the recent explosion in studies on the mechanism of cancer immunotherapy drug resistance, this article will focus on the processes of the immune response; summarize the immune evasion mechanisms in TNBC into three categories: loss of tumor-specific antigen, antigen presentation deficiency, and failure to initiate an immune response; together with the aberrant activation of a series of immune-critical signaling pathways, we will discuss how these activities jointly shape the immunosuppressive landscape within the tumor microenvironment. This review will attempt to elucidate the molecular mechanism of drug resistance in TNBC, identify potential targets that may assist in reversing drug resistance, and lay a foundation for research on identifying biomarkers for predicting immune efficacy and selection of breast cancer populations that may benefit from immunotherapy.
Tumor-associated macrophages: new insights on their metabolic regulation and their influence in cancer immunotherapy
Authors: Xiao Li , Wang Qiao , Peng Hongling
Published: June 2023

Tumor-associated macrophages (TAMs) are a dynamic and heterogeneous cell population of the tumor microenvironment (TME) that plays an essential role in tumor formation and progression. Cancer cells have a high metabolic demand for their rapid proliferation, survival, and progression. A comprehensive interpretation of pro-tumoral and antitumoral metabolic changes in TAMs is crucial for comprehending immune evasion mechanisms in cancer. The metabolic reprogramming of TAMs is a novel method for enhancing their antitumor effects. In this review, we provide an overview of the recent research on metabolic alterations of TAMs caused by TME, focusing primarily on glucose, amino acid, and fatty acid metabolism. In addition, this review discusses antitumor immunotherapies that influence the activity of TAMs by limiting their recruitment, triggering their depletion, and re-educate them, as well as metabolic profiles leading to an antitumoral phenotype. We highlighted the metabolic modulational roles of TAMs and their potential to enhance immunotherapy for cancer.
Brain transcriptomics reveal the activation of neuroinflammation pathways during acute Orientia tsutsugamushi infection in mice
Authors: Liang Yuejin , Aditi  , Onyoni Florence , Wang Hui , Gonzales Casey , Sunyakumthorn Piyanate , Wu Ping , Samir Parimal , Soong Lynn
Published: June 2023

Scrub typhus, an acute febrile illness caused by Orientia tsutsugamushi (Ot), is prevalent in endemic areas with one million new cases annually. Clinical observations suggest central nervous system (CNS) involvement in severe scrub typhus cases. Acute encephalitis syndrome (AES) associated with Ot infection is a major public health problem; however, the underlying mechanisms of neurological disorder remain poorly understood. By using a well-established murine model of severe scrub typhus and brain RNA-seq, we studied the brain transcriptome dynamics and identified the activated neuroinflammation pathways. Our data indicated a strong enrichment of several immune signaling and inflammation-related pathways at the onset of disease and prior to host death. The strongest upregulation of expression included genes involved in interferon (IFN) responses, defense response to bacteria, immunoglobulin-mediated immunity, IL-6/JAK-STAT signaling, and TNF signaling via NF-κB. We also found a significant increase in the expression of core genes related to blood-brain barrier (BBB) disruption and dysregulation in severe Ot infection. Brain tissue immunostaining and in vitro infection of microglia revealed microglial activation and proinflammatory cytokine production, suggesting a crucial role of microglia in neuroinflammation during scrub typhus. This study provides new insights into neuroinflammation in scrub typhus, highlighting the impact of excessive IFN responses, microglial activation, and BBB dysregulation on disease pathogenesis.
Citrullination of C1-inhibitor as a mechanism of impaired complement regulation in rheumatoid arthritis
Authors: Martin Myriam , Nilsson Sara C. , Eikrem David , Fromell Karin , Scavenius Carsten , Vogt Leonie M. , Bielecka Ewa , Potempa Jan , Enghild Jan J. , Nilsson Bo , Ekdahl Kristina N. , Kapetanovic Meliha C. , Blom Anna M.
Published: June 2023

Background

Dysregulated complement activation, increased protein citrullination, and production of autoantibodies against citrullinated proteins are hallmarks of rheumatoid arthritis (RA). Citrullination is induced by immune cell-derived peptidyl-Arg deiminases (PADs), which are overactivated in the inflamed synovium. We characterized the effect of PAD2- and PAD4-induced citrullination on the ability of the plasma-derived serpin C1-inhibitor (C1-INH) to inhibit complement and contact system activation.

Methods

Citrullination of the C1-INH was confirmed by ELISA and Western blotting using a biotinylated phenylglyoxal probe. C1-INH-mediated inhibition of complement activation was analyzed by C1-esterase activity assay. Downstream inhibition of complement was studied by C4b deposition on heat-aggregated IgGs by ELISA, using pooled normal human serum as a complement source. Inhibition of the contact system was investigated by chromogenic activity assays for factor XIIa, plasma kallikrein, and factor XIa. In addition, autoantibody reactivity to native and citrullinated C1-INH was measured by ELISA in 101 RA patient samples.

Results

C1-INH was efficiently citrullinated by PAD2 and PAD4. Citrullinated C1-INH was not able to bind the serine protease C1s and inhibit its activity. Citrullination of the C1-INH abrogated its ability to dissociate the C1-complex and thus inhibit complement activation. Consequently, citrullinated C1-INH had a decreased capacity to inhibit C4b deposition via the classical and lectin pathways. The inhibitory effect of C1-INH on the contact system components factor XIIa, plasma kallikrein, and factor XIa was also strongly reduced by citrullination. In RA patient samples, autoantibody binding to PAD2- and PAD4-citrullinated C1-INH was detected. Significantly more binding was observed in anti-citrullinated protein antibody (ACPA)-positive than in ACPA-negative samples.

Conclusion

Citrullination of the C1-INH by recombinant human PAD2 and PAD4 enzymes impaired its ability to inhibit the complement and contact systems in vitro. Citrullination seems to render C1-INH more immunogenic, and citrullinated C1-INH might thus be an additional target of the autoantibody response observed in RA patients.
From salty to thriving: plant growth promoting bacteria as nature’s allies in overcoming salinity stress in plants
Authors: Peng Mu , Jiang Zhihui , Zhou Fangzhen , Wang Zhiyong
Published: June 2023

Soil salinity is one of the main problems that affects global crop yield. Researchers have attempted to alleviate the effects of salt stress on plant growth using a variety of approaches, including genetic modification of salt-tolerant plants, screening the higher salt-tolerant genotypes, and the inoculation of beneficial plant microbiome, such as plant growth-promoting bacteria (PGPB). PGPB mainly exists in the rhizosphere soil, plant tissues and on the surfaces of leaves or stems, and can promote plant growth and increase plant tolerance to abiotic stress. Many halophytes recruit salt-resistant microorganisms, and therefore endophytic bacteria isolated from halophytes can help enhance plant stress responses. Beneficial plant-microbe interactions are widespread in nature, and microbial communities provide an opportunity to understand these beneficial interactions. In this study, we provide a brief overview of the current state of plant microbiomes and give particular emphasis on its influence factors and discuss various mechanisms used by PGPB in alleviating salt stress for plants. Then, we also describe the relationship between bacterial Type VI secretion system and plant growth promotion.
Absolute quantification of Mycoplasma pneumoniae in infected patients by droplet digital PCR to track disease severity and treatment efficacy
Authors: Zhao Hanqing , Yan Chao , Feng Yanling , Du Bing , Feng Junxia , Cui Xiaohu , Cui Jinghua , Gan Lin , Fan Zheng , Xu Ziying , Fu Tongtong , Yu Zihui , Yuan Jing , Xue Guanhua
Published: June 2023

Mycoplasma pneumoniae is a common causative pathogen of community-acquired pneumonia. An accurate and sensitive detection method is important for evaluating disease severity and treatment efficacy. Digital droplet PCR (ddPCR) is a competent method enabling the absolute quantification of DNA copy number with high precision and sensitivity. We established ddPCR for M. pneumoniae detection, using clinical specimens for validation, and this showed excellent specificity for M. pneumoniae. The limit of detection of ddPCR was 2.9 copies/reaction, while that for real-time PCR was 10.8 copies/reaction. In total, 178 clinical samples were used to evaluate the ddPCR assay, which correctly identified and differentiated 80 positive samples, whereas the real-time PCR tested 79 samples as positive. One sample that tested negative in real-time PCR was positive in ddPCR, with a bacterial load of three copies/test. For samples that tested positive in both methods, the cycle threshold of real-time PCR was highly correlated with the copy number of ddPCR. Bacterial loads in patients with severe M. pneumoniae pneumonia were significantly higher than those in patients with general M. pneumoniae pneumonia. The ddPCR showed that bacterial loads were significantly decreased after macrolide treatment, which could have reflected the treatment efficacy. The proposed ddPCR assay was sensitive and specific for the detection of M. pneumoniae. Quantitative monitoring of bacterial load in clinical samples could help clinicians to evaluate treatment efficacy.
Novel evidence on sepsis-inducing pathogens: from laboratory to bedside
Authors: Gatica Sebastian , Fuentes Brandon , Rivera-Asín Elizabeth , Ramírez-Céspedes Paula , Sepúlveda-Alfaro Javiera , Catalán Eduardo A. , Bueno Susan M. , Kalergis Alexis M. , Simon Felipe , Riedel Claudia A. , Melo-Gonzalez Felipe
Published: June 2023

Sepsis is a life-threatening condition and a significant cause of preventable morbidity and mortality globally. Among the leading causative agents of sepsis are bacterial pathogens Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pyogenes, along with fungal pathogens of the Candida species. Here, we focus on evidence from human studies but also include in vitro and in vivo cellular and molecular evidence, exploring how bacterial and fungal pathogens are associated with bloodstream infection and sepsis. This review presents a narrative update on pathogen epidemiology, virulence factors, host factors of susceptibility, mechanisms of immunomodulation, current therapies, antibiotic resistance, and opportunities for diagnosis, prognosis, and therapeutics, through the perspective of bloodstream infection and sepsis. A list of curated novel host and pathogen factors, diagnostic and prognostic markers, and potential therapeutical targets to tackle sepsis from the research laboratory is presented. Further, we discuss the complex nature of sepsis depending on the sepsis-inducing pathogen and host susceptibility, the more common strains associated with severe pathology and how these aspects may impact in the management of the clinical presentation of sepsis.
Microbiomes in the context of developing sustainable intensified aquaculture
Authors: Lorgen-Ritchie Marlene , Uren Webster Tamsyn , McMurtrie Jamie , Bass David , Tyler Charles R. , Rowley Andrew , Martin Samuel A. M.
Published: June 2023

With an ever-growing human population, the need for sustainable production of nutritional food sources has never been greater. Aquaculture is a key industry engaged in active development to increase production in line with this need while remaining sustainable in terms of environmental impact and promoting good welfare and health in farmed species. Microbiomes fundamentally underpin animal health, being a key part of their digestive, metabolic and defense systems, in the latter case protecting against opportunistic pathogens in the environment. The potential to manipulate the microbiome to the advantage of enhancing health, welfare and production is an intriguing prospect that has gained considerable traction in recent years. In this review we first set out what is known about the role of the microbiome in aquaculture production systems across the phylogenetic spectrum of cultured animals, from invertebrates to finfish. With a view to reducing environmental footprint and tightening biological and physical control, investment in “closed” aquaculture systems is on the rise, but little is known about how the microbial systems of these closed systems affect the health of cultured organisms. Through comparisons of the microbiomes and their dynamics across phylogenetically distinct animals and different aquaculture systems, we focus on microbial communities in terms of their functionality in order to identify what features within these microbiomes need to be harnessed for optimizing healthy intensified production in support of a sustainable future for aquaculture.
Prescribing patterns and determinants for elderly patients with Parkinson's disease in Japan: a retrospective observational study using insurance claims databases
Authors: Seki Morinobu , Kawata Yayoi , Hayashi Ayako , Arai Masaki , Fujimoto Shinji
Published: June 2023

Background

This study aimed to determine real-world prescribing patterns and determinants for Japanese patients with Parkinson's disease (PD), with a focus on patients ≥75 years.

Methods

This was a retrospective, observational, longitudinal study of patients with PD (≥30 years, ICD-10: G20 excluding Parkinson's syndrome) from three Japanese nationwide healthcare claim databases. Prescription drugs were tabulated using database receipt codes. Changes in treatment patterns were analyzed using network analysis. Factors associated with prescribing patterns and prescription duration were analyzed using multivariable analysis.

Results

Of 18 million insured people, 39,731 patients were eligible for inclusion (≥75-year group: 29,130; <75-year group: 10,601). PD prevalence was 1.21/100 people ≥75 years. Levodopa was the most commonly prescribed anti-PD drug (total: 85.4%; ≥75 years: 88.3%). Network analysis of prescribing patterns showed that most elderly patients switched from levodopa monotherapy to adjunct prescription patterns, as did younger patients, but with less complexity. Elderly patients who newly initiated PD treatment remained on levodopa monotherapy longer than younger patients; factors significantly associated with levodopa prescriptions were older age and cognitive impairment. Commonly prescribed adjunct therapies were monoamine oxidase type B inhibitors, non-ergot dopamine agonists, and zonisamide, regardless of age. Droxidopa and amantadine were prescribed as adjunct levodopa therapy slightly more frequently among elderly patients; levodopa adjunct therapy was prescribed when the levodopa dose was 300 mg, regardless of age.

Conclusion

Prescribing patterns for patients ≥75 years were levodopa centered and less complex than for those <75 years. Factors significantly associated with levodopa monotherapy and continued use of levodopa were older age and cognitive disorder.

Clinical trial registration

UMIN Clinical Trials Registry, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053425 (UMIN000046823).
Honokiol in glioblastoma recurrence: a case report
Authors: Wang Ce , Cai Zehao , Huang Yue , Liu Xinrui , Liu Xing , Chen Feng , Li Wenbin
Published: June 2023

Glioblastoma is the most common and aggressive primary tumor in the central nervous system. There is no standard of care for patients with recurrent GBM. Honokiol is a pleiotropic lignan and has the potential to be a potent and safe anticancer agent in human GBM when it is encapsulated by liposomes. We report an efficient and safe response to three phases of treatment with liposomal honokiol in a patient with recurrent glioblastoma.
Structural and functional characterization of the locus coeruleus in young and late middle-aged individuals
Authors: Berger Alexandre , Koshmanova Ekaterina , Beckers Elise , Sharifpour Roya , Paparella Ilenia , Campbell Islay , Mortazavi Nasrin , Balda Fermin , Yi Yeo-Jin , Lamalle Laurent , Dricot Laurence , Phillips Christophe , Jacobs Heidi I. L. , Talwar Puneet , El Tahry Riëm , Sherif Siya , Vandewalle Gilles
Published: June 2023

Introduction

The brainstem locus coeruleus (LC) influences a broad range of brain processes, including cognition. The so-called LC contrast is an accepted marker of the integrity of the LC that consists of a local hyperintensity on specific Magnetic Resonance Imaging (MRI) structural images. The small size of the LC has, however, rendered its functional characterization difficult in humans, including in aging. A full characterization of the structural and functional characteristics of the LC in healthy young and late middle-aged individuals is needed to determine the potential roles of the LC in different medical conditions. Here, we wanted to determine whether the activation of the LC in a mismatch negativity task changes in aging and whether the LC functional response was associated to the LC contrast.

Methods

We used Ultra-High Field (UHF) 7-Tesla functional MRI (fMRI) to record brain response during an auditory oddball task in 53 healthy volunteers, including 34 younger (age: 22.15y ± 3.27; 29 women) and 19 late middle-aged (age: 61.05y ± 5.3; 14 women) individuals.

Results

Whole-brain analyses confirmed brain responses in the typical cortical and subcortical regions previously associated with mismatch negativity. When focusing on the brainstem, we found a significant response in the rostral part of the LC probability mask generated based on individual LC images. Although bilateral, the activation was more extensive in the left LC. Individual LC activity was not significantly different between young and late middle-aged individuals. Importantly, while the LC contrast was higher in older individuals, the functional response of the LC was not significantly associated with its contrast.

Discussion

These findings may suggest that the age-related alterations of the LC structural integrity may not be related to changes in its functional response. The results further suggest that LC responses may remain stable in healthy individuals aged 20 to 70.
Building a novel strategic research agenda for METROFOOD-RI: design process and multi-stakeholder engagement towards thematic prioritization
Authors: Stelzl Tamara , Tsimidou Maria Z. , Belc Nastasia , Zoani Claudia , Rychlik Michael
Published: June 2023

Introduction

The European research landscape suffers widely from fragmentation and little cross-border research collaboration. Efforts are underway to bring the European Research Area to a higher level of performance and capacity in cutting-edge science, with high anticipations for the promotion of multidisciplinary research infrastructures of transnational engagement. A European distributed research infrastructure active in this framework is METROFOOD-RI, committed to promoting metrology in food and nutrition with particular focus on measurement research related to agrifood systems.

Methods

For research infrastructures, streamlining resources among partner organizations and establishing priorities around specific topics is critical for ensuring smooth operation. Similarly, METROFOOD-RI faced the challenge of exploring its strategic direction and research priorities as revealed in its first Strategic Research and Innovation Agenda (SRIA). This report details how the internal process of topic identification and prioritization progressed within the METROFOOD-RI SRIA and what obstacles were encountered along the way. A dual-track strategy was taken for locating future SRIA topics, applying a top-down and bottom-up approach, followed by internal consultation with METROFOOD-RI experts. The topic prioritization drew on a vote among the METROFOOD-RI Management Committee employing a custom-designed numerical rating scale questionnaire. Based on the maximum scores obtained for each topic, appropriate thresholds were introduced for classifying individual topics into high, medium, low, and very low priority ones.

Results

A total of 80 topics categorized into eight major clusters of challenges were located as potential SRIA candidates. Upon prioritization, 9 topics of very high priority and 16 topics of medium priority were identified as key research thematic areas of the newly developed SRIA.

Discussion

As a strategic framework, the SRIA occupies a central position and sets not only the scientific focus of the research infrastructure in the coming years, but also contributes to realizing the full potential and excellence of METROFOOD-RI, selectively expanding the existing portfolio and thus contributing to maximum efficiency and sustainability. It is anticipated that the lessons learned by METROFOOD-RI and its experiences shared are a valuable stimulus and guide for those who are taking on the challenge of setting-up a SRIA and are looking for edifying and constructive information on how to do so.
Perioperative intravenous lidocaine for postoperative pain in patients undergoing breast surgery: a meta-analysis with trial sequential analysis of randomized controlled trials
Authors: Li Jia , Huang Jiao , Yang Jiang-tao , Liu Jing-chen
Published: June 2023

Background

The effectiveness of intravenous lidocaine infusion in managing acute and chronic pain following breast surgery has been a topic of debate. This meta-analysis aims to assess the impact of perioperative intravenous lidocaine on the relief of postoperative pain among patients undergoing breast surgery.

Methods

A systematic search of databases was conducted to identify randomized controlled trials (RCTs) that compared the effects of intravenous lidocaine infusion with placebo or routine care in patients undergoing breast surgery. The primary outcome of interest was the occurrence of chronic post-surgical pain (CPSP) at the longest follow-up. Meta-analyses, incorporating trial sequential analysis, were performed using a random-effects model to assess the overall effect.

Results

A total of twelve trials, involving 879 patients, were included in the analysis. Perioperative intravenous lidocaine demonstrated a significant reduction in the incidence of CPSP at the longest follow-up (risk ratio [RR] 0.62, 95% confidence interval [CI] 0.48-0.81; P = 0.0005; I2 = 6%). Trial sequential analysis (TSA) indicated that the cumulative z curve crossed the trial sequential monitoring boundary for benefit, providing sufficient and conclusive evidence. Furthermore, intravenous lidocaine was associated with decreased opioid consumption and a shorter length of hospital stay.

Conclusion

Perioperative intravenous lidocaine is effective in relieving acute and CPSP in patients undergoing breast surgery.

Systematic review registration

https://inplasy.com/, identifier INPLASY2022100033.
In vivo total or partial hepatectomy followed by ex vivo liver resection and autotransplantation for malignant tumors: a single center experience
Authors: Xu Shaoyan , Hu Chenlu , Jiang Zedong , Li Guogang , Zhou Bo , Gao Zhenzhen , Wang Weilin , Yan Sheng
Published: June 2023

Background

Ex vivo liver resection and autotransplantation (ELRAT) may provide an opportunity for R0 resection of conventionally unresectable hepatobiliary cancers and hepatic metastases. To date, few studies of the surgery for malignant tumors have been conducted and there are no known reports of in vivo partial hepatectomy followed by ELRAT (IPH-ELRAT) for malignant tumors.

Methods

Between December 2021 and November 2022, ten patients with malignant hepatobiliary primary cancers or hepatic metastases underwent ELRAT at our institution. We shared the surgical skills and postoperative prognoses of these patients were assessed.

Results

The types of tumors were biliary tract cancer (BTC, n=8), hepatic metastasis of colonic carcinoma (n=1), and hepatic metastasis of small-bowel stromal tumor (n=1). Five patients underwent in vivo total hepatectomy followed by ex vivo liver resection and autotransplantation (ITH-ELRAT), The other five received in vivo partial hepatectomy followed by ex vivo liver resection and autotransplantation (IPH-ELRAT). Four patients underwent inferior vena cava replacement using artificial blood vessels. The survival rate of all ten patients one month after surgery was 100%. Nine patients (90%) are currently alive, with a median follow-up of 8.5 months (range 6–16.5 months). To date, seven of the nine surviving patients have had no cancer recurrence, including six with BTC.

Conclusions

We report the world first five cases that received IPH-ELRAT for malignancies. We also demonstrated relatively favorable outcomes in patients who underwent ELRAT. ELRAT may be a recommendable surgical option for selected patients with conventionally unresectable hepatobiliary malignant tumors.
Mitigating mode instabilities by controllable mode beating excitation with a photonic lantern
Authors: Lu Yao , Jiang Zongfu , Xiao Hu , Chen Zilun , Jiang Man , Chai Junyu , Yang Hao , Ding Lianchuang , Zhang Dan , Zhang Jiangbin , Zhou Qiong , Liu Wenguang
Published: June 2023

In this study, a method of stabilizing the output beam of a large-mode-area fiber amplifier operating above the mode instability threshold is demonstrated. A mode control system based on the photonic lantern is used to excite dynamic mode beatings as the seeding stage of a 42/250 µm Yb-doped fiber amplifier. We propose a theoretical explanation for the validity of this method: provided that the mode interference patterns generated by input mode beatings are antisymmetric to those in the main amplifier caused by thermally induced non-linear effects, the refractive index grating will not be formed to indicate the onset of mode instability. Experimentally, significant mode stability and beam quality improvement have been achieved in this system at power levels of up to nearly four times the mode instabilities threshold.
Inoculation with extreme endophytes improves performance and nutritional quality in crop species grown under exoplanetary conditions
Authors: Molina-Montenegro Marco A. , Escobedo Victor M. , Atala Cristian
Published: June 2023

Introduction

Technological advances have made possible long space travels and even exoplanetary colonies in the future. Nevertheless, the success of these activities depends on our ability to produce edible plants in stressful conditions such as high radiation, extreme temperatures and low oxygen levels. Since beneficial microorganisms, such as fungal endophytes from extreme environments, have helped agriculture cope with those difficulties, endophytic fungi may be a putative tool to ensure plant growth under exoplanetary conditions. Additionally, growing crops in polyculture has been shown to increase productivity and spatial efficiency, which is essential given the likely space restrictions in such conditions.

Methods

We evaluated the effect of the inoculation with a mix of two fungal endophytes from the Atacama Desert on performance (survival and biomass) and nutritional quality of three crop species (lettuce, chard and spinach) grown under exoplanetary conditions. In addition, we measured the amount of antioxidants (flavonoids and phenolics) as possible mechanisms to cope with such abiotic conditions. The exoplanetary conditions were; high UV radiation, low temperature, low water availability, and low oxygen levels. These crops were put in growing chambers in monoculture, dual culture and polyculture (the three species in the same pot) for 30 days.

Results and Discussion

Our results show that inoculation with extreme endophytes improved survival by ca. 15 - 35% and biomass by ca. 30 - 35% in all crop species. The most evident increase was when grown in polyculture, except for survival in spinach, where inoculated plants had higher survival only in dual culture. Nutritional quality and the amount of the antioxidant compounds antioxidants increased in all crop species when inoculated with the endophytes. Overall, fungal endophytes isolated from extreme environments such as the Atacama Desert, the driest desert in the world, could be a key biotechnological tool for future space agriculture, helping plants cope with environmental stress. Additionally, inoculated plants should be grown in polyculture to increase crop turnover and space-use efficiency. Lastly, these results provide useful insights to face the future challenges of space-farming.
Impact of dehydration on the physiochemical properties of Nostoc calcicola BOT1 and its untargeted metabolic profiling through UHPLC-HRMS
Authors: Yadav Priya , Singh Rahul Prasad , Alodaini Hissah Abdulrahman , Hatamleh Ashraf Atef , Santoyo Gustavo , Kumar Ajay , Gupta Rajan Kumar
Published: June 2023

The global population growth has led to a higher demand for food production, necessitating improvements in agricultural productivity. However, abiotic and biotic stresses pose significant challenges, reducing crop yields and impacting economic and social welfare. Drought, in particular, severely constrains agriculture, resulting in unproductive soil, reduced farmland, and jeopardized food security. Recently, the role of cyanobacteria from soil biocrusts in rehabilitating degraded land has gained attention due to their ability to enhance soil fertility and prevent erosion. The present study focused on Nostoc calcicola BOT1, an aquatic, diazotrophic cyanobacterial strain collected from an agricultural field at Banaras Hindu University, Varanasi, India. The aim was to investigate the effects of different dehydration treatments, specifically air drying (AD) and desiccator drying (DD) at various time intervals, on the physicochemical properties of N. calcicola BOT1. The impact of dehydration was assessed by analyzing the photosynthetic efficiency, pigments, biomolecules (carbohydrates, lipids, proteins, osmoprotectants), stress biomarkers, and non-enzymatic antioxidants. Furthermore, an analysis of the metabolic profiles of 96-hour DD and control mats was conducted using UHPLC-HRMS. Notably, there was a significant decrease in amino acid levels, while phenolic content, fatty acids, and lipids increased. These changes in metabolic activity during dehydration highlighted the presence of metabolite pools that contribute to the physiological and biochemical adjustments of N. calcicola BOT1, mitigating the impact of dehydration to some extent. Overall, present study demonstrated the accumulation of biochemical and non-enzymatic antioxidants in dehydrated mats, which could be utilized to stabilize unfavorable environmental conditions. Additionally, the strain N. calcicola BOT1 holds promise as a biofertilizer for semi-arid regions.