bluuebunny/crossref_metadata_2025 huggingface dataset:
Emergence of equine influenza virus H3Nx Florida clade 2 in Arabian racehorses in Egypt
Authors: Ahmed Basem Mohamed , Bayoumi Mahmoud Mohamed , Farrag Mohamed Ali , Elgamal Mahmoud Aly , Daly Janet Mary , Amer Haitham Mohamed
Published: November 2022

Background

Equine influenza is an important cause of respiratory disease in equids. The causative virus; EIV, is highly variable and can evolve by accumulation of mutations, particularly in the haemagglutinin (HA) gene. Currently, H3N8 is the sole subtype circulating worldwide with Florida clade 1 (FC1) is most prevalent in the Americas and FC2 in Asia and Europe. In Egypt, EIV was detected in two occasions: subtype H7N7 in 1989 and subtype H3N8 (FC1) in 2008. No data is available on the circulation pattern of EIV during the last decade despite frequent observation of suspected cases.

Methods

Twenty-two nasal swabs were collected from vaccinated and non-vaccinated horses showing respiratory signs suggestive of EIV infection in 2017–18. Three additional swabs were retrieved during a national race event in January 2018 from Arabian mares with high fever, gait stiffness and dry cough. Samples were screened by RT-qPCR and HA1 domain of the hemagglutinin gene was amplified and sequenced for sequence and phylogenetic analysis.

Results

RT-qPCR screening revealed that only the 3 samples from the race were positive with cycle thresholds ranging from 16 to 21 indicating high viral load. Isolation attempts in hen’s eggs were unsuccessful. Sequence analysis of the HA1 domain gene has revealed two identical nucleotide sequences, while the third contained 3 synonymous mutations. Phylogenetic analysis clustered study sequences with recent FC2 sequences from Europe. Amino acid alignments revealed 14 and 13 amino acid differences in the study sequences compared to A/equine/Egypt/6066NANRU-VSVRI/08 (H3N8) and A/equine/Kentucky/1997 (H3N8), respectively, available as EIV vaccines in Egypt. Nine amino acids were different from A/equine/Richmond/1/2007 (H3N8), the recommended FC2 vaccine strain by the world organization of animal health expert surveillance panel (OIE-ESP), two of which were unique to the Egyptian sequences while the remaining 7 changes were shared with the FC2-144V subgroup detected in the United Kingdom from late 2015 to 2016.

Conclusions

The study represents the first reported detection of FC2-144V related EIV from Arabian mares in Egypt, and probably from the entire middle east region. The presented information about EIV epidemiology and spread may require reconsideration of the vaccine strains used in the national vaccination programs.
An mRNA-based rabies vaccine induces strong protective immune responses in mice and dogs
Authors: Li Jianglong , Liu Qi , Liu Jun , Wu Xiaohong , Lei Yixin , Li Shuang , Zhao Danhua , Li Zhi , Luo Liping , Peng Sophia , Ou Yingrao , Yang Hong , Jin Jing , Li Yuhua , Peng Yucai
Published: November 2022

Rabies is a lethal zoonotic disease that is mainly caused by the rabies virus (RABV). Although effective vaccines have long existed, current vaccines take both time and cost to produce. Messenger RNA (mRNA) technology is an emergent vaccine platform that supports rapid vaccine development on a large scale. Here, an optimized mRNA vaccine construct (LVRNA001) expressing rabies virus glycoprotein (RABV-G) was developed in vitro and then evaluated in vivo for its immunogenicity and protective capacity in mice and dogs. LVRNA001 induced neutralizing antibody production and a strong Th1 cellular immune response in mice. In both mice and dogs, LVRNA001 provided protection against challenge with 50-fold lethal dose 50 (LD50) of RABV. With regards to protective efficiency, an extended dosing interval (14 days) induced greater antibody production than 3- or 7-day intervals in mice. Finally, post-exposure immunization against RABV was performed to evaluate the survival rates of dogs receiving two 25 μg doses of LVRNA001 vs. five doses of inactivated vaccine over the course of three months. Survival rate in the LVRNA001 group was 100%, whereas survival rate in the inactivated vaccine control group was only 33.33%. In conclusion, these results demonstrated that LVRNA001 induced strong protective immune responses in mice and dogs, which provides a new and promising prophylactic strategy for rabies.
Towards reconciling population nutrition goals and investment policy in Thailand: understanding how investment policy actors defined, framed and prioritised nutrition
Authors: Phulkerd Sirinya , Schram Ashley , Collin Jeff , Thow Anne-Marie , Ngqangashe Yandisa , Schneider Carmen Huckel , Friel Sharon
Published: November 2022

Background

Government’s investment policy is an important driver of food system activities, which in turn influence consumers practices, dietary consumption patterns and nutrition-related health of populations. While governments globally have committed to developing coherent public policies to advance population nutrition, the objectives of investment policies are seen as being divorced from nutrition and health goals. This study aimed to examine investment policy in Thailand and explore how key actors variously define and frame their objectives in food investment policy, how nutrition issues are represented by the actors, and what discursive effects of the nutrition results were represented within the field of investment in Thailand.

Methods

This study conducted semi-structured interviews with 16 actors (from 23 recruited actors) from government, civil society, academia and industry. A coding framework was developed based on Bacchi’s analytical framework encapsulated in the question “What’s the problem represented to be?” which examines the problem and assumptions underlying a policy. Data coding was first undertaken by a lead researcher and then double-coded and cross-checked by research team. Disagreements were resolved with discussion until consensus was achieved. The interview data were analysed using thematic analysis.

Results

The principal “problem” represented in food investment policy in Thailand was the perceived irrelevance of nutrition to governmental commitments towards increasing productivity and economic growth. Technological innovation in food production and processing such as ultra-processed foods was perceived as a key driver of economic growth. The key assumption underlying this representation was the primacy of a “productivist” policy paradigm, via which the government focuses on industrially driven food and agriculture and expansion to increase productivity and economic growth. This entails that the nutrition needs of Thai people are silenced and remain unacknowledged in investment policy contexts, and also does not take cognisance of the term “nutrition” and its importance to economic growth.

Conclusion

The findings show that nutrition was not perceived as a political priority for the government and other investment actors. Promoting productivity and economic growth were clearly positioned as the primary purposes of investment within the dominant discourse. Nutrition regulation, particularly of UPF, may conflict with current investment policy directions which prioritise development of modern food production and processing. The study suggests that comprehensive policy communication about nutrition and food classification is needed.
MGIDI: a powerful tool to analyze plant multivariate data
Authors: Olivoto Tiago , Diel Maria I. , Schmidt Denise , Lúcio Alessandro D.
Published: November 2022

Background

Commonly, several traits are assessed in agronomic experiments to better understand the factors under study. However, it is also common to see that even when several traits are available, researchers opt to follow the easiest way by applying univariate analyses and post-hoc tests for mean comparison for each trait, which arouses the hypothesis that the benefits of a multi-trait framework analysis may have not been fully exploited in this area.

Results

In this paper, we extended the theoretical foundations of the multi-trait genotype-ideotype distance index (MGIDI) to analyze multivariate data either in simple experiments (e.g., one-way layout with few treatments and traits) or complex experiments (e.g., with a factorial treatment structure). We proposed an optional weighting process that makes the ranking of treatments that stands out in traits with higher weights more likely. Its application is illustrated using (1) simulated data and (2) real data from a strawberry experiment that aims to select better factor combinations (namely, cultivar, transplant origin, and substrate mixture) based on the desired performance of 22 phenological, productive, physiological, and qualitative traits. Our results show that most of the strawberry traits are influenced by the cultivar, transplant origin, cultivation substrates, as well as by the interaction between cultivar and transplant origin. The MGIDI ranked the Albion cultivar originated from Imported transplants and the Camarosa cultivar originated from National transplants as the better factor combinations. The substrates with burned rice husk as the main component (70%) showed satisfactory physical proprieties, providing higher water use efficiency. The strengths and weakness view provided by the MGIDI revealed that looking for an ideal treatment should direct the efforts on increasing fruit production of Albion transplants from Imported origin. On the other hand, this treatment has strengths related to productive precocity, total soluble solids, and flesh firmness.

Conclusions

Overall, this study opens the door to the use of MGIDI beyond the plant breeding context, providing a unique, practical, robust, and easy-to-handle multi-trait-based framework to analyze multivariate data. There is an exciting possibility for this to open up new avenues of research, mainly because using the MGIDI in future studies will dramatically reduce the number of tables/figures needed, serving as a powerful tool to guide researchers toward better treatment recommendations.
Functional brain imaging interventions for radiation therapy planning in patients with glioblastoma: a systematic review
Authors: Ryan John T , Nakayama Masao , Gleeson Ian , Mannion Liam , Geso Moshi , Kelly Jennifer , Ng Sweet Ping , Hardcastle Nicholas
Published: November 2022

Rationale

This systematic review aims to synthesise the outcomes of different strategies of incorporating functional biological markers in the radiation therapy plans of patients with glioblastoma to support clinicians and further research.

Methods

The systematic review protocol was registered on PROSPERO (CRD42021221021). A structured search for publications was performed following PRISMA guidelines. Quality assessment was performed using the Newcastle–Ottawa Scale. Study characteristics, intervention methodology and outcomes were extracted using Covidence. Data analysis focused on radiation therapy target volumes, toxicity, dose distributions, recurrence and survival mapped to functional image-guided radiotherapy interventions.

Results

There were 5733 citations screened, with 53 citations (n = 32 studies) meeting review criteria. Studies compared standard radiation therapy planning volumes with functional image-derived volumes (n = 20 studies), treated radiation therapy volumes with recurrences (n = 15 studies), the impact on current standard target delineations (n = 9 studies), treated functional volumes and survival (n = 8 studies), functionally guided dose escalation (n = 8 studies), radiomics (n = 4 studies) and optimal organ at risk sparing (n = 3 studies). The approaches to target outlining and dose escalation were heterogeneous. The analysis indicated an improvement in median overall survival of over two months compared with a historical control group. Simultaneous-integrated-boost dose escalation of 72–76 Gy in 30 fractions appeared to have an acceptable toxicity profile when delivered with inverse planning to a volume smaller than 100 cm$$^3$$3.

Conclusion

There was significant heterogeneity between the approaches taken by different study groups when implementing functional image-guided radiotherapy. It is recommended that functional imaging data be incorporated into the gross tumour volume with appropriate technology-specific margins used to create the clinical target volume when designing radiation therapy plans for patients with glioblastoma.
Revascularization character of autologous fascia lata graft following shoulder superior capsule reconstruction by enhanced magnetic resonance imaging
Authors: Liao Ya-tao , Li Huai-sheng , Li Yan , Tang Kang-lai , Li Jing , Zhou Bing-hua
Published: November 2022

Background

Fascia lata has been used for arthroscopic superior capsule reconstruction (ASCR) and verified to achieve a good clinical outcome. However, it is still not known about revascularization character of the fascia lata after ASCR. This study was performed to evaluate the revascularization of autologous fascia lata grafts after ASCR by enhanced magnetic resonance imaging (MRI).

Methods

A prospective study of 19 patients with irreparable rotator cuff tears underwent ASCR with autologous fascia lata grafts from September 2019 to April 2021. Radiography examinations and clinical evaluations were performed preoperatively and postoperatively at 6 weeks and 3, 6, and 12 months. The signal-to-noise quotient (SNQ) value and enhancement index (EI) of autologous fascia lata grafts in the great tubercle insertion (GTI), midpoint of the graft (MG), and glenoid insertion (GI) were compared for radiography examination. Clinical evaluation included the American Shoulder and Elbow Surgeons (ASES) score, University of California Los Angeles (UCLA) shoulder score, and Visual Analog Scale (VAS) score.

Results

The SNQ values in T1WI enhancement at GI and GTI were significantly higher than those at the plain MRI scan at all postoperative observation timepoints; however, the SNQ values in T1WI enhancement at MG did not show a significant difference until 3 months postoperation. EI values at GTI and GI were significantly higher than those at MG at 6 weeks and 3 months postoperation, while there was no significant difference in the EI value between GTI and GI. At 6 months postoperation, the EI value at GI was significantly higher than those at MG. At 12 months postoperation, the EI value at GI was significantly higher than those at MG and GTI; however, there was no significant difference between GTI and MG. The EI values at GTI and MG peaked at 3 months and 6 months postoperation, respectively, and then plateaued at 12 months postoperation. However, there was no significant difference in the EI value among the different postoperative timepoints at GI. The EI value did not correlate with the VAS and ASES, UCLA scores at any time point or any postoperative observation location.

Conclusion

Revascularization of the fascia lata was dependent on the location of the fascia lata and plateaus at 12 months postoperation. The EI value did not correlate with the VAS and ASES, UCLA scores during12 months postoperation.
Emergence of psychiatric adverse events during antipsychotic treatment in AP-naïve children and adolescents
Authors: Menard Marie-Line , Auby Philippe , Cruzel Coralie , Cohen David , Bonnot Olivier , Askenazy Florence , Thümmler Susanne ,   ETAPE Study Group, Michel Boublil , Agnès Castaings , Alexandre Catanese , Jean Chambry , Dorothée Charvet , Mona Cseterky , Arnaud Fernandez , Eric Fontas , Pierre Fourneret , Marianna Giannitelli , Ludovic Gicquel , Bernard Kabuth , Bernard Leroy , Fanny Maria , Pamela Moceri , Bertrand Olliac , Jean-Philippe Raynaud , Jean-François Roche , Thierry Rochet
Published: November 2022

Background

Over the last decades, antipsychotic prescriptions in children have increased worldwide. However, adverse events are frequently observed, with some such as psychiatric adverse events remaining poorly documented.

Method

The French ETAPE study is a 12-month naturalistic prospective multisite study that included 190 antipsychotic-naïve pediatric patients (mean age = 12 ± 3 years), treated by antipsychotic for psychotic or non-psychotic symptoms. From the ETAPE database, we performed additional analyses focusing on psychiatric adverse events.

Results

Children received mainly second-generation antipsychotic for conditions out of regulatory approval, with risperidone and aripiprazole being the most frequent (respectively 52.5% and 30.83%). Clinicians reported 2447 adverse events, mainly non-psychiatric (n = 2073, 84.72%), including neuromuscular, metabolic, gastroenterological, and (n = 374, 15.28%) psychiatric. 55.88% of psychiatric adverse events were attributable to antipsychotic by the clinician, compared to 89% of non-psychiatric adverse events (p < 0.001). 63.2% (n = 120) of the 190 children and adolescents presented at least one psychiatric adverse event. The most frequent were externalized behaviors such as aggressiveness or agitation (22.7%), mood changes (18.4%) and suicidal ideas or behaviors (11.8%). Half of psychiatric adverse events occurred during the first quarter, 49.46%, compared to 23.79% during the second, 15.77% during the third, and 10.96% during the fourth.

Conclusion

This additional analysis from the French ETAPE study emphasizes that psychiatric adverse events might be more frequent than expected in the pediatric population. Also, the potential risk of psychiatric adverse events should be part of the benefit-risk evaluation and sub-sequent follow-up.
GNRHR-related central hypogonadism with spontaneous recovery – case report
Authors: Šmigoc Schweiger Darja , Davidović Povše Maja , Trebušak Podkrajšek Katarina , Battelino Tadej , Avbelj Stefanija Magdalena
Published: November 2022

Background

Congenital hypogonadotropic hypogonadism (CHH) is a clinically and genetically heterogeneous disease characterized by absent or incomplete puberty and infertility. Clinical characteristics are secondary to insufficient gonadotropin secretion, caused by deficient gonadotropin-releasing hormone (GnRH) production, secretion, or action. Loss-of-function variants of the gonadotropin-releasing hormone receptor (GNRHR) are associated with CHH without anosmia. CHH was previously considered a permanent condition, but in the past two decades, cases of spontaneous recovery of CHH have been reported. The reversal of hypogonadism in CHH is currently unpredictable, and can happen unnoticed.

Case presentation

The male proband was diagnosed with CHH due to compound heterozygosity for two previously reported pathogenic missense variants in the GNRHR gene, NM_000406.2:c.416G > A (NP_000397.1:p.Arg139His) and c.785G > A (p.Arg262Gln) at 16 years of age. In addition to arrested partial puberty, he had a low testosterone level, gonadotropins in the range of early puberty, and a normal inhibin B level. A therapy with increasing doses of intramuscular testosterone undecanoate was received for 2.5 years, while there was no change in testicular volume. At the age of 19 years, testosterone supplementation was interrupted. During the next two years, he had spontaneous pubertal development to achieve a testicular volume of 20 mL, with normal adult levels of gonadotropins and testosterone.

Conclusions

Genetic diagnostics can help discriminate congenital hypogonadotropic hypogonadism, deserving therapeutic intervention, from the self-limited constitutional delay of growth and puberty (CDGP). Patients with GNRHR associated hypogonadism can experience spontaneous recovery of the hypothalamic-pituitary–gonadal axis. Spontaneous testis enlargement in patients with central hypogonadism not taking gonadotropins or pulsatile GnRH therapy can indicate recovery of hypogonadism.
Host age structure reshapes parasite symbiosis: collaboration begets pathogens, competition begets virulent mutualists
Authors: Portner Carsten O. S. , Rong Edward G. , Ramirez Jared A. , Wolf Yuri I. , Bosse Angelique P. , Koonin Eugene V. , Rochman Nash D.
Published: November 2022

Background

Symbiotic relationships are ubiquitous in the biosphere. Inter-species symbiosis is impacted by intra-specific distinctions, in particular, those defined by the age structure of a population. Older individuals compete with younger individuals for resources despite being less likely to reproduce, diminishing the fitness of the population. Conversely, however, older individuals can support the reproduction of younger individuals, increasing the population fitness. Parasitic relationships are commonly age structured, typically, more adversely affecting older hosts.

Results

We employ mathematical modeling to explore the differential effects of collaborative or competitive host age structures on host-parasite relationships. A classical epidemiological compartment model is constructed with three disease states: susceptible, infected, and recovered. Each of these three states is partitioned into two compartments representing young, potentially reproductive, and old, post-reproductive, hosts, yielding 6 compartments in total. In order to describe competition and collaboration between old and young compartments, we model the reproductive success to depend on the fraction of young individuals in the population. Collaborative populations with relatively greater numbers of post-reproductive hosts enjoy greater reproductive success whereas in purely competitive populations, increasing the post-reproductive subpopulation reduces reproductive success.

Conclusions

We demonstrate that, in collaborative host populations, pathogens strictly impacting older, post-reproductive individuals can reduce population fitness even more than pathogens that directly impact younger, potentially reproductive individuals. In purely competitive populations, the reverse is observed, and we demonstrate that endemic, virulent pathogens can oxymoronically form a mutualistic relationship with the host, increasing the fitness of the host population. Applications to endangered species conservation and invasive species containment are discussed.
Lanthanum-based metal organic framework (La-MOF) use of 3,4-dihydroxycinnamic acid as drug delivery system linkers in human breast cancer therapy
Authors: Safinejad Moosareza , Rigi Amir , Zeraati Malihe , Heidary Zohreh , Jahani Shohreh , Chauhan Narendra Pal Singh , Sargazi Ghasem
Published: November 2022

Metal organic frameworks (MOFs) have received a lot of attention in the research community due to their unique physical properties, which make them ideal materials for targeted drug delivery systems. In this paper, we describe the synthesis of a non-toxic La-based MOF with 3,4-dihydroxycinnamic acid (3,4-DHCA) as a linker. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), nitrogen adsorption–desorption measurements, and X-ray powder diffraction (XRD) have all been used to characterize it thoroughly. The La-based MOF showed good biocompatibility with the human breast cancer cell line MDA-MB-468. The ability of 3,4-DHCA to treat MDA-MB-468 cells was confirmed by 40.35% cell viability with La-based MOF. Based on the findings, La-based MOF can be recommended as a promising candidate for anticancer delivery.
Design, synthesis and evaluation of novel 1,2,4-triazole derivatives as promising anticancer agents
Authors: Emami Leila , Sadeghian Sara , Mojaddami Ayyub , khabnadideh Soghra , Sakhteman Amirhossein , Sadeghpour Hossein , Faghih Zeinab , Fereidoonnezhad Masood , Rezaei Zahra
Published: November 2022

Herein, we reported the synthesis of nineteen novel 1,2,4-triazole derivatives including 1,3-diphenyl-2-(1H-1,2,4-triazol-1-yl) propan-1-ones (7a-e), 1-(1,3-diphenylpropan-2-yl)-1H-1,2,4-triazole (8a-c) and 1,4-diphenyl-2-(1H-1,2,4-triazol-1-yl) butane-1,4-diones (10a-k). The structures of these derivatives were confirmed by spectroscopic techniques like IR, 1H-NMR, Mass spectroscopy and Elemental analysis. The cytotoxic activities of the synthesized compounds were evaluated against three human cancer cell lines including MCF-7, Hela and A549 using MTT assay. Compounds 7d, 7e, 10a and 10d showed a promising cytotoxic activity lower than 12 μM against Hela cell line. The safety of these compounds was also, evaluated on MRC-5 as a normal cell line and relieved that most of the synthesized compounds have proper selectivity against normal and cytotoxic cancerous cell lines. Finally, molecular docking studies were also, done to understand the mechanism and binding modes of these derivatives in the binding pocket of aromatase enzyme as a possible target.
Synthesis, characterization, and cytotoxicity of doxorubicin-loaded polycaprolactone nanocapsules as controlled anti-hepatocellular carcinoma drug release system
Authors: Fahmi Abdelgawad , Abdur-Rahman Mariam , Mahareek Omnia , shemis Mohamed A.
Published: November 2022

Background

Free doxorubicin (Dox) is used as a chemotherapeutic agent against hepatocellular carcinoma (HCC), but it results in cardiotoxicty as a major side effect. Hence, a controlled Dox drug delivery system is extremely demanded.

Methods

Dox was loaded into the non-toxic biodegradable polycaprolactone (PCL) nanocapsules using the double emulsion method. Characterization of Dox-PCL nanocapsules was done using transmission electron microscopy and dynamic light scattering. Encapsulation efficiency and drug loading capacity were quantified using UV–visible spectrophotometry. Drug release was investigated in vitro at both normal (7.4) and cancer (4.8) pHs. Cytotoxicity of Dox-PCL nanocapsules against free Dox was evaluated using the MTT test on normal (Vero) and hepatic cancer (HepG2) cell lines.

Results

Spherical nanocapsules (212 ± 2 nm) were succeffully prepared with a zeta potential of (-22.3 ± 2 mv) and a polydisperse index of (0.019 ± 0.01) with a narrow size distribution pattern. The encapsulation efficiency was (73.15 ± 4%) with a drug loading capacity of (16.88 ± 2%). Importantlly, Dox-release from nanocapsules was faster at cancer pH (98%) than at physiological pH (26%). Moreover, although Dox-PCL nanocapsules were less toxic on the normal cell line (GI 50 = 17.99 ± 8.62 µg/ml) than free Dox (GI 50 = 16.53 ± 1.06 µg/ml), the encapsulated Dox showed higher toxic effect on cancer HepG2 cells compared to that caused by the free drug (GI 50 = 2.46 ± 0.49 and 4.22 ± 0.04 µg/ml, respectively).

Conclusion

The constructed Dox-PCL nanocapsules constitute a potentially controlled anti-HCC therapy with minimal systemic exposure.

Graphical Abstract
Gold nanoparticles loaded chitosan encapsulate 6-mercaptopurine as a novel nanocomposite for chemo-photothermal therapy on breast cancer
Authors: Faid Amna H. , Shouman Samia A. , Badr Yehia A. , Sharaky Marwa , Mostafa Elham M. , Sliem Mahmoud A.
Published: November 2022

Background

As a promising strategy to overcome the therapeutic disadvantages of 6-mercaptopurine (6MP), we proposed the encapsulation of 6MP in chitosan nanoparticles (CNPs) to form the 6MP-CNPs complexes. The encapsulation was followed by the loading of complexes on gold nanoparticles (AuNPs) to generate a novel 6MP-CNPs-AuNPs nanocomposite to facilitate the chemo-photothermal therapeutic effect.

Methods

CNPs were produced based on the ionic gelation method of tripolyphosphate (TPP). Moreover, 6MP-CNPs composite were prepared by the modified ionic gelation method and then loaded on AuNPs which were synthesized according to the standard wet chemical method using trisodium citrate as a reducing and capping agent. The synthesized nanocomposites were characterized by UV–VIS spectroscopy, dynamic light scattering, Fourier transform infrared spectroscopy, and transmission electron microscopy. The potential cytotoxicity of the prepared nanocomposites on MCF7 cell line was carried out using Sulphorhodamine-B (SRB) assay.

Results

Optimization of CNPs, 6MP-CNPs, and 6MP-CNPs-AuNPs revealed 130 ± 10, 200 ± 20, and 25 ± 5 nm particle size diameters with narrow size distributions and exhibited high stability with zeta potential 36.9 ± 4.11, 37, and 44.4 mV, respectively. The encapsulation efficiency of 6MP was found to be 57%. The cytotoxicity of 6MP-CNPs and 6MP-CNPs-AuNPs on breast cell line MCF7 was significantly increased and reached IC50 of 9.3 and 8.7 µM, respectively. The co-therapeutic effect of the nanocomposites resulted in an improvement of the therapeutic efficacy compared to the individual effect of chemo- and photothermal therapy. Irradiation of 6MP-CNPs and 6MP-CNPs-AuNPs with a diode laser (DPSS laser, 532 nm) was found to have more inhibition on cell viability with a decrease in IC50 to 5 and 4.4 µM, respectively.

Conclusion

The Chemo-Photothermal co-therapy treatment with novel prepared nanocomposite exhibits maximum therapeutic efficacy and limits the dosage-related side effects of 6MP.

Graphical Abstract
Arabinan saccharification by biogas reactor metagenome-derived arabinosyl hydrolases
Authors: Liu Yajing , Angelov Angel , Feiler Werner , Baudrexl Melanie , Zverlov Vladimir , Liebl Wolfgang , Vanderhaeghen Sonja
Published: November 2022

Background

Plant cell walls represent the most plentiful renewable organic resource on earth, but due to their heterogeneity, complex structure and partial recalcitrance, their use as biotechnological feedstock is still limited.

Results

In order to identify efficient enzymes for polysaccharide breakdown, we have carried out functional screening of metagenomic fosmid libraries from biogas fermenter microbial communities grown on sugar beet pulp, an arabinan-rich agricultural residue, or other sources containing microbes that efficiently depolymerize polysaccharides, using CPH (chromogenic polysaccharide hydrogel) or ICB (insoluble chromogenic biomass) labeled polysaccharide substrates. Seventy-one depolymerase-encoding genes were identified from 55 active fosmid clones by using Illumina and Sanger sequencing and dbCAN CAZyme (carbohydrate-active enzyme) annotation. An around 56 kb assembled DNA fragment putatively originating fromXylanivirga thermophilastrain or a close relative was analyzed in detail. It contained 48 ORFs (open reading frames), of which 31 were assigned to sugar metabolism. Interestingly, a large number of genes for enzymes putatively involved in degradation and utilization of arabinose-containing carbohydrates were found. Seven putative arabinosyl hydrolases from this DNA fragment belonging to glycoside hydrolase (GH) families GH51 and GH43 were biochemically characterized, revealing two with endo-arabinanase activity and four with exo-α-l-arabinofuranosidase activity but with complementary cleavage properties. These enzymes were found to act synergistically and can completely hydrolyze SBA (sugar beet arabinan) and DA (debranched arabinan).

Conclusions

We screened 32,776 fosmid clones from several metagenomic libraries with chromogenic lignocellulosic substrates for functional enzymes to advance the understanding about the saccharification of recalcitrant lignocellulose. Seven putativeX. thermophilaarabinosyl hydrolases were characterized for pectic substrate degradation.The arabinosyl hydrolases displayed maximum activity and significant long-term stability around 50 °C. The enzyme cocktails composed in this study fully degraded the arabinan substrates and thus could serve for arabinose production in food and biofuel industries.
Promising therapeutic aspects in human genetic imprinting disorders
Authors: Chao Yunqi , Qin Yifang , Zou Xinyi , Wang Xiangzhi , Hu Chenxi , Xia Fangling , Zou Chaochun
Published: November 2022

Genomic imprinting is an epigenetic phenomenon of monoallelic gene expression pattern depending on parental origin. In humans, congenital imprinting disruptions resulting from genetic or epigenetic mechanisms can cause a group of diseases known as genetic imprinting disorders (IDs). Genetic IDs involve several distinct syndromes sharing homologies in terms of genetic etiologies and phenotypic features. However, the molecular pathogenesis of genetic IDs is complex and remains largely uncharacterized, resulting in a lack of effective therapeutic approaches for patients. In this review, we begin with an overview of the genomic and epigenomic molecular basis of human genetic IDs. Notably, we address ethical aspects as a priority of employing emerging techniques for therapeutic applications in human IDs. With a particular focus, we delineate the current field of emerging therapeutics for genetic IDs. We briefly summarize novel symptomatic drugs and highlight the key milestones of new techniques and therapeutic programs as they stand today which can offer highly promising disease-modifying interventions for genetic IDs accompanied by various challenges.
Repression of the PRELP gene is relieved by histone deacetylase inhibitors through acetylation of histone H2B lysine 5 in bladder cancer
Authors: Shozu Kanto , Kaneko Syuzo , Shinkai Norio , Dozen Ai , Kosuge Hirofumi , Nakakido Makoto , Machino Hidenori , Takasawa Ken , Asada Ken , Komatsu Masaaki , Tsumoto Kouhei , Ohnuma Shin-Ichi , Hamamoto Ryuji
Published: November 2022

Background

Proline/arginine-rich end leucine-rich repeat protein (PRELP) is a member of the small leucine-rich proteoglycan family of extracellular matrix proteins, which is markedly suppressed in the majority of early-stage epithelial cancers and plays a role in regulating the epithelial–mesenchymal transition by altering cell–cell adhesion. Although PRELP is an important factor in the development and progression of bladder cancer, the mechanism of PRELP gene repression remains unclear.

Results

Here, we show that repression of PRELP mRNA expression in bladder cancer cells is alleviated by HDAC inhibitors (HDACi) through histone acetylation. Using ChIP-qPCR analysis, we found that acetylation of lysine residue 5 of histone H2B in the PRELP gene promoter region is a marker for the de-repression of PRELP expression.

Conclusions

These results suggest a mechanism through which HDACi may partially regulate the function of PRELP to suppress the development and progression of bladder cancer. Some HDACi are already in clinical use, and the findings of this study provide a mechanistic basis for further investigation of HDACi-based therapeutic strategies.
Budget impact analysis of the use of Souvenaid in patients with prodromal Alzheimer’s Disease in Spain
Authors: Mar Javier , Ibarrondo Oliver , Larrañaga Igor , Mar-Barrutia Lorea , Soto-Gordoa Myriam
Published: November 2022

Introduction

The effectiveness, safety, and cost-effectiveness of the use of Souvenaid for Alzheimer’s disease (AD) have been previously evidenced. To complete the economic analysis, there is a need to assess whether society can afford it. The objective of this study was to carry out a budget impact analysis of the use of Souvenaid in Spain under the conditions of the LipiDidiet clinical trial from a societal perspective.

Methods

We built a population model that took into account all the cohorts of individuals with AD, their individual progression, and the potential impact of Souvenaid treatment on their trajectories. Patient progression data were obtained from mixed models. The target population was estimated based on the population forecast for 2020–2035 and the incidence of dementia. Individual progression to dementia measured by the Clinical Dementia Rating-Sum of Boxes was reproduced using mixed models. Besides the costs of treatment and diagnosis, direct costs of medical and non-medical care and indirect costs were included.

Results

The epidemiological indicators and the distribution of life expectancy by stages validated the model. From the third year (2022), the differences in the cost of dementia offset the incremental cost of diagnosis and treatment. The costs of dependency reached €500 million/year while those of the intervention were limited to €40 million.

Conclusions

Souvenaid, with modest effectiveness in delaying dementia associated with AD, achieved a positive economic balance between costs and savings. Its use in the treatment of prodromal AD would imply an initial cost that would be ongoing, but this would be offset by savings in the care system for dependency associated with dementia from the third year. These results were based on adopting a societal perspective taking into account the effect of treatment on the use of health, social, and family resources.
Non-suicidal self-injury and its relation to suicide through acquired capability: investigating this causal mechanism in a mainly late-diagnosed autistic sample
Authors: Moseley Rachel L. , Gregory Nicola J. , Smith Paula , Allison Carrie , Cassidy Sarah , Baron-Cohen Simon
Published: November 2022

Background

Non-suicidal self-injury (NSSI) has been linked with a higher risk of suicide attempts in autistic and non-autistic people. In the general population, NSSI may confer acquired capability for suicide by eroding one’s fear and avoidance of pain and death. The present study aimed to explore acquired capability as the mediator of increased suicide risk conferred by NSSI in autistic and non-autistic adults.

Methods

Autistic and non-autistic adults (n = 314,n = 312) completed an online survey exploring lifetime suicide attempts, experience with NSSI, and acquired capability for suicide. We explored relationships between lifetime incidence of NSSI and lifetime suicide attempts via three facets of acquired capability (pain tolerance, reduced fear of death, and mental rehearsal of suicide). In self-harming participants (224 autistic and 156 non-autistic), we explored whether particular types and features of NSSI might be especially associated with capability and through that with suicide: namely engagement in scratching, cutting, and self-hitting, and engaging in more numerous forms of NSSI.

Results

While a higher frequency of NSSI was associated with all three facets of acquired capability, only reduced fear of death and mental rehearsal of suicide mediated an indirect relationship with lifetime suicide attempts. NSSI also directly predicted more numerous suicide attempts. Autistic people tended towards reduced fear of death and mental rehearsal regardless of NSSI status. Among self-harming autistic and non-autistic participants, cutting and an increased number of NSSI behaviours were associated with lifetime suicide attempts directly and indirectly via acquired capability. In both groups, self-hitting was associated with lifetime suicide attempts only via acquired capability.

Limitations

Our cross-sectional methodology negates inferences of directionality. While we controlled for age, our samples were poorly matched, with the autistic group two times older on average. The autistic sample, predominantly late-diagnosed, female and highly qualified, were unrepresentative of the whole autistic community.

Conclusions

Our data suggest that acquired capability, as measured herein, is an incomplete explanation for the association between NSSI and suicide risk. A broader construct with stable and transient facets may offer greater explanatory power, but it is probable that other variables explain or provide additional means through which this association arises.
Maternal vitamin D during pregnancy and offspring autism and autism-associated traits: a prospective cohort study
Authors: Madley-Dowd Paul , Dardani Christina , Wootton Robyn E. , Dack Kyle , Palmer Tom , Thurston Rupert , Havdahl Alexandra , Golding Jean , Lawlor Deborah , Rai Dheeraj
Published: November 2022

Background

There has been a growing interest in the association between maternal levels of vitamin D during pregnancy and offspring autism. However, whether any associations reflect causal effects is still inconclusive.

Methods

We used data from a UK-based pregnancy cohort study (Avon Longitudinal Study of Parents and Children) comprising 7689 births between 1991 and 1992 with maternal blood vitamin D levels recorded during pregnancy and at least one recorded outcome measure, including autism diagnosis and autism-associated traits. The association between each outcome with seasonal and gestational age-adjusted maternal serum 25-hydroxyvitamin D during pregnancy was estimated using confounder-adjusted regression models. Multiple imputation was used to account for missing data, and restricted cubic splines were used to investigate nonlinear associations. Mendelian randomization was used to strengthen causal inference.

Results

No strong evidence of an association between maternal serum 25-hydroxyvitamin D during pregnancy and any offspring autism-associated outcome was found using multivariable regression analysis (autism diagnosis: adjusted OR = 0.98, 95% CI = 0.90–1.06), including with multiple imputation (autism diagnosis: adjusted OR = 0.99, 95% CI = 0.93–1.06), and no evidence of a causal effect was suggested by Mendelian randomization (autism diagnosis: causal OR = 1.08, 95% CI = 0.46–2.55). Some evidence of increased odds of autism-associated traits at lower levels of maternal serum 25-hydroxyvitamin D was found using spline analysis.

Limitations

Our study was potentially limited by low power, particularly for diagnosed autism cases as an outcome. The cohort may not have captured the extreme lows of the distribution of serum 25-hydroxyvitamin D, and our analyses may have been biased by residual confounding and missing data.

Conclusions

The present study found no strong evidence of a causal link between maternal vitamin D levels in pregnancy and offspring diagnosis or traits of autism.
The use of artificial intelligence and machine learning monitoring to safely administer a fluid-restrictive goal-directed treatment protocol to minimize the risk of transfusion during major spine surgery of a Jehovah’s Witness: a case report
Authors: Denn Sara , Schneck Emmanuel , Jablawi Fidaa , Bender Michael , Schmidt Götz , Habicher Marit , Uhl Eberhard , Sander Michael
Published: November 2022

Background

The Hypotension Prediction Index (HPI) displays an innovative monitoring tool which predicts intraoperative hypotension before its onset.

Case presentation

We report the case of an 84-year-old Caucasian woman undergoing major spinal surgery with no possibility for the transfer of blood products given her status as a Jehovah’s Witness. The hemodynamic treatment algorithm we employed was based on HPI and resulted in a high degree of hemodynamic stability during the surgical procedure. Further, the patient was not at risk for either hypo- or hypervolemia, conditions which might have caused dilution anemia. By using HPI as a tool for patient blood management, it was possible to reduce the incidence of intraoperative hypotension to a minimum.

Conclusions

In sum, this HPI-based treatment algorithm represents a useful application for the treatment of complex anesthesia and perioperative patient blood management. It is a simple but powerful extension of standard monitoring for the prevention of intraoperative hypotension.
Combination of indirect revascularization and endothelial progenitor cell transplantation improved cerebral perfusion and ameliorated tauopathy in a rat model of bilateral ICA ligation
Authors: Wang Kuo-Chuan , Yang Ling-Yu , Lee Jing-Er , Wu Vicent , Chen Te-Fu , Hsieh Sung-Tsang , Kuo Meng-Fai
Published: November 2022

Objective

Endothelial progenitor cells (EPCs) contribute to the recovery of neurological function after ischemic stroke. Indirect revascularization has exhibited promising effects in the treatment of cerebral ischemia related to moyamoya disease and intracranial atherosclerotic disease. The role of EPCs in augmenting the revascularization effect is not clear. In this study, we investigated the therapeutic effects of indirect revascularization combined with EPC transplantation in rats with chronic cerebral ischemia.

Methods

Chronic cerebral ischemia was induced by bilateral internal carotid artery ligation (BICAL) in rats, and indirect revascularization by encephalo-myo-synangiosis (EMS) was performed 1 week later. During the EMS procedure, intramuscular injection of EPCs and the addition of stromal cell-derived factor 1 (SDF-1), and AMD3100, an SDF-1 inhibitor, were undertaken, respectively, to investigate their effects on indirect revascularization. Two weeks later, the cortical microcirculation, neuronal damage, and functional outcome were evaluated according to the microvasculature density and partial pressure of brain tissue oxygen (PbtO2), regional blood flow, expression of phosphorylated Tau (pTau), TUNEL staining and the rotarod performance test, respectively.

Results

The cortical microcirculation, according to PbtO2and regional blood flow, was impaired 3 weeks after BICAL. These impairments were improved by the EMS procedure. The regional blood flow was further increased by the addition of SDF-1 and decreased by the addition of AMD3100. Intramuscular injection of EPCs further increased the regional blood flow as compared with the EMS group. The rotarod test results showed that the functional outcome was best in the EMS combined with EPC injection group. Western blot analysis showed that the EMS combined with EPC treatment group had significantly decreased expressions of phosphorylated Tau and phosphorylated glycogen synthase kinase 3 beta (Y216 of GSK-3β). pTau and TUNEL-positive cells were markedly increased at 3 weeks after BICAL induction. Furthermore, the groups treated with EMS combined with SDF-1 or EPCs exhibited marked decreases in the pTau expression and TUNEL-positive cells, whereas AMD3100 treatment increased TUNEL-positive cells.

Conclusion

The results of this study suggested that indirect revascularization ameliorated the cerebral ischemic changes. EPCs played a key role in augmenting the effect of indirect revascularization in the treatment of chronic cerebral ischemia.
Human umbilical cord mesenchymal stromal cell-derived exosomes protect against MCD-induced NASH in a mouse model
Authors: Shi Ying , Yang Xiaoguang , Wang Shuyue , Wu Yulun , Zheng Lihua , Tang Yufang , Gao Yanhang , Niu Junqi
Published: November 2022

Background and aims

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are increasingly being studied in clinical trials of end-stage liver disease because of their good tissue repair and anti-inflammatory effects. hUC-MSC exosomes are vesicles with spherical structures secreted by cells that produce them. The diameter of exosomes is much smaller than that of hUC-MSCs, suggesting that exosomes might be a novel and safer therapeutic product of mesenchymal stem cells. As exosomes have been suggested to have biochemical functions similar to those of hUC-MSCs, this study investigated the efficiency of hUC-MSC-derived exosomes in protecting against nonalcoholic steatohepatitis using an MCD-induced mouse model.

Methods

Human umbilical cord mesenchymal stem cell-derived exosomes were extracted and purified. The effect of these exosomes on disease progression in an MCD-induced nonalcoholic steatohepatitis mouse model was investigated.

Results

The results showed that UC-MSC exosomes intravenously transplanted into mice with MCD-induced NASH improved MCD-induced body weight loss and liver damage in a mouse model. Additionally, the inflammatory cytokines in liver tissue were reduced, which may be caused by exosome-induced macrophage anti-inflammatory phenotypes both in vitro and in vivo. In addition, UC-MSC exosomes reversed PPARα level in ox-LDL-treated hepatocytes in vitro and in NASH mouse liver, which had been downregulated.

Conclusions

UC-MSC exosomes alleviate MCD-induced NASH in mice by regulating the anti-inflammatory phenotype of macrophages and by reversing PPARα protein expression in liver cells, which holds great potential in NASH therapy.