bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased abundance of bacteria of the family Muribaculaceae achieved by fecal microbiome transplantation correlates with the inhibition of kidney calcium oxalate stone deposition in experimental rats
Authors: Wang Yan , Sun JinBo , Xie Sen , Zhou Yu , Wang Tao , Liu ZhenYu , Li ChaoSheng , Gao Lei , Pan TieJun
Published: May 2023

Background

The incidence of nephrolithiasis is increasing rapidly worldwide. Calcium oxalate is the most common constituent, contributing to approximately 80% of all kidney stones. The gut microbiome, through its oxalate-degrading ability, may play a role in decreasing morbidity due to urinary calculus. Fecal microbiome transplantation (FMT) has been reported to be effective in restoring the gastrointestinal microbial community in different conditions. The transplantation of whole communities that have oxalate-degrading function may be a more effective strategy than the transplantation of isolated strains.

Methods

FMT was carried out in male guinea pigs and male Sprague–Dawley laboratory rats (SDRs). Fresh feces were collected from guinea pigs housed in metabolic cages. SDRs were divided into four groups: two groups received standard rat chow (SC) (groups SC and SC + FMT), and two groups were fed a 5% potassium oxalate diet (OD) (groups OD + phosphate-buffered saline (PBS) and OD + FMT). On day 14, groups OD + PBS, OD + FMT, and SC + FMT received either PBS or guinea pig feces by esophageal gavage. The composition of the microbiota of guinea pigs and SDRs was analyzed using a 16S rRNA gene sequencing approach. Biochemical analysis of urine samples from SDRs revealed the presence of calcium oxalate (CaOx) crystals, which were presumed to originate from kidney stones. Renal function was examined using real-time PCR analysis and immunohistochemical staining for renin, angiotensin-converting enzyme, and osteopontin (OPN) expression.

Results

FMT resulted in a gut microbiota that was a mixture of guinea pig and SDR bacteria. A microbial network involving Muribaculaceae, Lactobacillus, and Bifidobacterium was activated by FMT in group OD + FMT. As a result, urinary oxalate, calcium, uric acid, creatinine and urea in urine samples were reduced significantly. Similarly, significant reduction of uric acid and blood urea nitrogen to creatinine ratio in serum samples was observed (p < 0.05). Microscopic observations revealed a high CaOx crystal score (4+) in the kidneys of rats in group OD + PBS, whereas a lower score (2+) was observed in the rats in group OD + FMT. Up-regulation of OPN and down-regulation of renin were also associated with FMT.

Conclusion

A microbial network involving Muribaculaceae and other oxalate-degrading bacteria achieved by FMT was capable of reducing urinary oxalate excretion and CaOx crystal deposition in the kidney through increasing intestinal oxalate degradation. FMT may exert a renoprotective function in oxalate-related kidney stones.
Computer-assisted drug repurposing for thymidylate kinase drug target in monkeypox virus
Authors: Ajmal Amar , Mahmood Arif , Hayat Chandni , Hakami Mohammed Ageeli , Alotaibi Bader S. , Umair Muhammad , Abdalla Ashraf N. , Li Ping , He Pei , Wadood Abdul , Hu Junjian
Published: May 2023

Introduction

Monkeypox is a zoonotic disease caused by brick-shaped enveloped monkeypox (Mpox) virus that belongs to the family of ancient viruses known as Poxviridae. Subsequently, the viruses have been reported in various countries. The virus is transmitted by respiratory droplets, skin lesions, and infected body fluids. The infected patients experience fluid-filled blisters, maculopapular rash, myalgia, and fever. Due to the lack of effective drugs or vaccines, there is a need to identify the most potent and effective drugs to reduce the spread of monkeypox. The current study aimed to use computational methods to quickly identify potentially effective drugs against the Mpox virus.

Methods

In our study, the Mpox protein thymidylate kinase (A48R) was targeted because it is a unique drug target. We screened a library of 9000 FDA-approved compounds of the DrugBank database by using various in silico approaches, such as molecular docking and molecular dynamic (MD) simulation.

Results

Based on docking score and interaction analysis, compounds DB12380, DB13276, DB13276, DB11740, DB14675, DB11978, DB08526, DB06573, DB15796, DB08223, DB11736, DB16250, and DB16335 were predicted as the most potent. To examine the dynamic behavior and stability of the docked complexes, three compounds—DB16335, DB15796, and DB16250 —along with the Apo state were simulated for 300ns. The results revealed that compound DB16335 revealed the best docking score (-9.57 kcal/mol) against the Mpox protein thymidylate kinase.

Discussion

Additionally, during the 300 ns MD simulation period, thymidylate kinase DB16335 showed great stability. Further, in vitro and in vivo study is recommended for the final predicted compounds.
Successful translocation of Newell’s Shearwaters and Hawaiian Petrels to create a new, predator free breeding colony
Authors: Young Lindsay C. , Kohley Charles Robert , VanderWerf Eric A. , Fowlke Leilani , Casillas Daniela , Dalton Megan , Knight Marilou , Pesque Adrien , Dittmar Erika M. , Raine Andre F. , Vynne Megan
Published: May 2023

Newell’s Shearwater (Puffinus auricularis newelli; NESH) and Hawaiian Petrel (Pterodroma sandwichensis; HAPE) are listed under the U.S. Endangered Species Act and have declined by 94% and 78%, respectively, since 1993 due to habitat degradation, predation by introduced predators, collisions with powerlines and light attraction. Given the challenges in protecting nesting birds in their rugged montane habitats, it has long been desirable to create populations of both species in more accessible locations that offer a higher level of protection. We translocated 110 HAPE and 86 NESH chicks over a six-year period from 2015-2020 to a 2.5-ha predator-free enclosure on Kaua`i, Hawai`i. In addition to invasive plant removal and native plant out-planting, we installed 76 artificial burrows to provide nesting sites. Chicks were tube fed 1-20% of their body weight daily in the form of a slurry comprised of squid, fish, salmon oil, and Pedialyte. All NESH and 96% (N=106) of HAPE survived to fledging. Eight HAPE, including three breeding pairs, and one NESH have returned as adults to the translocation site and HAPE have bred at the site, resulting in the first predator-free breeding colony of this species.
The relationship between endogenous oxytocin and vasopressin levels and the Prader-Willi syndrome behaviour phenotype
Authors: Rice Lauren J. , Agu Josephine , Carter C. Sue , Harris James C. , Nazarloo Hans P. , Naanai Habiba , Einfeld Stewart L.
Published: May 2023

Background

Oxytocin and vasopressin systems are altered in Prader Willi syndrome (PWS). However, investigations into endogenous oxytocin and vasopressin levels as well as clinical trials evaluating the effect of exogenous oxytocin on PWS symptoms have had mixed results. It is also unknown whether endogenous oxytocin and vasopressin levels are associated with certain PWS behaviours.

Method

We compared plasma oxytocin and vasopressin and saliva oxytocin levels in 30 adolescents and adults with PWS to 30 typically developing age-matched controls. We also compared neuropeptide levels between gender and genetic subtypes within the PWS cohort and examined the relationship between neuropeptide levels and PWS behaviours.

Results

While we did not measure a group difference in plasma or saliva oxytocin levels, plasma vasopressin was significantly lower in individuals with PWS compared to controls. Within the PWS cohort, saliva oxytocin levels were higher in females compared to males and individuals with the mUPD compared to the deletion genetic subtype. We also found the neuropeptides correlated with different PWS behaviours for males and females and for genetic subtypes. For the deletion group, higher plasma and saliva oxytocin levels were related to fewer behaviour problems. For the mUPD group, higher plasma vasopressin levels were related to more behaviour problems.

Conclusion

These findings support existing evidence of a vasopressin system defect in PWS and for the first time identify potential differences in the oxytocin and vasopressin systems across PWS genetic subtypes.
Continuation of anti-PD-1 therapy plus physician-choice treatment beyond first progression is not associated with clinical benefit in patients with advanced non-small cell lung cancer
Authors: Wang Yixing , Fu Sha , Zhang Xuanye , Du Wei , Luo Linfeng , Jiang Yongluo , Zhou Yixin , Zhao Yuanyuan , Yang Yunpeng , Zhao Hongyun , Fang Wenfeng , Huang Yan , Zhang Li , Hong Shaodong
Published: May 2023

Objective

Few data are available on the optimal treatment options after disease progression from first-line treatment of immune checkpoint inhibitors (ICIs) plus chemotherapy. This study aimed to describe the safety and efficacy of continuing ICIs beyond first progress disease (PD) in non-small cell lung cancer (NSCLC).

Methods

Patients with NSCLC previously treated with first-line anti-PD-1 antibody plus platinum-doublet chemotherapy and hence had PD as per Response Evaluation Criteria in Solid Tumors v1.1 were enrolled. For the subsequent line, patients received physician’s choice (PsC) with or without an anti-PD-1 antibody. The primary outcome was progression-free survival after second-line treatment (PFS2). Secondary outcomes included overall survival (OS) from the initiation of first-line treatment, post-second-progression survival (P2PS), overall response rate (ORR), disease control rate (DCR), and safety during second-line treatment.

Results

Between July 2018 and January 2021, 59 patients were included. A total of 33 patients received a physician-decided second-line regimen plus ICIs (PsC plus ICIs group), and 26 patients did not continue ICIs (PsC group). There was no significant difference in PFS2 between the PsC plus ICIs group and the PsC group (median, 6.5 vs. 5.7 months, p = 0.46). median OS (28.8 vs. 29.2 months), P2PS (13.4 vs. 18.7 months), ORR (18.2% vs. 19.2%), and DCR (78.8% vs, 84.6%) were also similar between the two groups. No new safety signals were observed.

Conclusion

In this real-world setting, patients treated with continued ICIs beyond their first disease progression did not experience clinical benefit but without compromising safety.
Cuproptosis-related gene identification and immune infiltration analysis in systemic lupus erythematosus
Authors: Li Wuquan , Guan Xiaoran , Wang Yong , Lv Yan , Wu Yuyong , Yu Min , Sun Yeying
Published: May 2023

Background

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of tolerance to self-antigen, autoantibody production, and abnormal immune response. Cuproptosis is a recently reported cell death form correlated with the initiation and development of multiple diseases. This study intended to probe cuproptosis-related molecular clusters in SLE and constructed a predictive model.

Methods

We analyzed the expression profile and immune features of cuproptosis-related genes (CRGs) in SLE based on GSE61635 and GSE50772 datasets and identified core module genes associated with SLE occurrence using the weighted correlation network analysis (WGCNA). We selected the optimal machine-learning model by comparing the random forest (RF) model, support vector machine (SVM) model, generalized linear model (GLM), and the extreme gradient boosting (XGB) model. The predictive performance of the model was validated by nomogram, calibration curve, decision curve analysis (DCA), and external dataset GSE72326. Subsequently, a CeRNA network based on 5 core diagnostic markers was established. Drugs targeting core diagnostic markers were acquired using the CTD database, and Autodock vina software was employed to perform molecular docking.

Results

Blue module genes identified using WGCNA were highly related to SLE initiation. Among the four machine-learning models, the SVM model presented the best discriminative performance with relatively low residual and root-mean-square error (RMSE) and high area under the curve (AUC = 0.998). An SVM model was constructed based on 5 genes and performed favorably in the GSE72326 dataset for validation (AUC = 0.943). The nomogram, calibration curve, and DCA validated the predictive accuracy of the model for SLE as well. The CeRNA regulatory network includes 166 nodes (5 core diagnostic markers, 61 miRNAs, and 100 lncRNAs) and 175 lines. Drug detection showed that D00156 (Benzo (a) pyrene), D016604 (Aflatoxin B1), D014212 (Tretinoin), and D009532 (Nickel) could simultaneously act on the 5 core diagnostic markers.

Conclusion

We revealed the correlation between CRGs and immune cell infiltration in SLE patients. The SVM model using 5 genes was selected as the optimal machine learning model to accurately evaluate SLE patients. A CeRNA network based on 5 core diagnostic markers was constructed. Drugs targeting core diagnostic markers were retrieved with molecular docking performed.
Machine learning analysis of humoral and cellular responses to SARS-CoV-2 infection in young adults
Authors: Marcinkevics Ricards , Silva Pamuditha N. , Hankele Anna-Katharina , Dörnte Charlyn , Kadelka Sarah , Csik Katharina , Godbersen Svenja , Goga Algera , Hasenöhrl Lynn , Hirschi Pascale , Kabakci Hasan , LaPierre Mary P. , Mayrhofer Johanna , Title Alexandra C. , Shu Xuan , Baiioud Nouell , Bernal Sandra , Dassisti Laura , Saenz-de-Juano Mara D. , Schmidhauser Meret , Silvestrelli Giulia , Ulbrich Simon Z. , Ulbrich Thea J. , Wyss Tamara , Stekhoven Daniel J. , Al-Quaddoomi Faisal S. , Yu Shuqing , Binder Mascha , Schultheiβ Christoph , Zindel Claudia , Kolling Christoph , Goldhahn Jörg , Seighalani Bahram Kasmapour , Zjablovskaja Polina , Hardung Frank , Schuster Marc , Richter Anne , Huang Yi-Ju , Lauer Gereon , Baurmann Herrad , Low Jun Siong , Vaqueirinho Daniela , Jovic Sandra , Piccoli Luca , Ciesek Sandra , Vogt Julia E. , Sallusto Federica , Stoffel Markus , Ulbrich Susanne E.
Published: May 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces B and T cell responses, contributing to virus neutralization. In a cohort of 2,911 young adults, we identified 65 individuals who had an asymptomatic or mildly symptomatic SARS-CoV-2 infection and characterized their humoral and T cell responses to the Spike (S), Nucleocapsid (N) and Membrane (M) proteins. We found that previous infection induced CD4 T cells that vigorously responded to pools of peptides derived from the S and N proteins. By using statistical and machine learning models, we observed that the T cell response highly correlated with a compound titer of antibodies against the Receptor Binding Domain (RBD), S and N. However, while serum antibodies decayed over time, the cellular phenotype of these individuals remained stable over four months. Our computational analysis demonstrates that in young adults, asymptomatic and paucisymptomatic SARS-CoV-2 infections can induce robust and long-lasting CD4 T cell responses that exhibit slower decays than antibody titers. These observations imply that next-generation COVID-19 vaccines should be designed to induce stronger cellular responses to sustain the generation of potent neutralizing antibodies.
HLA allele and haplotype frequencies of registered stem cell donors in Chile
Authors: Solloch Ute V. , Giani Anette S. , Pattillo Garnham Maria Ignacia , Sauter Jürgen , Bernas Stefanie N. , Lange Vinzenz , Barriga Francisco , Fernández-Viña Marcelo A. , Schmidt Alexander H.
Published: May 2023

Patients in need of hematopoietic stem cell transplantation often rely on unrelated stem cell donors matched in certain human leukocyte antigen (HLA) genes. Donor search is complicated by the extensive allelic variability of the HLA system. Therefore, large registries of potential donors are maintained in many countries worldwide. Population-specific HLA characteristics determine the registry benefits for patients and also the need for further regional donor recruitment. In this work, we analyzed HLA allele and haplotype frequencies of donors of DKMS Chile, the first Chilean donor registry, with self-assessed “non-Indigenous” (n=92,788) and “Mapuche” (n=1,993) ancestry. We identified HLA alleles that were distinctly more abundant in the Chilean subpopulations than in worldwide reference populations, four of them particularly characteristic for the Mapuche subpopulation, namely B*39:09g, B*35:09, DRB1*04:07g, and DRB1*16:02g. Both population subsamples carried haplotypes of both Native American and European origin at high frequencies, reflecting Chile’s complex history of admixture and immigration. Matching probability analysis revealed limited benefits for Chilean patients (both non-Indigenous and Mapuche) from donor registries of non-Chilean donors, thus indicating a need for ongoing significant donor recruitment efforts in Chile.
The potential use of genomic methods in bottom trawl surveys to improve stock assessments in Europe
Authors: Rodríguez-Mendoza Rebeca , Saborido-Rey Fran
Published: May 2023

In Europe, research surveys carried out by state governments provide the great majority of fishery-independent data. Member States (MS) in the European Union (EU) regularly conduct research surveys to provide the necessary data to assess the status of exploited fish stocks and to monitor the general condition of the marine ecosystem. In the surveys, samplings are carried out throughout the distribution range of the targeted fish species using standardized gears (e.g., trawls and seines) and other methods (e.g., hydroacoustics and underwater cameras). In the context of fish stock assessment, survey data are important because they provide indices that help tuning the stock assessment models (e.g., the index of fish abundance) and key information about the size and age distributions of the stock, the size-age relationships, the proportion of fish mature at each age, and information on reproductive performance of the stocks. However, research surveys have a number of shortcomings that include, for example, a high economic cost coupled with complex logistics and a long time required for processing the collected data. In addition, some of the parameters that are needed in stock assessment cannot be estimated from survey data for certain commercially important species. For instance, age is usually determined using hard structures (such as otoliths) in fish target species. However, for European hake, age cannot be determined accurately because there are many difficulties in interpreting the ring patterns of the otoliths. This highlights the need to look for alternative methodologies such as genomics, that have the potential of improving the data obtained from research surveys and hence, improve fish stock assessments. Considering this, we carried out a review of the bottom trawl research surveys in the EU with the purpose of: 1) identifying the current approaches for monitoring fishery resources and the ecosystem and 2) determining how genomic techniques can be used to improve survey data, taking into account the needs of current and future stock assessment in Europe.
Human embryonic stem cells exert antitumor effects on prostate cancer cells in a co-culture microenvironment
Authors: Yang Xinyue , Lu Yang , Kuang Qin , Wu Yong , Tan Xin , Lan Jizhong , Qiang Zhe , Feng Tao
Published: May 2023

Prostate cancer is currently the most common malignancy among men. Given the limitations of current conventional anticancer therapies, new high-risk treatments are urgently needed. Previous studies have shown that embryonic stem cells (ESCs) can reverse the tumorigenic phenotype of tumor cells. However, there are still challenges in using human ESCs (hESCs) directly in cancer treatment. To facilitate the practical application of hESCs, we established a co-culture system consisting of prostate cancer cell lines and hESCs and investigated the antitumor activity of the supernatant of the co-culture system (Co-Sp) in vitro and in vivo, as well as the underlying mechanisms involved. The Co-Sp decreased the viability of prostate cancer cells in a concentration-dependent manner, significantly inhibited colony formation, and induced cell cycle arrest at the G0/G1 phase of the cell cycle. In addition, Co-Sp promoted apoptosis of prostate cancer cells and inhibited cell migration and invasion. In vivo studies also revealed that Co-Sp inhibited tumor growth in the xenograft model. Mechanistic studies showed that Co-Sp reduced the expression of cyclin D1, cyclin E, CDK4, CDK2, MMP-9, MMP-1, and Bcl-2, and increased the expression of p21, cleaved caspase-9, cleaved caspase-3, cleaved PARP, and Bax in prostate cancer cells. Furthermore, the Co-Sp decreased the phosphorylation of PI3K, AKT, and mTOR in cells and tumor tissues. Taken together, our results indicated that the Co-Sp has potent antitumor activity and could directly inhibit tumor growth. Our findings provide a new and effective way for the application of hESCs in cancer therapy and contribute to a new strategy for clinical stem cell therapy.
The impact of adipose tissue distribution on endometrial cancer: a systematic review
Authors: Bosch Anouk A. S. van den , Pijnenborg Johanna M. A. , Romano Andrea , Winkens Bjorn , Putten Louis J. M. van der , Kruitwagen Roy F. P. M. , Werner Henrica M. J.
Published: May 2023

Introduction

Endometrial cancer (EC) is the most common gynecological cancer with a rising incidence, attributed to advanced life expectancy and obesity. Adipose tissue (AT) is an important endocrine organ, and its metabolic activity is affected by the different anatomical distribution or locations. AT distribution influences a number of diseases. In EC, it remains unclear whether the type of AT distribution affects development or prognosis. This systematic review aimed to determine whether AT distribution is associated with patient characteristics, disease characteristics, and patient prognosis in EC.

Materials and methods

A search was conducted in Medline, MEDLINE EMBASE, and Cochrane Library. We included studies that enrolled patients with EC with any histological subtype and that distinguished between the visceral and subcutaneous AT compartment. In eligible studies, correlative analyses were performed for all outcome measures and AT distribution.

Results

Eleven retrospective studies were included, with a wide range of measurements for the visceral and subcutaneous AT compartments. AT distribution was found to be significantly correlated to a number of relevant (disease) characteristics including obesity measures, histological subtype, lymph node metastasis, and sex steroid levels. Five studies reported on survival parameters including overall survival, progression-free survival and disease-specific survival, and they found that increased VAT volume was statistically significantly associated with a worse survival.

Discussion/conclusion

This review demonstrates that there are significant correlations between AT distribution and prognosis, body mass index, sex steroid levels, and disease characteristics like histology. Well-designed, prospective, and larger-scale studies are needed to pinpoint these differences more specifically and understand how it can add in prediction and even therapy in EC.
RRx-001: a chimeric triple action NLRP3 inhibitor, Nrf2 inducer, and nitric oxide superagonist
Authors: Oronsky Bryan , Takahashi Lori , Gordon Richard , Cabrales Pedro , Caroen Scott , Reid Tony
Published: May 2023

RRx-001 is a shape shifting small molecule with Fast Track designation for the prevention/amelioration of chemoradiation-induced severe oral mucositis (SOM) in newly diagnosed Head and Neck cancer. It has been intentionally developed or “engineered” as a chimeric single molecular entity that targets multiple redox-based mechanisms. Like an antibody drug conjugate (ADC), RRx-001 contains, at one end a “targeting” moiety, which binds to the NLRP3 inflammasome and inhibits it as well as Kelch-like ECH-associated protein 1 (KEAP1), the negative regulator of Nrf2, and, at the other end, a conformationally constrained, dinitro containing 4 membered ring, which fragments under conditions of hypoxia and reduction to release therapeutically active metabolites i.e., the payload. This “payload”, which is delivered specifically to hypoperfused and inflamed areas, includes nitric oxide, nitric oxide related species and carbon-centered radicals. As observed with ADCs, RRx-001 contains a backbone amide “linker” attached to a binding site, which correlates with the Fab region of an antibody, and to the dinitroazetidine payload, which is microenvironmentally activated. However, unlike ADCs, whose large size impacts their pharmacokinetic properties, RRx-001 is a nonpolar small molecule that easily crosses cell membranes and the blood brain barrier (BBB) and distributes systemically. This short review is organized around the de novo design and in vivo pro-oxidant/pro-inflammatory and antioxidant/anti-inflammatory activity of RRx-001, which, in turn, depends on the reduced to oxidized glutathione ratio and the oxygenation status of tissues.
Enhancing Social Media Platforms with Machine Learning Algorithms and Neural Networks
Authors: Taherdoost Hamed
Published: May 2023

Network analysis aids management in reducing overall expenditures and maintenance workload. Social media platforms frequently use neural networks to suggest material that corresponds with user preferences. Machine learning is one of many methods for social network analysis. Machine learning algorithms operate on a collection of observable features that are taken from user data. Machine learning and neural network-based systems represent a topic of study that spans several fields. Computers can now recognize the emotions behind particular content uploaded by users to social media networks thanks to machine learning. This study examines research on machine learning and neural networks, with an emphasis on social analysis in the context of the current literature.
A Multidirectional Forearm Electromagnetic Generator Designed via Numerical Simulations
Authors: He Nanfei , King Colton , Xie Qizheng , Zhao Feng , Gao Wei
Published: May 2023

Harvesting biomechanical energy from daily human body motions provides a promising and sustainable power solution for wearable electronics, whose current power supplies, i.e., batteries, have unsatisfactory capacity and durability due to volume, shape, and flexibility constraints. Electromagnetic generators (EMGs) are favorable energy transducers because of their high energy-conversion efficiency, low dependence on frequencies, and long-term stability. However, an EMG that can effectively harvest energy from multi-directional arm motions at aperiodic low frequencies are yet to be created. Here, we introduce a unique EMG configuration by combining a linear and a helix frame into a monolithic unit (EMG-LH), enabling the EMG to scavenge energy from all kinds of arm motions up to 6 degrees of freedom (DOFs) (movement along XYZ axes and forearm rotations). The EMG frame geometry is designed and optimized according to numerical simulations. To clarify the working mechanism and maximize the power output, the copper coils’ winding pattern, the magnets’ velocity profiles, and the resulting voltage output are numerically simulated and then experimentally verified. Our EMG-LH outperforms linear EMGs (EMG-Ls) and helix EMGs (EMG-Hs) in harvesting energy from all arm motions. This work explicitly presents a forearm-wearable energy harvester as a sustainable power source for wearable electronics.
Importance of CEO Attention in Influencing Incumbent Responses to Disruptive Innovation
Authors: Gha Heesun , Kim Min Young , Ro Hyeon Jin , Choi Seungho
Published: May 2023

This study investigates incumbent firm responses to disruptive innovation in the rapidly evolving South Korean retail industry. The study explores the factors behind an incumbent firm’s decision-making processes when responding to disruptive innovation and examines the reasons behind varied incumbent responses. It investigates the agents that influence a firm’s decision by conducting the qualitative case study of a South Korean retail giant, Lotte. By collecting archival data from various sources, this paper was able to analyze different interviews and statements of the chief executive officer (CEO). From the analysis, it was determined that the firm’s overall actions were aligned with the CEO’s assertions. Thus, this paper asserts that Lotte’s response to disruptive innovation was directly influenced by the CEO’s attention. The results of this study further add to the discourse of disruptive innovation by highlighting the importance of CEO discretion in deciding a firm’s direction and by further emphasizing the relationship between managerial leadership and innovation.
Access to Dry Season Agricultural Content in the Broadcast Media and Dry Season Irrigation Farming among Smallholder Farmers in Nigeria
Authors: Ben-Enukora Charity A. , Ejem Agwu A. , Aremu Charity O. , Adeyeye Babatunde K. , Oloruntoba Ayomide F.
Published: May 2023

Inaccessibility to information could hinder the adoption of dry season agriculture which is very significant to ending the spate of food insecurity in Nigeria. This cross-sectional survey examined access to broadcast media agricultural content and the effect of such information on dry season agriculture practice among smallholder farmers in Nigeria’s Federal Capital Territory (FCT). Participants consisted of 381 smallholder farmers selected from rural settlements in Kuje and Kwali Area councils, through a multi-stage sampling procedure. Data for the study was generated via a self-designed questionnaire. The findings of this study show that access to the broadcast media agricultural content is high (94.2%) in the FCT and the majority (83.1%) of the farmers are particularly exposed to agricultural programmes on dry season farming. However, the regularity of exposure to such programmes is considered rare/occasional by a sizable proportion (44.8%) of the selected farmers. The research further confirms the general acceptability of the broadcast programmes on dry season agriculture but the major snag is that the majority (>50%) of the farmers think that the time at which the information is broadcast is inappropriate. In terms of the practical implications of the programmes, findings also revealed that <50% of the respondents believe that exposure to broadcast media content on dry season farming has helped them to improve their knowledge of dry season farming practices. Nonetheless, most respondents (>50%) remain adamant that dry-season farming is not achievable and productive; therefore, they have not engaged in dry season irrigation agriculture. We concluded that the knowledge gained from the dry season agricultural programmes in the broadcast media is not sufficient for farmers to successfully engage in dry season irrigation farming. The study recommends a long-term and sustained media campaign on dry season farming, the use of interactive programme content, and rescheduling agricultural programmes to farmers’ preferred time could yield the desired impact on dry season irrigation farming and food security in Nigeria.
Training in Honey Bee Veterinary Medicine in Italy: An Observational Study and Practical Proposals to Face Professional Challenges
Authors: D’Ascenzi Carlo , Power Karen , Maiolino Paola , Mortarino Michele
Published: May 2023

Honey bees, like other livestock, may be affected by infectious, parasitic, and abiotic diseases that need proper sanitary monitoring and control. Currently, there are limited opportunities for undergraduate students to receive education in Honey Bee Veterinary Medicine (HBVM) as part of their regular degree program, despite the professional requirements for veterinarians to carry out the increasing tasks related to honey bee health and production. Additionally, postgraduate training and specialization in HBVM is also underdeveloped. This study was an observational survey that evaluated the educational opportunities available in HBVM for current and future veterinarians in Italy. The survey analyzed both undergraduate and postgraduate programs, including Undergraduate Degree Programs in Veterinary Medicine (UDPVM), “Scuole di Specializzazione”, Masters, and other postgraduate courses. The results indicate that the current training available for veterinarians in the field of apiculture, both before and after graduation, is also insufficient in Italy, as already reported in other EU- and extra-EU countries. Finally, a roadmap for veterinary training in HBVM is developed here describing objectives and teachings aimed at fulfilling the needs of the profession in the field of beekeeping, considering the existing rules and regulations governing public health and possible evolution of this legal framework in the future.
Effects of Mangosteen (Garcinia mangostana) Peel Extract Loaded in Nanoemulsion on Growth Performance, Immune Response, and Disease Resistance of Nile Tilapia (Oreochromis niloticus) against Aeromonas veronii Infection
Authors: Yostawonkul Jakarwan , Kamble Manoj Tukaram , Sakuna Kitikarn , Madyod Sulaiman , Sukkarun Pimwarang , Medhe Seema Vijay , Rodkhum Channarong , Pirarat Nopadon , Sewaka Mariya
Published: May 2023

Nanotechnology can enhance nutrient delivery and bioavailability; hence, it has recently been considered the most practical alternative technology for nutritional supplements and disease control in fish farming. The present study was designed to evaluate the effects of mangosteen peel extract loaded in nanoemulsion (MSNE) on the inhibition of A. veronii (in vitro) and in vivo growth performance, serum biochemical parameters, the immune response, and the disease resistance of Nile tilapia (Oreochromis niloticus) against A. veronii challenge. The particle size, polydispersity index, and particle surface charge of MSNE were 151.9 ± 1.4 nm, >0.3, and −30 mV, respectively. Furthermore, MSNE, mangosteen peel extract (MPE), and nanoemulsion (NE) improved the antimicrobial activity against A. veronii. Fish fed MSNE, MPE, and NE-supplemented diets had a significantly lower (p < 0.05) feed conversion ratio (FCR) and higher specific growth rate (SGR) than fish fed the control diet. Furthermore, the MSNE had significantly higher serum glucose and protein levels than the control group in Nile tilapia. Total immunoglobulin, serum lysozyme, alternative complement activity, and survival of Nile tilapia fed with MSNE were significantly higher (p < 0.05) than the control diet. Therefore, MSNE has the potential to be employed as a supplement in sustainable Nile tilapia farming.
Influence of Intrauterine Fluid Detection, Number of Transfers and Age of the Recipient on Pregnancy Rate and Early Embryonic Loss in a Commercial Embryo Transfer Program
Authors: Donato Gian Guido , Necchi Denis , Vandaele Hilde , Vita Micaela Elizabeth , Bertero Alessia , Vincenti Leila , Nervo Tiziana
Published: May 2023

The selection of the recipient mare is one of the most important factors involved in the success of equine embryo transfer. The aim of this study was to determine whether the age of the recipient, the number of transfers and the detection of intrauterine fluid during the follicular phase or after ovulation can affect pregnancy rate at 14 and 45 days (PR 14 and PR 45) or early embryonic loss (EEL). A total of 1222 ETs were included in the study. Mares receiving the first embryo of the year had a higher PR 14 and 45 days compared to mares at the third transfer (78.8% and 70.1% vs. 65.6% and 54.1%, respectively). The detection of intrauterine fluid post ovulation negatively affected PR 14 (60.5% vs. 77.6%) and should therefore be considered an abnormal finding, probably being a sign of uterine inflammation or delayed uterine clearance. On the contrary, the age of the recipient mare and detection of fluid during follicular phase did not affect PR 14. Only the age of the recipient mare influenced the EEL, since mares aged 10–13 years had a higher EEL compared to mares aged 3–5 years (15.6% vs. 6.4%). Embryo size and grade affected PR 14 and 45.
Bloodstream Infection and Gram-Negative Resistance: The Role for Newer Antibiotics
Authors: Waters Jessica , Shorr Andrew F.
Published: May 2023

Gram-negative resistance remains a major challenge. Rates of in vitro resistance to commonly utilized antibiotics have skyrocketed over the last decade. Clinicians now encounter multidrug-resistant organisms routinely. Fortunately, newer agents, such as ceftazidime–avibactam, ceftolozone–tazobactam, meropenem–vaborbactam, and cefiderocol, have been developed and are now available for use against these pathogens. Clinical trials with these novel therapies have focused on multiple infection types ranging from complicated urinary tract infections to nosocomial pneumonia. Nonetheless, there remains little information about the efficacy of these drugs for bacteremia. To better appreciate the types and limitations of the evidence supporting the role for these unique molecules in bloodstream infection, one requires an appreciation of the initial clinical trials supporting the regulatory approval of these antibiotics. Furthermore, physicians must understand the subsequent case series and reports specifically focusing on outcomes for patients with bacteremia treated with these drugs. Despite the limitations of the data and reports relating to treatment for bacteremia with these antibiotics, each agent appears to be efficacious and can provide good outcomes in bloodstream infections due to resistant pathogens.
Systemic Antibiotic Therapy in Hidradenitis Suppurativa: A Review on Treatment Landscape and Current Issues
Authors: Molinelli Elisa , De Simoni Edoardo , Candelora Matteo , Sapigni Claudia , Brisigotti Valerio , Rizzetto Giulio , Offidani Annamaria , Simonetti Oriana
Published: May 2023

Hidradenitis suppurativa (HS) is a chronic, recurrent, and inflammatory skin disease characterized by painful, deep-seated, nodules, abscesses, and sinus tracts in sensitive areas of the body, including axillary, inguinal, and anogenital regions. Antibiotics represent the first-line pharmacological treatment of HS because of their anti-inflammatory properties and antimicrobial effects. This narrative review summarizes the most significant current issues on the role of systemic antibiotics in the management of HS, critically analyzing the main limits of their use (antibiotic resistance and toxicity). Although, in the last decades, several cytokines have been implicated in the pathomechanism of HS and the research on the use of novel biologic agents in HS has been intensified, antibiotics remain a valid therapeutic approach. Future challenges regarding antibiotic therapy in HS comprise their use in association with biologics in the management of acute flare or as a bridge therapy to surgery.
Altered Pharmacokinetics Parameters of Vancomycin in Patients with Hematological Malignancy with Febrile Neutropenia, a Bayesian Software Estimation
Authors: Alzahrani Abdullah M. , Naeem Anjum , AlAzmi Aeshah , Hakami Alqassem Y. , Karim Shahid , Ali Ahmed S. , Kamel Fatemah Omer , Alzhrani Rami M. , Alkhaldi Teaf S. , Maghrabi Loujayne A. , Alshehri Norah F. , Alzahrani Yahya A.
Published: May 2023

The pharmacokinetics of vancomycin vary significantly between specific groups of patients, such as critically ill patients and patients with hematological malignancy (HM) with febrile neutropenia (FN). Recent evidence suggests that the use of the usual standard dose of antibiotics in patients with FN may not offer adequate exposure due to pharmacokinetic variability (PK). Therefore, the purpose of this study is to assess the effect of FN on AUC0–24 as a key parameter for vancomycin monitoring, as well as to determine which vancomycin PK parameters are affected by the presence of FN using Bayesian software PrecisePK in HM with FN. This study was carried out in King Abdulaziz Medical City. All adult patients who were admitted to the Princess Norah Oncology Center PNOC between 1 January and 2017 and 31 December 2020, hospitalized and received vancomycin with a steady-state trough concentration measured before the fourth dose, were included. During the trial period, 297 patients received vancomycin during their stay at the oncology center, 217 of them meeting the inclusion criteria. Pharmacokinetic parameters were estimated for the neutropenic and non-FN patients using the precise PK Bayesian platform. The result showed that there was a significant difference (p < 0.05) in vancomycin clearance Clvan, the volume of distribution at a steady-state Vdss, the volume of distribution for peripheral compartment Vdp, half-life for the elimination phase t½β, and the first-order rate constant for the elimination process β in FN compared to non-FN patients. Furthermore, AUC0–24 was lower for FN patients compared to non-FN patients, p < 0.05. FN has a significant effect on the PK parameters of vancomycin and AUC0–24, which may require specific consideration during the treatment initiation.
Acetyl Zingerone: A Photostable Multifunctional Skincare Ingredient That Combats Features of Intrinsic and Extrinsic Skin Aging
Authors: Meyer Thomas A. , Swindell William R. , Chaudhuri Ratan K.
Published: May 2023

The cumulative damage skin sustains from exposure to environmental stressors throughout life exerts significant effects on skin aging and cancer development. One of the main ways by which environmental stressors mediate their effects within skin is through induction of reactive oxygen species (ROS). In this review, we chronicle the multiple properties by which acetyl zingerone (AZ) as a skincare ingredient can benefit skin (1) by helping manage overproduction of ROS through multiple routes as an antioxidant, physical quencher and selective chelator, (2) by fortifying protection after UV exposure ends to prevent the type of epidermal DNA damage that correlates with development of skin cancer, (3) by modulating matrisome activity and nurturing the integrity of the extracellular matrix (ECM) within the dermis and (4) through its proficient ability to neutralize singlet oxygen, by stabilizing the ascorbic acid precursor tetrahexyldecyl ascorbate (THDC) in the dermal microenvironment. This activity improves THDC bioavailability and may blunt pro-inflammatory effects of THDC, such as activation of type I interferon signaling. Moreover, AZ is photostable and can sustain its properties during UV exposure, in contrast to α-tocopherol. All these properties of AZ translate into measurable clinical benefits to improve the visual appearance of photoaged facial skin and to strengthen the skin’s own defenses against sun damage.
Oral Treatment with Plant-Derived Exosomes Restores Redox Balance in H2O2-Treated Mice
Authors: Di Raimo Rossella , Mizzoni Davide , Spada Massimo , Dolo Vincenza , Fais Stefano , Logozzi Mariantonia
Published: May 2023

Plant-derived exosomes (PDEs) are receiving much attention as a natural source of antioxidants. Previous research has shown that PDEs contain a series of bioactives and that their content varies depending on the fruit or vegetable source. It has also been shown that fruits and vegetables derived from organic agriculture produce more exosomes, are safer, free of toxic substances, and contain more bioactives. The aim of this study was to investigate the ability of orally administered mixes of PDE (Exocomplex®) to restore the physiological conditions of mice treated for two weeks with hydrogen peroxide (H2O2), compared with mice left untreated after the period of H2O2 administration and mice that received only water during the experimental period. The results showed that Exocomplex® had a high antioxidant capacity and contained a series of bioactives, including Catalase, Glutathione (GSH), Superoxide Dismutase (SOD), Ascorbic Acid, Melatonin, Phenolic compounds, and ATP. The oral administration of Exocomplex® to the H2O2-treated mice re-established redox balance with reduced serum levels of both reactive oxygen species (ROS) and malondialdehyde (MDA), but also a general recovery of the homeostatic condition at the organ level, supporting the future use of PDE for health care.
Heme Oxygenase-1 Expression in Dendritic Cells Contributes to Protective Immunity against Herpes Simplex Virus Skin Infection
Authors: Tognarelli Eduardo I. , Duarte Luisa F. , Farías Mónica A. , Cancino Felipe A. , Corrales Nicolás , Ibáñez Francisco J. , Riedel Claudia A. , Bueno Susan M. , Kalergis Alexis M. , González Pablo A.
Published: May 2023

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections are highly prevalent in the human population and produce mild to life-threatening diseases. These viruses interfere with the function and viability of dendritic cells (DCs), which are professional antigen-presenting cells that initiate and regulate the host’s antiviral immune responses. Heme oxygenase-1 (HO-1) is an inducible host enzyme with reported antiviral activity against HSVs in epithelial cells and neurons. Here, we sought to assess whether HO-1 modulates the function and viability of DCs upon infection with HSV-1 or HSV-2. We found that the stimulation of HO-1 expression in HSV-inoculated DCs significantly recovered the viability of these cells and hampered viral egress. Furthermore, HSV-infected DCs stimulated to express HO-1 promoted the expression of anti-inflammatory molecules, such as PDL-1 and IL-10, and the activation of virus-specific CD4+ T cells with regulatory (Treg), Th17 and Treg/Th17 phenotypes. Moreover, HSV-infected DCs stimulated to express HO-1 and then transferred into mice, promoted the activation of virus-specific T cells and improved the outcome of HSV-1 skin infection. These findings suggest that stimulation of HO-1 expression in DCs limits the deleterious effects of HSVs over these cells and induces a favorable virus-specific immune response in the skin against HSV-1.
Therapeutic Potential of Peucedanum japonicum Thunb. and Its Active Components in a Delayed Corneal Wound Healing Model Following Blue Light Irradiation-Induced Oxidative Stress
Authors: Kang Wan Seok , Kim Eun , Choi Hakjoon , Lee Ki Hoon , Kim Kyeong Jo , Lim Dosung , Choi Su-young , Kim Youngbae , Son Seon ah , Kim Jin Seok , Kim Sunoh
Published: May 2023

Blue light is reported to be harmful to eyes by inducing reactive oxygen species (ROS). Herein, the roles of Peucedanum japonicum Thunb. leaf extract (PJE) in corneal wound healing under blue light irradiation are investigated. Blue-light-irradiated human corneal epithelial cells (HCECs) show increased intracellular ROS levels and delayed wound healing without a change in survival, and these effects are reversed by PJE treatment. In acute toxicity tests, a single oral administration of PJE (5000 mg/kg) does not induce any signs of clinical toxicity or body weight changes for 15 days post-administration. Rats with OD (oculus dexter, right eye) corneal wounds are divided into seven treatment groups: NL (nonwounded OS (oculus sinister, left eye)), NR (wounded OD), BL (wounded OD + blue light (BL)), and PJE (BL + 25, 50, 100, 200 mg/kg). Blue-light-induced delayed wound healing is dose-dependently recovered by orally administering PJE once daily starting 5 days before wound generation. The reduced tear volume in both eyes in the BL group is also restored by PJE. Forty-eight hours after wound generation, the numbers of inflammatory and apoptotic cells and the expression levels of interleukin-6 (IL-6) largely increase in the BL group, but these values return to almost normal after PJE treatment. The key components of PJE, identified by high-performance liquid chromatography (HPLC) fractionation, are CA, neochlorogenic acid (NCA), and cryptochlorogenic acid (CCA). Each CA isomer effectively reverses the delayed wound healing and excessive ROS production, and their mixture synergistically enhances these effects. The expression of messenger RNAs (mRNAs) related to ROS, such as SOD1, CAT, GPX1, GSTM1, GSTP1, HO-1, and TRXR1, is significantly upregulated by PJE, its components, and the component mixture. Therefore, PJE protects against blue-light-induced delayed corneal wound healing via its antioxidative, anti-inflammatory, and antiapoptotic effects mechanistically related to ROS production.