bluuebunny/crossref_metadata_2025 huggingface dataset:
Leveraging the Lab: How Pre-Founding R&D Collaboration Influences the Internationalization Timing of Academic Spin-Offs
Authors: Walter Achim , Coviello Nicole , Sienknecht Monika , Ritter Thomas
Published: December 2022

Research shows that early internationalization is more likely when founders have international and business-related experience. But what if experience was obtained in other ways? We study the scientist-founders of 149 academic spin-offs (ASOs), using cognition theory to argue for a curvilinear relationship between breadth of pre-founding R&D collaboration and internationalization timing. Our longitudinal study combines survey and patent data to show that increased breadth of collaboration with international scientists increases and then decreases the likelihood of early internationalization. The results are similar but less robust for collaboration with industry partners. Our findings suggest that studies on experience in new venture internationalization underestimate the role of R&D collaboration and the research-based heritage of many new firms.
Psychometric Evaluation of the Parentification Inventory in a Polish Adolescent Sample
Authors: Borchet Judyta , Schneider Wei S. , Lewandowska-Walter Aleksandra , Tomek Sara , Hooper Lisa M.
Published: December 2022

There are only a few instruments that assess for parentification in adults and even fewer that examine current levels of parentification among adolescents. The original Parentification Inventory (PI; Hooper, 2009) was developed to assess for parentification—a family caregiving process abdicated by adults to children—among adults in the United States. The current study evaluated the psychometric properties of an adapted version of the PI scores for its use in Polish-speaking adolescents ( N = 272). The results of the confirmatory factor analysis showed that the current PI holds its original three-factor structure among the current sample and thus supports its use in Polish adolescents.
Zn[B3O4(OH)3] composites fabrication based on PVC pipes scrap via comparing melt mixing and casting procedures under the effect of electron beam irradiation
Authors: Fathy ES , Elnaggar Mona Y , Raslan Heba A , Hassan Medhat M
Published: December 2022

In several works, scientific researchers targeted the development of polymeric materials with good mechanical and thermal properties and resist heat and fire propagation. In a new approach, this article goals to the usage of waste polyvinyl chloride (WPVC) based polymer composites derived from PVC pipes scrap filled with fixed percent of zinc borate particles (ZnB), which were prepared via two different techniques named melt mixing WPVC/ZnB (M) and casting WPVC/ZnB (C). The fabricated composites by the two methods were irradiated in an electron beam accelerator (EB) at 30 kGy. A comparative study of the thermal and mechanical properties based on stress-strain curves, tensile strength (TS), elongation at break (E %), and tear strength were evaluated. Furthermore, the rate of heat burning (%) for the two methods has been performed. Moreover, differential scanning calorimetry (DSC), Thermogravimetric analysis (TGA), Infrared spectroscopy analysis (FTIR), X-ray diffraction (XRD), and the activation energy (Ea) calculation of the prepared samples have been considered. The observed improvements in the mechanical, thermal, and flammability behavior of WPVC were succeeded by incorporating ZnB particles. The irradiated WPVC loaded with zinc borate presented a superior flame propagation fraction when matched with their corresponding unirradiated composites. Also, WPVC composite films prepared via the melt mixing method reveal more excellent properties than those equipped by the casting process for the most investigated factors.
Complicating the Lone Voice Through Rewriting in Role
Authors: Coleman Claire
Published: December 2022

Rewriting in role emerged out of the necessity to make sense of multiple versions of the same event and create a coherent narrative. It became, however, a vital experimental method that challenges the authoritative voice, aligns with critical pedagogy, and invites the reader into a dynamic discourse. This methodological innovation is akin to performative ethnography, factionalization, writing as inquiry, and others; rewriting in role is a deliberate and transparent process of rewriting existing data through fictional characters. It generated an entertaining, juicy, and embodied rendering of events to stage and analyze research, not as inert knowing but as active questioning.
Mechanical Comaneci 17-stent angioplasty for a sub-optimally deployed flow-diverter stent
Authors: Vladev Georgi , Sirakov Alexander , Sirakova Kristina , Sirakov Sanimir S
Published: December 2022

Flow diverter stents are increasingly used as the sole endovascular treatment method for complex or wide-necked intracranial aneurysms. 1 Technical complications related to stent deployment are infrequently reported in the literature. During treatment, implant misbehaviors may occur, including incomplete tubular expansion with insufficient aneurysmal coverage and wall apposition, proximal or distal narrowing, and twisting along the axis. 2 – 4 Little is known about this phenomenon, especially if it relates to the operator experience, deployment techniques, different devices, and implant properties. The management of these complications requires technical precision and is often remediated by “massaging” the stent with the delivery system, balloon angioplasty, or placement of additional self-expandable stents. Lastly, if critically damaged, the stent could be taken out of the vessel with a combination of maneuvers called “stentectomy.” 5 These techniques often necessitate multiple navigations and the utilization of a larger microcatheter. We aim to highlight the feasibility of Comaneci 17 stent-angioplasty as an effective bailout strategy for inadequately deployed flow diverter stents. The suggested approach's technical aspects, including pros and cons, have been discussed.
Netflix, Spanish television, and La casa de papel: Growing global and local TV together in the multiplatform era
Authors: Edgerton Gary
Published: December 2022

This institutional-industrial analysis evaluates how Netflix’s post-2016 rebranding efforts resulted in its ongoing transition from a centrally-managed multinational corporation, based mainly in Silicon Valley, to a more decentralised transnational operation with multiple interconnected headquarters worldwide. Utilising a blended macro-micro critical perspective, Netflix’s October 2015 debut in Spain is examined as an inflection point for this subscription video on demand (SVOD) change agent, Spain’s then-traditional TV infrastructure and the transnational television industry. Netflix’s eventual integration into the Spanish television landscape and its transnational distribution of La casa de papel [ Money Heist] (2017–21) serve as a two-fold object lesson into how glocal relations occur during TVIV.
The Middle-Out Perspective: an approach to formalise ‘normal practice’ in public health advocacy
Authors: Mindell JS , Parag Y , Bartington SE , Stoll L , Barlow J , Janda KB
Published: December 2022

Aims:

The middle-out perspective (MOP) provides a lens to examine how actors positioned between government (top) and individuals (bottom) act to promote broader societal changes from the middle-out (rather than the top-down or bottom-up). The MOP has been used in recent years in the fields of energy, climate change, and development studies. We argue that public health practitioners involved with advocacy activities and creating alliances to amplify health promotion actions will be familiar with the general MOP concept if not the formal name. The article aims to demonstrate this argument.

Methods:

This article introduces the MOP conceptual framework and customises it for a public health audience by positioning it among existing concepts and theories for actions within public health. Using two UK case studies (increasing signalised crossing times for pedestrians and the campaign for smoke-free legislation), we illustrate who middle actors are and what they can do to result in better public health outcomes.

Results:

These case studies show that involving a wider range of middle actors, including those not traditionally involved in improving the public’s health, can broaden the range and reach of organisations and individuals involving in advocating for public health measures. They also demonstrate that middle actors are not neutral. They can be recruited to improve public health outcomes, but they may also be exploited by commercial interests to block healthy policies or even promote a health-diminishing agenda.

Conclusion:

Using the MOP as a formal approach can help public health organisations and practitioners consider potential ‘allies’ from outside traditional health-related bodies or professions. Formal mapping can expand the range of who are considered potential middle actors for a particular public health issue. By applying the MOP, public health organisations and staff can enlist the additional leverage that is brought to bear by involving additional middle actors in improving the public’s health.
Tetrastigma hemsleyanum Ethanolic Extract Inhibited the Growth of Nonsmall Cell Lung Cancer Cells by Suppressing Hypoxia-Inducible Factor-1α-Dependent Glycolysis and Angiogenesis
Authors: Wu Zhiqiang , Xu Bin , He Qin , Hu Zhuyuan , Yu Zhiyi
Published: December 2022

Background:The ethanolic extract of Tetrastigma hemsleyanum Diels et Gilg ( T hemsleyanum ethanolic extract [Te-EtOH]) showed positive effects against various tumors. However, there are few studies on the effects of Te-EtOH on nonsmall cell lung cancer (NSCLC). We attempted to examine the inhibiting effect of Te-EtOH on NSCLC cells and to elucidate the relevant mechanisms. Methods: A549 and H1299 cells were pretreated with Te-EtOH at different concentrations. Cell viability was analyzed by Cell Counting Kit-8, flow cytometry, and the 3-dimensional spheroid model; RNA-sequencing was also performed. Moreover, enzyme-linked immunosorbent assay and Western blot tests were performed to determine the metabolic capability, the expressions of energy metabolism-related proteins, and the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/hypoxia-inducible factor-1α (HIF-1α) pathway. Additionally, under hypoxic conditions, the ability of Te-EtOH to inhibit HIF-1α expression and the metabolic capability of NSCLC cells was tested. Results: Te-EtOH considerably repressed cell viability in a dose-dependent manner. RNA-sequencing revealed that Te-EtOH's inhibition of NSCLC cells activity was related to metabolism. In addition, Te-EtOH significantly inhibited glycolysis, and adenosine triphosphate and lactate accumulation in NSCLC cells. Furthermore, we found that Te-EtOH could block PI3K/AKT/HIF-1α pathway activation. Moreover, Te-EtOH significantly inhibited hypoxia-induced expression of HIF-1α, vascular endothelial growth factor, and metabolic capability. Conclusions: Our results suggested that Te-EtOH inhibited the growth of NSCLC cells by suppressing HIF-1α-dependent glycolysis and angiogenesis.
Phenolic Glycosides Citrulluside H and Citrulluside T Isolated From Young Watermelon (Citrullus lanatus) Fruit Have Beneficial Effects Against Cutibacterium acnes-Induced Skin Inflammation
Authors: Itoh Tomohiro , Muramatsu Mai , Miyazono Daiki , Koketsu Mamoru , Fujita Shingo , Hashizume Toshiharu
Published: December 2022

Acne vulgaris, typically caused by Cutibacterium acnes ( C. acnes) involves chronic inflammation of the sebaceous follicles and is the most common skin disease, afflicting 85% of adolescents. We previously isolated 2 novel phenolic glycosides, 2-caffeoyl-3-hydroxy-3-methylbutyric 4′-β-D-glucopyranosyloxy-3′-hydroxybenzyl ester (citrulluside H [CH]) and 2-caffeoyl-3-hydroxy-3-methylbutyric 4′-β-d-glucopyranosyloxybenzyl ester (citrulluside T [CT]), from young fruits of watermelon ( Citrullus lanatus). Both compounds suppressed UVB-induced photoaging in human fibroblasts by scavenging intracellular reactive oxygen species (ROS) and thus might be useful as natural skin care ingredients. In this study, we examined the inhibitory effects of these phenolic glycosides on C. acnes growth and C.acnes-induced inflammation. Neither phenolic glycoside inhibited the growth of C. acnes. However, they both significantly suppressed toll-like receptor (TLR) 1/2 or TLR2/6/nuclear factor κB (NF-κB) signaling in heat-killed C. acnes (hk- C. acnes) -stimulated RAW264.7 cells. Additionally, both phenolic glycosides decreased the expression of M1 macrophage biomarkers (cluster of differentiation [ CD] 80, CD86, and inducible NO synthase [ iNOS]), suggesting that they attenuate M1 macrophage activation. These results indicated that both CH and CT are potential therapeutic substances against C. acnes-induced skin inflammation.
Mechanism Underlying the Action of Berberine in the Treatment of Gouty Arthritis Based on Network Pharmacology
Authors: Fang Shan , Gao Yan , Fang Yuan , Sun Jing , Xie Zhijun
Published: December 2022

Introduction: Gouty arthritis (GA) is induced by a purine metabolism disorder and monosodium urate (MSU) crystal-related inflammation. Berberine (BBR), extracted from Coptis chinensis, ameliorates MSU-induced GA. However, the mechanisms of BBR against GA remain to be fully elucidated. This study aimed to identify the key targets and pathways mediating the effects of BBR against GA using network pharmacology. Methods: BBR and GA targets were obtained from several databases, and the network of BBR-GA common targets was visualized using Cytoscape software. Protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the STRING and Database for Annotation, Visualization, and Integrated Discovery databases, respectively. Animal experiments were performed to determine the outcomes of the BBB intervention. The serum levels of IL-1β, IL-8, and IL-6 were detected using enzyme-linked immunosorbent assay. Results: Thirty-three common targets (including NF-κB, RelA, MAPK1, IL-6, and IL-1β) of BBR and GA were identified, and a network of common targets between BBR and GA was constructed. PPI analysis demonstrated that IL-1β, IL-6, TNF, MAPK, and RelA are key targets with high degree values. GO and KEGG pathway analyses revealed the involvement of inflammation-related biological processes and signaling pathways, such as the NF-κB, MAPK, and TNF signaling pathways. Animal experiments demonstrated that the uric acid, IL-1β, IL-6, and IL-8 serum levels were significantly lower in the BBR group compared with those in hyperuricemic rats. Conclusions: Using systematic network analysis, potential targets mediating the effects of BBR on GA were detected. The pathways and inflammatory factors involved were identified using in vivo experiments, thus providing a reference for further basic research and clinical applications of BBR in the treatment of GA.
Phillyrin Inhibits Isoproterenol-Induced Cardiac Hypertrophy Via P38 and NF-κB Pathways
Authors: Liu Juanjuan , Li Jiahang , Yang Shengqian , She Yuanting , Li Xiaohui , Jia Yi
Published: December 2022

Cardiac hypertrophy (CH) is the main compensatory response to chronic heart stress and often progresses to a decompensation state potentially leading to heart failure. Phillyrin (PHI) is a novel compound derived from Forsythia, which has shown anti-inflammatory and anti-virus activities as well as renal protective effects on diabetic nephropathy. Therefore, we investigated the effects of PHI on CH induced by isoproterenol (ISO). Cardiac hypertrophy was induced by ISO in vivo, and the H9C2 cells were treated with ISO. PHI treatment alleviated CH in isoproterenol-induced mice in 7 and 14 days. Echocardiography showed that the PHI improved ISO-induced CH heart function and structure. PHI significantly decreased heart weight/body weight (HW/BW) and heart weight/tibia length (HW/TL) ratios and improved left ventricular (LV) function in ISO-treated mice. Hematoxylin and eosin staining revealed cardiomyocyte areas of the ISO group were significantly increased, and PHI was significantly reduced at 7 and 14 days, PHI-100 groups showed significantly better improvements than PHI-50. Sirius red staining indicated PHI significantly decreased collagen deposition in heart cross-sections induced by ISO, and PHI repressed ISO-induced cTn-I and NT-proBNP expression in mouse serum. In vitro data from H9C2 cells showed that PHI decreased cell areas and total cell protein levels in cells induced by ISO, whereas ANP, BNP, IL-6, and IL-1β expression was significantly inhibited by PHI. Also, PHI simultaneously inhibited P65 and P38 phosphorylation in vivo and in vitro. In conclusion, this study demonstrated the protective effect of PHI on CH in in vivo and in vitro, and this effect was related to the suppression of inflammation through the activation of the P38/NF-κB pathway.
Caregiver Faculty: Working through a Pandemic
Authors: Marshall Debra , Hoskin Sara
Published: December 2022

Myriad research examines benefits and drawbacks of working from home, both pre- and post-pandemic. Our research looks at how work from home mandates due to the COVID-19 pandemic were implemented, primarily by those who also had caregiver roles to fulfill. We used a convenience sample, drawing from full-time college faculty at a mid-sized state college in Florida, gathering information from caregivers and non-caregivers for comparative purposes. As we analyzed our data, we considered two additional concepts: Elmore’s backward mapping, which asks us to consider how employer mandates are implemented and will assist us in making policy recommendations, and Smith’s Standpoint, which allowed us to consider our own different gendered experiences as we analyzed survey responses. Our findings reveal that there are some employees well suited to working from home, while others are less enthusiastic about this initiative, and that a significant factor is household caregiving responsibilities, often considered to be the domain of women. Our insights shed light on differences in caregiver-employee statuses; we hope to help guide effective institutional policy should there be a need for workplaces to shut down again and to encourage administrators to consider faculty who may be a good work from home fit should it be considered for everyday work. Understanding where the strengths and weaknesses were/are for workers who work from home will benefit employers.
Biomechanical Comparison of Unilateral and Bilateral Pedicle Screw Fixation after Multilevel Lumbar Lateral Interbody Fusion
Authors: Mok James M. , Forsthoefel Craig , Diaz Roberto Leonardo , Lin Ye , Amirouche Farid
Published: December 2022

Study Design

Human Cadaveric Biomechanical Study

Objectives

Lumbar Lateral Interbody Fusion (LLIF) utilizing a wide cage has been reported as having favorable biomechanical characteristics. We examine the biomechanical stability of unilateral pedicle screw and rod fixation after multilevel LLIF utilizing 26 mm wide cages compared to bilateral fixation.

Methods

Eight human cadaveric specimens of L1-L5 were included. Specimens were attached to a universal testing machine (MTS 30/G). Three-dimensional specimen range of motion (ROM) was recorded using an optical motion-tracking device. Specimens were tested in 3 conditions: 1) intact, 2) L1-L5 LLIF (4 levels) with unilateral rod, 3) L1-L5 LLIF with bilateral rods.

Results

From the intact condition, LLIF with unilateral rod decreased flexion-extension by 77%, lateral bending by 53%, and axial rotation by 26%. In LLIF with bilateral rods, flexion-extension decreased by 83%, lateral bending by 64%, and axial rotation by 34%. Comparing unilateral and bilateral fixation, LLIF with bilateral rods reduced ROM by a further 23% in flexion-extension, 25% in lateral bending, and 11% in axial rotation. The difference was statistically significant in flexion-extension and lateral bending (P < .005).

Conclusions

Considerable decreases in ROM were observed after multilevel (4-level) LLIF utilizing 26 mm cages supplemented with both unilateral and bilateral pedicle screws and rods. The addition of bilateral fixation provides a 10-25% additional decrease in ROM. These results can inform surgeons of the incremental biomechanical benefit when considering unilateral or bilateral posterior fixation after multilevel LLIF.
A novel mouse whole blood thrombin generation assay sensitive to FXI- and FIX-mediated amplification of coagulation
Authors: Wan Jun , Tanratana Pansakorn , Roest Mark , Gruber Andras , Pawlinski Rafal , Wolberg Alisa S. , Mackman Nigel , Grover Steven P.
Published: December 2022

Thrombin generation (TG) assays serve as a valuable tool to study the amplifying roles of intrinsic pathway factors in human coagulation and provide functional insights into the increased bleeding observed in individuals deficient in factors (F) XI, IX, or VIII. Mice are used extensively in hemostasis research owing to the availability of coagulation factor–deficient mice. However, phenotypic differences between mouse and human TG have become apparent. In this study, we describe a novel, calibrated mouse whole blood (WB) TG assay used to assess the amplifying roles of intrinsic pathway factors in mouse coagulation. WB- and plasma-TG was triggered with either silica or tissue factor (TF) in samples from wild-type mice and mice deficient for FXII, FXI, or FIX. Expectedly, silica-triggered WB-TG and platelet-poor plasma (PPP)-TG were significantly reduced by deficiencies for FXII, FXI, or FIX. FXII deficiency had no effect on WB-TG or PPP-TG when triggered with TF. However, FXI deficiency resulted in significantly reduced WB-TG triggered by low concentrations of TF but had no effect on TF-triggered PPP-TG. FIX deficiency profoundly reduced WB-TG when triggered by low or high concentrations of TF whereas TG in PPP or platelet-rich plasma was only moderately reduced under these conditions. In conclusion, we have developed a novel mouse WB-TG assay with enhanced sensitivity to FXI- and FIX-dependent amplification of coagulation compared with an established plasma-TG assay. The enhanced sensitivity of WB-TG to FXI and FIX-dependent amplification of coagulation suggests an important role of blood cells in this process.
USP13 regulates HMGB1 stability and secretion through its deubiquitinase activity
Authors: Shin Jaemin , Kim Young Hun , Lee Bin , Chang Jae Ho , Choi Hee Youn , Lee Hoojung , Song Ki Chan , Kwak Man Sup , Choi Ji Eun , Shin Jeon-Soo
Published: December 2022

Background

High mobility group box 1 (HMGB1) is a damage-associated molecular pattern (DAMP) molecule that plays a central role in innate immunity. HMGB1 acts as a late mediator of inflammation when actively secreted in response to inflammatory stimuli. Several post-translational modifications (PTMs), including acetylation, phosphorylation, and oxidation, are involved in HMGB1 secretion. However, the E3 ligases of HMGB1 and the mechanism by which DUBs regulate HMGB1 deubiquitination are not well known.

Methods

LC–MS/MS, proximity ligation assay, immunoprecipitation were used to identify ubiquitin-specific protease 13 (USP13) as a binding partner of HMGB1 and to investigate ubiquitination of HMGB1. USP13 domain mutant was constructed for domain study and Spautin-1 was treated for inhibition of USP13. Confocal microscopy image showed localization of HMGB1 by USP13 overexpression. The data were analyzed using one-way analysis of variance with Tukey’s honestly significant differencepost-hoctest for multiple comparisons or a two-tailed Student’st-test.

Results

We identified ubiquitin-specific protease 13 (USP13) as a novel binding partner of HMGB1 and demonstrated that USP13 plays a role in stabilizing HMGB1 from ubiquitin-mediated degradation. USP13 overexpression increased nucleocytoplasmic translocation of HMGB1 and promoted its secretion, which was inhibited by treatment with Spautin-1, a selective inhibitor of USP13.

Conclusion

Taken together, we suggest that USP13 is a novel deubiquitinase of HMGB1 that regulates the stability and secretion of HMGB1.
Effects of agricultural land use on river biota: a meta-analysis
Authors: Schürings Christian , Feld Christian K. , Kail Jochem , Hering Daniel
Published: December 2022

Agriculture, the world’s most dominant land use type, burdens freshwater biodiversity with a multitude of stressors such as diffuse pollution and hydromorphological alteration. However, it is difficult to directly link agricultural land use with biota response as agricultural stressors can also originate from other causes. Also, there is evidence for positive and negative effects of agriculture on organisms, agricultural impact differs strongly with the biological metric and study region considered and agricultural impact differs among practice and type, which in turn affects different organism groups with varying severity. Against this background, our study aimed at assessing, if agricultural land use has a consistent effect on river biota. We conducted a systematic review of the literature, which yielded 43 studies and 76 relationships between agriculture and aquatic organism groups. The relationships were subjected to a meta-analysis using Hedge’s g to calculate the standardized mean difference of effects. Overall, we detected a medium to strong effectg = − 0.74 of agricultural land use on freshwater biota, only marginally influenced by study design, river type and region. Strong differences in biota response could be observed depending on the biological metric assessed, with ecological quality indices of agricultural impairment performing best. Sensitive taxa declined with agricultural impact, while tolerant taxa tended to benefit. In addition, the biota response differed among agricultural types and practices and organism group, with macroinvertebrates showing the strongest effect. Our results quantify the effects of agriculture on riverine biota and suggest biological metric types for assessing agricultural impact. Further research is needed to discriminate between agricultural types and account for intensity.
High-quality genome-scale metabolic network reconstruction of probiotic bacterium Escherichia coli Nissle 1917
Authors: van ‘t Hof Max , Mohite Omkar S. , Monk Jonathan M. , Weber Tilmann , Palsson Bernhard O. , Sommer Morten O. A.
Published: December 2022

Background

Escherichia coli Nissle 1917 (EcN) is a probiotic bacterium used to treat various gastrointestinal diseases. EcN is increasingly being used as a chassis for the engineering of advanced microbiome therapeutics. To aid in future engineering efforts, our aim was to construct an updated metabolic model of EcN with extended secondary metabolite representation.

Results

An updated high-quality genome-scale metabolic model of EcN, iHM1533, was developed based on comparison with 55 E. coli/Shigella reference GEMs and manual curation, including expanded secondary metabolite pathways (enterobactin, salmochelins, aerobactin, yersiniabactin, and colibactin). The model was validated and improved using phenotype microarray data, resulting in an 82.3% accuracy in predicting growth phenotypes on various nutrition sources. Flux variability analysis with previously published 13C fluxomics data validated prediction of the internal central carbon fluxes. A standardised test suite called Memote assessed the quality of iHM1533 to have an overall score of 89%. The model was applied by using constraint-based flux analysis to predict targets for optimisation of secondary metabolite production. Modelling predicted design targets from across amino acid metabolism, carbon metabolism, and other subsystems that are common or unique for influencing the production of various secondary metabolites.

Conclusion

iHM1533 represents a well-annotated metabolic model of EcN with extended secondary metabolite representation. Phenotype characterisation and the iHM1533 model provide a better understanding of the metabolic capabilities of EcN and will help future metabolic engineering efforts.
Isolation, complete genome sequencing and in silico genome mining of Burkholderia for secondary metabolites
Authors: Alam Khorshed , Zhao Yiming , Lu Xuefei , Gong Kai , Zhong Lin , Hao Jinfang , Islam Md. Mahmudul , Islam Saiful , Li Geng , Zhang Youming , Li Ruijuan , Li Aiying
Published: December 2022

Recent years, Burkholderia species have emerged as a new source of natural products (NPs) with increasing attractions. Genome mining suggests the Burkholderia genomes include many natural product biosynthetic gene clusters (BGCs) which are new targets for drug discovery. In order to collect more Burkholderia, here, a strain S-53 was isolated from the soil samples on a mountain area in Changde, P.R. China and verified by comparative genetic analysis to belong to Burkholderia. The complete genome of Burkholderia strain S-53 is 8.2 Mbps in size with an average G + C content of 66.35%. Its taxonomy was both characterized by 16S rRNA- and whole genome-based phylogenetic trees. Bioinformatic prediction in silico revealed it has a total of 15 NP BGCs, some of which may encode unknown products. It is expectable that availability of these BGCs will speed up the identification of new secondary metabolites from Burkholderia and help us understand how sophisticated BGC regulation works.
Biocontrol strategies: an eco-smart tool for integrated pest and diseases management
Authors: Jaiswal Durgesh Kumar , Gawande Suresh Janardhan , Soumia P. S. , Krishna Ram , Vaishnav Anukool , Ade Avinash Bapurao
Published: December 2022

For the burgeoning global population, sustainable agriculture practices are crucial for accomplishing the zero-hunger goal. The agriculture sector is very concerned about the rise in insecticide resistance and the Modern Environmental Health Hazards (MEHHs) that are problems for public health due to on pesticide exposure and residues. Currently, farming practices are being developed based on microbial bio-stimulants, which have fewer negative effects and are more efficient than synthetic agro-chemicals. In this context, one of the most important approaches in sustainable agriculture is the use of biocontrol microbes that can suppress phytopathogens and insects. Simultaneously, it is critical to comprehend the role of these microbes in promoting growth and disease control, and their application as biofertilizers and biopesticides, the success of which in the field is currently inconsistent. Therefore, editorial is part of a special issue titled "Biocontrol Strategies: An Eco-smart Tool for Integrated Pest and Disease Management" which focuses on biocontrol approaches that can suppress the biotic stresses, alter plant defense mechanisms, and offer new eco-smart ways for controlling plant pathogens and insect pests under sustainable agriculture.
(De)Prescribing of proton pump inhibitors: what has changed in recent years? an observational regional study from the French health insurance database
Authors: Gendre Pauline , Mocquard Julie , Artarit Pascal , Chaslerie Anicet , Caillet Pascal , Huon Jean-François
Published: December 2022

Background

Proton pump inhibitors (PPIs) are one of the most widely prescribed drug classes in the community and at hospital. The significant misuse of PPIs requires the implementation for a deprescribing strategy. Numerous studies aiming at evaluating the impact of deprescribing interventions have been set up, implying a precisely known evolution of consumption of PPIs in the population studied without intervention.

The main objective of the study was to study overall changes in PPI prescribing and deprescribing in a regional population of chronic consumers without intervention, according to health insurance databases.

Methods

This historical cohort study was based on the French National Health Data System databases. All adult patients living in the Pays de la Loire area and covered by the French National Health Insurance and who had at least one reimbursement for a PPI dispensing between 01 October 2016 and 31 December 2020 were included. Only chronic consumer patients were included, defined as patients who has had PPI dispensed for 3 consecutive months with a temporal coverage of at least 80%. Patients under 18 years of age and patients who received parenteral PPIs only were excluded.

Results

The percentage of chronic treatment discontinuation in 2017 was 12.5% and remained stable to reach 12.4% in 2020. The number of new chronic patients increased from year to year to reach 77,222 patients in 2020, with an increasing rate of 1.2 to 2% between 2017 and 2020. The prevalent patient population increased from year to year to reach 167 751 patients in 2020, with an increasing rate of 4.2 to 4.4% between 2017 and 2020.

Regarding the initiation of PPI therapy, in 2020, 87.1% of treatment initiations were done by general practitioners. They renewed 2,402,263 prescriptions (89.3%) between 2017 and 2020.

Conclusions

This study shows a stagnation over the last 4 years in the deprescribing of chronic PPI treatments in a French region despite the information on their inappropriate use reported by national agencies and in the literature with increasing frequency. This reinforces the interest of setting up a deprescribing project.
Nationwide handgrip strength values and factors associated with muscle weakness in older adults: findings from the Brazilian Longitudinal Study of Aging (ELSI-Brazil)
Authors: de Souza Moreira Bruno , de Souza Andrade Amanda Cristina , Lustosa Torres Juliana , de Souza Braga Luciana , de Carvalho Bastone Alessandra , de Melo Mambrini Juliana Vaz , Lima-Costa Maria Fernanda
Published: December 2022

Background

Handgrip strength (HGS) is a simple, quick, inexpensive, and highly reliable method for the assessment of muscle strength in clinical practice and epidemiological studies. This study aimed at describing the HGS values by age group and sex in Brazilians aged 50 years and over, determining age group- and sex-specific cutoff points for muscle weakness, and investigating sociodemographic and anthropometric variables associated with muscle weakness for each sex.

Methods

Data from the second wave of the Brazilian Longitudinal Study of Aging (ELSI-Brazil) were analyzed. HGS was measured in the dominant hand using a hydraulic hand dynamometer. Fractional polynomial regression models were fitted to estimate the percentiles (P5, P10, P20, P25, P50, P75, P90, and P95) of HGS by age group and sex. The P20 of the maximum HGS by age group and sex was used to define muscle weakness. Associations between sociodemographic (racial self-classification, place of residence, schooling, and monthly household income per capita in tertiles) and anthropometric variables (body mass index and waist circumference) and muscle weakness, by sex, were evaluated using logistic regression.

Results

The analytical sample included 7905 participants (63.1 ± 9.1 years; 60% women). HGS reduced with increasing age in both sexes. Men presented higher HGS than women in all age groups. The cutoff points for muscle weakness ranged from 28 to 15 kg for men and from 17 to 9 kg for women. In the adjusted analyses, low schooling (0–4 years) was positively associated with muscle weakness in both sexes (in men, odds ratio (OR) 2.45, 95% confidence interval (CI) 1.46–4.12; in women, OR 1.90, 95%CI 1.18–3.06). Low and middle monthly household income per capita also had a positive association with muscle weakness among women (OR 1.78, 95%CI 1.37–2.32; OR 1.32, 95%CI 1.01–1.73, respectively). Overweight had a negative association with muscle weakness among men (OR 0.66, 95%CI 0.52–0.83), and obesity was inversely associated with muscle weakness in both sexes (in men, OR 0.49, 95%CI 0.31–0.78; in women, OR 0.69, 95%CI 0.52–0.92).

Conclusions

This study provides HGS values and cutoff points for muscle weakness by age group and sex from a nationally representative sample of older Brazilian adults. The variables associated with muscle weakness slightly differed between men and women. HGS values and cutoff points generated can be used as benchmarks in clinical settings and foster future epidemiological research.
Dynamic changes of CSF clusterin levels across the Alzheimer’s disease continuum
Authors: Tang Lian , Wang Zhi-Bo , Ma Ling-Zhi , Cao Xi-Peng , Tan Lan , Tan Meng-Shan
Published: December 2022

Background

Clusterin is a multifunctional protein, which is associated with the pathogenesis and the development of Alzheimer’s disease (AD). Compared with normal controls, inconsistent results have yielded in previous studies for concentration of cerebrospinal fluid (CSF) clusterin in AD patients. We explored CSF clusterin levels in different pathological processes of AD.

Methods

Following the National Institute on Aging-Alzheimer’s Association (NIA-AA) criteria, we employed on the levels of CSF Aβ42(A), phosphorylated-Tau (T), and total-tau (N). Based on previously published cutoffs and the close correlation between CSF p-tau and t-tau, 276 participants from the publicly available ADNI database with CSF biomarkers were divided into four groups: A-(TN)- (normal Aβ42 and normal p-tau and t-tau; n = 50), A+(TN)- (abnormal Aβ42 and normal p-tau and t-tau; n = 39), A+(TN) + (abnormal Aβ42 and abnormal p-tau or t-tau; n = 147), A-(TN) + (normal Aβ42 and abnormal p-tau or t-tau; n = 40). To assess CSF clusterin levels in AD continuum, intergroup differences in four groups were compared. Pairwise comparisons were conducted as appropriate followed by Bonferroni post hoc analyses. To further study the relationships between CSF clusterin levels and AD core pathological biomarkers, we employed multiple linear regression method in subgroups.

Results

Compared with the A-(TN)- group, CSF clusterin levels were decreased in A+ (TN)- group (P = 0.002 after Bonferroni correction), but increased in the A+(TN) + group and the A-(TN) + group (both P <  0.001 after Bonferroni correction). Moreover, we found CSF clusterin levels are positively associated with CSF Aβ42 (β = 0.040, P <  0. 001), CSF p-tau (β = 0.325, P <  0.001) and CSF t-tau (β = 0.346, P <  0.001).

Conclusions

Our results indicated that there are differences levels of CSF clusterin in different stages of AD pathology. The CSF clusterin level decreased at the early stage are related to abnormal Aβ pathology; and the increased levels are associated with tau pathology and neurodegeneration.
Intense endoplasmic reticulum stress (ERS) / IRE1α enhanced Oxaliplatin efficacy by decreased ABCC10 in colorectal cancer cells
Authors: Liu Xiaohui , Wu Bo , Chen Hong , Sun Haimei , Guo Xiaoxia , Sun Tingyi , Zhou Deshan , Yang Shu
Published: December 2022

Background

Attenuated Oxaliplatin efficacy is a challenge in treating colorectal cancer (CRC) patients, contributory to the failure in chemotherapy and the risks in relapse and metastasis. However, the mechanism of Oxaliplatin de-efficacy during CRC treatment has not been completely elucidated.

Methods

Microarray screening, western blot and qPCR on clinic CRC samples were conducted to select the target gene ABCC10 transporter. The Cancer Genome Atlas data was analyzed to figure out the correlation between the clinical manifestation and ABCC10 expression. ABCC10 knock-down in CRC cells was conducted to identify its role in the Oxaliplatin resistance. Cell counting kit-8 assay was conducted to identify the CRC cell viability and Oxaliplatin IC50. Flow cytometry was conducted to detect the cell apoptosis exposed to Oxaliplatin. The intracellular Oxaliplatin accumulation was measured by ultra-high performance liquid chromatography coupled to tandem mass spectrometry.

Results

CRC patients with higher ABCC10 were prone to relapse and metastasis. Differential ABCC10 expression in multiple CRC cell lines revealed a strong positive correlation between ABCC10 expression level and decreased Oxaliplatin response. In ABCC10 knock-down CRC cells the Oxaliplatin sensitivity was evidently elevated due to an increase of intracellular Oxaliplatin accumulation resulted from the diminished drug efflux. To explore a strategy to block ABCC10 in CRC cells, we paid a special interest in the endoplasmic reticulum stress (ERS) / unfolded protein response (UPR) that plays a dual role in tumor development. We found that neither the inhibition of ERS nor the induction of mild ERS had anti-CRC effect. However, the CRC cell viability was profoundly decreased and the pro-apoptotic factor CHOP and apoptosis were increased by the induction of intense ERS. Significantly, the Oxaliplatin sensitivity of CRC cells was enhanced in response to the intense ERS, which was blocked by inhibiting IRE1α branch of UPR. Finally, we figured out that the intense ERS down-regulated ABCC10 expression via regulated IRE1-dependent decay activity.

Conclusion

Oxaliplatin was a substrate of ABCC10 efflux transporter. The intense ERS/IRE1α enhanced Oxaliplatin efficacy through down-regulating ABCC10 in addition to inducing CHOP. We suggested that introduction of intense ERS/UPR could be a promising strategy to restore chemo-sensitivity when used in combination with Oxaliplatin or other chemotherapeutic drugs pumped out by ABCC10.
Identifying factors associated with of blood pressure using Structural Equation Modeling: evidence from a large Kurdish cohort study in Iran
Authors: Najafi Farid , Moradinazar Mehdi , Rezayan Shahab , Azarpazhooh Reza , Jamshidi Parastoo
Published: December 2022

Background

Identifying the risk factors leading to hypertension can help explain why some populations are at a greater risk for developing hypertension than others. The present study seeks to identify the association between the risk factors of hypertension in 35- to 65-year-old participants in western Iran.

Methods

This cross-sectional study was conducted on 9705 adults from baseline data of Ravansar Non-Communicable Disease (RaNCD) cohort study, in the west region of Iran. Each of the latent variables were confirmed by confirmatory factor analysis. Using Structural Equation Modeling (SEM), we assessed the direct and indirect effects of factors associated with blood pressure.

Results

Socioeconomic status (SES), physical activity, mean of serum lipids, obesity, diabetes and family history of hypertension had a diverse impact on the blood pressure, directly and (or) indirectly. The standardized total effect of SES, physical activity, mean of serum lipids, and obesity were -0.09 vs. -0.14, -0.04 vs. -0.04, 0.13 vs. 0.13 and 0.24 vs. 0.15 in men and women, respectively. Diabetes had a direct relationship with the blood pressure in women (0.03).

Conclusion

With regard to control of high blood pressure, public health interventions must target obesity, lifestyle and other risk related to nutritional status such as hyperlipidemia and hyperglycemia in Iranian population and among those with higher SES.
Oral health status and barriers to oral healthcare among children with cerebral palsy attending a health care center in Kampala, Uganda
Authors: Kachwinya S. M. , Kemoli A. M. , Owino R. , Okullo I. , Bermudez J. , Seminario A. L.
Published: December 2022

Background

Cerebral palsy (CP) is a non-progressive neuromuscular condition diagnosed in childhood. CP as a form of disability, does not cause any specific oral disease. However, some oral conditions are more commonly associated with people with CP compared to the general population. The overarching aim of the current study was to determine the oral hygiene status, gingival status, and the prevalence of dental caries in children with CP attending a leading hospital institution for children with disabilities in Kampala, Uganda. Additionally, we determined the barriers faced by children with CP in accessing oral healthcare.

Methods

This cross-sectional study was carried out at the Comprehensive Rehabilitation Services Uganda hospital in Kampala, Uganda. Our study population consisted of a convenient sample of 90 children diagnosed with CP aged 3–17 years and their caregivers. A validated and interviewer administered structured questionnaire was used to collect socio-demographic data of the participants. A modified World Health Organization oral health assessment form for those aged 3–17 years was used to gather data on oral health status (plaque score, gingival bleeding and dental caries.) The data was subjected to statistical tests with critical value set up at 5%.

Results

Only 32.2% of the children evaluated had adequate oral hygiene, while 44.4% of the children experienced gingival bleeding. The prevalence of dental caries for both deciduous and permanent dentition was 63.3%, with DMFT values of 3.8 ± 4.5. The most common barrier reported by the caregivers was the challenge in modality of transportation availability from the children’s homes to the health facilities (34.4%).

Conclusions

Children with CP in the study population have a significant prevalence of oral diseases and face several barriers to oral healthcare. Results from this study aim to provide relevant support to advocate for a nationwide change in policy to improve access to dental care to decrease the burden of oral diseases in children with special healthcare needs.
Comparison of spheno-occipital synchondrosis maturation stages with three-dimensional assessment of mandibular growth
Authors: Al-Gumaei Waseem S. , Al-Attab Reem , Al-Tayar Barakat , Al-hadad Saba A. , Alyafrusee Enas S. , Al-mashraqi Abeer A. , Alhashimi Najah , Zheng Yan , Alhammadi Maged S.
Published: December 2022

Background

This study aimed to compare spheno-occipital synchondrosis (SOS) maturation stages with a three-dimensional assessment of mandibular growth.

Methods

This is a cross-sectional study of a retrospective type, in which cone-beam computed tomography (CBCT) images of 500 patients aged 6 to 25 years (226 males and 274 females) were analyzed. The SOS was evaluated using the four-stage scoring system; completely open, partially fused, semi-fused, or completely fused. The SOS scoring and three-dimensional cephalometric measurements were analyzed by Invivo 6.0.3 software. Descriptive and analytical statistics were performed, and aP-value < 0.05 was considered statistically significant.

Results

There was a statistically significant difference in mandibular measurements among SOS maturation stages in both sexes (P < 0.05). The skeletal growth increments of mandibular variables across the SOS stages had higher mean differences between SOS stages 2 and 3 than those between stages 1 and 2 and stages 3 and 4 in both sexes. The mandibular growth curves increased with chronological age (earlier in females) and SOS maturation stages (mostly in stages 1, 2, and 3 than stage 4).

Conclusions

The SOS maturation stages are valid and reliable mandibular skeletal indicators as evaluated with three-dimensional cephalometric mandibular measurements. The findings of growth increments and constructed growth curves of mandibular growth might be helpful in diagnosis and treatment planning.