bluuebunny/crossref_metadata_2025 huggingface dataset:
Calprotectin (S100A8/S100A9) detects inflammatory activity in rheumatoid arthritis patients receiving tocilizumab therapy
Authors: Gernert Michael , Schmalzing Marc , Tony Hans-Peter , Strunz Patrick-Pascal , Schwaneck Eva Christina , Fröhlich Matthias
Published: August 2022

Background

Assessing serological inflammation is difficult in tocilizumab (TCZ)-treated rheumatoid arthritis (RA) patients, as standard inflammation parameters, like erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), are influenced by interleukin-6-receptor inhibition. Calprotectin in the serum, also named S100A8/S100A9, might be a more useful inflammation parameter in TCZ-treated patients.

Methods

Sixty-nine RA patients taking TCZ were included. Serum-calprotectin levels were assessed, as well as ESR, CRP, need for a change in disease-modifying anti-rheumatic drugs due to RA activity (= active RA), and the RA clinical disease activity score (CDAI). Forty-five RA patients taking tumor-necrosis factor-inhibitors (TNFi) were investigated for the same parameters.

Results

TCZ-treated patients with active RA had higher calprotectin values than not active RA patients (4155.5 [inter quartile range 1865.3–6068.3] vs 1040.0 [676.0–1638.0] ng/ml, P < 0.001). A calprotectin cut-off value of 1916.5 ng/ml resulted in a sensitivity and specificity of 80.0 %, respectively, for the detection of RA disease activity. Calprotectin values correlated with CDAI-scores (r = 0.228; P = 0.011). ESR and CRP were less suitable to detect RA activity in TCZ-treated patients. Also TNFi-treated patients with active RA had higher calprotectin values compared to not active RA (5422.0 [3749.0–8150.8] vs 1845.0 [832.0–2569.0] ng/ml, P < 0.001). The calprotectin value with the best sensitivity and specificity for detecting RA activity was 3690.5 ng/ml among TNFi-treated patients.

Conclusion

Calprotectin in the serum can be a useful inflammation parameter despite TCZ-treatment.
First clinical application of cord blood mesenchymal stromal cells in children with multi-drug resistant nephrotic syndrome
Authors: Morello William , Budelli Silvia , Bernstein Daniel Ari , Montemurro Tiziana , Montelatici Elisa , Lavazza Cristiana , Ghio Luciana , Edefonti Alberto , Peruzzi Licia , Molino Daniela , Benetti Elisa , Gianoglio Bruno , Mehmeti Florian , Catenacci Laura , Rotella Jessica , Tamburello Chiara , Moretta Antonia , Lazzari Lorenza , Giordano Rosaria , Prati Daniele , Montini Giovanni
Published: August 2022

Background and objectives

Children with multi-drug resistant idiopathic nephrotic syndrome (MDR-INS) usually progress to end-stage kidney disease with a consistent risk of disease recurrence after transplantation. New therapeutic options are needed for these patients. Mesenchymal stromal cells (MSCs) are multipotential non-hematopoietic cells with several immunomodulatory properties and growing clinical applications. Cord blood-derived MSC have peculiar anti-inflammatory and immunosuppressive properties. We aimed at assessing safety and efficacy of cord-blood-derived MSCs (CB-MSCs) in children with MDR-INS.

Design, setting, participants

Prospective, open-label, single arm phase I–II pilot study. Pediatric patients with MDR-INS, resistant to at least two lines of therapy, were enrolled. Allogenic CB-MSCs were administered intravenously on days 0, 14, and 21 at a dose of 1.5 × 106 cells/kg. Patients were followed for at least 12 months. The primary outcomes were safety and toxicity. The secondary outcome was remission at 12 months evaluated by urinary protein/urinary creatinine ratio (uPr/uCr). Circulating regulatory T cells (Tregs) were monitored.

Results

Eleven pediatric patients with MDR-INS (10 females, median age 13 years) resistant to a median of 3 previous lines of therapy were enrolled. All patients completed the CB-MSC infusion schedule. No patient experienced any infusion-related adverse event or toxicity. Nine patients were assessable for efficacy. At the 12 months follow-up after the treatment, the median uPr/uCr did not change significantly from baseline (8.13 vs. 9.07; p = 0.98), while 3 patients were in partial or complete remission. A lower baseline uPr/uCr was a predictor of remission (2.55 vs. 8.74; p = 0.0238). Tregs count was not associated with CB-MSCs therapy.

Conclusions

CB-MSCs are safe and may have a role in the immunosuppressive therapy of pediatric patients with MDR-INS. This preliminary experience paves the way toward further phase II studies addressing MSC efficacy in immune-mediated kidney diseases.
Emerging role of mesenchymal stromal cells (MSCs)-derived exosome in neurodegeneration-associated conditions: a groundbreaking cell-free approach
Authors: Yari Hadi , Mikhailova Maria V. , Mardasi Mahsa , Jafarzadehgharehziaaddin Mohsen , Shahrokh Somayeh , Thangavelu Lakshmi , Ahmadi Hosein , Shomali Navid , Yaghoubi Yoda , Zamani Majid , Akbari Morteza , Alesaeidi Samira
Published: August 2022

Accumulating proofs signify that pleiotropic effects of mesenchymal stromal cells (MSCs) are not allied to their differentiation competencies but rather are mediated mainly by the releases of soluble paracrine mediators, making them a reasonable therapeutic option to enable damaged tissue repair. Due to their unique immunomodulatory and regenerative attributes, the MSC-derived exosomes hold great potential to treat neurodegeneration-associated neurological diseases. Exosome treatment circumvents drawbacks regarding the direct administration of MSCs, such as tumor formation or reduced infiltration and migration to brain tissue. Noteworthy, MSCs-derived exosomes can cross the blood–brain barrier (BBB) and then efficiently deliver their cargo (e.g., protein, miRNAs, lipid, and mRNA) to damaged brain tissue. These biomolecules influence various biological processes (e.g., survival, proliferation, migration, etc.) in neurons, oligodendrocytes, and astrocytes. Various studies have shown that the systemic or local administration of MSCs-derived exosome could lead to the favored outcome in animals with neurodegeneration-associated disease mainly by supporting BBB integrity, eliciting pro-angiogenic effects, attenuating neuroinflammation, and promoting neurogenesis in vivo. In the present review, we will deliver an overview of the therapeutic benefits of MSCs-derived exosome therapy to ameliorate the pathological symptoms of acute and chronic neurodegenerative disease. Also, the underlying mechanism behind these favored effects has been elucidated.
Widespread retina and optic nerve neuroinflammation in enucleated eyes from glaucoma patients
Authors: Rutigliani Carola , Tribble James R. , Hagström Anna , Lardner Emma , Jóhannesson Gauti , Stålhammar Gustav , Williams Pete A.
Published: August 2022

Neuroinflammation is recognized as a key component of neurodegenerative disease. In glaucoma, a common neurodegenerative disease and the leading cause of irreversible blindness, the evidence for neuroinflammation in patients is lacking. Animal models have demonstrated significant pro-inflammatory activation of resident glia in the retina, as well as influx of blood-derived monocytes and pro-inflammatory factors. Confirmation of this in human donor tissue has been challenging due to a lack of well-preserved and well-characterized post-mortem tissue. To address this we utilize archived, wax embedded eyes fixed immediately following enucleation from living glaucoma patients. We compared glaucoma to control eyes (enucleated for uveal melanoma where the tumor did not impact the central retina or optic nerve). We performed immunolabelling for neurodegenerative and glial markers (CD45, CD163, IBA1, GFAP, Vimentin) which were quantified by high-resolution light microscopy and image analysis in FIJI. Glaucoma eyes demonstrated significant neural loss consistent with advanced neurodegeneration. IBA1 and GFAP were significantly increased in the retina and optic nerve head of the glaucomatous eyes indicating that significant neuroinflammation had occurred which support findings in animal models. Inflammation is a treatable symptom of many diseases and as such, identification of earlier inflammatory processes in glaucoma could be important for potential future treatment options.
State capture through indemnification demands? Effects on equity in the global distribution of COVID-19 vaccines
Authors: Gorodensky Ariel , Kohler Jillian C.
Published: August 2022

Background

State capture by the pharmaceutical industry is a form of corruption whereby pharmaceutical companies shift laws or policies about their products away from the best interest of the public and toward their private benefit. State capture often limits equitable access to pharmaceutical products by inflating drug prices and increasing barriers to entry into the pharmaceutical industry. During the COVID-19 pandemic, the high demand and low supply of COVID-19 vaccines has put governments that manage vaccine procurement at risk of capture by COVID-19 vaccine manufacturers, both through bilateral deals and the COVID-19 Vaccine Global Access (COVAX) Facility; this threatens equity in the global distribution of these products. The purpose of this study is to determine whether COVID-19 vaccine manufacturers have been engaging in state capture and, if so, to examine the implications of state capture on equitable access to COVID-19 vaccines.

Methods

A targeted rapid literature search was conducted on state capture by the pharmaceutical industry. Results were limited to journal articles, books, and grey literature published between 2000 and 2021 in or translated to English. A literature search was also conducted for information about state capture during the COVID-19 pandemic. Results were limited to media articles published between March 2020 and July 2021 in or translated to English. All articles were qualitatively analyzed using thematic analysis.

Results

COVID-19 vaccine manufacturers have demanded financial indemnification from national governments who procure their vaccines. While most high-income countries are legislatively capable of indemnifying vaccine manufacturers, many low- and middle-income countries (LMICs) are not. A number of LMICs have thus changed their legislations to permit for manufacturers’ indemnification demands. Amending legislation in this way is state capture and has led to delays in LMICs and vaccine manufacturers signing procurement contracts. This has critically stalled access to vaccines in LMICs and created disparities in access to vaccines between high-income countries and LMICs.

Conclusions

COVID-19 vaccine manufacturers’ indemnification demands constitute state capture in many LMICs though not in high-income countries; this has enhanced global COVID-19 vaccine inequities. Results underscore the need to find alternatives to financial indemnification that do not hinder critical efforts to end the pandemic.
Pattern in ejecta curtain generated by the impact into granular targets of various sized particles and application to the ejecta curtain observed in the Hayabusa2 impact experiment
Authors: Kadono Toshihiko , Suzuki Ayako I. , Suetsugu Ryo , Shimaki Yuri , Hasegawa Sunao
Published: August 2022

We conducted impact experiments using targets composed of particles with size distributions and projectiles with a size larger than or comparable with the maximum size of particles in targets. The pattern and particle concentration in the ejecta curtain were investigated. The results show three types of ejecta curtain features: (i) filament pattern extending throughout the entire curtain and high concentration, (ii) filament pattern and low concentration, and (iii) mesh-like pattern with a structure on smaller scales than the entire curtain and low concentration. When the target consists of particles using a bimodal size distribution with size differences of more than one order of magnitude, the filament pattern appears, exhibiting case (i). If the target consists of particles with various sizes with size differences of more than one order of magnitude, the filament pattern appears, but the concentration decreases, appearing the features of case (ii). Case (iii) occurs when the target consists of particles with a single size or when the mass of particles with a certain size is dominant. Thus, the size distribution of the particles in the targets determines the pattern and particle concentration in the ejecta curtain. Based on these results, we confirm that the pattern in the ejecta curtain caused by the impact of the Small Carry-on Impactor (SCI) in the Hayabusa2 mission showing case (i) is consistent with the evaluated sizes and masses of grains and boulders in the ejecta curtain.

Graphical Abstract
Positron range in combination with point-spread-function correction: an evaluation of different implementations for [124I]-PET imaging
Authors: Kertész Hunor , Conti Maurizio , Panin Vladimir , Cabello Jorge , Bharkhada Deepak , Beyer Thomas , Papp Laszlo , Jentzen Walter , Cal-Gonzalez Jacobo , Herraiz Joaquín L. , López-Montes Alejandro , Rausch Ivo
Published: August 2022

Aim

To evaluate the effect of combining positron range correction (PRC) with point-spread-function (PSF) correction and to compare different methods of implementation into iterative image reconstruction for 124I-PET imaging.

Materials and methods

Uniform PR blurring kernels of 124I were generated using the GATE (GEANT4) framework in various material environments (lung, water, and bone) and matched to a 3D matrix. The kernels size was set to 11 × 11 × 11 based on the maximum PR in water and the voxel size of the PET system. PET image reconstruction was performed using the standard OSEM algorithm, OSEM with PRC implemented before the forward projection (OSEM+PRC simplified) and OSEM with PRC implemented in both forward- and back-projection steps (full implementation) (OSEM+PRC). Reconstructions were repeated with resolution recovery, point-spread function (PSF) included. The methods and kernel variation were validated using different phantoms filled with 124I acquired on a Siemens mCT PET/CT system. The data was evaluated for contrast recovery and image noise.

Results

Contrast recovery improved by 2–10% and 4–37% with OSEM+PRC simplified and OSEM+PRC, respectively, depending on the sphere size of the NEMA IQ phantom. Including PSF in the reconstructions further improved contrast by 4–19% and 3–16% with the PSF+PRC simplified and PSF+PRC, respectively. The benefit of PRC was more pronounced within low-density material. OSEM-PRC and OSEM-PSF as well as OSEM-PSF+PRC in its full- and simplified implementation showed comparable noise and convergence. OSEM-PRC simplified showed comparably faster convergence but at the cost of increased image noise.

Conclusions

The combination of the PSF and PRC leads to increased contrast recovery with reduced image noise compared to stand-alone PSF or PRC reconstruction. For OSEM-PRC reconstructions, a full implementation in the reconstruction is necessary to handle image noise. For the combination of PRC with PSF, a simplified PRC implementation can be used to reduce reconstruction times.
Central retinal artery occlusion secondary to presumed traumatic carotid artery dissection in a healthy child
Authors: Mazzeo Thiago José Muniz Machado , Freire Raimunda Cristina Mendonça , Filho Luciano Fuzzato , Machado Cleide Guimarães , Gomes André Marcelo Vieira
Published: August 2022

Purpose

To describe a rare case of a 13 years-old healthy child that presented CRAO secondary to carotid artery dissection, which occurred after a neck rotation movement.

Methods

Case report with prospective literature review.

Patients

One patient described in the case report.

Results

Not applicable.

Discussion/conclusion

Internal carotid artery dissection is a rare condition, specially in children, that can lead to serious cerebral-ocular ischemic events. It may occur due to direct vessel trauma or spontaneously. Prompt imaging screening is of paramount importance because early antithrombotic treatment or surgical intervention may significantly reduce the incidence of devastating ischemic events, such as stroke or central retinal artery occlusion.
Use of cefepime, meropenem, or piperacillin/tazobactam as initial treatment for febrile neutropenia in patients with hematological malignancy — a real-life experience
Authors: Karim Najmul , Kabir Alamgir , Islam Manirul , Biswas Akhil Ranjan , Wasim Mohammed , Alam Mahbubul , Chowdhury Nobendu , Islam Mohammed Nadimul , Tabassum Tamanna , Hasan Mohammad Jahid
Published: August 2022

Background

Antimicrobials like fourth-generation cephalosporins, carbapenems, or β-lactams are widely used in treatment of febrile neutropenia (FN). The present study aimed to compare the efficacy of cefepime, meropenem, and piperacillin/tazobactam as initial treatment for chemo-induced FN in patients with hematological malignancy.

Methods

This was an observational study conducted in the Department of Hematology of Dhaka Medical College Hospital from July 2020 to June 2021 including 99 adult FN patients with hematological malignancy who were randomized equally to three treatment arms to receive cefepime, meropenem, or piperacillin/tazobactam as an empirical antibiotic. Response to therapy was defined as improvement in symptoms (e.g., defervescence) or in laboratory values including neutrophil counts on day 3 and day 7 after the initiation of the therapy. Chi-square test and Fisher’s exact test were used to compare the efficacy of the treatment regimens.

Results

Response rate to initial treatment with different antibiotic regimens was similar without any statistically significant difference (60.6%, 63.6%, and 51.5% on day 3 and 63.6%, 75.8%, and 66.7% on day 7 for cefepime, meropenem, and piperacillin/tazobactam, respectively, p-value > 0.05) irrespective of underlying diagnosis, the severity of neutropenia, and cause of fever.

Conclusion

Initial therapy with cefepime, meropenem, or piperacillin/tazobactam is safe and equally effective in chemo-induced FN in patients with hematological malignancy. This finding may be considered in clinical practice for optimum therapeutic outcomes.
Utilization of an Electronic Patient-Reported Outcome Platform to Evaluate the Psychosocial and Quality-of-Life Experience Among a Community Sample of Ovarian Cancer Survivors
Authors: Hlubocky Fay J. , Daugherty Christopher K. , Peppercorn Jeffery , Young Karen , Wroblewski Kristen E. , Yamada Seiko Diane , Lee Nita K.
Published: August 2022

PURPOSE

Novel distress screening approaches using electronic patient-reported outcome (ePRO) measurements are critical for the provision of comprehensive quality community cancer care. Using an ePRO platform, the prevalence of psychosocial factors (distress, post-traumatic growth, resilience, and financial stress) affecting quality of life in ovarian cancer survivors (OCSs) was examined.

METHODS

A cross-sectional OCS sample from the National Ovarian Cancer Coalition-Illinois Chapter completed web-based clinical, sociodemographic, and psychosocial assessment using well-validated measures: Hospital Anxiety/Depression Scale-anxiety/depression, Post-traumatic Growth Inventory, Brief Resilience Scale, comprehensive score for financial toxicity, and Functional Assessment of Cancer Therapy-Ovarian (FACT-O/health-related quality of life [HRQOL]). Correlational analyses between variables were conducted.

RESULTS

Fifty-eight percent (174 of 300) of OCS completed virtual assessment: median age 59 (range 32-83) years, 94.2% White, 60.3% married/in domestic partnership, 59.6% stage III-IV, 48.8% employed full-time/part-time, 55.2% had college/postgraduate education, 71.9% completed primary treatment, and median disease duration 6 (range < 1-34) years. On average, OCS endorsed normal levels of anxiety (mean ± standard deviation = 6.9 ± 3.8), depression (4.1 ± 3.6), mild total distress (10.9 ± 8.9), high post-traumatic growth (72.6 ± 21.5), normal resilience (3.7 ± 0.72), good FACT-O-HRQOL (112.6 ± 22.8), and mild financial stress (26 ± 10). Poor FACT-O emotional well-being was associated with greater participant distress ( P < .001). Partial correlational analyses revealed negative correlations between FACT-O-HRQOL and anxiety ( r = –0.65, P < .001), depression ( r = –0.76, P < .001), and total distress ( r = –0.92, P < .001). Yet, high FACT-O-HRQOL was positively correlated with post-traumatic coping ( r = 0.27; P = .006) and resilience ( r = 0.63; P < .001).

CONCLUSION

ePRO assessment is feasible for identification of unique psychosocial factors, for example, financial toxicity and resilience, affecting HRQOL for OCS. Future investigation should explore large-scale, longitudinal ePRO assessment of the OCS psychosocial experience using innovative measures and community-based advocacy populations.
EphrinB2 Inhibition and Pembrolizumab in Metastatic Urothelial Carcinoma
Authors: Sadeghi Sarmad , Quinn David , Dorff Tanya , Pal Sumanta , Groshen Susan , Tsao-Wei Denice , Parikh Rahul , Devitt Michael , Parikh Mamta , Jackovich Alexandra , Ruel Nora , Vogelzang Nicholas , Burgess Earle , Siddiqi Imran , Gill Inderbir S. , Lara Primo N. , Dreicer Robert , Gill Parkash S.
Published: August 2022

PURPOSE

Patients with metastatic urothelial carcinoma have poor prognosis after failure of standard first-line chemotherapy. Immune check point programmed death 1-programmed death ligand 1 antibodies have low response rates and thus there exists a major unmet need.

MATERIALS AND METHODS

In this phase II trial, patients with metastatic urothelial carcinoma that recurred or progressed after platinum-based chemotherapy received soluble EphB4-human serum albumin (sEphB4-HSA) in combination with pembrolizumab. The primary end points were tolerability and overall survival (OS). The secondary end points were progression-free survival (PFS), objective response rate (ORR), duration of response, and toxicity. The expression of sEphB4-HSA target EphrinB2 was correlated with outcomes.

RESULTS

Seventy patients were enrolled. The median follow up was 22.9 months (range, 1.3-54.7). The regimen had acceptable toxicity. In the intent-to-treat analysis (N = 70), the median OS was 14.6 months (95% CI, 9.2 to 21.5). Twenty-six (37%) patients had an objective response (95% CI, 26 to 48). The median PFS was 4.1 (95% CI, 1.5 to 5.7) months. Forty-six (66%) patients expressed EphrinB2, and among them, the median OS was 21.5 months (95% CI, 12.4 to not reached), the ORR was 52% (95% CI, 37 to 67), including a complete response rate of 24% (11 of 46; 95% CI, 12 to 36). The median PFS was 5.7 (95% CI, 2.7 to 27.9) months. Response was maintained at 6, 12, and 24 months in 88%, 74%, and 69% of the patients, respectively.

CONCLUSION

The combination of sEphB4-HSA and pembrolizumab appears synergistic with improved OS and ORR compared with historical data for programmed death 1/programmed death ligand 1 monotherapy.
A Kiss across the Ocean
Authors: Rodríguez Richard T.
Published: August 2022

In A Kiss across the Ocean Richard T. Rodríguez examines the relationship between British post-punk musicians and their Latinx audiences in the United States since the 1980s. Melding memoir with cultural criticism, Rodríguez spotlights a host of influential bands and performers including Siouxsie and the Banshees, Adam Ant, Bauhaus, Soft Cell, Frankie Goes to Hollywood, and Pet Shop Boys. He recounts these bands’ importance for him and other Latinx kids and discusses their frequent identification with these bands’ glamorous performance of difference. Whether it was Siouxsie Sioux drawing inspiration from Latinx contemporaries and cultural practices or how Soft Cell singer Marc Almond’s lyrics were attuned to the vibrancy of queer Latinidad, Rodríguez shows how Latinx culture helped shape British post-punk. He traces the fandom networks that link these groups across space and time to illuminate how popular music establishes and facilitates intimate relations across the Atlantic. In so doing, he demonstrates how the music and styles that have come to define the 1980s hold significant sway over younger generations equally enthused by their matchlessly pleasurable and political reverberations.
Mutation patterns of resistance genes for macrolides, aminoglycosides, and rifampicin in nontuberculous mycobacteria isolates from Kenya
Authors: Mwangi Zakayo , Naeku Grace , Mureithi Marianne , Onyambu Frank , Bulimo Wallace
Published: August 2022

Background: Nontuberculous mycobacteria (NTM) treatment constitutes a macrolide-based antibiotic regimen in combination with aminoglycosides for Rapid-Growing mycobacteria (RGM), and rifampicin for Slow-Growing mycobacteria (SGM). Mutations in the anti-NTM drug target regions promote NTM evolution to mutant strains that are insusceptible to NTM drugs leading to treatment failure. We, therefore, described the mutation patterns of anti-NTM drug target genes including rrl, rrs, and rpoB in NTM isolates from Kenya. 

Methods: We carried out a cross-sectional study that included 122 NTM obtained from the sputum of symptomatic tuberculosis-negative patients in Kenya. All the 122 NTM underwent targeted sequencing of the rrl gene. The 54 RGM were also sequenced for rrs, and the 68 SGM were sequenced for rpoB genes using ABI 3730XL analyzer. The obtained sequences were aligned to their wild-type reference sequences for each gene using Geneious then mutations were identified. Pearson chi-square at 95% confidence interval tested the association of NTM to mutation patterns for each gene.

Results: Twenty-eight (23%) of the NTM were resistant to at least one of the antibiotics used in the macrolide-based treatment. Twelve (10.4%) of NTM were macrolide resistant, with 7(58.3%) of RGM and 5(41.7%) of SGM having mutations in the rrl gene. For ten (83.3%) NTM, mutations were found at position 2058, while for two (16.6%) NTM, mutations were found at position 2059. Six (11.1%) of the 54 RGM exhibited mutations in the aminoglycoside target gene rrs at location 1408. Ten (14.7%) of the 68 SGM were resistant to rifampicin, with 40 percent having mutations at codon 531 in the rpoB gene.  

Conclusion: We demonstrated a significant level of drug resistance for macrolides, aminoglycosides and rifampicin in NTM isolated from symptomatic TB negative patients in Kenya.
The Main Problems of Small Business in the Context of New Sanctions Against the Russian Federation
Authors: Levkina Nataliya
Published: August 2022

The introduction by Western countries of a new package of sanctions against the Russian Federation at the beginning of 2022 negatively affected the activities of almost all legal entities. Among the most affected economic entities are small enterprises, a significant part of which specializes in retail trade. This work is devoted to identifying the main problems of the small business sector in connection with the new sanctions against Russia and the retaliatory measures taken. The object of the study was the Ostrovok store, specializing in the retail trade of trendy toys and related products. The results of the study can be used to further study the impact of sanctions on the country's economy in general and certain categories of small businesses in particular, as well as to develop effective measures of state support.
Consolidation and Innovation Concept of Managing the Development of High-Tech Industrial Complexes
Authors: Daneykin Y.
Published: August 2022

The article is devoted to the actual topic of achieving technological sovereignty based on the innovative development of high-tech sectors of the Russian economy.The author's concept of managing the development of a high-tech industrial complex at the mesolevel is presented. The concept of a high-tech industrial complex has been clarified. The concept is formed on the basis of the interconnected development and use of methodological provisions of the theory of economic systems, ecosystem approach, mesoecnomics of network structures, theories of innovative development, the concept of open innovation, the concept of technological modernization, the concept of technological modes, technological trajectories, modes, models of innovative activity of companies based on a systematic approach. The choice of the principles of the new concept is substantiated: a systematic approach to solving problems, the priority of developing meso-level innovation ecosystems, consolidating efforts in critical (priority) and promising areas for achieving technological sovereignty, focusing on innovative activity and entrepreneurship, orienting planning of the future.
Estructuras y mecanismos mentales que desde una perspectiva geométrica modelan y articulan el aprendizaje de valor y vector propio en R2
Authors:   Pontificia Universidad Católica de Valparaíso, Parraguez González Marcela , Roa-Fuentes Solange ,   Universidad Industrial de Santander, Jiménez Alarcón Raúl ,   Universidad Católica del Norte, Betancur Sánchez Alexander ,   Universidad Industrial de Santander
Published: August 2022

Se proponen dos descomposiciones genéticas (DG’s) refinadas, como resultado de la aplicación del Ciclo de investigación de APOE, que describen estructuras y mecanismos mentales para el concepto de valor y vector propio en dos casos de estudio. La primera DG0 modela los conocimientos previos que estudiantes de secundaria (14 – 16 años) deben lograr para construir en la universidad dicho concepto en R2, —este modelo se sustenta en la rotación de vectores y el concepto de múltiplo escalar—. La segunda DG1 modela en R2 la construcción de valor y vector propio en estudiantes universitarios de primer año y muestra cómo apoyarse en tópicos de secundaria para estructurar dicho concepto a partir de relaciones entre la transformación lineal y el vector múltiplo escalar como generador de una recta. El análisis de datos permite validar las DG’s y bosquejar un camino cognitivo para el aprendizaje del concepto de valor y vector propio en R2.
Physician Discretion and Patient Pick-up: How Familiarity Encourages Multitasking in the Emergency Department
Authors: Niewoehner Robert J. , Diwas KC , Staats Bradley
Published: August 2022

Patient demand for emergency medical services has never been greater. In the United States, as fewer people access medical care through a primary care provider, more people access care through the hospital emergency department (ED). Unlike other types of queuing systems, however, the ED allows physicians discretion in whom they serve. That is, ED queues do not operate solely under a policy of “first-come, first-served, by severity.” Therefore, we wanted to know: “What leads physicians to select which patients, and how many patients, they will treat?” We explore how familiarity between peer physicians affects patient selection and the chosen multitasking level, a process more commonly known in the ED as “patient pick-up.” We find greater familiarity leads to an increase in patient pick-up rate, observed multitasking, and shorter patient wait time, with no identifiable negative impact to patient processing time or length of stay.
Rare health conditions 61: Binswanger's disease, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Huntington's disease and progressive supranuclear palsy
Authors: Barber Chris
Published: August 2022

The purpose of this series is to briefly highlight a range of rare health conditions. Rare health conditions are those that affect no more than 1 person in every 2000. Many healthcare assistants and nurses will encounter patients with these conditions given their wide range. This 61st article will explore four rare forms of dementia.
Advising patients on physical activity and asthma
Authors: Henry Heather
Published: August 2022

Heather Henry explains how nurses can provide information on how exercise can affect patients with asthma
Comparison of carbon fibre and titanium intramedullary nails in orthopaedic oncology
Authors: Yeung Caleb M. , Bhashyam Abhiram R. , Groot Olivier Q. , Merchan Nelson , Newman Erik T. , Raskin Kevin A. , Lozano-Calderón Santiago A.
Published: August 2022

Aims

Due to their radiolucency and favourable mechanical properties, carbon fibre nails may be a preferable alternative to titanium nails for oncology patients. We aim to compare the surgical characteristics and short-term results of patients who underwent intramedullary fixation with either a titanium or carbon fibre nail for pathological long-bone fracture.

Methods

This single tertiary-institutional, retrospectively matched case-control study included 72 patients who underwent prophylactic or therapeutic fixation for pathological fracture of the humerus, femur, or tibia with either a titanium (control group, n = 36) or carbon fibre (case group, n = 36) intramedullary nail between 2016 to 2020. Patients were excluded if intramedullary fixation was combined with any other surgical procedure/fixation method. Outcomes included operating time, blood loss, fluoroscopic time, and complications. Fisher’s exact test and Mann-Whitney U test were used for categorical and continuous outcomes, respectively.

Results

Patients receiving carbon nails as compared to those receiving titanium nails had higher blood loss (median 150 ml (interquartile range (IQR) 100 to 250) vs 100 ml (IQR 50 to 150); p = 0.042) and longer fluoroscopic time (median 150 seconds (IQR 114 to 182) vs 94 seconds (IQR 58 to 124); p = 0.001). Implant complications occurred in seven patients (19%) in the titanium group versus one patient (3%) in the carbon fibre group (p = 0.055). There were no notable differences between groups with regard to operating time, surgical wound infection, or survival.

Conclusion

This pilot study demonstrates a non-inferior surgical and short-term clinical profile supporting further consideration of carbon fibre nails for pathological fracture fixation in orthopaedic oncology patients. Given enhanced accommodation of imaging methods important for oncological surveillance and radiation therapy planning, as well as high tolerances to fatigue stress, carbon fibre implants possess important oncological advantages over titanium implants that merit further prospective investigation. Level of evidence: III, Retrospective study Cite this article: Bone Jt Open 2022;3(8):648–655.
Evaluation of low-cost capacitive moisture sensors in three types of soils in the Cerrado, Brazil
Authors: Pereira Rodrigo Moura , Sandri Delvio , Silva Júnior João José da
Published: August 2022

Soil moisture sensors enabled new automation and computerization solutions in agriculture. However, its use still requires prior calibrations to attest its accuracy to estimate soil moisture. Thus, in this study a prototype for soil moisture monitoring was developed using the capacitive sensor SKU:SEN0193 integrated with the Arduino microcontroller. The prototype was calibrated based on the relationship between volumetric moisture and sensor output voltage in deformed samples of Red-yellow Latosol (RYL), Regolitic Neosol (RN), and Red Latosol (RL) of the Cerrado region, Federal District, Brazil. The calibration of sensors resulted in a second-degree polynomial model with R² between 0.93 and 0.96 for RYL, 0.89 and 0.92 for RN, and 0.86 and 0.88 for RL. Root mean square errors (RMSE) of volumetric moisture were 0.08, 0.12, and 0.15 cm3.cm-3 for RYL, RN, and RL, respectively. Sensors at operating voltage of 5.00 V showed less variability of readings, with coefficient of variation (CV) between 0.21 and 1.54%, while sensors at 3.30 V showed CVs between 3.27 and 17.84%. It is recommended to calibrate the SKU:SEN0193 for each soil type in order to obtain reliable estimates of water content for RYL, RN, and RL.
Systemic RNA Interference Defective (SID) genes modulate dopaminergic neurodegeneration in C. elegans
Authors: Gaeta Anthony L. , Nourse J. Brucker , Willicott Karolina , McKay Luke E. , Keogh Candice M. , Peter Kylie , Russell Shannon N. , Hamamichi Shusei , Berkowitz Laura A. , Caldwell Kim A. , Caldwell Guy A.
Published: August 2022

The fine-tuning of gene expression is critical for all cellular processes; aberrations in this activity can lead to pathology, and conversely, resilience. As their role in coordinating organismal responses to both internal and external factors have increasingly come into focus, small non-coding RNAs have emerged as an essential component to disease etiology. Using Systemic RNA interference Defective (SID) mutants of the nematodeCaenorhabditis elegans, deficient in gene silencing, we examined the potential consequences of dysfunctional epigenomic regulation in the context of Parkinson’s disease (PD). Specifically, the loss of either thesid-1orsid-3genes, which encode a dsRNA transporter and an endocytic regulatory non-receptor tyrosine kinase, respectively, conferred neuroprotection to dopaminergic (DA) neurons in an established transgenicC.elegansstrain wherein overexpression of human α-synuclein (α-syn) from a chromosomally integrated multicopy transgene causes neurodegeneration. We further show that knockout of a specific microRNA,mir-2, attenuates α-syn neurotoxicity; suggesting that the native targets ofmir-2-dependent gene silencing represent putative neuroprotective modulators. In support of this, we demonstrated that RNAi knockdown of multiplemir-2targets enhanced α-syn-induced DA neurodegeneration. Moreover, we demonstrate thatmir-2overexpression originating in the intestine can induce neurodegeneration of DA neurons, an effect that was reversed by pharmacological inhibition of SID-3 activity. Interestingly,sid-1mutants retainedmir-2-induced enhancement of neurodegeneration. Transcriptomic analysis of α-syn animals with and without asid-1mutation revealed 27 differentially expressed genes with human orthologs related to a variety of diseases, including PD. Among these waspgp-8, encoding a P-glycoprotein-related ABC transporter. Notably,sid-1;pgp-8double mutants abolished the neurodegeneration resulting from intestinalmir-2overexpression. This research positions known regulators of small RNA-dependent gene silencing within a framework that facilitates mechanistic evaluation of epigenetic responses to exogenous and endogenous factors influencing DA neurodegeneration, revealing a path toward new targets for therapeutic intervention of PD.
Functional activity limitation of leprosy cases in an endemic area in Indonesia and recommendations for integrated participation program in society
Authors: Menaldi Sri Linuwih , Harini Melinda , Nelfidayani Nelfidayani , Irawati Yunia , Setiono Steven , Wahyuni Luh Karunia , Rahayu Tri , Andayani Gitalisa , Friska Dewi , Nugraha Boya
Published: August 2022

Background

Leprosy continues to be a health problem in Indonesia, with incidence reaching over 10,000 new cases by 2021. Leprosy-related disabilities cause limitation of patients’ activity and participation in social activities. To date, no studies have been conducted in Indonesia which investigates disability in terms of bodily function, structure impairment, limitations in performing daily activities, and restrictions in participation in social activities in leprosy patients. This study is aimed to determine the demographic and clinical characteristics that might affect functional activity limitations of leprosy patients in endemic areas in Indonesia.

Methods and findings

A cross-sectional study was conducted on 267 retrospectively-diagnosed cases of leprosy. The Screening of Activity Limitation and Safety Awareness (SALSA) scale was used to measure functional activity limitation, which comprises five domains: vision, mobility, self-care, work with hands, and dexterity. Differences among variables were evaluated using Kruskal-Wallis and Mann-Whitney test. The mean age of participants was 51.89±13.66 years, the majority of which were men (62.5%), uneducated (48.3%), and classified as type 2 in the World Health Organization (WHO) disability grading for hands and feet (66.3% and 68.2%, respectively). Assessment using the SALSA Scale showed 28.5% of subjects were without limitation, 43.8% with mild limitation, 13.5% with moderate limitation, 9.4% with severe limitation, and 4.9% with extreme limitation. Significant differences in the total SALSA Scale were found between age groups (p = 0.014), educational level (p = 0.005), occupation (p<0.001), and WHO disability grades (p<0.001). Multivariate analysis showed that the most significant factor influencing the total score of SALSA was disability grading for feet (score = 0.31, p <0.001) followed by occupational status, disability grading for eyes, and age. Limitation of functional activity was significantly correlated to becoming unemployed with the odds 2.59.

Conclusion

People affected by leprosy are prone to have functional activity limitation, especially the elderly, uneducated, unemployed and those with multiple disabilities. If they can overcome their barriers in functional activities, they will have better occupational opportunities.
Assessing the impact of Ascariasis and Trichuriasis on weight gain using a porcine model
Authors: Whitehead Bradley , Thamsborg Stig M. , Denwood Matthew J. , Nejsum Peter
Published: August 2022

Background

Infections with Ascaris lumbricoides and Trichuris trichiura remain significant contributors to the global burden of neglected tropical diseases. Infection may in particular affect child development as they are more likely to be infected with T. trichiura and/or A. lumbricoides and to carry higher worm burdens than adults. Whilst the impact of heavy infections are clear, the effects of moderate infection intensities on the growth and development of children remain elusive. Field studies are confounded by a lack of knowledge of infection history, nutritional status, presence of co-infections and levels of exposure to infective eggs. Therefore, animal models are required. Given the physiological similarities between humans and pigs but also between the helminths that infect them; A. suum and T. suis, growing pigs provide an excellent model to investigate the direct effects of Ascaris spp. and Trichuris spp. on weight gain.

Methods and results

We employed a trickle infection protocol to mimic natural co-infection to assess the effect of infection intensity, determined by worm count (A. suum) or eggs per gram of faeces (A. suum and T. suis), on weight gain in a large pig population (n = 195) with variable genetic susceptibility. Pig body weights were assessed over 14 weeks. Using a post-hoc statistical approach, we found a negative association between weight gain and T. suis infection. For A. suum, this association was not significant after adjusting for other covariates in a multivariable analysis. Estimates from generalized linear mixed effects models indicated that a 1 kg increase in weight gain was associated with 4.4% (p = 0.00217) decrease in T. suis EPG and a 2.8% (p = 0.02297) or 2.2% (p = 0.0488) decrease in A. suum EPG or burden, respectively.

Conclusions

Overall this study has demonstrated a negative association between STH and weight gain in growing pigs but also that T. suis infection may be more detrimental that A. suum on growth.
Ectopic expression of WRINKLED1 in rice improves lipid biosynthesis but retards plant growth and development
Authors: Liu Kaiqi , Tang Yuehui , Tang Yongyan , Li Meiru , Wu Guojiang , Chen Yaping , Jiang Huawu
Published: August 2022

WRINKLED1 (WRI1) is a transcription factor which is key to the regulation of seed oil biosynthesis in Arabidopsis. In the study, we identified two WRI1 genes in rice, named OsWRI1a and OsWRI1b, which share over 98% nucleotide similarity and are expressed only at very low levels in leaves and endosperms. The subcellular localization of Arabidopsis protoplasts showed that OsWRI1a encoded a nuclear localized protein. Overexpression of OsWRI1a under the control of the CaMV 35S promoter severely retarded plant growth and development in rice. Expressing the OsWRI1a gene under the control of the P1 promoter of Brittle2 (highly expressed in endosperm but low in leaves and roots) increased the oil content of both leaves and endosperms and upregulated the expression of several genes related to late glycolysis and fatty acid biosynthesis. However, the growth and development of the transgenic plants were also affected, with phenotypes including smaller plant size, later heading time, and fewer and lighter grains. The laminae (especially those of flag leaves) did not turn green and could not unroll normally. Thus, ectopic expression of OsWRI1a in rice enhances oil biosynthesis, but also leads to abnormal plant growth and development.
Genetically predicted cortisol levels and risk of venous thromboembolism
Authors: Allara Elias , Lee Wei-Hsuan , Burgess Stephen ,   the INVENT consortium, Larsson Susanna C.
Published: August 2022

Introduction

In observational studies, venous thromboembolism (VTE) has been associated with Cushing’s syndrome and with persistent mental stress, two conditions associated with higher cortisol levels. However, it remains unknown whether high cortisol levels within the usual range are causally associated with VTE risk. We aimed to assess the association between plasma cortisol levels and VTE risk using Mendelian randomization.

Methods

Three genetic variants in the SERPINA1/SERPINA6 locus (rs12589136, rs11621961 and rs2749527) were used to proxy plasma cortisol. The associations of the cortisol-associated genetic variants with VTE were acquired from the INVENT (28 907 cases and 157 243 non-cases) and FinnGen (6913 cases and 169 986 non-cases) consortia. Corresponding data for VTE subtypes were available from the FinnGen consortium and UK Biobank. Two-sample Mendelian randomization analyses (inverse-variance weighted method) were performed.

Results

Genetic predisposition to higher plasma cortisol levels was associated with a reduced risk of VTE (odds ratio [OR] per one standard deviation increment 0.73, 95% confidence interval [CI] 0.62–0.87, p<0.001). The association was stronger for deep vein thrombosis (OR 0.69, 95% CI 0.55–0.88, p = 0.003) than for pulmonary embolism which did not achieve statistical significance (OR 0.83, 95% CI 0.63–1.09, p = 0.184). Adjusting for genetically predicted systolic blood pressure inverted the direction of the point estimate for VTE, although the resulting CI was wide (OR 1.06, 95% CI 0.70–1.61, p = 0.780).

Conclusions

This study provides evidence that genetically predicted plasma cortisol levels in the high end of the normal range are associated with a decreased risk of VTE and that this association may be mediated by blood pressure. This study has implications for the planning of observational studies of cortisol and VTE, suggesting that blood pressure traits should be measured and accounted for.