bluuebunny/crossref_metadata_2025 huggingface dataset:
Worse sleep health predicts less frequent breakfast consumption among adolescents in a micro-longitudinal analysis
Authors: Mathew Gina Marie , Reichenberger David A. , Master Lindsay , Buxton Orfeu M. , Hale Lauren , Chang Anne-Marie
Published: June 2022

Background

Poor self-reported sleep health has been linked to not consuming breakfast in adolescents, but it is unknown whether poor sleep measured objectively predicts next-day breakfast consumption within adolescents. We investigated within- and between-person associations of objectively measured sleep dimensions and subjective sleep quality with adolescent breakfast consumption.

Methods

Data were collected from a micro-longitudinal substudy of the Year 15 wave of the Fragile Families and Child Wellbeing Study (n = 590). Adolescents wore an actigraphy device and completed daily diaries for ~ 1 week (M ± SD = 5.6 ± 1.4 nights per adolescent, range: 3–9), where they rated their sleep quality and reported whether they had eaten breakfast that day, with no specific definition of breakfast provided (M ± SD = 5.5 ± 1.4 days per adolescent, range: 3–9). Separate mixed models assessed whether actigraphy-measured sleep duration (linear and quadratic, sleep duration x sleep duration), timing, maintenance efficiency, and subjective quality predicted odds of breakfast consumption both within and between adolescents. Variability of sleep duration and timing (standard deviation per person), sleep regularity index (SRI), and social jetlag were tested as additional between-person predictors. Analyses with predictors other than sleep duration were adjusted for sleep duration.

Results

Following nights when adolescents had shorter or longer sleep duration (p = .005; curvilinear association), later sleep onset, or later sleep midpoint (both p = .025) than their own usual, they had lower odds of consuming breakfast the next day (within-person associations). Adolescents who on average had later sleep onset (p = .013) or midpoint (p = .013) or who reported lower sleep quality (p = .011) had lower average odds of consuming breakfast (between-person associations). Adolescents with greater variability of sleep duration (p = .005), midpoint (p = .004), or offset (p < .001) had lower average odds of consuming breakfast (between-person associations). Sleep maintenance efficiency (within or between adolescents), SRI, and social jetlag were not associated with breakfast consumption (all p > .10).

Conclusions

Multiple dimensions of sleep health are associated with breakfast consumption, both within and between adolescents. Poor sleep and dietary behaviors in adolescence may negatively impact future metabolic health.
Transdermal deferoxamine administration improves excisional wound healing in chronically irradiated murine skin
Authors: Lintel Hendrik , Abbas Darren B. , Lavin Christopher V. , Griffin Michelle , Guo Jason L. , Guardino Nicholas , Churukian Andrew , Gurtner Geoffrey C. , Momeni Arash , Longaker Michael T. , Wan Derrick C.
Published: June 2022

Background

Radiation-induced skin injury is a well-known risk factor for impaired wound healing. Over time, the deleterious effects of radiation on skin produce a fibrotic, hypovascular dermis poorly suited to wound healing. Despite increasing understanding of the underlying pathophysiology, therapeutic options remain elusive. Deferoxamine (DFO), an iron-chelating drug, has been shown in prior murine studies to ameliorate radiation-induced skin injury as well as improve wound healing outcomes in various pathologic conditions when administered transdermally. In this preclinical study, we evaluated the effects of deferoxamine on wound healing outcomes in chronically irradiated murine skin.

Methods

Wild-type mice received 30 Gy of irradiation to their dorsal skin and were left to develop chronic fibrosis. Stented excisional wounds were created on their dorsal skin. Wound healing outcomes were compared across 4 experimental conditions: DFO patch treatment, vehicle-only patch treatment, untreated irradiated wound, and untreated nonirradiated wounds. Gross closure rate, wound perfusion, scar elasticity, histology, and nitric oxide assays were compared across the conditions.

Results

Relative to vehicle and untreated irradiated wounds, DFO accelerated wound closure and reduced the frequency of healing failure in irradiated wounds. DFO augmented wound perfusion throughout healing and upregulated angiogenesis to levels observed in nonirradiated wounds. Histology revealed DFO increased wound thickness, collagen density, and improved collagen fiber organization to more closely resemble nonirradiated wounds, likely contributing to the observed improved scar elasticity. Lastly, DFO upregulated inducible nitric oxide synthase and increased nitric oxide production in early healing wounds.

Conclusion

Deferoxamine treatment presents a potential therapeutic avenue through which to target impaired wound healing in patients following radiotherapy.
Swine influenza virus triggers ferroptosis in A549 cells to enhance virus replication
Authors: Cheng Jinghua , Tao Jie , Li Benqiang , Shi Ying , Liu Huili
Published: June 2022

Background

Recently, Influenza A virus (IAV) has been shown to activate several programmed cell death pathways that play essential roles in host defense. Indeed, cell death caused by viral infection may be mediated by a mixed pattern of cell death instead of a certain single mode. Ferroptosis is a novel form of regulated cell death (RCD) that is mainly mediated by iron-dependent lipid peroxidation. Based on the proteomic data, we wondered whether IAV causes ferroptosis in host cells.

Method

In this study, a quantitative proteomics approach based on an iTRAQ combined with LC–MS/MS was used to profile proteins expressed in A549 cells infected with H1N1 swine influenza virus (SIV). Meanwhile, we measured the intracellular iron content, reactive oxygen species (ROS) release and lipid peroxidation in response to SIV infection. Finally, a drug experiment was conducted to investigate the effects of ferroptosis on modulating SIV survival.

Results

The bioinformatics analysis revealed several proteins closely relevant to iron homeostasis and transport, and the ferroptosis signaling pathway are highly enriched in response to SIV infection. In our experiment, aberrant expression of iron-binding proteins disrupted labile iron uptake and storage after SIV infection. Meanwhile, SIV infection inhibited system the Xc−/GPX4 axis resulting in GSH depletion and the accumulation of lipid peroxidation products. Notably, cell death caused by SIV as a result of iron-dependent lipid peroxidation can be partially rescued by ferroptosis inhibitor. Additionally, blockade of the ferroptotic pathway by ferrostatin-1 (Fer-1) treatment decreased viral titers and inflammatory response.

Conclusions

This study revealed a new mode of cell death induced by IAV infection, and our findings might improve the understanding of the underlying mechanism involved in the interaction of virus and host cells.
Role of stereotactic body radiation in the enhancement of the quality of life in locally advanced pancreatic adenocarcinoma: a systematic review
Authors: Vornhülz Marlies , Anton Sofia , Eross Balint , Szakács Zsolt , Hegyi Peter , Regel Ivonne , Belka Claus , Niyazi Maximilian , Mayerle Julia , Beyer Georg
Published: June 2022

Introduction

Up to 30% of pancreatic cancer patients initially present locally advanced (LAPC). Stereotactic body radiation therapy (SBRT) may be an additional palliative treatment option when curative resection is no longer achievable. Our systematic review aimed to assess the effect of SBRT on the quality of life in LAPC.

Methods

We searched five databases until June 29th, 2021, for original articles that reported on SBRT for histologically proven LAPC in adults. Data were extracted on study characteristics, SBRT and additional therapy regimen, pain, biliary complications, nutrition, quality of life and other patient-reported outcomes. Statistical analyses were performed for population and survival data.

Results

11 case series studies comprising 292 patients with a median age of 66 (range 34–89) years were included in the final analysis. The weighted average BED2;10 (radiation biologically effective dose, equivalent dose in 2 Gy fractions) was 54 Gy, delivered in 3 to 6 fractions. The individual studies used different scales and endpoints, not allowing a meta-analysis. Pain generally appeared to be improved by SBRT. SBRT significantly reduced jaundice. Local control was achieved in 71.7% of patients. Weight loss and nausea also tended to improve after SBRT.

Conclusion

SBRT of locally advanced irresectable pancreatic cancer is a promising approach for achieving local control and improving the quality of life. However, randomized controlled trials with larger cohorts are needed to assess the value of SBRT in pancreatic cancer therapy.
Are Blastocystis hominis and Cryptosporidium spp. playing a positive role in colorectal cancer risk? A systematic review and meta-analysis
Authors: Taghipour Ali , Rayatdoost Esmail , Bairami Amir , Bahadory Saeed , Abdoli Amir
Published: June 2022

Objective

Intestinal protozoa Blastocystis hominis and Cryptosporidium spp. are two influential factors in intestinal complications and malignancies. In present study, we estimated the pooled prevalence and odds ratio (OR) of the two parasites in colorectal cancer (CRC) patients and their possible association with the deadly disease.

Method

Our systematic search was conducted for published researches between January 1, 2000 and April 30, 2022 by using four international databases include Scopus, PubMed, and Web of Science as well as Google scholar search engine. The random- and fixed-effects models were used to estimate the pooled prevalence, OR, and 95% confidence interval (CI) by comprehensive meta-analysis (V2.2, Bio stat) software. Inclusion and exclusion criteria were applied.

Results

Thirteen papers (seven case–control and six cross-sectional studies) for B. hominis/CRC and six papers (two case–control and four cross-sectional studies) for Cryptosporidium spp./CRC were eligible to include in data synthesis. Pooled prevalence of B. hominis and Cryptosporidium spp. in CRC patients was calculated to be 26.8% (95% CI 19.4–35.7%) and 12.7% (95% CI 6.8–22.5%), respectively. Based on case–control studies, significant difference was found between case and controls in both protozoa (B. hominis OR 2.10; 95% CI 1.39–3.18% vs. Cryptosporidium spp. OR 5.06; 95% CI 1.8–13.6%). Considering the Blastocystis subtypes, ST1 (5/6; 83.33% studies) and ST3 (5/6; 83.33% studies) had the highest number of reports in CRC patients. Regarding the Cryptosporidium species, only C. parvum and C. hominis were reported.

Conclusion

Given the significant prevalence of both parasites in CRC patients and their statistically significant association, there is a need to pay more attention to these two intestinal parasites in under treatment patients.
mTORC1 function in hippocampal parvalbumin interneurons: regulation of firing and long-term potentiation of intrinsic excitability but not long-term contextual fear memory and context discrimination
Authors: Khlaifia Abdessattar , Honoré Eve , Artinian Julien , Laplante Isabel , Lacaille Jean-Claude
Published: June 2022

Hippocampal CA1 parvalbumin-expressing interneurons (PV INs) play a central role in controlling principal cell activity and orchestrating network oscillations. PV INs receive excitatory inputs from CA3 Schaffer collaterals and local CA1 pyramidal cells, and they provide perisomatic inhibition. Schaffer collateral excitatory synapses onto PV INs express Hebbian and anti-Hebbian types of long-term potentiation (LTP), as well as elicit LTP of intrinsic excitability (LTPIE). LTPIE requires the activation of type 5 metabotropic glutamate receptors (mGluR5) and is mediated by downregulation of potassium channels Kv1.1. It is sensitive to rapamycin and thus may involve activation of the mammalian target of rapamycin complex 1 (mTORC1). LTPIE facilitates PV INs recruitment in CA1 and maintains an excitatory-inhibitory balance. Impaired CA1 PV INs activity or LTP affects network oscillations and memory. However, whether LTPIE in PV INs plays a role in hippocampus-dependent memory remains unknown. Here, we used conditional deletion of the obligatory component of mTORC1, the Regulatory-Associated Protein of mTOR (Raptor), to directly manipulate mTORC1 in PV INs. We found that homozygous, but not heterozygous, conditional knock-out of Rptor resulted in a decrease in CA1 PV INs of mTORC1 signaling via its downstream effector S6 phosphorylation assessed by immunofluorescence. In whole-cell recordings from hippocampal slices, repetitive firing of CA1 PV INs was impaired in mice with either homozygous or heterozygous conditional knock-out of Rptor. High frequency stimulation of Schaffer collateral inputs that induce LTPIE in PV INs of control mice failed to do so in mice with either heterozygous or homozygous conditional knock-out of Rptor in PV INs. At the behavioral level, mice with homozygous or heterozygous conditional knock-out of Rptor showed similar long-term contextual fear memory or contextual fear memory discrimination relative to control mice. Thus, mTORC1 activity in CA1 PV INs regulates repetitive firing and LTPIE but not consolidation of long-term contextual fear memory and context discrimination. Our results indicate that mTORC1 plays cell-specific roles in synaptic plasticity of hippocampal inhibitory interneurons that are differentially involved in hippocampus-dependent learning and memory.
Combined inhibition of EZH2 and ATM is synthetic lethal in BRCA1-deficient breast cancer
Authors: Ratz Leonie , Brambillasca Chiara , Bartke Leandra , Huetzen Maxim A. , Goergens Jonas , Leidecker Orsolya , Jachimowicz Ron D. , van de Ven Marieke , Proost Natalie , Siteur Bjørn , de Korte-Grimmerink Renske , Bouwman Peter , Pulver Emilia M. , de Bruijn Roebi , Isensee Jörg , Hucho Tim , Pandey Gaurav , van Lohuizen Maarten , Mallmann Peter , Reinhardt Hans Christian , Jonkers Jos , Puppe Julian
Published: June 2022

Background

The majority of BRCA1-mutant breast cancers are characterized by a triple-negative phenotype and a basal-like molecular subtype, associated with aggressive clinical behavior. Current treatment options are limited, highlighting the need for the development of novel targeted therapies for this tumor subtype.

Methods

Our group previously showed that EZH2 is functionally relevant in BRCA1-deficient breast tumors and blocking EZH2 enzymatic activity could be a potent treatment strategy. To validate the role of EZH2 as a therapeutic target and to identify new synergistic drug combinations, we performed a high-throughput drug combination screen in various cell lines derived from BRCA1-deficient and -proficient mouse mammary tumors.

Results

We identified the combined inhibition of EZH2 and the proximal DNA damage response kinase ATM as a novel synthetic lethality-based therapy for the treatment of BRCA1-deficient breast tumors. We show that the combined treatment with the EZH2 inhibitor GSK126 and the ATM inhibitor AZD1390 led to reduced colony formation, increased genotoxic stress, and apoptosis-mediated cell death in BRCA1-deficient mammary tumor cells in vitro. These findings were corroborated by in vivo experiments showing that simultaneous inhibition of EZH2 and ATM significantly increased anti-tumor activity in mice bearing BRCA1-deficient mammary tumors.

Conclusion

Taken together, we identified a synthetic lethal interaction between EZH2 and ATM and propose this synergistic interaction as a novel molecular combination for the treatment of BRCA1-mutant breast cancer.
Reverse mentoring to enhance research integrity climate
Authors: Pizzolato Daniel , Dierickx Kris
Published: June 2022

Mentors have the responsibility to guide their mentees through academic and scientific challenges that they might encounter during their educational and professional development. In embodying the role of mentors, senior academics are also expected to transmit knowledge and competencies on the topic of research integrity to their junior colleagues. However, senior academics do not always succeed in transmitting responsible research practices and enhancing the research integrity climate. The implementation of the concept of reverse mentoring can be an option to overcome this issue. Different from traditional mentoring, the flow of information is reversed, going from juniors to seniors. Reverse mentoring, as a developmental partnership between mentees and mentors, has been already used successfully within the private sector and in medical education. In times in which most universities invest resources in organizing dedicated research integrity trainings for PhD candidates and junior researchers, it would be valuable to consider reverse mentoring for fostering responsible research practices and enhancing the research integrity climate. PhD candidates and junior researchers can join and fully contribute to the endeavor of enhancing the research integrity climate by co-creating, together with their senior colleagues a new-shared learning environment.
Variation of soil bacterial communities in a chronosequence of citrus orchard
Authors: Jin Ya-bo , Fang Zheng , Zhou Xin-bin
Published: June 2022

Purpose

Soil microorganisms are vital for soil ecosystems through bioconversion of soil nutrients and maintenance of soil fertility to promoting the growth and development of citrus. However, understanding of how different planting years affect the soil bacterial community structures as related to nutrient availability in citrus orchards is limited.

Methods

Here, Illumina MiSeq technology was used to investigate changes in bacterial community structures with different ages of citrus orchards that were 2, 5, 10, 15, and 18 years old.

Results

The data showed that (1) soil bacterial community structures changed over the different growth stages of citrus orchards. With the extension of plantation age, the microbial diversity of citrus orchards increased gradually so that it was highest in 10-year-old citrus plantations but then decreased where the diversity of 18-year-old citrus ages was significantly lower than that of 10 and 15-year-old ones. Proteobacteria, Actinobacteria, Acidobacteria, and Chloroflexi were the four dominant phyla in soil of citrus orchards, accounting for 30.85%, 24.89%, 14.27%, and 14.05% of the total soil bacterial communities, respectively. (2) Soil bacterial community structures in different succession stages were affected by soil pH and nutrients, in particular available potassium (AK).

Conclusion

This study advances the understanding of soil microbiota of orchards and their interactions related to environmental factors in citrus orchard, which will improve our ability to promote the function of soil bacteria, so as to improve soil pH and reduce potassium (K) fertilizer input and improve the fruit quality.
Sebaceous carcinoma of the lip: a case report and review of the literature
Authors: Di Cosola Michele , Spirito Francesca , Ambrosino Mariateresa , Somma Pasquale , Santarelli Andrea , Staibano Stefania , Lo Muzio Lorenzo
Published: June 2022

Background

Sebaceous carcinoma is a very rare, aggressive, malignant tumor arising in the adnexal epithelium of the sebaceous gland. Sebaceous carcinoma in the oral cavity is extremely rare, with only 14 cases reported in literature. We reported the fourth case of sebaceous carcinoma involving the lip

Case presentation

A 71-year-old Caucasian male smoker presented an ulcerated lesion in the lateral region of the lower lip. The patient stated that the lesion had been present for 1 year. The past medical history was unremarkable. Extraoral examination revealed a markedly ulcerated, exophytic, irregularly shaped, indurated mass of the lower right labial region, measuring 1.8 cm in size. The nodular lesion, located at the point of transition between mucosa and skin, showed a central ulceration. No other intraoral lesions were identified. The clinical differential diagnosis included squamous cell carcinoma, basal cell carcinoma with sebaceous differentiation, and salivary gland neoplasms. Operation was performed under local anesthesia. On histopathological examination, the tumor was composed by nodules or sheet of cells separated by a fibrovascular stroma. The neoplastic tissue was deeply infiltrating, involving the submucosa and even the underlying muscle. Neoplastic cells showed a range of sebaceous differentiation with finely vacuolated rather than clear cytoplasm. Neoplastic cells were positive for S-100 protein and epithelial membrane antigen, but negative for carcinoembryonic antigen. Based on these findings, a diagnosis of sebaceous carcinoma of the lower lip was rendered.

Conclusion

The histogenesis, differential diagnosis, and clinicopathological conditions of this disease according to literature are reviewed. Sebaceous carcinoma should be distinguished from other tumors full of vacuolated clear cells. A periodic acid-Schiff stain and immunohistochemical stain for Ki-67, P53, cytokeratin, S-100, epithelial membrane antigen, and androgen receptor can be useful for the diagnosis.
Intravenously transplanted mesenchymal stromal cells: a new endocrine reservoir for cardioprotection
Authors: Huang Anan , Liu Yue , Qi Xin , Chen Shang , Huang Haoyan , Zhang Jun , Han Zhibo , Han Zhong-Chao , Li Zongjin
Published: June 2022

Background

Intravenous administration of mesenchymal stromal cells (MSCs) has an acknowledged competence of cardiac repair, despite a lack of systematic description of the underlying biological mechanisms. The lung, but not the heart, is the main trapped site for intravenously transplanted MSCs, which leaves a spatial gap between intravenously transplanted MSCs and the injured myocardium. How lung-trapped MSCs after intravenous transplantation rejuvenate the injured myocardium remains unknown.

Methods

MSCs were isolated from human placenta tissue, and DF-MSCs or Gluc-MSCs were generated by transduced with firefly luciferase (Fluc)/enhanced green fluorescence protein (eGFP) or Gaussia luciferase (Gluc) lactadherin fusion protein. The therapeutic efficiency of intravenously transplanted MSCs was investigated in a murine model of doxorubicin (Dox)-induced cardiotoxicity. Trans-organ communication from the lung to the heart with the delivery of blood was investigated by testing the release of MSC-derived extracellular vesicles (MSC-EVs), and the potential miRNA inner MSC-EVs were screened out and verified. The potential therapeutic miRNA inner MSC-EVs were then upregulated or downregulated to assess the further therapeutic efficiency

Results

Dox-induced cardiotoxicity, characterized by cardiac atrophy, left ventricular dysfunction, and injured myocardium, was alleviated by consecutive doses of MSCs. These cardioprotective effects might be attributed to suppressing GRP78 triggering endoplasmic reticulum (ER) stress-induced apoptosis in cardiomyocytes. Our results confirmed that miR-181a-5p from MSCs-derived EVs (MSC-EVs) inhibited GRP78. Intravenous DF-MSCs were trapped in lung vasculature, secreted a certain number of EVs into serum, which could be confirmed by the detection of eGFP+ EVs. GLuc activity was increased in serum EVs from mice administrated with GLuc-MSCs. MiR-181a-5p, inhibiting GRP78 with high efficacy, was highly expressed in serum EVs and myocardium after injecting consecutive doses of MSCs into mice treated with Dox. Finally, upregulation or downregulation of miR-181a-5p levels in MSC-EVs enhanced or weakened therapeutic effects on Dox-induced cardiotoxicity through modulating ER stress-induced apoptosis.

Conclusions

This study identifies intravenously transplanted MSCs, as an endocrine reservoir, to secrete cardioprotective EVs into blood continuously and gradually to confer the trans-organ communication that relieves Dox-induced cardiotoxicity.
Modeling of mitochondrial bioenergetics and autophagy impairment in MELAS-mutant iPSC-derived retinal pigment epithelial cells
Authors: Bhattacharya Sujoy , Yin Jinggang , Huo Weihong , Chaum Edward
Published: June 2022

Background

Mitochondrial dysfunction and mitochondrial DNA (mtDNA) damage in the retinal pigment epithelium (RPE) have been implicated in the pathogenesis of age-related macular degeneration (AMD). However, a deeper understanding is required to determine the contribution of mitochondrial dysfunction and impaired mitochondrial autophagy (mitophagy) to RPE damage and AMD pathobiology. In this study, we model the impact of a prototypical systemic mitochondrial defect, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), in RPE health and homeostasis as an in vitro model for impaired mitochondrial bioenergetics.

Methods

We used induced pluripotent stem cells (iPSCs) derived from skin biopsies of MELAS patients (m.3243A > G tRNA leu mutation) with different levels of mtDNA heteroplasmy and differentiated them into RPE cells. Mitochondrial depletion of ARPE-19 cells (p0 cells) was also performed using 50 ng/mL ethidium bromide (EtBr) and 50 mg/ml uridine. Cell fusion of the human platelets with the p0 cells performed using polyethylene glycol (PEG)/suspension essential medium (SMEM) mixture to generate platelet/RPE “cybrids.” Confocal microscopy, FLowSight Imaging cytometry, and Seahorse XF Mito Stress test were used to analyze mitochondrial function. Western Blotting was used to analyze expression of autophagy and mitophagy proteins.

Results

We found that MELAS iPSC-derived RPE cells exhibited key characteristics of native RPE. We observed heteroplasmy-dependent impairment of mitochondrial bioenergetics and reliance on glycolysis for generating energy in the MELAS iPSC-derived RPE. The degree of heteroplasmy was directly associated with increased activation of signal transducer and activator of transcription 3 (STAT3), reduced adenosine monophosphate-activated protein kinase α (AMPKα) activation, and decreased autophagic activity. In addition, impaired autophagy was associated with aberrant lysosomal function, and failure of mitochondrial recycling. The mitochondria-depleted p0 cells replicated the effects on autophagy impairment and aberrant STAT3/AMPKα signaling and showed reduced mitochondrial respiration, demonstrating phenotypic similarities between p0 and MELAS iPSC-derived RPE cells.

Conclusions

Our studies demonstrate that the MELAS iPSC-derived disease models are powerful tools for dissecting the molecular mechanisms by which mitochondrial DNA alterations influence RPE function in aging and macular degeneration, and for testing novel therapeutics in patients harboring the MELAS genotype.
Characterization of metal(loid)s and antibiotic resistance in bacteria of human gut microbiota from chronic kidney disease subjects
Authors: Miranda María V. , González Fernanda C. , Paredes-Godoy Osvaldo S. , Maulén Mario A. , Vásquez† Claudio C. , Díaz-Vásquez Waldo A.
Published: June 2022

Background

Human Gut Microbiota (HGM) is composed of more than one thousand species, playing an important role in the health status of individuals. Dysbiosis (an HGM imbalance) is augmented as chronic kidney disease (CKD) progresses, as loss of kidney function accelerates. Increased antibiotic use in CKD subjects and consumption of nephrotoxic heavy metals and metalloids such as lead, cadmium, arsenic, and mercury in tap water increases the dysbiosis state. Studies in people with stage 3 CKD are complex to carry out, mainly because patients are self-reliant who rarely consult a specialist. The current work focused on this type of patient.

Results

Lead and arsenic-resistant bacteria were obtained from self-reliant (that stands on its own) stage 3 CKD subjects. Pathogen-related Firmicutes and Proteobacteria genus bacteria were observed. Resistance and potentiation of antibiotic effects in the presence of metal(loid)s in vitro were found. Furthermore, the presence of the following genes markers for antibiotic and metal(loid) resistance were identified by qPCR: oxa10, qnrB1, mphB, ermB, mefE1, arr2, sulll, tetA, floR, strB, dhfr1, acrB, cadA2k, cadA3k, arsC, pbrA. We observed a decrease in the number of metal resistance markers.

Conclusions

The presence of cadA and arsC genetic markers of antibiotics and metal(loid)s resistance were detected in samples from stage 3 CKD subjects. Lower gene amplification in advanced stages of CKD were also observed, possibly associated with a decrease in resident HGM during kidney disease progression.
Larval habitats characterization and population dynamics of Culex mosquitoes in two localities of the Menoua Division, Dschang and Santchou, West Cameroon
Authors: Djoufounna Joel , Mayi Marie Paul Audrey , Bamou Roland , Ningahi Laura Gilberine , Magatsing Falone Ornela , Djiappi-Tchamen Borel , Djamouko-Djonkam Landre , Antonio-Nkondjio Christophe , Tchuinkam Timoléon
Published: June 2022

Background

Choosing an appropriate strategy for mosquito vector control in an eco-climatic facies requires knowledge on vector ecology including population dynamics of species and productivity of the breeding sites. The aim of this study was to characterizeCulexmosquitoes breeding places and to determine their population dynamics in two localities (Dschang and Santchou) separated by a forest cliff in the West Region of Cameroon. Field surveys were conducted from November 2019 to June 2020 in Dschang and Santchou. Mosquito breeding sites were georeferenced, and for each breeding site, physical parameters were measured and immature stages were collected. The collected immatures were reared in the laboratory until adult stage. Adult mosquitoes were identified using a stereomicroscope and morphological identification keys.

Results

A total of 44 breeding sites were identified: 24 in Dschang and 20 in Santchou. They were grouped into seven types and were mostly shallow, close to human dwellings, sunny, with organic matters and of anthropogenic nature. A total of 2706 mosquitoes belonging to four genera were identified.Culexgenus was the most represented (90.4%) and was made up ofCulex pipienss.l. (61.79%),Culex duttoni(23.17%) andCulex (Culiciomyia) sp. (05.46%). High abundance ofCulexspecies was observed in Santchou (52.71%) compared to Dschang (47.28%), while Dschang (S = 3;H = 0.87;D = 0.54) recorded the greatest diversity compared to Santchou (S = 2;H = 0.23;D = 0.11).

Conclusions

The proliferation and persistence ofCulexmosquitoes independently of the breeding sites and localities might be attributable to the poor environmental management which favor the creation mosquito breeding sites. This study highlights the fact that prompt sanitation measures could be undertaken in these two localities to reduce mosquito abundance and the risk of vector-borne diseases.
Direct-Acting Antivirals as Primary Treatment for Hepatitis C Virus–Associated Indolent Non-Hodgkin Lymphomas: The BArT Study of the Fondazione Italiana Linfomi
Authors: Merli Michele , Rattotti Sara , Spina Michele , Re Francesca , Motta Marina , Piazza Francesco , Orsucci Lorella , Ferreri Andrés J.M. , Perbellini Omar , Dodero Anna , Vallisa Daniele , Pulsoni Alessandro , Santoro Armando , Sacchi Paolo , Zuccaro Valentina , Chimienti Emanuela , Russo Filomena , Visco Carlo , Zignego Anna Linda , Marcheselli Luigi , Passamonti Francesco , Luminari Stefano , Paulli Marco , Bruno Raffaele , Arcaini Luca ,   on behalf of Fondazione Italiana Linfomi
Published: June 2022

PURPOSE

We prospectively treated patients with hepatitis C virus (HCV)–associated indolent lymphomas with genotype-appropriate direct-acting antivirals (DAAs) with the aim to evaluate virologic and hematologic outcomes. No prospective studies in this setting have been published so far.

METHODS

FIL_BArT is a prospective, multicenter, phase II trial that evaluated genotype-appropriate DAAs in untreated HCV-positive patients with indolent lymphomas without criteria for immediate conventional antilymphoma treatment. The primary objective was sustained virologic response, whereas the main secondary objectives were overall response rate of lymphoma and progression-free survival.

RESULTS

Forty patients were enrolled, including 27 with marginal zone lymphoma. Median age was 68 years. Extranodal sites were involved in 14 cases (35%). Main genotypes were 1 in 16 patients and 2 in 21 patients. All patients received genotype-guided DAAs: 17 ledipasvir/sofosbuvir, eight sofosbuvir plus ribavirin, and 15 sofosbuvir/velpatasvir. All patients achieved sustained virologic response (100%). DAAs were well tolerated, with only two grade 3-4 adverse events. Overall response rate of lymphoma was 45%, including eight patients (20%) achieving complete response and 10 (25%) partial response, whereas 16 exhibited stable disease and six progressed. With a median follow-up of 37 months, two patients died (3-year overall survival 93%; 95% CI, 74 to 98) and three additional patients progressed, with a 3-year progression-free survival of 76% (95% CI, 57 to 87).

CONCLUSION

HCV eradication by DAAs was achieved in 100% of HCV-positive patients with indolent lymphomas not requiring immediate conventional treatment and resulted in non-negligible rate of lymphoma responses. Treatment with DAAs should be considered as the first-line therapy in this setting.
A New Perspective on Regulation of Pituitary Plasticity: The Network of SOX2-Positive Cells May Coordinate Responses to Challenge
Authors: Le Tissier Paul R , Murray Joanne F , Mollard Patrice
Published: June 2022

Plasticity of function is required for each of the anterior pituitary endocrine axes to support alterations in the demand for hormone with physiological status and in response to environmental challenge. This plasticity is mediated at the pituitary level by a change in functional cell mass resulting from a combination of alteration in the proportion of responding cells, the amount of hormone secreted from each cell, and the total number of cells within an endocrine cell population. The functional cell mass also depends on its organization into structural and functional networks. The mechanisms underlying alteration in gland output depend on the strength of the stimulus and are axis dependent but in all cases rely on sensing of output of the functional cell mass and its regulation. Here, we present evidence that the size of pituitary cell populations is constrained and suggest this is mediated by a form of quorum sensing. We propose that pituitary cell quorum sensing is mediated by interactions between the networks of endocrine cells and hormone-negative SOX2-positive (SOX2+ve) cells and speculate that the latter act as both a sentinel and actuator of cell number. Evidence for a role of the network of SOX2+ve cells in directly regulating secretion from multiple endocrine cell networks suggests that it also regulates other aspects of the endocrine cell functional mass. A decision-making role of SOX2+ve cells would allow precise coordination of pituitary axes, essential for their appropriate response to physiological status and challenge, as well as prioritization of axis modification.
Do Internal Migration Experiences Facilitate Migration Intentions and Behavior?
Authors: Bernard Aude , Kalemba Sunganani , Nguyen Toan
Published: June 2022

Growing evidence suggests that internal migration experience shapes future internal migration behavior. However, it remains unclear what stage of the decision-making process past internal migration facilitates and whether the impact depends on the distance moved. To advance understanding of the role of past migration, we explicitly and dynamically link migration experiences to the formation and realization of future internal migration intentions by blending the aspiration–ability framework with the learned behavior hypothesis. We empirically test our proposition by fitting a series of logistic regression models to longitudinal microdata from the Household, Income and Labour Dynamics in Australia (HILDA) Survey, which has been conducted annually since 2001. We use a two-step approach by first modeling internal migration intentions and then modeling the realization of these intentions, distinguishing between residential moves, onward interregional migration, and return interregional migration. We find that migration experience is positively associated with both the formation and realization of migration intentions and that the effect of past migration increases with the distance moved and the number of past migrations. These findings suggest that migration experiences accumulate over the life course to predispose individuals toward subsequent migration. Finally, we show that the effect of past migration is not the result of a lack of social capital among repeat migrants—a finding that reinforces the importance of conceptualizing internal migration as a life course trajectory rather than a series of discrete events.
Trans as Brain Intersex
Authors: Wang Thelma
Published: June 2022

There is an abundance of neuroscientific research seeking to pin down the origins of transgender people's gender identity in the brain. The established premise is that transgender people have a brain structure more in line with the sex group with which they identify than the one they are assigned to at birth. Transgender is imagined as a form of intersexuality—but of the brain, rather than the genitalia. This article aims to critically interrogate the neuroscientific notion of transgender as brain intersex by situating the neuroscientific understanding of trans people within the genealogy of the medical management of transgender and intersex people. The study also examines how medical authority consolidates itself through the “trans-intersex nexus”—a mechanism in which trans and intersex people are placed in a relationship of simultaneous separation and reinforcement under the control of medical knowledge and technologies.
Intersex Justice Pedagogy
Authors: Lewis Mel Michelle
Published: June 2022

This article coins the term Intersex Justice Pedagogy and outlines this practice as a decolonial and intersectional teaching and learning praxis that affirms bodily integrity and bodily autonomy as the practice of liberation for intersex people of color. The author examines the personal, political, and pedagogical exigency for a pedagogy that centers voices from overlapping and interlocking intersex, queer, trans, nonbinary, and feminist communities of color, and takes a critical approach to examining paradigms of power, sovereignty, and “the science of sex” in a social world. Using specific examples of texts and approaches to teaching and learning, this article inspires an examination of pedagogical approaches, not only to teaching intersex and trans studies, but also to teaching social justice, with an emphasis on bodily autonomy and bodily integrity from multiple disciplinary/interdisciplinary locations and perspectives.
Ethylene signaling increases reactive oxygen species accumulation to drive root hair initiation in Arabidopsis
Authors: Martin R. Emily , Marzol Eliana , Estevez Jose M. , Muday Gloria K.
Published: June 2022

Root hair initiation is a highly regulated aspect of root development. The plant hormone ethylene and its precursor, 1-amino-cyclopropane-1-carboxylic acid, induce formation and elongation of root hairs. Using confocal microscopy paired with redox biosensors and dyes, we demonstrated that treatments that elevate ethylene levels lead to increased hydrogen peroxide accumulation in hair cells prior to root hair formation. In the ethylene-insensitive receptor mutant, etr1-3, and the signaling double mutant, ein3eil1, the increase in root hair number or reactive oxygen species (ROS) accumulation after ACC and ethylene treatment was lost. Conversely, etr1-7, a constitutive ethylene signaling receptor mutant, has increased root hair formation and ROS accumulation, similar to ethylene-treated Col-0 seedlings. The caprice and werewolf transcription factor mutants have decreased and elevated ROS levels, respectively, which are correlated with levels of root hair initiation. The rhd2-6 mutant, with a defect in the gene encoding the ROS-synthesizing RESPIRATORY BURST OXIDASE HOMOLOG C (RBOHC), and the prx44-2 mutant, which is defective in a class III peroxidase, showed impaired ethylene-dependent ROS synthesis and root hair formation via EIN3EIL1-dependent transcriptional regulation. Together, these results indicate that ethylene increases ROS accumulation through RBOHC and PRX44 to drive root hair formation.
Bilateral upper extremity myositis after COVID-19 vaccination
Authors: Godoy Ivan Rodrigues Barros , Rodrigues Tatiane Cantarelli , Skaf Abdalla Youssef
Published: June 2022

Vaccination adverse reactions are common and usually are represented by transitory pain and edema. We present a case of bilateral muscle edema involving shoulders and arms due to myositis following COVID-19 vaccination, and focus on the imaging findings to differentiate with other diagnosis such as infection and tumors.
Rewards and recognition for Canadian distributed medical education preceptors: a qualitative analysis
Authors: Bell Amanda , Johnston Aaron , Makwarimba Edward , Malhi Rebecca
Published: June 2022

Background: Recognition of Distributed Medical Education (DME) preceptors by medical schools ensures that important community-based training opportunities remain available to learners. Yet the literature seldom explores what rewards are meaningful to this population of teachers. The goal of our national project was to provide guidance to medical schools about the financial remuneration and non-financial rewards that are most valued by DME preceptors.

Methods: In this qualitative study, we invited DME faculty members from all Canadian medical schools to participate in semi-structured interviews. Participants with a range of medical specialties, stages of career, and geographic locations were interviewed via Zoom videoconferencing. The sessions in English and French were audio-recorded and transcribed. We used line-by-line inductive coding and thematic analysis to examine participant talk about meaningful preceptor recognition.

Results: Fourteen participants from multiple provinces were interviewed. Results indicated that the DME faculty are a diverse group of people with diverse needs. Most of the interviewees appreciated the rewards and recognition provided by their medical schools but felt that there are areas for improvement. Recognition is not necessarily monetary and should be tailored to the needs and the values of the recipient. Other themes included: benefits and challenges of being a preceptor, current institutional structures and supports, and the impact of the pandemic on preceptors.

Conclusions: The interviews highlighted the importance placed by preceptors on personal rewards and a wide variety of forms of recognition. Based on the findings, we suggest specific steps that medical schools can take to support, engage, and recognize DME faculty.
The Influence of Modern Trends in the Development of the Creative Economy on the Education System
Authors: Vakhorina Marina
Published: June 2022

The need for research is caused by the influence of the development of modern trends in the creative economy (knowledge economy) on the education system. The aim of the study is to develop the theoretical provisions of the innovative format of education in the conditions of the information and creative economy. Based on the goal, the tasks of the study were determined and solved: an analysis was made of the essence and trends in the development of the creative economy for the formation of skills that a new type of specialist should possess; the influence of technological trends on the labor market is revealed in order to use the promising landscape of creative professions.

The article systematizes the review of the terms "creative economy" and "creative industries", used in professional literature and in normative sources. The historical aspects of the post-industrial development of the economy in Russia from mass production to personal production are revealed based on the requirements for human resources. The study used methods of comparison, generalization and critical evaluation. The practical significance of the topic is based on the international experience of integration using the Global Innovation Index and the Index of Innovative Cities. Based on the identification of the specifics of the creative economy, the provisions of the Concept for the Development of Creative (Creative) Industries until 2030, promising areas for the creative economy to human resources are identified.

The results obtained are accompanied by elements of scientific novelty: it is proposed to integrate the development trends of the creative economy in order to activate and effectively use the creative human potential, which is an important factor in the stabilization and sustainable development of the modern economy. The results of the study can be used as a theoretical basis for further research on this topic, in the practical activities of entrepreneurs and business owners who work in the field of creative industries, as well as individual research results can be used in the educational process of universities in the preparation of bachelors, masters in various fields.
The main Factors of Labor Productivity in the Regions of the Central Federal District
Authors: Basovskiy Leonid , Basovskaya Elena
Published: June 2022

To assess the impact of production factors on labor productivity in the regions of the Central Federal District, based on cross-regional data, econometric models were built. At the same time, the hypothesis was evaluated that in the process of transition to a post-industrial economy, along with traditional factors, labor productivity is significantly influenced by human capital and new technologies. When performing research, econometric models were obtained in the form of internally linear functions. As a factor of new technologies that determines labor productivity, we used data on the share of innovation costs in the total output of enterprises and organizations in the region. As human capital factors, we used data on the average level of education of employees in the region, which was estimated by the average length of their education in the education system, as well as on the shares of employed workers with different levels of education. The results obtained allow us to conclude that in the regions of the Central Federal District, labor productivity, new technologies in the form of innovation and the human capital of employed workers, measured by the level of education, have a significant positive impact on productivity. The use of labor of workers with higher education and the labor of workers with secondary vocational education who have been trained in training programs for mid-level specialists has a positive impact on labor productivity. Labor productivity is negatively affected by the use of labor of workers with secondary vocational education in training programs for skilled workers and employees, the use of labor of workers with secondary general education, basic general education, who also do not have basic general education.
Analysis of the Main Economic Results and Prospects for the Activities of Special Economic Zones in Russia
Authors: Ryzhov Yu. , Fedorova E.
Published: June 2022

2022 was a turning point for the Russian economy. In the context of geopolitical risks of full-scale investments, a complete outflow of foreign capital, collapsed value chains, inevitable and future decisions to review the effective management of structural transformations in the economy, reformatting or abandoning the partial effectiveness of development institutions.

In modern realities, an unbiased analysis of the prospects for the operation of special economic zones (SEZs), which are a widely used tool for regional economic development responsible for creating an investment climate, is needed.

This paper assesses the effectiveness of a number of SEZs, outlines the economic root causes of their insufficient budgetary efficiency, presents a point of view on the applicability and functionality of this institution in modern realities, and outlines the problems of state management of structural transformations in the economy using the example of SEZs.