bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractHippocampal 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

Abstract
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

AbstractMentors 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundChoosing 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.ResultsA 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).ConclusionsThe 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.