bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amplicon deep sequencing of five highly
polymorphic markers of Plasmodium falciparum reveals high parasite genetic diversity and moderate population
structure in Ethiopia
Authors: Reda Abeba Gebretsadik , Huwe Tiffany , Koepfli Cristian , Assefa Ashenafi , Tessema Sofonias Kifle , Messele Alebachew , Golassa Lemu , Mamo Hassen 
Published: December 2023

Abstract
Background
Plasmodium falciparum genetic diversity can add information on transmission intensity and can be used to track control and elimination interventions.

Methods
Dried blood spots (DBS) were collected from patients who were recruited for a P. falciparum malaria therapeutic efficacy trial in three malaria endemic sites in Ethiopia from October to December 2015, and November to December 2019. qPCR-confirmed infections were subject to amplicon sequencing of polymorphic markers ama1-D3, csp, cpp, cpmp, msp7. Genetic diversity, the proportion of multiclonal infections, multiplicity of infection, and population structure were analysed.

Results
Among 198 samples selected for sequencing, data was obtained for 181 samples. Mean MOI was 1.38 (95% CI 1.24–1.53) and 17% (31/181) of infections were polyclonal. Mean He across all markers was 0.730. Population structure was moderate; populations from Metema and Metehara 2015 were very similar to each other, but distinct from Wondogent 2015 and Metehara 2019.

Conclusion
The high level of parasite genetic diversity and moderate population structure in this study suggests frequent gene flow of parasites among sites. The results obtained can be used as a baseline for additional parasite genetic diversity and structure studies, aiding in the formulation of appropriate control strategies in Ethiopia.
Extracellular vesicles from hiPSC-NSCs can prevent peripheral inflammation-induced cognitive dysfunction with inflammasome inhibition and improved neurogenesis in the hippocampus
Authors: Ayyubova Gunel , Kodali Maheedhar , Upadhya Raghavendra , Madhu Leelavathi N. , Attaluri Sahithi , Somayaji Yogish , Shuai Bing , Rao Shama , Shankar Goutham , Shetty Ashok K. 
Published: December 2023

AbstractExtracellular vesicles (EVs) released by human induced pluripotent stem cell-derived neural stem cells (hiPSC-NSCs) are enriched with miRNAs and proteins capable of mediating robust antiinflammatory activity. The lack of tumorigenic and immunogenic properties and ability to permeate the entire brain to incorporate into microglia following intranasal (IN) administrations makes them an attractive biologic for curtailing chronic neuroinflammation in neurodegenerative disorders. We tested the hypothesis that IN administrations of hiPSC-NSC-EVs can alleviate chronic neuroinflammation and cognitive impairments induced by the peripheral lipopolysaccharide (LPS) challenge. Adult male, C57BL/6J mice received intraperitoneal injections of LPS (0.75 mg/kg) for seven consecutive days. Then, the mice received either vehicle (VEH) or hiPSC-NSC-EVs (~ 10 × 109 EVs/administration, thrice over 6 days). A month later, mice in all groups were investigated for cognitive function with behavioral tests and euthanized for histological and biochemical studies. Mice receiving VEH after LPS displayed deficits in associative recognition memory, temporal pattern processing, and pattern separation. Such impairments were associated with an increased incidence of activated microglia presenting NOD-, LRR-, and pyrin domain containing 3 (NLRP3) inflammasomes, elevated levels of NLRP3 inflammasome mediators and end products, and decreased neurogenesis in the hippocampus. In contrast, the various cognitive measures in mice receiving hiPSC-NSC-EVs after LPS were closer to naive mice. Significantly, these mice displayed diminished microglial activation, NLRP3 inflammasomes, proinflammatory cytokines, and a level of neurogenesis matching age-matched naïve controls. Thus, IN administrations of hiPSC-NSC-EVs are an efficacious approach to reducing chronic neuroinflammation-induced cognitive impairments.
Empagliflozin targets Mfn1 and Opa1 to attenuate microglia-mediated neuroinflammation in retinal ischemia and reperfusion injury
Authors: Yang Zhenlan , Liu Yidan , Chen Xuhao , Huang Shaofen , Li Yangyang , Ye Guitong , Cao Xu , Su Wenru , Zhuo Yehong 
Published: December 2023

Abstract
Background
Neuroinflammation and mitochondrial dysfunction play crucial roles in retinal ischemia and reperfusion (IR) injury. Recent studies have identified mitochondrial function as a promising target for immunomodulation. Empagliflozin (EMPA), an anti-diabetic drug, has exhibited great potential as both an anti-inflammatory agent and a protector of mitochondrial health. This study aimed to assess the therapeutic efficacy of EMPA in retinal IR injury.

Methods
To evaluate the protective effects of EMPA, the drug was injected into the vitreous body of mice post-retinal IR. Single-cell RNA sequencing (scRNA-seq) analysis was conducted to uncover the underlying mechanisms, and the results were further validated through in vivo and in vitro experiments.

Results
EMPA effectively protected retinal ganglion cells (RGCs) from IR injury by attenuating local retinal inflammation. The scRNA-seq analysis revealed that EMPA downregulated the nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) signaling pathway and restored mitochondrial dynamics by upregulating the expression of mitochondrial fusion-related genes, Mitofusin 1 (Mfn1) and optic atrophy 1 (Opa1). These findings were further corroborated by Western blotting. In vitro experiments provided additional insights, demonstrating that EMPA suppressed lipopolysaccharide (LPS)-induced cell inflammation and NLRP3 inflammasome activation. Moreover, EMPA enhanced mitochondrial fusion, neutralized mitochondrial reactive oxygen species (mtROS), and restored mitochondrial membrane potential (MMP) in BV2 microglia. Notably, genetic ablation of Mfn1 or Opa1 abolished the anti-inflammatory effects of EMPA.

Conclusions
Our findings highlight the positive contribution of Mfn1 and Opa1 to the anti-inflammatory therapeutic effect of EMPA. By restoring mitochondrial dynamics, EMPA effectively mitigates microglia-mediated neuroinflammation and prevents RGC loss in retinal IR injury.
Armstrong strain lymphocytic choriomeningitis virus infection after accidental laboratory exposure
Authors: Caron Laurence , Delisle Jean-Sébastien , Strong James E , Deschambault Yvon , Lombard-Vadnais Félix , Labbé Annie-Claude , Lesage Sylvie 
Published: December 2023

Abstract
Background
Lymphocytic choriomeningitis virus (LCMV) is a human pathogen naturally present in wild rodents. In addition, LCMV is routinely used in immunology research as a model of viral infection in mice. The Armstrong common laboratory strain and the Clone-13 variant induce acute and chronic infections in mice, respectively. The frequent use of this virus in laboratory settings is associated with a risk of human infection for laboratory personnel. In contrast to LCMV Clone-13, few human laboratory infections with LCMV Armstrong have been reported, leading to a poor understanding of symptoms related to infection with this specific LCMV strain.

Case presentation
A researcher accidentally infected herself percutaneously with LCMV Armstrong. Symptoms including headaches, dizziness, eye pain and nausea appeared seven days post-exposure and lasted ten days. LCMV-IgM antibodies were detected at 28 days post-infection and IgG seroconversion was observed later. Complete recovery was confirmed three months post exposure.

Conclusions
Research involving live viruses comes with the risk of infection for research personnel. This case is the first reported accidental human infection with LCMV Armstrong. The symptoms differed from reported infections with LCMV Clone-13, by the absence of fever and vomiting, and presence of leg numbness. This report will therefore help clinicians and public health authorities to recognize the symptoms associated with LCMV Armstrong infections and to offer appropriate counselling to individuals who accidentally expose themselves.
An environmental scan of residential treatment service provision in Ontario
Authors: Ali Farihah , Law Justine , Russell Cayley , Bozinoff Nikki , Rush Brian 
Published: December 2023

Abstract
Background
Ontario has one of the highest rates of substance-related harms in Canada. Residential treatment programs in the province provide a variety of in-house treatment services to support the needs of individuals with substance use disorders (SUD). However, these programs are not standardized, often varying in the type, quality, and availability of services offered, including evidence-based interventions such as Opioid Agonist Treatment (OAT). Local treatment systems are also rather fragmented and complex to navigate, creating barriers for potential services users to identify and make informed choices on available treatment options.

Methods
Between May to August 2023, we conducted an environmental scan to capture available information on all publicly-funded residential treatment programs in Ontario using the ConnexOntario service portal, a government-funded, health services information platform. Data were captured on organization name, geographical location, program description, program type (residential addictions treatment or supportive recovery programs), eligibility criteria, target population, the program’s OAT policies, number of available beds, minimum and maximum length of stay, projected wait times, funding source, and associated fees for program admission. Data were extracted and organized by geographic region, and findings were presented descriptively.

Results
A total of 102 residential addiction treatment programs and 36 residential supportive recovery programs in Ontario were identified. The scan noted substantial regional variations in program availability and wait times, along with a lack of programs tailored to unique populations such as women, youth, and Indigenous peoples. There is also a paucity of publicly-available information on program offerings, including detailed specifics on OAT policies within residential treatment programs that are crucial to ensuring that the services being offered are safe and grounded in evidence-based practice.

Conclusions
Findings from the scan highlight notable gaps in program types, offerings, and availability among residential treatment programs in the province, including a lack of standardization on OAT policies across programs. Efforts should be made to ensure access to treatment-specific program information relevant to potential service users and to enhance coordinated access to residential treatment services in the province.
Histopathologically confirmed radiation-induced damage of the brain – an in-depth analysis of radiation parameters and spatio-temporal occurrence
Authors: Kossmann Mario R. P. , Ehret Felix , Roohani Siyer , Winter Sebastian F. , Ghadjar Pirus , Acker Güliz , Senger Carolin , Schmid Simone , Zips Daniel , Kaul David 
Published: December 2023

Abstract
Background
Radiation-induced damage (RID) after radiotherapy (RT) of primary brain tumors and metastases can be challenging to clinico-radiographically distinguish from tumor progression. RID includes pseudoprogression and radiation necrosis; the latter being irreversible and often associated with severe symptoms. While histopathology constitutes the diagnostic gold standard, biopsy-controlled clinical studies investigating RID remain limited. Whether certain brain areas are potentially more vulnerable to RID remains an area of active investigation. Here, we analyze histopathologically confirmed cases of RID in relation to the temporal and spatial dose distribution.

Methods
Histopathologically confirmed cases of RID after photon-based RT for primary or secondary central nervous system malignancies were included. Demographic, clinical, and dosimetric data were collected from patient records and treatment planning systems. We calculated the equivalent dose in 2 Gy fractions (EQD22) and the biologically effective dose (BED2) for normal brain tissue (α/β ratio of 2 Gy) and analyzed the spatial and temporal distribution using frequency maps.

Results
Thirty-three patients were identified. High-grade glioma patients (n = 18) mostly received one normofractionated RT series (median cumulative EQD22 60 Gy) to a large planning target volume (PTV) (median 203.9 ccm) before diagnosis of RID. Despite the low EQD22 and BED2, three patients with an accelerated hyperfractionated RT developed RID. In contrast, brain metastases patients (n = 15; 16 RID lesions) were often treated with two or more RT courses and with radiosurgery or fractionated stereotactic RT, resulting in a higher cumulative EQD22 (median 162.4 Gy), to a small PTV (median 6.7 ccm). All (n = 34) RID lesions occurred within the PTV of at least one of the preceding RT courses. RID in the high-grade glioma group showed a frontotemporal distribution pattern, whereas, in metastatic patients, RID was observed throughout the brain with highest density in the parietal lobe. The cumulative EQD22 was significantly lower in RID lesions that involved the subventricular zone (SVZ) than in lesions without SVZ involvement (median 60 Gy vs. 141 Gy, p = 0.01).

Conclusions
Accelerated hyperfractionated RT can lead to RID despite computationally low EQD22 and BED2 in high-grade glioma patients. The anatomical location of RID corresponded to the general tumor distribution of gliomas and metastases. The SVZ might be a particularly vulnerable area.
AI algorithms for accurate prediction of osteoporotic fractures in patients with diabetes: an up-to-date review
Authors: Li Zeting , Zhao Wen , Lin Xiahong , Li Fangping 
Published: December 2023

AbstractOsteoporotic fractures impose a substantial burden on patients with diabetes due to their unique characteristics in bone metabolism, limiting the efficacy of conventional fracture prediction tools. Artificial intelligence (AI) algorithms have shown great promise in predicting osteoporotic fractures. This review aims to evaluate the application of traditional fracture prediction tools (FRAX, QFracture, and Garvan FRC) in patients with diabetes and osteoporosis, review AI-based fracture prediction achievements, and assess the potential efficiency of AI algorithms in this population. This comprehensive literature search was conducted in Pubmed and Web of Science. We found that conventional prediction tools exhibit limited accuracy in predicting fractures in patients with diabetes and osteoporosis due to their distinct bone metabolism characteristics. Conversely, AI algorithms show remarkable potential in enhancing predictive precision and improving patient outcomes. However, the utilization of AI algorithms for predicting osteoporotic fractures in diabetic patients is still in its nascent phase, further research is required to validate their efficacy and assess the potential advantages of their application in clinical practice.
Interleukin-30 subverts prostate cancer-endothelium crosstalk by fostering angiogenesis and activating immunoregulatory and oncogenic signaling pathways
Authors: Ciummo Stefania Livia , Sorrentino Carlo , Fieni Cristiano , Di Carlo Emma 
Published: December 2023

Abstract
Background
Cancer-endothelial interplay is crucial for tumor behavior, yet the molecular mechanisms involved are largely unknown. Interleukin(IL)-30, which is expressed as a membrane-anchored cytokine by human prostate cancer (PC) cells, promotes PC vascularization and progression, but the underlying mechanisms have yet to be fully explored.

Methods
PC-endothelial cell (EC) interactions were investigated, after coculture, by flow cytometry, transcriptional profiling, western blot, and ELISA assays. Proteome profiler phospho-kinase array unveiled the molecular pathways involved. The role of tumor-derived IL30 on the endothelium's capacity to generate autocrine circuits and vascular budding was determined following IL30 overexpression, by gene transfection, or its deletion by CRISPR/Cas9 genome editing. Clinical value of the experimental findings was determined through immunopathological study of experimental and patient-derived PC samples, and bioinformatics of gene expression profiles from PC patients.

Results
Contact with PC cells favors EC proliferation and production of angiogenic and angiocrine factors, which are boosted by PC expression of IL30, that feeds autocrine loops, mediated by IGF1, EDN1, ANG and CXCL10, and promotes vascular budding and inflammation, via phosphorylation of multiple signaling proteins, such as Src, Yes, STAT3, STAT6, RSK1/2, c-Jun, AKT and, primarily CREB, GSK-3α/β, HSP60 and p53. Deletion of the IL30 gene in PC cells inhibits endothelial expression of IGF1, EDN1, ANG and CXCL10 and substantially impairs tumor angiogenesis. In its interaction with IL30-overexpressing PC cells the endothelium boosts their expression of a wide range of immunity regulatory genes, including CCL28, CCL4, CCL5, CCR2, CCR7, CXCR4, IL10, IL13, IL17A, FASLG, IDO1, KITLG, TNFA, TNFSF10 and PDCD1, and cancer driver genes, including BCL2, CCND2, EGR3, IL6, VEGFA, KLK3, PTGS1, LGALS4, GNRH1 and SHBG. Immunopathological analyses of PC xenografts and in silico investigation of 1116 PC cases, from the Prostate Cancer Transcriptome Atlas, confirmed the correlation between the expression of IL30 and that of both pro-inflammatory genes, NOS2, TNFA, CXCR5 and IL12B, and cancer driver genes, LGALS4, GNRH1 and SHBG, which was validated in a cohort of 80 PC patients.

Conclusions
IL30 regulates the crosstalk between PC and EC and reshapes their transcriptional profiles, triggering angiogenic, immunoregulatory and oncogenic gene expression programs. These findings highlight the angiostatic and oncostatic efficacy of targeting IL30 to fight PC.
Study protocol for a randomized controlled trial of RealConsent2.0: a web-based intervention to promote prosocial alcohol-involved bystander behavior in young men
Authors: Salazar Laura F. , Parrott Dominic J. , DiLillo David , Gervais Sarah , Schipani-McLaughlin Anne Marie , Leone Ruschelle , Swartout Kevin , Simpson Lauren , Moore Renita , Wilson Tiffany , Flowers Nyla , Church Haley , Baildon Amanda 
Published: December 2023

Abstract
Background
Sexual violence (SV) is a significant, global public health problem, particularly among young adults. Promising interventions exist, including prosocial bystander intervention programs that train bystanders to intervene in situations at-risk for SV. However, these programs suffer from critical weaknesses: (1) they do not address the proximal effect of alcohol use on bystander decision-making and (2) they rely on self-report measures to evaluate outcomes. To overcome these limitations, we integrate new content specific to alcohol use within the context of prosocial bystander intervention into an existing, evidence-based program, RealConsent1.0. The resulting program, RealConsent2.0, aims to facilitate bystander behavior among sober and intoxicated bystanders and uses a virtual reality (VR) environment to assess bystander behavior in the context of acute alcohol use.

Methods
This protocol paper presents the design of a randomized controlled trial (RCT) in which we evaluate RealConsent2.0 for efficacy in increasing alcohol- and non-alcohol-involved bystander behavior compared to RealConsent1.0 or to an attention-control program (“Taking Charge”). The RCT is being implemented in Atlanta, GA, and Lincoln, NE. Participants will be 605, healthy men aged 21–25 years recruited through social media, community-based flyers, and university email lists. Eligible participants who provide informed consent and complete the baseline survey, which includes self-reported bystander behavior, are then randomized to one of six conditions: RealConsent2.0/alcohol, RealConsent2.0/placebo, RealConsent1.0/alcohol, RealConsent1.0/placebo, Taking Charge/alcohol, or Taking Charge/placebo. After completing their assigned program, participants complete a laboratory session in which they consume an alcohol (target BrAC: .08%) or placebo beverage and then engage in the Bystanders in Sexual Assault Virtual Environments (BSAVE), a virtual house party comprising situations in which participants have opportunities to intervene. Self-reported bystander behavior across alcohol and non-alcohol contexts is also assessed at 6- and 12-months post-intervention. Secondary outcomes include attitudes toward, outcome expectancies for, and self-efficacy for bystander behavior via self-report.

Discussion
RealConsent2.0 is the first web-based intervention for young men that encourages and teaches skills to engage in prosocial bystander behavior to prevent SV while intoxicated. This is also the first study to assess the proximal effect of alcohol on bystander behavior via a VR environment.

Trial registration
Clinicaltrials.gov, NCT04912492. Registered on 05 February 2021
Development of highly efficient and specific base editors in Actinobacillus succinogenes for enhancing succinic acid production
Authors: Chen Chunmei , Zheng Pu , Chen Pengcheng , Wu Dan 
Published: December 2023

AbstractThe production of bio-succinic acid (SA) from renewable feedstocks is a promising and sustainable approach to mitigating the high carbon emissions associated with the current energy crisis. Actinobacillus succinogenes was recognized as one of the most promising SA producers; however, lack of genetic background and the scarcity of genetic manipulation tools hinder the improvement in A. succinogenes by metabolic engineering. Here, for the first time, we successfully developed a series of A. succinogenes base editors (BEs) mediated by the fusion of Cas9 nickase and deaminase, including CBE, ABE, Td-GABE, and Td-CBE. Among these, ABE and Td-CBE based on a fusion of Cas9 nickase and TadA-8e variant (Escherichia coli TadA) can efficiently convert A to G and C to T, respectively, with editing efficiencies of up to 100%. We also investigated the multiplex base editing of ABE and Td-CBE, and the results showed that the editing efficiency of ABE reached 100% for six sites and 10% editing efficiency of Td-CBE for two sites. In addition, cytosine base editors were applied to inactivate hypothetical sugar and SA transporters of A. succinogenes. We found that the inactivation of Asuc_0914 encoding sucrose-specific IIBC subunit enhanced SA production, while the inactivation of hypothetical SA transporters Asuc_0715 and Asuc_0716 significantly reduced SA production. Therefore, the tools have great application potential in the metabolic engineering of A. succinogenes.
t(1;4) translocation in a child with acute lymphoblastic leukemia: a case report
Authors: El Mahdaoui Chaimae , Hda Nezha , Oukkache Bouchra , Dehbi Hind , Khoubila Nisrine , Madani Abdellah , Cherkaoui Siham 
Published: December 2023

Abstract
Background
Acute lymphoblastic leukemia is the most common childhood cancer, with an 80% frequency in children between 1 and 10 years old. The outcome and prognosis of acute lymphoblastic leukemia in children depends on various factors, such as age, clinical and biological features, and cytogenetic factors.

Case presentation
We report the case of a pediatric patient, a 4-year-old Moroccan female who was referred to the Hematology and Oncology Department of 20 August 1953 Hospital in Casablanca and diagnosed with B-cell acute lymphoblastic leukemia associated with a rare genetic chromosomal abnormality.

Conclusion
Translocation (1;4)(p21;p15) is a relatively rare chromosomal abnormality found in human leukemia and was never described isolated in pediatric B-cell acute lymphoblastic leukemia patients. It showed a good evolution by complete remission and recovery of this patient after receiving all chemotherapy and after 8 years of follow-up.