bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chiral nanomaterials for tumor therapy: autophagy, apoptosis, and photothermal ablation
Authors: Peng Zaihui , Yuan Long , XuHong Juncheng , Tian Hao , Zhang Yi , Deng Jun , Qi Xiaowei 
Published: July 2021

AbstractChirality is a fundamental characteristic of natural molecules and a crucial factor in the biochemical reactions of living cells and organisms. Recently, researchers have successfully introduced chiral molecules to the surfaces of nanomaterials, creating chiral nanomaterials that exhibit an upscaling of chiral behavior from the molecular scale to the nanoscale. These chiral nanomaterials can selectively induce autophagy, apoptosis, and photothermal ablation in tumor cells based on their chirality, making them promising for application in anti-tumor therapy. However, these interesting and important phenomena have hitherto received little attention. Accordingly, we herein present a review of recent research progress in the field of chiral nanomaterials for tumor therapy along with brief looks at the mechanistic details of their actions. Finally, the current challenges and future perspectives of chiral nanomaterials in terms of maximizing their potential in tumor therapy are discussed. Thus, this review provides a helpful introduction to the design of chiral nanomaterials and will hopefully highlight the importance of chirality in tumor therapy.
Cellular dynamics of EMT: lessons from live in vivo imaging of embryonic development
Authors: Amack Jeffrey D. 
Published: July 2021

AbstractEpithelial-mesenchymal transition (EMT) refers to a process in which epithelial cells lose apical-basal polarity and loosen cell–cell junctions to take on mesenchymal cell morphologies and invasive properties that facilitate migration through extracellular matrix. EMT—and the reverse mesenchymal-epithelial transition (MET)—are evolutionarily conserved processes that are used throughout embryonic development to drive tissue morphogenesis. During adult life, EMT is activated to close wounds after injury, but also can be used by cancers to promote metastasis. EMT is controlled by several mechanisms that depend on context. In response to cell–cell signaling and/or interactions with the local environment, cells undergoing EMT make rapid changes in kinase and adaptor proteins, adhesion and extracellular matrix molecules, and gene expression. Many of these changes modulate localization, activity, or expression of cytoskeletal proteins that mediate cell shape changes and cell motility. Since cellular changes during EMT are highly dynamic and context-dependent, it is ideal to analyze this process in situ in living organisms. Embryonic development of model organisms is amenable to live time-lapse microscopy, which provides an opportunity to watch EMT as it happens. Here, with a focus on functions of the actin cytoskeleton, I review recent examples of how live in vivo imaging of embryonic development has led to new insights into mechanisms of EMT. At the same time, I highlight specific developmental processes in model embryos—gastrulation in fly and mouse embryos, and neural crest cell development in zebrafish and frog embryos—that provide in vivo platforms for visualizing cellular dynamics during EMT. In addition, I introduce Kupffer’s vesicle in the zebrafish embryo as a new model system to investigate EMT and MET. I discuss how these systems have provided insights into the dynamics of adherens junction remodeling, planar cell polarity signaling, cadherin functions, and cytoskeletal organization during EMT, which are not only important for understanding development, but also cancer progression. These findings shed light on mechanisms of actin cytoskeletal dynamics during EMT, and feature live in vivo imaging strategies that can be exploited in future work to identify new mechanisms of EMT and MET.
Conflict and COVID-19 in Yemen: beyond the humanitarian crisis
Authors: Alsabri Mohammed , Alhadheri Ayman , Alsakkaf Luai M. , Cole Jennifer 
Published: July 2021

Abstract
Background
Yemen has been left in shambles and almost destroyed by its devastating civil war, and is now having to deal with the spread of coronavirus. The Yemeni people have been left to fend for themselves and faced many problems such as hunger, the ongoing war, infections, diseases and lack of equipment even before the COVID-19 pandemic. All together it is a humanitarian crisis. Only around 50% of the hospitals and healthcare facilities are in full working condition, and even those that are functioning are operating at nowhere near full potential. Healthcare staff and facilities lack necessary essential equipment and money.

Conclusion
As, sadly, is common in conflict-affected regions, the violence has brought with it a secondary disaster of infectious disease outbreaks. Yemen is not only battling COVID-19 amid a catastrophic war, but also has to deal with other diseases such as cholera, diphtheria and measles. A number of key measures are needed to support the current efforts against this deadly epidemic and its potential subsequent waves as well as to prevent further epidemics in Yemen.
The combined prevalence of classified rare rheumatic diseases is almost double that of ankylosing spondylitis
Authors: Leyens Judith , Bender Tim Th. A. , Mücke Martin , Stieber Christiane , Kravchenko Dmitrij , Dernbach Christian , Seidel Matthias F. 
Published: July 2021

Abstract
Background
Rare diseases (RDs) affect less than 5/10,000 people in Europe and fewer than 200,000 individuals in the United States. In rheumatology, RDs are heterogeneous and lack systemic classification. Clinical courses involve a variety of diverse symptoms, and patients may be misdiagnosed and not receive appropriate treatment. The objective of this study was to identify and classify some of the most important RDs in rheumatology. We also attempted to determine their combined prevalence to more precisely define this area of rheumatology and increase awareness of RDs in healthcare systems. We conducted a comprehensive literature search and analyzed each disease for the specified criteria, such as clinical symptoms, treatment regimens, prognoses, and point prevalences. If no epidemiological data were available, we estimated the prevalence as 1/1,000,000. The total point prevalence for all RDs in rheumatology was estimated as the sum of the individually determined prevalences.

Results
A total of 76 syndromes and diseases were identified, including vasculitis/vasculopathy (n = 15), arthritis/arthropathy (n = 11), autoinflammatory syndromes (n = 11), myositis (n = 9), bone disorders (n = 11), connective tissue diseases (n = 8), overgrowth syndromes (n = 3), and others (n = 8). Out of the 76 diseases, 61 (80%) are classified as chronic, with a remitting-relapsing course in 27 cases (35%) upon adequate treatment. Another 34 (45%) diseases were predominantly progressive and difficult to control. Corticosteroids are a therapeutic option in 49 (64%) syndromes. Mortality is variable and could not be determined precisely. Epidemiological studies and prevalence data were available for 33 syndromes and diseases. For an additional eight diseases, only incidence data were accessible. The summed prevalence of all RDs was 28.8/10,000.

Conclusions
RDs in rheumatology are frequently chronic, progressive, and present variable symptoms. Treatment options are often restricted to corticosteroids, presumably because of the scarcity of randomized controlled trials. The estimated combined prevalence is significant and almost double that of ankylosing spondylitis (18/10,000). Thus, healthcare systems should assign RDs similar importance as any other common disease in rheumatology.
Metabolic landscapes in sarcomas
Authors: Miallot Richard , Galland Franck , Millet Virginie , Blay Jean-Yves , Naquet Philippe 
Published: July 2021

AbstractMetabolic rewiring offers novel therapeutic opportunities in cancer. Until recently, there was scant information regarding soft tissue sarcomas, due to their heterogeneous tissue origin, histological definition and underlying genetic history. Novel large-scale genomic and metabolomics approaches are now helping stratify their physiopathology. In this review, we show how various genetic alterations skew activation pathways and orient metabolic rewiring in sarcomas. We provide an update on the contribution of newly described mechanisms of metabolic regulation. We underscore mechanisms that are relevant to sarcomagenesis or shared with other cancers. We then discuss how diverse metabolic landscapes condition the tumor microenvironment, anti-sarcoma immune responses and prognosis. Finally, we review current attempts to control sarcoma growth using metabolite-targeting drugs.
Optimizing cisplatin delivery to triple-negative breast cancer through novel EGFR aptamer-conjugated polymeric nanovectors
Authors: Agnello Lisa , Tortorella Silvia , d’Argenio Annachiara , Carbone Clarissa , Camorani Simona , Locatelli Erica , Auletta Luigi , Sorrentino Domenico , Fedele Monica , Zannetti Antonella , Franchini Mauro Comes , Cerchia Laura 
Published: July 2021

Abstract
Background
Management of triple-negative breast cancer (TNBC) is still challenging because of its aggressive clinical behavior and limited targeted treatment options. Cisplatin represents a promising chemotherapeutic compound in neoadjuvant approaches and in the metastatic setting, but its use is limited by scarce bioavailability, severe systemic side effects and drug resistance. Novel site-directed aptamer-based nanotherapeutics have the potential to overcome obstacles of chemotherapy. In this study we investigated the tumor targeting and the anti-tumorigenic effectiveness of novel cisplatin-loaded and aptamer-decorated nanosystems in TNBC.

Methods
Nanotechnological procedures were applied to entrap cisplatin at high efficacy into polymeric nanoparticles (PNPs) that were conjugated on their surface with the epidermal growth factor receptor (EGFR) selective and cell-internalizing CL4 aptamer to improve targeted therapy. Internalization into TNBC MDA-MB-231 and BT-549 cells of aptamer-decorated PNPs, loaded with BODIPY505-515, was monitored by confocal microscopy using EGFR-depleted cells as negative control. Tumor targeting and biodistribution was evaluated by fluorescence reflectance imaging upon intravenously injection of Cyanine7-labeled nanovectors in nude mice bearing subcutaneous MDA-MB-231 tumors. Cytotoxicity of cisplatin-loaded PNPs toward TNBC cells was evaluated by MTT assay and the antitumor effect was assessed by tumor growth experiments in vivo and ex vivo analyses.

Results
We demonstrate specific, high and rapid uptake into EGFR-positive TNBC cells of CL4-conjugated fluorescent PNPs which, when loaded with cisplatin, resulted considerably more cytotoxic than the free drug and nanovectors either unconjugated or conjugated with a scrambled aptamer. Importantly, animal studies showed that the CL4-equipped PNPs achieve significantly higher tumor targeting efficiency and enhanced therapeutic effects, without any signs of systemic toxicity, compared with free cisplatin and untargeted PNPs.

Conclusions
Our study proposes novel and safe drug-loaded targeted nanosystems for EGFR-positive TNBC with excellent potential for the application in cancer diagnosis and therapy.
A review of Dynamin 2 involvement in cancers highlights a promising therapeutic target
Authors: Trochet Delphine , Bitoun Marc 
Published: July 2021

AbstractDynamin 2 (DNM2) is an ubiquitously expressed large GTPase well known for its role in vesicle formation in endocytosis and intracellular membrane trafficking also acting as a regulator of cytoskeletons. During the last two decades, DNM2 involvement, through mutations or overexpression, emerged in an increasing number of cancers and often associated with poor prognosis. A wide panel of DNM2-dependent processes was described in cancer cells which explains DNM2 contribution to cancer pathomechanisms. First, DNM2 dysfunction may promote cell migration, invasion and metastasis. Second, DNM2 acts on intracellular signaling pathways fostering tumor cell proliferation and survival. Relative to these roles, DNM2 was demonstrated as a therapeutic target able to reduce cell proliferation, induce apoptosis, and reduce the invasive phenotype in a wide range of cancer cells in vitro. Moreover, proofs of concept of therapy by modulation of DNM2 expression was also achieved in vivo in several animal models. Consequently, DNM2 appears as a promising molecular target for the development of anti-invasive agents and the already provided proofs of concept in animal models represent an important step of preclinical development.
Advancing collaborations in health research and clinical trials in Sub-Saharan Africa: development and implementation of a biostatistical collaboration module in the Masters in Biostatistics Program at Stellenbosch University
Authors: Esterhuizen Tonya M. , Li Guowei , Young Taryn , Zeng Jie , Machekano Rhoderick , Thabane Lehana 
Published: July 2021

AbstractBackgroundSub-Saharan Africa continues to carry a high burden of communicable diseases such as TB and HIV and non-communicable diseases such as hypertension and other cardiovascular conditions. Although investment in research has led to advances in improvements in outcomes, a lot still remains to be done to build research capacity in health. Like many other regions in the world, Sub-Saharan Africa suffers from a critical shortage of biostatisticians and clinical trial methodologists.MethodsFunded through a Fogarty Global Health Training Program grant, the Faculty of Medicine and Health Sciences at Stellenbosch University in South Africa established a new Masters Program in Biostatistics which was launched in January 2017. In this paper, we describe the development of a biostatistical and clinical trials collaboration Module, adapted from a similar course offered in the Health Research Methodology program at McMaster University.DiscussionGuided by three core principles (experiential learning; multi-/inter-disciplinary approach; and formal mentorship), the Module aims to advance biostatistical collaboration skills of the trainees by facilitating learning in how to systematically apply fundamental statistical and trial methodological knowledge in practice while strengthening some soft skills which are necessary for effective collaborations with other healthcare researchers to solve health problems. We also share some preliminary findings from the first four cohorts that took the Module in January–November 2018 to 2021. We expect that this Module can provide an example of how to improve biostatistical and clinical trial collaborations and accelerate research capacity building in low-resource settings.Funding sourceFogarty International Center of the National Institutes of Health.
Mental health and resilience among Eritrean refugees at arrival and one-year post-registration in Switzerland: a cohort study
Authors: Chernet Afona , Probst-Hensch Nicole , Sydow Véronique , Paris Daniel H. , Labhardt Niklaus D. 
Published: July 2021

Abstract
Objective
Eritrea is the most frequent country of origin among asylum seekers in Switzerland. On their journey through the desert and across the Mediterranean Sea, Eritrea refugees are often exposed to traumatizing experiences. The aim of this study is to assess the mental health status and resilience of Eritrean migrants in Switzerland upon arrival and one-year post-arrival, using standardized mental health screening and resilience assessment tools.

Results
At baseline, 107 refugees (11.2% female, median age 25) were interviewed: 52 (48.6%) screened positive for Post-Traumatic Stress Disorder (score ≥ 30), 10.3% for anxiety (≥ 10) and 15.0% for depression (≥ 10); 17.8% scored as risk/hazardous drinkers (≥ 8). The majority (94.4%) had a high resilience score (≥ 65). For one-year follow-up, 48 asylum seekers could be reached. In interviews 18 (38%) of these reported imprisonment in a transit country and 28 (58%) that they had witnessed the death of a close person along the migration route. At the one year assessment, rates of risky/hazardous alcohol use remained unchanged, rates of positive PTSD screening tended to be lower (50.0% (24/48) at baseline vs 25.0% (12/48) at follow-up), as were rates of positive screening for anxiety (8.3% vs 4.2%) and depression (14.6 vs 6.3%).
CD8+ Tregs ameliorate inflammatory reactions in a murine model of allergic rhinitis
Authors: Lin Lin , Dai Fei , Wei Jinjin , Chen Zheng 
Published: July 2021

AbstractBackgroundCD8+CD25+fork-head box transcription factor (Foxp3)+regulatory T cells (CD8+Tregs) play a role in immune tolerance. However, the role of these cells in allergic rhinitis (AR) has not been elucidated. The study aimed to evaluate influences of CD8+Tregs on inflammatory conditions in a murine model of AR.MethodsA murine model of AR was established. CD8+Tregs were isolated from mice nasal mucosa and cultured in vitro. We examined interleukin (IL)-10 and transforming growth factor (TGF)-β in cell cultures. Then, we administered CD8+Tregs into mice nasal mucosal cultures, and examined eosinophil cation protein (ECP), IL-4, IL-5 and IL-13 in these cultures. Finally, we adoptively transferred CD8+Tregs into mice models, and evaluated percentages of CD8+Tregs, numbers of sneezing and nasal rubbing, and counts of eosinophils and contents of ECP, IL-4, IL-5, IL-13, IL-10 and TGF-β in nasal lavage fluid (NLF) in mice.ResultsThe percentage of CD8+Tregs from AR mice was reduced. IL-10 and TGF-β were increased in cell cultures from AR mice. ECP, IL-4, IL-5 and IL-13 were decreased after the AR mice CD8+Tregs administration in mucosal cultures. However, their contents were not changed after normal CD8+Tregs treatment. Additionally, the adoptive transfer of AR CD8+Tregs enhanced the percentage of CD8+Tregs and levels of IL-10 and TGF-β in NLF, reduced numbers of sneezing and nasal rubbing, and counts of eosinophils and concentrations of ECP, IL-4, IL-5 and IL-13 in NLF. However, normal CD8+Tregs could not change above parameters.ConclusionThese findings show that CD8+Tregs may inhibit inflammatory responses in the AR condition.
Perinatal post-mortem magnetic resonance imaging (MRI) of the central nervous system (CNS): a pictorial review
Authors: Pérez-Serrano Carlos , Bartolomé Álvaro , Bargalló Núria , Sebastià Carmen , Nadal Alfons , Gómez Olga , Oleaga Laura 
Published: July 2021

AbstractCentral nervous system (CNS) abnormalities cause approximately 32–37.7% of terminations of pregnancy (TOP). Autopsy is currently the gold standard for assessing dead foetuses and stillborn. However, it has limitations and is sometimes subject to parental rejection. Recent studies have described post-mortem foetal magnetic resonance imaging (MRI) as an alternative and even complementary to autopsy for CNS assessment. Radiologists now play a key role in the evaluation of perinatal deaths. Assessment of foetal CNS abnormalities is difficult, and interpretation of foetal studies requires familiarisation with normal and abnormal findings in post-mortem MRI studies as well as the strengths and limitations of the imaging studies. The purpose of this pictorial review is to report our experience in the post-mortem MRI evaluation of the CNS system, including a description of the protocol used, normal CNS findings related to post-mortem status, abnormal CNS findings in our sample, and the correlation of these findings with histopathological results.
Acute kidney injury with partial Fanconi syndrome in a patient with leptospirosis: a case report
Authors: Weiner Marc , Coen Matteo , Serratrice Jacques , Mavrakanas Thomas A. , Leidi Antonio 
Published: July 2021

Abstract
Background
Leptospirosis is an underdiagnosed bacterial infection with nonspecific symptoms, hence, a diagnostic challenge. Identifying a case of leptospirosis in Switzerland is uncommon. Although kidney complications are frequent in severe forms, including tubular dysfunction, observing this complication is rare in our country. We report the case of a patient with leptospirosis and kidney dysfunction, which was notable for proximal tubulopathy. This case report describes the diagnosis and management of this patient’s tubular dysfunction.

Case presentation
A 34-year-old Caucasian male known for alcohol and drug abuse presented to our emergency department suffering from severe pain in the lower limbs, jaundice, and fever with flu-like symptoms. Physical examination was not contributory. Blood tests showed cytopenia, elevated inflammatory markers, acute kidney injury, and altered liver function tests with predominant cholestasis. Urinalysis showed proteinuria and significant glycosuria without concomitant hyperglycemia. Leptospirosis was suspected and confirmed by both positive serum polymerase chain reaction and elevated immunoglobulin M for Leptospira interrogans. The patient was treated with intravenous amoxicillin–clavulanate and doxycycline for 7 days. After antibiotic treatment, symptoms disappeared, and kidney dysfunction completely resolved.

Conclusion
Our case focuses on the description of leptospirosis-related acute kidney injury with proximal tubular dysfunction, which is a rare finding in Switzerland.
EGR1 dysregulation defines an inflammatory and leukemic program in cell trajectory of human-aged hematopoietic stem cells (HSC)
Authors: Desterke Christophe , Bennaceur-Griscelli Annelise , Turhan Ali G. 
Published: July 2021

Abstract
Background
During aging, hematopoietic stem cells (HSC) lose progressively both their self-renewal and differentiation potential. The precise molecular mechanisms of this phenomenon are not well established. To uncover the molecular events underlying this event, we have performed a bioinformatics analysis of 650 single-cell transcriptomes.

Methods
Single-cell transcriptome analyses of expression heterogeneity, cell cycle, and cell trajectory in human cell compartment enriched in hematopoietic stem cell compartment were investigated in the bone marrow according to the age of the donors. Identification of aging-related nodules was identified by weighted correlation network analysis in this primitive compartment.

Results
The analysis of single-cell transcriptomes allowed to uncover a major upregulation of EGR1 in human-aged lineage−CD34+CD38− cells which present cell cycle dysregulation with reduction of G2/M phase according to less expression of CCND2 during S phase. EGR1 upregulation in aging hematopoietic stem cells was found to be independent of cell cycle phases and gender. EGR1 expression trajectory in aged HSC highlighted a signature enriched in hematopoietic and immune disorders with the best induction of AP-1 complex and quiescence regulators such as EGR1, BTG2, JUNB, and NR41A. Sonic Hedgehog-related TMEM107 transmembrane molecule followed also EGR1 cell trajectory. EGR1-dependent gene weighted network analysis in human HSC-associated IER2 target protein-specific regulators of PP2A activity, IL1B, TNFSF10 ligands, and CD69, SELP membrane molecules in old HSC module with immune and leukemogenic signature. In contrast, for young HSC which were found with different cell cycle phase progression, its specific module highlighted upregulation of HIF1A hypoxic factor, PDE4B immune marker, DRAK2 (STK17B) T cell apoptosis regulator, and MYADM myeloid-associated marker.

Conclusion
EGR1 was found to be connected to the aging of human HSC and highlighted a specific cell trajectory contributing to the dysregulation of an inflammatory and leukemia-related transcriptional program in aged human HSCs. EGR1 and its program were found to be connected to the aging of human HSC with dissociation of quiescence property and cell cycle phase progression in this primitive hematopoietic compartment.