bluuebunny/crossref_metadata_2025 huggingface dataset:
Report of trisomy 2q34-qter and monosomy 4q35.2-qter in a child with mild dysmorphic syndrome and karyotype 46,XY,der(4)t(2;4)(q34;q35.2)pat
Authors: Meza-Espinoza Juan Pablo , Sáinz González Enrique , León-León Christian J. N. , Arámbula-Meraz Eliakym , Contreras-Gutiérrez José Alfredo , García-Magallanes Noemí , Madueña-Molina Jesús , Luque-Ortega Fred , Cervín-Serrano Salvador , Picos-Cárdenas Verónica Judith
Published: May 2020

Background

Concomitant trisomy 2q3 and monosomy 4q3 have been rarely reported. Pure trisomy 2q3 has been associated with microcephaly, hypertelorism, low-set ears, micrognathia, visceral abnormalities, and growth retardation. Monosomy 4q3 includes a wide variety of dysmorphic features such an abnormal skull shape, hypertelorism, Pierre Robin sequence, short nose with abnormal bridge, fifth finger clinodactyly, congenital heart, and genitourinary defects, in addition to intellectual disability, developmental delay, and hypotonia, but more distal deletions involving 4q34-qter may result in milder phenotypes. Here, we present a child with a mild dysmorphic syndrome, resulted of a duplication 2q34-qter and a deletion 4q35.2-qter inherited of his father.

Case presentation

We report a child, who at birth presented hypotonia, dysmorphism, and bilateral cryptorchidism. At 2 years and 9 month of age he showed brachycephaly, narrow forehead, bilateral frontoparietal hypertrichosis, down slanting palpebral fissures, sparse eyebrows, sparse short eyelashes, hypertelorism, depressed nasal root, broad nasal bridge, bulbous nasal tip, prominent colummela, broad nasal ala, smooth filtrum, high arched palate, thin upper lips, and ears rotated backwards. He also showed telethelia, hypertrichosis from dorsal to the sacral region, hands with clinodactyly and hypoplasia of the terminal phalanx of the fifth finger, and broad thumbs, broad first toes, and right cryptorchidism. A chromosomal study revealed a karyotype 46,XY,der(4)t(2;4)(q34;q35.2), while an array comparative genomic hybridization showed a 31.12 Mb duplication of the chromosome 2q34-q37.3 and a 1.49 Mb deletion in the chromosome 4q35.2.

Conclusions

To our knowledge, only four families with translocation t(2;4) have been reported, two of them involving t(2q;4q), but the breakpoints involved in our patient have not been previously observed. The genomic imbalance in this patient was a duplication of 318 genes of the region 2q34-q37.3 and a deletion of 7 genes of 4q35.2. We discuss difficulty to assign specific congenital abnormalities to these duplicated/deleted regions and include some cases with terminal deletions of 4q with normal or just mildly detectable phenotypic effects.
PD1/PD-L1 targeting in advanced soft-tissue sarcomas: a pooled analysis of phase II trials
Authors: Italiano Antoine , Bellera Carine , D’Angelo Sandra
Published: May 2020

Immune checkpoint inhibitors, especially the programmed cell death receptor-1/ligand 1 (PD-1/L1) inhibitors, displayed promising efficacy in several solid tumor types and hematological malignancies. Data related to their activity in soft-tissue sarcomas (STS) are scarce.

We performed a pooled analysis of clinical trials investigating a PD1 or PD-L1 antagonist in patients with advanced STS. Three hundred eighty-four patients were included in the pooled analysis; of those, 153 (39.8%) received a PD1/PD-L1 antagonist as a single agent. In patients treated with anti-PD1/PDL1 as a single agent, the overall response rate (ORR) and non-progression rate (NPR) were 15.1% and 58.5% respectively. In patients treated with a combination regimen, the ORR and NPR were 13.4% and 55.8% respectively. Analysis by histological subtype revealed that patients with alveolar soft part sarcoma and undifferentiated pleomorphic sarcoma exhibited the highest response rates and leiomyosarcoma the lowest. PD-L1 expression rate was low and inconsistently associated with objective response.

PD-1/PD-L1 antagonists have limited activity in unselected STS. Future studies should implement histology and immune-based stratification of STS in their design as well as sequential blood and tissue sampling to better understand the mechanisms of resistance and response given sarcomas inherent heterogeneity.
Emerging role of RNA methyltransferase METTL3 in gastrointestinal cancer
Authors: Wang Qiang , Geng Wei , Guo Huimin , Wang Zhangding , Xu Kaiyue , Chen Chen , Wang Shouyu
Published: May 2020

Gastrointestinal cancer, the most common solid tumor, has a poor prognosis. With the development of high-throughput sequencing and detection technology, recent studies have suggested that many chemical modifications of human RNA are involved in the development of human diseases, including cancer. m6A, the most abundant modification, was revealed to participate in a series of aspects of cancer progression. Recent evidence has shown that methyltransferase-like 3 (METTL3), the first identified and a critical methyltransferase, catalyzes m6A methylation on mRNA or non-coding RNA in mammals, affecting RNA metabolism. Abnormal m6A levels caused by METTL3 have been reported to be involved in different aspects of cancer development, including proliferation, apoptosis, and metastasis. In this review, we will shed light on recent findings regarding the biological function of METTL3 in gastrointestinal cancer and discuss future research directions and potential clinical applications of METTL3 for gastrointestinal cancer.
ABCA8 is regulated by miR-374b-5p and inhibits proliferation and metastasis of hepatocellular carcinoma through the ERK/ZEB1 pathway
Authors: Cui Yifeng , Liang Shuhang , Zhang Shugeng , Zhang Congyi , Zhao Yunzheng , Wu Dehai , Wang Jiabei , Song Ruipeng , Wang Jizhou , Yin Dalong , Liu Yao , Pan Shangha , Liu Xirui , Wang Yan , Han Jihua , Meng Fanzheng , Zhang Bo , Guo Hongrui , Lu Zhaoyang , Liu Lianxin
Published: May 2020

Background

ATP binding cassette subfamily A member 8 (ABCA8) belongs to the ATP binding cassette (ABC) transporter superfamily. ABCA8 is a transmembrane transporter responsible for the transport of organics, such as cholesterol, and drug efflux. Some members of the ABC subfamily, such as ABCA1, may inhibit cancer development. However, the mechanism of ABCA8 in the process of cancer activation is still ambiguous.

Methods

The expression of ABCA8 in human hepatocellular carcinoma (HCC) tissues and cell lines was examined using qPCR, immunoblotting, and immunohistochemical staining. The effects of ABCA8 on the proliferation and metastasis of HCC were examined using in vitro and in vivo functional tests. A luciferase reporter assay was performed to explore the binding between microRNA-374b-5p (miR-374b-5p) and the ABCA8 3′-untranslated region (UTR).

Results

ABCA8 was frequently down-regulated in HCC and this down-regulation was negatively correlated with prognosis. The overexpression of ABCA8 inhibited growth and metastasis in HCC, whereas the knockdown of ABCA8 exerted the antithetical effects both in vivo and in vitro. ABCA8 was down-regulated by miR-374b-5p; this down-regulation can induce epithelial transformation to mesenchyme via the ERK/ZEB1 signaling pathway and promote HCC progression.

Conclusion

We exposed the prognostic value of ABCA8 in HCC, and illuminated a novel pathway in ABCA8-regulated inhibition of HCC tumorigenesis and metastasis. These findings may lead to a new targeted therapy for HCC through the regulation of ABCA8, and miR-374b-5p.
Humanization of care in pediatric wards: differences between perceptions of users and staff according to department type
Authors: Mandato C. , Siano M. A. , De Anseris A. G. E. , Tripodi M. , Massa G. , De Rosa R. , Buffoli M. , Lamanna A. , Siani P. , Vajro P.
Published: May 2020

Background

As the quality and quantity of patient-centered care may be perceived differently by recipients and independent observers, assessment of humanization of pediatric care remains an elusive issue. Herein we aim to analyze differences between the degrees of verified existing vs. perceived humanization issues of a pediatric ward. Furthermore, we examine whether there is concurrence between the degrees of humanization perceived by users (parents/visitors) vs. staff members.

Methods

The study was conducted in the pediatric wards of seven medical centers of the Campania region (Italy) categorized as general (n = 4), children’s (n = 1), and university (n = 2) hospitals. The degree of existing humanization was assessed by a multidisciplinary focus group for each hospital through a pediatric care-oriented checklist specifically developed to individuate the most critical areas (i.e., those with scores < 2.5). The degree of perceived humanization was assessed through four indicators: well-being, social aspects, safety and security, and health promotion.

Results

The focus groups showed that critical areas common to all centers were mainly concerned with welfare, mediation, translation, and interpretation services. Specific critical issues were care and organizational processes oriented to the respect and specificity of the person and care of the relationship with the patient. Perceived humanization questionnaires revealed a lack of recreational facilities and mediation and translation services.

As for specific features investigated by both tools, it was found that mediation and interpretation services were lacking in all facilities while patient perceptions and observer ratings for space, comfort, and orientation concurred only in the general hospital evaluations.

Conclusions

Future humanization interventions to ensure child- and family-friendly hospital care call for careful preliminary assessments, tailored to each pediatric ward category, which should consider possible differences between perceived and verified characteristics.
The Italian paediatric society raccomandations on children and adolescents extra-domestic activities during the SARS COV-2 emergency phase 2
Authors: Villani Alberto , Bozzola Elena , Siani Paolo , Corsello Giovanni
Published: May 2020

Background

Due to novel coronavirus infection emergency, restricting measures have been imposed in Italy. As well as adults, also children are limited in their daily routine.

Main text

As the lockdown period is expected to end on 3rd May 2020, we discuss the opportunity for children to practice safely recreational or physical activity outdoor.

Conclusion

The Italian Paediatric Society recommends specific recreational and physical activities according to the age of the children and respecting social distancing.
Antitumor activity of Z-endoxifen in aromatase inhibitor-sensitive and aromatase inhibitor-resistant estrogen receptor-positive breast cancer
Authors: Jayaraman Swaathi , Hou Xiaonan , Kuffel Mary J. , Suman Vera J. , Hoskin Tanya L. , Reinicke Kathryn E. , Monroe David G. , Kalari Krishna R. , Tang Xiaojia , Zeldenrust Megan A. , Cheng Jingfei , Bruinsma Elizabeth S. , Buhrow Sarah A. , McGovern Renee M. , Safgren Stephanie L. , Walden Chad A. , Carter Jodi M. , Reid Joel M. , Ingle James N. , Ames Matthew M. , Hawse John R. , Goetz Matthew P.
Published: May 2020

Background

The tamoxifen metabolite, Z-endoxifen, demonstrated promising antitumor activity in endocrine-resistant estrogen receptor-positive (ER+) breast cancer. We compared the antitumor activity of Z-endoxifen with tamoxifen and letrozole in the letrozole-sensitive MCF7 aromatase expressing model (MCF7AC1), as well as with tamoxifen, fulvestrant, exemestane, and exemestane plus everolimus in a letrozole-resistant MCF7 model (MCF7LR).

Methods

MCF7AC1 tumor-bearing mice were randomized to control (no drug), letrozole (10 μg/day), tamoxifen (500 μg/day), or Z-endoxifen (25 and 75 mg/kg). Treatment in the letrozole arm was continued until resistance developed. MCF7LR tumor-bearing mice were then randomized to Z-endoxifen (50 mg/kg) or tamoxifen for 4 weeks and tumors harvested for microarray and immunohistochemistry analysis. The antitumor activity of Z-endoxifen in the MCF7LR tumors was further compared in a second in vivo study with exemestane, exemestane plus everolimus, and fulvestrant.

Results

In the MCF7AC1 tumors, both Z-endoxifen doses were significantly superior to control and tamoxifen in reducing tumor volumes at 4 weeks. Additionally, the 75 mg/kg Z-endoxifen dose was additionally superior to letrozole. Prolonged letrozole exposure resulted in resistance at 25 weeks. In MCF7LR tumor-bearing mice, Z-endoxifen significantly reduced tumor volumes compared to tamoxifen, letrozole, and exemestane, with no significant differences compared to exemestane plus everolimus and fulvestrant. Additionally, compared to tamoxifen, Z-endoxifen markedly inhibited ERα target genes, Ki67 and Akt expression in vivo.

Conclusion

In endocrine-sensitive and letrozole-resistant breast tumors, Z-endoxifen results in robust antitumor and antiestrogenic activity compared to tamoxifen and aromatase inhibitor monotherapy. These data support the ongoing development of Z-endoxifen.
MHC-I genotype and tumor mutational burden predict response to immunotherapy
Authors: Goodman Aaron M. , Castro Andrea , Pyke Rachel Marty , Okamura Ryosuke , Kato Shumei , Riviere Paul , Frampton Garrett , Sokol Ethan , Zhang Xinlian , Ball Edward D. , Carter Hannah , Kurzrock Razelle
Published: May 2020

Background

Immune checkpoint blockade (ICB) with antibodies inhibiting cytotoxic T lymphocyte-associated protein-4 (CTLA-4) and programmed cell death protein-1 (PD-1) (or its ligand (PD-L1)) can stimulate immune responses against cancer and have revolutionized the treatment of tumors. The influence of host germline genetics and its interaction with tumor neoantigens remains poorly defined. We sought to determine the interaction between tumor mutational burden (TMB) and the ability of a patient’s major histocompatibility complex class I (MHC-I) to efficiently present mutated driver neoantigens in predicting response ICB.

Methods

Comprehensive genomic profiling was performed on 83 patients with diverse cancers treated with ICB to determine TMB and human leukocyte antigen-I (HLA-I) genotype. The ability of a patient’s MHC-I to efficiently present mutated driver neoantigens (defined by the Patient Harmonic-mean Best Rank (PHBR) score (with lower PHBR indicating more efficient presentation)) was calculated for each patient.

Results

The median progression-free survival (PFS) for PHBR score < 0.5 vs. ≥ 0.5 was 5.1 vs. 4.4 months (P = 0.04). Using a TMB cutoff of 10 mutations/mb, the stable disease > 6 months/partial response/complete response rate, median PFS, and median overall survival (OS) of TMB high/PHBR high vs. TMB high/PHBR low were 43% vs. 78% (P = 0.049), 5.8 vs. 26.8 months (P = 0.03), and 17.2 months vs. not reached (P = 0.23), respectively. These findings were confirmed in an independent validation cohort of 32 patients.

Conclusions

Poor presentation of driver mutation neoantigens by MHC-I may explain why some tumors (even with a high TMB) do not respond to ICB.
Modeling neuronal consequences of autism-associated gene regulatory variants with human induced pluripotent stem cells
Authors: Ross P. Joel , Mok Rebecca S. F. , Smith Brandon S. , Rodrigues Deivid C. , Mufteev Marat , Scherer Stephen W. , Ellis James
Published: May 2020

Genetic factors contribute to the development of autism spectrum disorder (ASD), and although non-protein-coding regions of the genome are being increasingly implicated in ASD, the functional consequences of these variants remain largely uncharacterized. Induced pluripotent stem cells (iPSCs) enable the production of personalized neurons that are genetically matched to people with ASD and can therefore be used to directly test the effects of genomic variation on neuronal gene expression, synapse function, and connectivity. The combined use of human pluripotent stem cells with genome editing to introduce or correct specific variants has proved to be a powerful approach for exploring the functional consequences of ASD-associated variants in protein-coding genes and, more recently, long non-coding RNAs (lncRNAs). Here, we review recent studies that implicate lncRNAs, other non-coding mutations, and regulatory variants in ASD susceptibility. We also discuss experimental design considerations for using iPSCs and genome editing to study the role of the non-protein-coding genome in ASD.
A novel role of vitronectin in promoting survival of mesenchymal stem cells under serum deprivation stress
Authors: Goyal Umesh , Ta Malancha
Published: May 2020

Background

Due to their immunomodulatory and trophic support functions, mesenchymal stem cells (MSCs) are promising in the field of cell-based regenerative medicine. However, MSC survival post-transplantation is challenged by various microenvironment stress factors. Here, we investigated the role of vitronectin (VTN) in the survival strategy of MSCs under serum deprivation stress condition.

Methods

Proliferation kinetics and cell adhesion of MSCs under serum deprivation were determined from population doublings and cell-matrix de-adhesion studies, respectively. mRNA and protein expression levels of VTN were confirmed by qRT-PCR and Western blotting, respectively. Immunofluorescence technique revealed distribution of VTN under serum deprivation stress. siRNA and inhibitor-based studies were performed to confirm the role and regulation of VTN. Apoptosis and cell cycle status of MSCs were assessed using flow cytometric analysis.

Results

Subjecting MSCs to serum deprivation led to significant increase in cell spread area and cell-matrix adhesion. An upregulation of VTN expression was noted with an arrest in G0/G1 phase of cell cycle and no appreciable apoptotic change. Pro-survival PI3kinase pathway inhibition led to further increase in VTN expression with no apoptotic change. siRNA-mediated inhibition of VTN resulted in reversal in G0/G1 cell cycle arrest and a marked increase in apoptosis, suggesting a role of VTN in preventing serum deprivation-induced apoptotic cell death. In addition, p65 knockdown resulted in downregulation of VTN establishing an association between NF-κβ pathway and VTN.

Conclusions

VTN was identified as a survival factor in providing protection from serum deprivation-induced apoptosis in MSCs.
Mesenchymal stem cells combined with liraglutide relieve acute lung injury through apoptotic signaling restrained by PKA/β-catenin
Authors: Yang Xiaotong , Ma Xiaoying , Don Ocholi , Song Yuanlin , Chen Xiaoyan , Liu Jianwen , Qu Jieming , Feng Yun
Published: May 2020

Background

ARDS and ALI are life-threatening diseases with extremely high mortality in patients. Different sources of MSCs could mitigate the symptoms of ALI from diverse mechanisms. Liraglutide is an activator of glucagon-like peptide-1 receptor (GLP-1R) that activates anti-apoptotic pathways and exerts anti-inflammatory effects. We mainly compared the effects of human chorionic villus-derived mesenchymal stem cells (hCMSCs), human bone marrow-derived mesenchymal stem cells (hBMSCs), and human adipose-derived mesenchymal stem cells (hAMSCs) on the treatment of ALI and explored the apoptosis mechanism of combination MSCs of liraglutide.

Methods

The proliferation of MSCs was detected by MTT assay. Western blot and RT-qPCR were used to detect the expression of GLP-1R, SPC, Ang-1, and KGF in MSCs stimulated by LPS and liraglutide. By using flow cytometry and TUNEL assay to compare the apoptosis of three MSCs under the action of LPS and liraglutide, we selected hCMSCs as the target cells to study the expression of apoptotic protein through the PKA/β-catenin pathway. In ALI animal models, we observed the effects of liraglutide alone, MSCs alone, and MSCs combined with liraglutide by H&E staining, cell counting, immunohistochemistry, and ELISA assay.

Results

We demonstrated that LPS attenuates the proliferation of the three MSCs and the expression of GLP-1R. Liraglutide could reverse the effects of LPS; increase the expression of SPC, Ang-1, and KGF; and can reduce the apoptosis of three MSCs through the PKA/β-catenin pathway. In the LPS-induced ALI model, MSCs combined with liraglutide showed a significant therapeutic effect, and hCMSCs combined with liraglutide have advantages in the treatment of ALI.

Conclusions

The therapeutic effect of combination MSCs of liraglutide on ALI was higher than that of MSCs alone or liraglutide alone, and liraglutide could alleviate the symptoms of ALI by reducing MSCs apoptosis.
Comparative separation methods and biological characteristics of human placental and umbilical cord mesenchymal stem cells in serum-free culture conditions
Authors: Yi Xiao , Chen Feng , Liu Fenghua , Peng Qing , Li Yang , Li Shao , Du Jiang , Gao Yi , Wang Yifeng
Published: May 2020

Background

Mesenchymal stem cells (MSCs) are considered to be an effective tool for regenerative medicine with promising applications for clinical therapy. However, incongruent data has been reported partially owing to their functional heterogeneity. To provide sufficient and suitable clinical seed cells derived from the placenta for MSC therapy, we compared the various current isolation methods, as well as the biological characteristics, of different human placenta mesenchymal stem cells (hPMSCs).

Methods

We selected placentas from 35 informed donors and exploited three commonly used methods. MSCs were isolated from different parts of placental tissue including umbilical cord (UC), amniotic membrane (AM), chorionic membrane (CM), chorionic villi (CV), and deciduae (DC). The appropriate isolation methods for each type of hPMSCs were first assessed. The resulting five MSC types from the same individuals were identified based on their surface marker expression, proliferation capacity, transcriptome, differentiation, multipotency and karyotype.

Results

All three methods successfully isolated the five hPMSC types from placental tissues. However, the UC-MSCs were most effectively separated via the tissue explant method, while the enzymatic digestion method was found to be more suitable for separating CV-MSCs, owing to its higher output efficiency compared to the other methods. Alternatively, the perfusion method was complicated and exhibited the lowest efficiency for cell isolation and uniformity. Furthermore, we determined that UC-MSCs and CV-MSCs express a higher level of paracrine cytokines and display much stronger proliferative capacity as well as superior extraction efficiency. Finally, karyotype analysis revealed that DC-MSCs are derived from the mother, while the other cell types are derived from the fetus. Moreover, the different hPMSCs exhibited unique gene expression profiles, which may prove advantageous in treatment of a broad range of diseases.

Conclusions

hPMSCs from different sources are similar yet also unique. Our results describe the biological characteristics of five hPMSCs and provide insights to aide in the selection process of candidates for MSCs treatment. Overall, UC- and CV-MSCs appear to be ideal sources of primary MSCs for clinical treatment and future research.
Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes
Authors: Paterson Y. Z. , Cribbs A. , Espenel M. , Smith E. J. , Henson F. M. D. , Guest D. J.
Published: May 2020

Background

Tendon injuries occur frequently in human and equine athletes. Treatment options are limited, and the prognosis is often poor with functionally deficient scar tissue resulting. Fetal tendon injuries in contrast are capable of healing without forming scar tissue. Embryonic stem cells (ESCs) may provide a potential cellular therapeutic to improve adult tendon regeneration; however, whether they can mimic the properties of fetal tenocytes is unknown. To this end, understanding the unique expression profile of normal adult and fetal tenocytes is crucial to allow validation of ESC-derived tenocytes as a cellular therapeutic.

Methods

Equine adult, fetal and ESC-derived tenocytes were cultured in a three-dimensional environment, with histological, morphological and transcriptomic differences compared. Additionally, the effects on gene expression of culturing adult and fetal tenocytes in either conventional two-dimensional monolayer culture or three-dimensional culture were compared using RNA sequencing.

Results

No qualitative differences in three-dimensional tendon constructs generated from adult, fetal and ESCs were found using histological and morphological analysis. However, genome-wide transcriptomic analysis using RNA sequencing revealed that ESC-derived tenocytes’ transcriptomic profile more closely resembled fetal tenocytes as opposed to adult tenocytes. Furthermore, this study adds to the growing evidence that monolayer cultured cells’ gene expression profiles converge, with adult and fetal tenocytes having only 10 significantly different genes when cultured in this manner. In contrast, when adult and fetal tenocytes were cultured in 3D, large distinctions in gene expression between these two developmental stages were found, with 542 genes being differentially expressed.

Conclusion

The information provided in this study makes a significant contribution to the investigation into the differences between adult reparative and fetal regenerative cells and supports the concept of using ESC-derived tenocytes as a cellular therapy. Comparing two- and three-dimensional culture also indicates three-dimensional culture as being a more physiologically relevant culture system for determining transcriptomic difference between the same cell types from different developmental stages.
Tetramethylpyrazine enhanced the therapeutic effects of human umbilical cord mesenchymal stem cells in experimental autoimmune encephalomyelitis mice through Nrf2/HO-1 signaling pathway
Authors: Zhang Lianshuang , Wang Xifeng , Lu Xueyan , Ma Yanchao , Xin Xin , Xu Xiaomin , Wang Siyuan , Hou Yun
Published: May 2020

Introduction

The therapeutic effects of mesenchymal stem cells (MSCs) have been limited by their apoptosis induced by oxidative stress after delivery into the injured sites. Therefore, strategies designed to improve the MSC therapeutic efficacy need to be explored. Tetramethylpyrazine (TMP) can promote the proliferation and differentiation of neural stem cells. In this study, we first evaluated the effects and mechanism of TMP on H2O2-stimulated human umbilical cord MSCs (hUCMSCs) and then further investigated the therapeutic effects of TMP-stimulated hUCMSCs on experimental autoimmune encephalomyelitis (EAE) mice.

Methods

The toxicity of hUCMSCs against of TMP was determined by cell count kit-8 (CCK-8) assay. The effects of TMP on the hUCMSC cell cycle, the reactive oxygen species (ROS) production, and the apoptosis of H2O2-stimulated hUCMSCs were determined by flow cytometry. The expression of malondialdehyde (MDA) and superoxide dismutase (SOD) were also measured by colorimetry. The signaling pathway of TMP induced on H2O2-stimulated hUCMSCs was investigated by western blot. EAE was induced using immunization with MOG35-55 in C57BL/6 mice. The inflammatory cell infiltration and demyelination were detected by immunofluorescence staining. The blood-brain barrier (BBB) disruption was detected by Evans blue (EB) stain and the expression of tight junction protein (ZO-1) by western blot.

Results

TMP significantly increased cell viability and changed the cell cycle of hUCMSCs. In addition, TMP (100 μM) significantly reduced intracellular ROS production, expression of MDA, and apoptosis, but increased expression of SOD through nuclear factor-erythroid 2-related factor-2 (Nrf2)/heme oxygenase 1 (HO-1) signaling pathway in H2O2-stimulated hUCMSCs. Most importantly, compared with wild hUCMSCs, TMP-stimulated hUCMSCs significantly ameliorated EAE, by attenuation of inflammation, demyelination, and BBB disruption.

Conclusion

The TMP-stimulated hUCMSCs provide a potential therapeutical protocol to enhance the therapeutic effects of hUCMSCs in multiple sclerosis.
Intestinal homeostasis: a communication between life and death
Authors: Bao Lingyu , Shi Bingyin , Shi Yun-Bo
Published: May 2020

Organ homeostasis is essential for organ physiology and disease prevention. In adult vertebrates, the intestinal epithelium is maintained through constant cell proliferation in the crypt and apoptosis of differentiated epithelial cells, mainly at the tip of the villus. Based on studies with altered cell proliferation and tissue damage in the adult mouse intestine, we hypothesize that there is a communication between cell proliferation in the crypt and cell death on the villus, likely via cell–cell and cell-ECM (extracellular matrix) interactions, to coordinate the rate of cell proliferation and death, thus ensuring epithelial homeostasis.
Swapped face detection using deep learning and subjective assessment
Authors: Ding Xinyi , Raziei Zohreh , Larson Eric C. , Olinick Eli V. , Krueger Paul , Hahsler Michael
Published: May 2020

The tremendous success of deep learning for imaging applications has resulted in numerous beneficial advances. Unfortunately, this success has also been a catalyst for malicious uses such as photo-realistic face swapping of parties without consent. In this study, we use deep transfer learning for face swapping detection, showing true positive rates greater than 96% with very few false alarms. Distinguished from existing methods that only provide detection accuracy, we also provide uncertainty for each prediction, which is critical for trust in the deployment of such detection systems. Moreover, we provide a comparison to human subjects. To capture human recognition performance, we build a website to collect pairwise comparisons of images from human subjects. Based on these comparisons, we infer a consensus ranking from the image perceived as most real to the image perceived as most fake. Overall, the results show the effectiveness of our method. As part of this study, we create a novel dataset that is, to the best of our knowledge, the largest swapped face dataset created using still images. This dataset will be available for academic research use per request. Our goal of this study is to inspire more research in the field of image forensics through the creation of a dataset and initial analysis.
Emergence of β-lactamase- and carbapenemase- producing Enterobacteriaceae at integrated fish farms
Authors: Hamza Dalia , Dorgham Sohad , Ismael Elshaimaa , El-Moez Sherein Ismail Abd , Elhariri Mahmoud , Elhelw Rehab , Hamza Eman
Published: May 2020

Background

Epidemiological studies suggested that determinants for antibiotic resistance have originated in aquaculture. Recently, the integrated agriculture-aquaculture system has been implemented, where fish are raised in ponds that receive agriculture drainage water. The present study aims to investigate the occurrence of β-lactamase and carbapenemase-producing Enterobacteriaceae in the integrated agriculture-aquaculture and the consequent public health implication.

Methods

Samples were collected from fish, fishpond water inlets, tap water, outlet water, and workers at sites of integrated agriculture-aquacultures. Samples were also taken from inhabitants of the aquaculture surrounding areas. All samples were cultured on MacConkey agar, the Enterobacteriaceae isolates were tested for susceptibility to cephalosporins and carbapenems, and screened for blaCTX-M-15, blaSHV, blaOXA-1, blaTEM, blaPER-1, blaKPC, blaOXA-48, and blaNDM. Strains having similar resistance phenotype and genotype were examined for the presence of Incompatible (Inc) plasmids.

Results

A major proportion of the Enterobacteriaceae isolates were resistant to cephalosporins and carbapenems. Among the 66 isolates from fish, 34 were resistant to both cephalosporin and carbapenem groups, 26 to carbapenems alone, and 4 to cephalosporins alone. Of the 15 isolates from fishpond water inlets, 8 showed resistance to both groups, 1 to carbapenems alone, and 5 to cephalosporins alone. Out of the 33 isolates from tap water, 17 were resistant to both groups, and 16 to cephalosporins alone. Similarly, of the 16 outlet water isolates, 10 were resistant to both groups, and 6 to cephalosporins alone. Furthermore, of the 30 examined workers, 15 carried Enterobacteriaceae resistant strains, 10 to both groups, and 5 to cephalosporins alone. Similar strains were isolated from the inhabitants of the aquaculture surrounding areas. Irrespective of source of samples, strains resistant to all examined antibiotics, carried predominantly the carbapenemase gene blaKPC either alone or with the β-lactamase genes (blaCTX-M-15, blaSHV, blaTEM, and blaPER-1). The isolates from fish, water, and workers harboured a wide-range of multi-drug-resistance Inc. plasmids, which were similar among all isolates.

Conclusion

The present findings suggest transmission of the resistance genes among Enterobacteriaceae strains from different sources. This reiterates the need for control strategies that focus on humans, animals, water, and sewage systems to solve the antibiotic resistance problem.
Implementing a combined infection prevention and control with antimicrobial stewardship joint program to prevent caesarean section surgical site infections and antimicrobial resistance: a Tanzanian tertiary hospital experience
Authors: Gentilotti Elisa , De Nardo Pasquale , Nguhuni Boniface , Piscini Alessandro , Damian Caroline , Vairo Francesco , Chaula Zainab , Mencarini Paola , Torokaa Peter , Zumla Alimuddin , Nicastri Emanuele , Ippolito Giuseppe
Published: May 2020

Background

Surgical site infections are a leading cause of morbidity and mortality after caesarean section, especially in Low and Middle Income Countries. We hypothesized that a combined infection prevention and control with antimicrobial stewardship joint program would decrease the rate of post- caesarean section surgical site infections at the Obstetrics & Gynaecology Department of a Tanzanian tertiary hospital.

Methods

The intervention included: 1. formal and on-job trainings on infection prevention and control; 2. evidence-based education on antimicrobial resistance and good antimicrobial prescribing practice. A second survey was performed to determine the impact of the intervention. The primary outcome of the study was post-caesarean section surgical site infections prevalence and secondary outcome the determinant factors of surgical site infections before/after the intervention and overall. The microbiological characteristics and patterns of antimicrobial resistance were ascertained.

Results

Total 464 and 573 women were surveyed before and after the intervention, respectively. After the intervention, the antibiotic prophylaxis was administered to a significantly higher number of patients (98% vs 2%, p < 0.001), caesarean sections were performed by more qualified operators (40% vs 28%, p = 0.001), with higher rates of Pfannenstiel skin incisions (29% vs 18%, p < 0.001) and of absorbable continuous intradermic sutures (30% vs 19%, p < 0.001). The total number of post-caesarean section surgical site infections was 225 (48%) in the pre-intervention and 95 (17%) in the post intervention group (p < 0.001). A low prevalence of gram-positive isolates and of methicillin-resistant Staphylococus aureus was detected in the post-intervention survey.

Conclusions

Further researches are needed to better understand the potential of a hospital-based multidisciplinary approach to surgical site infections and antimicrobial resistance prevention in resource-constrained settings.
Protection of glazed tiles in ancient buildings of China
Authors: Adili Dilireba , Zhao Jing , Yang Lu , Zhao Peng , Wang Cong , Luo Hongjie
Published: May 2020

Silicon materials containing fluorine with similar nanoscale particles (SIC-1 and SIC-2) and organic silicon resin materials with excellent hydrophobicity (SIC-3) were selected to deal with glaze shedding and damage of glazed tiles in ancient buildings. Experimental analysis on the hydrophobic properties and microscopic morphology of the materials, as well as the changes of the surface temperature and the shedding rate of glaze layer after adding protective materials indicated: the thermal expansion differences and the shedding rate of glaze layer following sharp changes of temperature and humidity had been decreased. In particular, with the help of protective material SIC-2, a silicon material containing fluorine, there was the smallest change in the color of the glaze layer; the hydrophobic property and the water vapor transmittance of matrix were also improved. In a nutshell, the results showed that the addition of these protective materials alleviated the effects of radical temperature and humidity changes on glaze layer and matrix, and effectively delayed the occurrence of glaze shedding.
Engraftment of human induced pluripotent stem cell-derived myogenic progenitors restores dystrophin in mice with duchenne muscular dystrophy
Authors: He Ruojie , Li Huan , Wang Liang , Li Yaqin , Zhang Yu , Chen Menglong , Zhu Yuling , Zhang Cheng
Published: May 2020

Background

Duchenne muscular dystrophy (DMD) is a devastating genetic muscular disorder with no effective treatment that is caused by the loss of dystrophin. Human induced pluripotent stem cells (hiPSCs) offer a promising unlimited resource for cell-based therapies of muscular dystrophy. However, their clinical applications are hindered by inefficient myogenic differentiation, and moreover, the engraftment of non-transgene hiPSC-derived myogenic progenitors has not been examined in the mdx mouse model of DMD.

Methods

We investigated the muscle regenerative potential of myogenic progenitors derived from hiPSCs in mdx mice. The hiPSCs were transfected with enhanced green fluorescent protein (EGFP) vector and defined as EGFP hiPSCs. Myogenic differentiation was performed on EGFP hiPSCs with supplementary of basic fibroblast growth factor, forskolin, 6-bromoindirubin-3′-oxime as well as horse serum. EGFP hiPSCs-derived myogenic progenitors were engrafted into mdx mice via both intramuscular and intravenous injection. The restoration of dystrophin expression, the ratio of central nuclear myofibers, and the transplanted cells-derived satellite cells were accessed after intramuscular and systemic transplantation.

Results

We report that abundant myogenic progenitors can be generated from hiPSCs after treatment with these three small molecules, with consequent terminal differentiation giving rise to mature myotubes in vitro. Upon intramuscular or systemic transplantation into mdx mice, these myogenic progenitors engrafted and contributed to human-derived myofiber regeneration in host muscles, restored dystrophin expression, ameliorated pathological lesions, and seeded the satellite cell compartment in dystrophic muscles.

Conclusions

This study demonstrates the muscle regeneration potential of myogenic progenitors derived from hiPSCs using non-transgenic induction methods. Engraftment of hiPSC-derived myogenic progenitors could be a potential future therapeutic strategy to treat DMD in a clinical setting.
Building inclusive cities: reflections from a knowledge exchange on the inclusion of newcomers by UK local authorities
Authors: Broadhead Jacqueline
Published: May 2020

Inclusive Cities, a university led knowledge exchange initiative works in collaboration with six UK city administrations facilitating the development of their strategic and practical approach to the inclusion of newcomers in the city. The paper places this case study into the context of the UK’s centralized asylum reception and resettlement policy framework, contrasting it with the increasing recognition of the importance of the local level in integration and inclusion policy and the intersections between these differing modes of governance and competencies.

The paper explores emerging learning from the programme in relation to the leadership role of local government, its ability to act as a place shaper in relation to inclusion and integration and it role in convening partners through horizontal, place-based, networks as well as the ways in which this case study can contribute to wider learning on the role of knowledge exchange in facilitating social change and policy framing at the city level and learning on the multi-level governance of reception and integration. The paper explores how mutual knowledge exchange may create space for a broadening out of the policy framing in relation to reception – in particular how a ‘newcomer’ frame may support increased innovation at the local level.
Synthesis, in vitro and in vivo evaluation of 11C-O-methylated arylpiperazines as potential serotonin 1A (5-HT1A) receptor antagonist radiotracers
Authors: Narayanaswami Vidya , Tong Junchao , Fiorino Ferdinando , Severino Beatrice , Sparaco Rosa , Magli Elisa , Giordano Flavia , Bloomfield Peter M. , Prabhakaran Jaya , Mann J. John , Vasdev Neil , Dahl Kenneth , Kumar J. S. Dileep
Published: May 2020

Background

Serotonin 1A (5-HT1A) receptors are implicated in the pathogenesis of several psychiatric and neurodegenerative disorders motivating the development of suitable radiotracers for in vivo positron emission tomography (PET) neuroimaging. The gold standard PET imaging agent for this target is [carbonyl-11C]WAY-100635, labeled via a technically challenging multi-step reaction that has limited its widespread use. While several antagonist and agonist-based PET radiotracers for 5-HT1Areceptors have been developed, their clinical translation has been hindered by methodological challenges and/or and non-specific binding. As a result, there is continued interest in the development of new and more selective 5-HT1APET tracers having a relatively easier and reliable radiosynthesis process for routine production and with favorable metabolism to facilitate tracer-kinetic modeling. The purpose of the current study was to develop and characterize a radioligand with suitable characteristics for imaging 5-HT1Areceptors in the brain. The current study reports the in vitro characterization and radiosyntheses of three candidate 5-HT1Areceptor antagonists, DF-100(1), DF-300(2)and DF-400(3), to explore their suitability as potential PET radiotracers.

Results

Syntheses of1–3and corresponding precursors for radiolabeling were achieved from isonicotinic, picolinic acid or picolino nitrile. In vitro binding studies demonstrated nanomolar affinity of the compounds for 5-HT1Areceptors. Binding of1–3for other biogenic amines, neurotransmitter receptors, and transporters was negligible with the exception of moderate affinities for α1-adrenergic receptors (4–6-fold less potent than that for 5-HT1Areceptor). Radioligands [11C]1–3were efficiently prepared by11C-O-methylation of the corresponding phenolic precursor in non-decay corrected radiochemical yields of 7–11% with > 99% chemical and radiochemical purities. Dynamic PET studies in rats demonstrated negligible brain uptake of [11C]1and [11C]2. In contrast, significant brain uptake of [11C]3was observed with an early peak SUV of 4–5. However, [11C]3displayed significant off-target binding attributed to α1-adrenergic receptors based on regional distribution (thalamus>hippocampus) and blocking studies.

Conclusion

Despite efficient radiolabeling, results from PET imaging experiments limit the application of [11C]3for in vivo quantification of 5-HT1Areceptors. Nevertheless, derivatives of compound 3 may provide a scaffold for alternative PET radiotracers with improved selectivity for 5-HT1Areceptors or α1-adrenergic receptors.
Collective intelligence in fingerprint analysis
Authors: Tangen Jason M. , Kent Kirsty M. , Searston Rachel A.
Published: May 2020

When a fingerprint is located at a crime scene, a human examiner is counted upon to manually compare this print to those stored in a database. Several experiments have now shown that these professional analysts are highly accurate, but not infallible, much like other fields that involve high-stakes decision-making. One method to offset mistakes in these safety-critical domains is to distribute these important decisions to groups of raters who independently assess the same information. This redundancy in the system allows it to continue operating effectively even in the face of rare and random errors. Here, we extend this “wisdom of crowds” approach to fingerprint analysis by comparing the performance of individuals to crowds of professional analysts. We replicate the previous findings that individual experts greatly outperform individual novices, particularly in their false-positive rate, but they do make mistakes. When we pool the decisions of small groups of experts by selecting the decision of the majority, however, their false-positive rate decreases by up to 8% and their false-negative rate decreases by up to 12%. Pooling the decisions of novices results in a similar drop in false negatives, but increases their false-positive rate by up to 11%. Aggregating people’s judgements by selecting the majority decision performs better than selecting the decision of the most confident or the most experienced rater. Our results show that combining independent judgements from small groups of fingerprint analysts can improve their performance and prevent these mistakes from entering courts.
Protective and therapeutic effects of garlic and tomato on cadmium-induced neuropathology in mice
Authors: Vijaya P. , Kaur Harsimran , Garg Nancy , Sharma Suman
Published: May 2020

Background

Heavy metals are natural components of the earth’s crust and are considered as constant environmental pollutants since they cannot be degraded or destroyed easily. Cadmium (Cd) is present primarily in the ores of zinc, copper, or lead; the extraction and processing of which releases large quantities of cadmium into the atmosphere, hydrosphere, and soil thereby contaminating the human environment. The present study aimed to investigate the possible protective and therapeutic effects of garlic and tomato extract on cadmium-induced AChE activity, biochemical parameters along with the pathological changes in the brain tissue of mice.

Methods

Male Swiss albino mice (n = 40) were divided into several experimental (protective and therapeutic) groups and were given single dose of cadmium (6 mg/kg bw) with supplementation of garlic (100 mg/kg bw) and tomato (50 mg/kg bw) extract for 15 and 30 days under protective and therapeutic study.

Results

Cadmium-treated mice showed a significant decline in AChE (p < 0.01) level and total proteins (p < 0.0001) but a nonsignificant decrease in glycogen, cholesterol in the brain tissue activity as compared to control group. The histological study also showed degeneration in the form of vacuolation, congestion, hyperemia, lymphocytic infiltration, and edema in the brain (cortex and hippocampus) of Cd-treated mice. But the antioxidant-treated groups showed significant increment in AChE level and other biochemical parameters in the protective study. But there were significant variations in the therapeutic study, and this was also confirmed by the histological analysis of the brain. Both tomato and garlic administration showed more attenuation in the brain AChE activity, and it may be due to the strong antioxidant potential of their constituents.

Conclusion

We can conclude that cadmium exposure should be avoided as it causes neuropathological effects. But in daily life, it may not be possible, so we should regularly intake natural antioxidants which may neutralize the effects of heavy metals to some extent.
Melanocytic lesions of the prostate
Authors: do Amaral Maria Estela Pompeu , Athanazio Daniel Abensur
Published: May 2020

Background

Benign melanocytic lesions of the prostate are rare and classified as blue nevus or melanosis. Both lesions have about 30 cases each reported in English literature.

Case presentation

We report here two illustrative cases, both incidental findings: a blue nevus at transurethral resection specimen and melanosis in needle biopsy. The second case was of a patient who underwent prostate biopsy due to a PI-RADS 5 finding in multiparametric MRI. Although no cancer was detected, findings suggestive of nodular hyperplasia and diagnostic of melanosis were observed.

Conclusion

Benign melanocytic lesions of the prostate are rare incidental findings with no clinical or prognostic relevance. Additional reports are warranted to evaluate whether such lesions may be associated with suspicious findings in imaging exams.