bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual and reproductive health services utilization and associated factors among adolescents attending secondary schools
Authors: Abdurahman Chaltu , Oljira Lemessa , Hailu Saba , Mengesha Melkamu Merid
Published: July 2022

Background

Sexual and reproductive health (SRH) is referring to physical and emotional wellbeing and includes the ability to be free from unwanted pregnancy, unsafe abortion, sexually transmitted infections including HIV/AIDS, and all forms of sexual violence and coercion. SRH is the main services packages that prevent and reduce adolescent reproductive health risks and problems. While the government of Ethiopia has undertaken several measures to improve SRH services, there was limited data on utilization among adolescents and associated factors.

Objective

To assess utilization of SRH services and associated factors among adolescents attending secondary schools in Haramaya District, Eastern Ethiopia.

Methods

A school-based cross-sectional study was conducted among adolescent students aged 15–19 years. A total of 692 adolescents were selected using a multi-stage sampling from two randomly selected secondary schools, each from rural and urban settings, in Haramaya district where 642 provided complete data and included in the analysis. A structured, pretested, and self-administered questionnaire was used to collect data. Data entry was conducted using Epi Data version 3.1 and exported to STATA version 16 for analysis. Bivariable and multivariable binary logistic regression were used to identify factors associated with school adolescents’ utilization of SRH. Statistically significant associations are declared at P-value < 0.05.

Result

A total of 642 completed the survey questionnaire, constituting a response rate of 92.7% (642/692). Male adolescents accounted 63.7% and the mean age of respondents was 17.71 years. Among those who completed the survey, 23.5% (95% CI: 20–26.8) utilized SRH services. Adolescents who were exposed to SRH information (adjusted odds ratio (AOR) = 2.11, 95% CI: 1.22–3.6), aware of SRH service providing facility (AOR = 1.83, 95% CI: 1.12–3.0) and SRH service components (AOR = 2.76, 95%, CI: 1.53–4.97), and distance from SRH facilities (AOR = 2.28, 95%, CI: 1.13–4.62) were significantly associated with the utilization of SRH services.

Conclusion

Nearly one-in-four secondary school adolescents (23.5%) utilized SRH services. Targeted promotion of SRH providing facilities and SRH service components aimed at awareness creation could improve adolescents’ utilization of SRH services. Improved SRH services utilization among adolescents who were far from SRH services providing facilities needs further investigation.
ST-T segment changes in prehospital emergency physicians in the field: a prospective observational trial
Authors: Maleczek Mathias , Schebesta Karl , Hamp Thomas , Burger Achim Leo , Pezawas Thomas , Krammel Mario , Roessler Bernhard
Published: July 2022

Aims

Due to time-critical decision-making, physical strain and the uncontrolled environment, prehospital emergency management is frequently associated with high levels of stress in medical personnel. Stress has been known to cause ischemia like changes in electrocardiograms (ECGs), including arrhythmias and deviations in ST-T segments. There is a lack of knowledge regarding the occurrence of changes in ST-T segments in prehospital emergency physicians. We hypothesized that ST-T segment deviations occur in prehospital emergency physicians in the field.

Methods

In this prospective observational trial, ST-T segments of emergency physicians were recorded using 12-lead Holter ECGs. The primary outcome parameter was defined as the incidence of ST-T segment changes greater than 0.1 mV in two corresponding leads for more than 30 s per 100 rescue missions. The secondary outcomes included T-wave inversions and ST-segment changes shorter than 30 s or smaller than 0.1 mV. Surrogate parameters of stress were measured using the NASA-Task Load Index and cognitive appraisal, and their correlation with ST-T segment changes were also assessed.

Results

Data from 20 physicians in 36 shifts (18 days, 18 nights) including 208 missions were analysed. Seventy percent of previously healthy emergency physicians had at least one ECG abnormality; the mean duration of these changes was 30 s. Significantly more missions with ECG changes were found during night than day shifts (39 vs. 17%, p < 0.001). Forty-nine ECG changes occurred between missions. No ST-T segment changes > 30 s and > 0.1 mV were found. Two ST-T segment changes < 30 s or < 0.1 mV (each during missions) and 122 episodes of T-wave inversions (74 during missions) were identified. ECG changes were found to be associated with alarms when asleep and NASA task load index.

Conclusion

ECG changes are frequent and occur in most healthy prehospital emergency physicians. Even when occurring for less than 30 s, such changes are important signs for high levels of stress. The long-term impact of these changes needs further investigation.

Trial registrationThe trial was registered at ClinicalTrials.gov (NCT04003883) on 1.7.2019: https://clinicaltrials.gov/ct2/show/NCT04003883?term=emergency+physician&rank=2
MiR-574-3p inhibits glucose toxicity-induced pancreatic β-cell dysfunction by suppressing PRMT1
Authors: Lv Lixia , Wang Xiumin , Shen Jinhua , Cao Ying , Zhang Qin
Published: July 2022

Background

Pancreatic β-cell dysfunction is commonly observed in patients with type 2 diabetes mellitus. Protein arginine methyltransferase 1 (PRMT1) plays an important role in pancreatic β-cell dysfunction. However, the detailed mechanisms remain largely unknown.

Methods

RT-qPCR, western blotting, and immunofluorescence assays were used to evaluate PRMT1 and miR-574-3p levels. Cell Counting Kit-8, Advanced Dlycation End products (AGEs), Reactive Oxygen Species (ROS), and glucose-stimulated insulin secretion were assayed, and flow cytometry and RT-qPCR were performed to detect the role of PRMT1 and miR-574-3p in MIN6 cells. Luciferase reporter assays were performed to determine the interactions between PRMT1 and miR-574-3p.

Results

High-glucose treatment resulted in the high expression of PRMT1. PRMT1 silencing could alleviate the reduced proliferation, insulin secretion, and GLUT1 level, in addition to suppressing the induced apoptosis, and AGEs and ROS levels, under high glucose conditions. MiR-574-3p was established as an upstream regulator of PRMT1 using luciferase reporter assays. More importantly, miR-574-3p reversed the effect of PRMT1 silencing in MIN6 cells.

Conclusions

miR-574-3p suppresses glucose toxicity-induced pancreatic β-cell dysfunction by targeting PRMT1.
Working toward improved monitoring of Cryptosporidium and Giardia (oo)cysts in water samples: testing alternatives to elution and immunomagnetic separation from USEPA Method 1623.1
Authors: Fradette Marie-Stéphanie , Charette Steve J.
Published: July 2022

Objective

This study was designed to find a method to enhance the recovery of Cryptosporidium spp. and Giardia spp. parasites from water samples for research purposes compared to the results that can be achieved with USEPA Method 1623.1. Four different approaches were used to test water samples that were artificially spiked with parasites. The approaches were: (i) Method 1623.1 itself, (ii) elution of Method 1623.1 combined with microfiltration, (iii) an elution technique based on grinding the filter membrane in a blender before the eluent was concentrated by immunomagnetic separation, and (iv) the blender elution followed by microfiltration. Fluorescence microscopy was used to determine which approach led to the highest parasite recovery rates.

Results

Method 1623.1 gave the best results for Giardia, while all four approaches were statistically equivalent for Cryptosporidium. We evaluated the costs and laboratory time requirements for each protocol to give readers a complete comparison of the methods tested. Elution of Method 1623.1 combined with microfiltration resulted in lower costs and less laboratory work time without compromising the recovery of the parasites.
Non-structural carbohydrates and morphological traits of leaves, stems and roots from tree species in different climates
Authors: Zhang Guangqi , Maillard Pascale , Mao Zhun , Brancheriau Loic , Engel Julien , Gérard Bastien , Fortunel Claire , Maeght Jean-Luc , Martínez-Vilalta Jordi , Ramel Merlin , Nourissier-Mountou Sophie , Fourtier Stéphane , Stokes Alexia
Published: July 2022

Objectives

Carbon fixed during photosynthesis is exported from leaves towards sink organs as non-structural carbohydrates (NSC), that are a key energy source for metabolic processes in trees. In xylem, NSC are mostly stored as soluble sugars and starch in radial and axial parenchyma. The multi-functional nature of xylem means that cells possess several functions, including water transport, storage and mechanical support. Little is known about how NSC impacts xylem multi-functionality, nor how NSC vary among species and climates. We collected leaves, stem and root xylem from tree species growing in three climates and estimated NSC in each organ. We also measured xylem traits linked to hydraulic and mechanical functioning.

Data description

The paper describes functional traits in leaves, stems and roots, including NSC, carbon, nitrogen, specific leaf area, stem and root wood density and xylem traits. Data are provided for up to 90 angiosperm species from temperate, Mediterranean and tropical climates. These data are useful for understanding the trade-offs in resource allocation from a whole-plant perspective, and to better quantify xylem structure and function related to water transportation, mechanical support and storage. Data will also give researchers keys to understanding the ability of trees to adjust to a changing climate.
Gel shift experiments with fragments of the Trypanosoma brucei RNA-binding protein RBP10
Authors: Liu Bin , Clayton Christine
Published: July 2022

Objective

Trypanosoma brucei is a parasite of mammals and Tsetse flies, and control of mRNA stability is critical for parasite survival in the two different hosts. T. brucei RBP10 is a protein with a single RNA Recognition Motif (RRM) which is expressed only in the mammalian (bloodstream) form. Numerous observations suggest that RBP10 binds to procyclic-specific mRNAs and targets them for destruction, and there is also some evidence for selective binding of RBP10 to RNAs containing the motif UA(U)6. We here investigated this binding further.

Results

We tested in vitro binding of RBP10 to two different probes in solution. One contained two copies of UA(U)6, and the other two copies of a mutant version, UACUCUCU, which is inactive in regulation. An N-terminal segment of RBP10, including the RRM domain and 90 residues to its C-terminus, could be produced as soluble protein. This could bind both probes in vitro with similar affinities in the low micromolar range, which is not atypical for a single RRM. Soluble RBP10 therefore did not distinguish between UA(U)6 and UACUCUCU. Since no other sequences were tested, the requirements for RBP10 RNA binding remain to be determined.
P-tau subgroups in AD relate to distinct amyloid production and synaptic integrity profiles
Authors: Wesenhagen Kirsten E. J. , Tijms Betty M. , Boonkamp Lynn , Hoede Patty L. , Goossens Julie , Dewit Nele , Scheltens Philip , Vanmechelen Eugeen , Visser Pieter Jelle , Teunissen Charlotte E.
Published: July 2022

Background

We previously identified four Alzheimer’s disease (AD) subgroups with increasingly higher cerebrospinal fluid (CSF) levels of tau phosphorylated at threonine 181 (p-tau). These subgroups included individuals across the cognitive spectrum, suggesting p-tau subgroups could reflect distinct biological changes in AD, rather than disease severity. Therefore, in the current study, we further investigated which potential processes may be related with p-tau subgroups, by comparing individuals on CSF markers for presynaptic structure [vesicle-associated membrane protein 2 (VAMP2)], postsynaptic structure [neurogranin (NRGN)], axonal damage [neurofilament light (NfL)], and amyloid production [beta-secretase 1 (BACE1) and amyloid-beta 1–40 (Aβ40)].

Methods

We selected 348 amyloid-positive (A+) individuals (53 preclinical, 102 prodromal, 193 AD dementia) and 112 amyloid-negative (A−) cognitively normal (CN) individuals from the Amsterdam Dementia Cohort (ADC). Individuals were labeled according to their p-tau subgroup (subgroup 1: p-tau ≤ 56 pg/ml; subgroup 2: 57–96 pg/ml; subgroup 3: 97–159 pg/ml; subgroup 4: > 159 pg/ml). CSF protein levels were measured with ELISA (NRGN, BACE1, Aβ40, NfL) or single-molecule array (Simoa) (VAMP2). We tested whether protein levels differed between the p-tau subgroups within A+ individuals with linear models corrected for age and sex and whether disease stage influenced these relationships.

Results

Among A+ individuals, higher p-tau subgroups showed a higher percentage of AD dementia [subgroup 1:n= 41/94 (44%); subgroup 2:n= 81/147 (55%); subgroup 3:n= 59/89 (66%); subgroup 4:n= 7/11 (64%)]. Relative to controls, subgroup 1 showed reduced CSF levels of BACE1, Aβ40, and VAMP2 and higher levels of NfL. Subgroups 2 to 4 showed gradually increased CSF levels of all measured proteins, either across the first three (NfL and Aβ40) or across all subgroups (VAMP2, NRGN, BACE1). The associations did not depend on the clinical stage (interactionp-values ranging between 0.19 and 0.87).

Conclusions

The results suggest that biological heterogeneity in p-tau levels in AD is related to amyloid metabolism and synaptic integrity independent of clinical stage. Biomarkers reflecting amyloid metabolism and synaptic integrity may be useful outcome measures in clinical trials targeting tau pathology.
The current role and future directions of imaging in failed back surgery syndrome patients: an educational review
Authors: Witkam Richard L. , Buckens Constantinus F. , van Goethem Johan W. M. , Vissers Kris C. P. , Henssen Dylan J. H. A.
Published: July 2022

Background

Failed back surgery syndrome (FBSS) is an umbrella term referring to painful sensations experienced by patients after spinal surgery, mostly of neuropathic nature. Adequate treatment of FBSS is challenging, as its etiology is believed to be multifactorial and still not fully clarified. Accurate identification of the source of pain is difficult but pivotal to establish the most appropriate treatment strategy. Although the clinical utility of imaging in FBSS patients is still contentious, objective parameters are highly warranted to map different phenotypes of FBSS and tailor each subsequent therapy.

Main body

Since technological developments have weakened the applicability of prior research, this educational review outlined the recent evidence (i.e., from January 2005 onwards) after a systematic literature search. The state of the art on multiple imaging modalities in FBSS patients was reviewed. Future directions related to functional MRI and the development of imaging biomarkers have also been discussed.

Conclusion

Besides the fact that more imaging studies correlated with symptomatology in the postoperative setting are warranted, the current educational review outlined that contrast-enhanced MRI and MR neurography have been suggested as valuable imaging protocols to assess alterations in the spine of FBSS patients. The use of imaging biomarkers to study correlations between imaging features and symptomatology might hold future potential; however, more research is required before any promising hypotheses can be drawn.
Clinical trials of stem cell-based therapies for pediatric diseases: a comprehensive analysis of trials registered on ClinicalTrials.gov and the ICTRP portal site
Authors: Ji Yinwen , Hu Chuan , Chen Zuxing , Li Ying , Dai Jiayong , Zhang Jin , Shu Qiang
Published: July 2022

Background

Research on clinical trials that employ stem cells to treat children’s diseases is limited. The clinical trial registry database provides a unique window to us to get known about clinical trial researches with different statuses. However, few studies aimed to perform a comprehensive and thorough analysis of those registered trials in the aforementioned field based on ClinicalTrials.gov and the ICTRP portal site.

Methods

Our study covered the clinical researches about stem cell therapy enrolling subjects aged under 18 years old registered on ClinicalTrials.gov and WHO ICTRP before May 18, 2021. A cross-sectional study was implemented to comprehensively describe and analyze the included trials that met the criteria. Results were available on ClinicalTrials.gov, and publications related to the included trials were identified. All analyses were performed utilizing the SPSS 25.0 software.

Results

Eventually, 202 clinical trials were included and evaluated. The participant number of trials tended to be small; 71.3% were enrolled < 50. And 93.5% of the subjects were without gender restrictions. Till May 2020, 112 trials had been preliminary completed, of which only 39 trials had published papers or uploaded results. Most (73.6%) of 186 interventional trials were in phase 1 and phase 2, where 131 (70.4%) trials were conducted without masking, and 26.3% trials were randomized; 55.4% trials were performed single group assignment. Of 16 observational trials, case-only/series took up 37.5%. Hematopoietic stem cells (37.1%) and mesenchymal stem cells (36.1%) were mostly employed, while umbilical cord blood (UCB)-derived cells (24.3%) and bone marrow (BM)-derived cells (20.8%) were the major sources.

Conclusions

This study provided an overall picture of utilizing stem cells for treatment and management of childhood diseases. Since clinical trials in this area are insufficient in quantity and quality, there is an urgent need of larger, better-designed trials. Increased investment in clinical research of stem cell treatment products should be carried out to achieve the transformation of results as soon as possible. Moreover, it is important to optimize the management of the registration platform and shorten the time it takes for research results to be published.
Stem cells differentiation into insulin-producing cells (IPCs): recent advances and current challenges
Authors: Silva Isaura Beatriz Borges , Kimura Camila Harumi , Colantoni Vitor Prado , Sogayar Mari Cleide
Published: July 2022

Type 1 diabetes mellitus (T1D) is a chronic disease characterized by an autoimmune destruction of insulin-producing β-pancreatic cells. Although many advances have been achieved in T1D treatment, current therapy strategies are often unable to maintain perfect control of glycemic levels. Several studies are searching for new and improved methodologies for expansion of β-cell cultures in vitro to increase the supply of these cells for pancreatic islets replacement therapy. A promising approach consists of differentiation of stem cells into insulin-producing cells (IPCs) in sufficient number and functional status to be transplanted. Differentiation protocols have been designed using consecutive cytokines or signaling modulator treatments, at specific dosages, to activate or inhibit the main signaling pathways that control the differentiation of induced pluripotent stem cells (iPSCs) into pancreatic β-cells. Here, we provide an overview of the current approaches and achievements in obtaining stem cell-derived β-cells and the numerous challenges, which still need to be overcome to achieve this goal. Clinical translation of stem cells-derived β-cells for efficient maintenance of long-term euglycemia remains a major issue. Therefore, research efforts have been directed to the final steps of in vitro differentiation, aiming at production of functional and mature β-cells and integration of interdisciplinary fields to generate efficient cell therapy strategies capable of reversing the clinical outcome of T1D.
IL-37 overexpression promotes endometrial regenerative cell-mediated inhibition of cardiac allograft rejection
Authors: Qin Hong , Sun Chenglu , Zhu Yanglin , Qin Yafei , Ren Shaohua , Wang Zhaobo , Li Chuan , Li Xiang , Zhang Baoren , Hao Jingpeng , Li Guangming , Wang Hongda , Shao Bo , Zhang Jingyi , Wang Hao
Published: July 2022

Background

Endometrial regenerative cells (ERCs) play an important role in attenuation of acute allograft rejection, while their effects are limited. IL-37, a newly discovered immunoregulatory cytokine of the IL-1 family, can regulate both innate and adaptive immunity. Whether IL-37 overexpression can enhance the therapeutic effects of ERCs in inhibition of acute cardiac allograft rejection remains unknown and will be explored in this study.

Methods

C57BL/6 mice recipients receiving BALB/c mouse heterotopic heart allografts were randomly divided into the phosphate-buffered saline (untreated), ERC treated, negative lentiviral control ERC (NC-ERC) treated, and IL-37 overexpressing ERC (IL-37-ERC) treated groups. Graft pathological changes were assessed by H&E staining. The intra-graft cell infiltration and splenic immune cell populations were analyzed by immunohistochemistry and flow cytometry, respectively. The stimulatory property of recipient DCs was tested by an MLR assay. Furthermore, serum cytokine profiles of recipients were measured by ELISA assay.

Results

Mice treated with IL-37-ERCs achieved significantly prolonged allograft survival compared with the ERC-treated group. Compared with all the other control groups, IL-37-ERC-treated group showed mitigated inflammatory response, a significant increase in tolerogenic dendritic cells (Tol-DCs), regulatory T cells (Tregs) in the grafts and spleens, while a reduction of Th1 and Th17 cell population. Additionally, there was a significant upregulation of immunoregulatory IL-10, while a reduction of IFN-γ, IL-17A, IL-12 was detected in the sera of IL-37-ERC-treated recipients.

Conclusion

IL-37 overexpression can promote the therapeutic effects of ERCs to inhibit acute allograft rejection and further prolong graft survival. This study suggests that gene-modified ERCs overexpressing IL-37 may pave the way for novel therapeutic options in the field of transplantation.
Anti-fibrotic effect of a selective estrogen receptor modulator in systemic sclerosis
Authors: Kim Yena , Nam Yoojun , Rim Yeri Alice , Ju Ji Hyeon
Published: July 2022

Background

The rarity of systemic sclerosis (SSc) has hampered the development of therapies for this intractable autoimmune disease. Induced pluripotent stem cell (iPSC) can be differentiated into the key disease-affected cells in vitro. The generation of patient-derived iPSCs has opened up possibilities for rare disease modeling. Since these cells can recapitulate the disease phenotypes of the cell in question, they are useful high-throughput platforms for screening for drugs that can reverse these abnormal phenotypes.

Methods

SSc iPSC was generated from PBMC by Sendai virus. Human iPSC lines from SSc patients were differentiated into dermal fibroblasts and keratinocytes. The iPSC-derived differentiated cells from the SSc patients were used on high-throughput platforms to screen for FDA-approved drugs that could be effective treatments for SSc.

Results

Skin organoids were generated from these cells exhibited fibrosis that resembled SSc skin. Screening of the 770-FDA-approved drug library showed that the anti-osteoporotic drug raloxifene reduced SSc iPSC-derived fibroblast proliferation and extracellular matrix production and skin fibrosis in organoids and bleomycin-induced SSc-model mice.

Conclusions

This study reveals that a disease model of systemic sclerosis generated using iPSCs-derived skin organoid is a novel tool for in vitro and in vivo dermatologic research. Since raloxifene and bazedoxifene are well-tolerated anti-osteoporotic drugs, our findings suggest that selective estrogen receptor modulator (SERM)-class drugs could treat SSc fibrosis.
A gene signature is critical for intrahepatic cholangiocarcinoma stem cell self-renewal and chemotherapeutic response
Authors: Huang Lifeng , Xu Dongwei , Qian Yawei , Zhang Xiaoqiang , Guo Han , Sha Meng , Hu Rui , Kong Xiaoni , Xia Qiang , Zhang Yi
Published: July 2022

Background

Improved understanding of the stemness regulation mechanism in intrahepatic cholangiocarcinoma (ICC) could identify targets and guidance for adjuvant transarterial chemoembolization (TACE).

Methods

TCGA database was excavated to identify the ICC stemness-associated genes. The pro-stemness effect of target genes was further analyzed by sphere formation assay, qRT-PCR, western blot, flow cytometric analysis, IHC, CCK8 assay and metabolomic analysis. Based on multivariate analysis, a nomogram for ICC patients with adjuvant TACE was established and our result was further confirmed by a validation cohort. Finally, the effect of dietary methionine intervention on chemotherapy was estimated by in vivo experiment and clinical data.

Results

In this study, we identified four ICC stemness-associated genes (SDHAF2, MRPS34, MRPL11, and COX8A) that are significantly upregulated in ICC tissues and negatively associated with clinical outcome. Functional studies indicated that these 4-key-genes are associated with self-renewal ability of ICC and transgenic expression of these 4-key-genes could enhance chemoresistance of cholangiocarcinoma cells. Mechanistically, the 4-key-genes-mediated pro-stemness requires the activation of methionine cycle, and their promotion on ICC stemness characteristic is dependent on MAT2A. Importantly, we established a novel nomogram to evaluate the effectiveness of TACE for ICC patients. Further dietary methionine intervene studies indicated that patients with adjuvant TACE might benefit from dietary methionine restriction if they have a relatively high nomogram score (≥ 135).

Conclusions

Our results show that four ICC stemness-associated genes could serve as novel biomarkers in predicting ICC patient’s response to adjuvant TACE and their pro-stemness ability may be attributed to the activation of the methionine cycle.
Biodistribution of allogenic umbilical cord-derived mesenchymal stromal cells after fetal repair of myelomeningocele in an ovine model
Authors: Athiel Yoann , Nasone Justine , Arakelian Lousineh , Faivre Lionel , Dugas Anaïs , Jouannic Jean-Marie , Larghero Jérôme , Guilbaud Lucie
Published: July 2022

Background

Myelomeningocele (MMC) is a spinal cord congenital defect that leads to paraplegia, sphincter disorders and potential neurocognitive disabilities. Prenatal surgery of MMC provides a significant benefit compared to surgery at birth. Mesenchymal stromal cell (MSC) therapy as an adjuvant treatment for prenatal surgery showed promising results in animal experiments which could be considered for clinical use in human fetuses. Despite numerous reassuring studies on the safety of MSCs administration in humans, no study focused on MSCs biodistribution after a local MSCs graft on the fetal spinal cord.

Aim

The purpose of our study was to assess the biodistribution of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) at birth in lambs who had a prenatal myelomeningocele repair using a fibrin patch seeded with allogenic UC-MSCs.

Methods

After isolation, UC-MSCs were tagged using a green fluorescent protein (GFP)-containing lentiviral vector. MMC defects were surgically created at 75 days of gestation and repaired 15 days later using UC-MSCs patch. Lambs were delivered at 142 days and sacrificed. DNA extraction was performed among biopsies of the different organs and q-PCR analysis was used to detect the expression of GFP (GFP DNA coding sequence).

Results

In our 6 surviving lambs grafted with UC-MSCs, GFP lentivirus genomic DNA was not detected in the organs.

Conclusion

These reassuring data will support translational application in humans, especially since the first human clinical trial using mesenchymal stromal cells for in-utero treatment of MMC started recently in U.S.A.
The therapeutic effect of stem cells from human exfoliated deciduous teeth on a rat model of tracheal fistula
Authors: Wang Fang , Li Zhangwen , Lyu Feng-Juan , Gao Jie , Lin Jinle , Liu Jianling , Chen Xiaowen , Li Zhongpeng , Shan Jiajie , Wu Jian
Published: July 2022

Background

Tracheal fistulas (TF) can be dangerous and even fatal in patients. The current treatment is really challenging. Previous studies reported that mesenchymal stem cells (MSCs) could be used to treat respiratory tract fistulas. Stem cells from human exfoliated deciduous teeth (SHED) are considered to be MSC-like cells that may also have the potential to treat the tracheal fistulas. In this study, we investigated the therapeutic effects of SHED in rat tracheal fistula models.

Methods

A total of 80 SD rats were randomly divided into five groups: a sham-operated group, a local PBS group (L-PBS), an intravenous PBS group (I-PBS), a local SHED treatment group (L-SHED), and an intravenous SHED treatment group (I-SHED). The L-SHED and I-SHED groups were given a topical application around the fistula or an intravenous injection of 1*107 SHED via the tail vein, respectively, while the L-PBS and I-PBS groups were given an equivalent volume of PBS through local or intravenous administration. A stereomicroscope was used to observe fistula healing on the 2nd, 3rd, and 5th days following transplantation. On the 7th day, the survival of SHED was observed by immunofluorescence. The pathology of the lungs and fistulas was observed by hematoxylin and eosin (H&E) and Masson staining. The expression levels of the Toll-like receptor 4 (TLR4), interleukin (IL)-1β, IL-33, and IL-4 were measured using immunohistochemistry. The expression levels of TLR4, high mobility group box 1 (HMGB1), and myeloid differentiation factor 88 (MYD88) were studied using western blotting. On day 14, airway responsiveness of rats was detected and analyzed.

Results

Fistula healing in the L-SHED and I-SHED groups was faster than that in their respective PBS groups after transplantation. The fistula diameters in the L-SHED and I-SHED groups were significantly smaller than those in the L-PBS and I-PBS groups on the 3rd day. Moreover, the phenomenon of fibroblast proliferation and new blood vessel growth around the fistula seemed more pronounced in the L-SHED and I-SHED groups. Although no discernible difference was found in airway responsiveness after SHED treatment, the degree of inflammation in the lungs was reduced by intravenous SHED treatment. However, there was no significant reduction in lung inflammation by local SHED treatment. The expression levels of IL-1β and IL-33 were decreased in the I-SHED group, while IL-4 was elevated compared with the I-PBS group. Interestingly, intravenous SHED treatment inhibited the activation of HMGB1/TLR4/MYD88 in the lung tissues of TF rats.

Conclusions

SHED transplantation accelerated the rate of fistula healing in rats. Intravenous SHED treatment reduced lung inflammation. Thus, SHED may have potential in the treatment of tracheal fistula, providing hope for future therapeutic development for TF.
Exosomal miR-132-3p from mesenchymal stromal cells improves synaptic dysfunction and cognitive decline in vascular dementia
Authors: Ma Xiaotang , Wang Yan , Shi Yumeng , Li Suqing , Liu Jinhua , Li Xiangyong , Zhong Wangtao , Pan Qunwen
Published: July 2022

Background/aims

Vascular dementia (VD) results in cognition and memory deficit. Exosomes and their carried microRNAs (miRs) contribute to the neuroprotective effects of mesenchymal stromal cells, and miR-132-3p plays a key role in neuron plasticity. Here, we investigated the role and underlying mechanism of MSC EX and their miR-132-3p cargo in rescuing cognition and memory deficit in VD mice.

Methods

Bilateral carotid artery occlusion was used to generate a VD mouse model. MiR-132-3p and MSC EX levels in the hippocampus and cortex were measured. At 24-h post-VD induction, mice were administered with MSC EX infected with control lentivirus (EXCon), pre-miR-132-3p-expressing lentivirus (EXmiR-132-3p), or miR-132-3p antago lentivirus (EXantagomiR-132-3p) intravenously. Behavioral and cognitive tests were performed, and the mice were killed in 21 days after VD. The effects of MSC EX on neuron number, synaptic plasticity, dendritic spine density, and Aβ and p-Tau levels in the hippocampus and cortex were determined. The effects of MSC EX on oxygen–glucose deprivation (OGD)-injured neurons with respect to apoptosis, and neurite elongation and branching were determined. Finally, the expression levels of Ras, phosphorylation of Akt, GSK-3β, and Tau were also measured.

Results

Compared with normal mice, VD mice exhibited significantly decreased miR-132-3p and MSC EX levels in the cortex and hippocampus. Compared with EXCon treatment, the infusion of EXmiR-132-3p was more effective at improving cognitive function and increasing miR-132-3p level, neuron number, synaptic plasticity, and dendritic spine density, while decreasing Aβ and p-Tau levels in the cortex and hippocampus of VD mice. Conversely, EXantagomiR-132-3p treatment significantly decreased miR-132-3p expression in cortex and hippocampus, as well as attenuated EXmiR-132-3p treatment-induced functional improvement. In vitro, EXmiR-132-3p treatment inhibited RASA1 protein expression, but increased Ras and the phosphorylation of Akt and GSK-3β, and decreased p-Tau levels in primary neurons by delivering miR-132-3p, which resulted in reduced apoptosis, and increased neurite elongation and branching in OGD-injured neurons.

Conclusions

Our studies suggest that miR-132-3p cluster-enriched MSC EX promotes the recovery of cognitive function by improving neuronal and synaptic dysfunction through activation of the Ras/Akt/GSK-3β pathway induced by downregulation of RASA1.
Bone marrow mesenchymal stem cells facilitate diabetic wound healing through the restoration of epidermal cell autophagy via the HIF-1α/TGF-β1/SMAD pathway
Authors: Shi Yan , Wang Shang , Zhang Weiwei , Zhu Yihan , Fan Zhiqiang , Huang Yuesheng , Li Furong , Yang Ronghua
Published: July 2022

Background

The biological activity and regenerative medicine of bone marrow mesenchymal stem cells (BMSCs) have been focal topics in the broad fields of diabetic wound repair. However, the molecular mechanisms are still largely elusive for other cellular processes that are regulated during BMSC treatment. Our previous studies have shown that hypoxia is not only a typical pathological phenomenon of wounds but also exerts a vital regulatory effect on cellular bioactivity. In this study, the beneficial effects of hypoxic BMSCs on the cellular behaviors of epidermal cells and diabetic wound healing were investigated.

Method

The viability and secretion ability of hypoxic BMSCs were detected. The autophagy, proliferation and migration of HaCaT cells cultured with hypoxic BMSCs-derived conditioned medium were assessed by estimating the expression of autophagy-related proteins, MTS, EdU proliferation and scratch assays. And the role of the SMAD signaling pathway during hypoxic BMSC-evoked HaCaT cell autophagy was explored through a series of in vitro gain- and loss-of-function experiments. Finally, the therapeutic effects of hypoxic BMSCs were evaluated using full-thickness cutaneous diabetic wound model.

Results

First, we demonstrated that hypoxic conditions intensify HIF-1α-mediated TGF-β1 secretion by BMSCs. Then, the further data revealed that BMSC-derived TGF-β1 was responsible for the activation of epidermal cell autophagy, which contributed to the induction of epidermal cell proliferation and migration. Here, the SMAD signaling pathway was identified as downstream of BMSC-derived TGF-β1 to regulate HaCaT cell autophagy. Moreover, the administration of BMSCs to diabetic wounds increased epidermal autophagy and the rate of re-epithelialization, leading to accelerated healing, and these effects were significantly attenuated, accompanied by the downregulation of Smad2 phosphorylation levels due to TGF-β1 interference in BMSCs.

Conclusion

In this report, we present evidence that uncovers a previously unidentified role of hypoxic BMSCs in regulating epidermal cell autophagy. The findings demonstrate that BMSC-based treatment by restoring epidermal cell autophagy could be an attractive therapeutic strategy for diabetic wounds and that the process is mediated by the HIF-1α/TGF-β1/SMAD pathway.
An efficient multi-objective optimization approach for sensor management via multi-Bernoulli filtering
Authors: Zhu Yun , Liang Shuang , Xue Guangran , Yang Rui , Wu Xiaojun
Published: July 2022

Intelligent sensor management is generally required for efficient and accurate data processing when the multi-sensor system is used for multi-target tracking (MTT). However, this is theoretically and computationally challenging. To deal with this problem, we propose a novel sensor management approach based on efficient multi-objective optimization for MTT under the framework of partially observed Markov decision process. The multi-Bernoulli filter is used in conjunction with two objective functions. To simplify the multi-objective optimization problem, we use the Euclidean distance (ED) between the feasible and utopian solution vectors as a measure of the objectives and then sequentially select sensors from the candidates. For the selected sensors, we rank them according to the obtained ED measure and implement the iterated-corrector fusion scheme after the ranking. Numerical studies demonstrate the effectiveness and efficiency of our approach in multi-sensor MTT scenarios.
PlugSonic: a web- and mobile-based platform for dynamic and navigable binaural audio
Authors: Comunità Marco , Gerino Andrea , Picinali Lorenzo
Published: July 2022

PlugSonic is a series of web- and mobile-based applications designed to edit samples and apply audio effects (PlugSonic Sample) and create and experience dynamic and navigable soundscapes and sonic narratives (PlugSonic Soundscape). The audio processing within PlugSonic is based on the Web Audio API while the binaural rendering uses the 3D Tune-In Toolkit. Exploration of soundscapes in a physical space is made possible by adopting Apple’s ARKit. The present paper describes the implementation details, the signal processing chain and the necessary steps to curate and experience a soundscape. We also include some metrics and performance details. The main goal of PlugSonic is to give users a complete set of tools, without the need for specific devices, external software and/or hardware specialised knowledge, or custom development, with the idea that spatial audio has the potential to become a readily accessible and easy to understand technology, for anyone to adopt, whether for creative or research purposes.
DOA estimation algorithm based on spread spectrum sequence in low signal-to-noise ratio
Authors: Zhou Feng , Zhang Wenbo , Zhang Baosheng , Ji Xiaofeng , Li Xuanze
Published: July 2022

Spread spectrum communication is a common communication method in underwater communication. Based on the space-time processor received by the array, it can filter the signals arriving along each path separately. Combined with the diversity of space-time clusters, it can effectively improve the communication system’s reliability. The core problem of the space-time processor is the direction of arrival (DOA) and signal source number estimation. Based on the good self-coherence of the spread spectrum sequence, this paper proposes a multiple signal classification algorithm (MUSIC) for accurate DOA estimation. However, since the MUSIC algorithm uses the received signal’s covariance matrix for DOA estimation, the number of sources needs to be predicted in advance. Under a low signal-to-noise ratio (SNR), the signal eigenvalues and the noise eigenvalues of the covariance matrix differ slightly, which makes signal source number estimation difficult. To address this issue, a singular value decomposition method using the delay structure information of the array element is proposed to estimate the number of sources of the spreading sequence under a low SNR. The method proposed in this paper can well estimate the DOA of the signal under a low SNR. Meanwhile, there is no need to convert the signal to the individual sub-bands, which effectively reduces the calculation overhead. At the same time, the Hankel matrix is used to solve the problem that the MUSIC algorithm cannot accurately estimate the number of signal sources under the condition of low SNR. Compared with the conventional algorithm, the Hankel matrix can more accurately estimate the number of signal sources in the case of low SNR. Through simulation experiments, the effectiveness of our DOA estimation algorithm is validated under a low SNR.
Duration of rectal colonization with extended-spectrum beta-lactamase-producing Escherichia coli: results of an open, dynamic cohort study in Dutch nursing home residents (2013–2019)
Authors: Weterings Veronica , van den Bijllaardt Wouter , Bootsma Martin , Hendriks Yvonne , Kilsdonk Linda , Mulders Ans , Kluytmans Jan
Published: July 2022

Background

In 2016, a study in a Dutch nursing home showed prolonged colonization duration of extended-spectrum β-lactamase-producing (ESBL)-ST131 compared to ESBL-non-ST131. In this study, we assessed the duration of rectal ESBL-producing E. coli (ESBL-EC) colonization in residents in the same nursing home for an extended period of six years. We aimed to estimate the influence of a possible bias when follow up is started during an outbreak.

Methods

Between 2013 and 2019, repetitive point prevalence surveys were performed by culturing rectal or faecal swabs from all residents. Kaplan–Meier survival analysis was performed to calculate the median time to clearance of ESBL-EC with a log-rank analysis to test for differences between ESBL-ST131 and ESBL-non-ST131.

Results

The study showed a median time to clearance of 13.0 months (95% CI 0.0–27.9) for ESBL-ST131 compared to 11.2 months (95% CI 4.8–17.6) for ESBL-non-ST131 (p = 0.044). In the subgroup analysis of residents who were ESBL-EC positive in their first survey, the median time to clearance for ST131 was 59.7 months (95% CI 23.7–95.6) compared to 16.2 months (95% CI 2.1–30.4) for ESBL-non-ST131 (p = 0.036). In the subgroup analysis of residents who acquired ESBL-EC, the median time to clearance for ST131 was 7.2 months (95% CI 2.1–12.2) compared to 7.9 months (95% CI 0.0–18.3) for ESBL-non-ST131 (p = 0.718). The median time to clearance in the ESBL-ST131 group was significantly longer in residents who were ESBL-ST131 colonised upon entering the study than in residents who acquired ESBL-ST131 during the study (p = 0.001).

Conclusion

A prolonged colonization with ESBL-ST131 was only found in the subgroup who was ESBL-EC positive upon entering the study. The prolonged duration with ESBL-ST131 in the previous study was probably biased by factors that occured during (the start of) the outbreak.
Costs and cost-effectiveness of HIV early infant diagnosis in low- and middle-income countries: a scoping review
Authors: Elsbernd Kira , Emmert-Fees Karl M. F. , Erbe Amanda , Ottobrino Veronica , Kroidl Arne , Bärnighausen Till , Geisler Benjamin P. , Kohler Stefan
Published: July 2022

Background

Continuing progress in the global pediatric human immunodeficiency virus (HIV) response depends on timely identification and care of infants with HIV. As countries scale-out improvements to HIV early infant diagnosis (EID), economic evaluations are needed to inform program design and implementation. This scoping review aimed to summarize the available evidence and discuss practical implications of cost and cost-effectiveness analyses of HIV EID.

Methods

We systematically searched bibliographic databases (Embase, MEDLINE and EconLit) and grey literature for economic analyses of HIV EID in low- and middle-income countries published between January 2008 and June 2021. We extracted data on unit costs, cost savings, and incremental cost-effectiveness ratios as well as outcomes related to health and the HIV EID care process and summarized results in narrative and tabular formats. We converted unit costs to 2021 USD for easier comparison of costs across studies.

Results

After title and abstract screening of 1278 records and full-text review of 99 records, we included 29 studies: 17 cost analyses and 12 model-based cost-effectiveness analyses. Unit costs were 21.46–51.80 USD for point-of-care EID tests and 16.21–42.73 USD for laboratory-based EID tests. All cost-effectiveness analyses stated at least one of the interventions evaluated to be cost-effective. Most studies reported costs of EID testing strategies; however, few studies assessed the same intervention or reported costs in the same way, making comparison of costs across studies challenging. Limited data availability of context-appropriate costs and outcomes of children with HIV as well as structural heterogeneity of cost-effectiveness modelling studies limits generalizability of economic analyses of HIV EID.

Conclusions

The available cost and cost-effectiveness evidence for EID of HIV, while not directly comparable across studies, covers a broad range of interventions and suggests most interventions designed to improve EID are cost-effective or cost-saving. Further studies capturing costs and benefits of EID services as they are delivered in real-world settings are needed.

Graphical Abstract
The psychological and subjective experience of catatonia: a qualitative study
Authors: Zingela Zukiswa , Stroud Louise , Cronje Johan , Fink Max , van Wyk Stephan
Published: July 2022

Background

Catatonia is a severe psychomotor disorder that presents as abnormality of movement which may also be excessive or severely slowed. It often inhibits communication when protracted or severe. In this study we investigated the emotive and cognitive experience of patients with catatonia during a prevalence study in an acute mental health unit from August 2020 to September 2021. The value of this study is the addition of the inner and often unexplored cognitive and emotive experience of patients in the description of the catatonic state, which lends an additional dimension to complement the medical and psychopathological descriptors that have been the focus of most studies on catatonia.

Methods

Ethical approval was received from the Nelson Mandela University Human Research Committee and convenience sampling was undertaken to recruit participants admitted into an acute mental health unit with catatonia, four to eight weeks after discharge, following admission. The BFCSI and BFCRS and a pre-designed data collection sheet were used to assess n = 241 participants, and collect data on descriptions of thoughts, feelings, and behaviours they experienced during the catatonic episode.

Results

Forty-four (18.3%) of the total 241 participants who were assessed had catatonia. Thirty (68.2%) of the 44 participants with catatonia provided data on their experience of catatonia. Twenty-three were males (76.7% of 30) and seven were females (23.3% of 30). All were within the age range of 17 to 65 years. The dominant themes of thoughts, feelings, and behaviors described centered around yearning for or missing loved ones, heightened fear, intense anxiety, negative affect, aggression, obedience, and withdrawal.

Conclusions

The common themes that emerged from this study were overwhelming anxiety, fear, and depression. These were found to occur frequently in patients with catatonia when describing their psychological experience. These experiences may possibly relate to the flight, fight, freeze and fawn response, as described in prior studies on the subjective experience of catatonia.

Trial registration: Not applicable.