bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Minimally Invasive Arthroscopy Technology in Sports Medicine—An Evaluation of Nano Silver Disinfectants
Authors: Ge Ruiyi , Zhang Jin , Yang Ziquan
Published: January 2021

Currently, nano silver fungicide prepared in the laboratory is used to disinfect arthroscopic surgical instruments. In this study, nano silver fungicides with stable properties were prepared and characterized. Afterwards, their bactericidal properties as well as mucus peeling properties
were further tested. The results show that the nano silver fungicide prepared here contains uniform particle size and displays material stability for 60 days. Nano silver fungicide can completely kill sulfate-reducing bacteria, anaerobic bacteria, and iron reducing bacteria, while the slime
stripping rate is 80.58%. Additionally, we propose the use of nano silver sterilization agents to kill the arthroscopic surgical instruments in conjunction with proper manual cleaning, as they can effectively kill all the bacteria on the surgical instruments, achieving a sterilization rate
of 99.99%.
Iron Oxide Nanomaterials for the Removal of Cr(VI) and Pb(II) from Contaminated River After Mariana Mining Disaster
Authors: Andrade Thainá Gusmão , Santos Mayra Soares , Maia Luiz Fernando Oliveira , Aquino Tamise Emanuele Oliveira de , Silva Lucas Zeferino da , Silva Vitor Chaves , Faria Márcia Cristina da Silva , Batista Bruno Lemos , Pedron Tatiana , Oliveira Luiz Carlos Alves de , Pereira Márcio César , Rodrigues Jairo Lisboa
Published: January 2021

If not properly treated, water contaminated with chromium (Cr(VI)) and lead (Pb(II)) can cause severe damage to health due to the accumulation of those toxic metals in the human body. Therefore, in this work, three iron oxides, i.e., δ-FeOOH, cystine-functionalized δ-FeOOH
(Cys-δ-FeOOH), and Fe3O4, were synthesized and used as adsorbents for Cr(VI) and Pb(II) in water. The results indicated that the Cr(VI) is best adsorbed on cys-δ-FeOOH followed by δ-FeOOH and Fe3O4. It was because of the enhanced
interaction between Cr(VI) and the cysteine functional groups on the δ-FeOOH surface. The Cr(VI) adsorption capacity of cys-δ-FeOOH, δ-FeOOH, and Fe3O4 was 217, 14, and 8 mg g−1, respectively. On the other hand, Pb(II) was preferentially
adsorbed directly on δ-FeOOH achieving a maximum Pb(II) adsorption capacity of 174 mg g−1. The Pb(II) adsorption capacity of cys-δ-FeOOH and Fe3O4 was 97 and 74 mg g−1, respectively. The Cr(VI) adsorption on cys-δ-FeOOH
was best described by the Langmuir-Freundlich model, whereas Pb(II) adsorption on δ-FeOOH followed the Langmuir model. Both Cr(VI) and Pb(II) adsorption on the adsorbents was well-fitted to pseudo-second-order kinetics. The Cr(VI) was more quickly adsorbed by cys-δ-FeOOH (h0
= 0.10 mg g−1 min−1) while the initial adsorption rate of Pb(II) onto δ-FeOOH was significantly faster (h0 = 16.34 mg g−1 min−1). Finally, the synthesized adsorbents were efficient to remove Cr(VI)
and Pb(II) from water samples of the Doce river after the environmental disaster of Mariana city, Brazil, thus showing its applicability to remediate real water samples.
Dynamic genome-wide association analysis and identification of candidate genes involved in anaerobic germination tolerance in rice
Authors: Su Ling , Yang Jing , Li Dandan , Peng Ziai , Xia Aoyun , Yang Meng , Luo Lixin , Huang Cuihong , Wang Jiafeng , Wang Hui , Chen Zhiqiang , Guo Tao
Published: January 2021

Background

In Asian rice production, an increasing number of countries now choose the direct seeding mode because of rising costs, labour shortages and water shortages. The ability of rice seeds to undergo anaerobic germination (AG) plays an important role in the success of direct seeding.

Results

In this study, we used 2,123,725 single nucleotide polymorphism (SNP) markers based on resequencing to conduct a dynamic genome-wide association study (GWAS) of coleoptile length (CL) and coleoptile diameter (CD) in 209 natural rice populations. A total of 26 SNP loci were detected in these two phenotypes, of which 5 overlapped with previously reported loci (S1_ 39674301, S6_ 20797781, S7_ 18722403, S8_ 9946213, S11_ 19165397), and two sites were detected repeatedly at different time points (S3_ 24689629 and S5_ 27918754). We suggest that these 7 loci (−log10 (P) value > 7.3271) are the key sites that affect AG tolerance. To screen the candidate genes more effectively, we sequenced the transcriptome of the flooding-tolerant variety R151 in six key stages, including anaerobic (AN) and the oxygen conversion point (AN-A), and obtained high-quality differential expression profiles. Four reliable candidate genes were identified: Os01g0911700 (OsVP1), Os05g0560900 (OsGA2ox8), Os05g0562200 (OsDi19–1) and Os06g0548200. Then qRT-PCR and LC-MS/ MS targeting metabolite detection technology were used to further verify that the up-regulated expression of these four candidate genes was closely related to AG.

Conclusion

The four novel candidate genes were associated with gibberellin (GA) and abscisic acid (ABA) regulation and cell wall metabolism under oxygen-deficiency conditions and promoted coleoptile elongation while avoiding adverse effects, allowing the coleoptile to obtain oxygen, escape the low-oxygen environment and germinate rapidly. The results of this study improve our understanding of the genetic basis of AG in rice seeds, which is conducive to the selection of flooding-tolerant varieties suitable for direct seeding.
Sturge-Weber syndrome coexisting with polydactyly: a case report
Authors: Wang Hongxi , Dong Nana , Tan Li , Huang Chukai
Published: January 2021

Background

Sturge-Weber syndrome (SWS) is a sporadic congenital disorder, characterized by unilateral facial nevus flammeus associated with ipsilateral glaucoma, choroidal angioma and leptomeningeal hemangiomas. SWS can comorbid with other disorders in some patients, however, there has been no prior described case of SWS and polydactyly occurring in the same patient.

Case presentation

A 15-year-old girl with diagnosis of SWS presented to our hospital. She had bilateral glaucoma and extensive port-wine stains distributing in bilateral faces, left neck and left upper limb. Meanwhile, the patient was noted to demonstrate the superfluous digit attaching on the left thumb and was diagnosed as polydactyly. Trabeculectomy, with intraoperative application of mitomycin C and postoperative subconjunctival injections of 5-fluorouracil, was successful in controlling the intraocular pressure in both eyes.

Conclusions

We report a case with bilateral SWS coexisting with unilateral polydactyly, which, to our knowledge, has not been recognized previously and adds further evidence to the existing literature. In view of the rare concurrence of SWS and polydactyly, the etiology is unclear and further investigation is required to explore the underlying pathogenesis.
A longitudinal analysis of the progression from normal blood pressure to stage 2 hypertension: A 12-year Korean cohort
Authors: Yu Eun Sun , Hong Kwan , Chun Byung Chul
Published: January 2021

Background

The study aimed to estimate the incidence of and period of progression to stage 2 hypertension from normal blood pressure.

Methods

We selected a total of 21,172 normotensive individuals between 2003 and 2004 from the National Health Insurance Service-Health Screening and followed them up until 2015. The criteria for blood pressure were based on the American College of Cardiology/American Heart Association 2017 guideline (normal BP: SBP < 120 and DBP < 80 mmHg, elevated BP: SBP 120–129 and DBP < 80 mmHg, stage 1 hypertension: SBP 130–139 or DBP 80–89 mmHg, stage 2 hypertension: SBP ≥140 or DBP ≥ 90 mmHg). We classified the participants into four courses (Course A: normal BP → elevated BP → stage 1 hypertension→ stage 2 hypertension, Course B: normal BP → elevated BP → stage 2 hypertension, Course C: normal BP → stage 1 hypertension → stage 2 hypertension, Course D: normal BP → stage 2 hypertension) according to their progression from normal blood pressure to stage 2 hypertension.

Results

During the median 12.23 years of follow-up period, 52.8% (n= 11,168) and 23.6% (n=5004) of the participants had stage 1 and stage 2 hypertension, respectively. In particular, over 60 years old had a 2.8-fold higher incidence of stage 2 hypertension than 40–49 years old. After the follow-up period, 77.5% (n=3879) of participants with stage 2 hypertension were found to be course C (n= 2378) and D (n=1501). After the follow-up period, 77.5% (n=3879) of participants with stage 2 hypertension were found to be course C (n= 2378) and D (n=1501). The mean years of progression from normal blood pressure to stage 2 hypertension were 8.7±2.6 years (course A), 6.1±2.9 years (course B), 7.5±2.8 years (course C) and 3.2±2.0 years, respectively.

Conclusions

This study found that the incidence of hypertension is associated with the progression at each stage. We suggest that the strategies necessary to prevent progression to stage 2 hypertension need to be set differently for each target course.
An infected aneurysm of the vertebral artery following cervical pyogenic spondylitis: a case report and literature review
Authors: Furukawa Takahiro , Masuda Keisuke , Shigematsu Hideki , Tanaka Masato , Okuda Akinori , Kawasaki Sachiko , Suga Yuma , Yamamoto Yusuke , Tanaka Yasuhito
Published: January 2021

Background

An important complication of pyogenic spondylitis is aneurysms in the adjacent arteries. There are reports of abdominal aortic or iliac aneurysms, but there are few reports describing infected aneurysms of the vertebral artery. Furthermore, there are no reports describing infected aneurysms of the vertebral arteries following cervical pyogenic spondylitis. We report a rare case of an infected aneurysm of the vertebral artery as a complication of cervical pyogenic spondylitis, which was successfully treated by endovascular treatment.

Case presentation

Cervical magnetic resonance imaging (MRI) of a 59-year-old man who complained of severe neck pain showed pyogenic spondylitis. Although he was treated extensively by antibiotic therapy, his neck pain did not improve. Follow-up MRI showed the presence of a cyst, which was initially considered an abscess, and therefore, treatment initially included guided tapping and suction under ultrasonography. However, under ultrasonographic examination an aneurysm was detected. The contrast-enhanced computed tomography (CT) scan showed an aneurysm of the vertebral artery. Following endovascular treatment (parent artery occlusion: PAO), the patient’s neck pain disappeared completely.

Conclusion

Although there are several reports of infected aneurysms of the vertebral arteries, this is the first report describing an infected aneurysm of the vertebral artery as a result of cervical pyogenic spondylitis.

Whenever a paraspinal cyst exist at the site of infection, we recommend that clinicians use not only X-ray, conventional CT, and MRI to examine the cyst, but ultrasonography and contrast-enhanced CT as well because of the possibility of an aneurysms in neighboring blood vessels. It is necessary to evaluate the morphology of the aneurysm to determine the treatment required.
Menstrual, reproductive and hormonal factors and thyroid cancer: a hospital-based case–control study in China
Authors: Wang Meng , Gong Wei-Wei , He Qing-Fang , Hu Ru-Ying , Yu Min
Published: January 2021

Background

There have been considerable studies on the effects of reproductive factors on thyroid cancer risk, while findings are inconsistent. In this analysis, we aimed to investigate the associations between menstrual, reproductive and hormonal factors with thyroid cancer occurrence in a population of Chinese women.

Methods

Using data from a 1:1 matched case–control study performed between 2015 and 2017 in Zhejiang Province of China, a second analysis of 2261 pairs of female subjects was conducted. The possible effects for thyroid cancer were evaluated in logistic regression models by odds ratios (ORs) with 95% confidence intervals (CIs).

Results

Later age at first pregnancy (for > 25 vs. ≦ 20 years, OR: 0.47, 95% CI 0.23–0.96) and longer duration of breast feeding (for 6–12 vs. ≦ 6 months, OR: 0.49, 95% CI 0.24–0.98) were significantly associated with decreased occurrence of thyroid cancer, while no trend was observed. Stratified by age at enrollment, only the association with duration of breast feeding remained significant, but limited to younger women (≦ 50 years).

Conclusions

Our results suggested that women with later age at first pregnancy or longer breast feeding duration were less likely to have thyroid cancer. These findings supported an influence role of reproductive factors in thyroid cancer risk.
Optogenetic inhibition of medial entorhinal cortex inputs to the hippocampus during a short period of time right after learning disrupts contextual fear memory formation
Authors: Kang Min Soo , Han Jin-Hee
Published: January 2021

Formation of temporal association memory and context-specific fear memory is thought to require medial entorhinal cortex (MEC) inputs to the hippocampus during learning events. However, whether the MEC inputs are also involved in memory formation during a post-learning period has not been directly tested yet. To examine this possibility, we optogenetically inhibited axons and terminals originating from bilateral dorsal MEC excitatory neurons in the dorsal hippocampus for 5 min right after contextual fear conditioning (CFC). Mice expressing eNpHR3.0 exhibited significantly less freezing compared to control mice expressing EGFP alone during retrieval test in the conditioned context 1 day after learning. In contrast, the same optogenetic inhibition of MEC inputs performed 30 min before retrieval test did not affect freezing during retrieval test, excluding the possibility of non-specific deleterious effect of optical inhibition on retrieval process. These results support that contextual fear memory formation requires MEC inputs to the hippocampus during a post-learning period.
NK cell-based cancer immunotherapy: from basic biology to clinical development
Authors: Liu Sizhe , Galat Vasiliy , Galat4 Yekaterina , Lee Yoo Kyung Annie , Wainwright Derek , Wu Jennifer
Published: January 2021

Natural killer (NK) cell is a specialized immune effector cell type that plays a critical role in immune activation against abnormal cells. Different from events required for T cell activation, NK cell activation is governed by the interaction of NK receptors with target cells, independent of antigen processing and presentation. Due to relatively unsophisticated cues for activation, NK cell has gained significant attention in the field of cancer immunotherapy. Many efforts are emerging for developing and engineering NK cell-based cancer immunotherapy. In this review, we provide our current understandings of NK cell biology, ongoing pre-clinical and clinical development of NK cell-based therapies and discuss the progress, challenges, and future perspectives.
Targeting oncogenic Notch signaling with SERCA inhibitors
Authors: Pagliaro Luca , Marchesini Matteo , Roti Giovanni
Published: January 2021

P-type ATPase inhibitors are among the most successful and widely prescribed therapeutics in modern pharmacology. Clinical transition has been safely achieved for H+/K+ATPase inhibitors such as omeprazole and Na+/K+-ATPase inhibitors like digoxin. However, this is more challenging for Ca2+-ATPase modulators due to the physiological role of Ca2+in cardiac dynamics. Over the past two decades, sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) modulators have been studied as potential chemotherapy agents because of their Ca2+-mediated pan-cancer lethal effects. Instead, recent evidence suggests that SERCA inhibition suppresses oncogenic Notch1 signaling emerging as an alternative to γ-secretase modulators that showed limited clinical activity due to severe side effects. In this review, we focus on how SERCA inhibitors alter Notch1 signaling and show that Notch on-target-mediated antileukemia properties of these molecules can be achieved without causing overt Ca2+cellular overload.
Maintenance therapy in acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation
Authors: Xuan Li , Liu Qifa
Published: January 2021

Relapse remains the main cause of treatment failure in acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Emerging evidence has demonstrated that AML patients might benefit from maintenance therapy post-transplantation, especially for high-risk AML patients. In this mini-review, we will summarize targeted drugs, such as hypomethylating agents, FLT3 inhibitors and isocitrate dehydrogenase inhibitors, as maintenance therapy post-transplantation in AML patients undergoing allo-HSCT.
How we treat mature B-cell neoplasms (indolent B-cell lymphomas)
Authors: Lumish Melissa , Falchi Lorenzo , Imber Brandon S. , Scordo Michael , von Keudell Gottfried , Joffe Erel
Published: January 2021

Mature B cell neoplasms, previously indolent non-Hodgkin lymphomas (iNHLs), are a heterogeneous group of malignancies sharing similar disease courses and treatment paradigms. Most patients with iNHL have an excellent prognosis, and in many, treatment can be deferred for years. However, some patients will have an accelerated course and may experience transformation into aggressive lymphomas. In this review, we focus on management concepts shared across iNHLs, as well as histology-specific strategies. We address open questions in the field, including the influence of genomics and molecular pathway alterations on treatment decisions. In addition, we review the management of uncommon clinical entities including nodular lymphocyte-predominant Hodgkin lymphoma, hairy cell leukemia, splenic lymphoma and primary lymphoma of extranodal sites. Finally, we include a perspective on novel targeted therapies, antibodies, antibody–drug conjugates, bispecific T cell engagers and chimeric antigen receptor T cell therapy.
Thrombospondin 4/integrin α2/HSF1 axis promotes proliferation and cancer stem-like traits of gallbladder cancer by enhancing reciprocal crosstalk between cancer-associated fibroblasts and tumor cells
Authors: Shi Yu , Sun Liankang , Zhang Rui , Hu Yuan , Wu Yinying , Dong Xuyuan , Dong Danfeng , Chen Chen , Geng Zhimin , Li Enxiao , Fan Yangwei
Published: January 2021

Background

Cancer-associated fibroblasts (CAFs), the primary component of tumor stroma in tumor microenvironments, are well-known contributors to the malignant progression of gallbladder cancer (GBC). Thrombospondins (THBSs or TSPs) comprise a family of five adhesive glycoproteins that are overexpressed in many types of cancers. However, the expression and potential roles of TSPs in the crosstalk between CAFs and GBC cells has remained unclear.

Methods

Peritumoral fibroblasts (PTFs) and CAFs were extracted from GBC tissues. Thrombospondin expression in GBC was screened by RT-qPCR. MTT viability assay, colony formation, EdU incorporation assay, flow cytometry analysis, Transwell assay, tumorsphere formation and western blot assays were performed to investigate the effects of CAF-derived TSP-4 on GBC cell proliferation, EMT and cancer stem-like features. Subcutaneous tumor formation models were established by co-implanting CAFs and GBC cells or GBC cells overexpressing heat shock factor 1 (HSF1) to evaluate the roles of TSP-4 and HSF1 in vivo. To characterize the mechanism by which TSP-4 is involved in the crosstalk between CAFs and GBC cells, the levels of a variety of signaling molecules were detected by coimmunoprecipitation, immunofluorescence staining, and ELISA assays.

Results

In the present study, we showed that TSP-4, as the stromal glycoprotein, is highly expressed in CAFs from GBC and that CAF-derived TSP-4 induces the proliferation, EMT and cancer stem-like features of GBC cells. Mechanistically, CAF-secreted TSP-4 binds to the transmembrane receptor integrin α2 on GBC cells to induce the phosphorylation of HSF1 at S326 and maintain the malignant phenotypes of GBC cells. Moreover, the TSP-4/integrin α2 axis-induced phosphorylation of HSF1 at S326 is mediated by Akt activation (p-Akt at S473) in GBC cells. In addition, activated HSF1 signaling increased the expression and paracrine signaling of TGF-β1 to induce the transdifferentiation of PTFs into CAFs, leading to their recruitment into GBC and increased TSP-4 expression in CAFs, thereby forming a positive feedback loop to drive the malignant progression of GBC.

Conclusions

Our data indicate that a complex TSP-4/integrin α2/HSF1/TGF-β cascade mediates reciprocal interactions between GBC cells and CAFs, providing a promising therapeutic target for gallbladder cancer patients.
Evaluation of safety, feasibility and efficacy of intra-ovarian transplantation of autologous adipose derived mesenchymal stromal cells in idiopathic premature ovarian failure patients: non-randomized clinical trial, phase I, first in human
Authors: Mashayekhi M. , Mirzadeh E. , Chekini Z. , Ahmadi F. , Eftekhari-Yazdi P. , Vesali S. , Madani T. , Aghdami N.
Published: January 2021

Background

Premature ovarian failure (POF) is characterized by the loss of ovarian activity before the age of 40 years. Stem cell therapy has the capability to create a regenerative microenvironment and is a proposed treatment for POF-related infertility due to the presence of renewal folliculogenesis and germ cells in the adult ovaries. In this study, we assessed the safety, feasibility, efficacy and dose adjustment of autologous adipose-derived stromal cells (ADSCs) and their ability to improve ovarian function in POF patients.

Methods

This study was a non-randomized clinical trial, phase I. Nine women with a definitive diagnosis of POF were divided into three groups (n = 3 per group) that received either 5 × 106, 10 × 106, or 15 × 106 autologous ADSCs suspension transplanted in the one ovary. Participants were followed-up at 24 h after the transplantation, and at 1 and 2 weeks, and 1, 2, 3, 6, and 12 months after the transplantation. The primary objective was to evaluate the safety of ADSCs transplantation. Secondary objectives included the effects of ADSCs transplantation on the resumption of menstruation, hormones level (Follicle-stimulating hormone (FSH) and anti-Müllerian hormone), ovarian function (Antral follicle count and ovary volume by ultrasonography evaluation) as well as dose escalation.

Results

Participants had not shown any early-onset possible side effects and secondary complications during follow-up. The menstruation resumption was observed in four patients which established for several months. In the 15 × 106 group, two POF patients had a return of menstruation second months after the intervention. Two other POF patients in 5 × 106 and 10 × 106 cell groups reported menstruation resumption at 1 month after the intervention. We observed decreased serum FSH levels of less than 25 IU/l in four patients. In two patients in 5 × 106 and 10 × 106 cell groups, serum FSH showed an inconsistent decline during a 1 year follow up after ADSCs transplantation. The ovarian volume, AMH, and AFC were variable during the follow-up and no significant differences between cell groups (p > 0.05).

Conclusions

We showed the intra-ovarian embedding of ADSCs is safe and feasible and is associated with an inconsistent decline in serum FSH. This should be further investigated with a large RCT.

Trial registration

NCT02603744, Registered 13 November 2015 - Retrospectively registered, http://www.Clinicaltrials.gov
Berberine inhibited metastasis through miR-145/MMP16 axis in vitro
Authors: Li Jie , Zhang Songlin , Wu Lei , Pei Meili , Jiang Yu
Published: January 2021

Ovarian cancer is the first leading cause of death in gynecological cancers. The continuous survival and metastasis of cancer cells are the main causes of death and poor prognosis in patients with ovarian cancer. Berberine is an effective component extracted from the rhizomes of coptis chinensis and phellodendron chinensis. In our study, we aim to explore the molecular mechanism underlying the regulation of proliferation, migration and invasion by berberine in ovarian cancer cells. CCK8 assay was used for detection of proliferative capacity of SKOV3 and 3AO cells. Wound healing assay was used to estimate cell migration and transwell assay was used to assess cell invasion. The mRNA expression of miR-145 and MMP16 were examined by quantitative real-time polymerase chain reaction (qRT-PCR). The protein level of MMP16 was detected by western blot analysis. In addition, luciferase reporter assays were used to demonstrate MMP16 was a target of miR-145. The results demonstrated berberine inhibited proliferation, migration and invasion, promoted miR-145 expression, and decreased MMP16 expression in SKOV3 and 3AO cells. MMP16 was a target of miR-145. Moreover, downregulation of MMP16 contributed to the inhibition of proliferation, migration and invasion by berberine. Together, our results revealed that berberine inhibited proliferation, migration and invasion through miR-145/MMP16 in SKOV3 and 3AO cells, highlighting the potentiality of berberine to be used as a therapeutic agent for ovarian cancer.
Predictors of recognition of out of hospital cardiac arrest by emergency medical services call handlers in England: a mixed methods diagnostic accuracy study
Authors: Watkins Caroline L. , Jones Stephanie P. , Hurley Margaret A. , Benedetto Valerio , Price Christopher I. , Sutton Christopher J. , Quinn Tom , Bangee Munirah , Chesworth Brigit , Miller Colette , Doran Dawn , Siriwardena Aloysius Niroshan , Gibson Josephine M. E.
Published: January 2021

Background

The aim of this study was to identify key indicator symptoms and patient factors associated with correct out of hospital cardiac arrest (OHCA) dispatch allocation. In previous studies, from 3% to 62% of OHCAs are not recognised by Emergency Medical Service call handlers, resulting in delayed arrival at scene.

Methods

Retrospective, mixed methods study including all suspected or confirmed OHCA patients transferred to one acute hospital from its associated regional Emergency Medical Service in England from 1/7/2013 to 30/6/2014. Emergency Medical Service and hospital data, including voice recordings of EMS calls, were analysed to identify predictors of recognition of OHCA by call handlers. Logistic regression was used to explore the role of the most frequently occurring (key) indicator symptoms and characteristics in predicting a correct dispatch for patients with OHCA.

Results

A total of 39,136 dispatches were made which resulted in transfer to the hospital within the study period, including 184 patients with OHCA. The use of the term ‘Unconscious’ plus one or more of symptoms ‘Not breathing/Ineffective breathing/Noisy breathing’ occurred in 79.8% of all OHCAs, but only 72.8% of OHCAs were correctly dispatched as such. ‘Not breathing’ was associated with recognition of OHCA by call handlers (Odds Ratio (OR) 3.76). The presence of key indicator symptoms ‘Breathing’ (OR 0.29), ‘Reduced or fluctuating level of consciousness’ (OR 0.24), abnormal pulse/heart rate (OR 0.26) and the characteristic ‘Female patient’ (OR 0.40) were associated with lack of recognition of OHCA by call handlers (p-values < 0.05).

Conclusions

There is a small proportion of calls in which cardiac arrest indicators are described but the call is not dispatched as such. Stricter adherence to dispatch protocols may improve call handlers’ OHCA recognition. The existing dispatch protocol would not be improved by the addition of further terms as this would be at the expense of dispatch specificity.
Dispersal patterns and population genetic structure of Aedes albopictus (Diptera: Culicidae) in three different climatic regions of China
Authors: Gao Jian , Zhang Heng-Duan , Guo Xiao-Xia , Xing Dan , Dong Yan-De , Lan Ce-Jie , Wang Ge , Li Chao-Jie , Li Chun-Xiao , Zhao Tong-Yan
Published: January 2021

Background

Aedes albopictus is an indigenous primary vector for dengue and Zika viruses in China. Compared with its insecticide resistance, biology and vector competence, little is known about its genetic variation, which corresponds to environmental variations. Thus, the present study examines how Ae. albopictus varies among different climatic regions in China and deciphers its potential dispersal patterns.

Methods

The genetic variation and population structure of 17 Ae. albopictus populations collected from three climatic regions of China were investigated with 11 microsatellite loci and the mitochondrial coxI gene.

Results

Of 44 isolated microsatellite markers, 11 pairs were chosen for genotyping analysis and had an average PIC value of 0.713, representing high polymorphism. The number of alleles was high in each population, with the ne value increasing from the temperate region (3.876) to the tropical region (4.144). Twenty-five coxI haplotypes were detected, and the highest diversity was observed in the tropical region. The mean Ho value (ca. 0.557) of all the regions was significantly lower than the mean He value (ca. 0.684), with nearly all populations significantly departing from HWE and displaying significant population expansion (p value < 0.05). Two genetically isolated groups and three haplotype clades were evaluated via STRUCTURE and haplotype phylogenetic analyses, and the tropical populations were significantly isolated from those in the other regions. Most genetic variation in Ae. albopictus was detected within populations and individuals at 31.40 and 63.04%, respectively, via the AMOVA test, and a relatively significant positive correlation was observed among only the temperate populations via IBD analysis (R2 = 0.6614, p = 0.048). Recent dispersions were observed among different Ae. albopictus populations, and four major migration trends with high gene flow (Nm > 0.4) were reconstructed between the tropical region and the other two regions. Environmental factors, especially temperature and rainfall, may be the leading causes of genetic diversity in different climatic regions.

Conclusions

Continuous dispersion contributes to the genetic communication of Ae. albopictus populations across different climatic regions, and environmental factors, especially temperature and rainfall, may be the leading causes of genetic variation.

Graphical Abstract
Chromatin accessibility maps provide evidence of multilineage gene priming in hematopoietic stem cells
Authors: Martin Eric W. , Krietsch Jana , Reggiardo Roman E. , Sousae Rebekah , Kim Daniel H. , Forsberg E. Camilla
Published: January 2021

Hematopoietic stem cells (HSCs) have the capacity to differentiate into vastly different types of mature blood cells. The epigenetic mechanisms regulating the multilineage ability, or multipotency, of HSCs are not well understood. To test the hypothesis that cis-regulatory elements that control fate decisions for all lineages are primed in HSCs, we used ATAC-seq to compare chromatin accessibility of HSCs with five unipotent cell types. We observed the highest similarity in accessibility profiles between megakaryocyte progenitors and HSCs, whereas B cells had the greatest number of regions with de novo gain in accessibility during differentiation. Despite these differences, we identified cis-regulatory elements from all lineages that displayed epigenetic priming in HSCs. These findings provide new insights into the regulation of stem cell multipotency, as well as a resource to identify functional drivers of lineage fate.
Combination therapy of flaxseed and hesperidin enhances the effectiveness of lifestyle modification in cardiovascular risk control in prediabetes: a randomized controlled trial
Authors: Yari Zahra , Naser-Nakhaee Zahra , Karimi‐Shahrbabak Elahe , Cheraghpour Makan , Hedayati Mehdi , Mohaghegh Seyede Marjan , Ommi Shahrzad , Hekmatdoost Azita
Published: January 2021

Background

Regarding the increasing prevalence of cardiometabolic abnormalities, and its association with non-communicable chronic diseases, providing preventive and therapeutic strategies is a priority. A randomized placebo-controlled study was conducted to assess the effects of combination therapy of milled brown flaxseed and hesperidin during lifestyle intervention on controlling cardiovascular risk in prediabetes.

Methods

A total of forty-eight subjects were randomly assigned to receive lifestyle intervention plus combination therapy of brown flaxseed (30 g milled) and hesperidin (two 500 mg capsules) or lifestyle modification alone for 12 weeks. Changes from baseline in anthropometric measures, lipid profile and atherogenic indices, glucose homeostasis parameters, and inflammatory biomarkers was assessed as a primary end point.

Results

Anthropometric data comparison between the two groups showed a significant reduction in weight (p = 0.048). Waist circumference reduction was about twice that of the control group (− 6.75 cm vs − 3.57 cm), but this difference was not statistically significant. Comparison of blood pressure changes throughout the study indicated a greater reduction in blood pressure in the intervention group rather than control group (− 5.66 vs. − 1.56 mmHg, P = 0.049). Improvements of lipid profile and atherogenic indices, glucose homeostasis parameters, and inflammatory biomarkers in flaxseed-hesperidin group was significantly more than the control group after 12 weeks of intervention (p < 0.05).

Conclusion

Our results indicate that co-administration of flaxseed and hesperidin as an adjunct to lifestyle modification program is more effective than lifestyle modification alone in the metabolic abnormalities remission of prediabetic patients.

Trial registration: The trial was registered with ClinicalTrials.gov, number NCT03737422. Registered 11 November 2018. Retrospectively registered, https://clinicaltrials.gov/ct2/results?cond=&term=NCT03737422&cntry=&state=&city=&dist=.
Time-dependent treatment effects of metronomic chemotherapy in unfit AML patients: a secondary analysis of a randomised controlled trial
Authors: Phinyo Phichayut , Patumanond Jayanton , Pongudom Saranya
Published: January 2021

Objectives

To examine the presence of the time-dependent effect of metronomic chemotherapy for the treatment of older patients with acute myeloid leukemia (AML) who were unfit for standard chemotherapy and to reanalyze the data using an appropriate statistical approach in the presence of non-proportional hazards, the restricted mean survival time (RMST).

Results

This was a secondary analysis of a multi-center, open-label, randomized controlled trial, which was conducted in seven tertiary care hospitals across Thailand. A total of 81 unfit AML patients were randomized into two treatment groups, metronomic chemotherapy and palliative treatment. The hazard ratio of metronomic chemotherapy over palliative treatment was time-dependent. At three landmark time points of 90, 180, 365 days, the restricted mean survival time differences were 13.3 (95% CI 1.9–24.7) days, 28.9 (95% CI 3.3–54.4) days, and 40.4 (95% CI − 1.3 to 82.0) days, respectively. With non-proportional hazards modeling and RMST analysis, we were able to conclude that metronomic chemotherapy is a potentially effective alternative treatment for elderly AML patients who were medically unfit for intensive chemotherapy. In the future clinical trials, non-proportional hazards should be carefully inspected and properly handled with appropriate statistical methods.

Trial registration Randomized clinical trial TCTR20150918001; registration date: 15/09/2015. Retrospectively registered
DNA methylation epi-signature is associated with two molecularly and phenotypically distinct clinical subtypes of Phelan-McDermid syndrome
Authors: Schenkel L. C. , Aref-Eshghi E. , Rooney K. , Kerkhof J. , Levy M. A. , McConkey H. , Rogers R. C. , Phelan K. , Sarasua S. M. , Jain L. , Pauly R. , Boccuto L. , DuPont B. , Cappuccio G. , Brunetti-Pierri N. , Schwartz C. E. , Sadikovic B.
Published: January 2021

Background

Phelan-McDermid syndrome is characterized by a range of neurodevelopmental phenotypes with incomplete penetrance and variable expressivity. It is caused by a variable size and breakpoint microdeletions in the distal long arm of chromosome 22, referred to as 22q13.3 deletion syndrome, including the SHANK3 gene. Genetic defects in a growing number of neurodevelopmental genes have been shown to cause genome-wide disruptions in epigenomic profiles referred to as epi-signatures in affected individuals.

Results

In this study we assessed genome-wide DNA methylation profiles in a cohort of 22 individuals with Phelan-McDermid syndrome, including 11 individuals with large (2 to 5.8 Mb) 22q13.3 deletions, 10 with small deletions (< 1 Mb) or intragenic variants in SHANK3 and one mosaic case. We describe a novel genome-wide DNA methylation epi-signature in a subset of individuals with Phelan-McDermid syndrome.

Conclusion

We identified the critical region including the BRD1 gene as responsible for the Phelan-McDermid syndrome epi-signature. Metabolomic profiles of individuals with the DNA methylation epi-signature showed significantly different metabolomic profiles indicating evidence of two molecularly and phenotypically distinct clinical subtypes of Phelan-McDermid syndrome.
Integrated analysis reveals the alterations that LMNA interacts with euchromatin in LMNA mutation-associated dilated cardiomyopathy
Authors: Zhang Xiaolin , Shao Xiuli , Zhang Ruijia , Zhu Rongli , Feng Rui
Published: January 2021

Background

Dilated cardiomyopathy (DCM) is a serious cardiac heterogeneous pathological disease, which may be caused by mutations in the LMNA gene. Lamins interact with not only lamina-associated domains (LADs) but also euchromatin by alone or associates with the lamina-associated polypeptide 2 alpha (LAP2α). Numerous studies have documented that LMNA regulates gene expression by interacting with LADs in heterochromatin. However, the role of LMNA in regulating euchromatin in DCM is poorly understood. Here, we determine the differential binding genes on euchromatin in DCM induced by LMNA mutation by performing an integrated analysis of bioinformatics and explore the possible molecular pathogenesis mechanism.

Results

Six hundred twenty-three and 4484 differential binding genes were identified by ChIP-seq technology. The ChIP-seq analysis results and matched RNA-Seq transcriptome data were integrated to further validate the differential binding genes of ChIP-seq. Five and 60 candidate genes involved in a series of downstream analysis were identified. Finally, 4 key genes (CREBBP, PPP2R2B, BMP4, and BMP7) were harvested, and these genes may regulate LMNA mutation-induced DCM through WNT/β-catenin or TGFβ-BMP pathways.

Conclusions

We identified four key genes that may serve as potential biomarkers and novel therapeutic targets. Our study also illuminates the possible molecular pathogenesis mechanism that the abnormal binding between LMNA or LAP2α-lamin A/C complexes and euchromatin DNA in LMNA mutations, which may cause DCM through the changes of CREBBP, PPP2R2B, BMP4, BMP7 expressions, and the dysregulation of WNT/β-catenin or TGFβ-BMP pathways, providing valuable insights to improve the occurrence and development of DCM.

Graphic abstract
Draft genome sequences of two Streptomyces albidoflavus strains DEF1AK and DEF147AK with plant growth-promoting and biocontrol potential
Authors: Kunova Andrea , Cortesi Paolo , Saracchi Marco , Migdal Guy , Pasquali Matias
Published: January 2021

Purpose

Bacteria belonging to the Streptomyces genus can be exploited in environmentally friendly approaches to food safety. Genome information can help to characterize bioactive strains opening the possibility to decipher their mechanisms of action.

Methods

The biocontrol and plant growth-promoting activity of two Streptomyces spp. strains, DEF1AK and DEF147AK, were assessed in vitro and in planta. The genome sequences were determined using the Illumina NextSeq sequencing system and were assembled using EvoCAT (Evogene Clustering and Assembly Toolbox).

Result

Streptomyces spp. DEF1AK and DEF147AK were able to improve seed germination and early plant development of maize, wheat, and tomato and inhibited the mycelium growth of diverse fungal plant pathogens in vitro. The genome sequence analysis identified both strains as S. albidoflavus (99% sequence identity). Both genomes were of 7.1-Mb length with an average GC content of 73.45%. AntiSMASH and MIBiG analyses revealed strain-specific sets of secondary metabolite gene clusters in the two strains as well as differences in the number and type of duplicated genes.

Conclusion

The combination of the biological activity and genomic data is the basis for in-depth studies aimed at the identification of secondary metabolites involved in plant growth-promoting and biocontrol activity of Streptomyces spp. The comparison of unique genomic features of the two strains will help to explain their diverse biocontrol and plant growth-promoting activities and warrant targeted functional genomics approaches to verify their mechanisms of action.
Identification of ALP+/CD73+ defining markers for enhanced osteogenic potential in human adipose-derived mesenchymal stromal cells by mass cytometry
Authors: Canepa Daisy D. , Casanova Elisa A. , Arvaniti Eirini , Tosevski Vinko , Märsmann Sonja , Eggerschwiler Benjamin , Halvachizadeh Sascha , Buschmann Johanna , Barth André A. , Plock Jan A. , Claassen Manfred , Pape Hans-Christoph , Cinelli Paolo
Published: January 2021

Background

The impressive progress in the field of stem cell research in the past decades has provided the ground for the development of cell-based therapy. Mesenchymal stromal cells obtained from adipose tissue (AD-MSCs) represent a viable source for the development of cell-based therapies. However, the heterogeneity and variable differentiation ability of AD-MSCs depend on the cellular composition and represent a strong limitation for their use in therapeutic applications. In order to fully understand the cellular composition of MSC preparations, it would be essential to analyze AD-MSCs at single-cell level.

Method

Recent advances in single-cell technologies have opened the way for high-dimensional, high-throughput, and high-resolution measurements of biological systems. We made use of the cytometry by time-of-flight (CyTOF) technology to explore the cellular composition of 17 human AD-MSCs, interrogating 31 markers at single-cell level. Subcellular composition of the AD-MSCs was investigated in their naïve state as well as during osteogenic commitment, via unsupervised dimensionality reduction as well as supervised representation learning approaches.

Result

This study showed a high heterogeneity and variability in the subcellular composition of AD-MSCs upon isolation and prolonged culture. Algorithm-guided identification of emerging subpopulations during osteogenic differentiation of AD-MSCs allowed the identification of an ALP+/CD73+ subpopulation of cells with enhanced osteogenic differentiation potential. We could demonstrate in vitro that the sorted ALP+/CD73+ subpopulation exhibited enhanced osteogenic potential and is moreover fundamental for osteogenic lineage commitment. We finally showed that this subpopulation was present in freshly isolated human adipose-derived stromal vascular fractions (SVFs) and that could ultimately be used for cell therapies.

Conclusion

The data obtained reveal, at single-cell level, the heterogeneity of AD-MSCs from several donors and highlight how cellular composition impacts the osteogenic differentiation capacity. The marker combination (ALP/CD73) can not only be used to assess the differentiation potential of undifferentiated AD-MSC preparations, but also could be employed to prospectively enrich AD-MSCs from the stromal vascular fraction of human adipose tissue for therapeutic applications.
Assessing the accuracy of record linkages with Markov chain based Monte Carlo simulation approach
Authors: Haque Shovanur , Mengersen Kerrie , Stern Steven
Published: January 2021

Record linkage is the process of finding matches and linking records from different data sources so that the linked records belong to the same entity. There is an increasing number of applications of record linkage in statistical, health, government and business organisations to link administrative, survey, population census and other files to create a complete set of information for more complete and comprehensive analysis. To make valid inferences using a linked file, it has become increasingly important to have effective and efficient methods for linking data from different sources. Therefore, it becomes necessary to assess the ability of a linking method to achieve high accuracy or to compare between methods with respect to accuracy. This motivates the development of a method for assessing the linking process and facilitating decisions about which linking method is likely to be more accurate for a particular linking task. This paper proposes a Markov Chain based Monte Carlo simulation approach, MaCSim for assessing a linking method and illustrates the utility of the approach using a realistic synthetic dataset received from the Australian Bureau of Statistics to avoid privacy issues associated with using real personal information. A linking method applied by MaCSim is also defined. To assess the defined linking method, correct re-link proportions for each record are calculated using our developed simulation approach. The accuracy is determined for a number of simulated datasets. The analyses indicated promising performance of the proposed method MaCSim of the assessment of accuracy of the linkages. The computational aspects of the methodology are also investigated to assess its feasibility for practical use.
Penetration of the electric fields of the geomagnetic sudden commencement over the globe as observed with the HF Doppler sounders and magnetometers
Authors: Kikuchi Takashi , Chum Jaroslav , Tomizawa Ichiro , Hashimoto Kumiko K. , Hosokawa Keisuke , Ebihara Yusuke , Hozumi Kornyanat , Supnithi Pornchai
Published: January 2021

Using the HF Doppler sounders at middle and low latitudes (Prague, Czech Republic; Tucuman, Argentina; Zhongli, Republic of China, and Sugadaira, Japan), we observed the electric fields of the geomagnetic sudden commencement (SC) propagating near-instantaneously (within 10 s) over the globe. We found that the electric fields of the preliminary impulse (PI) and main impulse (MI) of the SC are in opposite direction to each other and that the PI and MI electric fields are directed from the dusk to dawn and dawn to dusk, respectively, manifesting the nature of the curl-free potential electric field. We further found that the onset and peak of the PI electric field are simultaneous on the day and nightsides (0545, 1250, 1345 MLT) within the resolution of 10 s. With the magnetometer data, we confirmed the near-instantaneous development of the ionospheric currents from high latitudes to the equator and estimated the location of the field-aligned currents that supply the ionospheric currents. The global simultaneity of the electric and magnetic fields does not require the contribution of the magnetohydrodynamic waves in the magnetosphere nor in the F-region ionosphere. The global simultaneity and day–night asymmetry of the electric fields are explained with the ionospheric electric potentials transmitted at the speed of light by the TM0 mode waves in the Earth-ionosphere waveguide.