bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic literature review of instruments that measure the healthfulness of food and beverages sold in informal food outlets
Authors: Medina Catalina , Piña-Pozas Maricela , Aburto Tania C. , Chavira Julissa , López Uzzi , Moreno Mildred , Olvera Armando G. , Gonzalez Citlali , Huang Terry T-K , Barquera Simón
Published: July 2022

Background

Informal food outlets, defined as vendors who rarely have access to water and toilets, much less shelter and electricity, are a common component of the food environment, particularly in many non-Western countries. The purpose of this study was to review available instruments that measure the quality and particularly the healthfulness of food and beverages sold within informal food outlets.

Methods

PubMed, LILACS, Web of Science, and Scopus databases were used. Articles were included if they reported instruments that measured the availability or type of healthy and unhealthy foods and beverages by informal food outlets, were written in English or Spanish, and published between January 1, 2010, and July 31, 2020. Two trained researchers reviewed the title, abstract and full text of selected articles; discrepancies were solved by two independent researchers. In addition, the list of references for selected articles was reviewed for any additional articles of relevance. The quality of published articles and documents was evaluated using JBI Critical appraisal checklist for analytical cross-sectional studies.

Results

We identified 1078 articles of which 14 were included after applying the selection criteria. Three additional articles were considered after reviewing the references from the selected articles. From the final 17 articles, 13 measurement tools were identified. Most of the instruments were used in low- and middle-income countries (LMIC). Products were classified as healthy/unhealthy or produce/non-produce or processed/unprocessed based on availability and type. Six studies reported psychometric tests, whereas one was tested within the informal food sector.

Conclusions

Few instruments can measure the healthfulness of food and beverages sold in informal food outlets, of which the most valid and reliable have been used to measure formal food outlets as well. Therefore, it is necessary to develop an instrument that manages to measure, specifically, the elements available within an informal one. These actions are extremely important to better understand the food environment that is a central contributor to poor diets that are increasingly associated with the obesity and Non-communicable disease (NCD) pandemic.
A reduction of Syndecan-4 in macrophages promotes atherosclerosis by aggravating the proinflammatory capacity of macrophages
Authors: Hu Jiaxin , Zhang Ying , Hu Liaoping , Chen Haiting , Wu Han , Chen Jianzhou , Xie Jun , Xu Biao , Wei Zhonghai
Published: July 2022

Background

Cardiovascular diseases (CVDs) are a significant cause of mortality worldwide and are characterized by severe atherosclerosis (AS) in patients. However, the molecular mechanism of AS formation remains elusive. In the present study, we investigated the role of syndecan-4 (SDC4), a member of the syndecan family, in atherogenesis.

Methods and Results

The expression of SDC4 decreased in mouse severe AS models. Moreover, knockout of SDC4 accelerated high-cholesterol diets (HCD)-induced AS in ApoE−/− mice. Mechanistically, the decrease of SDC4 increased macrophage proinflammatory capacity may be through the PKCα-ABCA1/ABCG1 signaling pathway.

Conclusion

These findings provide evidence that SDC4 reduction links macrophages and inflammation to AS and that SDC4 in macrophages provides a therapeutic target for preventing AS formation.
The abnormal expression of circ-ARAP2 promotes ESCC progression through regulating miR-761/FOXM1 axis-mediated stemness and the endothelial–mesenchymal transition
Authors: Xu Pei , Wang Lei , Liu Qingtao , Gao Pengkai , Hu Fengqing , Xie Xiao , Jiang Lianyong , Bi Rui , Ding Fangbao , Yang Qi , Xiao Haibo
Published: July 2022

Circular RNAs (circRNAs) belong to a novel class of noncoding RNA that gained more attention in human cancer pathogenesis. The role of circRNA in esophageal squamous cell carcinoma (ESCC) is largely unclear. Present investigation was to characterize new circRNAs regulating ESCC progression and explore the regulatory mechanisms in ESCC. In this study, circRNAs differentially expressed in ESCC and adjacent normal tissues were characterized via high-throughput sequencing. Then the differentially expressed circRNA between ESCC and adjacent normal tissues were investigated using Rt-qPCR. The role of circ-ARAP2 expression on tumor progression were detected in both in vivo and in vitro. Luciferase reporter assays were used to identify the relationships among circ-ARAP2, microRNA (miR)-761 and the cell cycle regulator Forkhead Box M1 (FOXM1). The result of the expression profile analyses regarding human circRNAs in ESCC demonstrated that circ-ARAP2 was up-regulated significantly in both ESCC tissues and cell lines. Downregulation circ-ARAP2 suppressed ESCC proliferation, tumor growth and metastasis in both in vivo and in vitro. The data also suggested that miR-761 and FOXM1 were circ-ARAP2 downstream targets which were confirmed through luciferase reporter analysis. Overexpression of FOXM1 or inhibiting miR-761 restored ESCC cell proliferation and invasion ability after silencing circ-ARAP2. The study also found that circ-ARAP2 influenced the endothelial–mesenchymal transition (EMT) and cancer stem cells differently by regulating miR-761/FOXM1. In one word, the results demonstrated that abnormal circ-ARAP2 expression promoted ESCC progression by regulating miR-761/FOXM1 axis-mediated stemness and EMT.
Kaposi sarcoma (KS) with primary effusion lymphoma in HIV infected MSM (men having sex with men) co-infected with pulmonary tuberculosis and syphilis: a case report from India
Authors: Bangar Sampada , Vashisht Rohit , Sonar Pratiksha , Ghule Kunal , Rawat Leena , Mane Arati , Kadam Abhijit , Chandhiok Nomita , Sahay Seema
Published: July 2022

We describe a case of a 30-year-old MSM recently diagnosed with HIV, immunocompromised with a purplish or brown rash all over the body for 3 to 4 months. The histopathology of the cutaneous lesions and pleural effusion aspirate confirmed the diagnosis of Kaposi’s sarcoma (KS) and primary effusion lymphoma (PEL). While KS is one of the AIDS-defining illnesses seen in immunocompromised patients having low CD4 count, PEL is a rare and distinct subset of AIDS-related lymphoma. Despite the widespread availability of HIV testing, HIV diagnosis gets delayed due to stigma among MSM. This case report emphasizes the importance of early suspicion for symptoms of HIV-associated opportunistic infections in high-risk populations like MSM. The report reiterates the need for an ambient stigma-free environment for improving HIV screening in this high-risk population.
Puberty health intervention to improve menstrual health and school attendance among adolescent girls in The Gambia: study methodology of a cluster-randomised controlled trial in rural Gambia (MEGAMBO TRIAL)
Authors: Shah Vishna , Phillips-Howard Penelope , Hennegan Julie , Cavill Sue , Sonko Bakary , Sinjanka Edrisa , Camara Trawally Nyima , Kanteh Abdou , Mendy Francois , Bah Amadou B. , Saar Momodou , Ross Ian , Schmidt Wolf , Torondel Belen
Published: July 2022

Background

Menstrual health (MH) is a recognised global public health challenge. Poor MH may lead to absence from school and work, and adverse health outcomes. However, reviews suggest a lack of rigorous evidence for the effectiveness of MH interventions on health and education outcomes. The objective of this paper is to describe the methods used in a cluster-randomised controlled trial to estimate the effect of a multi-component intervention to improve MH and school attendance in The Gambia.

Methods

The design ensured half the schools (25) were randomised to receive the intervention which comprised of the following components: (i) Peer education camps and menstrual hygiene laboratories in schools, (ii) Mother’s outreach sessions, (iii) Community meetings, and (iv) minor improvements of school Water Sanitation and Hygiene (WASH) facilities and maintenance. The intervention was run over a three-month period, and the evaluation was conducted at least three months after the last intervention activity was completed in the school or community. The other 25 schools acted as controls. Of these 25 control schools one Arabic school dropped out due to COVID-19. The primary outcome was the prevalence of girls missing at least one day of school during their last period. Secondary outcomes included: Urinary Tract Infection (UTI) symptoms, biochemical markers of UTI in urine, Reproductive Tract Infection symptoms, self-reported menstruation related wellbeing, social support and knowledge, perceptions and practices towards menstruation and MH in target school girls. In addition, a process evaluation using observations, routine monitoring data, survey data and interviews was undertaken to assess dose and reach (quantitative data) and assess acceptability, fidelity, context and possible mechanisms of impact (qualitative data). Cost and cost-effectiveness of the intervention package will also be assessed.

Conclusion

Results will add to scarce resources available on effectiveness of MH interventions on school attendance. A positive result may encourage policy makers to increase their commitment to improve operation and maintenance of school WASH facilities and include more information on menstruation into the curriculum and help in the reporting and management of infections related to adolescent menstruation.

Trial Registration PACTR, PACTR201809769868245, Registered 14th August 2018, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=3539
Total hip arthroplasty has higher complication rates in stiff spine patients: a systematic review and network meta-analysis
Authors: Tsai Sung Huang Laurent , Lau Ngi Chiong , Chen Wei Cheng , Chien Ruei-Shyuan , Tischler Eric H. , Fu Tsai-Sheng , Chen Dave Wei-Chih
Published: July 2022

Background

Ankylosing spondylitis (AS) and spinal fusion (SF) classified as stiff spines have been associated with the increased rate of complications following total hip arthroplasty (THA). However, the differences between the two cohorts have inconsistent evidence.

Methods

We searched for studies comparing complications among stiff spine patients, including SF and AS, who underwent THA in PubMed/MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and Scopus until March 2021. Studies detailing rates of mechanical complications, aseptic loosening, dislocation, infection, and revisions were included. We performed network meta-analyses using frequentist random-effects models to compare differences between cohorts. We used P-score to rank the better exposure with the lowest complications.

Results

Fourteen studies were included in the final analysis. A total of 740,042 patients were included in the systematic review and network meta-analysis. Mechanical complications were highest among SF patients (OR 2.33, 95% CI 1.86, 2.92,p < 0.05), followed by AS patients (OR 1.18, 95% CI 0.87, 1.61,p = 0.82) compared to controls. Long Spinal Fusions had the highest aseptic loosening (OR 2.33, 95% CI 1.83, 2.95,p < 0.05), dislocations (OR 3.25, 95% CI 2.58, 4.10,p < 0.05), infections (OR 2.14, 95% CI 1.73, 2.65,p < 0.05), and revisions (OR 5.25, 95% CI 2.23, 12.32,p < 0.05) compared to AS and controls. Our results suggested that SF with longer constructs may be associated with higher complications in THA patients.

Conclusions

THAs following SFs have higher mechanical complications, aseptic loosening, dislocations, and infections, especially with longer constructs. AS patients may have fewer complications compared to this cohort.
Low cervical vertebral CT value increased early subsidence of titanium mesh cage after anterior cervical corpectomy and fusion
Authors: Wang Zhiqiang , Mei Jun , Feng Xiaoning , Deng Chen , Tian Xuefeng , Lv Junqiao , Sun Lin
Published: July 2022

Study design

This study was a retrospective review.

Objective

To study the predictive effect of Hounsfield units (HU) value in the cervical vertebral body derived from computed tomography (CT) on the early titanium mesh cage (TMC) subsidence after anterior cervical corpectomy and fusion (ACCF).

Methods

This retrospective study was conducted on patients who underwent ACCF at one institution between January 2014 and December 2018. We collected date included age, gender, body mass index (BMI), disease type, surgical segment, whether merge ACDF, HU value of the vertebral body and endplate, vertebral body height loss, cervical lordosis angle, and cervical sagittal alignment. VAS, JOA, and NDI were used to assess clinical efficacy. Univariate analysis was performed to screen the influencing factors of TMC subsidence, and then logistic regression was used to find out the independent risk factors. The ROC curve and area under curve (AUC) were used to analyze the HU value to predict the TMC subsidence.

Results

A total of 85 patients who accepted ACCF were included in this study, and early titanium mesh cage subsidence was demonstrated in 29 patients. The subsidence rate was 34.1%. The JOA, VAS, and NDI scores significantly improved in both groups after the operation. Between the subsidence and non-subsidence groups, there were significant differences in age, intervertebral distraction height, and HU value in both upper and lower vertebral body and endplate. The logistic regression analysis proved that the HU value of the lower vertebral body was an independent risk of TMC subsidence, the AUC was 0.866, and the most appropriate threshold of the HU value was 275 (sensitivity: 87.5%, specificity: 79.3%).

Conclusion

Preoperative cervical CT value is an independent correlative factor for early TMC subsidence after ACCF, and patients with a low CT value of the inferior vertebral body of the operative segment have a higher risk of TMC subsidence in the early postoperative period.

Trial registration: This study is undergoing retrospective registration.
Earlier or heavier spinal loading is more likely to lead to recurrent lumbar disc herniation after percutaneous endoscopic lumbar discectomy
Authors: Wang Fei , Chen Kai , Lin Qiushui , Ma Yuegang , Huang Hao , Wang Chuanfeng , Zhou Ping
Published: July 2022

Purpose

To evaluate the clinical features of and risk factors for recurrent lumbar disc herniation (rLDH) after percutaneous endoscopic lumbar discectomy (PELD) in our clinical practice.

Methods

A total of 942 consecutive patients who underwent single-level PELD from January 2013 to August 2019 were included. Patients were divided into the recurrence group and the nonrecurrence group. Patient characteristics, radiographic parameters and surgical variables were compared between the two groups. Univariate analysis and multiple logistic regression analysis were adopted to determine the risk factors for recurrence after PELD.

Results

The prevalence of rLDH was 6.05%. Age, sex, tobacco use, duration of low back pain, body mass index (BMI), occupational lifting, herniated disc type, facet joint degeneration, operation time and time to ambulation were significantly different between the two groups. Univariate analysis showed that age (P < 0.001), sex (P = 0.019), BMI (P = 0.001), current smoking (P < 0.001), occupational lifting (P < 0.001), facet joint degeneration (P = 0.001), operation time (P = 0.002), and time to ambulation (P < 0.001) could be significantly associated with the incidence of rLDH after PELD. Multivariate analysis suggested that an older age (P < 0.001), the male sex (P = 0.017), a high BMI (P < 0.001), heavy work (P = 0.003), grade II facet joint degeneration (P < 0.001) and early ambulation (P < 0.001) were significantly related to rLDH after PELD.

Conclusions

An older age, the male sex, a higher BMI, heavy work, grade II facet joint degeneration, and early ambulation are independent significant risk factors for rLDH after PELD. Great importance should be attached to these risk factors to prevent rLDH. We suggest that patients control their weight, avoid heavy work, ambulate at an appropriate time, and perform strengthening rehabilitation exercises to reduce the incidence of rLDH.
Modulation of B cell activation by extracellular vesicles and potential alteration of this pathway in patients with rheumatoid arthritis
Authors: Rincón-Arévalo Héctor , Burbano Catalina , Atehortúa Laura , Rojas Mauricio , Vanegas-García Adriana , Vásquez Gloria , Castaño Diana
Published: July 2022

Background

Extracellular vesicles are involved in the intercellular communication of the immune system. In rheumatoid arthritis (RA), these structures are considered a source of autoantigens that drive proinflammatory responses of innate immune cells. A high concentration of circulating medium/large size extracellular vesicles (m/lEVs) and m/lEVs forming immune complexes (m/lEV-ICs) have been associated with disease activity and systemic inflammation in patients with RA. B cells are central components of RA immunopathology because of their involvement in the production of autoantibodies, antigen presentation, and cytokine production. However, the effect of m/lEVs on B cell function in the context of RA and other autoimmune diseases remains unknown.

Methods

We evaluated the effect of m/lEVs obtained from healthy donors (HD) and patients with RA on B cell responses in vitro. In addition, we evaluated the effect of pre-exposition of monocyte-derived macrophages (MDM) to m/lEVs on activation of autologous B cells from HD and patients.

Results

The presence of m/lEVs reduced the frequency of CD69+ and CD86+ B cells from HD activated by an agonist of antigen receptor. This regulation of the B cell activation markers by m/lEVs was partially dependent on phosphatidylserine binging. These m/lEVs also reduced the proliferation, calcium mobilization, and global phosphorylation of tyrosine. Similar responses were observed in B cells from patients with RA. However, the presence of m/lEVs promoted high antibody levels in B cells cultured with T cell-dependent stimuli by 7 days. In addition, despite the direct inhibitory effect of m/lEVs on early B cell responses, when B cells were cocultured with autologous MDM previously exposed to m/lEVs or m/lEV-ICs, an increased frequency of CD69+ B cells from patients with RA was observed, albeit not with cells from HD.

Conclusions

These data together suggest that m/lEVs have a direct modulatory effect in early responses of B cells through B cell receptor that can potentially fail in patients with RA because of the impact of these vesicles over cells of the innate immune system. This phenomenon can potentially contribute to the loss of tolerance and disease activity in patients with RA.
CPAP pressure and flow data at 2 positive pressure levels and multiple controlled breathing rates from a trial of 30 adults
Authors: Guy Ella F. S. , Knopp Jennifer L. , Gilbertson Oliver , Blue Simon , Holder-Pearson Lui , Chase J. Geoffrey
Published: July 2022

Objectives

A unique dataset of airway flow/pressure from healthy subjects on Continuous Positive Airway Pressure (CPAP) ventilation was collected. This data can be used to develop or validate models of pulmonary mechanics, and/or to develop methods to identify patient-specific parameters which cannot be measured non-invasively, during CPAP therapy. These models and values, particularly if available breath-to-breath in real-time, could assist clinicians in the prescription or optimisation of CPAP therapy, including optimising PEEP settings.

Data description

Data was obtained from 30 subjects for model-based identification of patient-specific lung mechanics using a specially designed venturi sensor system comprising an array of differential and gauge pressure sensors. Relevant medical information was collected using a questionnaire, including: sex; age; weight; height; smoking history; and history of asthma. Subjects were tasked with breathing at five different rates (including passive), matched to an online pacing sound and video, at two different levels of PEEP (4 and 7 cmH2O) for between 50 and 180 s. Each data set comprises ~ 17 breaths of data, including rest periods between breathing rates and CPAP levels.
Dataset of fitness trackers and smartwatches to measuring physical activity in research
Authors: Henriksen André , Woldaregay Ashenafi Zebene , Muzny Miroslav , Hartvigsen Gunnar , Hopstock Laila Arnesdatter , Grimsgaard Sameline
Published: July 2022

Objectives

Accelerometer-based wrist-worn fitness trackers and smartwatches (wearables) appeared on the consumer market in 2011. Many wearable devices have been released since. The objective of this data paper is to describe a dataset of 423 wearables released before July 2017.

Data description

We identified wearables and extracted information from six online and offline databases. We also visited websites for all identified companies/brands to identify additional wearables, as well as obtained additional information for each identified device. Twelve attributes were collected: wearable name, company/brand name, release year, country of origin, whether the wearable was crowd funded, form factor (fitness tracker or smartwatch), and sensors supported. Support for the following sensors were mapped: accelerometer, magnetometer, gyroscope, altimeter or barometer, global-positioning-system, and optical pulse sensor (i.e., photoplethysmograph). The search was conducted between May 15th and July 1st, 2017. The included data gives an overview of most in-scope wearables released before July 2017 and allows researchers to conduct additional analysis not performed in the related article. Further insights can be achieved by complementing this list with wearable models released after July 2017.
Salivary neutrophil sampling feasibility in general population for gene expression analysis
Authors: Rachlin Kenneth , Wahbeh Helané , Delorme Arnaud , Radin Dean , Carpenter Loren , Ahmadzai Salma , Valletta Serena , Yount Garret
Published: July 2022

Objective

Human gene expression studies typically rely on peripheral blood samples as a cellular source, however there are numerous situations in which venipuncture is contraindicated. To this end, an oral rinse-based method for collecting salivary neutrophils as a cellular source for gene expression analyses was previously developed and shown in a pilot study with five male participants to yield mRNA expression results comparable to those obtained from peripheral blood samples. The objective of the current study was to characterize the generalizability of the oral rinse-based method by analyzing unpublished RNA quality data obtained through a parent study that collected salivary neutrophil samples using the method from a larger sample size and including both men and women.

Results

The 260/280 nm absorbance ratios of the RNA obtained from 48 participants using the oral rinse-based method were within the expected range (average = 1.88 ± 0.16) for the majority of the samples, and no significant differences in RNA quality were found between participants’ health, age group, or gender. Together with published data confirming the integrity of RNA obtained using the same method, these results support the feasibility of using this noninvasive method for obtaining samples for human gene expression analyses.
Isolation of cfDNA from spent culture media and its association with implantation rate and maternal immunomodulation
Authors: Alizadegan Amin , Akbarzadeh Maryam , Soltani-Zangbar Mohammad Sadegh , Sambrani Roshanak , Hamdi Kobra , Ghasemzadeh Alieh , Hakimi Parvin , Vahabzadeh Behnam , Dianat-Moghadam Hassan , Mehdizadeh Amir , Mohammadinejad Sina , Dolati Sanam , Baharaghdam Sina , Bayat Gholamreza , Nouri Mohammad , Yousefi Mehdi
Published: July 2022

Objectives

This investigation aims to evaluate the association between the concentration of cell-free DNA (cfDNA) in the spent culture medium (SCM) with implantation rate and the maternal immune system in the invitro fertilization (IVF). In this study, 30 embryos were cultured and scored according to Gardner's criteria. SCM was gathered on day five from every embryo to analyze the quantity of cfDNA. The real-time PCR technique evaluated the expression level of transcription factors, including Foxp3, RORγt, GATA3, and T-bet. The percentage of Th1, Th2, Th17, Treg, NK cells, and NK cells cytotoxicity was evaluated by flow cytometry.

Results

The concentration of cfDNA in the β-HCG (-), β-HCG ( +), and ongoing pregnancy groups were 20.70 ± 9.224 ng/µL, 27.97 ± 7.990 ng/µL, and 28.91 ± 8.566 ng/µL, respectively. The ratio of Th1/Th2 and Th17/Treg reduced significantly in pregnant women, as well as the level of NK cells and NK cytotoxicity cells fell dramatically in the ongoing pregnancy group. The expression level of RORγt and T-bet declined while the expression level of Foxp3 and GATA3 increased considerably in pregnant mothers. Our investigation revealed that the concentration level of cfDNA in SCM could not be associated with implantation rate, prediction of ongoing pregnancy, and maternal immune system.
Psychostimulant-induced aberrant DNA methylation in an in vitro model of human peripheral blood mononuclear cells
Authors: Anier Kaili , Somelar Kelli , Jaako Külli , Alttoa Margret , Sikk Kerli , Kokassaar Raul , Kisand Kai , Kalda Anti
Published: July 2022

Background

Several reports have provided crucial evidence in animal models that epigenetic modifications, such as DNA methylation, may be involved in psychostimulant-induced stable changes at the cellular level in the brain. Epigenetic editors DNA methyltransferases (DNMTs) and ten-eleven translocation enzymes (TETs) coordinate expression of gene networks, which then manifest as long-term behavioural changes. However, the extent to which aberrant DNA methylation is involved in the mechanisms of substance use disorder in humans is unclear. We previously demonstrated that cocaine modifies gene transcription, via DNA methylation, throughout the brain and in peripheral blood cells in mice.

Results

We treated human peripheral blood mononuclear cells (PBMCs) from healthy male donors (n = 18) in vitro with psychostimulants (amphetamine, cocaine). After treatment, we assessed mRNA levels and enzymatic activities of TETs and DNMTs, conducted genome-wide DNA methylation assays and next-generation sequencing. We found that repeated exposure to psychostimulants decreased mRNA levels and enzymatic activity of TETs and 5-hydroxymethylation levels in PBMCs. These data were in line with observed hyper- and hypomethylation and mRNA expression of marker genes (IL-10, ATP2B4). Additionally, we evaluated whether the effects of cocaine on epigenetic editors (DNMTs and TETs) and cytokines interleukin-6 (IL-6) and IL-10 could be reversed by the DNMT inhibitor decitabine.

Indeed, decitabine eliminated cocaine’s effect on the activity of TETs and DNMTs and decreased cytokine levels, whereas cocaine increased IL-6 and decreased IL-10.

Conclusions

Our data suggest that repeated psychostimulant exposure decreases TETs’ enzymatic activity in PBMCs. Co-treatment with decitabine reversed TETs’ levels and modulated immune response after repeated cocaine exposure. Further investigation is needed to clarify if TET could represent a putative biomarker of psychostimulant use and if DNMT inhibition could have therapeutic potential.
One-year follow-up study after patients with severe COVID-19 received human umbilical cord mesenchymal stem cells treatment
Authors: Shi Lei , Zheng You , Cheng Zhi , Ji Ningfei , Niu Changming , Wang Yan , Huang Tingrong , Li Ruyou , Huang Mao , Chen Xiaolin , Shu Lei , Wu Mingjing , Deng Kaili , Wei Jing , Wang Xueli , Cao Yang , Yan Jiaxin , Feng Ganzhu
Published: July 2022

Background

The novel coronavirus is still mutating, and the pandemic continues. Meanwhile, many COVID-19 survivors have residual postinfection clinical manifestations. Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been shown to be effective in the early stages of COVID-19.

Objectives

The aim of this study was to investigate long-term safety and efficacy of treatment in patients with severe COVID-19 patients who had received hUC-MSCs therapy.

Methods

Twenty-five discharged patients who had severe COVID-19 (including the standard treatment group and the standard treatment plus hUC-MSCs group) were enrolled in a 1-year follow-up. The assessment considered adverse effects (including effects on liver and kidney function, coagulation, ECG, tumor marker, and so on), pulmonary function, St George’s Respiratory Questionnaire (SGRQ), postinfection sequelae and serum concentration of Krebs von den Lungen-6 (KL-6), malondialdehyde (MDA), H2S, carnitine, and N-6 long-chain polyunsaturated fatty acids (N-6 LC-PUFAs).

Measurements and main results

Pulmonary ventilation function had significantly improved at the 1-year follow-up in both the hUC-MSCs group and the control group compared with the 3-month follow-up (P < 0.01). Fatigue (60% [15/25]) remained the most common symptom at the 1-year follow-up. The rate of fatigue relief was significantly reduced in the hUC-MSCs group (25% [2/8]) compared to the control group (76.5% [13/17]) (P = 0.028). The level of KL-6 was significantly lower in the hUC-MSCs group (2585.5 ± 186.5 U/ml) than in the control group (3120.7 ± 158.3 U/ml) (P < 0.001). Compared with the control group, the hUC-MSCs group had a lower level of MDA (9.27 ± 0.54 vs. 9.91 ± 0.72 nmol/ml, P = 0.036). No obvious adverse effects were observed in the hUC-MSCs treatment group at 1 year after discharge.

Conclusions

Intravenous transplantation of hUC-MSCs was a safe approach in the long term in the treatment of patients with severe COVID-19. In addition, hUC-MSCs had a positive effect on postinfection sequelae in COVID-19 survivors.

Trial registration

Chinese Clinical Trial Registration; ChiCTR2000031494; Registered 02 April 2020—Retrospectively registered, http://www.medresman.org
A defined road to tracheal reconstruction: laser structuring and cell support for rapid clinic translation
Authors: Fayzullin Alexey , Vladimirov Georgiy , Kuryanova Anastasia , Gafarova Elvira , Tkachev Sergei , Kosheleva Nastasia , Istranova Elena , Istranov Leonid , Efremov Yuri , Novikov Ivan , Bikmulina Polina , Puzakov Kirill , Petrov Pavel , Vyazankin Ivan , Nedorubov Andrey , Khlebnikova Tatyana , Kapustina Valentina , Trubnikov Pavel , Minaev Nikita , Kurkov Aleksandr , Royuk Valery , Mikhailov Vasily , Parshin Dmitriy , Solovieva Anna , Lipina Marina , Lychagin Alexey , Timashev Peter , Svistunov Andrey , Fomin Victor , Shpichka Anastasia
Published: July 2022

One of the severe complications occurring because of the patient’s intubation is tracheal stenosis. Its incidence has significantly risen because of the COVID-19 pandemic and tends only to increase. Here, we propose an alternative to the donor trachea and synthetic prostheses—the tracheal equivalent. To form it, we applied the donor trachea samples, which were decellularized, cross-linked, and treated with laser to make wells on their surface, and inoculated them with human gingiva-derived mesenchymal stromal cells. The fabricated construct was assessed in vivo using nude (immunodeficient), immunosuppressed, and normal mice and rabbits. In comparison with the matrix ones, the tracheal equivalent samples demonstrated the thinning of the capsule, the significant vessel ingrowth into surrounding tissues, and the increase in the submucosa resorption. The developed construct was shown to be highly biocompatible and efficient in trachea restoration. These results can facilitate its clinical translation and be a base to design clinical trials.

Graphical Abstract
Notch-activated mesenchymal stromal/stem cells enhance the protective effect against acetaminophen-induced acute liver injury by activating AMPK/SIRT1 pathway
Authors: Yu Mengxue , Zhou Min , Li Jiahui , Zong Ruobin , Yan Yufei , Kong Liangyi , Zhu Qiang , Li Changyong
Published: July 2022

Background

Notch signaling plays important roles in regulating innate immunity. However, little is known about the role of Notch in mesenchymal stromal/stem cell (MSC)-mediated immunomodulation during liver inflammatory response.

Methods

Notch activation in human umbilical cord-derived MSCs was performed by a tissue culture plate coated with Notch ligand, recombinant human Jagged1 (JAG1). Mice were given intravenous injection of Notch-activated MSCs after acetaminophen (APAP)-induced acute liver injury. Liver tissues were collected and analyzed by histology and immunohistochemistry.

Results

MSC administration reduced APAP-induced hepatocellular damage, as manifested by decreased serum ALT levels, intrahepatic macrophage/neutrophil infiltration, hepatocellular apoptosis and proinflammatory mediators. The anti-inflammatory activity and therapeutic effects of MSCs were greatly enhanced by Notch activation via its ligand JAG1. However, Notch2 disruption in MSCs markedly diminished the protective effect of MSCs against APAP-induced acute liver injury, even in the presence of JAG1 pretreatment. Strikingly, Notch-activated MSCs promoted AMP-activated protein kinase (AMPKα) phosphorylation, increased the sirtuins 1 (SIRT1) deacetylase expression, but downregulated spliced X-box-binding protein 1 (XBP1s) expression and consequently reduced NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation. Furthermore, SIRT1 disruption or XBP1s overexpression in macrophages exacerbated APAP-triggered liver inflammation and augmented NLRP3/caspase-1 activity in MSC-administrated mice. Mechanistic studies further demonstrated that JAG1-pretreated MSCs activated Notch2/COX2/PGE2 signaling, which in turn induced macrophage AMPK/SIRT1 activation, leading to XBP1s deacetylation and inhibition of NLRP3 activity.

Conclusions

Activation of Notch2 is required for the ability of MSCs to reduce the severity of APAP-induced liver damage in mice. Our findings underscore a novel molecular insights into MSCs-mediated immunomodulation by activating Notch2/COX2/AMPK/SIRT1 pathway and thus provide a new strategy for the treatment of liver inflammatory diseases.
Cell-free fat extract improves ovarian function and fertility in mice with premature ovarian insufficiency
Authors: Liu Mengyu , Zhang Dan , Zhou Xiaowei , Duan Jingru , Hu Yanqin , Zhang Wenjie , Liu Qiang , Xu Bufang , Zhang Aijun
Published: July 2022

Background

Premature ovarian insufficiency (POI) is a refractory disease that seriously affects the reproductive health of women and is increasing in incidence and prevalence globally. There is enormous demand to improve fertility in women with POI, while there is still lack of effective therapeutic methods in clinic. Cell-free fat extract (CEFFE) has been reported to contain thousands of active proteins which possess the ability to promote tissue repair in other diseases. In our study, we aimed to observe the efficacy and biosecurity of CEFFE on the repair of ovarian function and fertility of mice with POI and further explore the underlying mechanism.

Methods

In vivo, POI mice model, established by cyclophosphamide (CTX, 120 mg/kg) and busulfan (BUS, 12 mg/kg), was treated with CEFFE via the tail vein every two days for 2 weeks. Then, the weight of ovaries, estrous cycle and follicle count by H&E staining were measured. The content of AMH, E2and FSH in serum was measured by Enzyme-linked immunosorbent assay. Fertility was evaluated by the number of oocytes retrieved, the development of embryos in vitro and the litter size. Biosecurity of parent mice and their pups were examined by body mass and visceral index. The proliferation and apoptosis of cells in ovaries were examined by immunohistochemistry and transmission electron microscopy. Furthermore, the mRNA-Seq of mouse ovarian granulosa cells was performed to explore underlying mechanism of CEFFE. In vitro, KGN cell line and human primary ovarian granulosa cells (hGCs) were treated with 250 μM CTX for 48 h with/without CEFFE. The proliferative ability of cells was detected by cell counting kit-8 assay (CCK-8) and EDU test; the apoptosis of cells was detected by TUNEL and flow cytometry.

Results

CEFFE recovered the content of AMH, E2and FSH in serum, increased the number of follicles and the retrieved oocytes of POI mice (P < 0.05). CEFFE contributed to the development of embryos and improved the litter size of POI mice (P < 0.05). There was no side effect of CEFFE on parent mice and their pups. CEFFE contributed to the proliferation and inhibited the apoptosis of mouse granulosa cells in ovary, as well as in human ovarian granulosa cells (including KGN cell line and hGCs) (P < 0.05).

Conclusions

The treatment of CEFFE inhibited the apoptosis of granulosa cells and contributed to the recovery of ovarian function, as well as the fertility of mice with POI.
Implantation of dedifferentiated fat cells ameliorated antineutrophil cytoplasmic antibody glomerulonephritis by immunosuppression and increases in tumor necrosis factor-stimulated gene-6
Authors: Utsunomiya Kei , Maruyama Takashi , Shimizu Satoshi , Matsumoto Taro , Endo Morito , Kobayashi Hiroki , Kano Koichiro , Abe Masanori , Fukuda Noboru
Published: July 2022

Introduction

The implantation of dedifferentiated fat (DFAT) cells has been shown to exert immunosuppressive effects. To develop DFAT cell therapy for antineutrophil cytoplasmic antibody (ANCA) glomerulonephritis, the effects of the implantation of DFAT cells on ANCA glomerulonephritis were investigated in mice.

Methods

PKH26-labeled DFAT cells (105) were infused through the posterior orbital venous plexus to investigate delivery of DFAT cells in ICR mice. DFAT cells (105) were also implanted in SCG mice as a model for ANCA glomerulonephritis. Expression of tumor necrosis factor-stimulated gene-6 (TSG-6) mRNA and protein in kidney was evaluated, and the expression of microRNAs associated with TSG-6 in plasma, lung and kidney was analyzed. Expressions of CD44, prostaglandin (PG) E2, interleukin (IL)-10, IL-1β, tumor necrosis factor (TNF)-α mRNAs, C–C motif chemokine ligand 17 (CCL-17) and monocyte chemoattractant protein (MCP)-1 proteins were measured in kidney from SCG mice implanted with DFAT cells.

Results

After their intravenous infusion, almost all DFAT cells were trapped in the lung and not delivered into the kidney. Implantation of DFAT cells in SCG mice suppressed glomerular crescent formation, decreased urinary protein excretions and increased expression of TSG-6 mRNA, protein and immunostaining in kidney from these mice. Increased expression of microRNA 23b-3p in plasma, kidney and lung; decreased expression of CD44 mRNA; and increased expression of PGE2 and IL-10 mRNAs were also observed in kidney from these mice. Implantation of DFAT cells also decreased the expression of TNF-α and MCP-1 proteins and increased that of CCL-17 protein in kidney from the SCG mice. Survival rates were higher in SCG mice implanted with DFAT cells than in SCG mice without implantation.

Conclusion

Mechanisms underlying the effects of improvement of ANCA glomerulonephritis are associated with immunosuppressive effects by TSG-6 and the transition of M1–M2 macrophages, suggesting that implantation of DFAT cells may become a cell therapy for ANCA glomerulonephritis.
Diversity of epiphytic bacterial communities on male and female Sargassum thunbergii
Authors: Wang Jing , Yang Zhibo , Wang Gaoge , Shang Shuai , Tang Xuexi , Xiao Hui
Published: July 2022

The epiphytic bacteria are the most abundant microorganisms on marine macroalga. However, there are few studies on the distribution of these epiphytic bacteria on male and female Sargassum thunbergii. In this study, the composition and diversity of epiphytic bacterial communities on male and female S. thunbergii were investigated by using the traditional culture-based method and 16S rDNA high-throughput sequencing. The results showed that the dominant bacterial phyla and genera were the same on both male and female S. thunbergii. However, there were significant differences in the relative abundance of epiphytic bacteria at the genus level. Furthermore, male and female S. thunbergii had their own indicative species and specific bacteria. In addition, the predicted functions of the epiphytic bacteria mainly differed in transport and metabolism, environmental adaptation and spore development. This study enriches the baseline knowledge of epiphytic bacteria related to dioecious algae and paves the way for further studies of the relationships between epiphytic microbial communities and the sex of algae.
Evaluation of outcomes in the management of primary sporadic desmoid-type fibromatosis at a specialist soft tissue sarcoma unit
Authors: Khan Misbah , Almond Max , Ford Samuel , Desai Anant
Published: July 2022

Background

Desmoids are rare fibroblastic tumours whose treatment in any individual case presents a persistent challenge. We endeavoured to evaluate various clinicopathological factors contributing to tumour behaviour.

Methods

This is a retrospective review of 95 primary truncal sporadic fibromatosis managed between 2011 and 2020. We studied progression rate for wait and watch (WW) and recurrence rate for the surgically treated group as adverse events. Relevant event-free survivals and potential risk factors were analysed over a median follow-up of 27 months.

Results

66 patients (69.5%) received watchful surveillance and 28 upfront surgery. 2-year progression-free survival in WW group (88.9%) was higher than RFS in the surgical group (77.1%) p = 0.02. Adverse event rate compared favourably, 28.8% in WW and 28.6% in surgical group. At final follow-up, rate of stable disease for WW was 47%, and the regression rate was 24.2%. On Cox regression analysis, meantime to progress was 14 ± 2.0 months, with larger tumour size as a significant prognostic indicator (p = 0.05). Surgical group's mean time to recurrence was 13.8 ± 2.76 months, with tumour location a significant contributing factor (p = 0.05).

Conclusions

This study confirms to the safety of both treatment approaches. Adverse event rates remained comparable, but event-free survival was longer for the watchful surveillance group.
Association of multidrug resistance behavior of clinical Pseudomonas aeruginosa to pigment coloration
Authors: Kothari Ashish , Kumar Shyam Kishor , Singh Vanya , Kumar Prashant , Kaushal Karanvir , Pandey Atul , Jain Neeraj , Omar Balram Ji
Published: July 2022

Pseudomonas aeruginosa is an adaptable bacterial pathogen that infects a variety of organs, including the respiratory tract, vascular system, urinary tract, and central nervous system, causing significant morbidity and mortality. As the primary goal of this study, we wanted to determine how pigment color production differed between clinical strains of P. aeruginosa, and whether or not that variation was associated with multidrug resistance or the ability to form biofilms. We screened in total 30.1% of yellow, 39.8% green and 30.1% of no pigment-producing P. aeruginosa strains from a total of 143 various clinical isolates. Yellow pigment-producing strains presented significant resistance to antibiotics groups, including β-lactam (91.5%), aminoglycosides (70.5%), and carbapenems (51.9%) compared to green and non-pigmented strains. Notably, 16.3% of yellow pigment-producing strains were resistant to colistin which is used as a last-resort treatment for multidrug-resistant bacteria, whereas only 2.3% of non-pigmented and 1.8% of green pigmented strains were resistant to colistin. Aside from that, yellow pigment-producing strains were frequent producers of enzymes belonging to the lactamase family, including ESBL (55.6%), MBL (55.6%), and AmpC (50%). Compared to the green groups (7.14%) and non-pigmented groups (28.5%), they had a higher frequency of efflux positive groups (64.2%). Notably, when compared to non-pigmented groups, green pigment-producing strains also displayed antibiotic susceptibility behavior similar to yellow pigment-producing strains. The majority of yellow pigment-producing strains outperformed the green and non-pigmented strains in terms of MIC levels when compared to the other two groups of strains. Despite the fact that previous studies have demonstrated a direct correlation between multidrug resistance behaviors and biofilm production, no such statistically significant association between pigment and biofilm formation was found in our investigation. Our research has demonstrated that the correlation of bacterial pigments on their susceptibility to antimicrobial agents. Yellow pigment-producing P. aeruginosa strains posed a significant problem due to the lack of alternative agents against such transformed strains, which may be associated with the development of multidrug resistance.

Graphical Abstract
Real-world safety of ulinastatin: a post-marketing surveillance of 11,252 patients in China
Authors: Li Jin , Li Meijun , Li Liren , Ma Lin , Cao Ailin , Wen Aiping , Chen Wenge , Li Lingling , Liang Yan , Deng Jianxiong
Published: July 2022

Background

The safety assessment of ulinastatin can guide clinical practice. The present study aimed to investigate the real-world safety of ulinastatin in China.

Methods

This multicenter study retrospectively analyzed the post-marketing surveillance data of consecutive patients treated with ulinastatin between August 2014 and June 2017 in the general wards and the intensive care units (ICU) of nine hospitals in China. Adverse drug reactions/adverse drug events (ADRs/ADEs) were collected and evaluated in a post-marketing database.

Results

A total of 11,252 consecutive patients were included in the study: 7009 ICU patients and 4243 general ward patients. Eleven patients with ADRs/ADEs were observed, including nine ICU patients and two general ward patients. The clinical manifestations were liver dysfunction (n = 5 ICU cases, n = 1 general case), thrombocytopenia (n = 2 ICU cases, n = 1 general case), leukopenia (n = 1 ICU case), and rash (n = 1 ICU case). During the study period, the drug ADR/ADE rate of ulinastatin injection was 0.98‰ (11/11,252 × 1000‰). Among the 11,252 valid patients, only 327 received ulinastatin in accordance with the drug specifications. After excluding unreasonable drug use, the calculated ADR rate was 3.06‰ (1/327 × 1000‰) (95% confidence interval: 0.0‰-17.1‰). In ICU and general ward patients, the use of other drugs combined with ulinastatin was associated with the occurrence of ADRs/ADEs (100% with ADRs/ADEs vs. 0% in controls, P < 0.001).

Conclusions

The incidence of ADRs/ADEs of ulinastatin is < 5‰. The ADRs/ADEs involved limited organs, mainly the skin, gastrointestinal tract, and blood. In most cases, the ADRs/ADEs gradually alleviated or recovered after drug withdrawal. The inappropriate/off-label use of ulinastatin should be the focus of surveillance.
An efficient annealing-assisted differential evolution for multi-parameter adaptive latent factor analysis
Authors: Li Qing , Pang Guansong , Shang Mingsheng
Published: July 2022

A high-dimensional and incomplete (HDI) matrix is a typical representation of big data. However, advanced HDI data analysis models tend to have many extra parameters. Manual tuning of these parameters, generally adopting the empirical knowledge, unavoidably leads to additional overhead. Although variable adaptive mechanisms have been proposed, they cannot balance the exploration and exploitation with early convergence. Moreover, learning such multi-parameters brings high computational time, thereby suffering gross accuracy especially when solving a bilinear problem like conducting the commonly used latent factor analysis (LFA) on an HDI matrix. Herein, an efficient annealing-assisted differential evolution for multi-parameter adaptive latent factor analysis (ADMA) is proposed to address these problems. First, a periodic equilibrium mechanism is employed using the physical mechanism annealing, which is embedded in the mutation operation of differential evolution (DE). Then, to further improve its efficiency, we adopt a probabilistic evaluation mechanism consistent with the crossover probability of DE. Experimental results of both adaptive and non-adaptive state-of-the-art methods on industrial HDI datasets illustrate that ADMA achieves a desirable global optimum with reasonable overhead and prevails competing methods in terms of predicting the missing data in HDI matrices.