bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic kidney disease mediates cardiac dysfunction associated with increased resident cardiac macrophages
Authors: Mawhin M. A. , Bright R. G. , Fourre J. D. , Vloumidi E. I. , Tomlinson J. , Sardini A. , Pusey C. D. , Woollard K. J.
Published: January 2022

Background

The leading cause of death in end-stage kidney disease is related to cardiovascular disease. Macrophages are known to be involved in both chronic kidney disease (CKD) and heart failure, however their role in the development of cardiorenal syndrome is less clear. We thus sought to investigate the role of macrophages in uremic cardiac disease.

Methods

We assessed cardiac response in two experimental models of CKD and tested macrophage and chemokine implication in monocytopenic CCR2−/−and anti-CXCL10 treated mice. We quantified CXCL10 in human CKD plasma and tested the response of human iPSC-derived cardiomyocytes and primary cardiac fibroblasts to serum from CKD donors.

Results

We found that reduced kidney function resulted in the expansion of cardiac macrophages, in particular through local proliferation of resident populations. Influx of circulating monocytes contributed to this increase. We identified CXCL10 as a crucial factor for cardiac macrophage expansion in uremic disease. In humans, we found increased plasma CXCL10 concentrations in advanced CKD, and identified the production of CXCL10 in cardiomyocytes and cardiac fibroblasts.

Conclusions

This study provides new insight into the role of the innate immune system in uremic cardiomyopathy.
Criteria for identification of advanced Parkinson’s disease: the results of the Italian subgroup of OBSERVE-PD observational study
Authors: Stefani Alessandro , Tessitore Alessandro , Tambasco Nicola , Cossu Giovanni , Ceravolo Maria Gabriella , Defazio Giovanni , Morgante Francesca , Ramat Silvia , Melzi Gabriella , Gualberti Giuliana , Merolla Rocco , Onuk Koray , Lopiano Leonardo
Published: January 2022

Background

Frequency of Advanced Parkinson’s Disease (APD) and its clinical characteristics are still not well defined. Here, we aimed to assess APD prevalence in the Italian OBSERVE-PD cohort, as well as treatment eligibility to device-aided therapies (DAT), and to compare the APD clinical judgment with the established Delphi criteria.

Methods

This sub-group analysis of the OBSERVE-PD study was performed on patients enrolled by 9 Movement Disorders centers in Italy. Motor and non-motor symptoms, PD characteristics, activities of daily living, and quality of life were assessed. Patient eligibility for DAT, response to current PD treatments, referral process, and the concordance between APD physician’s judgment and Delphi criteria were also assessed.

Results

According to physician’s judgment, 60 out of 140 patients (43%) had APD. The correlation between physician’s judgment and the overall APD Delphi criteria was substantial (K = 0.743; 95%CI 0.633–0.853), mainly driven by a discrete concordance found for the presence of ≥ 2 h of daily OFF time, presence of troublesome dyskinesia, ≥ 5 times daily oral levodopa dosing, and activities of daily living limitation. Forty-four (73%) APD patients were considered eligible to DAT but only 18 of them (41%) used these therapies, while most patients, independently from their eligibility, continued to use 3–5 oral daily medications, due to fear of invasive solutions and need to have a longer time to decide.

Conclusion

APD was frequent in the Italian OBSERVE-PD population. DAT in the eligible APD population proved to be underused, in spite of unsatisfactory symptoms control with oral medications in 67% of patients.
Geographical variation and predictors of zero utilization for a standard maternal continuum of care among women in Ethiopia: a spatial and geographically weighted regression analysis
Authors: Melaku Mequannent Sharew , Aemro Agazhe , Aychiluhm Setognal Birara , Muche Amare , Bizuneh Gizachew Kassahun , Kebede Shimels Derso
Published: January 2022

Background

Maintaining and effectively utilizing maternal continuum of care could save an estimated 860,000 additional mothers and newborn lives each year. In Ethiopia, the number of maternal and neonatal deaths occurred during pregnancy, childbirth, and the postpartum period was very high. It is indisputable that area-based heterogeneity of zero utilization for a standard maternal continuum of care is critical to improve maternal and child health interventions. However, none of the previous studies explored the spatial distribution of zero utilization for maternal continuum of care. Hence, this study was aimed to explore geographical variation and predictors of zero utilization for a standard maternal continuum of care among women in Ethiopia.

Methods

A total of 4178 women who gave birth five years preceding the 2016 Ethiopian demographic and health survey were included. ArcGIS version 10.7, SaT Scan version 9.6, and GWR version 4.0 Software was used to handle mapping, hotspot, ordinary least square, Bernoulli model analysis, and to model spatial relationships. Finally, a statistical decision was made at a p-value< 0.05 and at 95% confidence interval.

Main findings

The proportion of mothers who had zero utilization of a standard maternal continuum of care was 48.8% (95% CI: 47.3–50.4). Hot spot (high risk) regions for zero utilization of maternal continuum of care was detected in Afder, Warder, Korahe and Gode Zones of Somali region and West Arsi Zone of Oromia region. Respondents who had poor wealth index, uneducated mothers, and mothers who declared distance as a big problem could increase zero utilization of maternal continuum of care by 0.24, 0.27, and 0.1 times.

Conclusion

Five women out of ten could not utilize any components of a standard maternal continuum of care. Hot spot (high risk) areas was detected in Afder, Warder, Korahe and Gode Zones of Somali region and West Arsi Zone of Oromia region. Poor wealth index, uneducated mothers, and mothers who declare distance as a big problem were factors significantly associated with zero utilization of maternal continuum of care. Thus, geographical based intervention could be held to curve the high prevalence of zero utilization of maternal continuum of care.
The expression and survival significance of sodium glucose transporters in pancreatic cancer
Authors: Du Jiali , Gu Jichun , Deng Junyuan , Kong Lei , Guo Yujie , Jin Chen , Bao Yun , Fu Deliang , Li Ji
Published: January 2022

Background

Sodium glucose transporters (SGLTs) play vital roles in glucose uptake in many solid cancers, including pancreatic cancer (PC). However, their expression profile in pancreatic cancer and correlation with prognosis are not clear. Thus, we aimed to analyse the expression profile and prognostic significance of SGLT-1 and SGLT-2 in PC.

Methods

Eighty-eight patients with pancreatic ductal adenocarcinoma (PDAC) undergoing surgery in Huashan Hospital, Fudan University, from July 2017 to June 2020 were enrolled in the study. Specimens for immunohistochemistry were obtained through surgical resection. Bioinformatics analysis was performed based on the Gene Expression Omnibus (GEO), Oncomine and The Cancer Genome Atlas (TCGA) databases. The statistics were calculated using IBM SPSS Statistics, version 20 and R 4.1.1. P values lower than 0.05 were considered to indicate statistical significance.

Results

SGLT-1 but not SGLT-2 was significantly overexpressed in PDAC. Survival analysis showed that the median overall survival (OS) and progression-free survival (PFS) of patients with high SGLT-1 expression were significantly longer than that of patients with low SGLT-1 expression. Cox regression indicated that high SGLT-1 expression was an independent predictor for a better prognosis, while residual tumour status (R1 and R2) was an independent risk factor for a poor prognosis. Finally, PDZK1-interacting protein 1 (PDZK1IP1), a protein participating in the generation of reactive oxygen species, was overexpressed in PDAC and its expression was significantly correlated with SGLT-1.

Conclusions

SGLT-1 but not SGLT-2 was overexpressed in PDAC, and the overexpression of SGLT-1 could be a predictor of a better prognosis. Residual tumour status (R1 and R2) was a risk factor for poor prognosis and disease progression.
Is having a 20-minute neighbourhood associated with eating out behaviours and takeaway home delivery? A cross-sectional analysis of ProjectPLAN
Authors: Oostenbach Laura H. , Lamb Karen E. , Thornton Lukar E.
Published: January 2022

Background

Through improved service provision and accessibility, 20-min neighbourhoods (20MNs) aim to enable people to meet most of their daily (non-work) needs within 20 min from home. Associations between 20MNs and food practices remain unknown. This study examines links with the frequency and location of eating out behaviours as well as the frequency of home food delivery.

Methods

This cross-sectional study used data from 769 adults from the Places and Locations for Activity and Nutrition study (ProjectPLAN) conducted in Melbourne and Adelaide, Australia, between 2018 and 2019. Outcomes were 1) visit frequency to i) cafés, ii) restaurants, bars or bistros, iii) major chain fast food outlets and iv) takeaway outlets to purchase food; 2) total number of different types of out-of-home food outlets visited; 3) use frequency of home food delivery services; 4) distance from home to the most frequented out-of-home food outlets. Exposure was whether participants had a 20MN (areas with high service/amenity provision) or a non-20MN (areas with low service/amenity provision). Ordinal regression models were fitted for the frequency outcomes. Poisson regression models were fitted for the number of different outlet types. Linear and spatial regression models were fitted for the distance outcomes.

Results

Results suggested no differences in frequency of visitations to out-of-home food outlets and use of food delivery services between those with a 20MN and those with a non-20MN. Yet, those with a 20MN were more likely to use a greater number of different types of outlets on a weekly basis. Where a regular eating out location was reported, it was nearer to home for those with a 20MN.

Conclusions

This study provides evidence supportive of 20MNs potentially facilitating more localised food practices, however, 20MNs may also encourage greater cumulative frequency of meals out across a variety of out-of-home food providers.
A CRISPR toolbox for generating intersectional genetic mouse models for functional, molecular, and anatomical circuit mapping
Authors: Lusk Savannah J. , McKinney Andrew , Hunt Patrick J. , Fahey Paul G. , Patel Jay , Chang Andersen , Sun Jenny J. , Martinez Vena K. , Zhu Ping Jun , Egbert Jeremy R. , Allen Genevera , Jiang Xiaolong , Arenkiel Benjamin R. , Tolias Andreas S. , Costa-Mattioli Mauro , Ray Russell S.
Published: January 2022

Background

The functional understanding of genetic interaction networks and cellular mechanisms governing health and disease requires the dissection, and multifaceted study, of discrete cell subtypes in developing and adult animal models. Recombinase-driven expression of transgenic effector alleles represents a significant and powerful approach to delineate cell populations for functional, molecular, and anatomical studies. In addition to single recombinase systems, the expression of two recombinases in distinct, but partially overlapping, populations allows for more defined target expression. Although the application of this method is becoming increasingly popular, its experimental implementation has been broadly restricted to manipulations of a limited set of common alleles that are often commercially produced at great expense, with costs and technical challenges associated with production of intersectional mouse lines hindering customized approaches to many researchers. Here, we present a simplified CRISPR toolkit for rapid, inexpensive, and facile intersectional allele production.

Results

Briefly, we produced 7 intersectional mouse lines using a dual recombinase system, one mouse line with a single recombinase system, and three embryonic stem (ES) cell lines that are designed to study the way functional, molecular, and anatomical features relate to each other in building circuits that underlie physiology and behavior. As a proof-of-principle, we applied three of these lines to different neuronal populations for anatomical mapping and functional in vivo investigation of respiratory control. We also generated a mouse line with a single recombinase-responsive allele that controls the expression of the calcium sensor Twitch-2B. This mouse line was applied globally to study the effects of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on calcium release in the ovarian follicle.

Conclusions

The lines presented here are representative examples of outcomes possible with the successful application of our genetic toolkit for the facile development of diverse, modifiable animal models. This toolkit will allow labs to create single or dual recombinase effector lines easily for any cell population or subpopulation of interest when paired with the appropriate Cre and FLP recombinase mouse lines or viral vectors. We have made our tools and derivative intersectional mouse and ES cell lines openly available for non-commercial use through publicly curated repositories for plasmid DNA, ES cells, and transgenic mouse lines.
CircPVT1: a pivotal circular node intersecting Long Non-Coding-PVT1 and c-MYC oncogenic signals
Authors: Palcau Alina Catalina , Canu Valeria , Donzelli Sara , Strano Sabrina , Pulito Claudio , Blandino Giovanni
Published: January 2022

The role of circular RNAs in oncogenesis has begun to be widely studied in recent years, due to the significant impact that these molecules have in disease pathogenesis, as well as their potential for the future of innovative therapies. Moreover, due to their characteristically circular shape, circular RNAs are very resistant molecules to RNA degradation whose levels are easily assessed in body fluids. Accordingly, they represent an opportunity for the discovery of new diagnostic and prognostic markers in a wide range of diseases. Among circular RNAs, circPVT1 is a rather peculiar one that originates from the circularization of the exon 2 of the PVT1 gene that encodes a pro-tumorigenic long non-coding RNA named lncPVT1. There are a few examples of circular RNAs that derive from a locus producing another non-coding RNA. Despite their apparent transcriptional independence, which occurs using two different promoters, a possible synergistic effect in tumorigenesis cannot be excluded considering that both have been reported to correlate with the oncogenic phenotype. This complex mechanism of regulation appears to also be controlled by c-MYC. Indeed, the PVT1 locus is located only 53 Kb downstream c-MYC gene, a well-known oncogene that regulates the expression levels of about 15% of all genes. Here, we review circPVT1 origin and biogenesis highlighting the most important mechanisms through which it plays a fundamental role in oncogenesis, such as the well-known sponge activity on microRNAs, as well as its paradigmatic interactome link with lncPVT1 and c-MYC expression.
How to make the best use of the workload indicators of staffing needs method in determining the proportion of time spent in each of the workload components and its implication in decision making: the experience of the Sultanate of Oman
Authors: Mohamed Nazar , Al-Lawati Nahida
Published: January 2022

Background

The Ministry of Health in the Sultanate of Oman decided to have better distribution of the health workforce among all health facilities through evidenced-based staffing norms. Four directorates worked together to develop the staffing norms through making use of the workload indicators of staffing needs (WISN) method. The aim of this study is to describe the process of applying the WISN method in Primary Health Care institutions and how to make the best use of method in determining the proportion of time spent in each of the workload components and its implication in decision making.

Methods

The WISN was applied for five priority categories, namely, doctors, nurses, pharmacists, laboratory technicians, and radiology technicians at PHC institutions. The WISN ratio has been translated into workload pressure as a percentage through applying the formula [workload pressure as % (in case of shortage) = (1 − WISN ratio) × 100%]. While the proportion of time spent in each of the workload components was calculated through making use of the category allowance standard, the individual allowance standard to determine the time spent in support and additional activities. The sum is subtracted from 100% to give the time spent in the health service activities.

Results

Determining the workload pressure as a percent and its interpretation is based on the fact that one cadre or as a group can bear up to 10% of extra workload. Thus, managers can undertake sensible short-term arrangements or decisions in redistributing the cadres among the health facilities on expectation of deploying more staff.

Discussion

Careful and detailed analysis of the proportion of time spent in each of the workload components will allow to have better understanding of the context and dynamics of work.

Conclusion

Decision makers and planners can undertake rational short-term decisions in redistributing the cadres among the health facilities based on the workload pressure. In addition, they can as well as easily decide on the optimal proportions of time for each staff category, and hence choose what activities and tasks to be shifted or delegated to other staff category.
Workload assessment of medical doctors at primary health care centers in the Duhok governorate
Authors: Al-Dabbagh Samim Ahmed , Sulaiman Hushyar Musa , Abdulkarim Nazik Abdulrahman
Published: January 2022

Background

A shortage in human resources, particularly physicians, has become a challenge confronting health authorities in the Duhok governorate, as these resources are the key input for delivering health care. It has become necessary to identify the most appropriate scientifically sound method for having adequate staffing levels. This study aimed to forecast the required number of physicians to cope with the current workload at the main primary health care centers in the Duhok governorate.

Methods

A cross-sectional study was adopted to collect data for 1 full year. Data collection included both primary and secondary data sources. A semi-structured questionnaire was developed to obtain information every month from health centers on activities related to training and leaves. Data analysis was performed using Workload Indicators of Staffing Need software.

Results

Sixty-one primary health care centers met the final criteria for analysis. The study revealed physician shortages and inequity in the distribution of staffing. In these centers, 145 physicians lacked an adequate delivery of health services based on the workload imposed on them. The ‘workload indicators of staffing need’ ratio was 0.33, indicating high work pressure on medical doctors. Some centers offered more health care than others, but had fewer doctors based on the current staffing practices.

Conclusions

This study pointed out the importance for the public health sector and academic medical institutions to use Workload Indicators of Staffing Needs software in health policy administration to restructure their efforts to address the physician shortages and distribution imbalances at primary health care facilities.
Lessons learned from implementation of the Workload Indicator of Staffing Need (WISN) methodology: an international Delphi study of expert users
Authors: Namaganda Grace Nyendwoha , Whitright Audrey , Maniple Everd Bikaitwoha
Published: January 2022

Background

Staffing of health services ought to consider the workload experienced to maximize efficiency. However, this is rarely the case, due to lack of an appropriate approach. The World Health Organization (WHO) developed and has promoted the Workload Indicators of Staffing Need (WISN) methodology globally. Due to its relative simplicity compared to previous methods, the WISN has been used extensively, particularly after its computerization in 2010. Many lessons have been learnt from the introduction and promotion of the methodology across the globe but have, hitherto, not been synthesized for technical and policy consideration. This study gathered, synthesized, and now shares the key adaptations, innovations, and lessons learned. These could facilitate lesson-learning and motivate the WHO’s WISN Thematic Working Group to review and further ease its application.

Methods

The study aimed to answer four questions: (1) how easy is it for the users to implement each step of the WISN methodology? (2) What innovations have been used to overcome implementation challenges? (3) What lessons have been learned that could inform future WISN implementation? and (4) what recommendations can be made to improve the WISN methodology? We used a three-round traditional Delphi method to conduct a case study of user-experiences during the adoption of the WISN methodology. We sent three email iterations to 23 purposively selected WISN expert users across 21 countries in five continents. Thematic analysis of each round was done simultaneously with data collection.

Results

Participants rated seven of the eight technical steps of the WISN as either “very easy” or “easy” to implement. The step considered most difficult was obtaining the Category Allowance Factors (CAF). Key lessons learned were that: the benefits gained from applying the WISN outweigh the challenges faced in understanding the technical steps; benchmarking during WISN implementation saves time; data quality is critical for successful implementation; and starting with small-scale projects sets the ground better for more effective scale-up than attempting massive national application of the methodology the first time round.

Conclusions

The study provides a good reference for easing WISN implementation for new users and for WHO to continue promoting and improving upon it.
Endoplasmic reticulum stress promotes the release of exosomal PD-L1 from head and neck cancer cells and facilitates M2 macrophage polarization
Authors: Yuan Yi , Jiao Pengfei , Wang Zeyu , Chen Mengqi , Du Hongming , Xu Liang , Xu Juanyong , Dai Youjin , Wu Fu-gen , Zhang Yaqin , Wu Heming
Published: January 2022

Background

Endoplasmic reticulum (ER) stress has been found to foster the escape of cancer cells from immune surveillance and upregulate PD-L1 expression. However, the underlying mechanisms are unknown.

Methods

While analyzing the protein levels using immunofluorescence and Western blotting, the RNA levels were measured using qRT-PCR. Ten injection of exosomes into six-week-old nude mice was made through the tail vein once every other day in total.

Results

The expression of certain ER stress markers such as PERK (PKR-like endoplasmic reticulum kinase), ATF6 (activating transcription factor 6), and GRP78 (glucose-regulated protein 78), was found to be upregulated in the oral squamous cell carcinoma (OSCC) tissues and related to poor overall survival. There is a positive relationship between the extent of ER stress-related proteins and a cluster of PD-L1 expression and macrophage infiltration among the OSCC tissues. Further, incubation with exosomes derived from ER-stressed HN4 cells (Exo-ER) was found to upregulate PD-L1 extents in macrophages in vitro and in vivo, and macrophage polarization toward the M2 subtype was promoted by upregulating PD-L1.

Conclusions

ER stress causes OSCC cells to secrete exosomal PD-L1 and upregulates PD-L1 expression in macrophages to drive M2 macrophage polarization. The delineation of a new exosome-modulated mechanism was made for OSCC–macrophage crosstalk driving tumor development and to be examined for its therapeutic use.

Graphical abstract

Exosomal PD-L1 secreted by ER-stressed OSCC cells promoted M2 macrophage polarization.
The pathogenesis of prevalent aerobic bacteria in aerobic vaginitis and adverse pregnancy outcomes: a narrative review
Authors: Ma Xiaotong , Wu Ming , Wang Chen , Li Huiyang , Fan Aiping , Wang Yingmei , Han Cha , Xue Fengxia
Published: January 2022

Background

Aerobic vaginitis is a common cause of vaginal discharge in reproductive-age women, increasing the risk of negative pregnancy outcomes such as premature delivery, abortion, premature rupture of membranes and stillbirth. However, the aetiology and pathogenesis of aerobic vaginitis causing negative pregnancy outcomes are still unclear, and there is no unified and standardized treatment method for aerobic vaginitis in the pregnancy period.

Methods

We conducted a literature search of published studies in the English language focusing on aerobic vaginitis and its association with adverse pregnancy outcomes utilizing PubMed and Web of Science from January 1973 through June 2021. The common pathogenic bacteria of aerobic vaginitis during pregnancy, such as group BStreptococcus,Escherichia coli,Staphylococcus aureus,Enterococcus faecalisandKlebsiella pneumoniae, as well as the related adverse pregnancy outcomes and existing treatments were reviewed.

Results

A total of 4534 articles were identified, and 97 studies that had inclusion criteria were subjected to careful review. The pathogenic bacteria of aerobic vaginitis can produce different toxins or affect the local immunity of patients and then lead to the occurrence of infection. Fresh wet mount microscopy is the preferred diagnostic method for aerobic vaginitis. Clindamycin is a common antibiotic used for aerobic vaginitis in pregnant women. The use of products combining probiotics has achieved excellent treatment success.

Conclusions

Future research in this field can provide insights regarding the mechanism of aerobic vaginitis-induced adverse pregnancy outcomes in humans and ways to prevent their occurrence.
“…the availability of contraceptives is everywhere.”: coordinated and integrated public family planning service delivery in Rwanda
Authors: Scanteianu Adriana , Schwandt Hilary M. , Boulware Angel , Corey Julia , Herrera Ana , Hudler Ethan , Imbabazi Claudette , King Ilia , Linus Jessica , Manzi Innocent , Merritt Madelyn , Mezier Lyn , Miller Abigail , Morris Haley , Musemakweli Dieudonne , Musekura Uwase , Mutuyimana Divine , Ntakarutimana Chimene , Patel Nirali , Shemeza Biganette-Evidente , Sterling-Donaldson Gi’anna , Umutoni Chantal , Uwera Lyse , Zeiler Madeleine , Feinberg Seth
Published: January 2022

Background

Contraceptive use in Rwanda tripled since 2005. This study aims to understand the role of coordinated and integrated public family planning service delivery in achieving this increase in contraceptive use in Rwanda.

Methods

This qualitative study in 2018 included eight focus group discussions with family planning providers and 32 in-depth interviews with experienced family planning users.

Results

Results indicate a well-coordinated public family planning service delivery system with community health workers and nurses filling different and complementary roles in meeting family planning client needs at the local level. In addition, integration of family planning into other maternal and child health services is the norm.

Conclusions

The coordination and integration of family planning across both providers and services may help explain the rapid increase in Rwanda’s contraceptive use and has potential applications for enhancing family planning service delivery in other settings.
Effects of Balance Exercise Assist Robot training for patients with hemiparetic stroke: a randomized controlled trial
Authors: Inoue Seigo , Otaka Yohei , Kumagai Masashi , Sugasawa Masafumi , Mori Naoki , Kondo Kunitsugu
Published: January 2022

Background

Robot-assisted rehabilitation for patients with stroke is promising. However, it is unclear whether additional balance training using a balance-focused robot combined with conventional rehabilitation programs supplements the balance function in patients with stroke. The purpose of this study was to compare the effects of Balance Exercise Assist Robot (BEAR) training combined with conventional inpatient rehabilitation training to those of conventional inpatient rehabilitation only in patients with hemiparetic stroke. We also aimed to determine whether BEAR training was superior to intensive balance training.

Methods

This assessor-blinded randomized controlled trial included 60 patients with first-ever hemiparetic stroke, admitted to rehabilitation wards between December 2016 and February 2019. Patients were randomly assigned to one of three groups, robotic balance training and conventional inpatient rehabilitation (BEAR group), intensive balance training and conventional inpatient rehabilitation (IBT group), or conventional inpatient rehabilitation-only (CR group). The intervention duration was 2 weeks, with assessments conducted pre- and post-intervention, and at 2 weeks follow-up. The primary outcome measure was a change in the Mini-Balance Evaluation Systems Test (Mini-BESTest) score from baseline.

Results

In total, 57 patients completed the intervention, and 48 patients were evaluated at the follow-up. Significant improvements in Mini-BESTest score were observed in the BEAR and IBT groups compared with in the CR group post-intervention and after the 2-week follow-up period (P < 0.05).

Conclusions

The addition of balance exercises using the BEAR alongside conventional inpatient rehabilitation improved balance in patients with subacute stroke.

Trial registration

https://www.umin.ac.jp/ctr; Unique Identifier: UMIN000025129. Registered on 2 December 2016.
miR-155 inhibits chondrocyte pyroptosis in knee osteoarthritis by targeting SMAD2 and inhibiting the NLRP3/Caspase-1 pathway
Authors: Li Gen , Xiu Lijun , Li Xiaoyun , Ma Lisha , Zhou Jihui
Published: January 2022

Objective

Knee osteoarthritis (KOA) is based on degenerative pathological changes. miR-155 is involved in regulating KOA. This study estimated the mechanism of miR-155 in mouse KOA chondrocytes.

Methods

Mouse KOA chondrocyte model was established by lipopolysaccharide (LPS) induction and identified through Collagen II immunofluorescence staining and toluidine blue staining. LPS-induced KOA chondrocytes were transfected with miR-155 inhibitor or/and si-SMAD2, followed by the evaluation of miR-155 expression, pyroptosis, the SMAD2/NLRP3/Caspase-1 axis-related protein levels, IL-1β and 1L-18 levels, and cell viability by RT-qPCR, FAM-FLICA Caspase-1 Detection Kit, Western blot, ELISA, and MTT assays, respectively. The binding sites between miR-155 and SMAD2 were predicted online and the binding relationship was verified by dual-luciferase assay.

Results

miR-155 was highly-expressed in LPS-induced KOA chondrocytes. miR-155 knockdown increased cell viability and decreased pyroptotic chondrocytes, and Caspase-1, 1L-1β and 1L-18 levels. miR-155 targeted SMAD2. SMAD2 knockdown partially annulled the effects of miR-155 silencing on inhibiting KOA chondrocyte pyroptosis. NLRP3 pathway was activated in LPS-induced KOA chondrocytes, inhibited after miR-155 knockdown, and activated again after further SMAD2 knockdown. NLRP3 inhibition suppressed Caspase-1, IL-1β, and IL-18 levels and chondrocyte pyroptosis and increased cell viability.

Conclusion

miR-155 knockdown inhibited the NLRP3/Caspase-1 pathway by targeting SMAD2, thus inhibiting mouse KOA chondrocyte pyroptosis.
Adipose-derived mesenchymal stem cells with hypoxic preconditioning improve tenogenic differentiation
Authors: Guo Xing , Huang Denghua , Li Dan , Zou Longfei , Lv Hui , Wang Yuanhui , Tan Meiyun
Published: January 2022

Background

Adipose-derived mesenchymal stem cells (ADSCs), as seed cells for tendon tissue engineering, are promising for tendon repair and regeneration. But for ADSCs, diverse oxygen tensions have different stimulatory effects. To explore this issue, we investigated the tenogenic differentiation capability of ADSCs under hypoxia condition (5% O2) and the possible signaling pathways correspondingly. The effects of different oxygen tensions on proliferation, migration, and tenogenic differentiation potential of ADSCs were investigated.

Methods

P4 ADSCs were divided into a hypoxic group and a normoxic group. The hypoxic group was incubated under a reduced O2 pressure (5% O2, 5% CO2, balanced N2). The normoxic group was cultured in 21% O2. Two groups were compared: HIF-1α inhibitor (2-MeOE2) in normoxic culturing conditions and hypoxic culturing conditions. Hypoxia-inducible factor-1α (HIF-1α) and VEGF were measured using RT-qPCR. Specific HIF-1α inhibitor 2-methoxyestradiol (2-MeOE2) was applied to investigate whether HIF-1α involved in ADSCs tenogenesis under hypoxia.

Results

Hypoxia significantly reduced proliferation and migration of ADSCs. Continuous treatment of ADSCs at 5% O2 resulted in a remarkable decrease in HIF-1α expression in comparison with 20% O2. Additionally, ADSCs of hypoxia preconditioning exhibited higher mRNA expression levels of the related key tenogenic makers and VEGF than normoxia via RT-qPCR measurement (p ˂ 0.05). Furthermore, the effects of hypoxia on tenogenic differentiation of ADSCs were inhibited by 2-MeOE2. Hypoxia can also stimulate VEGF production in ADSCs.

Conclusions

Our findings demonstrate that hypoxia preconditioning attenuates the proliferation and migration ability of ADSCs, but has positive impact on tenogenic differentiation through HIF-1α signaling pathway.
Epidemiology of emergency ambulance service calls related to COVID-19 in Scotland: a national record linkage study
Authors: Fitzpatrick David , Duncan Edward A. S. , Moore Matthew , Best Catherine , Andreis Federico , Esposito Martin , Dobbie Richard , Corfield Alasdair R. , Lowe David J.
Published: January 2022

Background

COVID-19 has overwhelmed health services across the world; its global death toll has exceeded 5.3 million and continues to grow. There have been almost 15 million cases of COVID-19 in the UK. The need for rapid accurate identification, appropriate clinical care and decision making, remains a priority for UK ambulance service. To support identification and conveyance decisions of patients presenting with COVID-19 symptoms the Scottish Ambulance Service introduced the revised Medical Priority Dispatch System Protocol 36, enhanced physician led decision support and prehospital clinical guidelines. This study aimed to characterise the impact of these changes on the pathways and outcomes of people attended by the SAS) with potential COVID-19.

Methods

A retrospective record linkage cohort study using National Data collected from NHS Scotland over a 5 month period (April–August 2020).

Results

The SAS responded to 214,082 emergency calls during the study time period. The positive predictive value of the Protocol 36 to identify potentially COVID-19 positive patients was low (17%). Approximately 60% of those identified by Protocol 36 as potentially COVID-19 positive were conveyed. The relationship between conveyance and mortality differed between Protocol 36 Covid-19 positive calls and those that were not. In those identified by Protocol 36 as Covid-19 negative, 30 day mortality was higher in those not conveyed (not conveyed 9.2%; conveyed 6.6%) but in the Protocol 36 Covid-19 positive calls, mortality was higher in those conveyed (not conveyed 4.3% conveyed 8.8%). Thirty-day mortality rates of those with COVID-19 diagnosed through virology was between 28.8 and 30.2%.

Conclusion

The low positive predictive value (17%) of Protocol 36 in identifying potential COVID-19 in patients emphasises the importance of ambulance clinicians approaching each call as involving COVID-19, reinforcing the importance of adhering to existing policy and continued use of PPE at all calls. The non-conveyance rate of people that were categorised as COVID-19 negative was higher than in the preceding year in the same service. The reasons for the higher rates of non-conveyance and the relationship between non conveyance rates and death at 3 and 30 days post index call are unknown and would benefit from further study.
Peptide hormone ELABELA promotes rat bone marrow-derived mesenchymal stem cell proliferation and migration by manipulating the cell cycle through the PI3K/AKT pathway under the hypoxia and ischemia microenvironment
Authors: Chen Xuxiang , Zhou Changqing , Xu Daishi , Liu Xin , Li Shuangmei , Hou Jingyu , Zhang Kanglong , Zeng Chaotao , Zheng Guanghui , Wu Haidong , Wu Hao , Wang Wuming , Fu Jiaying , Wang Tong
Published: January 2022

Background

Mesenchymal stem cells (MSCs) are emerging as a potential candidate for stem cell transplantation to repair myocardial tissue in myocardial infarctions (MI). However, there are some pivotal limitations such as poor survival and low migration capacity of MSCs in hypoxic and ischemic microenvironments of MI. Our previous work verified that ELABELA (also abbreviated as ELA), a peptide hormone, could play a role as a growth factor and prolong the life span of rat bone marrow-derived mesenchymal stem cells (RAT BM-MSCs) under hypoxic and ischemic conditions. Nevertheless, the influence of ELA on the cell cycle, proliferation, and migration remains elusive. This study will further explore the improvement of the biological functions of ELA-treated RAT BM-MSCs, so as to provide a reference for improving the efficacy of RAT BM-MSCs in MI.

Methods

Rat BM-MSCs were isolated from 80 to 120 g Sprague Dawley rats by flushing femurs and tibias under the aseptic condition. RAT BM-MSCs of the third passage were divided into control group, hypoxic/ischemic (H/I) group, ELA group, ELA-LY group and LY group. RAT BM-MSCs were cultured under normoxia in control group. In H/I group, RAT BM-MSCs were exposed to hypoxia (1% O2) and serum deprivation for 24 h. RAT BM-MSCs in ELA group were treated with 5 µM ELA prior to the H/I exposure for 24 h. The PI3K/AKT inhibitor, LY294002 (50 µM), was used in ELA-LY group and LY group to observe the effect of ELA on PI3K/AKT activation. Cell proliferation ability was examined by CCK-8. Cell cycle was assessed with flow cytometry. Cell migration was evaluated by Transwell assay. Expression levels of total-AKT, phosphorylated-AKT, and cell cycle-associated proteins were examined by Western blotting.

Results

ELA-treated RAT BM-MSCs exhibited significantly higher proliferation ability, cell viability, and migration under H/I conditions. The cell cycle analysis showed that an increased proportion of cells in the S and G2/M phases of the cell cycle were observed in ELA-treated RAT BM-MSCs. The addition of ELA activated the PI3K/AKT signaling pathway. Additionally, upon treating with the inhibitor of the PI3K/AKT signaling pathway, ELA-triggered proliferation, cell viability, and migration were abrogated.

Conclusions

ELA can be used to enhance the proliferation ability, cell viability, and migration of RAT BM-MSCs through the PI3K/AKT signaling pathway and alleviate cell cycle arrest at the G0/G1 phase under hypoxic and ischemic injury. Thus, this study provides a promising strategy that ELA may help to optimize the mesenchymal stem cell-based therapy in MI.
Prednisolone and mesenchymal stem cell preloading protect liver cell migration and mitigate extracellular matrix modification in transplanted decellularized rat liver
Authors: Yaghoubi Atefeh , Azarpira Negar , Karbalay-Doust Saied , Daneshi Sajad , Vojdani Zahra , Talaei-Khozani Tahereh
Published: January 2022

Introduction

Regenerative medicine provides promising approaches for treating chronic liver diseases. Previous studies indicate that decellularized liver architecture is damaged by invading non-hepatic inflammatory cells. This study aimed to use anti-inflammatory and regenerative potency of bone marrow-derived mesenchymal stem cells (BM-MSC) and prednisolone for reducing fibrosis and balancing inflammatory cell migration into the decellularized liver scaffold.

Material and method

The liver was decellularized by perfusing Sodium Lauryl Ether Sulfate (SLES), and nuclei depletion and extracellular matrix (ECM) retention were confirmed by DNA quantification, histochemical, and immunohistochemical assessments. Scaffolds were loaded with BM-MSCs, prednisolone, or a combination of both, implanted at the anatomical place in the rat partial hepatectomized and followed up for 2 and 4 weeks.

Results

Labeled-MSCs were traced in the transplanted scaffolds; however, they did not migrate into the intact liver. Immunohistochemistry showed that the hepatoblasts, cholangiocytes, stellate, and oval cells invaded into all the scaffolds. Bile ducts were more abundant in the border of the scaffolds and intact liver. Stereological assessments showed a significant reduction in the number of lymphocytes and neutrophils in prednisolone-loaded scaffolds. The regeneration process and angiogenesis were significantly higher in the group treated with cell/prednisolone-loaded bioscaffolds. Collagen fibers were significantly reduced in the scaffolds pre-treated with cell/prednisolone, prednisolone, or BM-MSCs, compared to the control group.

Conclusion

Loading prednisolone into the scaffolds can be a worthy approach to restrict inflammation after transplantation. Although pre-loading of the scaffolds with a combination of cells/prednisolone could not alleviate inflammation, it played an important role in regeneration and angiogenesis.
Ubiquitinated AIF is a major mediator of hypoxia-induced mitochondrial dysfunction and pulmonary artery smooth muscle cell proliferation
Authors: Ma Cui , Wang Xiaoying , He Siyu , Zhang Lixin , Bai June , Qu Lihui , Qi Jing , Zheng Xiaodong , Zhu Xiangrui , Mei Jian , Guan Xiaoyu , Yuan Hao , Zhu Daling
Published: January 2022

Background

Excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) is the main cause of hypoxic pulmonary hypertension (PH), and mitochondrial homeostasis plays a crucial role. However, the specific molecular regulatory mechanism of mitochondrial function in PASMCs remains unclear.

Methods

In this study, using the CCK8 assay, EdU incorporation, flow cytometry, Western blotting, co-IP, mass spectrometry, electron microscopy, immunofluorescence, Seahorse extracellular flux analysis and echocardiography, we investigated the specific involvement of apoptosis-inducing factor (AIF), a mitochondrial oxidoreductase in regulating mitochondrial energy metabolism and mitophagy in PASMCs.

Results

In vitro, AIF deficiency in hypoxia leads to impaired oxidative phosphorylation and increased glycolysis and ROS release because of the loss of mitochondrial complex I activity. AIF was also downregulated and ubiquitinated under hypoxia leading to the abnormal occurrence of mitophagy and autophagy through its interaction with ubiquitin protein UBA52. In vivo, treatment with the adeno-associated virus vector to overexpress AIF protected pulmonary vascular remodeling from dysfunctional and abnormal proliferation.

Conclusions

Taken together, our results identify AIF as a potential therapeutic target for PH and reveal a novel posttranscriptional regulatory mechanism in hypoxia-induced mitochondrial dysfunction.
Rough singular integrals associated to polynomial curves
Authors: Zhang Yulin , Liu Feng
Published: January 2022

In this paper, the authors establish the boundedness of singular integral operators associated to polynomial curves as well as the related maximal operators with rough kernels $\Omega \in H^{1}({\mathrm{S}}^{n-1})$
Ω
∈

H
1

(

S

n
−
1

)
and $h\in \Delta _{\gamma }(\mathbb{R}_{+})$
h
∈

Δ
γ

(

R
+

)
for some $\gamma >1$
γ
>
1
on the Triebel–Lizorkin spaces. It should be pointed out that the bounds are independent of the coefficients of the polynomials in the definition of the operators. The main results of this paper not only improve and generalize essentially some known results but also complement some recent boundedness results.
Stabilization of stochastic regime-switching Poisson jump equations by delay feedback control
Authors: Li Guangjie
Published: January 2022

This paper is concerned with the stabilization of stochastic regime-switching Poisson jump equations (also known as stochastic differential equations with Markovian switching and Poisson jumps, abbreviated as SDEwMJs). The aim of this paper is to design a feedback controller with delay δ ($\delta >0$
δ
>
0
) to make an unstable SDEwMJ become stable. It is proved that the delay δ is bounded by a constant δ̄. Moreover, an implicit lower bound for $\bar{\delta ,}$

δ
,

¯

which can be computed numerically, is provided. As a product, the almost sure exponential stability of the controlled SDEwMJ is obtained. Besides, an example is given to demonstrate the theoretical results.
Dual-plane coupled phase retrieval for non-prior holographic imaging
Authors: Huang Zhengzhong , Memmolo Pasquale , Ferraro Pietro , Cao Liangcai
Published: January 2022

Accurate depiction of waves in temporal and spatial is essential to the investigation of interactions between physical objects and waves. Digital holography (DH) can perform quantitative analysis of wave–matter interactions. Full detector-bandwidth reconstruction can be realized based on in-line DH. But the overlapping of twin images strongly prevents quantitative analysis. For off-axis DH, the object wave and the detector bandwidth need to satisfy certain conditions to perform reconstruction accurately. Here, we present a reliable approach involving a coupled configuration for combining two in-line holograms and one off-axis hologram, using a rapidly converging iterative procedure based on two-plane coupled phase retrieval (TwPCPR) method. It realizes a fast-convergence holographic calculation method. High-resolution and full-field reconstruction by exploiting the full bandwidth are demonstrated for complex-amplitude reconstruction. Off-axis optimization phase provides an effective initial guess to avoid stagnation and minimize the required measurements of multi-plane phase retrieval. The proposed strategy works well for more extended samples without any prior assumptions of the objects including support, non-negative, sparse constraints, etc. It helps to enhance and empower applications in wavefront sensing, computational microscopy and biological tissue analysis.