bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

AbstractBackgroundAerobic 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.MethodsWe 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.ResultsA 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.ConclusionsFuture 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundMesenchymal 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.MethodsRat 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.ResultsELA-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.ConclusionsELA 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

AbstractIntroductionRegenerative 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 methodThe 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.ResultsLabeled-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.ConclusionLoading 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

AbstractBackgroundExcessive 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.MethodsIn 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.ResultsIn 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.ConclusionsTaken together, our results identify AIF as a potential therapeutic target for PH and reveal a novel posttranscriptional regulatory mechanism in hypoxia-induced mitochondrial dysfunction.