bluuebunny/crossref_metadata_2025 huggingface dataset:
The neuropeptide calcitonin gene-related peptide links perineural invasion with lymph node metastasis in oral squamous cell carcinoma
Authors: Zhang Yu , Chen Mingtao , Liu Zheqi , Wang Xu , Ji Tong
Published: November 2021

Objective

Although perineural invasion (PNI) is well-known to be correlated with and able to predict lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC), the clinical and molecular correlation between PNI and LNM has not been elucidated, and preoperative biomarkers for LNM prediction in OSCC are urgently needed.

Materials and methods

The correlation between PNI and LNM was retrospectively evaluated using a cohort of 218 patients diagnosed with OSCC. Candidate neuropeptides were screened based on TCGA database and verified via immunohistochemistry and Western blot analyses. ELISA was used to detect calcitonin gene-related peptide (CGRP) in patient plasma. In vitro assays were used to explore the effects of CGRP on OSCC cells.

Results

OSCC patients with PNI had a higher incidence of LNM (69.86% vs. 26.2%, P < 0.0001, n = 218). CGRP expression was upregulated in the PNI niche and in metastatic lymph nodes, and was correlated with poor overall survival of OSCC patients. Preoperative plasma CGRP levels were higher in OSCC patients (n = 70) compared to healthy donors (n = 60) (48.59 vs. 14.58 pg/ml, P < 0.0001), and were correlated with LNM (P < 0.0001) and PNI (P = 0.0002). Preoperative plasma CGRP levels alone yielded an AUC value of 0.8088 to predict LNM, and CGRP levels combined with preoperative T stage reached an AUC value of 0.8590. CGRP promoted proliferation and migration abilities of OSCC cells, which could be antagonized by either pharmacological or genetic blockade of the CGRP receptor.

Conclusions

The neuropeptide CGRP links PNI and LNM in OSCC, and preoperative plasma CGRP levels can be used to predict LNM in OSCC.
Fatigue in children and adolescents perinatally infected with human immunodeficiency virus: an observational study
Authors: ter Haar A. M. , der Vlist M. M. Nap-van , Van den Hof M. , Nijhof S. L. , van Litsenburg R. R. L. , Oostrom K. J. , Pajkrt D.
Published: November 2021

Background

Fatigue is common among adults living with human immunodeficiency virus (HIV) as well as children with a chronic disease (CCD). Fatigue can have disastrous effects on health status, including health related quality of life (HRQOL). Even so, fatigue is underexplored in children and adolescents perinatally infected with HIV (PHIV+) in the Netherlands. The objective of this observational study is to explore fatigue in PHIV+ and its association with their HRQOL.

Methods

We measured HRQOL and fatigue using the Pediatric Quality of Life Inventory™ (PedsQL 4.0) and the PedsQL Multidimensional Fatigue Scale (MFS). The PedsQL MFS encompasses three subscales: general fatigue, sleep/rest fatigue and cognitive fatigue, and a total fatigue score. We compared outcomes of PHIV+ children and adolescents in the Amsterdam University Medical Centre with three groups: 1) HIV-uninfected controls (HIV-) matched for age, sex, region of birth, socioeconomic status and adoption status, 2) CCD, and 3) the general Dutch population. Within the PHIV+ group we explored associations between fatigue and HRQOL.

Results

We enrolled 14 PHIV+ (median age 10.2 years [IQR 9.2–11.4]) and 14 HIV-. Compared to CCD, PHIV+ significantly reported less general fatigue (mean difference 13.0, 95% CI 1.3 to 24.8). PHIV+ did not score significantly different on any of the other PedsQL MFS scales compared to HIV-, CCD or the general Dutch population. PHIV children scored relatively low on the cognitive fatigue scale in comparison to HIV-uninfected matched controls, CCD and the general population, although these differences did not reach significance. Among PHIV+, a lower score on total fatigue, general fatigue and cognitive fatigue was associated with a lower HRQOL score.

Conclusions

The results of this study suggest that PHIV children and adolescents do not experience more symptoms of fatigue than their healthy peers. However, PHIV children and adolescents may be more likely to experience cognitive fatigue. Fatigue in PHIV also appears to be associated with children’s HRQOL. Further research should confirm these exploratory findings.
The effects of self-management interventions on depressive symptoms in adults with chronic physical disease(s) experiencing depressive symptomatology: a systematic review and meta-analysis
Authors: Ould Brahim Lydia , Lambert Sylvie D. , Feeley Nancy , Coumoundouros Chelsea , Schaffler Jamie , McCusker Jane , Moodie Erica E. M. , Kayser John , Kolne Kendall , Belzile Eric , Genest Christine
Published: November 2021

Background

Chronic diseases are the leading cause of death worldwide. It is estimated that 20% of adults with chronic physical diseases experience concomitant depression, increasing their risk of morbidity and mortality. Low intensity psychosocial interventions, such as self-management, are part of recommended treatment; however, no systematic review has evaluated the effects of depression self-management interventions for this population. The primary objective was to examine the effect of self-management interventions on reducing depressive symptomatology in adults with chronic disease(s) and co-occurring depressive symptoms. Secondary objectives were to evaluate the effect of these interventions on improving other psychosocial and physiological outcomes (e.g., anxiety, glycemic control) and to assess potential differential effect based on key participant and intervention characteristics (e.g., chronic disease, provider).

Methods

Studies comparing depression self-management interventions to a control group were identified through a) systematic searches of databases to June 2018 [MEDLINE (1946 -), EMBASE (1996 -), PsycINFO (1967 -), CINAHL (1984 -)] and b) secondary ‘snowball’ search strategies. The methodological quality of included studies was critically reviewed. Screening of all titles, abstracts, and full texts for eligibility was assessed independently by two authors. Data were extracted by one author and verified by a second.

Results

Fifteen studies were retained: 12 for meta-analysis and three for descriptive review. In total, these trials included 2064 participants and most commonly evaluated interventions for people with cancer (n = 7) or diabetes (n = 4). From baseline to < 6-months (T1), the pooled mean effect size was − 0.47 [95% CI −0.73, − 0.21] as compared to control groups for the primary outcome of depression and − 0.53 [95% CI −0.91, − 0.15] at ≥ 6-months (T2). Results were also significant for anxiety (T1) and glycemic control (T2). Self-management skills of decision-making and taking action were significant moderators of depression at T1.

Conclusion

Self-management interventions show promise in improving depression and anxiety in those with concomitant chronic physical disease. The findings may contribute to the development of future Self-management interventions and delivering evidence-based care to this population. Further high-quality RCTs are needed to identify sources of heterogeneity and investigate key intervention components.
Using prediction polling to harness collective intelligence for disease forecasting
Authors: Sell Tara Kirk , Warmbrod Kelsey Lane , Watson Crystal , Trotochaud Marc , Martin Elena , Ravi Sanjana J. , Balick Maurice , Servan-Schreiber Emile
Published: November 2021

Background

The global spread of COVID-19 has shown that reliable forecasting of public health related outcomes is important but lacking.

Methods

We report the results of the first large-scale, long-term experiment in crowd-forecasting of infectious-disease outbreaks, where a total of 562 volunteer participants competed over 15 months to make forecasts on 61 questions with a total of 217 possible answers regarding 19 diseases.

Results

Consistent with the “wisdom of crowds” phenomenon, we found that crowd forecasts aggregated using best-practice adaptive algorithms are well-calibrated, accurate, timely, and outperform all individual forecasters.

Conclusions

Crowd forecasting efforts in public health may be a useful addition to traditional disease surveillance, modeling, and other approaches to evidence-based decision making for infectious disease outbreaks.
Preventing opioid use among justice-involved youth as they transition to adulthood: leveraging safe adults (LeSA)
Authors: Knight Danica Kalling , Yang Yang , Joseph Elizabeth D. , Tinius Elaine , Young Shatoya , Shelley Lillyan T. , Cross David R. , Knight Kevin
Published: November 2021

Background

Juvenile justice (JJ) youth are at high risk of opioid and other substance use (SU), dysfunctional family/social relationships, and complex trauma. The purpose of the Leveraging Safe Adults (LeSA) Project is to examine the effectiveness of Trust-Based Relational Intervention® (TBRI®; leveraging family systems by providing emotional and instrumental guidance, support, and role modeling) in preventing opioid and other SU among youth after release from secure residential facilities.

Methods

An effectiveness-implementation Hybrid Type 1 design is used to test the effectiveness of TBRI for preventing non-medical use of opioids among JJ-youth (delayed-start at the site level; a randomized controlled trial at participant level) and to gain insight into facility-level barriers to TBRI implementation as part of JJ re-entry protocols. Recruitment includes two samples (effectiveness: 360 youth/caregiver dyads; implementation: 203 JJ staff) from nine sites in two states over 3 years. Participant eligibility includes 15 to 18-year-olds disposed to community supervision and receiving care in a secure JJ facility, without active suicide risk, and with one caregiver willing to participate. Effectiveness data come from (1) youth and caregiver self-report on background, SU, psychosocial functioning, and youth-caregiver relationships (Months 0, 3, 6, 12, and 18), youth monthly post-release check-ins, and caregiver report on youth psychological/behavioral symptoms, and (2) JJ facility records (e.g., recidivism, treatment utilization). Fidelity assessment includes post-session checklists and measures of TBRI strategy use. Collected four times over four years, implementation data include (1) JJ staff self-report on facility and staff characteristics, use of trauma-informed care and TBRI strategies, and (2) focus groups (line staff, leadership separately) on use of trauma-informed strategies, uptake of new interventions, and penetration, sustainment, and expansion of TBRI practices.

Discussion

The LeSA study is testing TBRI as a means to empower caregivers to help prevent opioid use and other SU among JJ-youth. TBRI’s multiple components offer an opportunity for caregivers to supplement and extend gains during residential care. If effective and implemented successfully, the LeSA protocol will help expand the application of TBRI with a wider audience and provide guidance for implementing multi-component interventions in complex systems spanning multiple contexts.

Trial registration

ClinicalTrials.govNCT04678960; registered November 11, 2020; https://clinicaltrials.gov/ct2/show/NCT04678960.
Tobacco messages encountered in real-time among low socio-economic position groups: a descriptive study
Authors: Stevens Elise M. , Vázquez-Otero Coralia , Li Xiaoyan , Arya Monisha , Vallone Donna , Minsky Sara , Osgood Nathaniel D. , Viswanath Kasisomayajula
Published: November 2021

Background

Tobacco advertising disproportionately targets low socio-economic position (SEP) groups, causing higher rates of tobacco use in this population. Anti-tobacco public health education campaigns persuade against use. This study measured real-time exposure of pro- and anti-tobacco messages from low SEP groups in two American cities.

Methods

Individuals in low SEP groups (N = 95), aged 18–34 years old, who were smokers and non-smokers, from the Boston and Houston areas, took part in a mobile health study. They submitted images of tobacco-related messages they encountered via a mobile application for a 7-week period. Two coders analyzed the images for message characteristics. Intercoder reliability was established using Krippendorff’s alpha and data were analyzed descriptively.

Results

Of the submitted images (N = 131), 83 were pro-tobacco and 53 were anti-tobacco. Of the pro-tobacco messages, the majority were cigarette ads (80.7%) seen outside (36.1%) or inside (30.1%) a convenience store or gas station and used conventional themes (e.g., price promotion; 53.2%). Of the anti-tobacco messages, 56.6% were sponsored by public health campaigns or were signage prohibiting smoking in a public area (39.6%). Most focused on the health harms of smoking (28.3%).

Conclusion

Low SEP groups in this study encountered more pro-tobacco than anti-tobacco messages at places that were point-of-sale using price promotions to appeal to this group. Anti-tobacco messages at point-of-sale and/or advertising regulations may help combat tobacco use.
Combining prostate health index and multiparametric magnetic resonance imaging in estimating the histological diameter of prostate cancer
Authors: Hsieh Po-Fan , Li Tzung-Ruei , Lin Wei-Ching , Chang Han , Huang Chi-Ping , Chang Chao-Hsiang , Yang Chi-Rei , Yeh Chin-Chung , Huang Wen-Chin , Wu Hsi-Chin
Published: November 2021

Background

Although multiparametric magnetic resonance imaging (mpMRI) is widely used to assess the volume of prostate cancer, it often underestimates the histological tumor boundary. The aim of this study was to evaluate the feasibility of combining prostate health index (PHI) and mpMRI to estimate the histological tumor diameter and determine the safety margin during treatment of prostate cancer.

Methods

We retrospectively enrolled 72 prostate cancer patients who underwent radical prostatectomy and had received PHI tests and mpMRI before surgery. We compared the discrepancy between histological and radiological tumor diameter stratified by Prostate Imaging-Reporting and Data System (PI-RADS) score, and then assessed the influence of PHI on the discrepancy between low PI-RADS (2 or 3) and high PI-RADS (4 or 5) groups.

Results

The mean radiological and histological tumor diameters were 1.60 cm and 2.13 cm, respectively. The median discrepancy between radiological and histological tumor diameter of PI-RADS 4 or 5 lesions was significantly greater than that of PI-RADS 2 or 3 lesions (0.50 cm, IQR (0.00–0.90) vs. 0.00 cm, IQR (−0.10–0.20), p = 0.02). In the low PI-RADS group, the upper limit of the discrepancy was 0.2 cm; so the safety margin could be set at 0.1 cm. In the high PI-RADS group, the upper limits of the discrepancy were 1.2, 1.6, and 2.2 cm in men with PHI < 30, 30–60, and > 60; so the safety margin could be set at 0.6, 0.8, and 1.1 cm, respectively.

Conclusions

Radiological tumor diameter on mpMRI often underestimated the histological tumor diameter, especially for PI-RADS 4 or 5 lesions. Combining mpMRI and PHI may help to better estimate the histological tumor diameter.
The PARADIGHM (physicians advancing disease knowledge in hypoparathyroidism) registry for patients with chronic hypoparathyroidism: study protocol and interim baseline patient characteristics
Authors: Gittoes Neil , Rejnmark Lars , Ing Steven W. , Brandi Maria Luisa , Björnsdottir Sigridur , Hahner Stefanie , Hofbauer Lorenz C. , Houillier Pascal , Khan Aliya A. , Levine Michael A. , Mannstadt Michael , Shoback Dolores M. , Vokes Tamara J. , Zhang Pinggao , Marelli Claudio , Germak John , Clarke Bart L.
Published: November 2021

Background

The PARADIGHM registry of adult and pediatric patients with chronic hypoparathyroidism evaluates the long-term safety and effectiveness of treatment with recombinant human parathyroid hormone, rhPTH(1-84), and describes the clinical disease course under conditions of routine clinical practice. In this first report, we detail the registry protocol and describe the baseline characteristics of two adult patient cohorts from an interim database analysis. One cohort after study entry were prescribed rhPTH(1-84), and the other cohort received conventional therapy of calcium and active vitamin D.

Methods

An observational study of patients with chronic hypoparathyroidism in North America and Europe, collecting data for ≥10 years per patient. Main outcome measures were baseline patient demographics, clinical characteristics, medications, and disease outcome variables of symptoms, biochemical parameters, and health assessments. Baseline is the enrollment assessment for all variables except biochemical measurements in patients treated with rhPTH(1-84); those measurements were the most recent value before the first rhPTH(1-84) dose. Exclusion criteria applied to the analysis of specified outcomes included pediatric patients, patients who initiated rhPTH(1-84) prior to enrollment, and those who received rhPTH(1-34). Clinically implausible biochemical outlier data were excluded.

Results

As of 30 June 2019, data of 737 patients were analyzed from 64 centers; 587 (80%) were women, mean ± SD age 49.1±16.45 years. At enrollment, symptoms reported for patients later prescribed rhPTH(1-84) (n=60) and those who received conventional therapy (n=571), respectively, included fatigue (51.7%, 40.1%), paresthesia (51.7%, 29.6%), muscle twitching (48.3%, 21.9%), and muscle cramping (41.7%, 33.8%). Mean serum total calcium, serum phosphate, creatinine, and estimated glomerular filtration rate were similar between cohorts. Health-related quality of life (HRQoL) 36-item Short Form Health Survey questionnaire scores for those later prescribed rhPTH(1-84) were generally lower than those for patients in the conventional therapy cohort.

Conclusions

At enrollment, based on symptoms and HRQoL, a greater percentage of patients subsequently prescribed rhPTH(1-84) appeared to have an increased burden of disease than those who received conventional therapy despite having normal biochemistry measurements. PARADIGHM will provide valuable real-world insights on the clinical course of hypoparathyroidism in patients treated with rhPTH(1-84) or conventional therapy in routine clinical practice.

Trial registration

EUPAS16927, NCT01922440
Sinoacutine inhibits inflammatory responses to attenuates acute lung injury by regulating NF-κB and JNK signaling pathways
Authors: Zhao Yuancui , Cui Lili , Yang Xing Xin , Sun Xingqian , Liu Yunkuan , Yang Zixian , Zhu Liyuan , Peng Chaorui , Li Danye , Cai Junfei , Ma Yunshu
Published: November 2021

Background

Stephania yunnanensisH. S. Lo is widely used as an antipyretic, analgesic and anti-inflammatory herbal medicine in SouthWest China. In this study, we investigated the anti-inflammatory activity and mechanism of sinoacutine (sino), one of the primary components extracted from this plant.

Methods

A RAW264.7 cell model was established using lipopolysaccharide (LPS) induced for estimation of cytokines in vitro, qPCR was used to estimate gene expression, western blot analysis was used to estimate protein level and investigate the regulation of NF- κB, JNK and MAPK signal pathway. In addition, an acute lung injury model was established to determine lung index and levels of influencing factors.

Results

Using the RAW264.7 model, we found that sino reduced levels of nitric oxide (NO), tumour necrosis factor-α (TNF-α), interleukin (IL)-1β and prostaglandin E2(PGE2) but increased levels of IL-6. qPCR analysis revealed that sino (50, 25 μg/ml) inhibited gene expression of nitric oxide synthase (iNOS). western blot analysis showed that sino significantly inhibited protein levels of both iNOS and COX-2. Further signalling pathway analysis validated that sino also inhibited phosphorylation of p65 in the NF-κB and c-Jun NH2 terminal kinase (JNK) signalling pathways but promoted the phosphorylation of extracellular signal regulated kinase (ERK) and p38 in the MAPK signalling pathway. In addition, in a mouse model induced by LPS, we determined that sino reduced the lung index and the levels of myeloperoxidase (MPO), NO, IL-6 and TNF-α in lung tissues and bronchoalveolar lavage fluid (BALF) in acute lung injury (ALI).

Conclusion

Taken together, our results demonstrate that sino is a promising drug to alleviate LPS-induced inflammatory reactions.
Retaining interest in caring for underserved patients among future medicine subspecialists: Underserved Medicine and Public Health (UMPH) program
Authors: Catalanotti Jillian S. , Popiel David K. , Barbour April
Published: November 2021

Background

Accessing subspecialty care is hard for underserved patients in the U.S. Published curricula in underserved medicine for Internal Medicine residents target future-primary care physicians, with unknown impact on future medicine subspecialists.

Methods

The aim was to retain interest in caring for underserved patients among Internal Medicine residents who plan for subspecialist careers at an urban university hospital. The two-year Underserved Medicine and Public Health (UMPH) program features community-based clinics, evening seminars, reflection assignments and practicum projects for 3–7 Internal Medicine residents per year. All may apply regardless of anticipated career plans after residency. Seven years of graduates were surveyed. Data were analyzed using descriptive statistics.

Results

According to respondents, UMPH provided a meaningful forum to discuss important issues in underserved medicine, fostered interest in treating underserved populations and provided a sense of belonging to a community of providers committed to underserved medicine. After residency, 48% of UMPH graduates pursued subspecialty training and 34% practiced hospitalist medicine. 65% of respondents disagreed that “UMPH made me more likely to practice primary care” and 59% agreed “UMPH should target residents pursuing subpecialty careers.”

Conclusions

A curriculum in underserved medicine can retain interest in caring for underserved patients among future-medicine subspecialists. Lessons learned include [1] building relationships with local community health centers and community-practicing physicians was important for success and [2] thoughtful scheduling promoted high resident attendance at program events and avoided detracting from other activities required during residency for subspecialist career paths. We hope Internal Medicine residency programs consider training in underserved medicine for all trainees. Future work should investigate sustainability, whether training results in improved subspecialty access, and whether subspecialists face unique barriers caring for underserved patients. Future curricula should include advocacy skills to target systemic barriers.
A novel approach to educate hospitalized cardiovascular disease patients about lifestyle and behavior modifications
Authors: Saboktakin Atiyeh , Sepehri Mohammad Mehdi , Khasha Roghaye
Published: November 2021

Background

Cardiovascular diseases (CVDs) are always considered by healthcare specialists for different reasons, including extensive prevalence, increased costs, chronicity, and high risk of death. The control of CVDs is highly influenced by behavior and lifestyle and it seems necessary to train special abilities about lifestyle and behavior modification to improve self-care skills for patients, and their caregivers. As a result, the development of effective training systems should be considered by healthcare specialists.

Methods

Hence, in this study, a framework for improving cardiovascular patients’ education processes is presented. Initially, an existing training system for cardiovascular patients is reviewed. Using field observations and targeted interviews with hospital experts, all components of its educating processes are identified, and their process maps are drawn up. After that, challenges in the training system are extracted with the aid of in-depth semi-structured interviews with experts. Due to the importance and different influence of the identified challenges, they are prioritized using a Multiple Criteria Decision-making (MCDM) method, and then their root causes were investigated. Finally, a novel framework is proposed and evaluated with hospital experts' help to improve the main challenges.

Results

The most important challenges included high nursing workload and shortage of time, lack of understanding of training concepts by patients, lack of attention to training, disruption of the training processes by the patients’ caregivers, and patient's weakness in understanding the standard language. In identifying the root causes, learner, educator, and educational tools are the most effective in the training process; therefore, the improvement scenarios were designed accordingly in the proposed framework.

Conclusions

Our study indicated that presenting a framework with applying different quantitative and qualitative methods has great potential to improve the processes of patient education for chronic diseases such as cardiovascular disease.
Social inclusion and violence prevention in psychiatric inpatient care. A qualitative interview study with service users, staff members and ward managers
Authors: Pelto-Piri Veikko , Kjellin Lars
Published: November 2021

Background

Many psychiatric services include social inclusion as a policy with the aim to offer users the opportunity to participate in care and to form reciprocal relationships. The aim of this study was to explore opportunities and problems with regard to participation, reciprocity and social justice that different stakeholders experience when it comes to social inclusion for service users and minimizing violence in psychiatric inpatient care.

Methods

Qualitative interviews were performed with 12 service users, 15 staff members, and six ward managers in three different kinds of psychiatric wards in Sweden. The data were analyzed using the framework method and qualitative content analysis, which was based on the three following social inclusion values: participation, reciprocity, and social justice.

Results

Themes and subthemes were inductively constructed within the three social inclusion values. For participation, staff and ward managers reported difficulties in involving service users in their care, while service users did not feel that they participated and worried about what would happen after discharge. Staff gave more positive descriptions of their relationships with service users and the possibility for reciprocity. Service users described a lack of social justice, such as disruptive care, a lack of support from services, not having access to care, or negative experiences of coercive measures. Despite this, service users often saw the ward as being safer than outside the hospital. Staff and managers reported worries about staffing, staff competence, minimizing coercion and violence, and a lack of support from the management.

Conclusions

By applying the tentative model on empirical data we identified factors that can support or disrupt the process to create a safe ward where service users can feel socially included. Our results indicate that that staff and service users may have different views on the reciprocity of their relationships, and that users may experience a lack of social justice. The users may, due to harsh living conditions, be more concerned about the risk of violence in the community than as inpatients. Staff and ward managers need support from the management to foster a sense of community in the ward and to implement evidence-based prevention programs.
Implementation and performance of haemovigilance systems in 10 sub-saharan African countries is sub-optimal
Authors: Samukange Washington T. , Kluempers Verena , Porwal Manvi , Mudyiwenyama Linda , Mutoti Khamusi , Aineplan Noel , Gardarsdottir Helga , Mantel-Teeuwisse Aukje K. , Nuebling C. Micha
Published: November 2021

Background

Haemovigilance is an important element of blood regulation. It includes collecting and evaluating the information on adverse events resulting from the use of blood and blood components with the aim to improve donor and patient safety. We describe the results of the pilot of the integrated GBT+ Blood for the haemovigilance function in 10 sub-Saharan African countries.

Methods

We piloted the integrated WHO Global Benchmarking Tool plus Blood (GBT+ Blood) to assess the haemovigilance function of national regulatory authorities (NRAs) in Ethiopia, Kenya, Malawi, Nigeria, Liberia, Rwanda, South Africa, Tanzania, Uganda, and Zimbabwe. Data obtained from documents and face to face interviews were used to determine the status of implementation and performance of the following six indicators; legal provisions regulations and guidelines, organisation and governance, human resources, regulatory processes, transparency and accountability and finally, monitoring progress and assessing impact, by estimating median scores across 20 sub-indicators. In addition, a cluster analysis was performed.

Results

The countries showed inter-organisation variability in implementation and performance of the haemovigilance function. The overall median score (all sub-indicators) was 44 % (range: 7.5 % - 70 %). The lowest average performance scores were for the arrangement for effective organisation and coordination (35 %) and human resources (35 %) indicators. The highest average scores were observed for the mechanism to promote transparency and mechanism to monitor regulatory performance indicators (50 % and 60 %, respectively). We identified clusters of best-implemented sub-indicators from the procedures for haemovigilance and poorly implemented sub-indicators from the legal provisions, regulations and guidelines for haemovigilance and human resources.

Conclusions

Implementation of sub-indicators and performance of haemovigilance systems varied greatly for all countries with a few countries performing reasonably well in the implementation of some sub-indicators under procedures for haemovigilance. Most countries were poorly implementing sub-indicators in the legal provisions, arrangement for effective organisation and human resources indicators. The legislative provisions in most countries were at a nascent stage. There is a need to set up targeted and customised technical support coupled with prioritised interventions to strengthen the capacities of NRAs.
Functional analyses of phosphatidylserine/PI(4)P exchangers with diverse lipid species and membrane contexts reveal unanticipated rules on lipid transfer
Authors: Ikhlef Souade , Lipp Nicolas-Frédéric , Delfosse Vanessa , Fuggetta Nicolas , Bourguet William , Magdeleine Maud , Drin Guillaume
Published: November 2021

Background

Lipid species are accurately distributed in the eukaryotic cell so that organelle and plasma membranes have an adequate lipid composition to support numerous cellular functions. In the plasma membrane, a precise regulation of the level of lipids such as phosphatidylserine, PI(4)P, and PI(4,5)P2, is critical for maintaining the signaling competence of the cell. Several lipid transfer proteins of the ORP/Osh family contribute to this fine-tuning by delivering PS, synthesized in the endoplasmic reticulum, to the plasma membrane in exchange for PI(4)P. To get insights into the role of these PS/PI(4)P exchangers in regulating plasma membrane features, we question how they selectively recognize and transfer lipid ligands with different acyl chains, whether these proteins exchange PS exclusively for PI(4)P or additionally for PI(4,5)P2, and how sterol abundance in the plasma membrane impacts their activity.

Results

We measured in vitro how the yeast Osh6p and human ORP8 transported PS and PI(4)P subspecies of diverse length and unsaturation degree between membranes by fluorescence-based assays. We established that the exchange activity of Osh6p and ORP8 strongly depends on whether these ligands are saturated or not, and is high with representative cellular PS and PI(4)P subspecies. Unexpectedly, we found that the speed at which these proteins individually transfer lipid ligands between membranes is inversely related to their affinity for them and that high-affinity ligands must be exchanged to be transferred more rapidly. Next we determined that Osh6p and ORP8 cannot use PI(4,5)P2 for exchange processes, because it is a low-affinity ligand, and do not transfer more PS into sterol-rich membranes.

Conclusions

Our study provides new insights into PS/PI(4)P exchangers by indicating the degree to which they can regulate the acyl chain composition of the PM, and how they control PM phosphoinositide levels. Moreover, we establish general rules on how the activity of lipid transfer proteins relates to their affinity for ligands.
Changes in metabolic and hormonal profiles during transition period in dairy cattle – the role of spexin
Authors: Mikuła Robert , Pruszyńska-Oszmałek Ewa , Pszczola Marcin , Rząsińska Justyna , Sassek Maciej , Nowak Krzysztof W. , Nogowski Leszek , Kołodziejski Paweł A.
Published: November 2021

Background

This study aimed to evaluate spexin as a novel blood marker and to describe the relationship of this peptide with selected biochemical metabolites measured during the transition period in dairy cows. Additionally, mRNA expression of the spexin gene as well as spexin receptors – galanin receptor type 2 and galanin receptor type 3, was investigated in several bovine tissues. Blood samples were collected at weekly intervals starting at 21 days before the estimated parturition day until 21 days in milk to determine concentrations of spexin, nonesterified fatty acids, β-hydroxybutyrate acid, total and active ghrelin, progesterone, glucose, insulin, IGF–I, triglycerides, cholesterol, leptin, corticosterone and 17-β-estradiol as well as the activity of aspartate transaminase, alkaline phosphatase and gamma-glutamyl transferase.

Results

Spexin concentration decreased from 21 d before parturition to calving day and next it rose during the first 14 d of lactation. The lowest concentration of spexin was recorded on the calving day and it differed from the mean level of this peptide before parturition as well as postpartum. Moreover, differences were observed between mean spexin concentrations before and after calving. Spexin levels were moderately negatively correlated with NEFA (r = − 0.39) and total ghrelin contents (r = − 0.41), weakly correlated with BHBA (r = − 0.35) while they showed a moderate positive relationship with progesterone concentrations (r = 0.42). Moreover, we detected that mRNA expression of GALR2, GALR3 and SPX is present in various bovine tissues (kidney, bowel, rumen, spinal cord, lung, skeletal muscle, liver, heart, fat and spleen).

Conclusion

A negative correlation between spexin concentration and NEFA, BHBA and total ghrelin contents as well as a positive relationship with levels of progesterone, metabolites and hormones, which are key players in the dairy cow transition period, may confirm an important function of this peptide in metabolism regulation. Thus measurement of spexin concentration could provide useful supplementary information for dairy cow herd health monitoring.
Developmental endothelial locus-1 as a potential biomarker for the incidence of acute exacerbation in patients with chronic obstructive pulmonary disease
Authors: Joo Dong-Hyun , Lee Kyoung-Hee , Lee Chang-Hoon , Woo Jisu , Kim Jiyeon , Park Seoung Ju , Rhee Chin Kook , Lee Won-Yeon , Park Dongil , Lee Jae Seung , Jung Ki-Suck , Yoo Kwang Ha , Yoo Chul-Gyu
Published: November 2021

Background

Despite the high disease burden of chronic obstructive pulmonary disease (COPD) and risk of acute COPD exacerbation, few COPD biomarkers are available. As developmental endothelial locus-1 (DEL-1) has been proposed to possess beneficial effects, including anti-inflammatory effects, we hypothesized that DEL-1 could be a blood biomarker for COPD.

Objective

To elucidate the role of plasma DEL-1 as a biomarker of COPD in terms of pathogenesis and for predicting acute exacerbation.

Methods

Cigarette smoke extract (CSE) or saline was intratracheally administered to wild-type (WT) and DEL-1 knockout (KO) C57BL/6 mice. Subsequently, lung sections were obtained to quantify the degree of emphysema using the mean linear intercept (MLI). Additionally, plasma DEL-1 levels were compared between COPD and non-COPD participants recruited in ongoing prospective cohorts. Using negative binomial regression analysis, the association between the plasma DEL-1 level and subsequent acute exacerbation risk was evaluated in patients with COPD.

Results

In the in vivo study, DEL-1 KO induced emphysema (KO saline vs. WT saline; P = 0.003) and augmented CSE-induced emphysema (KO CSE vs. WT CSE; P < 0.001) in 29 mice. Among 537 participants, patients with COPD presented plasma log (DEL-1) levels lower than non-COPD participants (P = 0.04), especially non-COPD never smokers (P = 0.019). During 1.2 ± 0.3 years, patients with COPD in the lowest quartile of Log(DEL-1) demonstrated an increased risk of subsequent acute exacerbation, compared with those in the highest quartile of Log(DEL-1) (adjusted incidence rate ratio, 3.64; 95% confidence interval, 1.03–12.9).

Conclusion

Low DEL-1 levels are associated with COPD development and increased risk of subsequent COPD acute exacerbation. DEL-1 can be a useful biomarker in patients with COPD.
Time-varying regularity of changes in biomechanical properties of the corneas after removal of anterior corneal tissue
Authors: Zhang Di , Qin Xiao , Zhang Haixia , Li Lin
Published: November 2021

Background

The corneal biomechanical properties with the prolongation of time after corneal refractive surgery are important for providing a mechanical basis for the occurrence of clinical phenomena such as iatrogenic keratectasia and refractive regression. The aim of this study was to explore the changes of corneal elastic modulus, and stress relaxation properties from the 6-month follow-up observations of rabbits after a removal of anterior corneal tissue in simulation to corneal refractive surgery.

Methods

The anterior corneal tissue, 6 mm in diameter and 30–50% of the original corneal thickness, the left eye of the rabbit was removed, and the right eye was kept as the control. The rabbits were normally raised and nursed for 6 months, during which corneal morphology data, and both of corneal hysteresis (CH) and corneal resistance factor (CRF) were gathered. Uniaxial tensile tests of corneal strips were performed at months 1, 3, and 6 from 7 animals, and corneal collagen fibrils were observed at months 1, 3, and 6 from 1 rabbit, respectively.

Results

Compared with the control group, there were statistical differences in the curvature radius at week 2 and month 3, and both CH and CRF at months 1, 2, and 6 in experiment group; there were statistical differences in elastic modulus at 1, 3, and month 6, and stress relaxation degree at month 3 in experiment group. The differences in corneal elastic modulus, stress relaxation degree and the total number of collagen fibrils between experiment and control groups varied gradually with time, and showed significant changes at the 3rd month after the treatment.

Conclusions

Corneas after a removal of anterior corneal tissue undergo dynamic changes in corneal morphology and biomechanical properties. The first 3 months after treatment could be a critical period. The variation of corneal biomechanical properties is worth considering in predicting corneal deformation after a removal of anterior corneal tissue.
Inflammatory myofibroblastic tumour of an unusual presentation in the uterine cervix: a case report
Authors: López de Sa Alfonso , Pascual Alejandro , Garcia Santos Javier , Mendez Ramiro , Bellon Monica , Ramirez Mar , Matute Fatima , del Arco Cristina , Manzano Aránzazu , Coronado Pluvio , Casado Antonio , Marquina Gloria
Published: November 2021

Background

Inflammatory myofibroblastic tumour is an infrequent mesenchymal neoplasia of unknown aetiology and variable behaviour, ranging from rather benign lesions to locally aggressive and even metastatic disease. Its presence has been described in almost all organs; however, its location in the female genital tract has rarely been reported.

Case presentation

We present the case of a 47-year-old female, who was studied in our institution for a recent medical history of several weeks of dyspareunia and abdominal pain. She underwent pertinent studies including ultrasonography and CT scan. Under suspicion of degenerated leiomyoma, a total hysterectomy was performed. Unexpectedly, the pathological study of the surgical specimen showed very few tumour cells with focal fusiform morphology surrounded by an abundant inflammatory infiltrate; a thorough immunohistochemistry study lead to myofibroblastic tumour of the cervix diagnosis. A PET-CT scan did not show metastatic disease. The patient did not undergo any adjuvant treatment, and she is currently on surveillance with no evidence of disease relapse.

Conclusions

Inflammatory myofibroblastic tumour remains a rare entity yet to be fully elucidated. The diagnosis is based on pathological study due to the lack of typical clinical manifestations and typical radiological images. Surgical resection is the most frequent treatment, whereas chemotherapy and radiotherapy are restricted to locally advanced or metastatic disease. Tirosine kinase inhibitor crizotinib has shown promising results especially in tumours harbouring ALK mutation.
Effectiveness of checklist-based box system intervention (CBBSI) versus routine care on improving postnatal care utilization in Northwest Ethiopia: a cluster randomized controlled trial
Authors: Andargie Netsanet Belete , Debelew Gurmesa Tura
Published: November 2021

Background

The period after childbirth poses a substantial risk both to the mother and the newborn. Yet, this period received less attention as compared to the cares provided during pregnancy and childbirth. Hence, this study aimed to assess the effectiveness of checklist-based box system intervention on improving three postnatal care visit utilization.

Methods

A double blind, parallel group, two-arm cluster randomized controlled trial design was used to assess effectiveness of checklist-based box system intervention on improving third postnatal care visit. Pregnant mothers below 16 weeks of gestation were recruited from 15 intervention and 15 control clusters, which were randomized using simple randomization. Data from baseline and end line surveys were collected using open data kit and analyzed using STATA version 15.0. The status of three postnatal care visit between intervention and control groups over time was assessed using difference in difference estimator. The predictors of the outcome variable were then analysed using mixed effects multilevel logistic regression model.

Result

Of 1200 mothers considered from each of the baseline and end line studies, this study included data from 1162 and 1062 mothers at baseline and end line surveys, respectively. As it is shown from the difference-in-difference estimation (14.8%, 95%CI 5.4–24.2%, p = 0.002) and the final model (AOR 4.45, 95%CI 2.31–8.54), checklist-based box system intervention was effective on improving third postnatal care visit. In addition, institutional delivery (AOR 1.62, 95%CI 1.15–2.28) and knowledge on danger signs during postnatal period (AOR 5.20, 95%CI 3.71–7.29) were found to be significant predictors of the outcome variable. In the contrary, mothers who got influenced by older generations of individuals were (AOR 0.32, 95%CI 0.18–0.59) less likely to attend three postnatal care visit.

Conclusions

The implementation of checklist-based box system intervention was found to be effective in improving utilization of the recommended three postnatal care visits. The contribution of the trial on improving third postnatal care visit can be enhanced by minimizing practical level challenges, as well as expanding health messages to reach unreached mothers and significant others who can influence the mother’s decision.

Trial registration: ClinicalTrials.gov, NCT03891030, Retrospectively registered on 26 March, 2019, https://clinicaltrials.gov/ct2/show/NCT03891030.
Tools for public health policy: nudges and boosts as active support of the law in special situations such as the COVID-19 pandemic
Authors: Krawiec Jakub M. , Piaskowska Olga M. , Piesiewicz Piotr F. , Białaszek Wojciech
Published: November 2021

In recent years, “nudging” has become a standard behavioral intervention at the individual level and for the design of social policies. Although nudges are effective, such interventions seem to be limited to a given space and time, and there is only scant evidence to support the contrary view. On the other hand, choice architects may utilize another type of intervention called “boosting,” which shows the promise of generalized and lasting behavioral change. A government can use these tools to shape public policy. Behavioral interventions such as policy-making tools have their boundaries, as does the law. We argue that nudging and boosting may serve as active local or global aids in support of the legal system under certain circumstances. Nudging and boosting can also support the legal system, especially in relation to emerging social issues or events that are unprecedented, such as the recent global COVID-19 pandemic, where certain behavioral patterns are expected, but it would be difficult or impossible to enforce them through the law alone.
Towards effective and sustainable global academic partnerships through a maturity model informed by the capability approach
Authors: Fekadu Abebaw , Assefa Esubalew , Tesfaye Abraham , Hanlon Charlotte , Adefris Belete , Manyazewal Tsegahun , Newport Melanie J. , Davey Gail
Published: November 2021

Background

Shortage of skilled workforce is a global concern but represents a critical bottleneck to Africa’s development. While global academic partnerships have the potential to help tackle this development bottleneck, they are criticised for inadequate attention to equity, impact, and sustainability. We propose a new values-driven partnership model for sustainable and equitable global partnerships that achieve impact.

Method

The model was based on the authors’ experiences of participation in over 30 partnerships and used insights from the Capability Approach.

Results

We developed an Academic Partnership Maturity Model, with five levels of maturity, extending from pre-contemplative to mature partnerships. The level of maturity increases depending on the level of freedom, equity, diversity, and agency afforded to the partners. The approach offers a framework for establishing a forward-looking partnership anchored in mutual learning, empowerment, and autonomy.

Conclusion

This is a pragmatic model limited by the biases of experiential knowledge. Further development of the concept, including metrics and an evaluation tool kit are needed to assist partners and funders.