bluuebunny/crossref_metadata_2025 huggingface dataset:
First Nations Australians’ self-determination in health and alcohol policy development: a Delphi study
Authors: E. Stearne Annalee , Lee K. S. Kylie , Allsop Steve , Shakeshaft Anthony , Wright Michael
Published: January 2022

Background

Recognition of the role of structural, cultural, political and social determinants of health is increasing. A key principle of each of these is self-determination, and according to the United Nations (2007), this is a right of Indigenous Peoples. For First Nations Australians, opportunities to exercise this right appear to be limited. This paper explores First Nations Australian communities’ responses to reducing alcohol-related harms and improving the health and well-being of their communities, with a focus on understanding perceptions and experiences of their self-determination. It is noted that while including First Nations Australians in policies is not in and of itself self-determination, recognition of this right in the processes of developing health and alcohol policies is a critical element. This study aims to identify expert opinion on what is needed for First Nations Australians’ self-determination in the development of health- and alcohol-related policy.

Methods

This study used the Delphi technique to translate an expert panel’s opinions into group consensus. Perspectives were sought from First Nations Australians (n = 9) and non-Indigenous Peoples (n = 11) with experience in developing, evaluating and/or advocating for alcohol interventions led by First Nations Australians. Using a web-based survey, this study employed three survey rounds to identify and then gain consensus regarding the elements required for First Nations Australians’ self-determination in policy development.

Results

Twenty panellists (n = 9 First Nations Australian) participated in at least one of the three surveys. Following the qualitative round 1 survey, six main themes, 60 subthemes and six examples of policy were identified for ranking in round 2. In round 2, consensus was reached with 67% of elements (n = 40/60). Elements that did not reach consensus were repeated in round 3, with additional elements (n = 5). Overall, consensus was reached on two thirds of elements (66%, n = 43/65).

Conclusions

Self-determination is complex, with different meaning in each context. Despite some evidence of self-determination, systemic change in many areas is needed, including in government. This study has identified a starting point, with the identification of elements and structural changes necessary to facilitate First Nations Australian community-led policy development approaches, which are vital to ensuring self-determination.
Associations of lipoprotein particle profile and objectively measured physical activity and sedentary time in schoolchildren: a prospective cohort study
Authors: Jones Paul Remy , Rajalahti Tarja , Resaland Geir Kåre , Aadland Eivind , Steene-Johannessen Jostein , Anderssen Sigmund Alfred , Bathen Tone Frost , Andreassen Trygve , Kvalheim Olav Martin , Ekelund Ulf
Published: January 2022

Background

Our understanding of the mechanisms through which physical activity might benefit lipoprotein metabolism is inadequate. Here we characterise the continuous associations between physical activity of different intensities, sedentary time, and a comprehensive lipoprotein particle profile.

Methods

Our cohort included 762 fifth grade (mean [SD] age = 10.0 [0.3] y) Norwegian schoolchildren (49.6% girls) measured on two separate occasions across one school year. We used targeted proton nuclear magnetic resonance (1H NMR) spectroscopy to produce 57 lipoprotein measures from fasted blood serum samples. The children wore accelerometers for seven consecutive days to record time spent in light-, moderate-, and vigorous-intensity physical activity, and sedentary time. We used separate multivariable linear regression models to analyse associations between the device-measured activity variables—modelled both prospectively (baseline value) and as change scores (follow-up minus baseline value)—and each lipoprotein measure at follow-up.

Results

Higher baseline levels of moderate-intensity and vigorous-intensity physical activity were associated with a favourable lipoprotein particle profile at follow-up. The strongest associations were with the larger subclasses of triglyceride-rich lipoproteins. Sedentary time was associated with an unfavourable lipoprotein particle profile, the pattern of associations being the inverse of those in the moderate-intensity and vigorous-intensity physical activity analyses. The associations with light-intensity physical activity were more modest; those of the change models were weak.

Conclusion

We provide evidence of a prospective association between time spent active or sedentary and lipoprotein metabolism in schoolchildren. Change in activity levels across the school year is of limited influence in our young, healthy cohort.

Trial registration

ClinicalTrials.gov, #NCT02132494. Registered 7th April 2014
Heart-specific DNA methylation analysis in plasma for the investigation of myocardial damage
Authors: Ren Jie , Jiang Lin , Liu Xiaomeng , Liao Yuhan , Zhao Xueyan , Tang Fuchou , Yu Huimin , Shao Yibing , Wang Jizheng , Wen Lu , Song Lei
Published: January 2022

Background

Circulating cell-free DNA (cfDNA) can be released when myocardial damage occurs.

Methods

Here, we used the methylated CpG tandem amplification and sequencing (MCTA-seq) method for analyzing dynamic changes in heart-derived DNA in plasma samples from myocardial infarction (MI) patients.

Results

We identified six CGCGCGG loci showing heart-specific hypermethylation patterns. MCTA-seq deconvolution analysis combining these loci detected heart-released cfDNA in MI patients at hospital admission, and showed that the prominently elevated total cfDNA level after percutaneous coronary intervention (PCI) was derived from both the heart and white blood cells. Furthermore, for the top marker CORO6, we developed a digital droplet PCR (ddPCR) assay that clearly detected heart damage signals in cfDNA of MI patients at hospital admission.

Conclusions

Our study provides insights into MI pathologies and developed a new ddPCR assay for detecting myocardial damage in clinical applications.
RNA-binding proteins in ovarian cancer: a novel avenue of their roles in diagnosis and treatment
Authors: Wu Jiangchun , Wu Yong , Guo Qinhao , Wang Simin , Wu Xiaohua
Published: January 2022

Ovarian cancer (OC), an important cause of cancer-related death in women worldwide, is one of the most malignant cancers and is characterized by a poor prognosis. RNA-binding proteins (RBPs), a class of endogenous proteins that can bind to mRNAs and modify (or even determine) the amount of protein they can generate, have attracted great attention in the context of various diseases, especially cancers. Compelling studies have suggested that RBPs are aberrantly expressed in different cancer tissues and cell types, including OC tissues and cells. More specifically, RBPs can regulate proliferation, apoptosis, invasion, metastasis, tumorigenesis and chemosensitivity and serve as potential therapeutic targets in OC. Herein, we summarize what is currently known about the biogenesis, molecular functions and potential roles of human RBPs in OC and their prospects for application in the clinical treatment of OC.
An overlooked subset of Cx3cr1wt/wt microglia in the Cx3cr1CreER-Eyfp/wt mouse has a repopulation advantage over Cx3cr1CreER-Eyfp/wt microglia following microglial depletion
Authors: Zhou Kai , Han Jinming , Lund Harald , Boggavarapu Nageswara Rao , Lauschke Volker M , Goto Shinobu , Cheng Huaitao , Wang Yuyu , Tachi Asuka , Xie Cuicui , Zhu Keying , Sun Ying , Osman Ahmed M. , Liang Dong , Han Wei , Gemzell-Danielsson Kristina , Betsholtz Christer , Zhang Xing-Mei , Zhu Changlian , Enge Martin , Joseph Bertrand , Harris Robert A. , Blomgren Klas
Published: January 2022

Background

Fluorescent reporter labeling and promoter-driven Cre-recombinant technologies have facilitated cellular investigations of physiological and pathological processes, including the widespread use of the Cx3cr1CreER-Eyfp/wt mouse strain for studies of microglia.

Methods

Immunohistochemistry, Flow Cytometry, RNA sequencing and whole-genome sequencing were used to identify the subpopulation of microglia in Cx3cr1CreER-Eyfp/wt mouse brains. Genetically mediated microglia depletion using Cx3cr1CreER-Eyfp/wtRosa26DTA/wt mice and CSF1 receptor inhibitor PLX3397 were used to deplete microglia. Primary microglia proliferation and migration assay were used for in vitro studies.

Results

We unexpectedly identified a subpopulation of microglia devoid of genetic modification, exhibiting higher Cx3cr1 and CX3CR1 expression than Cx3cr1CreER-Eyfp/wtCre+Eyfp+ microglia in Cx3cr1CreER-Eyfp/wt mouse brains, thus termed Cx3cr1highCre−Eyfp− microglia. This subpopulation constituted less than 1% of all microglia under homeostatic conditions, but after Cre-driven DTA-mediated microglial depletion, Cx3cr1highCre−Eyfp− microglia escaped depletion and proliferated extensively, eventually occupying one-third of the total microglial pool. We further demonstrated that the Cx3cr1highCre−Eyfp− microglia had lost their genetic heterozygosity and become homozygous for wild-type Cx3cr1. Therefore, Cx3cr1highCre−Eyfp− microglia are Cx3cr1wt/wtCre−Eyfp−. Finally, we demonstrated that CX3CL1–CX3CR1 signaling regulates microglial repopulation both in vivo and in vitro.

Conclusions

Our results raise a cautionary note regarding the use of Cx3cr1CreER-Eyfp/wt mouse strains, particularly when interpreting the results of fate mapping, and microglial depletion and repopulation studies.
Coverage and determinants of modern contraceptive use in sub-Saharan Africa: further analysis of demographic and health surveys
Authors: Boadu Isaac
Published: January 2022

Background

The use of modern contraceptives (MC) in most African countries has been low despite the high fertility rate and unmet need for family planning. This study sought to determine the coverage and determinants of modern contraceptive use among women of reproductive age (15-49 years) in sub-Saharan Africa (SSA).

Methods

Data for the study were obtained from the Demographic and Health Surveys (DHS) conducted between 1995–2020 across 37 SSA countries. Women of reproductive age (15–49 years) was the unit of analysis. Analysis of data was done using STATA version 16 for windows. A bivariate Rao Scott’s Chi-square test of independence was done to determine factors associated with the use of modern contraceptives. Factors that showed significance (p < 0.05) were included in a multilevel logistic regression to determine significant predictors of modern contraceptives. Clustering, stratification and sample weighting were accounted for in the analyses.

Results

The overall prevalence of the use of MC was found to be 22.0%. This ranged from 3.5% in the Central Africa Republic to 49.7% in Namibia. The most common type of MC used were injections (39.4%), condoms (17.5%) and implants (26.5%). Women were less likely to use modern contraceptive if they: had no education (aOR = 0.4, 95% CI 0.38–0.44), had no children (aOR = 0.27–0.42), not told of family planning at a health facility (aOR = 0.69, 95% CI 0.67–0.71), not heard of family planning in the media (aOR = 0.77, 95% CI 0.74–0.79) and being poor (aOR = 0.76, 95% CI 0.73–0.79). On the other hand, women were more likely to use modern contraceptive if they were between the age of 35–39 years (aOR = 1.69, 95% CI 0.73–0.79), married (aOR = 2.66, 95% CI 2.50–2.83), had seven or more children (aOR = 1.27, 95% CI 1.17–0.38), had knowledge of any method of contraceptives (aOR = 303.8, 95% CI 89.9–1027.5) and when field worker visited and talked about family planning (aOR = 1.53, 95% CI 1.39–0.68).

Conclusion

The study showed a low prevalence of modern contraceptive use in sub-Saharan Africa. Findings from the study highlight the need to provide education to women to increase uptake of modern contraceptive and also re-enforce contraceptive interventions to improve women’s health and well-being.
Determinants associated with high-risk fertility behaviours among reproductive aged women in Bangladesh: a cross-sectional study
Authors: Howlader Md. Hasan , Roshid Harun Or , Kundu Satyajit , Halder Henry Ratul , Chanda Sanjoy Kumar , Rahman Md. Ashfikur
Published: January 2022

Background

We aimed to determine the factors that increase the risk of HRFB in Bangladeshi women of reproductive age 15–49 years.

Methods

The study utilised the latest Bangladesh Demographic and Health Survey (BDHS) 2017–18 dataset. The Pearson's chi-square test was performed to determine the relationships between the outcome and the independent variables, while multivariate logistic regression analysis was used to identify the potential determinants associated with HRFB.

Results

Overall 67.7% women had HRFB among them 45.6% were at single risk and 22.1% were at multiple high-risks. Women’s age (35–49 years: AOR = 6.42 95% CI 3.95–10.42), who were Muslims(AOR = 5.52, 95% CI 2.25–13.52), having normal childbirth (AOR = 1.47, 95% CI 1.22–1.69), having unwanted pregnancy (AOR = 10.79, 95% CI 5.67–18.64) and not using any contraceptive methods  (AOR = 1.37, 95% CI 1.24–1.81) were significantly associated with increasing risk of having HRFB. Alternatively, women and their partners’ higher education were associated with reducing HRFB.

Conclusion

A significant proportion of Bangladeshi women had high-risk fertility behaviour which is quite alarming. Therefore, the public health policy makers in Bangladesh should emphasis on this issue and design appropriate interventions to reduce the maternal HRFB.
Negeviruses isolated from mosquitoes in the Brazilian Amazon
Authors: da Silva Ribeiro Ana Cláudia , Martins Lívia Caricio , da Silva Sandro Patroca , de Almeida Medeiros Daniele Barbosa , Miranda Keissy Karoline Pinheiro , Nunes Neto Joaquim Pinto , de Oliveira Monteiro Hamilton Antônio , do Nascimento Bruna Lais Sena , Junior Jose Wilson Rosa , Cruz Ana Cecilia Ribeiro , da Costa Vasconcelos Pedro Fernando , Carvalho Valéria Lima , Rodrigues Sueli Guerreiro
Published: January 2022

Background

There are several groups of viruses including Insect Specific Viruses (ISV) such as the taxon Negevirus, a group of viruses phylogenetically related to plant viruses. Negeviruses replicate in mosquito cells, but not in vertebrate cells.

Methods

Pools of hematophagous arthropods were inoculated in Vero and C6/36 cells. The cells were observed to detect possible cytopathic effect. Then, indirect immunofluorescence, RT-PCR, and nucleotide sequencing were performed.

Results

Seven samples which presented negative results for flaviviruses, alphaviruses and bunyaviruses, but showed cytopathic effect in C6/36 cells were sequenced. We identified the occurrence of a variety of ISVs, most of them belonging to the taxon Negevirus: The Brejeira, Negev, Cordoba and Wallerfield viruses, including a new virus for science, tentatively named Feitosa virus.

Conclusions

We detected negeviruses in the Amazon region, including two viruses that were isolated for the first time in Brazil: Cordoba virus and the Negev virus and, a new virus for science: the Feitosa virus.
Antigenic and immunogenic properties of recombinant proteins consisting of two immunodominant African swine fever virus proteins fused with bacterial lipoprotein OprI
Authors: Zhang Guanglei , Liu Wei , Gao Zhan , Chang Yanyan , Yang Sicheng , Peng Qian , Ge Sudan , Kang Bijing , Shao Junjun , Chang Huiyun
Published: January 2022

Background

African swine fever (ASF) is a highly fatal swine disease, which threatens the global pig industry. There is no commercially available vaccine against ASF and effective subunit vaccines would represent a real breakthrough.

Methods

In this study, we expressed and purified two recombinant fusion proteins, OPM (OprI-p30-modified p54) and OPMT (OprI-p30-modified p54-T cell epitope), which combine the bacterial lipoprotein OprI with ASF virus proteins p30 and p54. Purified recombinant p30 and modified p54 expressed alone or fused served as controls. The activation of dendritic cells (DCs) by these proteins was first assessed. Then, humoral and cellular immunity induced by the proteins were evaluated in mice.

Results

Both OPM and OPMT activated DCs with elevated expression of relevant surface molecules and proinflammatory cytokines. Furthermore, OPMT elicited the highest levels of antigen-specific IgG responses, cytokines including interleukin-2, interferon-γ, and tumor necrosis factor-α, and proliferation of lymphocytes. Importantly, the sera from mice vaccinated with OPM or OPMT neutralized more than 86% of ASF virus in vitro.

Conclusions

Our results suggest that OPMT has good immunostimulatory activities and immunogenicity in mice, and might be an appropriate candidate to elicit immune responses in swine. Our study provides valuable information on further development of a subunit vaccine against ASF.
Inflammogenic effect of polyacrylic acid in rat lung following intratracheal instillation
Authors: Nishida Chinatsu , Tomonaga Taisuke , Izumi Hiroto , Wang Ke-Yong , Higashi Hidenori , Ishidao Toru , Takeshita Jun-ichi , Ono Ryohei , Sumiya Kazuki , Fujii Shota , Mochizuki Shinichi , Sakurai Kazuo , Yamasaki Kei , Yatera Kazuhiro , Morimoto Yasuo
Published: January 2022

Background

Some organic chemicals are known to cause allergic disorders such as bronchial asthma and hypersensitivity pneumonitis, and it has been considered that they do not cause irreversible pulmonary fibrosis. It has recently been reported, however, that cross-linked acrylic acid-based polymer, an organic chemical, might cause serious interstitial lung diseases, including pulmonary fibrosis. We investigated whether or not intratracheal instillation exposure to cross-linked polyacrylic acid (CL-PAA) can cause lung disorder in rats.

Methods

Male F344 rats were intratracheally instilled with dispersed CL-PAA at low (0.2 mg/rat) and high (1.0 mg/rat) doses, and were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months after exposure to examine inflammatory and fibrotic responses and related gene expressions in the lungs. Rat lungs exposed to crystalline silica, asbestos (chrysotile), and NiO and CeO2nanoparticles were used as comparators.

Results

Persistent increases in total cell count, neutrophil count and neutrophil percentage, and in the concentration of the cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2 and C-X-C motif chemokine 5 (CXCL5), which correlated with lung tissue gene expression, were observed in bronchoalveolar lavage fluid (BALF) from 3 days until at least 1 month following CL-PAA intratracheal instillation. Persistent increases in heme oxygenase-1 (HO-1) in the lung tissue were also observed from 3 days to 6 months after exposure. Histopathological findings of the lungs demonstrated that extensive inflammation at 3 days was greater than that in exposure to silica, NiO nanoparticles and CeO2nanoparticles, and equal to or greater than that in asbestos (chrysotile) exposure, and the inflammation continued until 1 month. Fibrotic changes also progressed after 1 month postexposure.

Conclusion

Our results suggested that CL-PAA potentially causes strong neutrophil inflammation in the rat and human lung.
Pandemic preparedness systems and diverging COVID-19 responses within similar public health regimes: a comparative study of expert perceptions of pandemic response in Denmark, Norway, and Sweden
Authors: Laage-Thomsen Jakob , Frandsen Søren Lund
Published: January 2022

Background

National responses to the COVID-19 pandemic depend on national preparedness systems that must be understood as components of global public health emergency preparedness systems, governed and coordinated through the World Health Organization’s 2005 International Health Regulations. The pandemic has raised the question of why countries belonging to similar public health regimes, coordinated through the same global system, responded differently to the same threat. Comparing the responses of Denmark, Sweden and Norway, countries with similar public health regimes, the paper investigates to what degree national differences in COVID-19 policy response reflect significant differences in the policy preferences of national expert groups.

Results

We employ a structured case comparison of Denmark, Norway, and Sweden to analyze their’ politico-administrative pandemic preparedness systems and policy responses during the first wave of the COVID-19 pandemic. We use the results of an interdisciplinary expert survey completed in 2020 to analyze expert perceptions in two ways. First, we analyze expert perceptions of COVID-19 responses while controlling for national COVID-19 trajectories and experts’ characteristics. Second, we analyze the distribution and effect of dominant global expert-held ideas across countries, showing the importance of dominant ideas for experts’ perceptions and preferences for COVID-19 response.

Conclusion

The study finds no evidence indicating that COVID-19 policy variation between the most similar cases of Denmark, Norway, and Sweden are the result of differences in the policy preferences of national expert groups. Instead, our study highlights the importance of other factors than cross-national expert dissensus for explaining variation in pandemic response such as the politico-administrative organization of pandemic preparedness systems. Further, we find that expert support for dominant ideas such as a ‘focused protection strategy’ is associated with consistent policy preferences across locational, disciplinary, and geographic affiliations. Recognition of the latter should be a part of future discussions about how global ideas of pandemic preparedness are diffused transnationally and embedded in national politico-administrative systems.
Global research activity on mathematical modeling of transmission and control of 23 selected infectious disease outbreak
Authors: Sweileh Waleed M.
Published: January 2022

Background

Mathematical analysis and modeling allow policymakers to understand and predict the dynamics of an infectious disease under several different scenarios. The current study aimed to analyze global research activity on mathematical modeling of transmission and control of several infectious diseases with a known history of serious outbreaks.

Methods

Relevant publications were retrieved using a comprehensive validated search query. The database used was SciVerse Scopus. Indicators related to evolution, growth of publications, infectious diseases encountered, key players, citations, and international research collaboration were presented.

Results

The search strategy found 5606. The growth of publications started in 1967 and showed a sharp rise in 2020 and 2021. The retrieved articles received relatively high citations (h-index = 158). Despite being multidisciplinary, Plos One journal made the highest contribution to the field. The main findings of the study are summarized as follows: (a) COVID-19 had a strong impact on the number of publications in the field, specifically during the years 2020 and 2021; (b) research in the field was published in a wide range of journals, mainly those in the field of infectious diseases and mathematical sciences; (c) research in the field was mainly published by scholars in the United States and the United Kingdom; (d) international research collaboration between active countries and less developed countries was poor; (e) research activity relied on research groups with a large number of researchers per group indicative of good author-author collaboration; (f) HIV/AIDS, coronavirus disease, influenza, and malaria were the most frequently researched diseases; (g) recently published articles on COVID-19 received the highest number of citations; and (h) researchers in the Eastern Mediterranian and South-East Asian regions made the least contribution to the retrieved articles.

Conclusion

Mathematical modeling is gaining popularity as a tool for understanding the dynamics of infectious diseases. The application of mathematical modeling on new emerging infectious disease outbreaks is a priority. Research collaboration with less developed countries in the field of mathematical epidemiology is needed and should be prioritized and funded.
Can facet joint block be a complementary or alternative therapeutic option for patients with osteoporotic vertebral fractures: a meta-analysis
Authors: Chen Zhi , Song Chenyang , Chen Jianwen , Sun Jun , Liu Wenge
Published: January 2022

Background

Recently facet joint block has been increasingly used to relief the residual pain after vertebral augmentation, but whether it can be a complementary or alternative to vertebral augmentation remain largely unknown. Thus, we conducted this meta-analysis to determine the effect of facet joint block in the treatment of osteoporotic vertebral compression fractures (OVCF).

Methods

Following PRISMA statement, a comprehensive literature search through Embase, PubMed, Web of Science, Wanfang Data, China National Knowledge Infrastructure and Chinese BioMedical Literature Database was performed to identify relevant studies. Studies comparing vertebral augmentation combined with facet joint block (combined therapy) with vertebral augmentation, and studies comparing facet joint block with vertebral augmentation were analyzed, respectively.

Results

A total of 10 studies were included. There were seven studies comparing combined therapy with vertebral augmentation, the results showed combined therapy was associated with significantly lower visual analog scale (VAS) scores on postoperative day 1, 7, month 1, 3, and lower oswestry disability index (ODI) scores on postoperative day 1, 7, and month 3. There were three studies comparing facet joint block with vertebral augmentation, the results demonstrated vertebral augmentation only provided better analgesia in month 1 after surgery, but it was associated with a higher incidence of refracture.

Conclusions

Current evidence suggested facet joint block might be considered as a complementary to vertebral augmentation in the treatment of OVCF, but it might not be effectively used as an alternative therapy.
High familial burden of cancer correlates with improved outcome from immunotherapy in patients with NSCLC independent of somatic DNA damage response gene status
Authors: Cortellini Alessio , Giusti Raffaele , Filetti Marco , Citarella Fabrizio , Adamo Vincenzo , Santini Daniele , Buti Sebastiano , Nigro Olga , Cantini Luca , Di Maio Massimo , Aerts Joachim G. J. V. , Bria Emilio , Bertolini Federica , Ferrara Miriam Grazia , Ghidini Michele , Grossi Francesco , Guida Annalisa , Berardi Rossana , Morabito Alessandro , Genova Carlo , Mazzoni Francesca , Antonuzzo Lorenzo , Gelibter Alain , Marchetti Paolo , Chiari Rita , Macerelli Marianna , Rastelli Francesca , Della Gravara Luigi , Gori Stefania , Tuzi Alessandro , De Tursi Michele , Di Marino Pietro , Mansueto Giovanni , Pecci Federica , Zoratto Federica , Ricciardi Serena , Migliorino Maria Rita , Passiglia Francesco , Metro Giulio , Spinelli Gian Paolo , Banna Giuseppe L. , Friedlaender Alex , Addeo Alfredo , Ficorella Corrado , Porzio Giampiero , Tiseo Marcello , Russano Marco , Russo Alessandro , Pinato David James
Published: January 2022

Family history of cancer (FHC) is a hallmark of cancer risk and an independent predictor of outcome, albeit with uncertain biologic foundations. We previously showed that FHC-high patients experienced prolonged overall (OS) and progression-free survival (PFS) following PD-1/PD-L1 checkpoint inhibitors. To validate our findings in patients with NSCLC, we evaluated two multicenter cohorts of patients with metastatic NSCLC receiving either first-line pembrolizumab or chemotherapy. From each cohort, 607 patients were randomly case–control matched accounting for FHC, age, performance status, and disease burden. Compared to FHC-low/negative, FHC-high patients experienced longer OS (HR 0.67 [95% CI 0.46–0.95], p = 0.0281), PFS (HR 0.65 [95% CI 0.48–0.89]; p = 0.0074) and higher disease control rates (DCR, 86.4% vs 67.5%, p = 0.0096), within the pembrolizumab cohort. No significant associations were found between FHC and OS/PFS/DCR within the chemotherapy cohort. We explored the association between FHC and somatic DNA damage response (DDR) gene alterations as underlying mechanism to our findings in a parallel cohort of 118 NSCLC, 16.9% of whom were FHC-high. The prevalence of ≥ 1 somatic DDR gene mutation was 20% and 24.5% (p = 0.6684) in FHC-high vs. FHC-low/negative, with no differences in tumor mutational burden (6.0 vs. 7.6 Mut/Mb, p = 0.6018) and tumor cell PD-L1 expression. FHC-high status identifies NSCLC patients with improved outcomes from pembrolizumab but not chemotherapy, independent of somatic DDR gene status. Prospective studies evaluating FHC alongside germline genetic testing are warranted.
Vitamin C improves microvascular reactivity and peripheral tissue perfusion in septic shock patients
Authors: Lavillegrand Jean-Rémi , Raia Lisa , Urbina Tomas , Hariri Geoffroy , Gabarre Paul , Bonny Vincent , Bigé Naïke , Baudel Jean-Luc , Bruneel Arnaud , Dupre Thierry , Guidet Bertrand , Maury Eric , Ait-Oufella Hafid
Published: January 2022

Background

Vitamin C has potential protective effects through antioxidant and anti-inflammatory properties. However, the effect of vitamin C supplementation on microvascular function and peripheral tissue perfusion in human sepsis remains unknown. We aimed to determine vitamin C effect on microvascular endothelial dysfunction and peripheral tissue perfusion in septic shock patients.

Methods

Patients with septic shock were prospectively included after initial resuscitation. Bedside peripheral tissue perfusion and skin microvascular reactivity in response to acetylcholine iontophoresis in the forearm area were measured before and 1 h after intravenous vitamin C supplementation (40 mg/kg). Norepinephrine dose was not modified during the studied period.

Results

We included 30 patients with septic shock. SOFA score was 11 [8–14], SAPS II was 66 [54–79], and in-hospital mortality was 33%. Half of these patients had vitamin C deficiency at inclusion. Vitamin C supplementation strongly improved microvascular reactivity (AUC 2263 [430–4246] vs 5362 [1744–10585] UI,p = 0.0004). In addition, vitamin C supplementation improved mottling score (p = 0.06), finger-tip (p = 0.0003) and knee capillary refill time (3.7 [2.6–5.5] vs 2.9 [1.9–4.7] s,p < 0.0001), as well as and central-to-periphery temperature gradient (6.1 [4.9–7.4] vs 4.6 [3.4–7.0] °C,p < 0.0001). The beneficial effects of vitamin C were observed both in patients with or without vitamin C deficiency.

Conclusion

In septic shock patients being resuscitated, vitamin C supplementation improved peripheral tissue perfusion and microvascular reactivity whatever plasma levels of vitamin C.

ClinicalTrials.gov Identifier: NCT04778605 registered 26 January 2021.
Effects of traditional Chinese medicine collaborative model (TCMCM) combined with adjuvant chemotherapy on IIIb and IIIc gastric cancer: a protocol for a randomized controlled trial
Authors: Li Zhaoyan , Zhang Guangtao , Cao Nida , Xu Jingjuan , Dong Jiahuan , Li Jia , Zhu Xiaohong , Xu Yan , Han Chen , Wang Rui , Xia Xiang , Zhao Gang , Huan Xiangkun , Fan Jin , Zhao Aiguang
Published: January 2022

Background

Metastasis and/or recurrence can decrease the survival time of gastric cancer patients undergoing radical operation. Among them, those with stage IIIb and IIIc are especially at a high risk of metastasis and recurrence. The traditional Chinese medicine collaborative model (TCMCM) has been used in the treatment of cancer; however, its effects have not been systematically evaluated. This study is designed to evaluate whether TCMCM can decrease adverse effects after chemotherapy and reduce the recurrence and metastasis of stage IIIb and IIIc gastric cancer.

Methods/design

This prospective, multicenter, randomized, open-label trial will recruit 260 patients with stage IIIb and IIIc gastric cancer who undergo radical surgery for D2 lymphadenectomy. The patients will be randomly assigned to receive usual adjuvant chemotherapy and TCMCM (intervention group) in a 1:1 ratio. Patients in the intervention group will receive an oral traditional Chinese formula, auricular acupressure, and acupoint therapy. All participants will receive usual adjuvant chemotherapy. The primary outcome is a 3-year disease-free survival rate. Secondary outcomes include quality of life, side effects caused by chemotherapy, and safety-related measures. Assessments will be performed during the screening period, at 4 and 8 cycles after adjuvant chemotherapy, and 9, 12, 18, 24, 30, and 36 months after randomization. Adverse events will be recorded. In addition, biological samples will be collected for mechanism analysis.

Discussion

This will be the first clinical trial to evaluate the effects of TCMCM on disease-free survival (DFS) and quality of life in patients with stage IIIb and IIIc gastric cancer. Our results may be used to standardize TCMCM. We will also perform a larger-scale clinical trial in the future.

Trial registration

ClinicalTrials.govNCT03607656. Registered on 1 July 2018. The final protocol version is V1.1.
Behind every great research project is great data management
Authors: Kanza Samantha , Knight Nicola J.
Published: January 2022

Research data management (RDM) is the cornerstone of a successful research project, and yet it often remains an underappreciated art that gets overlooked in the hustle and bustle of everyday project management even when required by funding bodies. If researchers are to strive for reproducible science that adheres to the principles of FAIR, then they need to manage the data associated with their research projects effectively. It is imperative to plan your RDM strategies early on, and setup your project organisation before embarking on the work. There are several different factors to consider: data management plans, data organisation and storage, publishing and sharing your data, ensuring reproducibility and adhering to data standards. Additionally it is important to reflect upon the ethical implications that might need to be planned for, and adverse issues that may need a mitigation strategy. This short article discusses these different areas, noting some best practices and detailing how to incorporate these strategies into your work. Finally, the article ends with a set of top ten tips for effective research data management.
Effect of intrabronchial administration of autologous adipose-derived mesenchymal stem cells on severe equine asthma
Authors: Adamič Neža , Prpar Mihevc Sonja , Blagus Rok , Kramarič Petra , Krapež Uroš , Majdič Gregor , Viel Laurent , Hoffman Andrew M. , Bienzle Dorothee , Vengust Modest
Published: January 2022

Background

Severe equine asthma (SEA) is a common chronic respiratory disease and a significant health and well-being problem in horses. Current therapeutic strategies improve pulmonary function and clinical signs in some horses, but in the long-term, return to full athletic function appears to be rare. The aim of this study was to assess the safety and the effect of intrabronchial administration of adipose-derived mesenchymal stem cells (AD-MSC) on pulmonary inflammatory and clinical parameters in horses with SEA.

Methods

This was a randomized controlled trial. Twenty adult horses diagnosed with SEA were randomly divided into two groups (n = 10), and treated either with a single intrabronchial application of autologous AD-MSC or oral dexamethasone for three weeks. A targeted clinical examination with determination of clinical score, maximal change in pleural pressure during the breathing cycle, and an endoscopic examination of the airways were performed at baseline and three weeks after treatment. Bronchoalveolar lavage fluid was analyzed cytologically, and IL-1β, IL-4, IL-8, IL-17, TNFα and IFNγ mRNA and protein concentrations were measured at baseline and three weeks. The horses were then monitored over one year for recurrence of SEA. A non-inferiority analysis and a linear mixed-effects model were performed to assess differences between treatments.

Results

The non-inferiority of AD-MSC treatment was not established. However, AD-MSC administration significantly ameliorated the clinical score (P = 0.01), decreased the expression of IL-17 mRNA (P = 0.05) and IL-1β (P ≤ 0.001), IL-4 (P ≤ 0.001), TNFα (P = 0.02) protein levels, and had a positive long-term effect on SEA-associated clinical signs (P = 0.02).

Conclusions

Intrabronchial administration of AD-MSC had limited short-term anti-inflammatory effects but improved the clinical signs of SEA at one year.
Toward UAV-based communication: improving throughput by optimum trajectory and power allocation
Authors: Nasrollahi Sedighe , Mirrezaei Seyed Masoud
Published: January 2022

It is predicted that the use of unmanned aerial vehicles (UAVs) in communication systems will be more extensive in future generations of wireless telecommunication networks, due to their facilitating advantages. In this paper, a UAV-based wireless communication system is considered in which a UAV is employed as a relay to connect two ground users. These two disconnected users make a communication pair. Our aim is to maximize the minimum achievable information rate for the communication link between the transmitter and receiver, by cooperatively optimizing UAV trajectory and transmitter and source power allocation. Motivated by the above, we formulate the optimization problem. The solving process is complicated because of the non-convexity of the formulated problem. To overcome this difficulty, we convert the main problem to some sub-problems by fixing some constraints and solving them with iterative algorithms such as successive convex optimization and reaching the solution for the main problem. Simulation results show the capability of the proposed algorithm.
On the improvement of Fickett’s theorem on bounded sets
Authors: Jung Soon-Mo , Roh Jaiok , Yang Dae-Jeong
Published: January 2022

Fickett proved the stability of isometries on bounded subsets of $\mathbb{R}^{n}$

R
n

for $n \ge 2$
n
≥
2
. Jung then improved Fickett’s theorem for $n \ge 3$
n
≥
3
. In this paper, we improve Fickett’s theorem for $n = 2$
n
=
2
and improve Jung’s result for $n = 3$
n
=
3
, by employing a fundamental analytic method, as it can be used to explain mathematically many practical engineering problems.
Changes of health related quality of life during pregnancy based on pregnancy context: a prospective study
Authors: Kazemi Ashraf , Dadkhah Aazam , Torabi Fatemeh
Published: January 2022

Background

The significance of planned pregnancy is an accepted principle for improving the health of pregnant women; and quality of life, as one of the important indicators of women’s health, is reduced in high-risk pregnancies. The aim of this research was to investigate the changes in the health related quality of life (HRQL) in low risk pregnancies in different groups based on pregnancy context.

Methods

The present study was a prospective study conducted on 250 pregnant women divided into three groups of women with planned pregnancy, unplanned/wanted pregnancy and unwanted pregnancy. Then, using WHOQOL-26 questionnaire, the quality of life of these women was measured in physical, psychological, social and environmental dimensions at the beginning of pregnancy as well as at the end of the first, second and third trimesters.

Results

Based on the results, the mean score of environmental-HRQL in women with unwanted pregnancy was significantly lower than the other two groups. All dimensions on HRQL were influenced by time and group. However, changes in the physical, psychological and social dimensions of HRQL varied within the groups. Physical- HRQL changes were different within the groups. The intergroup effect on environmental dimension of quality of life changes was significant.

Conclusions

It was observed in this study that HRQL in the women with unwanted pregnancy was lower than the women with planned pregnancy and those with unplanned /wanted pregnancy. Moreover, increase in gestational age would lower quality of life, but this decline had a similar pattern in different groups.
Evaluating agripreneurs’ satisfaction: exploring the effect of demographics and emporographics
Authors: Yoganandan G. , Rahman Abdul Aziz Abdul , Vasan M. , Meero Abdelrhman
Published: January 2022

This paper attempts to gauge the satisfaction of agripreneurs and seeks to explore the effect of demographics and emporographics on the agripreneurs’ satisfaction. This study proposes a seven-dimension survey instrument, called AprenSAT, for measuring agripreneurs’ satisfaction. Responses from 784 agripreneurs are analyzed by applying exploratory and confirmatory factor analysis and multiple linear regression. The extraction of seven factors confirms that agripreneurs’ satisfaction is influenced by material availability, government support, farm growth, farm income, market performance, cultivation & production and perceived farm image. The linear regression result delineates that demographic factors such as age, education level and farming experience significantly influence the agripreneurs’ satisfaction. Similarly, variables of emporographics such as farm age, farm size, annual income, land ownership, sources of funds, and intercropping have a substantial influence on agripreneurs’ satisfaction. We recommend information dissemination, hands-on training, the creation of adequate infrastructure and technology adoption to enhance agripreneurs’ satisfaction and rural development.
The challenge of preventing and containing outbreaks of multidrug-resistant organisms and Candida auris during the coronavirus disease 2019 pandemic: report of a carbapenem-resistant Acinetobacter baumannii outbreak and a systematic review of the literature
Authors: Thoma Reto , Seneghini Marco , Seiffert Salomé N. , Vuichard Gysin Danielle , Scanferla Giulia , Haller Sabine , Flury Domenica , Boggian Katia , Kleger Gian-Reto , Filipovic Miodrag , Nolte Oliver , Schlegel Matthias , Kohler Philipp
Published: January 2022

Background

Despite the adoption of strict infection prevention and control measures, many hospitals have reported outbreaks of multidrug-resistant organisms (MDRO) during the Coronavirus 2019 (COVID-19) pandemic. Following an outbreak of carbapenem-resistantAcinetobacter baumannii(CRAB) in our institution, we sought to systematically analyse characteristics of MDRO outbreaks in times of COVID-19, focussing on contributing factors and specific challenges in controlling these outbreaks.

Methods

We describe results of our own CRAB outbreak investigation and performed a systematic literature review for MDRO (includingCandida auris)outbreaks which occurred during the COVID-19 pandemic (between December 2019 and March 2021). Search terms were related to pathogens/resistance mechanisms AND COVID-19. We summarized outbreak characteristics in a narrative synthesis and contrasted contributing factors with implemented control measures.

Results

The CRAB outbreak occurred in our intensive care units between September and December 2020 and comprised 10 patients (thereof seven with COVID-19) within two distinct genetic clusters (both ST2 carrying OXA-23). Both clusters presumably originated from COVID-19 patients transferred from the Balkans. Including our outbreak, we identified 17 reports, mostly caused byCandida auris(n = 6) or CRAB (n = 5), with an overall patient mortality of 35% (68/193). All outbreaks involved intensive care settings. Non-adherence to personal protective equipment (PPE) or hand hygiene (n = 11), PPE shortage (n = 8) and high antibiotic use (n = 8) were most commonly reported as contributing factors, followed by environmental contamination (n = 7), prolonged critical illness (n = 7) and lack of trained HCW (n = 7). Implemented measures mainly focussed on PPE/hand hygiene audits (n = 9), environmental cleaning/disinfection (n = 9) and enhanced patient screening (n = 8). Comparing potentially modifiable risk factors and control measures, we found the largest discrepancies in the areas of PPE shortage (risk factor in 8 studies, addressed in 2 studies) and patient overcrowding (risk factor in 5 studies, addressed in 0 studies).

Conclusions

Reported MDRO outbreaks during the COVID-19 pandemic were most often caused by CRAB (including our outbreak) andC. auris.Inadequate PPE/hand hygiene adherence, PPE shortage, and high antibiotic use were the most commonly reported potentially modifiable factors contributing to the outbreaks. These findings should be considered for the prevention of MDRO outbreaks during future COVID-19 waves.
Antibiotic-resistance in medically important bacteria isolated from commercial herbal medicines in Africa from 2000 to 2021: a systematic review and meta-analysis
Authors: Walusansa Abdul , Asiimwe Savina , Nakavuma Jesca. L. , Ssenku Jamilu. E. , Katuura Esther , Kafeero Hussein. M. , Aruhomukama Dickson , Nabatanzi Alice , Anywar Godwin , Tugume Arthur K. , Kakudidi Esezah K.
Published: January 2022

Background

Antimicrobial resistance is swiftly increasing all over the world. In Africa, it manifests more in pathogenic bacteria in form of antibiotic resistance (ABR). On this continent, bacterial contamination of commonly used herbal medicine (HM) is on the increase, but information about antimicrobial resistance in these contaminants is limited due to fragmented studies. Here, we analyzed research that characterized ABR in pathogenic bacteria isolated from HM in Africa since 2000; to generate a comprehensive understanding of the drug-resistant bacterial contamination burden in this region.

Methods

The study was conducted according to standards of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). We searched for articles from 12 databases. These were: PubMed, Science Direct, Scifinder scholar, Google scholar, HerbMed, Medline, EMBASE, Cochrane Library, International Pharmaceutical Abstracts, Commonwealth Agricultural Bureau Abstracts, African Journal Online, and Biological Abstracts. Prevalence and ABR traits of bacterial isolates, Cochran’s Q test, and the I2 statistic for heterogeneity were evaluated using MedCalcs software. A random-effects model was used to determine the pooled prevalence of ABR traits. The potential sources of heterogeneity were examined through sensitivity analysis, subgroup analysis, and meta-regression at a 95% level of significance.

Findings

Eighteen studies met our inclusion criteria. The pooled prevalence of bacterial resistance to at least one conventional drug was 86.51% (95% CI = 61.247–99.357%). The studies were highly heterogeneous (I2 = 99.17%; p < 0.0001), with no evidence of publication bias. The most prevalent multidrug-resistant species was Escherichia coli (24.0%). The most highly resisted drug was Ceftazidime with a pooled prevalence of 95.10% (95% CI = 78.51–99.87%), while the drug-class was 3rd generation cephalosporins; 91.64% (95% CI = 78.64–96.73%). None of the eligible studies tested isolates for Carbapenem resistance. Extended Spectrum β-lactamase genes were detected in 89 (37.2%) isolates, mostly Salmonella spp., Proteus vulgaris, and K. pneumonia. Resistance plasmids were found in 6 (5.8%) isolates; the heaviest plasmid weighed 23,130 Kilobases, and Proteus vulgaris harbored the majority (n = 5; 83.3%).

Conclusions

Herbal medicines in Africa harbor bacterial contaminants which are highly resistant to conventional medicines. This points to a potential treatment failure when these contaminants are involved in diseases causation. More research on this subject is recommended, to fill the evidence gaps and support the formation of collaborative quality control mechanisms for the herbal medicine industry in Africa.