bluuebunny/crossref_metadata_2025 huggingface dataset:
Coordination mechanisms for COVID-19 in the WHO Regional office for Africa
Authors: Ngoy Nsenga , Oyugi Boniface , Ouma Paul O. , Conteh Ishata Nannie , Woldetsadik Solomon Fisseha , Nanyunja Miriam , Okeibunor Joseph Chukwudi , Yoti Zabulon , Gueye Abdou Salam
Published: May 2022

Aim

This study describes the coordination mechanisms that have been used for management of the COVID 19 pandemic in the WHO AFRO region; relate the patterns of the disease (length of time between onset of coordination and first case; length of the wave of the disease and peak attack rate) to coordination mechanisms established at the national level, and document best practices and lessons learned.

Method

We did a retrospective policy tracing of the COVID-19 coordination mechanisms from March 2020 (when first cases of COVID-19 in the AFRO region were reported) to the end of the third wave in September 2021. Data sources were from document and Literature review of COVID-19 response strategies, plans, regulations, press releases, government websites, grey and peer-reviewed literature. The data was extracted to Excel file database and coded then analysed using Stata (version 15). Analysis was done through descriptive statistical analysis (using measures of central tendencies (mean, SD, and median) and measures of central dispersion (range)), multiple linear regression, and thematic analysis of qualitative data.

Results

There are three distinct layered coordination mechanisms (strategic, operational, and tactical) that were either implemented singularly or in tandem with another coordination mechanism. 87.23% (n = 41) of the countries initiated strategic coordination, and 59.57% (n = 28) initiated some form of operational coordination. Some of countries (n = 26,55.32%) provided operational coordination using functional Public Health Emergency Operation Centres (PHEOCs) which were activated for the response. 31.91% (n = 15) of the countries initiated some form of tactical coordination which involved the decentralisation of the operations at the local/grassroot level/district/ county levels. Decentralisation strategies played a key role in coordination, as was the innovative strategies by the countries; some coordination mechanisms built on already existing coordination systems and the heads of states were effective in the success of the coordination process. Financing posed challenge to majority of the countries in initiating coordination.

Conclusion

Coordinating an emergency is a multidimensional process that includes having decision-makers and institutional agents define and prioritise policies and norms that contain the spread of the disease, regulate activities and behaviour and citizens, and respond to personnel who coordinate prevention.
Evaluation and perceptions of a nursing discharge plan among nurses from different healthcare settings in Spain
Authors: Reig-Garcia Gloria , Bonmatí-Tomàs Anna , Suñer-Soler Rosa , Malagón-Aguilera Mari Carmen , Gelabert-Vilella Sandra , Bosch-Farré Cristina , Mantas-Jimenez Susana , Juvinyà-Canal Dolors
Published: May 2022

Purpose

The exchange of information between different healthcare settings through a nursing discharge plan is essential for safe care. However, the factors contributing to achieving the most efficient exchange have not been well studied. This study aimed to evaluate and explore the perceptions of a nursing discharge plan from the perspective of nurses in different healthcare settings.

Methods

A mixed methods approach comprising a specifically designed ad hoc questionnaire (n = 437) and a focus group session (n = 8).

Findings

Overall, 66.1% out of 437 nurses, and especially those working in nursing homes, were satisfied with the nursing discharge plan.

Lack of time to complete the report and poor information about both nursing diagnoses and patients’ social assessment were identified as problem areas. Some proposals emerged from the focus group: providing sufficient time for its completion, giving the nursing discharge plan a more flexible structure permitting more open-ended responses, requiring more information to be provided about the social and psychological situation of the patients, training nurses to use standardized language to avoid possible misinterpretations, and getting nurses from the different health care settings to work together in designing continuity of care plans. Elderly and low-income patients are found to need greater attention when filling out nursing discharge plans.

Conclusions

The study has revealed key aspects that need to be improved and some recommendations in implementing the nursing discharge plan in our health area. These include that there should be more time provided to complete the NDP, and also specific details regarding the format, structure, content of the information that is communicated, and the prioritization of the patient profile.
Salvia miltiorrhiza polysaccharides ameliorates Staphylococcus aureus-induced mastitis in rats by inhibiting activation of the NF-κB and MAPK signaling pathways
Authors: Zhang Di , Jin Guozhong , Liu Wei , Dou Mengmeng , Wang Xiao , Shi Wanyu , Bao Yongzhan
Published: May 2022

The lactation capacity of dairy cows is critical to the productivity of the animals. Mastitis is a disease that directly affects the lactation capacity of cows. Staphylococcus aureus (S. aureus) is one of the most important pathogens that causes mastitis in dairy cows. The anti-inflammatory effect of Salvia miltiorrhiza polysaccharides (SMPs) has been demonstrated in mice and chickens. However, the effectiveness of SMPs in preventing and treating mastitis is unclear. Therefore, the purpose of this study was to explore the protective effect and mechanism of SMPs on mastitis caused by S. aureus. S. aureus was used to induce mastitis in rats, and three doses of SMPs (87.5, 175, 350 mg/kg, BW/d) were administered as treatments. The bacterial load, histopathology, and myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGase) activities of mammary glands were observed and measured. Cytokines, including interleukin (IL)-1β, interleukin (IL)-6, and tumor necrosis factor α (TNF-α), were examined by qRT–PCR and ELISA. Key proteins in the NF-κB and MAPK signaling pathways were analyzed by Western blotting. The results showed that SMP supplementation could significantly reduce the colonization of S. aureus and the recruitment of inflammatory cells in mammary glands. S. aureus-induced gene transcription and protein expression of IL-1β, IL-6, and TNF-α were significantly suppressed in mammary glands. In addition, the increase in NF-κB and MAPK protein phosphorylation was inhibited by SMPs. These results revealed that supplementation with SMPs protected the mammary gland of rats against damage caused by S. aureus and alleviated the inflammatory response. This study provides a certain experimental basis for the treatment of S. aureus-induced mastitis with SMPs in the future.
Carbon dioxide fixation via production of succinic acid from glycerol in engineered Saccharomyces cerevisiae
Authors: Malubhoy Zahabiya , Bahia Frederico Mendonça , de Valk Sophie Claire , de Hulster Erik , Rendulić Toni , Ortiz Juan Paulo Ragas , Xiberras Joeline , Klein Mathias , Mans Robert , Nevoigt Elke
Published: May 2022

Background

The microbial production of succinic acid (SA) from renewable carbon sources via the reverse TCA (rTCA) pathway is a process potentially accompanied by net-fixation of carbon dioxide (CO2). Among reduced carbon sources, glycerol is particularly attractive since it allows a nearly twofold higher CO2-fixation yield compared to sugars. Recently, we described an engineered Saccharomyces cerevisiae strain which allowed SA production in synthetic glycerol medium with a maximum yield of 0.23 Cmol Cmol−1. The results of that previous study suggested that the glyoxylate cycle considerably contributed to SA accumulation in the respective strain. The current study aimed at improving the flux into the rTCA pathway accompanied by a higher CO2-fixation and SA yield.

Results

By changing the design of the expression cassettes for the rTCA pathway, overexpressing PYC2, and adding CaCO3 to the batch fermentations, an SA yield on glycerol of 0.63 Cmol Cmol−1 was achieved (i.e. 47.1% of the theoretical maximum). The modifications in this 2nd-generation SA producer improved the maximum biomass-specific glycerol consumption rate by a factor of nearly four compared to the isogenic baseline strain solely equipped with the dihydroxyacetone (DHA) pathway for glycerol catabolism. The data also suggest that the glyoxylate cycle did not contribute to the SA production in the new strain. Cultivation conditions which directly or indirectly increased the concentration of bicarbonate, led to an accumulation of malate in addition to the predominant product SA (ca. 0.1 Cmol Cmol−1 at the time point when SA yield was highest). Off-gas analysis in controlled bioreactors with CO2-enriched gas-phase indicated that CO2 was fixed during the SA production phase.

Conclusions

The data strongly suggest that a major part of dicarboxylic acids in our 2nd-generation SA-producer was formed via the rTCA pathway enabling a net fixation of CO2. The greatly increased capacity of the rTCA pathway obviously allowed successful competition with other pathways for the common precursor pyruvate. The overexpression of PYC2 and the increased availability of bicarbonate, the co-substrate for the PYC reaction, further strengthened this capacity. The achievements are encouraging to invest in future efforts establishing a process for SA production from (crude) glycerol and CO2.
Regulatory mechanism of Haa1p and Tye7p in Saccharomyces cerevisiae when fermenting mixed glucose and xylose with or without inhibitors
Authors: Li Bo , Wang Li , Xie Jin-Yu , Xia Zi-Yuan , Xie Cai-Yun , Tang Yue-Qin
Published: May 2022

Background

Various inhibitors coexist in the hydrolysate derived from lignocellulosic biomass. They inhibit the performance of Saccharomyces cerevisiae and further restrict the development of industrial bioethanol production. Transcription factors are regarded as targets for constructing robust S. cerevisiae by genetic engineering. The tolerance-related transcription factors have been successively reported, while their regulatory mechanisms are not clear. In this study, we revealed the regulation mechanisms of Haa1p and Tye7p that had outstanding contributions to the improvement of the fermentation performance and multiple inhibitor tolerance of S. cerevisiae.

Results

Comparative transcriptomic analyses were applied to reveal the regulatory mechanisms of Haa1p and Tye7p under mixed sugar fermentation conditions with mixed inhibitors [acetic acid and furfural (AFur)] or without inhibitor (C) using the original strain s6 (S), the HAA1-overexpressing strain s6H3 (H), and the TYE7-overexpressing strain s6T3 (T). The expression of the pathways related to carbohydrate, amino acid, transcription, translation, cofactors, and vitamins metabolism was enhanced in the strains s6H3 and s6T3. Compared to C_H vs. C_S group, the unique DEGs in AFur_H vs. AFur_S group were further involved in oxidative phosphorylation, purine metabolism, vitamin B6 metabolism, and spliceosome under the regulation of Haa1p. A similar pattern appeared under the regulation of Tye7p, and the unique DEGs in AFur_T vs. AFur_S group were also involved in riboflavin metabolism and spliceosome. The most significant difference between the regulations of Haa1p and Tye7p was the intracellular energy supply. Haa1p preferred to enhance oxidative phosphorylation, while Tye7p tended to upregulate glycolysis/gluconeogenesis.

Conclusions

Global gene expressions could be rewired with the overexpression of HAA1 or TYE7. The positive perturbations of energy and amino acid metabolism were beneficial to the improvement of the fermentation performance of the strain. Furthermore, strengthening of key cofactor metabolism, and transcriptional and translational regulation were helpful in improving the strain tolerance. This work provides a novel and comprehensive understanding of the regulation mechanisms of Haa1p and Tye7p in S. cerevisiae.
Construction of liquid metal-based soft microfluidic sensors via soft lithography
Authors: Zhang Yang , Duan Haowei , Li Guoqiang , Peng Maoyu , Ma Xing , Li Ming , Yan Sheng
Published: May 2022

Background

Liquid metal (LM) can be integrated into microfluidic channel, bringing new functionalities of microfluidics and opening a new window for soft microfluidic electronics, due to the superior advantages of the conductivity and deformability of LMs. However, patterning the LMs into microfluidic channels requires either selective surface wetting or complex fabrication process.

Results

In this work, we develop a method to pattern the LMs onto the soft elastomer via soft lithographic process for fabrication of soft microfluidic sensors without the surface modification, bulky facilities, and complicated processes. The combination of the interfacial hydrogen bond and surface tension enables the LM patterns transfer to the soft elastomer. The transferred LM patterns with an ellipse-like cross-section further improve the stability under the mechanical deformation. Three proof-of-concept experiments were conducted to demonstrate the utilization of this method for development of thermochromic sensors, self-powered capacity sensors and flexible biosensor for glucose detection.

Conclusions

In summary, the proposed method offers a new patterning method to obtain soft microfluidic sensors and brings new possibilities for microfluidics-related wearable devices.

Graphical Abstract
Analysis of bowel function, urogenital function, and long-term follow-up outcomes associated with robotic and laparoscopic sphincter-preserving surgical approaches to total mesorectal excision in low rectal cancer: a retrospective cohort study
Authors: Yang Bo , Zhang Shangxin , Yang Xiaodong , Wang Yigao , Li Deguan , Zhao Jian , Li Yongxiang
Published: May 2022

Objective

The present study comparatively analyzed short-term clinical effectiveness and long-term follow-up endpoints associated with robotic-assisted sphincter-preserving surgery (RAS) and laparoscopic-assisted sphincter-preserving surgery (LAS) when used to treat low rectal cancer.

Method

Within such a single-center retrospective cohort analysis, low rectal cancer patients that underwent RAS (n=200) or LAS (n=486) between January 2015 and beginning of July 2018 were enrolled.

Results

The mean operative durations in the RAS and LAS cohorts were 249±64 min and 203±47 min, respectively (P<0.001). Temporary ileostomy rates in the RAS and LAS cohorts were 64.5% and 51.6% (P = 0.002). In addition, major variations across such cohorts regarding catheter removal timing, time to liquid intake, time to first leaving bed, and length of hospitalization (all P<0.001). This distal resection margin distance within the RAS cohort was diminished in comparison to LAS cohort (P=0.004). For patients within the LAS cohort, the time required to recover from reduced urinary/female sexual function was > 6 months post-surgery (P<0.0001), whereas within the RAS cohort this interval was 3 months (P<0.0001). At 6 months post-surgery, male sexual function within RAS cohort was improved in comparison to LAS cohort (P<0.001). At 6 months post-surgery, Wexner scores revealed similar results (P<0.001). No major variations within overall or disease-free survival were identified across these cohorts at 3 or 5 years post-surgery.

Conclusion

Robotic sphincter-preserving surgery is a safe and effective surgical technique in low rectal patients in terms of postoperative oncological safety and long-term endpoints. And the RAS strategy provides certain additional benefits with respect to short-term urogenital/anorectal functional recovery in treated patients compared to LAS.
Verification of genetic differences and immune cell infiltration subtypes in the neuroblastoma tumour microenvironment during immunotherapy
Authors: Qian Bo , Sun Jing , Zuo Pengcheng , Da Min , Mo Xuming , Fang Yongjun
Published: May 2022

Background

Improved understanding of the tumour microenvironment (TME) has enabled remarkable advancements in research on cancer progression in the past few years. It is crucial to understand the nature and function of the TME because precise treatment strategies, including immunotherapy, for managing specific cancers have received widespread attention. The immune infiltrative profiles of neuroblastoma (NB) have not yet been completely illustrated. The purpose of this research was to analyse tumour immune cell infiltration (ICI) in the microenvironment of NB.

Methods

We applied the CIBERSORT and ESTIMATE algorithms to evaluate the ICI status of 438 NB samples. Three ICI models were selected, and ICI scores were acquired. Subgroups with high ICI scores determined based on the presence of immune activation signalling pathways had better overall survival.

Results

Genes involved in the immunosuppressive heparan sulphate glycosaminoglycan biosynthesis signalling pathway were markedly enriched in the low ICI score subgroup. It was inferred that patients with high ICI NB subtypes were more likely to respond to immunotherapy and have a better prognosis than those of patients with low ICI NB subtypes.

Conclusion

Notably, our ICI data not only provide a new clinical and theoretical basis for mining NB prognostic markers related to the microenvironment but also offer new ideas for the development of NB precision immunotherapy methods.
Ahi1 regulates serotonin production by the GR/ERβ/TPH2 pathway involving sexual differences in depressive behaviors
Authors: Wang Bin , Shi Haixia , Ren Liyan , Miao Zhigang , Wan Bo , Yang Hao , Fan Xiaotang , Gustafsson Jan-Ake , Sun Miao , Xu Xingshun
Published: May 2022

Background

Depression is one of the most common psychiatric diseases. The monoamine transmitter theory suggests that neurotransmitters are involved in the mechanism of depression; however, the regulation on serotonin production is still unclear. We previously showed that Ahi1 knockout (KO) mice exhibited depression-like behavior accompanied by a significant decrease in brain serotonin.

Methods

In the present study, western blot, gene knockdown, immunofluorescence, dual-luciferase reporter assay, and rescue assay were used to detect changes in the Ahi1/GR/ERβ/TPH2 pathway in the brains of male stressed mice and male Ahi1 KO mice to explain the pathogenesis of depression-like behaviors. In addition, E2 levels in the blood and brain of male and female mice were measured to investigate the effect on the ERβ/TPH2 pathway and to reveal the mechanisms for the phenomenon of gender differences in depression-like behaviors.

Results

We found that the serotonin-producing pathway-the ERβ/TPH2 pathway was inhibited in male stressed mice and male Ahi1 KO mice. We further demonstrated that glucocorticoid receptor (GR) as a transcription factor bound to the promoter of ERβ that contains glucocorticoid response elements and inhibited the transcription of ERβ. Our recent study had indicated that Ahi1 regulates the nuclear translocation of GR upon stress, thus proposing the Ahi1/GR/ERβ/TPH2 pathway for serotonin production. Interestingly, female Ahi1 KO mice did not exhibit depressive behaviors, indicating sexual differences in depressive behaviors compared with male mice. Furthermore, we found that serum 17β-estradiol (E2) level was not changed in male and female mice; however, brain E2 level significantly decreased in male but not female Ahi1 KO mice. Further, ERβ agonist LY-500307 increased TPH2 expression and 5-HT production. Therefore, both Ahi1 and E2 regulate the ERβ/TPH2 pathway and involve sexual differences in brain serotonin production and depressive behaviors.

Conclusions

In conclusion, although it is unclear how Ahi1 controls E2 secretion in the brain, our findings demonstrate that Ahi1 regulates serotonin production by the GR/ERβ/TPH2 pathway in the brain and possibly involves the regulation on sex differences in depressive behaviors.
Identification of the key exosomal lncRNAs/mRNAs in the serum during distraction osteogenesis
Authors: Zhang Tao , Jiang Weidong , Liao Fengchun , Zhu Peiqi , Guo Lina , Zhao Zhenchen , Liu Yan , Huang Xuanping , Zhou Nuo
Published: May 2022

Background

Distraction osteogenesis (DO), a kind of bone regenerative process, is not only extremely effective, but the osteogenesis rate is far beyond ordinary bone fracture (BF) healing. Exosomes (Exo) are thought to play a part in bone regeneration and healing as key players in cell-to-cell contact. The object of this work was to determine whether exosomes derived from DO and BF serum could stimulate the Osteogenic Differentiation in these two processes, and if so, which genes could be involved.

Methods

The osteogenesis in DO-gap or BF-gap was evaluated using radiographic analysis and histological analysis. On the 14th postoperative day, DO-Exos and BF-Exos were isolated and cocultured with the jaw of bone marrow mesenchymal stem cells (JBMMSCs). Proliferation, migration and osteogenic differentiation of JBMMSCs were ascertained, after which exosomes RNA-seq was performed to identify the relevant gene.

Results

Radiographic and histological analyses manifested that osteogenesis was remarkably accelerated in DO-gap in comparison with BF-gap. Both of the two types of Exos were taken up by JBMMSCs, and their migration and osteogenic differentiation were also seen to improve. However, the proliferation showed no significant difference. Finally, exosome RNA-seq revealed that the lncRNA MSTRG.532277.1 and the mRNA F-box and leucine-rich repeat protein 14(FBXL14) may play a key role in DO.

Conclusions

Our findings suggest that exosomes from serum exert a critical effect on the rapid osteogenesis in DO. This promoting effect might have relevance with the co-expression of MSTRG.532277.1 and FBXL14. On the whole, these findings provide new insights into bone regeneration, thereby outlining possible therapeutic targets for clinical intervention.
SOCS7/HuR/FOXM1 signaling axis inhibited high-grade serous ovarian carcinoma progression
Authors: Du Yanhua , Xu Xiang , Lv Siang , Liu Han , Sun Hong , Wu Jun
Published: May 2022

Background

High-grade serous ovarian carcinoma (HGSOC) is clinically dominant and accounts for ~ 80% deaths in all types of ovarian cancer. The delayed diagnosis, rapid development, and wide dissemination of HGSOC collectively contribute to its high mortality rate and poor prognosis in the patients. Suppressors of cytokine signaling 7 (SOCS7) can regulate cytokine signaling and participate in cell cycle arrest and regulation of cell proliferation, which might also be involved in carcinogenesis. Here, we designated to investigate the functions and mechanisms of SOCS7 in HGSOC.

Methods

The clinical correlation between SOCS7 and HGSOC was examined by both bioinformatics and analysis of tissue samples in patients. Gain/Loss-of-function examinations were carried out to assess the effectiveness of SOCS7 in cell viability, cell cycle, and tumor growth of HGSOC. Furthermore, the underlying mechanisms were explored by identifying the downstream proteins and their interactions via proteomics analysis and immunoprecipitation.

Results

The expression of SOCS7, which was decreased in HGSOC tissues, was correlated with the clinical pathologic characteristics and overall survival of HGSOC patients. SOCS7 acted as a HGSOC suppressor by inhibiting cancer cell viability and tumor growth in vivo. The anti-HGSOC mechanism involves SOCS7’s regulatory effect on HuR by mediating its ubiquitination, the regulation of FOXM1 mRNA by HuR, as well as the interplays among these three clinically relevant factors.

Conclusions

The SOCS7 correlates with HGSOC and suppresses its tumorigenesis through regulating HuR and FOXM1, which also suggests that SOCS7 is a prospective biomarker for the clinical management of ovarian cancer, especially HGSOC.
Motivations, sources of influence and barriers to being a podiatrist: a national questionnaire of student views
Authors: Wallis Lucy , Faulkner James , Locke Rachel , Harden Beverley , Cowley Emma E.
Published: May 2022

Background

Podiatry is an allied health profession which has seen a substantial decline in numbers in recent years. Every effort is required to recruit more students to reverse this diminishing supply and meet national foot health needs. To increase the number of applications to podiatry courses and encourage individuals to choose podiatry careers, the aim of this study was to understand the key motivations, sources of influence and barriers to choosing a podiatry career among current podiatry students, and consider the influence of choosing podiatry before or after a first career.

Methods

An online questionnaire, comprising mainly Likert‐scale questions, was disseminated to podiatry students in England between February and March 2021. Respondents to the questionnaire were categorised as individuals who had either decided to engage in the profession ‘before’ or ‘after’ a first career. Mann‐Whitney U non‐parametric difference tests were performed to compare outcome questions relating to motivations, sources of influence and barriers between groups.

Results

One hundred and fifteen students completed the questionnaire. Overall, the study demonstrated many similarities between the groups (before and after a first career). However, there were distinct differences when considering some of the motivations (i.e., intellectually stimulating, student bursaries), sources of influence (i.e., own patient experience) and barriers (i.e., financial, job availability) associated with engaging in the podiatry profession. Overall, altruistic reasons were the key motivations for choosing podiatry. Personal sources of influence such as conducting own research, was the most important source of influence. Similar to other studies, a lack of awareness of the podiatry profession and what it entails remains problematic.

Conclusions

This is the first national questionnaire investigating career choice decision‐making for podiatry students in England or in any other country. The similarities suggest that marketing is applicable to both groups. However, an absolute must is a future national strategy that makes educational sources more impactful. Additionally, following the Covid‐19 pandemic, the increased interest in health and care professions suggests now is the right time to market podiatry to individuals looking for a career change. Finally, the influence of personal encounters with podiatrists shows the transformational role podiatrists can have in recruiting to the profession.
Are prime numbers special? Insights from the life sciences
Authors: Loconsole Maria , Regolin Lucia
Published: May 2022

Prime numbers have been attracting the interest of scientists since the first formulation of Euclid’s theorem in 300 B.C. Nowadays, physicists and mathematicians continue to formulate new theorems about prime numbers, trying to comprehensively explain their articulated properties. However, evidence from biology and experimental psychology suggest that prime numbers possess distinctive natural properties that pre-exist human grasping. The present work aims at reviewing the existing literature on prime numbers in the life sciences, including some recent experimental contributions employing newly hatched domestic chicks as animal model to test for spontaneous mechanisms allowing discrimination of primes from non-primes. Our overarching goal is that of discussing some instances of prime numbers in nature, with particular reference to their peculiar, non-mathematical, perceptual properties.
A refined and updated health impact assessment of the Global Programme to Eliminate Lymphatic Filariasis (2000–2020)
Authors: Turner Hugo C. , Ottesen Eric A. , Bradley Mark H.
Published: May 2022

Background

Lymphatic filariasis (LF) is a neglected tropical disease (NTD). In 2000 the World Health Organization (WHO) established the Global Programme to Eliminate Lymphatic Filariasis (GPELF). A key component of this programme is mass drug administration (MDA). Between 2000 and 2020, the GPELF has delivered over 8.6 billion treatments to at-risk populations. The last impact assessment of the programme evaluated the treatments provided between 2000–2014. The goal of this analysis is to provide an updated health impact assessment of the programme, based on the numbers treated between 2000–2020.

Methods

We updated and refined a previously established model that estimates the number of clinical manifestations and disability-adjusted life years (DALYs) averted by the treatments provided by the GPELF. The model comprises three different population cohorts that can benefit from MDA provided (those protected from acquiring infection, those with subclinical morbidity prevented from progressing and those with clinical disease alleviated). The treatment numbers were updated for all participating countries using data from the WHO. In addition, data relating to the estimated number of individuals initially at risk of LF infection were updated where possible. Finally, the DALY calculations were refined to use updated disability weights.

Results

Using the updated model and corresponding treatment data, we projected that the total benefit cohort of the GPELF (2000–2020) would consist of approximately 58.5 million individuals and the programme would avert 44.3 million chronic LF cases. Over the lifetime of the benefit cohorts, this corresponded to 244 million DALYs being averted.

Conclusion

This study indicates that substantial health benefits have resulted from the first 20 years of the GPELF. It is important to note that the GPELF would have both additional benefits not quantified by the DALY burden metric as well as benefits on other co-endemic diseases (such as soil-transmitted helminths, onchocerciasis and scabies)—making the total health benefit underestimated. As with the past impact assessments, these results further justify the value and importance of continued investment in the GPELF.

Graphical Abstract
Defining the mechanisms of action and mosquito larva midgut response to a yeast-encapsulated orange oil larvicide
Authors: Kelly Patrick H. , Yingling Alexandra V. , Ahmed Anwar , Hurwitz Ivy , Ramalho-Ortigao Marcelo
Published: May 2022

Background

Yeast-encapsulated orange oil (YEOO) is a novel, ingestible larvicide that combines the benefits of a low-cost essential oil with yeast, an attractive food source for mosquito larvae. In this work, we investigated the underlying mechanisms of action associated with YEOO ingestion by Aedes aegypti larvae.

Methods

Aedes aegypti third-stage larvae (L3) were treated with sublethal or lethal concentrations of YEOO. Genes associated with apoptosis, autophagy and innate immune responses were investigated by RT-qPCR in guts and carcasses dissected from treated and control larvae. Differential expression of cytochrome P450 genes in the CYP6 and CYP9 families were also investigated. Confocal and transmission electron microscopy were used to assess damage caused by YEOO throughout the larval alimentary canal. TUNEL was used to assess apoptosis via DNA fragmentation.

Results

The apoptosis genes IAP1 and IAP2 in larvae displayed opposing effects following exposure to lethal doses of YEOO, with a 26-fold induction of IAP1 at 8 h post YEOO ingestion. The effector caspase CASPS8 displayed a 6.7-fold induction in the gut and concomitant 70-fold induction in the carcass at 8 h post YEOO ingestion. The midgut epithelia regenerator, Vein, had an 11-fold induction in the gut after 4 h and was repressed 7.6-fold in the carcass at 24 h. Sublethal concentrations (< LC50) led to significant differential expression of CYP6 and CYP9 genes. Midgut epithelial damage was highlighted by the destruction of microvilli, vacuolization of midgut cells and damage to cell junctions and basal lamina as early as 30 min. Larval type 2 peritrophic matrix structural integrity and porosity remain unchanged.

Conclusion

Our results strongly suggest that the robust larvicidal activity of YEOO is due to a generalized broad-acting mechanism combining epithelial damage and apoptosis, with concomitant expression of multiple innate response genes involved in epithelial regeneration and detoxification. YEOO’s amenability for use as part of an integrated vector management program makes this novel larvicide a practical approach for mosquito larval control in the future.

Graphical Abstract
The effectiveness of the use of telehealth programs in the care of individuals with hypertension and, or diabetes mellitus: systematic review and meta-analysis
Authors: Santos Daniel Souza , Batistelli Clara Regina Santos , Lara Marina Marilac dos Santos , Ferreira Emily de Souza , Moreira Tiago Ricardo , Cotta Rosângela Minardi Mitre
Published: May 2022

Introduction

Diabetes Mellitus and Hypertension are some of the main Chronic Noncommunicable Diseases, representing a big challenge for global health. In this context, Telehealth programs are presented as a tool with exciting potential to complement and support health care. This paper aimed to analyze the effectiveness of the use of Telehealth programs in the care of individuals with Hypertension and/or Diabetes Mellitus.

Methods

A systematic review with meta-analysis was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol methodology. The following databases were used: PubMed, EMBASE, SciELO, ScienceDirect and Cochrane Library. Papers were included if they addressed the use of technologies that allow two-way communication at a distance between health professionals and patients affected by Hypertension and/or Diabetes Mellitus, type 1 or type 2. Experimental, cross-sectional, case–control, cohort, and clinical trials were included in the review.

Results

We included 164 papers in the review and 45 in the meta-analysis final synthesis. The systematic review results showed a prevalence of telemonitoring as the main form of Telehealth. The study showed a reduction in expenses with the use of Telehealth, both for the users and for the health systems providers, followed by greater satisfaction. Our meta-analysis showed that Telehealth is an effective tool in the care of diabetic patients, providing a 0.353% reduction in HbA1c compared to traditional care. No studies on Hypertension that met our eligibility criteria for inclusion in the meta-analysis were found.

Conclusions

Telehealth is an effective tool for the care of people with Diabetes Mellitus and/or Hypertension.
Designing a novel multi-epitope vaccine to evoke a robust immune response against pathogenic multidrug-resistant Enterococcus faecium bacterium
Authors: Dey Jyotirmayee , Mahapatra Soumya Ranjan , Raj T. Kiran , Kaur Taranjeet , Jain Parul , Tiwari Arushi , Patro Shubhransu , Misra Namrata , Suar Mrutyunjay
Published: May 2022

Enterococcus faecium is an emerging ESKAPE bacterium that is capable of causing severe public health complications in humans. There are currently no licensed treatments or vaccinations to combat the deadly pathogen. We aimed to design a potent and novel prophylactic chimeric vaccine against E. faecium through an immunoinformatics approach The antigenic Penicillin-binding protein 5 (PBP 5) protein was selected to identify B and T cell epitopes, followed by conservancy analysis, population coverage, physiochemical assessment, secondary and tertiary structural analysis. Using various immunoinformatics methods and tools, two linear B-cell epitopes, five CTL epitopes, and two HTL epitopes were finally selected for vaccine development. The constructed vaccine was determined to be highly immunogenic, cytokine-producing, antigenic, non-toxic, non-allergenic, and stable, as well as potentially effective against E. faecium. In addition, disulfide engineering, codon adaptation, and in silico cloning, were used to improve stability and expression efficiency in the host E. coli. Molecular docking and molecular dynamics simulations indicated that the structure of the vaccine is stable and has a high affinity for the TLR4 receptor. The immune simulation results revealed that both B and T cells had an increased response to the vaccination component. Conclusively, the in-depth in silico analysis suggests, the proposed vaccine to elicit a robust immune response against E. faecium infection and hence a promising target for further experimental trials.
Prediction of fluid responsiveness. What’s new?
Authors: Monnet Xavier , Shi Rui , Teboul Jean-Louis
Published: May 2022

Although the administration of fluid is the first treatment considered in almost all cases of circulatory failure, this therapeutic option poses two essential problems: the increase in cardiac output induced by a bolus of fluid is inconstant, and the deleterious effects of fluid overload are now clearly demonstrated. This is why many tests and indices have been developed to detect preload dependence and predict fluid responsiveness. In this review, we take stock of the data published in the field over the past three years. Regarding the passive leg raising test, we detail the different stroke volume surrogates that have recently been described to measure its effects using minimally invasive and easily accessible methods. We review the limits of the test, especially in patients with intra-abdominal hypertension. Regarding the end-expiratory occlusion test, we also present recent investigations that have sought to measure its effects without an invasive measurement of cardiac output. Although the limits of interpretation of the respiratory variation of pulse pressure and of the diameter of the vena cava during mechanical ventilation are now well known, several recent studies have shown how changes in pulse pressure variation itself during other tests reflect simultaneous changes in cardiac output, allowing these tests to be carried out without its direct measurement. This is particularly the case during the tidal volume challenge, a relatively recent test whose reliability is increasingly well established. The mini-fluid challenge has the advantage of being easy to perform, but it requires direct measurement of cardiac output, like the classic fluid challenge. Initially described with echocardiography, recent studies have investigated other means of judging its effects. We highlight the problem of their precision, which is necessary to evidence small changes in cardiac output. Finally, we point out other tests that have appeared more recently, such as the Trendelenburg manoeuvre, a potentially interesting alternative for patients in the prone position.
Matuyama–Brunhes geomagnetic reversal record and associated key tephra layers in Boso Peninsula: extraction of primary magnetization of geomagnetic fields from mixed magnetic minerals of depositional, diagenesis, and weathering processes
Authors: Oda Hirokuni , Nakazato Hiroomi , Nanayama Futoshi , Harigane Yumiko
Published: May 2022

We report paleomagnetic records of Matuyama–Brunhes geomagnetic polarity reversal and associated key tephra layers from the Early–Middle Pleistocene marine sedimentary succession in the Boso Peninsula. The outcrop is in Terasaki, Chiba, Japan and ~ 25 km northeast of the Chiba section. The sediment succession consists of a massive siltstone layer of the Kokumoto Formation, Kazusa Group. A tephra layer was identified in the middle of the outcrop with chemical composition comparable to that of the Byk-E tephra layer from the Chiba section defining the base of the Chibanian Stage. Oriented paleomagnetic samples were collected at intervals of 1–10 cm from the siltstone. To identify the primary remanent magnetization, progressive alternating field demagnetization (PAFD) and progressive thermal demagnetization (PThD) were conducted on pilot samples. Identification of primary magnetization with PAFD was not successful, especially for reversely magnetized samples. In addition, magnetization during PThD showed sharp drops around 175 °C, which decreased gradually between 175 °C and ~ 300 °C, and became unstable above ~ 350 °C. To extract the primary remanent magnetization while avoiding laboratory alteration by heating, a PThD up to 175 °C followed by PAFD was conducted. Combined analysis of remagnetization circles enables extraction of primary magnetization with improved reliability. Rock magnetic experiments were conducted during stepwise heating to understand the magnetic minerals involved and to evaluate the influence of laboratory heating. During heating, FORC-PCA revealed significant changes of magnetic minerals at 200 °C, 400 °C, 450 °C and 550 °C. Rock magnetic analyses and electron microscopy indicate that titanomagnetite/magnetite are magnetic minerals contributing to primary remanent magnetization. Greigite was also identified preserving secondary magnetizations during sub-seafloor diagenesis. The presence of feroxyhyte is suggested as secondary magnetization through the weathering of pyrite by exposure to the air after the Boso Peninsula uplift. The correlation of relative paleointensity with the Chiba section provides an age model with sedimentation rates of 30 cm/kyr and 18 cm/kr for the intervals above and below the Byk-E tephra. VGP latitudes are highly consistent with those from the Chiba section based on the age model, which assigns the main directional swing from reversed to normal polarities as 772.8 ± 0.5 ka.

Graphical Abstract
SIRT1 mediates nutritional regulation of SREBP-1c-driven hepatic PNPLA3 transcription via modulation of H3k9 acetylation
Authors: Xu Xiao , Deng Xiaojie , Chen Yunzhi , Xu Wen , Xu Fen , Liang Hua
Published: May 2022

Background

Patatin-like phospholipase domain containing 3 (PNPLA3) is the main nonalcoholic fatty liver disease (NAFLD) susceptibility. Its expression is regulated tightly by nutritional and energy status, but the mechanism of epigenetic regulation of PNPLA3 gene by nutritional dietary factors has not been reported. Here, we investigated the effect and mechanism of Sirtuin 1 (SIRT1) regulated H3K9 deacetylation on PNPLA3 transcriptional expression in vivo and in vitro.

Methods

Mouse models of fasting/re-feeding transition and nonalcoholic fatty liver induced by high Sucrose diet were constructed; and HepG2 cells were treated with serum- and glucose-free medium or exposed to high glucose and high insulin, to generate fasting and high-glucose-induced lipid deposition cell states. Enrichment levels of histone H3K9 acetylation and sterol responsive element binding protein-1c (SREBP-1c) at the PNPLA3 promoter were observed by ChIP-qPCR. PNPLA3 gene expression was detected by real-time PCR; SIRT1 protein expression was detected by western blot. And lipid deposition was detected by Oil Red O.

Results

H3K9ac levels at SRE regions of PNPLA3 promoter were found to be decreased in mice during fasting and increase during refeeding, and increased in mice with NAFLD induced by high-sucrose diet. The change pattern of PNPLA3 promoter H3K9Ac physiologically (fasting/refeeding) and pathologically was consistent with that of PNPLA3 gene expression, but opposite to that of SIRT1 protein expression. In HepG2 cells, overexpression of SIRT1 inhibited high-glucose induced hyper-acetylation of H3K9 at PNPLA3 promoter, and silent expression of SIRT1 suppressed fasting-induced hypo-acetylation of H3K9. Overexpression of SIRT1 prevented basal and SREBP-1c-driven PNPLA3 gene expression and also prevented the endogenous binding of SREBP-1c to PNPLA3.

Conclusions

We first preliminarily revealed SIRT1 may regulate PNPLA3 gene expression by affecting SREBP-1-driven transcription via acetylation modification of H3K9.
Adaptive optical microscopy via virtual-imaging-assisted wavefront sensing for high-resolution tissue imaging
Authors: Zhou Zhou , Huang Jiangfeng , Li Xiang , Gao Xiujuan , Chen Zhongyun , Jiao Zhenfei , Zhang Zhihong , Luo Qingming , Fu Ling
Published: May 2022

Adaptive optics (AO) is a powerful tool for optical microscopy to counteract the effects of optical aberrations and improve the imaging performance in biological tissues. The diversity of sample characteristics entails the use of different AO schemes to measure the underlying aberrations. Here, we present an indirect wavefront sensing method leveraging a virtual imaging scheme and a structural-similarity-based shift measurement algorithm to enable aberration measurement using intrinsic structures even with temporally varying signals. We achieved high-resolution two-photon imaging in a variety of biological samples, including fixed biological tissues and living animals, after aberration correction. We present AO-incorporated subtractive imaging to show that our method can be readily integrated with resolution enhancement techniques to obtain higher resolution in biological tissues. The robustness of our method to signal variation is demonstrated by both simulations and aberration measurement on neurons exhibiting spontaneous activity in a living larval zebrafish.
Colorectal Cancer Treatment Characteristics and Concordance With Guidelines in Sri Lanka: Results From a Hospital-Based Cancer Registry
Authors: Wijeratne Don Thiwanka , Gunasekara Sanjeeva , Booth Christopher M. , Berry Scott , Jalink Matthew , Carson Laura M. , Gyawali Bishal , Promod Hasitha , Jayarajah Umesh , Seneviratne Sanjeewa
Published: May 2022

PURPOSE

Colorectal cancer (CRC) ranks among the top five incident cancers in Sri Lanka (SL). Here, we describe disease characteristics and treatment patterns of patients with CRC in SL.

METHODS

All adult patients (age > 18 years) diagnosed with CRC during 2016-2020 were identified from the National Cancer Institute SL cancer registry. Cancer stage at diagnosis was defined according to the seventh edition of the TNM staging system. Concordance between recommendations for adjuvant therapy and actual rates of delivery was also analyzed. Descriptive statistics were used to describe the study cohort and treatment patterns.

RESULTS

A total of 1,578 patients were diagnosed with CRC during the study period, 53% (n = 830) with colon cancer and 47% (n = 748) with rectal cancer. Mean age was 61 (range, 18-91) years. Stage distribution was 13%, 28%, 46%, and 12% for stage I, II, III, and IV cancers, respectively. Adjuvant chemotherapy was delivered to 82% of patients with stage III colon cancer. There was a lack of concordance with delivery of neoadjuvant chemoradiotherapy, which was only delivered to 50% of patients with stage III rectal cancer for whom this treatment was indicated.

CONCLUSION

Aging population and advanced stage of CRC at diagnosis will continue to challenge the provision of high-quality CRC care in SL. Further quantitative and qualitative research may help better understand the nonconcordance with treatment guidelines. Such information would help ease the burden of advanced-stage CRC in SL.