bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific cytokines in the inflammatory cytokine storm of patients with COVID-19-associated acute respiratory distress syndrome and extrapulmonary multiple-organ dysfunction
Authors: Wang Jiajia , Yang Xinjing , Li Yongsheng , Huang Jian-an , Jiang Junhong , Su Nan
Published: June 2021

Background

To date, specific cytokines associated with development of acute respiratory distress syndrome (ARDS) and extrapulmonary multiple organ dysfunction (MOD) in COVID-19 patients have not been systematically described. We determined the levels of inflammatory cytokines in patients with COVID-19 and their relationships with ARDS and extrapulmonary MOD.

Methods

The clinical and laboratory data of 94 COVID-19 patients with and without ARDS were analyzed. The levels of inflammatory cytokines (interleukin 6 [IL-6], IL-8, IL-10, and tumor necrosis factor α [TNF-α]) were measured on days 1, 3, and 5 following admission. Seventeen healthy volunteers were recruited as controls. Correlations in the levels of inflammatory cytokines with clinical and laboratory variables were analyzed, furthermore, we also explored the relationships of different cytokines with ARDS and extrapulmonary MOD.

Results

The ARDS group had higher serum levels of all 4 inflammatory cytokines than the controls, and these levels steadily increased after admission. The ARDS group also had higher levels of IL-6, IL-8, and IL-10 than the non-ARDS group, and the levels of these cytokines correlated significantly with coagulation parameters and disseminated intravascular coagulation (DIC). The levels of IL-6 and TNF-α correlated with the levels of creatinine and urea nitrogen, and were also higher in ARDS patients with acute kidney injury (AKI). All 4 inflammatory cytokines had negative correlations with PaO2/FiO2. IL-6, IL-8, and TNF-α had positive correlations with the APACHE-II score. Relative to survivors, non-survivors had higher levels of IL-6 and IL-10 at admission, and increasing levels over time.

Conclusions

The cytokine storm apparently contributed to the development of ARDS and extrapulmonary MOD in COVID-19 patients. The levels of IL-6, IL-8, and IL-10 correlated with DIC, and the levels of IL-6 and TNF-α were associated with AKI. Relative to survivors, patients who died within 28 days had increased levels of IL-6 and IL-10.
Massive hemothorax caused by intercostal artery pseudoaneurysm:a case report
Authors: Liu Caiyang , Ran Ran , Li Xiaoliang , Liu Gaohua , Wang Chuanxi , Li Ji
Published: June 2021

Background

Intercostal artery pseudoaneurysm is rare and at the risk of rupture. The aetiology is always reported to be iatrogenic and traumatic injury. Embolisation is the most common therapeutic method. Here, we report a case of spontaneous intercostal artery pseudoaneurysm and cured by combining covered stent grafting and surgical management.

Case presentation

A 60-year-old man complained of acute right back pain for 5 h. Computed tomography showed right massive hemothorax and a giant mass with distinct feeding vessel originated from the thoracic aorta within the right hemithorax. Thoracocentesis was performed, and then a covered stent was positioned across the origin of the feeding vessel. The patient was diagnosed with intercostal artery pseudoaneurysm. Finally, we successfully resected the pseudoaneurysm and ligated the proximal part of the artery. Histologic examination have proved the diagnosis. The postoperative course was uneventful, and the patient was discharged on postoperative day 10. There is no recurrence reported during follow-up.

Conclusions

Spontaneous intercostal artery pseudoaneurysm is extremly rare. Delayed hemothorax due to rupture of the pseudoaneurysm may occur years after the formation. Early diagnosis is important and a combined treatment of endovascular intervention and surgical management is feasible, especially for the case of ruptured large tumour-like mass presentation of the pseudoaneurysm.
Lidocaine for postoperative pain after cardiac surgery: a systematic review
Authors: Boswell Michael R. , Moman Rajat N. , Burtoft Melissa , Gerdes Harrison , Martinez Jacob , Gerberi Danielle J. , Wittwer Erica , Murad M. Hassan , Hooten W. Michael
Published: June 2021

Objective

Lidocaine is one of the most widely used local anesthetics with well-known pharmacological properties. The purpose of this systematic review is to investigate the effects of lidocaine on postoperative pain scores and recovery after cardiac surgery.

Methods

A comprehensive database search was conducted by a reference librarian for randomized clinical trials (RCT) from January 1, 1980 to September 1, 2019. Eligible study designs included randomized controlled trials of lidocaine for postoperative pain management in adults undergoing cardiac surgery. After removal of duplicates, 947 records were screened for eligibility and 3 RCTs met inclusion criteria.

Results

Sources of bias were identified in 2 of 3 RCTs. Lidocaine was administered intravenously, topically, and intrapleurally. Key findings included [1] 2% lidocaine placed topically on chest tube prior to intraoperative insertion was associated with significantly lower pain scores and lower cumulative doses of fentanyl; and [2] 2% lidocaine administered intrapleurally was associated with significantly lower pain scores and significant improvements in pulmonary mechanics. Lidocaine infusions were not associated with significant changes in pain scores or measures of recovery. No significant associations were observed between lidocaine and overall mortality, hospital length of stay or ICU length of stay. No data were reported for postoperative nausea and vomiting or arrhythmias.

Conclusions

Due to the favorable risk profile of topical lidocaine and the need for further advancements in the postoperative care of adults after cardiac surgery, topically administered lidocaine could be considered for incorporation into established postoperative recovery protocols.
Identification of anti-inflammatory compounds from Zhongjing formulae by knowledge mining and high-content screening in a zebrafish model of inflammatory bowel diseases
Authors: Yu Yunru , Chen Jing , Zhang Xiaohui , Wang Yingchao , Wang Shufang , Zhao Lu , Wang Yi
Published: June 2021

Background

Inflammatory bowel diseases (IBD) are chronic relapsing intestinal inflammations with increasing global incidence, and new drug development remains in urgent demand for IBD management. To identify effective traditional Chinese medicine (TCM) formulae and compounds in IBD treatment, we innovatively combined the techniques of knowledge mining, high-content screening and high-resolution mass spectrometry, to conduct a systematic screening in Zhongjing formulae, which is a large collection of TCM prescriptions with most abundant clinical evidences.

Methods

Using Word2vec-based text learning, the correlations between 248 Zhongjing formulae and IBD typical symptoms were analyzed. Next, from the top three formulae with predicted relationship with IBD, TCM fractions were prepared and screened on a transgenic zebrafish IBD model for their therapeutic effects. Subsequently, the chemical compositions of the fraction hits were analyzed by mass spectrometry, and the major compounds were further studied for their anti-IBD effects and potential mechanisms.

Results

Through knowledge mining, Peach Blossom Decoction, Pulsatilla Decoction, and Gegen Qinlian Decoction were predicted to be the three Zhongjing formulae mostly related to symptoms typical of IBD. Seventy-four fractions were prepared from the three formulae and screened in TNBS-induced zebrafish IBD model by high-content analysis, with the inhibition on the intestinal neutrophil accumulation and ROS level quantified as the screening criteria. Six herbal fractions showed significant effects on both pathological processes, which were subsequently analyzed by mass spectrometry to determine their chemical composition. Based on the major compounds identified by mass spectrometry, a second-round screen was conducted and six compounds (palmatine, daidzin, oroxyloside, chlorogenic acid, baicalin, aesculin) showed strong inhibitory effects on the intestinal inflammation phenotypes. The expression of multiple inflammatory factors, includingil1β,clcx8a,mmpandtnfα, were increased in TNBS-treated fish, which were variously inhibited by the compounds, with aesculin showing the most potent effects. Moreover, aesculin and daidzin also upregulatede-cadherin’sexpression.

Conclusion

Taken together, we demonstrated the regulatory effects of several TCM formulae and their active compounds in the treatment of IBD, through a highly efficient research strategy, which can be applied in the discovery of effective TCM formulae and components in other diseases.

Graphic abstract
RPE65-associated inherited retinal diseases: consensus recommendations for eligibility to gene therapy
Authors: Sodi Andrea , Banfi Sandro , Testa Francesco , Della Corte Michele , Passerini Ilaria , Pelo Elisabetta , Rossi Settimio , Simonelli Francesca ,   Italian IRD Working Group
Published: June 2021

Background

This research aimed to establish recommendations on the clinical and genetic characteristics necessary to confirm patient eligibility for gene supplementation with voretigene neparvovec.

Methods

An expert steering committee comprising an interdisciplinary panel of Italian experts in the three fields of medical specialisation involved in the management ofRPE65-associated inherited retinal disease (IRD) (medical retina, genetics, vitreoretinal surgery) proposed clinical questions necessary to determine the correct identification of patients with the disease, determine the fundamental clinical and genetics tests to reach the correct diagnosis and to evaluate the urgency to treat patients eligible to receive treatment with voretigene neparvovec. Supported by an extensive review of the literature, a series of statements were developed and refined to prepare precisely constructed questionnaires that were circulated among an external panel of experts comprising ophthalmologists (retina specialists, vitreoretinal surgeons) and geneticists with extensive experience in IRDs in Italy in a two-round Delphi process.

Results

The categories addressed in the questionnaires included clinical manifestations ofRPE65-related IRD, IRD screening and diagnosis, gene testing and genotyping, ocular gene therapy for IRDs, patient eligibility and prioritisation and surgical issues. Response rates by the survey participants were over 90% for the majority of items in both Delphi rounds. The steering committee developed the key consensus recommendations on each category that came from the two Delphi rounds into a simple and linear diagnostic algorithm designed to illustrate the patient pathway leading from the patient’s referral centre to the retinal specialist centre.

Conclusions

Consensus guidelines were developed to guide paediatricians and general ophthalmologists to arrive at the correct diagnosis ofRPE65-associated IRD and make informed clinical decisions regarding eligibility for a gene therapy approach toRPE65-associated IRD. The guidelines aim to ensure the best outcome for the patient, based on expert opinion, the published literature, and practical experience in the field of IRDs.
Characterization of genotype–phenotype correlation with MORC2 mutated Axonal Charcot–Marie–Tooth disease in a cohort of Chinese patients
Authors: Duan Xiaohui , Liu Xiaoxuan , Wang Guochun , Gu Weihong , Xu Min , Hao Ying , Dong Mingrui , Sun Qing , Sun Shaojie , Chen Yuanyuan , Wang Wei , Li Jing , Zhang Yuting , Cao Zhenhua , Fan Dongsheng , Wang Renbin , Da Yuwei
Published: June 2021

Background

Charcot–Marie–Tooth (CMT) disease is an exciting field of study, with a growing number of causal genes and an expanding phenotypic spectrum. The microrchidia family CW-type zinc finger 2 gene (MORC2) was newly identified as a causative gene of CMT2Z in 2016. We aimed to describe the phenotypic-genetic spectrum of MORC2-related diseases in the Chinese population.

Methods

With the use of Sanger sequencing and Next Generation Sequencing (NGS) technologies, we screened a cohort of 284 unrelated Chinese CMT2 families. Pathogenicity assessments of MORC2 variants were interpreted according to the ACMG guidelines. Potential pathogenic variants were confirmed by Sanger sequencing.

Results

We identified 4 different heterozygous MORC2 mutations in four unrelated families, accounting for 1.4% (4/284). A novel mutation c.1397A>G p. D466G was detected in family 1 and all affected patients presented with later onset axonal CMT with hyperCKemia. The patient in family 2 showed a spinal muscular atrophy (SMA)-like disease with cerebellar hypoplasia and mental retardation, with a hot spot de novo mutation c.260C>T p. S87L. The twin sisters in family 3 were identified as having the most common mutation c.754C>T p. R252W and suffered from axonal motor neuropathy with high variability in disease severity and duration. The patient in family 4 developed an early onset axonal motor and sensory neuropathy, with a reported mutation c.1220G>A p.C407Y. All identified mutations associated with MORC2-related neuropathies are localized in the N-terminal ATPase module.

Conclusions

Our study confirmed that MORC2-related neuropathies exist in the Chinese population at a relatively high mutation rate. We revealed a complex genotype–phenotype correlation with MORC2 mutations. This report adds a new piece to the puzzle of the genetics of CMT and contributes to a better understanding of the disease mechanisms.
Program evaluation of a student-led peer support service at a Canadian university
Authors: Suresh Rahul , Karkossa Zoe , Richard Jérémie , Karia Maharshee
Published: June 2021

Background

University students often experience numerous financial, social and emotional stressors that can affect their mental health. The Peer Support Centre (PSC) is a pilot project that was established to provide peer support to students in these stressful conditions. We wanted to investigate whether peer support is a viable form of support that would benefit university students. The objective of this study is to determine whether the organization was indeed providing a beneficial service to students and if it was fulfilling the needs of the students that visited the service.

Methods

After a support session, students and peer support providers completed an anonymous questionnaire regarding their self-reported mental wellbeing using the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder-7 (GAD-7) metrics, and Outcome Rating Scale (ORS). They were also asked about their experience with previous professional mental health services as well as their experience at the PSC. With the data collected from 1043 students and 797 volunteers from September 2016–March 2020, a program evaluation was conducted for quality improvement purposes.

Results

The PSC is used by students of different sexes, genders, and ethnicities. Students reported having a low ORS score, moderate anxiety as per the GAD-7 and moderate depression according to the PHQ-9. They find it easy to use and rely on it as an alternative form of support when they approach barriers that prevent them from accessing professional services. Lastly, the peer support providers feel very validated in their role and overall quite prepared and helpful when helping their fellow peers.

Conclusions

The establishment of a student service that provides peer support would be beneficial to the members of a university/college campus.
Hemophagocytic lymphohistiocytosis after COVID-19 vaccination
Authors: Tang Liang V. , Hu Yu
Published: June 2021

Cases of thrombotic thrombocytopenia induced by coronavirus disease 2019 (COVID-19) vaccines have been reported recently. Herein, we describe the first case of another critical disorder, hemophagocytic lymphohistiocytosis (HLH), in a healthy individual after COVID-19 vaccination. A 43-year-old Chinese farmer developed malaise, vomiting, and persistent high fever (up to 39.7 °C) shortly after receiving the first dose of the inactivated SARS-CoV-2 vaccine. The initial evaluation showed pancytopenia (neutrophil count, 0.70 × 109/L; hemoglobin, 113 g/L; platelet, 27 × 109/L), elevated triglyceride (2.43 mmol/L), and decreased fibrinogen (1.41 g/L). Further tests showed high serum ferritin levels (8140.4 μg/L), low NK cell cytotoxicity (50.13%–60.83%), and positive tests for Epstein–Barr virus (EBV) DNA. Hemophagocytosis was observed in the bone marrow. Therefore, HLH was confirmed, and dexamethasone acetate (10 mg/day) was immediately prescribed without etoposide. Signs and abnormal laboratory results resolved gradually, and the patient was discharged. HLH is a life-threatening hyperinflammatory syndrome caused by aberrantly activated macrophages and cytotoxic T cells, which may rapidly progress to terminal multiple organ failure. In this case, HLH was induced by the COVID-19 vaccination immuno-stimulation on a chronic EBV infection background. This report indicates that it is crucial to exclude the presence of active EBV infection or other common viruses before COVID-19 vaccination.
Prioritizing health care workers and first responders for access to the COVID19 vaccine is not unethical, but both fair and effective – an ethical analysis
Authors: Thorsteinsdottir Bjorg , Madsen Bo Enemark
Published: June 2021

The Nordic countries have differed in their approach as to how much priority for COVID19 vaccine access should be given to health care workers. Two countries decided not to give health care workers highest priority, raising some controversy. The rationale was that those at highest risk of dying needed to come first. However, when it comes to protecting those at the highest risk of dying from COVID19, their needs and vulnerabilities need to be considered more broadly than just in terms of the individual protection that vaccination will afford them. Likewise, when considering whether to prioritize health care workers for the vaccine, their crucial role in keeping the health care system operational, and right to a safe work environment need to be factored in. Below we review several ethical arguments for why frontline health care workers and first responders should receive priority access to the COVID19 vaccine.
Field study to investigate the effectiveness and safety of a novel orally administered combination drug product containing milbemycin oxime and lotilaner (Credelio® Plus) against natural flea and tick infestations on dogs presented as veterinary patients in Europe
Authors: Forster Sophie , Wiseman Scott , Snyder Daniel E.
Published: June 2021

Background

A pivotal randomised, blinded, positive-controlled, multicentre, European field study was conducted to evaluate the effectiveness and safety of a novel combination tablet of lotilaner and milbemycin oxime (Credelio® Plus) administered orally to client-owned dogs naturally infested with fleas and/or ticks.

Methods

In this field study, households with flea- or tick-infested dog(s) were enrolled on Day 0 into the study to provide data for either the tick or flea infestation cohorts. Households were randomised in a 2:1 ratio to receive either the combination investigational product (IP, Credelio Plus® tablets) or the control product (CP: Nexgard Spectra® tablets). Dogs were administered IP (flea cohort n = 135; tick cohort: n = 147) or CP (flea cohort: n = 67; tick cohort: n = 74) once every 4 weeks for a total of three times at a dose rate of 20.0–41.5 mg/kg bodyweight lotilaner and 0.75–1.53 mg/kg bodyweight milbemycin oxime (IP) or as recommended (CP). Percentage reduction was calculated by comparing individual dog flea and tick counts at each assessed post-treatment time point to their respective baseline (pre-treatment) infestation. Resolution of the clinical signs of flea allergy dermatitis (FAD) was assessed in flea-allergic dogs on the days that flea counts were performed.

Results

Flea effectiveness of Credelio Plus® after 3 consecutive monthly treatments was 100% against Ctenocephalides felis, C. canis and Pulex irritans. Tick effectiveness of Credelio Plus® over the same time frame was 99.3% for Ixodes ricinus and 100% against Rhipicephalus sanguineus (s.l.). Flea effectiveness of the CP after three consecutive monthly treatments was 100% against C. felis, C. canis and P. irritans. Tick effectiveness of the CP over the same time frame was 99.8% for I. ricinus and 100% against R. sanguineus. Credelio Plus® was well tolerated based on the safety assessments in all treated dogs in this field study. Within both treatment groups there was a reduction in total FAD scores from baseline.

Conclusions

This pivotal European field study demonstrated the excellent effectiveness and safety of a combination of lotilaner and milbemycin oxime (Credelio Plus®) administered orally to dogs naturally infested with fleas and/or ticks.

Graphical Abstract
Helicobacter pylori in the Indonesian Malay’s descendants might be imported from other ethnicities
Authors: Syam Ari Fahrial , Waskito Langgeng Agung , Rezkitha Yudith Annisa Ayu , Simamora Rentha Monica , Yusuf Fauzi , Danchi Kanserina Esthera , Bakry Ahmad Fuad , Arnelis  , Mulya Erwin , Siregar Gontar Alamsyah , Sugihartono Titong , Maulahela Hasan , Doohan Dalla , Miftahussurur Muhammad , Yamaoka Yoshio
Published: June 2021

Background

Even though the incidence of H. pylori infection among Malays in the Malay Peninsula is low, we observed a high H. pylori prevalence in Sumatra, which is the main residence of Indonesian Malays. H. pylori prevalence among Indonesian Malay descendants was investigated.

Results

Using a combination of five tests, 232 recruited participants were tested for H- pylori and participants were considered positive if at least one test positive. The results showed that the overall H. pylori prevalence was 17.2%. Participants were then categorized into Malay (Aceh, Malay, and Minang), Java (Javanese and Sundanese), Nias, and Bataknese groups. The prevalence of H. pylori was very low among the Malay group (2.8%) and no H. pylori was observed among the Aceh. Similarly, no H. pylori was observed among the Java group. However, the prevalence of H. pylori was high among the Bataknese (52.2%) and moderate among the Nias (6.1%). Multilocus sequence typing showed that H. pylori in Indonesian Malays classified as hpEastAsia with a subpopulation of hspMaori, suggesting that the isolated H. pylori were not a specific Malays H. pylori.

Conclusions

Even though the ethnic groups live together as a community, we observed an extremely low H. pylori infection rate among Indonesian Malay descendants with no specific Indonesian Malay H. pylori. The results suggest that H. pylori was not originally among these groups and H. pylori was imported from other ethnic groups.
Antibiotic resistance pattern and frequency of cagA and vacA genes in Helicobacter pylori strains isolated from patients in Tabriz city, Iran
Authors: Rasi-Bonab Farnaz , Jafari-Sales Abolfazl , Shaverdi Mohammad Amin , Navidifar Tahereh , Saki Morteza , Ghorbani Atosa , Adekanmbi Abimbola Olumide , Jafari Behboud , Naebi Sara
Published: June 2021

Objective

Helicobacter pylori is one of the most common causes of gastric infections in humans. It is estimated that approximately 50% of people around the world are infected with this bacterium. This study aimed to determine the antibiotic resistance pattern, as well as the frequency of cagA and vacA genes in H. pylori isolates obtained from patients in the clinical centers in Tabriz city, Iran.

Results

The culture method detected 100 (45.25%) H. pylori isolates from 221 biopsy samples during 3 years. The results showed that 63% and 81% of the isolates were positive for cagA and vacA genes, respectively. The highest resistance of isolates was seen against metronidazole (79%) and amoxicillin (36%), respectively. Also, the isolates showed the least resistance to tetracycline (8%).
Exploring the mechanisms of collaboration between the Tuberculosis and Diabetes Programs for the control of TB-DM Comorbidity in Ghana
Authors: Salifu Rita Suhuyini , Hlongwana Khumbulani W.
Published: June 2021

Objectives

To explore the mechanisms of collaboration between the stakeholders, including National Tuberculosis Control Program (NTP) and the Non-Communicable Disease Control and Prevention Program (NCDCP) at the national, regional, and local (health facility) levels of the health care system in Ghana. This is one of the objectives in a study on the “Barriers and Facilitators to the Implementation of the Collaborative Framework for the Care and Control of Tuberculosis and Diabetes in Ghana”

Results

The data analysis revealed 4 key themes. These were (1) Increased support for communicable diseases (CDs) compared to stagnant support for non-communicable diseases (NCDs), (2) Donor support, (3) Poor collaboration between NTP and NCDCP, and (4) Low Tuberculosis-Diabetes Mellitus (TB-DM) case detection.
Correlating natural language processing and automated speech analysis with clinician assessment to quantify speech-language changes in mild cognitive impairment and Alzheimer’s dementia
Authors: Yeung Anthony , Iaboni Andrea , Rochon Elizabeth , Lavoie Monica , Santiago Calvin , Yancheva Maria , Novikova Jekaterina , Xu Mengdan , Robin Jessica , Kaufman Liam D. , Mostafa Fariya
Published: June 2021

Background

Language impairment is an important marker of neurodegenerative disorders. Despite this, there is no universal system of terminology used to describe these impairments and large inter-rater variability can exist between clinicians assessing language. The use of natural language processing (NLP) and automated speech analysis (ASA) is emerging as a novel and potentially more objective method to assess language in individuals with mild cognitive impairment (MCI) and Alzheimer’s dementia (AD). No studies have analyzed how variables extracted through NLP and ASA might also be correlated to language impairments identified by a clinician.

Methods

Audio recordings (n=30) from participants with AD, MCI, and controls were rated by clinicians for word-finding difficulty, incoherence, perseveration, and errors in speech. Speech recordings were also transcribed, and linguistic and acoustic variables were extracted through NLP and ASA. Correlations between clinician-rated speech characteristics and the variables were compared using Spearman’s correlation. Exploratory factor analysis was applied to find common factors between variables for each speech characteristic.

Results

Clinician agreement was high in three of the four speech characteristics: word-finding difficulty (ICC = 0.92, p<0.001), incoherence (ICC = 0.91, p<0.001), and perseveration (ICC = 0.88, p<0.001). Word-finding difficulty and incoherence were useful constructs at distinguishing MCI and AD from controls, while perseveration and speech errors were less relevant. Word-finding difficulty as a construct was explained by three factors, including number and duration of pauses, word duration, and syntactic complexity. Incoherence was explained by two factors, including increased average word duration, use of past tense, and changes in age of acquisition, and more negative valence.

Conclusions

Variables extracted through automated acoustic and linguistic analysis of MCI and AD speech were significantly correlated with clinician ratings of speech and language characteristics. Our results suggest that correlating NLP and ASA with clinician observations is an objective and novel approach to measuring speech and language changes in neurodegenerative disorders.
Investing preventive care and economic development in ageing societies: empirical evidences from OECD countries
Authors: Wang Fuhmei , Wang Jung-Der
Published: June 2021

Background

The proportion of the elderly aged 65 years old or above will reach 16% in 2050 worldwide. Early investment in effective prevention would generally reduce the morbidity, complication, functional disability, and mortality of most chronic illnesses and save resources in both healthcare and social services. This research aims to investigate how the optimal allocation of medical resources between prevention and treatment adds value to the population’s health as well as examine the interaction between ageing, health, and economic performance.

Methods

This research undertakes ageing-health analyses by developing an economic growth model. Based on the Organization for Economic Co-Operation and Development (OECD) countries’ experiences over the period from 2000 to 2017, this research further examines the hypothesis that an ageing society could increase demand for preventive and curative healthcare.

Results

Theoretical analysis found that the prevention share for maximizing growth is the same as that for minimizing ill health and maximizing welfare; this share increases with treatment share and ageing ratios. Estimation results from OECD countries’ experiences indicate that when treatment share increases by 1%, the prevention demand increases by 0.036%. A one-percent increase in the ageing ratio yields a change in prevention share of 0.0368%. The optimal share of prevention health expenditure to GDP would be 1.175% when the prevalence rate of ill health isat 6.13%; a higher or lower share of prevention would be accompanied with a higher prevalence of ill health. For example, a zero and 1.358% preventive health expenditure would be associated with an 18.01% prevalence of ill health, while the current share of prevention of 0.237% is associated with a 10.26% prevalence of ill health.

Conclusion

This study shows that appropriate prevention is associated with decreases in the prevalence rates of ill health, which in turn attains sustainable growth in productivity. Too much prevention, however, could lead to higher detection of new chronic diseases with mild severity, which would result in longer illness duration, and higher prevalence rates of ill health. With suitable allocation of medical resources, the economic growth rate will help to cancel out increases in healthcare spending for the elderly and for expenses needed for the improvement of the population’s health as a whole.
Effects of novel bioorganic fertilizer application on soil enzymes and bacterial community in multi-site rice paddies in China
Authors: Li Zuren , Han Jincai , Bai Haodong , Peng Di , Wang Lifeng , Bai Lianyang
Published: June 2021

Application of a novel bioorganic fertilizer (BIO) has been effectively used to inhibit weeds in rice paddies. To identify changes in soil bacterial community and enzymes in response to BIO treatments, field experiments were carried out in five major rice-growing areas in China. The dominant phylogenetic groups recorded included Proteobacteria, Actinobacteria, Bacteroidetes, Firmicutes and Acidobacteria. Anaeromyxobacter, Bacteroides, Bifidobacterium, Escherichia- Shigella, Geobacter and Haliangium were significantly different between BIO-treatment and untreated control and aided in general function (R), amino acid transport, metabolism (E) and transcription (K) clusters. The soil chemical properties and enzyme activities were less affected by BIO at these study sites. RDA analysis showed that soil bacterial community had a significant positive correlations among northern latitude, eastern longitude, exchangeable K, total K, total P, soil pH, and total N, except for organic matter, hydrolytic N and extractable P. Overall, our work showed that application of BIO does not alter the main community structure and functional diversity of soil bacteria in rice paddies and should be encouraged for use as a sustainable weed management strategy.
Examining local perspectives on the influence of climate change on the health of Hamer pastoralists and their livestock in Ethiopia
Authors: Lumborg Samuel , Tefera Samuel , Munslow Barry , Mor Siobhan M.
Published: June 2021

This study explores the perceived influence of climate change on the health of Hamer pastoralists and their livestock in south-western Ethiopia. A combination of focus group discussions and key informant interviews were conducted with Hamer communities as well as local health workers, animal health workers and non-governmental organisation (NGO) staff. Thematic framework analysis was used to analyse the data. Reductions in rangeland, erratic rainfall, recurrent droughts and loss of seasonality were perceived to be the biggest climate challenges influencing the health and livelihoods of the Hamer. Communities were travelling greater distances to access sufficient grazing lands, and this was leading to livestock deaths and increases in ethnic violence. Reductions in suitable rangeland were also precipitating disease outbreaks in animals due to increased mixing of different herds. Negative health impacts in the community stemmed indirectly from decreases in livestock production, uncertain crop harvests and increased water scarcity. The remoteness of grazing lands has resulted in decreased availability of animal milk, contributing to malnutrition in vulnerable groups, including children. Water scarcity in the region has led to utilisation of unsafe water sources resulting in diarrhoeal illnesses. Further, seasonal shifts in climate-sensitive diseases such as malaria were also acknowledged. Poorly resourced healthcare facilities with limited accessibility combined with an absence of health education has amplified the community’s vulnerability to health challenges. The resilience and ambition for livelihood diversification amongst the Hamer was evident. The introduction of camels, increase in permanent settlements and new commercial ideas were transforming their livelihood strategies. However, the Hamer lack a voice to express their perspectives, challenges and ambitions. There needs to be collaborative dynamic dialogue between pastoral communities and the policy-makers to drive sustainable development in the area without compromising the values, traditions and knowledge of the pastoralists.
Emerging roles of non-histone protein crotonylation in biomedicine
Authors: Hou Jia-Yi , Zhou Lan , Li Jia-Lei , Wang De-Ping , Cao Ji-Min
Published: June 2021

Crotonylation of proteins is a newly found type of post-translational modifications (PTMs) which occurs leadingly on the lysine residue, namely, lysine crotonylation (Kcr). Kcr is conserved and is regulated by a series of enzymes and co-enzymes including lysine crotonyltransferase (writer), lysine decrotonylase (eraser), certain YEATS proteins (reader), and crotonyl-coenzyme A (donor). Histone Kcr has been substantially studied since 2011, but the Kcr of non-histone proteins is just an emerging field since its finding in 2017. Recent advances in the identification and quantification of non-histone protein Kcr by mass spectrometry have increased our understanding of Kcr. In this review, we summarized the main proteomic characteristics of non-histone protein Kcr and discussed its biological functions, including gene transcription, DNA damage response, enzymes regulation, metabolic pathways, cell cycle, and localization of heterochromatin in cells. We further proposed the performance of non-histone protein Kcr in diseases and the prospect of Kcr manipulators as potential therapeutic candidates in the diseases.
YTHDF1 promotes hepatocellular carcinoma progression via activating PI3K/AKT/mTOR signaling pathway and inducing epithelial-mesenchymal transition
Authors: Luo Xiangyuan , Cao Mengdie , Gao Fan , He Xingxing
Published: June 2021

Background

N6-methyladenosine (m6A) modification, as the most abundant RNA modification, widely participates in the physiological process and is involved in multiple disease progression, especially cancer. YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) is a pivotal m6A “reader” protein, which has been reported in multiple cancers. However, the role and molecular mechanism of YTHDF1 in HCC are still not fully elucidated.

Methods

Based on various bioinformatics databases, q-RT PCR, western blot, and a tissue microarray containing 90 HCC samples, we examined the expression of YTHDF1 in HCC. Then, we applied the loss-of-function experiments to explore the role of YTHDF1 in HCC by in vitro and in vivo assays. Finally, we performed the gene set enrichment analysis (GSEA) to predict the potential signaling pathway of YTHDF1 involved in HCC and further verified this prediction.

Results

YTHDF1 was overexpressed in HCC and associated with HCC grade. Depletion of YTHDF1 markedly impaired the proliferation, migration, invasion, and cell cycle process of HCC cells. Mechanistically, YTHDF1 promoted the growth of HCC cells via activating the PI3K/AKT/mTOR signaling pathway. Moreover, we also demonstrated that the epithelial-mesenchymal transition (EMT) mediated the promoting effect of YTHDF1 on the migration and invasion of HCC cells.

Conclusions

YTHDF1 contributes to the progression of HCC by activating PI3K/AKT/mTOR signaling pathway and inducing EMT.
A copper alloy light cannon from Grodno: an example of early firearms from Eastern Europe
Authors: Żabiński Grzegorz , Strzyż Piotr , Goryczka Tomasz , Aniołek Krzysztof , Miśta-Jakubowska Ewelina
Published: June 2021

The paper discusses a recent find of a copper alloy light cannon discovered at the Old Castle in Grodno, Belarus. The research aim was to analyse the artefact in all its possible aspects, including archaeological and historical contexts, possible analogies, and the gun’s technology of manufacture. This latter was done against a broad comparative background of what is known on manufacturing technologies of late medieval and modern period copper alloy firearms. First, the archaeological and historical contexts of the discovery are dealt with. Then, the morphology and typochronology of the cannon are discussed and relevant analogies are proposed. Next, the technology of manufacture of the cannon is studied on the basis of metallographic examinations and EDS analyses of the metal’s elemental composition. It was found out that the artefact had been made of leaded copper. The cannon can be dated with reasonable certainty to the late 14th c., as implied both by the find context, the morphology and the chemical composition of the artefact. Its deposition can be related to fights over the Old Castle in Grodno in this period, waged by Teutonic, Polish and Lithuanian forces. It can tentatively be proposed that the cannon was manufactured in a Teutonic Order’s workshop, but further research is necessary to verify this supposition.
Antioxidant property, anti-inflammatory and analgesic effects of aqueous extracts of two onion bulbs varieties (Allium cepa L.)
Authors: Dimitry Mang Yannick , Emmanuel Panyo’o Akdowa , Edith Djiogue Manejo Josiane , Armand Abdou Bouba , Nicolas Njintang Yanou
Published: June 2021

Background

oxidative stress and inflammation remain the main health problems often linked to degenerative diseases. The aim of this study was to evaluate antioxidant, analgesic and anti-inflammatory properties of onion growth in Cameroon.

Methods

Aqueous extracts were produced from two varieties of onion (Violet of galmi; Goudami) and were quantified for their polyphenols content. Concentrations of extracts (0.1, 0.5, 1, 1.5 mg/mL) were also prepared, their in vitro antioxidant properties evaluated by using standard methods. Anti-inflammatory effect of onion extracts was assessed by applying carrageenan sub plantar test to Wistar rats, but acetic acid test was used to study analgesic effect.

Results

The polyphenols content and antioxidant activities of onion extracts changed significantly (p < 0.05) with variety and increased (p < 0.05) with concentration. Total phenolic (range 58.03–67.43%), Total Reducing power (range 0.27–0.94%), DPPH radical scavenging (range 37.33–202.08%) were higher in Violet of galmi extracts, while Ferrous ion chelating power (range 23.15–97.42%) was higher in Goudami extract. The two varieties of onion extracts reduce (p < 0.05) rat paw edema in a dose dependent manner compared with negative control group. Violet of Galmi variety (1.5 mg/kg) reaches 100% of inhibition after 2 h whereas the Goudami variety (1.5 mg/kg) reaches 100% of inhibition after 3 h. In terms of analgesic activity, aqueous extract of the two varieties of onion exhibited analgesic effect characterized by reduction in writhes. Analgesic activity increased significantly (p < 0.05) with concentration of onion but Violet of galmi extracts has also shown more efficacy than Goudami extracts.

Conclusion

The present findings suggest that aqueous extract of violet of galmi and Goudami bulb onions have antioxidant activity and protective effects against inflammation and pain.
Mid-infrared supercontinuum generation in chalcogenide glass fibers: a brief review
Authors: Wang Yingying , Dai Shixun
Published: June 2021

Chalcogenide (ChG) glasses have the characteristics of a wide transparency window (over 20 μm) and high optical nonlinearity (up to 103 times greater than that of silica glasses), exhibiting great advantages over silica and other soft glasses in optical property at mid-infrared (MIR) wavelength range. These make them excellent candidates for MIR supercontinuum (SC) generation. Over the past decades, great progress has been made in MIR SC generation based on ChG fibers in terms of spectral extension and output power improvement. In this paper, we introduce briefly the properties of ChG glasses and fibers including transmission, nonlinearity, and dispersion, etc. Recent progress in MIR SC generation based on ChG fibers is reviewed from the perspective of pump schemes. We also present novel ChG fibers such as As-free, Te-based, and chalcohalide fibers, which have been explored and employed as nonlinear fibers to achieve broadband SC generation. Moreover, the potential applications of MIR SC sources based on ChG fibers are discussed.
Response to Induction Neoadjuvant Hormonal Therapy Using Upfront 21-Gene Breast Recurrence Score Assay—Results From the SAFIA Phase III Trial
Authors: AlSaleh Khalid , Al Zahwahry Heba , Bounedjar Adda , Oukkal Mohammed , Saadeddine Ahmed , Mahfouf Hassen , Bouzid Kamel , Bensalem Assia , Filali Taha , Abdel-Razeq Hikmat , Larbaoui Blaha , Kandil Alaa , Abulkhair Omalkhair , Al Foheidi Meteb , Errihani Hassan , Ghosn Marwan , Abdel-Aziz Nashwa , Arafah Maria , Boussen Hamouda , Dabouz Farida , Rasool Haleem , Bahadoor Mohun , Ayari Jihen , Kullab Sharif , Nabholtz Jean-Marc
Published: June 2021

PURPOSE

Luminal, human epidermal growth factor receptor 2–negative breast cancer represents the most common subtype of breast malignancies. Neoadjuvant strategies of operable breast cancer are mostly based on chemotherapy, whereas it is not completely understood which patients might benefit from neoadjuvant hormone therapy (NAHT).

MATERIALS AND METHODS

The SAFIA trial is a prospective multicenter, international, double-blind, neoadjuvant phase III trial, using upfront 21-gene Oncotype DX Breast Recurrence Score assay (recurrence score [RS] < 31) to select operable luminal human epidermal growth factor receptor 2–negative patients, for induction hormonal therapy HT (fulvestrant 500 mg with or without goserelin) before randomly assigning responding patients to fulvestrant 500 mg (with or without goserelin) plus either palbociclib (cyclin-dependent kinase 4/6 inhibitor) or placebo. The objectives of this interim analysis were to assess the feasibility of upfront RS determination on core biopsies in the Middle-East and North Africa region and evaluate the efficacy of induction NAHT in patients with an RS < 31.

RESULTS

At the time of this interim analysis, 258 patients with relative risk were accrued, including 202 patients (RS < 31% to 78.3%) treated with induction NAHT and 182 patients evaluable so far for response. The feasibility of performing the Oncotype DX assays on core biopsy specimens was optimal in 96.4% of cases. Overall, 93.4% of patients showed hormone sensitivity and no difference in NAHT efficacy was noticed between RS 0-10, 11-25, and 26-30. Interestingly, patients with high RS (26-30) showed a trend toward a higher major response rate ( P = .05).

CONCLUSION

The upfront 21-gene assay performed on biopsies is feasible in our population and has allowed us to select patients with high hormone sensitivity (RS < 31). This approach could be an alternative to upfront surgery without significant risk of progression, particularly during pandemic times.
Adjuvant Versus Early Salvage Radiation Therapy for Men at High Risk for Recurrence Following Radical Prostatectomy for Prostate Cancer and the Risk of Death
Authors: Tilki Derya , Chen Ming-Hui , Wu Jing , Huland Hartwig , Graefen Markus , Wiegel Thomas , Böhmer Dirk , Mohamad Osama , Cowan Janet E. , Feng Felix Y. , Carroll Peter R. , Trock Bruce J. , Partin Alan W. , D'Amico Anthony V.
Published: June 2021

PURPOSE

Adjuvant compared with early salvage radiation therapy (sRT) following radical prostatectomy (RP) has not been shown to reduce progression-free survival in randomized controlled trials. However, these trials might have missed a benefit in men with adverse pathology at RP given that these men were under-represented and immortal time bias might have been present; herein, we investigate this possibility.

METHODS

We evaluated the impact of adjuvant versus early sRT on all-cause mortality (ACM) risk in men with adverse pathology defined as positive pelvic lymph nodes (pN1) or pGleason score 8-10 prostate cancer (PC) and disease extending beyond the prostate (pT3/4). We used a treatment propensity score to minimize potential treatment selection bias when estimating the causal effect of adjuvant versus early sRT on ACM risk and a sensitivity analysis to assess the impact that varying definitions of adverse pathology had on ACM risk adjusting for age at RP, PC prognostic factors, site, and the time-dependent use of post-RP androgen deprivation therapy.

RESULTS

After a median follow-up (interquartile range) of 8.16 (6.00-12.10) years, of the 26,118 men in the study cohort, 2,104 (8.06%) died, of which 539 (25.62%) were from PC. After excluding men with a persistent prostate-specific antigen, adjuvant compared with early sRT was associated with a significantly lower ACM risk among men with adverse pathology at RP when men with pN1 PC were excluded (0.33 [0.13-0.85]; P = .02) or included (0.66 [0.44-0.99]; P = .04).

CONCLUSION

Adjuvant radiation therapy should be considered in men with pN1 or pGleason score 8 to 10 and pT3/4 PC given the possibility that a significant reduction in ACM risk exists.