bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

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

Abstract
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

Abstract
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

AbstractCases 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

AbstractThe 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

Abstract
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

Abstract
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

Abstract
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

AbstractObjectivesTo 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”ResultsThe 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

AbstractBackgroundLanguage 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.MethodsAudio 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.ResultsClinician 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.ConclusionsVariables 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

Abstract
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

AbstractApplication 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.