bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance evaluation of the highly sensitive histidine‐rich protein 2 rapid test for Plasmodium falciparum malaria in North-West Tanzania
Authors: Manjurano Alphaxard , Omolo Justin J. , Lyimo Eric , Miyaye Donald , Kishamawe Coleman , Matemba Lucas E. , Massaga Julius J. , Changalucha John , Kazyoba Paul E.
Published: January 2021

Background

Precise detection of Plasmodium infections in community surveys is essential for effective malaria control. Microscopy and rapid diagnostic tests (RDTs) are the major techniques used to identify malaria infections in the field-based surveys. Although microscopy is still considered as the gold standard, RDTs are increasingly becoming versatile due to their rapid and adequate performance characteristics.

Methods

A malaria prevalence cross-sectional survey was carried out in north-western Tanzania in 2016, aimed at appraising the performance of high sensitivity Plasmodium falciparum (HSPf) tests compared to SD Bioline Pf and microscopy in detecting P. falciparum infections. A total of 397 individuals aged five years and above were tested for P. falciparum infections. The sensitivity, specificity, positive, and negative predictive values (PPV and NPV) of microscopy, Pf RDT and HSPf RDT was determined using PCR as the gold standard method.

Results

The prevalence of P. falciparum infections determined by microscopy, SD Bioline Pf, HSPf and PCR was 21.9, 27.7, 33.3 and 43.2%, respectively. The new HSPf RDT had significantly higher sensitivity (98.2%) and specificity (91.6%) compared to the routinely used SD Bioline Pf RDT(P < 0.001). The positive predictive value (PPV) was 81.8% and the negative predictive value (NPV) was 99.2% for the routinely used SD Bioline Pf RDT. Moreover, HSPf RDT had sensitivity of 69% and specificity of 76.8% compared to microscopy. The PPV was 45.5% and the NPV was 89.8% for microscopy. Furthermore, the analytical sensitivity test indicated that the newly developed HSPf RDT had lower detection limits compared to routinely used SD Bioline RDT.

Conclusions

HSPf RDT had better performance when compared to both microscopy and the currently used malaria RDTs. The false negativity could be associated with the low parasite density of the samples. False positivity may be related to the limitations of the expertise of microscopists or persistent antigenicity from previous infections in the case of RDTs. Nevertheless, HS PfRDT performed better compared to routinely used Pf RDT, and microscopy in detecting malaria infections. Therefore, HS Pf RDT presents the best alternative to the existing commercial/regularly available RDTs due to its sensitivity and specificity, and reliability in diagnosing malaria infections.
Progress and challenges in the use of fluorescence‐based flow cytometric assays for anti‐malarial drug susceptibility tests
Authors: Kulkeaw Kasem
Published: January 2021

Drug-resistantPlasmodiumis a frequent global threat in malaria eradication programmes, highlighting the need for new anti-malarial drugs and efficient detection of treatment failure.Plasmodium falciparumculture is essential in drug discovery and resistance surveillance. Microscopy of Giemsa-stained erythrocytes is common for determining anti-malarial effects on the intraerythrocytic development of culturedPlasmodiumparasites. Giemsa-based microscopy use is conventional but laborious, and its accuracy depends largely on examiner skill. Given the availability of nucleic acid-binding fluorescent dyes and advances in flow cytometry, the use of various fluorochromes has been frequently attempted for the enumeration of parasitaemia and discrimination ofP. falciparumgrowth in drug susceptibility assays. However, fluorochromes do not meet the requirements of being fast, simple, reliable and sensitive. Thus, this review revisits the utility of fluorochromes, notes previously reported hindrances, and highlights the challenges and opportunities for using fluorochromes in flow cytometer-based drug susceptibility tests. It aims to improve drug discovery and support a resistance surveillance system, an essential feature in combatting malaria.
Evaluation of malaria preventive measures among adult patients attending the Bamendjou and Foumbot district hospitals of the West Region of Cameroon
Authors: Nlinwe Nfor Omarine , Singong Yengong Clinton , Florentine Tenkam Makamdoum Ruth
Published: January 2021

Background

Although a significant decrease in entomological and epidemiological indicators was reported in Cameroon since the introduction of insecticide-treated bed nets, malaria prevalence remains high also in some parts of the West Region of Cameroon. This study was designed to evaluate malaria preventive measures among patients attending the Bamendjou and Foumbot District hospitals of the West Region of Cameroon.

Methods

This was a cross-sectional study carried out within a period of 3 months, from January to March 2020. Data was obtained using a structured questionnaire and laboratory analysis. The CareStart™ Pf Malaria HRP2 qualitative rapid diagnostic test was used for malaria diagnosis. The questionnaire was designed to collect information on respondent’s socio-demographic characteristics, and the use of malaria preventive measures. Data were analysed using descriptive statistics, regression analysis, and Chi-square (and Fisher’s exact) test.

Results

A total of 170 study participants were recruited in Foumbot and 197 in Bamendjou. Malaria was significantly (P < 0.0001) more prevalent in Foumbot (47.06%) than in Bamendjou (19.8%). In Foumbot, non-use of insect repellent spray (P = 0.0214), insect repellent body cream (P = 0.0009), mosquito spray (P = 0.0001) and not draining stagnant water (P = 0.0004) predisposed to higher risk of malaria. In Bamendjou, non-use of insect repellent spray (P = 0.0012), long-lasting insecticidal bed nets (P = 0.0001), window and door nets (P = 0.0286), predisposed to a higher risk of malaria.

Conclusions

Malaria prevalence was high among the study participants especially in Foumbot. An adequate follow-up to ensure effective execution of the recently launched third phase of LLINs distribution campaign in Cameroon is recommended. Additionally, integrated vector management is required to ensure effective control of malaria transmission in Foumbot and Bamendjou.
Sulfadoxine-pyrimethamine parasitological efficacy against Plasmodium falciparum among pregnant women and molecular markers of resistance in Zambia: an observational cohort study
Authors: Chaponda Enesia Banda , Mharakurwa Sungano , Michelo Charles , Bruce Jane , Chandramoha Daniel , Matthew Chico R.
Published: January 2021

Background

The World Health Organization recommends the provision of intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) at 4-week intervals from gestational week 13 to delivery in areas of moderate to high malaria transmission intensity. However, the effect of IPTp-SP has been compromised in some areas due to parasite resistance, raising the importance of parasitological and chemoprophylactic surveillance, and monitoring SP-resistance markers in the Plasmodium falciparum population.

Methods

Between November 2013 and April 2014 in Nchelenge, Zambia, 1086 pregnant women received IPTp-SP at antenatal-care bookings. Blood samples were collected on day 0, and on day 28 post-treatment to test for malaria parasites and to estimate SP parasitological efficacy in the treatment and prevention of parasitaemia. A random sample of 96, day 0 malaria-positive samples were analysed to estimate the prevalence of SP-resistance markers in the P. falciparum population.

Results

The overall parasitological and prophylactic failure among women who had paired day 0 and day 28 blood slides was 18.6% (95% CI 15.5, 21.8; 109 of 590). Among pregnant women who had asymptomatic parasitaemia on day 0, the day 28 PCR-uncorrected parasitological failure was 30.0% (95% CI 23.7, 36.2; 62 of 207) and the day 28 PCR-corrected parasitological failure was 15.6% (95% CI: 10.6, 20.6; 32 of 205). Among women who tested negative at day 0, 12.3% (95% CI: 9.0, 15.6; 47 of 383) developed parasitaemia at day 28. Among the 96 malaria-positive samples assayed from day 0, 70.8% (95% CI: 60.8, 79.2) contained the DHPS double (Gly-437 + Glu-540) mutation and 92.7% (95% CI: 85.3, 96.5) had the DHFR triple (Asn-108 + Ile-51 + Arg-59) mutation. The quintuple mutation (DHFR triple + DHPS double) and the sextuple mutant (DHFR triple + DHPS double + Arg-581) were found among 68.8% (95% CI: 58.6, 77.3) and 9.4% (95% CI: 4.2, 16.0) of samples, respectively.

Conclusion

The parasitological and chemoprophylactic failure of SP, and the prevalence of resistance markers in Nchelenge is alarmingly high. Alternative therapies are urgently needed to safeguard pregnant women against malarial infection.
A hidden side of the COVID-19 pandemic in children: the double burden of undernutrition and overnutrition
Authors: Zemrani Boutaina , Gehri Mario , Masserey Eric , Knob Cyril , Pellaton Rachel
Published: January 2021

The COVID-19 pandemic has deteriorated key determinants of health and caused major upheavals around the world. Children, although less directly affected by the virus, are paying a heavy price through the indirect effects of the crisis, including poor diet, mental health impact, social isolation, addiction to screens and lack of schooling and health care, particularly among vulnerable groups. This paper is aimed at discussing the potential impact of this pandemic on children’s nutrition and lifestyle. Preliminary data from the literature and from our survey show significant disruptions in nutrition and lifestyle habits of children. While undernutrition is expected to worsen in poor countries, obesity rates could increase in middle- and high-income countries especially among precarious groups widening the gap in health and social inequalities.

The real impact of the COVID-19 pandemic on children extends well beyond that of a viral infection. This crisis has public health implications that could have life-long consequences on children. It requires effective and targeted measures mainly for vulnerable children and households to guarantee children’s basic rights for optimal nutrition, health and development.
Factors associated with child delivery expenditure during the transition to the national implementation of the two-child policy in China
Authors: Zang Shuang , OuYang Jing , Zhao Meizhen , Zhu Yalan , Liu Jia , Wang Xin
Published: January 2021

Background

This study aimed to analyze the status of birthrates and the characteristics of child delivery expenditure under the Chinese two-child policy’s transition period. We evaluated the socioeconomic factors associated with child delivery and provide evidence for decisions relating to health support for childbirth.

Methods

Child delivery expense data were obtained from 2015 to 2017 in Dalian, China. A total of 13,535 obstetric records were enrolled using stratified random sampling and the proportional probability to size method. First, we calculated the current curative expenditure of child delivery and health financing in childbirth costs based on the System of Health Accounts 2011 (SHA 2011). Second, univariate analysis of variance and generalized linear modeling were performed to examine factors associated with child delivery expenditure. Third, we classified the included hospitals into the county, district, and municipal hospitals and compared maternal characteristics between these categories.

Results

Overall, out-of-pocket payments accounted for more than 35% of the total expenditure on child delivery. Median (interquartile range) delivery expenditure at the county and district level hospitals [county-level: 5128.50 (3311.75–5769.00) CNY; district-level: 4064.00 (2824.00–6599.00) CNY] was higher than that at the municipal level hospitals: 3824.50 (2096.50–5908.00) CNY. The increase of child delivery expenditure was associated with an increased ratio of reimbursement, admissions to county and district level hospitals, cesarean sections, and length of stay, as well as a decline in average maternal age (p < 0.05).

Conclusions

Health financing for childbirth expenditure was not rational during the transition period of the family planning policy in China. Higher delivery expenditure at county and district level hospitals may indicate variations in medical professionalism. Poorly managed hospitalization expenditure and/or nonstandard medical charges for childbirth, all of which may require the development of appropriate public health policies to regulate such emerging phenomena.
Effectiveness of an intrauterine device informative intervention among post-natal women in Western Jamaica
Authors: Franklin Sarah G. , O’Neal Maya , Arneus Ambreanna , Colvin Calvin , Aung Maung , Jolly Pauline E.
Published: January 2021

Introduction

Intrauterine devices are the most effective long-acting reversible contraceptives, but in many developing countries, such as Jamaica, these devices remain underutilized.

Methods

A cross-sectional informative intervention was conducted among women ≥ 18 years of age attending postnatal clinics in western Jamaica from May to August 2018. Data were collected using an investigator-administered questionnaire/pre-test followed by a 12-slide PowerPoint® presentation and a post-test.

Results

Most of the 299 women who participated were 18–29 years of age, with a mean age of 27.1 (SD ± 6.1) years. Most had their first pregnancy between ages 18 and 24 years, with mean age at first pregnancy of 20.2 (SD ± 4.0) years. Only 3.0% of participants reported current use of an intrauterine device; 3.5% reported using an intrauterine device in the past. For nearly every measure of knowledge of intrauterine devices, there was a significant change in the proportion of participants who got the correct answer from the pre-test to the post-test. The mean summed pre-test knowledge score was 9.54 (SD ± 3.46) and the post-test score was 15.23 (SD ± 1.92); the possible total score is 18. The difference between the mean scores (5.69 points) was also significant.

Conclusion

The intervention resulted in significant change in knowledge of intrauterine devices among the women and cleared up many misconceptions that may have contributed to reluctance of women to use intrauterine devices. Women of reproductive age in Jamaica should be counseled on contraceptive methods including intrauterine devices so that these devices can be considered in their contraceptive choices.
Sooty bark disease of maples: the risk for hypersensitivity pneumonitis by fungal spores not only for woodman
Authors: Braun Markus , Klingelhöfer Doris , Groneberg David A.
Published: January 2021

In the middle of the twentieth century, the from North America sooty bark disease (SBD) of maples was first discovered in England and has spread in the last decades in Central Europe, in particular. The trigger of SBD is the mould fungus Cryptostroma (C.) corticale. The most common infested maple is the sycamore, Acer pseudoplatanus, a common tree in woods and parks. The disease is characterised by peeling of the outer layer of the bark and brownish-black spores under the peeled off bark. These spores can cause maple bark disease (MBD) in humans, a hypersensitivity pneumonitis (HP) with similar symptoms like COPD, allergic asthma, influenza or flu-like infections and interstitial pneumonia. Persons who have intensive respectively occupational contact with infested trees or wood, e.g., woodman, foresters, sawyers or paper mill workers, are at risk in particular. Since C. corticale favours hot summers and host trees weakened by drought, SBD will increasingly spread in the future due to ongoing climate change. Consequently, the risk of developing MBD will increase, too. As with all HPs, e.g., farmer’s lung and pigeon breeder’s disease, the diagnosis of MBD is intricate because it has no clear distinguishing characteristics compared to other interstitial lung diseases. Therefore, the establishment of consistent diagnosis guidelines is required. For correct diagnosis and successful therapy, multidisciplinary expertise including pulmonologists, radiologists, pathologists and occupational physicians is recommended. If MBD is diagnosed in time, the removal of the triggering fungus or the infested maple wood leads to complete recovery in most cases. Chronic HP can lead to lung fibrosis and a total loss of lung function culminating in death. HP and, thus, MBD, is a disease with a very high occupational amount. To avoid contact with spores of C. corticale, persons working on infested wood or trees have to wear personal protective equipment. To protect the public, areas with infested maples have to be cordoned off, and the trees should be removed. This is also for impeding further spreading of the spores.
Factors associated with delayed initiation of breastfeeding in health facilities: secondary analysis of Bangladesh demographic and health survey 2014
Authors: Raihana Shahreen , Alam Ashraful , Huda Tanvir M. , Dibley Michael J.
Published: January 2021

Background

Irrespective of the place and mode of delivery, ‘delayed’ initiation of breastfeeding beyond the first hour of birth can negatively influence maternal and newborn health outcomes. In Bangladesh, 49% of newborns initiate breastfeeding after the first hour. The rate is higher among deliveries at a health facility (62%). This study investigates the maternal, health service, infant, and household characteristics associated with delayed initiation of breastfeeding among health facility deliveries in Bangladesh.

Methods

We used data from the 2014 Bangladesh Demographic and Health Survey. We included 1277 last-born children born at a health facility in the 2 years preceding the survey. ‘Delayed’ breastfeeding was defined using WHO recommendations as initiating after 1 h of birth. We performed univariate and multivariable logistic regression to determine factors associated with delayed initiation.

Results

About three-fifth (n = 785, 62%) of the children born at a health facility delayed initiation of breastfeeding beyond 1 h. After adjusting for potential confounders, we found delayed initiation to be common among women, who delivered by caesarean section (adjusted Odds Ratio (aOR): 2.93; 95% CI 2.17, 3.98), and who were exposed to media less than once a week (aOR: 1.53; 95% CI 1.07, 2.19). Women with a higher body mass index had an increased likelihood of delaying initiation (aOR: 1.05; 95% CI 1.01, 1.11). Multiparous women were less likely to delay (aOR: 0.71; 95% CI 0.53, 0.96).

Conclusions

Delayed initiation of breastfeeding following caesarean deliveries continues to be a challenge, but several other health facility and maternal factors also contributed to delayed initiation. Interventions to promote early breastfeeding should include strengthening the capacity of healthcare providers to encourage early initiation, especially for caesarean deliveries.
Delayed postoperative radiotherapy increases the incidence of radiographic local tumor progression before radiotherapy and leads to poor prognosis in spinal metastases
Authors: Gong Yining , Zhuang Hongqing , Chong Shan , Shi Qianyu , Wei Feng , Liu Zhongjun , Ouyang Hanqiang , Liu Xiaoguang , Jiang Liang
Published: January 2021

Background

Most previous studies focused on the minimum interval between surgery and radiotherapy in spinal metastases, leaving the maximum interval under-investigated. However, in real world, limited radiotherapist and equipment cannot meet the needs of a large patient population to obtain timely radiotherapy after the index spine surgery in developing countries. This study aimed to estimate the clinical risks of delayed radiotherapy after surgery in patients with spinal metastases in developing country.

Methods

Data from 89 patients who underwent surgery and postoperative radiotherapy at a single site in a developing country were retrospectively reviewed. Patients were divided into the progression before radiotherapy (PBR) and no progression before radiotherapy (NPBR) groups. Kaplan–Meier analysis and log-rank tests were used to compare the local control (LC) and overall survival (OS) between groups.

Results

Within 1 month after surgery, only 20.2% of patients underwent radiotherapy. Risk of local progression before radiotherapy at 1, 3, and 6 months was 1.2%, 24.1%, and 45.1%, respectively. The LC rate at 1 year was lower in the PBR group than in the NPBR group (53.3% vs. 76.3%, P = 0.040). The OS rate at 1 year was 61.9% and 79.6% in the PBR and NPBR groups, respectively (P = 0.001). The Karnofsky performance status significantly improved only in the NPBR group (52.5 ± 17.6 vs. 66.8 ± 26.3, P < 0.001). The sphincter dysfunction significantly improved in the NPBR group (0.3 ± 0.5 vs. 0.1 ± 0.3, P = 0.007) but it tended to be deteriorated in the PBR group (0.1 ± 0.4 vs. 0.3 ± 0.5, P = 0.500).

Conclusions

In real world, about 80% of patients had delayed radiotherapy 1 month after spine surgery for metastases in our developing country. Patients had a higher risk for radiographic local progression before radiotherapy and poorer LC, OS, and quality of life as time to radiotherapy increased.
Risk factors of postoperative delirium in the knee and hip replacement patients: a systematic review and meta-analysis
Authors: Rong Xiao , Ding Zi-chuan , Yu Hao-da , Yao Shun-Yu , Zhou Zong-Ke
Published: January 2021

Background

The risk factors of postoperative delirium (POD), a serious while preventable complication, developed by patients undergoing knee and replacement surgery are still under investigation. In this systematic review and meta-analysis, we identified risk factors associated with POD in knee and hip replacement.

Methods

PubMed, Ovid MEDLINE, and Ovid EMBASE were used to identify original researches. The studies evaluating the risk factors of POD after knee and hip replacement were reviewed, and the qualities of the included studies were assessed with Newcastle–Ottawa Scale. Data were extracted, pooled, and a meta-analysis was completed

Result

Twenty-two studies were finally included with a total of 11934 patients who underwent knee or hip replacement and 1841 developed POD with an incidence of 17.6% (95% confidential interval (CI) 13.2–22.0%). Eighteen significant risk factors were identified including advanced age (odds ratio (OR) 1.15 95% CI 1.08–1.22), cognitive impairment (OR 6.84, 95% CI 3.27–14.33), history of cerebrovascular events (OR 2.51, 95% CI 1.28–4.91), knee replacement (OR 1.42, 95% CI 1.00–2.02), blood loss (standardized mean difference (SMD) 0.30, 95% CI 0.15–0.44), dementia (OR 3.09, 95% CI 2.10–4.56), neurologic disorders (OR 2.26, 95% CI 1.23–4.15), psychiatric illness (OR 2.74, 95% CI 1.34–5.62), and obstructive sleep apnea (OR 4.17, 95% CI 1.72–10.09) along with several comorbidity evaluation scores and laboratory markers.

Conclusion

We identified risk factors consistently associated with the incidence of POD in knee and hip replacement. Strategies and interventions should be implemented to the patients receiving knee or hip replacement with potential risk factors identified in this meta-analysis.
Analgesic effect of single-shot ropivacaine at different layers of the surgical site in primary total hip arthroplasty: a randomised, controlled, observer-blinded study
Authors: Xiao Qiang , Xu Bing , Wang Haoyang , Luo Zhenyu , Yuan Mingcheng , Zhou Zongke , Pei Fuxing
Published: January 2021

Objectives

The aim of this study was to evaluate the efficacy of local infiltration anaesthesia (LIA) during primary total hip arthroplasty (THA) via a posterolateral approach under general anaesthesia and to compare the efficacy of LIA in all layers with LIA in the deep and superficial fascia.

Patients and methods

One hundred twenty patients were randomised into three groups: LIA in the deep and superficial fascia (group A), LIA in all layers (group B) and the control (group C). The primary outcomes were the visual analogue scale (VAS) pain scores at rest and on movement within 72 h (h) postoperatively. The secondary outcomes included opioid consumption, patient satisfaction, range of motion (ROM), straight leg raise completion rate, length of hospital stay, opioid-related side effects and wound complications. We followed the patients until 6 months after discharge.

Results

At 2 and 6 h, groups A and B had lower resting VAS scores than group C (p< 0.01); at 12 h, group B had a lower resting VAS score than group C (p< 0.05). At 6 and 12 h, the movement VAS scores in groups A and B were lower than those in group C (p< 0.01). Groups A and B had similar VAS scores during the observation period. Groups A and B had higher levels of patient satisfaction than group C (p= 0.03 andp= 0.018, respectively). Opioid consumption was similar in the three groups. There were no significant differences in the other secondary outcomes amongst the three groups. No difference was found in hip rehabilitation or chronic pain during the follow-up period.

Conclusion

Single-shot LIA with ropivacaine alone reduces the pain score during the first 12 postoperative hours and improves patients’ satisfaction with THA. LIA in the deep and superficial fascia and LIA in all layers have similar analgesic effects. LIA in the deep and superficial fascia may be an alternative method to LIA in all layers.
Effects of exogenous nerve growth factor on the expression of BMP-9 and VEGF in the healing of rabbit mandible fracture with local nerve injury
Authors: Yang Sen , Cheng Jiao , Man Cheng , Jiang Lian , Long Guogeng , Zhao Wenjun , Zheng Dexin
Published: January 2021

Background

Mandibular fracture healing is a complex process involving nerves and growth factors. Nerve growth factor (NGF) not only facilitates the maintenance of sympathetic neurite growth but also stimulates other growth factors that can promote the essential osteogenesis and angiogenesis for fracture healing. Therefore, it is necessary to analyze the combined effects of NGF, bone morphogenic protein-9 (BMP-9), and vascular endothelial growth factor (VEGF) to accelerate the healing of mandible fractures.

Methods

The models of mandible fracture with local nerve injury established in 48 rabbits were randomly divided into nerve growth factor group (NGF group), gelatin sponge group (GS group), blank group, and intact group. The recovery of nerve reflex was assessed by observing the number of rabbits with lower lip responses to acupuncture. The fracture healing was observed with visual and CBCT, and then callus tissues from the mandibular fracture area were collected for hematoxylin and eosin (HE) staining observation, and the expression of BMP-9 and VEGF in callus at different stages was detected by quantitative real-time PCR (qRT-PCR).

Results

Needling reaction in the lower lip showed the number of animals with nerve reflex recovery was significantly higher in the NGF group than that in the GS and blank groups at the 2nd and 4th weeks after the operation. The combined results of macroscopic observation, CBCT examination, and histological analysis showed that a large number of osteoblasts and some vascular endothelial cells were found around the trabecular bone in the NGF group and the amount of callus formation and reconstruction was better than that in the GS group at the 2nd week after the operation. The qRT-PCR results indicated that the expression levels of BMP-9 and VEGF in the four groups reached the highest values at the 2nd week, while the expression levels of both in the NGF group were significantly higher than that in the GS group.

Conclusion

The exogenous NGF could accelerate the healing of mandible fractures. This work will provide a new foundation and theoretical basis for clarifying the mechanism of fracture healing, thereby promoting fracture healing and reducing the disability rate of patients.
Myopia-26, the female-limited form of early-onset high myopia, occurring in a European family
Authors: Széll Noémi , Fehér Tamás , Maróti Zoltán , Kalmár Tibor , Latinovics Dóra , Nagy István , Orosz Zsuzsanna Z. , Janáky Márta , Facskó Andrea , Sohajda Zoltán
Published: January 2021

Background

Female-limited early-onset high myopia, also called Myopia-26 is a rare monogenic disorder characterized by severe short sightedness starting in early childhood and progressing to blindness potentially by the middle ages. Despite the X-linked locus of the mutated ARR3 gene, the disease paradoxically affects females only, with males being asymptomatic carriers. Previously, this disease has only been observed in Asian families and has not gone through detailed investigation concerning collateral symptoms or pathogenesis.

Results

We found a large Hungarian family displaying female-limited early-onset high myopia. Whole exome sequencing of two individuals identified a novel nonsense mutation (c.214C>T, p.Arg72*) in the ARR3 gene. We carried out basic ophthalmological testing for 18 family members, as well as detailed ophthalmological examination (intraocular pressure, axial length, fundus appearance, optical coherence tomography, visual field- testing) as well as colour vision- and electrophysiology tests (standard and multifocal electroretinography, pattern electroretinography and visual evoked potentials) for eight individuals. Ophthalmological examinations did not reveal any signs of cone dystrophy as opposed to animal models. Electrophysiology and colour vision tests similarly did not evidence a general cone system alteration, rather a central macular dysfunction affecting both the inner and outer (postreceptoral and receptoral) retinal structures in all patients with ARR3 mutation.

Conclusions

This is the first description of a Caucasian family displaying Myopia-26. We present two hypotheses that could potentially explain the pathomechanism of this disease.
Methods to investigate intrathecal adaptive immunity in neurodegeneration
Authors: Oh Hamilton , Leventhal Olivia , Channappa Divya , Henderson Victor W. , Wyss-Coray Tony , Lehallier Benoit , Gate David
Published: January 2021

Background

Cerebrospinal fluid (CSF) provides basic mechanical and immunological protection to the brain. Historically, analysis of CSF has focused on protein changes, yet recent studies have shed light on cellular alterations. Evidence now exists for involvement of intrathecal T cells in the pathobiology of neurodegenerative diseases. However, a standardized method for long-term preservation of CSF immune cells is lacking. Further, the functional role of CSF T cells and their cognate antigens in neurodegenerative diseases are largely unknown.

Results

We present a method for long-term cryopreservation of CSF immune cells for downstream single cell RNA and T cell receptor sequencing (scRNA-TCRseq) analysis. We observe preservation of CSF immune cells, consisting primarily of memory CD4+ and CD8+ T cells. We then utilize unbiased bioinformatics approaches to quantify and visualize TCR sequence similarity within and between disease groups. By this method, we identify clusters of disease-associated, antigen-specific TCRs from clonally expanded CSF T cells of patients with neurodegenerative diseases.

Conclusions

Here, we provide a standardized approach for long-term storage of CSF immune cells. Additionally, we present unbiased bioinformatic approaches that will facilitate the discovery of target antigens of clonally expanded T cells in neurodegenerative diseases. These novel methods will help improve our understanding of adaptive immunity in the central nervous system.
Privacy-preserving chi-squared test of independence for small samples
Authors: Sei Yuichi , Ohsuga Akihiko
Published: January 2021

Background

The importance of privacy protection in analyses of personal data, such as genome-wide association studies (GWAS), has grown in recent years. GWAS focuses on identifying single-nucleotide polymorphisms (SNPs) associated with certain diseases such as cancer and diabetes, and the chi-squared (χ2) hypothesis test of independence can be utilized for this identification. However, recent studies have shown that publishing the results of χ2 tests of SNPs or personal data could lead to privacy violations. Several studies have proposed anonymization methods for χ2 testing with ε-differential privacy, which is the cryptographic community’s de facto privacy metric. However, existing methods can only be applied to 2×2 or 2×3 contingency tables, otherwise their accuracy is low for small numbers of samples. It is difficult to collect numerous high-sensitive samples in many cases such as COVID-19 analysis in its early propagation stage.

Results

We propose a novel anonymization method (RandChiDist), which anonymizes χ2 testing for small samples. We prove that RandChiDist satisfies differential privacy. We also experimentally evaluate its analysis using synthetic datasets and real two genomic datasets. RandChiDist achieved the least number of Type II errors among existing and baseline methods that can control the ratio of Type I errors.

Conclusions

We propose a new differentially private method, named RandChiDist, for anonymizing χ2 values for an I×J contingency table with a small number of samples. The experimental results show that RandChiDist outperforms existing methods for small numbers of samples.
Bedside POCUS during ward emergencies is associated with improved diagnosis and outcome: an observational, prospective, controlled study
Authors: Zieleskiewicz Laurent , Lopez Alexandre , Hraiech Sami , Baumstarck Karine , Pastene Bruno , Di Bisceglie Mathieu , Coiffard Benjamin , Duclos Gary , Boussuges Alain , Bobbia Xavier , Einav Sharon , Papazian Laurent , Leone Marc
Published: January 2021

Background

Rapid response teams are intended to improve early diagnosis and intervention in ward patients who develop acute respiratory or circulatory failure. A management protocol including the use of a handheld ultrasound device for immediate point-of-care ultrasound (POCUS) examination at the bedside may improve team performance. The main objective of the study was to assess the impact of implementing such a POCUS-guided management on the proportion of adequate immediate diagnoses in two groups. Secondary endpoints included time to treatment and patient outcomes.

Methods

A prospective, observational, controlled study was conducted in a single university hospital. Two teams alternated every other day for managing in-hospital ward patients developing acute respiratory and/or circulatory failures. Only one of the team used an ultrasound device (POCUS group).

Results

We included 165 patients (POCUS group 83, control group 82). Proportion of adequate immediate diagnoses was 94% in the POCUS group and 80% in the control group (p = 0.009). Time to first treatment/intervention was shorter in the POCUS group (15 [10–25] min vs. 34 [15–40] min, p < 0.001). In-hospital mortality rates were 17% in the POCUS group and 35% in the control group (p = 0.007), but this difference was not confirmed in the propensity score sample (29% vs. 34%, p = 0.53).

Conclusion

Our study suggests that protocolized use of a handheld POCUS device at the bedside in the ward may improve the proportion of adequate diagnosis, the time to initial treatment and perhaps also survival of ward patients developing acute respiratory or circulatory failure.

Clinical Trial Registration NCT02967809. Registered 18 November 2016, https://clinicaltrials.gov/ct2/show/NCT02967809.
MicroExonator enables systematic discovery and quantification of microexons across mouse embryonic development
Authors: Parada Guillermo E. , Munita Roberto , Georgakopoulos-Soares Ilias , Fernandes Hugo J. R. , Kedlian Veronika R. , Metzakopian Emmanouil , Andres Maria Estela , Miska Eric A. , Hemberg Martin
Published: January 2021

Background

Microexons, exons that are ≤ 30 nucleotides, are a highly conserved and dynamically regulated set of cassette exons. They have key roles in nervous system development and function, as evidenced by recent results demonstrating the impact of microexons on behaviour and cognition. However, microexons are often overlooked due to the difficulty of detecting them using standard RNA-seq aligners.

Results

Here, we present MicroExonator, a novel pipeline for reproducible de novo discovery and quantification of microexons. We process 289 RNA-seq datasets from eighteen mouse tissues corresponding to nine embryonic and postnatal stages, providing the most comprehensive survey of microexons available for mice. We detect 2984 microexons, 332 of which are differentially spliced throughout mouse embryonic brain development, including 29 that are not present in mouse transcript annotation databases. Unsupervised clustering of microexons based on their inclusion patterns segregates brain tissues by developmental time, and further analysis suggests a key function for microexons in axon growth and synapse formation. Finally, we analyse single-cell RNA-seq data from the mouse visual cortex, and for the first time, we report differential inclusion between neuronal subpopulations, suggesting that some microexons could be cell type-specific.

Conclusions

MicroExonator facilitates the investigation of microexons in transcriptome studies, particularly when analysing large volumes of data. As a proof of principle, we use MicroExonator to analyse a large collection of both mouse bulk and single-cell RNA-seq datasets. The analyses enabled the discovery of previously uncharacterized microexons, and our study provides a comprehensive microexon inclusion catalogue during mouse development.
Integrative analyses of TEDDY Omics data reveal lipid metabolism abnormalities, increased intracellular ROS and heightened inflammation prior to autoimmunity for type 1 diabetes
Authors: Balzano-Nogueira Leandro , Ramirez Ricardo , Zamkovaya Tatyana , Dailey Jordan , Ardissone Alexandria N. , Chamala Srikar , Serrano-Quílez Joan , Rubio Teresa , Haller Michael J. , Concannon Patrick , Atkinson Mark A. , Schatz Desmond A. , Triplett Eric W. , Conesa Ana
Published: January 2021

Background

The Environmental Determinants of Diabetes in the Young (TEDDY) is a prospective birth cohort designed to study type 1 diabetes (T1D) by following children with high genetic risk. An integrative multi-omics approach was used to evaluate islet autoimmunity etiology, identify disease biomarkers, and understand progression over time.

Results

We identify a multi-omics signature that was predictive of islet autoimmunity (IA) as early as 1 year before seroconversion. At this time, abnormalities in lipid metabolism, decreased capacity for nutrient absorption, and intracellular ROS accumulation are detected in children progressing towards IA. Additionally, extracellular matrix remodeling, inflammation, cytotoxicity, angiogenesis, and increased activity of antigen-presenting cells are observed, which may contribute to beta cell destruction. Our results indicate that altered molecular homeostasis is present in IA-developing children months before the actual detection of islet autoantibodies, which opens an interesting window of opportunity for therapeutic intervention.

Conclusions

The approach employed herein for assessment of the TEDDY cohort showcases the utilization of multi-omics data for the modeling of complex, multifactorial diseases, like T1D.
Effect of early sleep apnoea treatment with adaptive servo-ventilation in acute stroke patients on cerebral lesion evolution and neurological outcomes: study protocol for a multicentre, randomized controlled, rater-blinded, clinical trial (eSATIS: early Sleep Apnoea Treatment in Stroke)
Authors: Duss Simone B. , Brill Anne-Kathrin , Baillieul Sébastien , Horvath Thomas , Zubler Frédéric , Flügel Dominique , Kägi Georg , Benz Gabriel , Bernasconi Corrado , Ott Sebastian R. , Korostovtseva Lyudmila , Sviryaev Yurii , Salih Farid , Endres Matthias , Tamisier Renaud , Gouveris Haralampos , Winter Yaroslav , Denier Niklaus , Wiest Roland , Arnold Marcel , Schmidt Markus H. , Pépin Jean-Louis , Bassetti Claudio L. A.
Published: January 2021

Background

Sleep-disordered breathing (SDB) is highly prevalent in acute ischaemic stroke and is associated with worse functional outcome and increased risk of recurrence. Recent meta-analyses suggest the possibility of beneficial effects of nocturnal ventilatory treatments (continuous positive airway pressure (CPAP) or adaptive servo-ventilation (ASV)) in stroke patients with SDB. The evidence for a favourable effect of early SDB treatment in acute stroke patients remains, however, uncertain.

Methods

eSATIS is an open-label, multicentre (6 centres in 4 countries), interventional, randomized controlled trial in patients with acute ischaemic stroke and significant SDB. Primary outcome of the study is the impact of immediate SDB treatment with non-invasive ASV on infarct progression measured with magnetic resonance imaging in the first 3 months after stroke. Secondary outcomes are the effects of immediate SDB treatment vs non-treatment on clinical outcome (independence in daily functioning, new cardio-/cerebrovascular events including death, cognition) and physiological parameters (blood pressure, endothelial functioning/arterial stiffness). After respiratory polygraphy in the first night after stroke, patients are classified as having significant SDB (apnoea-hypopnoea index (AHI) > 20/h) or no SDB (AHI < 5/h). Patients with significant SDB are randomized to treatment (ASV+ group) or no treatment (ASV− group) from the second night after stroke. In all patients, clinical, physiological and magnetic resonance imaging studies are performed between day 1 (visit 1) and days 4–7 (visit 4) and repeated at day 90 ± 7 (visit 6) after stroke.

Discussion

The trial will give information on the feasibility and efficacy of ASV treatment in patients with acute stroke and SDB and allows assessing the impact of SDB on stroke outcome. Diagnosing and treating SDB during the acute phase of stroke is not yet current medical practice. Evidence in favour of ASV treatment from a randomized multicentre trial may lead to a change in stroke care and to improved outcomes.

Trial registration

ClinicalTrials.gov NCT02554487, retrospectively registered on 16 September 2015 (actual study start date, 13 August 2015), and www.kofam.ch (SNCTP000001521).
Quantifying the advantages of conducting a prospective meta-analysis (PMA): a case study of early childhood obesity prevention
Authors:   on behalf of the EPOCH Collaboration, Seidler A. L. , Hunter K. E. , Espinoza D. , Mihrshahi S. , Askie L. M.
Published: January 2021

Background

For prospective meta-analyses (PMAs), eligible studies are identified, and the PMA hypotheses, selection criteria, and analysis methods are pre-specifiedbeforethe results of any of the studies are known. This reduces publication bias and selective outcome reporting and provides a unique opportunity for outcome standardisation/harmonisation. We conducted a world-first PMA of four trials investigating interventions to prevent early childhood obesity. The aims of this study were to quantitatively analyse the effects of prospective planning on variations across trials, outcome harmonisation, and the power to detect intervention effects, and to derive recommendations for future PMA.

Methods

We examined intervention design, participant characteristics, and outcomes collected across the four trials included in the EPOCH PMA using their registration records, protocol publications, and variable lists. The outcomes that trials planned to collect prior to inclusion in the PMA were compared to the outcomes that trials collected after PMA inclusion. We analysed the proportion of matching outcome definitions across trials, the number of outcomes per trial, and how collaboration increased the statistical power to detect intervention effects.

Results

The included trials varied in intervention design and participants, this improved external validity and the ability to perform subgroup analyses for the meta-analysis. While individual trials had limited power to detect the main intervention effect (BMIz-score), synthesising data substantially increased statistical power. Prospective planning led to an increase in the number of collected outcome categories (e.g. weight, child’s diet, sleep), and greater outcome harmonisation. Prior to PMA inclusion, only 18% of outcome categories were included in all trials. After PMA inclusion, this increased to 91% of outcome categories. However, while trials mostly collected the same outcome categories after PMA inclusion, some inconsistencies in how the outcomes were measured remained (such as measuring physical activity by hours of outside play versus using an activity monitor).

Conclusion

Prospective planning led to greater outcome harmonisation and greater power to detect intervention effects, while maintaining acceptable variation in trial designs and populations, which improved external validity. Recommendations for future PMA include more detailed harmonisation of outcome measures and careful pre-specification of analyses to avoid research waste by unnecessary over-collection of data.
The coArtHA trial—identifying the most effective treatment strategies to control arterial hypertension in sub-Saharan Africa: study protocol for a randomized controlled trial
Authors: Mapesi Herry , Gupta Ravi , Wilson Herieth Ismael , Lukau Blaise , Amstutz Alain , Lyimo Aza , Muhairwe Josephine , Senkoro Elizabeth , Byakuzana Theonestina , Mphunyane Madavida , Bresser Moniek , Glass Tracy Renée , Lambiris Mark , Fink Günther , Gingo Winfrid , Battegay Manuel , Paris Daniel Henry , Rohacek Martin , Vanobberghen Fiona , Labhardt Niklaus Daniel , Burkard Thilo , Weisser Maja
Published: January 2021

Background

Arterial hypertension is the most prevalent risk factor for cardiovascular disease in sub-Saharan Africa. Only a few and mostly small randomized trials have studied antihypertensive treatments in people of African descent living in sub-Saharan Africa.

Methods

In this open-label, three-arm, parallel randomized controlled trial conducted at two rural hospitals in Lesotho and Tanzania, we compare the efficacy and cost-effectiveness of three antihypertensive treatment strategies among participants aged ≥ 18 years. The study includes patients with untreated uncomplicated arterial hypertension diagnosed by a standardized office blood pressure ≥ 140/90 mmHg. The trial encompasses a superiority comparison between a triple low-dose antihypertensive drug combination versus the current standard of care (monotherapy followed by dual treatment), as well as a non-inferiority comparison for a dual drug combination versus standard of care with optional dose titration after 4 and 8 weeks for participants not reaching the target blood pressure. The sample size is 1268 participants with parallel allocation and a randomization ratio of 2:1:2 for the dual, triple and control arms, respectively. The primary endpoint is the proportion of participants reaching a target blood pressure at 12 weeks of ≤ 130/80 mmHg and ≤ 140/90 mmHg among those aged < 65 years and ≥ 65 years, respectively. Clinical manifestations of end-organ damage and cost-effectiveness at 6 months are secondary endpoints.

Discussion

This trial will help to identify the most effective and cost-effective treatment strategies for uncomplicated arterial hypertension among people of African descent living in rural sub-Saharan Africa and inform future clinical guidelines on antihypertensive management in the region.

Trial registration

Clinicaltrials.govNCT04129840. Registered on 17 October 2019 (https://www.clinicaltrials.gov/).