bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world effectiveness of primary screening with high-risk human papillomavirus testing in the cervical cancer screening programme in China: a nationwide, population-based study
Authors: Zhao Yanxia , Bao Heling , Ma Lan , Song Bo , Di Jiangli , Wang Linhong , Gao Yanqiu , Ren Wenhui , Wang Shi , Wang Hai-Jun , Wu Jiuling
Published: July 2021

Background

Randomized controlled trials have shown a higher sensitivity and longer negative predictive value of high-risk human papillomavirus (HPV) testing than cytology for cervical cancer screening; however, little is known about the effectiveness of HPV testing in middle-income countries. Understanding the characteristics of HPV testing may increase the priority of HPV testing in health policies. The study aims to evaluate the effectiveness of HPV testing in the national cervical cancer screening programme in China.

Methods

We performed a nationwide, population-based study using individual data from the national cervical cancer screening programme in rural China between 2015 and 2017. The analyses included 1,160,981 women aged 35–64 years who underwent cytology alone or high-risk HPV testing with cytology or genotyping triage. The main outcome was cervical intraepithelial neoplasia 2 or worse (CIN2+). We used multivariate logistic regressions and performed sensitivity analyses with propensity score matching to compare the screening positive, colposcopy referral, detection rate, and positive predictive value (PPV).

Results

The screening positive rates for HPV testing and cytology were 10.1% and 4.0%, respectively. The per protocol colposcopy referral rate of HPV testing was significantly lower than that of cytology (3.5% vs 4.0%), and this difference was mostly due to the low referral threshold of cytology (≥ASC-US). Overall, HPV testing detected more CIN2+ (5.5 vs. 4.4 per 1000, adjusted odds ratio [aOR]=1.18, 95% confidence interval 1.11–1.25) and had a higher PPV (13.8% vs 10.9%, aOR 1.29, 95% CI 1.21–1.37) than cytology. The colposcopy referrals of HPV testing in comparison to cytology differed by income status; it significantly increased in lower-middle-income areas (3.7% vs 3.1%, aOR 1.21, 95% CI 1.17–1.25) and significantly decreased in upper-middle-income areas (3.4% vs 4.9%, aOR 0.69, 95% CI 0.67–0.71). Sensitivity analyses demonstrated the reliability and robustness of the results.

Conclusions

The introduction of HPV testing could improve both the CIN2+ detection rate and efficiency of cervical cancer screening programme, supporting the introduction of primary screening with high-risk HPV testing in China. Further study is needed to investigate the long-term effect of this change.
CNKSR2-related neurodevelopmental and epilepsy disorder: a cohort of 13 new families and literature review indicating a predominance of loss of function pathogenic variants
Authors: Higa Leigh Ann , Wardley Jennifer , Wardley Christopher , Singh Susan , Foster Timothy , Shen Joseph J.
Published: July 2021

Background

Pathogenic variants in connector enhancer of kinase suppressor of Ras-2 (CNKSR2) located on the X chromosome (Xp22.12) lead to a disorder characterized by developmental delay and a characteristic seizure phenotype. To date, 20 affected males representing 13 different pathogenic variants have been published.

Case presentation

We identified an 8-year-old male with seizures, abnormal electroencephalogram (EEG) with epileptiform abnormalities in the right hemisphere, and developmental delay with notable loss of speech following seizure onset. Additional concerns include multiple nighttime awakenings, hyperactivity, and autism spectrum disorder. Genetic testing identified a de novo pathogenic nonsense variant in CNKSR2.

Through an active family support group, an additional 12 males are described, each harboring a different CNKSR2 variant. The clinical presentation and natural history consistently show early developmental delay, sleep disturbances, and seizure onset in childhood that is initially intractable but later becomes better controlled. Virtually all of the pathogenic variants are predicted to be loss of function, including genomic deletions, nonsense variants, splice site mutations, and small insertions or deletions.

Conclusions

This expanded knowledge, combined with functional studies and work with animal models currently underway, will enable a better understanding and improved ability to care for individuals with CNKSR2-related neurodevelopmental and epilepsy disorder.
RETRACTED ARTICLE: Downregulating lncRNA NEAT1 induces proliferation and represses apoptosis of ovarian granulosa cells in polycystic ovary syndrome via microRNA-381/IGF1 axis
Authors: Zhen Jingran , Li Jiangli , Li Xia , Wang Xue , Xiao Yaling , Sun Zhengyi , Yu Qi
Published: July 2021

Objective

Researchers have revealed the combined functions of long noncoding RNAs (lncRNAs) and microRNA (miRNAs) in polycystic ovary syndrome (PCOS). This study aimed to understand the role of nuclear-enriched abundant transcript 1 (NEAT1) and miR-381 involving insulin-like growth factor 1 (IGF1) in PCOS.

Methods

PCOS rat model was established by dehydroepiandrosterone induction. NEAT1, miR-381 and IGF1 expression in ovarian granulosa cells of PCOS patients and ovarian tissues of PCOS rats were tested. Bioinformatics website and dual luciferase reporter gene assay were utilized to verify the relationship between NEAT1 and miR-381 and that between miR-381 and IGF1. Levels of sex hormone, pathological changes and ovarian granulosa cell apoptosis in ovarian tissues of PCOS rats were detected. Ovarian granulosa cell proliferation and apoptosis were analyzed in vitro.

Results

NEAT1 and IGF1 expression increased while miR-381 expression decreased in the ovarian granulosa cells of patients with PCOS and the ovarian tissues of PCOS rats. In in vivo experiments, interference with NEAT1 improved the levels of sex hormones, alleviated pathological changes and suppressed ovarian granulosa cell apoptosis in the ovarian tissues of PCOS rats. In in vitro cell experiments, interference with NEAT1 suppressed apoptosis and enhanced cell proliferation of ovarian granulosa cells. NEAT1 interference-mediated effect would be reversed by up-regulating miR-381. NEAT1 acted as a ceRNA to adsorb miR-381 to target IGF1. Overexpression of IGF1 reversed the inhibitory effect of miR-381 on ovarian granulosa cell apoptosis.

Conclusion

Interference with NEAT1 increases miR-381 and reduces IGF1 levels, effectively improving the levels of sex hormones and reducing the pathological damage of ovarian tissue in rats with PCOS.
Turnover of type I and III collagen predicts progression of idiopathic pulmonary fibrosis
Authors: Jessen H. , Hoyer N. , Prior T. S. , Frederiksen P. , Karsdal M. A. , Leeming D. J. , Bendstrup E. , Sand J. M. B. , Shaker S. B.
Published: July 2021

Background

Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of fibrillar collagens in the alveolar space resulting in reduced pulmonary function and a high mortality rate. Biomarkers measuring the turnover of type I and III collagen could provide valuable information for prognosis and treatment decisions in IPF.

Methods

Serological biomarkers reflecting the formation of type III collagen (PRO-C3) and degradation of type I (C1M) and III collagen (C3M) were evaluated in a real-world cohort of 178 newly diagnosed IPF patients. Blood samples and clinical data were collected at baseline, six, and 12 months. Baseline and longitudinal biomarker levels were related to disease progression of IPF (defined as ≥ 5% decline in forced vital capacity (FVC) and/or ≥ 10% decline in diffusing capacity for carbon monoxide (DLco) and/or all-cause mortality at 12 months). Furthermore, we analysed differences in percentage change of biomarker levels from baseline between patients receiving antifibrotic treatment or not.

Results

Increased baseline levels of type I and III collagen turnover biomarkers were associated with a greater risk of disease progression within 12 months compared to patients with a low baseline type I and III collagen turnover. Patients with progressive disease had higher serum levels of C1M (P = 0.038) and PRO-C3 (P = 0.0022) compared to those with stable disease over one year. There were no differences in biomarker levels between patients receiving pirfenidone, nintedanib, or no antifibrotics.

Conclusion

Baseline levels of type I and III collagen turnover were associated with disease progression within 12 months in a real-world cohort of IPF patients. Longitudinal biomarker levels of type I and III collagen turnover were related to progressive disease. Moreover, antifibrotic therapy did not affect type I and III collagen turnover biomarkers in these patients. PRO-C3 and C1M may be potential biomarkers for a progressive disease behavior in IPF.
Graphene-based nanomaterials for breast cancer treatment: promising therapeutic strategies
Authors: Cui Guangman , Wu Junrong , Lin Jiaying , Liu Wenjing , Chen Peixian , Yu Meng , Zhou Dan , Yao Guangyu
Published: July 2021

Breast cancer is the most common malignancy in women, and its incidence increases annually. Traditional therapies have several side effects, leading to the urgent need to explore new smart drug-delivery systems and find new therapeutic strategies. Graphene-based nanomaterials (GBNs) are potential drug carriers due to their target selectivity, easy functionalization, chemosensitization and high drug-loading capacity. Previous studies have revealed that GBNs play an important role in fighting breast cancer. Here, we have summarized the superior properties of GBNs and modifications to shape GBNs for improved function. Then, we focus on the applications of GBNs in breast cancer treatment, including drug delivery, gene therapy, phototherapy, and magnetothermal therapy (MTT), and as a platform to combine multiple therapies. Their advantages in enhancing therapeutic effects, reducing the toxicity of chemotherapeutic drugs, overcoming multidrug resistance (MDR) and inhibiting tumor metastasis are highlighted. This review aims to help evaluate GBNs as therapeutic strategies and provide additional novel ideas for their application in breast cancer therapy.
An evaluation of the Victorian Salt Reduction Partnership’s advocacy strategy for policy change
Authors: Rosewarne Emalie , Moore Michael , Chislett Wai-Kwan , Jones Alexandra , Trieu Kathy , Webster Jacqui
Published: July 2021

Background

Public health advocacy strategies facilitate policy change by bringing key health issues to the forefront of public and political discourse, influencing decision-makers and public opinion, and increasing policy demand. The Victorian Salt Reduction Partnership (VSRP) was established in 2014 in response to inadequate government action to improve population diets in Australia. This study aimed to evaluate the success of the VSRP’s advocacy strategy in achieving policy change.

Methods

Documentation of VSRP activities and outputs were collected, and semi-structured interviews conducted as part of a comprehensive process evaluation. For this study, the Kotter Plus 10-step public health advocacy evaluation framework was used to guide data extraction, analysis, and synthesis.

Results

A sense of urgency for salt reduction was generated by producing evidence and outlining the potential impact of a state-based salt reduction programme. This enabled the creation of a coalition with diverse skills and expertise, which facilitated the development of an innovative and collaborative advocacy action plan. A clear change vision was established, but communication of the vision to decision-makers was lacking, which reduced the impact of the programme as decision-makers were not provided with a clear incentive for policy change. As a result, while programme outputs were achieved, these did not translate to achieving broader strategic goals during a limited-term intervention in a political climate unconcerned with salt.

Conclusions

The Kotter Plus 10-step framework was a useful tool for evaluating the success of the VSRP advocacy strategy. The framework enabled the identification of key strengths, including the creation of the guiding coalition, and areas where efforts could be improved in future similar strategies, such as effective communication within partnerships and to decision-makers, to better influence policy and improve public health impact.
The impact of gut microbiota metabolites on cellular bioenergetics and cardiometabolic health
Authors: Tomasova Lenka , Grman Marian , Ondrias Karol , Ufnal Marcin
Published: July 2021

Recent research demonstrates a reciprocal relationship between gut microbiota-derived metabolites and the host in controlling the energy homeostasis in mammals. On the one hand, to thrive, gut bacteria exploit nutrients digested by the host. On the other hand, the host utilizes numerous products of gut bacteria metabolism as a substrate for ATP production in the colon. Finally, bacterial metabolites seep from the gut into the bloodstream and interfere with the host’s cellular bioenergetics machinery. Notably, there is an association between alterations in microbiota composition and the development of metabolic diseases and their cardiovascular complications. Some metabolites, like short-chain fatty acids and trimethylamine, are considered markers of cardiometabolic health. Others, like hydrogen sulfide and nitrite, demonstrate antihypertensive properties. Scientific databases were searched for pre-clinical and clinical studies to summarize current knowledge on the role of gut microbiota metabolites in the regulation of mammalian bioenergetics and discuss their potential involvement in the development of cardiometabolic disorders. Overall, the available data demonstrates that gut bacteria products affect physiological and pathological processes controlling energy and vascular homeostasis. Thus, the modulation of microbiota-derived metabolites may represent a new approach for treating obesity, hypertension and type 2 diabetes.
Comparison of walking variations during treadmill walking test between neurogenic and vascular claudication: a crossover study
Authors: Houle Mariève , O’Shaughnessy Julie , Tétreau Charles , Châtillon Claude-Édouard , Marchand Andrée-Anne , Descarreaux Martin
Published: July 2021

Background

Lumbar spinal stenosis (LSS) and peripheral arterial disease (PAD) are two distinct conditions characterized by similar symptoms including leg pain and walking limitations due to claudication. Differentiation between both origins can be difficult and characteristics such as symptom manifestations, time to relief in rest position and pain localization should be considered when determining diagnosis and the treatment plan. The objectives of this study were to compare changes in walking time to symptom change during treadmill tests and self-reported outcomes measures related to claudication, kinesophobia and global health between individuals with LSS, PAD and non-specific low back pain (nLBP).

Method

Fifty-five patients (23 with LSS, 14 with PAD and 18 with nLBP) were recruited from May 2018 to March 2020 to complete a treadmill walking test involving two 5-min walking tasks (Upright and Forward Leaning Trunk (FLT) Walking tasks). The speed was set at 1.9 km/h (1.2 mph), and each task was followed by a 5-min rest period.Walking time to symptom changeandTotal walking timewere recorded during each walking task. Patients were asked to complete four questionnaires related to the impact of claudication, walking impairment, kinesiophobia and global health. One-way ANOVAs were performed to compare walking time difference from theUprightto theFLT walking tasksand to compare questionnaires results between groups.

Results

One-way ANOVAs showed a significant difference between groups regarding difference in Walking time to symptom change between both tasks (F = 4.12,p = 0.022). The LSS group improved its Walking time to symptom change from the Upright to the FLT walking tasks more than the PAD (p = 0.34) and the nLBP group (p = 0.12). The nLBP group was less impacted by claudication and less impaired during walking compared to the LSS and PAD groups (ps < 0.001). The nLBP group also had less kinesiophobia than the LSS one (p < 0.001), but was similar to the PAD group. The global health rating was not statistically different between groups (p = 0.118).

Conclusion

The test was able to distinguish neurogenic from vascular or nLBP related claudication. However, further studies are needed to validate this new treadmill walking test.

Trial registration

clinicaltrials.gov (NCT04058171), Registered August 15, 2019 –Registered during recruitment
Raman spectroscopy enables phenotyping and assessment of nutrition values of plants: a review
Authors: Payne William Z. , Kurouski Dmitry
Published: July 2021

Our civilization has to enhance food production to feed world’s expected population of 9.7 billion by 2050. These food demands can be met by implementation of innovative technologies in agriculture. This transformative agricultural concept, also known as digital farming, aims to maximize the crop yield without an increase in the field footprint while simultaneously minimizing environmental impact of farming. There is a growing body of evidence that Raman spectroscopy, a non-invasive, non-destructive, and laser-based analytical approach, can be used to: (i) detect plant diseases, (ii) abiotic stresses, and (iii) enable label-free phenotyping and digital selection of plants in breeding programs. In this review, we critically discuss the most recent reports on the use of Raman spectroscopy for confirmatory identification of plant species and their varieties, as well as Raman-based analysis of the nutrition value of seeds. We show that high selectivity and specificity of Raman makes this technique ideal for optical surveillance of fields, which can be used to improve agriculture around the world. We also discuss potential advances in synergetic use of RS and already established imaging and molecular techniques. This combinatorial approach can be used to reduce associated time and cost, as well as enhance the accuracy of diagnostics of biotic and abiotic stresses.
High-dose thoracic radiation therapy for non-small cell lung cancer: a novel grading scale of radiation-induced lung injury for symptomatic radiation pneumonitis
Authors: Szejniuk Weronika Maria , Nielsen Martin Skovmos , Takács-Szabó Zsuzsanna , Pawlowski Jacek , Al-Saadi Sahar Sulaiman , Maidas Panagiotis , Bøgsted Martin , McCulloch Tine , Frøkjær Jens Brøndum , Falkmer Ursula Gerda , Røe Oluf Dimitri
Published: July 2021

Background

Symptomatic radiation pneumonitis (RP) may be a serious complication after thoracic radiation therapy (RT) for non-small cell lung cancer (NSCLC). This prospective observational study sought to evaluate the utility of a novel radiation-induced lung injury (RILI) grading scale (RGS) for the prediction of RP.

Materials and methods

Data of 41 patients with NSCLC treated with thoracic RT of 60–66 Gy were analysed. CT scans were scheduled before RT, one month post-RT, and every three months thereafter for one year. Symptomatic RP was defined as Common Terminology Criteria for Adverse Events grade ≥ 2. RGS grading ranged from 0 to 3. The inter-observer variability of the RGS was assessed by four senior radiologists. CT scans performed 28 ± 10 days after RT were used to analyse the predictive value of the RGS. The change in the RGS severity was correlated to dosimetric parameters.

Results

The CT obtained one month post-RT showed RILI in 36 (88%) of patients (RGS grade 0 [5 patients], 1 [25 patients], 2 [6 patients], and 3 [5 patients]). The inter-observer agreement of the RGS grading was high (Kendall’s W coefficient of concordance = 0.80, p < 0.01). Patients with RGS grades 2–3 had a significantly higher risk for development of RP (relative risk (RR): 2.4, 95% CI 1.6–3.7, p < 0.01) and RP symptoms within 8 weeks after RT (RR: 4.8, 95% CI 1.3–17.6, p < 0.01) compared to RGS grades 0–1. The specificity and sensitivity of the RGS grades 2–3 in predicting symptomatic RP was 100% (95% CI 80.5–100%) and 45.4% (95% CI 24.4–67.8%), respectively. Increase in RGS severity correlated to mean lung dose and the percentage of the total lung volume receiving 5 Gy.

Conclusions

The RGS is a simple radiologic tool associated with symptomatic RP. A validation study is warranted.
Historical and future carbon stocks in forests of northern Ontario, Canada
Authors: Ter-Mikaelian Michael T. , Gonsamo Alemu , Chen Jing M. , Mo Gang , Chen Jiaxin
Published: July 2021

Background

Forests in the Far North of Ontario (FNO), Canada, are likely the least studied in North America, and quantifying their current and future carbon (C) stocks is the first step in assessing their potential role in climate change mitigation. Although the FNO forests are unmanaged, the latter task is made more important by growing interest in developing the region’s natural resources, primarily for timber harvesting. In this study, we used a combination of field and remotely sensed observations with a land surface model to estimate forest C stocks in the FNO forests and to project their future dynamics. The specific objective was to simulate historical C stocks for 1901–2014 and future C stocks for 2015–2100 for five shared socioeconomic pathway (SSP) scenarios selected as high priority scenarios for the 6th Assessment Report on Climate Change.

Results

Carbon stocks in live vegetation in the FNO forests remained relatively stable between 1901 and 2014 while soil organic carbon (SOC) stocks steadily declined, losing about 16% of their initial value. At the end of the historical simulation (in 2014), the stocks were estimated at 19.8, 46.4, and 66.2 tCha−1in live vegetation, SOC, and total ecosystem pools, respectively. Projections for 2015–2100 indicated effectively no substantial change in SOC stocks, while live vegetation C stocks increased, accelerating their growth in the second half of the twenty-first century. These results were consistent among all simulated SSP scenarios. Consequently, increase in total forest ecosystem C stocks by 2100 ranged from 16.7 to 20.7% of their value in 2015. Simulations with and without wildfires showed the strong effect of fire on forest C stock dynamics during 2015–2100: inclusion of wildfires reduced the live vegetation increase by half while increasing the SOC pool due to higher turnover of vegetation C to SOC.

Conclusions

Forest ecosystem C stock estimates at the end of historical simulation period were at the lower end but within the range of values reported in the literature for northern boreal forests. These estimates may be treated as conservatively low since the area included in the estimates is poorly studied and some of the forests may be on peat deposits rather than mineral soils. Future C stocks were projected to increase in all simulated SSP scenarios, especially in the second half of the twenty-first century. Thus, during the projected period forest ecosystems of the FNO are likely to act as a C sink. In light of growing interest in developing natural resources in the FNO, collecting more data on the status and dynamics of its forests is needed to verify the above-presented estimates and design management activities that would maintain their projected C sink status.
Glaucoma in mucopolysaccharidoses
Authors: Kong Weijing , Zhang Jing , Lu Cheng , Ding Yingxue , Meng Yan
Published: July 2021

Mucopolysaccharidoses are a group of lysosomal storage disorders that are caused by deficiency of enzymes involved in glycosaminoglycans degradation. Due to low prevalence and high childhood mortality, researches on mucopolysaccharidoses were mainly focused on the fatal manifestations. With the development of treatments, more and more mucopolysaccharidoses patients were treated by approved therapies, thereby getting prolonged life span and improved quality of life. Abnormal accumulation of glycosaminoglycans in the eye may block trabecular meshwork, thicken sclera and change mechanical behavior of lamina cribrosa, which, by increasing intraocular pressure and damaging optic nerve, could cause glaucoma. Glaucoma was the leading cause of irreversible blindness worldwide, but it was rarely reported in mucopolysaccharidoses patients. Although non-fatal, it seriously affected quality of life. Prevalence of glaucoma in mucopolysaccharidoses patients (ranged from 2.1 to 12.5%) indicated that glaucoma in patients with mucopolysaccharidoses was worthy of attention and further study, thereby improving the quality of life for MPSs patients.
Navigating the U.S. health insurance landscape for children with rare diseases: a qualitative study of parents’ experiences
Authors: Pasquini Tai L. S. , Goff Sarah L. , Whitehill Jennifer M.
Published: July 2021

Background

Parents of children with rare diseases often face uncertainty about diagnosis, treatment, and costs associated with healthcare for their child. Health insurance status impacts each of these areas, but no U.S. study has explored parents’ perceptions of the health insurance impacts on their child’s care. This study aimed to qualitatively explore how these parents navigate the complex health insurance system for their children and their experiences in doing so.

Methods

Semi-structured interviews were conducted with parents of children with metachromatic leukodystrophy (MLD) and spinal muscular atrophy (SMA), chosen for specific disease characteristics and orphan drug status. Participants were recruited via e-mail through patient advocacy organizations between September and December 2018. Interviews were conducted via Skype, were recorded, and professionally transcribed. Modified grounded theory was utilized as a methodology to analyze transcripts in an iterative process to determine themes and sub-themes based on participant described experiences.

Results

Major themes and subthemes that emerged across the 15 interviews included: (1) difficulties obtaining secondary insurance based on state eligibility criteria; (2) difficulty accessing needed healthcare services; and (3) need for repeated interactions with insurance representatives. The absence of clearly documented or widely recognized clinical guidelines exacerbated the difficulty accessing care identified as necessary by their healthcare team, such as therapy and equipment. An explanatory model for parent’s experiences was developed from the themes and subthemes. The model includes the cyclical nature of interacting with insurance for redundant reauthorizations and the outside support and financial assistance that is often necessary to address their child’s healthcare needs.

Conclusions

With complex health conditions, small setbacks can become costly and disruptive to the health of the child and the life of the family. This study suggests that patients with rare diseases may benefit from time limits for processing coverage decisions, increasing transparency in the claims and preauthorization processes, and more expansive authorizations for on-going needs. Additional studies are needed to understand the full scope of barriers and to inform policies that can facilitate better access for families living with rare diseases.
Haploidentical haematopoietic stem cell transplantation for malignant infantile osteopetrosis and intermediate osteopetrosis: a retrospective analysis of a single centre
Authors: Zhu Guanghua , Wei Ang , Wang Bin , Yang Jun , Yan Yan , Wang Kai , Jia Chenguang , Luo Yanhui , Li Sidan , Zhou Xuan , Wang Tianyou , Zheng Huyong , Qin Maoquan
Published: July 2021

Objective

To evaluate the clinical efficacy of haploidentical haematopoietic stem cell transplantation (haplo-HSCT) for the treatment of malignant infantile osteopetrosis (MIOP) and intermediate osteopetrosis.

Methods

Children with MIOP and IOP who underwent haplo-HSCT in Beijing Children’s Hospital, Capital Medical University, from January 2010 to May 2018 were retrospectively analysed. Data relating to the clinical manifestations, engraftment, and prognosis of the children were extracted from medical records.

Results

Twenty-seven patients, including 18 males and 9 females, with an onset age of 12 (0.04–72) months were enrolled in this study. The median time from diagnosis to transplantation was 4 (1–23) months. All patients received haplo-HSCT with a myeloablative conditioning regimen (including fludarabine, busulfan, and cyclophosphamide). Graft versus host disease (GVHD) prophylaxis was based on anti-human T lymphocyte porcine immunoglobulin/anti-human thymus globulin, methotrexate, and mycophenolate mofetil. The median observation time was 55.2 (0.3–126.2) months. By the end of follow-up, twenty patients survived and seven patients died. The 5 year overall survival rate was 73.9%. Stage I-II acute GVHD was observed in 20 patients, stage III GVHD in 1 patient and no patients had stage IV disease. Chronic GVHD was observed in 11 patients (40.7%) and was controlled by anti-GVHD therapy.

Conclusions

Haplo-HSCT was an effective treatment for MIOP and IOP, with a high survival rate and significantly improved clinical symptoms. For patients with a vision impairment before HSCT, the improvement was slow after transplantation. The incidence of GVHD was high but mild and was effectively controlled by appropriate treatment. These data indicated that haplo-HSCT was a feasible treatment for MIOP and IOP.
Knock-in models related to Alzheimer’s disease: synaptic transmission, plaques and the role of microglia
Authors: Benitez Diana P. , Jiang Shenyi , Wood Jack , Wang Rui , Hall Chloe M. , Peerboom Carlijn , Wong Natalie , Stringer Katie M. , Vitanova Karina S. , Smith Victoria C. , Joshi Dhaval , Saito Takashi , Saido Takaomi C. , Hardy John , Hanrieder Jörg , De Strooper Bart , Salih Dervis A. , Tripathi Takshashila , Edwards Frances A. , Cummings Damian M.
Published: July 2021

Background

Microglia are active modulators of Alzheimer’s disease but their role in relation to amyloid plaques and synaptic changes due to rising amyloid beta is unclear. We add novel findings concerning these relationships and investigate which of our previously reported results from transgenic mice can be validated in knock-in mice, in which overexpression and other artefacts of transgenic technology are avoided.

Methods

AppNL-F and AppNL-G-F knock-in mice expressing humanised amyloid beta with mutations in App that cause familial Alzheimer’s disease were compared to wild type mice throughout life. In vitro approaches were used to understand microglial alterations at the genetic and protein levels and synaptic function and plasticity in CA1 hippocampal neurones, each in relationship to both age and stage of amyloid beta pathology. The contribution of microglia to neuronal function was further investigated by ablating microglia with CSF1R inhibitor PLX5622.

Results

Both App knock-in lines showed increased glutamate release probability prior to detection of plaques. Consistent with results in transgenic mice, this persisted throughout life in AppNL-F mice but was not evident in AppNL-G-F with sparse plaques. Unlike transgenic mice, loss of spontaneous excitatory activity only occurred at the latest stages, while no change could be detected in spontaneous inhibitory synaptic transmission or magnitude of long-term potentiation. Also, in contrast to transgenic mice, the microglial response in both App knock-in lines was delayed until a moderate plaque load developed. Surviving PLX5266-depleted microglia tended to be CD68-positive. Partial microglial ablation led to aged but not young wild type animals mimicking the increased glutamate release probability in App knock-ins and exacerbated the App knock-in phenotype. Complete ablation was less effective in altering synaptic function, while neither treatment altered plaque load.

Conclusions

Increased glutamate release probability is similar across knock-in and transgenic mouse models of Alzheimer’s disease, likely reflecting acute physiological effects of soluble amyloid beta. Microglia respond later to increased amyloid beta levels by proliferating and upregulating Cd68 and Trem2. Partial depletion of microglia suggests that, in wild type mice, alteration of surviving phagocytic microglia, rather than microglial loss, drives age-dependent effects on glutamate release that become exacerbated in Alzheimer’s disease.
Adherence to clinical guidelines in integration of mental health services into primary health care in Mbarara, southwestern Uganda: a medical records review
Authors: Wakida Edith K. , Ocan Moses , Rukundo Godfrey Z. , Maling Samuel , Ssebutinde Peter , Okello Elialilia S. , Talib Zohray M. , Obua Celestino
Published: July 2021

Background

The Ugandan Ministry of Health decentralized mental healthcare to the district level; developed the Uganda Clinical Guidelines (UCG); and trained primary health care (PHC) providers in identification, management, and referral of individuals with common mental disorders. This was intended to promote integration of mental health services into PHC in the country. ‘Common mental disorders’ here refers to mental, neurological and substance use conditions as indicated in the UCG. However, the extent of integration of mental health into general healthcare remains unknown. This study aimed to establish the level of adherence of PHC providers to the UCG in the identification and management of mental disorders.

Methods

This was a prospective medical record review of patient information collected in November and December 2018, and March and April 2019 at two health centers (III and IV) in southwestern Uganda. Data (health facility level; sex and age of the patient; and mental disorder diagnosis, management) was collected using a checklist. Continuous data was analyzed using means and standard deviation while categorical data was analyzed using Chi-square. Multivariable logistic regression analysis was performed to establish predictors of PHC provider adherence to the clinical guidelines on integration of mental health services into PHC. The analysis was conducted at a 95% level of significance.

Results

Of the 6093 records of patients at the study health facilities during the study period, 146 (2.4%) had a mental or neurological disorder diagnosis. The commonly diagnosed disorders were epilepsy 91 (1.5%) and bipolar 25 (0.4%). The most prescribed medications were carbamazepine 65 (44.5%), and phenobarbital 26 (17.8%). The medicines inappropriately prescribed at health center III for a mental diagnosis included chlorpromazine for epilepsy 3 (2.1%) and haloperidol for epilepsy 1 (0.7%). Female gender (aOR: 0.52, 95% CI 0.39–0.69) and age 61+ years (aOR: 3.02, 95% CI 1.40–6.49) were predictors of a mental disorder entry into the HMIS register.

Conclusion

There was a noticeable change of practice by PHC providers in integrating mental health services in routine care as reflected by the rise in the number of mental disorders diagnosed and treated and entered into the modified paper based HMIS registers.
Laser-assisted hatching in lower grade cleavage stage embryos improves blastocyst formation: results from a retrospective study
Authors: Xu Weihai , Zhang Ling , Zhang Lin , Jin Zhen , Wu Limei , Li Shishi , Shu Jing
Published: July 2021

Background

Laser-assisted hatching (LAH) has been widely applied to facilitate blastocyst hatching in IVF-ET treatment, however, the effect of LAH on subsequent development and clinical outcomes of the lower grade cleavage stage embryos (LGCE) remains unknown. Our study aimed at evaluating the effect of LAH on blastocyst formation and the clinical pregnancy outcomes of LGCE embryos after transfer.

Methods

A total of 608 cycles of IVF/ICSI treatment from November 2017 to September 2019 were included in our study as follows: 296 in the LAH group and 312 in the N-LAH group. The total blastocyst rate, usable blastocyst rate, good-grade blastocyst rate and clinical pregnancy rate were statistically compared between the two groups.

Results

The total blastocyst rate (50.7% vs 40.2%, P < 0.001), usable blastocyst rate (31.0% vs 18.6%, P < 0.001) were significantly higher in the LAH group than those in the N-LAH group. After analysis of generalized estimating equations, LAH was positively correlated with the blastocyst rate (B = 0.201, OR 95% CI = 1.074–1.393, P = 0.002), usable blastocyst rate (B = 0.478, OR 95% CI = 1.331–1.955, P < 0.001). However, the clinical pregnancy rate after blastocyst transfer did not differ between LAH group and N-LAH group (49.4% vs 40.0%, P > 0.05, respectively).

Conclusions

A higher proportion of total blastocysts and usable blastocysts can be obtained by LAH in LGCE, which may be beneficial to the outcome of the IVF/ICSI-ET cycle.
An RCT of a decision aid to support informed choices about taking aspirin to prevent colorectal cancer and other chronic diseases: a study protocol for the SITA (Should I Take Aspirin?) trial
Authors: Milton Shakira , McIntosh Jennifer , Macrae Finlay , Chondros Patty , Trevena Lyndal , Jenkins Mark , Walter Fiona M. , Taylor Natalie , Boyd Lucy , Saya Sibel , Karnchanachari Napin , Novy Kitty , Forbes Carmody , Gutierrez Javiera Martinez , Broun Kate , Whitburn Sara , McGill Sarah , Fishman George , Marker Julie , Shub Max , Emery Jon
Published: July 2021

Background

Australian guidelines recommend that all people aged 50–70 years old actively consider taking daily low-dose aspirin (100–300 mg per day) for 2.5 to 5 years to reduce their risk of colorectal cancer (CRC). Despite the change of national CRC prevention guidelines, there has been no active implementation of the guidelines into clinical practice.

We aim to test the efficacy of a health consultation and decision aid, using a novel expected frequency tree (EFT) to present the benefits and harms of low dose aspirin prior to a general practice consultation with patients aged 50–70 years, on informed decision-making and uptake of aspirin.

Methods

Approximately five to seven general practices in Victoria, Australia, will be recruited to participate. Patients 50–70 years old, attending an appointment with their general practitioner (GP) for any reason, will be invited to participate in the trial. Two hundred fifty-eight eligible participants will be randomly allocated 1:1 to intervention or active control arms using a computer-generated allocation sequence stratified by general practice, sex, and mode of trial delivery (face-to-face or teletrial).

There are two co-primary outcomes: informed decision-making at 1-month post randomisation, measured by the Multi-dimensional Measure of Informed Choice (MMIC), and self-reported daily use of aspirin at 6 months. Secondary outcomes include decisional conflict at 1-month and other behavioural changes to reduce CRC risk at both time points.

Discussion

This trial will test the efficacy of novel methods for implementing national guidelines to support informed decision-making about taking aspirin in 50–70-year-olds to reduce the risk of CRC and other chronic diseases.

Trial registration

The Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620001003965. Registered on 10 October 2020.
Differences in the individual curative effect of acupuncture for obese women with polycystic ovary syndrome based on metagenomic analysis: study protocol for a randomized controlled trial
Authors: Fan Huaying , Hong Xiaojuan , Zeng Jiuzhi , Wang Xue , Chen Jiao
Published: July 2021

Background

Polycystic ovary syndrome is a common cause of infertility and shows a high incidence in women of reproductive age. Acupuncture is an appropriate adjunctive treatment for PCOS. However, the add-on effect of acupuncture as an adjunctive treatment for obese women with PCOS has not been studied, and previous studies indicate that there are individual differences in the curative effect of acupuncture, while deeper research on the mechanism of differences in the individual curative effect of acupuncture for obese women with PCOS is still lacking. This trial aims to assess the add-on treatment efficacy of acupuncture for obese women with PCOS and to explore the role of the gut microbiome on the differences in the individual curative effect of acupuncture based on metagenomic analysis.

Methods/design

This is an open-label, randomized, controlled trial. A total of 86 obese women with PCOS will be recruited. Subjects will be randomly assigned to a study group and a control group in a 1:1 ratio, with 43 subjects in each group (10 patients from each group who meet the study criteria will participate in the metagenomic analysis). An additional 10 subjects who meet the study criteria will be recruited to a healthy control group. The study group will receive acupuncture and clomiphene citrate treatment; the control group will only receive clomiphene citrate. Acupuncture treatment will be conducted three times a week from the fifth day of menstruation or withdrawal bleeding until the start of the next menstruation, for up to three menstrual cycles. The primary outcome will be LH/FSH. The secondary outcomes will comprise biometric features, hormone biomarkers, metabolic biomarkers, inflammatory biomarkers, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and metagenomic analysis. The outcomes will be measured at baseline and post-intervention. Data will be analyzed using SPSS 19.0, and the gut microbiome will be analyzed using metagenomic analysis.

Discussion

In this study, we are evaluating the add-on effects of acupuncture and exploring the mechanism of the differences in the individual curative effect of acupuncture based on the gut microbiome, which may provide evidence to explain the different outcomes of different trials on acupuncture for PCOS and hopefully to provide a new aspect to study the mechanism of acupuncture’s treatment effect.

Trial registration

Chinese Clinical Trial Registry ChiCTR2000029882. Registered on 16 February 2020
Molecular identification and biological characterization of Cryptosporidium muris from camels (Camelus bactrianus) in China
Authors: Wang Luyang , Cao Letian , Zheng Shuangjian , Chang Yankai , Zhang Kaihui , Zhang Sumei , Zhang Longxian
Published: July 2021

Background

Cryptosporidium is an opportunistic pathogen that infects a wide variety of vertebrates. The aim of the present study was to characterize Cryptosporidium spp. isolates from Bactrian camels and to foster further understanding of the biological characteristics of the pathogen.

Methods

Fecal specimens were collected from two 4-year-old Bactrian camels resident at the Kaifeng City Zoo in China and examined for Cryptosporidium. Fecal specimens were screened using the floatation method, and then genomic DNA was extracted from the oocysts and identified by nested-PCR amplification of the small subunit ribosomal RNA (SSU rRNA) gene, the actin gene and the Cryptosporidium oocyst wall-protein (COWP) gene. Subtype analysis was performed based on four minisatellite (MS) loci (MS1, MS2, MS3 and MS16) that were aligned and phylogenetically analyzed to determine the species and subtype of Cryptosporidium. We then established a BALB/c mice infection model and further verified the results through clinical status, pattern of oocyst excretion and histological examination.

Results

Cryptosporidium oocyst isolates from the two Bactrian camels had an average (± standard deviation) size of 7.49 ± 0.13 × 5.70 ± 0.10 μm (n = 50). The sequencing and phylogenetic analysis confirmed the species as C. muris. Multilocus sequence typing analysis indicated that the subtypes were M13, M4, M1 and M5. Following the inoculation of BALB/c mice, we found that the prepatent period and number of oocysts per gram increased with increasing infective dose. Oocysts were first detected in the feces of BALB/c mice at 7–8 days post-infection (dpi), with levels peaking twice thereafter, at 15–16 dpi and 19–20 dpi. Histology and scanning electron microscopy studies showed that the stomach contained gastric pits filled with Cryptosporidium that adhered to the surface of gastric mucosa gland epithelial cells, causing the latter to deform, swell and become disordered.

Conclusions

The findings of this study indicated that oocysts isolated from Bactrian camels were from C. muris. This is the first report of C. muris isolated from camels in China. More epidemiological data are needed to understand the prevalence and transmission of C. muris in camels in different geographic areas.

Graphical abstract
An international policy on returning genomic research results
Authors: Lewis Anna C. F. , Knoppers Bartha Maria , Green Robert C.
Published: July 2021

The Global Alliance for Genomics and Health has approved a policy for the return of clinically actionable genomic research results, the first such policy approved by an international body. The policy acknowledges the potential medical benefits to millions of individuals who are participating in genomics research. It ties the pace of implementation to each country’s clinical standards, including for the return of secondary findings, and urges funders to set aside resources to support responsible return.
DNA sonification for public engagement in bioinformatics
Authors: Plaisier Heleen , Meagher Thomas R. , Barker Daniel
Published: July 2021

Objective

Visualisation methods, primarily color-coded representation of sequence data, have been a predominant means of representation of DNA data. Algorithmic conversion of DNA sequence data to sound—sonification—represents an alternative means of representation that uses a different range of human sensory perception. We propose that sonification has value for public engagement with DNA sequence information because it has potential to be entertaining as well as informative. We conduct preliminary work to explore the potential of DNA sequence sonification in public engagement with bioinformatics. We apply a simple sonification technique for DNA, in which each DNA base is represented by a specific note. Additionally, a beat may be added to indicate codon boundaries or for musical effect. We report a brief analysis from public engagement events we conducted that featured this method of sonification.

Results

We report on use of DNA sequence sonification at two public events. Sonification has potential in public engagement with bioinformatics, both as a means of data representation and as a means to attract audience to a drop-in stand. We also discuss further directions for research on integration of sonification into bioinformatics public engagement and education.
A pragmatic evidence-based approach to post-mortem perinatal imaging
Authors: Shelmerdine Susan C. , Hutchinson J. Ciaran , Lewis Celine , Simcock Ian C. , Sekar Thivya , Sebire Neil J. , Arthurs Owen J.
Published: July 2021

Post-mortem imaging has a high acceptance rate amongst parents and healthcare professionals as a non-invasive method for investigating perinatal deaths. Previously viewed as a ‘niche’ subspecialty, it is becoming increasingly requested, with general radiologists now more frequently asked to oversee and advise on appropriate imaging protocols. Much of the current literature to date has focussed on diagnostic accuracy and clinical experiences of individual centres and their imaging techniques (e.g. post-mortem CT, MRI, ultrasound and micro-CT), and pragmatic, evidence-based guidance for how to approach such referrals in real-world practice is lacking. In this review, we summarise the latest research and provide an approach and flowchart to aid decision-making for perinatal post-mortem imaging. We highlight key aspects of the maternal and antenatal history that radiologists should consider when protocolling studies (e.g. antenatal imaging findings and history), and emphasise important factors that could impact the diagnostic quality of post-mortem imaging examinations (e.g. post-mortem weight and time interval). Considerations regarding when ancillary post-mortem image-guided biopsy tests are beneficial are also addressed, and we provide key references for imaging protocols for a variety of cross-sectional imaging modalities.