bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of mortality in patients with hereditary hemorrhagic telangiectasia
Authors:   the Brain Vascular Malformation Consortium HHT Investigator Group, Thompson K. P. , Nelson J. , Kim H. , Pawlikowska L. , Marchuk D. A. , Lawton M. T. , Faughnan Marie E.
Published: January 2021

Background

Retrospective questionnaire and healthcare administrative data suggest reduced life expectancy in untreated hereditary hemorrhagic telangiectasia (HHT). Prospective data suggests similar mortality, to the general population, in Denmark’s centre-treated HHT patients. However, clinical phenotypes vary widely in HHT, likely affecting mortality. We aimed to measure predictors of mortality among centre-treated HHT patients. HHT patients were recruited at 14 HHT centres of the Brain Vascular Malformation Consortium (BVMC) since 2010 and followed annually. Vital status, organ vascular malformations (VMs) and clinical symptoms data were collected at baseline and during follow-up (N = 1286). We tested whether organ VMs, HHT symptoms and HHT genes were associated with increased mortality using Cox regression analysis, adjusting for patient age, sex, and smoking status.

Results

59 deaths occurred over average follow-up time of 3.4 years (max 8.6 years). A history of anemia was associated with increased mortality (HR = 2.93, 95% CI 1.37–6.26, p = 0.006), as were gastro-intestinal (GI) bleeding (HR = 2.63, 95% CI 1.46–4.74, p = 0.001), and symptomatic liver VMs (HR = 2.10, 95% CI 1.15–3.84, p = 0.015). Brain VMs and pulmonary arteriovenous malformations (AVMs) were not associated with mortality (p > 0.05). Patients with SMAD4 mutation had significantly higher mortality (HR = 18.36, 95% CI 5.60–60.20, p < 0.001) compared to patients with ACVRL1 or ENG mutation, but this estimate is imprecise given the rarity of SMAD4 patients (n = 33, 4 deaths).

Conclusions

Chronic GI bleeding, anemia and symptomatic liver VMs are associated with increased mortality in HHT patients, independent of age, and in keeping with the limited treatment options for these aspects of HHT. Conversely, mortality does not appear to be associated with pulmonary AVMs or brain VMs, for which patients are routinely screened and treated preventatively at HHT Centres. This demonstrates the need for development of new therapies to treat chronic anemia, GI bleeding, and symptomatic liver VMs in order to reduce mortality among HHT patients.
Bone fragility in patients affected by congenital diseases non skeletal in origin
Authors: Masi L. , Ferrari S. , Javaid M. K. , Papapoulos S. , Pierroz D. D. , Brandi M. L. ,   IOF Skeletal Rare Diseases Working Group
Published: January 2021

Background

Bone tissue represents a large systemic compartment of the human body, with an active metabolism, that controls mineral deposition and removal, and where several factors may play a role. For these reasons, several non-skeletal diseases may influence bone metabolism. It is of a crucial importance to classify these disorders in order to facilitate diagnosis and clinical management. This article reports a taxonomic classification of non-skeletal rare congenital disorders, which have an impact on bone metabolism

Methods

The International Osteoporosis Foundation (IOF) Skeletal Rare Diseases Working Group (SRD-WG), comprised of basic and clinical scientists, has decided to review the taxonomy of non-skeletal rare disorders that may alter bone physiology.

Results

The taxonomy of non-skeletal rare congenital disorders which impact bone comprises a total of 6 groups of disorders that may influence the activity of bone cells or the characteristics of bone matrix.

Conclusions

This paper provides the first comprehensive taxonomy of non-skeletal rare congenital disorders with impact on bone physiology.
Quality of life of children with spinal muscular atrophy and their caregivers from the perspective of caregivers: a Chinese cross-sectional study
Authors: Yao Mei , Ma Ying , Qian Ruiying , Xia Yu , Yuan Changzheng , Bai Guannan , Mao Shanshan
Published: January 2021

Background

Spinal muscular atrophy (SMA) is an autosomal-recessive motor neuron disease leading to dysfunction of multiple organs. SMA can impair the quality of life (QoL) of patients and family. We aimed to evaluate the QoL of children with SMA and their caregivers and to identify the factors associated with QoL in a cross-sectional study conducted in China.

Methods

We recruited 101 children aged 0–17 years with SMA and their caregivers from a children’s hospital in China. Twenty-six children had type I SMA, 56 type II and 19 type III. Each child’s QoL was measured by the Pediatric Quality of Life Inventory 3.0 Neuromuscular Module (PedsQL NMM), which was completed by the child’s caregivers. The caregiver’s QoL was measured by the Pediatric Quality of Life Inventory Family Impact Module (PedsQL FIM). Information on sociodemographic characteristics, disease-specific characteristics, and treatments were collected using the proxy-reported questionnaire. Two-sample t tests and one-way ANOVA were used to compare differences in average scores of QoL across subgroups.

Results

Children with type III SMA had a higher average Total score of PedsQL NMM and higher average scores in domains Neuromuscular disease and Family resources than children with type I or type II SMA (p < 0.001). Caregivers of children with type III SMA reported higher average scores in the domains of Physical, Emotional, Social, and Cognitive functioning of the PedsQL FIM than those of children with types I or II SMA (p < 0.05). In addition, disease-related characteristics (e.g. limited mobility, stable course of disease, skeleton deformity, and digestive system dysfunction) and respiratory support were associated with lower average scores of PedsQL NMM and PedsQL FIM (p < 0.05). Exercise training, multidisciplinary team management and use of the medication Nusinersen were each associated with higher average scores in both PedsQL NMM and FIM (p < 0.05).

Conclusion

Our study has demonstrated factors that may impair or improve QoL of children patients with SMA and their parents. Particularly, QoL was relatively poor in children with type I and type II SMA as well as in their caregivers compared to those with type III SMA. We strongly recommend that standard of care in a multidisciplinary team be strengthened to improve the QoL of SMA patients. Our study called for increased attention from clinical physicians on measuring QoL in their clinical practices in order to enhance the understanding of impacts of SMA and to make better decisions regarding treatment.
Clinical, biochemical and molecular phenotype of congenital disorders of glycosylation: long-term follow-up
Authors: Bogdańska Anna , Lipiński Patryk , Szymańska-Rożek Paulina , Jezela-Stanek Aleksandra , Rokicki Dariusz , Socha Piotr , Tylki-Szymańska Anna
Published: January 2021

Background

Congenital disorders of glycosylation (CDG) result from defects in the synthesis of glycans and the attachment of glycans to proteins and lipids. Our study aimed to describe the clinical, biochemical, and molecular findings of CDG patients, and to present the long-term follow-up.

Material and methods

A single-center study (1995–2019 years) of patients with congenital disorders of N-glycosylation and combined N- and O-hypoglycosylation was performed.

Results

Among 32 patients included into the study, there were 12 PMM2-CDG, 3 ALG13-CDG, 3 ALG1-CDG, 1 ALG3-CDG, 3 MPI-CDG, 1 PGM1-CDG, 4 SRD5A3-CDG, 1 DPAGT1-CDG, 3 ATP6AP1-CDG, 1 ATP6V0A2-CDG. The phenotypic and genotypic spectrum during long-term (in some cases over 20 years) observation was characterised and several measurements of serum Tf isoforms taken. Statistical analysis revealed strong negative correlation between asialo-Tf and tetrasialo-Tf, as well as between disialo-Tf and tetrasialo-Tf. Within CDG type I, no difference in % Tf isoforms was revealed between PMM2-CDG and non-PMM2-CDG patients. However, these two groups differed significantly in such diagnostic features as: cerebellar ataxia, failure to thrive, hypothyroidism, pericardial effusion, cardiomyopathy, inverted nipples, prolonged INR.

The effect of treatment with mannose in 2 patients with MPI-CDG was assessed and we found that % of asialo-Tf, monosialo-Tf, and disialo-Tf was significantly lowered, whereas tetrasialo-Tf and pentasialo-Tf rose, coming closer or falling into the reference range.

Conclusions

The novel finding was an abnormal Tf IEF pattern in two ALG13-CDG patients and normal in one ALG1-CDG patient. Clinical manifestation of presented CDG patients was similar to that reported in the literature. Mannose supplementation in MPI-CDG patients, as well as galactose supplementation in PGM1-CDG patient, improved patients’ clinical picture and Tf isoform profiles.
Depressive symptoms and health service utilization among Chinese middle-aged and older adults: a national population-based longitudinal survey
Authors: Guo Jing , Kong Dexia , Fang Liming , Zhu Yingxue , Zhang Bo
Published: January 2021

Objectives

This study aimed to (1) examine the cross-sectional and longitudinal relationships between depressive symptoms and health services utilization among Chinese middle-aged and older adults; and (2) evaluate whether there exists a rural–urban difference in such relationships.

Methods

Data was obtained from China Health and Retirement Longitudinal Study (CHARLS) in 2013 and 2015, a nationally representative survey of 13,551 adults aged 45 years and above in China.

Results

Depressive symptoms were positively associated with a greater likelihood of outpatient and inpatient health services utilization. This association was consistent across rural and urban settings, indicating the robustness of such findings across geographic areas.

Conclusions

Findings indicate that depressive symptoms are significantly associated with both in-patient and out-patient health service utilization among Chinese adults. Screening for depressive symptoms needs to be incorporated in these care settings in China.
Rational design of nonstoichiometric bioceramic scaffolds via digital light processing: tuning chemical composition and pore geometry evaluation
Authors: Li Yifan , Wu Ronghuan , Yu Li , Shen Miaoda , Ding Xiaoquan , Lu Fengling , Liu Mengtao , Yang Xianyan , Gou Zhongru , Xu Sanzhong
Published: January 2021

Bioactive ceramics are promising candidates as 3D porous substrates for bone repair in bone regenerative medicine. However, they are often inefficient in clinical applications due to mismatching mechanical properties and compromised biological performances. Herein, the additional Sr dopant is hypothesized to readily adjust the mechanical and biodegradable properties of the dilute Mg-doped wollastonite bioceramic scaffolds with different pore geometries (cylindrical-, cubic-, gyroid-) by ceramic stereolithography. The results indicate that the compressive strength of Mg/Sr co-doped bioceramic scaffolds could be tuned simultaneously by the Sr dopant and pore geometry. The cylindrical-pore scaffolds exhibit strength decay with increasing Sr content, whereas the gyroid-pore scaffolds show increasing strength and Young’s modulus as the Sr concentration is increased from 0 to 5%. The ion release could also be adjusted by pore geometry in Tris buffer, and the high Sr content may trigger a faster scaffold bio-dissolution. These results demonstrate that the mechanical strengths of the bioceramic scaffolds can be controlled from the point at which their porous structures are designed. Moreover, scaffold bio-dissolution can be tuned by pore geometry and doping foreign ions. It is reasonable to consider the nonstoichiometric bioceramic scaffolds are promising for bone regeneration, especially when dealing with pathological bone defects.
Noninvasive prenatal testing for assessing foetal sex chromosome aneuploidy: a retrospective study of 45,773 cases
Authors: Lu Xinran , Wang Chaohong , Sun Yuxiu , Tang Junxiang , Tong Keting , Zhu Jiansheng
Published: January 2021

Objective

To assess the positive predictive value (PPV) of noninvasive prenatal testing (NIPT) as a screening test for sex chromosome aneuploidy (SCA) with different maternal characteristics and prenatal decisions in positive cases.

Materials and methods

We retrospectively analysed 45,773 singleton pregnancies with different characteristics that were subjected to NIPT in the Maternity and Child Health Hospital of Anhui Province. The results were validated by karyotyping. Clinical data, diagnostic results, and data on pregnancy outcomes were collected.

Results

In total, 314 cases were SCA positive by NIPT; among those, 143 underwent invasive prenatal diagnostic testing, and 58 were true-positive. Overall, the PPVs for 45,X, 47,XXX, 47,XXY and 47,XYY were 12.5%, 51.72%, 66.67% and 83.33%, respectively. Interestingly, when only pregnant women of advanced maternal age (AMA) were screened, the PPVs for 45,X, 47,XXX, 47,XXY and 47,XYY were 23.81%, 53.33%, 78.95%, and 66.67%, respectively. The frequency of SCA was significantly higher in the AMA group than in the non-AMA group. The frequencies of 47,XXX and 47,XXY were significantly correlated with maternal age.

Conclusion

NIPT performed better in predicting sex chromosome trisomies than monosomy X, and patients with 45,X positive foetuses were more eager to terminate pregnancy than those with 47,XXX and 47,XYY. AMA may be a risk factor of having a foetus with SCA. Our findings may assist in genetic counselling of AMA pregnant women. Our pre- and posttest counselling are essential for familiarizing pregnant women with the benefits and limitations of NIPT, which may ease their anxiety and enable them to make informed choices for further diagnosis and pregnancy decisions.
Cystic fibrosis in Tuscany: evolution of newborn screening strategies over time to the present
Authors: Botti Matteo , Terlizzi Vito , Francalanci Michela , Dolce Daniela , Cavicchi Maria Chiara , Neri Anna Silvia , Galici Valeria , Mergni Gianfranco , Zavataro Lucia , Centrone Claudia , Festini Filippo , Taccetti Giovanni
Published: January 2021

Background

Cystic fibrosis (CF) is a life-threatening disease affecting about 1:3000 newborns in Caucasian populations. The introduction of newborn screening for cystic fibrosis (CF NBS) has improved the clinical outcomes of individuals with CF through early diagnosis and early treatment. NBS strategies have been implemented over time. CF NBS was introduced extensively in 1984 in Tuscany, a region with 3.7 million people, characterized by a high allelic heterogeneity of CFTR gene.

Aim and methods

The aim of the study is to present the results from 34 years (1984–2018) of CF NBS, retrospectively evaluating the sensitivity, specificity and predictive values of the tests. In particular, we studied the impact of the introduction of DNA molecular analysis in NBS in a region with high allelic heterogeneity, such as Tuscany.

Results

Over these 34 years, 919,520 neonates were screened, using four different NBS strategies. From 1984 to 1991, CF NBS was performed by the determination of albumin on dried meconium (sensitivity 68.75%; specificity 99.82%). Subsequently, the analysis of immunoreactive trypsinogen on a blood spot was adopted as CF NBS protocol (sensitivity 83.33%; specificity 99.77%). From 1992 to 2010, this strategy was associated with lactase meconium dosage:IRT1/IRT2 + LACT protocol(sensitivity 87.50%; specificity 99.82%). From 2011, when the existing algorithm was integrated by analysis of CF causing variants of the CFTR gene (IRT1/IRT2 + LACT + IRT1/DNA protocol), a substantial improvement in sensitivity was seen (senisitivity 96.15%; specificity 99.75%). Other improved parameters with DNA analysis in the NBS programme, compared with the previous method, were the diagnosis time (52 days vs. 38 days) and the recall rate (0.58 to 0.38%).

Conclusion

The inclusion of DNA analysis in the NBS was a fundamental step in improving sensitivity, even in a region with high allelic variability.
Synchronous choroid plexus papilloma and Wilms tumor in a girl, disclosing a Li-Fraumeni syndrome
Authors: Cruz Ofelia , Caloretti Victoria , Salvador Hector , Celis Veronica , Santa-Maria Vicente , Morales La Madrid Andrés , Suñol Mariona , Puerta Patricia , Muchart Jordi , Krauel Lucas , Lavarino Cinzia
Published: January 2021

Background

Li-Fraumeni Syndrome (LFS) is a cancer predisposition syndrome characterized by the early-onset of multiple primary cancers which can occur at different moments (metachronous onset) or, more rarely, coincidentally (synchronous onset). Here we describe a previously unreported patient with presentation of synchronous Wilms tumor and Choroid plexus papilloma, leading to the diagnosis of a Li-Fraumeni Syndrome (LFS).

Case presentation

A 6-year-old girl without previous complains presented with abdominal pain. Abdominal US and MRI showed a left renal tumor with subcapsular hematoma. Due to mild headaches, the diagnostic workup included a brain MRI that unexpectedly identified a large left parietal lobe tumor. Histopathological analysis determined the diagnosis of classic Wilms tumor and choroid-plexus papilloma (CPP), respectively. Both neoplasms showed intense nuclear p53 immunostaining associated with the pathogenic TP53 mutation c.844C > T (p.Arg282Trp). Our patient and her father shared the same heterozygous germline TP53 mutation, confirming the diagnosis of familiar Li-Fraumeni syndrome in the girl. The treatment was tailored to simultaneous tumor presentations.

Conclusions

LFS has been associated with Choroid plexus carcinoma (CPC), but rarely with CPP as in our patient. That suggests that it may be advisable to consider the possibility of analyzing TP53 mutation, not only in all patients with CPC, but also in some patients with CPP, especially when histological or clinical evidences point out to perform this study. The dissimilar presentation of LFS among our patient’s father, not having so far any neoplasia diagnosed, while her daughter presented precociously with two simultaneous different tumors, could be related to possible effects of modifier genes on the underlying mutant p53 genotype.
Mechanical power during extracorporeal membrane oxygenation and hospital mortality in patients with acute respiratory distress syndrome
Authors: Chiu Li-Chung , Lin Shih-Wei , Chuang Li-Pang , Li Hsin-Hsien , Liu Pi-Hua , Tsai Feng-Chun , Chang Chih-Hao , Hung Chen-Yiu , Lee Chung-Shu , Leu Shaw-Woei , Hu Han-Chung , Huang Chung-Chi , Wu Huang-Pin , Kao Kuo-Chin
Published: January 2021

Background

Mechanical power (MP) refers to the energy delivered by a ventilator to the respiratory system per unit of time. MP referenced to predicted body weight (PBW) or respiratory system compliance have better predictive value for mortality than MP alone in acute respiratory distress syndrome (ARDS). Our objective was to assess the potential impact of consecutive changes of MP on hospital mortality among ARDS patients receiving extracorporeal membrane oxygenation (ECMO).

Methods

We performed a retrospective analysis of patients with severe ARDS receiving ECMO in a tertiary care referral center in Taiwan between May 2006 and October 2015. Serial changes of MP during ECMO were recorded.

Results

A total of 152 patients with severe ARDS rescued with ECMO were analyzed. Overall hospital mortality was 53.3%. There were no significant differences between survivors and nonsurvivors in terms of baseline values of MP or other ventilator settings. Cox regression models demonstrated that mean MP alone, MP referenced to PBW, and MP referenced to compliance during the first 3 days of ECMO were all independently associated with hospital mortality. Higher MP referenced to compliance (HR 2.289 [95% CI 1.214–4.314], p = 0.010) was associated with a higher risk of death than MP itself (HR 1.060 [95% CI 1.018–1.104], p = 0.005) or MP referenced to PBW (HR 1.004 [95% CI 1.002–1.007], p < 0.001). The 90-day hospital mortality of patients with high MP (> 14.4 J/min) during the first 3 days of ECMO was significantly higher than that of patients with low MP (≦ 14.4 J/min) (70.7% vs. 46.8%, p = 0.004), and the 90-day hospital mortality of patients with high MP referenced to compliance (> 0.53 J/min/ml/cm H2O) during the first 3 days of ECMO was significantly higher than that of patients with low MP referenced to compliance (≦ 0.53 J/min/ml/cm H2O) (63.6% vs. 29.7%, p < 0.001).

Conclusions

MP during the first 3 days of ECMO was the only ventilatory variable independently associated with 90-day hospital mortality, and MP referenced to compliance during ECMO was more predictive for mortality than was MP alone.
Acquired mutations and transcriptional remodeling in long-term estrogen-deprived locoregional breast cancer recurrences
Authors: Priedigkeit Nolan , Ding Kai , Horne William , Kolls Jay K. , Du Tian , Lucas Peter C. , Blohmer Jens-Uwe , Denkert Carsten , Machleidt Anna , Ingold-Heppner Barbara , Oesterreich Steffi , Lee Adrian V.
Published: January 2021

Background

Endocrine therapy resistance is a hallmark of advanced estrogen receptor (ER)-positive breast cancer. In this study, we aimed to determine acquired genomic changes in endocrine-resistant disease.

Methods

We performed DNA/RNA hybrid-capture sequencing on 12 locoregional recurrences after long-term estrogen deprivation and identified acquired genomic changes versus each tumor’s matched primary.

Results

Despite being up to 7 years removed from the primary lesion, most recurrences harbored similar intrinsic transcriptional and copy number profiles. Only two genes, AKAP9 and KMT2C, were found to have single nucleotide variant (SNV) enrichments in more than one recurrence. Enriched mutations in single cases included SNVs within transcriptional regulators such as ARID1A, TP53, FOXO1, BRD1, NCOA1, and NCOR2 with one local recurrence gaining three PIK3CA mutations. In contrast to DNA-level changes, we discovered recurrent outlier mRNA expression alterations were common—including outlier gains in TP63 (n = 5 cases [42%]), NTRK3 (n = 5 [42%]), NTRK2 (n = 4 [33%]), PAX3 (n = 4 [33%]), FGFR4 (n = 3 [25%]), and TERT (n = 3 [25%]). Recurrent losses involved ESR1 (n = 5 [42%]), RELN (n = 5 [42%]), SFRP4 (n = 4 [33%]), and FOSB (n = 4 [33%]). ESR1-depleted recurrences harbored shared transcriptional remodeling events including upregulation of PROM1 and other basal cancer markers.

Conclusions

Taken together, this study defines acquired genomic changes in long-term, estrogen-deprived disease; highlights the importance of longitudinal RNA profiling; and identifies a common ESR1-depleted endocrine-resistant breast cancer subtype with basal-like transcriptional reprogramming.
A comparison of approaches for combining predictive markers for personalised treatment recommendations
Authors: Pierce Matthias , Emsley Richard
Published: January 2021

Background

In the presence of heterogeneous treatment effects, it is desirable to divide patients into subgroups based on their expected response to treatment. This is formalised via a personalised treatment recommendation: an algorithm that uses biomarker measurements to select treatments. It could be that multiple, rather than single, biomarkers better predict these subgroups. However, finding the optimal combination of multiple biomarkers can be a difficult prediction problem.

Methods

We described three parametric methods for finding the optimal combination of biomarkers in a personalised treatment recommendation, using randomised trial data: a regression approach that models outcome using treatment by biomarker interactions; an approach proposed by Kraemer that forms a combined measure from individual biomarker weights, calculated on all treated and control pairs; and a novel modification of Kraemer’s approach that utilises a prognostic score to sample matched treated and control subjects. Using Monte Carlo simulations under multiple data-generating models, we compare these approaches and draw conclusions based on a measure of improvement under a personalised treatment recommendation compared to a standard treatment. The three methods are applied to data from a randomised trial of home-delivered pragmatic rehabilitation versus treatment as usual for patients with chronic fatigue syndrome (the FINE trial). Prior analysis of this data indicated some treatment effect heterogeneity from multiple, correlated biomarkers.

Results

The regression approach outperformed Kraemer’s approach across all data-generating scenarios. The modification of Kraemer’s approach leads to improved treatment recommendations, except in the case where there was a strong unobserved prognostic biomarker. In the FINE example, the regression method indicated a weak improvement under its personalised treatment recommendation algorithm.

Conclusions

The method proposed by Kraemer does not perform better than a regression approach for combining multiple biomarkers. All methods are sensitive to misspecification of the parametric models.
Reporting guidelines for clinical trials of artificial intelligence interventions: the SPIRIT-AI and CONSORT-AI guidelines
Authors: Ibrahim Hussein , Liu Xiaoxuan , Rivera Samantha Cruz , Moher David , Chan An-Wen , Sydes Matthew R. , Calvert Melanie J. , Denniston Alastair K.
Published: January 2021

Background

The application of artificial intelligence (AI) in healthcare is an area of immense interest. The high profile of ‘AI in health’ means that there are unusually strong drivers to accelerate the introduction and implementation of innovative AI interventions, which may not be supported by the available evidence, and for which the usual systems of appraisal may not yet be sufficient.

Main text

We are beginning to see the emergence of randomised clinical trials evaluating AI interventions in real-world settings. It is imperative that these studies are conducted and reported to the highest standards to enable effective evaluation because they will potentially be a key part of the evidence that is used when deciding whether an AI intervention is sufficiently safe and effective to be approved and commissioned. Minimum reporting guidelines for clinical trial protocols and reports have been instrumental in improving the quality of clinical trials and promoting completeness and transparency of reporting for the evaluation of new health interventions. The current guidelines—SPIRIT and CONSORT—are suited to traditional health interventions but research has revealed that they do not adequately address potential sources of bias specific to AI systems. Examples of elements that require specific reporting include algorithm version and the procedure for acquiring input data. In response, the SPIRIT-AI and CONSORT-AI guidelines were developed by a multidisciplinary group of international experts using a consensus building methodological process. The extensions include a number of new items that should be reported in addition to the core items. Each item, where possible, was informed by challenges identified in existing studies of AI systems in health settings.

Conclusion

The SPIRIT-AI and CONSORT-AI guidelines provide the first international standards for clinical trials of AI systems. The guidelines are designed to ensure complete and transparent reporting of clinical trial protocols and reports involving AI interventions and have the potential to improve the quality of these clinical trials through improvements in their design and delivery. Their use will help to efficiently identify the safest and most effective AI interventions and commission them with confidence for the benefit of patients and the public.
A fixed nitrous oxide/oxygen mixture as an analgesic for patients with postherpetic neuralgia: study protocol for a randomized controlled trial
Authors: Gao Hai-Xiang , Zhang Jun-Jun , Liu Ning , Wang Yi , Ma Chun-Xiang , Gao Lu-Lu , Liu Qiang , Zhang Ting-Ting , Wang Yi-Ling , Bao Wen-Qiang , Li Yu-Xiang
Published: January 2021

Background

The pain management of postherpetic neuralgia (PHN) remains a major challenge, with no immediate relief. Nitrous oxide/oxygen mixture has the advantages of quick analgesic effect and well-tolerated. The purpose of this study is to investigate the analgesic effect and safety of nitrous oxide/oxygen mixture in patients with PHN.

Methods/design

This study is a single-center, two-group (1:1), randomized, placebo-controlled, double-blind clinical trial. A total of 42 patients with postherpetic neuralgia will be recruited and randomly divided into the intervention group and the control group. The control group will receive routine treatment plus oxygen, and the intervention group will receive routine treatment plus nitrous oxide/oxygen mixture. Data collectors, patients, and clinicians are all blind to the therapy. The outcomes of each group will be monitored at baseline (T0), 5 min (T1), and 15 min (T2) after the start of the therapy and at 5 min after the end of the therapy (T3). The primary outcome measure will be the pain intensity. Secondary outcomes included physiological parameters, adverse effects, patients’ acceptance of analgesia, and satisfaction from patients.

Discussion

Previous studies have shown that nitrous oxide/oxygen mixture can effectively relieve cancer patients with breakthrough pain. This study will explore the analgesic effect of oxide/oxygen mixture on PHN. If beneficial to patients with PHN, it will contribute to the pain management of PHN.

Trial registration

Chinese Clinical Trial Register ChiCTR1900023730. Registered on 9 June 2019
Lymphocyte subset abnormalities in early diffuse cutaneous systemic sclerosis
Authors: Fox David A. , Lundy Steven K. , Whitfield Michael L. , Berrocal Veronica , Campbell Phillip , Rasmussen Stephanie , Ohara Ray , Stinson Alexander , Gurrea-Rubio Mikel , Wiewiora Evan , Spino Catherine , Bush Erica , Furst Daniel , Pillai Shiv , Khanna Dinesh
Published: January 2021

Background

Abnormalities in lymphocyte surface markers and functions have been described in systemic sclerosis (SSc), but conflicting results abound, and these studies often examined patients with heterogeneous disease duration, severity, clinical phenotype, and concurrent immunosuppressive agents. We studied a clinically homogeneous group of early diffuse cutaneous SSc patients not exposed to immunosuppressive drugs who were enrolled in a clinical trial and compared their immune parameters to healthy control subjects.

Methods

Lymphocyte subsets were enumerated by multi-parameter flow cytometry of peripheral blood mononuclear cells at baseline visit. Production of the cytokines IL-4 and IL-17 was measured by intracellular flow cytometry following T cell activation.

Results

SSc patients had increased percentages of CD4+ T cells but lower percentages of CD8+ T cells versus controls. The CD28-negative population was expanded in SSc, in the CD4 subset. Striking expansion of CD319+ T cells was noted among the CD4+ cells, in which they were barely detectable in healthy subjects. Frequencies of IL-4 producing cells did not differ between SSc and controls, but expansion of IL-17 producing cells was observed in SSc. A higher proportion of CD319+ cells produced cytokines, compared to other CD4+ cells. Numbers of activated T cells, regulatory T cells, and B cells were similar in SSc and control groups. Circulating follicular helper but not peripheral helper T cells were slightly expanded in SSc.

Conclusion

In this carefully selected group of early diffuse cutaneous SSc patients, analysis of immune cell parameters has identified abnormalities that likely reflect disease pathogenesis and that are candidate biomarkers for sub-classification and targeted treatment. The CD4+CD319+ (SLAM-F7+) cells are cytotoxic and oligoclonal, were recently shown to be a dominant T cell population in perivascular lymphocytic infiltrates in SSc skin, actively secrete cytokines, and are emerging as a target for novel treatments of SSc.
Catechin synergistically potentiates mast cell-stabilizing property of caffeine
Authors: Yashima Misaki , Sato Yukine , Kazama Itsuro
Published: January 2021

Caffeine and catechin, contained in coffee and tea, are commonly consumed substances worldwide. Studies revealed their health promoting functions, such as anti-oxidant, anti-cancer and anti-bacterial properties. Additionally, studies also revealed their roles in ameliorating the symptoms of allergic disorders, indicating their anti-allergic properties. In the present study, using the differential-interference contrast (DIC) microscopy, we examined the effects of caffeine and catechin on the degranulation from rat peritoneal mast cells. Both caffeine and catechin dose-dependently decreased the numbers of degranulating mast cells. At concentrations equal to or higher than 25 mM, caffeine and catechin markedly suppressed the numbers of degranulating mast cells. In contrast, at relatively lower concentrations, both substances did not significantly affect the numbers of degranulating mast cells. However, surprisingly enough, low concentrations of catechin (1, 2.5 mM) synergistically enhanced the suppressive effect of 10 mM caffeine on mast cell degranulation. These results provided direct evidence for the first time that caffeine and catechin dose-dependently inhibited the process of exocytosis. At relatively lower concentrations, caffeine or catechin alone did not stabilize mast cells. However, low concentrations of catechin synergistically potentiated the mast cell-stabilizing property of caffeine.
Three cases of BRAF mutation negative Erdheim-Chester disease with a challenging distinction from IgG4-related disease
Authors: Spoerl David , André Raphaël , Bornand Aurélie , Seebach Jörg D.
Published: January 2021

Background

Erdheim-Chester disease (ECD) is a rare non-Langerhans histiocytosis with slow progression over the years that is particularly difficult to diagnose.

Cases

Here we report three cases of ECD without BRAF mutation presenting with a renal mass, hairy kidney appearance, and a rather benign course, for which the diagnosis of ECD was delayed, characterized by multiple investigations and unsuccessful treatments attempts. In two cases the distinction from IgG4-related disease required multiple investigations and reevaluation of the clinical, radiological, histological, and immunological characteristics.

Conclusion

A correct diagnosis of ECD may take several years and often requires revisiting previous hypotheses. Reassessment of histological slides and more modern complementary exams such as PET-CT or BRAF and MAPK-ERK mutation analysis can help to confirm the diagnosis of ECD and to select effective therapy.
Successful sublingual immunotherapy for severe egg allergy in children: a case report
Authors: Sagara Nagatoshi , Fujita Satoshi , Suzuki Ryohei , Aota Akiko , Akashi Kenichi , Katsunuma Toshio
Published: January 2021

Background

Egg allergy is one of the most common food allergies in children. To date, oral immunotherapy (OIT) has been considered as a promising treatment option for egg allergy. However, safety issues remain concerning severe adverse events requiring epinephrine injection. Hence, establishing a safer method to treat egg allergy would be beneficial. We report here two children with egg allergy who were safely treated with sublingual immunotherapy (SLIT) before transitioning to OIT.

Case presentation

Patient 1 was a 7-year-old girl and Patient 2 was a 5-year-old girl. Although OIT for egg had been attempted in both patients, severe anaphylactic symptoms were induced by ingesting only 0.1 g of heated whole egg. Therefore, SLIT was conducted with aqueous suspensions consisting of water and heated whole egg powder. Suspensions were administered sublingually, kept in the mouth for 2 min, and spat out immediately thereafter. SLIT was continued for 7 months for Patient 1 and 8 months for Patient 2 due to the exploratory character of the study. Afterwards, the patients successfully transferred to low-dose OIT with 1 g of heated whole egg (≒170 mg of egg protein) daily, and are continuing the therapy as of June 2020. As for adverse reactions, Patient 1 expressed oral cavity itchiness once at the beginning of SLIT. Patient 2 had no adverse reaction. The levels of antigen-specific IgE decreased in both patients after SLIT, and further decreased after switching to OIT.

Conclusions

Few clinical studies have evaluated the efficacy and safety of SLIT for egg allergy. Although the treatment was conducted in only two patients, our results have shown that SLIT is a promising treatment procedure for egg allergy. Further clinical trials will be needed to additionally assess the efficacy and safety of SLIT in children with food allergy.
Asthma and COVID-19: a systematic review
Authors: Mendes Natália F. , Jara Carlos P. , Mansour Eli , Araújo Eliana P. , Velloso Licio A.
Published: January 2021

Background

Severe coronavirus disease-19 (COVID-19) presents with progressive dyspnea, which results from acute lung inflammatory edema leading to hypoxia. As with other infectious diseases that affect the respiratory tract, asthma has been cited as a potential risk factor for severe COVID-19. However, conflicting results have been published over the last few months and the putative association between these two diseases is still unproven.

Methods

Here, we systematically reviewed all reports on COVID-19 published since its emergence in December 2019 to June 30, 2020, looking into the description of asthma as a premorbid condition, which could indicate its potential involvement in disease progression.

Results

We found 372 articles describing the underlying diseases of 161,271 patients diagnosed with COVID-19. Asthma was reported as a premorbid condition in only 2623 patients accounting for 1.6% of all patients.

Conclusions

As the global prevalence of asthma is 4.4%, we conclude that either asthma is not a premorbid condition that contributes to the development of COVID-19 or clinicians and researchers are not accurately describing the premorbidities in COVID-19 patients.
Adipose tissue-derived stem cells in breast reconstruction: a brief review on biology and translation
Authors: Fang Jun , Chen Feng , Liu Dong , Gu Feiying , Wang Yuezhen
Published: January 2021

Recent developments in adipose-derived stromal/stem cell (ADSC) biology provide new hopes for tissue engineering and regeneration medicine. Due to their pluripotent activity, paracrine activity, and immunomodulatory function, ADSCs have been widely administrated and exhibited significant therapeutic effects in the treatment for autoimmune disorders, neurodegenerative diseases, and ischemic conditions both in animals and human clinical trials. Cell-assisted lipotransfer (CAL) based on ADSCs has emerged as a promising cell therapy technology and significantly improved the fat graft retention. Initially applied for cosmetic breast and facial enhancement, CAL has found a potential use for breast reconstruction in breast cancer patients. However, more challenges emerge related to CAL including lack of a standardized surgical procedure, the controversy in the effectiveness of CAL, and the potential oncogenic risk of ADSCs in cancer patients. In this review, we summarized the latest research and intended to give an outline involving the biological characteristics of ADSCs as well as the preclinical and clinical application of ADSCs.
patRoon: open source software platform for environmental mass spectrometry based non-target screening
Authors: Helmus Rick , ter Laak Thomas L. , van Wezel Annemarie P. , de Voogt Pim , Schymanski Emma L.
Published: January 2021

Mass spectrometry based non-target analysis is increasingly adopted in environmental sciences to screen and identify numerous chemicals simultaneously in highly complex samples. However, current data processing software either lack functionality for environmental sciences, solve only part of the workflow, are not openly available and/or are restricted in input data formats. In this paper we presentpatRoon, a newRbased open-source software platform, which provides comprehensive, fully tailored and straightforward non-target analysis workflows. This platform makes the use, evaluation and mixing of well-tested algorithms seamless by harmonizing various common (primarily open) software tools under a consistent interface. In addition,patRoonoffers various functionality and strategies to simplify and perform automated processing of complex (environmental) data effectively.patRoonimplements several effective optimization strategies to significantly reduce computational times. The ability ofpatRoonto perform time-efficient and automated non-target data annotation of environmental samples is demonstrated with a simple and reproducible workflow using open-access data of spiked samples from a drinking water treatment plant study. In addition, the ability to easily use, combine and evaluate different algorithms was demonstrated for three commonly used feature finding algorithms. This article, combined with already published works, demonstrate thatpatRoonhelps make comprehensive (environmental) non-target analysis readily accessible to a wider community of researchers.
A hybrid service selection optimization algorithm in internet of things
Authors: Zhang Xiaofei , Geng Juncheng , Ma Jianwei , Liu Hao , Niu Shuangxia , Mao Wandeng
Published: January 2021

With the scale of Internet of Things (IoT) continues to increase, it brings big challenges for service selection in a large-scale IoT. For solving this problem, a service selection method based on the enhanced genetic algorithm is proposed in this paper. To decrease the scale of service selection, this paper uses the lexicographic optimization approach and quality of service (QoS) constraint relaxation technique to find the candidate service with height QoS. Then, the IoT service selection problem is transformed into a single-objective optimization problem adopting a simple weighting method, and the final composite service meeting the user's QoS needs are obtained from the candidate service. The simulation results show that the proposed algorithm can efficiently and quickly achieve a composite service satisfying user's QoS needs, and is more suitable for solving the service composite problem in large-scale IoT services.
Enterprise adoption of cloud computing with application portfolio profiling and application portfolio assessment
Authors: Ramchand Kent , Baruwal Chhetri Mohan , Kowalczyk Ryszard
Published: January 2021

With the continued appeal and adoption of cloud computing, an assessment of cloud run costs and migration affordability prior to adoption would assist enterprises that have several legacy applications targeted for cloud migration. However, as cloud migrations have become more prevalent, many have been characterised by unsuccessful migration or application modernisation attempts. The primary reason behind the failed attempts is insufficient planning upfront, to identify which legacy applications are suitable to realise the benefits of public or private cloud, leading to time and cost overruns. There is a need for strategic decision making for application portfolios to mitigate the risks of cost overruns and migration delays. Thus, a Rough Order of Magnitude (ROM) of cloud run costs for an application portfolio is required in the planning phase as an input into IT governance. To obtain the ROM cloud run costs, it is necessary to baseline application data, preferably through automated discovery, and perform quantitative analysis of the applications. Therefore, we propose an approach to (a) baseline application data using Application Portfolio Profiling (APP), and (b) perform quantitative analysis of applications using an Application Portfolio Assessment (APA), to inform the legacy application migration decision. APP and APA are proposed as part of a Cloud Computing Considerations for Companies (CCCC) framework that enables an enterprise to make an informed decision regarding which legacy applications are to be migrated as part of enterprise Cloud Computing adoption. This decision is important because of the change in operating model, infrastructure requirements, hidden costs and commercial models inherent with cloud computing adoption. We validate the proposed framework through applying it to a real-world use case scenario that provides the necessary coverage to test the proposed framework.
Injuries in Netball-A Systematic Review
Authors: Downs Christopher , Snodgrass Suzanne J. , Weerasekara Ishanka , Valkenborghs Sarah R. , Callister Robin
Published: January 2021

Background

Netball is estimated to be played by more than 20 million people worldwide, but there is evidence of high injury incidence. A thorough understanding of the types and rates of netball injuries is essential for effective injury management and prevention strategies to be developed and implemented. This systematic review summarises the published findings with respect to injury types, participant characteristics and any identified risk factors for netball injuries.

Methods

A librarian-assisted computer search of seven scientific databases was conducted for studies reporting on netball injuries. Inclusion criteria were studies published in English, in peer-reviewed journals, which reported data on injuries and variables (e.g. age and competition level) that have been proposed as possibly associated with netball injury risk.

Results

Forty-six studies (43.5% prospective, 37% hospital/insurance records, 19.5% retrospective) from 45 articles were included after screening. The majority of studies (74%) were conducted in Australia or New Zealand. There was little consistency in the definition of ‘injury’. Elite or sub-elite level players were included in 69% of studies where the level of competition was reported. The duration of injury surveillance was generally related to the format of competition from which data were collected. Self-report questionnaires were used in 48% of studies and only 26% of studies used qualified health professionals to collect data courtside. Injuries to the ankle and knee were the most common (in 19 studies) although the incidence varied considerably across the studies (ankle 13–84% and knee 8–50% of injuries). Prevention of ankle and knee injuries should be a priority. Children sustained more upper limb injuries (e.g. fractures) compared with adults who sustained more lower limb injuries (e.g. ankle and knee sprains/strains). A large number of potential risk factors for injury in netball have been investigated in small numbers of studies. The main circumstances of injury are landings, collisions and falls.

Conclusion

Further studies should be directed towards recreational netball, reporting on injury incidence in players by age and utilising high-quality, standardised methods and criteria. Specific injury diagnosis and a better understanding of the circumstances and mechanisms of injury would provide more meaningful data for developing prevention strategies.
Legionnaires’ disease in the time of COVID-19
Authors: Cassell Kelsie , Davis J Lucian , Berkelman Ruth
Published: January 2021

Due to similarities in initial disease presentation, clinicians may be inclined to repeatedly test community-acquired pneumonia cases for COVID-19 before recognizing the need to test for Legionnaires’ disease. Legionnaires’ disease is an illness characterized by pneumonia that has a summer/early fall seasonality due to favorable conditions forLegionellagrowth and exposure.Legionellaproliferate in warm water environments and stagnant sections of indoor plumbing and cooling systems. During the ongoing pandemic crisis, exposures to aerosolized water from recently reopened office or retail buildings should be considered as an epidemiologic risk factor forLegionellaexposure and an indication to test. The majority of Legionnaires’ disease cases occurring each year are not diagnosed, and some experts recommend that all patients hospitalized with community-acquired pneumonia without a known etiology be tested forLegionellainfection. Proper diagnosis can increase the likelihood of appropriate and timely antibiotic treatment, identify potential clusters of disease, and facilitate source attribution.