bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of genotype and phenotype in 32 patients with hereditary hemochromatosis in China
Authors: Wu Liyan , Zhang Wei , Li Yanmeng , Zhou Donghu , Zhang Bei , Xu Anjian , Wu Zhen , Wu Lina , Li Shuxiang , Wang Xiaoming , Zhao Xinyan , Wang Qianyi , Li Min , Wang Yu , You Hong , Huang Jian , Ou Xiaojuan , Jia Jidong 
Published: September 2021

Abstract
Background
Hereditary hemochromatosis (HH) is widely recognized and clinical manifestations of hemochromatosis-related (HFE-related) HH is well studied in European populations. Less is known about the clinical and laboratory characteristics of non-HFE related HH in Asian population. We aimed to explore the relationship between genotype and clinical phenotype in Chinese patients with non-HFE related hereditary hemochromatosis.

Methods
Peripheral blood samples and clinical data of patients with primary iron overload were collected from the China Registry of Genetic/Metabolic Liver Diseases. Sanger sequencing was performed in cases with primary iron overload, for 5 known HH related genes (HFE, HJV, HAMP, TFR2 and SLC40A1) and 2 novel iron homeostasis-related genes (DENND3 and SUGP2). The correlation of genotype and clinical phenotype in these patients was analyzed.

Results
Of the 32 patients with primary iron overload (23 were males and 9 were females), non-HFE variants were detected in 31 (31/32, 97%), including 8 pathogenic variants in HJV, 7 pathogenic variants in SLC40A1, 8 likely pathogenic variants in SUGP2 and 5 likely pathogenic variants in DENND3 cases. Among these 31 cases, 4 cases harbored homozygous variants, 2 cases harbored homozygous + heterozygous variants, 19 cases harbored heterozygous or combined heterozygous variants, and 6 cases harbored no any damaging variants. None of investigated cases carried damaging HAMP and TFR2 variants were found. 8 cases were classified as type 2A HH and 6 cases as type 4 HH, 10 cases as non-classical genotype, and 6 cases had no pathogenic variants from 31 cases. During the statistical analysis, we excluded one case (SLC40A1 IVS3 + 10delGTT + SUGP2 p. R639Q(homo)) with difficulty in grouping due to combined damaging variants. Cases with type 2A HH have an earlier age at diagnosis (p = 0.007). The iron index of cases in type 2A HH and type 4 HH was higher than that in other groups (p = 0.01). Arthropathy was relatively rare in all groups. None of cases with type 2A HH developed cirrhosis. Cirrhosis and diabetes are more prevalent in type 4 HH. The incidence of cirrhosis (p = 0.011), cardiac involvement (p = 0.042), diabetes (p = 0.035) and hypogonadism (p = 0.020) was statistically significant in the four groups. However, due to the limited sample size, the pairwise comparison showed no significant difference.

Conclusions
This is the first comprehensive analysis about the gene variant spectrum and phenotypic aspects of non-HFE HH in China. The results will be useful to the identification, diagnosis and management of HH in China.
Are rare diseases overlooked by medical education? Awareness of rare diseases among physicians in Poland: an explanatory study
Authors: Walkowiak Dariusz , Domaradzki Jan 
Published: September 2021

Abstract
Background
During their studies, future physicians are often taught that while evaluating a patient they should first consider a common diagnosis and not a rare one. Consequently, although most physicians will face the diagnosis or treatment of a rare disease (RD) at some point in their professional lives, many assume that they might never meet a patient with a specific RD. Moreover, many physicians lack knowledge about RDs and are not prepared for caring for RD patients. Thus, the aim of this paper was to assess the awareness of RDs among Polish physicians.

Methods
The study was conducted among 165 medical doctors taking their specialization courses at the Poznan University of Medical Sciences, Poland. The questionnaire assessed physicians’ knowledge about the number, examples, etiology and estimated frequency of RDs. It also checked the self-assessment of physicians competence in RDs, as well as their opinions about university curricula in this respect.

Results
The study shows that while most physicians lacked basic knowledge about the etiology, epidemiology and prevalence of RDs, many had also problems with separating RDs from more common disorders. Moreover, 94.6% of physicians perceived their knowledge on RDs as insufficient or very poor and less than 5% feel prepared for caring for patients with RDs. Simultaneously, while over 83% of physicians believed that RDs constitute a serious public health issue, 17% were of the opinion that mandatory courses on RDs are not necessary in medical curricula and 6.7% were not interested in broadening their knowledge of such diseases. Most respondents derived their knowledge on RDs from university courses, scientific literature and research, as well as from the Internet.

Conclusion
Since the study shows that there is a urgent need to fill the gap in physicians’ knowledge on RDs, it seems advisable that extra courses on these diseases should be added to medical curricula and physicians’ postgraduate training. Furthermore, as the Internet is the main source of information on RDs, e-learning programs and courses for all medical professionals should be organized.
Targeting mutant p53 for cancer therapy: direct and indirect strategies
Authors: Hu Jiahao , Cao Jiasheng , Topatana Win , Juengpanich Sarun , Li Shijie , Zhang Bin , Shen Jiliang , Cai Liuxin , Cai Xiujun , Chen Mingyu 
Published: September 2021

AbstractTP53 is a critical tumor-suppressor gene that is mutated in more than half of all human cancers. Mutations in TP53 not only impair its antitumor activity, but also confer mutant p53 protein oncogenic properties. The p53-targeted therapy approach began with the identification of compounds capable of restoring/reactivating wild-type p53 functions or eliminating mutant p53. Treatments that directly target mutant p53 are extremely structure and drug-species-dependent. Due to the mutation of wild-type p53, multiple survival pathways that are normally maintained by wild-type p53 are disrupted, necessitating the activation of compensatory genes or pathways to promote cancer cell survival. Additionally, because the oncogenic functions of mutant p53 contribute to cancer proliferation and metastasis, targeting the signaling pathways altered by p53 mutation appears to be an attractive strategy. Synthetic lethality implies that while disruption of either gene alone is permissible among two genes with synthetic lethal interactions, complete disruption of both genes results in cell death. Thus, rather than directly targeting p53, exploiting mutant p53 synthetic lethal genes may provide additional therapeutic benefits. Additionally, research progress on the functions of noncoding RNAs has made it clear that disrupting noncoding RNA networks has a favorable antitumor effect, supporting the hypothesis that targeting noncoding RNAs may have potential synthetic lethal effects in cancers with p53 mutations. The purpose of this review is to discuss treatments for cancers with mutant p53 that focus on directly targeting mutant p53, restoring wild-type functions, and exploiting synthetic lethal interactions with mutant p53. Additionally, the possibility of noncoding RNAs acting as synthetic lethal targets for mutant p53 will be discussed.
Head-to-head comparison of sirolimus- versus paclitaxel-coated balloon angioplasty in the femoropopliteal artery: study protocol for the randomized controlled SIRONA trial
Authors: Teichgräber Ulf , Ingwersen Maja , Platzer Stephanie , Lehmann Thomas , Zeller Thomas , Aschenbach René , Scheinert Dierk 
Published: September 2021

Abstract
Background
Endovascular revascularization has established as the first-line therapy of femoropopliteal artery disease. Paclitaxel-coated balloon angioplasty proved to be superior to plain old balloon angioplasty (POBA) regarding prevention of restenosis and need for recurrent revascularization. Over the past years, paclitaxel was the only active drug to inhibit neointimal proliferation which could be processed to an appropriate balloon coating. The purpose of this study is to assess whether efficacy and safety of sirolimus-coated balloon angioplasty is noninferior to paclitaxel-coated balloon angioplasty.

Methods
This randomized controlled, single-blinded, multicentre, investigator-initiated noninferiority trial aims to enrol a total of 478 participants with symptomatic femoropopliteal artery disease of Rutherford category 2 to 4 due to de novo stenosis or restenosis. After pre-dilation, participants will be allocated in a 1:1 ratio to either sirolimus- or paclitaxel-coated balloon angioplasty. Post-dilation with the drug-coated balloon (DCB) used or standard balloon is mandatory in case ≥ 50%, and optional in case of ≥ 30% residual diameter stenosis. Bailout stenting with bare-metal nitinol stents should be conducted in case of flow-limiting dissection. Primary noninferiority endpoints are primary patency and the composite of all-cause mortality, major target limb amputation, and clinically driven target lesion revascularization at 12 months. Secondary outcomes are clinical and hemodynamic improvement, change in health-related quality of life, and safety throughout 60 months.

Discussion
Although concerns about long-term safety of paclitaxel-coated devices were not confirmed by recent patient-level data analyses, conflicting evidence contributed to a loss of confidence among patients and physicians. Therefore, sirolimus, known for a broader therapeutic range than paclitaxel, may serve as a welcome alternative. This will be justified if noninferiority of sirolimus-coated balloon angioplasty against the current standard of paclitaxel-coated balloon angioplasty can be demonstrated.

Trial registration
ClinicalTrials.govNCT04475783. Registered on 17 July 2020
EUDAMED No. CIV-20-11-035172, DRKS00022452
Toxoplasmosis is a risk factor for acquiring SARS-CoV-2 infection and a severe course of COVID-19 in the Czech and Slovak population: a preregistered exploratory internet cross-sectional study
Authors: Flegr Jaroslav 
Published: September 2021

AbstractBackgroundLatent toxoplasmosis, i.e. a lifelong infection with the protozoan parasiteToxoplasma gondii, affects about a third of the human population worldwide. In the past 10 years, numerous studies have shown that infected individuals have a significantly higher incidence of mental and physical health problems and are more prone to exhibiting the adverse effects of various diseases.MethodsA cross-sectional internet study was performed on a population of 4499 (786Toxoplasma-infected) participants and looked for factors which positively or negatively affect the risk of SARS-CoV-2 infection and likelihood of a severe course of COVID-19.ResultsLogistic regression and partial Kendall correlation controlling for sex, age, and size of the place of residence showed that latent toxoplasmosis had the strongest effect on the risk of infection (OR = 1.50) before sport (OR = 1.30) and borreliosis (1.27). It also had the strongest effect on the risk of severe course of infection (Tau = 0.146), before autoimmunity, immunodeficiency, male sex, keeping a cat, being overweight, borreliosis, higher age, or chronic obstructive pulmonary disease. Toxoplasmosis augmented the adverse effects of other risk factors but was not the proximal cause of the effect of cat-keeping on higher likelihood of COVID infection and higher severity of the course of infection because the effect of cat-keeping was also observed (and in particular) in a subset ofToxoplasma-infected respondents (Tau = 0.153). Effects of keeping a cat were detected only in respondents from multi-member families, suggesting that a cat could be a vector for the transmission of SARS-CoV-2 within a family.ConclusionsToxoplasmosis is currently not considered a risk factor for COVID-19, andToxoplasma-infected individuals are neither informed about their higher risk nor prioritised in vaccination programs. Because toxoplasmosis affects a large segment of the human population, its impact on COVID-19-associated effects on public health could be considerable.Graphical abstract
Challenge of coexisting type 2 diabetes mellitus and insulinoma: a case report
Authors: Singbo Joseph , Locketz Michael , Ross Ian Louis 
Published: September 2021

Abstract
Background
Insulinomas are rare clinical entities, but concurrent diabetes mellitus is even more uncommon, and the combination is easily missed. Recurrent hypoglycemia could be misconstrued as improved glycemic control. We present an unusual patient with type 2 diabetes and neuroglycopenia, with apparent improved glycemic control due to an insulinoma.

Case presentation
A 54-year-old mixed ancestry man with a positive family history of type 2 diabetes mellitus was diagnosed with type 2 diabetes mellitus and hypertension 8 years prior to admission. He presented with episodes of abnormal behavior and hypoglycemia. Inappropriately high insulin and C-peptide concentrations were identified at the time of hypoglycemia. Despite poor adherence to his diabetic treatment, he had no target organ damage relating to diabetes, and his hemoglobin A1c (HbA1c) was 5.3%. A diagnosis of insulinoma was made, and he was started on diazoxide, with endoscopic ultrasound revealing a possible lesion in the pancreatic tail measuring 12 mm × 12 mm. A fine-needle aspiration biopsy could not be performed due to overlying splenic arteries and the risk of vascular perforation. An intraoperative ultrasound confirmed a 15 mm × 10 mm tumor in the pancreatic tail, necessitating a partial pancreatectomy and splenectomy, which were curative. A well-differentiated intermediate grade 2 pancreatic neuroendocrine tumor producing insulin was confirmed on histopathology.

Conclusions
Recurrent, progressive hypoglycemia and improved glycemic control in a diabetic, without an alternative explanation, may suggest an insulinoma. Insulinomas that exist with type 1 diabetes mellitus, particularly malignant insulinomas, must have escaped autoimmune attack through lack of autoantigen expression. Computed tomography on its own may be insufficiently sensitive for diagnosis of insulinomas, whereas endoscopic and intraoperative ultrasonography may improve the identification of the culprit lesion.
Professional reliability of engineering: ratio of research approaches
Authors: Balakshina Elena 
Published: September 2021

The article deals with the problem of professional reliability and efficiency. The prerequisites for the development of grounds for the study of this psychological category on the example of engineering specialties are indicated. Special attention is paid to laying of structure of professionally important qualities and professional competences (knowledge, abilities, skills) at a stage of vocational education in a higher educational institution. A number of labor fields are given, for whose specialists this characteristic is especially significant. An attempt is made to clarify the criteria for the professional reliability of an organization employee in the work of domestic scientists. It has been established that psychophysiological, individual-psychological, personal and moral parameters are most often mentioned.
The methods most often used by numerous authors in revealing the mechanisms of reliability of activity within the framework of labor psychology are listed. It is noted that the initial achievements were carried out on professional activities related to the operation of complex technical means and systems (engineering). Lists the traditional types of engineering activities and modern trends in the dynamics of engineering professions. Based on theoretical analysis and the professional method, universal psychological reliability indicators are derived for engineers of different professional orientations. On the basis of the center for psychological support of the Tver State Technical University, psychodiagnostic tools are selected and the corresponding student contingent (students in technical areas) are examined. The results of the study are described and conclusions are formed. A general opinion on the article is drawn up.
Ensuring of the safety of internal affairs bodies during professional psychological selection for service using printing devices
Authors: Ermakov Andrey , Belyankina Valentina , Sitnikov Valeriy , Shakhmatov Alexander , Kochin Andrey 
Published: September 2021

the article discloses the main results of the study, describing the dependence of the presence of risk factors on the personal characteristics of candidates for service in the internal affairs bodies in the process of conducting a special psychophysiological study using a polygraph.
The main conclusions in this study were obtained using comparative, qualitative, correlation and frequency analyses, which is confirmed by the existence of numerous relationships of personal characteristics, according to which the presence or absence of risk factors can be predicted. This empirical study has made it possible to draw up a table of the distribution of specific gravity and a formula according to which an employee working with printing devices can calculate the probability of identifying a risk factor in each candidate for service in the internal affairs bodies on the basis of a psychological examination. The obtained data on the results of the methods used, describing various aspects of the external manifestations of a person, were presented by groups, in matrix form and analyzed by a number of indicators such as: the risk factor was not identified, the risk factor was identified, and in groups where the result was not determined, but there is a suspicion of the presence of a risk factor. Data were compared with intergroup measures of personality traits. Analysis of personality characteristics showed that in a sample of candidates for service, the most important of the suitability markers correlate with personal features. An employee working with printing devices at the stage of familiarization with the candidate's questionnaire, analyzing his personal and business qualities, can predict, with a high degree of probability, the identification of risk factors, even before the start of the study using a polygraph, or the manifestation of various kinds of opposition, in order to hide the identification of risk factors.
The use of this formula by psychologists and polygraphologists in professional psychological selection greatly contributes to ensuring the safety of internal affairs bodies at the stage of personnel screening, which is aimed at detecting and preventing emergency incidents among the personnel of internal affairs bodies and occupies a decisive role in forming a positive image of the Ministry of Internal Affairs.
Nudging Drivers to Safety: Evidence from a Field Experiment
Authors: Choudhary Vivek , Shunko Masha , Netessine Serguei , Koo Seongjoon 
Published: September 2021

Driving is an integral component of many operational systems, and any small improvement in driving quality can have a significant effect on accidents, traffic, pollution, and the economy in general. However, making improvements is challenging given the complexity and multidimensionality of driving as a task. In this paper, we investigate the effectiveness of nudging to improve driving performance. In particular, we leverage a smartphone application launched by our industry partners to send three types of nudges through notifications to drivers, indicating how they performed on the current trip with respect to their personal best, personal average, and latest driving performance. We measure the resulting driving performance using telematics technology (i.e., real-time sensor data from an accelerometer, Global Positioning System (GPS), and gyroscope in a mobile device). Compared with the “no-nudge” control group, we find that personal best and personal average nudges improve driving performance by approximately 18% standard deviations of the performance scores calculated by the application. In addition, these nudges improve interaccident times (by nearly 1.8 years) and driving performance consistency, as measured by the standard deviation of the performance score. Noting that driving abilities and feedback seeking may vary across individuals, we adopt a generalized random forest approach, which shows that high-performing drivers who are not frequent feedback seekers benefit the most from personal best nudges, whereas low-performing drivers who are also frequent feedback seekers benefit the most from the personal average nudges. Finally, we investigate the potential mechanism behind the results by conducting an online experiment in a nondriving context. The experiment shows that the performance improvements are directly driven by the changes in participants’ effort in response to different nudges and that our key findings are robust in alternative (nondriving) settings. Our analysis further shows that nudges are effective when the variability in reference points is low, which explains why the personal best and personal average nudges are effective, whereas the last score nudge is not. This paper was accepted by Vishal Gaur, operations management.
Complaints handling
Authors: Wright George 
Published: September 2021

George Wright gives a step-by-step guide for dental nurses Aims & Objectives By the end of this article, you will gain an understanding of: The definition of a complaint The regulatory requirements for handling complaints How complaint handling should be approached including a step-by-step guide for responding to complaints The differing requirements for responding to verbal and written complaints The importance of self-care when in receipt of a complaint
Validity and reliability of smartphone-based application for chronic ankle instability
Authors: Yoon Taelim , Lee Jihyun 
Published: September 2021

Background/aims Ankle instability is one of the most common injuries that can occur during everyday life, sports and exercise. Recently, smartphone accelerometers have been used to measure single leg balance associated with ankle instability, because they are easy to use, inexpensive and can be used in small spaces. Thus, the purpose of this study was to introduce and investigate the intra- and inter-rater reliability of the smartphone accelerometer when assessing ankle instability. Methods A total of 26 individuals who had ankle instability were recruited. The single leg stance balance was measured using a smartphone accelerometer (Accelerometer application) and a force platform (I-Balance) for 5 seconds with their eyes open or their eyes closed. Results In the eyes open position, intra-rater reliability of the smartphone accelerometer was excellent for both raters (intraclass correlation coefficient: 0.87–0.90); and the inter-rater reliability was moderate (intraclass correlation coefficient: 0.71). In the eyes closed position, the intra-rater reliability of the smartphone accelerometer was excellent for both raters (intraclass correlation coefficient: 0.90–0.93); the inter-rater reliability was good (intraclass correlation coefficient: 0.82). Additionally, there were fair positive correlations between the smartphone accelerometer and the Cumberland Ankle Instability Tool, and between the smartphone accelerometer and I-Balance (r=0.33, 0.30 respectively). Conclusions The present study demonstrated excellent intra-rater reliabilities of two raters and moderate to good inter-rater reliabilities. The smartphone accelerometer offers several important advantages as a potential portable medical device to assess ankle instability accurately. Although there was a positive correlation, the relationships between the smartphone accelerometer and Cumberland Ankle Instability Tool and that between the smartphone accelerometer and I-Balance were fair. Future studies should investigate the validity of the smartphone accelerometer as a portable medical device for determining ankle instability.