bluuebunny/crossref_metadata_2025 huggingface dataset:
Bystander Cardiopulmonary Resuscitation Quality: Potential for Improvements in Cardiac Arrest Resuscitation
Authors: Chocron Richard , Jobe Julia , Guan Sally , Kim Madeleine , Shigemura Mia , Fahrenbruch Carol , Rea Thomas
Published: March 2021

Background

Bystander cardiopulmonary resuscitation (CPR) is a critical intervention to improve survival following out‐of‐hospital cardiac arrest. We evaluated the quality of bystander CPR and whether performance varied according to the number of bystanders or provision of telecommunicator CPR (TCPR).

Methods and Results

We investigated non‐traumatic out‐of‐hospital cardiac arrest occurring in a large metropolitan emergency medical system during a 6‐month period. Information about bystander care was ascertained through review of the 9‐1‐1 recordings in addition to emergency medical system and hospital records to determine bystander CPR status (none versus TCPR versus unassisted), the number of bystanders on‐scene, and CPR performance metrics of compression fraction and compression rate. Of the 428 eligible out‐of‐hospital cardiac arrest, 76.4% received bystander CPR including 43.7% unassisted CPR and 56.3% TCPR; 35.2% had one bystander, 33.3% had 2 bystanders, and 31.5% had ≥3 bystanders. Overall compression fraction was 59% with a compression rate of 88 per minute. CPR differed according to TCPR status (fraction=52%, rate=87 per minute for TCPR versus fraction=69%, rate=102 for unassisted CPR,
P
<0.05 for each comparison) and the number of bystanders (fraction=55%, rate=87 per minute for 1 bystander, fraction=59%, rate=89 for 2 bystanders, fraction=65%, rate=97 for ≥3 bystanders, test for trend
P
<0.05 for each metric). Additional bystander actions were uncommon to include rotation of compressors (3.1%) or application of an automated external defibrillator (8.0%).

Conclusions

Bystander CPR quality as gauged by compression fraction and rate approached guideline goals though performance depended upon the type of CPR and number of bystanders.
Discontinuity of Cardiac Follow‐Up in Young People With Congenital Heart Disease Transitioning to Adulthood: A Systematic Review and Meta‐Analysis
Authors: Moons Philip , Skogby Sandra , Bratt Ewa‐Lena , Zühlke Liesl , Marelli Ariane , Goossens Eva
Published: March 2021

Background

The majority of people born with congenital heart disease require lifelong cardiac follow‐up. However, discontinuity of care is a recognized problem and appears to increase around the transition to adulthood. We performed a systematic review and meta‐analysis to estimate the proportion of adolescents and emerging adults with congenital heart disease discontinuing cardiac follow‐up. In pooled data, we investigated regional differences, disparities by disease complexity, and the impact of transition programs on the discontinuity of care.

Methods and Results

Searches were performed in PubMed, Embase, Cinahl, and Web of Science. We identified 17 studies, which enrolled 6847 patients. A random effects meta‐analysis of single proportions was performed according to the DerSimonian‐Laird method. Moderator effects were computed to explore sources for heterogeneity. Discontinuity proportions ranged from 3.6% to 62.7%, with a pooled estimated proportion of 26.1% (95% CI, 19.2%–34.6%). A trend toward more discontinuity was observed in simple heart defects (33.7%; 95% CI, 15.6%–58.3%), compared with moderate (25.7%; 95% CI, 15.2%–40.1%) or complex congenital heart disease (22.3%; 95% CI, 16.5%–29.4%) (
P
=0.2372). Studies from the United States (34.0%; 95% CI, 24.3%–45.4%), Canada (25.7%; 95% CI, 17.0%–36.7%), and Europe (6.5%; 95% CI, 5.3%–7.9%) differed significantly (
P
=0.0004). Transition programs were shown to have the potential to reduce discontinuity of care (12.7%; 95% CI, 2.8%–42.3%) compared with usual care (36.2%; 95% CI, 22.8%–52.2%) (
P
=0.1119).

Conclusions

This meta‐analysis showed that there is a high proportion of discontinuity of care in young people with congenital heart disease. The highest discontinuity proportions were observed in studies from the United States and in patients with simple heart defects. It is suggested that transition programs have a protective effect.

Registration

URL:
www.crd.york.ac.uk/prospero
. Unique identifier: CRD42020182413.
Pseudopestalotiopsis gilvanii sp. nov. and Neopestalotiopsis formicarum leaves spot pathogens from guarana plant: a new threat to global tropical hosts
Authors: GUALBERTO GILVANA F. , CATARINO ARICLÉIA DE M. , SOUSA THIAGO F. , CRUZ JEFERSON C. , HANADA ROGÉRIO E. , CANIATO FERNANDA F. , SILVA GILVAN F.
Published: March 2021

Pestalotioid species (Pestalotiopsis, Pseudopestalotiopsis and Neopestalotiopsis) cause extremely damaging diseases in a wide range of hosts across the word. Recently, pestalotioid strains isolated from damaged guarana leaf tissue were subject to morphological and molecular characterization. Six monosporic isolates were obtained and analysed based on the following conidial characters: length, width, septation, absence or presence of basal appendage, number and length of apical appendages. For phylogenetic inference, sequences of the Internal Transcribed Spacer region (ITS), partial sequences of the genes encoding the translation elongation factor 1-α (tef1-α) and β-tubulin (tub2) were used. Three out of six strains analysed were identified as Neopestalotiopsis formicarum, while the three other isolates are described here as a new species of Pseudopestalotiopsis, named Ps. gilvanii sp. nov.. The pathogenicity of N. formicarum and Ps. gilvanii were confirmed following Koch’s postulate. Besides guarana, the potential of N. formicaram and Ps. gilvanii to cause diseases in other economically important tropical plants were investigated. Ps. gilvanii was pathogenic to açaí palms (Euterpe oleracea, E. precatoria), and oil palm (Elaeis guineensis), but not to banana (Musa paradisiaca var. pacovan) and rubber trees (Hevea brasiliensis). N. formicarum was not pathogenic to rubber trees but was pathogenic to other species tested. To our knowledge this is the first report of N. formicarum as a plant pathogen in the guarana plant, and Ps. gilvanii as novel plant pathogen capable of causing disease in important plant crops from tropical regions.
A new species of Fomitiporia (Hymenochaetales) from Australia

Authors: CHEN JIA-JIA , WU YING-DA , JI XIAO-HONG , GATES GENEVIEVE , XU XIANG
Published: March 2021

A new species of Fomitiporia, F. tasmanica, is described from Tasmania (Australia) based on morphological examination and phylogenetic analysis of the nuc rDNA region encompassing the internal transcribed spacers 1 and 2, along with the 5.8S rDNA and nuc 28S rDNA D1-D2 domains. The new species is characterized by perennial, resupinate basidiocarps, very small pores (10–12 per mm), a dimitic hyphal system, presence of hymenial setae and cystidioles, and subglobose basidiospores measuring 5.5–6.6 × 5–6 µm.
Age-specific reference intervals of serum anti-Müllerian hormone in Chinese girls
Authors: Wang Jin , Yao Ting , Zhang Xinxin , Chen Qi , Gong Shuo , Jiang Li , Yao Hui , Hu Xijiang
Published: March 2021

Background

This study aimed to establish anti-Mullerian hormone age-specific reference intervals and determine the correlation between the anti-Mullerian hormone concentration and age, body mass index and concentrations of follicle-stimulating hormones and luteinizing hormone in healthy Chinese girls.

Methods

Serum anti-Mullerian hormone concentrations of 1702 healthy girls (0−12 years), recruited between March 2018 and December 2019, were determined using the Beckman Access 2 automated chemiluminescence immunoassay. Single-year-specific medians of anti-Mullerian hormone and effects of age, body mass index, follicle-stimulating hormone and luteinizing hormone on anti-Mullerian hormone concentration were analysed.

Results

The anti-Mullerian hormone median level continued increasing from birth, reached its peak at age 9 at 4.45 ng/mL (interquartile range [IQR] 2.58–6.90) and then gradually decreased. At age 12, the median reached 1.98 ng/mL (IQR 1.05–3.46). Age-specific reference intervals for anti-Mullerian hormone were established in healthy Chinese girls aged 0–12 years. Anti-Mullerian hormone concentrations showed a moderately positive correlation with age (r = 0.33, P < 0.001). In contrast, follicle-stimulating hormone (r = –0.29, P < 0.001) concentrations were weakly negatively correlated with the serum anti-Mullerian hormone concentration.

Conclusion

We established single-year-specific reference intervals for anti-Mullerian hormone in Chinese girls using the Beckman chemiluminescent platform. This reference range can help clinicians accurately understand anti-Mullerian hormone secretion in healthy girls and promote its clinical use.
Modeling of aortic valve stenosis using fluid-structure interaction method
Authors: Ghasemi Pour Mohammad Javad , Hassani Kamran , Khayat Morteza , Etemadi Haghighi Shahram
Published: March 2021

Background and objectives:

Fluid structure interaction (FSI) is defined as interaction of the structures with contacting fluids. The aortic valve experiences the interaction with blood flow in systolic phase. In this study, we have tried to predict the hemodynamics of blood flow through a normal and stenotic aortic valve in two relaxation and exercise conditions using a three-dimensional FSI method.

Methods:

The aorta valve was modeled as a three-dimensional geometry including a normal model and two others with 25% and 50% stenosis. The geometry of the aortic valve was extracted from CT images and the models were generated by MMIMCS software and then they were implemented in ANSYS software. The pulsatile flow rate was used for all cases and the numerical simulations were conducted based on a time-dependent domain.

Results:

The obtained results including the velocity, pressure, and shear stress contours in different systolic time sequences were explained and discussed. The maximum blood flow velocity in relaxation phase was obtained 1.62 m/s (normal valve), 3.78 m/s (25% stenosed valve), and 4.73 m/s (50% stenosed valve). In exercise condition, the maximum velocities are 2.86, 4.32, and 5.42 m/s respectively. The maximum blood pressure in relaxation phase was calculated 111.45 mmHg (normal), 148.66 mmHg (25% stenosed), and 164.21 mmHg (50% stenosed). However, the calculated values in exercise situation were 129.57, 163.58, and 191.26 mmHg. The validation of the predicted results was also conducted using existing literature.

Conclusions:

We believe that such model are useful tools for biomechanical experts. The further studies should be done using experimental data and the data are implemented on the boundary conditions for better comparison of the results.
Visualization of wrist ligaments with 3D and 2D magnetic resonance imaging at 3 Tesla
Authors: Götestrand Simon , Björkman Anders , Björkman-Burtscher Isabella M , Ab-Fawaz Rana , Kristiansson Ingvar , Lundin Björn , Geijer Mats
Published: March 2021

Background

Wrist ligaments are challenging to visualize using magnetic resonance imaging (MRI). Injuries involving the scapholunate ligament (SLL), the lunotriquetral ligament (LTL), and the triangular fibrocartilage complex (TFCC) are common and difficult to diagnose, often requiring diagnostic arthroscopy.

Purpose

To compare the visualization of wrist ligaments on a three-dimensional (3D) sequence with two-dimensional (2D) sequences on 3-T MRI.

Material and Methods

Eighteen healthy volunteers were examined with a 3D SPACE (sampling perfection with application optimized contrasts using different flip angle evolution) sequence and 2D coronal, axial, and sagittal proton density-weighted (PD) sequences. Four musculoskeletal radiologists graded the anatomical visibility of the SLL, LTL, TFCC, and the image quality, using five grades in a visual grading characteristics (VGC) evaluation. After Bonferroni correction, a P value ≤0.005 was considered statistically significant.

Results

The 3D images were graded significantly better than the 2D images in the visualization of the dorsal and palmar parts of the SLL and the LTL. Regarding the TFCC, the 3D images were graded significantly better for visualization of the foveal attachment. 2D imaging was not found significantly superior to 3D imaging in any aspect.

Conclusion

The 3D SPACE sequence was scored as superior to the 2D sequences at 3 T in the assessment of the SLL, the LTL, and the foveal attachment of the TFCC. Thus, 3D SPACE can replace 2D PD sequences when these ligaments need to be assessed.
Attitude Toward Family Involvement in End-of-Life Care Among Older Chinese Americans: How Do Family Relationships Matter?
Authors: Wang Kaipeng , Sun Fei , Liu Yanqin , Kong Dexia , De Fries Carson M.
Published: March 2021

Family involvement is critical to end-of-life (EOL) care among older adults. This study aims to examine the association and pathways between family relationships and older Chinese Americans’ attitude toward family involvement in EOL care discussions. Data were collected from 260 Chinese Americans aged 55 years and above. Structural equation modeling was used to examine the total and indirect effects of family relationships on attitude toward family involvement in discussing EOL care plans. Family relationships had a significant positive total effect on attitude toward family involvement in EOL care. Indirect effects of family relationships on attitude toward family involvement in EOL care through self-efficacy, perceived benefits, and perceived barriers of discussing EOL care with family members were all significant. Findings provide empirical evidence of how family relationships affect older Chinese Americans’ attitude toward family involvement in EOL care and underline the need for family-centered EOL interventions for this population.
Correctional nursing in Canada’s Prairie provinces: Roles, responsibilities, and learning needs
Authors: Woods Phil , Peternelj-Taylor Cindy
Published: March 2021

Background

Nurses represent the largest group of health care professionals working with incarcerated persons, yet there is limited understanding of their learning needs, or their roles and responsibilities; and what is known is poorly disseminated.

Purpose

The goal of this research was to describe the roles, responsibilities, and learning needs of correctional nurses practicing in provincial correctional facilities in Alberta and Manitoba, and to add these data to the existing data set from Saskatchewan.

Methods

Three hundred and forty nurses working in provincial correctional facilities in western Canada were invited to complete a self-administered online survey consisting of a Learning Needs Assessment questionnaire (demographic information, knowledge and learning needs, and professional development); and the Staff Questionnaire (which targeted specific skill sets relevant to clinical practice in secure environments). Eighty-two nurses completed the online survey (overall response rate 24%).

Results

Overall, those who participated were experienced in nursing and correctional nursing. The learning needs they identified aligned with their correctional nursing roles and unique practice settings. In particular, issues related to the care of incarcerated persons with mental health disorders and related care were paramount (self-harming behaviours, suicide, mental health assessments in general). In response to the five comprehensive skill sets assessed in the Staff Questionnaire, respondents rated their involvement and importance of the individual skills as important to varying degrees.

Conclusions

The results of this survey shed light on contemporary developments in correctional nursing within provincial correctional facilities in western Canada and provide a foundation for continuing professional education and development, practice, and future research initiatives.
Drinking motives and their associations with alcohol use among adolescents in Sweden
Authors: Sjödin Lars , Larm Peter , Karlsson Patrik , Livingston Michael , Raninen Jonas
Published: March 2021

Aims:

Previous studies have shown a close association between drinking motives and drinking behaviour among adolescents. However, there is a lack of evidence from the Nordic countries since few studies covering this topic have been carried out in this context. The present study among Swedish adolescents aims to examine (1) the prevalence of different drinking motives, (2) how drinking motives are associated with drinking frequency and heavy drinking frequency, and (3) whether the associations are moderated by sex.

Methods:

A nationally representative sample ( n = 5,549) of Swedish adolescents (aged 15–16 years) answered a questionnaire in school. Of these, 2,076 were drinkers and were included in our study. Eighteen items from the Modified Drinking Motives Questionnaire-Revised (Modified DMQ-R) were used. Bivariate relationships between motives and drinking were examined with correlations. Linear regression models were used to assess the links between motives and drinking. Moderating effects of sex were examined with interactions.

Results:

Most common were social motives, followed by enhancement, coping-anxiety, coping-depression, and conformity motives. Coping-depression motives were slightly more common among girls. Conformity motives were associated with a lower frequency of drinking and heavy drinking while enhancement, social and coping-depression motives were associated with a higher frequency of both outcomes. No associations were found for coping-anxiety motives. No moderation effect of sex was found.

Conclusions:

Approach motives (social/enhancement) are the most prevalent drinking motives among Swedish adolescents. These also have the strongest association for both frequency of drinking and frequency of heavy drinking. This shows that Swedish adolescents drink to achieve something positive, rather than to avoid something negative, raising implications for prevention and intervention.
An efficient procedure to predict the dynamic loads for piston liner systems in marine engines
Authors: Xiuyi Lyu , Azam Abdullah , Yuechang Wang , Xiqun Lu , Tongyang Li , Dequan Zou , Xuan Ma , Wilson Mark CT , Neville Anne
Published: March 2021

The piston ring-cylinder liner (PRCL) is one of the most important parts of marine diesel engines and contributes 25% to 50% of total friction loss. The lubrication simulation analysis of the PRCL system is a challenging task. Complete understanding and precise prediction of lubrication loads is a key to understanding the friction behavior of PRCL systems as the accuracy of the friction prediction depends upon precise prediction of lubrication loads. Therefore, this paper focuses on the gas pressure calculation which is the primary source of lubrication loads. The procedure presented combines the advantages of two mainstream methods to predict loads in the PRCL system. The result is a significant reduction in the computation time without compromising on accuracy. Firstly, a comparison of both approaches is presented which suggests that each technique has its limitations (one is time-bound, and one is accuracy-bound). Then, the results from both calculation methods are verified against literature and a parametric study is performed to identify the key structural parameters of PRCL system that affect the calculation efficiency. Finally, a correlation coefficient is introduced into the analysis to combine the two approaches which then identifies the conditions under which the use of the faster method becomes invalid and replaces it with the more accurate approach. This ensures optimum performance of the calculation procedure by switching between the fast and the accurate method depending upon the accuracy requirement under given conditions, thereby, simplifying the dynamic and lubrication model of PRCL systems. The study has direct implications for the tribological design of the PRCL interface.
A Preliminary Study of Personalized Head CT Scan in Pediatric Patients
Authors: Bingyang Bian , Gang Wang , Zhiqing Shao , Li Nan , Zhou BoXu , Xu ShuJia , Li Dan
Published: March 2021

Objectives:

In the present study, we introduced a practical approach to quantify organ-specific radiation doses and investigated whether low-dose head circumference (HC)-based protocols for non-enhanced head computed tomography (CT) could reduce organs-specific radiation dose in pediatric patients while maintaining high image quality.

Methods:

A total of 83 pediatric patients were prospectively recruited. Without limits to the HC, 15 patients were selected as a convention group (CON group) and underwent non-enhanced head CT scan with standard-dose protocols (tube current-time products of 250mAs). Low-dose group (LD group), including remaining 68 pediatrics were divided into 3 subgroups based on the HC: 54.1-57.0 cm for LD200mAs group (HC-based protocols of 200mAs), 51.1-54.0 cm for LD150mAs group (HC-based protocols of 150mAs), 48.1-51.0 cm for LD100mAs group (HC-based protocols of 100mAs). Subjective and objective image quality was evaluated and measured by 2 experienced radiologists. Radimetrics was used to calculate organs-specific radiation dose, including the brain, eye lenses, and salivary glands.

Results:

In CON250mAs group, radiation doses in the brain and salivary glands were conversely correlated with HC, and pediatric patients with smaller HC received higher organs-specific radiation dose. Reducing tube current-time product from 250 to 100mAs could significantly reduce the organ-specific radiation dose. The subjective image quality score ≥ 3.0 is acceptable for diagnosis purposes. The signal to noise ratio (SNR) and the contrast to noise ratio (CNR) of bilateral thalamus and centrum semiovale in 3 LD subgroups were not statistically different compared with the CON group.

Conclusion:

Our research indicated that low-dose HC-based protocols of non-enhanced head CT scan can evidently reduce the organ-specific radiation doses, while maintaining high image quality. HC can serve as a vital tool to guide personalized low-dose head CT scan for pediatric patients.
Nomogram for predicting overall survival in colorectal cancer with distant metastasis
Authors: Liu Zheng , Xu Yao , Xu Guijun , Baklaushev Vladimir P. , Chekhonin Vladimir P. , Peltzer Karl , Ma Wenjuan , Wang Xin , Wang Guowen , Zhang Chao
Published: March 2021

Background

Colorectal cancer (CRC) is a major cancer burden, and prognosis is determined by many demographic and clinicopathologic factors. The present study aimed to construct a prognostic nomogram for colorectal cancer patients with distant metastasis.

Methods

Colorectal cancer patients with distant metastasis diagnosed between 2010 and 2016 were selected from the Surveillance, Epidemiology, and End Results database. Cox proportional hazards regression was used to identify independent prognostic factors. A nomogram was constructed to predict survival, and validation was performed.

Results

A total of 7099 stage IV colorectal cancer patients were enrolled in the construction cohort. The median overall survival was 20.0 (95% CI 19.3–20.7) months. Age at diagnosis, marital status, race, primary tumour site, tumour grade, CEA level, T stage, N stage, presence of bone, brain, liver and lung metastasis, surgery for primary site and performance of chemotherapy were independent prognostic factors. The nomogram was constructed and the calibration curve showed satisfactory agreement. The C-index was 0.742 (95% CI 0.726–0.758). In the validation cohort (7098 patients), the nomogram showed satisfactory discrimination and calibration with a C-index of 0.746 (95% CI 0.730–0.762).

Conclusion

A series of factors associated with the survival of CRC patients with distant metastasis were found. Based on the identified factors, a nomogram was generated to predict the survival of stage IV colorectal cancer patients. The predictive model showed satisfactory discrimination and calibration, which can provide a reference for survival estimation and individualized treatment decisions.
The microfoundations of physicians’ managerial attitude
Authors: Di Vincenzo Fausto , Angelozzi Daria , Morandi Federica
Published: March 2021

Background

Accountable care has profoundly changed the organizational models adopted by health care organizations and, consequently, the skill set required for doctor-managers who have become middle managers and must deal with the operational management of their units. The aim of this study was to identify the psychological microfoundations (i.e., traits) of physicians’ managerial attitude. Specifically, we analysed the roles played by narcissism, specialization choices and identification with the organization.

Methods

We collected primary data on a population of ward unit heads in the Italian National Health Service. A logistic regression model predicting the levels of managerial attitude was employed.

Results

The results indicate that high levels of narcissism and identification with the organization are related to higher managerial attitude (instead of clinical attitude). Additionally, we found that physicians with a technique-oriented specialization present a higher probability of manifesting managerial attitude (in comparison to clinical attitude).

Conclusions

Hospital managers can benefit from the use of these findings by developing a strategic approach to human resource management that allows them to identify, train and select the right mix of technical knowledge and managerial skills for middle-management roles.
Lipoprotein glomerulopathy induced by ApoE Kyoto mutation in ApoE-deficient mice
Authors: Wu Hongyan , Yang Jing , Liu Yun-Qiang , Lei Song , Yang Mei , Yang Zhi , Yang Yuan , Hu Zhangxue
Published: March 2021

Background

Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant kidney disease that is most commonly caused by mutations in ApoE Kyoto (p.R43C) and ApoE Sendai (p.R163P). Differences in phenotype among the various ApoE mutations have been suggested, but the pathogenic role of ApoE Kyoto has not been validated in an animal model. This study intended to establish an ApoE Kyoto murine model and to further compare the pathologic differences between ApoE Kyoto and ApoE Sendai.

Method

Male ApoE-deficient mice, 3 months of age, were divided into five groups, including the AD-ApoE Sendai, AD-ApoE Kyoto, AD-ApoE3, AD-eGFP, and ApoE (−/−) groups. The first four groups received recombinant adenovirus that contained the entire coding regions of the humanApoE SendaiandApoE Kyoto,apoE3, andeGFPgenes, respectively. Fasting blood and urine samples were collected at multiple time points. Lipid profiles and urine albumin–creatinine ratio were measured. Renal and aortic histopathologic alterations were analyzed.

Results

After virus injection, plasma human ApoE was detected and rapidly reached the maximum level at 4–6 days in the AD-ApoE Kyoto and AD-ApoE Sendai groups (17.4 ± 3.1 µg/mL vs.: 22.2 ± 4.5 µg/mL, respectively) and at 2 days in the AD-ApoE3 group (38.4 µg/mL). The serum total cholesterol decreased by 63%, 65%, and 73% in the AD-ApoE Kyoto, AD-ApoE Sendai and AD-ApoE3 groups, respectively. There were no significant changes in serum triglyceride and urinary albumin–creatinine ratio among the five groups. Typical lipoprotein thrombi with positive ApoE staining were detected in the AD-ApoE Kyoto and AD-ApoE Sendai groups. The Oil-red O-positive glomerular area tended to be higher in the AD-ApoE Kyoto group (9.2%) than in the AD-ApoE Sendai (3.9%), AD-ApoE3 (4.8%), AD-eGFP (2.9%), and ApoE (−/−) (3.6%) groups. The atherosclerotic plaque area in the aorta was lower in the group injected with various ApoE mutations than in the group without injection of ApoE mutation.

Conclusions

In this animal study, we first established an ApoE Kyoto mutation murine model and confirmed its pathogenic role in LPG. Our results suggested that LPG may be more severe with the ApoE Kyoto than with the ApoE Sendai.
Altered network properties in C9ORF72 repeat expansion cortical neurons are due to synaptic dysfunction
Authors: Perkins Emma M. , Burr Karen , Banerjee Poulomi , Mehta Arpan R. , Dando Owen , Selvaraj Bhuvaneish T. , Suminaite Daumante , Nanda Jyoti , Henstridge Christopher M. , Gillingwater Thomas H. , Hardingham Giles E. , Wyllie David J. A. , Chandran Siddharthan , Livesey Matthew R.
Published: March 2021

Background

Physiological disturbances in cortical network excitability and plasticity are established and widespread in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients, including those harbouring the C9ORF72 repeat expansion (C9ORF72RE) mutation – the most common genetic impairment causal to ALS and FTD. Noting that perturbations in cortical function are evidenced pre-symptomatically, and that the cortex is associated with widespread pathology, cortical dysfunction is thought to be an early driver of neurodegenerative disease progression. However, our understanding of how altered network function manifests at the cellular and molecular level is not clear.

Methods

To address this we have generated cortical neurons from patient-derived iPSCs harbouring C9ORF72RE mutations, as well as from their isogenic expansion-corrected controls. We have established a model of network activity in these neurons using multi-electrode array electrophysiology. We have then mechanistically examined the physiological processes underpinning network dysfunction using a combination of patch-clamp electrophysiology, immunocytochemistry, pharmacology and transcriptomic profiling.

Results

We find that C9ORF72RE causes elevated network burst activity, associated with enhanced synaptic input, yet lower burst duration, attributable to impaired pre-synaptic vesicle dynamics. We also show that the C9ORF72RE is associated with impaired synaptic plasticity. Moreover, RNA-seq analysis revealed dysregulated molecular pathways impacting on synaptic function. All molecular, cellular and network deficits are rescued by CRISPR/Cas9 correction of C9ORF72RE. Our study provides a mechanistic view of the early dysregulated processes that underpin cortical network dysfunction in ALS-FTD.

Conclusion

These findings suggest synaptic pathophysiology is widespread in ALS-FTD and has an early and fundamental role in driving altered network function that is thought to contribute to neurodegenerative processes in these patients. The overall importance is the identification of previously unidentified defects in pre and postsynaptic compartments affecting synaptic plasticity, synaptic vesicle stores, and network propagation, which directly impact upon cortical function.
Central precocious puberty in a girl with LEGIUS syndrome: an accidental association?
Authors: Orlandi Valentina , Cavarzere Paolo , Palma Laura , Gaudino Rossella , Antoniazzi Franco
Published: March 2021

Background

Central precocious puberty is a condition characterized by precocious activation of the hypothalamic-pituitary-gonadal axis. It may be idiopathic or secondary to organic causes, including syndromes such as Neurofibromatosis type 1 (NF1).

Case presentation

We presented a girl of 6 years and 10 months with almost 11 café-au-lait skin macules, without other clinical or radiological signs typical of NF1, and with a central precocious puberty. Genetic analysis evidenced the new variant NM-152594.2:c.304delAp. (Thr102Argfs*19) in SPRED1 gene, which allowed to diagnose Legius syndrome.

Conclusions

We report for the first time a case of central precocious puberty in a girl with Legius syndrome. The presence of central precocious puberty in a child with characteristic café-au-lait macules should suggest pediatricians to perform genetic analysis in order to reach a definitive diagnosis. Further studies on timing of puberty in patients with RASopathies are needed to better elucidate if this clinical association is casual or secondary to their clinical condition.
Systematic review of available software for multi-arm multi-stage and platform clinical trial design
Authors:   on behalf of EU-PEARL (EU Patient-cEntric clinicAl tRial pLatforms) Consortium, Meyer Elias Laurin , Mesenbrink Peter , Mielke Tobias , Parke Tom , Evans Daniel , König Franz
Published: March 2021

Background

In recent years, the popularity of multi-arm multi-stage, seamless adaptive, and platform trials has increased. However, many design-related questions and questions regarding which operating characteristics should be evaluated to determine the potential performance of a specific trial design remain and are often further complicated by the complexity of such trial designs.

Methods

A systematic search was conducted to review existing software for the design of platform trials, whereby multi-arm multi-stage trials were also included. The results of this search are reported both on the literature level and the software level, highlighting the software judged to be particularly useful.

Results

In recent years, many highly specialized software packages targeting single design elements on platform studies have been released. Only a few of the developed software packages provide extensive design flexibility, at the cost of limited access due to being commercial or not being usable as out-of-the-box solutions.

Conclusions

We believe that both an open-source modular software similar to OCTOPUS and a collaborative effort will be necessary to create software that takes advantage of and investigates the impact of all the flexibility that platform trials potentially provide.
Records of three mammal tick species parasitizing an atypical host, the multi-ocellated racerunner lizard, in arid regions of Xinjiang, China
Authors: Zhou Qi , Li Jiao , Guo Xianguang , Liu Jinlong , Song Qi , Gong Xiong , Chen Han , Zhang Jianhui , He Jinlei , Zheng Zhiwan , Chen Dali , Chen Jianping
Published: March 2021

Background

Ticks are ectoparasites that feed on blood of a broad taxonomical range of terrestrial and flying vertebrates and are distributed across a wide range of environmental settings. To date, the species identity, diversity, and relationships among the ticks on lizards in China have been poorly understood.

Methods

In this study, 30 ticks, collected from the multi-ocellated racerunner (Eremias multiocellata) lizard in the Tarim Basin and adjacent Yanqi Basin of the Xinjiang Uygur Autonomous Region in China, were identified by morphological observation and confirmed by DNA-based techniques. The mitochondrially encoded 12S rRNA, 16S rRNA, and COI gene fragments of ticks were amplified and sequenced. To understand the genetic polymorphisms, 47 ticks collected from hedgehogs and 1 from brushwood in the Tarim Basin were also included. Species identification was based on both morphological and molecular characters. The median-joining network approach was used to evaluate the intraspecific genealogies of the ticks and their relatedness with the geographical origin or hosts.

Results

The sequence similarity analysis confirmed that the 30 ticks belong to three genera and three species including 11 individuals of Hyalomma asiaticum, 3 of Rhipicephalus turanicus, and 16 of Haemaphysalis sulcata. A network approach revealed paraphyletic populations of R. turanicus and Hy. asiaticum at the intraspecies level regarding geographical origin and low host specificity. For R. turanicus and Hy. asiaticum, common ancestry was observed between COI sequences from lizards and other sequence types from different hosts and countries.

Conclusions

To our knowledge, our study is the first to conduct a molecular survey of ticks from lizards in the arid regions of Xinjiang, China. Eremias multiocellata is an atypical host of the three tick species. Notably, two species of ticks, Hy. asiaticum and R. turanicus, have been collected and identified from lizards in China for the first time. Star-like networks suggest both of them might have experienced recent population expansion. The discoveries are closely related to the geographical environments in Xinjiang and will provide information for the control of ticks and tick-borne pathogens in Northwest China.

Graphical Abstract
DNA methylation mediates the effect of maternal smoking on offspring birthweight: a birth cohort study of multi-ethnic US mother–newborn pairs
Authors: Xu Richard , Hong Xiumei , Zhang Boyang , Huang Wanyu , Hou Wenpin , Wang Guoying , Wang Xiaobin , Igusa Tak , Liang Liming , Ji Hongkai
Published: March 2021

Background

Maternal smoking affects more than half a million pregnancies each year in the US and is known to result in fetal growth restriction as measured by lower birthweight and its associated long-term consequences. Maternal smoking also has been linked to altered fetal DNA methylation (DNAm). However, what remains largely unexplored is whether these DNAm alterations are merely markers of smoking exposure or if they also have implications for health outcomes. This study tested the hypothesis that fetal DNAm mediates the effect of maternal smoking on newborn birthweight.

Methods

This study included mother–newborn pairs from a US predominantly urban, low-income multi-ethnic birth cohort. DNAm in cord blood were determined using the Illumina Infinium MethylationEPIC BeadChip. After standard quality control and normalization procedures, an epigenome-wide association study (EWAS) of maternal smoking was performed using linear regression models, controlling for maternal age, education, race, parity, pre-pregnancy body mass index, alcohol consumption, gestational age, maternal pregestational/gestational diabetes, child sex, cord blood cell compositions and batch effects. To quantify the degree to which cord DNAm mediates the smoking-birthweight association, the VanderWeele-Vansteelandt approach for single mediator and structural equational model for multiple mediators were used, adjusting for pertinent covariates.

Results

The study included 954 mother–newborn pairs. Among mothers, 165 (17.3%) ever smoked before or during pregnancy. Newborns with smoking exposure had on average 258 g lower birthweight than newborns without exposure (P < 0.001). Using a false discovery rate (FDR) < 0.05 as the significance cutoff, the EWAS identified 38 differentially methylated CpG sites associated with maternal smoking. Of those, 17 CpG sites were mapped to previously reported genes:GFI1, AHRR, CYP1A1, and CNTNAP2;8 of those, located in the first three genes, were Bonferroni significantly associated with newborn birthweight and mediated the smoking-birthweight association. The combined mediation effect of the three genes explained 67.8% of the smoking-birthweight association.

Conclusions

Our study not only lends further support that maternal smoking alters fetal DNAm in a multiethnic population, but also suggests that fetal DNAm substantially mediates the maternal smoking–birthweight association. Our findings, if further validated, indicate that DNAm modification is likely an important pathway by which maternal smoking impairs fetal growth and, perhaps, even long-term health outcomes.
Controversy of indomethacin eye drops in the treatment of rheumatoid arthritis-induced corneal ulceration: a case report
Authors: Nicoară Simona Delia , Damian Ioana
Published: March 2021

Background

Perforation of the cornea is a rare finding in patients with rheumatoid arthritis (RA). Addressing a perforated cornea associated with RA is challenging, since its pathogenesis is not fully elucidated. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) were developed to prevent cystoid macular edema following cataract surgery in patients at risk. Their prescription in inflammation of the anterior segment of the eye may induce negative effects on the ocular surface. We bring into focus a corneal perforation in a patient with RA who used indomethacin eye drops to treat corneal ulceration, but responded promptly to drug discontinuation and initiation of topical cyclosporine 0.1%. Our aim is to emphasize two issues: the contraindication of topical indomethacin in corneal defects, and the immediate positive impact of topical cyclosporine 0.1% on corneal healing.

Case presentation

A 73-year-old Caucasian woman with a 13-year history of RA was treated for corneal ulceration in her oculus sinister (OS) with topical indomethacin and gentamicin. The patient was being treated with systemic immunosuppression and NSAIDs for the underlying RA and artificial tears in both eyes. No bandage contact lens was used. After 3 weeks of treatment, perforation of the left cornea occurred and the patient was referred to our hospital. Upon admission, visual acuity (VA) in the OS was 20/630. Slit lamp examination of the OS revealed paracentral corneal perforation, iris plugging the perforation site, shallow anterior chamber, clear aqueous humor, and clear lens. Anterior segment optical coherence tomography showed the inclavated iris in the perforation site and minimum corneal thickness of 101 µm. Topical NSAIDs were discontinued and topical treatment was initiated with tobramycin, tropicamide 1%, phenylephrine 10%, and artificial tears five times a day, and occlusive patch. For 5 days, there was no improvement, so topical cyclosporine 0.1% was started, one drop every evening. Within 7 days, the cornea had healed, the iris was liberated from the perforation site, the minimum corneal thickness increased to 250 µm, VA improved to 20/25, and the patient was free of symptoms.

Conclusions

The main “takeaway” lessons from this case are that topical indomethacin should not be prescribed in cases of inflammation of the anterior segment of the eye, and that topical cyclosporine was efficacious in healing corneal perforation in our patient.
The joint use of 99mTc-MAA-SPECT/CT and cone-beam CT optimizes radioembolization planning
Authors: Rodríguez-Fraile Macarena , Ezponda Ana , Grisanti Fabiana , Morán Verónica , Calvo Marta , Berián Pablo , de la Cuesta Antonio Martínez , Sancho Lidia , Iñarrairaegui Mercedes , Sangro Bruno , Bilbao José Ignacio
Published: March 2021

Purpose

To determine which imaging method used during radioembolization (RE) work-up: contrast-enhanced computed tomography (CECT), 99mTc-MAA-SPECT/CT or cone beam-CT (CBCT), more accurately predicts the final target volume (TgV) as well as the influence that each modality has in the dosimetric calculation.

Methods

TgVs from 99mTc-MAA-SPECT/CT, CECT and CBCT were consecutively obtained in 24 patients treated with RE and compared with 90Y PET/CT TgV. Using the TgVs estimated by each imaging modality and a fictitious activity of 1 GBq, the corresponding absorbed doses by tumor and non-tumoral parenchyma were calculated for each patient. The absorbed doses for each modality were compared with the ones obtained using 90Y PET/CT TgV.

Results

99mTc-MAA-SPECT/CT predicted 90Y PET/CT TgV better than CBCT or CECT, even for selective or superselective administrations. Likewise, 99mTc-MAA-SPECT/CT showed dosimetric values more similar to those obtained with 90Y PET/CT. Nevertheless, CBCT provided essential information for RE planning, such as ensuring the total coverage of the tumor and, in cases with more than one feeding artery, splitting the activity according to the volume of tumor perfused by each artery.

Conclusion

The joint use of 99mTc-MAA-SPECT/CT and CBCT optimizes dosimetric planning for RE procedures, enabling a more accurate personalized approach.
Engineering a lipoxygenase from cyclocybe aegerita towards long chain polyunsaturated fatty acids
Authors: Karrer Dominik , Gand Martin , Rühl Martin
Published: March 2021

The basidiomycetous lipoxygenase Lox1 fromCyclocybe aegeritacatalyzes the oxygenation of polyunsaturated fatty acids (PUFAs) with a high preference towards the C18-PUFA linoleic acid (C18:2 (ω-6)). In contrast, longer PUFAs, generally not present in the fungal cell such as eicosatrienoic acid (C20:3(ω-3)) and docosatrienoic acid (C22:3 (ω-3)), are converted with drastically lower activities. With site-directed mutagenesis, we were able to create two variants with enhanced activities towards longer chain PUFAs. The W330L variant showed a ~ 20 % increased specific activity towards C20:3(ω-3), while a ~ 2.5-fold increased activity against C22:3 (ω-3) was accomplished by the V581 variant.
Centrosome-phagy: implications for human diseases
Authors: Wu Qi , Yu Xin , Liu Le , Sun Shengrong , Sun Si
Published: March 2021

Autophagy is a prominent mechanism to preserve homeostasis and the response to intracellular or extracellular stress. Autophagic degradation can be selectively targeted to dysfunctional subcellular compartments. Centrosome homeostasis is pivotal for healthy proliferating cells, but centrosome aberration is a hallmark of diverse human disorders. Recently, a process called centrosome-phagy has been identified. The process involves a panel of centrosomal proteins and centrosome-related pathways that mediate the specific degradation of centrosomal components via the autophagic machinery. Although autophagy normally mediates centrosome homeostasis, autophagy defects facilitate ageing and multiple human diseases, such as ciliopathies and cancer, which benefit from centrosome aberration. Here, we discuss the molecular systems that trigger centrosome-phagy and its role in human disorders.
Cognitive rehabilitation interventions after stroke: protocol for a systematic review and meta-analysis of randomized controlled trials
Authors: Zhao Qing , Wang Xue , Wang Tao , Dmytriw Adam A. , Zhang Xiao , Yang Kun , Luo Jichang , Bai Xuesong , Jiang Nan , Yang Bin , Ma Yan , Jiao Liqun , Xie Yunyan
Published: March 2021

Background

Stroke is the second leading cause of death worldwide, and 53.4% of stroke survivors suffer from post-stroke cognitive impairment. Post-stroke cognitive impairment can increase hospitalization rate and cost of care and decrease the quality of life of stroke patients. To date, multiple cognitive rehabilitation interventions have been tested in stroke populations with post-stroke cognitive impairment. However, the most efficacious intervention has not been established. This systematic review aims to compare the efficacy of cognitive rehabilitation interventions for patients with post-stroke cognitive impairment.

Methods

We will search MEDLINE, EMBASE, CENTRAL, PsycINFO, CINAHL, PubMed, and clinical trial registries to identify eligible randomized clinical trials with no restrictions in the date of publication and language. Studies conducted with patients aged 18 or over, with the presence of cognitive impairment after being diagnosed with stroke will be included. Studies will be restricted to randomized controlled trials comparing a cognitive rehabilitation intervention with another intervention. The primary outcome is any clinical changes in the general or specific cognitive domain (e.g., executive function, attention, memory, or perception). The secondary outcomes that will be collected include adverse effects (e.g., stroke, disability, or mortality) and quality of life. Two independent reviewers will assess articles to identify trials eligible for inclusion. Data extraction and risk of bias assessment of the included studies will also be done independently. Any discrepancies will be solved by discussion, or a third reviewer will be consulted if necessary. A meta-analysis will be carried out if appropriate.

Discussion

This systematic review for patients with post-stroke cognitive impairment will assess the efficacy of cognitive rehabilitation interventions. And our results will help clinical decision-making and support the development of clinical practice guidelines.

Trial registration

Systematic review registration: PROSPERO CRD42020173988