bluuebunny/crossref_metadata_2025 huggingface dataset:
A CLIMATOLOGY BASED FORECAST TOOL FOR COASTAL FLOODING IN THE LOWCOUNTRY
Authors: Coz Joseph , Alsheimer Frank , Lindner Bernhard Lee
Published: May 2021

Coastal nuisance flooding has increased by an order of magnitude over the past half century, but the National Weather Service has a limited suite of statistical tools to forecast them. Such a tool was developed using coastal flood events from 1996—2014 in Charleston, South Carolina, which were identified and classified by prevailing synoptic conditions based on composite mean sea level pressure anomalies. The synoptic climatology indicated low level northeasterly winds dominated the forcing in anticyclonic and cyclonic events, while a southeasterly surge was the main forcing component for frontal events. Tidal anomalies between flood events and previous low tides were used to create linear regression models for each composite classification studied for forecasting levels of coastal flood magnitude. Beta tests using data from 2018—2019 confirmed the effectiveness of the models with RMSE values less than 0.3 ft and MAE values less than 0.25 ft for each event type. The veracity of the methods was further verified by a multiple day case study from November 2018, where the model was tested against both statistically predicted heights and heights based on ETSS Model (v2.2). The RMSE and MAE for the statical model were 0.18 and 0.15 respectively, while the same values for the ETSS model were 0.28 and 0.23 respectively.
Establishing a high-precision ZHD model of China using 8 years of radiosonde data
Authors: Pengfei Xia , Shirong Ye , Caijun Xu , Weiping Jiang
Published: May 2021

Tropospheric hydrostatic delay is one of the major source of errors in Global Navigation Satellite System (GNSS) navigation and positioning, and an important parameter in GNSS meteorology. This work first proposes a new method of computing zenith hydrostatic delay (ZHD) based on precipitable water vapor (PWV), using radiosonde data. Next, using these calculations as a reference, the performance of three empirical ZHD models and three ZHD integral models in China is assessed using benchmark values obtained from 8 years (2010-2017) of radiosonde data recorded at 75 stations across China. Finally, we provide a new revised ZHD model that can be applied to China and validate its performance using radiosonde data collected in China in 2018. The statistical results indicate that the ZHD can be estimated by this new model with an accuracy of several millimeters. Due to its performance and simplicity, this new model is shown to be the optimal ZHD model for use in China.
Low-burden TP53 mutations in CLL: clinical impact and clonal evolution within the context of different treatment options
Authors: Malcikova Jitka , Pavlova Sarka , Kunt Vonkova Barbara , Radova Lenka , Plevova Karla , Kotaskova Jana , Pal Karol , Dvorackova Barbara , Zenatova Marcela , Hynst Jakub , Ondrouskova Eva , Panovska Anna , Brychtova Yvona , Zavacka Kristyna , Tichy Boris , Tom Nikola , Mayer Jiri , Doubek Michael , Pospisilova Sarka
Published: May 2021

Patients with chronic lymphocytic leukemia (CLL) bearing TP53 mutations experience chemorefractory disease and are therefore candidates for targeted therapy. However, the significance of low-burden TP53 mutations with <10% variant allele frequency (VAF) remains a matter for debate. Herein, we describe clonal evolution scenarios of low-burden TP53 mutations, the clinical impact of which we analyzed in a “real-world” CLL cohort. TP53 status was assessed by targeted next-generation sequencing (NGS) in 511 patients entering first-line treatment with chemo- and/or immunotherapy and 159 patients in relapse before treatment with targeted agents. Within the pretherapy cohort, 16% of patients carried low-burden TP53 mutations (0.1% to 10% VAF). Although their presence did not significantly shorten event-free survival after first-line therapy, it affected overall survival (OS). In a subgroup with TP53 mutations of 1% to 10% VAF, the impact on OS was observed only in patients with unmutated IGHV who had not received targeted therapy, as patients benefited from switching to targeted agents, regardless of initial TP53 mutational status. Analysis of the clonal evolution of low-burden TP53 mutations showed that the highest expansion rates were associated with fludarabine, cyclophosphamide, and rituximab regimen in both first- and second-line treatments (median VAF increase, 14.8× and 11.8×, respectively) in contrast to treatment with less intense treatment regimens (1.6×) and no treatment (0.8×). In the relapse cohort, 33% of patients carried low-burden TP53 mutations, which did not expand significantly upon targeted treatment (median VAF change, 1×). Sporadic cases of TP53 mutations' clonal shifts were connected with the development of resistance-associated mutations. Altogether, our data support the incorporation of low-burden TP53 variants in clinical decision making.
BCORgene alterations in hematologic diseases
Authors: Sportoletti Paolo , Sorcini Daniele , Falini Brunangelo
Published: May 2021

The BCL6 corepressor (BCOR) is a transcription factor involved in the control of embryogenesis, mesenchymal stem cells function, hematopoiesis, and lymphoid development. Recurrent somatic clonal mutations of the BCOR gene and its homolog BCORL1 have been detected in several hematologic malignancies and aplastic anemia. They are scattered across the whole gene length and mostly represent frameshifts (deletions, insertions), nonsense, and missence mutations. These disruptive events lead to the loss of full-length BCOR protein and to the lack or low expression of a truncated form of the protein, both consistent with the tumor suppressor role of BCOR.BCOR and BCORL1 mutations are similar to those causing 2 rare X-linked diseases: oculofaciocardiodental (OFCD) and Shukla-Vernon syndromes, respectively. Here, we focus on the structure and function of normal BCOR and BCORL1 in normal hematopoietic and lymphoid tissues and review the frequency and clinical significance of the mutations of these genes in malignant and nonmalignant hematologic diseases. Moreover, we discuss the importance of mouse models to better understand the role of Bcor loss, alone and combined with alterations of other genes (eg, Dnmt3a and Tet2), in promoting hematologic malignancies and in providing a useful platform for the development of new targeted therapies.
Changes of gut microbiome composition and metabolites associated with hypertensive heart failure rats
Authors: Li Lin , Zhong Sen-jie , Hu Si-yuan , Cheng Bin , Qiu Hong , Hu Zhi-xi
Published: May 2021

Background

The potential role of the gut microbiome (GM) in heart failure (HF) had recently been revealed. However, the underlying mechanisms of the GM and fecal metabolome in HF have not been characterized. The Dahl salt-sensitive rat model of hypertensive heart failure (H-HF) was used to study the clinical symptoms and characteristics. To elucidate the pathogenesis of HF, we combined 16S rRNA gene sequencing and metabolomics to analyze gut microbial compositions and fecal metabolomic profiles of rats with H-HF.

Results

PCoA of beta diversity shown that the gut microbiome composition profiles among the three groups were separated. Gut microbial composition was significantly altered in H-HF rats, the ratio of Firmicutes to Bacteroidetes(F/B) increased and the abundance of Muribaculaceae, Lachnospiraceae, and Lactobacillaceae decreased. Significantly altered levels of 17 genera and 35 metabolites were identified as the potential biomarker of H-HF. Correlation analysis revealed that specific altered genera were strongly correlated with changed fecal metabolites. The reduction in short-chain fatty acids (SCFA)-producing bacteria and trimethylamine N-oxide (TMAO) might be a notable characteristic for H-HF.

Conclusions

This is the first study to characterize the fecal microbiome of hypertensive heart failure by integrating 16S rRNA gene sequencing and LC–MS-based metabolomics approaches. Collectively, the results suggesting changes of gut microbiome composition and metabolites are associated with hypertensive heart failure rats.
Echocardiographic and laboratory findings in coronary slow flow phenomenon: cross-sectional study and review
Authors: Seyyed Mohammadzad Mir Hosein , Khademvatani Kamal , Gardeshkhah Salar , Sedokani Amin
Published: May 2021

Background

Coronary sow-flow phenomenon (CSFP) is defined as slow passage of the contrast injected into the coronary arteries without distal obstruction of the vessel.

Methods

The present study was a cross-sectional, descriptive-analytical study performed at the Seyed-al-Shohada Heart Center during 2018–2019. The eligible patients based on the inclusion and exclusion criteria were divided into the study group showing the CSFP and the control group with normal epicardial coronary arteries.

Results

The study included 124 patients. 67.9% of the study group and 39.4% of the control group were male patients (p-value = 0.001), and the mean patient age was 52.18 ± 12.55 and 51.77 ± 10.36 years in the study and control groups, respectively (p-value = 0.18). The study group had a significantly higher BMI than the control group (p < 0.05) and also a higher prevalence of smoking and hypertension. The variables of ALC, Hct, Plt, MPV, RDW, Cr, triglyceride, TC, and LDL, were higher in the study group. Given the echocardiographic findings, the mean E wave was significantly lower in the study group, while the control group had a significantly higher GLS (p-value = 0.01). Also, left anterior descending artery was the most common artery involved with CSFP.

Conclusion

The CSFP was significantly more common in men, smokers, hypertensive patients, and patients with high BMI. Moreover, these patients had significantly higher platelet count, MPV, LDL, and FBS. Some other laboratory variables were also higher in these patients. Given the echocardiographic findings, mild diastolic dysfunction and low GLS were also observed in the study group.
Estimating effects of intervention measures on COVID-19 outbreak in Wuhan taking account of improving diagnostic capabilities using a modelling approach
Authors: Liang Jingbo , Yuan Hsiang-Yu , Wu Lindsey , Pfeiffer Dirk Udo
Published: May 2021

Background

Although by late February 2020 the COVID-19 epidemic was effectively controlled in Wuhan, China, estimating the effects of interventions, such as transportation restrictions and quarantine measures, on the early COVID-19 transmission dynamics in Wuhan is critical for guiding future virus containment strategies. Since the exact number of infected cases is unknown, the number of documented cases was used by many disease transmission models to infer epidemiological parameters. This means that it was possible to produce biased estimates of epidemiological parameters and hence of the effects of intervention measures, because the percentage of all cases that were documented changed during the first 2 months of the epidemic, as a consequence of a gradually improving diagnostic capability.

Methods

To overcome these limitations, we constructed a stochastic susceptible-exposed-infected-quarantined-recovered (SEIQR) model, accounting for intervention measures and temporal changes in the proportion of new documented infections out of total new infections, to characterize the transmission dynamics of COVID-19 in Wuhan across different stages of the outbreak. Pre-symptomatic transmission was taken into account in our model, and all epidemiological parameters were estimated using the Particle Markov-chain Monte Carlo (PMCMC) method.

Results

Our model captured the local Wuhan epidemic pattern as two-peak transmission dynamics, with one peak on February 4 and the other on February 12, 2020. The impact of intervention measures determined the timing of the first peak, leading to an 86% drop in the Re from 3.23 (95% CI, 2.22 to 4.20) to 0.45 (95% CI, 0.20 to 0.69). The improved diagnostic capability led to the second peak and a higher proportion of documented infections. Our estimated proportion of new documented infections out of the total new infections increased from 11% (95% CI 1–43%) to 28% (95% CI 4–62%) after January 26 when more detection kits were released. After the introduction of a new diagnostic criterion (case definition) on February 12, a higher proportion of daily infected cases were documented (49% (95% CI 7–79%)).

Conclusions

Transportation restrictions and quarantine measures together in Wuhan were able to contain local epidemic growth.
Annual wellness visits and care management before and after dialysis initiation
Authors: Wang Virginia , Zepel Lindsay , Diamantidis Clarissa J. , Smith Valerie A. , Scholle Sarah Hudson , Maciejewski Matthew L.
Published: May 2021

Introduction

Demands of dialysis regimens may pose challenges for primary care provider (PCP) engagement and timely preventive care. This is especially the case for patients initiating dialysis adjusting to new logistical challenges and management of symptoms and existing comorbid conditions. Since 2011, Medicare has provided coverage for annual wellness visits (AWV), which are primarily conducted by PCPs and may be useful for older adults undergoing dialysis.

Methods

We used the OptumLabs® Data Warehouse to identify a cohort of 1,794 Medicare Advantage (MA) enrollees initiating dialysis in 2014–2017 and examined whether MA enrollees (1) were seen by a PCP during an outpatient visit and (2) received an AWV in the year following dialysis initiation.

Results

In the year after initiating dialysis, 93 % of MA enrollees had an outpatient PCP visit but only 24 % received an annual wellness visit. MA enrollees were less likely to see a PCP if they had Charlson comorbidity scores between 0 and 5 than those with scores 6–9 (odds ratio (OR) = 0.59, 95 % CI: 0.37–0.95), but more likely if seen by a nephrologist (OR = 1.60, 95 % CI: 1.01–2.52) or a PCP (OR = 15.65, 95 % CI: 9.26–26.46) prior to initiation. Following dialysis initiation, 24 % of MA enrollees had an AWV. Hispanic MA enrollees were less likely (OR = 0.57, 95 % CI: 0.39–0.84) to have an AWV than White MA enrollees, but enrollees were more likely if they initiated peritoneal dialysis (OR = 1.54, 95 % CI: 1.07–2.23) or had an AWV in the year before dialysis initiation (OR = 4.96, 95 % CI: 3.88–6.34).

Conclusions

AWVs are provided at low rates to MA enrollees initiating dialysis, particularly Hispanic enrollees, and represent a missed opportunity for better care management for patients with ESKD. Increasing patient awareness and provider provision of AWV use among dialysis patients may be needed, to realize better preventive care for dialysis patients.
Maternal plasma pro-atrial and C-type natriuretic peptide levels and their associations with cardiovascular and renal function in the second half of normal pregnancy: a longitudinal study
Authors: Yarlagadda Rima D. , Johnson Jonas , Vårtun Åse , Flo Kari , Acharya Ganesh
Published: May 2021

Background

Physiological adaptation in pregnancy is characterized by remodeling of endocrine, cardiovascular and renal functions leading to fluid retention, volume expansion, altered cardiac loading conditions and hyperdynamic circulation. Natriuretic peptides have been used as biomarkers of cardiovascular function, but their associations with gestational age-related changes in maternal cardiac, endothelial and renal function have not been elucidated. The aim of this study was to establish longitudinal reference values for maternal plasma atrial natriuretic peptide (proANP) and C-type natriuretic peptide (CNP) and investigate their temporal association with cardiovascular and renal function in the second half of pregnancy.

Methods

This study was a prospective longitudinal study of 53 low-risk pregnancies. Women were examined every 3–5 weeks during 22–40 weeks of gestation (252 observations). Fasting maternal blood samples were obtained to measure proANP, CNP, creatinine, cystatin C, uric acid, and fibrinogen levels. Cardiac function and systemic hemodynamics were assessed noninvasively by impedance cardiography (ICG) and vascular endothelial function by flow-mediated vasodilation of brachial artery (FMD).

Results

The plasma proANP (R2adj = 0.79; P = 0.007), CNP (R2adj = 0.54; P = 0.005) decreased between 22 and 40 weeks. The creatinine (R2adj = 0.90; P < 0.001), cystatin C (R2adj = 0.93; P = < 0.001) and uric acid (R2adj = 0.83; P < 0.001) increased significantly, whereas the estimated glomerular filtration rate (R2adj = 0.93; P < 0.001) decreased with gestational age. The FMD did not change significantly but fibrinogen (R2adj = 0.79; P < 0.001) increased with advancing gestation. The maternal systemic vascular resistance index (R2adj = 0.50; P < 0.001) increased, stroke index (R2adj = 0.62; P < 0.001) decreased, whereas the cardiac index (R2adj = 0.62; P = 0.438) and thoracic fluid content (R2adj = 0.72; P = 0.132) did not change significantly with gestation. The proANP was associated with thoracic fluid content (R2adj = 0.74; P < 0.001) and fibrinogen (R2adj = 0.78; P = 0.034) but not with other variables of systemic hemodynamics, endothelial function, or renal function. The CNP was not associated significantly with parameters of cardiovascular or renal function.

Conclusion

Longitudinal reference values for maternal plasma proANP and CNP were established. These natriuretic peptides decreased slightly with advancing gestation, but they did not reflect the temporal physiological changes in maternal systemic hemodynamics, vascular endothelial function and renal function during the second half of pregnancy. The proANP correlated with the thoracic fluid content reflecting volume load in pregnancy.
Prediction of labour onset in women who present with symptoms of preterm labour using cervical length
Authors: Wong Tiffany Tuck Chin , Yong Xiaoqi , Tung Janice Su Zhen , Lee Beatrice Jia Ying , Chan Joanne Mei Xin , Du Ruochen , Yeo Tai Wai , Yeo George Seow Heong
Published: May 2021

Background

Diagnosis of preterm labour is difficult because initial symptoms and signs are often mild and may occur in continuing pregnancies. This study aims to investigate the utility of measuring cervical length, using transvaginal ultrasound, in women presenting to the delivery suite with symptoms of preterm labour.

Methods

This was a prospective cohort study performed in KK Women’s and Children’s Hospital, Singapore from September 2017 to July 2018. Women with singleton pregnancies, presenting with symptoms of contraction pain, between 24+ 0 to 36+ 6 weeks gestation, were included. Transvaginal ultrasound cervical length measurements were done at presentation to the labour ward, after four hours and in the following morning. The primary outcome of the study was delivery within 1 week. All statistical analyses were conducted with Microsoft Excel and Statistical Package for the Social Sciences.

Results

A total of 95 subjects were included. A one-millimeter increase in the 1st cervical length increases scan-to-delivery time by 0.802 days (p-value 0.003, CI 0.280–1.323). Receiver Operator Characteristic (ROC) curve analysis for prediction of delivery within 1 week showed an Area Under Curve (AUC) of 0.667, optimal cut-off value of 27.5mm (sensitivity 77.8 %, specificity 61.6 %). A one-millimetre increase in the 3rd cervical length increases scan-to-delivery time by 0.770 days (p-value 0.023, CI 0.108–1.432). ROC curve analysis for prediction of delivery within 1 week showed an AUC of 0.915, optimal cut-off value of 25.5mm (sensitivity 100 %, specificity 73.6 %). However, the change in cervical length over a period of 1 day was not significant in predicting delivery within 1 week.

Conclusions

Our results indicate that by using a cervical length cut off of 27.5mm at presentation, we would have predicted 77.8 % of deliveries within 1 week. If we were to repeat the cervical length scan the next day, with the same cut-off of 27.5mm, we would have predicted 100 % of deliveries within 1 week. In our study, measuring the transvaginal ultrasound cervical length is a reliable diagnostic test for delivery within 1 week. However, the results are limited by the small sample size. Further studies should be conducted with a larger sample size.
Bidimensional structure and measurement equivalence of the Patient Health Questionnaire-9: sex-sensitive assessment of depressive symptoms in three representative German cohort studies
Authors: Tibubos Ana N. , Otten Daniëlle , Zöller Daniela , Binder Harald , Wild Philipp S. , Fleischer Toni , Johar Hamimatunnisa , Atasoy Seryan , Schulze Lara , Ladwig Karl-Heinz , Schomerus Georg , Linkohr Birgit , Grabe Hans J. , Kruse Johannes , Schmidt Carsten-Oliver , Münzel Thomas , König Jochem , Brähler Elmar , Beutel Manfred E.
Published: May 2021

Background

The Patient Health Questionnaire-9 (PHQ-9) has been proposed as a reliable and valid screening instrument for depressive symptoms with one latent factor. However, studies explicitly testing alternative model structures found support for a two-dimensional structure reflecting a somatic and a cognitive-affective dimension. We investigated the bidimensional structure of the PHQ-9, with a somatic (sleeping problems, fatigability, appetitive problems, and psychomotor retardation) and a cognitive-affective dimension (lack of interest, depressed mood, negative feelings about self, concentration problems, and suicidal ideation), and tested for sex- and regional-differences.

Methods

We have included data from the GEnder-Sensitive Analyses of mental health trajectories and implications for prevention: A multi-cohort consortium (GESA). Privacy-preserving analyses to provide information on the overall population and cohort-specific information and analyses of variance to compare depressive, somatic and cognitive-affective symptoms between sexes and cohorts were executed in DataSHIELD. In order to determine the dimensionality and measurement invariance of the PHQ-9 we tested three models (1 factor, 2 correlated factors, and bifactor) via confirmatory analyses and performed multi-group confirmatory factor analysis.

Results

Differences between sex and cohorts exist for PHQ-9 and for both of its dimensions. Women reported depressive symptoms in general as well as somatic and cognitive-affective symptoms more frequently. For all tested models an acceptable to excellent fit was found, consistently indicating a better model fit for the two-factor and bifactor model. Scalar measurement invariance was established between women and men, the three cohorts, and their interaction.

Conclusions

The two facets of depression should be taken into account when using PHQ-9, while data also render support to a general factor. Somatic and cognitive-affective symptoms assessed by the PHQ-9 can be considered equivalent across women and men and between different German populations from different regions.
Perceived COVID-19 risk is attenuated by ingroup trust: evidence from three empirical studies
Authors: Cruwys Tegan , Stevens Mark , Donaldson Jessica L. , Cárdenas Diana , Platow Michael J. , Reynolds Katherine J. , Fong Polly
Published: May 2021

Background

The social identity model of risk taking proposes that people take more risks with ingroup members because they trust them more. While this can be beneficial in some circumstances, in the context of the COVID-19 pandemic it has the potential to undermine an effective public health response if people underestimate the risk of contagion posed by ingroup members, or overestimate the risk of vaccines or treatments developed by outgroup members.

Methods

Three studies (two prospective surveys, one experiment) with community-based adults tested the potential for the social identity model of risk taking to explain risk perception and risk taking in the context of COVID-19.

Results

Study 1 was a two-wave study with a pre-COVID baseline, and found that people who identified more strongly as a member of their neighborhood pre-COVID tended to trust their neighbors more, and perceive interacting with them during COVID-19 lockdown to be less risky. Study 2 (N = 2033) replicated these findings in a two-wave nationally representative Australian sample. Study 3 (N = 216) was a pre-registered experiment which found that people indicated greater willingness to take a vaccine, and perceived it to be less risky, when it was developed by an ingroup compared to an outgroup source. We interpret this as evidence that the tendency to trust ingroup members more could be harnessed to enhance the COVID-19 response.

Conclusions

Across all three studies, ingroup members were trusted more and were perceived to pose less health risk. These findings are discussed with a focus on how group processes can be more effectively incorporated into public health policy, both for the current pandemic and for future contagious disease threats.
Key indicators of repetitive overuse-induced neuromuscular inflammation and fibrosis are prevented by manual therapy in a rat model
Authors: Barbe Mary F. , Harris Michele Y. , Cruz Geneva E. , Amin Mamta , Billett Nathan M. , Dorotan Jocelynne T. , Day Emily P. , Kim Seung Y. , Bove Geoffrey M.
Published: May 2021

Background

We examined the effectiveness of a manual therapy consisting of forearm skin rolling, muscle mobilization, and upper extremity traction as a preventive treatment for rats performing an intensive lever-pulling task. We hypothesized that this treatment would reduce task-induced neuromuscular and tendon inflammation, fibrosis, and sensorimotor declines.

Methods

Sprague-Dawley rats performed a reaching and lever pulling task for a food reward, 2 h/day, 3 days/week, for 12 weeks, while simultaneously receiving the manual therapy treatment 3 times per week for 12 weeks to either the task-involved upper extremities (TASK-Tx), or the lower extremities as an active control group (TASK-Ac). Results were compared to similarly treated control rats (C-Tx and C-Ac).

Results

Median nerves and forearm flexor muscles and tendons of TASK-Ac rats showed higher numbers of inflammatory CD68+ and fibrogenic CD206+ macrophages, particularly in epineurium, endomysium and epitendons than TASK-Tx rats. CD68+ and CD206+ macrophages numbers in TASK-Tx rats were comparable to the non-task control groups. TASK-Ac rats had more extraneural fibrosis in median nerves, pro-collagen type I levels and immunoexpression in flexor digitorum muscles, and fibrogenic changes in flexor digitorum epitendons, than TASK-Tx rats (which showed comparable responses as control groups). TASK-Ac rats showed cold temperature, lower reflexive grip strength, and task avoidance, responses not seen in TASK-Tx rats (which showed comparable responses as the control groups).

Conclusions

Manual therapy of forelimbs involved in performing the reaching and grasping task prevented the development of inflammatory and fibrogenic changes in forearm nerves, muscle, and tendons, and sensorimotor declines.
Possible involvement of the autonomic nervous system in cervical muscles of patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS)
Authors: Matsui Takayoshi , Hara Kazuhiro , Iwata Makoto , Hojo Shuntaro , Shitara Nobuyuki , Endo Yuzo , Fukuoka Hideoki , Matsui Masaki , Kawaguchi Hiroshi
Published: May 2021

Background

Patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) sometimes present with stiffness of the cervical muscles. To investigate the pathophysiology of ME/CFS, this observational study compared patients with versus without recovery from ME/CFS through local modulation of the cervical muscles.

Methods

Over a period of 11 years, a total of 1226 inpatients with ME/CFS who did not respond to outpatient care were enrolled in this study. All patients received daily cervical muscle physical therapy during hospitalization. Self-rated records documenting the presence or absence of ME/CFS, as well as the representative eight symptoms that frequently accompany it at admission and discharge, were compared. Pupil diameter was also measured to examine autonomic nervous system function involvement.

Results

The recovery rate of ME/CFS after local therapy was 55.5%, and did not differ significantly by sex, age strata, and hospitalization period. The recovery rates of the eight symptoms were variable (36.6–86.9%); however, those of ME/CFS in the symptom subpopulations were similar (52.3–55.8%). The recovery rates of all symptoms showed strong associations with that of ME/CFS (p < 0.001). The pupil diameter was more constricted in the ME/CFS-recovered patients than in the ME/CFS-unrecovered patients in the total population and the subpopulations stratified by sex, age, and hospitalization period.

Conclusions

There was a strong association between the recovery of ME/CFS and other related whole-body symptoms. The recovery of ME/CFS may be partly linked to amelioration of the autonomic nervous system in the cervical muscles.

Trial registration

UMIN000036634. Registered 1 May 2019 - Retrospectively registered.
–A cross-sectional study of clinical learning environments across four undergraduate programs using the undergraduate clinical education environment measure
Authors: Sellberg Malin , Palmgren Per J. , Möller Riitta
Published: May 2021

Background

The clinical learning environment (CLE) influences students’ achievement of learning outcomes and the development of their professional behaviors. However, CLEs are not always optimal for learning because of clinical productivity expectations and a lack of support from supervisors. The purpose of this study was to describe and compare students’ perceptions of their CLEs across four undergraduate programs.

Methods

This study is cross-sectional. In total, 735 students who were registered in the medical, nursing, physiotherapy, and speech-language pathology (SLP) programs were invited to participate. Data were collected using an online survey, which included demographics and the Undergraduate Clinical Education Environment Measure (UCEEM). The UCEEM consists of 26 items congregated into two overarching dimensions—experiential learning and social participation—with four subscales: opportunities to learn in and through work and quality of supervision, preparedness for student entry, workplace interaction patterns and student inclusion, and equal treatment.

Results

In total 280 students (median age 28; range: 20–52; 72% females) returned the questionnaire. The mean total UCEEM score was 98.3 (SD 18.4; range: 91–130), with physiotherapy students giving the highest scores and medical students the lowest. The mean scores for the dimensions experiential learning and social participation for all the students were 62.8 (SD 13.6; range 59–85) and 35.5 (SD 6.2; range 13–45), respectively. Medical students rated the lowest for all subscales. The items receiving the highest ratings concerned equal treatment, whereas those receiving the lowest ratings concerned supervisors’ familiarity with the learning objectives. There were few statistically significant differences between the semesters within each program.

Conclusions

The students generally hold positive perceptions toward their CLEs. However, the students from the medical and nursing programs rated their learning environment lower than did the students from the physiotherapy and SLP programs. Importantly, in several aspects, the medical students provided significantly lower ratings for their CLE compared with the students from the other programs. The medical students’ low ratings for their supervisors’ familiarity with the learning objectives underscore the need to ensure that the prerequisites for optimal supervision are met.
Knowledge and preparedness of healthcare providers towards bioterrorism
Authors: Nofal Abdullah , AlFayyad Isamme , AlJerian Nawfal , Alowais Jalal , AlMarshady Meshal , Khan Anas , Heena Humariya , AlSarheed Ayah Sulaiman , Abu-Shaheen Amani
Published: May 2021

Background

Several emergent circumstances require healthcare providers to recognize the unusual and dangerous and pathogenic agents. An in-depth literature review showed that studies about bioterrorism preparedness amongst healthcare providers are lacking. Therefore, this study aimed to investigate the knowledge and preparedness level of first emergency respondents towards bioterrorism events.

Methods

This study has a cross-sectional design and was carried out at the Emergency departments and poison control centers/clinical laboratories three in major tertiary care hospitals in Riyadh, Saudi Arabia. The subjects were randomly selected to complete the self-administered questionnaire to collect study outcomes.

Results

A total of 1030 participants were included in the final data analysis. The mean knowledge score in the basic concepts of bioterrorism and introductory clinical presentations of bioterrorism-related agents was 4.92 ± 1.86 out of 12 points.

Moreover, the findings showed a mean knowledge score of 22.80 ± 3.92 out of 38 in the bioterrorism preparedness and governing policies and procedures. Respondents who received previous training in bioterrorism preparedness had a significantly higher number of perceived benefits than those not sure and without prior training (z = − 2.67, p = 0.008) and (z = − 4.4, p < 0.0001), respectively. About 79.4% of participants did not have previous training in bioterrorism preparedness, but 68.7% expressed willingness in the institution’s response and control to assist in a bioterrorist attack incident.

Conclusion

Although healthcare professionals have reported their desire to help in bioterrorism events, they need to enhance their knowledge of bioterrorism preparedness.
Correction to: Genetic architecture of cardiometabolic risks in people living with HIV
Authors: Cheng Haoxiang , Sewda Anshuman , Marquez-Luna Carla , White Sierra R. , Whitney Bridget M. , Williams-Nguyen Jessica , Nance Robin M. , Lee Won Jun , Kitahata Mari M. , Saag Michael S. , Willig Amanda , Eron Joseph J. , Mathews W. Christopher , Hunt Peter W. , Moore Richard D. , Webel Allison , Mayer Kenneth H. , Delaney Joseph A. , Crane Paul K. , Crane Heidi M. , Hao Ke , Peter Inga
Published: May 2021

An amendment to this paper has been published and can be accessed via the original article.
The impact of E-cigarette vaping and vapour constituents on bone health
Authors: Nicholson Thomas , Scott Aaron , Newton Ede Matthew , Jones Simon W.
Published: May 2021

Background

In contrast to cigarettes, electronic cigarette use (E-cigarettes) has grown substantially over the last decade. This is due to their promotion as both a safer alternative to cigarettes and as an aide to stop smoking. Critically, upon E-cigarette use, the user may be exposed to high doses of nicotine in addition to other compounds including flavouring chemicals, metal particulates and carbonyl compounds, particularly in highly vascularised tissues such as bone. However, there has been limited investigation into the impact of E-cigarette usage on bone physiology, particularly over extended time periods and there are no clinical recommendations regarding E-cigarette usage in relation to orthopaedic surgery. This literature review draws together data from studies that have investigated the impact of E-cigarette vapour and its major constituents on bone, detailing the models utilised and the relevant mechanistic and functional results.

Main body

Currently there is a lack of studies both in vivo and in vitro that have utilised E-cigarette vapour, necessary to account for changes in chemical composition of E-cigarette liquids upon vaping. There is however evidence that human bone and bone cells express nicotine receptors and exposure of both osteoblasts and osteoclasts to nicotine, in high concentrations may reduce their viability and impair function. Similarly, it appears that aldehydes and flavouring chemicals may also negatively impact osteoblast viability and their ability to form bone. However, such functional findings are predominantly the result of studies utilising bone cell lines such as MG-63 or Saos-2 cells, with limited use of human osteoblasts or osteoclasts. Additionally, there is limited consideration for a possible impact on mesenchymal stem cells, which can also play an import role in bone repair.

Conclusion

Understanding the function and mechanism of action of the various components of E-cigarette vapour in mediating human bone cell function, in addition to long term studies to determine the potential harm of chronic E-cigarette use on human bone will be important to inform users of potential risks, particularly regarding bone healing following orthopaedic surgery and injury.
The unpredictable carbon nanotube biocorona and a functionalization method to prevent protein biofouling
Authors: García-Hevia Lorena , Saramiforoshani Mahsa , Monge Jorge , Iturrioz-Rodríguez Nerea , Padín-González Esperanza , González Fernando , González-Legarreta Lorena , González Jesús , Fanarraga Mónica L.
Published: May 2021

Background

The intrinsic physicochemical properties of carbon nanotubes (CNTs) make them unique tools in nanotechnology. Their elemental composition, resilience, thermal properties, and surface reactivity make CNTs also of undisputed interest in biotechnology. In particular, their extraordinary ability to capture biomolecules on their surface makes them essential in this field. The proteins adsorbed on the CNTs create a biological coating that endows them the ability to interact with some cell receptors, penetrate membranes or interfere with cell biomechanics, thus behaving as an active bio-camouflage. But some of these proteins unfold, triggering an immune response that unpredictably changes the biological activity of CNTs. For this reason, the control of the biocorona is fundamental in the nanobiotechnology of CNTs.

Results

Using TEM and AFM here we demonstrate a significant increase in CNTs diameter after protein functionalization. A quantitative analysis using TGA revealed that between 20 and 60% of the mass of functionalized nanotubes corresponds to protein, with single-walled CNTs capturing the highest amounts. To qualitatively/quantitatively characterize these biocoatings, we studied the biochemical "landscape" of the proteins captured by the different nanotubes after functionalization under various conditions. This study revealed a significant variability of the proteins in the corona as a function of the type of nanotube, the functionalization temperature, or the time after exposure to serum. Remarkably, the functionalization of a single type of CNT with sera from various human donors also resulted in different protein landscapes. Given the unpredictable assortment of proteins captured by the corona and the biological implications of this biocoating, we finally designed a method to genetically engineer and produce proteins to functionalize nanotubes in a controlled and customizable way.

Conclusions

We demonstrate the high unpredictability of the spontaneous protein corona on CNTs and propose a versatile functionalization technique that prevents the binding of nonspecific proteins to the nanotube to improve the use of CNTs in biomedical applications.
Evaluation of vitamin D receptor expression in uterine leiomyoma and nonneoplastic myometrial tissue: a cross‐sectional controlled study
Authors: Lima Maria Simone Oliveira , da Silva Benedito Borges , de Medeiros Menandro Lima , dos Santos Alesse Ribeiro , do Nascimento Brazil Emerson Davi , Filho Walberto Monteiro Neiva Eulálio , Ibiapina Jerusia Oliveira , Brito Antônio Gilberto Albuquerque , Costa Pedro Vitor Lopes
Published: May 2021

Background

Uterine myomas are the most frequent benign solid pelvic tumors in women of reproductive age. At present, uterine myomas are the most common indication for hysterectomy because of the morbidity they cause, including intense bleeding, compression of adjacent organs, pain, and infertility. Some studies show that vitamin D receptor (VDR) expression is correlated with the etiology of uterine leiomyomas. This study aimed to assess the expression of VDR in uterine leiomyoma and nonneoplastic myometrial tissue.

Methods

A controlled cross-sectional study involving 40 women who underwent abdominal hysterectomy the Department of Gynecology of the Getúlio Vargas Hospital of Federal University of Piauí, Brazil, was performed to compare the immunohistochemical expression of VDR in samples of uterine leiomyoma tissue with adjacent nonneoplastic myometrial tissue. The mean percetages of stained nuclei in the two groups was compared by Student’s t teste, with significance established at p < 0.05.

Results

The percentage of cells with nuclei stained by anti-VDR in the myometrial and leiomyoma tissue was 79.52 % (± 4.32) and 60.22 % (± 7.24), respectively (p < 0.0001).

Conclusions

The mean percentage of nuclei expressing VDR was significantly lower in the uterine leiomyoma than in nonneoplastic myometrial tissue.
Case report: histopathology and molecular pathology analysis on enteric tissue of a COVID-19 patient
Authors: Feng Yanling , Zeng Dong , Hu Lvyin , Yang Yuexiang , Song Shu , Shi Yuhan , Xu Jingjing , Guo Wenjuan , Ling Yun , Qi Tangkai , Wu Qingguo , Li Feng , Cheng Jilin , Lu Hongzhou
Published: May 2021

Aims

Patients with COVID-19 can also have enteric symptoms. Here we analyzed the histopathology of intestinal detachment tissue from a patient with COVID-19.

Methods

The enteric tissue was examined by hematoxylin & eosin stain, PAS (Periodic acid–Schiff) staining, Gram staining, Ziehl–Neelsen stain and Grocott’s Methenamine Silver (GMS) Stain. The distribution of CD3, CD4, CK20 and CD68, cytomegalovirus (CMV) and Herpes Simplex Virus (HSV) antigen were determined by immunohistochemistry. In situ hybridization (ISH) of SARS-CoV-2 and Epstein-Barr virus-encoded small RNA (EBER) were also performed.

Results

We observed mucosal epithelium shedding, intestinal mucosal erosion, focal inflammatory necrosis with hemorrhage, massive neutrophil infiltration, macrophage proliferation accompanied by minor lymphocyte infiltration. Fungal spores and gram positive cocci but not mycobacteria tuberculosis were identified. Immunohistochemistry staining showed abundant CD68+ macrophages but few lymphocytes infiltration. HSV, CMV and EBV were negative. ISH of SARS-CoV-2 RNA showed positive signal which mostly overlapped with CD68 positivity.

Conclusions

The in situ detection of SARS-CoV-2 RNA in intestinal macrophages implicates a possible route for gastrointestinal infection. Further study is needed to further characterize the susceptibility of enteric cells to SARS-CoV-2 infection.
High-throughput soybean seeds phenotyping with convolutional neural networks and transfer learning
Authors: Yang Si , Zheng Lihua , He Peng , Wu Tingting , Sun Shi , Wang Minjuan
Published: May 2021

Background

Effective soybean seed phenotyping demands large-scale accurate quantities of morphological parameters. The traditional manual acquisition of soybean seed morphological phenotype information is error-prone, and time-consuming, which is not feasible for large-scale collection. The segmentation of individual soybean seed is the prerequisite step for obtaining phenotypic traits such as seed length and seed width. Nevertheless, traditional image-based methods for obtaining high-throughput soybean seed phenotype are not robust and practical. Although deep learning-based algorithms can achieve accurate training and strong generalization capabilities, it requires a large amount of ground truth data which is often the limitation step.

Results

We showed a novel synthetic image generation and augmentation method based on domain randomization. We synthesized a plenty of labeled image dataset automatedly by our method to train instance segmentation network for high throughput soybean seeds segmentation. It can pronouncedly decrease the cost of manual annotation and facilitate the preparation of training dataset. And the convolutional neural network can be purely trained by our synthetic image dataset to achieve a good performance. In the process of training Mask R-CNN, we proposed a transfer learning method which can reduce the computing costs significantly by finetuning the pre-trained model weights. We demonstrated the robustness and generalization ability of our method by analyzing the result of synthetic test datasets with different resolution and the real-world soybean seeds test dataset.

Conclusion

The experimental results show that the proposed method realized the effective segmentation of individual soybean seed and the efficient calculation of the morphological parameters of each seed and it is practical to use this approach for high-throughput objects instance segmentation and high-throughput seeds phenotyping.
Down regulation of the expression of mitochondrial phosphopantetheinyl-proteins in pantothenate kinase-associated neurodegeneration: pathophysiological consequences and therapeutic perspectives
Authors: Álvarez-Córdoba Mónica , Talaverón-Rey Marta , Villalón-García Irene , Povea-Cabello Suleva , Suárez-Rivero Juan M. , Suárez-Carrillo Alejandra , Munuera-Cabeza Manuel , Salas Joaquín J. , Sánchez-Alcázar José A.
Published: May 2021

Background

Neurodegeneration with brain iron accumulation (NBIA) is a group of genetic neurological disorders frequently associated with iron accumulation in the basal nuclei of the brain characterized by progressive spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration or optic nerve atrophy. Pantothenate kinase-associated neurodegeneration (PKAN) is the most widespread NBIA disorder. It is caused by mutations in the gene of pantothenate kinase 2 (PANK2) which catalyzes the first reaction of coenzyme A (CoA) biosynthesis. Thus, altered PANK2 activity is expected to induce CoA deficiency as well as low levels of essential metabolic intermediates such as 4′-phosphopantetheine which is a necessary cofactor for critical proteins involved in cytosolic and mitochondrial pathways such as fatty acid biosynthesis, mitochondrial respiratory complex I assembly and lysine and tetrahydrofolate metabolism, among other metabolic processes.

Methods

In this manuscript, we examined the effect of PANK2 mutations on the expression levels of proteins with phosphopantetheine cofactors in fibroblast derived from PKAN patients. These proteins include cytosolic acyl carrier protein (ACP), which is integrated within the multifunctional polypeptide chain of the fatty acid synthase involved in cytosolic fatty acid biosynthesis type I (FASI); mitochondrial ACP (mtACP) associated with mitocondrial fatty acid biosynthesis type II (FASII); mitochondrial alpha-aminoadipic semialdehyde synthase (AASS); and 10-formyltetrahydrofolate dehydrogenases (cytosolic, ALD1L1, and mitochondrial, ALD1L2).

Results

In PKAN fibroblasts the expression levels of cytosolic FAS and ALD1L1 were not affected while the expression levels of mtACP, AASS and ALD1L2 were markedly reduced, suggesting that 4′-phosphopantetheinylation of mitochondrial but no cytosolic proteins were markedly affected in PKAN patients. Furthermore, the correction of PANK2 expression levels by treatment with pantothenate in selected mutations with residual enzyme content was able to correct the expression levels of mitochondrial phosphopantetheinyl-proteins and restore the affected pathways. The positive effects of pantothenate in particular mutations were also corroborated in induced neurons obtained by direct reprograming of mutant PANK2 fibroblasts.

Conclusions

Our results suggest that the expression levels of mitochondrial phosphopantetheinyl-proteins are severely reduced in PKAN cells and that in selected mutations pantothenate increases the expression levels of both PANK2 and mitochondrial phosphopantetheinyl-proteins associated with remarkable improvement of cell pathophysiology.