bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparing your intensive care unit for the COVID-19 pandemic: practical considerations and strategies
Authors: Goh Ken Junyang , Wong Jolin , Tien Jong-Chie Claudia , Ng Shin Yi , Duu Wen Sewa , Phua Ghee Chee , Leong Carrie Kah-Lai
Published: May 2020

The coronavirus disease 2019 (COVID-19) has rapidly evolved into a worldwide pandemic. Preparing intensive care units (ICU) is an integral part of any pandemic response. In this review, we discuss the key principles and strategies for ICU preparedness. We also describe our initial outbreak measures and share some of the challenges faced. To achieve sustainable ICU services, we propose the need to 1) prepare and implement rapid identification and isolation protocols, and a surge in ICU bed capacity; (2) provide a sustainable workforce with a focus on infection control; (3) ensure adequate supplies to equip ICUs and protect healthcare workers; and (4) maintain quality clinical management, as well as effective communication.
Defining the relative and combined contribution of CTCF and CTCFL to genomic regulation
Authors: Nishana Mayilaadumveettil , Ha Caryn , Rodriguez-Hernaez Javier , Ranjbaran Ali , Chio Erica , Nora Elphege P. , Badri Sana B. , Kloetgen Andreas , Bruneau Benoit G. , Tsirigos Aristotelis , Skok Jane A.
Published: May 2020

Background

Ubiquitously expressed CTCF is involved in numerous cellular functions, such as organizing chromatin into TAD structures. In contrast, its paralog, CTCFL, is normally only present in the testis. However, it is also aberrantly expressed in many cancers. While it is known that shared and unique zinc finger sequences in CTCF and CTCFL enable CTCFL to bind competitively to a subset of CTCF binding sites as well as its own unique locations, the impact of CTCFL on chromosome organization and gene expression has not been comprehensively analyzed in the context of CTCF function. Using an inducible complementation system, we analyze the impact of expressing CTCFL and CTCF-CTCFL chimeric proteins in the presence or absence of endogenous CTCF to clarify the relative and combined contribution of CTCF and CTCFL to chromosome organization and transcription.

Results

We demonstrate that the N terminus of CTCF interacts with cohesin which explains the requirement for convergent CTCF binding sites in loop formation. By analyzing CTCF and CTCFL binding in tandem, we identify phenotypically distinct sites with respect to motifs, targeting to promoter/intronic intergenic regions and chromatin folding. Finally, we reveal that the N, C, and zinc finger terminal domains play unique roles in targeting each paralog to distinct binding sites to regulate transcription, chromatin looping, and insulation.

Conclusion

This study clarifies the unique and combined contribution of CTCF and CTCFL to chromosome organization and transcription, with direct implications for understanding how their co-expression deregulates transcription in cancer.
Frequency of KCNQ1 variants causing loss of methylation of Imprinting Centre 2 in Beckwith-Wiedemann syndrome
Authors: Eßinger Carla , Karch Stephanie , Moog Ute , Fekete György , Lengyel Anna , Pinti Eva , Eggermann Thomas , Begemann Matthias
Published: May 2020

Background

Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder caused by disturbances of the chromosomal region 11p15.5. The most frequent molecular finding in BWS is loss of methylation (LOM) of the Imprinting Centre 2 (IC2) region on the maternal allele, which is localised in intron 10 of theKCNQ1gene. In rare cases, LOM of IC2 has been reported in families withKCNQ1germline variants which additionally cause long-QT syndrome (LQTS). Thus, a functional link between disruptedKCNQ1transcripts and altered IC2 methylation has been suggested, resulting in the co-occurrence of LQTS and BWS in case of maternal inheritance. Whereas these cases were identified by chance or in patients with abnormal electrocardiograms, a systematic screen forKCNQ1variants in IC2 LOM carriers has not yet been performed.

Results

We analysed 52 BWS patients with IC2 LOM to determine the frequency of germline variants inKCNQ1by MLPA and an amplicon-based next generation sequencing approach. We identified one patient with a splice site variant causing premature transcription termination ofKCNQ1.

Conclusions

Our study strengthens the hypothesis that properKCNQ1transcription is required for the establishment of IC2 methylation, but thatKCNQ1variants cause IC2 LOM only in a small number of BWS patients.
DNA methylation changes during preimplantation development reveal inter-species differences and reprogramming events at imprinted genes
Authors: Ivanova Elena , Canovas Sebastian , Garcia-Martínez Soledad , Romar Raquel , Lopes Jordana S. , Rizos Dimitrios , Sanchez-Calabuig Maria J. , Krueger Felix , Andrews Simon , Perez-Sanz Fernando , Kelsey Gavin , Coy Pilar
Published: May 2020

Preimplantation embryos experience profound resetting of epigenetic information inherited from the gametes. Genome-wide analysis at single-base resolution has shown similarities but also species differences between human and mouse preimplantation embryos in DNA methylation patterns and reprogramming. Here, we have extended such analysis to two key livestock species, the pig and the cow. We generated genome-wide DNA methylation and whole-transcriptome datasets from gametes to blastocysts in both species. In oocytes from both species, a distinctive bimodal methylation landscape is present, with hypermethylated domains prevalent over hypomethylated domains, similar to human, while in the mouse the proportions are reversed.

An oocyte-like pattern of methylation persists in the cleavage stages, albeit with some reduction in methylation level, persisting to blastocysts in cow, while pig blastocysts have a highly hypomethylated landscape. In the pig, there was evidence of transient de novo methylation at the 8–16 cell stages of domains unmethylated in oocytes, revealing a complex dynamic of methylation reprogramming. The methylation datasets were used to identify germline differentially methylated regions (gDMRs) of known imprinted genes and for the basis of detection of novel imprinted loci. Strikingly in the pig, we detected a consistent reduction in gDMR methylation at the 8–16 cell stages, followed by recovery to the blastocyst stage, suggesting an active period of imprint stabilization in preimplantation embryos. Transcriptome analysis revealed absence of expression in oocytes of both species of ZFP57, a key factor in the mouse for gDMR methylation maintenance, but presence of the alternative imprint regulator ZNF445. In conclusion, our study reveals species differences in DNA methylation reprogramming and suggests that porcine or bovine models may be closer to human in key aspects than in the mouse model.
Longitudinal trajectories of Alzheimer’s ATN biomarkers in elderly persons without dementia
Authors:   Alzheimer’s Disease Neuroimaging Initiative, Tan Meng-Shan , Ji Xi , Li Jie-Qiong , Xu Wei , Wang Hui-Fu , Tan Chen-Chen , Dong Qiang , Zuo Chuan-Tao , Tan Lan , Suckling John , Yu Jin-Tai
Published: May 2020

Background

Models of Alzheimer’s disease (AD) pathophysiology posit that amyloidosis [A] precedes and accelerates tau pathology [T] that leads to neurodegeneration [N]. Besides this A-T-N sequence, other biomarker sequences are possible. This current work investigates and compares the longitudinal trajectories of Alzheimer’s ATN biomarker profiles in non-demented elderly adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort.

Methods

Based on the ATN classification system, 262 individuals were identified before dementia diagnosis and accompanied by baseline and follow-up data of ATN biomarkers (CSF Aβ42, p-tau, and FDG-PET). We recorded the conversion processes in ATN biomarkers during follow-up, then analyzed the possible longitudinal trajectories and estimated the conversion rate and temporal evolution of biomarker changes. To evaluate how biomarkers changed over time, we used linear mixed-effects models.

Results

During a 6–120-month follow-up period, there were four patterns of longitudinal changes in Alzheimer’s ATN biomarker profiles, from all negative to positive through the course of the disease. The most common pattern is that A pathology biomarker first emerges. As well as the classical A-T-N sequence, other “A-first,” “T-first,” and “N-first” biomarker pathways were found. The N-A-T sequence had the fastest rate of pathological progression (mean 65.00 months), followed by A-T-N (mean 67.07 months), T-A-N (mean 68.85 months), and A-N-T sequences (mean 98.14 months).

Conclusions

Our current work presents a comprehensive analysis of longitudinal trajectories of Alzheimer’s ATN biomarkers in non-demented elderly adults. Stratifying disease into subtypes depending on the temporal evolution of biomarkers will benefit the early recognition and treatment.
Exploring the mechanisms underlying excitation/inhibition imbalance in human iPSC-derived models of ASD
Authors: Culotta Lorenza , Penzes Peter
Published: May 2020

Autism spectrum disorder (ASD) is a range of neurodevelopmental disorders characterized by impaired social interaction and communication, and repetitive or restricted behaviors. ASD subjects exhibit complex genetic and clinical heterogeneity, thus hindering the discovery of pathophysiological mechanisms. Considering that several ASD-risk genes encode proteins involved in the regulation of synaptic plasticity, neuronal excitability, and neuronal connectivity, one hypothesis that has emerged is that ASD arises from a disruption of the neuronal network activity due to perturbation of the synaptic excitation and inhibition (E/I) balance. The development of induced pluripotent stem cell (iPSC) technology and recent advances in neuronal differentiation techniques provide a unique opportunity to model complex neuronal connectivity and to test the E/I hypothesis of ASD in human-based models. Here, we aim to review the latest advances in studying the different cellular and molecular mechanisms contributing to E/I balance using iPSC-based in vitro models of ASD.
MSC-derived exosomes attenuate cell death through suppressing AIF nucleus translocation and enhance cutaneous wound healing
Authors: Zhao Guifang , Liu Feilin , Liu Zinan , Zuo Kuiyang , Wang Bo , Zhang Yuying , Han Xing , Lian Aobo , Wang Yuan , Liu Mingsheng , Zou Fei , Li Pengdong , Liu Xiaomei , Jin Minghua , Liu Jin Yu
Published: May 2020

Background

Skin wounding is very common and may be slow to heal. Increasing evidence shows that exosomes derived from mesenchymal stem cells (MSCs) dramatically enhance skin wound healing in a paracrine manner. However, the mechanism underlying this phenomenon has not yet been elucidated. Thus, the objective of the present study was to identify the signaling pathways and paracrine factors by which MSC-derived exosomes promote de novo skin tissue regeneration in response to wound healing.

Methods

In vitro and in vivo skin wound healing models were created by treating immortalized human keratinocytes (HaCaT) with hydrogen peroxide (H2O2) and excising full-thickness mouse skin, respectively. Exosomes were extracted from human umbilical cord Wharton’s jelly MSCs (hucMSC-Ex) by ultracentrifugation of cell culture supernatant.

Results

The hucMSC-Ex treatment significantly increased HaCaT cell proliferation and migration in a time- and dose-dependent manner, suppressed HaCaT apoptosis induced with H2O2by inhibiting nuclear translocation of apoptosis-inducing factor (AIF) and upregulating poly ADP ribose polymerase 1 (PARP-1) and poly (ADP-ribose) (PAR). The animal experiments showed that relative to hucMSCs, hucMSC-Ex attenuated full-thickness skin wounding by enhancing epidermal re-epithelialization and dermal angiogenesis.

Conclusions

These findings indicated that direct administration of hucMSC-Ex may effectively treat cutaneous wounding and could be of great value in clinical settings.
Sex differences in traumatic stress reactivity in rats with and without a history of alcohol drinking
Authors: Albrechet-Souza Lucas , Schratz Connor L. , Gilpin Nicholas W.
Published: May 2020

Background

Alcohol misuse and post-traumatic stress disorder (PTSD) are highly comorbid, and treatment outcomes are worse in individuals with both conditions. Although more men report experiencing traumatic events than women, the lifetime prevalence of PTSD is twice as high in females. Despite these data trends in humans, preclinical studies of traumatic stress reactivity have been performed almost exclusively in male animals.

Methods

This study was designed to examine sex differences in traumatic stress reactivity in alcohol-naive rats (experiment 1) and rats given intermittent access to 20% ethanol in a 2-bottle choice paradigm for 5 weeks (experiment 2). Animals were exposed to predator odor (bobcat urine) and tested for contextual avoidance 24 h later; unstressed controls were never exposed to predator odor. We evaluated changes in physiological arousal using the acoustic startle response (ASR) test at day 2 post-stress and anxiety-like behavior measured in the elevated plus-maze (EPM) at day 17 post-stress. In experiment 3, time course of corticosterone response was examined in male and female rats following exposure to predator odor stress.

Results

Alcohol-naive males and females exposed to predator odor displayed blunted weight gain 24 h post-stress, but only a subset of stressed animals exhibited avoidance behavior. In alcohol-drinking animals, the proportion of avoiders was higher in males than females, and predator odor exposure increased ASR in males only. Stressed females exhibited blunted ASR relative to unstressed females and stressed males, regardless of alcohol drinking history. Alcohol-experienced females presented lower anxiety-like behavior and higher general activity in the EPM in comparison with alcohol-experienced males. Plasma corticosterone levels were higher in females immediately after predator odor exposure until 60 min post-stress relative to males.

Conclusions

We report robust sex differences in behavioral and endocrine responses to bobcat urine exposure in adult Wistar rats. Also, males with a history of chronic moderate alcohol drinking exhibited increased traumatic stress reactivity relative to alcohol-drinking females. Our findings emphasize the importance of considering sex as a biological variable in the investigation of traumatic stress effects on physiology and behavior.
Positive explicit and implicit computational techniques for reaction–diffusion epidemic model of dengue disease dynamics
Authors: Ahmed Nauman , Rafiq Muhammad , Baleanu Dumitru , Alshomrani Ali Saleh , Rehman Muhammad Aziz-ur
Published: May 2020

The aim of this work is to develop a novel explicit unconditionally positivity preserving finite difference (FD) scheme and an implicit positive FD scheme for the numerical solution of dengue epidemic reaction–diffusion model with incubation period of virus. The proposed schemes are unconditionally stable and preserve all the essential properties of the solution of the dengue reaction diffusion model. This proposed FD schemes are unconditionally dynamically consistent with positivity property and converge to the true equilibrium points of dengue epidemic reaction diffusion system. Comparison of the proposed scheme with the well-known existing techniques is also presented. The time efficiency of both the proposed schemes is also compared, with the two widely used techniques.
An ensemble-learning method for potential traffic hotspots detection on heterogeneous spatio-temporal data in highway domain
Authors: Ding Weilong , Xia Yanqing , Wang Zhe , Chen Zhenyu , Gao Xingyu
Published: May 2020

Inter-city highway plays an important role in modern urban life and generates sensory data with spatio-temporal characteristics. Its current situation and future trends are valuable for vehicles guidance and transportation security management. As a domain routine analysis, daily detection of traffic hotspots faces challenges in efficiency and precision, because huge data deteriorates processing latency and many correlative factors cannot be fully considered. In this paper, an ensemble-learning based method for potential traffic hotspots detection is proposed. Considering time, space, meteorology, and calendar conditions, daily traffic volume is modeled on heterogeneous data, and trends predictive error can be reduced through gradient boosting regression technology. Using real-world data from one Chinese provincial highway, extensive experiments and case studies show our methods with second-level executive latency with a distinct improvement in predictive precision.
Screening for triazole resistance in clinically significant Aspergillus species; report from Pakistan
Authors: Moin Safia , Farooqi Joveria , Jabeen Kauser , Laiq Sidra , Zafar Afia
Published: May 2020

Background

Burden of aspergillosis is reported to be significant from developing countries including those in South Asia. The estimated burden in Pakistan is also high on the background of tuberculosis and chronic lung diseases. There is concern for management of aspergillosis with the emergence of azole resistant Aspergillus species in neighbouring countries in Central and South Asia.

Hence the aim of this study was to screen significant Aspergillus species isolates at the Microbiology Section of Aga Khan Clinical Laboratories, Pakistan, for triazole resistance.

Methods

A descriptive cross-sectional study, conducted at the Aga Khan University Laboratories, Karachi, from September 2016–May 2019. One hundred and fourteen, clinically significant Aspergillus isolates [A. fumigatus (38; 33.3%), A. flavus (64; 56.1%), A. niger (9; 7.9%) A. terreus (3; 2.6%)] were included. The clinical spectrum ranged from invasive aspergillosis (IA) (n = 25; 21.9%), chronic pulmonary aspergillosis (CPA) (n = 58; 50.9%), allergic bronchopulmonary aspergillosis (ABPA) (n = 4; 3.5%), severe asthma with fungal sensitization (SAFS) (n = 4; 3.5%), saprophytic tracheobronchial aspergillosis (n = 23; 20.2%). Screening for triazole resistance was performed by antifungal agar screening method. The minimum inhibitory concentration (MIC) of 41 representative isolates were tested and interpreted according to the Clinical and Laboratory Standards Institute broth microdilution method.

Results

All the isolates were triazole-susceptible on agar screening. MICs of three azole antifungals for 41 tested isolates were found to be ≤1 ml/L; all isolates tested were categorized as triazole-susceptible, including 4 isolates from patients previously on triazole therapy for more than 2 weeks. The minimum inhibitory concentration required to inhibit the growth of 90% organisms (MIC90) of itraconazole, voriconazole and posaconazole of the representative Aspergillus isolates was 1 mg/L, 1 mg/L and 0.5 mg/L, respectively.

Conclusion

Triazole resistance could not be detected amongst clinical Aspergillus isolates from the South of Pakistan. However, environmental strains remain to be tested for a holistic assessment of the situation. This study will set precedence for future periodic antifungal resistance surveillance in our region on Aspergillus isolates.
CXCL9 and CXCL10 display an age-dependent profile in Chagas patients: a cohort study of aging in Bambui, Brazil
Authors: de Araújo Fernanda Fortes , Lima Torres Karen Cecília , Viana Peixoto Sérgio , Pinho Ribeiro Antonio Luiz , Vaz Melo Mambrini Juliana , Bortolo Rezende Vitor , Lima Silva Maria Luiza , Loyola Filho Antônio Ignácio , Teixeira-Carvalho Andréa , Lima-Costa Maria Fernanda , Martins-Filho Olindo Assis
Published: May 2020

Background

Chagas disease is endemic in Latin America and still represents an important public health problem in the region. Chronic cardiomyopathy is the most significant chronic form due to its association with morbidity and mortality. The last decade has seen increasing evidence that inflammatory cytokines and chemokines are responsible for the generation of inflammatory infiltrate and tissue damage, with chronic chagasic cardiomyopathy patients presenting a pro-inflammatory immune response. Although studies have evaluated the role of chemokines in experimental T. cruzi infection, few have addressed their systemic profile, especially for human infection and in aging populations. The present work aimed to use the data from a large population based study of older adults, conducted in an endemic area for Chagas disease, to examine the association between serum levels of cytokines and chemokines, T. cruzi infection and electrocardiogram (ECG) abnormality.

Methods

The present work evaluated serum levels of CCL2, CXCL9, CXCL10, CCL5, CXCL8, IL-1β, IL-6, TNF, IL-12 and IL-10 by Flow Cytometric Bead Array assay (CBA) and the results expressed in pg/ml. The baseline survey started in January 1st 1997, with 1284 participants of an aged population-based cohort. Participants signed an informed consent at baseline and at each subsequent visit and authorized death certificate and medical records verification.

Results

Our results demonstrated that Chagas disease patients had higher serum levels of CXCL9, CXCL10 and IL-1β and lower serum levels of CCL5 than non-infected subjects. Moreover, our data demonstrated that CXCL9 and CXCL10 increased in an age-dependent profile in Chagas disease patients.

Conclusion

Together, this study provided evidences that serum biomarkers increase along the age continuum and may have potential implications for establishing clinical management protocols and therapeutic intervention in Chagas disease patients.
Does treatment method matter? A meta-analysis of the past 20 years of research on therapeutic interventions for self-harm and suicidal ideation in adolescents
Authors: Kothgassner Oswald D. , Robinson Kealagh , Goreis Andreas , Ougrin Dennis , Plener Paul L.
Published: May 2020

Background

Self-harm is a clinically relevant and prevalent behaviour which peaks in adolescence. Given the high prevalence of self-harm, the high levels of psychiatric comorbidity, and its role as a risk factor for suicide, delivering evidence-based care is critical.

Methods

We conducted a systematic review and meta-analysis of the literature on treating self-harm in adolescents (12–19 years) published in the last 20 years, identifying 25 randomised controlled trials. We calculated the effect of treatment interventions relative to active control conditions in reducing self-harm, suicidal ideation and depressive symptoms.

Results

Overall, treatment interventions fared slightly better than active controls in decreasing self-harm (d = 0.13, 95% CI 0.04–0.22,p = .004), suicidal ideation (d = 0.31, 95% CI 0.12–0.50,p = .001) and depressive symptoms (d = 0.22, 95% CI 0.07–0.38,p = .006). Subgroup analysis of specific therapies revealed moderate effects of DBT-A in reducing self-harm (d = 0.51, 95% CI 0.18–0.85,p = .002) and suicidal ideation (d = 0.48, 95% CI 0.17–0.80,p = .003), as well as moderate effects of family-centred therapy in the treating suicidal ideation (d = 0.58, 95% CI 0.01–1.15,p = .049).

Conclusions

The findings of our meta-analysis indicate that, overall, currently available treatments are effective in treating self-harm, suicidal ideation, and depressive symptoms in adolescence. Although the treatment intervention conditions showed only small to moderate effects in comparison to active controls, these differences were statistically significant and are clinically important. Further research is needed to understand the reduction in self-harm within active controls, which may arise due to the natural course of self-harm, or the potential efficacy of treatment as usual and enhanced usual care. Given the significant reduction of self-harm in active control conditions, delivering effective care to a large number of adolescents with self-harm may require developing stepped-care models in clinical practice. Expensive and poorly available treatments should be targeted at young people who most need them.
Job satisfaction among pharmacy professionals working in public hospitals and its associated factors, eastern Ethiopia
Authors: Ayele Yohanes , Hawulte Behailu , Feto Tilayie , Basker G. Vijai , Bacha Yadeta Dessie
Published: May 2020

Background

Poor job satisfaction has been associated with less productivity and high staff turnover. Various factors are thought to contribute for job dissatisfaction among pharmacy professionals and very limited studies have been conducted in eastern part of Ethiopia. Therefore, the current study was aimed to assess the level of job satisfaction among pharmacy professionals and its predictors.

Methods

A cross-sectional study was conducted among 232 pharmacy professionals to assess level of job satisfaction in public hospitals located in the eastern Ethiopia. The data were collected using self- administered semi-structured questionnaires. Data were entered into Epi-Data version 3.1 and exported to STATA version 14.2 for analysis. Associations between the dependent and independent variables were assessed by multivariate analysis using an Adjusted Odds Ratio (AOR) at a 95% confidence interval (CI) and p-value less than 0.05 was considered as significant.

Results

A total 220 questionnaires were found complete and included in the analysis. The mean age of participants was 27.6(SD + 4.1). More than half of the respondents (55.4%) had a bachelor degree and the majority (86.4%) were working less than 40 h per week, mostly in dispensing units (75.4%). About one third of the participants (32.7, 95% CI; 26.8–39.2) were found to be satisfied with their job. Age category of 20 to 25 years in reference to age greater than 30 years (AOR = 3.5, 95% CI; 1.1–9.7), holding a bachelor degree in reference to having diploma (AOR = 4.2, 95% CI; 1.8–10.00), working for more than 40 h per week (AOR = 6.2, 95% CI, 2.4–16), and working in dispensing units (AOR = 2.4, 95% CI; 1.1–5.5) were found to have strong association with job dissatisfaction.

Conclusion

In this study, the job satisfaction levels of pharmacy professionals were found to be very low. The age category of 20 to 25, holding a bachelor degree, working for more than 40 h per week, and working in dispensing unit were found to be strong predictors of job dissatisfaction. Hence, pharmacy directors and hospital administrators should work to reduce unnecessary workload on the staffs and create good working climate.
Frictional and structural controls of seismic super-cycles at the Japan trench
Authors: Barbot Sylvain
Published: May 2020

The diverse mechanical behaviors of subduction zones during the seismic cycle emerge from the nonlinear dynamics of a complex mechanical system with interacting brittle and ductile deformation. The 2011 Tohoku mega-quake represents the culmination of a super-cycle of partial and full ruptures of the plate interface, but the physical controls on the down-dip segmentation of the megathrust remain unclear. Here, we propose a two-dimensional rheological model of the Japan trench to explain the variability of earthquake size at the Miyagi section, in northern Honshu, during the last century. We simulate seismicity in a continuum with a physics-based rate- and state-dependent constitutive law for fault slip, producing aperiodic earthquake sequences with a power-law distribution of rupture sizes. Although some partial ruptures of the megathrust are the result of self-emergent behavior, others are structurally controlled. The 1978 and 2005 Mj$$\sim$$∼7 interplate earthquakes took place in a metamorphic belt in the mantle wedge corner bounded up-dip by the arc Moho that constitutes a permanent structural boundary. We explain the succession of the great 1981 Mw = 7.1 and 2003 Mw = 6.9 earthquakes within the forearc and the 2011 giant earthquake as the natural response of a large continuously velocity-weakening fault with a small nucleation size. The shallow segment below the frontal prism only slips in giant through-going ruptures that unzip the whole velocity-weakening interface. The model consistently explains the size, recurrence time, and hypocenter location of historical earthquakes in the Miyagi segment, the slow-slip and foreshock preparatory phase of the 2011 Tohoku earthquake, the large slip near the trench during the giant rupture, and important features of its postseismic deformation. The complex patterns of seismicity at the Japan trench can be better understood by assimilating geological and geophysical observations at various periods of the seismic cycle within an explicative physical framework.
Personalized radiation dosimetry for PRRT—how many scans are really required?
Authors: Freedman Nanette , Sandström Mattias , Kuten Jonathan , Shtraus Natan , Ospovat Inna , Schlocker Albert , Even-Sapir Einat
Published: May 2020

Purpose

Over recent years, peptide receptor radiotherapy (PRRT) has been recognized as an effective treatment for patients with metastatic neuroendocrine tumors (NETs). Personalized dosimetry can contribute to improve the outcome of peptide receptor radiotherapy (PRRT) in patients with metastatic NETs. Dosimetry can aid treatment planning, ensuring that absorbed dose to vulnerable normal organs (kidneys and bone marrow) does not exceed safe limits over serial treatments, and that absorbed dose to tumor is sufficient. Absorbed dose is estimated from a series of post-treatment SPECT/CT images. Total self-dose is proportional to the integral under the time activity concentration curve (TACC). Method dependence of image-based absorbed dose calculations has been previously investigated, and we set out here to extend previous work by examining implications of number of data points in the TACC and the numerical integration methods used in estimating absorbed dose.

Methods

In this retrospective study, absorbed dose estimates and effective half-lives were calculated by fitting curves to TACCs for normal organs and tumors in 30 consecutive patients who underwent a series of 4 post-treatment SPECT/CT scans at 4 h, 24 h, 4–5 days, and 1 week following 177Lu-DOTATATE PRRT. We examined the effects of including only 2 or 3 rather than all 4 data points in the TACC, and the effect of numerical integration method (mono-exponential alone or in combination with trapezoidal rule) on the absorbed dose and half-life estimates. Our current method is the combination of trapezoidal rule over the first 24 h, with mono-exponential fit thereafter extrapolated to infinity. The other methods were compared to this current method.

Results

Differences in absorbed dose and effective half-life between the current method and estimates based only on the second, third, and fourth scans were very small (mean differences < 2.5%), whereas differences between the current method and 4-point mono-exponential fit were higher (mean differences < 5%) with a larger range. It appears that in a 4-point mono-exponential fit the early (4 h) time point may skew results, causing some large errors. Differences between the current method and values based on only 2 time points were relatively small (mean differences < 3.5%) when the 24 h and 1 week scans were used, but when the 24 h and 4–5 days scans, or the 4–5 days and 1 week scans were used, differences were greater.

Conclusion

This study indicates that for 177Lu-DOTATATE PRRT, accurate estimates of absorbed dose for organs and tumors may be estimated from scans at 24 h, 72 h, and 1 week post-treatment without an earlier scan. It may even be possible to cut out the 72 h scan, though the uncertainty increases. However, further work on more patients is required to validate this.
Implementation of policy, system and environment changes in early childhood education settings
Authors: Farewell Charlotte V. , Powers Jamie N. , Maiurro Emily , Scarbro Sharon , Quinlan Jennie , Puma Jini
Published: May 2020

Background

Changing Policy, System, and Environmental features focused on physical activity and healthy eating behaviors can play a key role in obesity prevention strategies in early childhood education settings because of their broad reach and because they can be sustained over time. The primary aims of this study were to examine the implementation and sustainability of health-promoting PSE changes after facilitation of an innovative strategic planning process in child care settings.

Methods

The evidence-based policy, system, and environment change process is a strategic planning tool derived from intervention mapping that involves convening interdisciplinary wellness teams at child care settings to implement healthy eating and physical activity-related policy changes. The process was conducted with 43 wellness teams representing 68 child care centers.

Results

The average number of health-promoting evidence-based changes implemented across all child care centers was 5.07; the most common type of changes were environment changes. Overall, 42% of changes were partially implemented and 47% of changes were fully implemented at 6 months. Head Start wellness teams implemented 1.52 fewer health-promoting changes compared to private fee-based wellness teams (p < .05).

Conclusions

Identifying health-promoting policy, system and environment changes that are most readily implemented and sustained in child care centers can inform systems-level interventions and resource allocation related to early childhood obesity. This strategic planning process is a successful tool to translate sustainable changes related to healthy eating and physical activity, improve the quality rating of diverse child care centers, and promote healthy behaviors in early childhood.
Perceived infection transmission routes, infection control practices, psychosocial changes, and management of COVID-19 infected healthcare workers in a tertiary acute care hospital in Wuhan: a cross-sectional survey
Authors: Jin Ying-Hui , Huang Qiao , Wang Yun-Yun , Zeng Xian-Tao , Luo Li-Sha , Pan Zhen-Yu , Yuan Yu-Feng , Chen Zhi-Min , Cheng Zhen-Shun , Huang Xing , Wang Na , Li Bing-Hui , Zi Hao , Zhao Ming-Juan , Ma Lin-Lu , Deng Tong , Wang Ying , Wang Xing-Huan
Published: May 2020

Background

Many healthcare workers were infected by coronavirus disease 2019 (COVID-19) early in the epidemic posing a big challenge for epidemic control. Hence, this study aims to explore perceived infection routes, influencing factors, psychosocial changes, and management procedures for COVID-19 infected healthcare workers.

Methods

This is a cross-sectional, single hospital-based study. We recruited all 105 confirmed COVID-19 healthcare workers in the Zhongnan Hospital of Wuhan University from February 15 to 29, 2020. All participants completed a validated questionnaire. Electronic consent was obtained from all participants. Perceived causes of infection, infection prevention, control knowledge and behaviour, psychological changes, symptoms and treatment were measured.

Results

Finally, 103 professional staff with COVID-19 finished the questionnaire and was included (response rate: 98.1%). Of them, 87 cases (84.5%) thought they were infected in working environment in hospital, one (1.0%) thought their infection was due to the laboratory environment, and 5 (4.9%) thought they were infected in daily life or community environment. Swab of throat collection and physical examination were the procedures perceived as most likely causing their infection by nurses and doctors respectively. Forty-three (41.8%) thought their infection was related to protective equipment, utilization of common equipment (masks and gloves). The top three first symptoms displayed before diagnosis were fever (41.8%), lethargy (33.0%) and muscle aches (30.1%). After diagnosis, 88.3% staff experienced psychological stress or emotional changes during their isolation period, only 11.7% had almost no emotional changes. Arbidol (Umifenovir; an anti-influza drug; 69.2%) was the drug most commonly used to target infection in mild and moderate symptoms.

Conclusion

The main perceived mode of transmission was not maintaining protection when working at a close distance and having intimate contact with infected cases. Positive psychological intervention is necessary.
Mucosa-associated lymphoid tissue (MALT) lymphoma developing in ectopic mediastinal thyroid tissue: a case report
Authors: Uchida Naotaka , Yoshida Manabu
Published: May 2020

Background

Normally located in the neck, ectopic mediastinal thyroid tissue consists of very rare ectopic thyroid tissue that does not connect to the thyroid gland. A patient with mucosa-associated lymphoid tissue (MALT) lymphoma that has developed in mediastinal thyroid tissue, to our best knowledge, has not been previously reported.

Case presentation

A 67-year-old woman presented with a superior mediastinal mass that was revealed by chest computed tomography (CT), an optional examination she hoped, during a medical checkup. Contrast-enhanced CT scan performed in our hospital for close examination confirmed the presence of a 2 × 1.3 cm poorly enhanced mass anterior to the trachea during the arterial phase. Magnetic resonance imaging depicted low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. I-131 meta-iodobenzylguanidine did not accumulate in the mass. Serum levels of interleukin-2 receptor, catecholamine, and anti-acetylcholine receptor antibody were within the normal range. The mass was resected through a transverse neck incision for the diagnosis and treatment. The histopathological diagnosis of the specimen was ectopic mediastinal thyroid tissue associated with MALT lymphoma and chronic thyroiditis. Immunoglobulin heavy chain class switch recombination was identified. Fine-needle aspiration biopsy of the cervical thyroid showed chronic thyroiditis but not lymphoma. The patient’s postoperative thyroid function was normal. To date, the patient’s recovery has been uneventful, and she is being monitored without further treatment.

Conclusion

We treated the patient with MALT lymphoma that developed in ectopic mediastinal thyroid tissue. This novel case illustrates a new differential diagnosis associated with ectopic mediastinal thyroid tissue.
A study protocol to assess the feasibility of conducting an evaluation trial of the ADVANCE integrated intervention to address both substance use and intimate partner abuse perpetration to men in substance use treatment
Authors: Gilchrist Gail , Landau Sabine , Radcliffe Polly , McMurran Mary , Feder Gene , Easton Caroline , Parrott Steve , Kirkpatrick Sara , Henderson Juliet , Potts Laura , Stephens-Lewis Danielle , Johnson Amy , Love Beverly , Halliwell Gemma , Dheensa Sandi , Berbary Cassandra , Li Jinshuo , Strang John , Gilchrist Elizabeth
Published: May 2020

Background

Strong evidence exists that substance use is a contributory risk factor for intimate partner abuse (IPA) perpetration. Men in substance use treatment are more likely to perpetrate IPA than men from the general population. Despite this, referral pathways are lacking for this group. This trial will assess the feasibility of conducting an evaluation trial of a tailored integrated intervention to address substance use and IPA perpetration to men in substance use treatment.

Methods/design

ADVANCE is a multicentre, parallel-group individually randomised controlled feasibility trial, with a nested formative evaluation, comparing an integrated intervention to reduce IPA + substance use treatment as usual (TAU) to TAU only. One hundred and eight men who have perpetrated IPA in the past 12 months from community substance use treatment in London, the West Midlands, and the South West will be recruited. ADVANCE is a manualised intervention comprising 2–4 individual sessions (2 compulsory) with a keyworker to set goals, develop a personal safety plan and increase motivation and readiness, followed by a 12-session weekly group intervention delivered in substance use services. Men will be randomly allocated (ratio 1:1) to receive the ADVANCE intervention + TAU or TAU only. Men’s female (ex) partners will be invited to provide outcome data and offered support from integrated safety services (ISS). Regular case management meetings between substance use and ISS will manage risk. Outcome measures will be obtained at the end of the intervention (approximately 4 months post-randomisation) for all male and female participants. The main objective of this feasibility trial is to estimate parameters required for planning a definitive trial including rates of consent, recruitment, and follow-up by site and group allocation. Nested formative evaluation including focus groups and in-depth interviews will explore the intervention’s acceptability to participants, group facilitators, keyworkers and ISS workers. Secondary outcomes include substance use, IPA, mental health, self-management, health and social care service use, criminal justice contacts, and quality of life.

Discussion

Findings from this feasibility trial will inform the design of a multicentre randomised controlled trial evaluating the efficacy and cost-effectiveness of the ADVANCE intervention for reducing IPA and improving the well-being of female (ex)partners.

Trial registration

ISRCTN79435190.
Landiolol hydrochloride for prevention of atrial fibrillation during esophagectomy: a randomized controlled trial
Authors: Aoki Yoshitaka , Kawasaki Yohei , Ide Kazuki , Shimizu Yuichiro , Sato Shinsuke , Yokoyama Junichiro
Published: May 2020

Introduction

Landiolol hydrochloride reduces the incidence of perioperative atrial fibrillation (AF) in cardiac surgery; however, little evidence is available regarding its effects in other types of surgery, including esophagectomy. We assessed the hypothesis that landiolol reduces perioperative AF and other complications associated with esophagectomy.

Methods

This single-center, randomized, double-blind, parallel-group study enrolled patients scheduled for esophagectomy. Patients were divided into those given landiolol at 3 μg/kg/min or placebo for 24 h. The primary outcome was the proportion of patients who developed AF within 96 h starting at 9:00 am on the day of surgery. The secondary outcomes were the proportion of patients whose AF appeared within 24 h, other complications based on the Clavien–Dindo classification, and the intensive care unit and hospital stays.

Results

Despite early study termination, 80 patients were screened, and 56 were enrolled (28/group) from September 2016 to June 2018. AF occurred within 96 h of surgery in six (21.4%) patients in the landiolol group and five (17.9%) patients in the placebo group (odds ratio, 1.26; 95% confidence interval, 0.33–4.7) and within 24 h of surgery in three (10.7%) patients in the landiolol group and two (7.1%) patients in the placebo group. There were no significant differences in the incidence of complications or in the number of intensive care unit or hospital stays between the groups.

Conclusion

Although our small sample size prevents definitive conclusions, landiolol might not reduce the occurrence of AF or other complications.

Trial registration

UMIN, UMIN000024040. Registered 13 September 2016, http://www.umin.ac.jp/ctr/index/htm
Evaluation of 511 keV photon attenuation by a novel 32-channel phased array prospectively designed for cardiovascular hybrid PET/MRI imaging
Authors: Farag Adam , Thompson R. Terry , Thiessen Jonathan D. , Biernaski Heather , Prato Frank S. , Théberge Jean
Published: May 2020

Background

Simultaneous cardiovascular imaging with positron emission tomography (PET) and magnetic resonance imaging (MRI) requires tools such as radio frequency (RF) phased arrays to achieve high temporal and spatial resolution in the MRI, as well as accurate quantification of PET. Today, high-density phased arrays (> 16 channels) used for cardiovascular PET/MRI are not designed to achieve low PET attenuation, and correcting the PET attenuation they cause requires off-line reconstruction, extra time and resources.

Purpose

Motivated by previous work assessing the MRI performance of a novel prospectively designed 32-channel phased array, this study assessed the PET image quality with this array in place. Guided by NEMA standards, PET performance was measured using global PET counts, regional background variation (BV), contrast recovery (CR) and contrast-to-noise ratio (CNR) for both the novel array and standard arrays (mMR 12-channel and MRI 32-channel). Nonattenuation-corrected (NAC) data from all arrays (and each part of the array) were processed and compared to no-array, and relative percentage difference (RPD) of the global means was estimated and reported for each part of the arrays. Attenuation correction (AC) of PET images (water in the phantom) using two approaches, MR-based AC map (MRAC) and dual-energy CT-based map (DCTAC), was performed, and RPD compared for each part of the arrays. Percent mean attenuation within regions of interests of the phantom images from each array were compared using a two-way analysis of variance (ANOVA).

Results

The NAC data of the anterior part of the novel array recorded the least PET attenuation (≤ 2%); while the full novel array (anterior and posterior together) AC data, produced by MRAC and DCTAC approaches, recorded attenuation of 1.5 ± 2.9% and 0.0 ± 2.5%, respectively. The novel array PET count loss was significantly lower (p = 0.001) than those caused by the standard arrays.

Conclusions

Results of this novel 32-channel cardiac array PET performance evaluation, together with its previously reported MRI performance assessment, suggest the novel array to be a strong alternative to the standard arrays currently used for cardiovascular hybrid PET/MRI imaging. It enables accurate PET quantification and high-temporal and spatial resolution for MR imaging.
Isolation and efficacy of native chitinolytic rhizobacteria for biocontrol activities against Fusarium wilt and plant growth promotion in pigeon pea (Cajanus cajan L.)
Authors: Dukare Ajinath , Paul Sangeeta , Arambam Asha
Published: May 2020

The present study aimed to identify, characterize, and evaluate native chitinolytic rhizobacteria as biocontrol potential against pigeon pea wilt disease, caused by Fusarium udum. A total of 53 isolated rhizobacteria was evaluated for their chitinolytic potential and possession of different antifungal traits. From the successive in vitro experiments and in vivo bioassay, 2 promising bacterial strains (NS-1 and NS-22) that exhibited strong chitinolytic activities and mycolytic action were biochemically characterized and identified as Pseudomonas spp. NS-1 (NCBI GenBank accession number- KT175909) and Bacillus spp. NS-22 (NCBI GenBank accession number-MH425454), using 16S rDNA sequencing. In planta, disease severities for Pseudomonas spp. NS-1- and Bacillus spp. NS-22-treated plants were only about 14.62 and 23.08%, respectively, as compared to pathogen-only control (67.34%) at the end of 4 weeks. Additionally, these bacteria improved plant germination and fresh and dry plant biomasses under pathogen-challenged conditions. Further, both the strains were able to cause a considerable amount of reduction in the fungal biomass, as revealed by bacteria-pathogen interaction studies in liquid culture. Scanning electron microscopy studies also revealed the strong antifungal activities of these 2 chitinolytic bacteria on the pathogen hyphae and mycelia. The curling, bulging, breakdown, and other dysfunctionalities in fungal hyphae were induced by the biocontrol bacteria. In nutshell, the present exclusive investigation demonstrated mycolytic potential and biocontrol prospects of the 2 promising bacteria (Pseudomonas spp. NS-1 and Bacillus spp. NS-22) for the sustainable Fusarium wilt management and as a phytostimulator in pigeon pea.