bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyruvate dehydrogenase complex deficiency: updating the clinical, metabolic and mutational landscapes in a cohort of Portuguese patients
Authors: Pavlu-Pereira Hana , Silva Maria João , Florindo Cristina , Sequeira Sílvia , Ferreira Ana Cristina , Duarte Sofia , Rodrigues Ana Luísa , Janeiro Patrícia , Oliveira Anabela , Gomes Daniel , Bandeira Anabela , Martins Esmeralda , Gomes Roseli , Soares Sérgia , Tavares de Almeida Isabel , Vicente João B. , Rivera Isabel
Published: October 2020

Background

The pyruvate dehydrogenase complex (PDC) catalyzes the irreversible decarboxylation of pyruvate into acetyl-CoA. PDC deficiency can be caused by alterations in any of the genes encoding its several subunits. The resulting phenotype, though very heterogeneous, mainly affects the central nervous system. The aim of this study is to describe and discuss the clinical, biochemical and genotypic information from thirteen PDC deficient patients, thus seeking to establish possible genotype–phenotype correlations.

Results

The mutational spectrum showed that seven patients carry mutations in the PDHA1 gene encoding the E1α subunit, five patients carry mutations in the PDHX gene encoding the E3 binding protein, and the remaining patient carries mutations in the DLD gene encoding the E3 subunit. These data corroborate earlier reports describing PDHA1 mutations as the predominant cause of PDC deficiency but also reveal a notable prevalence of PDHX mutations among Portuguese patients, most of them carrying what seems to be a private mutation (p.R284X). The biochemical analyses revealed high lactate and pyruvate plasma levels whereas the lactate/pyruvate ratio was below 16; enzymatic activities, when compared to control values, indicated to be independent from the genotype and ranged from 8.5% to 30%, the latter being considered a cut-off value for primary PDC deficiency. Concerning the clinical features, all patients displayed psychomotor retardation/developmental delay, the severity of which seems to correlate with the type and localization of the mutation carried by the patient. The therapeutic options essentially include the administration of a ketogenic diet and supplementation with thiamine, although arginine aspartate intake revealed to be beneficial in some patients. Moreover, in silico analysis of the missense mutations present in this PDC deficient population allowed to envisage the molecular mechanism underlying these pathogenic variants.

Conclusion

The identification of the disease-causing mutations, together with the functional and structural characterization of the mutant protein variants, allow to obtain an insight on the severity of the clinical phenotype and the selection of the most appropriate therapy.
The psychosocial profile of family caregivers of children with chronic diseases: a cross-sectional study
Authors: Toledano-Toledano Filiberto , Luna David
Published: October 2020

Background

A family caregiver is defined as a person who has a significant emotional bond with the patient; this caregiver is a family member who is a part of the patient’s family life cycle; offers emotional-expressive, instrumental, and tangible support; and provides assistance and comprehensive care during the chronic illness, acute illness, or disability of a child, adult, or elderly person. The objectives of this study were to identify the psychosocial profiles of family caregivers of children with chronic diseases and to establish the relationship between these profiles and sociodemographic variables.

Methods

A cross-sectional study was conducted involving 401 family caregivers of children with chronic diseases at the National Institute of Health in Mexico City. The participants responded to the Sociodemographic Variables Questionnaire (Q-SV) for research on family caregivers of children with chronic disease and a battery of 7 instruments that examined anxiety, caregiver burden, family support, depression, resilience, parental stress, and the World Health Organization Well-Being Index.

Results

A hierarchical cluster analysis and its confirmation through a nonhierarchical cluster analysis confirmed two profiles of caregivers of pediatric patients with chronic diseases. Profile 1, called Vulnerability of family caregivers, is characterized by high levels of anxiety, depression, parental stress and caregiver burden, accompanied by low levels of family support, resilience, and well-being. Profile 2, called Adversity of family caregivers, shows an inverse pattern, with high levels of family support, resilience, and well-being and low levels of anxiety, depression, parental stress and caregiver burden. The sociodemographic characteristics are similar for both profiles, with the exception of the caregiver’s family type. Profile 1 shows more single-parent caregivers, while profile 2 includes more caregivers with a nuclear family. However, the type of family did not reach significance for predicting the caregiver’s profile in a bivariate logistic regression model.

Conclusions

The psychosocial profile of family caregivers of children with chronic diseases can be structured according to their psychosocial characteristics. Although no causal factors were detected that define criteria for belonging to one or another profile, the characteristics identified for each indicate the need for specific and differentiated intervention strategies for families facing adversity, risk and vulnerability during a child’s disease.
Gravitational distribution of regional opening and closing pressures, hysteresis and atelectrauma in ARDS evaluated by electrical impedance tomography
Authors: Scaramuzzo Gaetano , Spinelli Elena , Spadaro Savino , Santini Alessandro , Tortolani Donatella , Dalla Corte Francesca , Pesenti Antonio , Volta Carlo Alberto , Grasselli Giacomo , Mauri Tommaso
Published: October 2020

Background

The physiological behavior of lungs affected by the acute respiratory distress syndrome (ARDS) differs between inspiration and expiration and presents heterogeneous gravity-dependent distribution. This phenomenon, highlighted by the different distribution of opening/closing pressure and by the hysteresis of the pressure–volume curve, can be studied by CT scan, but the technique expose the patient to radiations, cannot track changes during time and is not feasible at the bedside. Electrical impedance tomography (EIT) could help in assessing at the bedside regional inspiratory and expiratory mechanical properties. We evaluated regional opening/closing pressures, hysteresis and atelectrauma during inspiratory and expiratory low-flow pressure–volume curves in ARDS using electrical impedance tomography.

Methods

Pixel-level inspiratory and expiratory PV curves (PVpixel) between 5 and 40 cmH2O were constructed integrating EIT images and airway opening pressure signal from 8 ARDS patients. The lower inflection point in the inspiratory and expiratory PVpixel were used to find opening (OPpixel) and closing (CPpixel) pressures. A novel atelectrauma index (AtI) was calculated as the percentage of pixels opening during the inspiratory and closing during the expiratory PV curves. The maximal hysteresis (HysMax) was calculated as the maximal difference between normalized expiratory and inspiratory PV curves. Analyses were conducted in the global, dependent and non-dependent lung regions.

Results

Gaussian distribution was confirmed for both global OPpixel (r2 = 0.90) and global CPpixel (r2 = 0.94). The two distributions were significantly different with higher values for OPpixel (p < 0.0001). Regional OPpixel and CPpixel distributions were Gaussian, and in the dependent lung regions, both were significantly higher than in the non-dependent ones (p < 0.001). Both AtI and the HysMax were significantly higher in the dependent regions compared to the non-dependent ones (p < 0.05 for both).

Conclusions

Gravity impacts the regional distribution of opening and closing pressure, hysteresis and atelectrauma, with higher values in the dorsal lung. Regional differences between inspiratory and expiratory lung physiology are detectable at the bedside using EIT and could allow in-depth characterization of ARDS phenotypes and guide personalized ventilation settings.

Graphic abstract
Compromised browning plasticity of primary subcutaneous adipocytes derived from overweight Chinese adults
Authors: Qiu Yao , Sun Lizhi , Hu Xiaolin , Zhao Xin , Shi Hongyan , Liu Zhao , Yin Xiao
Published: October 2020

Purpose

People with obesity have a compromised browning capacity of adipose tissue when faced with sympathetic stimuli. This study aimed to determine whether norepinephrine treatment can enhance the induction of precursor cells from human white adipose tissue to differentiate into adipocytes that express key markers of beige adipocytes, and if there is a difference in this capacity between normal weight and overweight individuals.

Methods

Stromal vascular cells derived from subcutaneous white adipose tissue of normal weight and overweight groups were induced to differentiation, with or without norepinephrine, into adipocytes. Oxygen consumption rate, lipolysis, the expression of uncoupling protein 1 and other thermogenic genes were compared between different adiposity and treatment groups.

Results

Peroxisome proliferator activated receptor γ- coactivator-1 alpha (PGC-1 α) and uncoupling protein 1 gene expression increased significantly in the normal weight group, but not in the overweight group, with norepinephrine treatment. The increments of lipolysis and oxygen consumption rate were also higher in adipocytes from the normal weight group with norepinephrine treatment, as compared with those of the overweight group. PR domain containing protein 16 (PRDM 16) gene expression was higher in the normal weight group compared with that in the overweight group, while there were no significant changes found with norepinephrine treatment in either the normal weight or overweight group.

Conclusions

Adipogenic precursor cells derived from overweight individuals were less prone to differentiate into beige-like adipocytes when facing sympathetic stimuli than normal weight ones, resulting in the compromised sympathetic-induced browning capacity in subcutaneous white adipose tissue in overweight individuals, which occurred before the onset of overt obesity.
Effects of a single mental chronometry training session in subacute stroke patients – a randomized controlled trial
Authors: Liepert Joachim , Stürner Jana , Büsching Imke , Sehle Aida , Schoenfeld Mircea A.
Published: October 2020

Background

Motor imagery training might be helpful in stroke rehabilitation. This study explored if a single session of motor imagery (MI) training induces performance changes in mental chronometry (MC), motor execution, or changes of motor excitability.

Methods

Subacute stroke patients (n = 33) participated in two training sessions. The order was randomized. One training consisted of a mental chronometry task, the other training was a hand identification task, each lasting 30 min. Before and after the training session, the Box and Block Test (BBT) was fully executed and also performed as a mental version which served as a measure of MC. A subgroup analysis based on the presence of sensory deficits was performed. Patients were allocated to three groups (no sensory deficits, moderate sensory deficits, severe sensory deficits). Motor excitability was measured by transcranial magnetic stimulation (TMS) pre and post training. Amplitudes of motor evoked potentials at rest and during pre-innervation as well as the duration of cortical silent period were measured in the affected and the non-affected hand.

Results

Pre-post differences of MC showed an improved MC after the MI training, whereas MC was worse after the hand identification training. Motor execution of the BBT was significantly improved after mental chronometry training but not after hand identification task training. Patients with severe sensory deficits performed significantly inferior in BBT execution and MC abilities prior to the training session compared to patients without sensory deficits or with moderate sensory deficits. However, pre-post differences of MC were similar in the 3 groups. TMS results were not different between pre and post training but showed significant differences between affected and unaffected side.

Conclusion

Even a single training session can modulate MC abilities and BBT motor execution in a task-specific way. Severe sensory deficits are associated with poorer motor performance and poorer MC ability, but do not have a negative impact on training-associated changes of mental chronometry. Studies with longer treatment periods should explore if the observed changes can further be expanded.

Trial registration

DRKS, DRKS00020355, registered March 9th, 2020, retrospectively registered
Reliability and minimal detectable change of the ‘Imperial Spine’ marker set for the evaluation of spinal and lower limb kinematics in adults
Authors: Deane J. A. , Papi E. , Phillips A. T. M. , McGregor A. H.
Published: October 2020

Objectives

As a step towards the comprehensive evaluation of movement in patients with low back pain, the aim of this study is to design a marker set (three rigid segment spine, pelvic and lower limb model) and evaluate the reliability and minimal detectable change (MDC) of this marker set in healthy adults during gait and sit to stand (STS) tasks using three dimensional motion capture.

Results

The ‘Imperial Spine’ marker set was used to assess relative peak angles during gait and STS tasks using the minimum recommended sample size (n = 10) for reliability studies with minimum Intraclass Correlation Coefficient (ICC) of 0.70, optimum ICC 0.90 and 9 trials replicated per subject per task. Intra- and inter-tester reliability between an experienced and inexperienced user was examined. ICC, mean, standard error (SEM), Bland Altman 95% limits of agreement (LOA) and MDC were computed.

ICC values demonstrated excellent intra- and inter-tester reliability in both tasks, particularly in the sagittal plane (majority ICCs > 0.80). SEM measurements were lower in gait (0.8–5.5°) than STS tasks (1°-12.6°) as were MDC values. LOA demonstrated good agreement. The ‘Imperial Spine’ marker set is reliable for use in healthy adults during functional tasks. Future evaluation in patients is required.
Immediate impact of stay-at-home orders to control COVID-19 transmission on mental well-being in Bangladeshi adults: Patterns, Explanations, and future directions
Authors: Ali Mohammad , Ahsan Gias U. , Khan Risliana , Khan Hasinur Rahman , Hossain Ahmed
Published: October 2020

Objective

We aim to evaluate the immediate impacts of COVID-19 stay-at-home orders on the mental well-being of Bangladeshi adults. We recruited 1404 healthy adults following the Bangladesh government's lockdown announcement. A questionnaire comprising the Warwick Edinburgh Mental Well-being Scale was used to define mental health.

Results

The overall mean score for well-being was 42.4, indicating that 51.9% of adults suffered from poor mental health. And within that 48% of males and 57% of females were depressed. The mean scores for government workers, unemployed workers, and business employees were 45.1, 39.6, and 39.5, respectively. Confounding adjustments in multivariable linear regression models revealed that married women, unemployed and business communities, and individuals returning to villages were heavily depressed. Stay-at-home orders had significant repercussions on mental health and created a gender disparity in depression among adults. Suggestions include promoting mental health for women, unemployed, and business individuals. Married women need to be taken into special consideration as their mental well-being is worse. Older people (50 years of age and over) reported a high day-to-day variation in their mental health. These results should be factored in when discussing the mental health of adults and communities to cope with quarantine.
Genetic and environmental causes of variation in epigenetic aging across the lifespan
Authors: Li Shuai , Nguyen Tuong L. , Wong Ee Ming , Dugué Pierre-Antoine , Dite Gillian S. , Armstrong Nicola J. , Craig Jeffrey M. , Mather Karen A. , Sachdev Perminder S. , Saffery Richard , Sung Joohon , Tan Qihua , Thalamuthu Anbupalam , Milne Roger L. , Giles Graham G. , Southey Melissa C. , Hopper John L.
Published: October 2020

Background

DNA methylation-based biological age (DNAm age) is an important biomarker for adult health. Studies in specific age ranges have found widely varying results about its genetic and environmental causes of variation. However, these studies are not able to provide a comprehensive view of the causes of variation over the lifespan.

Results

In order to investigate the genetic and environmental causes of DNAm age variation across the lifespan, we pooled genome-wide DNA methylation data for 4217 people aged 0–92 years from 1871 families. DNAm age was calculated using the Horvath epigenetic clock. We estimated familial correlations in DNAm age for monozygotic (MZ) twin, dizygotic (DZ) twin, sibling, parent–offspring, and spouse pairs by cohabitation status. Genetic and environmental variance components models were fitted and compared. We found that twin pair correlations were − 0.12 to 0.18 around birth, not different from zero (all P > 0.29). For all pairs of relatives, their correlations increased with time spent living together (all P < 0.02) at different rates (MZ > DZ and siblings > parent–offspring; P < 0.001) and decreased with time spent living apart (P = 0.02) at similar rates. These correlation patterns were best explained by cohabitation-dependent shared environmental factors, the effects of which were 1.41 (95% confidence interval [CI] 1.16 to 1.66) times greater for MZ pairs than for DZ and sibling pairs, and the latter were 2.03 (95% CI 1.13 to 9.47) times greater than for parent–offspring pairs. Genetic factors explained 13% (95% CI − 10 to 35%) of variation (P = 0.27). Similar results were found for another two epigenetic clocks, suggesting that our observations are robust to how DNAm age is measured. In addition, results for the other clocks were consistent with there also being a role for prenatal environmental factors in determining their variation.

Conclusions

Variation in DNAm age is mostly caused by environmental factors, including those shared to different extents by relatives while living together and whose effects persist into old age. The equal environment assumption of the classic twin study might not hold for epigenetic aging.
Correction to: Epidermal stem cells in wound healing and their clinical applications
Authors: Yang Ronghua , Liu Fengxia , Wang Jingru , Chen Xiaodong , Xie Julin , Xiong Kun
Published: October 2020

An amendment to this paper has been published and can be accessed via the original article.
Gallium-68 prostate-specific membrane antigen ([68Ga]Ga-PSMA-11) PET for imaging of thyroid cancer: a feasibility study
Authors: Lawhn-Heath Courtney , Yom Sue S. , Liu Chienying , Villanueva-Meyer Javier E. , Aslam Maya , Smith Raven , Narwal Manpreet , Juarez Roxanna , Behr Spencer C. , Pampaloni Miguel Hernandez , Chan Jason W. , Glastonbury Christine M. , Hope Thomas A. , Flavell Robert R.
Published: October 2020

Background

Prostate-specific membrane antigen (PSMA) is expressed in the microvasculature of thyroid cancer. This suggests the potential use of PSMA as a diagnostic agent in patients with aggressive forms of thyroid cancer. The purpose of the current study was to determine the feasibility and utility of [68Ga]Ga-PSMA-11 PET/MRI in thyroid cancer patients.

Methods

Eligible patients for this prospective pilot study were adults with a history of pathology-proven thyroid cancer who had abnormal radiotracer uptake on an 2-[18F]FDG PET and/or 131I scintigraphy performed in the 12 months prior to study enrollment. Patients underwent a [68Ga]Ga-PSMA-11 PET/MRI, and comparison was made to the prior qualifying 2-[18F]FDG PET CT/MRI for lesion location and relative intensity.

Results

Twelve patients underwent [68Ga]Ga-PSMA-11 PET/MRI, one of which was excluded from analysis due to debulking surgery prior to the PSMA PET. Of the remaining patients, 7/11 had differentiated disease (3 papillary, 2 follicular, 2 Hurthle cell) and 4/11 had dedifferentiated disease (2 poorly differentiated papillary, 2 anaplastic). Out of 43 lesions, 41 were visually 2-[18F]FDG positive (uptake greater than background, detection rate 95.3%) and 28 were PSMA positive (uptake greater than background, detection rate 65.1%). Uptake was heterogeneous between patients, and in some cases within patients. 3/11 patients (1 poorly differentiated papillary, 2 follicular) had PSMA uptake which was greater than FDG uptake. For the remaining 8 patients, 2-[18F]FDG uptake was greater than PSMA. Using one eligibility guideline in the prostate cancer literature for PSMA radioligand therapy (RLT), 8/11 could be considered eligible for possible future PSMA RLT. This was not predictable based on thyroid cancer subtype.

Conclusions

[68Ga]Ga-PSMA-11 PET demonstrated lower detection rate when compared to 2-[18F]FDG PET for thyroid cancer lesion visualization. Thyroid cancer subtype alone may not be sufficient to predict PSMA uptake, and radiotracer uptake may vary between patients and even within patients.
Integrating pathology, chromosomal instability and mutations for risk stratification in early-stage endometrioid endometrial carcinoma
Authors: Li Yuan , Li Jiaqi , Guo Ensong , Huang Jia , Fang Guangguang , Chen Shaohua , Yang Bin , Fu Yu , Li Fuxia , Wang Zizhuo , Xiao Rourou , Liu Chen , Huang Yuhan , Wu Xue , Lu Funian , You Lixin , Feng Ling , Xi Ling , Wu Peng , Ma Ding , Sun Chaoyang , Wang Beibei , Chen Gang
Published: October 2020

Background

Risk stratifications for endometrial carcinoma (EC) depend on histopathology and molecular pathology. Histopathological risk stratification lacks reproducibility, neglects heterogeneity and contributes little to surgical procedures. Existing molecular stratification is useless in patients with specific pathological or molecular characteristics and cannot guide postoperative adjuvant radiotherapies. Chromosomal instability (CIN), the numerical and structural alterations of chromosomes resulting from ongoing errors of chromosome segregation, is an intrinsic biological mechanism for the evolution of different prognostic factors of histopathology and molecular pathology and may be applicable to the risk stratification of EC.

Results

By analyzing CIN25 and CIN70, two reliable gene expression signatures for CIN, we found that EC with unfavorable prognostic factors of histopathology or molecular pathology had serious CIN. However, the POLE mutant, as a favorable prognostic factor, had elevated CIN signatures, and the CTNNB1 mutant, as an unfavorable prognostic factor, had decreased CIN signatures. Only if these two mutations were excluded were CIN signatures strongly prognostic for outcomes in different adjuvant radiotherapy subgroups. Integrating pathology, CIN signatures and POLE/CTNNB1 mutation stratified stageIendometrioid EC into four groups with improved risk prognostication and treatment recommendations.

Conclusions

We revealed the possibility of integrating histopathology and molecular pathology by CIN for risk stratification in early-stage EC. Our integrated risk model deserves further improvement and validation.
Fungal and bacterial microbiome dysbiosis and imbalance of trans-kingdom network in asthma
Authors: Huang Chunrong , Yu Youchao , Du Wei , Liu Yahui , Dai Ranran , Tang Wei , Wang Ping , Zhang Chenhong , Shi Guochao
Published: October 2020

Background

Fungal and bacterial microbiota play an important role in development of asthma. We aim to characterize airway microbiome (mycobiome, bacteriome) and functional genes in asthmatics and controls.

Methods

Sputum microbiome of controls, untreated asthma patients and inhaled corticosteroid (ICS) receiving patients was detected using high throughput sequencing. Metagenomic sequencing was used to examine the functional genes of microbiome.

Results

1. Mycobiome: α diversity was lower in untreated asthma group than that in controls. Mycobiome compositions differed among the three groups. Compared with controls, untreated asthma group has higher abundance of Wallemia, Mortierella and Fusarium. Compared with untreated asthma patients, ICS receiving patients has higher abundance of Fusarium and Mortierella, lower frequency of Wallemia, Alternaria and Aspergillus. 2. Bacteriome: α diversity was lower in untreated asthma group than that in controls. There are some overlaps of bacteriome compositions between controls and untreated asthma patients which were distinct from ICS receiving patients. Untreated asthma group has higher Streptococcus than controls. 3. Potential fungal and bacterial biomarkers of asthma: Trametes, Aspergillus, Streptococcus, Gemella, Neisseria, etc. 4. Correlation network: There are dense and homogenous correlations in controls but a dramatically unbalanced network in untreated asthma and ICS receiving patients, which suggested the existence of disease-specific inter-kingdom and intra-kingdom alterations. 5. Metagenomic analysis: functional pathways were associated with the status of asthma, microbiome and functional genes showed different correlations in different environment.

Conclusion

We showed mycobiome and bacteriome dysbiosis in asthma featured by alterations in biodiversity, community composition, inter-kingdom and intra-kingdom network. We also observed several functional genes associated with asthma.
The penetration effect of HMME-mediated low-frequency and low-intensity ultrasound against the Staphylococcus aureus bacterial biofilm
Authors: Wang Tao , Ma Wei , Jiang Zhinan , Bi Liangjia
Published: October 2020

Background

The purpose of this study was to observe the effect of hematoporphyrin monomethyl ether (HMME)-mediated low-frequency and low-intensity ultrasound on mature and stable Staphylococcus aureus (S. aureus) biofilms under different ultrasound parameters.

Methods

The biofilm was formed after 48-h culture with stable concentration of bacterial solution. Different types of ultrasound and time were applied to the biofilm, and the ultrasonic type and time of our experiments were determined when the biofilm was not damaged. The penetration effects of low-frequency and low-intensity ultrasound were decided by the amount of HMME that penetrated into the biofilm which was determined by fluorescence spectrometry.

Results

The destruction of biofilms by pulse waveform was the strongest. Sinusoidal low-frequency and low-intensity ultrasound can enhance the biofilm permeability. For a period of time after the ultrasound was applied, the biofilm permeability increased, however, changes faded away over time.

Conclusions

Low-frequency and low-intensity sinusoidal ultrasound significantly increased the permeability of the biofilms, which was positively correlated with the time and the intensity of ultrasound. Simultaneous action of ultrasound and HMME was the most effective way to increase the permeability of the biofilms.
Geomagnetic core field models and secular variation forecasts for the 13th International Geomagnetic Reference Field (IGRF-13)
Authors: Wardinski I. , Saturnino D. , Amit H. , Chambodut A. , Langlais B. , Mandea M. , Thébault E.
Published: October 2020

Observations of the geomagnetic field taken at Earth’s surface and at satellite altitude are combined to construct continuous models of the geomagnetic field and its secular variation from 1957 to 2020. From these parent models, we derive candidate main field models for the epochs 2015 and 2020 to the 13th generation of the International Geomagnetic Reference Field (IGRF). The secular variation candidate model for the period 2020–2025 is derived from a forecast of the secular variation in 2022.5, which results from a multi-variate singular spectrum analysis of the secular variation from 1957 to 2020.
Driving stress and seismotectonic implications of the 2013 Mw5.8 Awaji Island earthquake, southwestern Japan, based on earthquake focal mechanisms before and after the mainshock
Authors: Imanishi Kazutoshi , Ohtani Makiko , Uchide Takahiko
Published: October 2020

A driving stress of the Mw5.8 reverse-faulting Awaji Island earthquake (2013), southwest Japan, was investigated using focal mechanism solutions of earthquakes before and after the mainshock. The seismic records from regional high-sensitivity seismic stations were used. Further, the stress tensor inversion method was applied to infer the stress fields in the source region. The results of the stress tensor inversion and the slip tendency analysis revealed that the stress field within the source region deviates from the surrounding area, in which the stress field locally contains a reverse-faulting component with ENE–WSW compression. This local fluctuation in the stress field is key to producing reverse-faulting earthquakes. The existing knowledge on regional-scale stress (tens to hundreds of km) cannot predict the occurrence of the Awaji Island earthquake, emphasizing the importance of estimating local-scale (< tens of km) stress information. It is possible that the local-scale stress heterogeneity has been formed by local tectonic movement, i.e., the formation of flexures in combination with recurring deep aseismic slips. The coseismic Coulomb stress change, induced by the disastrous 1995 Mw6.9 Kobe earthquake, increased along the fault plane of the Awaji Island earthquake; however, the postseismic stress change was negative. We concluded that the gradual stress build-up, due to the interseismic plate locking along the Nankai trough, overcame the postseismic stress reduction in a few years, pushing the Awaji Island earthquake fault over its failure threshold in 2013. The observation that the earthquake occurred in response to the interseismic plate locking has an important implication in terms of seismotectonics in southwest Japan, facilitating further research on the causal relationship between the inland earthquake activity and the Nankai trough earthquake. Furthermore, this study highlighted that the dataset before the mainshock may not have sufficient information to reflect the stress field in the source region due to the lack of earthquakes in that region. This is because the earthquake fault is generally locked prior to the mainshock. Further research is needed for estimating the stress field in the vicinity of an earthquake fault via seismicity before the mainshock alone.
Adjoint-based direct data assimilation of GNSS time series for optimizing frictional parameters and predicting postseismic deformation following the 2003 Tokachi-oki earthquake
Authors: Kano Masayuki , Miyazaki Shin’ichi , Ishikawa Yoichi , Hirahara Kazuro
Published: October 2020

Postseismic Global Navigation Satellite System (GNSS) time series followed by megathrust earthquakes can be interpreted as a result of afterslip on the plate interface, especially in its early phase. Afterslip is a stress release process accumulated by adjacent coseismic slip and can be considered a recovery process for future events during earthquake cycles. Spatio-temporal evolution of afterslip often triggers subsequent earthquakes through stress perturbation. Therefore, it is important to quantitatively capture the spatio-temporal evolution of afterslip and related postseismic crustal deformation and to predict their future evolution with a physics-based simulation. We developed an adjoint data assimilation method, which directly assimilates GNSS time series into a physics-based model to optimize the frictional parameters that control the slip behavior on the fault. The developed method was validated with synthetic data. Through the optimization of frictional parameters, the spatial distributions of afterslip could roughly (but not in detail) be reproduced if the observation noise was included. The optimization of frictional parameters reproduced not only the postseismic displacements used for the assimilation, but also improved the prediction skill of the following time series. Then, we applied the developed method to the observed GNSS time series for the first 15 days following the 2003 Tokachi-oki earthquake. The frictional parameters in the afterslip regions were optimized to A–B ~ O(10 kPa), A ~ O(100 kPa), and L ~ O(10 mm). A large afterslip is inferred on the shallower side of the coseismic slip area. The optimized frictional parameters quantitatively predicted the postseismic GNSS time series for the following 15 days. These characteristics can also be detected if the simulation variables can be simultaneously optimized. The developed data assimilation method, which can be directly applied to GNSS time series following megathrust earthquakes, is an effective quantitative evaluation method for assessing risks of subsequent earthquakes and for monitoring the recovery process of megathrust earthquakes.
The role of pregnancy intendedness and prenatal contraceptive counseling on postpartum contraceptive use
Authors: Shreffler Karina M. , Tiemeyer Stacy , Price Jameca R. , Frye Lance T.
Published: October 2020

Background

The study was conducted to prospectively examine how pregnancy intendedness and prenatal provider counseling about postpartum contraceptive options are associated with lack of contraception use at 6 months post-birth (e.g., increased risk for a short interpregnancy interval).

Methods

Logistic regression models were used to examine risk for no postpartum contraception use among a sample of low-income and racially/ethnically diverse women recruited from two metropolitan perinatal clinics in Tulsa, OK.

Results

Women who reported that they were trying to get pregnant or “okay either way” about getting pregnant had significantly lower odds of using contraception at 6 months post childbirth than those who had unintended pregnancies. Having providers who discussed postpartum contraceptive options during pregnancy significantly increased the odds of contraceptive uptake among those who were planning or ambivalent about their pregnancies.

Conclusions

Intentions of a current pregnancy and provider contraceptive counseling matter for postpartum contraceptive use and the associated risk for a short interval subsequent pregnancy. Provider contraceptive counseling that accounts for the intendedness of a current pregnancy may offer a more targeted approach to prevent a short interval subsequent pregnancy.
Longitudinal trajectory analysis of antipsychotic response in patients with schizophrenia: 6-week, randomised, open-label, multicentre clinical trial
Authors: Dai Minhan , Wu Yulu , Tang Yiguo , Yue Weihua , Yan Hao , Zhang Yamin , Tan Liwen , Deng Wei , Chen Qi , Yang Guigang , Lu Tianlan , Wang Lifang , Yang Fude , Zhang Fuquan , Yang Jianli , Li Keqing , Lv Luxian , Tan Qingrong , Zhang Hongyan , Ma Xin , Li Lingjiang , Wang Chuanyue , Ma Xiaohong , Zhang Dai , Yu Hao , Zhao Liansheng , Ren Hongyan , Wang Yingcheng , Hu Xun , Zhang Guangya , Du Xiaodong , Wang Qiang , Li Tao ,   for the Chinese Antipsychotics Pharmacogenomics Consortium
Published: October 2020

Background

Understanding the patterns of treatment response is critical for the treatment of patients with schizophrenia; one way to achieve this is through using a longitudinal dynamic process study design.

Aims

This study aims to explore the response trajectory of antipsychotics and compare the treatment responses of seven different antipsychotics over 6 weeks in patients with schizoprenia (trial registration: Chinese Clinical Trials Registry Identifier: ChiCTR-TRC-10000934).

Method

Data were collected from a multicentre, randomised open-label clinical trial. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up at weeks 2, 4 and 6. Trajectory groups were classified by the method of k-means cluster modelling for longitudinal data. Trajectory analyses were also employed for the seven antipsychotic groups.

Results

The early treatment response trajectories were classified into a high-trajectory group of better responders and a low-trajectory group of worse responders. The results of trajectory analysis showed differences compared with the classification method characterised by a 50% reduction in PANSS scores at week 6. A total of 349 patients were inconsistently grouped by the two methods, with a significant difference in the composition ratio of treatment response groups using these two methods (χ2 = 43.37, P < 0.001). There was no differential contribution of high- and low trajectories to different drugs (χ2 = 12.52, P = 0.051); olanzapine and risperidone, which had a larger proportion in the >50% reduction at week 6, performed better than aripiprazole, quetiapine, ziprasidone and perphenazine.

Conclusions

The trajectory analysis of treatment response to schizophrenia revealed two distinct trajectories. Comparing the treatment responses to different antipsychotics through longitudinal analysis may offer a new perspective for evaluating antipsychotics.
Performance of 4 Creatinine-based Equations in Assessing Glomerular Filtration Rate in Adults with Diabetes
Authors: Zafari Neda , Lotfaliany Mojtaba , O’Keefe Graeme J , Kishore Kartik , Torkamani Niloufar , MacIsaac Richard J , Churilov Leonid , Ekinci Elif I
Published: October 2020

Aims

To evaluate diagnostic performance of glomerular filtration rate (GFR) estimated by modification of diet in renal disease (MDRD), chronic kidney disease epidemiology collaboration (CKD-EPI), full age spectrum (FAS), and revised Lund–Malmö (r-LM) equations in adults with diabetes.

Methods

Individuals were included in this cross-sectional study if they had at least 1 measurement of technetium-99m diethylenetriamine-pentaacetic acid (99mTc-DTPA) GFR (mGFR) and serum creatinine (1487 patients with 2703 measures). GFR calculated by estimation equations was compared with mGFR. Diagnostic performance was assessed using concordance correlation coefficient (CCC), bias, precision, accuracy, reduced major axis regression (RMAR), and Bland–Altman plot. Analysis was repeated in subgroups based on sex, diabetes type, Hemoglobin A1C, and GFR level.

Results

Of all patients, 1189 (86%) had type 2 diabetes. Mean mGFR, MDRD, CKD-EPI, FAS, and revised Lund-Malmö eGFR were 66, 72, 74, 71, and 67 mL/min/1.73m2, respectively. Overall, the r-LM had the highest CCC (0.83), lowest bias (–1.4 mL/min/1.73 m2), highest precision (16.2 mL/min/1.73 m2), and highest accuracy (P10 = 39%). The RMAR (slope, intercept) in r-LM, FAS, MDRD, and CKD-EPI was 1.18, –13.35; 0.97, –2.9; 1, -6.4, and 1.04, –11.3, respectively. The Bland–Altman plot showed that r-LM had the lowest mean difference and the narrowest 95% limit of agreement (–1.0, 54.1 mL/min/1.73 m2), while mean difference was more than 5-fold higher in FAS, MDRD, and CKD-EPI (–5.2, –6.3, and –8.2, respectively).

Conclusions

In adults with diabetes the revised Lund-Malmö performs better than MDRD, CKD-EPI, and FAS in calculating point estimates of GFR.
Predicting experimental success: a retrospective case-control study using the rat intraluminal thread model of stroke
Authors: Liebenstund Lisa , Coburn Mark , Fitzner Christina , Willuweit Antje , Langen Karl-Josef , Liu Jingjin , Veldeman Michael , Höllig Anke
Published: October 2020

The poor translational success rate of preclinical stroke research may partly be due to inaccurate modelling of the disease. We provide data on transient middle cerebral artery occlusion (tMCAO) experiments, including detailed intraoperative monitoring to elaborate predictors indicating experimental success (ischemia without occurrence of confounding pathologies). The tMCAO monitoring data (bilateral cerebral blood flow, CBF; heart rate, HR; and mean arterial pressure, MAP) of 16 animals with an ‘ideal’ outcome (MCA-ischemia), and 48 animals with additional or other pathologies (subdural haematoma or subarachnoid haemorrhage), were checked for their prognostic performance (receiver operating characteristic curve and area under the curve, AUC). Animals showing a decrease in the contralateral CBF at the time of MCA occlusion suffered from unintended pathologies. Implementation of baseline MAP, in addition to baseline HR (AUC, 0.83, 95% c.i. 0.68 to 0.97), increased prognostic relevance (AUC, 0.89, 95% c.i. 0.79 to 0.98). Prediction performance improved when two additional predictors referring to differences in left and right CBF were considered (AUC, 1.00, 95% c.i. 1.0 to 1.0). Our data underline the importance of peri-interventional monitoring to verify a successful experimental performance in order to ensure a disease model as homogeneous as possible.
Biomechanical regulation of focal adhesion and invadopodia formation
Authors: Revach Or-Yam , Grosheva Inna , Geiger Benjamin
Published: October 2020

Integrin adhesions are a structurally and functionally diverse family of transmembrane, multi-protein complexes that link the intracellular cytoskeleton to the extracellular matrix (ECM). The different members of this family, including focal adhesions (FAs), focal complexes, fibrillar adhesions, podosomes and invadopodia, contain many shared scaffolding and signaling ‘adhesome’ components, as well as distinct molecules that perform specific functions, unique to each adhesion form. In this Hypothesis, we address the pivotal roles of mechanical forces, generated by local actin polymerization or actomyosin-based contractility, in the formation, maturation and functionality of two members of the integrin adhesions family, namely FAs and invadopodia, which display distinct structures and functional properties. FAs are robust and stable ECM contacts, associated with contractile stress fibers, while invadopodia are invasive adhesions that degrade the underlying matrix and penetrate into it. We discuss here the mechanisms, whereby these two types of adhesion utilize a similar molecular machinery to drive very different – often opposing cellular activities, and hypothesize that early stages of FAs and invadopodia assembly use similar biomechanical principles, whereas maturation of the two structures, and their ‘adhesive’ and ‘invasive’ functionalities require distinct sources of biomechanical reinforcement.
Unc-13 homologue D mediates an antiviral effect of the chromosome 19 microRNA cluster miR-517a
Authors: Krawczynski Kamil , Ouyang Yingshi , Mouillet Jean-Francois , Chu Tianjiao , Coyne Carolyn B , Sadovsky Yoel
Published: October 2020

The function of microRNAs (miRNAs) can be cell autonomous or communicated to other cell types, and has been implicated in diverse biological processes. We previously demonstrated that miR-517a-3p (miR-517a), the highly expressed member of the chromosome 19 miRNA cluster (C19MC) that are transcribed almost exclusively in human trophoblasts, attenuates viral replication via induction of autophagy in non-trophoblastic, recipient cells. However, the molecular mechanisms underlying these effects remain unknown. Here we identified Unc-13 homologue D (UNC13D) as a direct, autophagy-related gene target of miR-517a, leading to repression of UNC13D. In line with the antiviral activity of miR-517a, silencing UNC13D suppressed replication of vesicular stomatitis virus (VSV), whereas overexpression of UNC13D increased VSV levels, suggesting a role for UNC13D silencing in the antiviral activity of miR-517a. We also found that miR-517a activated NFκB signaling in HEK-293XL cells expressing TLR8, but the effect was not-specific to C19MC miRNA. Together, we define mechanistic pathways that link C19MC miRNA with inhibition of viral replication.
Thorpe-Ingold Effect on Polymer Conformations. Photophysical Behavior as a Probe for Folding of Alt-Dialkylsilylene-divinylarene Copolymers
Authors: Luh Tien-Yau , Chen Chih-Hsien , Lai Guo-Qiao
Published: October 2020

The alt-silylene-conjugated motif copolymers consist of one to three kinds of chromophores regioselectively arranged as part of the polymeric backbone and two adjacent chromophores are linked by a trtrahedral dialkylsilylene insulating spacer. These polymers are highly folded, and a bulkier alkyl substituent (such as the isopropyl group) on silicon may exert Thorpe-Ingold effect that can bring the adjacent chromophores to closer proximity resulting in changes of photophysical properties. Interactions between chromophores include ground state interaction, formation of charge transfer complex, through-space interaction between chromophores, observation of CT emission, and photoinduced electron transfer. Notably, the Marcus inverted region is observed in such silicon-containing polymers using aminostyrene donor and a range of acceptors with different −ΔG° values. Since polymer folding is crucially related to the photophysical properties, a series of small molecules (monomer to tetramer) having the same pair of chromophores as those of the polymer are synthesized. The properties of tetramer already behave similarly to those of the corresponding polymer. Replacement of silylene linkers in polymers with substituted methylene groups also demonstrates similar kinds of interactions among chromophores, but with different intensities.
Supramolecular Association and Nanostructure Formation of Liquid Crystals and Polymers for New Functional Materials
Authors: Kato Takashi , Gupta Monika , Yamaguchi Daisuke , Gan Kian Ping , Nakayama Masanari
Published: October 2020

We here describe our various concepts and achievements for material science, which have been introduced through liquid-crystalline (LC) and polymer chemistry. They have resulted in the development of new classes of functional organic, polymer, and hybrid materials. Supramolecular LC complexes and polymers with well-defined structures were found to be built through complimentary hydrogen bonding between carboxylic acid and pyridine. Since then, a variety of intermolecular interactions such as hydrogen bonding, ionic interactions, ion-dipolar interactions, and halogen bonding were used for the formation of supramolecular liquid crystal organic materials and polymers. The nanosegregation in molecular assemblies in liquid crystals leads to the various 1D, 2D and 3D self-assembled nanostructures. These strategy and material designs lead to the development of new dynamically functional materials, which exhibit stimuli-responsive properties, photoluminescence, transport of charge, ions, and molecules, electro-optic properties, and templates. We also show new hybrid liquid crystals, biomineral-inspired nanorod and nanodisk liquid crystals. These nanomaterials form colloidal LC solutions, which exhibit stimuli-responsive properties.
Gallbladder cancer revisited: the evolving role of a radiologist
Authors: Ramachandran Anupama , Srivastava Deep Narayan , Madhusudhan Kumble Seetharama
Published: October 2020

Gallbladder cancer is the most common malignancy of the biliary tract. It is also the most aggressive biliary tumor with the shortest median survival duration. Complete surgical resection, the only potentially curative treatment, can be accomplished only in those patients who are diagnosed at an early stage of the disease. Majority (90%) of the patients present at an advanced stage and the management involves a multidisciplinary approach. The role of imaging in gallbladder cancer cannot be overemphasized. Imaging is crucial not only in detecting, staging, and planning management but also in guiding radiological interventions. This article discusses the role of a radiologist in the diagnosis and management of gallbladder cancer.
Hyper-dominance of the left anterior descending artery—a large territory
Authors: Sen Gautam , Veitch Alice , Sinha Manas
Published: October 2020

Coronary artery anomalies are rare and a potential cause of significant morbidity and mortality. A hyper-dominant left anterior descending artery is extremely rare with only 17 cases reported in the literature. Occlusion of a hyper-dominant left anterior descending artery can cause a massive myocardial infarction affecting a large myocardial territory and therefore clinicians should be aware of its importance.