bluuebunny/crossref_metadata_2025 huggingface dataset:
A quantitative metric of pioneer activity reveals that HNF4A has stronger in vivo pioneer activity than FOXA1
Authors: Hansen Jeffrey L. , Cohen Barak A.
Published: October 2022

Background

We and others have suggested that pioneer activity — a transcription factor’s (TF’s) ability to bind and open inaccessible loci — is not a qualitative trait limited to a select class of pioneer TFs. We hypothesize that most TFs display pioneering activity that depends on the TF concentration and the motif content at their target loci.

Results

Here, we present a quantitative in vivo measure of pioneer activity that captures the relative difference in a TF’s ability to bind accessible versus inaccessible DNA. The metric is based on experiments that use CUT&Tag to measure the binding of doxycycline-inducible TFs. For each location across the genome, we determine the concentration of doxycycline required for a TF to reach half-maximal occupancy; lower concentrations reflect higher affinity. We propose that the relative difference in a TF’s affinity between ATAC-seq labeled accessible and inaccessible binding sites is a measure of its pioneer activity. We estimate binding affinities at tens of thousands of genomic loci for the endodermal TFs FOXA1 and HNF4A and show that HNF4A has stronger pioneer activity than FOXA1. We show that both FOXA1 and HNF4A display higher binding affinity at inaccessible sites with more copies of their respective motifs. The quantitative analysis of binding suggests different modes of binding for FOXA1, including an anti-cooperative mode of binding at certain accessible loci.

Conclusions

Our results suggest that relative binding affinities are reasonable measures of pioneer activity and support the model wherein most TFs have some degree of context-dependent pioneer activity.
Genetic diversity in the transmission-blocking vaccine candidate Plasmodium vivax gametocyte protein Pvs230 from the China–Myanmar border area and central Myanmar
Authors: Zhao Xin , Hu Yubing , Zhao Yan , Wang Lin , Wu Zifang , Soe Myat Thu , Kyaw Myat Phone , Cui Liwang , Zhu Xiaotong , Cao Yaming
Published: October 2022

Background

Sexual stage surface antigens are potential targets of transmission-blocking vaccines (TBVs). The gametocyte and gamete surface antigen P230, a leading TBV candidate, is critical for red blood cell binding during exflagellation and subsequent oocyst development. Here, the genetic diversity ofPvs230was studied inPlasmodium vivaxparasite isolates from the China–Myanmar border (CMB) and central Myanmar.

Methods

Plasmodium vivaxisolates were collected in clinics from malaria-endemic areas of the CMB (143 samples) and Myanmar (23 samples). The interspecies variable part (IVP, nucleotides 1–807) and interspecies conserved part (ICP, 808–2862) ofPvs230were amplified by PCR and sequenced. Molecular evolution studies were conducted to evaluate the genetic diversity, signature of selection, population differentiation, haplotype network, and population structure of the study parasite populations and publicly availablePvs230sequences from six globalP. vivaxpopulations.

Results

Limited genetic diversity was observed for the CMB (π = 0.002) and Myanmar (π = 0.001) isolates. Most amino acid substitutions were located in the IVP and cysteine-rich domain ofPvs230. Evidence of positive selection was observed for IVP and purifying selection for ICP. Codon-based tests identified specific codons under natural selection in both IVP and ICP. The fixation index (FST) showed low genetic differentiation between East and Southeast Asian populations, withFSTranging from 0.018 to 0.119. The highestFSTvalue (FST = 0.503) was detected between the Turkey and Papua New Guinea populations. A total of 92 haplotypes were identified in global isolates, with the major haplotypes 2 and 9 being the most abundant and circulating in East and Southeast Asia populations. Several detected non-synonymous substitutions were mapped in the predicted structure and B-cell epitopes of Pvs230.

Conclusions

We detected low levels of genetic diversity ofPvs230in globalP. vivaxpopulations. Geographically specific haplotypes were identified forPvs230. Some mutations are located within a potential B-cell epitope region and need to be considered in future TBV designs.

Graphical Abstract
Cationic amino acid transporter-1 (CAT-1) promotes fibroblast-like synoviocyte proliferation and cytokine secretion by taking up L-arginine in rheumatoid arthritis
Authors: Lu Ying , Hao Chongbo , Yu Shanshan , Ma Zuan , Fu Xuelian , Qin Mingqing , Ding Menglei , Xu Zengguang , Fan Lieying
Published: October 2022

Background

Abnormal proliferation of fibroblast-like synoviocytes (FLSs) in the synovial lining layer is the primary cause of synovial hyperplasia and joint destruction in rheumatoid arthritis (RA). Currently, the relationship between metabolic abnormalities and FLS proliferation is a new focus of investigation. However, little is known regarding the relationship between amino acid metabolism and RA.

Methods

The concentrations of amino acids and cytokines in the synovial fluid of RA (n = 9) and osteoarthritis (OA, n = 9) were detected by LC–MS/MS and CBA assay, respectively. The mRNA and protein expression of cationic amino acid transporter-1 (CAT-1) were determined in FLSs isolated from RA and OA patients by real-time PCR and western blotting. MTT assay, cell cycle, apoptosis, invasion, and cytokine secretion were determined in FLSs knocked down of CAT-1 using siRNA or treated with D-arginine under normoxic and hypoxic culture conditions. A mouse collagen-induced arthritis (CIA) model was applied to test the therapeutic potential of blocking the uptake of L-arginine in vivo.

Results

L-rginine was upregulated in the synovial fluid of RA patients and was positively correlated with the elevation of the cytokines IL-1β, IL-6, and IL-8. Further examination demonstrated that CAT-1 was the primary transporter for L-arginine and was overexpressed on RA FLSs compared to OA FLSs. Moreover, knockdown of CAT-1 using siRNA or inhibition of L-arginine uptake using D-arginine significantly suppressed L-arginine metabolism, cell proliferation, migration, and cytokine secretion in RA FLSs under normoxic and hypoxic culture conditions in vitro but increased cell apoptosis in a dose-dependent manner. Meanwhile, in vivo assays revealed that an L-arginine-free diet or blocking the uptake of L-arginine using D-arginine suppressed arthritis progression in CIA mice.

Conclusion

CAT-1 is upregulated and promotes FLS proliferation by taking up L-arginine, thereby promoting RA progression.
Resuscitative endovascular balloon occlusion of the aorta in civilian pre-hospital care: a systematic review of the literature
Authors: Caicedo Yaset , Gallego Linda M. , Clavijo Hugo JC. , Padilla-Londoño Natalia , Gallego Cindy-Natalia , Caicedo-Holguín Isabella , Guzmán-Rodríguez Mónica , Meléndez-Lugo Juan J. , García Alberto F. , Salcedo Alexander E. , Parra Michael W. , Rodríguez-Holguín Fernando , Ordoñez Carlos A.
Published: October 2022

Background

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a damage control tool with a potential role in the hemodynamic resuscitation of severely ill patients in the civilian pre-hospital setting. REBOA ensures blood flow to vital organs by early proximal control of the source of bleeding. However, there is no consensus on the use of REBOA in the pre-hospital setting. This article aims to perform a systematic review of the literature about the feasibility, survival, indications, complications, and potential candidates for civilian pre-hospital REBOA.

Methods

A literature search was conducted using Medline, EMBASE, LILACS and Web of Science databases. Primary outcome variables included overall survival and feasibility. Secondary outcome variables included complications and potential candidates for endovascular occlusion.

Results

The search identified 8 articles. Five studies described the use of REBOA in pre-hospital settings, reporting a total of 47 patients in whom the procedure was attempted. Pre-hospital REBOA was feasible in 68–100% of trauma patients and 100% of non-traumatic patients with cardiac arrest. Survival rates and complications varied widely. Pre-hospital REBOA requires a coordinated and integrated emergency health care system with a well-trained and equipped team. The remaining three studies performed a retrospective analysis identifying 784 potential REBOA candidates.

Conclusions

Pre-hospital REBOA could be a feasible intervention for a significant portion of severely ill patients in the civilian setting. However, the evidence is limited. The impact of pre-hospital REBOA should be assessed in future studies.
Intestine-derived α-synuclein initiates and aggravates pathogenesis of Parkinson’s disease in Drosophila
Authors: Liu Wei , Lim Kah-Leong , Tan Eng-King
Published: October 2022

Background

Aberrant aggregation of α-synuclein (α-syn) is a key pathological feature of Parkinson’s disease (PD), but the precise role of intestinal α-syn in the progression of PD is unclear. In a number of genetic Drosophila models of PD, α-syn was frequently ectopically expressed in the neural system to investigate the pathobiology.

Method

We investigated the potential role of intestinal α-syn in PD pathogenesis using a Drosophila model. Human α-syn was overexpressed in Drosophila guts, and life span, survival, immunofluorescence and climbing were evaluated. Immunofluorescence, Western blotting and reactive oxygen species (ROS) staining were performed to assess the effects of intestinal α-syn on intestinal dysplasia. High‐throughput RNA and 16S rRNA gene sequencing, quantitative RT‐PCR, immunofluorescence, and ROS staining were performed to determine the underlying molecular mechanism.

Results

We found that the intestinal α-syn alone recapitulated many phenotypic and pathological features of PD, including impaired life span, loss of dopaminergic neurons, and progressive motor defects. The intestine-derived α-syn disrupted intestinal homeostasis and accelerated the onset of intestinal ageing. Moreover, intestinal expression of α-syn induced dysbiosis, while microbiome depletion was efficient to restore intestinal homeostasis and ameliorate the progression of PD. Intestinal α-syn triggered ROS, and eventually led to the activation of the dual oxidase (DUOX)–ROS–Jun N-terminal Kinase (JNK) pathway. In addition, α-syn from both the gut and the brain synergized to accelerate the progression of PD.

Conclusions

The intestinal expression of α-syn recapitulates many phenotypic and pathologic features of PD, and induces dysbiosis that aggravates the pathology through the DUOX–ROS–JNK pathway in Drosophila. Our findings provide new insights into the role of intestinal α-syn in PD pathophysiology.
Production of pyruvic acid with Candida glabrata using self-fermenting spent yeast cell dry powder as a seed nitrogen source
Authors: Lu Qiyuan , Shan Xiaoyu , Zeng Weizhu , Zhou Jingwen
Published: October 2022

Pyruvic acid is an important organic acid and a key industrial raw material. It is widely used in the chemical, agricultural, and food fields. Candida glabrata is the preferred strain for pyruvic acid production. The waste yeast cell for pyruvic acid fermentation with C. glabrata are rich in protein, amino acid, nucleic acid, and vitamins, as potential and cost-effective nitrogen source raw material. In this study, the potential of C. glabrata to produce pyruvic acid using spent yeast cell dry powder was evaluated. When 30 g/L of spray-dried spent yeast cell powder was used as the seed nitrogen source, a high titer of pyruvic acid was obtained. The pyruvic acid production reached 63.4 g/L with a yield of 0.59 g/g in a 5 L bioreactor. After scale-up to a 50 L bioreactor using the fermented spent yeast cell dry powder as a seed nitrogen source, 65.1 g/L of pyruvic acid was harvested, with a yield of 0.61 g/g. This study proposes a promising

approach for increasing the pyruvic acid titer and reducing the costs.

Graphical Abstract
Power system transient stability assessment based on the multiple paralleled convolutional neural network and gated recurrent unit
Authors: Cheng Shan , Yu Zihao , Liu Ye , Zuo Xianwang
Published: October 2022

In order to accurately evaluate power system stability in a timely manner after faults, and further improve the feature extraction ability of the model, this paper presents an improved transient stability assessment (TSA) method of CNN + GRU. This comprises a convolutional neural network (CNN) and gated recurrent unit (GRU). CNN has the feature extraction capability for a micro short-term time sequence, while GRU can extract characteristics contained in a macro long-term time sequence. The two are integrated to comprehensively extract the high-order features that are contained in a transient process. To overcome the difficulty of sample misclassification, a multiple parallel (MP) CNN + GRU, with multiple CNN + GRU connected in parallel, is created. Additionally, an improved focal loss (FL) function which can implement self-adaptive adjustment according to the neural network training is introduced to guide model training. Finally, the proposed methods are verified on the IEEE 39 and 145-bus systems. The simulation results indicate that the proposed methods have better TSA performance than other existing methods.
Race-related differences in the economic, healthcare-access, and psychological impact of COVID-19: personal resources associated with resilience
Authors: Schwartz Carolyn E. , Borowiec Katrina , Biletch Elijah , Rapkin Bruce D.
Published: October 2022

Background

The impact of the coronavirus disease 2019 (COVID) is worse among those with fewer financial resources, in jobs not amenable to remote work, and in denser living conditions. People of color are more likely to be among these vulnerable groups. Although race itself is a social construction and not based on underlying genetic/biological differences, this study investigated race/ethnicity differences in the negative repercussions of COVID and in the benefits of psychological and social resources.

Methods

This cross-sectional, web-based study (n = 4817) was administered to a heterogeneous United States sample in Spring/Summer 2020. Information was gathered on the following COVID-specific variables: Infection Status, Coping with Lockdown, Social Support, Post-traumatic Growth, Interpersonal Conflict, Worry about Self, Financial Impact on Family, Lack of Money, Inadequate Access to Healthcare, and Housing Instability. Resilience was operationalized as the ability to maintain a sense of wellness in the face of the pandemic, using the DeltaQuest Wellness measure. Multivariate linear regression (adjusting for demographics) and propensity-matched cohort analysis (matched on demographics) evaluated the impact of COVID-specific variables on Wellness in separate models for Whites and Non-Whites.

Findings

Both sets of models retained the same COVID-specific variables and explained about half of the variance in wellness. Coping with Lockdown, Social Support, and Post-traumatic Growth were associated with higher levels of Wellness in both Whites and Non-Whites, while Interpersonal Conflict and Worry about Self were associated with lower levels of Wellness. While these associations are similar, Non-Whites reported worse levels of some positive resources (e.g., social support) and more challenging levels of negative stressors (e.g., interpersonal, worry, financial). Non-Whites also reported much higher levels of post-traumatic growth.

Conclusion

COVID was a source of worry and even conflict, but also unlocked people’s resources in use of health-enhancing behavioral strategies, social support, and renewed gratitude for sources of personal meaning and value. The similar relationships between Whites and Non-Whites on wellness and COVID-specific stressors across racial groups underscore that race is a social construction, not a biological fact. Focusing on a renewed appreciation for sources of personal meaning, and particularly faith, seemed to buffer much of the COVID-related stress for Non-Whites.
Spectral CT in peritoneal carcinomatosis from ovarian cancer: a tool for differential diagnosis of small nodules?
Authors: Zorzetto Giada , Coppola Andrea , Molinelli Valeria , Angeretti Maria Gloria , Casarin Jvan , Fontana Federico , Piacentino Filippo , Carcano Giulio , Ghezzi Fabio , Venturini Massimo
Published: October 2022

The detection of peritoneal carcinomatosis in patients with ovarian cancer is crucial to establish the correct therapeutic planning (debulking surgery versus neoadjuvant chemotherapy).

Often, however, the nodules of peritoneal carcinomatosis are very small in size or have a reticular appearance that can mimic the fat stranding that is typical of acute inflammation conditions. Our hypothesis is that the use of dual-layer spectral computed tomography with its applications, such as virtual monoenergetic imaging and Z-effective imaging, might improve the detection and the characterisation of peritoneal nodules, increasing sensitivity and diagnostic accuracy, as recently described for other oncological diseases.
Could surgical transepicondylar axis be identified accurately in preoperative 3D planning for total knee arthroplasty? A reproducibility study based on 3D-CT
Authors: Lei Kai , Liu Li Ming , Luo Jiang Ming , Ma Chao , Feng Qing , Yang Liu , Guo Lin
Published: October 2022

Background

Surgical transepicondylar axis (sTEA) is frequently used for positioning of femoral component rotation in total knee arthroplasty (TKA). Previous studies showed that intraoperative identification of sTEA was not reliable. While surgeons or engineers need to identify sTEA with three-dimensional (3D) computer-aid techniques pre- or intraoperatively, the reproducibility of sTEA identification on preoperative 3D images has not been explored yet. This study aimed to investigate the reproducibility of identifying sTEA in preoperative planning based on computed tomography (CT).

Methods

Fifty-nine consecutive patients (60 knees involved) who received TKA in our center from April 2019 to June 2019 were included in this study. Six experienced TKA surgeons identified sTEA three times on 3D model established on the basis of knee CT data. The projection angle of each sTEA and the posterior condyle axis on the transverse plane were measured and analyzed.

Results

The overall intra-observer reproducibility was moderate. The median intra-observer variation was 1.27°, with a maximum being up to 14.07°. The median inter-observer variation was 1.24°, and the maximum was 11.47°. The overall intra-class correlation coefficient (ICC) for inter-observer was 0.528 (95% CI 0.417, 0.643).

Conclusion

The identification of sTEA on a 3D model established on the basis of knee CT data may not be reliable. Combined with the previous cadaveric and surgical studies, caution should be exercised in determining femoral component rotation by referencing sTEA both preoperatively and intraoperatively.

Level of evidence

III
Heritage tourism evolution in Guangfu Ancient City, Hebei Province, China: an analysis with the improved creative destruction model
Authors: Wang Menghan , Bai Xiaoran , Su Mingming
Published: October 2022

Ancient cities and towns are popular tourism destinations worldwide. In this paper, Guangfu Ancient City in Yongnian County, Hebei Province, China, is taken as the case study and the modified creative destruction model is applied as the analytical framework to evaluate the multiactor dynamics of heritage tourism development. A mixed method approach is adopted, including a local resident survey, in-depth interviews with staff of the Guangfu Ancient City tourism site and government officials responsible for the heritage conservation and tourism development of the site, and a review of online tourist reviews, relevant government documents and reports. Based on the modified creative destruction model, local residents’ attitudes towards tourism development, changes in tourist numbers, the level of business and government investments, and the motivations of different stakeholders in tourism development are assessed by synthesising on-site research, historical data and other materials. Then, the tourism development stages for Guangfu Ancient City are identified as the precommodification stage before 2006, the early commodification stage from 2006 to 2011 and the advanced commodification stage from 2012 to 2017. The findings indicate that with rapid increases in investments from both corporate and government sources and in the number of tourists, the attitude of local residents towards tourism development remained positive. The results show that instead of entering the initial destruction stage, Guangfu Ancient City is in the transition stage from advanced commodification to creative enhancement given the government’s dominant role in tourism development, the heritage conservation motives of tourism entrepreneurs, the benefits to residents from tourism development ensured by government policies, and the shift in tourist type to postmodern tourists with double demands. The applicability of the modified creative destruction model is further discussed, and policy and management recommendations are generated to support the sustainable development of Guangfu Ancient City after the COVID-19 pandemic.
Maternal Glycaemic and Insulinemic Status and Newborn DNA Methylation: Findings in Women With Overweight and Obesity
Authors: Lecorguillé Marion , McAuliffe Fionnuala M , Twomey Patrick J , Viljoen Karien , Mehegan John , Kelleher Cecily C , Suderman Matthew , Phillips Catherine M
Published: October 2022

Context

Maternal dysglycaemia and prepregnancy obesity are associated with adverse offspring outcomes. Epigenetic mechanisms such as DNA methylation (DNAm) could contribute.

Objective

To examine relationships between maternal glycaemia, insulinemic status, and dietary glycemic indices during pregnancy and an antenatal behavioral-lifestyle intervention with newborn DNAm.

Methods

We investigated 172 women from a randomized controlled trial of a lifestyle intervention in pregnant women who were overweight or obese. Fasting glucose and insulin concentrations and derived indices of insulin resistance (HOMA-IR), β-cell function (HOMA-%B), and insulin sensitivity were determined at baseline (15) and 28 weeks’ gestation. Dietary glycemic load (GL) and index (GI) were calculated from 3-day food diaries. Newborn cord blood DNAm levels of 850K CpG sites were measured using the Illumina Infinium HumanMethylationEPIC array. Associations of each biomarker, dietary index and intervention with DNAm were examined.

Results

Early pregnancy HOMA-IR and HOMA-%B were associated with lower DNAm at CpG sites cg03158092 and cg05985988, respectively. Early pregnancy insulin sensitivity was associated with higher DNAm at cg04976151. Higher late pregnancy insulin concentrations and GL scores were positively associated with DNAm at CpGs cg12082129 and cg11955198 and changes in maternal GI with lower DNAm at CpG cg03403995 (Bonferroni corrected P < 5.99 × 10−8). These later associations were located at genes previously implicated in growth or regulation of insulin processes. No effects of the intervention on cord blood DNAm were observed. None of our findings were replicated in previous studies.

Conclusion

Among women who were overweight or obese, maternal pregnancy dietary glycemic indices, glucose, and insulin homeostasis were associated with modest changes in their newborn methylome.

Trial registration

ISRCTN29316280
Utility of In Vivo Magnetic Resonance Imaging Is Predictive of Gestational Diabetes Mellitus During Early Pregnancy
Authors: Lee Brian , Janzen Carla , Wu Holden , Vangala Sitaram S , Devaskar Sherin U , Sung Kyunghyun
Published: October 2022

Context

Gestational diabetes (GDM) imposes long-term adverse health effects on the mother and fetus. The role of magnetic resonance imaging (MRI) during early gestation in GDM has not been well-studied.

Objective

To investigate the role of quantitative MRI measurements of placental volume and perfusion, with distribution of maternal adiposity, during early gestation in GDM.

Methods

At UCLA outpatient antenatal obstetrics clinics, ∼200 pregnant women recruited in the first trimester were followed temporally through pregnancy until parturition. Two placental MRI scans were prospectively performed at 14 to 16 weeks and 19 to 24 weeks gestational age (GA). Placental volume and blood flow (PBF) were calculated from placental regions of interest; maternal adiposity distribution was assessed by subcutaneous fat area ratio (SFAR) and visceral fat area ratio (VFAR). Statistical comparisons were performed using the two-tailed t test. Predictive logistic regression modeling was evaluated by area under the curve (AUC).

Results

Of a total 186 subjects, 21 subjects (11.3%) developed GDM. VFAR was higher in GDM vs the control group, at both time points (P < 0.001 each). Placental volume was greater in GDM vs the control group at 19 to 24 weeks GA (P = 0.01). Combining VFAR, placental volume and perfusion, improved the AUC to 0.83 at 14 to 16 weeks (positive predictive value [PPV] = 0.77, negative predictive value [NPV] = 0.83), and 0.81 at 19 to 24 weeks GA (PPV = 0.73, NPV = 0.86).

Conclusion

A combination of MRI-based placental volume, perfusion, and visceral adiposity during early pregnancy demonstrates significant changes in GDM and provides a proof of concept for predicting the subsequent development of GDM.
Tracking and Cumulative Lifetime Exposure to IGF-I in 6459 Healthy Individuals and in SGA Children Treated With GH
Authors: Kjaer Anna Sophie L , Jensen Rikke Beck , Petersen Jørgen H , Linneberg Allan , Kårhus Line Lund , Henriksen Louise Scheutz , Johannsen Trine Holm , Main Katharina M , Hoffman Andrew R , Juul Anders
Published: October 2022

Context

Supraphysiological serum insulin-like growth factor-I (IGF-I) concentrations have been a matter of concern in children treated with GH because high IGF-I levels were associated with risk of later disease in former epidemiological studies.

Objective

To determine whether a single IGF-I measurement reliably reflects lifetime IGF-I exposure we evaluated intraindividual longitudinal tracking of IGF-I and IGF-binding protein-3 (IGFBP-3) levels and we estimated cumulative lifetime exposure to IGF-I in healthy and GH-treated individuals.

Methods

We included 6459 healthy participants (cross-sectional = 5326; longitudinal = 1133) aged 0-76 years (9963 serum samples) and 9 patients born small-for-gestational-age (SGA) with 238 serum samples during GH treatment. Intraindividual tracking of IGF-I and IGFBP-3 (SD score [SDS]) was determined by intraclass correlation coefficients (ICCs). Cumulative lifetime IGF-I exposure was estimated by area under the curve of the predicted SDS trajectory from 0 to 76 years.

Results

For IGF-I (SDS), ICCs were 0.50 (95% CI, 0.47-0.53) for male and 0.53 (0.50-0.56) for female participants. Lifetime IGF-I exposure was significantly higher in female (mean 12 723 ± 3691 SD) than in male participants (12 563 ± 3393); P = 0.02. In SGA children, treatment with GH increased the lifetime exposure to IGF-I from 9512 ± 1889 to 11 271 ± 1689, corresponding to an increase in lifetime IGF-I trajectory from −0.89 SD ± 0.57 to −0.35 SD ± 0.49.

Conclusion

Because IGF-I and IGFBP-3 levels track throughout life, a single measurement reliably reflects lifetime exposure. GH therapy increased the lifetime exposure to IGF-I only slightly and it remained below the average lifetime exposure in the reference population.
Serum IGF-1 to IGFBP-3 Molar Ratio: A Promising Diagnostic Tool for Growth Hormone Deficiency in Children
Authors: Haj-Ahmad Laith M , Mahmoud Muhannad M , Sweis Nabil W G , Bsisu Isam , Alghrabli Ahmad M , Ibrahim Alaa M , Zayed Ayman A
Published: October 2022

Background

The serum insulin-like growth factor-1 (IGF-1)/insulin-like growth factor binding protein-3 (IGFBP-3) ratio has various potential applications in growth hormone-related disorders. This study aimed to investigate the performance of the IGF-1/IGFBP-3 ratio, independently and in combination with serum IGF-1 and IGFBP-3, in the diagnosis of growth hormone deficiency (GHD) in children with short stature (SS).

Methods

A 7-year cross-sectional observational study was conducted on 235 children with SS. Participants with known disorders that may affect IGF-1 other than GHD were excluded. Participants were classified into GHD (n = 64) and non-GHD (n = 171) groups. GHD was defined as a slow growth rate (<25th percentile over 1 year) and suboptimal growth hormone (GH) response to 2 GH stimulation tests (peak GH < 6.25 ng/mL using the DiaSorin Liaison assay). The sensitivity and specificity of serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 molar ratio, independently and in various combinations, were determined.

Results

GHD was diagnosed in 27.2% of participants. Among all studied variables, a low serum IGF-1/IGFBP-3 ratio demonstrated the greatest sensitivity for GHD (87.5%), with a comparable specificity (83.0%). The combination of low serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 ratio demonstrated the greatest specificity for GHD (97.7%), whereas the combination of normal serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 ratio demonstrated the greatest specificity for a non-GHD cause of SS (100.0%).

Conclusion

Our data suggest that the serum IGF-1/IGFBP-3 ratio is a useful marker for the diagnosis of GHD in children who do not have other disorders that may affect serum IGF-1 levels. Further large studies are needed to confirm the diagnostic utility of the serum IGF-1/IGFBP-3 ratio.
Estrogen Receptor Beta 1: A Potential Therapeutic Target for Female Triple Negative Breast Cancer
Authors: Dey Parama , Wang Alexander , Ziegler Yvonne , Kumar Sandeep , Yan Shunchao , Kim Sung Hoon , Katzenellenbogen John A , Katzenellenbogen Benita S
Published: October 2022

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of estrogen receptor alpha, progesterone receptor, and HER2. These receptors often serve as targets in breast cancer treatment. As a result, TNBCs are difficult to treat and have a high propensity to metastasize to distant organs. For these reasons, TNBCs are responsible for over 50% of all breast cancer mortalities while only accounting for 15% to 20% of breast cancer cases. However, estrogen receptor beta 1 (ERβ1), an isoform of the ESR2 gene, has emerged as a potential therapeutic target in the treatment of TNBCs. Using an in vivo xenograft preclinical mouse model with human TNBC, we found that expression of ERβ1 significantly reduced both primary tumor growth and metastasis. Moreover, TNBCs with elevated levels of ERβ1 showed reduction in epithelial to mesenchymal transition markers and breast cancer stem cell markers, and increases in the expression of genes associated with inhibition of cancer cell invasiveness and metastasis, suggesting possible mechanisms underlying the antitumor activity of ERβ1. Gene expression analysis by quantitative polymerase chain reaction and RNA-seq revealed that treatment with chloroindazole, an ERβ-selective agonist ligand, often enhanced the suppressive activity of ERβ1 in TNBCs in vivo or in TNBC cells in culture, suggesting the potential utility of ERβ1 and ERβ ligand in improving TNBC treatment. The findings enable understanding of the mechanisms by which ERβ1 impedes TNBC growth, invasiveness, and metastasis and consideration of ways by which treatments involving ERβ might improve TNBC patient outcome.
The Significance of Hypothalamic Inflammation and Gliosis for the Pathogenesis of Obesity in Humans
Authors: Sewaybricker Leticia E , Huang Alyssa , Chandrasekaran Suchitra , Melhorn Susan J , Schur Ellen A
Published: October 2022

Accumulated preclinical literature demonstrates that hypothalamic inflammation and gliosis are underlying causal components of diet-induced obesity in rodent models. This review summarizes and synthesizes available translational data to better understand the applicability of preclinical findings to human obesity and its comorbidities. The published literature in humans includes histopathologic analyses performed postmortem and in vivo neuroimaging studies measuring indirect markers of hypothalamic tissue microstructure. Both support the presence of hypothalamic inflammation and gliosis in children and adults with obesity. Findings predominantly point to tissue changes in the region of the arcuate nucleus of the hypothalamus, although findings of altered tissue characteristics in whole hypothalamus or other hypothalamic regions also emerged. Moreover, the severity of hypothalamic inflammation and gliosis has been related to comorbid conditions, including glucose intolerance, insulin resistance, type 2 diabetes, and low testosterone levels in men, independent of elevated body adiposity. Cross-sectional findings are augmented by a small number of prospective studies suggesting that a greater degree of hypothalamic inflammation and gliosis may predict adiposity gain and worsening insulin sensitivity in susceptible individuals. In conclusion, existing human studies corroborate a large preclinical literature demonstrating that hypothalamic neuroinflammatory responses play a role in obesity pathogenesis. Extensive or permanent hypothalamic tissue remodeling may negatively affect the function of neuroendocrine regulatory circuits and promote the development and maintenance of elevated body weight in obesity and/or comorbid endocrine disorders.
The Drifting Influence of Hall's Random-Walk Hypothesis on Consumption Modeling
Authors: García Carlos , Otero Daniel , Salazar Boris
Published: October 2022

Hall's 1978 article titled “Stochastic Implications of the Life Cycle–Permanent Income Hypothesis” was meant to revolutionize consumption modeling. It indeed delivered, but not by becoming the dominant modeling strategy, but by unleashing a complex process of interaction between researchers in consumption and interconnected fields that transformed Hall's original object, from a local theory of consumption into a growing research area spanning the fields of consumption, finance, monetary policy and econometric modeling, and becoming, at the turn of the century, a building block of the DSGE modeling framework. Researchers reacting to innovative work produced new models that acted modified the context of research inducing a feedback system responsible for a connected set of innovations in the fields mentioned above. Along that process the practice of consumption modeling drifted away from Hall's original proposal, suggesting the necessity of a more nuanced view of the notion of influence in contemporary macroeconomics. In this particular case, we found that drifting occurred within the bounds set by the Euler equation and the assumptions of intertemporal optimization and rational expectations.
A Note on the Early Versions of the Tableau économique
Authors: Charles Loïc , Théré Christine
Published: October 2022

This article uses materials that have been recently discovered as well as completely new documents, in particular a previously missing copy of the first printed edition of the Tableau économique that the authors found in the French National Archives and that they reproduce here in the appendix of the article. The authors combine these new sources of information with a close reading of materials—in particular the two letters sent by Quesnay to Mirabeau when he worked on the first two versions of the Tableau to provide a largely revised chronology of the conception and circulation of the three early versions of the Tableau. One of the points the authors make is that Madame de Pailly, Mirabeau's lover, acted as a go-between for the two men at that time and was instrumental in convincing Quesnay to share the Tableau with the marquis and to publish it in the sequel of the latter's best seller, L'Ami des hommes.
(Re)Embodying the Disembodied Voice of Lyric: The Radio Poems of Derek Walcott and Sylvia Plath
Authors: Berry Sarah
Published: October 2022

Derek Walcott’s Harry Dernier and Sylvia Plath’s Three Women, two little-known, midcentury radio plays, cultivate characters who sound like the speaker of a lyric poem, even as they foreground the invisible bodies behind the voices. In offering us voices that both invite and obstruct lyric reading, Plath and Walcott make manifest a tension present in all lyric poetry—between the embodied individual, on the one hand, and the lyric speaker, on the other. Harry Dernier parodies prominent instances of poetic address, dramatizing the inadequacy of the Western literary tradition in the face of a real catastrophe. Three Women invites the audience to interpret its speakers lyrically, but then undermines the possibility of such interpretation by pointing to the ways that these voices belong to specific, gendered bodies. In this way, Plath highlights the ambiguity in how the term “voice” is used in relation to lyric and, in this, shapes a critique of lyric voicing.
Two closely related ureotelic fish species of the genus Alcolapia express different levels of ammonium transporters in gills
Authors: White Lewis J. , Rose Matthew , Lawson Michael , Joyce Domino , Smith Alan M. , Thomas Gavin H. , Dasmahapatra Kanchon K. , Pownall Mary E.
Published: October 2022

Most fish excrete their nitrogenous waste across the gills as ammonia through the activity of the Rhesus glycoprotein ammonium transporters. In contrast, fish of the subgenus Alcolapia (Oreochromis) are the only vertebrates that survive the extreme conditions of the soda lakes of Natron and Magadi in East Africa and have evolved adaptations to the highly alkaline waters including the ability to excrete their nitrogenous waste as urea. Nevertheless, Alcolapia retain the Rhesus glycoprotein genes in their genomes and using two heterologous expression systems, we demonstrate that Alcolapia Rhbg is capable of moving ammonia. Comparing ammonia and urea excretion from two closely related Alcolapia species from the same aquarium, we found that while Alcolapia grahami remains fully ureotelic after many generations in lab conditions, Alcolapia alcalica excretes some of its nitrogenous waste as ammonia. Using in situ hybridisation, we demonstrate robust, localised gene expression of Rhbg, rhcg1 and rhcg2 in the gill tissue in both A. alcalica embryos and adults, similar to that in other ammoniotelic fish. In contrast, the expression of these genes in A. grahami gills is much lower than in A. alcalica, suggesting the rapid evolution of a molecular mechanism underlying the complete ureotelism of A. grahami.
Plap-1 lineage tracing and single-cell transcriptomics reveal cellular dynamics in the periodontal ligament
Authors: Iwayama Tomoaki , Iwashita Mizuho , Miyashita Kazuya , Sakashita Hiromi , Matsumoto Shuji , Tomita Kiwako , Bhongsatiern Phan , Kitayama Tomomi , Ikegami Kentaro , Shimbo Takashi , Tamai Katsuto , Murayama Masanori A. , Ogawa Shuhei , Iwakura Yoichiro , Yamada Satoru , Olson Lorin E. , Takedachi Masahide , Murakami Shinya
Published: October 2022

Periodontal tissue supports teeth in the alveolar bone socket via fibrous attachment of the periodontal ligament (PDL). The PDL contains periodontal fibroblasts and stem/progenitor cells, collectively known as PDL cells (PDLCs), on top of osteoblasts and cementoblasts on the surface of alveolar bone and cementum, respectively. However, the characteristics and lineage hierarchy of each cell type remain poorly defined. This study identified periodontal ligament associated protein-1 (Plap-1) as a PDL-specific extracellular matrix protein. We generated knock-in mice expressing CreERT2 and GFP specifically in Plap-1-positive PDLCs. Genetic lineage tracing confirmed the long-standing hypothesis that PDLCs differentiate into osteoblasts and cementoblasts. A PDL single-cell atlas defined cementoblasts and osteoblasts as Plap-1−Ibsp+Sparcl1+ and Plap-1−Ibsp+Col11a2+, respectively. Other populations, such as Nes+ mural cells, S100B+ Schwann cells, and other non-stromal cells, were also identified. RNA velocity analysis suggested that a Plap-1highLy6a+ cell population was the source of PDLCs. Lineage tracing of Plap-1+ PDLCs during periodontal injury showed periodontal tissue regeneration by PDLCs. Our study defines diverse cell populations in PDL and clarifies the role of PDLCs in periodontal tissue homeostasis and repair.
Feasibility and Acceptability of Wearable Sensor Placement for Measuring Screen Time of Children
Authors: Willis Erik A. , Hales Derek , Smith Falon T. , Burney Regan , El-Zaatari Helal M. , Rzepka Michelle C. , Amft Oliver , Barr Rachel , Evenson Kelly R. , Kosorok Michael R. , Ward Dianne S.
Published: October 2022

Introduction/Purpose

Wearables that include a color light sensor are a promising measure of electronic screen use in adults. However, to extend this approach to children, we need to understand feasibility of wear placement. The purpose of this study was to examine parent perceptions of children’s acceptability of different sensor placements and feasibility of free-living 3- to 7-d wear protocols.

Methods

This study was conducted in three phases. In phase 1, caregivers (n = 161) of 3- to 8-yr-old children completed an online survey to rate aspects of fitting and likelihood of wear for seven methods (headband, eyeglasses, skin adhesive patch, shirt clip/badge, mask, necklace, and vest). In phase 2, children (n = 31) were recruited to wear one of the top five prototypes for 3 d (n = 6 per method). In phase 3, children (n = 23) were recruited to wear one of the top three prototypes from phase 2 (n = 8 per method) for 7 d. In phases 2 and 3, parents completed wear logs and surveys about their experiences. Parents scored each wearable on three domains (ease of use, likelihood of wear, and child enjoyment). Scores were averaged to compute an everyday “usability” score (0, worst, to 200, best).

Results

Phase 1 results suggested that the headband, eyeglasses, patch, clip/badge, and vest had the best potential for long-term wear. In phase 2, time spent wearing prototypes and usability scores were highest for the eyeglasses (10.4 h·d−1; score, 155.4), clip/badge (9.8 h·d−1; score, 145.8), and vest (7.1 h·d−1; score, 141.7). In phase 3, wearing time and usability scores were higher for the clip/badge (9.4 h·d−1; score, 169.6) and eyeglasses (6.5 h·d−1; score, 145.3) compared with the vest (4.8 h·d−1; score, 112.5).

Conclusions

Results indicate that wearable sensors clipped to a child’s shirt or embedded into eyeglasses are feasible and acceptable wear methods in free-living settings. The next step is to assess the quality, validity, and reliability of data captured using these wear methods.
Development and implementation of a tool for measuring the training effectiveness of the patient-centered consultation model
Authors: Jorgensen Merete , Thorsen Hanne , Siersma Volkert , Winther Bang Christine
Published: October 2022

Background: The patient-centered consultation model comprises four elements: exploring health, illness and disease experiences, understanding the whole person, finding common ground, and enhancing the patient-doctor relationship. This method is taught at the course in general practice at Copenhagen University. The aim of the study was to develop a simple tool consisting of a questionnaire about the patient-centered elements and a test video consultation. The outcome is the change in the students’ ability to identify these elements. Used as a pre-course and post-course test it can inform the teachers which elements of the patient-centered consultation need intensifying in the teaching.

Methods: The students from a course in general practice volunteered to participate in all steps of the development. They took part in individual interviews to select items from an already existing questionnaire (DanSCORE). The preliminary questionnaire was tested for face and content validity, pilot-tested and tested for test-retest reliability. All video consultations were transcribed and assessed for patient-centered elements through a conversation analysis. The videos showed medical students seeing real patients.

Results: The preliminary version of the questionnaire (called DanOBS) had 23 items. In the subsequent interviews, items were reduced to 17, each with three response options. After a pilot test, the questionnaire was further reduced to 13 items, all strictly relevant to the model and with two response options. The final questionnaire had acceptable test-retest reliability. The number of test consultation videos underwent a reduction from six videos to one.

Conclusions: The DanOBS combined with a test video consultation, used as a pre-and post-course test demonstrates for teachers which elements in the patient-centered consultation need to be intensified in the teaching.
Jornalismo cultural e temporalidade nos dossiês da revista brasileira Cult (2019).
Authors: Cavalcanti Anna , Golin Cida
Published: October 2022

Este artigo propõe uma leitura da dimensão temporal do jornalismo cultural, enfatizando a característica recorrente desse segmento editorial de atualizar o passado e de construir memória ao mediar a cultura. Valemonos da experiência da Cult, a mais longeva revista cultural brasileira, há 25 anos em circulação no mercado editorial. Com base no aporte teórico e metodológico da hermenêutica de Paul Ricoeur, particularmente de sua proposta de tríplice mímesis, analisamos uma amostra de seis edições mensais publicadas entre julho e dezembro de 2019, concentrando-nos na seção principal, intitulada Dossiês, por meio das chamadas de capa e dos textos internos. A partir da categoria temporal da diacronia e dos enquadramentos encontrados na amostra de dossiês, encontramos evidências do caráter contextualizador das narrativas comum ao perfil do jornalismo de revista. Identificamos a diacronia por intermédio de uma recorrente ausência dos tradicionais marcadores cronológicos jornalísticos, uma das características que impulsiona o potencial da publicação analisada de recircular ao longo do tempo, ainda que visando a um leitor restrito. Entendemos que os dossiês da Cult são recursos afirmativos de um jornalismo cultural que está em fricção com o passado por meio de um tempo presente lento e distendido, mostrando-se em contraponto à temporalidade jornalística comumente associada à velocidade, à aceleração e ao instantâneo.
Sob a lâmina da guilhotina: contribuição de Albert Camus para a Ecologia das Mídias contribuição de Albert Camus para a Ecologia das Mídias.
Authors: Simões Pires Arthur Freire
Published: October 2022

Este artigo tem como objetivo acrescentar à vertente da Ecologia das mídias as contribuições oportunizadas por Albert Camus em seu ensaio filosófico Reflexões sobre a guilhotina ([1957] 2022). Para isso, foi esboçada uma breve cronologia da tradição ecológica das mídias — amparada, sobretudo, no legado deixado por Marshall McLuhan ([1962] 1972; [1964] 1993) e Neil Postman (1993) — como forma de apresentar algumas de suas principais referências. Posto isso, por meio de uma metodologia, elaborada a partir do que o trabalho pretende alcançar, de abordagem qualitativa, de natureza teórica, lastreada em epistemologia construída na fundamentação do diálogo entre a perspectiva teórica mencionada e o ensaísmo de Albert Camus. Considerando a presença epistemológica de complementaridade, este dialogismo embutido no arrazoamento, pretende-se discorrer criticamente sobre a arguição do escritor argelino a fim de elucidar como esse contribui para a continuidade dos estudos ecológicos das mídias. Pode-se destacar, portanto, que os argumentos camusianos dão conta das as repercussões sociais e psicológicas proporcionadas pela inserção da guilhotina na sociedade francesa; representadas, em especial, pelo fomento da lei de talião no tecido social, estimulando que a noção de justiça se torne sinônimo de vingança e estimulando o despertar do sadismo incutido no coração dos seres. A invenção que deveria simbolizar o fim dos privilégios, na realidade, exime o Estado de culpa e centraliza toda a responsabilidade do desequilíbrio social em um sentenciado. Ao fim e ao cabo, a herança da guilhotina é a distorção da noção de justiça e individualização dos problemas coletivos.