bluuebunny/crossref_metadata_2025 huggingface dataset:
GLIS3 regulates transcription of thyroid hormone biosynthetic genes in coordination with other thyroid transcription factors
Authors: Kang Hong Soon , Grimm Sara A. , Jothi Raja , Santisteban Pilar , Jetten Anton M.
Published: February 2023

Background

Loss of the transcription factor GLI-Similar 3 (GLIS3) function causes congenital hypothyroidism (CH) in both humans and mice due to decreased expression of several thyroid hormone (TH) biosynthetic genes in thyroid follicular cells. Whether and to what extent, GLIS3 regulates thyroid gene transcription in coordination with other thyroid transcriptional factors (TFs), such as PAX8, NKX2.1 and FOXE1, is poorly understood.

Methods

PAX8, NKX2.1, and FOXE1 ChIP-Seq analysis with mouse thyroid glands and rat thyrocyte PCCl3 cells was performed and compared to that of GLIS3 to analyze the co-regulation of gene transcription in thyroid follicular cells by these TFs.

Results

Analysis of the PAX8, NKX2.1, and FOXE1 cistromes identified extensive overlaps between these TF binding loci and those of GLIS3 indicating that GLIS3 shares many of the same regulatory regions with PAX8, NKX2.1, and FOXE1, particularly in genes associated with TH biosynthesis, induced by thyroid stimulating hormone (TSH), and suppressed in Glis3KO thyroid glands, including Slc5a5 (Nis), Slc26a4, Cdh16, and Adm2. ChIP-QPCR analysis showed that loss of GLIS3 did not significantly affect PAX8 or NKX2.1 binding and did not cause major alterations in H3K4me3 and H3K27me3 epigenetic signals.

Conclusions

Our study indicates that GLIS3 regulates transcription of TH biosynthetic and TSH-inducible genes in thyroid follicular cells in coordination with PAX8, NKX2.1, and FOXE1 by binding within the same regulatory hub. GLIS3 does not cause major changes in chromatin structure at these common regulatory regions. GLIS3 may induce transcriptional activation by enhancing the interaction of these regulatory regions with other enhancers and/or RNA Polymerase II (Pol II) complexes.
Short and Long RC Columns with Internal WWM Reinforcement under Concentric and Eccentric Compression
Authors: El-Kholy Ahmed M. , Abd El-Rahman Safaa F. , El-Assaly Mohamed M.
Published: February 2023

Recently, various types of steel meshes were used as additional internal reinforcement for improving the confinement, ductility, and strength of the reinforced concrete (RC) columns. In this experimental study, a welded wire mesh (WWM) layer was used as an internal reinforcement in addition to the traditional steel reinforcement (longitudinal bars and transverse ties) for short and long RC columns under concentric and eccentric compression. Thirty-six square RC columns with two slenderness ratios λ (height to width ratio) of 9 and 18 were tested under compression with eccentricity ratios e/t (eccentricity to section thickness ratio) of 0, 0.13, and 0.26. The reference columns were traditionally reinforced with longitudinal steel bars and transverse ties with a reference volumetric ratio ρr of 0.44%. The other columns comprised a WWM layer wrapped outside the ties whose volumetric ratio ranged from 0.22% to 0.44%. The results demonstrated that the columns reinforced with a WWM layer in addition to traditional reinforcement showed an improvement in ductility and strength compared to those reinforced with longitudinal bars and transverse ties only. A WWM layer increased the ultimate load of the columns comprising ρr ties by approximately 16% and 9% for short and long columns, respectively. These improvements were proportional to the ties volumetric ratio.
Amino acid nutrition and metabolism in domestic cats and dogs
Authors: Li Peng , Wu Guoyao
Published: February 2023

Domestic cats and dogs are carnivores that have evolved differentially in the nutrition and metabolism of amino acids. This article highlights both proteinogenic and nonproteinogenic amino acids. Dogs inadequately synthesize citrulline (the precursor of arginine) from glutamine, glutamate, and proline in the small intestine. Although most breeds of dogs have potential for adequately converting cysteine into taurine in the liver, a small proportion (1.3%–2.5%) of the Newfoundland dogs fed commercially available balanced diets exhibit a deficiency of taurine possibly due to gene mutations. Certain breeds of dogs (e.g., golden retrievers) are more prone to taurine deficiency possibly due to lower hepatic activities of cysteine dioxygenase and cysteine sulfinate decarboxylase. De novo synthesis of arginine and taurine is very limited in cats. Thus, concentrations of both taurine and arginine in feline milk are the greatest among domestic mammals. Compared with dogs, cats have greater endogenous nitrogen losses and higher dietary requirements for many amino acids (e.g., arginine, taurine, cysteine, and tyrosine), and are less sensitive to amino acid imbalances and antagonisms. Throughout adulthood, cats and dogs may lose 34% and 21% of their lean body mass, respectively. Adequate intakes of high-quality protein (i.e., 32% and 40% animal protein in diets of aging dogs and cats, respectively; dry matter basis) are recommended to alleviate aging-associated reductions in the mass and function of skeletal muscles and bones. Pet-food grade animal-sourced foodstuffs are excellent sources of both proteinogenic amino acids and taurine for cats and dogs, and can help to optimize their growth, development, and health.
Dimethyl itaconate ameliorates cognitive impairment induced by a high-fat diet via the gut-brain axis in mice
Authors: Pan Wei , Zhao Jinxiu , Wu Jiacheng , Xu Daxiang , Meng Xianran , Jiang Pengfei , Shi Hongli , Ge Xing , Yang Xiaoying , Hu Minmin , Zhang Peng , Tang Renxian , Nagaratnam Nathan , Zheng Kuiyang , Huang Xu-Feng , Yu Yinghua
Published: February 2023

Background

Gut homeostasis, including intestinal immunity and microbiome, is essential for cognitive function via the gut-brain axis. This axis is altered in high-fat diet (HFD)-induced cognitive impairment and is closely associated with neurodegenerative diseases. Dimethyl itaconate (DI) is an itaconate derivative and has recently attracted extensive interest due to its anti-inflammatory effect. This study investigated whether intraperitoneal administration of DI improves the gut-brain axis and prevents cognitive deficits in HF diet-fed mice.

Results

DI effectively attenuated HFD-induced cognitive decline in behavioral tests of object location, novel object recognition, and nesting building, concurrent with the improvement of hippocampal RNA transcription profiles of genes associated with cognition and synaptic plasticity. In agreement, DI reduced the damage of synaptic ultrastructure and deficit of proteins (BDNF, SYN, and PSD95), the microglial activation, and neuroinflammation in the HFD-fed mice. In the colon, DI significantly lowered macrophage infiltration and the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in mice on the HF diet, while upregulating the expression of immune homeostasis-related cytokines (IL-22, IL-23) and antimicrobial peptide Reg3γ. Moreover, DI alleviated HFD-induced gut barrier impairments, including elevation of colonic mucus thickness and expression of tight junction proteins (zonula occludens-1, occludin). Notably, HFD-induced microbiome alteration was improved by DI supplementation, characterized by the increase of propionate- and butyrate-producing bacteria. Correspondingly, DI increased the levels of propionate and butyrate in the serum of HFD mice. Intriguingly, fecal microbiome transplantation from DI-treated HF mice facilitated cognitive variables compared with HF mice, including higher cognitive indexes in behavior tests and optimization of hippocampal synaptic ultrastructure. These results highlight the gut microbiota is necessary for the effects of DI in improving cognitive impairment.

Conclusions

The present study provides the first evidence that DI improves cognition and brain function with significant beneficial effects via the gut-brain axis, suggesting that DI may serve as a novel drug for treating obesity-associated neurodegenerative diseases.
The impact of correctional officer gender on prison suicide
Authors: Carter TaLisa J. , Whittle Tanya N.
Published: February 2023

Correctional officers are critical members of the prison community. However, scholarship rarely considers how correctional officers contribute to prison outcomes instead largely focusing on importation (individual) and deprivation (organizational) factors related to the incarcerated population. This is also true regarding how scholars and practitioners approach suicide committed by incarcerated people, one of the leading causes of death in US carceral institutions. Using quantitative data from confinement facilities across the United States, this study answers the research question: What is the relationship between prison suicide rates and correctional officer gender? Results show that deprivation factors (variables related to the carceral environment) influence prison suicide. Additionally, gender diversity among correctional officers reduces the rate of prison suicide. Implications for future research and practice and limitations of the study are also discussed.
CAR-T cell therapy followed by allogenic hematopoietic stem cell transplantation yielded comparable outcome between Ph like ALL and other high-risk ALL
Authors: Dai Hai-ping , Kong Dan-qing , Shen Hong-jie , Cui Wei , Wang Qian , Li Zheng , Yin Jia , Kang Li-qing , Yu Lei , Wu De-pei , Tang Xiao-wen
Published: February 2023

It was previously believed that patients with Ph-like ALL had poorer prognosis compared with other B-ALL subgroups due to resistance to conventional chemotherapy and lack of targeted drugs. CAR-T therapy has been successfully applied in the treatment of relapsed and refractory B-ALL. Currently, there are few data on whether CAR-T therapy can alter the outcome of Ph-like ALL. Here we included 17 Ph-like, 23 Ph+ and 51 other B-ALL patients, who received autologous CAR T-cell therapy and subsequently allogenic stem cell transplantation. Patients in the Ph-like group and B-ALL-others group were younger that those in the Ph+ group (P=0.001). Ph-like and Ph+ ALL patients showed higher white blood cell counts at diagnosis (P=0.025). The percentage of patients with active disease before receiving CAR T-cells infusion was 64.7%, 39.1% and 62.7% in the Ph-like, Ph+ and B-ALL-others groups. The response rates to CAR-T therapy were 94.1% (16/17), 95.6% (22/23) and 98.0% (50/51) in the Ph-like, Ph+ and B-ALL-others groups. Measurable residual disease negative CR was achieved in 64.7% (11/17), 60.9% (14/23) and 54.9% (28/51) in the Ph-like, Ph+ and B-ALL-others groups, respectively. The estimated rates of 3-year overall survival (65.9%±16.5%, 59.7%±10.5% and 61.6%±7.3%, P=0.758) and 3-year relapse-free survival (59.8%±14.8%, 63.1%±10.5% and 56.3%±7.1%, P=0.764) were comparable among the Ph-like, Ph+ and B-ALL-others groups. Estimated 3-year cumulative relapse rate was 7.8%±0.6%, 23.4%±0.9% and 29.0%±0.4% (P=0.241). Our findings suggest that CART followed by allo-HSCT results in a comparable prognosis in Ph-like ALL and other high-risk B-ALL.

Trial registration ClinicalTrials. gov, NCT03275493, Registered on September 7, 2017, prospectively registered and NCT03614858, Registered on August 3, 2018, prospectively registered.
A comparative study on the audio-visual evaluation of the grand Song of the Dong soundscape
Authors: Mao Linqing , Zhang Xin , Ma Jianjun , Jia Yihong
Published: February 2023

Soundscape heritage records the cultural connotations of different ethnic groups, the destruction, and the disappearance of certain heritage makes its preservation urgent. This work aims to explore the influence of audio-visual different sensory stimuli on the subjective cognition, perceptual dimension and value evaluation of the Grand Song of the Dong soundscape heritage. We have conducted an audio-visual interaction experiment, using 2D video and high-fidelity audio systems to show typical visual elements and cultural scenes of the Grand Song of the Dong, and combined them with questionnaires to collect subjective data. The results show that the visual stimuli have no effect on the subjective evaluation of the Grand Song of the Dong soundscape, and that the different social characteristics of the participants are the main reason for the variations. The influence of audio-visual interaction on the perception of the of the Grand Song of the Dong soundscape is greater, with an enhanced perceptual dimension than the single auditory sensory, i.e., the scale dimension, indicating that visual stimuli can enhance the sensing of spatial limitation. The introduction of the visual element results in higher scores for each heritage value than the auditory element alone, indicating a positive impact on the value evaluation. The results of these studies provide a theoretical basis for the living transmission and holistic conservation of the Grand Song of the Dong and their scenes.
Prediction of hepatic lymph node metastases based on magnetic resonance imaging before and after preoperative chemotherapy in patients with colorectal liver metastases underwent surgical resection
Authors: Zhu Hai-bin , Xu Da , Sun Xue-Feng , Li Xiao-Ting , Zhang Xiao-Yan , Wang Kun , Xing Bao-Cai , Sun Ying-Shi
Published: February 2023

Background

Patients with colorectal liver metastases (CRLM) combined with hepatic lymph node (HLN) metastases have a poor prognosis. In this study, we developed and validated a model using clinical and magnetic resonance imaging (MRI) parameters to predict HLN status before surgery.

Methods

A total of 104 CRLM patients undergoing hepatic lymphonodectomy with pathologically confirmed HLN status after preoperative chemotherapy were enrolled in this study. The patients were further divided into a training group (n = 52) and a validation group (n = 52). The apparent diffusion coefficient (ADC) values, including ADCmean and ADCmin of the largest HLN before and after treatment, were measured. rADC was calculated referring to the target liver metastases, spleen, and psoas major muscle (rADC-LM, rADC-SP, rADC-m). In addition, ADC change rate (Δ% ADC) was quantitatively calculated. A multivariate logistic regression model for predicting HLN status in CRLM patients was constructed using the training group and further tested in the validation group.

Results

In the training cohort, post-ADCmean (P = 0.018) and the short diameter of the largest lymph node after treatment (P = 0.001) were independent predictors for metastatic HLN in CRLM patients. The model’s AUC was 0.859 (95% CI, 0.757-0.961) and 0.767 (95% CI 0.634-0.900) in the training and validation cohorts, respectively. Patients with metastatic HLN showed significantly worse overall survival (p = 0.035) and recurrence-free survival (p = 0.015) than patients with negative HLN.

Conclusions

The developed model using MRI parameters could accurately predict HLN metastases in CRLM patients and could be used to preoperatively assess the HLN status and facilitate surgical treatment decisions in patients with CRLM.
The 2022 focused update of the 2018 Korean Hypertension Society Guidelines for the management of hypertension
Authors: Kim Hack-Lyoung , Lee Eun Mi , Ahn Shin Young , Kim Kwang-il , Kim Hyeon Chang , Kim Ju Han , Lee Hae-Young , Lee Jang Hoon , Park Jong-Moo , Cho Eun Joo , Park Sungha , Shin Jinho , Kim Young-Kwon
Published: February 2023

Hypertension is the leading cause of death in human being, which shows high prevalence and associated complications that increase the mortality and morbidity. Controlling blood pressure (BP) is very important because it is well known that lowering high BP effectively improves patients’ prognosis. This review aims to provide a focused update of the 2018 Korean Hypertension Society Guidelines for the management of hypertension. The importance of ambulatory BP and home BP monitoring was further emphasized not only for the diagnosis but also for treatment target. By adopting corresponding BPs, the updated guideline recommended out-of-office BP targets for both standard and intensive treatment. Based on the consensus on corresponding BPs and Systolic Blood Pressure Intervention Trial (SPRINT) revisit, the updated guidelines recommended target BP in high-risk patients below 130/80 mmHg and it applies to hypertensive patients with three or more additional cardiovascular risk factors, one or more risk factors with diabetes, or hypertensive patients with subclinical organ damages, coronary or vascular diseases, heart failure, chronic kidney disease with proteinuria, and cerebral lacunar infarction. Cerebral infarction and chronic kidney disease are also high-risk factors for cardiovascular disease. However, due to lack of evidence, the target BP was generally determined at < 140/90 mmHg in patients with those conditions as well as in the elderly. Updated contents regarding the management of hypertension in special situations are also discussed.
Sex-specific differences in neuromuscular activation of the knee stabilizing muscles in adults - a systematic review
Authors: Steiner Martina , Baur Heiner , Blasimann Angela
Published: February 2023

Introduction

The rupture of the anterior cruciate ligament (ACL) is one of the most common injuries of the knee. Women have a higher injury rate for ACL ruptures than men. Various indicators for this sex-specific difference are controversially discussed.

Aim

A systematic review of the literature that compares surface electromyography (EMG) values of adult female and male subjects to find out if there is a difference in neuromuscular activation of the knee stabilizing muscles.

Methods

This systematic review has been guided and informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Studies which examined sex-specific differences with surface EMG measurements (integral, root mean squares, mean values, analysis of time and amplitude) of the knee stabilizing muscles were retrieved via searches from the databases PubMed, CINAHL, Embase, CENTRAL and SPORTDiscus. The risk of bias of included studies was assessed with the National Heart, Lung and Blood Institute (NHLBI) study quality assessment tool. A synthesis of results was performed for relevant outcomes.

Results

Fifteen studies with 462 healthy participants, 233 women (mean age 21.9 (± 2.29) years) and 299 men (mean age 22.6 (± 2.43) years), were included in the systematic review. The methodological quality of the studies was mostly rated “fair” (40%). A significantly higher activity of the muscles vastus lateralis and vastus medialis was found in females, in three studies. Two studies found significantly lower neuromuscular activity in the muscles biceps femoris and semitendinosus in females. All other included studies found no significant differences or reported even contradicting results.

Conclusion

The controversial findings do not allow for a concluding answer to the question of a sex-specific neuromuscular activation. Further research with higher statistical power and a more homogeneous methodical procedure (tasks and data normalisation) of the included studies may provide insight into possibly existing sex-specific differences in neuromuscular activation. This systematic review could help to improve the methodical design of future studies to get a more valid conclusion of the issue.

Trial registration

CRD42020189504.
Carbon neutral Bhutan: sustaining carbon neutral status under growth pressures
Authors: Yangka Dorji , Rauland Vanessa , Newman Peter
Published: February 2023

Background

Bhutan has pledged to remain carbon neutral (CN) in perpetuity. Whether they can sustain this is questionable due to the country’s increasing economic growth (GDP) and commitment to gross national happiness (GNH) outcomes, both of which can lead to a rise in greenhouse gas (GHG) emissions. The nexus between GHG, GNH and GDP is the essence of the Paris Agreement and Sustainable Development Goals global project.

Results

Through scenario modelling using the Long-range Energy Alternative Planning (LEAP) model, the study finds that the carbon neutral declaration will derail between 2037 and 2050 without mitigation measures. By putting in place mitigation measures especially in the industry and transport sectors, CN can be retained even under high growth pressure, which may cost just 2% of GDP. CN can be easily retained under low economic growth, but this could undermine GNH. High growth will require immediate interventions to enable electrification of industry and transport.

Conclusions

The options to remain CN will require Bhutan to adopt more efficient technologies and electrify industry and transport under both low and high growth scenarios. The additional cost to the Bhutanese economy is feasible through low and high growth opportunities. The options are similar to those confronting emerging nations struggling with issues of climate commitments under economic growth pressures. All will need to adapt their specific economic contexts to achieve the simultaneous objectives of the Sustainable Development Goals whilst addressing the net zero Paris agenda. Bhutan shows it is possible.
The impact of UAS aerial ignition on prescribed fire: a case study in multiple ecoregions of Texas and Louisiana
Authors: Lawrence Brett L. , Mundorff Kevin , Keith Eric
Published: February 2023

Background

Small Unmanned Aerial System (UAS) technologies and their applications have expanded in recent years, to include aerial ignition support in prescribed fire and wildland fire settings. In 2019, we incorporated the use of UAS aerial ignition into our existing prescribed fire program of over 20 years. To assess its impact, comparisons of UAS and non-UAS burns were performed on burn data from 2012 to 2021, with 58 total UAS burns conducted from 2019 to 2021. A subset of these burns conducted at Cook’s Branch Conservancy in Montgomery County, TX, included post-burn assessment data, which we used to compare UAS and non-UAS fire effects.

Results

Non-parametric significance tests were used to analyze and compare non-UAS burning before (2012–2018) and after (2019–2021) the incorporation of the UAS, and UAS burning from 2019 to 2021. Response variables included ha day−1 burned and six different post-burn assessment metrics. Principal findings were that from 2019 to 2021, UAS burns were 61 ha day−1 or 129% more efficient than non-UAS burning and required one extra staff member to pilot the UAS on average. This increase enabled a previously unachievable efficiency in terms of hectares burned each year vs days burned each year when using the UAS. While fire effects were less severe for most post-burn assessment metrics during UAS burning, burn results still met fuel management goals when compared to non-UAS burning.

Conclusions

A large increase in ha day−1 was previously unachievable, making the UAS a viable tool for accomplishing safer and more effective prescribed burn operations in the limited number of suitable days available. When managed responsibly, UAS aerial ignition is poised to have a positive impact on the safe and effective application of prescribed fire, resulting in more achievable conservation and fuel management goals.
Knowledge and awareness of physical therapy role in evaluating and treating temporomandibular disorders among physical therapists in Saudi Arabia
Authors: Almutairi Sattam M. , Alqoussi Taif F. , Alassaf Fai S. , Alharbi Amirah S. , Alrumihe Sara M. , Alharbi Majd S. , Almutairi Marzouq K.
Published: February 2023

Background

Practitioners, including physical therapists, are not proficiently trained to evaluate and treat individuals with temporomandibular disorders. The purpose of this study is to evaluate the knowledge and awareness of examining and treating temporomandibular disorders among physical therapists in Saudi Arabia.

Methods

An online questionnaire was distributed to physical therapists on different social media platforms. The survey covered demographics characteristics and knowledge of examining and treating temporomandibular disorders. Descriptive statistics were used for data analysis.

Results

A total of 143 participants with a mean of age of 30 (± 6.6) years participated in this study. The majority of participants (n = 109; 76.2%) did not take educational courses on temporomandibular disorders; more than half (n = 84; 58.7%) had never evaluated or treated individuals with temporomandibular disorders. Most physical therapists were aware that they could treat individuals with temporomandibular disorders (n = 121, 84.6%). The most common evaluation methods were temporomandibular joint palpation, jaw movement during opening and closing, and palpation of the masticatory muscles (n = 56, 95%); (n = 49, 83%); (n = 48, 81%), respectively. The common methods used for treatment were therapeutic exercise strengthening, manual therapy, and patient education (n = 49; 83%; n = 46; 78%; n = 33; 56%), respectively. Thirty-one participants (53%) referred patients to other practitioners.

Conclusion

This preliminary study indicates there is a fair level of knowledge, low confidence, low education, and low clinical experience for physical therapists in the evaluation and treatment of temporomandibular disorders in Saudi Arabia. More attention is needed on physical therapy education programs and post-graduate education courses on temporomandibular disorders.
Longitudinal trajectories in negative symptoms and changes in brain cortical thickness: 10-year follow-up study
Authors: Canal-Rivero Manuel , Ruiz-Veguilla Miguel , Ortiz-García de la Foz Victor , López-Díaz Alvaro , Garrido-Torres Nathalia , Ayesa-Arriola Rosa , Vazquez-Bourgon Javier , Mayoral-van Son Jacqueline , Brambilla Paolo , Kircher Tilo , Romero-García Rafael , Crespo-Facorro Benedicto
Published: February 2023

Background

Understanding the evolution of negative symptoms in first-episode psychosis (FEP) requires long-term longitudinal study designs that capture the progression of this condition and the associated brain changes.

Aims

To explore the factors underlying negative symptoms and their association with long-term abnormal brain trajectories.

Method

We followed up 357 people with FEP over a 10-year period. Factor analyses were conducted to explore negative symptom dimensionality. Latent growth mixture modelling (LGMM) was used to identify the latent classes. Analysis of variance (ANOVA) was conducted to investigate developmental trajectories of cortical thickness. Finally, the resulting ANOVA maps were correlated with a wide set of regional molecular profiles derived from public databases.

Results

Three trajectories (stable, decreasing and increasing) were found in each of the three factors (expressivity, experiential and attention) identified by the factor analyses. Patients with an increasing trajectory in the expressivity factor showed cortical thinning in caudal middle frontal, pars triangularis, rostral middle frontal and superior frontal regions from the third to the tenth year after the onset of the psychotic disorder. The F-statistic map of cortical thickness expressivity differences was associated with a receptor density map derived from positron emission tomography data.

Conclusions

Stable and decreasing were the most common trajectories. Additionally, cortical thickness abnormalities found at relatively late stages of FEP onset could be exploited as a biomarker of poor symptom outcome in the expressivity dimension. Finally, the brain areas with less density of receptors spatially overlap areas that discriminate the trajectories of the expressivity dimension.
Unstructured Data Are Superior to Structured Data for Eliciting Quantitative Smoking History From the Electronic Health Record
Authors: Ruckdeschel John C. , Riley Mark , Parsatharathy Sriram , Chamarthi Rajesh , Rajagopal Chakethraman , Hsu Hui Shuang , Mangold Doug , Driscoll Chiny
Published: February 2023

PURPOSE

Develop a method for extracting smoking status and quantitative smoking history from clinician notes to facilitate cohort identification for low-dose computed tomography (LDCT) scanning for early detection of lung cancer.

MATERIALS AND METHODS

A sample of 4,615 adult patients were randomly selected from the Multiparameter Intelligent Monitoring in Critical Care (MIMIC-III) database. The structured data were obtained by queries of the diagnosis tables using the International Classification of Diseases codes in use at that time. Unstructured data were drawn from clinician notes via natural language processing (NLP) using named entity recognition and our clinical data processing and extraction algorithms to identify two main clinical criteria for each smoking patient: (1) pack years smoked and (2) time from quit date (if applicable). A subset of 10% of the patient charts were manually reviewed for accuracy and precision.

RESULTS

The structured data revealed 575 (12.5%) ever smokers (current plus past use). None of these patients had quantification of their smoking history, and 4,040 (87.5%) had no smoking information in the diagnosis tables; consequently, a cohort of patients eligible for LDCT could not be determined. Review of the physician notes by NLP disclosed 1,930 (41.8%) ever smokers of whom 537 were active smokers and 1,299 former smokers, and in 94 cases, it could not be determined if they were active or former smokers. A total of 1365 patients (29.6%) had no smoking data recorded. When the smoking and the age criteria for LDCT were applied to this group, 276 were found to be eligible for LDCT using the USPSTF criteria. As determined by clinician review, our F-score for identifying patients eligible for LDCT was 0.88.

CONCLUSION

Unstructured data, obtained by NLP, can accurately identify a precise cohort that meets the USPSTF guidelines for LDCT.
High-Grade Serous Carcinoma at Risk-Reducing Salpingo-Oophorectomy in Asymptomatic Carriers of BRCA1/2 Pathogenic Variants: Prevalence and Clinical Factors
Authors: Stroot Iris A.S. , Brouwer Jan , Bart Joost , Hollema Harry , Stommel-Jenner Denise J. , Wagner Marise M. , van Doorn Helena C. , de Hullu Joanne A. , Gaarenstroom Katja N. , Beurden Marc , van Lonkhuijzen Luc R.C.W. , Slangen Brigitte F.M. , Zweemer Ronald P. , Gómez Garcia Encarna B. , Ausems Margreet G.E.M. , Boere Ingrid A. , van Engelen Klaartje , van Asperen Christi J. , Schmidt Marjanka K. , Wevers Marijke R. , de Bock Geertruida H. , Mourits Marian J.E. ,   on behalf of the HEBON Investigators
Published: February 2023

PURPOSE

To investigate the prevalence of and clinical factors associated with high-grade serous carcinoma (HGSC) at risk-reducing salpingo-oophorectomy (RRSO) in asymptomatic BRCA1/2-pathogenic variant (PV) carriers.

PATIENTS AND METHODS

We included BRCA1/2-PV carriers who underwent RRSO between 1995 and 2018 from the Hereditary Breast and Ovarian cancer in the Netherlands study. All pathology reports were screened, and histopathology reviews were performed for RRSO specimens with epithelial abnormalities or where HGSC developed after normal RRSO. We then compared clinical characteristics, including parity and oral contraceptive pill (OCP) use, for women with and without HGSC at RRSO.

RESULTS

Of the 2,557 included women, 1,624 had BRCA1, 930 had BRCA2, and three had both BRCA1/2-PV. The median age at RRSO was 43.0 years (range: 25.3-73.8) for BRCA1-PV and 46.8 years (27.6-77.9) for BRCA2-PV carriers. Histopathologic review confirmed 28 of 29 HGSCs and two further HGSCs from among 20 apparently normal RRSO specimens. Thus, 24 (1.5%) BRCA1-PV and 6 (0.6%) BRCA2-PV carriers had HGSC at RRSO, with the fallopian tube identified as the primary site in 73%. The prevalence of HGSC in women who underwent RRSO at the recommended age was 0.4%. Among BRCA1/2-PV carriers, older age at RRSO increased the risk of HGSC and long-term OCP use was protective.

CONCLUSION

We detected HGSC in 1.5% ( BRCA1-PV) and 0.6% ( BRCA2-PV) of RRSO specimens from asymptomatic BRCA1/2-PV carriers. Consistent with the fallopian tube hypothesis, we found most lesions in the fallopian tube. Our results highlight the importance of timely RRSO with total removal and assessment of the fallopian tubes and show the protective effects of long-term OCP.
Aldosterone- and Cortisol Co-secreting Adrenal Cortical Neoplasm With Lipomatous and Myelolipomatous Metaplasia
Authors: Jinna Sruthi , Taftaf Rokana , Petros Firas G , Jun John Y
Published: February 2023

We report a case of a 58-year-old woman with a history of hypertension diagnosed at aged 35 years, on 5 antihypertensive agents and a history of intermittent spontaneous hypokalemia, was found to have a 6-cm left adrenal mass on computed tomography scan of the abdomen. The unenhanced computed tomography attenuation of the adrenal mass was −16 Hounsfield units (HU). The biochemical evaluation showed potassium of 2.8 mEq/L (SI unit, mmol/L) (reference range, 3.5-5.0), plasma aldosterone concentration of 61.3 ng/dL (SI unit, 1701 pmol/L) with plasma renin activity of 0.4 ng/mL/h (SI unit, μg/L/h). An overnight 1-mg dexamethasone suppression test showed nonsuppressible serum cortisol of 10.8 μg/dL (SI unit, 298 nmol/L). Dehydroepiandrosterone sulfate and ACTH were measured at 24.5 μg/dL (age-adjusted, 26-200) (SI unit, 0.66 μmol/L; 0.70-5.43) and <5 pg/mL (SI unit, < 1.1 pmol/L), respectively. Left adrenalectomy was performed and hydrocortisone therapy was initiated. Postoperatively and thereafter, her blood pressure was controlled with no antihypertensive agent. Seven months later, hydrocortisone therapy was stopped once her cortisol level had normalized. Pathology showed adrenal cortical neoplasm of uncertain malignant potential with associated lipomatous and myelolipomatous metaplasia. This is a rare case of aldosterone and cortisol co-secreting adrenal cortical neoplasm of uncertain malignant potential with lipomatous and myelolipomatous metaplasia. Although the majority of cases of myelolipoma are benign and nonfunctioning, this case emphasizes the importance of thorough hormonal and morphologic evaluation of the tumor.
SARS-CoV-2 infection alkalinizes the ERGIC and lysosomes through the viroporin activity of the viral envelope protein
Authors: Wang Wen-An , Carreras-Sureda Amado , Demaurex Nicolas
Published: February 2023

The coronavirus SARS-CoV-2, the agent of the deadly COVID-19 pandemic, is an enveloped virus propagating within the endocytic and secretory organelles of host mammalian cells. Enveloped viruses modify the ionic homeostasis of organelles to render their intra-luminal milieu permissive for viral entry, replication and egress. Here, we show that infection of Vero E6 cells with the delta variant of the SARS-CoV-2 alkalinizes the endoplasmic reticulum (ER)–Golgi intermediate compartment (ERGIC) as well as lysosomes, mimicking the effect of inhibitors of vacuolar proton ATPases. We further show the envelope protein of SARS-CoV-2 accumulates in the ERGIC when expressed in mammalian cells and selectively dissipates the ERGIC pH. This viroporin action is prevented by mutations of Val25 but not Asn15 within the channel pore of the envelope (E) protein. We conclude that the envelope protein acts as a proton channel in the ERGIC to mitigate the acidity of this intermediate compartment. The altered pH homeostasis of the ERGIC likely contributes to the virus fitness and pathogenicity, making the E channel an attractive drug target for the treatment of COVID-19.
Detection of vertical root fractures by cone-beam computed tomography based on deep learning
Authors: Yang Pan , Guo Xiaolong , Mu Chuangchuang , Qi Senrong , Li Gang
Published: February 2023

Objectives:

This study aims to evaluate the performance of ResNet models in the detection of in vitro and in vivo vertical root fractures (VRF) in Cone-beam Computed Tomography (CBCT) images.

Methods:

A CBCT image dataset consisting of 28 teeth (14 intact and 14 teeth with VRF, 1641 slices) from 14 patients, and another dataset containing 60 teeth (30 intact and 30 teeth with VRF, 3665 slices) from an in vitro model were used for the establishment of VRFconvolutional neural network (CNN) models. The most popular CNN architecture ResNet with different layers was fine-tuned for the detection of VRF. Sensitivity, specificity, accuracy, PPV (positive predictive value), NPV (negative predictive value), and AUC (the area under the receiver operating characteristic curve) of the VRF slices classified by the CNN in the test set were compared. Two oral and maxillofacial radiologists independently reviewed all the CBCT images of the test set, and intraclass correlation coefficients (ICCs) were calculated to assess the interobserver agreement for the oral maxillofacial radiologists.

Results:

The AUC of the models on the patient data were: 0.827(ResNet-18), 0.929(ResNet-50), and 0.882(ResNet-101). The AUC of the models on the mixed data get improved as:0.927(ResNet-18), 0.936(ResNet-50), and 0.893(ResNet-101). The maximum AUC were: 0.929 (0.908–0.950, 95% CI) and 0.936 (0.924–0.948, 95% CI) for the patient data and mixed data from ResNet-50, which is comparable to the AUC (0.937 and 0.950) for patient data and (0.915 and 0.935) for the mixed data obtained from the two oral and maxillofacial radiologists, respectively.

Conclusions:

Deep-learning models showed high accuracy in the detection of VRF using CBCT images. The data obtained from the in vitro VRF model increases the data scale, which is beneficial to the training of deep-learning models.
Τα χαρακτηριστικά και οι μέθοδοι ανάδειξης της Γυναίκας-Ηγέτη στην Τραγωδία και Κωμωδία
Authors: Παππά Χαρίκλεια
Published: February 2023

Στην παρούσα διδακτορική διατριβή εξετάζουμε τα χαρακτηριστικά και τις μεθόδους ανάδειξης του ρόλου της γυναίκας ως ηγέτιδος στην Αρχαία ελληνική Τραγωδία και Κωμωδία. Συγκεκριμένα, παρουσιάζουμε τα μέσα και τις τεχνικές που μετέρχονται οι γυναίκες, προκειμένου να διεκδικήσουν την εξουσία και να εξασφαλίσουν την ηγετική τους θέση, καθώς και τους τρόπους με τους οποίους υπερισχύουν των ανδρών. Είναι εντυπωσιακό το γεγονός ότι μια κοινωνία που επέβαλλε τη σιωπή των γυναικών, παρήγε, προέβαλλε και προωθούσε με εντυπωσιακό τρόπο ένα λογοτεχνικό είδος, τη δραματική ποίηση και τις θεατρικές παραστάσεις, όπου ο γυναικείος λόγος ακούγεται και μάλιστα με τρόπο ιδιαίτερα ευφραδή. Τόσο η Τραγωδία όσο και η Κωμωδία δίνουν με προκλητικό τρόπο φωνή στις γυναίκες και τους επιτρέπουν, έτσι, να αντιτεθούν στο σύστημα αξιών της πόλεως. Οι γυναικείες φωνές στην Αρχαία Τραγωδία και στην Αττική Κωμωδία προκαλούν ρωγμές στις κυρίαρχες ιδεολογικές παραδοχές για τις γυναίκες. Οι ρήσεις της Αντιγόνης και της Μήδειας, αλλά και της Λυσιστράτης και της Πραξαγόρας, καθώς και τόσων άλλων γυναικών στη θεατρική σκηνή δείχνουν ότι η περιθωριοποίηση και η απαξίωση των γυναικών από τους άνδρες αρχίζει να προκαλεί αντιδράσεις και να αποδοκιμάζεται. Στην ανάλυσή μας εφαρμόζουμε τη μέθοδο της δομικής ανθρωπολογίας, δηλαδή του στρουκτουραλισμού, αφού κάθε προσπάθεια ανάληψης εξουσίας, κάθε μορφή εξουσίας δεν μπορεί να γίνει αντιληπτή και να εξηγηθεί, παρά μόνο όταν εξετάζουμε το φαινόμενο στο πλαίσιο των βασικών δομών της κοινωνίας στην οποία αυτό επιτελείται, καθώς και στο πλαίσιο συγκεκριμένων πολιτικών και θρησκευτικών δομών.
Genomic profiles of Indonesian colorectal cancer patients
Authors: Abdullah Murdani , Meilany Sofy , Trimarsanto Hidayat , Malik Safarina G. , Sukartini Ninik , Idrus Firhat , Nursyirwan Saskia A. , Muzellina Virly N. , Pribadi Rabbinu R. , Utari Amanda P. , Maulahela Hasan , Syam Ari F.
Published: February 2023

Background: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide and genetic mutation plays a vital role in CRC development. A previous study has suggested that genetic alterations among Indonesian patients with CRC might differ from those known in developed countries. This study aimed to describe the genomic profiles of Indonesian patients with CRC.

Methods: A total of 13 patients were recruited for this study from May to July 2019. Tissue samples were collected, and genomic DNA was extracted from the samples. AmpliSeq for Illumina Cancer HotSpot Panel v2 Next-generation sequencing was used for DNA sequencing and a genome analysis toolkit was used for local realignment around the discovered variants.

Results: A total of 45 genes comprising 391 single nucleotide variants (SNVs) with a depth >10 were observed. The genes with the most variants were STK11, SMAD4, EGFR, and ERBB4 and the genes with the most non-synonymous variants were SMAD4, TP53, FGFR3, CDKN2A, and STK11. Genes and SNVs in at least 90% of all samples consisted of 43 genes comprising 286 variants. Genes with the most non-synonymous SNVs were EGFR, SMO, FGFR3, TP53, STK11, CDKN2A. Genes related to the chromosomal instability pathway, such as TP53, SMAD4, KRAS, and APC, are also found in the analysis.

Conclusions: Our findings showed that all patients with CRC in this study had genetic mutations in the chromosomal instability pathway. Analysis of genetic mutation of Indonesian patients with CRC might be crucial for advanced targeted therapy and for better clinical outcomes.
Determinants of pre-lacteal feeding practice in Ethiopia: Evidence from the 2019 Mini Demographic and Health Survey (MDHS), a community-based cross-sectional study
Authors: Molla Gebeyaw , Getachew Fikreselassie , Tadele Ashenif , Taye Girum , Taddele Tefera , Gonfa Geremew , Getnet Misrak , Shumet Tigist , Defar Atkure , Teklie Habtamu , Achamyeleh Hiwot , Tesfaye Hanim , Getachew Theodros
Published: February 2023

Background: Every year, 10.9 million people die around the world. More than two-thirds of deaths were associated with inappropriate feeding practices. Within the first three days after birth, nearly two out of every five newborns are given fluids other than breast milk. The aim of this study was to assess the determinants of pre-lacteal feeding practice in Ethiopia among mothers who had a live birth child under the age of 24 months.

Methods: Secondary data from Ethiopia's 2019 Mini Demographic and Health Survey (MDHS) were used. A stratified, two-stage cluster sampling method was employed in the MDHS. A total of 8,885 reproductive-age women were interviewed in the survey, but only 2,061 women with a live birth child under the age of two years were included. Our study focused on the details obtained for these 2,061 women. Logistic regression analysis was used to identify factors associated with pre-lacteal feeding practices among them. A Hosmer-Lemeshow goodness of fit test was used to check the model fitness and a multicollinearity test was used to diagnosis collinearity between independent variables.

Results: The results revealed that 12.1% (95%CI; 10.30%, 13.9%) of the women practiced pre-lacteal feeding. Mothers who lived in pastoralist regions (AOR:3.2; 95%CI: 1.5-6.84), who hadn’t attended antenatal care (ANC) visits (AOR:3.83; 95%CI: 1.55-6.27), who had attended 1-3 visits (AOR:1.65; 95%CI: 1.15-3.94), who delivered at home (AOR:1.72, 95%CI: 1.20-2.43), those who delivered by Caesarean section (AOR:3.72; 95%CI: 2.32-5.96), mothers who started breastfeeding after one hour (AOR:4.41; 95%CI: 3.23-6.02) were identified as the groups most associated with pre-lacteal feeding.

Conclusions: Pre-lacteal feeding was practiced by a significant number of women in this study. Living in a pastoralist region, attending 1-3 ANC visits, home delivery, caesarean section delivery, and late initiation of breastfeeding were the determinant factors of prelacteal feeding among the women.
A Prospective Study on the Transmission dynamics of Corona virus disease (2019) (COVID-19) among Household contacts in Delhi, India.
Authors: Sharma Pragya , Rao Shivani , Saxena Sonal , Manchanda Vikas , Chawla Rohit , Mariam Warisha , Basu Saurav , Rahman Anisur , Singh Meghachandra , Rana Neha , Athotra Aditya , Sharma Himanshi , Ahmad Mohammad
Published: February 2023

Background: This study was conducted to understand the transmission dynamics of COVID-19 virus among the household contacts of RT-PCR confirmed cases to have an insight on key epidemiological characteristics of the infection.

Methods: This was a prospective case-ascertained study conducted among the contacts of laboratory-confirmed COVID-19 cases residing in the same household in the Central and North-East districts of Delhi between 28th December 2020, and 28th June 2021. Data and specimen for reverse transcription polymerase chain reaction (RT-PCR) and serology were collected from the primary case and their contacts on day one of the visit, and follow-up collection of data and specimen was done on day 7, 14 and 28. A daily symptom diary was also maintained for all the primary cases and their contacts till 28 days from enrolment in the study. A total of 109 houses were enrolled in the study.

Results: The secondary attack rate (SAR) estimated among the household contacts was 13.86% [95% C.I. 9.71%, 19.39%] and the secondary infection rate was 33.16% [95% C.I. 26.97%, 40.00%]. The serial interval and basic reproduction number (R0) within the household were estimated to be 3.6± 5.73 days and 1.26 [95% C.I. 1.21—1.31], respectively. Significant predictors of the infection were location of household in central district (SAR = 20% [13.75, 28.16]) versus North-East District (SAR = 4.87% [1.83-12.35]) p= 0.002, sharing of utensils (SAR= 42.85% [14.26—77.11], p=0.02), and using the room to sleep where a specific case has been isolated (SAR= 25% [12.97—42.71], p=0.047). Transmission from the symptomatic primary case was observed to be five times higher.

Conclusion: Our analysis showed that the secondary infection rate was higher among household contacts. This study suggests a dose-response association between severity of the primary case of SARS CoV-2 and infection among contacts.
Multi-layer modelling of masonry structures strengthened through textile-reinforced mortar
Authors: Boem Ingrid
Published: February 2023

Background

Textile-reinforced mortar (TRM) is an innovative strategy for the reduction of the seismic vulnerability of existing masonry buildings consisting in the application on the masonry surface, of a mortar coating with fiber-based grids or textiles embedded. The paper presents the calibration and application of a simplified modelling approach, based on multi-layered elements, for the simulation of existing masonry elements and structures strengthened through TRM.

Methods

The strengthened masonry is modelled by using 20-nodes brick elements formed by a stacking sequence of layers representing the different material components (the masonry, the mortar coating and the embedded reinforcement). The nonlinear behavior of the materials is considered and calibrated on the basis of experimental characterization tests on individual components available in the literature. The simplified assumption of perfect bond among layers is considered.

Results

Non-linear static analyses are performed on samples of increasing complexity: elementary panels, structural elements (piers and spandrels) and a pilot building. The results of some tests on TRM strengthened masonry, available in the literature, are considered to assess the model reliability in terms of capacity curves and collapse mode. The model is capable of detecting the typical failure mechanism of both unstrengthened and TRM strengthened masonry, namely the diagonal cracking, the in-plane bending and the out-of-plane bending and is able to detect the activation also of mixed failure modes, that often occur in actual configurations.

Conclusions

Given the coarse mesh size and the smear plasticization assumption, the model is not suitable for the rigorous reproduction of individual cracks but represents a good compromise between the goal to grasp the structural performances at the wide scale, including failure modes, and the analysis optimization.