bluuebunny/crossref_metadata_2025 huggingface dataset:
LRG1: an emerging player in disease pathogenesis
Authors: Camilli Carlotta , Hoeh Alexandra E. , De Rossi Giulia , Moss Stephen E. , Greenwood John
Published: January 2022

The secreted glycoprotein leucine-rich α-2 glycoprotein 1 (LRG1) was first described as a key player in pathogenic ocular neovascularization almost a decade ago. Since then, an increasing number of publications have reported the involvement of LRG1 in multiple human conditions including cancer, diabetes, cardiovascular disease, neurological disease, and inflammatory disorders. The purpose of this review is to provide, for the first time, a comprehensive overview of the LRG1 literature considering its role in health and disease. Although LRG1 is constitutively expressed by hepatocytes and neutrophils,Lrg1−/−mice show no overt phenotypic abnormality suggesting that LRG1 is essentially redundant in development and homeostasis. However, emerging data are challenging this view by suggesting a novel role for LRG1 in innate immunity and preservation of tissue integrity. While our understanding of beneficial LRG1 functions in physiology remains limited, a consistent body of evidence shows that, in response to various inflammatory stimuli, LRG1 expression is induced and directly contributes to disease pathogenesis. Its potential role as a biomarker for the diagnosis, prognosis and monitoring of multiple conditions is widely discussed while dissecting the mechanisms underlying LRG1 pathogenic functions. Emphasis is given to the role that LRG1 plays as a vasculopathic factor where it disrupts the cellular interactions normally required for the formation and maintenance of mature vessels, thereby indirectly contributing to the establishment of a highly hypoxic and immunosuppressive microenvironment. In addition, LRG1 has also been reported to affect other cell types (including epithelial, immune, mesenchymal and cancer cells) mostly by modulating the TGFβ signalling pathway in a context-dependent manner. Crucially, animal studies have shown that LRG1 inhibition, through gene deletion or a function-blocking antibody, is sufficient to attenuate disease progression. In view of this, and taking into consideration its role as an upstream modifier of TGFβ signalling, LRG1 is suggested as a potentially important therapeutic target. While further investigations are needed to fill gaps in our current understanding of LRG1 function, the studies reviewed here confirm LRG1 as a pleiotropic and pathogenic signalling molecule providing a strong rationale for its use in the clinic as a biomarker and therapeutic target.
Sonosensitive capsules for brain thrombolysis increase ischemic damage in a stroke model
Authors: Correa-Paz Clara , Navarro Poupard María F. , Polo Ester , Rodríguez-Pérez Manuel , Migliavacca Martina , Iglesias-Rey Ramón , Ouro Alberto , Maqueda Elena , Hervella Pablo , Sobrino Tomás , Castillo José , del Pino Pablo , Pelaz Beatriz , Campos Francisco
Published: January 2022

Background

Ischemic stroke is the most common cerebrovascular disease and is caused by interruption of blood supply to the brain. To date, recombinant tissue plasminogen activator (rtPA) has been the main pharmacological treatment in the acute phase. However, this treatment has some drawbacks, such as a short half-life, low reperfusion rate, risk of hemorrhagic transformations, and neurotoxic effects. To overcome the limitations of rtPA and improve its effectiveness, we recently designed sonosensitive sub-micrometric capsules (SCs) loaded with rtPA with a size of approximately 600 nm, synthesized using the layer-by-layer (LbL) technique, and coated with gelatine for clot targeting. In this study, we evaluated the rtPA release of ultrasound (US)-responsive SCs in healthy mice and the therapeutic effect in a thromboembolic stroke model.

Results

In healthy mice, SCs loaded with rtPA 1 mg/kg responded properly to external US exposure, extending the half-life of the drug in the blood stream more than the group treated with free rtPA solution. The gelatine coating also contributed to stabilizing the encapsulation and maintaining the response to US. When the same particles were administered in the stroke model, these SCs appeared to aggregate in the ischemic brain region, probably generating secondary embolisms and limiting the thrombolytic effect of rtPA. Despite the promising results of these thrombolytic particles, at least under the dose and size conditions used in this study, the administration of these capsules represents a risk factor for stroke.

Conclusions

This is the first study to report the aggregation risk of a drug carrier in neurological pathologies such as stroke. Biocompatibility analysis related to the use of nano-and microparticles should be deeply studied to anticipate the limitations and orientate the design of new nanoparticles for translation to humans.

Graphical Abstract
Urinary incontinence in pregnant women and its impact on health-related quality of life
Authors: Wang Xiaojuan , Jin Ying , Xu Ping , Feng Suwen
Published: January 2022

Background

Urinary incontinence is a common and distressing condition affecting women worldwide. However, urinary incontinence during pregnancy was less studied. The study aims to investigate the prevalence and risk factors of urinary incontinence during pregnancy, its impact on health-related quality of life as well as associated help-seeking behavior.

Methods

Eligible women were enrolled in the obstetric wards of a tertiary maternity hospital. Urinary incontinence, generic and specific health-related quality of life were assessed using the International Consultation on Incontinence Modular Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF), the 12-Item Short Form Health Survey version 2 (SF-12v2), Urogenital Distress Inventory short form (UDI-6) and Incontinence Impact Questionnaire short form (IIQ-7), respectively. Multiple logistic regression and multiple linear regression analysis were used to examine risk factors of urinary incontinence during pregnancy and the impact of incontinence on health-related quality of life of pregnant women, respectively.

Results

A total of 1243 women were enrolled in the study. The prevalence of urinary incontinence during pregnancy was 52.0%. Most women suffered from mild or moderate incontinence. Five risk factors were identified by multiple logistic regression. Urinary incontinence before pregnancy was the strongest predictor for incontinence during pregnancy (OR = 4.178, 95% CI = 2.690–6.490), followed by history of vaginal birth, coffee consumption, childhood enuresis and history of urinary tract infection. Urinary incontinence had significant impact on health-related quality of life during pregnancy. Only 14.8% of pregnant women sought professional help for urinary symptoms.

Conclusions

Urinary incontinence was highly prevalent in pregnant women, with a broad detrimental effect on health-related quality of life. Five factors were confirmed to be associated with increasing the risk of developing urinary incontinence during pregnancy. The help-seeking behavior during pregnancy was discouraging. Targeted interventions are warranted to facilitate the prevention of urinary incontinence and improvement of health-related quality of life in pregnant women.
Novel nomogram for predicting risk of early postoperative small bowel obstruction after right colectomy for cancer
Authors: Zheng Huida , Liu Yurong , Chen Zhenze , Sun Yafeng , Xu Jianhua
Published: January 2022

Background

Early postoperative small bowel obstruction (EPSBO) is a common complication after colorectal cancer surgery. Few studies have specifically studied risk factors for early small bowel obstruction after right colectomy, especially in establishing predictive models. The purpose of the current study was to establish an effective nomogram to predict the incidence of EPSBO after right colectomy.

Methods

The current study retrospectively analyzed data from a total of 424 patients who underwent right colectomy in a local hospital from January 2014 to March 2021. A logistic regression model was used to identify potential risk factors for EPSBO after right colectomy. A nomogram was established by independent risk factors, and the prediction performance of the model was evaluated using an area under the receiver operating characteristic (ROC) curve and calibration chart.

Results

A total of 45 patients (10.6%) developed early small bowel obstruction after right colectomy. Male sex, history of abdominal surgery, open surgery, long operative time, anastomotic leakage, and preoperative albumin were closely related to EPSBO. Analysis of postoperative rehabilitation indices showed that EPSBO remarkably slowed the postoperative rehabilitation speed of patients. Multivariate logistic regression analysis showed that male sex, open surgery, operative time, and anastomotic leakage were independent risk factors (P < 0.05), and the operation time had the greatest impact on EPSBO. On the basis of multivariate logistic regression, a nomogram was constructed, which showed moderate accuracy in predicting EPSBO, with a C-statistic of 0.716. The calibration chart showed good consistency between the predicted probability and ideal probability.

Conclusion

The current study constructed a nomogram based on the clinical data of patients who underwent right colectomy, which had moderate predictability and could provide reference value for clinicians to evaluate the risk of EPSBO.
Association between hospital and ICU structural factors and patient outcomes in China: a secondary analysis of the National Clinical Improvement System Data in 2019
Authors: Li Zhen , Ma Xudong , Gao Sifa , Li Qi , Luo Hongbo , Sun Jianhua , Du Wei , Su Longxiang , Wang Lu , Zhang Qing , Li Zunzhu , Zhou Xiang , Liu Dawei ,   China National Critical Care Quality Control Center Group, Wang Xue , Guan Xiangdong , Kang Yan , Xiong Bin , Qin Bingyu , Qian Kejian , Wang Chunting , Zhao Mingyan , Ma Xiaochun , Yu Xiangyou , Lin Jiandong , Pan Aijun , Qiu Haibo , Shen Feng , Li Shusheng , Ai Yuhang , Xie Xiaohong , Yan Jing , Wu Weidong , Duan Meili , Wan Linjun , Yang Xiaojun , Liu Jian , Xu Hang , Jiang Dongpo , Xu Lei , Chen Zhuang , Lin Guoying , Yang Zhengping , Hu Zhenjie
Published: January 2022

Background

Hospital and ICU structural factors are key factors affecting the quality of care as well as ICU patient outcomes. However, the data from China are scarce. This study was designed to investigate how differences in patient outcomes are associated with differences in hospital and ICU structure variables in China throughout 2019.

Methods

This was a multicenter observational study. Data from a total of 2820 hospitals were collected using the National Clinical Improvement System Data that reports ICU information in China. Data collection consisted of a) information on the hospital and ICU structural factors, including the hospital type, number of beds, staffing, among others, and b) ICU patient outcomes, including the mortality rate as well as the incidence of ventilator-associated pneumonia (VAP), catheter-related bloodstream infections (CRBSIs), and catheter-associated urinary tract infections (CAUTIs). Generalized linear mixed models were used to analyse the association between hospital and ICU structural factors and patient outcomes.

Results

The median ICU patient mortality was 8.02% (3.78%, 14.35%), and the incidences of VAP, CRBSI, and CAUTI were 5.58 (1.55, 11.67) per 1000 ventilator days, 0.63 (0, 2.01) per 1000 catheter days, and 1.42 (0.37, 3.40) per 1000 catheter days, respectively. Mortality was significantly lower in public hospitals (β =  − 0.018 (− 0.031, − 0.005), p = 0.006), hospitals with an ICU-to-hospital bed percentage of more than 2% (β =  − 0.027 (− 0.034, -0.019), p < 0.001) and higher in hospitals with a bed-to-nurse ratio of more than 0.5:1 (β = 0.009 (0.001, 0.017), p = 0.027). The incidence of VAP was lower in public hospitals (β =  − 0.036 (− 0.054, − 0.018), p < 0.001). The incidence of CRBSIs was lower in public hospitals (β =  − 0.008 (− 0.014, − 0.002), p = 0.011) and higher in secondary hospitals (β = 0.005 (0.001, 0.009), p = 0.010), while the incidence of CAUTIs was higher in secondary hospitals (β = 0.010 (0.002, 0.018), p = 0.015).

Conclusion

This study highlights the association between specific ICU structural factors and patient outcomes. Modifying structural factors is a potential opportunity that could improve patient outcomes in ICUs.
Sustained low disease activity measured by ASDAS slow radiographic spinal progression in axial spondyloarthritis patients treated with TNF-inhibitors: data from REGISPONSERBIO
Authors: Llop Maria , Moreno Mireia , Navarro-Compán Victoria , Juanola Xavier , de Miguel Eugenio , Almodóvar Raquel , Quintana Eduardo Cuende , Sanz Jesús Sanz , Beltrán Emma , Montesinos M. Dolores Ruiz , Calvet Joan , Berenguer-Llergo Antoni , Gratacós Jordi ,   the Regisponserbio group, Montejo Pedro Zarco , Joven Beatriz , Almirall Miriam , Espartero Ma Cruz Fernandez , Gualda Enrique Batlle , Campos Cristina , Estevez Eduardo Collantes , Font Pilar , Poch Teresa Clavaguera , Linares Ferrando Luis F. , Lozano Carlos Rodríguez , Yoldi Beatriz
Published: January 2022

Background

To evaluate the influence of the disease activity on radiographic progression in axial spondyloarthritis (axSpA) patients treated with TNF inhibitors (TNFi).

Methods

The study included 101 axSpA patients from the Spanish Register of Biological Therapy in Spondyloarthritides (REGISPONSERBIO), which had clinical data and radiographic assessment available. Patients were classified into 2 groups based on the duration of TNFi treatment at baseline: (i) long-term treatment (≥4 years) and (ii) no long-term treatment (< 4 years). Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. Disease activity differences between patients’ groups at each time point were assessed using a linear mixed-effect model.

Results

Radiographic progression was defined as an increase in ≥2 mSASSS units.At inclusion, approximately half of the patients (45.5%) were receiving long-term treatment with TNFi (≥4 years). In this group of subjects, a significant difference in averaged Ankylosing Spondylitis disease Activity Score (ASDAS) across follow-up was found between progressors and non-progressors (2.33 vs 1.76,p=0.027, respectively). In patients not under long-term TNFi treatment (54.5%) though, no significant ASDAS differences were observed between progressors and non-progressors until the third year of follow-up. Furthermore, no significant differences were found in progression status, when disease activity was measured by Bath Ankylosing spondylitis Disease Activity Index (BASDAI) and C reactive protein (CRP).

Conclusions

Patients on long-term TNFi treatment with a mean sustained low disease activity measures by ASDAS presented lower radiographic progression than those with active disease.
Discovering the key genes and important DNA methylation regions in breast cancer
Authors: Cao Yan-Ni , Li Qian-Zhong , Liu Yu-Xian , Jin Wen , Hou Rui
Published: January 2022

Background

Breast cancer is the malignant tumor with the highest incidence in women. DNA methylation has an important effect on breast cancer, but the effect of abnormal DNA methylation on gene expression in breast cancer is still unclear. Therefore, it is very important to find therapeutic targets related to DNA methylation.

Results

In this work, we calculated the DNA methylation distribution and gene expression level in cancer and para-cancerous tissues for breast cancer samples. We found that DNA methylation in key regions is closely related to gene expression by analyzing the relationship between the distribution characteristics of DNA methylation in different regions and the change of gene expression level. Finally, the 18 key genes (17 tumor suppressor genes and 1 oncogene) related to prognosis were confirmed by the survival analysis of clinical data. Some important DNA methylation regions in these genes that result in breast cancer were found.

Conclusions

We believe that 17 TSGs and 1 oncogene may be breast cancer biomarkers regulated by DNA methylation in key regions. These results will help to explore DNA methylation biomarkers as potential therapeutic targets for breast cancer.
Applying the design-based learning model to foster undergraduates’ web design skills: the role of knowledge integration
Authors: Tsai Chun-Yen , Shih Wen-Ling , Hsieh Fu-Pei , Chen Yun-An , Lin Chien-Liang
Published: January 2022

The purpose of this research was to design a course based on the design-based learning (DBL) model to improve undergraduates’ web design skills, and to explore the differences in learning effectiveness of students with different levels of knowledge integration. The quasi-experimental design was adopted in this study. Ninety-two participants studying general education courses in a university in southern Taiwan were selected to participate in this study. The instruments included the Web Design Skills Test and the Knowledge Integration Scale. The study found that the use of the DBL strategy in teaching could improve the web design skills of the experimental group students, especially those students with insufficient web design skills in the initial stage. In addition, students with a high level of knowledge integration had better improvement in their web design skills. The implication of this research is that DBL is a suitable web design skills training strategy for students with insufficient web design skills. If students could be reminded to integrate knowledge while studying, their learning outcomes may be better.
Capturing the patient experience in systemic lupus erythematosus: Are widely used measures fit-for-purpose and adherent to FDA PRO guidance recommendations?
Authors: Majercak Kayleigh R. , Perfetto Eleanor M. , Villalonga-Olives Ester
Published: January 2022

Background

The 2009 Food and Drug Administration (FDA) patient-reported outcome (PRO) guidance outlines characteristics of rigorous PRO-measure development. There are a number of widely used PRO measures for Systemic Lupus Erythematosus (SLE), but it is unknown how well the development processes of SLE PRO measures align with FDA guidance; including updated versions. The objective of this study was to assess how well the LupusQoL and LupusPRO, and corresponding updated versions, LupusQoL-US and LupusPROv1.8, align with Food and Drug Administration (FDA) 2009 patient-reported outcome (PRO) guidance.

Methods

LupusQoL and LupusPRO were selected as the most widely studied and used Lupus PROs in the UK and US. Original (LupusQoL (2007) and LupusQoL-US (2010)) and revised (LupusPROVv1.7 (2012) and LupusPROv1.8 (2018)) versions were reviewed. We used FDA PRO guidance to create evaluation criteria for key components: target population, concepts measured, measurement properties, documentation across the phases of content validity (item-generation and cognitive interviewing, separately) and other psychometric-property testing. Two reviewers abstracted data independently, compared results, and resolved discrepancies.

Results

For all measures, the target population was unclear as population characteristics (e.g., ethnicity, education, disease severity) varied, and/or were not consistently reported or not considered across the three phases (e.g., LupusQoL item-generation lacked male involvement, LupusPRO cognitive-interviewing population characteristics were not reported). The item-generation phase for both original measures was conducted with concepts elicited via patient-engagement interviews and item derivation from experts. Cognitive interviewing was conducted via patient feedback with limited item-tracking for original measures. In contrast, the revised measures assumed content validity. Other psychometric testing recommendations (reliability, construct validity, ability to detect change) were reported for both original and revised measures, except for ability to detect change for revised measures.

Conclusions

The SLE PRO measures adhere to some but not all FDA PRO guidance recommendations. Limitations in processes and documentation of the study population, make it unclear for which target population(s) the current Lupus measures are fit-for-purpose.
Impact of patient-reported outcomes on symptom monitoring during treatment with checkpoint inhibitors: health-related quality of life among melanoma patients in a randomized controlled trial
Authors: Tolstrup Lærke K. , Pappot Helle , Bastholt Lars , Möller Sören , Dieperink Karin B.
Published: January 2022

Introduction

In a randomized controlled trial, we previously investigated if melanoma patients receiving checkpoint inhibitors had fewer severe immune-related adverse events (irAEs) when they reported symptoms using electronic patient-reported outcomes (ePRO) with triggered alerts as an add-on to standard care, compared to standard care alone. The aim of this study is to examine between-group differences in health-related quality of life (HRQoL) and associations between irAEs severity and HRQoL.

Methods

The study population of 138 patients completed the EuroQol EQ-5D-5L Index and FACT-M questionnaires at baseline and weeks 24 and 48. We analyzed HRQoL from all patients who completed at least one questionnaire. Missing FACT-M items were imputed following existing guidelines.

Results

There was no difference in HRQoL at baseline as measured EQ-5D-5L between the intervention and the control group. Between baseline and 48 weeks, mean EQ-5D-5L scores were unchanged among patients in the intervention group (p = 0.81) but decreased significantly among patients in the control group (p = 0.03). Consequently, patients in the intervention group had higher mean scores than those in the control group (p = 0.05) at 48 weeks. Mean FACT-M scores did not differ significantly between the two groups at any of the time points. There were observed no between-group differences in mean EQ-5D-5 and mean FACT-M scores between patients with severe irAEs and patients who had none.

Conclusion

Melanoma patients receiving CPIs who self-reported irAEs using ePRO with triggered alerts as a supplement to standard care maintained their HRQoL compared to patients who received standard care alone. Patients in the intervention group had a significantly better HRQoL measured by EQ-5D-5L than controls 48 weeks after baseline. The results suggest that including ePRO in standard care increases melanoma patients´ well-being. Further and larger studies are needed to confirm this finding and examine the impact of severe irAEs on cancer patients’ HRQoL.

Trial registration: Clinicaltrials.gov NCT03073031 Registered 8 March 2017, Retrospectively registeredhttps://clinicaltrials.gov/.
Compositional analysis of the tonsil microbiota in relationship to Streptococcus suis disease in nursery pigs in Ontario
Authors: Niazy Maysa , Hill Sarah , Nadeem Khurram , Ricker Nicole , Farzan Abdolvahab
Published: January 2022

Background

The tonsil of the soft palate in pigs is the colonization site of both commensal and pathogenic microbial agents.Streptococcus suisinfections are a significant economic problem in the swine industry. The development ofS. suisdisease remains poorly understood. The purpose of this study was to identify whether the tonsillar microbiota profile in nursery pigs is altered withS. suisdisease. Here, the dynamics of the tonsillar microbiota from 20 healthy pigs and 43 diseased pigs withS. suisclinical signs was characterized.

Results

Based on the presence or absence ofS. suisin the systemic sites, diseased pigs were classified into confirmed (n = 20) or probable (n = 23) group, respectively. Microbiota composition was assessed using the V3-V4 hypervariable region of the 16S rRNA, and results were analyzed to identify the diversity of the tonsillar microbiota. The taxonomic composition of the tonsil microbiota proved to be highly diverse between individuals, and the results showed statistically significant microbial community structure among the diagnosis groups. The confirmed group had the lowest observed species richness while the probable group had higher phylogenetics diversity level compared to the healthy group. Un-weighted Unifrac also demonstrated that the probable group had a higher beta diversity than both the healthy and the confirmed group. A Dirichlet-multinomial mixture (DMM) model-based clustering method partitioned the tonsil microbiota into two distinct community types that did not correspond with disease status. However, there was an association betweenStreptococcus suisserotype 2 and DMM community type 1 (p = 0.03). ANCOM-BC identified 24Streptococcusamplicon sequence variants (ASVs) that were differentially abundant between the DMM community types.

Conclusions

This study provides a comprehensive analysis of the structure and membership of the tonsil microbiota in nursery pigs and uncovers differences and similarities across varyingS. suisdisease status. While the overall abundance ofStreptococcuswas not different among the diagnosis groups, the unique profile of DMM community type 1 and the observed correlation withS. suisserotype 2 could provide insight into potential tonsillar microbiota involvement inS. suisdisease.
A simple method to valorize silica sludges into sustainable coatings for indoor humidity buffering
Authors: Kuok Chi-Hong , Dianbudiyanto Wahid , Liu Shou-Heng
Published: January 2022

In this study, the production of indoor humidity-buffering coatings (IHC-s) from recycling waste silica sludges by using a room-temperature sol-gel method which is a simple and energy-efficient route is reported. The properties of these IHC-s are identified by scanning electron microscope, X-ray diffraction, X-ray fluorescence spectrometer, laser particle size analyzer, N2 adsorption-desorption isotherms and toxicity characteristic leaching procedure (TCLP). The moisture adsorption-desorption tests show that the IHC-s have moisture buffering values of ca. 270–316 g m− 2 and moisture contents of 23.6–26.7% in the range of 50–90% relative humidity (RH). Furthermore, the humidity buffering capacities, moisture adsorption-desorption rate and stability are significantly superior to commercially available coatings in the range of 50–75% RH. The enhancement may be due to the formation of porous structure in the coatings via the dispersed waste silica sludges and gypsum which transformed from bassanite by self-assembly process. Most importantly, the prepared IHC-s show surpassing antimicrobial efficacy (> 99.99%) and no detectable leaching heavy metals based on TCLP tests, which provides an economic and environmental-friendly route for recovering and valorizing industrial wastes.
Direct Evidence of Black Phosphorus Formation in Carbon Nanospaces by Quasi-high Pressure Effect
Authors: Komine Yuki , Urita Koki , Notohara Hiroo , Moriguchi Isamu
Published: January 2022

Black phosphorus (BP) has attracted attention as an anode material for lithium or sodium ion batteries due to its high electrical conductivity and theoretical specific capacity (2596 mAh/g). However, the synthesis of BP requires high-pressure conditions at >1 GPa. We directly demonstrated that carbon nanospaces with the pore size around 4 nm are effective to synthesize BP without an external high-pressure apparatus.
The PIWI/piRNA response is relaxed in a rodent that lacks mobilizing transposable elements
Authors: Vandewege Michael W. , Patt Roy N. , Merriman Dana K. , Ray David A. , Hoffmann Federico G.
Published: January 2022

Transposable elements (TEs) are genomic parasites that can propagate throughout host genomes. Mammalian genomes are typically dominated by LINE retrotransposons and their associated SINEs, and germline mobilization is a challenge to genome integrity. There are defenses against TE proliferation and the PIWI/piRNA defense is among the most well understood. However, the PIWI/piRNA system has been investigated largely in animals with actively mobilizing TEs and it is unclear how the PIWI/piRNA system functions in the absence of mobilizing TEs. The 13-lined ground squirrel provides the opportunity to examine PIWI/piRNA and TE dynamics within the context of minimal, and possibly nonexistent, TE accumulation. To do so, we compared the PIWI/piRNA dynamics in squirrels to observations from the rabbit and mouse. Despite a lack of young insertions in squirrels, TEs were still actively transcribed at higher levels compared to mouse and rabbit. All three Piwi genes were not expressed, prior to P8 in squirrel testis, and there was little TE expression change with the onset of Piwi expression. We also demonstrated there was not a major expression change in the young squirrel LINE families in the transition from juvenile to adult testis in contrast to young mouse and rabbit LINE families. These observations lead us to conclude that PIWI suppression, was weaker for squirrel LINEs and SINEs and did not strongly reduce their transcription. We speculate that, although the PIWI/piRNA system is adaptable to novel TE threats, transcripts from TEs that are no longer threatening receive less attention from PIWI proteins.
Differential expression of cancer associated plasma miRNAs in the ordnance factory workers, exposed to 2,4,6-Trinitrotoluene
Authors: Aamir Muhammad , Naveed Abdul Khaliq , Afzal Muhammad , Siddique Aamir
Published: January 2022

Objectives: To determine differential expression of microRNAs (miRNAs) in plasma of 2, 4, 6-Trinitrotoluene (TNT) exposed ordnance factory workers.

Methods: A case control study was conducted at the Department of Toxicology, Armed Forces Institute of Pathology, Rawalpindi from July to December 2020. A total 30 subjects were recruited from an ordnance factory that were directly exposed to TNT and 120 non-exposed individuals from non-factory healthy population. Plasma levels of five miRNAs including miRNA-let-7a-2, miRNA-34a-1, miRNA-21-2, miRNA-106b-1, miRNA-122a-1 were measured by quantitative real-time polymerase chain reaction (RT-PCR).

Results: Micro RNAs showed a wide range of Ct (cycle threshold) values ranging from 23.48 to 41.94. Among the five miRNAs let-7a-2 and miRNA-122a-1 displayed relatively high expression with Ct values ranging from 26.58 ± 2.25 to 27.18 ± 0.80 respectively. Relative fold change expression for all five miRNAs of exposed individuals were found high (p <0.0001) vs non-exposed. Dividing fold change expression of exposed individuals into two groups as ≤ 10 and > 10, the individuals having ≤ 10-fold change expression were19 (63.3%) in miRNA-let-7a-2, 30 (100%) in miRNA-34a-1 and 23 (76.7%) in miRNA-122a-1 while in miRNA-21-2 and miR-106b-1, 23 (76.7%) and 18(60%) individuals had > 10-fold change expression respectively. Among the five miRNAs in exposed individuals, miRNA-let-7a-2, miR-21-2, miR-106b-1 and miR-122a-1 were found highly expressed with fold change expression > 10 (p <0.0001). No significant association was found between miRNAs expression levels with age and working duration.

Conclusion: The study shows upregulation of all five miRNAs in TNT exposed subjects with no significant association of expression levels with age and working duration.

doi: https://doi.org/10.12669/pjms.38.3.4928

How to cite this:Aamir M, Naveed AK, Afzal M, Siddique A. Differential expression of cancer associated plasma miRNAs in the ordnance factory workers, exposed to 2,4,6-Trinitrotoluene. Pak J Med Sci. 2022;38(3):---------. doi: https://doi.org/10.12669/pjms.38.3.4928

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Alternative Types of Ambiguity and their Effects on Climate Change Regulation
Authors: Koundouri Phoebe , Pittis Nikitas , Samartzis Panagiotis , Englezos Nikolaos , Papandreou Andreas
Published: January 2022

This paper focuses on different types of ambiguity that affect climate change regulation. In particular, we analyze the effects of the interaction among three types of agents, namely, the decision-maker (DM), the climate change experts, and the society, on the probabilistic properties of green-house gas (GHG) emissions and the formation of environmental policy. These effects are analyzed under two types of ambiguity: "deferential ambiguity" and "preferential ambiguity". Deferential ambiguity refers to the uncertainty that the experts face concerning whose forecast (scenario) the DM will defer to. Preferential ambiguity stems from the potential inability of the DM to correctly discern the society's preferences about the desired change of GHG emissions. This paper shows that the existence of deferential and preferential ambiguities have significant effects on GHG emissions regulation.
Study Pre-protocol for “BronchStart - The Impact of the COVID-19 Pandemic on the Timing, Age and Severity of Respiratory Syncytial Virus (RSV) Emergency Presentations; a Multi-Centre Prospective Observational Cohort Study”
Authors: Williams Thomas C. , Lyttle Mark D. , Cunningham Steve , Sinha Ian , Swann Olivia V. , Maxwell-Hodkinson Abigail , Marlow Robin , Roland Damian ,   Paediatric Emergency Research in the UK and Ireland (PERUKI)
Published: January 2022

Background: Bronchiolitis (most frequently caused by respiratory syncytial virus; RSV) is a common winter disease predominantly affecting children under one year of age. It is a common reason for presentations to an emergency department (ED) and frequently results in hospital admission, contributing to paediatric units approaching or exceeding capacity each winter. During the SARS-CoV-2 pandemic, the circulation of RSV was dramatically reduced in the United Kingdom and Ireland. Evidence from the Southern Hemisphere and other European countries suggests that as social distancing restrictions for SARS-CoV-2 are relaxed, RSV infection returns, causing delayed or even summer epidemics, with different age distributions.

Study question: The ability to track, anticipate and respond to a surge in RSV cases is critical for planning acute care delivery. There is an urgent need to understand the onset of RSV spread at the earliest opportunity. This will influence service planning, to inform clinicians whether the population at risk is a wider age range than normal, and whether there are changes in disease severity. This information is also needed to inform decision on the timing of passive immunisation of children at higher risk of hospitalisation, intensive care admission or death with RSV infection, which is a public health priority.

Methods and likely impact: This multi-centre prospective observational cohort study will use a well-established research network (Paediatric Emergency Research in the UK and Ireland, PERUKI) to report in real time cases of RSV infection in children aged under two years, through the collection of  essential, but non-identifying patient information. Forty-five centres will gather initial data on age, index of multiple deprivation quintile, clinical features on presentation, and co-morbidities. Each case will be followed up at seven days to identify treatment, viral diagnosis and outcome.  Information be released on a weekly basis and used to support clinical decision making.
As territorialidades da natureza na América portuguesa (c. 1580/c.1640): exploração, conflitos e contrabando do pau-brasil.
Authors: de Siqueira Maria Isabel
Published: January 2022

Discutir sobre a exploração dos recursos naturais, com destaque para o pau-brasil, no território da América portuguesa, mais precisamente na capitania do Rio de Janeiro nas quatro primeiras décadas da União Ibérica, é o objetivo deste artigo. Buscar-se-á analisar as normas estabelecidas pela Coroa para a utilização racional do ambiente e, ainda, os conflitos e atividades ilícitas que envolviam a questão.
Arquitectos e ingenieros. Proyectos fallidos para un cuartel de caballería en el Palacio Real de México.
Authors: Nieto Márquez Miguel Ángel
Published: January 2022

En 1761, el virrey marqués de Cruillas encomendó a Lorenzo Rodríguez el proyecto de ampliación del cuartel de caballería del Palacio Virreinal, si bien posteriormente los ingenieros militares Agustín López de la Cámara Alta y Pedro Ponce presentaron otras propuestas. Este estudio analiza detalladamente dichos proyectos, así como los motivos que llevaron a su suspensión.
Entre el viejo continente y un nuevo mundo: la revista Caras y Caretas (1898-1910).
Authors: A Gómez Silvana
Published: January 2022

En este artículo exploramos a la revista argentina Caras y Caretas entre su lanzamiento en 1898 hasta 1910. Considerando el papel ejercido por españoles y lo español en el semanario, buscamos visibilizar la circulación de la revista argentina en España, la de personas entre dos continentes, así como el rol desempeñado por Caras y Caretas en la difusión de un ideario español respecto a la Argentina del Centenario.
When Is Society Susceptible to Manipulation?
Authors: Mostagir Mohamed , Ozdaglar Asuman , Siderius James
Published: January 2022

We consider a social learning model where agents learn about an underlying state of the world from individual observations as well as from exchanging information with each other. A principal (e.g., a firm or a government) interferes with the learning process in order to manipulate the beliefs of the agents. By utilizing the same forces that give rise to the “wisdom of the crowd” phenomenon, the principal can get the agents to take an action that is not necessarily optimal for them but is in the principal’s best interest. We characterize the social norms and network structures that are susceptible to this kind of manipulation and derive conditions under which a social network is impervious and cannot be manipulated. In the process, we develop a new centrality measure and describe how our model offers insights into designing networks that are resistant to manipulation.

This paper was accepted by Gabriel Weintraub, revenue management and market analytics.
Asymptotically Optimal Control of a Centralized Dynamic Matching Market with General Utilities
Authors: Blanchet Jose H. , Reiman Martin I. , Shah Virag , Wein Lawrence M. , Wu Linjia
Published: January 2022

The utility of a match in a two-sided matching market often depends on a variety of characteristics of the two agents (e.g., a buyer and a seller) to be matched. In contrast to the matching market literature, this utility may best be modeled by a general matching utility distribution. In “Asymptotically Optimal Control of a Centralized Dynamic Matching Market with General Utilities,” Blanchet, Reiman, Shah, Wein, and Wu consider general matching utilities in the context of a centralized dynamic matching market. To analyze this difficult problem, they combine two asymptotic techniques: extreme value theory (and regularly varying functions) and fluid asymptotics of queueing systems. A key trade-off in this problem is market thickness: Do we myopically make the best match that is currently available, or do we allow the market to thicken in the hope of making a better match in the future while avoiding agent abandonment? Their asymptotic analysis derives quite explicit results for this problem and reveals how the optimal amount of market thickness increases with the right tail of the matching utility distribution and the amount of market imbalance. Their use of regularly varying functions also allows them to consider correlated matching utilities (e.g., buyers have positively correlated utilities with a given seller), which is ubiquitous in matching markets.
The seroepidemiology of dengue in a US military population based in Puerto Rico during the early phase of the Zika pandemic
Authors: Pollett Simon , Kuklis Caitlin H. , Barvir David A. , Jarman Richard G. , Romaine Rachel M. , Forshey Brett M. , Gromowski Gregory D.
Published: January 2022

Understanding the burden and risk factors of dengue virus (DENV) infection in Puerto Rico is important for the prevention of dengue in local, traveler and military populations. Using sera from the Department of Defense Serum Repository, we estimated the prevalence and predictors of DENV seropositivity in those who had served in Puerto Rico, stratified by birth or prior residence (“birth/residence”) in dengue-endemic versus non-endemic regions. We selected sera collected in early 2015 from 500 U.S. military members, a time-point also permitting detection of early cryptic Zika virus (ZIKV) circulation. 87.2% were born or resided in a DENV-endemic area before their military service in Puerto Rico. A high-throughput, flow-cytometry-based neutralization assay was employed to screen sera for ZIKV and DENV neutralizing antibodies, and confirmatory testing was done by plaque-reduction neutralization test (PRNT). We identified one Puerto Rico resident who seroconverted to ZIKV by June 2015, suggesting cryptic ZIKV circulation in Puerto Rico at least 4 months before the first reported cases. A further six PRNT-positive presumptive ZIKV infections which were resolved as DENV infections only by the use of paired sera. We noted 66.8% of the total study sample was DENV seropositive by early 2015. Logistic regression analysis indicated that birth/residence in a dengue non-endemic region (before military service in Puerto Rico) was associated with a lower odds of DENV exposure by January—June 2015 (aOR = 0.28, p = 0.001). Among those with birth/residence in a non-endemic country, we noted moderate evidence to support increase in odds of DENV exposure for each year of military service in Puerto Rico (aOR = 1.58, p = 0.06), but no association with age. In those with birth/residence in dengue-endemic regions (before military service in Puerto Rico), we noted that age (aOR = 1.04, p = 0.02), rather than duration of Puerto Rico service, was associated with dengue seropositivity, suggesting earlier lifetime DENV exposure. Our findings provide insights into the burden and predictors of DENV infection in local, traveler and military populations in Puerto Rico. Our study also highlights substantial PRNT ZIKV false-positivity when paired sera are not available, even during periods of very low ZIKV prevalence.
Emergency capacity analysis in Ethiopia: Results of a baseline emergency facility assessment
Authors: Firew Tsion , Mishra Diksha , Makonnen Tirsit , Fantaye Helena Hailu , Workeye Bethlehem , Kebede Sofia , Ebrahim Yimer Fatuma , Abebe Yonas , Shiferaw Betelehem , Gebreyesus Alegnta , Sultan Menbeu , Azazh Aklilu
Published: January 2022

Introduction

In Ethiopia, the specialty of Emergency Medicine is a relatively new discipline. In the last few decades, policymakers have made Emergency Medicine a priority for improving population health. This study aims to contribute to this strengthening of Emergency Medicine, by conducting the country’s first baseline gap analysis of Emergency Medicine Capacity at the pre-hospital and hospital level in order to help identify needs and areas for intervention.

Methods

This is a cross sectional investigation that utilized a convenience sampling of 22 primary, general and tertiary hospitals. Trained personnel visited the hospitals and conducted 4-hour interviews with hospital administrators and emergency care area personnel. The tool used in the interview was the Columbia University sidHARTe Program Emergency Services Resource Assessment Tool (ESRAT) to evaluate both emergency and trauma capacity in different regions of Ethiopia. The findings of this survey were then compared against two established standards: the World Health Organization’s Essential Package of Emergency Care (EPEC), as well as those set by Ethiopia’s Federal Ministry of Health.

Results

The tool assessed the services provided at each hospital and evaluated the infrastructure of emergency care at the facility. Triage systems differed amongst the hospitals surveyed though triaging and emergency unit infrastructures were relatively similar amongst the hospitals. There was a marked variability in the level of training, guidelines, staffing, disaster preparedness, drug availability, procedures performed, and quality assurance measures from hospital to hospital. Most regional and district hospitals did not have nurses or doctors trained in Emergency Medicine and over 70% of the hospitals did not have written guidelines for standardized emergency care.

Conclusion

This gap analysis has revealed numerous inconsistencies in health care practice, resources, and infrastructure within the scope of Emergency Medicine in Ethiopia. Major gaps were identified, and the results of this assessment were used to devise action priorities for the Ministry of Health. Much remains to be done to strengthen Emergency Medicine in Ethiopia, and numerous opportunities exist to make additional short and long-term improvements.
Homologous recombination DNA repair gene RAD51, XRCC2 & XRCC3 polymorphisms and breast cancer risk in South Indian women
Authors: Rajagopal Taruna , Seshachalam Arun , Rathnam Krishna Kumar , Talluri Srikanth , Venkatabalasubramanian Sivaramakrishnan , Dunna Nageswara Rao
Published: January 2022

Background

Homologous recombination repair (HRR) accurately repairs the DNA double-strand breaks (DSBs) and is crucial for genome stability. Genetic polymorphisms in crucial HRR pathway genes might affect genome stability and promote tumorigenesis. Up to our knowledge, the present study is the first to investigate the impact of HRR gene polymorphisms on BC development in South Indian women. The present population-based case-control study investigated the association of polymorphisms in three key HRR genes (XRCC2-Arg188His,XRCC3-Thr241Met andRAD51-G135C) with BC risk.

Materials and methods

Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping the HRR variants in 491 BC cases and 493 healthy women.

Results

We observed that theXRCC3Met allele was significantly associated with BC risk [OR:1.27 (95% CI: 1.02–1.60); p = 0.035]. In addition, the homozygous mutant (C/C) genotype ofRAD51G135C variant conferred 2.19 fold elevated risk of BC [OR: 2.19 (95% CI: 1.06–4.54); p = 0.034]. Stratified analysis of HRR variants and BC clinicopathological features revealed that theXRCC3-Thr241Met andRAD51-G135C variants are associated with BC progression. Combined SNP analysis revealed that the individuals withRAD51-C/C,XRCC2-Arg/Arg, andXRCC3-Thr/Thr genotype combination have three-fold increased BC risk.

Conclusion

The present study imparts additional evidence that genetic variants in crucial HRR pathway genes might play a pivotal role in modulating BC risk in South Indian women.
Web-based sensitivity training for interacting with facial paralysis
Authors: Zhang Nicole , Bogart Kathleen , Michael John , McEllin Luke
Published: January 2022

Previous research has shown that observers tend to form inaccurate and negatively biased first impressions of people with facial paralysis (FP). It has been hypothesised that this may be ameliorated by encouraging people to focus on channels of expression other than the face. This was tested in a web-based study of 466 participants. Participants in the Trained Condition received tips for perceiving expressiveness in individuals with FP, while those in the Untrained Condition received general medical information about FP. We observed no significant differences between groups for accuracy of emotion recognition, but a significant effect of the training upon perception of emotional intensity. These results show that attending to non-facial cues may improve social perception and reduce bias.