bluuebunny/crossref_metadata_2025 huggingface dataset:
How Priming Fairness and Priming Constitutionality Impact the Effect of Partisan Self-Interest on Citizen Support for Election Reforms
Authors: Biggers Daniel R , Bowler Shaun
Published: March 2023

Prior research suggests that citizen attitudes toward electoral laws and reforms derive from how individuals weigh two competing considerations: the rule’s procedural fairness and one’s partisan self-interest (or how they perceive the policy affects their party’s electoral prospects). Recent experimental work shows that despite a role for fairness concerns, policy support levels shift (at least to a degree) based on its anticipated impact on who votes. We examine how the presentation of the trade-off between fairness and partisan advantage influences election reform opinions. Using two sets of survey experiments, we find that priming fairness reduces, but does not eliminate, the effect of partisan self-interest in shaping policy evaluations. Priming a reform’s constitutionality so as to provide cover to infringe upon fairness considerations, however, does not exacerbate the impact of partisan self-interest on support for adoption. These results expand our understanding of how citizens weigh different factors when assessing electoral policies.
Twist-2 light-quark distribution functions in a singly heavy baryon in the largeNclimit
Authors: Son Hyeon-Dong , Kim Hyun-Chul
Published: March 2023

A singly heavy baryon can be considered as a state consisting of the Nc − 1 light valence quarks that create the pion mean field in the large Nc limit. In the limit of the infinitely heavy quark mass, a heavy quark inside a singly heavy baryon is regarded as a mere static color source. It is required only to make the singly heavy baryon a color singlet. Thus, the Nc − 1 valence quarks govern quark dynamics inside the singly heavy baryon. Within this pion mean field framework, we investigate the twist-2 unpolarized and longitudinally polarized light-quark distribution functions inside charmed and bottom baryons at a low renormalization point. We observe that the light quarks inside a heavy baryon carry less momentum than those inside a nucleon. This feature is more prominent as the heavy quark mass increases. We discuss the baryon sum rule, momentum sum rule, and the Bjorken spin sum rule for singly heavy baryons. We also discuss the inequality conditions for the quark distribution functions. In addition, we present the results for the light-quark quasi-distribution functions.
Psychometric testing of the British English Workplace Activity Limitations Scale in four rheumatic and musculoskeletal conditions
Authors: Hammond Alison , Tennant Alan , Ching Angela , Parker Jennifer , Prior Yeliz , Gignac Monique A M , Verstappen Suzanne M M , O’Brien Rachel
Published: March 2023

Objectives

The aims were to validate a British English version of the Workplace Activity Limitations Scale (WALS) linguistically, then test this psychometrically in RA, axial spondyloarthritis (axSpA), OA and FM.

Methods

The WALS was forward translated, reviewed by an expert panel, and cognitive debriefing interviews were conducted. Participants completed a postal questionnaire booklet. Construct (structural) validity was examined by fit to the Rasch measurement model. Concurrent validity included testing between the WALS and the Work Limitations Questionnaire-25 (WLQ-25). Two weeks later, participants were mailed a second questionnaire booklet for test–retest reliability.

Results

Minor wording changes were made to the WALS, then 831 employed participants completed questionnaires: 267 men and 564 women; 53.5 (s.d. 8.9) years of age; with condition duration 7.7 (s.d. 8.0) years. The WALS satisfied Rasch model requirements, and a WALS Rasch transformation table was created. Concurrent validity was strong with the WLQ-25 (RA rs = 0.78; axSpA rs = 0.83; OA rs = 0.63; FM rs = 0.64). Internal consistency was consistent with group use (α = 0.80–0.87). Test–retest reliability was excellent, with intraclass correlation coefficient (2,1) at ≥0.90.

Conclusion

A reliable, valid British English version of the WALS is now available for use in the UK.
Adjuvant Human Papillomavirus Vaccination After Excisional Procedure for Cervical Intraepithelial Neoplasia
Authors: Chaiken Sarina R. , Bruegl Amanda S. , Caughey Aaron B. , Emerson Jenna , Munro Elizabeth G.
Published: March 2023

OBJECTIVE:

To examine the cost effectiveness of human papillomavirus (HPV) vaccination after excisional procedure compared with no vaccination.

METHODS:

We constructed a decision-analytic model (TreeAge Pro 2021) to compare outcomes between patients who underwent an excisional procedure followed by nonavalent HPV vaccination to those who underwent an excisional procedure without vaccination. Our theoretical cohort contained 250,000 patients, the approximate number undergoing excisional procedures annually in the United States. Our outcomes were costs, quality-adjusted life-years (QALYs), recurrence events, number of surveillance Pap tests with co-testing, number of colposcopies, and second excisional procedures. Probabilities of recurrence were based on a recently published meta-analysis. All values were derived from the literature, and QALYs were discounted at a rate of 3%. Outcomes were applied for 4 years after the initial excisional procedure. Our cost-effectiveness threshold was $100,000 per QALY. Sensitivity analyses were performed to evaluate the robustness of the model.

RESULTS:

In our theoretical cohort of patients who underwent an excisional procedure, the HPV vaccination strategy was associated with 17,281 fewer recurrences of cervical intraepithelial neoplasia (CIN) (8,360 fewer cases of CIN 1 and 8,921 fewer cases of CIN 2 or 3), 26,203 fewer Pap tests (1,025,368 vs 1,051,570), 17,281 fewer colposcopies (20,588 vs 37,869), and 8,921 fewer second excisional procedures (4,779 vs 13,701). The vaccination strategy was associated with a higher cost of $135 million. Vaccination was a cost-effective strategy, with an incremental cost-effectiveness ratio of $29,181 per QALY, compared with no vaccination. In our sensitivity analyses, the HPV vaccination strategy remained cost effective until the cost of the three-dose HPV vaccine series reached $1,899 or the baseline (nonvaccinated) probability of recurrence was less than 4.8%.

CONCLUSION:

In our model, HPV vaccination for patients with a prior excisional procedure led to improved outcomes and was cost effective. Our study suggests that clinicians should consider offering the three-dose HPV vaccine series to patients who have undergone an excisional procedure to decrease the risk of CIN recurrence and its sequelae.
Association Between Parapapillary Microvasculature Dropout and Central Retinal Vessel Trunk in Primary Open Angle Glaucoma
Authors: Zhang Haowei , Piao Helong , Sung Mi Sun , Park Sang Woo
Published: March 2023

Précis:

Central retinal vessel trunk displacement is an important factor in the generation and development of deep-layer microvasculature dropout in primary open angle glaucoma.

Purpose:

To investigate the association between the microvasculature dropout and the central retinal vessel trunk in primary open angle glaucoma eyes.

Methods:

In total, 112 eyes from 112 patients with primary open-angle glaucoma were included. Matched 26 no microvasculature dropout eyes and 26 microvasculature dropout eyes, they had similar axial length and global retinal nerve fiber layer thickness. Central retinal vessel trunk shift index was calculated as the distance of the central retinal vessel trunk from the Bruch membrane opening center relative to that of the Bruch membrane opening border. The correlation of the presence, extent, and location of microvasculature dropout and the displacement extent and location of the central retina vessel trunk was analyzed.

Results:

The central retinal vessel trunk shift index differed significantly between the 2 matched groups. Multivariate logistic analyses showed that in 112 eyes from 112 patients, eyes with microvasculature dropout was significantly associated with larger shift index than eyes without microvasculature dropout. The angular circumference of microvasculature dropout was significantly associated with adjusted shift index (a linear mixed model was constructed, exclude the influence of axial length and global retinal nerve fiber layer thickness on shift index). The location of the microvasculature dropout and central retinal vessel trunk contralateral were significantly correlated.

Conclusions:

In primary open angle glaucoma eyes, microvasculature dropout and the central retinal vessel trunk were significantly correlated. Because the central retinal vessel trunk represents the structural stability of the lamina cribrosa, microvasculature dropout seems to correlate with lamina cribrosa’s structural stability.
KCNH2 regulates the growth and metastasis of pancreatic cancer
Authors: Lei Jinghao , Wang Qiang , Qu Tengfei , Cha Lichao , Zhan Hanxiang , Xu Jianwei , Liu Shanglong , Tian Lantian , Sun Chuandong , Cao Jingyu , Qiu Fabo , Guo Weidong , Zhou Bin
Published: March 2023

Objective:

Due to the characteristics of insidious onset and early metastasis of pancreatic cancer (PC), patients are often diagnosed at an advanced stage and often delayed in completing surgical resection timely, resulting in poor prognosis. Therefore, this study aims to explore the expression of potassium voltage-gated channel subfamily H member 2 (KCNH2) in PC and its relationship with clinicopathological parameters and the related mechanisms.

Methods:

GEPIA database and immunohistochemical staining were used to analyze the difference in KCNH2 expression between PC and adjacent tissue in RNA and protein levels. Chi-squared test was used to evaluate the relationship between KCNH2 expression and clinicopathological features. The Cox regression model was used for multivariate analysis and univariate analysis. Histological diagnosis was performed according to World Health Organization (WHO) criteria to evaluate the relationship between KCNH2 expression and clinicopathological features.

Results:

KCNH2 expression was upregulated in PC compared with normal pancreatic tissue. In addition, the knockdown of KCNH2 inhibits PC cell proliferation, migration, invasion, and epithelial-mesenchymal transformation and promotes their apoptosis. In addition, clinical data showed that the abnormal expression of KCNH2 in PC was related to the tumor stage. Patients with high expression of KCNH2 had a poor prognosis.

Conclusions:

KCNH2 is expected to be a novel targeted molecule in treating PC.
The construction of a novel ferroptosis-related lncRNA model to predict prognosis in colorectal cancer patients
Authors: Chen Weihong , Deng Jianzhi , Zhou Yuehan
Published: March 2023

Colorectal cancer (CRC) is the most common gastrointestinal tumor with poor prognosis. Ferroptosis is a pivotal form of programmed iron-dependent cell death different from autophagy and apoptosis, and long noncoding RNA (lncRNA) can influence the prognosis of CRC via regulating ferroptosis. To explore the role and prognostic value of the constructed ferroptosis-related lncRNA model in CRC, a prognostic model was constructed and validated by screening ferroptosis-related lncRNAs associated with prognosis based on the transcriptome data and survival data of CRC patients in The Cancer Genome Atlas database. Regarding the established prognostic models, differences in signaling pathways and immune infiltration, as well as differences in immune function, immune checkpoints, and N6-methyladenosine-related genes were also analyzed. A total of 6 prognostic ferroptosis-related lncRNAs were obtained, including AP003555.1, AC010973.2, LINC01857, AP001469.3, ITGB1-DT and AC129492.1. Univariate independent prognostic analysis, multivariate independent prognostic analysis and receiver operating characteristic curves showed that ferroptosis-related lncRNAs could be recognized as independent prognostic factors. The Kaplan–Meier survival curves and the risk curves showed that the survival time of the high-risk group was shorter. Gene set enrichment analysis enrichment analysis showed that ATP-binding cassette transporters, taste transduction and VEGF signaling pathway were more active in high-risk groups that than in low-risk groups. However, the citrate cycle tricarboxylic acid cycle, fatty acid metabolism and peroxisome were significantly more active in the low-risk group than in the high-risk group. In addition, there were also differences in immune infiltration in the high-low-risk groups based on different methods, including antigen-presenting cell co-stimulation, chemokine receptor, parainflammation, and Type II IFN Response. Further analysis of Immune checkpoints showed that most of the Immune checkpoints such as TNFRSF18, LGALS9 and CTLA4 in the high-risk group were significantly higher than those in the low-risk group, and the expressions of N6-methyladenosine related genes METTL3, YTHDH2 and YTHDC1 were also significantly different in the high-risk group. Ferroptosis-related lncRNAs are closely related to the survival of colorectal cancer patients, which can be used as new biomarkers and potential therapeutic targets for the prognosis of colorectal cancer.
Clinical impact of molecular breast imaging as adjunct diagnostic modality in evaluation of indeterminate breast abnormalities and unresolved diagnostic concerns
Authors: van Loevezijn Ariane A. , Corion Christinne L.S. , Zeillemaker Anneke M. , Wijers Lidy M.H. , Smithuis Robin H.M. , Valdés Olmos Renato A. , van der Hage Jos A. , de Geus-Oei Lioe-Fee , Benard Menno , Pereira Arias-Bouda Lenka M.
Published: March 2023

Purpose

Improvements in molecular breast imaging (MBI) have increased the use of MBI as adjunct diagnostic modality and alternative to MRI. We aimed to assess the value of MBI in patients with equivocal breast lesions on conventional imaging, especially in terms of its ability to rule out malignancy.

Methods

We selected patients who underwent MBI in addition to conventional diagnostics due to equivocal breast lesions between 2012 and 2015. All patients underwent digital mammography, target ultrasound and MBI. MBI was performed using a single-head Dilon 6800 gamma camera after administration of 600 MBq 99mTc-sestamibi. Imaging was reported according to BI-RADS classification and compared with pathology or follow-up of ≥6 months.

Results

Of 226 women included, pathology was obtained in 106 (47%) and (pre)malignant lesions were found in 25 (11%). Median follow-up was 5.4 years (IQR 3.9–7.1). Sensitivity was higher for MBI compared to conventional diagnostics (84% vs. 32%; P = 0.002), identifying malignancy in 21 and 6 patients, respectively, but specificity did not differ (86% vs. 81%; P = 0.161). Positive and negative predictive value were 43% and 98% for MBI and 17% and 91% for conventional diagnostics. MBI was discordant with conventional diagnostics in 68 (30%) patients and correctly changed diagnosis in 46 (20%) patients, identifying 15 malignant lesions. In subgroups with nipple discharge (N = 42) and BI-RADS 3 lesions (N = 113) MBI detected 7 of 8 occult malignancies.

Conclusion

MBI correctly adjusted treatment in 20% of patients with diagnostic concerns after conventional work-up, and could rule out malignancy with a high negative predictive value of 98%.
Seroprevalence of Hepatitis A, B, and C in Syrian Refugee Children Newly Diagnosed With Cancer
Authors: Genc D. Bahar , Yildirmak Z. Yildiz , Apaydin Sebnem
Published: March 2023

Adult survivors of childhood cancer have an increased incidence of hepatitis due to immunosuppression and frequent blood transfusions. The immunization of children with cancer is critical for hepatitis prevention, however, access to vaccination may be restricted during times of war, such as the Syrian armed conflict. The goal of this study was to assess the pretreatment serological status of hepatitis A, B, and C in 48 Syrian refugee children with cancer diagnosed in our center between 2014 and 2021. The control group consisted of 48 Turkish children with cancer who were age, sex, and disease-matched. Fifty-eight boys and 38 girls, with a median age of 4.8 years, were included. There were 42 patients with hematological malignancies, 20 with central nervous tumors, and 34 with other solid tumors. The frequency of hepatitis A seroprevalence was not statistically different between Syrian and Turkish patients, whereas hepatitis B seroprotectivity was found to be significantly lower in Syrian children with cancer than in Turkish children. Two Syrian patients were hepatitis C virus-positive. Thirty-seven percent and 45% of all patients were seronegative for hepatitis B and hepatitis A, respectively. Our findings support the need for hepatitis screening and, if necessary, vaccination of this vulnerable population before chemotherapy.
Measuring residual limb health in persons with upper limb amputation: Modifications of the Prosthetic Evaluation Questionnaire residual limb health scale
Authors: Resnik Linda , Borgia Matthew , Clark Melissa A. , Ni Pengsheng
Published: March 2023

Background:

Assessing the user perspective on residual limb health problems is particularly important for amputation care, given the relationship between residual limb health and prosthetic satisfaction. Only 1 measure, the Residual Limb Health scale of the Prosthetic Evaluation Questionnaire (PEQ) has been validated for use in lower limb amputation, but not examined in persons with upper limb amputation (ULA).

Objectives:

The objective of this study was to examine the psychometric properties of a modified PEQ Residual Limb Health scale in a sample of persons with ULA.

Study design:

The study involved a telephone survey of 392 prosthesis users with ULA, with a 40-person retest sample.

Methods:

The PEQ item response scale was modified to a Likert scale. The item set and instructions were refined in cognitive and pilot testing. Descriptive analyses characterized the prevalence of residual limb issues. Factor analyses and Rasch analyses evaluated unidimensionality, monotonicity, item fit, differential item functioning, and reliability. Test–retest reliability was assessed by an intraclass correlation coefficient.

Results:

Sweating and prosthesis odor were prevalent at 90.7% and 72.5%, respectively; blisters/sores (12.1%) and ingrown hairs (7.7%) were the least prevalent problems. Response categories were dichotomized for 3 items and trichotomized for 3 items to improve monotonicity. After adjusting for residual correlations, confirmatory factor analyses showed acceptable fit (comparative fit index = 0.984, Tucker–Lewis index = 0.970, and root mean square error approximation = 0.032). Person reliability was 0.65. No items had moderate-to-severe differential item functioning by age or sex. Intraclass correlation coefficient for test–retest reliability was 0.87 (95% CI, 0.76–0.93).

Conclusions:

The modified scale had excellent structural validity, fair person reliability, very good test–retest reliability, and no floor or ceiling effects. The scale is recommended for use with persons with wrist disarticulation, transradial amputation, elbow disarticulation, and above-elbow amputation.
Experience with Impedance Planimetry for Surgical Foregut Disease in 1097 Cases
Authors: Amundson Julia R , Kuchta Kristine , VanDruff Vanessa N , Wu Hoover , Campbell Michelle , Hedberg H Mason , Ujiki Michael B
Published: March 2023

Background:

The geometry and compliance of gastrointestinal sphincters may be assessed by impedance planimetry using a functional lumen imaging probe (FLIP). We describe our institutional foregut surgeon experience utilizing FLIP in 1097 cases, highlighting instances where FLIP changed operative decision making.

Study Design:

A retrospective review of an IRB approved prospective quality database was performed. This included operative and endoscopic suite foregut procedures utilizing FLIP between February 2013 and May 2022.

Results:

During the study period, FLIP was utilized a total of 1097 times in 919 unique patients by two foregut surgeons. Intraoperative FLIP was used during 573 anti-reflux procedures and 272 endoscopic myotomies. FLIP was also used during 252 endoscopic suite procedures. For those undergoing preoperative workup of GERD, starting in 2021, esophageal panometry was performed in addition to standard FLIP measurements at the lower esophageal sphincter. In 77 cases, intraoperative FLIP changed operative decision making. During anti-reflux procedures, changes included adding or removing crural sutures, adjusting a fundoplication tightness, choice of full vs. partial wrap, and magnetic sphincter augmentation sizing. For endoscopic procedures, changes included aborting POEM or ZPOEM, performing a myotomy when preoperative diagnosis was unclear, or performing additional myotomy.

Conclusion:

FLIP is a useful tool for assessing the upper esophageal sphincter, lower esophageal sphincter, pylorus, and secondary esophageal peristalsis that can be utilized in a wide variety of clinical situations within a foregut surgeons practice. It can also function as an adjunct in intraoperative decision making.
Glaucoma Detection and Feature Visualization from OCT Images Using Deep Learning
Authors: Akter Nahida , Perry Stuart , Fletcher John , Simunovic Matthew P. , Stapleton Fiona , Roy Maitreyee
Published: March 2023

Purpose

In this paper, we aimed to clinically interpret Temporal-Superior-Nasal-Inferior-Temporal (TSNIT) retinal optical coherence tomography (OCT) images in a convolutional neural network (CNN) model to differentiate between normal and glaucomatous optic neuropathy.

Methods

Three modified pre-trained deep learning (DL) models: SqueezeNet, ResNet18, and VGG16, were fine-tuned for transfer learning to visualize CNN features and detect glaucoma using 780 segmented and 780 raw TSNIT OCT B-scans of 370 glaucomatous and 410 normal images. The performance of the DL models was further investigated with Grad-CAM activation function to visualize which regions of the images are considered for the prediction of the two classes.

Results

For glaucoma detection, VGG16 performed better than SqueezeNet and ResNet18 models, with the highest AUC (0.988) on validation data and accuracy of 93% for test data. Moreover, identical classification results were obtained from raw and segmented images. For feature localization, three models accurately identify the distinct retinal regions of the TSNIT images for glaucoma and normal eyes.

Conclusion

This evidence-based result demonstrates the remarkable effectiveness of using raw TSNIT OCT B-scan for automated glaucoma detection using DL techniques which mitigates the black box problem of artificial intelligence (AI) and increases the transparency and reliability of the DL model for clinical interpretation. Moreover, the results imply that the raw TSNIT OCT scan can be used to detect glaucoma without any prior segmentation or pre-processing, which may be an attractive feature in large-scale screening applications.
Predicting Decision-Making Time for Diagnosis over NGS Cycles: An Interpretable Machine Learning Approach
Authors: Khodabakhsh Athar , Loka Tobias P. , Boutin Sébastien , Nurjadi Dennis , Renard Bernhard Y.
Published: March 2023

Motivation

Genome sequencing processes are commonly followed by computational analysis in medical diagnosis. The analyses are generally performed once the sequencing process has finished. However, in time-critical applications, it is crucial to start diagnosis once sufficient evidence has been accumulated. This research aims to define a proof-of-principle for predicting earlier time for decision-making using a machine learning approach. The method is evaluated on Illumina sequencing cycles for pathogen diagnosis.

Results

We utilized a Long-Short Term Memory (LSTM) approach to make predictions for the early decision-making time in time-critical clinical applications. We modeled the (meta-)information obtained from NGS intermediate cycles to investigate whether there are any changes to expect in the remaining sequencing cycles. We tested our model on different patient datasets, resulting in high accuracy of over 98%, indicating the model is independent of a dataset. Furthermore, we can save several hours of turnaround time by using the early prediction results. We used the SHapley Additive exPlanations (SHAP) framework for the interpretation and assessment of the LSTM classifier.

Availability

The source code is available athttps://gitlab.com/dacs-hpi/ngs-biclass.

Contact

Bernhard.Renard@hpi.de
An axis-referenced morphometric model reshaping the hippocampus following its longitudinal organization
Authors: Na Gao , Ye Chenfei , Chen Hantao , Ma Ting
Published: March 2023

The anterior-posterior gradient of the human hippocampus on coronal slices is commonly referred to as the long axis, which exhibits morphological heterogeneity related to aging and neurodegeneration. However, the actual longitudinal organization follows a laminar architecture along a longitudinal trajectory that terminates not in the absolute anterior tip of the hippocampus, but rather traces the folding uncus. This study proposes an axis-referenced morphometric model (ARMM) to reshape the hippocampus based on its anatomical nature. An atlas of the hippocampus derived from large samples of 7T ex-vivo MRI and histology serves as the prototype of the model. We set up an orthogonal curvilinear coordinate system within the hippocampus, where the internal coordinate lines correspond naturally to longitudinal and transversal axes of the hippocampus through conformal mapping, providing reference when measuring structural features like thickness, width, length, etc. The inverse mapping allows the hippocampal grey matter to unfold onto a two-dimensional rectangle, facilitating point-wise morphological correspondence across individuals. To evaluate the ARMM, we perform a detailed shape representation of the hippocampus from 7T-MRI and compare it with three state-of-the-art shape models. The results show that the ARMM performs best in metrics measuring shape similarity between the reshaped hippocampus and the ground truth, particularly in head folds (Dice=0.9934). Moreover, our examination of ARMM on longitudinal 7T images revealed its ability to capture subtle structural variations due to neurodegeneration. The ARMM offers a unique anatomically motivated morphometric model of hippocampus, and sheds light on discovering new image markers for diseases associated with hippocampal damage.
Multi-omics of the gut microbial ecosystem in the immunotherapy resistance in microsatellite instability-high gastrointestinal cancer patients
Authors: Cheng Siyuan , Han Zihan , Yin Xiaochen , Dai Die , Li Fang , Zhang Xiaotian , Lu Ming , Lu Zhihao , Wang Xicheng , Zhou Jun , Li Jian , Guo Xiaohuan , Song Panwei , Qiu Chuanzhao , Shen Wei , Zhang Qi , Zhu Ning , Wang Xi , Tan Yan , Shen Lin , Kou Yan , Peng Zhi
Published: March 2023

Despite the encouraging efficacy of anti-PD-1/PD-L1 immunotherapy in microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) advanced gastrointestinal cancer, many patients exhibit primary or acquired resistance. Using multi-omics approaches, we interrogated gut microbiome, blood metabolome and cytokines/chemokines of MSI-H/dMMR advanced gastrointestinal cancer patients (N=77) and identified a number of microbes (e.g. Alistipes putredinis) and metabolites (e.g. arginine and SCFA) highly associated with primary resistance. Fecal microbiota transplantation of patients’ stool replicated the clinical responsiveness as well as certain molecular signatures. Based on the clinical microbiome data, we developed a predictive machine learning model for primary resistance and achieved accuracy at 0.83 on an external validation set. Furthermore, several microbes were pinpointed which gradually changed during the process of acquired resistance. In summary, our study demonstrated the essential role of gut microbiome in drug resistance, and this could be utilized as a preventative diagnosis tool as well as therapeutic targets in the future.
Cellular dynamics under time-varying conditions
Authors: Joshi Kunaal , Roy Shaswata , Biswas Rudro R. , Iyer-Biswas Srividya
Published: March 2023

Building on the known scaling law that a single timescale, a cellular unit of time, governs stochastic growth and division of individual bacterial cells under constant growth conditions, here we articulate an analogous ansatz for time-varying growth conditions. We propose that a dynamic rescaling of the cellular unit of time captures the predominant effect of external variations in conditions. Using this temporal scaling ansatz, we derive exact analytic results for how the time-dependent cell age distribution adapts to changing conditions. Our results reveal the natural representation for these time-dependent dynamics. When recast in terms of the new representation, the cell age distribution evolves under time-invariant rules even as growth conditions remain dynamic! This result corresponds to the generalization of the scaling law for constant growth condition. Finally, we provide a prescription for convenient experimental tests of the temporal scaling ansatz.
Measuring single-cell susceptibility to antibiotics within monoclonal bacterial populations
Authors: Quellec Lena Le , Aristov Andrey , Gutiérrez Ramos Salomé , Amselem Gabriel , Bos Julia , Baharoglu Zeynep , Mazel Didier , Baroud Charles N.
Published: March 2023

Given the emergence of antimicrobial drug resistance, it is critical to understand the heterogeneity of response to an antibiotic within a population of cells. Since the drug can exert a selection pressure that leads to the emergence of resistant phenotypes. To date, neither bulk nor single-cell methods are able to link the heterogeneity of single-cell susceptibility to the population-scale response to antibiotics. Here we present a platform that measures the ability of individualE. colicells to form small colonies at different ciprofloxacin concentrations, by using anchored microfluidic drops and an image and data analysis pipelines. The microfluidic results are benchmarked against classical microbiology measurements of antibiotic susceptibility, showing an agreement between the pooled microfluidic chip and replated bulk measurements. Further, the experimental likelihood of a single cell to form a colony is used to provide a probabilistic antibiotic susceptibility curve. In addition to the probabilistic viewpoint, the microfluidic format enables the characterization of morphological features over time for a large number of individual cells. This pipeline can be used to compare the response of different bacterial strains to antibiotics with different action mechanisms.
Integrated analyses of single-cell RNA-seq public data reveal the gene regulatory network landscape of respiratory epithelial and peripheral immune cells in COVID-19 patients
Authors: Zhang Lin , Nishi Hafumi , Kinoshita Kengo
Published: March 2023

Introduction

Infection with SARS-CoV-2 leads to coronavirus disease 2019 (COVID-19), which can result in acute respiratory distress syndrome and multiple organ failure. However, its comprehensive influence on pathological immune responses in the respiratory epithelium and peripheral immune cells is not yet fully understood.

Methods

In this study, we integrated multiple public scRNA-seq datasets of nasopharyngeal swab and peripheral blood results to investigate the gene regulatory networks (GRNs) of healthy individuals and COVID-19 patients with mild/moderate and severe disease, respectively. Similar and dissimilar regulons were identified within or between epithelial and immune cells during COVID-19 severity progression. The relative transcription factors (TFs) and their targets were used to construct GRNs among different infection sites and conditions.

Results

Between respiratory epithelial and peripheral immune cells, different TFs tended to be used to regulate the activity of a cell between healthy individuals and COVID-19 patients, although they had some TFs in common. For example, XBP1, FOS, STAT1, and STAT2 were activated in both the epithelial and immune cells of virus-infected individuals. In contrast, severe COVID-19 cases exhibited activation of CEBPD in peripheral immune cells, while CEBPB was exclusively activated in respiratory epithelial cells. Moreover, in patients with severe COVID-19, CEBPD upregulated S100A8 and S100A9 in CD14 and CD16 monocytes, while S100A9 genes were co-upregulated by different regulators (SPEDEF and ELF3) in goblet and squamous cells. The cell-cell communication analysis suggested that epidermal growth factor receptor signaling among epithelial cells contributes to mild/moderate disease, and chemokine signaling among immune cells contributes to severe disease.

Conclusions

This study identified cell type- and condition-specific regulons in a wide range of cell types from the initial infection site to the peripheral blood, and clarified the diverse mechanisms of maladaptive responses to SARS-CoV-2 infection.
Availability and utilization of new technologies for prevention and control of healthcare-associated infections
Authors: Veríssimo Pérola Figueiredo , da Silva André Ricardo Araujo
Published: March 2023

Background and Aim

Recently new technologies have emerged to improve prevention and control of healthcare-associated infections. Our aim is to verify availability and use of new technologies for infection controllers.

Methods

We conducted a survey in infection controllers from the whole state of Rio de Janeiro state, Brazil, by invitation of a social media group, in August 2022. Nine different technologies were evaluated about availability and use. Categoricals and continuous variables were evaluated by the chi-square test and Mann-Whitney U test, respectively. A value of p less than .05 was considered as statistically significant.

Results

One hundred-eight persons answered the questionnaire. The mean age was 42.8 years (24-64 years) and 53/108 (49.1%) reported most workload in public hospitals, 45/108 (41.7%) in private hospitals and 10/108 (9.2%) reported the same workload in public and private hospitals. Out of 108, 63% reported teaching activities in his institutions. There was no correlation between the existence of teaching activities and hospital profile (p=0.42). The most common new technology available was molecular biology (PCR) for microbiological samples research for 73/108 (67.6%) participants. The second new technology available was APP for HAI prevention and control for 33/108 (30.6%), 19/108 (17.6%) reported availability of none technology.

Conclusion

Molecular biology (PCR) for microbiological samples research was the most common technology available for infection controllers of an important state of Brazil.
Engineered allostery in light-regulated LOV-Turbo enables precise spatiotemporal control of proximity labeling in living cells
Authors: Lee Song-Yi , Cheah Joleen S. , Zhao Boxuan , Xu Charles , Roh Heegwang , Kim Christina K. , Cho Kelvin F. , Udeshi Namrata D. , Carr Steven A. , Ting Alice Y.
Published: March 2023

The incorporation of light-responsive domains into engineered proteins has enabled control of protein localization, interactions, and function with light. We integrated optogenetic control into proximity labeling (PL), a cornerstone technique for high-resolution proteomic mapping of organelles and interactomes in living cells. Through structure-guided screening and directed evolution, we installed the light-sensitive LOV domain into the PL enzyme TurboID to rapidly and reversibly control its labeling activity with low-power blue light. “LOV-Turbo” works in multiple contexts and dramatically reduces background in biotin-rich environments such as neurons. We used LOV-Turbo for pulse-chase labeling to discover proteins that traffick between endoplasmic reticulum, nuclear, and mitochondrial compartments under cellular stress. We also showed that instead of external light, LOV-Turbo can be activated by BRET from luciferase, enabling interaction-dependent PL. Overall, LOV-Turbo increases the spatial and temporal precision of PL, expanding the scope of experimental questions that can be addressed with PL.
A single C-terminal residue controls SARS-CoV-2 spike trafficking and virion assembly
Authors: Dey Debajit , Qing Enya , He Yanan , Chen Yihong , Jennings Benjamin , Cohn Whitaker , Singh Suruchi , Gakhar Lokesh , Schnicker Nicholas J. , Pierce Brian G. , Whitelegge Julian P. , Doray Balraj , Orban John P. , Gallagher Tom , Hasan S. Saif
Published: March 2023

The spike (S) protein of SARS-CoV-2 is delivered to the virion assembly site in the ER-Golgi Intermediate Compartment (ERGIC) from both the ER and cis-Golgi in infected cells1-3. However, the relevance and modulatory mechanism of this bidirectional trafficking are unclear. Here, using structure-function analyses, we show that S incorporation into virions and viral fusogenicity are determined by coatomer-dependent S delivery from the cis-Golgi and restricted by S-coatomer dissociation. Although S mimicry of the host coatomer-binding dibasic motif ensures retrograde trafficking to the ERGIC, avoidance of the host-like C-terminal acidic residue is critical for S-coatomer dissociation and therefore incorporation into virions or export for cell-cell fusion. Because this C-terminal residue is the key determinant of SARS-CoV-2 assembly and fusogenicity, our work provides a framework for the export of S protein encoded in genetic vaccines for surface display and immune activation.
Sustainable digitalisation and implementation of ISO standards for facilities management
Authors: Lok Ka Leung , van der Pool Ian , Smith Andrew J. , Opoku Alex , Cheung Ka Lam
Published: March 2023

Purpose

This viewpoint paper aims to discuss sustainable digitalisation of facilities management (FM) through the implementation of the newly recognised International Organization for Standardization (ISO) standards within the ISO 41000 series.

Design/methodology/approach

This viewpoint paper provides a review of the literature of the recent ISO documents and academic study. The content is also dependent on the authors’ opinions and interpretation.

Findings

FM is currently shifting emphasis towards a strategic focus through the adoption of the new recognised international ISO standards that consider sustainable digitalisation in business decisions. However, the FM sector is encountering potential risks to the implementation of the new recognised international ISO standards. Digitalisation is one kind of force that has shaped the management of the built environment and FM recently and rapidly, especially in the Covid-19 period. This is impacting the FM industry. As standardisation aims at establishing a constantly evolving baseline of proven practices, standardisation can be considered a part of sustainable FM. It is believed that standardised and strategic level support is crucial for the smooth adoption of sustainable FM practices and processes. Standards such as the ISO standards, applied to the global FM industry, help in objectively quantifying the added value of FM to the core business. Advanced technology and digitalisation can contribute to the sustainability of any profession and industry, but it also requires a community to tackle the problems.

Originality/value

This paper contributes to the FM industry by making recommendations for improvement in the use of digitalisation. In summary, the significant finding of this viewpoint paper is that digitalisation offers both possibilities and problems in the application of the new recognised international ISO standards within the FM industry.
Explaining IFRS reluctance with case study vignettes
Authors: Hsu Yu-Lin , Reid Gavin C.
Published: March 2023

Purpose

This study aims to analyze why listed Taiwanese firms uniquely rejected the early adoption of International Financial Reporting Standards (IFRS) in 2012. It investigates the underlying decision-making processes behind this policy reluctance to further understand the continuous phenomenon of rare voluntary IFRS adoption.

Design/methodology/approach

It reports on fieldwork evidence obtainedin situby in-depth interviewing in Mandarin. It uses qualitative methods, complemented by quantitative cost-benefit metrics of IFRS adoption. It presents five diverse illustrative case-study vignettes, using a judgment sample based on expert opinion.

Findings

While the net-benefits of implementing IFRS varied across firms, this study’s unanimous finding was that no firms (in the sample or population) adopted IFRS early, despite stated intentions to the contrary. The key reasons for shunning early IFRS adoption were found to be frequent changes in regulations, insufficient benefits from adopting IFRS and the undermining of comparability across companies, compounded with scarce preparation time. Further, this study found that the Taiwanese accounting regulator’s reluctance toward IFRS adoption, partly caused by a long-standing US influence, contributed to this anomalous outcome.

Practical implications

This study recommends two critical policy changes: more realistic timelines and less frequent regulatory changes.

Originality/value

To the best of the authors’ knowledge, this is the first study to investigate the reasons behind the anomaly of no early adoption of IFRS in Taiwan, using new primary data and illustrative case studies. Its novelty lies in extending understanding beyond the existing quantitative literature on accounting standards, using new “thick” qualitative evidence on motives for such choices and decision-making processes, which have been neglected in previous work.
Open data-set identifier for open innovation and knowledge management
Authors: Ortiz-de-Urbina-Criado Marta , Abella Alberto , García-Luna Diego
Published: March 2023

Purpose

This paper aims to highlight the importance of open data and the role that knowledge management and open innovation can play in its identification and use. Open data has great potential to create social and economic value, but its main problem is that it is often not easily reusable. The aim of this paper is to propose a unique identifier for open data-sets that would facilitate search and access to them and help to reduce heterogeneity in the publication of data in open data portals.

Design/methodology/approach

Considering a model of the impact process of open data reuse and based on the digital object identifier system, this paper develops a proposal of a unique identifier for open data-sets called Open Data-set Identifier (OpenDatId).

Findings

This paper presents some examples of the application and advantages of OpenDatId. For example, users can easily consult the available content catalogues, search the data in an automated way and examine the content for reuse. It is also possible to find out where this data comes from, solving the problems caused by the increasingly frequent federation of data in open data portals and enabling the creation of additional services based on open data.

Originality/value

From an integrated perspective of knowledge management and open innovation, this paper presents a new unique identifier for open data-sets (OpenDatId) and a new concept for data-set, the FAIR Open Data-sets.
Doctor sahab: Doctors and the public in the ‘golden era’ of the Indian medical profession
Authors: Kumbhar Kiran
Published: March 2023

This essay analyses and historicises a contemporary dominant narrative among India’s biomedical doctors, that the early post‐independence period (1940s–1970s) was characterised by immense public trust and confidence in the biomedical profession, with the patient‐doctor relationship experiencing a ‘golden era’. By exploring people’s experiences with and perceptions of doctors during these decades, I show that contrary to contemporary understanding, public dissatisfaction with doctors was substantial even in the early post‐independence period. I argue that the dominance of privileged‐caste and ‐class Indians in the medical profession nurtured a caste privilege‐based elitist outlook within the mainstream profession and its leadership and created an insurmountable socioeconomic distance between doctors and the large majority of the public. What doctors deemed as people’s ‘trust’ in them and their profession was often simply a manifestation of people’s general deference towards the elites of the society. This incorrect interpretation of patient‐doctor dynamics in the past has been a constant feature of mainstream narratives around the doctor‐society relationship in post‐independence India and has remained largely under‐explored and under‐historicised in the medical, scholarly and public discourses.
The genetic era of childhood cancer: Identification of high‐risk patients and germline sequencing approaches
Authors: Alonso‐Luna Oscar , Mercado‐Celis Gabriela E , Melendez‐Zajgla Jorge , Zapata‐Tarres Marta , Mendoza‐Caamal Elvia
Published: March 2023

Childhood cancer is a leading cause of death by disease in children ages 5–14, for which there are no preventive strategies. Due to early‐age of diagnosis and short period of exposure to environmental factors, increasing evidence suggests childhood cancer could have strong association with germline alterations in predisposition cancer genes but, their frequency and distribution are largely unknown. Several efforts have been made to develop tools to identify children with increased risk of cancer who may benefit from genetic testing but their validation and application on a large scale is necessary. Research on genetic bases of childhood cancer is ongoing, in which several approaches for the identification of genetic variants related to cancer predisposition have been used. In this paper, we discuss the updated efforts, strategies, molecular mechanisms and clinical implications for germline predisposition gene alterations and the characterization of risk variants in childhood cancer.
A de novo low‐frequency mosaic variant of KIF1A causes hereditary spastic paraplegia: A literature review
Authors: Liu Mengyuan , Li Bing , Wang Xiaona , Li Dongxiao , Xie Zhenhua , Li Yuke , Gao Yang , Chen Baiyun , Zhang Huichun , Wang Yanli , Gao Chao
Published: March 2023

Objective

The objective of this study was to investigate the pathogenesis and inheritance pattern of a Chinese Han family with hereditary spastic paraplegia and to retrospectively analyze the characteristics of KIF1A gene variants and related clinical manifestations.

Methods

High‐throughput whole‐exome sequencing was performed on members of a Chinese Han family with a clinical diagnosis of hereditary spastic paraplegia, and the sequencing results were validated by Sanger sequencing. Deep high‐throughput sequencing was performed on subjects with suspected mosaic variants. The previously reported pathogenic variant loci of the KIF1A gene with complete data were collected, and the clinical manifestations and characteristics of the pathogenic KIF1A gene variant were analyzed.

Results

A pathogenic heterozygous variant located in the neck coil of the KIF1A gene (c.1139G>C, p.Arg380Pro) was identified in the proband and four additional members of the family. It was derived from the de novo low‐frequency somatic‐gonadal mosaicism of the proband's grandmother and had a rate of 10.95%.

Interpretation

This study helps us to better understand the pathogenic mode and characteristics of mosaic variants, and to understand the location and clinical characteristics of pathogenic variants in KIF1A.