bluuebunny/crossref_metadata_2025 huggingface dataset:
USP25 promotes hepatocellular carcinoma progression by interacting with TRIM21 via the Wnt/β-catenin signaling pathway
Authors: Liu Yinghui , Ma Jingjing , Lu Shimin , He Pengzhan , Dong Weiguo
Published: July 2023

Background:

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. The ubiquitin-specific peptidase 25 (USP25) protein has been reported to participate in the development of several cancers. However, few studies have reported its association with HCC. In this study, we aimed to investigate the function and mechanism of USP25 in the progression of HCC.

Methods:

We analyzed USP25 protein expression in HCC based on The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database cohorts. Then, we constructed USP25-overexpressing and USP25-knockdown HepG2, MHCC97H, and L-O2 cells. We detected the biological function of USP25 by performing a series of assays, such as Cell Counting Kit-8 (CCK-8), colony formation, transwell, and wound healing assays. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were performed to detect the interaction between USP25 and the Wnt/β-catenin signaling pathway. The relationship between USP25 and tripartite motif-containing 21 (TRIM21) was assessed through mass spectrometry and co-immunoprecipitation (Co-IP) analysis. Finally, we constructed a mouse liver cancer model with the USP25 gene deletion to verify in vivo role of USP25.

Results:

USP25 was highly expressed in HCC tissue and HCC cell lines. Importantly, high expression of USP25 in tissues was closely related to a poor prognosis. USP25 knockdown markedly reduced the proliferation, migration, and invasion of HepG2 and MHCC97H cells, whereas USP25 overexpression led to the opposite effects. In addition, we demonstrated that USP25 interacts with TRIM21 to regulate the expression of proteins related to epithelial–mesenchymal transition (EMT; E-cadherin, N-cadherin, and Snail) and the Wnt/β-catenin pathway (β-catenin, Adenomatous polyposis coli, Axin2 and Glycogen synthase kinase 3 beta) and those of their downstream proteins (C-myc and Cyclin D1). Finally, we verified that knocking out USP25 inhibited tumor growth and distant metastasis in vivo.

Conclusions:

In summary, our data showed that USP25 was overexpressed in HCC. USP25 promoted the proliferation, migration, invasion, and EMT of HCC cells by interacting with TRIM21 to activate the β-catenin signaling pathway.
Vaccination against coronavirus disease 2019 in patients with pulmonary hypertension: A national prospective cohort study
Authors: Wu Xiaohan , Li Jingyi , Ma Jieling , Liu Qianqian , Wang Lan , Zhu Yongjian , Cui Yue , Wang Anyi , Wen Cenjin , Qiu Luhong , Yang Yinjian , Lu Dan , Xu Xiqi , Zhu Xijie , Cheng Chunyan , Wang Duolao , Jing Zhicheng
Published: July 2023

Background:

Coronavirus disease 2019 (COVID-19) has potential risks for both clinically worsening pulmonary hypertension (PH) and increasing mortality. However, the data regarding the protective role of vaccination in this population are still lacking. This study aimed to assess the safety of approved vaccination for patients with PH.

Methods:

In this national prospective cohort study, patients diagnosed with PH (World Health Organization [WHO] groups 1 and 4) were enrolled from October 2021 to April 2022. The primary outcome was the composite of PH-related major adverse events. We used an inverse probability weighting (IPW) approach to control for possible confounding factors in the baseline characteristics of patients.

Results:

In total, 706 patients with PH participated in this study (mean age, 40.3 years; mean duration after diagnosis of PH, 8.2 years). All patients received standardized treatment for PH in accordance with guidelines for the diagnosis and treatment of PH in China. Among them, 278 patients did not receive vaccination, whereas 428 patients completed the vaccination series. None of the participants were infected with COVID-19 during our study period. Overall, 398 patients received inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, whereas 30 received recombinant protein subunit vaccine. After adjusting for baseline covariates using the IPW approach, the odds of any adverse events due to PH in the vaccinated group did not statistically significantly increase (27/428 [6.3%] vs. 24/278 [8.6%], odds ratio = 0.72, P = 0.302). Approximately half of the vaccinated patients reported at least one post-vaccination side effects, most of which were mild, including pain at the injection site (159/428, 37.1%), fever (11/428, 2.6%), and fatigue (26/428, 6.1%).

Conclusions:

COVID-19 vaccination did not significantly augment the PH-related major adverse events for patients with WHO groups 1 and 4 PH, although there were some tolerable side effects. A large-scale randomized controlled trial is warranted to confirm this finding. The final approval of the COVID-19 vaccination for patients with PH as a public health strategy is promising.
Choice of intraocular lens calculation formula for cataract patients with prior pars plana vitrectomy
Authors: Zhang Jiaqing , Han Xiaotong , Chen Xiaoyun , Liu Zhenzhen , Zhang Yu , Qiu Xiaozhang , Tan Xuhua , Luo Lixia , Liu Yizhi
Published: July 2023

Purpose:

To determine the optimal intraocular lens (IOL) calculation formula for vitrectomized eyes with diverse surgical and biometric characteristics.

Setting:

Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Design:

Retrospective consecutive case series study.

Methods:

This study included 974 vitrectomized eyes (974 patients) scheduled for phacoemulsification with IOL implantation. 11 formulas were evaluated: Barrett Universal II (BUII), Emmetropia Verifying Optical, Hoffer-QST, Kane, Ladas Super Formula, Pearl-DGS, Radial Basis Function (RBF), Haigis, HofferQ, Holladay1, and SRK/T. Risk factors for prediction error (PE) exceeding 1 diopter (D) were determined using multiple logistic regression. Subgroup analyses were performed based on surgical history and biometric parameters.

Results:

The risk of hyperopic PE (>1 D) was higher in patients with silicone oil tamponade (odds ratio [OR], 1.82) and longer axial length (AL) (OR, 1.55), while patients with previous scleral buckling (OR, 2.43) or ciliary sulcus IOL implantation (OR, 6.65) were more susceptible to myopic PE (<−1 D). The Kane formula had the highest overall prediction accuracy, and also the best in silicone oil-filled eyes and the flat cornea subgroup. The BUII and RBF displayed the optimal performance in eyes with previous scleral buckle and steep cornea, respectively. In eyes with an AL ≥ 26 mm, the Holladay1 with the nonlinear version of the Wang-Koch AL adjustment (Holladay1-WKn) showed the lowest absolute PE and highest percentage within ± 1.0 D of PE.

Conclusions:

The Kane achieved the highest overall prediction accuracy in vitrectomized eyes. The optimal formula for eyes with previous scleral buckle, steep cornea, or long AL was BUII, RBF, and Holladay1-WKn, respectively.
Participant Heterogeneity of Systemic Scleroderma Interventional Trials Worldwide
Authors: Shi Li-Qing , Zhou Shi-Hang , Ruan Ping-Lang , Zhang Bo , Xin Yue , Zhao Cheng , Yao Xu , Tian Jing-Ru , Lu Qian-Jin
Published: July 2023

Objective:

Heterogeneity of participants in clinical trials distorts intervention efficacy. However, factors associated with participant heterogeneity in randomized clinical trials (RCTs) focusing on systemic sclerosis (SSc) are not clear. We conducted this systematic review to establish normative standards for future research and help develop management guidelines.

Methods:

Three databases and 4 registries were searched to identify characteristics of SSc RCTs across different countries. Risk of bias was assessed by the Cochrane Collaboration’s tool and logistic regression was performed to calculate crude and adjusted odds ratios.

Results:

In total, 261 trials met our inclusion criteria. The quality of SSc RCTs worldwide was relatively poor, with no trend of improvement in recent years, and only 12.2% were ranked as having a low risk of bias. Trials with a low risk of bias as well as single-center, single-country, or open-label trials tended to have better participant adherence than trials with a high risk of bias and multiple-center, multiple-country, or double-blind trials. Interestingly, trial registration and primary outcome definition contributed to high withdrawal. National income was also relevant; participant adherence in high-income countries, but not in upper- and lower-middle-income countries, was significantly altered by different variables.

Conclusion:

Overall, the risk of bias, national income, and trial design may lead to participant heterogeneity of SSc RCTs and ultimately confound the general clinical utility of the results. Trials with a rigorous design and transparent conduction protocol are crucial for obtaining unbiased data that can serve as a reference and for maintaining the fundamental repeatability of SSc RCTs.
EFFICACY OF 308 NM MONOCHROMATIC EXCIMER LAMP AND TOPICAL TACROLIMUS COMBINATION THERAPY IN LOCALIZED VITILIGO: A STUDY IN VIETNAM
Authors: Do Thi Thu Hien , Nguyen Thai Minh Hao , Kanekura Takuro
Published: July 2023

Objective:

Combination therapy of a 308 nm monochromatic excimer lamp and topical tacrolimus is widely used in the treatment of localized vitiligo; however, there are no published studies investigating this combination therapy in Vietnamese patients with vitiligo. This study was performed to evaluate the efficacy of combined excimer lamp and topical tacrolimus therapy for patients with localised vitiligo in Vietnam.

Methods:

We performed a pre-post clinical trial of 30 patients diagnosed with localised vitiligo in Vietnam. The patients were treated with an excimer lamp twice weekly and with topical tacrolimus twice daily. Effectiveness was evaluated based on the reduction rate of the vitiligo area scoring index (VASI).

Results:

After 12 weeks of treatment, response was excellent or good in 16 patients (53.3%), moderate in 8 patients (26.7%), and poor in 6 patients (20%). The excellent or good responses increased over time from 3 patients (10%) at 6 weeks to 16 patients (53.3%) at 12 weeks (p=0.001). Earlier initiation of repigmentation was associated with a better response to treatment (r=-0.71; p=0.02). Patients with a perifollicular repigmentation pattern responded better to treatment than those with combined or marginal repigmentation patterns (p=0.003). Side effects occurred in 13 patients (43.3%), including burning (43.3%), pruritus (10%), and mild blistering (6.7%), and none of these interrupted the treatment.

Conclusion:

Combination therapy with excimer lamp and topical tacrolimus appears to be effective and safe in treating patients with localised vitiligo in Vietnam.
An Educational Intervention for Coronary Heart Disease Patients With Type D Personality: A Randomized Controlled Trial
Authors: CAO Xi , CHAIR Sek Ying , WONG Eliza M. L. , TAO Mei Yi
Published: July 2023

Background

Type D personality, a newly specified personality type defined as the interaction of high levels of negative affectivity and social inhibition, is associated with poor health outcomes. Few interventional studies have been performed to improve health outcomes in this subpopulation.

Purpose

This study was developed to examine the effects of an educational intervention on psychological health, health-promoting behaviors, and quality of life in coronary heart disease (CHD) patients with type D personality in China.

Methods

A randomized controlled trial was adopted. One hundred twenty-eight patients with CHD and type D personality were randomly assigned. The intervention group received the 12-week educational intervention in addition to usual care, whereas the control group received usual care only. Data on anxiety and depression, health-promoting behaviors, and quality of life were collected at baseline and at 1 and 3 months after enrollment. After controlling for the covariates, the generalized estimating equation model was used to examine the intervention effects.

Results

The mean age of the participants was 61.02 years, and more than 70% were male. Results of the generalized estimating equation analysis showed significantly greater improvements in anxiety, depression, and health-promoting behaviors in the intervention group than in the control group. In addition, quality of life, the domains of angina limitation, angina stability, and treatment satisfaction were found to have improved more significantly in the intervention group than the control group, whereas the posttest changes in angina frequency and disease perception were found to be similar in both groups.

Conclusions/Implications for Practice

The educational intervention was shown to be effective in improving psychological health, health-promoting behaviors, and certain domains of quality of life in patients with CHD and type D personality. Nurses should identify patients with this personality type and provide tailored care to improve their health outcomes in clinical practice.
Workplace Measures Against COVID-19 and Mistreatment in the Workplace Among Japanese Employees
Authors: Tsukahara Keita , Ishimaru Tomohiro , Matsugaki Ryutaro , Ando Hajime , Mafune Kosuke , Nagata Tomohisa , Tateishi Seiichiro , Tsuji Mayumi , Kataoka Masaharu , Fujino Yoshihisa ,   for the CORoNaWork Project
Published: July 2023

Objective

The purpose of this study was to identify the COVID-19 infection prevention measures that are at risk of being perceived by employees as mistreatment in the workplace.

Methods

This study included full-time workers who enrolled as subjects in a nationwide prospective cohort study. Baseline surveys performed during the pandemic were used to identify the workplace measures against COVID-19. A tracing survey was conducted 1 year later to assess workplace mistreatment.

Results

Of the 18,170 participants, 276 judged that they had experienced mistreatment by the measures. “Enforcing daily temperature measurement” and “stopping business trips” were associated with mistreatment. Meanwhile, “requesting that employees refrain from going to work when ill” and “restricting work-related social gatherings and entertainment” had the potential to reduce workplace mistreatment.

Conclusions

Certain measures against COVID-19 can reduce or increase the burden on employees.
Cellular crosstalk of regulatory T cells in pancreatic ductal adenocarcinoma
Authors: Shi Xuqing , Liu Hangqi , Liang Zhiyong
Published: July 2023

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid tumors and is characterized by dense desmoplasia and immune desert. Regulatory T cells (Tregs) are critical components of the immune tumor microenvironment (TIME) of PDAC. Treg-induced immune evasion presents a significant hurdle in enhancing the efficacy of conventional and emerging therapeutic strategies. Nonetheless, Treg deficiency alone led to inconsistent outcomes. To unveil the underlying potential reasons for these results and to determine the role of Tregs in other therapeutic strategies, in-depth insights into the crosstalk between Tregs and other cells in PDAC are indispensable and currently lacking. Therefore, in this review, we comprehensively delineate the direct and indirect interplay between Tregs and various cellular constituents ranging from cancer cells and immune cells to stromal cells in PDAC in an attempt to uncover potential leads for the development of Treg-associated therapies.
Risk stratification of pulmonary embolism
Authors: Chowdhury Junad M. , Brown Patrick , Kasarabada Aditya
Published: July 2023

Purpose of review

Pulmonary embolism is the third most frequent type of cardiovascular disease behind coronary artery disease and stroke. Patients with acute pulmonary embolism have significant variability in short-term mortality from less than 0.6% in low-risk patients to 19% in high-risk patients. Risk stratification plays an important role in the management of acute pulmonary embolism as it can determine the need for urgent reperfusion therapies versus conservative strategies.

Recent findings

The three fundamental steps of risk stratification include the immediate identification of patients that are at high risk for mortality, the identification of patients that are at an increased risk of complications from pulmonary embolism that requires hospital monitoring and potential escalation of therapies, and the identification of patients at a low risk that can be treated as an outpatient.

It is vital to immediately identify high-risk patients for mortality so that they can be evaluated for urgent reperfusion therapies to improve outcomes. Risk stratification for intermediate-risk patients is based on right ventricular dysfunction in patients with hemodynamic stability. RV dysfunction can be assessed by clinical signs and symptoms along with ECHO and cardiac biomarkers. Identifying the low-risk population can help reduce the healthcare burden by allowing for early discharge and outpatient management.
Moving Beyond Central Line-Associated Bloodstream Infections: Enhancement of the Prevention Process
Authors: Garcia Robert
Published: July 2023

The provision of medications and other treatments via intravenous (IV) therapy has provided millions of health care patients with extended benefits. IV therapy, however, is also associated with complications, such as associated bloodstream infections. Understanding the mechanisms of development and the factors that have contributed to the recent increases in such health care-acquired infections assists in formulating new preventive strategies that include the implementation of hospital-onset bacteremia, an innovative model that requires surveillance and prevention of bloodstream infections associated with all types of vascular access devices, expansion of vascular access service teams (VAST), and use of advanced antimicrobial dressings designed to reduce bacterial proliferation over the currently recommended time periods for maintenance of IV catheters.
Impact of a Pediatric Emergency Medicine Pharmacist, Institutional Guideline, and Electronic Order Set on Empiric Antimicrobial Use for Febrile Neutropenia
Authors: Aluisio Yancey M. , Sanchez Alicia C. , Norris Kelley R. , Waller Jennifer , Campbell Christopher T.
Published: July 2023

Objectives

This study evaluated the difference in appropriateness of antimicrobial selection in pediatric patients with febrile neutropenia (FN) after implementation of an institutional guideline, a dedicated pediatric emergency medicine (EM) pharmacist, and an electronic order set.

Methods

This was a retrospective cohort study that included febrile patients aged younger than 18 years who were at risk of neutropenia, as defined by our institutional algorithm. Charts were evaluated for inclusion by searching for patients who presented to the emergency department (ED) between February 2018 and January 2022 who had International Classification of Diseases, Tenth Revision (ICD-10) codes for patients at risk of FN. Three independent groups were compared before, during, and after interventions. A historical control group (group 1), postdedicated EM pharmacist and institutional guideline cohort (group 2), and postdedicated EM pharmacist, institutional guideline, and electronic order set cohort (group 3) were compared. Secondary outcomes included time from registration in the ED to administration of the first dose of empiric antimicrobials, days to defervescence, pediatric intensive care unit length of stay, and hospital length of stay.

Results

Seventy-eight charts were reviewed for inclusion. Among those included (n = 38), there was an increase in appropriate use of antimicrobials from 71% to 92% to 100% (P = 0.1534) between group 1, group 2, and group 3, respectively. In addition, the interventions in this study lead to an overall decrease in the median time from registration to first dose of antibiotics from 142 minutes to 72 minutes (P = 0.1370).

Conclusions

This study demonstrated the positive impact a pediatric EM pharmacist along with an institutional guideline and an electronic order set have on appropriate antimicrobial selection in pediatric FN patients. Institutions should consider multipronged approaches to improve the selection and time to administration of appropriate empiric antimicrobials in the ED.
Analysis of Nasal Bone Fractures: A 17-year Study of 3785 Patients
Authors: Hwang Kun , Yoon Jin Myung
Published: July 2023

In our previous study, we classified nasal bone fractures into 6 types based on computed tomography and the patterns of the nasal bone fractures (NBF) in 503 patients treated between 1998 and 2004. In the present study, we analyzed 3785 patients treated between 2005 and 2021.

The age, sex, etiology, associated injuries, pattern of fractures, and treatments were reviewed, and radiographic studies were analyzed.

The highest incidence was in the age group of 10 to 19 years (N=870, 23.0%), followed by 20 to 29 years (N=792, 20.9%) and 30 to 39 years (N=635, 16.8%). The most common causes of injury were slip or fall-down (42.3%), violence (24.3%), sports (19.2%), traffic accidents (8.9%), and work-related (5.3%). Most of the patients had tenderness (96.1%) and swelling (78.8%). Other findings were depression (27.1%) and nasal deviation (25.8%). Crepitus was heard in only 0.4% of the patients. The patterns of the NBFs classified by computed tomography findings were type IIA (unilateral simple fracture with displacement/without telescoping, 1283 cases, 33.9%), IIB (bilateral simple fracture with displacement/without telescoping, 786 cases, 20.8%), IIAs (unilateral simple fracture with septal fracture and displacement/without telescoping, 566 cases, 14.9%), IIBs (bilateral simple fracture with septal fracture and displacement/without telescoping 530 cases, 14.0%), I (simple fracture without displacement, 522 cases, 13.8%), and III (comminuted with telescoping or depression, 98 cases, 2.6%). In most of the cases (3,666, 96.9%), closed reduction was performed.

The present analysis is one of the largest data sets on NBF in Korea, which could provide reference values for diagnosing and managing nasal bone fractures.
Mismatched Postsurgical Opioid Prescription to Liver Transplant Patients: A Retrospective Cohort Study From a Single High-Volume Transplant Center
Authors: Chen Victoria J. , Guan Lucy S. , Bokoch Michael P. , Langnas Erica , Kothari Rishi , Croci Rhiannon , Campbell Liam J. , Quan David , Freise Chris , Guan Zhonghui
Published: July 2023

Background.

Improper opioid prescription after surgery is a well-documented iatrogenic contributor to the current opioid epidemic in North America. In fact, opioids are known to be overprescribed to liver transplant patients, and liver transplant patients with high doses or prolonged postsurgical opioid use have higher risks of graft failure and death.

Methods.

This is a retrospective cohort study of 552 opioid-naive patients undergoing liver transplant at an academic center between 2012 and 2019. The primary outcome was the discrepancy between the prescribed discharge opioid daily dose and each patient’s own inpatient opioid consumption 24 h before discharge. Variables were analyzed with Wilcoxon and chi-square tests and logistic regression.

Results.

Opioids were overprescribed in 65.9% of patients, and 54.3% of patients who required no opioids the day before discharge were discharged with opioid prescriptions. In contrast, opioids were underprescribed in 13.4% of patients, among whom 27.0% consumed inpatient opioids but received no discharge opioid prescription. The median prescribed opioid daily dose was 333.3% and 56.3% of the median inpatient opioid daily dose in opioid overprescribed and underprescribed patients, respectively. Importantly, opioid underprescribed patients had higher rates of opioid refill 1 to 30 and 31 to 90 d after discharge, and the rate of opioid underprescription more than doubled from 2016 to 2019.

Conclusions.

Opioids are both over- and underprescribed to liver transplant patients, and opioid underprescribed patients had higher rates of opioid refill. Therefore, we proposed to prescribe discharge opioid prescriptions based on liver transplant patients’ inpatient opioid consumption to provide patient-centered opioid prescriptions.
The Vibrio vulnificus stressosome is dispensable in nutrient-rich media
Authors: Cutugno Laura , Mc Cafferty Jennifer , Pané-Farré Jan , O'Byrne Conor , Boyd Aoife
Published: July 2023

The stressosome is a protein complex that senses environmental stresses and mediates the stress response in several Gram-positive bacteria through the activation of the alternative sigma factor SigB. The stressosome locus is found in 44 % of Gram-negative

Vibrio vulnificus

isolates. However,

V. vulnificus

does not possess SigB. Nonetheless, in nutrient-limited media, the stressosome modulates gene transcription and bacterial behaviour. In this work, the expression of the stressosome genes was proven during stationary phase in nutrient-rich media and co-transcription as one operonic unit of the stressosome locus and its putative downstream regulatory locus was demonstrated. The construction of a stressosome mutant lacking the genes encoding the four proteins constituting the stressosome complex (VvRsbR, VvRsbS, VvRsbT, VvRsbX) allowed us to examine the role of this complex in vivo. Extensive phenotypic characterization of the ΔRSTX mutant in nutrient-rich media showed that the stressosome does not contribute to growth of

V. vulnificus

. Moreover, the stressosome did not modulate the tolerance or survival response of

V. vulnificus

to the range of stresses tested, which included ethanol, hyperosmolarity, hypoxia, high temperature, acidity and oxidative stress. Furthermore, the stressosome was dispensable for motility and exoenzyme production of

V. vulnificus

in nutrient-rich media. Therefore, in conclusion, although stressosome gene transcription occurs in nutrient-rich media, the stressosome neither has an essential role in stress responses of

V. vulnificus

nor does it seem to modulate these activities in these conditions. We hypothesise that the stressosome is expressed in nutrient-rich conditions as a sensor complex, but that activation of the complex does not occur in this environment.
National Health Examination Surveys: an essential piece of the health planning puzzle
Authors: Margozzini Paula , Tolonen Hanna , Bernabe-Ortiz Antonio , Cuschieri Sarah , Donfrancesco Chiara , Palmieri Luigi , Sanchez Romero Luz Maria , Mindell Jennifer S , Oyebode Oyinlola
Published: July 2023

National health examination surveys (HESs) have been developed to provide important information that cannot be obtained from other sources. A HES combines information obtained by asking participants questions with biophysical measurements taken by trained field staff. They are observational studies with the highest external validity and make specific contributions to both population (public health) and individual health. Few countries have a track record of a regular wide-ranging HES, but these are the basis of many reports and scientific papers. Despite this, little evidence about HES usefulness and impact or the factors that influence HES effectiveness have been disseminated. This paper presents examples of HES contributions to society in both Europe and the Americas. We sought information by emailing a wide list of people involved in running or using national HESs across Europe and the Americas. We asked for examples of where examination data from their HES had been used in national or regional policymaking. We found multiple examples of HES data being used for agenda-setting, including by highlighting nutritional needs and identifying underdiagnosis and poor management of certain conditions. We also found many ways in which HES have been used to monitor the impact of policies and define population norms. HES data have also been used in policy formation and implementation. HES data are influential and powerful. There is need for global support, financing and networking to transfer capacities and innovation in both fieldwork and laboratory technology.
Natural Language Processing Can Automate Extraction of Barrett’s Esophagus Endoscopy Quality Metrics
Authors: Soroush Ali , Diamond Courtney J. , Zylberberg Haley M. , May Benjamin , Tatonetti Nicholas , Abrams Julian A. , Weng Chunhua
Published: July 2023

Objectives

To develop an automated natural language processing (NLP) method for extracting high-fidelity Barrett’s Esophagus (BE) endoscopic surveillance and treatment data from the electronic health record (EHR).

Methods

Patients who underwent BE-related endoscopies between 2016 and 2020 at a single medical center were randomly assigned to a development or validation set. Those not aged 40 to 80 and those without confirmed BE were excluded. For each patient, free text pathology reports and structured procedure data were obtained. Gastroenterologists assigned ground truth labels. An NLP method leveraging MetaMap Lite generated endoscopy-level diagnosis and treatment data. Performance metrics were assessed for this data. The NLP methodology was then adapted to label key endoscopic eradication therapy (EET)-related endoscopy events and thereby facilitate calculation of patient-level pre-EET diagnosis, endotherapy time, and time to CE-IM.

Results

99 patients (377 endoscopies) and 115 patients (399 endoscopies) were included in the development and validation sets respectively. When assigning high-fidelity labels to the validation set, NLP achieved high performance (recall: 0.976, precision: 0.970, accuracy: 0.985, and F1-score: 0.972). 77 patients initiated EET and underwent 554 endoscopies. Key EET-related clinical event labels had high accuracy (EET start: 0.974, CE-D: 1.00, and CE-IM: 1.00), facilitating extraction of pre-treatment diagnosis, endotherapy time, and time to CE-IM.

Conclusions

High-fidelity BE endoscopic surveillance and treatment data can be extracted from routine EHR data using our automated, transparent NLP method. This method produces high-level clinical datasets for clinical research and quality metric assessment.

Study Highlights

1)

WHAT IS KNOWN:

-

Existing BE clinical data extraction methods are limited.

2)

WHAT IS NEW HERE:

-

An NLP pipeline for granular BE clinical data.
Chromosomal-level genome assembly ofPopulus adenopoda
Authors: Liu Shuyu , Wang Zeng , Shi Tingting , Dan Xuming , Zhang Yulin , Liu Jianquan , Wang Jing
Published: July 2023

High-quality reference genomes for several species have promoted breeding and functional studies of poplar trees. By resequencing numerous accessions of these and closely related species, single nucleotide polymorphisms (SNPs) and small insertion/deletions (InDels) have been identified to assist in clarifying local adaptation and phenotypic diversification. A chromosome-level genome assembly forP. adenopodawas assembled based on Illumina and PacBio sequencing platforms, facilitated by Hi-C technology. The assembled genome size was about 383 Mb, with 99.70% of the contigs anchored to 19 pseudo-chromosomes, and a total of 33,505 protein-coding genes were annotated. This high-quality genome provided the genomic basis for the subsequent detection of various variants.
Moderate intensity aerobic exercise in 6-OHDA-lesioned rats alleviates established motor deficits and reduces neurofilament light and glial fibrillary acidic protein serum levels without increased striatal dopamine or tyrosine hydroxylase protein
Authors: Kasanga Ella A. , Soto Isabel , Centner Ashley , McManus Robert , Shifflet Marla K. , Navarrete Walter , Han Yoonhee , Lisk Jerome , Wheeler Ken , Mhatre-Winters Isha , Richardson Jason R. , Bishop Christopher , Nejtek Vicki A. , Salvatore Michael F.
Published: July 2023

Background

Alleviation of motor impairment by aerobic exercise (AE) in Parkinson’s disease (PD) points to a CNS response that could be targeted by therapeutic approaches, but recovery of striatal dopamine (DA) or tyrosine hydroxylase (TH) has been inconsistent in rodent studies.

Objective

To increase translation of AE, 3 components were implemented into AE design to determine if recovery of established motor impairment, concomitant with >80% striatal DA and TH loss, was possible. We also evaluated if serum levels of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), blood-based biomarkers of disease severity in human PD, were affected.

Methods

We used a 6-OHDA hemiparkinson rat model featuring progressive nigrostriatal neuron loss over 28 days, with impaired forelimb use 7 days post-lesion, and hypokinesia onset 21 days post-lesion. After establishing forelimb use deficits, moderate intensity AE began 1-3 days later, 3x per week, for 40 min/session. Motor assessments were conducted weekly for 3 wks, followed by determination of striatal DA, TH protein and mRNA, and NfL and GFAP serum levels.

Results

Seven days after 6-OHDA lesion, recovery of depolarization-stimulated extracellular DA and DA tissue content was <10%, representing severity of DA loss in human PD, concomitant with 50% reduction in forelimb use. Despite severe DA loss, recovery of forelimb use deficits and alleviation of hypokinesia progression began after 2 weeks of AE and was maintained. Increased NfLand GFAP levels from lesion were reduced by AE. Despite these AE-driven changes, striatal DA tissue and TH protein levels were unaffected.

Conclusions

This proof-of-concept study shows AE, using exercise parameters within the capabilities most PD patients, promotes recovery of established motor deficits in a rodent PD model, concomitant with reduced levels of blood-based biomarkers associated with PD severity, without commensurate increase in striatal DA or TH protein.
The impact of spectral basis set composition on estimated levels of cingulate glutamate and its associations with different personality traits
Authors: Demler Verena , Sterner Elisabeth F. , Wilson Martin , Zimmer Claus , Knolle Franziska
Published: July 2023

Background

1H-MRS is increasingly used in basic and clinical research to explain brain function and alterations respectively. In psychosis research it is now one of the main tools to investigate imbalances in the glutamatergic system. Interestingly, however, the findings are extremely variable even within patients of similar disease states. One reason may be the variability in analysis strategies, despite suggestions for standardization. Therefore, our study aimed to investigate the extent to which the basis set configuration – which metabolites are included in the basis set used for analysis – would affect the spectral fit and estimated glutamate (Glu) concentrations in the anterior cingulate cortex (ACC), and whether any changes in levels of glutamate would be associated with psychotic-like experiences and autistic traits.

Methods

To ensure comparability, we utilized five different exemplar basis sets, used in research, and two different analysis tools, r-based spant applying the ABfit method andOspreyusing the LCModel.

Results

Our findings revealed that the types of metabolites included in the basis set significantly affected the glutamate concentration. We observed that three basis sets led to more consistent results across different concentration types (i.e., absolute Glu in mol/kg, Glx (glutamate+glutamine), Glu/tCr), spectral fit and quality measurements. Interestingly, all three basis sets included phosphocreatine. Importantly, our findings also revealed that glutamate levels were differently associated with both schizotypal and autistic traits depending on basis set configuration and analysis tool, with the same three basis sets showing more consistent results.

Conclusions

Our study highlights that scientific results may be significantly altered depending on the choices of metabolites included in the basis set, and with that emphasizes the importance of carefully selecting the configuration of the basis set to ensure accurate and consistent results, when using MR spectroscopy. Overall, our study points out the need for standardized analysis pipelines and reporting.
Cooperative thalamocortical circuit mechanism for sensory prediction errors
Authors: Furutachi Shohei , Franklin Alexis D. , Mrsic-Flogel Thomas D. , Hofer Sonja B.
Published: July 2023

The brain functions as a prediction machine, utilizing an internal model of the world to anticipate sensations and the outcomes of our actions. Discrepancies between expected and actual events, referred to as prediction errors, are leveraged to update the internal model and guide our attention towards unexpected events1–10. Despite the importance of prediction error signals for various neural computations across multiple brain regions, surprisingly little is known about the neural circuit mechanisms responsible for their implementation. Here we describe a thalamocortical disinhibitory circuit required for generating sensory prediction errors in mouse primary visual cortex (V1). Using calcium imaging with optogenetic manipulations as mice traverse a familiar virtual environment, we show that violation of animals’ predictions by an unexpected visual stimulus preferentially boosts responses of layer 2/3 V1 neurons most selective for that stimulus. Prediction errors specifically amplify the unexpected visual input, rather than representing a non-specific surprise or difference signal about how the visual input deviates from animals’ predictions. Selective amplification of unexpected visual input is implemented by a cooperative mechanism requiring thalamic input from the pulvinar, and cortical vasoactive-intestinal-peptide-expressing (VIP) inhibitory interneurons. In response to prediction errors, VIP neurons inhibit a specific subpopulation of somatostatin-expressing (SOM) inhibitory interneurons that gate excitatory pulvinar input to V1, resulting in specific pulvinar-driven response-amplification of the most stimulus-selective neurons in V1. Therefore, the brain prioritizes unpredicted sensory information by selectively increasing the salience of unpredicted sensory features through the synergistic interaction of thalamic input and neocortical disinhibitory circuits.
Fungivorous protists in the rhizosphere ofArabidopsis thaliana– Diversity, functions, and publicly available cultures for experimental exploration
Authors: Estermann Antonie H. , Pereira Bassiaridis Justin Teixeira , Loos Anne , Solbach Marcel Dominik , Bonkowski Michael , Hess Sebastian , Dumack Kenneth
Published: July 2023

In the context of the soil food web, the transfer of plant-fixed energy and carbon to higher trophic levels has traditionally been attributed to two main energy channels: the fungal energy channel and the bacterial energy channel. Historically, protists were overlooked in the fungal energy channel, which was believed to be controlled by fungivorous microarthropods and nematodes. In this study, we investigated fungivorous protists in the rhizosphere ofArabidopsis thaliana. Our findings revealed a notable abundance and diversity of protists that have developed specialized strategies to overcome the protective cell wall of fungi. Among the identified species were two Vampyrellida (Rhizaria) species, namelyTheratromyxa weberiandPlatyreta germanica, as well as one Arcellinida (Amoebozoa) species, calledCryptodifflugia oviformis. WhileT. weberitypically consumed entire fungal cells, the other two species perforated fungal cell walls and extracted the cellular contents. We elucidate the feeding strategies and dietary ranges of the amoebae, highlighting the non-uniform nature of fungivory in protists, as different taxa have evolved distinct approaches to access fungi as a food source. Moreover, we provide publicly available cultures of these protists to facilitate further experimental investigations within the research community.
The Medical Action Ontology: A Tool for Annotating and Analyzing Treatments and Clinical Management of Human Disease
Authors: Carmody Leigh C , Gargano Michael A , Toro Sabrina , Vasilevsky Nicole A , Adam Margaret P , Blau Hannah , Chan Lauren E , Gomez-Andres David , Horvath Rita , Kraus Megan L , Ladewig Markus S , Lewis-Smith David , Lochmüller Hanns , Matentzoglu Nicolas A , Munoz-Torres Monica C , Schuetz Catharina , Seitz Berthold , Similuk Morgan N , Sparks Teresa N , Strauss Timmy , Swietlik Emilia M , Thompson Rachel , Zhang Xingmin Aaron , Mungall Christopher J , Haendel Melissa A , Robinson Peter N
Published: July 2023

Navigating the vast landscape of clinical literature to find optimal treatments and management strategies can be a challenging task, especially for rare diseases. To address this task, we introduce the Medical Action Ontology (MAxO), the first ontology specifically designed to organize medical procedures, therapies, and interventions in a structured way. Currently, MAxO contains 1757 medical action terms added through a combination of manual and semi-automated processes. MAxO was developed with logical structures that make it compatible with several other ontologies within the Open Biological and Biomedical Ontologies (OBO) Foundry. These cover a wide range of biomedical domains, from human anatomy and investigations to the chemical and protein entities involved in biological processes.

We have created a database of over 16000 annotations that describe diagnostic modalities for specific phenotypic abnormalities as defined by the Human Phenotype Ontology (HPO). Additionally, 413 annotations are provided for medical actions for 189 rare diseases. We have developed a web application called POET (https://poet.jax.org/) for the community to use to contribute MAxO annotations.

MAxO provides a computational representation of treatments and other actions taken for the clinical management of patients. The development of MAxO is closely coupled to the Mondo Disease Ontology (Mondo) and the Human Phenotype Ontology (HPO) and expands the scope of our computational modeling of diseases and phenotypic features to include diagnostics and therapeutic actions. MAxO is available under the open-source CC-BY 4.0 license (https://github.com/monarch-initiative/MAxO).
Evolutionary conservation of the structure and function of meiotic Rec114−Mei4 and Mer2 complexes
Authors: Daccache Dima , De Jonge Emma , Liloku Pascaline , Mechleb Karen , Haddad Marita , Corthaut Sam , Sterckx Yann G.-J. , Volkov Alexander N. , Claeys Bouuaert Corentin
Published: July 2023

Meiosis-specific Rec114−Mei4 and Mer2 complexes are thought to enable Spo11-mediated DNA double-strand break (DSB) formation through a mechanism that involves DNA-dependent condensation. However, the structure, molecular properties, and evolutionary conservation of Rec114−Mei4 and Mer2 are unclear. Here, we present AlphaFold models of Rec114−Mei4 and Mer2 complexes supported by nuclear magnetic resonance (NMR) spectroscopy, small-angle X-ray scattering (SAXS), and mutagenesis. We show that dimers composed of the Rec114 C terminus form α-helical chains that cup an N-terminal Mei4 α helix, and that Mer2 forms a parallel homotetrameric coiled coil. Both Rec114−Mei4 and Mer2 bind preferentially to branched DNA substrates, indicative of multivalent protein–DNA interactions. Indeed, the Rec114−Mei4 interaction domain contains two DNA-binding sites that point in opposite directions and drive condensation. The Mer2 coiled-coil domain bridges coaligned DNA duplexes, likely through extensive electrostatic interactions along the length of the coiled coil. Finally, we show that the structures of Rec114−Mei4 and Mer2 are conserved across eukaryotes, while DNA-binding properties vary significantly. This work provides insights into the mechanism whereby Rec114−Mei4 and Mer2 complexes promote the assembly of the meiotic DSB machinery and suggests a model in which Mer2 condensation is the essential driver of assembly, with the DNA-binding activity of Rec114−Mei4 playing a supportive role.
Investigating physician churn in online health communities from a social influence perspective
Authors: Chen Qin , Jin Jiahua , Zhang Tingting , Yan Xiangbin
Published: July 2023

Purpose

The success of online health communities (OHCs) depends on maintaining long-term relationships with physicians and preventing churn. Even so, the reasons for physician churn are poorly understood. In this study, an empirical model was proposed from a social influence perspective to explore the effects of online social influence and offline social influence on physician churn, as well as the moderating effect of their online returns.

Design/methodology/approach

The empirical data of 4,145 physicians from a Chinese OHC, and probit regression models were employed to verify the proposed theoretical model.

Findings

The results suggest that physicians' churn intention is influenced by online and offline social influences, and the offline social influence is more powerful. Physicians' reputational and economic returns could weaken the effect of online social influence on churn intention. However, physicians' economic returns could strengthen the effect of offline social influence on churn intention.

Originality/value

This research study is the first attempt to explore physician churn and divides the social influence into online and offline social influences according to the source of social relationship. The findings contribute to the literature on e-Health, user churn and social influence and provide management implications for OHC managers.
Co-creating organizational performance and project success through customer participation, requirement risk and knowledge integration: a multi-study evidence
Authors: Tabassum Marya , Raziq Muhammad Mustafa , Rice John Lewis , Borini Felipe Mendes , Wajid Anees
Published: July 2023

Purpose

Taking a co-creation perspective and integrating knowledge-based and resource-based perspectives, the authors examine the role of customer participation in organizational performance and project success. The authors also investigate the mediating role of knowledge integration and the moderating role of requirement risk for these relationships in uncertain contexts.

Design/methodology/approach

The authors undertook two studies. The first study was carried out in 2018 in which the authors drew on survey data from 150 information technology (IT) sector employees and examined the mediating role of knowledge integration in the relationship of customer participation with organizational performance and project success. In the second study undertaken in 2020, the authors drew on data from 92 IT and telecom sector employees and examined the moderating role of requirement risk in the relationship between customer participation and knowledge integration. Study 2 was conducted during the COVID-19 pandemic when employees were largely working from home and were more sensitive to risks and uncertainty about the scope and system requirements. Both studies were survey-based, and analysis was carried out using structural equation modeling.

Findings

The authors’ two-study examination indicated that knowledge integration positively mediates the relationship of customer participation with organizational performance and project success during the co-creation process. Furthermore, the authors demonstrate that when requirement risks are high, customer participation relationship with knowledge integration is weaker.

Originality/value

The authors show that integrating customer knowledge is critical to project success and organizational performance. By identifying risk uncertainties and environmental contingencies, the authors highlight the constraints of customer participation for knowledge integration, organizational performance and project success. The authors provide some key study findings based on survey data obtained from project teams during two periods (normal and pandemic).