bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticoagulant therapy for splanchnic vein thrombosis: an individual patient data meta-analysis
Authors: Candeloro Matteo , Valeriani Emanuele , Monreal Manuel , Ageno Walter , Riva Nicoletta , Lopez-Reyes Raquel , Peris Maria Luisa , Beyer Westendorf Jan , Schulman Sam , Rosa Vladimir , López-Núñez Juan José , Garcia-Pagan Juan-Carlos , Magaz Marta , Senzolo Marco , De Gottardi Andrea , Di Nisio Marcello
Published: May 2022

Robust evidence on the optimal management of splanchnic vein thrombosis (SVT) is lacking. We conducted an individual-patient meta-analysis to evaluate the effectiveness and safety of anticoagulation for SVT. Medline, Embase, and clincaltrials.gov were searched up to June 2021 for prospective cohorts or randomized clinical trials including patients with SVT. Data from individual datasets were merged, and any discrepancy with published data was resolved by contacting study authors. Three studies of a total of 1635 patients were included. Eighty-five percent of patients received anticoagulation for a median duration of 316 days (range, 1-730 days). Overall, incidence rates for recurrent venous thromboembolism (VTE), major bleeding, and mortality were 5.3 per 100 patient-years (p-y; 95% confidence interval [CI], 5.1-5.5), 4.4 per 100 p-y (95% CI, 4.2-4.6), and 13.0 per 100 p-y (95% CI, 12.4-13.6), respectively. The incidence rates of all outcomes were lower during anticoagulation and higher after treatment discontinuation or when anticoagulation was not administered. In multivariable analysis, anticoagulant treatment appeared to be associated with a lower risk of recurrent VTE (hazard ratio [HR], 0.42; 95% CI, 0.27-0.64), major bleeding (HR, 0.47; 95% CI, 0.30-0.74), and mortality (HR, 0.23; 95% CI, 0.17-0.31). Results were consistent in patients with cirrhosis, solid cancers, myeloproliferative neoplasms, unprovoked SVT, and SVT associated with transient or persistent nonmalignant risk factors. In patients with SVT, the risk of recurrent VTE and major bleeding is substantial. Anticoagulant treatment is associated with reduced risk of both outcomes.
Optics-guided Robotic System for Dental Implant Surgery
Authors: Yan Biao , Zhang Wenlong , Cai Lijing , Zheng Lingxiang , Bao Kaiyang , Rao Yuming , Yang Lin , Ye Weitao , Guan Peifeng , Yang Wei , Li Jiang , Yang Rongqian
Published: May 2022

At present, dental implant surgery mainly relies on the clinical experience of the doctor and the assistance of preoperative medical imaging. However, there are some problems in dental implant surgery, such as narrow space, sight obstruction, inaccurate positioning, and high requirements of doctors' proficiency. Therefore, a dental implant robot system (DIRS) guided by optical navigation is developed in this study, with an x-shaped tool and an irregular pentagonal tracer are designed for spatial registration and needle tip positioning strategy respectively. The coordinate system of each unit in DIRS is unified through system calibration, spatial registration, and needle tip positioning strategy. Then the surgical path is planned on the computed tomography (CT) images in the navigation software before operation. The automatic positioning method and the auxiliary positioning method can be used in the operation to achieve accurate positioning and assist doctors to complete the operation. The errors of spatial registration, needle tip positioning strategy, and the overall accuracy of the system were evaluated respectively, and the results showed that they all met the needs of clinical surgery. This study preliminarily verified the feasibility of the precise positioning method for dental surgery robots and provided certain ideas for subsequent related research.
High-sensitivity C-reactive protein and low-density lipoprotein cholesterol association with incident of cardiovascular events: Isfahan cohort study
Authors: Nafari Amirhossein , Mohammadifard Noushin , Haghighatdoost Fahimeh , Nasirian Shima , Najafian Jamshid , Sadeghi Masoumeh , Roohafza Hamidreza , Sarrafzadegan Nizal
Published: May 2022

Background

There are many studies on high-sensitivity C-reactive protein (hs-CRP) association with cardiovascular disease (CVD); however, just a few studies investigated whether the low-density lipoprotein cholesterol (LDL-C) could participate in hs-CRP prognostic strength. This study aimed to determine the alliance of hs-CRP and LDL-C in different concentrations in occurrence cardiovascular events in the Isfahan Cohort Study (ICS).

Methods

3277 participants aged 35 and above were included in the current analysis. We evaluated the association of elevated hs-CRP levels (≥ 3 mg/dL) and CVD events including myocardial infarction, ischemic heart disease, stroke, CVD, CVD mortality, and all-cause mortality in those with LDL-C ≥ or < 130 mg/dL Cox frailty models was used to determine possible interactions.

Results

In both crude and fully adjusted models, there was no significant interaction between LDL-C and hs-CRP levels with the incidence of MI, stroke, CVD mortality, and all-cause death. Neither elevated LDL-C alone nor elevated CRP alone were associated with the risk of all cardiovascular events and all-cause death. However, participants with elevated concentrations of both hs-CRP and LDL-C had a greater risk of ischemic heart disease (IHD) (hazards ratio (HR) 1.44; 95% CI 1.03–2.02) and CVD (HR 1.36; 95% CI 1.01–1.83) than those with low LDL-C and hs-CRP.

Conclusion

These results indicate that despite a null association between elevated levels of CRP or LDL-C alone and CVD events, concurrent rise in LDL-C and hs-CRP levels is associated with higher risk of IHD and CVD.
Clinical genetic testing in four highly suspected pediatric restrictive cardiomyopathy cases
Authors: Zheng Min , Huang Hong , Zhu Xu , Ho Harvey , Li Liling , Ji Xiaojuan
Published: May 2022

Background

Restrictive cardiomyopathy (RCM) presents a high risk for sudden cardiac death in pediatric patients. Constrictive pericarditis (CP) exhibits a similar clinical presentation to RCM and requires differential diagnosis. While mutations of genes that encode sarcomeric and cytoskeletal proteins may lead to RCM, infection, rather than gene mutation, is the main cause of CP. Genetic testing may be helpful in the clinical diagnosis of RCM.

Methods

In this case series study, we screened for TNNI3, TNNT2, and DES gene mutations that are known to be etiologically linked to RCM in four pediatric patients with suspected RCM.

Results

We identified one novel heterozygous mutation, c.517C>T (substitution, position 517 C → T) (amino acid conversion, p.Leu173Phe), and two already known heterozygous mutations, c.508C>T (substitution, position 508, C → T) (amino acid conversion, p.Arg170Trp) and c.575G>A (substitution, position 575, G → A) (amino acid conversion, p.Arg192His), in the TNNI3 gene in three of the four patients.

Conclusion

Our findings support the notion that genetic testing may be helpful in the clinical diagnosis of RCM.
Management strategies and outcomes of acute coronary syndrome (ACS) during Covid-19 pandemic
Authors: Zuo Mingliang , Xiang Shoubo , Bhattacharyya Sanjib , Chen Qiuyi , Zeng Jie , Li Chunmei , Deng Yan , Siu Chungwah , Yin Lixue
Published: May 2022

Background

The COVID-19 outbreak represents a significant challenge to international health. Several studies have reported a substantial decrease in the number of patients attending emergency departments with acute coronary syndromes (ACS) and there has been a concomitant rise in early mortality or complications during the COVID-19 pandemic. A modified management system that emphasizes nearby treatment, safety, and protection, alongside a closer and more effective multiple discipline collaborative team was developed by our Chest Pain Center at an early stage of the pandemic. It was therefore necessary to evaluate whether the newly adopted management strategies improved the clinical outcomes of ACS patients in the early stages of the COVID-19 pandemic.

Methods

Patients admitted to our Chest Pain Center from January 25th to April 30th, 2020 based on electronic data in the hospitals ACS registry, were included in the COVID-19 group. Patients admitted during the same period (25 January to 30 April) in 2019 were included in the pre-COVID-19 group. The characteristics and clinical outcomes of the ACS patients in the COVID-19 period group were compared with those of the ACS patients in the pre-COVID-19 group. Multivariate logistic regression analyses were used to identify the risk factors associated with clinical outcomes.

Results

The number of patients presenting to the Chest Pain Center was reduced by 45% (p = 0.01) in the COVID-19 group, a total of 223 ACS patients were included in the analysis. There was a longer average delay from the onset of symptom to first medical contact (FMC) (1176.9 min vs. 625.2 min, p = 0.001) in the COVID-19 period group compared to the pre-COVID-19 group. Moreover, immediate percutaneous coronary intervention (PCI) (80.1% vs. 92.3%, p = 0.008) was performed less frequently on ACS patients in the COVID-19 group compared to the pre-COVID-19 group. However, more ACS patients received thrombolytic therapy (5.8% vs. 0.6%, p = 0.0052) in the COVID-19 group than observed in the pre-COVID-19 group. Interestingly, clinical outcome did not worsen in the COVID-19 group when cardiogenic shock, sustained ventricular tachycardia, ventricular fibrillation or use of mechanical circulatory support (MCS) were compared against the pre-COVID-19 group (13.5% vs. 11.6%, p = 0.55). Only age was independently associated with composite clinical outcomes (HR = 1.3; 95% CI 1.12–1.50, p = 0.003).

Conclusion

This retrospective study showed that the adverse outcomes were not different during the COVID-19 pandemic compared to historical control data, suggesting that newly adopted management strategies might provide optimal care for ACS patients. Larger sample sizes and longer follow-up periods on this issue are needed in the future.
Comment on “Bayesian additional evidence for decision making under small sample uncertainty”
Authors: Pawel Samuel , Held Leonhard , Matthews Robert
Published: May 2022

We examine the concept of Bayesian Additional Evidence (BAE) recently proposed by Sondhi et al. We derive simple closed-form expressions for BAE and compare its properties with other methods for assessing findings in the light of new evidence. We find that while BAE is easy to apply, it lacks both a compelling rationale and clarity of use needed for reliable decision-making.
The association between fear of malpractice and burnout among Chinese medical workers: The mediating role of legal consciousness
Authors: Liang Fei , Hu Shu , Guo Youqi
Published: May 2022

Background

As a major reason for defensive medicine, the status and effect of “fear of malpractice” among Chinese medical staff is an important topic that needs to be studied. Our study investigated fear of malpractice among Chinese medical workers, assessed its association with burnout, and explored the mediating role of legal consciousness between these factors.

Design

A quantitative, cross-sectional study.

Setting

All respondents were investigated using a self-report questionnaire. Demographic characteristics and measurements including a fear of malpractice scale, and a burnout and legal consciousness scale were employed. The effect of fear of malpractice on burnout was examined by carrying out a binary regression analysis. A mediation model was used to test the mediating role of legal consciousness.

Participants

The study sample included 1031 doctors and nurses (297 male and 734 female; age = 36.3 ± 8.98).

Results

The average score of fear of malpractice was 20.97 ± 5.34. Respondents with higher levels of fear of malpractice were more prone to burnout ([OR] = 2.865; 95% CI 1.942–4.226). Legal consciousness partially and negatively mediated the effect of fear of malpractice on burnout.

Conclusion

High levels of fear of malpractice were found among Chinese medical workers, and this fear had a significant effect on burnout. Legal consciousness may be a resource that can alleviate burnout.
Influenza vaccination coverage of professionals working in nursing homes in France and related determinants, 2018–2019 season: a cross-sectional survey
Authors: Vaux Sophie , Fonteneau Laure , Venier Anne-Gaëlle , Gautier Arnaud , Soing Altrach Sophan , Parneix Pierre , Lévy-Bruhl Daniel
Published: May 2022

Background

The burden of influenza morbidity and mortality in nursing homes (NH) is high. Vaccination of residents and professionals working in NH is the main prevention strategy. Despite recommendations, vaccination coverage among professionals is generally low.

Methods

We performed a nationwide cross-sectional survey of NH using a single-stage stratified random sampling design to estimate influenza vaccination coverage in NH healthcare workers (HCW) and non-medical professionals in France during the 2018–2019 season, and to identify measures likely to increase it. For each NH, a questionnaire was completed with aggregated data by one member of the management team. A multivariate analysis was performed using a negative binomial regression.

Results

Five-hundred and eighty nine NH filled in the study questionnaire (response rate: 49.5%). When considering all professionals (i.e., HCW and non-medical professionals), overall vaccination coverage was 30.6% (95%CI [28.2–33.0], range: 1.6–96.2). Overall influenza vaccination coverage in HCW was 31.9% [29.7–34.1]. It varied according to occupational category: 75.5% [69.3–81.7] for physicians, 42.9% [39.4–46.4] for nurses, 26.7% [24.5–29.0] for nursing assistants, and 34.0% [30.1–38.0] for other paramedical personnel. Vaccination coverage was higher i) in private nursing homes (RRa: 1.3, [1.1–1.5]), ii) in small nursing homes (0.9 [0.8–0.9]), iii) when vaccination was offered free of charge (1.4, [1.1–1.8]), iv) when vaccination promotion for professionals included individual (1.6 [1.1–2.1]) or collective (1.3 [1.1–1.5]) information sessions, videos or games (1.4 [1.2–1.6], v) when information on influenza vaccines was provided (1.2 [1.0–1.3], and finally, vi) when a vaccination point of contact—defined as an HCW who could provide reliable information on vaccination—was nominated within the nursing home (1.7 [1.3–2.2]).

Conclusions

Urgent and innovative actions are required to increase coverage in HCW. Vaccination programmes should include free on-site vaccination and education campaigns, and particularly target nursing assistants. The results of this nationwide study provide keys for improving influenza vaccination coverage in HCW. Programmes should ensure that information on influenza vaccines is provided by a vaccination point of contact in NH using attractive media. Combining the different prevention measures proposed could increase coverage in NH nationwide by over 50%.
High-resolution computed tomography features of asbestosis versus fibrotic hypersensitivity pneumonitis: an observational study
Authors: Ma Ruimin , Li Shuang , Wang Yuanying , Yang Shuqiao , Bao Na , Ye Qiao
Published: May 2022

Background

Asbestosis and fibrotic hypersensitivity pneumonitis (FHP) share the pathogenetic mechanisms induced bronchiolocentric fibrotic process secondary to inhalation exposure. Under the occupational and environmental mixed exposures, asbestosis and FHP are needed to make the differential diagnoses on high-resolution computed tomography (HRCT), especially in the countries still using asbestos. The study aimed to analyze the HRCT features of asbestosis versus FHP.

Methods

The patients with asbestosis or with HP were sequentially recruited in this comparative study at Beijing Chaoyang Hospital between January 2006 and December 2016. Patients’ clinical data were obtained from a predesigned charts. The international classification of HRCT for occupational and environmental respiratory diseases was used to categorize chest imaging findings in patients. The calculation of test statistics was used to compare the imaging features of asbestosis and FHP.

Results

341 patients with asbestosis and 158 patients with HP were sequentially recruited, among which 204 patients with asbestosis and 74 patients with FHP were eligible for data analysis. Patients with asbestosis were older and had a longer latent period until disease manifestation than those with FHP. Asbestosis was characterized by irregular and/or linear opacities, with lower lung preponderance, accompanied by ground-glass opacities and mosaic attenuation. Notably, 98.5% of patients with asbestosis showed benign pleural abnormalities, and 39.7% of these patients had diffuse pleural thickening with parenchymal bands and/or rounded atelectasis. Abnormalities of the mediastinal and diaphragmatic pleura were observed only in cases of asbestosis, and this finding showed high specificity for the diagnosis for asbestosis compared with that for FHP. Subpleural dots or diaphragmatic pleural abnormalities showed moderate sensitivity and high specificity for diagnosis of asbestosis compared with that for FHP. Interobserver reliability was good for evaluation of imaging findings including honeycombing, pleural calcification, lymphadenectasis, and lymph node calcification.

Conclusions

HRCT-based imaging findings can distinguish between asbestosis and FHP to a certain extent, particularly with regard to subpleural dots and diaphragmatic pleural abnormalities that characterize the former.
Measurement properties, interpretability and feasibility of instruments measuring oral health and orofacial pain in dependent adults: a systematic review
Authors: BaHammam Fahad A. , McCracken Giles I. , Wassall Rebecca , Durham Justin , Abdulmohsen Bana
Published: May 2022

Background

Dependent adults have been shown to have a greater experience of oral health deterioration and orofacial pain. This is partly because their non-dental caregivers may not easily identify oral health problems and orofacial pain experienced by them. Thus, this systematic review aimed to investigate measurement properties, interpretability and feasibility of instruments assessing oral health and orofacial pain in dependent adults, which can be used by the non-dental caregivers to establish oral care plans for those who are dependent upon them.

Methods

Seven bibliographic databases were searched: MEDLINE, Embase, CINAHL, CENTRAL, HTA, OATD and OpenGrey. Citations and reference lists of the included studies were also manually searched. Two authors independently screened titles and abstracts, and then full texts. A quality assessment of included studies was conducted independently by two authors using the COSMIN Risk of Bias checklist. The best evidence synthesis method was used to synthesise results from different studies for each measurement property per measurement instrument by integrating the overall rating for each measurement property per measurement instrument with its quality level of evidence.

Results

Nineteen eligible studies were included, which reported the development, measurement properties’ evaluation, interpretability and feasibility of nine oral health and three orofacial pain measurement instruments. Methodological quality of the included studies ranged from very good to inadequate. None of the identified measurement instruments has been adequately and comprehensively tested.

Conclusions

While several measurement instruments were identified in this systematic review, more evidence is needed to be able to more comprehensively evaluate these instruments. Among those identified, the OPS-NVI demonstrated sufficient construct validity, while the OHAT and the THROAT demonstrated sufficient reliability. These instruments therefore have potential for future use with more confidence once other measurement properties, interpretability and feasibility have been sufficiently tested and evaluated.
Minimum accepted competency examination: test item analysis
Authors: McCrossan Paddy , Nicholson Alf , McCallion Naomi
Published: May 2022

Background

To ascertain if undergraduate medical students attain adequate knowledge to practice in paediatrics, we designed the minimum accepted competency (MAC) examination. This was a set of MCQ’s designed to test the most basic, ‘must know’ knowledge as determined by non-faculty paediatric clinicians. Only two-thirds of undergraduate students passed this exam, despite 96% of the same cohort passing their official university paediatric examination.

We aim to describe the psychometric properties of the MAC examination to explore why there was a difference in student performance between these two assessments which should, in theory, be testing the same subject area. We will also investigate if the MAC examination is a potentially reliable method of assessing undergraduate knowledge.

Methods

The MAC examination was sat by three groups of undergraduate medical students and paediatric trainee doctors. Test item analysis was performed using facility index, discrimination index and Cronbach’s alpha.

Results

Test item difficulty on the MAC between each group was positively correlated. Correlation of item difficulty with the standard set for each item showed a statistically significant positive relationship. However, for 10 of the items, the mean score achieved by the candidates did not even reach two standard deviations below the standard set by the faculty. Medical students outperformed the trainee doctors on three items. 18 of 30 items achieved a discrimination index > 0.2. Cronbach’s alpha ranged from 0.22–0.59.

Conclusion

Despite faculty correctly judging that this would be a difficult paper for the candidates, there were a significant number of items on which students performed particularly badly. It is possible that the clinical emphasis in these non-faculty derived questions was juxtaposed with the factual recall often required for university examinations.

The MAC examination highlights the difference in the level of knowledge expected of a junior doctor starting work in paediatrics between faculty and non-faculty clinicians and can identify gaps between the current curriculum and the ‘hidden curriculum’ required for real world clinical practice. The faculty comprises physicians in employment by the University whose role it is to design the paediatric curriculum and deliver teaching to undergraduate students. Non-faculty clinicians are paediatric physicians who work soley as clinicians with no affiliation to an educational institution.

The concept of a MAC examination to test basic medical knowledge is feasible and the study presented is an encouraging first step towards this method of assessment.
The experience of pre-hospital emergency personnel in breaking death news: a phenomenological study
Authors: Safari Reza , Khashmin Mohammad Mehdi , Abdi Alireza
Published: May 2022

Background

Today, breaking the death of patients to their families has become one of the challenges for medical staff. Considering the lack of study in the pre-hospital emergency, the present study aimed to explore the experience of pre-hospital emergency personnel regarding the breaking death news to families.

Method

In this qualitative study with a descriptive phenomenological method, data were collected by purposeful sampling method through in-depth interviews with thirteen pre-hospital emergency personnel in Kermanshah and Kurdistan provinces. After recording and writing the interviews, the data were managed by MAQUDA-10 software and analyzed using the Collaizi approach.

Results

Of 13 participants, five from Kermanshah, eight from Kurdistan, and 12 (92%) were married. The mean age and work experience were 34.38 and 10.38 years, respectively. Five main extracted themes were 1) perceived stress, 2) challenge factors of breaking death news, 3) unnecessary actions, 4) death breaking precautions, and 5) BDN requirements. They were covered fifteen sub-themes.

Conclusion

In this study, emergency medical employees were always faced with stress and challenges to announce the patient's death to families, including the stress of violence against employees. Hereof, personnel had to take unnecessary care actions such as slow resuscitation to transfer the patient to the hospital.
Improved hypertension control at six months using an adapted WHO HEARTS-based implementation strategy at a large urban HIV clinic in Uganda
Authors: Muddu Martin , Semitala Fred C. , Kimera Isaac , Mbuliro Mary , Ssennyonjo Rebecca , Kigozi Simon P. , Katwesigye Rodgers , Ayebare Florence , Namugenyi Christabellah , Mugabe Frank , Mutungi Gerald , Longenecker Chris T. , Katahoire Anne R. , Ssinabulya Isaac , Schwartz Jeremy I.
Published: May 2022

Objectives

To adapt a World Health Organization HEARTS-based implementation strategy for hypertension (HTN) control at a large urban HIV clinic in Uganda and determine six-month HTN and HIV outcomes among a cohort of adult persons living with HIV (PLHIV).

Methods

Our implementation strategy included six elements: health education, medication adherence, and lifestyle counseling; routine HTN screening; task shifting of HTN treatment; evidence-based HTN treatment protocol; consistent supply of HTN medicines free to patients; and inclusion of HTN-specific monitoring and evaluation tools. We conducted a pre-post study from October 2019 to March 2020 to determine the effect of this strategy on HTN and HIV outcomes at baseline and six months. Our cohort comprised adult PLHIV diagnosed with HTN who made at least one clinic visit within two months prior to study onset.

Findings

We enrolled 1,015 hypertensive PLHIV. The mean age was 50.1 ± 9.5 years and 62.6% were female. HTN outcomes improved between baseline and six months: mean systolic BP (154.3 ± 20.0 to 132.3 ± 13.8 mmHg,p < 0.001); mean diastolic BP (97.7 ± 13.1 to 85.3 ± 9.5 mmHg,p < 0.001) and proportion of patients with controlled HTN (9.3% to 74.1%,p < 0.001). The HTN care cascade also improved: treatment initiation (13.4% to 100%), retention in care (16.2% to 98.5%), monitoring (16.2% to 98.5%), and BP control among those initiated on HTN treatment (2.2% to 75.2%). HIV cascade steps remained high (> 95% at baseline and six months) and viral suppression was unchanged (98.7% to 99.2%,p = 0.712). Taking ART for more than two years and HIV viral suppression were independent predictors of HTN control at six months.

Conclusions

A HEARTS-based implementation strategy at a large, urban HIV center facilitates integration of HTN and HIV care and improves HTN outcomes while sustaining HIV control. Further implementation research is needed to study HTN/HIV integration in varied clinical settings among diverse populations.
Role of EZH2-mediated H3K27me3 in placental ADAM12-S expression: implications for fetoplacental growth
Authors: Zhu Ya-nan , Gan Xiao-wen , Pan Fan , Ni Xiao-tian , Myatt Leslie , Wang Wang-sheng , Sun Kang
Published: May 2022

Background

Enhancer of zeste homolog 2 (EZH2)-mediated histone 3 lysine 27 trimethylation (H3K27me3) is a transcription silencing mark, which is indispensable for cell lineage specification at the early blastocyst stage. This epigenetic repression is maintained in placental cytotrophoblasts but is lifted when cytotrophoblasts differentiate into syncytiotrophoblasts. However, the physiological impact of this lift remains elusive. Here, we investigated whether lifting EZH2-mediated H3K27me3 during syncytialization upregulates the expression of a short secretory isoform of a disintegrin and metalloprotease 12 (ADAM12-S), a well-recognized placenta-derived protease that cleaves insulin-like growth factor binding protein 3 to increase insulin-like growth factor (IGF) bioavailability for the stimulation of fetoplacental growth. The transcription factor and the upstream signal involved were also explored.

Methods

Human placenta tissue and cultured primary human placental cytotrophoblasts were utilized to investigate the role of EZH2-mediated H3K27me3 in ADAM12-S expression and the associated transcription factor and upstream signal during syncytialization. A mouse model was used to examine whether inhibition of EZH2-mediated H3K27me3 regulates placental ADAM12-S expression and fetoplacental growth.

Results

EZH2 and ADAM12 are distributed primarily in villous cytotrophoblasts and syncytiotrophoblasts, respectively. Increased ADAM12-S expression, decreased EZH2 expression, and decreased EZH2/H3K27me3 enrichment at the ADAM12 promoter were observed during syncytialization. Knock-down of EZH2 further increased ADAM12-S expression in trophoblasts. Syncytialization was also accompanied by increased STAT5B expression and phosphorylation as well as its enrichment at the ADAM12 promoter. Knock-down of STAT5B attenuated ADAM12-S expression during syncytialization. Epidermal growth factor (EGF) was capable of inducing ADAM12-S expression via stimulation of STAT5B expression and phosphorylation during syncytialization. Mouse studies revealed that administration of an EZH2 inhibitor significantly increased ADAM12-S levels in maternal blood and fetoplacental weights along with decreased H3K27me3 abundance and increased ADAM12-S expression in the placenta.

Conclusions

Lifting EZH2-mediated H3K27me3 increases ADAM12-S expression during syncytialization with the participation of EGF-activated STAT5B, which may lead to elevation of ADAM12-S level in maternal blood resulting in increased IGF bioavailability for the stimulation of fetoplacental growth in pregnancy. Our studies suggest that the role of EZH2-mediated H3K27me3 may switch from cell lineage specification at the early blastocyst stage to regulation of fetoplacental growth in later gestation.
Signals of increasing co-use of stimulants and opioids from online drug forum data
Authors: Sarker Abeed , Al-Garadi Mohammed Ali , Ge Yao , Nataraj Nisha , Jones Christopher M. , Sumner Steven A.
Published: May 2022

Background

Despite recent rises in fatal overdoses involving multiple substances, there is a paucity of knowledge about stimulant co-use patterns among people who use opioids (PWUO) or people being treated with medications for opioid use disorder (PTMOUD). A better understanding of the timing and patterns in stimulant co-use among PWUO based on mentions of these substances on social media can help inform prevention programs, policy, and future research directions. This study examines stimulant co-mention trends among PWUO/PTMOUD on social media over multiple years.

Methods

We collected publicly available data from 14 forums on Reddit (subreddits) that focused on prescription and illicit opioids, and medications for opioid use disorder (MOUD). Collected data ranged from 2011 to 2020, and we also collected timelines comprising past posts from a sample of Reddit users (Redditors) on these forums. We applied natural language processing to generate lexical variants of all included prescription and illicit opioids and stimulants and detect mentions of them on the chosen subreddits. Finally, we analyzed and described trends and patterns in co-mentions.

Results

Posts collected for 13,812 Redditors showed that 12,306 (89.1%) mentioned at least 1 opioid, opioid-related medication, or stimulant. Analyses revealed that the number and proportion of Redditors mentioning both opioids and/or opioid-related medications and stimulants steadily increased over time. Relative rates of co-mentions by the same Redditor of heroin and methamphetamine, the substances most commonly co-mentioned, decreased in recent years, while co-mentions of both fentanyl and MOUD with methamphetamine increased.

Conclusion

Our analyses reflect increasing mentions of stimulants, particularly methamphetamine, among PWUO/PTMOUD, which closely resembles the growth in overdose deaths involving both opioids and stimulants. These findings are consistent with recent reports suggesting increasing stimulant use among people receiving treatment for opioid use disorder. These data offer insights on emerging trends in the overdose epidemic and underscore the importance of scaling efforts to address co-occurring opioid and stimulant use including harm reduction and comprehensive healthcare access spanning mental-health services and substance use disorder treatment.
Problems undermining the health-related quality of life of people living with HIV in Spain: a qualitative study to inform the development of a novel clinic screening tool
Authors: Safreed-Harmon Kelly , Fuster-RuizdeApodaca Maria J. , Pastor de la Cal Marta , Lazarus Jeffrey V.
Published: May 2022

Background

In settings with high antiretroviral therapy coverage, numerous health-related issues continue to undermine the health and health-related quality of life (HRQoL) of people living with HIV (PLHIV). As part of a larger study to develop and validate a new patient-reported outcome measure for use in HIV clinical care in Spain, we sought to identify the most burdensome health-related issues experienced by PLHIV in order to determine which issues should be addressed in the new instrument.

Methods

We conducted a literature review and a qualitative study based on four focus group discussions (FGDs) with key informants in Spain. Participants were selected via purposive sampling. Two FGDs convened 16 expert HIV service providers, and two convened 15 PLHIV with diverse epidemiological profiles. FGDs followed semi-structured interview scripts and incorporated an exercise to prioritise the most critical health-related issues among those named in the discussions. Content analysis was conducted using MAXQDA 12.

Results

The analysis of FGD data identified several broad categories of issues that were perceived to negatively affect PLHIV. The most frequently named issues fell within the categories of social problems; physical symptoms; psychological problems; and sexuality-related problems. Regarding social problems, stigma/discrimination was by far the issue raised the most frequently. In the prioritisation exercise, stigma/discrimination was also ranked as the most burdensome issue by both service providers and PLHIV. Within the physical symptoms category, the issues named most frequently were sleep-related problems, fatigue, physical pain and body fat changes. Regarding psychological problems, FGD participants most commonly spoke of emotional distress in general terms, and also called attention to depression and anxiety. In the prioritisation exercise, both service providers and PLHIV ranked psychological well-being as the second-most important issue following stigma. Sexuality-related problems that were reported included sexually transmitted infections, hormonal problems, lack of libido, and general sexual dissatisfaction.

Conclusions

PLHIV are negatively affected by a wide range of health-related issues. HIV-related stigma and psychological well-being remain major challenges. Identifying and addressing these and other issues in routine clinical care supports healthy aging and may ultimately contribute to better health and HRQoL outcomes in this population.
Postmortem gene expression profiles in the habenulae of suicides: implication of endothelial dysfunction in the neurovascular system
Authors: Kim Hyun Jung , Yoo Hyeijung , Kim Ji Yeon , Yang Soo Hyun , Lee Hyun Woo , Lee Heon-Jeong , Son Gi Hoon , Kim Hyun
Published: May 2022

The habenula (Hb) is an epithalamic structure that links multiple forebrain areas with the mid/hindbrain monoaminergic systems. As an anti-reward center, it has been implicated in the etiology of various neuropsychiatric disorders, particularly those associated with dysregulated reward circuitry. In this regard, Hb has been proposed as a therapeutic target for treatment-resistant depression associated with a higher risk of suicide. Therefore, we aimed to gain insight into the molecular signatures of the Hb in association with suicide in individuals with major depression. Postmortem gene expression analysis identified 251 differentially expressed genes (DEGs) in the Hb tissue of suicides in comparison with Hb tissues from neurotypical individuals. Subsequent bioinformatic analyses using single-cell transcriptome data from the mouse Hb showed that the levels of a subset of endothelial cell-enriched genes encoding cell–cell junctional complex and plasma membrane-associated proteins, as well as the levels of their putative upstream transcriptional regulators, were significantly affected in suicides. Although our findings are based on a limited number of samples, the present study suggests a potential association of endothelial dysfunction in the Hb with depression and suicidal behavior.
Diagnostic utility of a conventional MRI-based analysis and texture analysis for discriminating between ovarian thecoma-fibroma groups and ovarian granulosa cell tumors
Authors: Nagawa Keita , Kishigami Tomoki , Yokoyama Fumitaka , Murakami Sho , Yasugi Toshiharu , Takaki Yasunobu , Inoue Kaiji , Tsuchihashi Saki , Seki Satoshi , Okada Yoshitaka , Baba Yasutaka , Hasegawa Kosei , Yasuda Masanori , Kozawa Eito
Published: May 2022

Objective

To evaluate the diagnostic utility of conventional magnetic resonance imaging (MRI)-based characteristics and a texture analysis (TA) for discriminating between ovarian thecoma-fibroma groups (OTFGs) and ovarian granulosa cell tumors (OGCTs).

Methods

This retrospective multicenter study enrolled 52 patients with 32 OGCTs and 21 OTFGs, which were dissected and pathologically diagnosed between January 2008 and December 2019.

MRI-based features (MBFs) and texture features (TFs) were evaluated and compared between OTFGs and OGCTs. A least absolute shrinkage and selection operator (LASSO) regression analysis was performed to select features and construct the discriminating model. ROC analyses were conducted on MBFs, TFs, and their combination to discriminate between the two diseases.

Results

We selected 3 features with the highest absolute value of the LASSO regression coefficient for each model: the apparent diffusion coefficient (ADC), peripheral cystic area, and contrast enhancement in the venous phase (VCE) for the MRI-based model; the 10th percentile, difference variance, and maximal correlation coefficient for the TA-based model; and ADC, VCE, and the difference variance for the combination model. The areas under the curves of the constructed models were 0.938, 0.817, and 0.941, respectively. The diagnostic performance of the MRI-based and combination models was similar (p = 0.38), but significantly better than that of the TA-based model (p < 0.05).

Conclusions

The conventional MRI-based analysis has potential as a method to differentiate OTFGs from OGCTs. TA did not appear to be of any additional benefit. Further studies are needed on the use of these methods for a preoperative differential diagnosis of these two diseases.
Physics-informed neural networks approach for 1D and 2D Gray-Scott systems
Authors: Giampaolo Fabio , De Rosa Mariapia , Qi Pian , Izzo Stefano , Cuomo Salvatore
Published: May 2022

Nowadays, in the Scientific Machine Learning (SML) research field, the traditional machine learning (ML) tools and scientific computing approaches are fruitfully intersected for solving problems modelled by Partial Differential Equations (PDEs) in science and engineering applications. Challenging SML methodologies are the new computational paradigms named Physics-Informed Neural Networks (PINNs). PINN has revolutionized the classical adoption of ML in scientific computing, representing a novel class of promising algorithms where the learning process is constrained to satisfy known physical laws described by differential equations. In this paper, we propose a PINN-based computational study to deal with a non-linear partial differential equations system. In particular, using this approach, we solve the Gray-Scott model, a reaction–diffusion system that involves an irreversible chemical reaction between two reactants. In the unstable region of the model, we consider some a priori information related to dynamical behaviors, i. e. a supervised approach that relies on a finite difference method (FDM). Finally, simulation results show that PINNs can successfully provide an approximated Grey-Scott system solution, reproducing the characteristic Turing patterns for different parameter configurations.
Bone morphogenetic protein 2 is a new molecular target linked to non-alcoholic fatty liver disease with potential value as non-invasive screening tool
Authors: Marañón Patricia , Fernández-García Carlos Ernesto , Isaza Stephania C. , Rey Esther , Gallego-Durán Rocío , Montero-Vallejo Rocío , de Cía Javier Rodríguez , Ampuero Javier , Romero-Gómez Manuel , García-Monzón Carmelo , González-Rodríguez Águeda
Published: May 2022

Background

Non-alcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease worldwide, being non-alcoholic steatohepatitis (NASH) its most clinically relevant form. Given the risks associated with taking a liver biopsy, the design of accurate non-invasive methods to identify NASH patients is of upmost importance. BMP2 plays a key role in metabolic homeostasis; however, little is known about its involvement in NAFLD onset and progression. This study aimed to elucidate the impact of BMP2 in NAFLD pathophysiology.

Methods

Hepatic and circulating levels of BMP2 were quantified in serum and liver specimens from 115 biopsy-proven NAFLD patients and 75 subjects with histologically normal liver (NL). In addition, BMP2 content and release was determined in cultured human hepatocytes upon palmitic acid (PA) overload.

Results

We found that BMP2 expression was abnormally increased in livers from NAFLD patients than in subjects with NL and this was reflected in higher serum BMP2 levels. Notably, we observed that PA upregulated BMP2 expression and secretion by human hepatocytes. An algorithm based on serum BMP2 levels and clinically relevant variables to NAFLD showed an AUROC of 0.886 (95%CI, 0.83–0.94) to discriminate NASH. We used this algorithm to develop SAN (Screening Algorithm for NASH): a SAN < 0.2 implied a low risk and a SAN ≥ 0.6 indicated high risk of NASH diagnosis.

Conclusion

This proof-of-concept study shows BMP2 as a new molecular target linked to NAFLD and introduces SAN as a simple and efficient algorithm to screen individuals at risk for NASH.
Organic phosphorus leaching risk from agricultural soils across China
Authors: Sun Xiaolei , Bol Roland , Klumpp Erwin , Li Meng
Published: May 2022

Background

Leaching from agricultural land is one of the major pathways of phosphorus (P) loss from soils to waterbody and may induce adverse effect on territorial environment. Past studies usually focused on the loss of inorganic P (PI) while ignored the role of organic P (PO) in leaching process. A total of 63 agricultural soil samples were collected from across China with various soil types including 21 paddy soils, 13 chernozems, 11 red soils and other type soils (n = 18) to identify the potential risk of PO and PI leaching from agricultural lands and to explore their relationships with soil basic properties, Fe/Al oxides, and P status.

Results

CaCl2-extractable organic P (CaCl2-PO) accounted for 8–89% (35% on average) of CaCl2-extractable total P (CaCl2-PT) and available organic P (APO) accounted to over half of available total P (APT) (57 ± 25%). CaCl2-PT was positively correlated with APT under all soil types except paddy soils. CaCl2-extractable inorganic P (CaCl2-PI) and available inorganic P (API) were strongly correlated for chernozem (r = 0.968), while CaCl2-PO the was strongly correlated with APO for red soils (r = 0.901).

Conclusions

PO greatly contributed to the potential P leaching risk and should be included in the risk assessment of total P leaching. The control of soil APT excess accumulation in both PO and PI fractions in agricultural land is the key point to cut down P leaching. Mitigation measures to limit PO leaching should be established based on the soil types.

Graphical abstract
Electroactive nano-Biohybrid actuator composed of gold nanoparticle-embedded muscle bundle on molybdenum disulfide nanosheet-modified electrode for motion enhancement of biohybrid robot
Authors: Shin Minkyu , Choi Jin-Ha , Lim Joungpyo , Cho Sungwoo , Ha Taehyeong , Jeong Jae Hyun , Choi Jeong-Woo
Published: May 2022

There have been several trials to develop the bioactuator using skeletal muscle cells for controllable biobybird robot. However, due to the weak contraction force of muscle cells, the muscle cells could not be used for practical applications such as biorobotic hand for carrying objects, and actuator of biohybrid robot for toxicity test and drug screening. Based on reported hyaluronic acid-modified gold nanoparticles (HA@GNPs)-embedded muscle bundle on PDMS substrate, in this study for augmented actuation, we developed the electroactive nano-biohybrid actuator composed of the HA@GNP-embedded muscle bundle and molybdenum disulfide nanosheet (MoS2 NS)-modified electrode to enhance the motion performance. The MoS2 NS-modified Au-coated polyimide (PI) electrode to be worked in mild pH condition for viable muscle cell was utilized as supporting- and motion enhancing- substrate since it was electrochemically active, which caused the movement of flexible PI electrode. The motion performance of this electroactive nano-biohybrid actuator by electrical stimulation was increased about 3.18 times compared with that of only HA@GNPs embedded-muscle bundle on bare PI substrate. The proposed electroactive nano-biohybrid actuator can be applied to the biorobotic hand and biohybrid robot.
A social cognitive perspective on gender disparities in self-efficacy, interest, and aspirations in science, technology, engineering, and mathematics (STEM): the influence of cultural and gender norms
Authors: Chan Randolph C. H.
Published: May 2022

Background

The underrepresentation of women in science, technology, engineering, and mathematics (STEM) fields is well documented in developed countries, and yet public discussion of gender disparities in STEM in China is still in its nascent stage. Endorsement of traditional gender role beliefs and conformity to social norms are pertinent to Chinese culture, which may even exacerbate the gender disparities in STEM engagement. Grounded in social cognitive career theory, the present study drew on a national sample of secondary school students (N = 3020) in China to estimate gender disparities in self-efficacy, interest, and aspirations in STEM and examine how cultural and gender norms influence STEM engagement.

Results

The proposed sequential mediation model was supported, in which girls were more likely to show lower levels of self-efficacy than boys; this was associated with lower interest in STEM and lower motivation to pursue STEM careers. The results also supported the moderating effect of traditional gender role beliefs and found that gender differences in self-efficacy, interest, and aspirations in STEM were more apparent among students who strongly endorsed stereotypical views of male and female roles.

Conclusions

The findings provide important implications for efforts to improve girls’ access to STEM education through curriculum enrichment and out-of-school time programs to bridge the gender gap in STEM. Access to female role models and gender-responsive pedagogy is also essential to boost girls’ self-efficacy in STEM and eradicate traditional gender role beliefs among all students.
Subcellular localization of fungal specialized metabolites
Authors: Skellam Elizabeth
Published: May 2022

Fungal specialized metabolites play an important role in the environment and have impacted human health and survival significantly. These specialized metabolites are often the end product of a series of sequential and collaborating biosynthetic enzymes that reside within different subcellular compartments. A wide variety of methods have been developed to understand fungal specialized metabolite biosynthesis in terms of the chemical conversions and the biosynthetic enzymes required, however there are far fewer studies elucidating the compartmentalization of the same enzymes. This review illustrates the biosynthesis of specialized metabolites where the localization of all, or some, of the biosynthetic enzymes have been determined and describes the methods used to identify the sub-cellular localization.