bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of artificial intelligence in pancreaticobiliary diseases
Authors: Goyal Hemant , Mann Rupinder , Gandhi Zainab , Perisetti Abhilash , Zhang Zhongheng , Sharma Neil , Saligram Shreyas , Inamdar Sumant , Tharian Benjamin
Published: February 2021

The role of artificial intelligence and its applications has been increasing at a rapid pace in the field of gastroenterology. The application of artificial intelligence in gastroenterology ranges from colon cancer screening and characterization of dysplastic and neoplastic polyps to the endoscopic ultrasonographic evaluation of pancreatic diseases. Artificial intelligence has been found to be useful in the evaluation and enhancement of the quality measure for endoscopic retrograde cholangiopancreatography. Similarly, artificial intelligence techniques like artificial neural networks and faster region-based convolution network are showing promising results in early and accurate diagnosis of pancreatic cancer and its differentiation from chronic pancreatitis. Other artificial intelligence techniques like radiomics-based computer-aided diagnosis systems could help to differentiate between various types of cystic pancreatic lesions. Artificial intelligence and computer-aided systems also showing promising results in the diagnosis of cholangiocarcinoma and the prediction of choledocholithiasis. In this review, we discuss the role of artificial intelligence in establishing diagnosis, prognosis, predicting response to treatment, and guiding therapeutics in the pancreaticobiliary system.
A novel LUMNAqSoP approach for prioritising groundwater monitoring stations for implementation of the Nitrates Directive
Authors: Ondrasek G. , Bakić Begić H. , Romić D. , Brkić Ž. , Husnjak S. , Bubalo Kovačić M.
Published: February 2021

Background

The Nitrates Directive (ND) is an EU anti-pollution legislative that, for almost 30 years, has controlled and protected hydro-resources against excessive levels of nitrates originating from agroecosystems, striving to prevent the further exacerbation of the nitrates in aquatic environments. ND sets several principal goals that member states must accomplish, such as performing spatiotemporal nitrate analyses in ground/surface water networks to achieve national water quality monitoring programme.

Results

In this study, using the novel LUMNAqSoP approach, the prioritisation of 151 candidate groundwater stations for ND monitoring in Croatia was performed. The LUMNAqSoP integratively evaluates: (i) the most dominant loads from the agroecosystem (land use and management, net nitrogen application) and (ii) environmental (aquifer and soil) vulnerabilities and sensitivities of groundwater resources to nitrate pollution. By comparing stations which scored the most agro-environmental loads vs. the data from water stations containing elevated mean nitrate concentrations (from existing monitoring programmes) a very good agreement was confirmed. Moreover, deviations close to large urban zones were detected, suggesting that elevated nitrates in groundwaters in those areas likely originated from municipal/industrial rather than agricultural sources; however, further studies are needed for elucidation.

Conclusions

The presented approach can serve as a useful tool to policy makers and regulators for: (i) more efficient and reliable establishment of water monitoring programme pursuant to ND, as well as (ii) better management and shaping (designating/derogating) of nitrate-vulnerable zones, especially in diverse environmental conditions and dynamic agroecosystems as have been confirmed in recent decades across the EU member states.
Pineal gland transcriptomic profiling reveals the differential regulation of lncRNA and mRNA related to prolificacy in STH sheep with two FecB genotypes
Authors: Li Chunyan , He Xiaoyun , Zhang Zijun , Ren Chunhuan , Chu Mingxing
Published: February 2021

Background

Long noncoding RNA (lncRNA) has been identified as important regulator in hypothalamic-pituitary-ovarian axis associated with sheep prolificacy. However, little is known of their expression pattern and potential roles in the pineal gland of sheep. Herein, RNA-Seq was used to detect transcriptome expression pattern in pineal gland between follicular phase (FP) and luteal phase (LP) in FecBBB (MM) and FecB++ (ww) STH sheep, respectively, and differentially expressed (DE) lncRNAs and mRNAs associated with reproduction were identified.

Results

Overall, 135 DE lncRNAs and 1360 DE mRNAs in pineal gland between MM and ww sheep were screened. Wherein, 39 DE lncRNAs and 764 DE mRNAs were identified (FP vs LP) in MM sheep, 96 DE lncRNAs and 596 DE mRNAs were identified (FP vs LP) in ww sheep. Moreover, GO and KEGG enrichment analysis indicated that the targets of DE lncRNAs and DE mRNAs were annotated to multiple biological processes such as phototransduction, circadian rhythm, melanogenesis, GSH metabolism and steroid biosynthesis, which directly or indirectly participate in hormone activities to affect sheep reproductive performance. Additionally, co-expression of lncRNAs-mRNAs and the network construction were performed based on correlation analysis, DE lncRNAs can modulate target genes involved in related pathways to affect sheep fecundity. Specifically, XLOC_466330, XLOC_532771, XLOC_028449 targeting RRM2B and GSTK1, XLOC_391199 targeting STMN1, XLOC_503926 targeting RAG2, XLOC_187711 targeting DLG4 were included.

Conclusion

All of these differential lncRNAs and mRNAs expression profiles in pineal gland provide a novel resource for elucidating regulatory mechanism underlying STH sheep prolificacy.
Correction to: Acute cardiovascular events in patients with community acquired pneumonia: results from the observational prospective FADOI-ICECAP study
Authors:   for the FADOI-ICECAP Study Group, Pieralli Filippo , Vannucchi Vieri , Nozzoli Carlo , Augello Giuseppe , Dentali Francesco , De Marzi Giulia , Uomo Generoso , Risaliti Filippo , Morbidoni Laura , Mazzone Antonino , Santini Claudio , Tirotta Daniela , Corradi Francesco , Gerloni Riccardo , Gnerre Paola , Gussoni Gualberto , Valerio Antonella , Campanini Mauro , Manfellotto Dario , Fontanella Andrea
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Intracranial mass lesions and skin discoloration in the armpits as unusual clues to Erdheim-Chester disease: a case report
Authors: Rodrigues Pedro Gustavo Barros , Pereira Isabelle de Sousa , Lima Filho Valter Barbalho , Dias Daniel Aguiar , Nóbrega Paulo Ribeiro , Braga-Neto Pedro
Published: February 2021

Background

Erdheim–Chester disease (ECD) is a non-Langerhans histiocytosis that results in multi-organ disease involving the skin, bones, lungs and kidneys. Central nervous system (CNS) involvement occurs in about 50 % of patients, and diabetes insipidus, visual disturbances, and cerebellar ataxia are the most frequent neurological signs. We report a case of Erdheim-Chester disease with central nervous system involvement in the form of enhancing intracranial mass lesions with massive edema.

Case presentation

The patient presented with vertigo, ataxia, encephalopathy and pyramidal signs. Diagnosis was suggested by xanthomatous skin lesions and a biopsy was compatible with Erdheim-Chester disease demonstrating xanthogranulomas CD68 positive (clone KP1) and CD1a and S100 negative. Testing for BRAF mutation was negative, which precluded treatment with Vemurafenib. Treatment with steroids and interferon resulted in improvement of neurological signs and regression of edema on MRI.

Conclusions

The diagnosis of Erdheim-Chester disease should be considered in intracranial mass lesions. Xanthomatous skin lesions are a clue to the diagnosis.
Sleep quality in women with nausea and vomiting of pregnancy: a cross-sectional study
Authors: Laitinen Linda , Nurmi Miina , Rautava Päivi , Koivisto Mari , Polo-Kantola Päivi
Published: February 2021

Background

Nausea and vomiting of pregnancy (NVP) deteriorates many aspects of daily lives of women. However, little is known about associations between NVP and sleep quality.

Methods

Women attending to routine mid-pregnancy visits in maternity health care clinics in Turku city area and surrounding municipalities, Finland, during 2011–2014, were invited to participate. A cohort of 1203 volunteers (mean age 30 years, mean gestational week 16.6, mean BMI 24.4 kg/m2, nulliparous 46%) was recruited. The severity of NVP in the worst 12-h period of current pregnancy was assessed with Pregnancy Unique Quantification of Emesis Questionnaire (PUQE) and categorized accordingly into no/mild/moderate and severe NVP. Sleep disturbances during the past 3 months were assessed with selected questions (difficulty falling asleep, night awakenings, too early morning awakenings and sleepiness during the day) from Basic Nordic Sleep Questionnaire (BNSQ). In addition, general sleep quality, as well as physical and mental quality of life (QoL) were rated with three visual analog scales (VAS). Associations between PUQE categories (severity of NVP) and sleep disturbances, general sleep quality, physical QoL and mental QoL were evaluated with multinomial regression analysis.

Results

According to PUQE, NVP was most frequently moderate (n = 629, 52.3%), followed by mild (n = 361, 30.0%) and severe (n = 77, 6.4%). Only 11.3% had no NVP (n = 136). The most frequent sleep disturbance was night awakenings (69.9%, n = 837), followed by sleepiness during the day (35.7%, n = 427), too early morning awakenings (12.0%, n = 143) and difficulty falling asleep (7.1%, n = 81). In adjusted analysis (age, parity, body mass index, smoking, employment), more severe NVP was associated with night awakenings (AOR 3.9, 95% CI 1.79–8.47, P < 0.0001) and sleepiness during the day (AOR 4.7, 95% CI 2.20–9.94, P < 0.0001). In VAS, women with more severe NVP rated worse general sleep quality and worse physical and mental QoL. However, in multivariable analysis, the association between the severity of NVP and physical and mental QoL was stronger than that of sleep .

Conclusions

More severe NVP is associated with sleep disturbances and in close relation to lower physical and mental QoL. Thus, in comprehensive care of women with NVP, also sleep quality should be evaluated.
Activation of WNT7b autocrine eases metastasis of colorectal cancer via epithelial to mesenchymal transition and predicts poor prognosis
Authors: Jiang Shuai , Li Qiwen , Liu Yimin , Zhang Huimin , Wang Qianyu , Chen Yu , Shi Xiaoyang , Li Jun , Zhang Hailing , Zhang Yi , Xia Dongqing , Wu Man , Lin Jiajia , Zhang Chenglin , Pang Suhua , Jiang Jiamin , Wen Yan , Zhang Peipei
Published: February 2021

Background

Aberrant activation of the Wnt/β-catenin signaling pathway is one of the most frequent abnormalities in human cancer, including colorectal cancer (CRC). Previous studies revealed pivotal functions of WNT family members in colorectal cancer, as well as their prognostic values. Nevertheless, the prognostic role and mechanisms underlying WNT7b in colorectal cancer development remains unclear.

Methods

In this study, WNT7b expression was measured by immunohistochemical staining of 100 cases of surgically resected human colorectal cancerous tissues as well as matched adjacent normal tissues constructed as tissue microarrays. In vitro studies, we attempted to substantiate the WNT7b expressional pattern previously found in immunohistochemistry staining. We used the colorectal cancer cell-line HCT116 and normal colorectal cell-line FHC for immunofluorescence staining and nuclear/cytoplasmic separated western blotting. We measured epithelial–mesenchymal transition (EMT) markers and migration capacity of HCT116 in the context of WNT7b knocked-down using short interfering RNA. Finally, clinical and prognostic values of WNT7b activation levels were examined.

Results

WNT7b was expressed in the nucleus in adjacent normal tissues. In CRC tissues, nuclear expression of WNT7b was similar; however, membrane and cytoplasmic expression was strikingly enhanced. Consistently, in vitro analysis confirmed the same expression pattern of WNT7b. Compared with FHC cells, HCT116 cells displayed higher levels of WNT7b membrane and cytoplasmic enrichment, as well as higher migration capacity with a sensitized EMT process. Either partial knockdown of WNT7b or blockade of the Wnt/β-catenin signaling pathway reversed EMT process and inhibited the migration of HCT116 cells. Finally, elevated secretion levels of WNT7b were significantly associated with lymphatic and remote metastasis and predicted worse prognosis in the CRC cohort.

Conclusion

In summary, we demonstrated that the activation of WNT7b autocrine probably contributes to CRC metastasis by triggering EMT process through the Wnt/β-catenin signaling pathway. High levels of WNT7b autocrine secretion predicts poor outcome in patients with CRC. This molecule is a promising candidate for clinical CRC treatments.
Suicidality, function and associated negative life events in an adolescent psychiatric population at 3-year follow-up
Authors: Gårdvik Kari Skulstad , Torgersen Terje , Rygg Marite , Lydersen Stian , Indredavik Marit Sæbø
Published: February 2021

Background

We aimed to examine psychosocial function, suicidality and school dropout in a clinical psychiatric population over a 3-year period from adolescence to young adulthood and explore associations with negative life events.

Methods

This study is part of the Health Survey in Department of Children and Youth, St. Olavs hospital, Norway. In the first study visit (T1), 717 (43.5% of eligible) participated, aged 13–18 years (2009–2011), and 3 years later (T2), 570 answered a questionnaire (school functioning and negative life events), and 549 completed Kiddie SADS as telephone interview assessing DSM-IV diagnoses, psychosocial functioning and suicidality.

Results

Suicidal ideation was more frequent among girls (17.9%) than among boys (5.4%) (risk difference; RD = 12.5%, CI (7.2 to 17.7), p < 0.001), as was suicidal behavior (25.0% vs. 9.5%, RD = 15.5%, CI (9.2 to 21.4), p < 0.001). Girls had lower psychosocial functioning than boys (Children’s Global Assessment Scale; Mean score 68.2 vs. 75.2, Mean difference = − 7.0, CI (− 9.4 to − 4.7), p < 0.001), and more school dropout (22.5% vs. 13.2%, RD = 9.3%, CI (2.8 to 15.5), p = 0.006). For those with a psychiatric disorder, 24.8% of girls had suicidal ideation and 30.0% suicidal behavior, which was larger than for boys (RD = 18.0%, CI (10.8 to 24.7), p < 0.001, and RD = 18.3%, CI (10.2 to 25.8), p < 0.001, respectively). Exposure to negative life events was frequent for both genders, but more girls had experienced sexually uncomfortable or abusive situations, the last 3 years (23.5% vs. 2.9%, RD = 20.6%, CI (15.4 to 25.7), p < 0.001), and ever (44.4% vs. 7.9%, RD = 36.5%, CI (29.9 to 42.7), p < 0.001). Suicidal behavior was associated with having been threatened, physically harassed or violently hurt (RD = 16.7%, CI (9.5 to 23.9), p < 0.001), and for girls been put into sexually uncomfortable or abusive situations (RD = 20.1%, CI (10.4 to 29.9), p < 0.001) and seen others violently hurt (RD = 14.6%, CI (3.4 to 25.8), p = 0.011).

Conclusions

The high frequency of suicidality and school dropout confirms the severity of adolescent psychiatric disorders, especially among girls. Specific life events were associated risk factors and should be target points for prevention and intervention.
The link between problematic internet use, problematic gaming, and psychological distress: does sleep quality matter?
Authors: Wang Qian , Mati Komi , Cai Yong
Published: February 2021

Introduction

This study aimed to examine the mediating role of sleep quality in the association of problematic internet use (PIU) and problematic gaming with psychological distress among college students in China.

Methods

Data of 1040 full-time students from multiple colleges in China were examined. Respondents were asked about their internet use and gaming behaviors, sleep quality, psychological distress, and sociodemographic characteristics. The mediating role of sleep quality in the PIU- and problematic gaming-psychological distress link was examined respectively.

Results

PIU was associated with decreased sleep quality (r = .32, p < .001) and increased psychological distress (r = .46, p < .001). Problematic gaming was also associated with decreased sleep quality (r = .22, p < .001) and increased psychological distress (r = .46, p < .001). Sleep quality accounted for 23.5% of the indirect effect of PIU on psychological distress, and 17.9% of the indirect effect of problematic gaming on psychological distress.

Conclusions

Sleep quality had a meaningful mediating effect on the PIU-psychological distress link, but only exerted a small mediating effect on the problematic gaming-psychological distress link. In addition to promoting healthy internet usage, strategies aimed at mitigating the negative effect of excessive internet use on psychological health might benefit from those aimed at improving sleep quality.
Development of multifactor index for assessing quality of life of a tribal population of India: multilevel analysis approach
Authors: Bagavandas M.
Published: February 2021

Background

The main objective of this study is to develop a multilevel multi-factor index to assess the quality of life of the Malayali tribal population of India at the household and village levels based on nine domains, namely, Demography, Economy, Health, Human Development, Infrastructure Development, Work Participation, Recreation, Social Capital and Self Perception. An attempt is made to classify the individuals as well as villages by the overall scores of a multi-factor -index within a community which will help policymakers to develop concrete policy recommendations for the improvement of the quality of life of this tribal group.

Method

Multilevel factor analysis is utilized to determine uncorrelated meaningful factors and their respective weights using Mplus software from the nested dataset consists of values of nine domains of 1096 individuals collected from 19 villages. A multilevel multi-factor index is constructed using the weights of these factors. The qualities of the lives of different households and different villages are assessed using the scores of this index.

Results

Three different factors are identified at household as well as village levels. The quality of life at Households and Village levels are classified as poor, low, moderate, good, and excellent based on five quintiles of the scores of the multi-factor index, and the contribution of each domain in this classification is ascertained.

Discussion

This study finds that at household as well as at village levels, the quality of life of the individuals of this tribal population increases with an increase in education, income, and occupation status which make them lead a healthy life and also make them to find time and money to spend on recreation. Infrastructure is not important at the household level but not so at the village level.

Conclusion

The main purpose of developing this kind of multi-factor index at different levels is to provide a tool for tribal development based on realistic data that can be used to monitor the key factors that encompass the social, health, environmental, and economic dimensions of quality of lives at the household and community levels of these tribal people.
Safe and effective performance of pediatric spinal deformity surgery in patients unwilling to accept blood transfusion: a clinical study and review of literature
Authors: Mihas Alexander , Ramchandran Subaraman , Rivera Sebastian , Mansour Ali , Asghar Jahangir , Shufflebarger Harry , George Stephen
Published: February 2021

Background

Pediatric deformity surgery traditionally involves major blood loss. Patients refusing blood transfusion add extra clinical and medicolegal challenges; specifically the Jehovah’s witnesses population. The objective of this study is to review the safety and effectiveness of blood conservation techniques in patients undergoing pediatric spine deformity surgery who refuse blood transfusion.

Methods

After obtaining institutional review board approval, we retrospectively reviewed 20 consecutive patients who underwent spinal deformity surgery and refused blood transfusion at a single institution between 2014 and 2018. We collected pertinent preoperative, intraoperative and most recent clinical and radiological data with latest follow-up (minimum two-year follow-up).

Results

Twenty patients (13 females) with a mean age of 14.1 years were identified. The type of scoliotic deformities were adolescent idiopathic (14), juvenile idiopathic (1), neuromuscular (3) and congenital (2). The major coronal Cobb angle was corrected from 55.4° to 11.2° (80% correction, p <  0.001) at the latest follow-up. A mean of 11.4 levels were fused and 5.6 levels of Pontes osteotomies were performed. One patient underwent L1 hemivertebra resection and three patients had fusion to pelvis. Estimated blood loss, percent estimated blood volume loss, and cell saver returned averaged 307.9 mL, 8.5%, and 80 mL, respectively. Average operative time was 214 min. The average drop in hemoglobin after surgery was 2.9 g/dL. The length of hospital stay averaged 5.1 days. There were no intraoperative complications. Three postoperative complications were identified, none related to their refusal of transfusion. One patient had in-hospital respiratory complication, one patient developed a late infection, and one patient developed asymptomatic radiographic distal junctional kyphosis.

Conclusions

Blood conservation techniques allow for safe and effective spine deformity surgery in pediatric patients refusing blood transfusion without major anesthetic or medical complications, when performed by an experienced multidisciplinary team.

Level of evidence

Level IV.
Comparison of self and simulated patient assessments of first-year medical students’ Interpersonal and Communication Skills (ICS) during Objective Structured Clinical Examinations (OSCE)
Authors: Roshal Joshua A. , Chefitz Dalya , Terregino Carol A. , Petrova Anna
Published: February 2021

Background

Interpersonal and communication skills (ICS) are important core competencies in medical education and certification. In this study, we identified self- and simulated patient (SP)-reported ratings of US first-year medical students’ ICS and the influence of age and gender on performance appraisal during the Objective-Structured Clinical Examination (OSCE).

Methods

OSCE participants, including 172 first-year medical students and 15 SPs were asked to evaluate the students’ ICS using the American Board of Internal Medicine–Patient-Satisfaction Questionnaire (ABIM–PSQ), electronically and via paper, respectively. Self- and SP-reported ratings of students’ ICS were presented as the median on a 5-point Likert-scale and as three categories defined as “good,” “very good,” and “inadequate.”

Results

SPs assessed all 172 students in the OSCE, while 43.6% of students assessed their own performance. The majority of students and SPs evaluated the students’ ICS as very good. 23.3% of SPs and 5.3% of students rated the medical students’ ability to encourage patient question-asking and answer questions as inadequate (P <  0.002). Neither age nor gender influenced the medical students’ self-assessment of ICS. Female SPs assigned lower scores to students in regard to respecting patients and encouraging patient question-asking and answering. Older SPs was more likely to assign lower scores on all survey questions.

Conclusions

In the present study, self- and SP-reported ratings of first-year medical students’ ICS were mainly “very good” with no influence of students’ age or gender. Older age and female gender among the SPs were associated with a reduction in SP-reported ratings of students’ ICS.
Experiences of early graduate medical students working in New York hospitals during the COVID-19 pandemic: a mixed methods study
Authors: Pravder Harrison D. , Langdon-Embry Liana , Hernandez Rafael J. , Berbari Nicholas , Shelov Steven P. , Kinzler Wendy L.
Published: February 2021

Background

The coronavirus disease 2019 (COVID-19) pandemic presented the world with a sudden need for additional medical professionals. Senior medical students were identified as potential workers and many worldwide graduated early to serve as Junior Physicians in hospitals. The authors sought to identify factors that informed the decision to work, describe experiences in this capacity, and elucidate benefits for trainees.

Methods

The investigators conducted a mixed-methods observational cohort study of early medical graduates eligible to work as Junior Physicians at two New York medical centers in April/May 2020 during an initial surge in COVID-19 hospitalizations. Graduates were surveyed, and a sample of Junior Physicians participated in a focus group. Survey responses of those who worked were compared to those who did not. Focus group responses were transcribed, coded, and thematically analyzed.

Results

Fifty-nine graduates completed the study methods and 39 worked as Junior Physicians. Primary reasons for working included duty to help (39 [100%]), financial incentive (32 [82%]), desire to learn about pandemic response (25 [64%]), and educational incentive (24 [62%]). All had direct contact with COVID-19 patients, believed working was beneficial to their medical training, and were glad they worked. None contracted a symptomatic infection while working. Compared with non-Junior Physicians, Junior Physicians reported increased comfort levels in completing medical intern-level actions like transitions of care functions, such as writing transfer notes (P < 0.01), writing discharge orders (P = 0.01), and providing verbal sign out (P = 0.05), and they reported more comfort in managing COVID-19 patients. Sixteen themes emerged from the focus group and were placed into four categories: development of skills, patient care, safety, and wellness.

Conclusions

Senior medical students chose to work as Junior Physicians for both personal and educational reasons. Experiences were beneficial to trainees and can inform future innovations in medical education.
Evaluation of a clinical decision support system for rare diseases: a qualitative study
Authors: Schaaf Jannik , Sedlmayr Martin , Sedlmayr Brita , Prokosch Hans-Ulrich , Storf Holger
Published: February 2021

Background

Rare Diseases (RDs) are difficult to diagnose. Clinical Decision Support Systems (CDSS) could support the diagnosis for RDs. The Medical Informatics in Research and Medicine (MIRACUM) consortium developed a CDSS for RDs based on distributed clinical data from eight German university hospitals. To support the diagnosis for difficult patient cases, the CDSS uses data from the different hospitals to perform a patient similarity analysis to obtain an indication of a diagnosis. To optimize our CDSS, we conducted a qualitative study to investigate usability and functionality of our designed CDSS.

Methods

We performed a Thinking Aloud Test (TA-Test) with RDs experts working in Rare Diseases Centers (RDCs) at MIRACUM locations which are specialized in diagnosis and treatment of RDs. An instruction sheet with tasks was prepared that the participants should perform with the CDSS during the study. The TA-Test was recorded on audio and video, whereas the resulting transcripts were analysed with a qualitative content analysis, as a ruled-guided fixed procedure to analyse text-based data. Furthermore, a questionnaire was handed out at the end of the study including the System Usability Scale (SUS).

Results

A total of eight experts from eight MIRACUM locations with an established RDC were included in the study. Results indicate that more detailed information about patients, such as descriptive attributes or findings, can help the system perform better. The system was rated positively in terms of functionality, such as functions that enable the user to obtain an overview of similar patients or medical history of a patient. However, there is a lack of transparency in the results of the CDSS patient similarity analysis. The study participants often stated that the system should present the user with an overview of exact symptoms, diagnosis, and other characteristics that define two patients as similar. In the usability section, the CDSS received a score of 73.21 points, which is ranked as good usability.

Conclusions

This qualitative study investigated the usability and functionality of a CDSS of RDs. Despite positive feedback about functionality of system, the CDSS still requires some revisions and improvement in transparency of the patient similarity analysis.
Extensive antimicrobial resistance and plasmid-carrying resistance genes in mcr-1-positive E. coli sampled in swine, in Guangxi, South China
Authors: Yuan Jingzhi , Wang Xiaoye , Shi Dali , Ge Qiang , Song Xingxing , Hu Wen , Wei Deyuan , Ge Chenling , Li Xun , Hu Chuanhuo
Published: February 2021

Background

The discovery of the superbug mcr-1-positive Escherichia coli (MCRPEC) has drew greet attention. Swine-origin multi-drug resistant MCRPEC has been a potential threat to public health and safety. However, there were few detailed studies have been reported on swine MCRPEC in Guangxi, South China.

Results

In this study, thirty-three MCRPEC strains were detected from 142 E. coli strains from 116 samples in Guangxi in 2018. Which could be classified into eight unique STs and a total of six incompatibility plasmid groups (IncFI, IncHI1, IncY, IncN, IncI1 and IncX1). After that, the susceptibility of MCRPEC isolates to 27 antimicrobial agents belonging to 17 antimicrobial categories was tested. There were nineteen E. coli resistant to 3rd and 4th generation cephalosporins and twelve E. coli resistant to carbapenem resistan. Importantly, the MCRPEC showed high resistance highly resistance for imipenem and meropenem, which were forbidden to use in livestock production. Three MCRPEC strains were further proved to be extensively drug-resistant (XDR), and the other isolates were multi-drug-resistant (MDR). Furthermore, we found that the plasmid-carrying resistance genes coexisted with the mcr-1 gene of the MCRPEC isolates. Which were listed as follows: β-lactamase antimicrobial resistance genes e.g. ESBL genes (blaCTX-M14, blaCTX-M24, blaCTX-M123, blaOXA-1), plasmid-mediated AmpC (pAmpC) gene (blaCMY-2), the carbapenem resistance gene (blaNDM-5), and non-β-lactamase antimicrobial resistance genes (qnrA, qnrB, qnrS, aac (6′)-Ib-cr, tetA, tetB, sul1, sul2, floR, aadA).

Conclusion

Thirty-three mcr-1-positive E. coli isolates in Guangxi displayed a wide profile of antimicrobial resistance. Plasmid-carrying resistance genes might be the main cause of MCRPEC multidrug resistance. This study highlighted the necessity for long-term surveillance of mcr-1-positive E. coli in pigs.
Identification of biomarkers and pathogenesis in severe asthma by coexpression network analysis
Authors: Zhang Zeyi , Wang Jingjing , Chen Ou
Published: February 2021

Background

Severe asthma is a heterogeneous inflammatory disease. The increase in precise immunotherapy for severe asthmatics requires a greater understanding of molecular mechanisms and biomarkers. In this study, we aimed to identify the underlying mechanisms and hub genes that determine asthma severity.

Methods

Differentially expressed genes (DEGs) were identified based on bronchial epithelial brushings from mild and severe asthmatics. Then, weighted gene coexpression network analysis (WGCNA) was used to identify gene networks and the module most significantly associated with asthma severity. Furthermore, hub gene screening and functional enrichment analysis were performed. Replication with another dataset was conducted to validate the hub genes.

Results

DEGs from 14 mild and 11 severe asthmatics were subjected to WGCNA. Six modules associated with asthma severity were identified. Three modules were positively correlated (P < 0.001) with asthma severity and contained genes that were upregulated in severe asthmatics. Functional enrichment analysis showed that genes in the most significant module were mainly enriched in neutrophil activation and degranulation, and cytokine receptor interaction. Hub genes included CXCR1, CXCR2, CCR1, CCR7, TLR2, FPR1, FCGR3B, FCGR2A, ITGAM, and PLEK; CXCR1, CXCR2, and TLR2 were significantly related to asthma severity in the validation dataset. The combination of ten hub genes exhibited a moderate ability to distinguish between severe and mild-moderate asthmatics.

Conclusion

Our results identified biomarkers and characterized potential pathogenesis of severe asthma, providing insight into treatment targets and prognostic markers.
Telomere length dynamics over 10-years and related outcomes in patients with COPD
Authors: Córdoba-Lanús E. , Cazorla-Rivero S. , García-Bello M. A. , Mayato D. , Gonzalvo F. , Ayra-Plasencia J. , Celli B. , Casanova C.
Published: February 2021

Background

Chronic obstructive pulmonary disease (COPD) has been proposed as a disease of accelerated aging. Several cross-sectional studies have related a shorter telomere length (TL), a marker of biological aging, with COPD outcomes. Whether accelerated telomere shortening over time relates to worse outcomes in COPD patients, is not known.

Methods

Relative telomere length (T/S) was determined by qPCR in DNA samples from peripheral blood in 263 patients at baseline and up to 10 years post enrolment. Yearly clinical and lung function data of 134 patients with at least two-time measures of T/S over this time were included in the analysis.

Results

At baseline, T/S inversely correlated with age (r = − 0.236; p < 0.001), but there was no relationship between T/S and clinical and lung function variables (p > 0.05). Over 10 years of observation, there was a median shortening of TL of 183 bp/year for COPD patients. After adjusting for age, gender, active smoking and mean T/S, patients that shortened their telomeres the most over time, had worse gas exchange, more lung hyperinflation and extrapulmonary affection during the follow-up, (PaO2 p < 0.0001; KCO p = 0.042; IC/TLC p < 0.0001; 6MWD p = 0.004 and BODE index p = 0.009). Patients in the lowest tertile of T/S through the follow-up period had an increased risk of death [HR = 5.48, (1.23–24.42) p = 0.026].

Conclusions

This prospective study shows an association between accelerated telomere shortening and progressive worsening of pulmonary gas exchange, lung hyperinflation and extrapulmonary affection in COPD patients. Moreover, persistently shorter telomeres over this observation time increase the risk for all-cause mortality.
Asthma-related inflammation promotes lung metastasis of breast cancer cells through CCL11–CCR3 pathway
Authors: Bekaert S. , Rocks N. , Vanwinge C. , Noel A. , Cataldo D.
Published: February 2021

Background

Mechanisms that preclude lung metastasis are still barely understood. The possible consequences of allergic airways inflammation on cancer dissemination were studied in a mouse model of breast cancer.

Methods

Balb/c mice were immunized and daily exposed to ovalbumin (OVA) from day 21. They were subcutaneously injected with 4T1 mammary tumor cells on day 45 and sacrificed on day 67. Lung metastases were measured by biophotonic imaging (IVIS® 200 Imaging System) and histological measurement of tumor area (Cytomine software). Effects of CCL11 were assessed in vivo by intratracheal instillations of recCCL11 and in vitro using Boyden chambers. CCR3 expression on cell surface was assessed by flow cytometry.

Results

The extent of tumor metastases was significantly higher in lungs of OVA-exposed mice and increased levels of CCL11 expression were measured after OVA exposure. Migration of 4T1 cells and neutrophils was stimulated in vitro and in vivo by recCCL11. 4T1 cells and neutrophils express CCR3 as shown by flow cytometry and a selective CCR3 antagonist (SB-297006) inhibited the induction of 4T1 cells migration and proliferation in response to recCCL11.

Conclusions

Allergic inflammation generated by exposure to allergens triggers the implantation of metastatic cells from primary breast tumor into lung tissues plausibly in a CCL11–CCR3-dependent manner. This indicates that asthma related inflammation in lungs might be a risk factor for lung metastasis in breast cancer patients.
Safety of denervation following targeted lung denervation therapy for COPD: AIRFLOW-1 3-year outcomes
Authors: Pison Christophe , Shah Pallav L. , Slebos Dirk-Jan , Ninane Vincent , Janssens Wim , Perez Thierry , Kessler Romain , Deslee Gaetan , Garner Justin L. , Hartman Jorine E. , Degano Bruno , Mayr Anna , Mayse Martin , Peterson Alexander D. , Valipour Arschang
Published: February 2021

Background

Targeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung reducing clinical consequences of cholinergic hyperactivity. The AIRFLOW-1 study assessed safety and TLD dose in patients with moderate-to-severe, symptomatic COPD. This analysis evaluated the long-term impact of TLD on COPD exacerbations, pulmonary function, and quality of life over 3 years of follow up.

Methods

TLD was performed in a prospective, energy-level randomized (29 W vs 32 W power), multicenter study (NCT02058459). Additional patients were enrolled in an open label confirmation phase to confirm improved gastrointestinal safety after procedural modifications. Durability of TLD was evaluated at 1, 2, and 3 years post-treatment and assessed through analysis of COPD exacerbations, pulmonary lung function, and quality of life.

Results

Three-year follow-up data were available for 73.9% of patients (n = 34). The annualized rate of moderate to severe COPD exacerbations remained stable over the duration of the study. Lung function (FEV1, FVC, RV, and TLC) and quality of life (SGRQ-C and CAT) remained stable over 3 years of follow-up. No new gastrointestinal adverse events and no unexpected serious adverse events were observed.

Conclusion

TLD in COPD patients demonstrated a positive safety profile out to 3 years, with no late-onset serious adverse events related to denervation therapy. Clinical stability in lung function, quality of life, and exacerbations were observed in TLD treated patients over 3 years of follow up.
Correction to: Individual and structural correlates of willingness for intravenous buprenorphine treatment among people who inject sublingual buprenorphine in France
Authors: Mezaache Salim , Carrieri Patrizia , Briand‑Madrid Laelia , Laporte Virginie , Morel Alain , Castro Daniela Rojas , Roux Perrine
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
The drug war must end: The right to life, liberty and security of the person during the COVID-19 pandemic for people who use drugs
Authors:   VANDU, Maynard Russ ,   WAHRS,   BCAPOM, Jozaghi Ehsan
Published: February 2021

Since the start of the opioid epidemic in 2016, the Downtown Eastside community of Vancouver, Canada, has lost many pioneering leaders, activists and visionaries to the war on drugs. The Vancouver Area Network of Drug Users (VANDU), the Western Aboriginal Harm Reduction Society (WAHRS), and the British Columbia Association People on Opiate Maintenance (BCAPOM) are truly concerned about the increasing overdose deaths that have continued since 2016 and have been exacerbated by the novel coronavirus (SARS-COVID-19) despite many unique and timely harm reduction announcements by the British Columbia (B.C.) government. Some of these unique interventions in B.C., although in many cases only mere announcements with limited scope, are based on the philosophy of safe supply to illegal street drugs. Despite all the efforts during the pandemic, overdose deaths have spiked by over 100% compared to the previous year. Therefore, we urge the Canadian federal government, specifically the Honorable Patty Hajdu, the federal Minister of Health, to decriminalize simple possession immediately by granting exemption under the Controlled Drugs and Substances Act. The Canadian federal government has a moral obligation under Sect. 7 of the Canadian Charter of Rights and Freedoms to protect the basic human rights of marginalized Canadians.
Critical roles of sphingosine kinase 1 in the regulation of neuroinflammation and neuronal injury after spinal cord injury
Authors: Wang Chenjian , Xu Tianzhen , Lachance Brittany Bolduc , Zhong Xiqiang , Shen Guangjie , Xu Tao , Tang Chengxuan , Jia Xiaofeng
Published: February 2021

Background

The pathological process of traumatic spinal cord injury (SCI) involves excessive activation of microglia leading to the overproduction of proinflammatory cytokines and causing neuronal injury. Sphingosine kinase 1 (Sphk1), a key enzyme responsible for phosphorylating sphingosine into sphingosine-1-phosphate (S1P), plays an important role in mediating inflammation, cell proliferation, survival, and immunity.

Methods

We aim to investigate the mechanism and pathway of the Sphk1-mediated neuroinflammatory response in a rodent model of SCI. Sixty Sprague-Dawley rats were randomly assigned to sham surgery, SCI, or PF543 (a specific Sphk1 inhibitor) groups. Functional outcomes included blinded hindlimb locomotor rating and inclined plane test.

Results

We discovered that Sphk1 is upregulated in injured spinal cord tissue of rats after SCI and is associated with production of S1P and subsequent NF-κB p65 activation. PF543 attenuated p65 activation, reduced inflammatory response, and relieved neuronal damage, leading to improved functional recovery. Western blot analysis confirmed that expression of S1P receptor 3 (S1PR3) and phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) are activated in microglia of SCI rats and mitigated by PF543. In vitro, we demonstrated that Bay11-7085 suppressed NF-κB p65 and inhibited amplification of the inflammation cascade by S1P, reducing the release of proinflammatory TNF-α. We further confirmed that phosphorylation of p38 MAPK and activation of NF-κB p65 is inhibited by PF543 and CAY10444. p38 MAPK phosphorylation and NF-κB p65 activation were enhanced by exogenous S1P and inhibited by the specific inhibitor SB204580, ultimately indicating that the S1P/S1PR3/p38 MAPK pathway contributes to the NF-κB p65 inflammatory response.

Conclusion

Our results demonstrate a critical role of Sphk1 in the post-traumatic SCI inflammatory cascade and present the Sphk1/S1P/S1PR3 axis as a potential target for therapeutic intervention to control neuroinflammation, relieve neuronal damage, and improve functional outcomes in SCI.
Accuracy of an MR-only workflow for prostate radiotherapy using semi-automatically burned-in fiducial markers
Authors: Goudschaal Karin , Beeksma F. , Boon M. , Bijveld M. , Visser J. , Hinnen K. , van Kesteren Z.
Published: February 2021

Background

The benefit of MR-only workflow compared to current CT-based workflow for prostate radiotherapy is reduction of systematic errors in the radiotherapy chain by 2–3 mm. Nowadays, MRI is used for target delineation while CT is needed for position verification. In MR-only workflows, MRI based synthetic CT (sCT) replaces CT. Intraprostatic fiducial markers (FMs) are used as a surrogate for the position of the prostate improving targeting. However, FMs are not visible on sCT. Therefore, a semi-automatic method for burning-in FMs on sCT was developed. Accuracy of MR-only workflow using semi-automatically burned-in FMs was assessed and compared to CT/MR workflow.

Methods

Thirty-one prostate cancer patients receiving radiotherapy, underwent an additional MR sequence (mDIXON) to create an sCT for MR-only workflow simulation. Three sources of accuracy in the CT/MR- and MR-only workflow were investigated. To compare image registrations for target delineation, the inter-observer error (IOE) of FM-based CT-to-MR image registrations and soft-tissue-based MR-to-MR image registrations were determined on twenty patients. Secondly, the inter-observer variation of the resulting FM positions was determined on twenty patients. Thirdly, on 26 patients CBCTs were retrospectively registered on sCT with burned-in FMs and compared to CT-CBCT registrations.

Results

Image registration for target delineation shows a three times smaller IOE for MR-only workflow compared to CT/MR workflow. All observers agreed in correctly identifying all FMs for 18 out of 20 patients (90%). The IOE in CC direction of the center of mass (COM) position of the markers was within the CT slice thickness (2.5 mm), the IOE in AP and RL direction were below 1.0 mm and 1.5 mm, respectively. Registrations for IGRT position verification in MR-only workflow compared to CT/MR workflow were equivalent in RL-, CC- and AP-direction, except for a significant difference for random error in rotation.

Conclusions

MR-only workflow using sCT with burned-in FMs is an improvement compared to the current CT/MR workflow, with a three times smaller inter observer error in CT-MR registration and comparable CBCT registration results between CT and sCT reference scans.

Trial registry Medical Research Involving Human Subjects Act (WMO) does apply to this study and was approved by the Medical Ethics review Committee of the Academic Medical Center. Registration number: NL65414.018.18. Date of registration: 21–08-2018.
Correlation between growth differentiation factor 5 (rs143383) gene polymorphism and knee osteoarthritis: an updated systematic review and meta-analysis
Authors: Jia Bin , Jiang Yaping , Xu Yingxing , Wang Yingzhen , Li Tao
Published: February 2021

Background

A great deal of evidence has supported that growth differentiation factor 5 (GDF5) is associated with the occurrence of knee osteoarthritis (KOA), while their results are not consistent. In the present study, we aimed to explore the association between GDF5 gene polymorphism and KOA for a more credible conclusion.

Methods

Comprehensive literature searches were carried out in English databases, including PubMed, Embase, Web of Science (WOS), and Cochrane, and Chinese databases, including China National Knowledge Infrastructure (CNKI), WANFANG, and VIP database. After the data were extracted from the required studies, the odds ratios (ORs) and their 95% confidence intervals (CIs) were determined to assess the correlation between GDF5 gene polymorphism and KOA. The publication bias was evaluated by funnel plot.

Results

According to the inclusion and exclusion criteria, 15 studies on the correlation between GDF5 gene polymorphism and KOA occurrence were eligible for meta-analysis. Among these articles, four studies showed no apparent correlation, while the other 11 studies indicated an obvious correlation. Meanwhile, we also carried out a subgroup analysis of the population. Due to the inevitable heterogeneity, three genetic models were finally selected for analysis. With the allele model (C versus T: OR = 0.79, 95% CI = 0.73~0.87), recessive model (CC versus CT + TT: OR = 0.76, 95% CI = 0.68~0.86), and homozygous model (CC versus TT: OR = 0.66, 95% CI = 0.58~0.76), GDF5 gene polymorphism decreased the risk of KOA. Besides, a significant association was observed in Caucasians, Asians, and Africans. Meanwhile, the protective effect of genotype C (or CC) in the Asian group was little obvious than that in the Caucasian group and the African group. Although the quality of the included studies was above medium-quality, we obtained results with a low level of evidence.

Conclusions

The results of the meta-analysis showed that the genotype C (or CC) of GDF5 protected against KOA occurrence in Caucasian, Asian, and African populations.