bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulatory, scientific, and ethical issues arising from institutional activity in one of the 90 Italian Research Ethics Committees
Authors: Benfatto G. ,   Regulatory Group, Longo Laura , Mansueto Silvana , Gozzo Lucia , Vitale Daniela C. ,   Ethics Committee Catania 1 (Group), Amato Salvatore , Basile Francesco , Blanco Adele , Borzì Vito , Cavallaro Patrizia , Cilia Sonia , Conti Mario , Cristaudo Concetto , Daidone Letterio D. , Di Fazzio Salvatore , Di Mauro Maurizio , Garozzo Rosaria , Giardina Gaetano , Gulino Antonio , Iachelli Liliana , La Bella Maria L. , La Rosa Agata , Lazzara Antonio , Leonardi Francesco , Monaco Francesca Lo , Malatino Lorenzo , Mattina Teresa , Negro Matteo , Palermo Filippo , Puleo Stefano , Raciti Rosa , Ruggieri Martino , Sapuppo Antonio , Scillieri Renato , Squatrito Sebastiano , Tanasi Francesco , Drago F.
Published: April 2021

Background

This paper highlights the issues that one of the 90 Italian Research Ethics Committees (RECs) might encounter during the approval phase of a clinical trial to identify corrective and preventive actions for promoting a more efficient review process and ensuring review quality. Publications on the subject from Italy and the rest of Europe are limited; encouraging constructive debate can improve RECs’ service to the subject of the clinical trial.

Methods

We retrospectively reviewed a cohort of 822 clinical trial protocols, initially reviewed by REC, from June 2014 to December 2018. Data collected for each protocol were type of trial, sample size, use of placebo, number and kind of revisions requested by the REC before approval, and time taken for approval. Data for each protocol were collected by a trained clinical research assistant using the REC’s files and electronic archives.

Results

Almost 45% of the reviewed studies (374/822) required clarifications, significant changes to the documentation, or minor changes before final approval.

Conclusions

Preventive measures are needed to reduce the number of requested corrections and thus also the time required for approval, while maintaining review quality. All critical points and proposals presented in this paper require harmonization through updates to European regulations, as regulatory harmonization produces better compliance with rules and reduces the number of changes required before the trials’ final approval. Such updates include the development of standardized formats for informed consent, the verification of any evidence in favor of using off-label treatments over placebo as comparators, using multidisciplinary staff in clinical trials with children and adolescents, improving the legal definition of RECs to assign responsibilities and ensure independence, and providing guidance for RECs to engage clinical research assistants in internal audits.
Ethical concerns in suicide research: thematic analysis of the views of human research ethics committees in Australia
Authors: Barnard Emma , Dempster Georgia , Krysinska Karolina , Reifels Lennart , Robinson Jo , Pirkis Jane , Andriessen Karl
Published: April 2021

Background

Suicide research aims to contribute to a better understanding of suicidal behaviour and its prevention. However, there are many ethical challenges in this research field, for example, regarding consent and potential risks to participants. While studies to-date have focused on the perspective of the researchers, this study aimed to investigate the views and experiences of members of Human Research Ethics Committees (HRECs) in dealing with suicide-related study applications.

Methods

This qualitative study entailed a thematic analysis using an inductive approach. We conducted semi-structured interviews with a purposive sample (N = 15) of HREC Chairs or their delegates from Australian research-intensive universities. The interview guide included questions regarding the ethical concerns and challenges in suicide-related research raised by HREC members, how they dealt with those challenges and what advice they could give to researchers.

Results

The analysis identified four main themes: (1) HREC members’ experiences of reviewing suicide-related study applications, (2) HREC members’ perceptions of suicide, suicide research, and study participants, (3) Complexity in HREC members’ decision-making processes, and (4) HREC members’ relationships with researchers.

Conclusions

Reliance on ethical guidelines and dialogue with researchers are crucial in the assessment of suicide-related study applications. Both researchers and HREC members may benefit from guidance and resources on how to conduct ethically sound suicide-related studies. Developing working relationships will be likely to help HRECs to facilitate high quality, ethical suicide-related research and researchers to conduct such research.
Correction to: A clinical trials corpus annotated with UMLS entities to enhance the access to evidence‑based medicine
Authors: Campillos-Llanos Leonardo , Valverde-Mateos Ana , Capllonch-Carrión Adrián , Moreno-Sandoval Antonio
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Knowledge of mothers and fathers’ experiences of the early in-home care of premature infants supported by video consultations with a neonatal nurse
Authors: Hägi-Pedersen Mai-Britt , Kronborg Hanne , Norlyk Annelise
Published: April 2021

Aim

To gain in-depth knowledge of mothers’ and fathers’ experiences of the whole trajectory of an early in-home care programme supported by video consultations with a neonatal nurse.

Design

A qualitative interview study.

Methods

Data were collected through dyadic semi-structured interviews with mothers and fathers participating in virtual early in-home care programmes and were subjected to inductive content analysis.

Findings

The mothers and fathers were anxious about mastering the care of their premature infants at the start of the early in-home care phase but gradually developed confidence by the completion of the early in-home care programme. Being at home during the early in-home care programme gave the mothers and fathers an opportunity to test their decision making concerning the care of the infant while having the ability to obtain support from nurses when needed.

Conclusion

Our findings indicate that the trajectory of early in-home care programmes combined with video consultations contributes to parents’ increased confidence as mothers and fathers.

Trial registration

Clinical trial registration: REG-113-2014 and SJ-431.
Students’ perspectives of factors related to delayed completion of online RN-BSN programs
Authors: Iheduru-Anderson Kechinyere C.
Published: April 2021

Background

There are multiple educational programs for individuals to become registered nurses (RNs), and the transition from an associate degree or diploma to a Bachelor of Science in Nursing (BSN) degree is vital to healthcare. This study examined the factors contributing to delayed completion or withdrawal from online RN-BSN nursing programs from students’ perspectives.

Method

Thematic content analyses were conducted on qualitative data obtained from semi-structured interviews (N = 26).

Results

Complex factors contributed to delayed completion of online RN-BSN programs, including student-, institutional-, and faculty-related factors.

Conclusion

This study validated and extends previous studies without delineating students in fully online programs from hybrid and face-to-face programs. Students, faculty, and institutions all have a role to play in facilitating on-time program completion. Recognizing and mitigating the barriers that delay on-time program completion is required to foster nurses to obtain a BSN degree.
Healthcare services utilization among international students in Ankara, Turkey: a cross-sectional study
Authors: Masai Abednego Nzyuko , Güçiz-Doğan Bahar , Ouma Polet Njeri , Nyadera Israel Nyaburi , Ruto Victor Kipkoech
Published: April 2021

Background

While international students form an increasing population of higher education students in Turkey, there is limited empirical evidence about their health services utilization. The study aim was to investigate healthcare access among a group of international students studying in Ankara city and identify potential barriers that affect full healthcare utilization.

Method

A total of 535 international students from 83 countries completed an online-based questionnaire. The survey was conducted from September until October 2020. Variables between groups within the study sample were compared using ANOVA and Chi-square tests (with Fisher’s exact test). Logistic regression analysis was used to evaluate the relationships between variables related to access to health services.

Results

Of the study population, 80.6% accessed the general practitioner (GP), 40% accessed the student health centres, and 11.4% were admitted to the hospital at least once. About 80% of international students reported changing their views to access healthcare more because of the COVID-19 pandemic.

Conclusion

Lack of awareness of healthcare support systems, perceived stigma associated with mental health services, and language barriers were the main barriers affecting healthcare access by international students.

Implications

Study findings indicate the need for education of international students on available healthcare, targeted health promotion, and training of health providers on effective communication.
Exploring the differences in ICD and hospital morbidity data collection features across countries: an international survey
Authors: Otero Varela Lucia , Doktorchik Chelsea , Wiebe Natalie , Quan Hude , Eastwood Catherine
Published: April 2021

Background

The International Classification of Diseases (ICD) is the reference standard for reporting diseases and health conditions globally. Variations in ICD use and data collection across countries can hinder meaningful comparisons of morbidity data. Thus, we aimed to characterize ICD and hospital morbidity data collection features worldwide.

Methods

An online questionnaire was created to poll the World Health Organization (WHO) member countries that were using ICD. The survey included questions focused on ICD meta-features and hospital data collection systems, and was distributed via SurveyMonkey using purposive and snowball sampling. Accordingly, senior representatives from organizations specialized in the topic, such as WHO Collaborating Centers, and other experts in ICD coding were invited to fill out the survey and forward the questionnaire to their peers. Answers were collated by country, analyzed, and presented in a narrative form with descriptive analysis.

Results

Responses from 47 participants were collected, representing 26 different countries using ICD. Results indicated worldwide disparities in the ICD meta-features regarding the maximum allowable coding fields for diagnosis, the definition of main condition, and the mandatory type of data fields in the hospital morbidity database. Accordingly, the most frequently reported answers were “reason for admission” as main condition definition (n = 14), having 31 or more diagnostic fields available (n = 12), and “Diagnoses” (n = 26) and “Patient demographics” (n = 25) for mandatory data fields. Discrepancies in data collection systems occurred between but also within countries, thereby revealing a lack of standardization both at the international and national level. Additionally, some countries reported specific data collection features, including the use or misuse of ICD coding, the national standards for coding or lack thereof, and the electronic abstracting systems utilized in hospitals.

Conclusions

Harmonizing ICD coding standards/guidelines should be a common goal to enhance international comparisons of health data. The current international status of ICD data collection highlights the need for the promotion of ICD and the adoption of the newest version, ICD-11. Furthermore, it will encourage further research on how to improve and standardize ICD coding.
Professional courage to create a pathway within midwives’ fields of work: a grounded theory study
Authors: Hansson Malin , Lundgren Ingela , Hensing Gunnel , Dencker Anna , Eriksson Monica , Carlsson Ing-Marie
Published: April 2021

Background

The theory of salutogenesis focuses on resources for health and health-promoting processes. In the context of midwives’ work, this is not well described despite the importance for occupational health and the intention to remain in the profession. In order to promote a healthy workplace, it is necessary to consider the facilitating conditions that contribute to a sustainable working life. Therefore, the aim of this study was to explore health-promoting facilitative conditions in the work situation on labour wards according to midwives.

Methods

A constant comparative analysis was applied to face-to-face interviews with midwives that constituted the empirical material in this classical grounded theory study.

Results

The substantive theory of Professional courage to create a pathway within midwives’ fields of work emerged as an explanation of the health-promoting facilitative conditions in midwives’ work situation. The theory consists of a four-stage process with prerequisite contextual conditions: visualising midwifery, organisational resources and a reflective and learning environment, that were needed to fulfil the midwives’ main concern a Feasibility of working as a midwife. This meant being able to work according to best-known midwifery theory and practice in each situation. Positive consequences of a fulfilled main concern were a professional identity and grounded knowledge that enabled the development of the resistant resource professional courage. The courage made it feasible for midwives to move freely on their pathway within the different fields of work extending between normal and medicalised birth and being autonomous and regulated.

Conclusions

A professional courage was required to create a pathway within midwives’ fields of work, to move freely depending on what actions were needed in a particular work situation. Professional courage could be seen as a resistance resource, enabling midwives to become resilient when dealing with the unpredictable work situation. However, there are vital organisational preconditions that needed to be fulfilled for workplaces to become facilitative, organisational resources, visualising midwifery and a reflective environment.

The theory can be used to foster health-promoting and sustainable work situations for midwives, which is possible if the organisational preconditions are met. This could be a key factor in retaining midwives in the profession.
Dexamethasone induces an imbalanced fetal-placental-maternal bile acid circulation: involvement of placental transporters
Authors: Huang Wen , Zhou Jin , Guo Juanjuan , Hu Wen , Chen Guanghui , Li Bin , Wen Yajie , Jiang Yimin , Fu Kaili , Bi Huichang , Zhang Yuanzhen , Wang Hui
Published: April 2021

Background

The use of prenatal dexamethasone remains controversial. Our recent studies found that prenatal dexamethasone exposure can induce maternal intrahepatic cholestasis and have a lasting adverse influence on bile acid (BA) metabolism in the offspring. The purpose of this study was to investigate the effects of dexamethasone on fetal-placental-maternal BA circulation during the intrauterine period, as well as its placental mechanism.

Methods

Clinical data and human placentas were collected and analyzed. Pregnant Wistar rats were injected subcutaneously with dexamethasone (0.2 mg/kg per day) from gestational day 9 to 20. The metabolomic spectra of BAs in maternal and fetal rat serum were determined by LC-MS. Human and rat placentas were collected for histological and gene expression analysis. BeWo human placental cell line was treated with dexamethasone (20–500 nM).

Results

Human male neonates born after prenatal dexamethasone treatment showed an increased serum BA level while no significant change was observed in females. Moreover, the expression of organic anion transporter polypeptide-related protein 2B1 (OATP2B1) and breast cancer resistance protein (BCRP) in the male neonates’ placenta was decreased, while multidrug resistance-associated protein 4 (MRP4) was upregulated. In experimental rats, dexamethasone increased male but decreased female fetal serum total bile acid (TBA) level. LC-MS revealed that primary BAs were the major component that increased in both male and female fetal serum, and all kinds of BAs were significantly increased in maternal serum. The expression of Oatp2b1 and Bcrp were reduced, while Mrp4 expression was increased in the dexamethasone-treated rat placentas. Moreover, dexamethasone increased glucocorticoid receptor (GR) expression and decreased farnesoid X receptor (FXR) expression in the rat placenta. In BeWo cells, dexamethasone induced GR translocation into the nucleus; decreased FXR, OATP2B1, and BCRP expression; and increased MRP4 expression. Furthermore, GR was verified to mediate the downregulation of OATP2B1, while FXR mediated dexamethasone-altered expression of BCRP and MRP4.

Conclusions

By affecting placental BA transporters, dexamethasone induces an imbalanced fetal-placental-maternal BA circulation, as showed by the increase of primary BA levels in the fetal serum. This study provides an important experimental and theoretical basis for elucidating the mechanism of dexamethasone-induced alteration of maternal and fetal BA metabolism and for exploring early prevention and treatment strategies.
Spoligotype-specific risk of finding lesions in tissues from cattle infected by Mycobacterium bovis
Authors: Gomez-Buendia Alberto , Romero Beatriz , Bezos Javier , Lozano Francisco , de Juan Lucía , Alvarez Julio
Published: April 2021

Background

Although the pathogenic effect of members of the Mycobacterium tuberculosis complex in susceptible hosts is well known, differences in clinical signs and pathological findings observed in infected animals have been reported, likely due to a combination of host and pathogen-related factors. Here, we investigated whether Mycobacterium bovis strains belonging to different spoligotypes were associated with a higher risk of occurrence of visible/more severe lesions in target organs (lungs and/or lymph nodes) from infected animals. A large collection of 8889 samples belonging to cattle were classified depending on the presence/absence of tuberculosis-like lesions and its degree of severity. All samples were subjected to culture irrespective of the presence of lesions, and isolates retrieved were identified and subjected to spoligotyping. The association between the presence/severity of the lesions and the isolation of strains from a given spoligotype was assessed using non-parametric tests and Bayesian mixed multivariable logistic regression models that accounted for origin (region and herd) effects.

Results

Results suggested a difference in severity in lesioned samples depending on the strain’s spoligotype. An association between specific spoligotypes and presence of lesions was observed, with a higher risk of finding lesions in animals infected with strains with spoligotypes SB0120, SB0295 and SB1142 compared with SB0121, and in those coming from certain regions in Spain.

Conclusions

Our results suggest that strains belonging to certain spoligotypes may be associated with a higher probability in the occurrence of gross/macroscopic lesions in infected cattle, although these observational findings should be confirmed in further studies that allow accounting for the effect of other possible confounders not considered here, and ultimately through experimental studies.
Cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors in diabetic and nondiabetic patients
Authors: Xiang Boyang , Zhao Xiaoya , Zhou Xiang
Published: April 2021

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were developed as antidiabetic agents, but accumulating evidence has shown their beneficial effects on the cardiovascular system. Analyses of the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) suggested that these benefits are independent of glycemic control. Several large-scale outcome trials of SGLT2i also showed cardiovascular benefits in nondiabetic patients, strengthening this perspective. Extensive animal and clinical studies have likewise shown that mechanisms other than the antihyperglycemic effect underlie the cardiovascular benefits. Recent clinical guidelines recommend the use of SGLT2i in patients with type 2 diabetes mellitus and cardiovascular diseases because of the proven cardiovascular protective effects. Since the cardiovascular benefits are independent of glycemic control, the therapeutic spectrum of SGLT2i will likely be extended to nondiabetic patients.
Trehalose alleviates high‐temperature stress in Pleurotus ostreatus by affecting central carbon metabolism
Authors: Yan Zhi-Yu , Zhao Meng-Ran , Huang Chen-Yang , Zhang Li-Jiao , Zhang Jin-Xia
Published: April 2021

Background

Trehalose, an intracellular protective agent reported to mediate defense against many stresses, can alleviate high-temperature-induced damage inPleurotus ostreatus. In this study, the mechanism by which trehalose relieves heat stress was explored by the addition of exogenous trehalose and the use of trehalose-6-phosphate synthase 1 (tps1) overexpression transformants.

Results

The results suggested that treatment with exogenous trehalose or overexpression oftps1 alleviated the accumulation of lactic acid under heat stress and downregulated the expression of the phosphofructokinase (pfk) and pyruvate kinase (pk) genes, suggesting an ameliorative effect of trehalose on the enhanced glycolysis inP. ostreatusunder heat stress. However, the upregulation of hexokinase (hk) gene expression by trehalose indicated the involvement of the pentose phosphate pathway (PPP) in heat stress resistance. Moreover, treatment with exogenous trehalose or overexpression oftps1 increased the gene expression level and enzymatic activity of glucose-6-phosphate dehydrogenase (g6pdh) and increased the production of both the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH), confirming the effect of trehalose on alleviating oxidative damage by enhancing PPP inP. ostreatusunder heat stress. Furthermore, treatment with exogenous trehalose or overexpression oftps1 ameliorated the decrease in the oxygen consumption rate (OCR) caused by heat stress, suggesting a relationship between trehalose and mitochondrial function under heat stress.

Conclusions

Trehalose alleviates high-temperature stress inP. ostreatusby inhibiting glycolysis and stimulating PPP activity. This study may provide further insights into the heat stress defense mechanism of trehalose in edible fungi from the perspective of intracellular metabolism.
Molecular surveillance of drug resistance: Plasmodium falciparum artemisinin resistance single nucleotide polymorphisms in Kelch protein propeller (K13) domain from Southern Pakistan
Authors: Ghanchi Najia Karim , Qurashi Bushra , Raees Hadiqa , Beg Mohammad Asim
Published: April 2021

Background

K13 propeller (k13) polymorphism are useful molecular markers for tracking the emergence and spread of artemisinin resistance in Plasmodium falciparum. Polymorphisms are reported from Cambodia with rapid invasion of the population and almost near fixation in south East Asia. The study describes single nucleotide polymorphisms in Kelch protein propeller domain of P. falciparum associated with artemisinin resistance from Southern Pakistan.

Methods

Two hundred and forty-nine samples were collected from patients with microscopy confirmed P. falciparum malaria attending Aga Khan University Hospital during September 2015-April 2018. DNA was isolated using the whole blood protocol for the QIAmp DNA Blood Kit. The k13 propeller gene (k13) was amplified using nested PCR. Double-strand sequencing of PCR products was performed using Sanger sequencing methodology. Sequences were analysed with MEGA 6 and Bio edit software to identify specific SNP combinations.

Results

All isolates analysed for k13 propeller allele were observed as wild-type in samples collected post implementation of ACT in Pakistan. C580Y, A675V, Y493H and R539T variants associated with reduced susceptibility to artemisinin-based combination therapy (ACT) were not found. Low frequency of M476I and C469Y polymorphisms was found, which is significantly associated with artemisinin resistance.

Conclusion

Low frequencies of both nonsynonymous and synonymous polymorphisms were observed in P. falciparum isolates circulating in Southern Pakistan. The absence of known molecular markers of artemisinin resistance in this region is favourable for anti-malarial efficacy of ACT. Surveillance of anti-malarial drug resistance to detect its emergence and spread need to be strengthened in Pakistan.
Toward a priori noise characterization for real-time edge-aware denoising in fluoroscopic devices
Authors: Andreozzi Emilio , Fratini Antonio , Esposito Daniele , Cesarelli Mario , Bifulco Paolo
Published: April 2021

Background

Low-dose X-ray images have become increasingly popular in the last decades, due to the need to guarantee the lowest reasonable patient’s exposure. Dose reduction causes a substantial increase of quantum noise, which needs to be suitably suppressed. In particular, real-time denoising is required to support common interventional fluoroscopy procedures. The knowledge of noise statistics provides precious information that helps to improve denoising performances, thus making noise estimation a crucial task for effective denoising strategies. Noise statistics depend on different factors, but are mainly influenced by the X-ray tube settings, which may vary even within the same procedure. This complicates real-time denoising, because noise estimation should be repeated after any changes in tube settings, which would be hardly feasible in practice. This work investigates the feasibility of an a priori characterization of noise for a single fluoroscopic device, which would obviate the need for inferring noise statics prior to each new images acquisition. The noise estimation algorithm used in this study was tested in silico to assess its accuracy and reliability. Then, real sequences were acquired by imaging two different X-ray phantoms via a commercial fluoroscopic device at various X-ray tube settings. Finally, noise estimation was performed to assess the matching of noise statistics inferred from two different sequences, acquired independently in the same operating conditions.

Results

The noise estimation algorithm proved capable of retrieving noise statistics, regardless of the particular imaged scene, also achieving good results even by using only 10 frames (mean percentage error lower than 2%). The tests performed on the real fluoroscopic sequences confirmed that the estimated noise statistics are independent of the particular informational content of the scene from which they have been inferred, as they turned out to be consistent in sequences of the two different phantoms acquired independently with the same X-ray tube settings.

Conclusions

The encouraging results suggest that an a priori characterization of noise for a single fluoroscopic device is feasible and could improve the actual implementation of real-time denoising strategies that take advantage of noise statistics to improve the trade-off between noise reduction and details preservation.
The convergence of racial and income disparities in health insurance coverage in the United States
Authors: Lee De-Chih , Liang Hailun , Shi Leiyu
Published: April 2021

Objective

This study applied the vulnerability framework and examined the combined effect of race and income on health insurance coverage in the US.

Data source

The household component of the US Medical Expenditure Panel Survey (MEPS-HC) of 2017 was used for the study.

Study design

Logistic regression models were used to estimate the associations between insurance coverage status and vulnerability measure, comparing insured with uninsured or insured for part of the year, insured for part of the year only, and uninsured only, respectively.

Data collection/extraction methods

We constructed a vulnerability measure that reflects the convergence of predisposing (race/ethnicity), enabling (income), and need (self-perceived health status) attributes of risk.

Principal findings

While income was a significant predictor of health insurance coverage (a difference of 6.1–7.2% between high- and low-income Americans), race/ethnicity was independently associated with lack of insurance. The combined effect of income and race on insurance coverage was devastating as low-income minorities with bad health had 68% less odds of being insured than high-income Whites with good health.

Conclusion

Results of the study could assist policymakers in targeting limited resources on subpopulations likely most in need of assistance for insurance coverage. Policymakers should target insurance coverage for the most vulnerable subpopulation, i.e., those who have low income and poor health as well as are racial/ethnic minorities.
Cross-cultural adaptation, reliability and validity of the Fremantle Knee Awareness Questionnaire in Italian subjects with painful knee osteoarthritis
Authors: Monticone Marco , Sconza Cristiano , Portoghese Igor , Nishigami Tomohiko , Wand Benedict M. , Sorrentino Gregorio , Lemorini Giulia , Respizzi Stefano , Giordano Andrea , Franchignoni Franco
Published: April 2021

Background and aim

Growing attention is being given to utilising physical function measures to better understand and manage knee osteoarthritis (OA). The Fremantle Knee Awareness Questionnaire (FreKAQ), a self-reported measure of body-perception specific to the knee, has never been validated in Italian patients. The aims of this study were to culturally adapt and validate the Italian version of the FreKAQ (FreKAQ-I), to allow for its use with Italian-speaking patients with painful knee OA.

Methods

The FreKAQ-I was developed by means of forward–backward translation, a final review by an expert committee and a test of the pre-final version to evaluate its comprehensibility. The psychometric testing included: internal structural validity by Rasch analysis; construct validity by assessing hypotheses of FreKAQ correlations with the knee injury and osteoarthritis outcome score (KOOS), a pain intensity numerical rating scale (PI-NRS), the pain catastrophising scale (PCS), and the Hospital anxiety and depression score (HADS) (Pearson’s correlations); known-group validity by evaluating the ability of FreKAQ scores to discriminate between two groups of participants with different clinical profiles (Mann–Whitney U test); reliability by internal consistency (Cronbach’s alpha) and test–retest reliability (intraclass correlation coefficient, ICC2.1); and measurement error by calculating the minimum detectable change (MDC).

Results

It took one month to develop a consensus-based version of the FreKAQ-I. The questionnaire was administered to 102 subjects with painful knee OA and was well accepted. Internal structural validity confirmed the substantial unidimensionality of the FreKAQ-I: variance explained was 53.3%, the unexplained variance in the first contrast showed an eigenvalue of 1.8, and no local dependence was detected. Construct validity was good as all of the hypotheses were met; correlations: KOOS (rho = 0.38–0.51), PI-NRS (rho = 0.35–0.37), PCS (rho = 0.47) and HADS (Anxiety rho = 0.36; Depression rho = 0.43). Regarding known-groups validity, FreKAQ scores were significantly different between groups of participants demonstrating high and low levels of pain intensity, pain catastrophising, anxiety, depression and the four KOOS subscales (p ≤ 0.004). Internal consistency was acceptable (α = 0.74) and test–retest reliability was excellent (ICC = 0.92, CI 0.87–0.94). The MDC95 was 5.22 scale points.

Conclusion

The FreKAQ-I is unidimensional, reliable and valid in Italian patients with painful knee OA. Its use is recommended for clinical and research purposes.
Impact of quality certification of multidisciplinary head and neck tumor centers
Authors: Modabber Ali , Schick Daniel , Goloborodko Evgeny , Peters Florian , Heitzer Marius , Bock Anna , Kniha Kristian , Hölzle Frank , Schreiber Elke M. , Möhlhenrich Stephan Christian
Published: April 2021

Background

Certification of multidisciplinary tumor centers is nowadays seen as the gold standard in modern oncological therapy for optimization and realization of guideline-based therapy and better outcomes. Single cases are reimbursed based on diagnosis-related groups (DRG). We aimed to review efficiency, cost analysis, and profitability following a certification.

Methods

Tumor board certification at the university hospital Aachen was implemented in 2013. We compared 1251 cases of oropharyngeal cancer treated from 2008 to 2017 before and after certification. For this purpose, several patient characteristics, surgery, and stay-related constants, as well as expenses and reimbursement heights were analyzed statistically.

Results

Following certification, the total case and patient number, surgery duration, hours of mechanical ventilation, case mix index points, DRG reimbursements as well as the costs increased significantly, whereas days of intensive care unit, amount of blood transfusions, patient clinical complexity level (PCCL) and the overall stay were significantly lowered. No changes were observed for the patient’s age and gender distribution. Also, the predetermined stay duration stayed constant.

Conclusions

Certification of head-neck tumor centers causes a concentration of more complex cases requiring higher surgical efforts, which can be processed more efficiently due to a higher level of professionalism. Despite their benefits in cancer care, without compensation, centers may be struggling to cover their expenses in a system, which continuously underestimates them.
Longitudinal trajectories of diet quality and subsequent mortality among Chinese adults: results from the China health and nutrition survey 1997–2015
Authors: Liu Ming-wei , McNaughton Sarah A. , He Qi-qiang , Leech Rebecca
Published: April 2021

Background

China has witnessed a significant nutritional transition. However, there is a gap in the literature investigating the association between change of diet and mortality among Chinese. Thus, we aimed to explore the longitudinal trajectories of diet quality over 10 years (from 1997 to 2006) and the subsequent risk of death till 2015 among Chinese adults.

Methods

Data from the China Health and Nutrition Survey were analyzed in 6398 adults. Dietary intake was assessed using three consecutive 24-h recalls. Diet quality was assessed by the Chinese Healthy Eating Index (CHEI), which includes 17 components and is based on the Dietary Guidelines for Chinese. Latent Class Growth Analysis was conducted to derive trajectories of diet quality over 10 years. Cox proportional hazard regression was used to calculate hazard ratios for total mortality.

Results

Four distinct CHEI trajectories were identified: 1) worsening; 2) low-moderate-low; 3) improving; 4) high-moderate-high. Group 3 had the lowest mortality rate (5.6%) in the subsequent 9 years, while the groups with worsening or low diet quality had a higher mortality rate (Group 1: 7.5%; Group 2: 10.8%). In the fully adjusted model, compared to group 2, mortality rates were lower for group 3 (RR = 0.73; 95% CI: 0.55, 0.97) and group 4 (RR = 0.76; 95% CI: 0.59, 0.98). No associations with mortality were found for the group 1, when compared to group 2.

Conclusions

Long-term improved diet quality and adherence to the Dietary Guidelines for Chinese may decrease the risk of death in Chinese adults.
Relationship between gait quality measures and modular neuromuscular control parameters in chronic post-stroke individuals
Authors: Shin Sung Yul , Kim Yusung , Jayaraman Arun , Park Hyung-Soon
Published: April 2021

Background

Recent evidence suggests that disinhibition and/or hyperexcitation of the brainstem descending pathways and intraspinal motor network diffuse spastic synergistic activation patterns after stroke. This results in simplified or merged muscle sets (i.e., muscle modules or synergies) compared to non-impaired individuals and this leads to poor walking performance. However, the relations of how these neuromuscular deficits influence gait quality (e.g., symmetry or natural walking patterns) are still unclear. The objective of this exploratory study was to investigate the relations of modular neuromuscular framework and gait quality measures in chronic stroke individuals.

Methods

Sixteen chronic post-stroke individuals participated in this study. Full lower body three-dimensional kinematics and electromyography (EMG) were concurrently measured during overground walking at a comfortable speed. We first examined changes in gait quality measures across the number of muscle modules using linear regression model. Then, a stepwise multiple regression was used to investigate the optimal combination of the neuromuscular parameters that associates with gait quality measures.

Results

We observed that subjects who had a lower number of muscle modules revealed reduced function (i.e., speed) and greater asymmetry in the kinematic parameters including limb length, footpath area, knee flexion/extension, and hip abduction/adduction (all p < 0.05). We also found that the combination of input variables from the modular neuromuscular control framework significantly associated with gait quality measures (average $${R}^{2}=42.5\mathrm{\%}$$

R

2

=
42.5
%

). Those variables included variability accounted for ($$VAF$$

VAF

) information from the muscle modules and area under the EMG envelope curves of the quadriceps (i.e., rectus femoris and vastus lateralis) and tibialis anterior muscles.

Conclusions

The results suggest that there exists a significant correlation between the neuromuscular control framework and the gait quality measures. This study helps to understand the underlying mechanism of disturbances in gait quality and provides insight for a more comprehensive outcome measure to assess gait impairment after stroke.
Discriminating the eight genotypes of the porcine circovirus type 2 with TaqMan-based real-time PCR
Authors: Link Ellen Kathrin , Eddicks Matthias , Nan Liangliang , Ritzmann Mathias , Sutter Gerd , Fux Robert
Published: April 2021

Background

The porcine circovirus type 2 (PCV2) is divided into eight genotypes including the previously described genotypes PCV2a to PCV2f and the two new genotypes PCV2g and PCV2h. PCV2 genotyping has become an important task in molecular epidemiology and to advance research on the prophylaxis and pathogenesis of PCV2 associated diseases. Standard genotyping of PCV2 is based on the sequencing of the viral genome or at least of the open reading frame 2. Although, the circovirus genome is small, classical sequencing is time consuming, expensive, less sensitive and less compatible with mass testing compared with modern real-time PCR assays. Here we report about a new PCV2 genotyping method using qPCR.

Methods

Based on the analysis of several hundred PCV2 full genome sequences, we identified PCV2 genotype specific sequences or single-nucleotide polymorphisms. We designed six TaqMan PCR assays that are specific for single genotypes PCV2a to PCV2f and two qPCRs targeting two genotypes simultaneously (PCV2g/PCV2d and PCV2h/PCV2c). To improve specific binding of oligonucleotide primers and TaqMan probes, we used locked nucleic acid technology. We evaluated amplification efficiency, diagnostic sensitivity and tested assay specificity for the respective genotypes.

Results

All eight PCV2 genotype specific qPCRs demonstrated appropriate amplification efficiencies between 91 and 97%. Testing samples from an epidemiological field study demonstrated a diagnostic sensitivity of the respective genotype specific qPCR that was comparable to a highly sensitive pan-PCV2 qPCR system. Genotype specificity of most qPCRs was excellent. Limited unspecific signals were obtained when a high viral load of PCV2b was tested with qPCRs targeting PCV2d or PCV2g. The same was true for the PCV2a specific qPCR when high copy numbers of PCV2d were tested. The qPCR targeting PCV2h/PCV2c showed some minor cross-reaction with PCV2d, PCV2f and PCV2g.

Conclusion

Genotyping of PCV2 is important for routine diagnosis as well as for epidemiological studies. The introduced genotyping qPCR system is ideal for mass testing and should be a valuable complement to PCV2 sequencing, especially in the case of simultaneous infections with multiple PCV2 genotypes, subclinically infected animals or research studies that require large sample numbers.
Obesity and intestinal stem cell susceptibility to carcinogenesis
Authors: Pourvali Katayoun , Monji Hadi
Published: April 2021

Background

Obesity is a top public health problem associated with an increase in colorectal cancer incidence. Stem cells are the chief cells in tissue homeostasis that self-renew and differentiate into other cells to regenerate the organ. It is speculated that an increase in stem cell pool makes cells susceptible to carcinogenesis. In this review, we looked at the recent investigations linking obesity/high-fat diet-induced obesity to intestinal carcinogenesis with regard to intestinal stem cells and their niche.

Findings

High-fat diet-induced obesity may rise intestinal carcinogenesis by increased Intestinal stem cells (ISC)/progenitor’s population, stemness, and niche independence through activation of PPAR-δ with fatty acids, hormonal alterations related to obesity, and low-grade inflammation. However, these effects may possibly relate to the interaction between fats and carbohydrates, and not a fatty acid per se. Nonetheless, literature studies are inconsistency in their results, probably due to the differences in the diet components and limitations of genetic models used.

Conclusion

High-fat diet-induced obesity affects carcinogenesis by changing ISC proliferation and function. However, a well-matched diet and the reliable colorectal cancer models that mimic human carcinogenesis is necessary to clearly elucidate the influence of high-fat diet-induced obesity on ISC behavior.
Massive parallel sequencing in a family with rectal cancer
Authors: Wallander Karin , Thutkawkorapin Jessada , Sahlin Ellika , Lindblom Annika , Lagerstedt-Robinson Kristina
Published: April 2021

Background

We have previously reported a family with a suspected autosomal dominant rectal and gastric cancer syndrome without any obvious causative genetic variant. Here, we focused the study on a potentially isolated rectal cancer syndrome in this family.

Methods

We included seven family members (six obligate carriers). Whole-exome sequencing and whole-genome sequencing data were analyzed and filtered for shared coding and splicing sequence and structural variants among the affected individuals.

Results

When considering family members with rectal cancer or advanced adenomas as affected, we found six new potentially cancer-associated variants in the genes CENPB, ZBTB20, CLINK, LRRC26, TRPM1, and NPEPL1. All variants were missense variants and none of the genes have previously been linked to inherited rectal cancer. No structural variant was found.

Conclusion

By massive parallel sequencing in a family suspected of carrying a highly penetrant rectal cancer predisposing genetic variant, we found six genetic missense variants with a potential connection to the rectal cancer in this family. One of them could be a high-risk genetic variant, or one or more of them could be low risk variants. The p.(Glu438Lys) variant in the CENPB gene was found to be of particular interest. The CENPB protein binds DNA and helps form centromeres during mitosis. It is involved in the WNT signaling pathway, which is critical for colorectal cancer development and its role in inherited rectal cancer needs to be further examined.
FDG-PET/CT in intensive care patients with bloodstream infection
Authors: Pijl Jordy P. , Londema Mark , Kwee Thomas C. , Nijsten Maarten W. N. , Slart Riemer H. J. A. , Dierckx Rudi A. J. O. , van der Voort Peter H. J. , Glaudemans Andor W. J. M. , Pillay Janesh
Published: April 2021

Background

2-Deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) is an advanced imaging technique that can be used to examine the whole body for an infection focus in a single examination in patients with bloodstream infection (BSI) of unknown origin. However, literature on the use of this technique in intensive care patients is scarce. The purpose of this study was to evaluate the diagnostic yield of FDG-PET/CT in intensive care patients with BSI.

Methods

In this retrospective cohort study, all intensive care patients from our Dutch university medical center who had culture-proven BSI between 2010 and 2020 and underwent FDG-PET/CT to find the focus of infection were included. Diagnostic performance was calculated and logistic regression analysis was performed to evaluate the association between FDG-PET/CT outcome and C-reactive protein level (CRP), leukocyte count, duration of antibiotic treatment, duration of ICU stay, quality of FDG-PET/CT, and dependency on mechanical ventilation. In addition, the impact of FDG-PET/CT on clinical treatment was evaluated.

Results

30 intensive care patients with BSI were included. In 21 patients, an infection focus was found on FDG-PET/CT which led to changes in clinical management in 14 patients. FDG-PET/CT achieved a sensitivity of 90.9% and specificity of 87.5% for identifying the focus of infection. Poor quality of the FDG-PET images significantly decreased the likelihood of finding an infection focus as compared to reasonable or good image quality (OR 0.16, P = 0.034). No other variables were significantly associated with FDG-PET/CT outcome. No adverse events during the FDG-PET/CT procedure were reported.

Conclusion

FDG-PET/CT has a high diagnostic yield for detecting the infection focus in patients with BSI admitted to intensive care. Poor PET image quality was significantly associated with a decreased likelihood of finding the infection focus in patients with BSI. This could be improved by adequate dietary preparation and cessation of intravenous glucose and glucose-regulating drugs. Recent advances in PET/CT technology enable higher image quality with shorter imaging time and may contribute to routinely performing FDG-PET/CT in intensive care patients with BSI of unknown origin.
Correction to: Calling for improved quality in the registration of traditional Chinese medicine during the public health emergency: a survey of trial registries for COVID-19, H1N1, and SARS
Authors:   on behalf of the Evidence-based Traditional and Integrative Medicine Working Group for Public Health Emergency, Kuang Zhuoran , Li Xiaoyan , Cai Jianxiong , Chen Yaolong , Qiu Xiaoyuan , Ni Xiaojia
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.