bluuebunny/crossref_metadata_2025 huggingface dataset:
Platform work in Europe: Lessons learned, legal developments and challenges ahead
Authors: Aloisi Antonio
Published: January 2022

Several years since first emerging in Europe, platform work continues to represent a ‘social dilemma’ for workers, social partners, policymakers and society as a whole. As a result of intense litigation, analysis and reporting, much is known about the contractual and working conditions in this growing labour market segment. While the European Union (EU) institutions are considering adopting a new Directive based on Art. 153 TFEU, there are a number of significant top-down and bottom-up national cases worth discussing. Workers across Europe have been reclassified by many courts; some governments have taken regulatory initiatives to address the risk of precariousness and have implemented new comprehensive legal instruments to safeguard a level playing field for both workers and platforms. This article discusses how existing and new domestic and EU labour law provisions can improve the labour conditions of platform workers. Its overarching goal is to address possible policy gaps and the implications for EU social law by exploring the lessons that can be drawn from recent policies and legal developments.

Section two briefly touches upon the policymaking initiatives in France, Spain and Italy. Moreover, it presents and reviews the main outcomes of litigation at the domestic level, focusing on the pervasive role played by algorithmic management. After introducing the Pillar of Social Rights (EPSR), section three critically analyses two key achievements at the EU level: the Directive on transparent and predictable working conditions and the Recommendation on access to social protection for workers and the self-employed. Section four explores the elasticity of the triad of Directives that regulate atypical forms of employment (part-time, fixed-term and temporary agency work). It is argued that the narrow construction of the Directives’ scope of application could represent an obstacle. However, an adaptive and purposive approach by the Court of Justice of the European Union (CJEU) could result in the classification of platform workers as falling within the scope of the social acquis in certain fields. Finally, section five concludes by providing concrete policy proposals focussed on cross-border issues, algorithmic transparency, the introduction of a presumption of employment status and collective bargaining.
Evaluation of step-down oral antibiotic therapy for uncomplicated streptococcal bloodstream infections on clinical outcomes
Authors: Kang Amy , Beuttler Richard , Minejima Emi
Published: January 2022

Background:

Despite the severity and frequency of streptococcal bloodstream infections (BSIs), the effectiveness of oral definitive therapy remains unknown. The objective of this study was to evaluate the clinical outcomes of step-down oral antibiotics for the treatment of uncomplicated streptococcal BSIs.

Methods:

In this retrospective cohort study, adult patients admitted with uncomplicated streptococcal BSI between June 2015 and June 2017 were included. Patients were excluded if they received <48 h of antibiotic therapy; therapy was started >48 h after first positive culture; had complicated infections of endocarditis, bone and joint infections, or central nervous system infections; Pitt bacteremia score (PBS) ⩾ 4; or failed to respond to effective therapy necessitating continued intravenous (IV) therapy. Patients were grouped by receipt of step-down oral antibiotic therapy (PO group) versus continued IV therapy (IV group). Outcomes included hospital length of stay (LOS), 30-day recurrence of BSI, 30-day readmission, 30-day all-cause mortality, and catheter-related or drug-related adverse events (AEs).

Results:

Of 244 patients included, 40% received step-down oral therapy ( n = 98). Overall, the most common source of BSI was pneumonia (22%), followed by skin and soft tissue infections (SSTI) (18%). Severity of illness measured by intensive care unit (ICU) admission and PBS was similar. The IV group had significantly longer LOS [median 10 (interquartile range [IQR] = 5–21) versus 5 (4–6) days, p < 0.01] compared with the PO group. BSI recurrence, readmission, all-cause mortality within 30 days, and AEs were similar between the groups ( p = ns).

Conclusion:

In uncomplicated streptococcal BSI, patients treated with step-down oral antibiotic therapy had significantly shorter LOS compared with continued IV therapy without compromise of clinical outcomes.
Feeling and Learning: A Study of Students’ Emotions in the Sonography Classroom
Authors: Kurtz Abby
Published: January 2022

Objective:

The aim of this study was to explore the phenomenon of academic emotions experienced by sonography students.

Materials and Methods:

In this hermeneutic phenomenological study, in-depth, semi-structured phenomenological interviews were conducted to learn about participants’ emotional experiences while learning sonography. Thematic analysis was utilized in an effort to understand participants’ experiences with the phenomenon.

Results:

This study yielded the following interpretive themes: (1) the classroom emotional climate impacts students’ thoughts about learning sonography, (2) academic emotions can either boost or detract from students’ interest, motivation, and enthusiasm for the course material, and (3) relationships with their teachers matter to sonography students.

Conclusion:

An increased awareness of the interrelatedness of emotion and cognition in sonography education would benefit not only sonography educators and students but ultimately the patients whom those students will care for by improving the quality of education that students receive.
Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome: an EBMT Inborn Errors Working Party analysis
Authors: Albert Michael H. , Slatter Mary A. , Gennery Andrew R. , Güngör Tayfun , Bakunina Katerina , Markovitch Benyamin , Hazelaar Sheree , Sirait Tiarlan , Courteille Virginie , Aiuti Alessandro , Aleinikova Olga V. , Balashov Dmitry , Bernardo Maria Ester , Bodova Ivana , Bruno Benedicte , Cavazzana Marina , Chiesa Robert , Fischer Alain , Hauck Fabian , Ifversen Marianne , Kałwak Krzysztof , Klein Christoph , Kulagin Alexander , Kupesiz Alphan , Kuskonmaz Baris , Lindemans Caroline A. , Locatelli Franco , Lum Su Han , Maschan Alexey , Meisel Roland , Moshous Despina , Porta Fulvio , Sauer Martin G. , Sedlacek Petr , Schulz Ansgar , Suarez Felipe , Vallée Tanja C. , Winiarski Jacek H. , Zecca Marco , Neven Bénédicte , Veys Paul , Lankester Arjan C.
Published: January 2022

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for patients affected by Wiskott-Aldrich syndrome (WAS). Reported HSCT outcomes have improved over time with respect to overall survival, but some studies have identified older age and HSCT from alternative donors as risk factors predicting poorer outcome. We analyzed 197 patients undergoing transplant at European Society for Blood and Marrow Transplantation centers between 2006 and 2017 who received conditioning as recommended by the Inborn Errors Working Party (IEWP): either busulfan (n = 103) or treosulfan (n = 94) combined with fludarabine ± thiotepa. After a median follow-up post-HSCT of 44.9 months, 176 patients were alive, resulting in a 3-year overall survival of 88.7% and chronic graft-versus-host disease (GVHD)-free survival (events include death, graft failure, and severe chronic GVHD) of 81.7%. Overall survival and chronic GVHD-free survival were not significantly affected by conditioning regimen (busulfan- vs treosulfan-based), donor type (matched sibling donor/matched family donor vs matched unrelated donor/mismatched unrelated donor vs mismatched family donor), or period of HSCT (2006-2013 vs 2014-2017). Patients aged <5 years at HSCT had a significantly better overall survival. The overall cumulative incidences of grade III to IV acute GVHD and extensive/moderate/severe chronic GVHD were 6.6% and 2.1%, respectively. Patients receiving treosulfan-based conditioning had a higher incidence of graft failure and mixed donor chimerism and more frequently underwent secondary procedures (second HSCT, unconditioned stem cell boost, donor lymphocyte infusion, or splenectomy). In summary, HSCT for WAS with conditioning regimens currently recommended by IEWP results in excellent survival and low rates of GVHD, regardless of donor or stem cell source, but age ≥5 years remains a risk factor for overall survival.
ddRAD-seq reveals the genetic structure and detects signals of selection in Italian brown trout
Authors: Magris Gabriele , Marroni Fabio , D’Agaro Edo , Vischi Massimo , Chiabà Cristina , Scaglione Davide , Kijas James , Messina Maria , Tibaldi Emilio , Morgante Michele
Published: January 2022

Background

Brown trout is one of the most widespread fresh-water fish species in Europe. The evolutionary history of and phylogenetic relationships between brown trout populations are complex, and this is especially true for Italian populations, which are heavily influenced in different ways by stocking practices. The characterization of the genetic structure of Italian brown trout populations may give information on the risk of losing endemic Italian populations due to lack of genetic diversity or to admixture with stocking populations. The identification of signatures of selection, and the information deriving from dense genotyping data will help genotype-informed breeding programs. We used a ddRAD-seq approach to obtain more than 100,000 single nucleotide polymorphisms (SNPs), and to characterize the population structure and signatures of selection in 90 brown trout samples.

Results

Italian brown trout populations are genetically differentiated, although the stocking practices have introduced strong admixture in endemic Italian trout, especially with the Atlantic lineage. Most of the analysed populations showed high levels of kinship and inbreeding. We detected putative signatures of selection using different approaches, and investigated if the regions were enriched for functional categories. Several regions putatively under selection and characterized by a reduction in heterozygosity across all the studied populations are enriched for genes involved in the response to viral infections.

Conclusions

Our results, which show evidence of admixture with the Atlantic lineage (commonly used for stocking), confirm the need for controlling stocking practices, in order to avoid the erosion of the endemic gene pool; given the apparently high levels of kinship and inbreeding in local populations, our results also show the need to take action for increasing gene diversity. In addition, we used the genetically-distinct lineages to detect signatures of selection and we identified putative signatures of selection in several regions associated with resistance to infectious diseases. These constitute candidate regions for the study of resistance to infections in wild and farmed trout.
NanoBRET in C. elegans illuminates functional receptor interactions in real time
Authors: Groß Victoria Elisabeth , Gershkovich Miron Mikhailowitsch , Schöneberg Torsten , Kaiser Anette , Prömel Simone
Published: January 2022

Background

Protein-protein interactions form the basis of every organism and thus, investigating their dynamics, intracellular protein localization, trafficking and interactions of distinct proteins such as receptors and their ligand-binding are of general interest. Bioluminescence resonance energy transfer (BRET) is a powerful tool to investigate these aspects in vitro. Since in vitro approaches mostly neglect the more complex in vivo situation, we established BRET as an in vivo tool for studying protein interactions in the nematode C. elegans.

Results

We generated worms expressing NanoBRET sensors and elucidated the interaction of two ligand-G protein-coupled receptor (GPCR) pairs, the neuropeptide receptor NPR-11 and the Adhesion GPCR LAT-1. Furthermore, we adapted the enhanced bystander BRET technology to measure subcellular protein localization. Using this approach, we traced ligand-induced internalization of NPR-11 in vivo.

Conclusions

Our results indicate that in vivo NanoBRET is a tool to investigate specific protein interactions and localization in a physiological setting in real time in the living organism C. elegans.
Context dependency of nucleotide probabilities and variants in human DNA
Authors: Liang Yuhu , Grønbæk Christian , Fariselli Piero , Krogh Anders
Published: January 2022

Background

Genomic DNA has been shaped by mutational processes through evolution. The cellular machinery for error correction and repair has left its marks in the nucleotide composition along with structural and functional constraints. Therefore, the probability of observing a base in a certain position in the human genome is highly context-dependent.

Results

Here we develop context-dependent nucleotide models. We first investigate models of nucleotides conditioned on sequence context. We develop a bidirectional Markov model that use an average of the probability from a Markov model applied to both strands of the sequence and thus depends on up to 14 bases to each side of the nucleotide. We show how the genome predictability varies across different types of genomic regions. Surprisingly, this model can predict a base from its context with an average of more than 50% accuracy. For somatic variants we show a tendency towards higher probability for the variant base than for the reference base. Inspired by DNA substitution models, we develop a model of mutability that estimates a mutation matrix (called the alpha matrix) on top of the nucleotide distribution. The alpha matrix can be estimated from a much smaller context than the nucleotide model, but the final model will still depend on the full context of the nucleotide model. With the bidirectional Markov model of order 14 and an alpha matrix dependent on just one base to each side, we obtain a model that compares well with a model of mutability that estimates mutation probabilities directly conditioned on three nucleotides to each side. For somatic variants in particular, our model fits better than the simpler model. Interestingly, the model is not very sensitive to the size of the context for the alpha matrix.

Conclusions

Our study found strong context dependencies of nucleotides in the human genome. The best model uses a context of 14 nucleotides to each side. Based on these models, a substitution model was constructed that separates into the context model and a matrix dependent on a small context. The model fit somatic variants particularly well.
Comparative genomic analyses of Polymyxin-resistant Enterobacteriaceae strains from China
Authors: He Zhien , Yang Yongqiang , Li Wei , Ma Xiaoling , Zhang Changfeng , Zhang Jingxiang , Sun Baolin , Ding Tao , Tian Guo-bao
Published: January 2022

Background

Mobile colistin resistance like gene (mcr-like gene) is a new type of polymyxin resistance gene that can be horizontally transferred in the Enterobacteriaceae. This has brought great challenges to the treatment of multidrug-resistant Escherichia coli and K. pneumoniae.

Results

K. pneumoniae 16BU137 and E. coli 17MR471 were isolated from the bus and subway handrails in Guangzhou, China. K. pneumoniae 19PDR22 and KP20191015 were isolated from patients with urinary tract infection and severe pneumonia in Anhui, China. Sequence analysis indicated that the mcr-1.1 gene was present on the chromosome of E. coli 17MR471, and the gene was in the gene cassette containing pap2 and two copies of ISApl1.The mcr-1.1 was found in the putative IncX4 type plasmid p16BU137_mcr-1.1 of K. pneumoniae 16BU137, but ISApl1 was not found in its flanking sequence. Mcr-8 variants were found in the putative IncFIB/ IncFII plasmid pKP20191015_mcr-8 of K. pneumoniae KP20191015 and flanked by ISEcl1 and ISKpn26.

Conclusion

This study provides timely information on Enterobacteriaceae bacteria carrying mcr-like genes, and provides a reference for studying the spread of mcr-1 in China and globally.
Prevalence of Hepatitis B Virus infection and associated factors among female sex workers using respondent-driven sampling in Hawassa City, Southern Ethiopia
Authors: Daka Deresse , Hailemeskel Getahun , Fenta Demissie Assegu
Published: January 2022

Background

Female sex workers (FSWs) are a marginalized group notoriously having limited healthcare access and poor-quality care. Inevitably, they are vulnerable to sexually transmitted infections including hepatitis B virus. However; Hepatitis B virus infection is one of the most serious infections and major public health problem considered to be at soaring risk for transmission and acquisition of the infection. Hence, this study was aimed to assess the prevalence and associated factors of HBV infections among FSWs in southern Ethiopia.

Methods

A cross-sectional study was conducted from November to February 2019 at Hawassa city in ISHDO confidential clinic among 383 FSWs. Respondent-drivenconsecutivesampling was used to select study participants using a standardized questionnaire. Blood sample was collected and viral surface antigen was detected using ELISA from separated serum. Data were entered to SPSS version 21.0. Descriptive and logistic regression analyses were used.

Result

The overall prevalence of FSWs who were tested for HBV using ELISA was 35(9.2%) (95% CI: 6.3–12.1). Among 381 FSWs 249(65.4%) were stayed for 2–5 years in sexual work and 240(63%) of them were used condom consistently during sexual practice. In multivariate logistic regression analysis, FSWs who didn’t use condom were six and two times more risk full to acquire HBV than those who used condom commonly (AOR = 6.38, CI 2.04–18.51) and condom breakage (AOR = 2.10, CI 1.95–4.65), during sexual practice respectively. Similarly, use of stimulants (AOR = 3.25, CI 1.59–18.63), previous history of STI (AOR = 2.15, CI 1.02–6.93), genital ulcer (AOR = 4.64, CI 1.31–11.35), number of sexual partners (AOR = 3.25, CI 1.59–7.47), sex during menses (AOR = 5.85, CI (1.29–21.44), sexual assault (AOR = 2.93, CI 1.23–9.01), sharp material sharing, (AOR = 4.98, CI 1.34–10.95) and history of abortion, (AOR = 2.46, CI 1.18, 12.19), were statistically associated with HBV infection. Factors such as age, residence, and alcohol consumption were not associated with HBV infection.

Conclusion

The prevalence of HBV infection in this study was relatively high compared to the general population. Factors like sociodemographic, behavioral, and previous history-related information were associated with HBV infection shows the need for ongoing screening of high-risk population to inform planning for vaccination and preventive measures.
Development of a new serotyping ELISA for Toxoplasma gondii type II, type III and Africa 1 lineages using in silico peptide discovery methods, well categorized feline and human outbreak serum samples
Authors: Can Hüseyin , Aksoy Gökmen Ayşegül , Döşkaya Mert , Erkunt Alak Sedef , Değirmenci Döşkaya Aysu , Karakavuk Muhammet , Köseoğlu Ahmet Efe , Karakavuk Tuğba , Gül Ceren , Güvendi Mervenur , Gül Aytül , Gürüz Adnan Yüksel , Kaya Selçuk , Mercier Aurélien , Ün Cemal
Published: January 2022

Background

Discovery of new Toxoplasma gondii serotyping epitopes is important due to reports showing the influence of genotype on the severity of toxoplasmosis. In Turkey, genotypes belonging to type II, type III and Africa 1 lineages were mainly detected. The present study focused on to find out epitopes with high discriminative capacity to serotype these genotypes using well characterized strains isolated from Turkey.

Methods

To meet this objective, GRA6 and GRA7 genes were sequenced from strains belonging to the type II, III and Africa 1 lineages, and B cell epitopes inside these sequences were predicted by Bcepred and additional docking analysis was performed with B cell receptor. Based on these analyses, 22 peptides harboring lineage specific epitopes were synthesized. Then, the serotyping potency of these peptides was tested using peptide ELISA and well categorized serum samples collected from stray cats infected with genotypes of the different lineages type II (n:9), III (n:1) and Africa 1 (n:1). As a result of peptide-ELISA, a serotyping schema was constructed with peptides that show high discriminative capacity and this assay was validated by sera collected from humans after an outbreak (n:30) and mother/newborn pair sera (n:3). Later, the validated serotyping schema was used to serotype a larger group of human (n:38) and cat (n:24) sera.

Results

Among 22 peptides, GRA6II/c, GRA7III/d, and GRA6 Africa 1/b epitopes have shown discriminative capacity. During the validation of peptide-ELISA, the serotype of toxoplasmosis outbreak and mother/newborn cases were detected to be serotype II. Moreover, the analyses in a larger group showed that serotype II was prevalent in humans and stray cats.

Conclusions

Overall, the results showed that the serotyping schema could be successfully used to serotype T. gondii infections caused by type II, III and Africa 1 genotype.
Ceftazidime and cefepime antagonize 5-fluorouracil’s effect in colon cancer cells
Authors: Pfab Christina , Abgaryan Anush , Danzer Barbara , Mourtada Fatme , Ali Weaam , Gessner André , El-Najjar Nahed
Published: January 2022

Background

Drug-drug interaction (DDI), which can occur at the pharmacokinetics and/or the pharmacodynamics (PD) levels, can increase or decrease the therapeutic or adverse response of a drug itself or a combination of drugs. Cancer patients often receive, along their antineoplastic agents, antibiotics such as ß-lactams to treat or prevent infection. Despite the narrow therapeutic indices of antibiotics and antineoplastic agents, data about their potential interaction are insufficient. 5-fluorouracil (5-FU), widely used against colon cancer, is known for its toxicity and large intra- and inter- individual variability. Therefore, knowledge about its interaction with antibiotics is crucial.

Methods

In this study, we evaluated at the PD levels, against HCT-116 colon cancer cells, DDI between 5-FU and several ß-lactams (ampicillin, benzypenicillin, piperacillin, meropenem, flucloxacillin, ceftazidime (CFT), and cefepime (CFP)), widely used in intensive care units. All drugs were tested at clinically achieved concentrations. MTT assay was used to measure the metabolic activity of the cells. Cell cycle profile and apoptosis induction were monitored, in HCT-116 and DLD-1 cells, using propidium iodide staining and Caspase-3/7 activity assay. The uptake of CFT and CFP by the cells was measured using LC-MS/MS method.

Results

Our data indicate that despite their limited uptake by the cells, CFT and CFP (two cephalosporins) antagonized significantly 5-FU-induced S-phase arrest (DLD-1 cells) and apoptosis induction (HCT-116 cells). Remarkably, while CFP did not affect the proliferation of colon cancer cells, CFT inhibited, at clinically relevant concentrations, the proliferation of DLD-1 cells via apoptosis induction, as evidenced by an increase in caspase 3/7 activation. Unexpectedly, 5-FU also antagonized CFT’s induced cell death in DLD-1 cells.

Conclusion

This study shows that CFP and CFT have adverse effects on 5-FU’s action while CFT is a potent anticancer agent that inhibits DLD-1 cells by inducing apoptotic cell death. Further studies are needed to decipher the mechanism(s) responsible for CFT’s effects against colon cancer as well as the observed antagonism between CFT, CFP, and 5-FU with the ultimate aim of translating the findings to the clinical settings.
Number of negative lymph nodes with a positive impact on survival of stage III colon cancer; a retrospective observation study for right side and left side colon
Authors: Kuo Yi-Hung , You Jeng-Fu , Hung Hsin-Yuan , Chin Chih-Chien , Chiang Jy-Ming , Chang Chia-Hao
Published: January 2022

Background

The purpose was to examine the effect of negative lymph nodes (NLN) number on survival in stage III colon cancer. To reduce the interference of acute inflammation, we included patients with stage III colon cancer who had undergone elective surgery and excluded those who had tumor perforation, obstruction, ischemia, or massive tumor bleeding.

Methods

This retrospective cohort study included 2244 patients with stage III colon cancer between 1995 and 2016 at a single center. The effect of NLN on 5-year relapse-free survival (RFS), 5-year overall survival (OS), and comparison of multivariate factors was assessed according to tumor locations.

Results

The two optimal cutoff values of NLN for proximal and distal colon, namely 27 and 12, were determined by plotting the time-dependent receiver operating characteristic curve. Overall, 499 of 891 and 1020 of 1353 patients with right-side and left-side colon cancer, respectively, had high NLN. In right-side colon cancer, patients with high NLN (≥ 27) had superior OS (74.9% vs. 62.7%, P <  0.001) and RFS (75.0% vs. 61.9%, P <  0.001) than did those with low NLN. Moreover, in left-side colon cancer, patients with high NLN (≥12) experienced significantly superior OS (80.8% vs. 68.6%, P <  0.001) and RFS (77.3% vs. 66.2%, P <  0.001) than did those with low NLN. Among the different subgroups of stage III colon cancer, the high NLN group showed significantly superior RFS and OS in stage IIIB (RFS: 77.0% vs. 68.0%, P = 0.001; OS: 78.6% vs. 67.9%, P <  0.001) and IIIC (RFS: 58.2% vs. 44.1%, P = 0.001; OS: 65.7% vs. 51.1%, P <  0.001) colon cancer. However, in stage IIIA colon cancer, high NLN only showed survival benefit in OS (91.5% vs. 89.8%, P = 0.041). Multivariate analyses confirmed that high NLN, high carcinoembryonic antigen (≥ 5 ng/mL) level, and stage IIIC status are three independent prognostic factors in both the proximal and distal colon.

Conclusions

NLN is a crucial prognostic factor for stage III colon cancer in various tumor locations or in the subgroups of stage III disease. In advanced stage III colon cancer, the importance of NLN and its role in anti-cancer immune response could be highlighted.
Efficacy of vision therapy for unilateral refractive amblyopia in children aged 7–10 years
Authors: Hsieh Yi-Ching , Liao Wen-Ling , Tsai Yi-Yu , Lin Hui-Ju
Published: January 2022

Background

There is a critical period for visual development, conventionally considered to be the first 6 years of life. Children aged 7 years and older are significantly less responsive to amblyopia treatment. This study investigated the efficacy of binocular vision therapy in amblyopic children aged 7–10 years.

Methods

This retrospective study enrolled 36 children with unilateral amblyopia who were divided into a case group (receiving vision therapy, optical correction, and part-time patching of the weaker eye) and a control group (receiving optical correction and part-time patching of the weaker eye). Visual acuity (VA) was measured at baseline, at the 3-month, 6-month, and 9-month visits, and 3 months after cessation of treatment.

Results

There were 19 subjects in the case group and 17 subjects in the control group. Mean VA in the case group improved from 0.39 ± 0.24 logMAR at baseline to 0.10 ± 0.23 logMAR at the endpoint of treatment (p < 0.001, paired t-test). Mean VA in the control group improved from 0.64 ± 0.30 logMAR at baseline to 0.52 ± 0.27 logMAR at the endpoint of treatment (p = 0.015, paired t-test). The improvement was significantly greater in the case group than in the control group (p = 0.006, two-samples independent t-test). All subjects underwent follow-up examinations within 6 to 12 months. There was no regression of VA in the case group 3 months after cessation of vision therapy. The patients in the case group who received visual therapy were with better VA improvement then patients with only optic correction and patching.

Conclusions

Vision therapy combined with conventional treatment (optical correction and part-time patching) is more effective than conventional treatment alone in children aged 7–10 years with unilateral refractive amblyopia. The treatment results not only in greater vision gain, but also in shorter duration of treatment.
Effectiveness of non-bedside teaching during the COVID-19 pandemic: a quasi-experimental study
Authors: Heitmann Henrik , Wagner Philipp , Fischer Elisabeth , Gartmeier Martin , Schmidt-Graf Friederike
Published: January 2022

Background

The COVID-19 pandemic poses a huge challenge for clinical teaching due to contact restrictions and social distancing. Medical teachers have to balance potential risks and benefits of bedside teaching, especially in course formats intended to foster practical clinical skills. In this context, we aimed to address the question, whether presence-based teaching formats without patient involvement are suitable to teach practical skills.

Methods

In this quasi-experimental study, presence-based teaching formats with and without patient contact were retrospectively compared regarding their effects on medical students’ theoretical knowledge and practical skills, i.e. the performance and clinical interpretation of the neurological exam. To this end, evaluations from 102 students and their lecturers participating in a neurological bedside teaching course at a German university hospital between October 2020 and April 2021 were obtained. Students were initially randomly assigned to course dates. However, 53 students assigned to courses in November and December 2020, were not able to go bedside due to contact restrictions. These students formed the interventional group and the remaining 49 students the control group. The primary outcome measures were students’ overall grading of the course (school grades, 1–6) as well as ratings of knowledge and skills provided by the students themselves and their lecturers on a numerical rating scale (0–10). Comparison between groups was performed using frequentist and Bayesian t-statistics.

Results

The teaching format without patient contact received a significantly poorer overall grade by the students (p = 0.018). However, improvements in the students’ self-ratings of knowledge and skills did not differ between the two formats (all p > 0.05, BF10max = 0.42). Moreover, especially practical skills were even rated significantly better in the group without patient contact by the lecturers (p < 0.001).

Conclusions

Teaching formats without patient contact are less well-received by the students. However, they are able to teach practical skills regarding the performance and clinical interpretation of examination techniques. Still, the evaluations obtained might not adequately capture the importance of bedside teaching in preparing future physicians for their practice. Perspectively, hybrid teaching approaches including flipped-classroom concepts hold considerable potential to enhance effectiveness of bedside teaching in the present pandemic situation and in the future.
E-health literacy in older adults: an evolutionary concept analysis
Authors: Jung Sun Ok , Son Yoon Hee , Choi Eunju
Published: January 2022

Background

Internet technologies have become important for older adults to not only seek, understand, and evaluate information on health management but also apply and share acquired knowledge. Despite the disparity in e-health literacy among older adults, which affects health outcomes, its conceptual definition has not been distinctly clarified in previous studies. This study aimed to analyse the concept of e-health literacy among older adults and to identify its contexts in the nursing field.

Methods

We identified concepts, attributes, antecedents, and consequences of e-health literacy in older adults using Rodgers’ evolutionary approach to various fields of study, time, and cultural differences. A literature search was conducted using the National Assembly Library, Research Information Sharing Service, National Digital Science Library, DataBase Periodical Information Academic, PubMed, Cumulative Index to Nursing and Allied Health Literature, Excerpta Medica database, and Cochrane.

Results

A total of 28 studies were included, and we categorised the following three attributes: active information seeking, two-way interactive communication, and information utilization/sharing. The antecedents included personal factors, health status, socioeconomic factors, cultural factors, and attitudes toward the Internet while the consequences included increased health interest, health behaviour promotion, and active decision-making.

Conclusions

As e-health literacy in older adults affects their health and quality of life, this study clarifies the concept and provides a conceptual framework for nursing practice and research. Further studies are needed to identify and expand the constantly evolving concept of e-health literacy in older adults.
Overcoming institutionalised barriers to digital health systems: an autoethnographic case study of the judicialization of a digital health tool
Authors: Mureyi Dudzai
Published: January 2022

Background

The deployment of digital health systems may be impeded by barriers that are, or are linked to underlying enduring institutions. Attempting to challenge the barriers without addressing the underpinning institution may be ineffective. This study reflects on ways actors may surmount institutionalised barriers to the uptake of digital tools in health systems.

Methods

I applied Institutional theory concepts to an autoethnographic case study of efforts to introduce a digital tool to provide citizens with medicines information.

Results

The tool’s uptake was impeded because of state regulators’ institutionalised interpretation of pharmaceutical advertising laws, which rendered the tool illegal. I, along with allies beyond the health sector, successfully challenged the regulators’ institutionalised interpretation of pharmaceutical advertising laws through various actions. These actions included: framing the tool as legal and constitutional, litigation, and redefining these concepts: ‘advertising’, ‘health institution’, and the role of regulatory bodies vis a vis innovation.

Conclusion

After identifying a barrier as being institutionalised or linked to an institution, actors might challenge such barriers by engaging in institutional work; i.e. deliberate efforts to challenge the relevant institution (e.g. a law, norm or shared belief). Institutional work may require the actions of multiple actors within and beyond the health sector, including judicial actors. Such cross-sectoral alliances are efficacious because they provide institutional workers with a broader range of strategies, framings, concepts and forums with which to challenge institutionalised barriers. However, actors beyond the health system (e.g. the judiciary) must be inquisitive about the potential implications of the digital health interventions they champion. This case justifies recent calls for more deliberate explorations within global health scholarships and practice, of synergies between law and health.
Use and diagnostic outcomes of cancer patient pathways in Denmark – is the place of initial diagnostic work-up an important factor?
Authors: Damhus Christina Sadolin , Siersma Volkert , Birkmose Anna Rubach , Dalton Susanne Oksbjerg , Brodersen John
Published: January 2022

Introduction

The Cancer Patient Pathway for Non-specific Symptoms and Signs of Cancer (NSSC-CPP) has been implemented in Denmark with regional and intra-regional differences. In some places, the initial diagnostic work-up (often including a CT scan) is performed by general practitioners (GPs) and in others by hospitals. Variations may influence the use of Organ Specific Cancer Patient Pathways (OS-CPPs) and prognostic outcomes for the patients. Therefore, the aims were: 1) To analyse how a CT scan referred from GP or hospital is followed by OS-CPPs and NSSC-CPPs at the national and regional level, and 2) To analyse, nationally and regionally, the diagnostic outcomes of persons referred to CT scan by either GP or hospital six months after and mortality one year after CT scan.

Methods

A nationwide population-based study including individuals with a first CT scan in 2013-2016, either referred from GP or hospital.

Results

Overall, individuals with a CT scan referred from GPs were more likely to start a NSSC-CPP or an OS-CPP than individuals with a CT scan referred by hospitals. Across the five Regions in Denmark, CT scans referred by GPs were associated with reduced odds of total mortality in all regions; (North, OR=0.78 [0.73 0.83], Central, OR=0.92 [0.87 0.96], South, OR=0.85 [0.81 0.89], Capital, OR=0.96 [0.91 1.00] and Zealand, OR=0.85 [0.79 0.90]) and increased odds of cancer-specific mortality in four regions, ORs ranging from 1.15-1.51 with no difference in Region North (1.00 [0.91 1.10]).

Conclusion

No obvious association between more CT scans and CPPs and reduced diagnoses and mortality was observed. The different diagnostic models might not explain the prognostic outcomes, but the different use of CT scans in, and between Regions play a large role in the differences in incidence and mortality.
High-level production of the agmatine in engineered Corynebacterium crenatum with the inhibition-releasing arginine decarboxylase
Authors: Yang Fengyu , Xu Jiayu , Zhu Yichun , Wang Yi , Xu Meijuan , Rao Zhiming
Published: January 2022

Background

Agmatine is a member of biogenic amines and is an important medicine which is widely used to regulate body balance and neuroprotective effects. At present, the industrial production of agmatine mainly depends on the chemical method, but it is often accompanied by problems including cumbersome processes, harsh reaction conditions, toxic substances production and heavy environmental pollution. Therefore, to tackle the above issues, arginine decarboxylase was overexpressed heterologously and rationally designed in Corynebacterium crenatum to produce agmatine from glucose by one-step fermentation.

Results

In this study, we report the development in the Generally Regarded as Safe (GRAS) l-arginine-overproducing C. crenatum for high-titer agmatine biosynthesis through overexpressing arginine decarboxylase based on metabolic engineering. Then, arginine decarboxylase was mutated to release feedback inhibition and improve catalytic activity. Subsequently, the specific enzyme activity and half-inhibitory concentration of I534D mutant were increased 35.7% and 48.1%, respectively. The agmatine production of the whole-cell bioconversion with AGM3 was increased by 19.3% than the AGM2. Finally, 45.26 g/L agmatine with the yield of 0.31 g/g glucose was achieved by one-step fermentation of the engineered C. crenatum with overexpression of speAI534D.

Conclusions

The engineered C. crenatum strain AGM3 in this work was proved as an efficient microbial cell factory for the industrial fermentative production of agmatine. Based on the insights from this work, further producing other valuable biochemicals derived from l-arginine by Corynebacterium crenatum is feasible.
LINC00665 up-regulates SIN3A expression to modulate the progression of colorectal cancer via sponging miR-138-5p
Authors: Nan Shoushan , Zhang Shuangxia , Jin Rong , Wang Juelei
Published: January 2022

Background

Colorectal cancer (CRC) is a malignant tumor affecting people worldwide. Long noncoding RNAs (lncRNAs) is a crucial factor modulating various cancer progression, including CRC. Long intergenic non-protein coding RNA 665 (LINC00665) has been proven as an oncogene in several cancers, but its function in CRC is still unclear.

Methods

QRT-PCR was performed for RNA quantification. Functional assays were designed and carried to test cell phenotype while mechanism experiments were adopted for detecting the interaction of LINC00665, microRNA-138-5p (miR-138-5p) and SIN3 transcription regulator family member A (SIN3A). In vivo experiments were conducted to test LINC00665 function on modulating CRC tumor progression.

Results

LINC00665 displayed high expression in CRC tissues and cells, and promoted tumor progression in vivo. MiR-138-5p displayed abnormally low expression in CRC, and was verified to be sponged by LINC00665. Furthermore, SIN3A, as the downstream mRNA of miR-138-5p, exerted promoting impacts on CRC cells. Rescue experiments certified that overexpressed SIN3A or silenced miR-138-5p could offset the repressed function of LINC00665 knockdown on CRC progression.

Conclusions

LINC00665 could sponge miR-138-5p to up-regulate SIN3A expression, thus accelerating CRC progression.

Graphic abstract
Progress in cancer drug delivery based on AS1411 oriented nanomaterials
Authors: Tong Xin , Ga Lu , Ai Jun , Wang Yong
Published: January 2022

Targeted cancer therapy has become one of the most important medical methods because of the spreading and metastatic nature of cancer. Based on the introduction of AS1411 and its four-chain structure, this paper reviews the research progress in cancer detection and drug delivery systems by modifying AS1411 aptamers based on graphene, mesoporous silica, silver and gold. The application of AS1411 in cancer treatment and drug delivery and the use of AS1411 as a targeting agent for the detection of cancer markers such as nucleoli were summarized from three aspects of active targeting, passive targeting and targeted nucleic acid apharmers. Although AS1411 has been withdrawn from clinical trials, the research surrounding its structural optimization is still very popular. Further progress has been made in the modification of nanoparticles loaded with TCM extracts by AS1411.

Graphical Abstract
TGF-β1 inhibits human trophoblast cell invasion by upregulating kisspeptin expression through ERK1/2 but not SMAD signaling pathway
Authors: Fang Lanlan , Yan Yang , Gao Yibo , Wu Ze , Wang Zhen , Yang Sizhu , Cheng Jung-Chien , Sun Ying-Pu
Published: January 2022

Background

Tightly regulation of extravillous cytotrophoblast (EVT) cell invasion is critical for the placentation and establishment of a successful pregnancy. Insufficient EVT cell invasion leads to the development of preeclampsia (PE) which is a leading cause of maternal and perinatal mortality and morbidity. Transforming growth factor-beta1 (TGF-β1) and kisspeptin are expressed in the human placenta and have been shown to inhibit EVT cell invasion. Kisspeptin is a downstream target of TGF-β1 in human breast cancer cells. However, whether kisspeptin is regulated by TGF-β1 and mediates TGF-β1-suppressed human EVT cell invasion remains unclear.

Methods

The effect of TGF-β1 on kisspeptin expression and the underlying mechanisms were explored by a series of in vitro experiments in a human EVT cell line, HTR-8/SVneo, and primary cultures of human EVT cells. Serum levels of TGF-β1 and kisspeptin in patients with or without PE were measured by ELISA.

Results

TGF-β1 upregulates kisspeptin expression in HTR-8/SVneo cells and primary cultures of human EVT cells. Using pharmacological inhibitor and siRNA, we demonstrate that the stimulatory effect of TGF-β1 on kisspeptin expression is mediated via the ALK5 receptor. Treatment with TGF-β1 activates SMAD2/3 canonical pathways as well as ERK1/2 and PI3K/AKT non-canonical pathways. However, only inhibition of ERK1/2 activation attenuates the stimulatory effect of TGF-β1 on kisspeptin expression. In addition, siRNA-mediated knockdown of kisspeptin attenuated TGF-β1-suppressed EVT cell invasion. Moreover, we report that serum levels of TGF-β1 and kisspeptin are significantly upregulated in patients with PE.

Conclusions

By illustrating the potential physiological role of TGF-β1 in the regulation of kisspeptin expression, our results may serve to improve current strategies used to treat placental diseases.
Effects of focus training on heart rate variability in post-stroke fatigue patients
Authors: Wang Yao , Xiao Gonglian , Zeng Qing , He Mingjun , Li Fei , Lin Jiaxin , Luo Xun , Wang Yulong
Published: January 2022

Objective

This study discusses the effects of focus training on heart rate variability (HRV) in post-stroke fatigue (PoSF) patients.

Methods

Self-generate physiological coherence system (SPCS) was used for the focus training of PoSF patients for 12 weeks. Then, fatigue severity scale (FSS), Hamilton depression scale (HAMD), HRV and satisfaction scale (SASC-19) before and after the training were assessed.

Results

Compared with the control group, FSS score, HAMD score, RMSSD, PNN50% were significantly lower in the research group at the end of the intervention (P < 0.05); SDNN, SDANN, LF, HF, LF/HF intervention satisfaction rate increased significantly in the research group at the end of the intervention (P < 0.05).

Conclusion

The use of SPCS software during the focus training of PoSF patients reduced the fatigue and depression, meanwhile improved the HRV of the patients. Therefore, these patients were greatly satisfied with the intervention.
Transforming Nepal’s primary health care delivery system in global health era: addressing historical and current implementation challenges
Authors: Adhikari Bipin , Mishra Shiva Raj , Schwarz Ryan
Published: January 2022

Nepal’s Primary Health Care (PHC) is aligned vertically with disease control programs at the core and a vast network of community health workers at the periphery. Aligning with the globalization of health and the factors affecting global burden of diseases, Nepal echoes the progressive increase in life expectancy, changes in diseases patterns, including the current impact of COVID-19. Nepal’s health system is also accommodating recent federalization, and thus it is critical to explore how the primary health care system is grappling the challenges amidst these changes. In this review, we conducted a narrative synthesis of literature to explore the challenges related to transformation of Nepal’s primary health care delivery system to meet the demands incurred by impact of globalization and recent federalization, covering following database: PubMED, Embase and Google Scholar. Of the 49 articles abstracted for full text review, 37 were included in the analyses. Existing theories were used for constructing the conceptual framework to explain the study findings. The results are divided into four themes. Additional searches were conducted to further support the narrative synthesis: a total of 46 articles were further included in the articulation of main findings. Transforming Nepal’s primary health care system requires a clear focus on following priority areas that include i) Revised efforts towards strengthening of community based primary health care units; ii) Adapting vertical programs to federal governance; iii) Reinforcing the health insurance scheme; and iv) Strengthening an existing network of community health workers and health human resources. This review discusses how these broad goals bear challenges and opportunities.