bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Auxenochlorella protothecoides acyltransferases and potential of their protein interactions to promote the enrichment of oleic acid
Authors: Liu Kui , Li Jinyu , Xing Chao , Yuan Hongli , Yang Jinshui
Published: April 2023

Background

After centuries of heavy reliance on fossil fuel energy, the world suffers from an energy crisis and global warming, calling for carbon emission reduction and a transition to clean energy. Microalgae have attracted much attention as a potential feedstock for biofuel production due to their high triacylglycerol content and CO2 sequestration ability. Many diacylglycerol acyltransferases (DGAT) species have been characterized, which catalyze the final committed step in triacylglycerol biosynthesis. However, the detailed structure–function features of DGATs and the role of the interactions among DGAT proteins in lipid metabolism remained largely unknown.

Results

In this study, the three characterized DGATs of Auxenochlorella protothecoides 2341 showed distinct structural and functional conservation. Functional complementation analyses showed that ApDGAT1 had higher activity than ApDGAT2b in yeast and model microalgae, and ApDGAT2a had no activity in yeast. The N-terminus was not essential to the catalysis function of ApDGAT1 but was crucial to ApDGAT2b as its enzyme activity was sensitive to any N-terminus modifications. Similarly, when acyl-CoA binding proteins (ACBPs) were fused to the N-terminus of ApDGAT1 and ApDGAT2b, zero and significant activity changes were observed, respectively. Interestingly, the ApACBP3 + ApDGAT1 variant contributed to higher oil accumulation than the original DGAT1, and ApACBP1 + ApDGAT1 fusion boosted oleic acid content in yeast. Overexpression of the three DGATs and the variation of ApACBP3 + ApDGAT1 increased the content of C18:1 of Chlamydomonas reinhardtii CC-5235. Significantly, ApDGAT1 interacted with itself, ApDGAT2b, and ApACBP1, which indicated that these three lipid metabolic proteins might have been a part of a dynamic protein interactome that facilitated the enrichment of oleic acid.

Conclusions

This study provided new insights into the functional and structural characteristics of DGATs and elucidated the importance of these physical interactions in potential lipid channeling.
Parvicapsula pseudobranchicola in the northeast Pacific Ocean is rare in farmed Atlantic salmon Salmo salar despite widespread occurrence and pathology in wild Pacific salmon Oncorhynchus spp.
Authors: Jones Simon R. M. , Low Jessica C. , Goodall Aidan
Published: April 2023

Background

Infection with the myxozoan parasite Parvicapsula pseudobranchicola causes disease in wild and farmed salmonids in Norway. In the northeast Pacific Ocean, the parasite has been reported in Pacific salmon Oncorhynchus spp. without evidence of disease. The objectives of the present study were to confirm the identity of P. pseudobranchicola in the Pacific, document its host and geographic ranges, and describe associated pathological changes.

Methods

Ocean-entry year wild pink salmon Oncorhynchus gorbuscha, chum salmon O. keta, Chinook salmon O. tshawytscha, coho salmon O. kisutch and sockeye salmon O. nerka were collected in summer and autumn surveys near Vancouver Island (VI) and from a winter survey in the Gulf of Alaska. Samples were also obtained from farmed Atlantic salmon Salmo salar and Chinook salmon near VI. Samples were analysed by qPCR and histology using conventional staining or in situ hybridisation. Parasite sequence was obtained from small subunit ribosomal RNA gene (SSU rDNA).

Results

Identical 1525 base-pair SSU rDNA sequences from infected pink salmon, chum salmon and Chinook salmon shared 99.93% identity with a P. pseudobranchicola sequence from Norwegian Atlantic salmon. In autumn surveys, the prevalence was greatest in chum salmon (91.8%) and pink salmon (85.9%) and less so in Chinook salmon (68.8%) and sockeye salmon (8.3%). In farmed salmon, the prevalence was zero in Atlantic salmon (n = 967) and 41% in Chinook salmon (n = 118). Infections were preferentially sited in pseudobranch and visualised by in situ hybridisation. Heavy parasite burdens in all species of Pacific salmon were inconsistently associated with focal granulomatous pseudobranchitis.

Conclusions

In the northeast Pacific, widespread occurrence of P. pseudobranchicola in Pacific salmon together with its absence or sporadic occurrence in farmed Atlantic salmon differs from its epidemiology in Norway, despite similar pathological development in the pseudobranch. Consequences of the infections to the health of wild Pacific salmon, identity of the invertebrate host and the distribution and abundance of infective actinospores are unknown and remain high priorities for research.

Graphical Abstract
Five-mer peptides prevent short-term spatial memory deficits in Aβ25-35-induced Alzheimer’s model mouse by suppressing Aβ25-35 aggregation and resolving its aggregate form
Authors: Nakamura Rina , Konishi Motomi , Higashi Youichirou , Saito Motoaki , Akizawa Toshifumi
Published: April 2023

Background

The development of drugs for Alzheimer’s disease (AD), which is related to the misfolding and aggregation of amyloid-β (Aβ), is high in demand due to the growing number of AD patients. In this study, we screened 22 kinds of 5-mer synthetic peptides derived from the Box A region of Tob1 protein to find a peptide effective against Aβ aggregation.

Methods

A Thioflavin T (ThT) assay was performed to evaluate aggregation and screen aggregation inhibitors. Male ICR mice (6 weeks old) were administered saline, 9 nmol Aβ25-35, or a mixture of 9 nmol Aβ25-35 and 9 nmol GSGFK in the right lateral ventricle. Short-term spatial memory was assessed through Y-maze. Microglia cells (BV-)2 cells were plated on 24-well plates (4 × 104 cells/well) and incubated for 48 h, and then, the cells were treated with 0.01, 0.05, 0.1, 0.2, or 0.5 mM GSGFK. After incubation for 24 h, bead uptake was evaluated using a laser confocal microscope and Cytation 5.

Results

We found two kinds of peptides, GSGNR and GSGFK, that were not only suppressed by aggregation of Aβ25-35 but also resolved the aggregated Aβ25-35. Results obtained from the Y-maze test on an Aβ25-35-induced AD model mouse indicated that GSGFK prevents the deficits in short-term memory induced by Aβ25-35. The effect of GSGFK on phagocytosis in BV-2 cells proved that GSGFK activates the phagocytic ability of microglia.

Conclusions

In conclusion, 5-mer peptides prevent short-term memory deficit in Aβ25-35 induced AD model mouse by reducing the aggregated Aβ25-35. They may also upregulate the phagocytic ability of microglia, which makes 5-mer peptides suitable candidates as therapeutic drugs against AD.
Amyloidosis: a case series and review of the literature
Authors: Senecal Justin B. , Abou-Akl Romel , Allevato Pat , Mazzetti Ian , Hamm Caroline , Parikh Richa , Woldie Indryas
Published: April 2023

Background

Systemic amyloidosis is group of disorders characterized by the accumulation of insoluble proteins in tissues. The most common form of systemic amyloidosis is light chain amyloidosis, which results from the accumulation of misfolded immunoglobulins. The disease is progressive, with treatment targeted at the underlying plasma cell dyscrasia. Since essentially any organ system can be affected, the presentation is variable and delays in diagnosis are common. Given this diagnostic difficulty, we discuss four different manifestations of light chain amyloidosis.

Case presentations

In this case series, we discuss four cases of light chain amyloidosis. These include cardiac, hepatic, and gastrointestinal as well as autonomic and peripheral nerve involvement with amyloidosis. The patients in our series are of Caucasian background and include a  69-year-old female, a 29-year-old female, a 68-year-old male, and a 70-year-old male, respectively. The case discussions highlight variability in presentation and diagnostic challenges.

Conclusions

Amyloidosis is a rare but serious disease that is often complicated by long delays in diagnosis. Morbidity and mortality can sometimes be limited if diagnosed earlier. We hope our real life cases will contribute to understanding and to early suspicion that can lead to early diagnosis and management.
Understanding and addressing populations whose prior experience has led to mistrust in healthcare
Authors: Even Dan , Shvarts Shifra
Published: April 2023

Background

Policy makers need to maintain public trust in healthcare systems in order to foster citizen engagement in recommended behaviors and treatments. The importance of such commitment has been highlighted by the recent COVID-19 pandemic. Central to public trust is the extent of the accountability of health authorities held responsible for long-term effects of past treatments. This paper addresses the topic of manifestations of trust among patients damaged by radiation treatments for ringworm.

Methods

For this mixed-methods case study (quan/qual), we sampled 600 files of Israeli patients submitting claims to the National Center for Compensation of Scalp Ringworm Victims in the years 1995–2014, following damage from radiation treatments received between 1946 and 1960 in Israel and/or abroad. Qualitative data were analyzed with descriptive statistics, and correlations were analyzed with chi-square tests. Verbal data were analyzed by the use of systematic content analysis.

Results

Among 527 patients whose files were included in the final analysis, 42% held authorities responsible. Assigning responsibility to authorities was more prevalent among claimants born in Israel than among those born and treated abroad (χ2 = 6.613, df = 1, p = 0.01), claimants reporting trauma (χ2 = 4.864, df = 1, p = 0.027), and claimants living in central cities compared with those in suburban areas (χ2 = 18.859, df = 6, p < 0.01). Men, younger claimants, patients with a psychiatric diagnosis, and patients from minority populations expressed mistrust in health regulators.

Conclusions

Examining populations' perceived trust in healthcare institutions and tailoring health messages to vulnerable populations can promote public trust in healthcare systems.
Long-term expansion of human hematopoietic stem cells
Authors: Liang Guixian , Liu Feng
Published: April 2023

Hematopoietic stem cells (HSCs) are critical for the treatment of a variety of hematological diseases. However, the low number of HSCs lead to the clinical application difficult. To gain more functional human HSCs ex vivo, Sakurai et al. established a recombinant-cytokine-free and albumin-free culture system, i.e. PCL-PVAc-PEG-based culture, in combination with 740Y-P, butyzamide and UM171, to improve the long-term expansion of human cord blood HSCs.
A systematic outbreak investigation of SARS-CoV-2 transmission clusters in a tertiary academic care center
Authors: von Rotz Matthias , Kuehl Richard , Durovic Ana , Zingg Sandra , Apitz Anett , Wegner Fanny , Seth-Smith Helena M. B. , Roloff Tim , Leuzinger Karoline , Hirsch Hans H. , Kuster Sabine , Battegay Manuel , Mariani Luigi , Schaeren Stefan , Bassetti Stefano , Banderet-Uglioni Florian , Egli Adrian , Tschudin-Sutter Sarah
Published: April 2023

Background

We sought to decipher transmission pathways in healthcare-associated infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within our hospital by epidemiological work-up and complementary whole genome sequencing (WGS). We report the findings of the four largest epidemiologic clusters of SARS-CoV-2 transmission occurring during the second wave of the pandemic from 11/2020 to 12/2020.

Methods

At the University Hospital Basel, Switzerland, systematic outbreak investigation is initiated at detection of any nosocomial case of SARS-CoV-2 infection, as confirmed by polymerase chain reaction, occurring more than five days after admission. Clusters of nosocomial infections, defined as the detection of at least two positive patients and/or healthcare workers (HCWs) within one week with an epidemiological link, were further investigated by WGS on respective strains.

Results

The four epidemiologic clusters included 40 patients and 60 HCWs. Sequencing data was available for 70% of all involved cases (28 patients and 42 HCWs), confirmed epidemiologically suspected in house transmission in 33 cases (47.1% of sequenced cases) and excluded transmission in the remaining 37 cases (52.9%). Among cases with identical strains, epidemiologic work-up suggested transmission mainly through a ward-based exposure (24/33, 72.7%), more commonly affecting HCWs (16/24, 66.7%) than patients (8/24, 33.3%), followed by transmission between patients (6/33, 18.2%), and among HCWs and patients (3/33, 9.1%, respectively two HCWs and one patient).

Conclusions

Phylogenetic analyses revealed important insights into transmission pathways supporting less than 50% of epidemiologically suspected SARS-CoV-2 transmissions. The remainder of cases most likely reflect community-acquired infection randomly detected by outbreak investigation. Notably, most transmissions occurred between HCWs, possibly indicating lower perception of the risk of infection during contacts among HCWs.
Serum vascular endothelial growth factor affects tissue fluid accumulation and is associated with deteriorating tissue perfusion and oxygenation in severe sepsis: a prospective observational study
Authors: Lin Chin-Kuo , Tsai Ying-Huang , Kao Kuo-Chin , Lin Chieh-Mo , Zhou Shao-Kui , Ho Meng-Chin , Huang Shu-Yi , Fang Yu-Hung , Chang Che-Chia , Lee Wei-Chun , Lee Yueh-Lin , Chen Min-Chi , Hsieh Meng-Jer , Lin Yu-Ching , Hung Ming-Szu , Kuo Wen-Chun , Lin Bor-Shyh
Published: April 2023

Background

Positive fluid balance and tissue fluid accumulation are associated with adverse outcomes in sepsis. Vascular endothelial growth factor (VEGF) increases in sepsis, promotes vascular permeability, and may affect tissue fluid accumulation and oxygenation. We used near-infrared spectroscopy (NIRS) to estimate tissue hemoglobin (Hb) oxygenation and water (H2O) levels to investigate their relationship with serum VEGF levels.

Material and methods

New-onset severe sepsis patients admitted to the intensive care unit were enrolled. Relative tissue concentrations of oxy-Hb ([HbO2]), deoxy-Hb ([HbR]), total Hb ([HbT]), and H2O ([H2O]) were estimated by near-infrared spectroscopy (NIRS) for three consecutive days and serum VEGF levels were measured. Comparisons between oliguric and non-oliguric patients were conducted and the correlations between variables were analyzed.

Results

Among 75 eligible patients, compared with non-oliguric patients, oliguric patients were administrated more intravascular fluids (median [IQR], 1926.00 [1348.50–3092.00] mL/day vs. 1069.00 [722.00–1486.75] mL/day, p < 0.001) and had more positive daily net intake and output (mean [SD], 1,235.06 [1303.14] mL/day vs. 313.17 [744.75] mL/day, p = 0.012), lower [HbO2] and [HbT] over the three-day measurement (analyzed by GEE p = 0.01 and 0.043, respectively) and significantly higher [H2O] on the third day than on the first two days (analyzed by GEE p = 0.034 and 0.018, respectively). Overall, serum VEGF levels were significantly negatively correlated with [HbO2] and [HbT] (rho = − 0.246 and − 0.266, p = 0.042 and 0.027, respectively) but positively correlated with [H2O] (rho = 0.449, p < 0.001). Subgroup analysis revealed a significant correlation between serum VEGF and [H2O] in oliguric patients (rho = 0.532, p = 0.003). Multiple regression analysis determined the independent effect of serum VEGF on [H2O] (standardized coefficient = 0.281, p = 0.038).

Conclusions

In severe sepsis, oliguria relates to higher positive fluid balance, lower tissue perfusion and oxygenation, and progressive tissue fluid accumulation. Elevated serum VEGF is associated with worsening tissue perfusion and oxygenation and independently affects tissue fluid accumulation.
Mucin-microbiome signatures shape the tumor microenvironment in gastric cancer
Authors: Oosterlinck Baptiste , Ceuleers Hannah , Arras Wout , De Man Joris G. , Geboes Karen , De Schepper Heiko , Peeters Marc , Lebeer Sarah , Skieceviciene Jurgita , Hold Georgina L. , Kupcinskas Juozas , Link Alexander , De Winter Benedicte Y. , Smet Annemieke
Published: April 2023

Background and aims

We aimed to identify mucin-microbiome signatures shaping the tumor microenvironment in gastric adenocarcinomas and clinical outcomes.

Methods

We performed high-throughput profiling of the mucin phenotypes present in 108 gastric adenocarcinomas and 20 functional dyspepsia cases using validated mucin-based RT-qPCRs with subsequent immunohistochemistry validation and correlated the data with clinical outcome parameters. The gastric microbiota was assessed by 16S rRNA gene sequencing, taxonomy, and community composition determined, microbial networks analyzed, and the metagenome inferred in association with mucin phenotypes and expression.

Results

Gastric adenocarcinomas with an intestinal mucin environment or high-level MUC13 expression are associated with poor survival. On the contrary, gastric MUC5AC or MUC6 abundance was associated with a more favorable outcome. The oral taxa Neisseria, Prevotella, and Veillonella had centralities in tumors with intestinal and mixed phenotypes and were associated with MUC13 overexpression, highlighting their role as potential drivers in MUC13 signaling in GC. Furthermore, dense bacterial networks were observed in intestinal and mixed mucin phenotype tumors whereas the lowest community complexity was shown in null mucin phenotype tumors due to higher Helicobacter abundance resulting in a more decreased diversity. Enrichment of oral or intestinal microbes was mucin phenotype dependent. More specifically, intestinal mucin phenotype tumors favored the establishment of pro-inflammatory oral taxa forming strong co-occurrence networks.

Conclusions

Our results emphasize key roles for mucins in gastric cancer prognosis and shaping microbial networks in the tumor microenvironment. Specifically, the enriched oral taxa associated with aberrant MUC13 expression can be potential biomarkers in predicting disease outcomes.
Anti-aging of phenolic-rich Acanthus ebracteatus Vahl. extracts
Authors: Kanlayavattanakul Mayuree , Chaikul Puxvadee , Kongkow Mattaka , Iempridee Tawin , Lourith Nattaya
Published: April 2023

Background

Sea holly has long been used in traditional Thai medicine for longevity, skin inflammation, skin dullness and as a treatment for itchy skin. The white flower cultivar Acanthus ebracteatus Vahl. has been documented to perform better remedies than the purple flower A. ilicifolius. Nonetheless, preparation of the phenolic-rich extract of A. ebracteatus, including safety and cellular assessments relevant for inflammation and aging treatment is sparingly presented. In this study, the extracts of A. ebracteatus were prepared and comparatively quantified on total phenolic contents. In vitro activities by means of ABTS, DPPH, FRAP and mushroom tyrosinase inhibitory assays were undertaken. The extracts were UPLC analyzed and examined on cellular safety and activities.

Results

The phenolic-rich extracts of A. ebracteatus were prepared and standardized in verbascoside. The extracts were noted to have in vitro antioxidant and anti-tyrosinase activities. Cellular activities, co-cultures and ex vivo human skin appointed for cutaneous aging treatment, i.e., photoaging, are promising including antioxidant, anti-melanogenesis, anti-inflammatory (IL-6 and IL-8), anti-MMP and collagen production stimulating as well as anti-senescence activities.

Conclusions

Sea holly is highlighted as a potential source for beneficial cutaneous phenolics, especially verbascoside. The extracts were proven to be safe and efficient for cutaneous aging treatment indicated by their antioxidant, anti-melanogenesis, collagen stimulating, anti-inflame and anti-senescence activities. The plant extracts are therefore appointed for use as innovative agents for anti-aging purposes.

Graphical Abstract
In situ isolation of nuclei or nuclear proteins from adherent cells: a simple, effective method with less cytoplasmic contamination
Authors: Qin Ying , Zhou Yun , Wang Kun , Gu Jiaxuan , Xiong Zhihao , Zhang Wendiao , Chen Yong
Published: April 2023

Background

Isolation of nuclei or nuclear proteins is a prerequisite for western blot, nuclear proteome profiling, and other evaluations of nuclear proteins. Here, we developed a simple method for in situ isolation of nuclei or nuclear proteins by in situ removing the extranuclear part of adherent cells via a classical nonionic detergent triton X-100.

Results

First, the feasibility of our method was confirmed by confocal microscopy, atomic force microscopy, scanning electron microscopy, dynamic light scattering, immunofluorescence imaging, and time-lapse dynamic observation. Next, the optimal concentration range (approximately 0.1–1% for ~ 10 min) of triton X-100 and the optimal treatment time (< 30 min) of 0.1–1% Triton X-100 for our method were determined via western blotting of eight extra-/intra-nuclear proteins. Subsequently, the effectiveness, sensitivity, and cytoplasmic contamination of our method were tested by investigating the levels of phosphorylated p65 (a NF-κB subunit) in the nuclei of endothelial or tumor cells treated with/without lipopolysaccharide (LPS) via western blotting and by comparing with a commercial nuclear protein extraction kit (a classical detergent-based method). The data show that compared with the commercial kit our method obtained a higher yield of total nuclear proteins, a higher pP65 level in both control and LPS groups, and much lower content of GAPDH (as a reference for cytoplasmic contamination) in nuclei.

Conclusions

The in situ isolation of nuclei or nuclear proteins from adherent cells in this study is a simple, effective method with less cytoplasmic contamination. This method/strategy has the potential of improving the quality of downstream evaluations including western blotting and proteomic profiling.
Feasibility and acceptability of an evidence-informed digital intervention to support self-management in people with non-alcoholic fatty liver disease: protocol for a non-randomised feasibility study (VITALISE)
Authors: Avery Leah , Smith Hollie , McPherson Stuart , Hallsworth Kate
Published: April 2023

Background

Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of disease ranging from simple fatty liver to non-alcoholic steatohepatitis, cirrhosis, liver cancer and liver failure. NAFLD affects up to 30–40% of adults in Western countries and is directly linked to overweight and obesity. There are no approved drugs to specifically target NAFLD, therefore weight loss achieved through changes in dietary and physical activity behaviours is the recommended management approach. However, achieving and sustaining weight loss is challenging for patients with NAFLD. We developed a NAFLD-specific digital lifestyle intervention (VITALISE) to target changes in dietary and physical activity behaviours of patients with NAFLD to initiate weight loss and weight loss maintenance. This study aims to evaluate the feasibility and acceptability of VITALISE in a secondary care clinical setting.

Methods

A single-centre, one-arm, prospective design will be used to assess the feasibility and acceptability of recruitment, uptake, engagement and completion of VITALISE. Health-related outcomes will be assessed at baseline and 6-months. An interim measure of self-reported weight, physical activity and self-efficacy will be recorded at 12-weeks. Qualitative semi-structured interviews conducted at 6 months follow up will further explore acceptability and feasibility and fidelity of receipt and enactment. The study aims to recruit 35 patients with newly diagnosed NAFLD over a 6-month time period. Eligible patients will have continuous access to VITALISE and monthly tele-coaching support for 6 months prior to follow-up with a hepatologist.

Discussion

VITALISE offers access to evidence and theory-informed tailored dietary and physical activity support for patients with NAFLD. The intervention is designed for use by patients in their own time, outside of the hospital setting to overcome well documented challenges including attending additional appointments, and lack of time during routine appointments to adequately address lifestyle behaviour change. This feasibility study will determine the feasibility of VITALISE to support clinical care delivery.

Trial registration

ISRCTN12893503.
Assessment of artificial intelligence-aided computed tomography in lung cancer screening
Authors: Aboelenin Noha A. , Elserafi Ahmed , Zaki Noha , Rashed Essam A. , al-Shatouri Mohammad
Published: April 2023

Background

Lung cancer is one of the most common causes of cancer-related deaths in developed and developing countries. Therefore, early detection of lung cancer has a significant impact on lung cancer surveillance. Interpretation of lung CT scans for cancer screening is considered an intensive task for most radiologists, and long experience is required for accurate diagnosis through visual processing. This cross-sectional study introduces automated CAD software (Careline Soft’s AVIEW Metric software). This software can detect and classify lung nodules in CT scans. The performance of a deep learning (DL) model embedded in that software will be compared with that of the radiologists. Also, the feasibility of lung cancer screening protocol is evaluated in Suez Canal University Hospital, Ismailia, Egypt, by implementing Lung Imaging Reporting and Data System (Lung-RADS).

Results

As for the detection of the pulmonary nodules, the initial review by the CAD system (without validation by the researcher radiologist) has high sensitivity (93.0%) and specificity (95.5%) with overall accuracy of 93.6%. After review of the automatically detected nodules by the researcher radiologist was done, the final CAD has higher sensitivity (98.2%) and comparable specificity (95.5%) for the detection of pulmonary nodules with overall accuracy of 97.4%. As for lung cancer screening (categorization of Lung-RADS 3 and 4 nodules), unrevised initial computer-aided detection has 97.9% specificity and 96.9% for lung cancer screening with overall accuracy of 97.4%. After second look and review of the CAD result by the researcher radiologist, there is total agreement in total number of nodules and categorization of Lung-RADS 3 and 4. This gives an excellent agreement of 88.6% (κ = 0.951) between the CAD system and reference radiologist in the overall categorization of all lung nodules according to Lung-RADS classification.

Conclusions

The application of CAD system demonstrated increased sensitivity and specificity for the detection of lung nodules and total agreement in the detection of suspicious and probably benign nodules (lung cancer screening) and excellent level of agreement in the overall lung nodule categorization (Lung-RADS).
Refining Expert Recommendations for Implementing Change (ERIC) strategy surveys using cognitive interviews with frontline providers
Authors: Yakovchenko Vera , Chinman Matthew J. , Lamorte Carolyn , Powell Byron J. , Waltz Thomas J. , Merante Monica , Gibson Sandra , Neely Brittney , Morgan Timothy R. , Rogal Shari S.
Published: April 2023

Background

The Expert Recommendations for Implementing Change (ERIC) compilation includes 73 defined implementation strategies clustered into nine content areas. This taxonomy has been used to track implementation strategies over time using surveys. This study aimed to improve the ERIC survey using cognitive interviews with non-implementation scientist clinicians.

Methods

Starting in 2015, we developed and fielded annual ERIC surveys to evaluate liver care in the Veterans Health Administration (VA). We invited providers who had completed at least three surveys to participate in cognitive interviews (October 2020 to October 2021). Before the interviews, participants reviewed the complete 73-item ERIC survey and marked which strategies were unclear due to wording, conceptual confusion, or overlap with other strategies. They then engaged in semi-structured cognitive interviews to describe the experience of completing the survey and elaborate on which strategies required further clarification.

Results

Twelve VA providers completed surveys followed by cognitive interviews. The “Engage Consumer” and “Support Clinicians” clusters were rated most highly in terms of conceptual and wording clarity. In contrast, the “Financial” cluster had the most wording and conceptual confusion. The “Adapt and Tailor to Context” cluster strategies were considered to have the most redundancy. Providers outlined ways in which the strategies could be clearer in terms of wording (32%), conceptual clarity (51%), and clarifying the distinction between strategies (51%).

Conclusions

Cognitive interviews with ERIC survey participants allowed us to identify and address issues with strategy wording, combine conceptually indistinct strategies, and disaggregate multi-barreled strategies. Improvements made to the ERIC survey based on these findings will ultimately assist VA and other institutions in designing, evaluating, and replicating quality improvement efforts.
Biosimilar Use Among 38 ASCO PracticeNET Practices, 2019-2021
Authors: Bourbeau Brian , Lyman Gary H. , Lei Xiudong Jennifer , Jones Lee , Rosenthal Jon , Kozlik Mary May , Oettel Kurt R. , Tinger Alfred , Page Ray
Published: April 2023

PURPOSE

Biosimilars offer increased patient choice and potential cost-savings, compared with originator biologics. We studied 3 years of prescribed biologics among US physician practices to determine the relationship of practice type and payment source to oncology biosimilar use.

METHODS

We acquired biologic utilization data from 38 practices participating in PracticeNET. We focused on six biologics (bevacizumab, epoetin alfa, filgrastim, pegfilgrastim, rituximab, and trastuzumab) for the period from 2019 to 2021. We complemented our quantitative analysis with a survey of PracticeNET participants (prescribers and practice leaders) to reveal potential motivators and barriers to biosimilar use. We implemented logistic regression to evaluate the biosimilar use for each biologic, with covariates including time, practice type, and payment source, and accounted for clusters of practices.

RESULTS

Use of biosimilars increased over the 3-year period, reaching between 51% and 80% of administered doses by the fourth quarter of 2021, depending on the biologic. Biosimilar use varied by practice, with independent physician practices having higher use of biosimilars for epoetin alfa, filgrastim, rituximab, and trastuzumab. Compared with commercial health plans, Medicaid plans had lower biosimilar use for four biologics; traditional Medicare had lower use for five biologics. The average cost per dose decreased between 24% and 41%, dependent on the biologic.

CONCLUSION

Biosimilars have, through increased use, lowered the average cost per dose of the studied biologics. Biosimilar use differed by originator biologic, practice type, and payment source. There remains further opportunity for increases in biosimilar use among certain practices and payers.
Immigrant Wealth Stratification and Return Migration: The Case of Mexican Immigrants in the United States During the Twentieth Century
Authors: Sheftel Mara Getz
Published: April 2023

Considerable wealth stratification exists between U.S.-born and foreign-born populations (Campbell and Kaufman 2006), with low wealth attainment documented among Mexican immigrants (Hao 2007). High rates of Mexican return migration (Azose and Raftery 2019) suggest that nonrandom selection into return migration on wealth is a potential driver of stratification. Existing theories do not conclusively predict asset accumulation among returnees versus stayers, and empirical research on return migration and wealth stratification is scarce. Combining data from the 2000 U.S. Health and Retirement Study and the 2001 Mexican Health and Aging Study to create a novel data set representing all Mexicans aged 50 and older with a history of migration to the United States and adopting a life course perspective, I find that return migration at younger and older ages is associated with higher wealth accumulation and might be a way to maximize assets at older ages. Thus, return migration may contribute to nativity-based wealth stratification in the United States. The study's findings point to the greater financial risks for new cohorts of immigrants aging in place, suggest caution in interpreting wealth stratification as a measure of mobility, and inform theories about the links between return migration and wealth across the life course.
Defender of the Nation, Champion of Science: The Agency for Defense Development as a Nexus for the Technological Transformation of South Korea
Authors: Kwon Peter Banseok
Published: April 2023

The Agency for Defense Development (ADD) has functioned as South Korea’s central institute for weapons research and development (R&D) since 1970, when it was established by the Park Chung Hee regime (1961–79). As argued in this article, this quasi-private, quasi-public military institute also fostered major advancements of science and technology during the transformative decade of South Korea’s “militarized industrialization,” the 1970s, with a lasting impact on the private sector and business relations with the state. Drawing from in-person interviews with living scientists who worked on military projects of the Park state, as well as official records of the ADD and recently declassified government documents, the article tells the story of the ADD’s founding and details how, as a key player in Park’s pursuit of security independence, the agency spurred technological innovation and industrialization. Through weapons development, the ADD localized R&D, facilitated technological collaboration, established quality control and standardization methods within corporations, and enhanced the scientific workforce with advanced training, altogether promoting the scientization of the Korean private sector. By merging state and business efforts, and by combining military with civilian strengths, the ADD led a process of national scientization and technological governance that still operates at the heart of Korean economic growth today.
Voluntary Outsiders in Their Anthropocentric Nation: Korean Vegan Youth Navigating between National Ruins and Transnational Mobilities
Authors: Choi Su Young
Published: April 2023

This study asks why and how a segment of young people have led the emergence of veganism in contemporary South Korea since the mid-2010s, and what this appearance means—especially against the backdrop of the wide interpretation of Korean youth as disillusioned and depoliticized individuals who distrust the possibility of any positive social change. The article argues that the youth-driven Korean veganism has played a role in filling the void of the postdevelopmental, postindustrial, and postliberation era of climate crisis and planetary challenges by working as a broad vision for a good life and meaningful social change. Based on qualitative interviews, textual analysis, and participant observation, the article shows why veganism has worked as a way of alternative survival for vegan youth, how veganism as the source of voice and personal growth has been validated and cultivated by the transnational youth culture, and what has enabled veganism’s solidarity from and coalition with other social movements. The article contributes to diversifying the representation of Korean youth and their agencies beyond the ruins and pessimism of the neoliberalized Korean society.
BMP4 triggers regulatory circuits specifying the cardiac mesoderm lineage
Authors: Tsaytler Pavel , Liu Jinhua , Blaess Gaby , Schifferl Dennis , Veenvliet Jesse V. , Wittler Lars , Timmermann Bernd , Herrmann Bernhard G. , Koch Frederic
Published: April 2023

Cardiac lineage specification in the mouse is controlled by TGFβ and WNT signaling. From fly to fish, BMP has been identified as an indispensable heart inducer. A detailed analysis of the role of Bmp4 and its effectors Smad1/5, however, was still missing. We show that Bmp4 induces cardiac mesoderm formation in murine embryonic stem cells in vitro. Bmp4 first activates Wnt3 and upregulates Nodal. pSmad1/5 and the WNT effector Tcf3 form a complex, and together with pSmad2/3 activate mesoderm enhancers and Eomes. They then cooperate with Eomes to consolidate the expression of many mesoderm factors, including T. Eomes and T form a positive- feedback loop and open additional enhancers regulating early mesoderm genes, including the transcription factor Mesp1, establishing the cardiac mesoderm lineage. In parallel, the neural fate is suppressed. Our data confirm the pivotal role of Bmp4 in cardiac mesoderm formation in the mouse. We describe in detail the consecutive and cooperative actions of three signaling pathways, BMP, WNT and Nodal, and their effector transcription factors, during cardiac mesoderm specification.
Probing the pathogenicity of patient-derived variants of MT-ATP6 in yeast
Authors: Baranowska Emilia , Niedzwiecka Katarzyna , Panja Chiranjit , Charles Camille , Dautant Alain , Poznanski Jarosław , di Rago Jean-Paul , Tribouillard-Tanvier Déborah , Kucharczyk Roza
Published: April 2023

The list of mitochondrial DNA (mtDNA) variants detected in individuals with neurodegenerative diseases is constantly growing. Evaluating their functional consequences and pathogenicity is not easy, especially when they are found in only a limited number of patients together with wild-type mtDNA (heteroplasmy). Owing to its amenability to mitochondrial genetic transformation and incapacity to stably maintain heteroplasmy, and the strong evolutionary conservation of the proteins encoded in mitochondria, Saccharomyces cerevisiae provides a convenient model to investigate the functional consequences of human mtDNA variants. We herein report the construction and energy-transducing properties of yeast models of eight MT-ATP6 gene variants identified in patients with various disorders: m.8843T>C, m.8950G>A, m.9016A>G, m.9025G>A, m.9029A>G, m.9058A>G, m.9139G>A and m.9160T>C. Significant defect in growth dependent on respiration and deficits in ATP production were observed in yeast models of m.8950G>A, m.9025G>A and m.9029A>G, providing evidence of pathogenicity for these variants. Yeast models of the five other variants showed very mild, if any, effect on mitochondrial function, suggesting that the variants do not have, at least alone, the potential to compromise human health.
Upregulation of Tribbles decreases body weight and increases sleep duration
Authors: Popovic Rebeka , Yu Yizhou , Leal Nuno Santos , Fedele Giorgio , Loh Samantha H. Y. , Martins L. Miguel
Published: April 2023

Eukaryotic Tribbles proteins are pseudoenzymes that regulate multiple aspects of intracellular signalling. Both Drosophila melanogaster and mammalian members of this family of pseudokinases act as negative regulators of insulin signalling. Mammalian tribbles pseudokinase (TRIB) genes have also been linked to insulin resistance and type 2 diabetes mellitus. Type 2 diabetes mellitus is associated with increased body weight, sleep problems and increased long-term mortality. Here, we investigated how manipulating the expression of Tribbles impacts body weight, sleep and mortality. We showed that the overexpression of Drosophila tribbles (trbl) in the fly fat body reduces both body weight and lifespan in adult flies without affecting food intake. Furthermore, it decreases the levels of Drosophila insulin-like peptide 2 (DILP2; ILP2) and increases night-time sleep. The three genes encoding TRIBs of mammals, TRIB1, TRIB2 and TRIB3, show both common and unique features. As the three human TRIB genes share features with Drosophila trbl, we further explored the links between TRIB genetic variants and both body weight and sleep in the human population. We identified associations between the polymorphisms and expression levels of the pseudokinases and markers of body weight and sleep duration. We conclude that Tribbles pseudokinases are involved in the control of body weight, lifespan and sleep.
Artificial intelligence in lung cancer diagnostic imaging: a review of the reporting and conduct of research published 2018–2019
Authors: Logullo Patricia , MacCarthy Angela , Dhiman Paula , Kirtley Shona , Ma Jie , Bullock Garrett , Collins Gary S.
Published: April 2023

Objective:

This study aimed to describe the methodologies used to develop and evaluate models that use artificial intelligence (AI) to analyse lung images in order to detect, segment (outline borders of), or classify pulmonary nodules as benign or malignant.

Methods:

In October 2019, we systematically searched the literature for original studies published between 2018 and 2019 that described prediction models using AI to evaluate human pulmonary nodules on diagnostic chest images. Two evaluators independently extracted information from studies, such as study aims, sample size, AI type, patient characteristics, and performance. We summarised data descriptively.

Results:

The review included 153 studies: 136 (89%) development-only studies, 12 (8%) development and validation, and 5 (3%) validation-only. CT scans were the most common type of image type used (83%), often acquired from public databases (58%). Eight studies (5%) compared model outputs with biopsy results. 41 studies (26.8%) reported patient characteristics. The models were based on different units of analysis, such as patients, images, nodules, or image slices or patches.

Conclusion:

The methods used to develop and evaluate prediction models using AI to detect, segment, or classify pulmonary nodules in medical imaging vary, are poorly reported, and therefore difficult to evaluate. Transparent and complete reporting of methods, results and code would fill the gaps in information we observed in the study publications.

Advances in knowledge:

We reviewed the methodology of AI models detecting nodules on lung images and found that the models were poorly reported and had no description of patient characteristics, with just a few comparing models’ outputs with biopsies results. When lung biopsy is not available, lung-RADS could help standardise the comparisons between the human radiologist and the machine. The field of radiology should not give up principles from the diagnostic accuracy studies, such as the choice for the correct ground truth, just because AI is used. Clear and complete reporting of the reference standard used would help radiologists trust in the performance that AI models claim to have. This review presents clear recommendations about the essential methodological aspects of diagnostic models that should be incorporated in studies using AI to help detect or segmentate lung nodules. The manuscript also reinforces the need for more complete and transparent reporting, which can be helped using the recommended reporting guidelines.
ΕΚΠΑΙΔΕΥΤΙΚΟ ΝΤΟΚΙΜΑΝΤΕΡ «Οάσεις Πρασίνου στην Αθήνα»
Authors: Αθανασιάδη Δανάη-Γεωργία , Ελευθερίου Ιωάννα
Published: April 2023

The film «Green Oases in Athens» is an educational documentary which aims at informing its viewers about the urban green areas which can be found in the city of Athens. The educational documentary focuses its interest on three specific areas: the National Garden, the Firing Range of Kaisariani as well as the Veikou Grove. Through this film, the city of Athens is presented in detail, while issues such as those of lack of natural resources, pollution as well as the lack of green spaces in the capital city are addressed. The presentation of the «green oases» raises the attention of the audience towards the areas of green in Athens while it aims at altering the perception of the city as a mere concrete jungle. The interviews which take place along with the conclusion of the film are intended to puzzle the viewers and to offer them several ideas and choices regarding a certain area of green which they could potentially choose as «green» way out of the hustle and bustle of the metropolis.

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Η εκπαιδευτική ταινία “Ο Κούρος του Σουνίου” ως διδακτικό εργαλείο στο πλαίσιο του μαθήματος της Ιστορίας
Authors: Λεωνίδα Ελευθερία , Μιχαηλίδου Χρυσούλα , Σκούρτη Σοφία , Τάταρη Παναγιώτα , Τσαγγαρή Γεωργία , Σοφός Αλιβίζος (Λοΐζος)
Published: April 2023

“ Είμαι ο Κούρος του Σουνίου και έχω μια ιστορία να σας πω.” Με αυτή τη φράση η εκπαιδευτική ταινία μικρού μήκους με τίτλο “ Ο Κούρος του Σουνίου” επηρεασμένη από μυθοπλαστικά στοιχεία εξιστορεί τη ζωή και πορεία του Κούρου του Σουνίου διαμέσου των αιώνων. Ο Κούρος σε πρώτο πρόσωπο διηγείται την πορεία του από τη δημιουργία του έως τη θέση του σήμερα, περιγράφοντας με γλαφυρό τρόπο την απρόσμενη τροπή που πήρε η ζωή του. Από ένα άγαλμα στο Ναό του Ποσειδώνα κατέληξε σε ένα πηγάδι και μετά από πολλά χρόνια αναδύθηκε στην επιφάνεια όπου μέχρι σήμερα στέκεται στο Εθνικό και Αρχαιολογικό Μουσείο. Η διάρκεια της εκπαιδευτικής ταινίας είναι  13:44 και ο εκπαιδευτικός στόχος της συγκεκριμένης ταινίας είναι η αξιοποίηση των οπτικοακουστικών μέσων για την παρουσίαση μιας διαφορετικής διάστασης των μαρμάρινων αγαλμάτων μέσα από τα μάτια ενός από αυτά. Η χρήση του μέσου αυτού θα ενισχύσει τα κίνητρα των θεατών για μάθηση, ενώ θα αυξήσει και το ενδιαφέρον τους. Η προσωποποίηση του Κούρου θα τους ευαισθητοποιήσει, ενώ παράλληλα θα μάθουν πληροφορίες τόσο για τη γλυπτική των αγαλμάτων όσο και για τις καταστροφικές συνέπειες ενός πολέμου.
Καλλιεργώντας την κατανόηση κειμένου στο πλαίσιο προ-αναγνωστικών στρατηγικών
Authors: Αγγελόπουλος Γεώργιος , Μπακοπούλου Ιωάννα , Αγγελόπουλος Νικόλαος
Published: April 2023

Σκοπός του άρθρου είναι η παρουσίαση της κατανόησης του κειμένου μέσω των προ-αναγνωστικών στρατηγικών Οι στρατηγικές προ-ανάγνωσης παρουσιάζονται σε ένα πρώτο επίπεδο θεωρητικά από τη σύγχρονη βιβλιογραφία και σε ένα δεύτερο επίπεδο πρακτικά με συγκεκριμένα διδακτικά παραδείγματα που τις συνοδεύουν και αντλούνται από τα σχολικά εγχειρίδια. Αναλύοντας το πρακτικό μέρος δίνεται η δυνατότητα να αναδειχθούν οι επιμέρους πτυχές της καθεμίας στρατηγικής, καθώς επισημαίνεται ο τρόπος εισαγωγής τους από τον/την εκπαιδευτικό στη μαθησιακή διαδικασία. Το άρθρο αναδεικνύει τη σημασία των προ-αναγνωστικών στρατηγικών ως διδακτικών εργαλείων που συμβάλλουν στη διαφοροποίηση της διδασκαλίας.
Η επικοινωνία και συνεργασία διευθυντών/τριών, δασκάλων και εκπαιδευτικών δεύτερης ξένης γλώσσας στην Πρωτοβάθμια εκπαίδευση
Authors: Τσακαλίδου Σοφία , Γκούτζιου Χρυσάνθη
Published: April 2023

Στο παρόν άρθρο εξετάζονται συγκριτικά οι επικοινωνιακές και συνεργατικές σχέσεις που έχουν αναπτύξει οι εκπαιδευτικοί δεύτερης ξένης γλώσσας και οι δάσκαλοι/ες με τους/τις διευθυντές/ύντριες σε σχολικές μονάδες της Πρωτοβάθμιας Εκπαίδευσης. Στο θεωρητικό πλαίσιο εξετάζουμε τα στιλ ηγεσίας, οριοθετούμε την έννοια «επικοινωνία» και αναφέρουμε τα είδη της, πραγματευόμαστε τις συνεργατικές σχέσεις στο πλαίσιο της σχολικής μονάδας και την επικοινωνία σε συνάρτηση με τη διοίκηση. Επίσης, ασχολούμαστε με τα δομικά στοιχεία της επικοινωνιακής διαδικασίας στους σχολικούς οργανισμούς, τις επικοινωνιακές δεξιότητες του/της διευθυντή/ύντριας και τη σχέση της επικοινωνίας και της αποτελεσματικότητας της σχολικής ηγεσίας. Η μελέτη που πραγματοποιήθηκε κατά στο σχολικό έτος 2020-2021 ήταν μια δειγματοληπτική έρευνα με τη χρήση ερωτηματολογίου και συμμετείχαν συνολικά 216 εκπαιδευτικοί (ΠΕ05, ΠΕ07 και ΠΕ70) σε πανελλαδικό επίπεδο. Στις περισσότερες περιπτώσεις σημειώθηκε μεγάλη απόκλιση ως προς τις απαντήσεις που δόθηκαν από τους δύο πληθυσμούς υπό εξέταση, ωστόσο σε ορισμένα ζητήματα υπήρχε ταύτιση των απόψεών τους. Πιο συγκεκριμένα, οι εκπαιδευτικοί ξενόγλωσσων ειδικοτήτων αρκετά συχνά δεν ενημερώνονται σχετικά με τις αλλαγές στο καθημερινό πρόγραμμα ή σχετικά με τους/τις μαθητές/ήτριες, σε αντίθεση με τους/τις δασκάλους/ες. Αρκετά μεγαλύτερο ποσοστό των δασκάλων θεωρεί ότι ο/η διευθυντής/ύντρια ακούει με προσοχή όταν αντιμετωπίζει προβλήματα προσωπικά σε σχέση με τους/τις εκπαιδευτικούς ξενόγλωσσων ειδικοτήτων. Επιπλέον, στην παρούσα εργασία διατυπώνονται και αρκετές προτάσεις για τη βελτίωση των εργασιακών συνθηκών για τους/τις εκπαιδευτικούς δεύτερης ξένης γλώσσας με στόχο την εξάλειψη φαινομένων επαγγελματικής εξουθένωσης και έλλειψης ικανοποίησης στον χώρο εργασίας τους, καθώς και προτάσεις για μελλοντική διερεύνηση σε σχέση με το εν λόγω θέμα.