bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient large-scale single-step evaluations and indirect genomic prediction of genotyped selection candidates
Authors: Vandenplas Jeremie , ten Napel Jan , Darbaghshahi Saeid Naderi , Evans Ross , Calus Mario P. L. , Veerkamp Roel , Cromie Andrew , Mäntysaari Esa A. , Strandén Ismo
Published: June 2023

Background

Single-step genomic best linear unbiased prediction (ssGBLUP) models allow the combination of genomic, pedigree, and phenotypic data into a single model, which is computationally challenging for large genotyped populations. In practice, genotypes of animals without their own phenotype and progeny, so-called genotyped selection candidates, can become available after genomic breeding values have been estimated by ssGBLUP. In some breeding programmes, genomic estimated breeding values (GEBV) for these animals should be known shortly after obtaining genotype information but recomputing GEBV using the full ssGBLUP takes too much time. In this study, first we compare two equivalent formulations of ssGBLUP models, i.e. one that is based on the Woodbury matrix identity applied to the inverse of the genomic relationship matrix, and one that is based on marker equations. Second, we present computationally-fast approaches to indirectly compute GEBV for genotyped selection candidates, without the need to do the full ssGBLUP evaluation.

Results

The indirect approaches use information from the latest ssGBLUP evaluation and rely on the decomposition of GEBV into its components. The two equivalent ssGBLUP models and indirect approaches were tested on a six-trait calving difficulty model using Irish dairy and beef cattle data that include 2.6 million genotyped animals of which about 500,000 were considered as genotyped selection candidates. When using the same computational approaches, the solving phase of the two equivalent ssGBLUP models showed similar requirements for memory and time per iteration. The computational differences between them were due to the preprocessing phase of the genomic information. Regarding the indirect approaches, compared to GEBV obtained from single-step evaluations including all genotypes, indirect GEBV had correlations higher than 0.99 for all traits while showing little dispersion and level bias.

Conclusions

In conclusion, ssGBLUP predictions for the genotyped selection candidates were accurately approximated using the presented indirect approaches, which are more memory efficient and computationally fast, compared to solving a full ssGBLUP evaluation. Thus, indirect approaches can be used even on a weekly basis to estimate GEBV for newly genotyped animals, while the full single-step evaluation is done only a few times within a year.
Rebounds of sevoflurane concentration during simulated trigger-free pediatric and adult anesthesia
Authors: Zumsande Simon , Thoben Christian , Dennhardt Nils , Krauß Terence , Sümpelmann Robert , Zimmermann Stefan , Rüffert Henrik , Heiderich Sebastian
Published: June 2023

Background

In trigger-free anesthesia a volatile anesthetic concentration of 5 parts per million (ppm) should not be exceeded. According to European Malignant Hyperthermia Group (EMHG) guideline, this may be achieved by removing the vapor, changing the anesthetic breathing circuit and renewing the soda lime canister followed by flushing with O2or air for a workstation specific time. Reduction of the fresh gas flow (FGF) or stand-by modes are known to cause rebound effects. In this study, simulated trigger-free pediatric and adult ventilation was carried out on test lungs including ventilation maneuvers commonly used in clinical practice. The goal of this study was to evaluate whether rebounds of sevoflurane develop during trigger-free anesthesia.

Methods

A Dräger® Primus® was contaminated with decreasing concentrations of sevoflurane for 120 min. Then, the machine was prepared for trigger-free anesthesia according to EMHG guideline by changing recommended parts and flushing the breathing circuits using 10 or 18 l⋅min− 1FGF. The machine was neither switched off after preparation nor was FGF reduced. Simulated trigger-free ventilation was performed with volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) including various ventilation maneuvers like pressure support ventilation (PSV), apnea, decreased lung compliance (DLC), recruitment maneuvers, prolonged expiration and manual ventilation (MV). A high-resolution ion mobility spectrometer with gas chromatographic pre-separation was used to measure sevoflurane in the ventilation gas mixture in a 20 s interval.

Results

Immediately after start of simulated anesthesia, there was an initial peak of 11–18 ppm sevoflurane in all experiments. The concentration dropped below 5 ppm after 2–3 min during adult and 4–18 min during pediatric ventilation. Other rebounds of sevoflurane > 5 ppm occurred after apnea, DLC and PSV. MV resulted in a decrease of sevoflurane < 5 ppm within 1 min.

Conclusion

This study shows that after guideline-compliant preparation for trigger-free ventilation anesthetic machines may develop rebounds of sevoflurane > 5 ppm during typical maneuvers used in clinical practice. The changes in rate and direction of internal gas flow during different ventilation modes and maneuvers are possible explanations. Therefore, manufacturers should provide machine-specific washout protocols or emphasize the use of active charcoal filters (ACF) for trigger-free anesthesia.
A randomized controlled trial of iliopsoas plane block vs. femoral nerve block for hip arthroplasty
Authors: Wang Chun-guang , Zhang Zhi-qiang , Yang Yang , Long Yu-bin , Wang Xiu-li , Ding Yan-ling
Published: June 2023

Background

Iliopsoas plane block (IPB) is a novel analgesic technique for hip surgery that retains quadriceps strength. However, evidence from randomized controlled trial is remains unavailable. We hypothesized that IPB, as a motor-sparing analgesic technique, could match the femoral nerve block (FNB) in pain management and morphine consumption, providing an advantage for earlier functional training in patients underwent hip arthroplasty.

Methods

We recruited ninety patients with femoral neck fracture, femoral head necrosis or hip osteoarthritis who were scheduled for unilateral primary hip arthroplasty were recruited and received either IPB or FNB. Primary outcome was the pain score during hip flexion at 4 h after surgery. Secondary outcomes included quadriceps strength and pain scores upon arrival at post anesthesia care unit (PACU) and at 2, 4, 6, 24, 48 h after surgery, the first time out of bed, total opioids consumption, patient satisfaction, and complications.

Results

There was no significant difference in terms of pain score during hip flexion at 4 h after surgery between the IPB group and FNB group. The quadriceps strength of patients receiving IPB was superior to those receiving FNB upon arrival at PACU and at 2, 4, 6 and 24 h after surgery. The IPB group showed a shorter first time out of bed compared to the FNB group. However, there were no significant differences in terms of pain scores within 48 h after surgery, total opioids consumption, patient satisfaction and complications between the two groups.

Conclusion

IPB was not superior to FNB in terms of postoperative analgesia for hip arthroplasty. However, IPB could serve as an effective motor-sparing analgesic technique for hip arthroplasty, which would facilitate early recovery and rehabilitation. This makes IPB worth considering as an alternative to FNB.

Trial registration

The trial was registered prior to patient enrollment at the Chinese Clinical Trial Registry (ChiCTR2200055493; registration date: January 10, 2022; enrollment date: January 18, 2022;https://www.chictr.org.cn/searchprojEN.html).
Characterization of stemness features and construction of a stemness subtype classifier to predict survival and treatment responses in lung squamous cell carcinoma
Authors: Lai Jinzhi , Lin Xinyi , Zheng Huangna , Xie Bilan , Fu Deqiang
Published: June 2023

Background

Cancer stemness has been proven to affect tumorigenesis, metastasis, and drug resistance in various cancers, including lung squamous cell carcinoma (LUSC). We intended to develop a clinically applicable stemness subtype classifier that could assist physicians in predicting patient prognosis and treatment response.

Methods

This study collected RNA-seq data from TCGA and GEO databases to calculate transcriptional stemness indices (mRNAsi) using the one-class logistic regression machine learning algorithm. Unsupervised consensus clustering was conducted to identify a stemness-based classification. Immune infiltration analysis (ESTIMATE and ssGSEA algorithms) methods were used to investigate the immune infiltration status of different subtypes. Tumor Immune Dysfunction and Exclusion (TIDE) and Immunophenotype Score (IPS) were used to evaluate the immunotherapy response. The pRRophetic algorithm was used to estimate the efficiency of chemotherapeutic and targeted agents. Two machine learning algorithms (LASSO and RF) and multivariate logistic regression analysis were performed to construct a novel stemness-related classifier.

Results

We observed that patients in the high-mRNAsi group had a better prognosis than those in the low-mRNAsi group. Next, we identified 190 stemness-related differentially expressed genes (DEGs) that could categorize LUSC patients into two stemness subtypes. Patients in the stemness subtype B group with higher mRNAsi scores exhibited better overall survival (OS) than those in the stemness subtype A group. Immunotherapy prediction demonstrated that stemness subtype A has a better response to immune checkpoint inhibitors (ICIs). Furthermore, the drug response prediction indicated that stemness subtype A had a better response to chemotherapy but was more resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Finally, we constructed a nine-gene-based classifier to predict patients’ stemness subtype and validated it in independent GEO validation sets. The expression levels of these genes were also validated in clinical tumor specimens.

Conclusion

The stemness-related classifier could serve as a potential prognostic and treatment predictor and assist physicians in selecting effective treatment strategies for patients with LUSC in clinical practice.
Expression and regulatory network of E3 ubiquitin ligase NEDD4 family in cancers
Authors: Cao Liangzi , Li Hao , Liu Xiaofang , Wang Yubang , Zheng Bowen , Xing Chengzhong , Zhang Naijin , Liu Jingwei
Published: June 2023

NEDD4 family represent an important group of E3 ligases, which regulate various cellular pathways of cell proliferation, cell junction and inflammation. Emerging evidence suggested that NEDD4 family members participate in the initiation and development of tumor. In this study, we systematically investigated the molecular alterations as well as the clinical relevance regarding NEDD4 family genes in 33 cancer types. Finally, we found that NEDD4 members showed increased expression in pancreas cancer and decreased expression in thyroid cancer. NEDD4 E3 ligase family genes had an average mutation frequency in the range of 0-32.1%, of which HECW1 and HECW2 demonstrated relatively high mutation rate. Breast cancer harbors large amount of NEDD4 copy number amplification. NEDD4 family members interacted proteins were enriched in various pathways including p53, Akt, apoptosis and autophagy, which were confirmed by further western blot and flow cytometric analysis in A549 and H1299 lung cancer cells. In addition, expression of NEDD4 family genes were associated with survival of cancer patients. Our findings provide novel insight into the effect of NEDD4 E3 ligase genes on cancer progression and treatment in the future.
Transcriptomic and functional analysis of ANGPTL4 overexpression in pancreatic cancer nominates targets that reverse chemoresistance
Authors: Gordon Emily R. , Wright Carter A. , James Mikayla , Cooper Sara J.
Published: June 2023

Background

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers based on five-year survival rates. Genes contributing to chemoresistance represent novel therapeutic targets that can improve treatment response. Increased expression of ANGPTL4 in tumors correlates with poor outcomes in pancreatic cancer.

Methods

We used statistical analysis of publicly available gene expression data (TCGA-PAAD) to test whether expression of ANGPTL4 and its downstream targets, ITGB4 and APOL1, were correlated with patient survival. We measured the impact of ANGPTL4 overexpression in a common pancreatic cancer cell line, MIA PaCa-2 cells, using CRISPRa for overexpression and DsiRNA for knockdown. We characterized global gene expression changes associated with high levels of ANGPTL4 and response to gemcitabine treatment using RNA-sequencing. Gemcitabine dose response curves were calculated on modified cell lines by measuring cell viability with CellTiter-Glo (Promega). Impacts on cell migration were measured using a time course scratch assay.

Results

We show that ANGPTL4 overexpression leads to in vitro resistance to gemcitabine and reduced survival times in patients. Overexpression of ANGPTL4 induces transcriptional signatures of tumor invasion and metastasis, proliferation and differentiation, and inhibition of apoptosis. Analyses revealed an overlapping signature of genes associated with both ANGPTL4 activation and gemcitabine response. Increased expression of the genes in this signature in patient PDAC tissues was significantly associated with shorter patient survival. We identified 42 genes that were both co-regulated with ANGPTL4 and were responsive to gemcitabine treatment. ITGB4 and APOL1 were among these genes. Knockdown of either of these genes in cell lines overexpressing ANGPTL4 reversed the observed gemcitabine resistance and inhibited cellular migration associated with epithelial to mesenchymal transition (EMT) and ANGPTL4 overexpression.

Conclusions

These data suggest that ANGPTL4 promotes EMT and regulates the genes APOL1 and ITGB4. Importantly, we show that inhibition of both targets reverses chemoresistance and decreases migratory potential. Our findings have revealed a novel pathway regulating tumor response to treatment and suggest relevant therapeutic targets in pancreatic cancer.
The relationship between pepsinogen C and gastric carcinogenesis: a transgene and population study
Authors: E. Ying , Yu Qian , Sun Tao , Xue Hang , Zhao Xue-rong , Zheng Hua-chuan
Published: June 2023

Background

Pepsinogen C (PGC) is expressed in chief cells, fundic mucous neck cells, and pyloric gland cells of gastric epithelium and also in breast, prostate, lung, and seminal vesicles.

Methods

We explored the clinicopathological and prognostic significances of PGC mRNA using pathological and bioinformatics analyses. We generated PGC knockout and PGC-cre transgenic mice to observe the effects of PGC deletion and PTEN abrogation in PGC-positive cells on gastric carcinogenesis. Finally, we observed the effects of altered PGC expression on aggressive phenotypes by CCK8, Annexin V staining, wound healing and transwell assays and analyzed the partner proteins of PGC using co-IP (co-immunoprecipitation) and double fluorescence staining.

Results

PGC mRNA level was inversely correlated with the T and G stage and a short survival of gastric cancer (p < 0.05). PGC protein expression was negatively linked to lymph node metastasis, dedifferentiation, and low Her-2 expression of gastric cancer (p < 0.05). No difference in body weight or length was evident between wild-type (WT) and PGC knockout (KO) mice (p > 0.05), but PGC KO mice had a shorter survival than WT mice (p < 0.05). No gastric lesions were observed in the mucosa of the granular stomach in PGC KO mice, which displayed lower frequency and severity of gastric lesion than in WT mice after treated with MNU. Transgenic PGC-cre mice showed high cre expression and activity in the lung, stomach, kidney, and breast. Gastric cancer and triple-negative lobular breast adenocarcinoma were found in PGC-cre/PTENf/f mice with two previous pregnancies and breast feeding, but breast cancer was not seen in transgenic mice exposed to either estrogen or progesterone, or those with two previous pregnancies and no breast feeding. PGC suppressed proliferation, migration, invasion, and induced apoptosis, and interacted with CCNT1, CNDP2 and CTSB.

Conclusion

PGC downregulation was seen in gastric cancer, but PGC deletion resulted in resistance to chemically-induced gastric carcinogenesis. PGC expression suppressed the proliferation and invasion of gastric cancer cells possibly by interacting with CCNT1, CNDP2 and CTSB. Spontaneous triple-negative lobular adenocarcinoma and gastric cancer were seen in PGC-cre/PTENf/f mice, and the breast carcinogenesis was closely linked to pregnancy and breast feeding, but not to single exposure to estrogen or progesterone, or pregnancy. Limiting either pregnancy or breast feeding might help to prevent hereditary breast cancer.
Temporal reciprocal relationships among anxiety, depression, and posttraumatic stress disorder for family surrogates from intensive care units over their first two bereavement years
Authors: Wen Fur-Hsing , Juang Yeong-Yuh , Prigerson Holly G. , Chou Wen-Chi , Huang Chung-Chi , Hu Tsung-Hui , Chiang Ming Chu , Chuang Li-Pang , Tang Siew Tzuh
Published: June 2023

Background/Objective

Bereaved family surrogates from intensive care units (ICU) are at risk of comorbid anxiety, depression, and post-traumatic stress disorder (PTSD), but the temporal reciprocal relationships among them have only been examined once among veterans. This study aimed to longitudinally investigate these never-before-examined temporal reciprocal relationships for ICU family members over their first two bereavement years.

Methods

In this prospective, longitudinal, observational study, symptoms of anxiety, depression, and PTSD were assessed among 321 family surrogates of ICU decedents from 2 academically affiliated hospitals in Taiwan by the anxiety and depression subscales of the Hospital Anxiety and Depression Scale, and the Impact of Event Scale-Revised, respectively at 1, 3, 6, 13, 18, and 24 months postloss. Cross-lagged panel modeling was conducted to longitudinally examine the temporal reciprocal relationships among anxiety, depression, and PTSD.

Results

Examined psychological-distress levels were markedly stable over the first 2 bereavement years: autoregressive coefficients for symptoms of anxiety, depression, and PTSD were 0.585–0.770, 0.546–0.780, and 0.440–0.780, respectively. Cross-lag coefficients showed depressive symptoms predicted PTSD symptoms in the first bereavement year, whereas PTSD symptoms predicted depressive symptoms in the second bereavement year. Anxiety symptoms predicted symptoms of depression and PTSD at 13 and 24 months postloss, whereas depressive symptoms predicted anxiety symptoms at 3 and 6 months postloss while PTSD symptoms predicted anxiety symptoms during the second bereavement year.

Conclusions

Different patterns of temporal relationships among symptoms of anxiety, depression, and PTSD over the first 2 bereavement years present important opportunities to target symptoms of specific psychological distress at different points during bereavement to prevent the onset, exacerbation, or maintenance of subsequent psychological distress.
Constructing an emergency preparedness evaluation index system for public use during major emerging infectious disease outbreaks: a Delphi study
Authors: Wei Wei , Liu Yubei , Zhou Na , Tian Min , Xie Longsheng , Watson Roger , Dai Fengling , Chen Yanhua , Hu Weili
Published: June 2023

Background

The major emerging infectious diseases (MEIDs) have occurred frequently and become increasingly serious in the world. Sufficient personal emergency preparedness is critical for the general people in efficiently responding to and recovering from MEIDs. Nevertheless, few specific indicators are available for assessing the individual emergency preparedness of the general public during these periods. Therefore, the aim of this study was to construct an index system for comprehensively evaluating the personal emergency preparedness of the public regarding MEIDs.

Methods

Based on the global national-level emergency preparedness index framework and a literature review, a preliminary index system was constructed. From June 2022 to September 2022, a panel of 20 experts from nine provinces and municipalities across multiple research areas participated in this Delphi study. They rated the importance of pre-defined indicators using a five-point Likert scale and provided their qualitative comments. According to the feedback of each round of experts, the indicators of the evaluation index system were revised.

Results

After two rounds of expert consultation the evaluation index system reached a consensus, containing five first-level indicators, cooperating with prevention and control work, improving emergency response capacity, securing supplies and equipment, preparing economic resources, maintaining physical and mental health with affiliated 20 s-level indicators and 53 third-level indicators. The expert authority coefficient of consultation was 0.88 and 0.90. The Kendall’s coefficient of concordance of expert consultations was 0.294 and 0.322, respectively. The differences were statistically significant (P < 0.05).

Conclusion

A valid, reliable and scientific evaluation index system was established. This personal emergency preparedness index system, as a precursor form, will further lay the foundation for the formation of an assessment instrument. At the same time, it could provide a reference for future education and training of emergency preparedness for the general public.
Reliability and repeatability of 2021 ARCO classification and its guiding significance in treatment of nontraumatic osteonecrosis of the femoral head
Authors: Yue Ju’an , Guo Xiaozhong , Wang Randong , Li Bing , Sun Qiang , Liu Wangyan , Chen Jiao , Zhao Fengnian
Published: June 2023

Background

The study was designed to evaluate the interobserver reliability and intraobserver repeatability of the 2021 Association Research Circulation Osseous (ARCO) classification and explore its guiding significance in the treatment of nontraumatic osteonecrosis of the femoral head (ONFH).

Methods

In this retrospective study, we randomly selected and investigated 50 sets of preoperative computed tomography or magnetic resonance imaging scans from 96 patients (139 hips) to validate the reliability and repeatability of the 2021 ARCO classification. Patients with a nano-hydroxyapatite/polyamide-66 support rod were included in the clinical efficacy study. The Harris hip score (HHS) was used to assess hip function. Femoral head collapse of > 2 mm was considered radiological failure. Total hip arthroplasty (THA) was performed for clinical failure, and follow-up was discontinued.

Results

The average kappa value of interobserver consistency was 0.652. The average rate of consistency was 90.25%, and the average kappa value of intraobserver consistency was 0.836. Eighty-two patients (122 hips) were enrolled and followed up for a mean of 43.57 ± 9.64 months. There was no significant difference in the HHS among the three groups before surgery, but the difference was statistically significant at the last follow-up. Among them, types 1 and 2 had significantly higher scores at the last follow-up than preoperatively (P < 0.05), whereas type 3 had a lower score at the last follow-up than preoperatively, although the difference was not statistically significant (P > 0.05).According to the imaging evaluation, the failure rate of type 1, 2, and 3 at the last follow-up was 0%, 19%, and 87%, respectively. Univariate analysis showed that the femoral head survival rate of radiography was significantly affected by the new classification system (P = 0.00). At the last follow-up, the incidence rate of THA in type 1, 2, and 3 was 5%, 7%, and 31%, respectively. Univariate analysis showed that the femoral head survival rate was significantly affected by the new classification system (P = 0.001).

Conclusions

The 2021 ARCO classification for early-stage ONFH shows substantial consistency and repeatability. We do not recommend femoral head-preserving surgery for patients with type 3 ONFH.
Correlation between serum α-Klotho levels and different stages of periodontitis
Authors: Ni Can , Bao Dongyu , Yan Fuhua , Chen Bin
Published: June 2023

Background

Periodontitis is an inflammatory disease characterized by inflammation and progressive destruction of periodontal tissues including alveolar bone. α-klotho protein is a multifunctional protein related to age-related diseases, inflammatory diseases, and bone metabolism-related diseases. However, large-sample epidemiological research evidence on the correlation between α-Klotho and the aggravation of periodontitis stages is still lacking.

Methods

Cross-sectional study data of participants aged between 40 and 79 years in the National Health and Nutrition Examination Survey 2013‒2014 were selected and analyzed. The stages of periodontitis of the participants were determined according to the 2018 World Workshop Classification of Periodontal and Peri-implant Diseases. The serum α-Klotho levels in people with periodontitis in different stages were evaluated. Then the correlation between serum α-Klotho levels and different stages of periodontitis was analyzed by multiple linear regression (stepwise regression method).

Results

A total of 2378 participants were included in the study. The serum α-Klotho levels in people with stage I/II, III and IV periodontitis were 896.16 ± 304.84, 871.08 ± 266.42 and 840.52 ± 286.24 pg/mL, respectively. The levels of α-Klotho in people with stage IV periodontitis were significantly lower than those in people with stage I/II and III periodontitis. Linear regression analysis results showed that compared to stage I/II periodontitis, serum α-Klotho levels were significantly negatively correlated with stage III (B ± SE = -37.28 ± 16.00, 95% CI: -68.66 ~ -25.91, P = 0.020) and stage IV (B ± SE = -69.37 ± 16.11, 95% CI: -100.97 ~ -37.77, P < 0.001) periodontitis.

Conclusion

The serum α-Klotho levels were negatively correlated with the severity of periodontitis. With the aggravation of periodontitis stages, the serum α-Klotho levels gradually decreased.
Designing for digital transformation of residency education – a post-pandemic pedagogical response
Authors: Vallo Hult Helena , Master Östlund Christian , Pålsson Paul , Jood Katarina
Published: June 2023

Background

The forced transition to emergency remote teaching (ERT) during the COVID-19 pandemic has significantly impacted health professions education worldwide. In Sweden, the need for alternative solutions for the training of junior doctors became urgent, as many of the mandatory onsite courses required for residents to qualify as specialists were canceled. The purpose of this study was to understand course leaders' perceptions and experiences of using digital technologies, such as video conferencing, to teach medical residents (ST) during the pandemic and beyond.

Methods

A qualitative study using semi-structured interviews was conducted with seven course leaders responsible for residency courses during the first year of the pandemic to capture their perceptions and experiences. The interviews were transcribed verbatim and analyzed using thematic analysis, drawing on the technology affordances and constraints theory (TACT) as a framework to explore pedagogical strategies and new teaching practices emerging from the forced use of digital technologies for remote teaching.

Results

The data analysis revealed affordances of, as well as constraints to, teaching specialist medical training during the pandemic. The findings show that the use of digital conference technologies for ERT can both enable and inhibit social interactions, the interactive learning environment and the utilization of technological features, depending on the individual course leaders’ goals of using the technology and the situated context of the teaching.

Conclusions

The study reflects the course leaders' pedagogical response to the pandemic, as remote teaching became the only way to provide residency education. Initially, the sudden shift was perceived as constraining, but over time they found new affordances through the enforced use of digital technology that helped them not only to cope with the transition but also to innovate their pedagogical methods. After a rapid, forced shift from on-site to digital courses, it is crucial to utilize experiences to create better preconditions for digital technology to facilitate learning in the future.
Moral distress and positive experiences of ICU staff during the COVID-19 pandemic: lessons learned
Authors: van Zuylen Mark L. , de Snoo-Trimp Janine C. , Metselaar Suzanne , Dongelmans Dave A. , Molewijk Bert
Published: June 2023

Background

The COVID-19 pandemic causes moral challenges and moral distress for healthcare professionals and, due to an increased work load, reduces time and opportunities for clinical ethics support services. Nevertheless, healthcare professionals could also identify essential elements to maintain or change in the future, as moral distress and moral challenges can indicate opportunities to strengthen moral resilience of healthcare professionals and organisations.

This study describes 1) the experienced moral distress, challenges and ethical climate concerning end-of-life care of Intensive Care Unit staff during the first wave of the COVID-19 pandemic and 2) their positive experiences and lessons learned, which function as directions for future forms of ethics support.

Methods

A cross-sectional survey combining quantitative and qualitative elements was sent to all healthcare professionals who worked at the Intensive Care Unit of the Amsterdam UMC - Location AMC during the first wave of the COVID-19 pandemic. The survey consisted of 36 items about moral distress (concerning quality of care and emotional stress), team cooperation, ethical climate and (ways of dealing with) end-of-life decisions, and two open questions about positive experiences and suggestions for work improvement.

Results

All 178 respondents (response rate: 25–32%) showed signs of moral distress, and experienced moral dilemmas in end-of-life decisions, whereas they experienced a relatively positive ethical climate. Nurses scored significantly higher than physicians on most items. Positive experiences were mostly related to ‘team cooperation’, ‘team solidarity’ and ‘work ethic’. Lessons learned were mostly related to ‘quality of care’ and ‘professional qualities’.

Conclusions

Despite the crisis, positive experiences related to ethical climate, team members and overall work ethic were reported by Intensive Care Unit staff and quality and organisation of care lessons were learned. Ethics support services can be tailored to reflect on morally challenging situations, restore moral resilience, create space for self-care and strengthen team spirit. This can improve healthcare professionals’ dealing of inherent moral challenges and moral distress in order to strengthen both individual and organisational moral resilience.

Trial registration

The trial was registered on The Netherlands Trial Register, number NL9177.
A mixed methods study assessing the adoption potential of a saliva-based malaria rapid test in the Democratic Republic of Congo
Authors: Diaz John , Gusto Cody , McCoy Kaci , Silvert Colby , Bala Joseph A. , Atibu Joseph , Tshefu Antoinette , Mwandagalirwa Melchior , Dinglasan Rhoel R.
Published: June 2023

Background

The reliance on blood for thin and thick blood smear microscopy—using a relatively invasive procedure has presented challenges to the use of reliable diagnostic tests in non-clinical settings at the point-of-need (PON). To improve the capacity of non-blood-based rapid diagnostic tests to confirm subclinical infections, and thereby identify and quantify the human reservoir at the PON, a cross-sectoral collaboration between university researchers and commercial partners produced an innovative, non-invasive saliva-based RDT capable of identifying novel, non-hrp2/3 parasite biomarkers. While this new saliva-based malaria asymptomatic and asexual rapid test (SMAART-1) shows increased detection sensitivity and precision potential by identifying a new P. falciparum protein marker (PSSP17), appraising its utility in the field—particularly with respect to its adoption potential with children and adults in high risk, endemic regions—is necessary to warrant its continued development.

Methods

The purpose of this study was to assess the acceptability and adoption potential of the SMAART-1 at select PON sites in the Kinshasa Province. Teachers, community health workers, nurses, and laboratory technicians participated in data collection at three distinct community sites in Kinshasa Province, Democratic Republic of the Congo. Three data collection methods were utilized in this mixed methods study to provide an overarching acceptability evaluation of the SMAART-1 at PON field sites: observation checklists of SMAART-1 implementation, focus group discussions, and surveys with local health care practitioners—particularly teachers and community health workers.

Results

Findings indicate participants were interested in and supportive of the SMAART-1 protocol, with approximately 99% of the participants surveyed indicating that they either “agreed” or “strongly agreed” with the statement that they “would use the saliva-based malaria asymptomatic rapid test as part of a community malaria detection and treatment programme.” Data also suggest that the protocol was broadly appealing for its testing sensitivity and ease of use.

Conclusions

The SMAART-1 protocol’s clinically reliable results demonstrate a promising new level of sensitivity and precision for detecting parasite biomarkers. This study’s mixed-methods assessment of the protocol’s utility and adoption potential in the field, with a target user audience, advances its development and points to opportunities to formalize and expand evaluation efforts.
Analysis of AT7519 as a pro-resolution compound in an acetaminophen-induced mouse model of acute inflammation by UPLC-MS/MS
Authors: Cartwright Jennifer A. , Simpson Joanna P. , Homer Natalie Z. M. , Rossi Adriano G.
Published: June 2023

Background

Uncontrolled inflammation contributes to the progression of organ damage in acute conditions, such as acetaminophen-induced acute liver injury (APAP-ALI) and there are limited treatments for this condition. AT7519, a cyclic-dependent kinase inhibitor (CDKI), has been used successfully in several conditions, to resolve inflammation and return tissue homeostatic functions. AT7519 has not been assessed in APAP-ALI and its effect on APAP metabolism is unknown. Targeted chromatography and mass spectrometry can be used to assess multiple compounds simultaneously and this approach has not been applied yet to measure APAP and AT7519 in a mouse model.

Results

We show an optimised simple and sensitive LC–MS/MS method for determining concentrations of AT7519 and APAP in low volumes of mouse serum. Using positive ion mode electrospray ionisation, separation of AT7519 and APAP and their corresponding isotopically labelled internal standards [2H]8-AT16043M (d8-AT7519) and [2H]8-APAP (d4-APAP), was achieved on an Acquity UPLC BEH C18 column (100 × 2.1 mm; 1.7μm). A gradient mobile phase system of water and methanol was delivered at a flow rate of 0.5 mL/min with a run time of 9 min. Calibration curves were linear, intra-day and inter-day precision and accuracy were acceptable and the covariates of all standards and quality control replicates were less than 15%. The method was successfully applied to evaluate AT7519 and APAP levels 20 h post AT7519 (10 mg/mg) in C57Bl6J wild type mouse serum treated with either vehicle or APAP. Serum AT7519 was significantly higher in mice that had received APAP compared to control, but there was no correlation between APAP and AT7519 quantification. There was also no correlation of AT7519 and hepatic damage or proliferation markers.

Conclusion

We optimised an LC–MS/MS method to quantify both AT7519 and APAP in mouse serum (50 µL), using labelled internal standards. Application of this method to a mouse model of APAP toxicity proved effective in accurately measuring APAP and AT7519 concentrations after i.p. dosing. AT7519 was significantly higher in mice with APAP toxicity, indicating hepatic metabolism of this CDKI, but there was no correlation with markers of hepatic damage or proliferation, demonstrating that this dose of AT7519 (10 mg/kg) does not contribute to hepatic damage or repair. This optimised method can be used for future investigations of AT7519 in APAP in mice.
Assessment of 24-hour physical behaviour in adults via wearables: a systematic review of validation studies under laboratory conditions
Authors: Giurgiu Marco , Ketelhut Sascha , Kubica Claudia , Nissen Rebecca , Doster Ann-Kathrin , Thron Maximiliane , Timm Irina , Giurgiu Valeria , Nigg Claudio R. , Woll Alexander , Ebner-Priemer Ulrich W. , Bussmann Johannes B.J.
Published: June 2023

Background

Wearable technology is used by consumers and researchers worldwide for continuous activity monitoring in daily life. Results of high-quality laboratory-based validation studies enable us to make a guided decision on which study to rely on and which device to use. However, reviews in adults that focus on the quality of existing laboratory studies are missing.

Methods

We conducted a systematic review of wearable validation studies with adults. Eligibility criteria were: (i) study under laboratory conditions with humans (age ≥ 18 years); (ii) validated device outcome must belong to one dimension of the 24-hour physical behavior construct (i.e., intensity, posture/activity type, and biological state); (iii) study protocol must include a criterion measure; (iv) study had to be published in a peer-reviewed English language journal. Studies were identified via a systematic search in five electronic databases as well as back- and forward citation searches. The risk of bias was assessed based on the QUADAS-2 tool with eight signaling questions.

Results

Out of 13,285 unique search results, 545 published articles between 1994 and 2022 were included. Most studies (73.8% (N = 420)) validated an intensity measure outcome such as energy expenditure; only 14% (N = 80) and 12.2% (N = 70) of studies validated biological state or posture/activity type outcomes, respectively. Most protocols validated wearables in healthy adults between 18 and 65 years. Most wearables were only validated once. Further, we identified six wearables (i.e., ActiGraph GT3X+, ActiGraph GT9X, Apple Watch 2, Axivity AX3, Fitbit Charge 2, Fitbit, and GENEActiv) that had been used to validate outcomes from all three dimensions, but none of them were consistently ranked with moderate to high validity. Risk of bias assessment resulted in 4.4% (N = 24) of all studies being classified as “low risk”, while 16.5% (N = 90) were classified as “some concerns” and 79.1% (N = 431) as “high risk”.

Conclusion

Laboratory validation studies of wearables assessing physical behaviour in adults are characterized by low methodological quality, large variability in design, and a focus on intensity. Future research should more strongly aim at all components of the 24-hour physical behaviour construct, and strive for standardized protocols embedded in a validation framework.
Identification of colorectal cancer progression-associated intestinal microbiome and predictive signature construction
Authors: Liu Jungang , Huang Xiaoliang , Chen Chuanbin , Wang Zhen , Huang Zigui , Qin Mingjian , He Fuhai , Tang Binzhe , Long Chenyan , Hu Hong , Pan Shuibo , Wu Junduan , Tang Weizhong
Published: June 2023

Objective

The relationship between intestinal microbiome and colorectal cancer (CRC) progression is unclear. This study aims to identify the intestinal microbiome associated with CRC progression and construct predictive labels to support the accurate assessment and treatment of CRC.

Method

The 192 patients included in the study were divided into stage I-II and stage III-IV CRC patients according to the pathological stages, and preoperative stools were collected from both groups for 16S rDNA sequencing of the intestinal microbiota. Pearson correlation and Spearman correlation coefficient analysis were used to analyze the differential intestinal microbiome and the correlation with tumor microenvironment and to predict the functional pathway. XGBoost model (XGB) and Random Forest model (RF) were used to construct the microbiome-based signature. The total RNA extraction from 17 CRC tumor simples was used for transcriptome sequencing.

Result

The Simpson index of intestinal microbiome in stage III-IV CRC were significantly lower than those in stage I-II CRC. Proteus, Parabacteroides, Alistipes and Ruminococcus etc. are significantly enriched genus in feces of CRC patients with stage III-IV. ko00514: Other types of O − glycan biosynthesis pathway is relevant with CRC progression. Alistipes indistinctus was positively correlated with mast cells, immune activators IL-6 and IL6R, and GOBP_PROTEIN_FOLDING_IN_ENDOPLASMIC_RETICULUM dominantly. The Random Forest (RF) model and eXtreme Gradient Boosting (XGBoost) model constructed with 42 CRC progression-associated differential bacteria were effective in distinguishing CRC patients between stage I-II and stage III-IV.

Conclusions

The abundance and diversity of intestinal microbiome may increase gradually with the occurrence and progression of CRC. Elevated fetal abundance of Proteus, Parabacteroides, Alistipes and Ruminococcus may contribute to CRC progression. Enhanced synthesis of O − glycans may result in CRC progression. Alistipes indistinctus may play a facilitated role in mast cell maturation by boosting IL-6 production. Alistipes indistinctus may work in the correct folding of endoplasmic reticulum proteins in CRC, reducing ER stress and prompting the survival and deterioration of CRC, which may owe to the enhanced PERK expression and activation of downstream UPR by Alistipes indistinctus. The CRC progression-associated differential intestinal microbiome identified in our study can be served as potential microbial markers for CRC staging prediction.
Pharmacists are initiators in palliative care for patients with rare diseases
Authors: Dooms M.
Published: June 2023

The World Health Organization supports early delivery of palliative care as it reduces unnecessary hospital admissions and the inappropriate use of health care services. A community pharmacist can play a key role in advocating timely access to palliative care. Medication reconciliation must alert them to start communicating with the patient and/or his relatives about refocusing treatment and care as part of palliative and terminal care. Pharmaceutical activities for these patients include dispensing of devices and medicinal products, compounding personalized medication and participating as a member of the Palliative Support Team. Most of the several thousands of rare diseases are caused by genetic defects and up to now have no cure and a late diagnosis.
Systematic review and meta-analysis of calculating degree of comorbidity of irritable bowel syndrome with migraine
Authors: Todor Tatvan S. , Fukudo Shin
Published: June 2023

Background

Irritable bowel syndrome (IBS) and migraines are often comorbid each other. These disorders are likely to be bidirectionally linked through the gut-brain axis and share several underlying mechanisms including central nervous system sensitization. However, quantitative analysis of comorbidity was not reported enough. The aim of this systematic review and meta-analysis was to calculate the present degree of comorbidity of these two disorders.

Methods

A literature search was performed searching for articles describing IBS or migraine patients with the same inverse comorbidity. Pooled odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were then extracted. The total effect estimates were determined and presented by random effect forest plots for the group of articles with IBS patients with migraine and the group of articles on migraine sufferers with comorbid IBS separately. The average results of these plots were compared.

Results

The literature search resulted in initial 358 articles and final 22 articles for the meta-analysis. The total OR values obtained were 2.09 [1.79 – 2.43] in IBS with comorbid migraine or headache, 2.51 [1.76 – 3.58] for migraineurs with comorbid IBS and an overall HR of 1 .62 [1.29 – 2.03] was found for cohort studies of migraine sufferers with comorbid IBS. A similar expression of a selection of other comorbidities was found in IBS and migraine patients, especially for depression and fibromyalgia a strong similarity was found in their expression rate.

Conclusions

This systematic review with meta-analysis was the first to combine data on IBS patients with comorbid migraine and migraineurs with comorbid IBS. The fact that closely related existential rates were observed between these two groups should be used as motivation for future research to further investigate these disorders for why this similarity occurs. Mechanisms involved in central hypersensitivity such as genetic risk factors, mitochondrial dysfunction and microbiota are particularly good candidates. Experimental designs in which therapeutic methods for these conditions can be exchanged or combined may also lead to the discovery of more efficient treatment methods.
Leishmania (Viannia) naiffi Lainson & Shaw 1989
Authors: Cantanhêde Lilian Motta , Cupolillo Elisa
Published: June 2023

Just over 30 years ago, a new species of Leishmania of the subgenus Leishmania (Viannia) was described infecting the armadillo Dasypus novemcinctus; then, a report of human infection followed. From the Brazilian Amazon and apparently restricted to this region and its close borders, Leishmania (Viannia) naiffi has been characterized as a species that grows easily in axenic culture medium and causes few to no lesions after inoculation in experimental animal models. Results in the last decade indicate the occurrence of L. naiffi in vectors and human infections, including a report of therapeutic failure possibly associated with Leishmania RNA virus 1. Overall, such accounts suggest that the parasite is more dispersed and the disease less self-healing than previously expected.

Graphical Abstract
Paravertebral paraganglioma with spinal extension: a case report
Authors: Anavi K. , Daya R. , Daya S. , Purbhoo K. , Profyris C. , Mpanza M. N. , Nel C. E. , Bayat Z.
Published: June 2023

Background

Paragangliomas are rare neuroendocrine tumors. While paragangliomas of the spine are rare, those located in non-cauda equina areas with spinal canal extension are even rarer.

Case presentation

We present a case of a 23-year-old female of African descent with a primary thoracic paraganglioma with intervertebral extension resulting in displacement and compression of the spinal cord and extensive local invasion of the surrounding structures. This paraganglioma was functional with typical symptoms of catecholamine excess. Despite the aggressive nature of the paraganglioma, the patient only had isolated sensory symptoms in the left shoulder. Adequate alpha and beta-blockade were instituted prior to her undergoing surgery with near-total resection and complete preserved neurology. There was no underlying pathogenic genetic mutation found.

Conclusions

Even though rare, paraganglioma should be considered in the differential diagnosis of spinal tumors. Genetic testing should be performed in patients with paragangliomas. One should exercise extreme caution in treating such rare tumors that may cause neurological deficits and careful surgical planning should be undertaken to avoid possible catastrophic complications.